Nova Scotia Health Authority

During the last 2 decades, major advances have been made in understanding the development of executive functions (EFs) in early childhood. This article reviews the EF literature during the preschool period using an integrative framework. The framework adopted considers EF to be a unitary construct with partially dissociable components (A. Miyake et al., 2000). The authors focus on 3 EF components: working memory, response inhibition, and shifting. For the present purposes, the central executive is conceived of as a central attention system that is involved in all EF component operations. Research to date suggests that elementary forms of the core EF components are present early during the preschool period. Changes in EF during the latter half of the preschool period appear to be due to the development of attention and integration of component EFs. Finally, the review outlines a number of areas that warrant further investigation if researchers are to move forward in understanding early EF development.

BACKGROUND: Many definitions of frailty exist, but few have been directly compared. We compared the relationship between a definition of frailty based on a specific phenotype with one based on an index of deficit accumulation. METHODS: The data come from all 2305 people 70 years old and older who composed the clinical examination cohort of the second wave of the Canadian Study of Health and Aging. We tested convergent validity by correlating the measures with each other and with other health status measures, and analyzed cumulative index distributions in relation to phenotype. To test criterion validity, we evaluated survival (institutionalization and all-cause mortality) by frailty index (FI) score, stratified by the phenotypic definitions as "robust," "pre-frail," and "frail." RESULTS: The measures correlated moderately well with each other (R=0.65) and with measures of function (phenotypic definition R=0.66; FI R=0.73) but less well with cognition (phenotypic definition R=-0.35; FI R=-0.58). The median FI scores increased from 0.12 for the robust to 0.30 for the pre-frail and 0.44 for the frail. Survival was also lower with increasing frailty, and institutionalization was more common, but within each phenotypic class, there were marked differences in outcomes based on the FI values-e.g., among robust people, the median 5-year survival for those with lower FI values was 85%, compared with 55% for those with higher FI values. CONCLUSION: The phenotypic definition of frailty, which offers ready clinical operationalization, discriminates broad levels of risk. The FI requires additional clinical translation, but allows the risk of adverse outcomes to be defined more precisely.

BACKGROUND: A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70). METHODS: This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. RESULTS: In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. CONCLUSIONS: In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. (Funded by GlaxoSmithKline Biologicals; ZOE-50 and ZOE-70 ClinicalTrials.gov numbers, NCT01165177 and NCT01165229 .).

BACKGROUND: Patients with chronic limb-threatening ischemia (CLTI) require revascularization to improve limb perfusion and thereby limit the risk of amputation. It is uncertain whether an initial strategy of endovascular therapy or surgical revascularization for CLTI is superior for improving limb outcomes. METHODS: In this international, randomized trial, we enrolled 1830 patients with CLTI and infrainguinal peripheral artery disease in two parallel-cohort trials. Patients who had a single segment of great saphenous vein that could be used for surgery were assigned to cohort 1. Patients who needed an alternative bypass conduit were assigned to cohort 2. The primary outcome was a composite of a major adverse limb event - which was defined as amputation above the ankle or a major limb reintervention (a new bypass graft or graft revision, thrombectomy, or thrombolysis) - or death from any cause. RESULTS: In cohort 1, after a median follow-up of 2.7 years, a primary-outcome event occurred in 302 of 709 patients (42.6%) in the surgical group and in 408 of 711 patients (57.4%) in the endovascular group (hazard ratio, 0.68; 95% confidence interval [CI], 0.59 to 0.79; P<0.001). In cohort 2, a primary-outcome event occurred in 83 of 194 patients (42.8%) in the surgical group and in 95 of 199 patients (47.7%) in the endovascular group (hazard ratio, 0.79; 95% CI, 0.58 to 1.06; P = 0.12) after a median follow-up of 1.6 years. The incidence of adverse events was similar in the two groups in the two cohorts. CONCLUSIONS: Among patients with CLTI who had an adequate great saphenous vein for surgical revascularization (cohort 1), the incidence of a major adverse limb event or death was significantly lower in the surgical group than in the endovascular group. Among the patients who lacked an adequate saphenous vein conduit (cohort 2), the outcomes in the two groups were similar. (Funded by the National Heart, Lung, and Blood Institute; BEST-CLI ClinicalTrials.gov number, NCT02060630.).

BACKGROUND: Patients with active cancer have an increased risk of venous thromboembolism, which results in substantial morbidity, mortality, and health care expenditures. The Khorana score (range, 0 to 6, with higher scores indicating a higher risk of venous thromboembolism) has been validated to identify patients with cancer at elevated risk for this complication and may help select those who could benefit from thromboprophylaxis. METHODS: We conducted a randomized, placebo-controlled, double-blind clinical trial assessing the efficacy and safety of apixaban (2.5 mg twice daily) for thromboprophylaxis in ambulatory patients with cancer who were at intermediate-to-high risk for venous thromboembolism (Khorana score, ≥2) and were initiating chemotherapy. The primary efficacy outcome was objectively documented venous thromboembolism over a follow-up period of 180 days. The main safety outcome was a major bleeding episode. RESULTS: Of the 574 patients who underwent randomization, 563 were included in the modified intention-to-treat analysis. Venous thromboembolism occurred in 12 of 288 patients (4.2%) in the apixaban group and in 28 of 275 patients (10.2%) in the placebo group (hazard ratio, 0.41; 95% confidence interval [CI], 0.26 to 0.65; P<0.001). In the modified intention-to-treat analysis, major bleeding occurred in 10 patients (3.5%) in the apixaban group and in 5 patients (1.8%) in the placebo group (hazard ratio, 2.00; 95% CI, 1.01 to 3.95; P = 0.046). During the treatment period, major bleeding occurred in 6 patients (2.1%) in the apixaban group and in 3 patients (1.1%) in the placebo group (hazard ratio, 1.89; 95% CI, 0.39 to 9.24). CONCLUSIONS: Apixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo. (Funded by the Canadian Institutes of Health Research and Bristol-Myers Squibb-Pfizer Alliance; AVERT ClinicalTrials.gov number, NCT02048865.).

An odds ratio (OR) is a measure of association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. Odds ratios are most commonly used in case-control studies, however they can also be used in cross-sectional and cohort study designs as well (with some modifications and/or assumptions). Odds ratios and logistic regression When a logistic regression is calculated, the regression coefficient (b1) is the estimated increase in the log odds of the outcome per unit increase in the value of the exposure. In other words, the exponential function of the regression coefficient (e b1 ) is the odds ratio associated with a one-unit increase in the exposure.

These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009, prior to the 2009 H1N1 influenza pandemic. This document addresses new information regarding diagnostic testing, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal influenza. It is intended for use by primary care clinicians, obstetricians, emergency medicine providers, hospitalists, laboratorians, and infectious disease specialists, as well as other clinicians managing patients with suspected or laboratory-confirmed influenza. The guidelines consider the care of children and adults, including special populations such as pregnant and postpartum women and immunocompromised patients.

BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of acute respiratory infection, lower respiratory tract disease, clinical complications, and death in older adults. There is currently no licensed vaccine against RSV infection. METHODS: -adjuvanted RSV prefusion F protein-based candidate vaccine (RSVPreF3 OA) or placebo before the RSV season. The primary objective was to show vaccine efficacy of one dose of the RSVPreF3 OA vaccine against RSV-related lower respiratory tract disease, confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), during one RSV season. The criterion for meeting the primary objective was a lower limit of the confidence interval around the efficacy estimate of more than 20%. Efficacy against severe RSV-related lower respiratory tract disease and RSV-related acute respiratory infection was assessed, and analyses according to RSV subtype (A and B) were performed. Safety was evaluated. RESULTS: A total of 24,966 participants received one dose of the RSVPreF3 OA vaccine (12,467 participants) or placebo (12,499). Over a median follow-up of 6.7 months, vaccine efficacy against RT-PCR-confirmed RSV-related lower respiratory tract disease was 82.6% (96.95% confidence interval [CI], 57.9 to 94.1), with 7 cases (1.0 per 1000 participant-years) in the vaccine group and 40 cases (5.8 per 1000 participant-years) in the placebo group. Vaccine efficacy was 94.1% (95% CI, 62.4 to 99.9) against severe RSV-related lower respiratory tract disease (assessed on the basis of clinical signs or by the investigator) and 71.7% (95% CI, 56.2 to 82.3) against RSV-related acute respiratory infection. Vaccine efficacy was similar against the RSV A and B subtypes (for RSV-related lower respiratory tract disease: 84.6% and 80.9%, respectively; for RSV-related acute respiratory infection: 71.9% and 70.6%, respectively). High vaccine efficacy was observed in various age groups and in participants with coexisting conditions. The RSVPreF3 OA vaccine was more reactogenic than placebo, but most adverse events for which reports were solicited were transient, with mild-to-moderate severity. The incidences of serious adverse events and potential immune-mediated diseases were similar in the two groups. CONCLUSIONS: A single dose of the RSVPreF3 OA vaccine had an acceptable safety profile and prevented RSV-related acute respiratory infection and lower respiratory tract disease and severe RSV-related lower respiratory tract disease in adults 60 years of age or older, regardless of RSV subtype and the presence of underlying coexisting conditions. (Funded by GlaxoSmithKline Biologicals; AReSVi-006 ClinicalTrials.gov number, NCT04886596.).

BACKGROUND: Renin-angiotensin system (RAS) signaling and angiotensin-converting enzyme 2 (ACE2) have been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). We postulated that repleting ACE2 using GSK2586881, a recombinant form of human angiotensin-converting enzyme 2 (rhACE2), could attenuate acute lung injury. METHODS: We conducted a two-part phase II trial comprising an open-label intrapatient dose escalation and a randomized, double-blind, placebo-controlled phase in ten intensive care units in North America. Patients were between the ages of 18 and 80 years, had an American-European Consensus Criteria consensus diagnosis of ARDS, and had been mechanically ventilated for less than 72 h. In part A, open-label GSK2586881 was administered at doses from 0.1 mg/kg to 0.8 mg/kg to assess safety, pharmacokinetics, and pharmacodynamics. Following review of data from part A, a randomized, double-blind, placebo-controlled investigation of twice-daily doses of GSK2586881 (0.4 mg/kg) for 3 days was conducted (part B). Biomarkers, physiological assessments, and clinical endpoints were collected over the dosing period and during follow-up. RESULTS: Dose escalation in part A was well-tolerated without clinically significant hemodynamic changes. Part B was terminated after 39 of the planned 60 patients following a planned futility analysis. Angiotensin II levels decreased rapidly following infusion of GSK2586881, whereas angiotensin-(1-7) and angiotensin-(1-5) levels increased and remained elevated for 48 h. Surfactant protein D concentrations were increased, whereas there was a trend for a decrease in interleukin-6 concentrations in rhACE2-treated subjects compared with placebo. No significant differences were noted in ratio of partial pressure of arterial oxygen to fraction of inspired oxygen, oxygenation index, or Sequential Organ Failure Assessment score. CONCLUSIONS: GSK2586881 was well-tolerated in patients with ARDS, and the rapid modulation of RAS peptides suggests target engagement, although the study was not powered to detect changes in acute physiology or clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01597635 . Registered on 26 January 2012.

BACKGROUND: Global vaccine development efforts have been accelerated in response to the devastating coronavirus disease 2019 (COVID-19) pandemic. We evaluated the impact of a 2-dose COVID-19 vaccination campaign on reducing incidence, hospitalizations, and deaths in the United States. METHODS: We developed an agent-based model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and parameterized it with US demographics and age-specific COVID-19 outcomes. Healthcare workers and high-risk individuals were prioritized for vaccination, whereas children under 18 years of age were not vaccinated. We considered a vaccine efficacy of 95% against disease following 2 doses administered 21 days apart achieving 40% vaccine coverage of the overall population within 284 days. We varied vaccine efficacy against infection and specified 10% preexisting population immunity for the base-case scenario. The model was calibrated to an effective reproduction number of 1.2, accounting for current nonpharmaceutical interventions in the United States. RESULTS: Vaccination reduced the overall attack rate to 4.6% (95% credible interval [CrI]: 4.3%-5.0%) from 9.0% (95% CrI: 8.4%-9.4%) without vaccination, over 300 days. The highest relative reduction (54%-62%) was observed among individuals aged 65 and older. Vaccination markedly reduced adverse outcomes, with non-intensive care unit (ICU) hospitalizations, ICU hospitalizations, and deaths decreasing by 63.5% (95% CrI: 60.3%-66.7%), 65.6% (95% CrI: 62.2%-68.6%), and 69.3% (95% CrI: 65.5%-73.1%), respectively, across the same period. CONCLUSIONS: Our results indicate that vaccination can have a substantial impact on mitigating COVID-19 outbreaks, even with limited protection against infection. However, continued compliance with nonpharmaceutical interventions is essential to achieve this impact.

BACKGROUND: Prognosis research aims to identify factors associated with the course of health conditions. It is often challenging to judge the overall quality of research evidence in systematic reviews about prognosis due to the nature of the primary studies. Standards aimed at improving the quality of primary studies on the prognosis of health conditions have been created, but these standards are often not adequately followed causing confusion about how to judge the evidence. METHODS: This article presents a proposed adaptation of Grading of Recommendations Assessment, Development and Evaluation (GRADE), which was developed to rate the quality of evidence in intervention research, to judge the quality of prognostic evidence. RESULTS: We propose modifications to the GRADE framework for use in prognosis research along with illustrative examples from an ongoing systematic review in the pediatric pain literature. We propose six factors that can decrease the quality of evidence (phase of investigation, study limitations, inconsistency, indirectness, imprecision, publication bias) and two factors that can increase it (moderate or large effect size, exposure-response gradient). CONCLUSIONS: We describe criteria for evaluating the potential impact of each of these factors on the quality of evidence when conducting a review including a narrative synthesis or a meta-analysis. These recommendations require further investigation and testing.

BACKGROUND: Mental health literacy has received increasing attention as a useful strategy to promote early identification of mental disorders, reduce stigma and enhance help-seeking behaviors. However, despite the abundance of research on mental health literacy interventions, there is the absence of evaluations of current available mental health literacy measures and related psychometrics. We conducted a scoping review to bridge the gap. METHODS: We searched PubMed, PsycINFO, Embase, CINAHL, Cochrane Library, and ERIC for relevant studies. We only focused on quantitative studies and English publications, however, we didn't limit study participants, locations, or publication dates. We excluded non-English studies, and did not check the grey literature (non peer-reviewed publications or documents of any type) and therefore may have missed some eligible measures. RESULTS: We located 401 studies that include 69 knowledge measures (14 validated), 111 stigma measures (65 validated), and 35 help-seeking related measures (10 validated). Knowledge measures mainly investigated the ability of illness identification, and factual knowledge of mental disorders such as terminology, etiology, diagnosis, prognosis, and consequences. Stigma measures include those focused on stigma against mental illness or the mentally ill; self-stigma ; experienced stigma; and stigma against mental health treatment and help-seeking. Help-seeking measures included those of help-seeking attitudes, intentions to seek help, and actual help-seeking behaviors. CONCLUSIONS: Our review provides a compendium of available mental health literacy measures to facilitate applying existing measures or developing new measures. It also provides a solid database for future research on systematically assessing the quality of the included measures.

Preterm birth is commonly defined as any birth before 37 weeks completed weeks of gestation. An estimated 15 million infants are born preterm globally, disproportionately affecting low and middle income countries (LMIC). It contributes directly to estimated one million neonatal deaths annually and is a significant contributor to childhood morbidity. However, in many clinical settings, the information available to calculate completed weeks of gestation varies widely. Accurate dating of the last menstrual period (LMP), as well as access to clinical and ultrasonographic evaluation are important components of gestational age assessment antenatally. This case definition assign levels of confidence to categorisation of births as preterm, utilising assessment modalities which may be available across different settings. These are designed to enable systematic safety evaluation of vaccine clinical trials and post-implementation programmes of immunisations in pregnancy.

BACKGROUND: Excess deaths have occurred among pregnant women during influenza pandemics, but the impact of influenza during nonpandemic years is unclear. We evaluated the impact of exposure during nonpandemic influenza seasons on the rates of hospital admissions and physician visits because of respiratory illness among pregnant women. METHODS: We conducted a 13-year (1990-2002) population-based cohort study involving pregnant women in Nova Scotia. We compared rates of hospital admissions and physician office visits because of respiratory illness during the influenza season in each trimester of pregnancy with rates during the influenza season in the year before pregnancy and with rates in non-influenza seasons. Poisson regression analyses were performed to estimate rate ratios and 95% confidence intervals (CIs). RESULTS: Of 134,188 pregnant women in the study cohort, 510 (0.4%) were admitted to hospital because of a respiratory illness during pregnancy and 33,775 (25.2%) visited their physician for the same reason during pregnancy. During the influenza seasons, the rate ratio of hospital admissions in the third trimester compared with admissions in the year before pregnancy was 7.9 (95% CI 5.0-12.5) among women with comorbidities and 5.1 (95% CI 3.6-7.3) among those without comorbidities. The rate of hospital admissions in the third trimester among women without comorbidities was 7.4 per 10,000 woman-months during the influenza season, compared with 5.4 and 3.1 per 10,000 woman-months during the peri-and non-influenza seasons respectively. Corresponding rates among women with comorbidities were 44.9, 9.3 and 18.9 per 10,000 woman-months. Only 6.7% of women with comorbidities had received influenza immunization. INTERPRETATION: Our data support the recommendation that pregnant women with comorbidities should receive influenza vaccination regardless of their stage of pregnancy during the influenza season. Since hospital admissions because of respiratory illness during the influenza season were also increased among pregnant women without comorbidities, all pregnant women are likely to benefit from influenza vaccination.

BACKGROUND: Clinical trials and meta-analyses have suggested that aspirin may be effective for the prevention of venous thromboembolism (proximal deep-vein thrombosis or pulmonary embolism) after total hip or total knee arthroplasty, but comparisons with direct oral anticoagulants are lacking for prophylaxis beyond hospital discharge. METHODS: We performed a multicenter, double-blind, randomized, controlled trial involving patients who were undergoing total hip or knee arthroplasty. All the patients received once-daily oral rivaroxaban (10 mg) until postoperative day 5 and then were randomly assigned to continue rivaroxaban or switch to aspirin (81 mg daily) for an additional 9 days after total knee arthroplasty or for 30 days after total hip arthroplasty. Patients were followed for 90 days for symptomatic venous thromboembolism (the primary effectiveness outcome) and bleeding complications, including major or clinically relevant nonmajor bleeding (the primary safety outcome). RESULTS: A total of 3424 patients (1804 undergoing total hip arthroplasty and 1620 undergoing total knee arthroplasty) were enrolled in the trial. Venous thromboembolism occurred in 11 of 1707 patients (0.64%) in the aspirin group and in 12 of 1717 patients (0.70%) in the rivaroxaban group (difference, 0.06 percentage points; 95% confidence interval [CI], -0.55 to 0.66; P<0.001 for noninferiority and P=0.84 for superiority). Major bleeding complications occurred in 8 patients (0.47%) in the aspirin group and in 5 (0.29%) in the rivaroxaban group (difference, 0.18 percentage points; 95% CI, -0.65 to 0.29; P=0.42). Clinically important bleeding occurred in 22 patients (1.29%) in the aspirin group and in 17 (0.99%) in the rivaroxaban group (difference, 0.30 percentage points; 95% CI, -1.07 to 0.47; P=0.43). CONCLUSIONS: Among patients who received 5 days of rivaroxaban prophylaxis after total hip or total knee arthroplasty, extended prophylaxis with aspirin was not significantly different from rivaroxaban in the prevention of symptomatic venous thromboembolism. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT01720108 .).

Seasonal influenza A and B virus epidemics are associated with significant morbidity and mortality each year in the United States and worldwide. One study estimated that during 2010–2016, the seasonal incidence of symptomatic influenza among all ages in the United States was approximately 8% and varied from 3% to 11% [1]. Most people recover from uncomplicated influenza, but influenza can cause complications that result in severe illness and death, particularly among very young children, older adults, pregnant and postpartum women within 2 weeks of delivery, people with neurologic disorders, and people with certain chronic medical conditions including chronic pulmonary, cardiac, and metabolic disease, and those who are immunocompromised [2–8]. During 2010–2018, seasonal influenza epidemics were associated with an estimated 4.3–23 million medical visits, 140 000–960 000 hospitalizations, and 12 000–79 000 respiratory and circulatory deaths each year in the United States [9]. A recent modeling study estimated that 291 243–645 832 seasonal influenza–associated respiratory deaths occur annually worldwide [10]. Use of available diagnostic modalities and proper interpretation of results can accurately identify patients presenting with influenza. Timely diagnosis may decrease unnecessary laboratory testing for other etiologies and use of antibiotics, improve the effectiveness of infection prevention and control measures, and increase appropriate use of antiviral medications [11, 12]. Early treatment with antivirals reduces the duration of symptoms and risk of some complications (bronchitis, otitis media, and pneumonia) and hospitalization, and may decrease mortality among high-risk populations [13–16]. Annual vaccination is the best method for preventing or mitigating the impact of influenza, but in certain situations, chemoprophylaxis with antiviral medications can be used for preexposure or postexposure prevention and can help control outbreaks in certain populations. These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009 [17]. The guidelines consider the care of children, pregnant and postpartum women, and nonpregnant adults and include special considerations for patients who are severely immunocompromised such as hematopoietic stem cell and solid organ transplant recipients. The target audience includes primary care clinicians, obstetricians, emergency medicine providers, hospitalists, and infectious disease specialists. The guidelines may be also useful for occupational health physicians and clinicians working in long-term care facilities. It adds new information on diagnostic testing, use of antivirals, and considerations of when to use antibiotics and when to test for antiviral resistance, and presents evidence on harm associated with routine use of corticosteroids. The panel followed a process used in the development of previous IDSA guidelines that included a systematic weighting of the strength of recommendations and quality of evidence based upon the US Public Health Service Grading System for ranking recommendations in clinical guidelines as utilized in the previous 2009 guidelines (Table 1) [17]. Summarized below are the recommendations. A detailed description of background, methods, evidence summary, and rationale that support each recommendation, and research needs are included in the full document. Infectious Diseases Society of America–US Public Health Service Grading System for Ranking Recommendations in Clinical Guidelines Adapted from the Canadian Task Force on the Periodic Health Examination [6]. Infectious Diseases Society of America–US Public Health Service Grading System for Ranking Recommendations in Clinical Guidelines Adapted from the Canadian Task Force on the Periodic Health Examination [6]. Because prevention and control of influenza is a dynamic field, clinicians should consult the website of the Centers for Disease Control and Prevention (CDC) for the latest information about influenza vaccines, influenza tests, and approved antiviral medications. 1. During influenza activity (defined as the circulation of seasonal influenza A and B viruses among persons in the local community): Clinicians should test for influenza in high-risk patients, including immunocompromised persons who present with influenza-like illness, pneumonia, or nonspecific respiratory illness (eg, cough without fever) if the testing result will influence clinical management (A-III). Clinicians should test for influenza in patients who present with acute onset of respiratory symptoms with or without fever, and either exacerbation of chronic medical conditions (eg, asthma, chronic obstructive pulmonary disease [COPD], heart failure) or known complications of influenza (eg, pneumonia) if the testing result will influence clinical management (A-III) (see Table 3). Clinicians can consider influenza testing for patients not at high risk for influenza complications who present with influenza-like illness, pneumonia, or nonspecific respiratory illness (eg, cough without fever) and who are likely to be discharged home if the results might influence antiviral treatment decisions or reduce use of unnecessary antibiotics, further diagnostic testing, and time in the emergency department, or if the results might influence antiviral treatment or chemoprophylaxis decisions for high-risk household contacts (see recommendations 40–42) (C-III). 2. During low influenza activity without any link to an influenza outbreak: Clinicians can consider influenza testing in patients with acute onset of respiratory symptoms with or without fever, especially for immunocompromised and high-risk patients (B-III). Clinical Manifestations and Complications Associated With Influenza Adapted from Jani AA, Uyeki TM. Chapter 46. Influenza. In: Emergency management of infectious diseases. 2nd ed. Chin RL, ed. Cambridge, UK: Cambridge University Press, 2018. Clinical Manifestations and Complications Associated With Influenza Adapted from Jani AA, Uyeki TM. Chapter 46. Influenza. In: Emergency management of infectious diseases. 2nd ed. Chin RL, ed. Cambridge, UK: Cambridge University Press, 2018. 3. During influenza activity: Clinicians should test influenza on admission in all patients requiring hospitalization with acute respiratory illness, including pneumonia, with or without fever (A-II). Clinicians should test for influenza on admission in all patients with acute worsening of chronic cardiopulmonary disease (eg, COPD, asthma, coronary artery disease, or heart failure), as influenza can be associated with exacerbation of underlying conditions (A-III). Clinicians should test for influenza on admission in all patients who are immunocompromised or at high risk of complications and present with acute onset of respiratory symptoms with or without fever, as the manifestations of influenza in such patients are frequently less characteristic than in immunocompetent individuals (A-III). Clinicians should test for influenza in all patients who, while hospitalized, develop acute onset of respiratory symptoms, with or without fever, or respiratory distress, without a clear alternative diagnosis (A-III). 4. During periods of low influenza activity: Clinicians should test for influenza on admission in all patients requiring hospitalization with acute respiratory illness, with or without fever, who have an epidemiological link to a person diagnosed with influenza, an influenza outbreak or outbreak of acute febrile respiratory illness of uncertain cause, or who recently traveled from an area with known influenza activity (A-II). Clinicians can consider testing for influenza in patients with acute, febrile respiratory tract illness, especially children and adults who are immunocompromised or at high risk of complications, or if the results might influence antiviral treatment or chemoprophylaxis decisions for high-risk household contacts (see recommendations 41–43) (B-III). 5. Clinicians should collect upper respiratory tract specimens from outpatients for influenza testing as soon after illness onset as possible, preferably within 4 days of symptom onset (A-II). Nasopharyngeal specimens should be collected over other upper respiratory tract specimens to increase detection of influenza viruses (A-II). If nasopharyngeal specimens are not available, nasal and throat swab specimens should be collected and combined together for influenza testing over single specimens from either site (particularly over throat swabs) to increase detection of influenza viruses (A-II). Mid-turbinate nasal swab specimens should be collected over throat swab specimens to increase detection of influenza viruses (A-II). Flocked swab specimens should be collected over nonflocked swab specimens to improve detection of influenza viruses (A-II). 6. Clinicians should collect nasopharyngeal (optimally, as for outpatients), mid-turbinate nasal, or combined nasal–throat specimens from hospitalized patients without severe lower respiratory tract disease for influenza testing as soon as possible (A-II). 7. Clinicians should collect endotracheal aspirate or bronchoalveolar lavage fluid specimens from hospitalized patients with respiratory failure receiving mechanical ventilation, including patients with negative influenza testing results on upper respiratory tract specimens, for influenza testing as soon as possible (A-II). 8. Clinicians should not collect or routinely test specimens for influenza from nonrespiratory sites such as blood, plasma, serum, cerebrospinal fluid, urine, and stool (A-III). 9. Clinicians should not collect serum specimens, including single or paired sera, for serological diagnosis of seasonal influenza virus infection for clinical management purposes (A-III). 10. Clinicians should use rapid molecular assays (ie, nucleic acid amplification tests) over rapid influenza diagnostic tests (RIDTs) in outpatients to improve detection of influenza virus infection (A-II) (see Table 6). 11. Clinicians should use reverse-transcription polymerase chain reaction (RT-PCR) or other molecular assays over other influenza tests in hospitalized patients to improve detection of influenza virus infection (A-II) (see Table 6). 12. Clinicians should use multiplex RT-PCR assays targeting a panel of respiratory pathogens, including influenza viruses, in hospitalized immunocompromised patients (A-III). 13. Clinicians can consider using multiplex RT-PCR assays targeting a panel of respiratory pathogens, including influenza viruses, in hospitalized patients who are not immunocompromised if it might influence care (eg, aid in cohorting decisions, reduce testing, or decrease antibiotic use) (B-III). 14. Clinicians should not use immunofluorescence assays for influenza virus antigen detection in hospitalized patients except when more sensitive molecular assays are not available (A-II), and follow-up testing with RT-PCR or other molecular assays should be performed to confirm negative immunofluorescence test results (A-III). 15. Clinicians should not use RIDTs in hospitalized patients except when more sensitive molecular assays are not available (A-II), and follow-up testing with RT-PCR or other molecular assays should be performed to confirm negative RIDT results (A-II). 16. Clinicians should not use viral culture for initial or primary diagnosis of influenza because results will not be available in a timely manner to inform clinical management (A-III), but viral culture can be considered to confirm negative test results from RIDTs and immunofluorescence assays, such as during an institutional outbreak, and to provide isolates for further characterization (C-II). 17. Clinicians should not use serologic testing for diagnosis of influenza because results from a single serum specimen cannot be reliably interpreted, and collection of paired (acute/convalescent) sera 2–3 weeks apart are needed for serological testing (A-III). Influenza Diagnostic Tests for Respiratory Specimens Negative results may not rule out influenza. Respiratory tract specimens should be collected as close to illness onset as possible for testing. Clinicians should consult the manufacturer’s package insert for the specific test for the approved respiratory specimen(s). Most US Food and Drug Administration (FDA)–cleared influenza diagnostic tests are approved for upper respiratory tract specimens but not for sputum or lower respiratory tract specimens. Specificities are generally high (>90%) for all tests compared to RT-PCR. FDA-cleared rapid influenza diagnostic tests are Clinical Laboratory Improvement Amendments (CLIA)–waived; most FDA-cleared rapid influenza molecular assays are CLIA-waived, depending on the specimen. Abbreviation: RT-PCR, reverse-transcription polymerase chain reaction. Influenza Diagnostic Tests for Respiratory Specimens Negative results may not rule out influenza. Respiratory tract specimens should be collected as close to illness onset as possible for testing. Clinicians should consult the manufacturer’s package insert for the specific test for the approved respiratory specimen(s). Most US Food and Drug Administration (FDA)–cleared influenza diagnostic tests are approved for upper respiratory tract specimens but not for sputum or lower respiratory tract specimens. Specificities are generally high (>90%) for all tests compared to RT-PCR. FDA-cleared rapid influenza diagnostic tests are Clinical Laboratory Improvement Amendments (CLIA)–waived; most FDA-cleared rapid influenza molecular assays are CLIA-waived, depending on the specimen. Abbreviation: RT-PCR, reverse-transcription polymerase chain reaction. 18. Clinicians should start antiviral treatment as soon as possible for adults and children with documented or suspected influenza, irrespective of influenza vaccination history, who meet the following criteria: Persons of any age who are hospitalized with influenza, regardless of illness duration prior to hospitalization (A-II). Outpatients of any age with severe or progressive illness, regardless of illness duration (A-III). Outpatients who are at high risk of complications from influenza, including those with chronic medical conditions and immunocompromised patients (A-II). Children younger than 2 years and adults ≥65 years (A-III). Pregnant women and those within 2 weeks postpartum (A-III). 19. Clinicians can consider antiviral treatment for adults and children who are not at high risk of influenza complications, with documented or suspected influenza, irrespective of influenza vaccination history, who are either: Outpatients with illness onset ≤2 days before presentation (C-I). Symptomatic outpatients who are household contacts of persons who are at high risk of developing complications from influenza, particularly those who are severely immunocompromised (C-III). Symptomatic healthcare providers who care for patients who are at high risk of developing complications from influenza, particularly those who are severely immunocompromised (C-III). 20. Clinicians should start antiviral treatment as soon as possible with a single neuraminidase inhibitor (NAI) (either oral oseltamivir, inhaled zanamivir, or intravenous peramivir) and not use a combination of NAIs (A-1). 21. Clinicians should not routinely use higher doses of US Food and Drug Administration–approved NAI drugs for the treatment of seasonal influenza (A-II). 22. Clinicians should treat uncomplicated influenza in otherwise healthy ambulatory patients for 5 days with oral oseltamivir or inhaled zanamivir, or a single dose of intravenous peramivir (A-1). 23. Clinicians can consider longer duration of antiviral treatment for patients with a documented or suspected immunocompromising condition or patients requiring hospitalization for severe lower respiratory tract disease (especially pneumonia or acute respiratory distress syndrome [ARDS]), as influenza viral replication is often protracted (C-III). 24. Clinicians should investigate and empirically treat bacterial coinfection in patients with suspected or laboratory-confirmed influenza who present initially with severe disease (extensive pneumonia, respiratory failure, hypotension, and fever), in addition to antiviral treatment for influenza (A-II). 25. Clinicians should investigate and empirically treat bacterial coinfection in patients who deteriorate after initial improvement, particularly in those treated with antivirals (A-III). 26. Clinicians can consider investigating bacterial coinfection in patients who fail to improve after 3–5 days of antiviral treatment (C-III). 27. Clinicians should investigate other causes besides influenza virus infection in influenza patients who fail to improve or deteriorate despite antiviral treatment (A-III). 28. Influenza NAI resistance testing can be considered for: Patients who develop laboratory-confirmed influenza while on or immediately after NAI chemoprophylaxis (C-III). Patients with an immunocompromising condition and evidence of persistent influenza viral replication (eg, after 7–10 days, demonstrated by persistently positive RT-PCR or viral culture results) and remain ill during or after NAI treatment (B-III). Patients with laboratory-confirmed influenza who inadvertently received subtherapeutic NAI dosing (C-III). Patients with severe influenza who do not improve with NAI treatment and have evidence of persistent influenza viral replication (eg, after 7–10 days) (C-II). 29. Clinicians should remain informed on current CDC and World Health Organization surveillance data on the frequency and geographic distribution of NAI-resistant influenza viruses during influenza season, and with the latest CDC antiviral treatment recommendations (A-III). 30. Clinicians should not administer corticosteroid adjunctive therapy for the treatment of adults or children with suspected or confirmed seasonal influenza, influenza-associated pneumonia, respiratory failure, or ARDS, unless clinically indicated for other reasons (A-III). 31. Clinicians should not routinely administer immunomodulation using immunoglobulin preparations such as intravenous immunoglobulin for treatment of adults or children with suspected or confirmed seasonal influenza (A-III). Antiviral drugs should not be used for routine or widespread chemoprophylaxis outside of institutional outbreaks; antiviral chemoprophylaxis can be considered in certain situations: 32. Clinicians can consider antiviral chemoprophylaxis for the duration of the influenza season for adults and children aged ≥3 months who are at very high risk of developing complications from influenza and for whom influenza vaccination is contraindicated, unavailable, or expected to have low effectiveness (eg, persons who are severely immunocompromised) (C-II). 33. Clinicians can consider antiviral chemoprophylaxis for the duration of the influenza season for adults and children aged ≥3 months who have the highest risk of influenza-associated complications, such as recipients of hematopoietic stem cell transplant in the first 6–12 months posttransplant and lung transplant recipients (B-II). 34. Clinicians can consider short-term antiviral chemoprophylaxis in conjunction with prompt administration of inactivated influenza vaccine for unvaccinated adults and children aged ≥3 months who are at high risk of developing complications from influenza in whom influenza vaccination is expected to be effective (but not yet administered) when influenza activity has been detected in the community (C-II). 35. Clinicians can consider short-term antiviral chemoprophylaxis for unvaccinated adults, including healthcare personnel, and for children aged ≥3 months who are in close contact with persons at high risk of developing influenza complications during periods of influenza activity when influenza vaccination is contraindicated or unavailable and these high-risk persons are to antiviral chemoprophylaxis (C-III). Clinicians can consider patients and of patients to for of antiviral treatment as an alternative to antiviral chemoprophylaxis (C-III). Clinicians should use an NAI oseltamivir or inhaled if preexposure chemoprophylaxis for influenza is than an antiviral (A-II). Clinicians should administer preexposure antiviral chemoprophylaxis for adults and children aged ≥3 months who are at very high risk of developing complications from influenza (eg, severely immunocompromised persons such as hematopoietic stem cell transplant for whom influenza vaccination is contraindicated, unavailable, or expected to have low as soon as influenza activity is detected in the community and for the duration of community influenza activity (A-II). Clinicians should test for influenza and to antiviral treatment dosing in persons receiving preexposure antiviral chemoprophylaxis who preferably with an antiviral with a resistance if not contraindicated (A-II). Clinicians can consider postexposure antiviral chemoprophylaxis for adults and children aged ≥3 months who are at very high risk of developing complications from influenza (eg, severely immunocompromised and for whom influenza vaccination is contraindicated, unavailable, or expected to have low after household to influenza (C-II). Clinicians can consider postexposure antiviral chemoprophylaxis conjunction with influenza for adults and children aged ≥3 months who are unvaccinated and are household contacts of a person at very high risk of complications from influenza (eg, severely immunocompromised after to influenza (C-II). Clinicians can consider patients and for of antiviral treatment as an alternative to postexposure antiviral chemoprophylaxis (C-III). If chemoprophylaxis is clinicians should administer postexposure antiviral chemoprophylaxis as soon as possible after than after (A-III). Clinicians should not administer postexposure antiviral chemoprophylaxis if has antiviral treatment should be as soon as symptoms if treatment is indicated (A-III). Antiviral Clinicians should administer postexposure antiviral chemoprophylaxis in a for days after the most recent to a close contact with influenza (A-III). 46. Clinicians should test for influenza and to antiviral treatment dosing in persons receiving postexposure antiviral chemoprophylaxis who preferably with an antiviral with a resistance if not contraindicated (A-III). Antiviral for Clinicians should administer an NAI or oral if postexposure chemoprophylaxis for influenza is than an antiviral (A-II). surveillance for should be as soon as possible when laboratory-confirmed influenza is in a or of laboratory-confirmed influenza is in a long-term care (A-III). control should be as soon as possible, including antiviral chemoprophylaxis of and surveillance for new when 2 of laboratory-confirmed influenza are within of each other in or patients of the or (A-III). of outbreak control can be considered as soon as possible if or more or patients has suspected influenza and results of influenza molecular testing are not available on the of specimen collection (B-III). an influenza outbreak has been in a long-term care or influenza testing should be for any with or more acute respiratory symptoms, with or without fever, or any of the following without respiratory or or (A-III). antiviral treatment should be as soon as possible to any or with suspected influenza during an influenza outbreak without for the results of influenza diagnostic testing (A-III). Antiviral chemoprophylaxis should be as soon as possible to all or patients who do not have suspected or laboratory-confirmed influenza regardless of influenza vaccination history, in addition to of all other influenza outbreak control measures, when an influenza outbreak has been in a long-term care or (A-III). Antiviral chemoprophylaxis should be to on in addition to surveillance for new influenza the (A-II). Clinicians can consider antiviral chemoprophylaxis for unvaccinated including those for whom chemoprophylaxis may be indicated based upon underlying conditions of the or household (see recommendations 41–43) for the duration of the outbreak (C-III). Clinicians can consider antiviral chemoprophylaxis for who inactivated influenza vaccine during an institutional influenza outbreak for days (C-III). Clinicians can consider antiviral chemoprophylaxis for regardless of influenza vaccination to reduce the risk of in and clinical is and to reduce to care for patients with suspected influenza (C-III). Clinicians should administer antiviral chemoprophylaxis for days and for at days after the onset of symptoms in the during an institutional influenza outbreak (A-III). The panel for of an by and The panel and for and in of the for with systematic and for in and recommendations. IDSA to present and the information in these guidelines is without any of or either or IDSA or will be for any or with to any including or in with these guidelines or on the information The and in are those of the and do not the of the for these guidelines was by the Infectious Diseases Society of of The following is a of has been to the provide the IDSA full of all regardless of to the of such as of is by a process that includes by the and Guidelines the to the development panel and the of to the and if the Task Force of the of for possible will be based on the of the (ie, and the of the (ie, the to an might be by an as to the or of The of these guidelines should be of when the of is from the of Health and from in the of Public and the of is a of the on at is an of the on Infectious Diseases at and is an of the at from and the and from the and outside the from and during the of the and support from and from and the Society of and from the of Health and from the World Health Organization and the University of Antiviral Drug and other from and support and to a and for and for in developing influenza or and from support from and from the the Health and the Centers for and and the of Emergency System outside the from and from and during the of the and for on a data from from and the Canadian of Health and for infection surveillance from the Public Health of outside the and other from and and from and the outside the as a to the and in as a for the of and as a for as a to from the and for and for and and for from the of and Infectious Diseases and the other from and from and outside the other of have the for of of that the consider to the of the have been

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory disease coronavirus 2 (SARS-CoV-2), has led to millions of confirmed cases and deaths worldwide. Efficient diagnostic tools are in high demand, as rapid and large-scale testing plays a pivotal role in patient management and decelerating disease spread. This paper reviews current technologies used to detect SARS-CoV-2 in clinical laboratories as well as advances made for molecular, antigen-based, and immunological point-of-care testing, including recent developments in sensor and biosensor devices. The importance of the timing and type of specimen collection is discussed, along with factors such as disease prevalence, setting, and methods. Details of the mechanisms of action of the various methodologies are presented, along with their application span and known performance characteristics. Diagnostic imaging techniques and biomarkers are also covered, with an emphasis on their use for assessing COVID-19 or monitoring disease severity or complications. While the SARS-CoV-2 literature is rapidly evolving, this review highlights topics of interest that have occurred during the pandemic and the lessons learned throughout. Exploring a broad armamentarium of techniques for detecting SARS-CoV-2 will ensure continued diagnostic support for clinicians, public health, and infection prevention and control for this pandemic and provide advice for future pandemic preparedness.

Depression is a common mental health condition for which many mobile apps aim to provide support. This review aims to identify self-help apps available exclusively for people with depression and evaluate those that offer cognitive behavioural therapy (CBT) or behavioural activation (BA). One hundred and seventeen apps have been identified after searching both the scientific literature and the commercial market. 10.26% (n = 12) of these apps identified through our search offer support that seems to be consistent with evidence-based principles of CBT or BA. Taking into account the non existence of effectiveness/efficacy studies, and the low level of adherence to the core ingredients of the CBT/BA models, the utility of these CBT/BA apps are questionable. The usability of reviewed apps is highly variable and they rarely are accompanied by explicit privacy or safety policies. Despite the growing public demand, there is a concerning lack of appropiate CBT or BA apps, especially from a clinical and legal point of view. The application of superior scientific, technological, and legal knowledge is needed to improve the development, testing, and accessibility of apps for people with depression.

Our knowledge of the prevalence and sources of pain within hospital is limited. The present study is an epidemiological investigation of pain in a pediatric hospital. All children who were inpatients in a tertiary care hospital (excluding Neonatal ICU and psychiatry patients) and one parent per child were potential subjects. Interviews were conducted on three weekdays. Parent interviews were used for children less than 5 years of age (n = 102); child interviews were used for children age 5 years and older (n = 98). Subjects reported the intensity and source of the worst, usual and current pain during the past 24 h, and help received for pain. Medical and demographic variables and analgesics prescribed and administered were obtained from the medical record. Forty-nine percent of subjects reported clinically significant levels of worst pain. Twenty-one percent of subjects had clinically significant levels of usual pain. Causes of pain were variable and included disease, surgery, and intravenous lines (I.V.). Pain intensity was not significantly related to age, gender, patient type (medical, surgical), or diagnostic category. Children were given significantly less medication than was prescribed, regardless of their reported pain level. Nurses, mothers, and 'no-one' were frequently reported as helping with pain. Medications and nonpharmacological methods were reported as helpful in managing pain. Many children endure unacceptable levels of pain during hospitalization. Pain prevention and management must be more aggressive. Pain assessment should be approached with the same attention as vital signs. Improvements in analgesic prescription and administration practices and non-pharmacological pain control methods are needed.

BACKGROUND: The ability of acute care providers to cope with the influx of frail older patients is increasingly stressed, and changes need to be made to improve care provided to older adults. Our purpose was to conduct a scoping review to map and synthesize the literature addressing frailty in the acute care setting in order to understand how to tackle this challenge. We also aimed to highlight the current gaps in frailty research. METHODS: This scoping review included original research articles with acutely-ill Emergency Medical Services (EMS) or hospitalized older patients who were identified as frail by the authors. We searched Medline, CINAHL, Embase, PsycINFO, Eric, and Cochrane from January 2000 to September 2015. RESULTS: Our database search initially resulted in 8658 articles and 617 were eligible. In 67% of the articles the authors identified their participants as frail but did not report on how they measured frailty. Among the 204 articles that did measure frailty, the most common disciplines were geriatrics (14%), emergency department (14%), and general medicine (11%). In total, 89 measures were used. This included 13 established tools, used in 51% of the articles, and 35 non-frailty tools, used in 24% of the articles. The most commonly used tools were the Clinical Frailty Scale, the Frailty Index, and the Frailty Phenotype (12% each). Most often (44%) researchers used frailty tools to predict adverse health outcomes. In 74% of the cases frailty predicted the outcome examined, typically mortality and length of stay. CONCLUSIONS: Most studies (83%) were conducted in non-geriatric disciplines and two thirds of the articles identified participants as frail without measuring frailty. There was great variability in tools used and more recently published studies were more likely to use established frailty tools. Overall, frailty appears to be a good predictor of adverse health outcomes. For frailty to be implemented in clinical practice frailty tools should help formulate the care plan and improve shared decision making. How this will happen has yet to be determined.