Clinical correlates of a high cardiorespiratory risk score for very low birth weight infants.

BACKGROUND: A pulse oximetry warning system (POWS) to analyze heart rate and oxygen saturation data and predict risk of sepsis was developed for very low birth weight (VLBW) infants. METHODS: We determined the clinical correlates and positive predictive value (PPV) of a high POWS score in VLBW infants. In a two-NICU retrospective study, we identified times when POWS increased above 6 (POWS spike). We selected an equal number of control times, matched for gestational and chronologic age. We reviewed records for infection and non-infection events around POWS spikes and control times. We calculated the frequencies and PPV of a POWS spike for infection or another significant event. RESULTS: We reviewed 111 POWS spike times and 111 control times. Days near POWS spikes were more likely to have clinical events than control days (77% vs 50%). A POWS spike had 52% PPV for suspected or confirmed infection and 77% for any clinically significant event. Respiratory deterioration occurred near more POWS spike times than control times (34% vs 18%). CONCLUSIONS: In a retrospective cohort, infection and respiratory deterioration were common clinical correlations of a POWS spike. POWS had a high PPV for significant clinical events with or without infection. IMPACT: There are significant gaps in understanding the best approach to implementing continuous sepsis prediction models so that clinicians can best respond to early signals of deterioration. Infection and respiratory deterioration were common clinical events identified at the time of a high predictive model score. Understanding the clinical correlates of a high-risk early warning score will inform future implementation efforts.

Do Naturalistic Developmental Behavioral Interventions improve family quality of life? A systematic review and meta-analysis.

LAY ABSTRACT: Naturalistic Developmental Behavioral Interventions have been described as culturally responsive and family-friendly interventions, with research demonstrating improvements in children's development following the receipt of these interventions. Given the child-directed nature of Naturalistic Developmental Behavioral Interventions and the intervention's integration within families' daily routines, many studies have examined the impact of Naturalistic Developmental Behavioral Interventions on family and family member quality of life. We conducted a systematic review and meta-analysis to explore the relationship between Naturalistic Developmental Behavioral Interventions and family quality of life. Results suggest that the provision of a Naturalistic Developmental Behavioral Intervention neither improved nor worsened family or family member quality of life. For those involved in delivering Naturalistic Developmental Behavioral Intervention services, there is an immediate need to convey to families that children's improvements will likely not translate into improvements in family quality of life.

Listening to Trainee Concerns and Suggestions During COVID-19: a Report from the Canadian Consortium on Neurodegeneration in Aging (CCNA).

Background: The COVID-19 pandemic has caused significant disruption to research activities across Canada. The Training and Capacity Building (T&CB) Program of the Canadian Consortium on Neurodegeneration in Aging (CCNA) conducted a survey between May 11th, 2020 and May 19th, 2020 to identify the challenges faced by CCNA trainees because of the pandemic and how to best support trainees in response to those challenges. Methods: Graduate students and postdoctoral researchers working under the supervision of CCNA investigators (n=113) were invited to complete a web-based survey of 13 questions. Trainees were asked questions about the impact of COVID-19 on their research activities, degree progression, funding status, and suggestions for support from the T&CB Program during the COVID-19 pandemic. Results: A total of 41 trainees responded to the survey (response rate: 36.3%); 83% of respondents reported that they experienced changes to their research activities as a result of COVID-19, and 50% anticipated that their degree completion would be delayed. Respondents requested information from the T&CB Program on funding for non-COVID-19 projects, alternative datasets, and short educational workshops. Conclusion: The majority of CCNA trainees surveyed experienced significant changes to their research activities as a result of the COVID-19 pandemic. The T&CB Program responded by switching to online programming and facilitating remote research. Further engagement with trainees is needed to ensure continued progress of research in age-related neurodegenerative disease in Canada post-pandemic.

T cell recognition of Mycobacterium tuberculosis peptides presented by HLA-E derived from infected human cells.

HLA-E is a non-conventional MHC Class I molecule that has been recently demonstrated to present pathogen-derived ligands, resulting in the TCR-dependent activation of αß CD8+ T cells. The goal of this study was to characterize the ligandome displayed by HLA-E following infection with Mycobacterium tuberculosis (Mtb) using an in-depth mass spectrometry approach. Here we identified 28 Mtb ligands derived from 13 different source proteins, including the Esx family of proteins. When tested for activity with CD8+ T cells isolated from sixteen donors, nine of the ligands elicited an IFN-γ response from at least one donor, with fourteen of 16 donors responding to the Rv0634A19-29 peptide. Further evaluation of this immunodominant peptide response confirmed HLA-E restriction and the presence of Rv0634A19-29-reactive CD8+ T cells in the peripheral blood of human donors. The identification of an Mtb HLA-E ligand that is commonly recognized may provide a target for a non-traditional vaccine strategy.

Adenovirally-Induced Polyfunctional T Cells Do Not Necessarily Recognize the Infected Target: Lessons from a Phase I Trial of the AERAS-402 Vaccine.

The development of a vaccine for Mycobacterium tuberculosis (Mtb) has been impeded by the absence of correlates of protective immunity. One correlate would be the ability of cells induced by vaccination to recognize the Mtb-infected cell. AERAS-402 is a replication-deficient serotype 35 adenovirus containing DNA expressing a fusion protein of Mtb antigens 85A, 85B and TB10.4. We undertook a phase I double-blind, randomized placebo controlled trial of vaccination with AERAS-402 following BCG. Analysis of the vaccine-induced immune response revealed strong antigen-specific polyfunctional CD4+ and CD8+ T cell responses. However, analysis of the vaccine-induced CD8+ T cells revealed that in many instances these cells did not recognize the Mtb-infected cell. Our findings highlight the measurement of vaccine-induced, polyfunctional T cells may not reflect the extent or degree to which these cells are capable of identifying the Mtb-infected cell and correspondingly, the value of detailed experimental medicine studies early in vaccine development.

Do pigeons prefer alternatives that include near-hit outcomes?

Pigeons show suboptimal choice on a gambling-like task similar to that shown by humans. Humans also show a preference for gambles in which there are near hits (losses that come close to winning). In the present research, we asked if pigeons would show a preference for alternatives with near-hit-like trials. In Experiment 1, we included an alternative that presented a near hit, in which a stimulus associated with reinforcement (a presumed conditioned reinforcer) changed to a stimulus associated with the absence of reinforcement (a presumed conditioned inhibitor). The pigeons tended to avoid this alternative. In Experiment 2, we varied the duration of the presumed conditioned reinforcer (2 vs. 8 s) that changed to a presumed conditioned inhibitor (8 vs. 2 s) and found that the longer the conditioned reinforcer was presented, the more the pigeons avoided it. In Experiment 3, the near-hit alternative involved an ambiguous stimulus for 8 s that changed to a presumed conditioned reinforcer (or a presumed conditioned inhibitor) for 2 s, but the pigeons still avoided it. In Experiment 4, we controlled for the duration of the conditioned reinforcer by presenting it first for 2 s followed by the ambiguous stimulus for 8 s. Once again, the pigeons avoided the alternative with the near-hit trials. In all 4 experiments, the pigeons tended to avoid alternatives that provided near-hit-like trials. We concluded that humans may be attracted to near-hit trials because near-hit trials give them the illusion of control, whereas this does not appear to be a factor for pigeons.

A secondary meta-synthesis of qualitative studies of gender and access to cardiac rehabilitation.

AIMS: To discuss issues in the theorization and study of gender observed during a qualitative meta-synthesis of influences on uptake of secondary prevention and cardiac rehabilitation services. BACKGROUND: Women and men can equally benefit from secondary prevention/cardiac rehabilitation and there is a need to understand gender barriers to uptake. DESIGN: Meta-method analysis secondary to meta-synthesis. For the meta-synthesis, a systematic search was performed to identify and retrieve studies published as full papers during or after 1995 and contained: a qualitative research component wholly or in a mixed method design, extractable population specific data or themes for referral to secondary prevention programmes and adults ≥18 years. DATA SOURCES: Databases searched between January 1995-31 October 2011 included: CSA Sociological Abstracts, EBSCOhost CINAHL, EBSCOhost Gender Studies, EBSCOhost Health Source Nursing: Academic Edition, EBSCOhost SPORTDiscus, EBSCOhost SocINDEX. REVIEW METHODS: Studies were reviewed against inclusion/exclusion criteria. Included studies were subject to quality appraisal and standardized data extraction. RESULTS: Of 2264 screened articles, 69 were included in the meta-method analysis. Only four studies defined gender or used gender theories. Findings were mostly presented as inherently the characteristic of gendered worldviews of participants. The major themes suggest a mismatch between secondary prevention/cardiac rehabilitation services and consumers' needs, which are usually portrayed as differing according to gender but may also be subject to intersecting influences such as age or socioeconomic status. CONCLUSION: There is a persistent lack of theoretically informed gender analysis in qualitative literature in this field. Theory-driven gender analysis will improve the conceptual clarity of the evidence base for gender-sensitive cardiac rehabilitation programme development.

Factors influencing referral to cardiac rehabilitation and secondary prevention programs: a systematic review.

BACKGROUND: Referral to cardiac rehabilitation and secondary prevention programs remains very low, despite evidence suggesting strong clinical efficacy. To develop evidence-based interventions to promote referral, the complex factors and processes influencing referral need to be better understood. DESIGN: We performed a systematic review using qualitative meta-synthesis. METHODS: A comprehensive search of 11 databases was conducted. To be included, studies had to contain a qualitative research component wholly or in a mixed method design. Population specific data or themes had to be extractable for referral to programs. Studies had to contain extractable data from adults >18 years and published as full papers or theses during or after 1995. RESULTS: A total of 2620 articles were retrieved: out of 1687 studies examined, 87 studies contained data pertaining to decisions to participate in programs, 34 of which included data on referral. Healthcare professional, system and patient factors influenced referrals. The main professional barriers were low knowledge or scepticism about benefits, an over-reliance on physicians as gatekeepers and judgments that patients were not likely to participate. Systems factors related to territory, remuneration and insufficient time and workload capacity. Patients had limited knowledge of programs and saw physicians as key elements of referral but found the process of attaining a referral confusing and challenging. CONCLUSIONS: The greatest increases in patient referral to programs could be achieved by allowing referral from non-physicians or alternatively, automatic referral to a choice of hospital or home-based programs. All referring health professionals should receive educational outreach visits or workshops around the ethical and clinical aspects of programs.

Factors influencing participation in cardiac rehabilitation programmes after referral and initial attendance: qualitative systematic review and meta-synthesis.

BACKGROUND: Greater participation in cardiac rehabilitation improves morbidity and mortality in people with coronary heart disease, but little is understood of patients' decisions to participate. METHODS: To develop interventions aimed at increasing completion of programmes, we conducted a qualitative systematic review and meta-synthesis to explore the complex factors and processes influencing participation in cardiac rehabilitation programmes after referral and initial access. To be included in the review, studies had to contain a qualitative research component, population specific data on programme participation in adults >18 years, and be published ≥1995 as full articles or theses. Ten databases were searched (31 October 2011) using 100+ search terms. RESULTS: Of 2264 citations identified, 62 studies were included involving: 1646 patients (57% female; mean age 64.2), 143 caregivers, and 79 professionals. Patients' participation was most strongly influenced by perceptions of the nature, suitability and scheduling of programmes, social comparisons made possible by programmes, and the degree to which programmes, providers, and programme users met expectations. Women's experiences of these factors rendered them less likely to complete. Comparatively, perceptions of programme benefits had little influence on participation. CONCLUSIONS: Factors reducing participation in programmes are varied but amenable to intervention. Participation should be viewed as a 'consumer behaviour' and interventions should mobilize family support, promote 'patient friendly' scheduling, and actively harness the social, identity-related, and experiential aspects of participation.

A qualitative systematic review of influences on attendance at cardiac rehabilitation programs after referral.

BACKGROUND: Cardiac rehabilitation and secondary prevention programs can prevent heart disease in high-risk populations. However, up to half of all patients referred to these programs do not subsequently participate. Although age, sex, and social factors are common predictors of attendance, to increase attendance rates after referral, the complex range of factors and processes influencing attendance needs to be better understood. METHODS: A systematic review using qualitative meta-synthesis was conducted. Ten databases were systematically searched using 100+ search terms until October 31, 2011. To be included, studies had to contain a qualitative research component and population-specific primary data pertaining to program attendance after referral for adults older than 18 years and be published as full articles in or after 1995. RESULTS: Ninety studies were included (2010 patients, 120 caregivers, 312 professionals). Personal and contextual barriers and facilitators were intricately linked and consistently influenced patients' decisions to attend. The main personal factors affecting attendance after referral included patients' knowledge of services, patient identity, perceptions of heart disease, and financial or occupational constraints. These were consistently derived from social as opposed to clinical sources. Contextual factors also influenced patient attendance, including family and, less commonly, health professionals. Regardless of the perceived severity of heart disease, patients could view risk as inherently uncontrollable and any attempts to manage risk as futile. CONCLUSIONS: Decisions to attend programs are influenced more by social factors than by health professional advice or clinical information. Interventions to increase patient attendance should involve patients and their families and harness social mechanisms.

Understanding help-seeking decisions in people with heart failure: a qualitative systematic review.

OBJECTIVE: To understand the process of help-seeking among heart failure patients from the perspectives of patients, caregivers and health professionals. DESIGN: Systematic review using qualitative meta-synthesis. METHODS: A systematic search (20th May 2011) was conducted to identify studies published in English as full papers ≥1995 reporting primary qualitative data with extractable heart failure-specific data or themes related to help-seeking in patients, caregivers or health professionals. Databases searched were: CINAHL, Medline, PsycInfo, Social Science Citation Index, Embase, Social policy/Practice, SocIndex, Ageline, Health Source Nursing, Scopus; additionally, we consulted with experts and manually searched references. RESULTS: 58 studies (990 patients; 274 female, 527 male, 189 sex not described; 229 caregivers, 79 health professionals) were included. Heart failure help-seeking was embedded in daily experiences of heart failure but ongoing symptoms were confusing, ambiguous and disruptive; little support was available from professionals to interpret the presence and significance of fluctuations in symptoms for help-seeking. Other significant barriers to help-seeking were: avoidance-based coping, fear of hospitals and misplaced reluctance to be burdensome. Help-seeking was facilitated by good involvement and frank communication between patients, caregivers and health professionals and the presence of a sense of elevated personal risk. CONCLUSION: Health services should harness primary care providers and support patients and caregivers to prioritize development of objective symptom monitoring skills, recognize and personally assimilate the elevated risks of heart failure and help-seeking delays and discourage avoidance-based coping and unwarranted concerns that downplay the significance of heart failure and urgency to address symptoms.

Effective communication and ethical consent in decisions related to ICDs.

This Review examines recommendations and principles that promote good decision-making with regard to the insertion, deactivation, and potential malfunction of implantable cardioverter-defibrillators (ICDs). This guidance is important because ICDs are now used for primary and secondary prevention of arrhythmias in more than 20 diverse clinical populations, which accounts for the exponential increase in insertion rates over the past decade. Current guidelines require clinicians to provide personalized, culturally appropriate, and easy to understand information to patients on the benefits and harms of proposed treatment choices; however, obtaining valid informed consent for insertion and deactivation of ICDs is challenging. Initiating early conversations with patients and continuing this dialogue over time, implementation of localized care protocols, increased collaboration (particularly between cardiac and palliative care teams), and the provision of training for all health professionals involved in the care of these patients, can help to ensure that adequate informed consent is maintained throughout their care. In addition to providing information, health professionals should identify and address high levels of anxiety in patients and their next of kin and promote effective communication throughout decision making. In the future, use of standardized checklists or decision aids based on a clear understanding of the principles underlying key topics could support this process.

Healthy diet in Canadians of low socioeconomic status with coronary heart disease: Not just a matter of knowledge and choice.

People of low socioeconomic status (SES) are prone to premature coronary heart disease (CHD) and tend to have more risk factors and worse health and mortality. Yet, little is understood about the specific challenges faced by people of low SES with CHD in changing behavior around the consumption of dietary risk factors, such as salt, fat, and cholesterol, and adding heart-healthy foods, such as fruit, vegetables, lean meat, and fish. The aim of this study was to understand factors promoting and reducing willingness and capacity to consume a healthy diet in people of low SES with CHD. Qualitative research via semistructured interviewing and a critical realist theoretic framework was used, along with a questionnaire to provide context for the interviews. Food consumption and diet were not principally related to knowledge but were constrained by an ever-present scarcity of resources and the need to prioritize other daily living expenses perceived as being more important than diet. Having use of a vehicle also promoted access to dietary support from physicians and cardiac rehabilitation.

Understanding and promoting effective self-care during heart failure.

OPINION STATEMENT: Heart failure (HF) self-care relates to the decisions made outside clinical settings by the individual with HF to maintain life, healthy functioning, and well-being. The people who help patients most (ie, caregivers/family members) should be involved in care, and general principles of health behavior change should be used to guide support. Medicines should be prescribed with once-daily dosing, with pharmacists providing medication review and support. Pill boxes should be provided and patients' health literacy levels assessed. Psychosocial interventions for smoking cessation should be undertaken. Regular aerobic exercise may benefit patients with mild to moderate HF and some with severe but stable HF; therefore, referral to cardiac rehabilitation should be considered. Exercise regimen must take into account patient-related factors, including functional status, comorbid conditions, and patient preferences. Intake of salt, alcohol, and fluid should be restricted, although these steps are supported by limited evidence. Patients should be educated on appropriate sources of help. They should seek help immediately for persistent chest pain, palpitations, syncope, breathlessness at rest, or a weight increase of ≥ 2 lb. Depression, if present, should be addressed with antidepressants (sertraline and citalopram), cognitive behavioral therapy, and regular exercise. HF disease management programs should be offered if available.

Socioeconomic status and cardiovascular disease: risks and implications for care.

Socioeconomic status (SES) refers to an individual's social position relative to other members of a society. Low SES is associated with large increases in cardiovascular disease (CVD) risk in men and women. The inverse association between SES and CVD risk in high-income countries is the result of the high prevalence and compounding effects of multiple behavioral and psychosocial risk factors in people of low SES. However, strong and consistent evidence shows that parental SES, childhood and early-life factors, and inequalities in health services also contribute to elevated CVD risk in people of low SES who live in high-income countries. In addition, place of residence can affect CVD risk, although the data on the influence of wealth distribution and work-related factors are inconsistent. Studies on the effects of SES on CVD risk in low-income and middle-income countries is scarce, but evidence is emerging that the increasing wealth of these countries is beginning to lead to replication of the patterns seen in high-income countries. Clinicians should address the association between SES and CVD by incorporating SES into CVD risk calculations and screening tools, reducing behavioral and psychosocial risk factors via effective and equitable primary and secondary prevention, undertaking health equity audits to assess inequalities in care provision and outcomes, and by use of multidisciplinary teams to address risk factors over the life course.

Mixed Candida albicans strain populations in colonized and infected mucosal tissues.

Multilocus sequence typing of six Candida albicans colonies from primary isolation plates revealed instances of colony-to-colony microvariation and carriage of two strain types in single oropharyngeal and vaginal samples. Higher rates of colony variation in commensal samples suggest selection of types from mixed populations either in the shift to pathogenicity or the response to antifungal treatment.