Prevalence of Obesity and Malnutrition in Four Cohorts of Very Old Adults, 2000-2017.

OBJECTIVES: Investigate trends in the prevalence of obesity and malnutrition among very old adults (age ≥ 85 years) between 2000 and 2017. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: A study with data from the Umeå 85+/Gerontological regional database population-based cohort study of very old adults in northern Sweden. Every 5 years from 2000-2002 to 2015-2017, comprehensive assessments of participants were performed during home visits (N=1602). Body mass index (BMI) classified participants as underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30.0 kg/m2). Mini Nutritional Assessment (MNA) scores classified participants as malnourished (0 to <17), at risk of malnutrition (17-23.5), and having good nutritional status (24-30). Prevalence and trends were examined using analysis of variance and chi-squared tests, including subgroup analyses of nursing home residents. RESULTS: Between 2000-2002 and 2015-2017, the mean BMI increased from 24.8± 4.7 to 26.0± 4.7 kg/m2. The prevalence of obesity and underweight were 13.4% and 7.6%, respectively, in 2000-2002 and 18.3% and 3.0%, respectively, in 2015-2017. The mean MNA score increased between 2000-2002 and 2010-2012 (from 23.2± 4.7 to 24.2± 3.6), and had decreased (to 23.3± 4.2) by 2015-2017. The prevalence of malnutrition was 12.2%, 5.1%, and 8.7% in 2000-2002, 2010-2012, and 2015-2017, respectively. Subgroup analyses revealed similar BMI and MNA score patterns among nursing home residents. CONCLUSIONS: Among very old adults, the mean BMI and prevalence of obesity seemed to increase between 2000-2002 and 2015-2017. Meanwhile, the nutritional status (according to MNA scores) seemed to improve between 2000-2002 and 2010-2012, it declined by 2015-2017.

Development of dementia in patients with femoral neck fracture who experience postoperative delirium-A three-year follow-up study.

OBJECTIVES: It remains unclear to what extent postoperative delirium (POD) affects the incidence of dementia in hip fracture patients, and the methods used to detect delirium and dementia require validation. The aim of this study was to investigate the development of dementia within 3 years of femoral neck fracture repair surgery, with a focus on POD as a potential predictive factor. METHODS: Patients were assessed for cognition, delirium, depression, psychological well-being, and nutritional status during their hospitalization as well as 4, 12, and 36 months after the operation. Logistic regression models were used to analyse factors associated with POD and factors associated with the development of dementia. RESULTS: The study sample consisted of 135 patients without a history of dementia, of whom 20 (14.8%) were delirious preoperatively and 75 (55.5%) postoperatively. Three years after their operations, 43/135 patients (31.8%) were diagnosed with dementia. A greater portion of patients diagnosed with dementia (39/43, 90.6%) than patients with no dementia (36/92, 39.1%) were included among the 75 patients who had experienced POD (P < 0.001). In a logistic regression model, after adjustment for covariates (age, sex, diabetes, delirium pre-and postoperatively, hyperactive delirium, days with delirium, urinary tract infection, and Mini Nutritional Assessment score), POD emerged an independent predictor for the development of new dementia (odds ratio, 15.6; 95% confidence interval, 2.6-91.6) within 3 years after the operation. CONCLUSION: Geriatric hip fracture patients who exhibit POD should be monitored closely for the development of dementia.

The risk of overestimating the risk-metal leaching to groundwater near contaminated glass waste deposits and exposure via drinking water.

This study investigates metal contamination patterns and exposure to Sb, As, Ba, Cd and Pb via intake of drinking water in a region in southeastern Sweden where the production of artistic glass has resulted in a large number of contaminated sites. Despite high total concentrations of metals in soil and groundwater at the glassworks sites properties, all drinking water samples from households with private wells, located at a 30-640m distance from a glassworks site, were below drinking water criteria from the WHO for Sb, As, Ba and Cd. A few drinking water samples showed concentrations of Pb above the WHO guideline, but As was the only element found in concentrations that could result in human exposure near toxicological reference values. An efficient retention of metals in the natural soil close to the source areas, which results in a moderate impact on local drinking water, is implied. Firstly, by the lack of significant difference in metal concentrations when comparing households located upstream and downstream of the main waste deposits, and secondly, by the lack of correlation between the metal concentration in drinking water and distance to the nearest glassworks site. However, elevated Pb and Cd concentrations in drinking water around glassworks sites when compared to regional groundwater indicate that diffuse contamination of the soils found outside the glassworks properties, and not only the glass waste landfills, may have a significant impact on groundwater quality. We further demonstrate that different mobilization patterns apply to different metals. Regarding the need to use reliable data to assess drinking water contamination and human exposure, we finally show that the conservative modelling approaches that are frequently used in routine risk assessments may result in exposure estimates many times higher than those based on measured concentrations in the drinking water that is actually being used for consumption.

Risk factors for hip fracture in very old people: a population-based study.

SUMMARY: Knowledge of risk factors for hip fracture among very old people is limited. Walking indoors with help from ≤1 person, Parkinson's disease, currently smoking, delirium in the previous month, underweight, and age were associated with increased risk of hip fracture and could be important for preventive strategy development. INTRODUCTION: The purpose of this study is to investigate risk factors for hip fracture among a representative sample of very old people. METHODS: In total, 953 participants from the Umeå 85+/Gerontological Regional Database population-based cohort study were interviewed and assessed during home visits. Associations of baseline characteristics with hip fracture during the maximum 5-year follow-up period were analyzed using Cox proportional hazards regression. RESULTS: Participants had a mean age of 89.3 ± 4.7 years; 65.8% were women, 36.8% lived in residential care facilities, 33.6% had dementia, and 20.4% had histories of hip fracture. During a mean follow-up period of 2.7 years, 96 (10.1%) individuals sustained hip fracture. Walking indoors with help from no more than one person (hazard ratio [HR] = 8.57; 95% confidence interval [CI], 1.90-38.71), Parkinson's disease (HR = 5.12; 95% CI, 1.82-14.44), currently smoking (HR = 4.38; 95% CI 2.06-9.33), delirium in the previous month (HR = 2.01; 95% CI, 1.15-3.49), underweight (body mass index <22; HR = 1.74, 95% CI, 1.09-2.77), and age (HR = 1.09; 95% CI, 1.04-1.14) were associated independently with an increased risk of hip fracture. Hip prosthesis at baseline decreased the risk of hip fracture (HR = 0.37; 95% CI, 0.15-0.91), but only for those with bilateral hip prostheses. CONCLUSIONS: Seven factors were associated independently with incident hip fracture during follow-up in this sample of very old people. These factors could have important clinical implications in identifying persons at high risk of hip fracture, as well as in the development of effective preventive strategies.

Body mass index, Mini Nutritional Assessment, and their association with five-year mortality in very old people.

OBJECTIVES: to investigate the prevalence of malnutrition and the association between Body Mass Index (BMI), Mini Nutritional Assessment (MNA) and five-year mortality in a representative population of very old (>85 years) people. DESIGN: A prospective cohort study. SETTING: A population-based study of very old people in northern Sweden and western Finland, living in institutional care or in the community. PARTICIPANTS: Out of 1195 potential participants, 832 were included (mean age 90.2±4.6 years). MEASUREMENTS: Nutritional status was assessed using BMI and MNA and the association of those two variables with five-year mortality was analyzed. RESULTS: The mean BMI value for the whole population was 25.1±4.5 kg/m2, with no difference between genders (P=0.938). The mean MNA score was 22.5±4.6 for the whole sample, and it was lower for women than for men (P<0.001). Thirteen percent were malnourished (MNA<17) and 40.3% at risk of malnutrition (MNA 17-23.5) according to MNA. Also, 34.8% of those with a MNA score <17 still had a BMI value ≥22.2 kg/m2. A BMI value <22.2 kg/m2 and a MNA score<17 were associated with lower survival. The association with mortality seemed to be J-shaped for BMI, and linear for MNA. CONCLUSIONS: Malnutrition according to MNA was common, but a substantial portion of those with a low MNA score still had a high BMI value, and vice versa. The association with mortality appeared to be J-shaped for BMI, and linear for MNA. The MNA seems to be a good measurement of malnutrition in very old people, and BMI might be misleading and could underestimate the prevalence of malnutrition, especially in women.

Consensus and variations in opinions on delirium care: a survey of European delirium specialists.

BACKGROUND: There are still substantial uncertainties over best practice in delirium care. The European Delirium Association (EDA) conducted a survey of its members and other interested parties on various aspects of delirium care. METHODS: The invitation to participate in the online survey was distributed among the EDA membership. The survey covered assessment, treatment of hyperactive and hypoactive delirium, and organizational management. RESULTS: A total of 200 responses were collected (United Kingdom 28.6%, Netherlands 25.3%, Italy 15%, Switzerland 9.7%, Germany 7.1%, Spain 3.8%, Portugal 2.5%, Ireland 2.5%, Sweden 0.6%, Denmark 0.6%, Austria 0.6%, and others 3.2%). Most of the responders were doctors (80%), working in geriatrics (45%) or internal medicine (14%). Ninety-two per cent of the responders assessed patients for delirium daily. The most commonly used assessment tools were the Confusion Assessment Method (52%) and the Delirium Observation Screening Scale (30%). The first-line choice in the management of hyperactive delirium was a combination of non-pharmacological and pharmacological approaches (61%). Conversely, non-pharmacological management was the first-line choice in hypoactive delirium (67%). Delirium awareness (34%), knowledge (33%), and lack of education (13%) were the most commonly reported barriers to improving the detection of delirium. Interestingly, 63% of the responders referred patients after an episode of delirium to a follow-up clinic. CONCLUSIONS: This is the first systematic survey involving an international group of specialists in delirium. Several areas of lack of consensus were found. These results emphasise the importance of further research to improve care of this major unmet medical need.

Pharmacokinetic interaction study with fixed high dose combinations of candesartan cilexetil and hydrochlorothiazide.

OBJECTIVE: Combination treatment with candesartan and hydrochlorothiazide (HCT) has been shown to provide the full additive antihypertensive effect of the components. A clinical program has been undertaken to study the efficacy and safety of the fixed dose combinations of candesartan 32 mg and HCT 12.5 or 25 mg in patients with mild to moderate hypertension. This study evaluated the drug-drug interaction potential of the highest dose combination of candesartan 32 mg and HCT 25 mg. SUBJECTS AND METHODS: 53 healthy male and female subjects were randomized to sequential treatment with single doses of one candesartan/ HCT 32/25 mg tablet, two 16/12.5 mg tablets, one candesartan 32 mg tablet and one HCT 25 mg tablet using an open 4-way cross-over design. RESULTS: There was no pharmacokinetic interaction between candesartan 32 mg and HCT 25 mg during concomitant administration. AUC and Cmax were within the accepted confidence limits of 0.8 - 1.25 compared to the monocomponents, and tmax and t1/2 were similar to those of the monocomponents. There were no unexpected safety findings, and no subject discontinued study treatment due to an adverse event. CONCLUSION: There was no pharmacokinetic interaction found between the high doses of candesartan 32 mg and HCT 25 mg.

Profound cardiac conduction delay predicts mortality in myotonic dystrophy type 1.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is known to affect mainly the musculoskeletal system. Early mortality is related to respiratory disease and possibly additional cardiovascular complications. AIMS: To identify possible cardiovascular disturbances that could predict survival of DM1 patients. METHODS: We studied 30 DM1 patients (mean age 41 +/- 13.5 years, range 16-71, 15 women) who were cardiovascularly stable and compared them with 29 controls (mean age 55 +/- 7.8 years, range 42-66, 14 women) using electrocardiography (ECG) and conventional transthoracic echocardiography. The subgroup that survived a follow-up period of 17 years was re-examined using the same protocol. RESULTS: Of the 30 patients, 10 died of a documented respiratory cause and three of acute myocardial incidents. Compared with controls, left ventricular cavity size, corrected to body surface area, was slightly enlarged at end systole (P < 0.05) and hence fractional shortening was reduced (P < 0.01). Nine patients had first-degree heart block and 15 had a QRS duration >90 ms. Of all ECG and echocardiographic measurements, the sum of QRS duration + PR interval was the best predictor of mortality as shown by the area under the receiver operating characteristic curve of 85%, sensitivity of 70% and specificity of 84%. CONCLUSIONS: These findings suggest that silent cardiac dysfunction in DM1 patients may cause significant disturbances that over time result in serious complications. Regular follow-up of such patients with detailed electrical and mechanical cardiac assessment may suggest a need for early intervention that may avoid early mortality in some.

Ventricular dysfunction in type 1 myotonic dystrophy: electrical, mechanical, or both?

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a systemic disease which affects the heart and may be a cause of sudden death. Conduction disturbances are the major cardiac abnormalities seen in this condition. We sought to assess electrical and mechanical cardiac functions to identify abnormalities that might explain sudden cardiac death in DM1. METHODS: Thirty six patients with DM1 and 16 controls were studied using echocardiography including myocardial Doppler. ECG recordings were also obtained. RESULTS: Left ventricular (LV) dimensions were maintained but systolic function was reduced (p<0.001), including stroke volume (p<0.05). LV segmental myocardial isovolumic contraction time was prolonged (p<0.001) and correlated with PR interval (p<0.001). Isovolumic relaxation time was prolonged (p<0.05) and filling time was reduced (p<0.001). LV cavity was significantly asynchronous demonstrated by prolonged total isovolumic time (t-IVT) (p<0.001), high Tei index (p<0.001) and low ejection index (p<0.001). Right ventricular (RV) strain was reduced (p<0.001) as were its systolic and diastolic velocities (p<0.05 for both). 22/36 patients had prolonged LV t-IVT>12.3 s/min (upper 95% normal CI), 13 of whom had PR≥200 ms, 11 had QRS duration>120 ms (5 had combined abnormality) and the remaining 5 had neither. Over the 3 years follow up 10 patients had events, 6 of them cardiac. t-IVT was prolonged in 5/6 patients, PR interval in 4 and QRS duration in one. CONCLUSIONS: In DM1 patients, LV conventional measurements are modestly impaired but cardiac time relations suggest marked asynchronous cavity function. Although our findings were primarily explained on the basis of long PR interval or broad QRS duration a minority presented an evidence for myocardial cause of asynchrony rather than electrical. Early identification of such abnormalities may guide towards a need for additional electrical resynchronization therapy which may improve survival in a way similar to what has been shown in heart failure trials.

Evaluation of a fall-prevention program in older people after femoral neck fracture: a one-year follow-up.

UNLABELLED: A randomized, controlled fall-prevention study including 199 patients operated on for femoral neck fracture reduced inpatient falls and injuries. No statistically significant effects of the intervention program could be detected after discharge. It seems that fall-prevention must be part of everyday life in fall-prone old people. INTRODUCTION: This study evaluates whether a postoperative multidisciplinary, multifactorial fall-prevention program performed by a geriatric team that reduced inpatient falls and injuries had any continuing effect after discharge. The intervention consisted of staff education, systematic assessment and treatment of fall risk factors and vitamin D and calcium supplementation. METHODS: The randomized, controlled trial with a one-year follow-up at Umeå University Hospital, Sweden, included 199 patients operated on for femoral neck fracture, aged > or = 70 years. RESULTS: After one year 44 participants had fallen 138 times in the intervention group compared with 55 participants and 191 falls in the control group. The crude postoperative fall incidence was 4.16/1,000 days in the intervention group vs. 6.43/1,000 days in the control group. The incidence rate ratio was 0.64 (95% CI: 0.40-1.02, p = 0.063). Seven new fractures occurred in the intervention group and 11 in the control group. CONCLUSION: A team applying comprehensive geriatric assessment and rehabilitation, including prevention and treatment of fall-risk factors, reduced inpatient falls and injuries, but no statistically significant effects of the program could be detected after discharge. It seems that fall-prevention must be part of everyday life in fall-prone elderly.

Being burdened and balancing boundaries: a qualitative study of nurses' experiences caring for patients who self-harm.

Although nurses encounter self-harm patients in various settings, self-harm has seldom been addressed in psychiatric nursing research. The research question was: 'What are nurses' descriptions of experiences of caring for psychiatric patients who self-harm?' The data were comprised of text based on narrative interviews with six nurses employed in a psychiatric hospital in Sweden. By using qualitative content analysis, two themes and seven sub-themes were constructed. The theme 'Being burdened with feelings' involved the sub-themes: 'Fearing for the patient's life-threatening actions', 'Feeling overwhelmed by frustration' and 'Feeling abandoned by co-workers and management'. The theme 'Balancing professional boundaries' involved the sub-themes: 'Maintaining professional boundaries between self and patient', 'Managing personal feelings', 'Feeling confirmed by co-workers' and 'Imagining better ways of care'. Of significance are the nurses' feelings of fear, frustration and abandonment creating the sense of being burdened. This study points to the importance of releasing these burdens, not only for the sake of the nurses, but to improve the care of the patients. The importance of increased knowledge, support and supervision for professionals working with people who self-harm, not only in psychiatric care, needs to be addressed in research, education and development of practice.

A multidisciplinary, multifactorial intervention program reduces postoperative falls and injuries after femoral neck fracture.

INTRODUCTION: This study evaluates whether a postoperative multidisciplinary, intervention program, including systematic assessment and treatment of fall risk factors, active prevention, detection, and treatment of postoperative complications, could reduce inpatient falls and fall-related injuries after a femoral neck fracture. METHODS: A randomized, controlled trial at the orthopedic and geriatric departments at Umeå University Hospital, Sweden, included 199 patients with femoral neck fracture, aged >or=70 years. RESULTS: Twelve patients fell 18 times in the intervention group compared with 26 patients suffering 60 falls in the control group. Only one patient with dementia fell in the intervention group compared with 11 in the control group. The crude postoperative fall incidence rate was 6.29/1,000 days in the intervention group vs 16.28/1,000 days in the control group. The incidence rate ratio was 0.38 [95% confidence interval (CI): 0.20 - 0.76, p=0.006] for the total sample and 0.07 (95% CI: 0.01-0.57, p=0.013) among patients with dementia. There were no new fractures in the intervention group but four in the control group. CONCLUSION: A team applying comprehensive geriatric assessment and rehabilitation, including prevention, detection, and treatment of fall risk factors, can successfully prevent inpatient falls and injuries, even in patients with dementia.

Altered homeostasis of extracellular matrix proteins in joints of standardbred trotters during a long-term training programme.

This study evaluates how strenuous training, age and lameness influence the release of cartilage oligomeric matrix protein (sf-COMP), aggrecan and collagen type II into synovial fluid in 28 (19.5-40 months) Standardbred trotters (STB), during a long-term training programme (24 months). All the horses were trained by the same trainer and were healthy on entering the training programme. Synovial fluid (sf) from the left middle carpal joint in each subject was sampled every third month. Enzyme-linked immunosorbent assay was used to determine the concentrations of sf-COMP, sf-aggrecan and sf-collagen type II. Concentration of sf-COMP decreased with increasing age and total days of training. The concentration of sf-COMP was found similarly related to both age and total days of training, so they could not be differentiated. It was also shown that the concentration of collagen type II degradation products increased with total days of training. The study shows that extensive and long-term training programme induces metabolic changes in articular cartilage exemplified by reduced release and synthesis of COMP. This is most likely due to strenuous training leading to inappropriate load on the articular cartilage.

Pulsed tissue Doppler and strain imaging discloses early signs of infiltrative cardiac disease: a study on patients with familial amyloidotic polyneuropathy.

BACKGROUND: Familial amyloidotic polyneuropathy (FAP) is a hereditary systemic amyloidosis with cardiac involvement. As early identification of the cardiac involvement is of major clinical interest we performed this study to test the hypothesis that tissue Doppler imaging (TDI) and strain imaging (SI) might disclose cardiac involvement in patients with early stages of FAP. METHODS: Twenty-two patients with FAP and 36 healthy controls were studied. Standard M-mode and Doppler echocardiography were performed. TDI and SI were used to assess the regional longitudinal left ventricular (LV) lateral and septal and right ventricular (RV) wall functions. All time intervals were corrected for heart rate by dividing with R-R interval and presented as percentage. RESULTS: We found that patients in comparison with controls had increased LV and RV wall thickness and by using TDI a prolonged isovolumic relaxation time (IVRt) at the septal segment (15.0+/-7.0 vs 10.7+/-4.1%, p<0.05) and prolonged isovolumic contraction time (IVCt) at LV lateral (12.8+/-4.3 vs 10.1+/-3.3%, p<0.05), septal (12.5+/-3.5 vs 8.9+/-1.9%, p<0.001) and RV free wall segments (12.0+/-3.6 vs 8.3+/-2.1%, p<0.001). Strain was reduced at LV lateral basal segment (-4.6+/-14.0 vs -20.2+9.1, p<0.001), RV free wall mid segment (-16.2+/-12.8 vs -29.4+/-15.2) as well as both septal segments (-4.1+/-11.7 vs -16.2+/-9.0%, p<0.001, -8.8+/-11.5 vs -19.4+/-8.4%, p<0.001 for septal basal and mid-segment). Even in the absence of septal hypertrophy the septal strain was reduced and the regional IVCt was prolonged. CONCLUSIONS: This is the first clinical study using TDI and strain in patients with FAP showing functional abnormalities before any morphological echocardiographic abnormalities were present. Both the left and right heart functions are involved and the disease should therefore be regarded as biventricular.

RhoGDI-3, a promising system to investigate the regulatory function of rhoGDIs: uncoupling of inhibitory and shuttling functions of rhoGDIs.

rhoGDIs (Rho GDP dissociation inhibitors) are postulated to regulate the activity and the localization of small G-proteins of the Rho family by a shuttling process involving extraction of Rho from donor membranes, formation of inhibitory cytosolic rhoGDI/Rho complexes, and delivery of Rho to target membranes. However, the role of rhoGDIs in site-specific membrane targeting or extraction of Rho is still poorly understood. We investigated here the in vivo functions of two mammalian rhoGDIs: the specific rhoGDI-3 and the well-studied rhoGDI-1 (rhoGDI) after structure-based mutagenesis. We identified two sites in rhoGDIs, forming conserved interactions with their Rho target, whose mutation results in the uncoupling of inhibitory and shuttling functions of rhoGDIs in vivo. Remarkably, these rhoGDI mutants were detected at Rho-induced membrane ruffles or protrusions, where they co-localized with RhoG or Cdc42, probably identifying for the first time the site of extraction of a Rho protein by a rhoGDI in vivo. We propose that these mutations act by modifying the steady-state kinetics of the shuttling process regulated by rhoGDIs, such that transient steps at the cell membranes now become detectable. They should provide valuable tools for future investigations of the dynamics of membrane extraction or delivery of Rho proteins and their regulation by cellular partners.

Opening up: psychiatric nurses' experiences of participating in reflection groups focusing on the use of coercion.

Psychiatric staff report that the use of coercion towards patients in psychiatric care engenders feelings of discomfort and conflicts. The aim of this study was to describe psychiatric nurses' experiences of participating in reflection groups focused on the use of coercion, in relation to their views regarding systematic clinical supervision and staff support. Twenty-one nurses who had participated in reflection groups were interviewed retrospectively. The structured interview focused on: (i) their views of clinical supervision and support in general; (ii) their views of clinical supervision and support specifically concerning the use of coercion; and (iii) their experiences of participating in groups reflecting the use of coercion. Nurses were largely positive about participating in reflection groups, as expressed in the subthemes: having time for reflection; being confirmed; gaining new perspectives; sharing fellowship with colleagues; and relating more effectively to patients. Complications concerning participation in the reflection groups and other forms of clinical supervision as reported by nurses were: providing time for participation; having a common aim; being vulnerable in difficult situations; and assuming that the need for supervision and support could indicate that they were not coping with their job.

Struggling for hopefulness: a qualitative study of Swedish women who self-harm.

There has been an increase in the number of Swedish psychiatric patients who self-harm, yet self-harm is seldom described in published research. The aim of this study was to describe how people who self-harm experience received care and their desired care. Nine participants, all Swedish women who had been treated for inpatient or outpatient psychiatric care, narrated their experiences of care for self-harm. Using qualitative content analysis, two themes were formulated: 'Expecting to be confirmed while being confirmed fosters hopefulness'; and, 'Expecting to be confirmed while not being confirmed stifles hopefulness'. Each of these themes emerged from five subthemes that clustered around positive and negative aspects of being seen-not being seen, being valued-being stigmatized, being connected-disconnected, being believed-doubted, and being understood-not being understood. Of significance is for nurses to view persons who self-harm as human beings and to grasp the importance of being confirmed by staff that can foster hopefulness in persons who self-harm, yet realize the possibility of the paradoxical nature of hopefulness and being confirmed.

Health-related quality of life during treatment of elderly patients with hypertension: results from the Study on COgnition and Prognosis in the Elderly (SCOPE).

The Study on COgnition and Prognosis in the Elderly (SCOPE) was a multinational, randomised, double-blind study to assess the effects of candesartan 8-16 mg daily on cardiovascular events and cognitive function in elderly patients (aged 70-89 years) with mild to moderate hypertension. A total of 4937 patients were randomised to candesartan or placebo with other antihypertensive drugs (mostly diuretics, beta-blockers, and calcium antagonists) added as needed to control blood pressure. Only 16% of the patients in the control group received placebo alone. The mean follow-up was 3.7 years. The aim of this health-related quality of life (HRQL) substudy analysis was to investigate changes in HRQL during antihypertensive treatment, and possible differences in patients receiving candesartan-based or other antihypertensive treatment. Three validated HRQL instruments were used: the Psychological General Well-being (PGWB) Index, the Subjective Symptoms Assessment Profile (SSA-P), and the EuroQoL Health Utility Index (EuroQoL). The HRQL was generally good at baseline and well preserved during follow-up in the presence of substantial blood pressure reductions in both treatment groups. Several of the observed changes in score from baseline to last visit favoured candesartan-based compared to control treatment, particularly the changes in PGWB Anxiety (-0.5 vs -1.0, P=0.01), PGWB Positive well-being (-0.8 vs -1.1, P=0.04), SSA-P Cardiac symptoms (0.03 vs 0.10, P=0.03), and EuroQoL Current health (-3.1 vs -5.3, P=0.008). This favourable result may be related to the somewhat lower blood pressure associated with candesartan-based treatment. In conclusion, there should be no reason to withhold modern antihypertensive therapy in elderly patients due to concerns for a negative effect on HRQL.

Clinical features and contemporary management of patients with low and preserved ejection fraction heart failure: baseline characteristics of patients in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme.

AIMS: To describe the clinical characteristics and contemporary treatment of a broad spectrum of patients with chronic heart failure (CHF) randomised in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme, consisting of three component studies comparing placebo to candesartan. METHODS AND RESULTS: CHARM Alternative, CHARM Added and CHARM Preserved enrolled 2028 low left ventricular ejection fraction (LVEF) ACE inhibitor intolerant patients, 2548 low LVEF ACE inhibitor treated patients and 3025 preserved LVEF patients, respectively. Patients in CHARM Preserved were more often female. The proportion of women in CHARM Preserved was 40% compared to 32% in CHARM Alternative and 21% in CHARM Added. Patients in CHARM Preserved were also more often hypertensive than in the other two trials (64% vs. 50% and 48%, respectively). Symptoms and signs (with the exception of a third heart sound) were similar in all three patient groups. Beta-blockers were used in over half of patients in all three groups. Digoxin and spironolactone were used less frequently and calcium antagonists more frequently in CHARM Preserved. Spironolactone was used most frequently in CHARM Alternative, i.e. in ACE inhibitor intolerant patients. CONCLUSIONS: The CHARM Programme provides the largest and most detailed comparison to date of patients low- and preserved-LVEF CHF. It also describes the causes of ACE-inhibitor intolerance in a large cohort of patients and the other treatment which these patients receive.

Vascular endothelial growth factor-B-deficient mice display an atrial conduction defect.

BACKGROUND: Vascular endothelial growth factors (VEGFs) and their receptors are essential regulators of vasculogenesis and angiogenesis in both embryos and adults. One of the factors with a still unknown physiological function is VEGF-B, which is expressed in many tissues, including the heart. METHODS AND RESULTS: Mice carrying a targeted deletion in the VEGF-B gene were developed. In VEGF-B(-/-) animals, no gross abnormalities were observed in organs that normally show high expression of VEGF-B, such as the heart, muscle, and kidney. Analysis of heart function by ECG showed that adult VEGF-B(-/-) mice have an atrial conduction abnormality characterized by a prolonged PQ interval. VEGF- or basic fibroblast growth factor-induced corneal angiogenesis was similar in normal and VEGF-B(-/-) mice. CONCLUSIONS: VEGF-B seems to be required for normal heart function in adult animals but is not required for proper development of the cardiovascular system either during development or for angiogenesis in adults.