Mechanisms by which the cystic fibrosis transmembrane conductance regulator may influence SARS-CoV-2 infection and COVID-19 disease severity.

Patients with cystic fibrosis (CF) exhibit pronounced respiratory damage and were initially considered among those at highest risk for serious harm from SARS-CoV-2 infection. Numerous clinical studies have subsequently reported that individuals with CF in North America and Europe-while susceptible to severe COVID-19-are often spared from the highest levels of virus-associated mortality. To understand features that might influence COVID-19 among patients with cystic fibrosis, we studied relationships between SARS-CoV-2 and the gene responsible for CF (i.e., the cystic fibrosis transmembrane conductance regulator, CFTR). In contrast to previous reports, we found no association between CFTR carrier status (mutation heterozygosity) and more severe COVID-19 clinical outcomes. We did observe an unexpected trend toward higher mortality among control individuals compared with silent carriers of the common F508del CFTR variant-a finding that will require further study. We next performed experiments to test the influence of homozygous CFTR deficiency on viral propagation and showed that SARS-CoV-2 production in primary airway cells was not altered by the absence of functional CFTR using two independent protocols. On the contrary, experiments performed in vitro strongly indicated that virus proliferation depended on features of the mucosal fluid layer known to be disrupted by absent CFTR in patients with CF, including both low pH and increased viscosity. These results point to the acidic, viscous, and mucus-obstructed airways in patients with cystic fibrosis as unfavorable for the establishment of coronaviral infection. Our findings provide new and important information concerning relationships between the CF clinical phenotype and severity of COVID-19.

Association of Neighborhood-Level Material Deprivation With Atrial Fibrillation Care in a Single-Payer Health Care System: A Population-Based Cohort Study.

BACKGROUND: There are limited data on the association of material deprivation with clinical care and outcomes after atrial fibrillation (AF) diagnosis in jurisdictions with universal health care. METHODS: This was a population-based cohort study of individuals ≥66 years of age with first diagnosis of AF between April 1, 2007, and March 31, 2019, in the Canadian province of Ontario, which provides public funding and prohibits private payment for medically necessary physician and hospital services. Prescription medications are subsidized for residents >65 years of age. The primary exposure was neighborhood material deprivation, a metric derived from Canadian census data to estimate inability to attain basic material needs. Neighborhoods were categorized by quintile from Q1 (least deprived) to Q5 (most deprived). Cause-specific hazards regression was used to study the association of material deprivation quintile with time to AF-related adverse events (death or hospitalization for stroke, heart failure, or bleeding), clinical services (physician visits, cardiac diagnostics), and interventions (anticoagulation, cardioversion, ablation) while adjusting for individual characteristics and regional cardiologist supply. RESULTS: Among 347 632 individuals with AF (median age 79 years, 48.9% female), individuals in the most deprived neighborhoods (Q5) had higher prevalence of cardiovascular disease, risk factors, and noncardiovascular comorbidity relative to residents of the least deprived neighborhoods (Q1). After adjustment, Q5 residents had higher hazards of death (hazard ratio [HR], 1.16 [95% CI, 1.13-1.20]) and hospitalization for stroke (HR, 1.16 [95% CI, 1.07-1.27]), heart failure (HR, 1.14 [95% CI, 1.11-1.18]), or bleeding (HR, 1.16 [95% CI, 1.07-1.25]) relative to Q1. There were small differences across quintiles in primary care physician visits (HR, Q5 versus Q1, 0.91 [95% CI, 0.89-0.92]), echocardiography (HR, Q5 versus Q1, 0.97 [95% CI, 0.96-0.99]), and dispensation of anticoagulation (HR, Q5 versus Q1, 0.97 [95% CI, 0.95-0.98]). There were more prominent disparities for Q5 versus Q1 in cardiologist visits (HR, 0.84 [95% CI, 0.82-0.86]), cardioversion (HR, 0.80 [95% CI, 0.76-0.84]), and ablation (HR, 0.45 [95% CI, 0.30-0.67]). CONCLUSIONS: Despite universal health care and prescription medication coverage, residents of more deprived neighborhoods were less likely to visit cardiologists or receive rhythm control interventions after AF diagnosis, even though they exhibited higher cardiovascular disease burden and higher risk of adverse outcomes.

Three patients highlighting potential pitfalls in platelet refractory testing.

BACKGROUND: Platelet-transfusion refractory (PR) patients do not achieve expected post-transfusion platelet counts. We investigate suspected PR patients with post-transfusion platelet counts, indirect platelet antibody screens (ind-PAS), Class I HLA antibody tests (HLA-Scr), and physical platelet crossmatch (PXM) studies. STUDY DESIGN AND METHODS: The three following cases describe possible pitfalls of laboratory tests used in PR workup and management. RESULTS: Case #1: Antibody testing detected antibodies to only HLA-B13, corresponding to a 4% calculated panel reactive antibodies (CPRA; 96% predicted donor compatibility). However, PXM showed the patient compatible with 11/14 (79%) donors; two of the PXM-incompatible units were ABO-incompatible. Case #2: PXM revealed compatibility with 1/14 screened donors; however, the patient did not respond to the product from the compatible donor. The patient did respond to HLA-matched product. Dilution studies provided evidence of the prozone effect, which caused negative PXM despite clinically relevant antibodies. Case #3: There was a discrepancy between the ind-PAS and HLA-Scr. Ind-PAS was negative for HLA antibodies, while HLA-Scr was positive and specificity testing corresponded to 38% CPRA. Per the package insert, the sensitivity of ind-PAS is ~85% compared to HLA-Scr. DISCUSSION: These cases highlight the importance of investigating incongruent results. Cases #1 and #2 demonstrate PXM pitfalls: ABO incompatibility can result in positive PXM and false-negative PXM can occur in the setting of the prozone effect. Case #3 reveals the importance of knowing a test's sensitivity. Centers that only perform ind-PAS may fail to detect HLA antibodies.

Comparison of Antibody Class-Specific SARS-CoV-2 Serologies for the Diagnosis of Acute COVID-19.

Accurate diagnosis of acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical for appropriate management of patients with this disease. We examined the possible complementary role of laboratory-developed class-specific clinical serology in assessing SARS-CoV-2 infection in hospitalized patients. Serological tests for immunoglobulin G (IgG), IgA, and IgM antibodies against the receptor binding domain (RBD) of SARS-CoV-2 were evaluated using samples from real-time reverse transcription-quantitative PCR (qRT-PCR)-confirmed inpatient coronavirus disease 2019 (COVID-19) cases. We analyzed the influence of timing and clinical severity on the diagnostic value of class-specific COVID-19 serology testing. Cross-sectional analysis revealed higher sensitivity and specificity at lower optical density cutoffs for IgA in hospitalized patients than for IgG and IgM serology (IgG area under the curve [AUC] of 0.91 [95% confidence interval {CI}, 0.89 to 0.93] versus IgA AUC of 0.97 [95% CI, 0.96 to 0.98] versus IgM AUC of 0.95 [95% CI, 0.92 to 0.97]). The enhanced performance of IgA serology was apparent in the first 2 weeks after symptom onset and the first week after PCR testing. In patients requiring intubation, all three tests exhibit enhanced sensitivity. Among PCR-negative patients under investigation for SARS-CoV-2 infection, 2 out of 61 showed clear evidence of seroconversion IgG, IgA, and IgM. Suspected false-positive results in the latter population were most frequently observed in IgG and IgM serology tests. Our findings suggest the potential utility of IgA serology in the acute setting and explore the benefits and limitations of class-specific serology as a complementary diagnostic tool to PCR for COVID-19 in the acute setting.

Impact of socioeconomic status on end-of-life costs: a systematic review and meta-analysis.

BACKGROUND: Socioeconomic inequalities in access to, and utilization of medical care have been shown in many jurisdictions. However, the extent to which they exist at end-of-life (EOL) remains unclear. METHODS: Studies in MEDLINE, EMBASE, CINAHL, ProQuest, Web of Science, Web of Knowledge, and OpenGrey databases were searched through December 2019 with hand-searching of in-text citations. No publication date or language limitations were set. Studies assessing SES (e.g. income) in adults, correlated to EOL costs in last year(s) or month(s) of life were selected. Two independent reviewers performed data abstraction and quality assessment, with inconsistencies resolved by consensus. RESULTS: A total of twenty articles met eligibility criteria. Two meta-analyses were performed on studies that examined total costs in last year of life - the first examined costs without adjustments for confounders (n = 4), the second examined costs that adjusted for confounders, including comorbidities (n = 2). Among studies which did not adjust for comorbidities, SES was positively correlated with EOL costs (standardized mean difference, 0.13 [95% confidence interval, 0.03 to 0.24]). However, among studies adjusting for comorbidities, SES was inversely correlated with EOL expenditures (regression coefficient, -$150.94 [95% confidence interval, -$177.69 to -$124.19], 2015 United States Dollars (USD)). Higher ambulatory care and drug expenditure were consistently found among higher SES patients irrespective of whether or not comorbidity adjustment was employed. CONCLUSION: Overall, an inequality leading to higher end-of-life expenditure for higher SES patients existed to varying extents, even within countries providing universal health care, with greatest differences seen for outpatient and prescription drug costs. The magnitude and directionality of the relationship in part depended on whether comorbidity risk-adjustment methodology was employed.

Trends in the incidence and outcomes of patients with aortic stenosis hospitalization.

BACKGROUND: Although the burden of aortic stenosis (AS) on our health care system is expected to rise, little is known regarding its epidemiology at the population level. Our primary objective was to evaluate trends in AS hospitalization, treatment and outcomes. METHODS: We performed a population-based observational study including 37,970 patients newly hospitalized with AS from 2004 and 2013 in Ontario, Canada. We calculated age- and sex-standardized rate of AS hospitalization through direct standardization. The independent association between year of the hospitalization, and 30-day and 1-year mortality rate was evaluated using logistic regression models to account for temporal changes in patient characteristics. RESULTS: The overall age- and sex-standardized AS hospitalization rate increased slightly from 36 per 100,000 in 2004 to 39 per 100,000 in 2013. A substantial increase was seen in patients ≥85years, where hospitalization rates increased 29% from 400 to 516 per 100,000 from 2004 to 2013 (P<.001). In this study period, 36.2% of patients received aortic valve interventions within 30days of hospitalization. Among treated patients, an improving mortality trend was observed in which the adjusted odds ratio (OR) was significantly lower in 2013 as compared to 2004 (OR 0.55 for 30-day mortality, 0.74 for 1-year morality). In contrast, no significant temporal change in mortality was seen among patients without aortic valve intervention. CONCLUSION: AS hospitalizations in the elderly increased significantly beyond that was expected from population growth. Many AS patients did not receive aortic valve intervention after hospitalization. Mortality among the treated patients improved significantly over time.

The energy expenditure benefits of reallocating sedentary time with physical activity: a systematic review and meta-analysis.

Background: We compared direct and daily cumulative energy expenditure (EE) differences associated with reallocating sedentary time to physical activity in adults for meaningful EE changes. Methods: Peer-reviewed studies in PubMed, Medline, EMBASE, CINAHL, PsycINFO, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews were searched from inception to March 2017. Randomized and non-randomized interventions with sedentary time and EE outcomes in adults were included. Study quality was assessed by the National Heart Lung and Blood Institute tool, and summarized using random-effects meta-analysis and meta-regression. Results: In total, 26 studies were reviewed, and 24 studies examined by meta-analysis. Reallocating 6-9 h of sedentary time to light-intensity physical activity (LIPA) (standardized mean difference [SMD], 2.501 [CI: 1.204-5.363]) had lower cumulative EE than 6-9 h of combined LIPA and moderate-vigorous intensity physical activity (LIPA and moderate-vigorous physical activity [MVPA]) (SMD, 5.218 [CI: 3.822-6.613]). Reallocating 1 h of MVPA resulted in greater cumulative EE than 3-5 h of LIPA and MVPA, but <6-9 h of LIPA and MVPA. Conclusions: Comparable EE can be achieved by different strategies, and promoting MVPA might be effective for those individuals where a combination of MVPA and LIPA is challenging.

Reducing the number of unnecessary routine laboratory tests through education of internal medicine residents.

INTRODUCTION: The Choosing Wisely guidelines advise against ordering routine blood tests for hospitalised patients unless they change management. Unnecessary testing can lead to adverse effects (eg, iatrogenic anaemia, poor sleep quality, risk for infections and increased cost of care). METHODS: An 8-week quality initiative aimed at reducing unnecessary blood tests was implemented in three internal medicine resident inpatient services. The initiative included a 30 min educational session, reminders prior to rotation and midrotation and posters in work areas that displayed lab pricing and urged judicious testing. Residents were encouraged to justify the purpose of ordering tests in their daily progress notes. Attending physicians were made aware of the initiative. Preintervention and postintervention time points were used to compare key metrics. A >10% decrease between time periods was used as an evaluation criterion. RESULTS: There were 293 patient records reviewed in the preintervention period and 419 in the postintervention period. The two groups were similar in terms of age and gender. Median blood test count (complete blood count/basic metabolic profile/comprehensive metabolic profile) decreased from 4 to 2 tests per patient per day (50 % decrease) after the intervention. The median length of hospital stay decreased from 4.9 to 3.9 days (21% decrease). A decreased percentage of people requiring transfusions was also noted (2016: 6.1%, 2017: 2.9%). CONCLUSION: The frequency of unnecessary routine blood tests ordered in the hospital can be decreased by educating resident physicians, making them cost conscious and aware of the indications for ordering routine labs. Frequent reminders are needed to sustain the educational benefit.

Primary Care Physician Volume and Quality of Diabetes Care: A Population-Based Cohort Study.

BACKGROUND: A relationship between higher patient volume and both better quality of care and better outcomes has been shown for many acute care conditions. Whether a volume-quality relationship exists for the outpatient management of chronic diseases is uncertain. OBJECTIVE: To explore the association between primary care physician volume and quality of diabetes care. DESIGN: Cohort study. SETTING: The study was conducted using linked population-based health care administrative data in Ontario, Canada. PATIENTS: 1 018 647 adults with diabetes in 2011 who received care from 9014 primary care physicians. Two measures of volume were ascertained for each physician: overall ambulatory volume (representing time available to devote to chronic disease management during patient encounters) and diabetes-specific volume (representing disease-specific expertise). MEASUREMENTS: Quality of care was measured over a 2-year period using 6 indicators: disease monitoring (eye examination, hemoglobin A1c testing, and low-density lipoprotein cholesterol testing), prescribing appropriate medications (angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers and statins), and adverse clinical outcomes (emergency department visits for hypoglycemia or hyperglycemia). RESULTS: Higher overall ambulatory volume was associated with lower rates of appropriate disease monitoring and medication prescription. In contrast, higher diabetes-specific volume was associated with better quality of care across all 6 indicators. LIMITATION: Only a select set of quality indicators and potential confounders could be ascertained from available data. CONCLUSION: Primary care physicians with busier ambulatory patient practices delivered lower-quality diabetes care, but those with greater diabetes-specific experience delivered higher-quality care. These findings show that relationships between physician volume and quality can be extended from acute care to outpatient chronic disease care. Health policies or programs to support physicians with a low volume of patients with diabetes may improve care. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Regional variations in ambulatory care and incidence of cardiovascular events.

BACKGROUND: Variations in the prevalence of traditional cardiac risk factors only partially account for geographic variations in the incidence of cardiovascular disease. We examined the extent to which preventive ambulatory health care services contribute to geographic variations in cardiovascular event rates. METHODS: We conducted a cohort study involving 5.5 million patients aged 40 to 79 years in Ontario, Canada, with no hospital stays for cardiovascular disease as of January 2008, through linkage of multiple population-based health databases. The primary outcome was the occurrence of a major cardiovascular event (myocardial infarction, stroke or cardiovascular-related death) over the following 5 years. We compared patient demographics, cardiac risk factors and ambulatory health care services across the province's 14 health service regions, known as Local Health Integration Networks (LHINs), and evaluated the contribution of these variables to regional variations in cardiovascular event rates. RESULTS: Cardiovascular event rates across LHINs varied from 3.2 to 5.7 events per 1000 person-years. Compared with residents of high-rate LHINs, those of low-rate health regions received physician services more often (e.g., 4.2 v. 3.5 mean annual family physician visits, p value for LHIN-level trend = 0.01) and were screened for risk factors more often. Low-rate LHINs were also more likely to achieve treatment targets for hypercholes-terolemia (51.8% v. 49.6% of patients, p = 0.03) and controlled hypertension (67.4% v. 53.3%, p = 0.04). Differences in patient and health system factors accounted for 74.5% of the variation in events between LHINs, of which 15.5% was attributable to health system factors alone. INTERPRETATION: Preventive ambulatory health care services were provided more frequently in health regions with lower cardiovascular event rates. Health system interventions to improve equitable access to preventive care might improve cardiovascular outcomes.

The Incidence of Major Cardiovascular Events in Immigrants to Ontario, Canada: The CANHEART Immigrant Study.

BACKGROUND: Immigrants from ethnic minority groups represent an increasing proportion of the population in many high-income countries but little is known about the causes and amount of variation between various immigrant groups in the incidence of major cardiovascular events. METHODS AND RESULTS: We conducted the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) Immigrant study, a big data initiative, linking information from Citizenship and Immigration Canada's Permanent Resident database to nine population-based health databases. A cohort of 824 662 first-generation immigrants aged 30 to 74 as of January 2002 from eight major ethnic groups and 201 countries of birth who immigrated to Ontario, Canada between 1985 and 2000 were compared to a reference group of 5.2 million long-term residents. The overall 10-year age-standardized incidence of major cardiovascular events was 30% lower among immigrants compared with long-term residents. East Asian immigrants (predominantly ethnic Chinese) had the lowest incidence overall (2.4 in males, 1.1 in females per 1000 person-years) but this increased with greater duration of stay in Canada. South Asian immigrants, including those born in Guyana had the highest event rates (8.9 in males, 3.6 in females per 1000 person-years), along with immigrants born in Iraq and Afghanistan. Adjustment for traditional risk factors reduced but did not eliminate differences in cardiovascular risk between various ethnic groups and long-term residents. CONCLUSIONS: Striking differences in the incidence of cardiovascular events exist among immigrants to Canada from different ethnic backgrounds. Traditional risk factors explain part but not all of these differences.

Prognosis after maternal placental events and revascularization: PAMPER study.

BACKGROUND: Middle-aged women are at higher risk than men of death after coronary artery revascularization. Maternal placental syndromes (gestational hypertension, preeclampsia, placental abruption, and placental infarction) are associated with premature coronary artery disease, but their influence on survival after coronary artery revascularization is unknown. OBJECTIVE: The purpose of this study was to determine whether a history of maternal placental syndromes alters the risk of death after coronary artery revascularization in middle-aged women. STUDY DESIGN: We completed a population-based retrospective cohort study among all hospitals in Ontario, Canada, where universal health care includes all aspects of antenatal and delivery care as well as all outpatient and inpatient health care, which includes coronary revascularization. We included 1985 middle-aged women who underwent a first percutaneous coronary intervention or coronary artery bypass grafting between 1993 and 2012 and who had ≥1 previous delivery. We excluded those with cardiovascular disease ≤1 year before or coronary revascularization ≤90 days after any delivery. The main study outcome, determined a priori, was all-cause death. Hazard ratios were adjusted for age, socioeconomic status, parity, revascularization type, time since last delivery, hypertension, diabetes mellitus, obesity, dyslipidemia, tobacco or drug dependence, and kidney disease. RESULTS: Three hundred sixty-two of 1985 women (18.2%) who underwent coronary artery revascularization had a previous maternal placental syndrome event. The mean age at index coronary revascularization was 45 years; percutaneous coronary intervention comprised approximately 80% of procedures. After a mean follow-up time of approximately 5 years, 41 deaths (2.2 per 100 person-years) occurred in women with previous maternal placental syndromes and 83 deaths (1.1 per 100 person-years) in women without maternal placental syndrome (adjusted hazard ratio, 1.96; 95% confidence interval, 1.29-2.99). Of the maternal placental syndrome subtypes, the risk of death was significant in women with placental abruption (adjusted hazard ratio, 2.79; 95% confidence interval, 1.31-5.96), placental infarction (adjusted hazard ratio, 3.09; 95% confidence interval, 1.23-7.74), and preeclampsia (adjusted hazard ratio, 1.61; 95% confidence interval, 1.00-2.58). Women with maternal placental syndrome in ≥2 pregnancies had the highest adjusted hazard ratio of death (4.31; 95% confidence interval, 1.71-10.89). CONCLUSION: In middle-aged women who undergo coronary revascularization, previous maternal placental syndrome doubles the risk of death; recurrent maternal placental syndrome quadruples that risk. Some covariates and secondary measures may not have been well-captured and classified herein, leading to residual confounding.

Sedentary time and its association with risk for disease incidence, mortality, and hospitalization in adults: a systematic review and meta-analysis.

BACKGROUND: The magnitude, consistency, and manner of association between sedentary time and outcomes independent of physical activity remain unclear. PURPOSE: To quantify the association between sedentary time and hospitalizations, all-cause mortality, cardiovascular disease, diabetes, and cancer in adults independent of physical activity. DATA SOURCES: English-language studies in MEDLINE, PubMed, EMBASE, CINAHL, Cochrane Library, Web of Knowledge, and Google Scholar databases were searched through August 2014 with hand-searching of in-text citations and no publication date limitations. STUDY SELECTION: Studies assessing sedentary behavior in adults, adjusted for physical activity and correlated to at least 1 outcome. DATA EXTRACTION: Two independent reviewers performed data abstraction and quality assessment, and a third reviewer resolved inconsistencies. DATA SYNTHESIS: Forty-seven articles met our eligibility criteria. Meta-analyses were performed on outcomes for cardiovascular disease and diabetes (14 studies), cancer (14 studies), and all-cause mortality (13 studies). Prospective cohort designs were used in all but 3 studies; sedentary times were quantified using self-report in all but 1 study. Significant hazard ratio (HR) associations were found with all-cause mortality (HR, 1.240 [95% CI, 1.090 to 1.410]), cardiovascular disease mortality (HR, 1.179 [CI, 1.106 to 1.257]), cardiovascular disease incidence (HR, 1.143 [CI, 1.002 to 1.729]), cancer mortality (HR, 1.173 [CI, 1.108 to 1.242]), cancer incidence (HR, 1.130 [CI, 1.053 to 1.213]), and type 2 diabetes incidence (HR, 1.910 [CI, 1.642 to 2.222]). Hazard ratios associated with sedentary time and outcomes were generally more pronounced at lower levels of physical activity than at higher levels. LIMITATION: There was marked heterogeneity in research designs and the assessment of sedentary time and physical activity. CONCLUSION: Prolonged sedentary time was independently associated with deleterious health outcomes regardless of physical activity. PRIMARY FUNDING SOURCE: None.

Serum ferritin is a biomarker for liver mortality in the Hemochromatosis and Iron Overload Screening Study.

BACKGROUND: We identified no reports of long-term follow-up of participants in hemochromatosis screening programs. We evaluated causes of death and survival in non-C282Y homozygous Canadian participants in the primary care-based hemochromatosis and iron overload screening (HEIRS) study. MATERIAL AND METHODS: Initial screening (IS) included transferrin saturation (TS), serum ferritin (SF), HFE genotyping (C282Y, H63D), and health questionnaire responses. By definition, participants without C282Y or H63D had HFE wt/wt. We linked 20,306 Canadian participants to the Ontario Death Registry for dates and causes of death 9 y after IS. We computed Cox proportional hazards to identify factors with increased death risks and Kaplan-Meier curves to estimate survival of non-C282Y homozygous participants with SF ≤ 1,000 µg/L and > 1,000 µg/dL. RESULTS: There were 19,052 evaluable participants (IS mean age 49 y; 60% women; 93 C282Y homozygotes). There were 988 deaths. Significantly increased hazard ratios for all-cause mortality were positively associated with TS, SF, men, and C282Y homozygosity, and liver disease, diabetes, and heart failure reports. Non-C282Y homozygous participants with SF > 1,000 µg/L had lower survival than those with SF ≤ 1,000 µg/L (p < 0.0001). CONCLUSIONS: Nine years after initial screening, non-C282Y homozygous participants and SF > 1,000 µg/L was associated with decreased survival.

Care in the Home for the Management of Chronic Heart Failure: Systematic Review and Cost-Effectiveness Analysis.

BACKGROUND: The objective of this study was to determine the effect of care in the home (CHM) compared with usual care (UC) in patients with chronic heart failure (CHF) on clinical outcomes and healthcare use including a cost-effectiveness analysis. METHODS: A systematic literature search on MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, as well as Centre for Reviews and Dissemination was conducted to identify randomized controlled trials comparing CHM with UC in CHF. The randomized controlled trials meeting inclusion criteria were meta-analyzed by outcome, and the quality of evidence for each outcome was evaluated using Grading of Recommendations Assessment, Development, and Evaluation system. A cost-effectiveness model was developed to estimate costs and quality-adjusted life years. RESULTS: Six randomized controlled trials were identified from 1277 citations. Care in the home was predominately provided by a single health professional consisting of nurse-led education of varying duration and frequency. One study included pharmacist-led CHM. Care in the home showed a decreased risk for all-cause mortality and hospitalizations combined (risk ratio, 0.88; 95% confidence interval [CI], 0.80-0.97), but not all-cause mortality alone (risk ratio, 0.92; 95% CI, 0.81-1.04). Care in the home resulted in fewer hospitalizations (mean difference, -1.03; 95% CI, -1.53 to -0.53) and fewer emergency department visits (mean difference, -1.32; 95% CI, -1.87 to -0.77). Quality of life also improved with CHM delivered by nurses. Critical appraisal of the quality of evidence suggests uncertainty in the estimates for a number of outcomes. Care in the home resulted in a savings of $10,665 and a gain of 0.11 quality-adjusted life years compared with UC. CONCLUSIONS: In conclusion, the beneficial effect of CHM in CHF is by reducing mortality and hospitalizations combined. Care in the home in CHF seems to be more effective and less costly compared with UC.

Associative learning, priming, and the fostering of adaptive flexibility.

Therapies, including those incorporating clinical hypnosis, occur in the context of consciously mediated interpersonal interactions. While the presence of the non-conscious and its content is often acknowledged, how non-conscious content is accessed and utilized in the training curricula to which clinical hypnosis students are exposed is under-emphasized. This article explores two phenomena - priming and the innate tendency of the human brain to engage in associative learning - that, when incorporated into the interpersonal process that constitutes clinical hypnosis, could expand and enrich outcomes for clients. The processes by which non-conscious processing shapes conscious experience, the role of the social environment in prioritizing and predisposing certain content that later makes its way into consciousness, and examples of how that content can be used to enhance clients' adaptive flexibility are discussed.