Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.

BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction

Healthy Hearts – A community-based primary prevention programme to reduce coronary heart disease

Background The ten year probability of cardiovascular events can be calculated, but many people are unaware of their risk and unclear how to reduce it. The aim of this study was to assess whether a community based intervention, for men and women aged between 45 and 64 years without pre-existing coronary heart disease, would reduce their Framingham scores when reassessed one year later. Methods Individuals in the relevant age group from a defined geographical area were sent an invitation to attend for an assessment of their cardiovascular risk. Individuals with pre-existing cardiovascular disease or terminal illness were excluded. The invitation was in the form of a "Many Happy Returns" card with a number of self-screening questions including the question, "If you put the enclosed string around your waist, is it too short?" The card contained a red 80 cm piece of string in the case of women, or a green 90 cm piece of string in the case of men. At the assessment appointment, Framingham scores were calculated and a printout was given to each individual. Advice was provided for relevant risk factors identified using agreed guidelines. If appropriate, onward referral was also made to a GP, dietician, an exercise referral scheme, or to smoking cessation services, using a set of guidelines. Individuals were sent a second invitation one year later to return for re-assessment. Results and discussion 2031 individuals were asked to self-assess their eligibility to participate, 596 individuals attended for assessment and 313 of these attended for follow-up one year later. The mean reduction in the Framingham risk score, was significantly lower at one year (0.876, 95% CI 0.211 to 1.541, p = 0.01). The mean 10-year risk of CHD at baseline was 13.14% (SD 9.18) and had fallen at follow-up to 12.34% (SD 8.71), a mean reduction of 6.7% of the initial 10-year Framingham risk. If sustained, the estimated NNT to prevent each year of CHD would be 1141 (95% CI 4739 to 649) individual appointments. Conclusion This community intervention for primary prevention of CHD reduces Framingham risk scores at one year in those who engage with the programme

Are Racial and Ethnic Minorities Less Willing to Participate in Health Research?

BACKGROUND: It is widely claimed that racial and ethnic minorities, especially in the US, are less willing than non-minority individuals to participate in health research. Yet, there is a paucity of empirical data to substantiate this claim. METHODS AND FINDINGS: We performed a comprehensive literature search to identify all published health research studies that report consent rates by race or ethnicity. We found 20 health research studies that reported consent rates by race or ethnicity. These 20 studies reported the enrollment decisions of over 70,000 individuals for a broad range of research, from interviews to drug treatment to surgical trials. Eighteen of the twenty studies were single-site studies conducted exclusively in the US or multi-site studies where the majority of sites (i.e., at least 2/3) were in the US. Of the remaining two studies, the Concorde study was conducted at 74 sites in the United Kingdom, Ireland, and France, while the Delta study was conducted at 152 sites in Europe and 23 sites in Australia and New Zealand. For the three interview or non-intervention studies, African-Americans had a nonsignificantly lower overall consent rate than non-Hispanic whites (82.2% versus 83.5%; odds ratio [OR] = 0.92; 95% confidence interval [CI] 0.84–1.02). For these same three studies, Hispanics had a nonsignificantly higher overall consent rate than non-Hispanic whites (86.1% versus 83.5%; OR = 1.37; 95% CI 0.94–1.98). For the ten clinical intervention studies, African-Americans' overall consent rate was nonsignificantly higher than that of non-Hispanic whites (45.3% versus 41.8%; OR = 1.06; 95% CI 0.78–1.45). For these same ten studies, Hispanics had a statistically significant higher overall consent rate than non-Hispanic whites (55.9% versus 41.8%; OR = 1.33; 95% CI 1.08–1.65). For the seven surgery trials, which report all minority groups together, minorities as a group had a nonsignificantly higher overall consent rate than non-Hispanic whites (65.8% versus 47.8%; OR = 1.26; 95% CI 0.89–1.77). Given the preponderance of US sites, the vast majority of these individuals from minority groups were African-Americans or Hispanics from the US. CONCLUSIONS: We found very small differences in the willingness of minorities, most of whom were African-Americans and Hispanics in the US, to participate in health research compared to non-Hispanic whites. These findings, based on the research enrollment decisions of over 70,000 individuals, the vast majority from the US, suggest that racial and ethnic minorities in the US are as willing as non-Hispanic whites to participate in health research. Hence, efforts to increase minority participation in health research should focus on ensuring access to health research for all groups, rather than changing minority attitudes

Towards an asset-based approach to promoting and sustaining well-being for people with aphasia and their families: an international exploratory study

Background: There is growing interest in interventions that promote positive outcomes and well-being for people with aphasia (PWA) and their families, but provision is inconsistent. An asset-based approach, based on the theory of salutogenesis, focuses on what makes you well rather than ill. This approach has been used successfully across a variety of research fields, including health and social care research and practice, and has the potential to provide coherent strategies to support people living successfully with aphasia. Aim: To explore the relevance and potential of an asset-based approach to promoting and sustaining well-being for PWA and their families, across contexts and cultures. Methods & procedures: Exploratory case studies were carried out in the United Kingdom (UK), Norway, Israel, Ireland, and Denmark in a variety of settings. Following an interpretative paradigm, we used qualitative methods including: interviews; appreciative inquiry; group discussions; and participatory action research. 95 PWA and 25 family members were asked to identify assets within themselves and their communities that promote, sustain and maintain well-being, by responding to: “What makes you feel good/well/healthy?” Data were analysed using thematic analysis. Outcomes & results: An asset-based approach proved to be a powerful means for PWA and family members to explore what helps them live well with aphasia. Key themes were identified: (1) personal journey; (2) helping others; (3) connecting to self; (4) connecting to others; (5) recreation; and (6) personal attributes. Self-identification of assets, within the person and their community, and connections to these, helped PWA and their family members to maintain well-being, overcome barriers and regain confidence. Using this approach, focusing on the person’s recognition, activation and mobilisation of assets, could enhance the person’s understanding and restore meaning around the stroke and onset of aphasia. Conclusion: This novel exploratory research demonstrates the relevance and potential across diverse cultural contexts of taking an asset-based approach to promoting and sustaining well-being for PWA and their families. Focusing on maintaining connections to these assets and developing meaning around the event, could prevent some of the negative sequela of stroke. The “patient–professional” relationship must transform into a collaborative partnership, with time and flexibility needed to introduce this approach. Further research should examine how service providers and PWA could develop and operationalise an asset-based approach in clinical and community settings and identify if there is an optimum timing for introducing this approach along the stroke pathway

Patient and general practitioner attitudes to taking medication to prevent cardiovascular disease after receiving detailed information on risks and benefits of treatment: a qualitative study

Abstract Background There are now effective drugs to prevent cardiovascular disease and guidelines recommend their use. Patients do not always choose to accept preventive medication at levels of risk reduction recommended in guidelines. The purpose of the study was to identify and explore the attitudes of patients and general practitioners towards preventative medication for cardiovascular disease (CVD) after they have received information about it; to identify implications for practice and prescribing. Methods Qualitative interviews with GPs and patients following presentation of in depth information about CVD risks and the absolute effects of medication. Setting: GP practices in Birmingham, United Kingdom. Results In both populations: wide variation on attitudes to preventative medication; concerns about unnecessary drug taking & side effects; preferring to consider lifestyle changes first. In patient population: whatever their attitudes to medication were, the vast majority explained that they would ultimately do what their GP recommended; there was some misunderstanding of the distinction between curative and preventative medication. A common theme was the degree of trust in their doctors' judgement and recommendations, which contrasted with scepticism of the role of pharmaceutical companies and academics. Scepticism in guidelines was also common among doctors although many nevertheless recommended treatment for their patients Conclusions A guideline approach to prescribing preventative medication could be against the interests and preferences of the patient. GPs must take extra care to explain what preventative medication is and why it is recommended, attempt to discern preferences and make recommendations balancing these potentially conflicting concerns.</p

Long-term declines in ADLs, IADLs, and mobility among older Medicare beneficiaries

<p>Abstract</p> <p>Background</p> <p>Most prior studies have focused on short-term (≤ 2 years) functional declines. But those studies cannot address aging effects inasmuch as all participants have aged the same amount. Therefore, the authors studied the extent of long-term functional decline in older Medicare beneficiaries who were followed for varying time lengths, and the authors also identified the risk factors associated with those declines.</p> <p>Methods</p> <p>The analytic sample included 5,871 self- or proxy-respondents who had complete baseline and follow-up survey data that could be linked to their Medicare claims for 1993-2007. Functional status was assessed using activities of daily living (ADLs), instrumental ADLs (IADLs), and mobility limitations, with declines defined as the development of two of more new difficulties. Multiple logistic regression analysis was used to focus on the associations involving respondent status, health lifestyle, continuity of care, managed care status, health shocks, and terminal drop.</p> <p>Results</p> <p>The average amount of time between the first and final interviews was 8.0 years. Declines were observed for 36.6% on ADL abilities, 32.3% on IADL abilities, and 30.9% on mobility abilities. Functional decline was more likely to occur when proxy-reports were used, and the effects of baseline function on decline were reduced when proxy-reports were used. Engaging in vigorous physical activity consistently and substantially protected against functional decline, whereas obesity, cigarette smoking, and alcohol consumption were only associated with mobility declines. Post-baseline hospitalizations were the most robust predictors of functional decline, exhibiting a dose-response effect such that the greater the average annual number of hospital episodes, the greater the likelihood of functional status decline. Participants whose final interview preceded their death by one year or less had substantially greater odds of functional status decline.</p> <p>Conclusions</p> <p>Both the additive and interactive (with functional status) effects of respondent status should be taken into consideration whenever proxy-reports are used. Encouraging exercise could broadly reduce the risk of functional decline across all three outcomes, although interventions encouraging weight reduction and smoking cessation would only affect mobility declines. Reducing hospitalization and re-hospitalization rates could also broadly reduce the risk of functional decline across all three outcomes.</p

Ultrasound-Enhanced Drug Transport and Distribution in the Brain

Drug delivery in the brain is limited by slow drug diffusion in the brain tissue. This study tested the hypothesis that ultrasound can safely enhance the permeation of drugs in the brain. In vitro exposure to ultrasound at various frequencies (85 kHz, 174 kHz, and 1 MHz) enhanced the permeation of tritium-labeled molecules with molecular weight up to 70 kDa across porcine brain tissue. A maximum enhancement of 24-fold was observed at 85 kHz and 1,200 J/cm2. In vivo exposure to 1-MHz ultrasound further demonstrated the ability of ultrasound to facilitate molecule distribution in the brain of a non-human primate. Finally, ultrasound under conditions similar to those used in vivo was shown to cause no damage to plasmid DNA, siRNA, adeno-associated virus, and fetal rat cortical neurons over a range of conditions. Altogether, these studies demonstrate that ultrasound can increase drug permeation in the brain in vitro and in vivo under conditions that did not cause detectable damage

Potentially inappropriate prescriptions for older patients in long-term care

BACKGROUND: Inappropriate medication use is a major healthcare issue for the elderly population. This study explored the prevalence of potentially inappropriate prescriptions (PIPs) in long-term care in metropolitan Quebec. METHODS: A cross sectional chart review of 2,633 long-term care older patients of the Quebec City area was performed. An explicit criteria list for PIPs was developed based on the literature and validated by a modified Delphi method. Medication orders were reviewed to describe prescribing patterns and to determine the prevalence of PIPs. A multivariate analysis was performed to identify predictors of PIPs. RESULTS: Almost all residents (94.0%) were receiving one or more prescribed medication; on average patients had 4.8 prescribed medications. A majority (54.7%) of treated patients had a potentially inappropriate prescription (PIP). Most common PIPs were drug interactions (33.9% of treated patients), followed by potentially inappropriate duration (23.6%), potentially inappropriate medication (14.7%) and potentially inappropriate dosage (9.6%). PIPs were most frequent for medications of the central nervous system (10.8% of prescribed medication). The likelihood of PIP increased significantly as the number of drugs prescribed increased (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 1.33 – 1.43) and with the length of stay (OR: 1.78, CI: 1.43 – 2.20). On the other hand, the risk of receiving a PIP decreased with age. CONCLUSION: Potentially inappropriate prescribing is a serious problem in the highly medicated long-term care population in metropolitan Quebec. Use of explicit criteria lists may help identify the most critical issues and prioritize interventions to improve quality of care and patient safety

Is it pleasure or health from leisure that we benefit from most?:An analysis of well-being alternatives and implications for policy

International policy now constantly advocates a need for populations to engage in more physical activity to promote health and to reduce society’s health care costs. Such policy has developed guidelines on recommended levels and intensity of physical activity and implicitly equates health with well-being. It is assumed that individual, and hence social welfare will be enhanced if the activity guidelines are met. This paper challenges that claim and raises questions for public policy priorities. Using an instrumental variable analysis to value the well-being from active leisure, it is shown that the well-being experienced from active leisure that is not of a recommended intensity to generate health benefits, perhaps due to its social, recreational or fun purpose, has a higher value of well-being than active leisure that does meet the guidelines. This suggests rethinking the motivation and foundation of existing policy and perhaps a realignment of priorities towards activity that has a greater contribution to social welfare through its intrinsic fun and possibly social interaction

Hypoglycemia Revisited in the Acute Care Setting

Hypoglycemia is a common finding in both daily clinical practice and acute care settings. The causes of severe hypoglycemia (SH) are multi-factorial and the major etiologies are iatrogenic, infectious diseases with sepsis and tumor or autoimmune diseases. With the advent of aggressive lowering of HbA1c values to achieve optimal glycemic control, patients are at increased risk of hypoglycemic episodes. Iatrogenic hypoglycemia can cause recurrent morbidity, sometime irreversible neurologic complications and even death, and further preclude maintenance of euglycemia over a lifetime of diabetes. Recent studies have shown that hypoglycemia is associated with adverse outcomes in many acute illnesses. In addition, hypoglycemia is associated with increased mortality among elderly and non-diabetic hospitalized patients. Clinicians should have high clinical suspicion of subtle symptoms of hypoglycemia and provide prompt treatment. Clinicians should know that hypoglycemia is associated with considerable adverse outcomes in many acute critical illnesses. In order to reduce hypoglycemia-associated morbidity and mortality, timely health education programs and close monitoring should be applied to those diabetic patients presenting to the Emergency Department with SH. ED disposition strategies should be further validated and justified to achieve balance between the benefits of euglycemia and the risks of SH. We discuss relevant issues regarding hypoglycemia in emergency and critical care settings