Reliability, validity and clinical correlates of the Quality of Life in Alzheimer's disease (QoL-AD) scale in medical inpatients.

BACKGROUND: There is a lack of standardisation in quality of life (QoL) measurements to be used in older multimorbid patients. An ideal QoL measurement should be reliable, valid, subjective, multidimensional, feasible and generic. We hypothesised that the QoL-AD (Quality of Life in Alzheimer's Disease) scale could have these properties. Our aim was to determine the psychometric properties and clinical correlations of QoL-AD in a population of elderly, multimorbid medical inpatients. METHODS: QoL-AD was performed in 200 medical inpatients, and available caregivers. Reliability was determined using cronbach's alpha and corrected item-total correlations. The agreement between patient and proxy ratings were examined using intra-class correlations (ICC). Correlations between QoL-AD and demographic data, comorbidity, cognitive tests, ADL (activities of daily living) and depression were examined. To characterise the underlying constructs of QoL-AD, an exploratory factor analysis was performed. RESULTS: In total, 199 patients fulfilled the QoL-AD rating, with 139 proxy ratings. Cronbach's alpha (95 % CI) was 0.74 (0.68-0.79) for patients and 0.86 (0.83-0.90) for proxies. Patient-proxy ICC (95 % CI) was 0.31 (0.16-0.46). Lower QoL was correlated to depression, cognitive impairment, ADL impairment and solitary living, but not with comorbidity. The factor analysis gave a three-factor solution, with factors representing phsyical, social and psychological well-being. CONCLUSION: The QoL-AD scale showed some promising properties but more research is needed before it can be recommended in this setting. If replicated, the finding that cognitive impairment, depression and ADL impairment were more associated with lower QoL than somatic comorbidity could have clinical implications for further studies aiming to improve QoL in this population.

Medial temporal lobe atrophy is underreported and may have important clinical correlates in medical inpatients.

BACKGROUND: The diagnostic workup in dementia includes brain imaging with reading focussed on signs of cerebrovascular and neurodegenerative disease. We hypothesised that these findings may be underreported in hospital patients, where imaging is often performed to rule out obvious pathology such as haemorrhage. In this study, we review cranial computed tomography (CT) in medical inpatients for white matter changes and atrophy. Our aim was to determine the clinical relevance of such findings and to what extent they were underreported. METHODS: Records from 200 inpatients aged over 60 years, who had been subjected to MMSE (mini-mental state examination) and CDT (clock-drawing test), were reviewed for cranial CT. Transverse and coronal slices were reassessed using visual rating scales regarding white matter changes (WMC), global cortical atrophy (GCA) and medial temporal lobe atrophy (MTA). Findings were compared with the original radiology reports and cognitive test results. RESULTS: Cranial CT had been performed in 94 of 200(47 %) patients. Of these, 58(62 %) had abnormal WMC, 35(37 %) abnormal GCA and 34(36 %) abnormal MTA. All three findings had associations with cognitive test results. Abnormal MTA was associated with lower results on the overall score on MMSE and on orientation, memory and language items. All three measurements were underreported in the original radiology reports; none of the 34 patients with abnormal MTA had been reported originally. CONCLUSIONS: Signs of neurodegenerative disease, especially MTA, were highly underreported in cranial CT scans performed in medical inpatients. At the same time, MTA seemed to hold the most important clinical correlates. Our results suggest that MTA should be reported more regularly in this setting.

Cognitive impairment is undetected in medical inpatients: a study of mortality and recognition amongst healthcare professionals.

BACKGROUND: Detecting cognitive impairment in medical inpatients is important due to its association with adverse outcomes. Our aim was to study recognition of cognitive impairment and its association with mortality. METHODS: 200 inpatients aged over 60 years were recruited at the Department of General Internal Medicine at University Hospital MAS in Malmö, Sweden. The MMSE (Mini-Mental State Examination) and the CDT (Clock-Drawing Test) were performed and related to recognition rates by patients, staff physicians, nurses and informants. The impact of abnormal cognitive test results on mortality was studied using a multivariable Cox proportional hazards regression. RESULTS: 55 patients (28%) had no cognitive impairment while 68 patients (34%) had 1 abnormal test result (on MMSE or CDT) and 77 patients (39%) had 2 abnormal test results. Recognition by healthcare professionals was 12% in the group with 1 abnormal test and 44-64% in the group with 2 abnormal test results. In our model, cognitive impairment predicted 12-month mortality with a hazard ratio (95% CI) of 2.86 (1.28-6.39) for the group with 1 abnormal cognitive test and 3.39 (1.54-7.45) for the group with 2 abnormal test results. CONCLUSIONS: Cognitive impairment is frequent in medical inpatients and associated with increased mortality. Recognition rates of cognitive impairment need to be improved in hospitals.

Orthostatic hypotension predicts all-cause mortality and coronary events in middle-aged individuals (The Malmo Preventive Project).

AIMS: Orthostatic hypotension (OH) has been linked to increased mortality and incidence of cardiovascular disease in various risk groups, but determinants and consequences of OH in the general population are poorly studied. METHODS AND RESULTS: Prospective data of the Swedish 'Malmö Preventive Project' (n = 33 346, 67.3% men, mean age 45.7 +/- 7.4 years, mean follow-up 22.7 +/- 6.0 years) were analysed. Orthostatic hypotension was found in 6.2% of study participants and was associated with age, female gender, hypertension, antihypertensive treatment, increased heart rate, diabetes, low BMI, and current smoking. In Cox regression analysis, individuals with OH had significantly increased all-cause mortality (in particular those aged less than 42 years) and coronary event (CE) risk. Mortality and CE risk were distinctly higher in those with systolic blood pressure (BP) fall >or=30 mmHg [hazard ratio (HR): 1.6, 95% CI 1.3-1.9, P < 0.0001 and 1.6, 95% CI 1.2-2.1, P = 0.001] and diastolic BP fall >or=15 mmHg (HR: 1.4, 95% CI 1.1-1.9, P = 0.024 and 1.7, 95% CI 1.1-2.5, P = 0.01). In addition, impaired diastolic BP response had relatively greater impact (per mmHg) on CE incidence than systolic reaction. CONCLUSION: Orthostatic hypotension can be detected in approximately 6% of middle-aged individuals and is often associated with such comorbidities as hypertension or diabetes. Presence of OH increases mortality and CE risk, independently of traditional risk factors. Although both impaired systolic and diastolic responses predict adverse events, the diastolic impairment shows stronger association with coronary disease.

Importance and added value of functional impairment to predict mortality: a cohort study in Swedish medical inpatients.

BACKGROUND: Accurate estimation of prognosis in multimorbid hospital patients could improve quality of care. This study aims to determine the relative importance and added value of a performance-based activities of daily living (ADL) measure with regard to mortality prediction. METHODS: 200 inpatients, aged over 60 years, were recruited at the Department of General Internal Medicine at a tertiary university hospital. Two nested survival models were built, one with established risk factors (age, sex, Charlson comorbidity index, haemoglobin, albumin, body mass index and glomerular filtration rate), and one using the same covariates with the Gottfries-Bråne-Steen (GBS)-ADL measure added. The relative importance of GBS-ADL was evaluated in the full model. The added value of GBS-ADL was determined by comparing the nested models using four approaches: difference in overall χ2, discrimination, continuous net reclassification index (NRI >0) and integrated discrimination improvement (IDI). RESULTS: In the full model, GBS-ADL was the single most important predictor of mortality (χ2-df=30, p<0.001). The likelihood ratio χ2 test showed significant added value of ADL (p<0.001). The C-statistic was 0.78 with ADL and 0.72 without (difference 0.058, 95% CI 0.022 to 0.094). The NRI >0 was 0.42 (95% CI 0.20 to 0.58) and IDI 0.15 (95% CI 0.07 to 0.22). CONCLUSIONS: Compared with a set of available clinical risk factors, impairment in ADL was a stronger predictor of all-cause mortality, showing substantial added value. Implementing quantitative ADL measurements could enable more appropriate and individual care for the elderly.

Fatality of future coronary events is related to inflammation-sensitive plasma proteins: a population-based prospective cohort study.

BACKGROUND: Approximately 40% of men suffering a first acute coronary event die the first day; most of them never reach hospital. It is largely unknown whether a low-grade inflammation in healthy men predicts the fatality of future coronary events. METHODS AND RESULTS: Five inflammation-sensitive plasma proteins (ISPs; fibrinogen, orosomucoid, alpha(1)-antitrypsin, haptoglobin, and ceruloplasmin) were measured in 6075 apparently healthy men, 680 of whom had a first coronary event [nonfatal myocardial infarction (MI) or death from coronary heart disease (CHD)] over a mean follow-up of 19 years. Of the 680 men who had a coronary event, 197 died the first day and 228 died within 28 days. Elevated ISPs were significantly associated with both nonfatal MI and CHD death, but the relative risks for CHD death were higher than for nonfatal MI. Among men who subsequently had a coronary event, the proportion of fatal events was related to the number of elevated ISPs at the baseline examination. The proportions who died the first day were 26%, 25%, 29%, and 35%, respectively, among men with 0, 1, 2, and > or =3 elevated ISPs (trend: P=0.01, adjusted for risk factors). The corresponding proportions who died within 28 days were 30%, 31%, 34%, and 38%, respectively (trend: P=0.03). CONCLUSIONS: Men who have been exposed to a low-grade inflammation many years earlier have higher fatality in future coronary events, with a higher proportion of CHD deaths and less nonfatal MI. This relation should be regarded when inflammatory markers are considered for risk assessment in primary prevention.

Inflammation-sensitive plasma proteins are associated with future weight gain.

Cross-sectional studies have associated obesity and other components of the so-called metabolic syndrome with low-grade inflammation. The temporal and causal relations of this association have not been fully explored. This study explored whether elevated levels of inflammation-sensitive plasma proteins (ISPs) (fibrinogen, orosomucoid, alpha1-antitrypsin, haptoglobin, and ceruloplasmin) are associated with future weight gain. Five ISPs were measured in 2,821 nondiabetic healthy men (38-50 years of age) who were reexamined after a mean follow-up of 6.1 years. Future weight gain was studied in relation to the number of elevated ISPs (i.e., in the top quartile). The proportion with a large weight gain (75th percentile >/= 3.8 kg) was 21.0, 25.9, 26.8, and 28.3%, respectively, among men with none, one, two, and three or more ISPs in the top quartile (P for trend 0.0005). This relation remained significant after adjustments for weight at baseline, follow-up time, height (at baseline and follow-up), physical inactivity (at baseline and follow-up), smoking (at baseline and follow-up), high alcohol consumption, and insulin resistance. The relations were largely similar for all individual ISPs. Elevated ISP levels predict a large weight gain in middle-aged men. This relation could contribute to the relation between inflammation, the metabolic syndrome, and cardiovascular disease.

Inflammation-sensitive plasma proteins, diabetes, and mortality and incidence of myocardial infarction and stroke: a population-based study.

This study explores the relationship of inflammation-sensitive plasma proteins (ISPs) with the prevalence of diabetes and the interrelationships between ISPs and diabetes in the prediction of death and incidence of myocardial infarction and stroke. Plasma levels of fibrinogen, alpha1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were assessed in 6,050 men, aged 28-61 years. All-cause and cardiovascular mortality and incidence of myocardial infarction and stroke were monitored over 18.7 +/- 3.7 years. Prevalence of diabetes (n = 321) was significantly associated with ISP levels among overweight and obese men but not among men with BMI <25 kg/m(2). The association was similar for insulin resistance according to homeostasis model assessment. High ISP levels (two or more ISPs in the top quartile) increased the cardiovascular risk among diabetic men. The risk factor-adjusted relative risks for cardiovascular mortality, myocardial infarction, and stroke were 2.8 (CI 1.8-4.5), 2.2 (1.5-3.2), and 2.5 (1.4-4.6), respectively, for diabetic men with high ISP levels (reference: nondiabetic men with low ISP levels). The corresponding risks for diabetic men with low ISP levels were 1.8 (1.1-3.0), 1.3 (0.8-2.1), and 1.2 (0.6-2.5), respectively. In conclusion, in this population-based cohort, diabetes was associated with increased ISP levels among overweight and obese men but not among men with normal weight. High ISP levels increased the cardiovascular risk similarly in diabetic as compared with nondiabetic men.

Incidence of obesity-associated cardiovascular disease is related to inflammation-sensitive plasma proteins: a population-based cohort study.

BACKGROUND: Although obesity is associated with increased inflammation, it is unclear whether this accounts for the increased cardiovascular risk in obesity. This population-based study explored whether inflammation-sensitive plasma proteins (ISPs) modify the cardiovascular risk in overweight or obese men. METHODS AND RESULTS: The ISPs (fibrinogen, orosomucoid, alpha1-antitrypsin, haptoglobin, ceruloplasmin) were measured in 6075 healthy men, aged 28 to 61 years. The incidences of cardiovascular events (myocardial infarction, stroke, cardiovascular deaths), cardiac events (fatal or nonfatal myocardial infarction), and stroke were followed-up over 18+/-4 years. High ISPs were associated with an increased cardiovascular risk in all categories of body mass index (BMI). The age-adjusted relative risks for cardiovascular events in obese men (BMI >30) were 2.1 (95% CI, 1.4 to 3.4), 2.4 (CI, 1.5 to 3.7), 3.7 (CI, 2.3 to 6.0), and 4.5 (CI, 3.0 to 6.6), respectively, for those with 0, 1, 2, and > or =3 ISPs in the top quartile (trend P=0.002) (reference: BMI <25 and no elevated ISP). This trend persisted after adjustments for several potential confounders (P=0.02). Incidence of cardiac events showed similar relations with the number of elevated ISPs in obese men. CONCLUSIONS: The cardiovascular risk varies widely between obese or overweight men with high and low ISPs. Relationships with ISPs contribute to, but cannot fully explain, the increased cardiovascular risk in obese men.

Blood pressure increase and incidence of hypertension in relation to inflammation-sensitive plasma proteins.

OBJECTIVE: The reasons for the relationship between inflammation-sensitive plasma proteins (ISPs) and incidence of cardiovascular diseases are poorly understood. This study explored the hypothesis that ISPs are associated with future hypertension and age-related blood pressure increase. METHODS AND RESULTS: Blood pressure and plasma levels of fibrinogen, alpha1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were determined in 2262 healthy men aged 35 to 50 years, initially without treatment for hypertension. The cohort was re-examined after 15.7 (+/-2.2) years. Incidence of hypertension and blood pressure increase was studied in relation to number of elevated proteins (ie, in the top quartile) at baseline. Among men without treatment for hypertension at follow-up, mean (+/-SD) increase in systolic blood pressure was 18.8+/-17, 19.2+/-17, 19.3+/-17, and 22.1+/-18 mm Hg, respectively, for men with 0, 1, 2, and > or =3 elevated proteins (P for trend=0.02, adjusted for confounders). The corresponding values for pulse pressure increase was 15.5+/-14, 15.8+/-14, 17.4+/-14, and 17.8+/-15 mm Hg, respectively (P=0.02). Incidence of hypertension (> or =160/95 mm Hg or treatment) and future blood pressure treatment showed similar associations with ISPs. Increase in diastolic blood pressure showed no association with ISPs. CONCLUSIONS: Plasma levels of ISPs are associated with a future increase in blood pressure. This could contribute to the relationship between ISP levels and cardiovascular disease.

Inflammation-sensitive plasma proteins and incidence of myocardial infarction in men with low cardiovascular risk.

OBJECTIVE: Myocardial infarction (MI) is sometimes experienced by individuals without any traditional risk factor. This prospective study explored whether incidence of MI in nonsmoking, nondiabetic men with normal blood pressure and serum lipids is related to inflammation-sensitive plasma proteins (ISPs). METHODS AND RESULTS: Five ISPs (alpha1-antitrypsin, haptoglobin, ceruloplasmin, fibrinogen, orosomucoid) were analyzed in 6075 men, 47+/-3.6 years old. A low-risk group (no traditional risk factor, n=1108) and a high-risk group (> or =2 major risk factors, n=1011) were defined. Incidence of MI (n=227) was monitored over 18.1+/-4.3 years of follow-up. In the low-risk group, the age-adjusted relative risks (RRs) were 1.00 (reference), 1.9 (95% CI, 0.8 to 4.2), 1.8 (95% CI, 0.6 to 5.4), and 2.9 (95% CI, 1.05 to 8.1), respectively, for men with 0, 1, 2 and > or =3 ISPs in the top quartile (trend: P=0.03). In this group, the increased risk was observed only after > or =10 years of follow-up. In the high-risk group, the age-adjusted RRs were 1.00, 1.4 (95% CI, 0.9 to 2.2), 1.9 (95% CI, 1.2 to 3.1), and 2.0 (95% CI, 1.3 to 3.1), respectively, for men with 0, 1, 2, and > or =3 ISPs in the top quartile (trend: P=0.0004). CONCLUSIONS: Incidence of MI in nonsmoking, nondiabetic men with normal blood pressure and lipids was related to ISPs. The causes for this relationship remain to be explored.

Incidence of myocardial infarction and death in relation to walking-induced calf pain and plasma levels of inflammation-sensitive proteins.

Walking-induced calf pain as well as levels of different inflammation-sensitive plasma proteins (ISPs) are related to cardiovascular disease (CVD). This prospective cohort study explored the relationship between ISPs and walking-related calf pain and the interrelationships between ISPs and calf pain in the prediction of death and incidence of coronary events (CE). In 5,725 apparently healthy men, 46 +/-3.0 years old, plasma concentrations of orosomucoid (alpha(1)-acid glycoprotein), alpha(1)-antitrypsin, haptoglobin, fibrinogen, and ceruloplasmin were measured. Walking-induced calf pain was assessed by questionnaire. Mortality and incidence of CE were monitored over a mean follow-up of 18 years in subjects defined by the presence of calf pain and ISP level (0 to 1 or 2 to 5 ISP(s) in the top quartile). The prevalence of calf pain (7.3%) was significantly related to age, lifestyle, and traditional risk factors of CVD and ISP levels. The risk factor-adjusted relative risks for CE, CVD- and all-cause mortality were 1.89 (CI: 1.27 to 2.82), 2.90 (CI: 1.82 to 4.62), and 2.67 (CI: 1.97 to 3.57), respectively, for men with calf pain and high ISP levels (reference: no calf pain and low ISP levels). The corresponding risk for those with calf pain and low ISP levels were 1.34 (CI: 0.91 to 1.97), 1.47 (CI: 0.90 to 2.41), and 1.31 (CI: 0.95 to 1.81), respectively. These results indicate, on the one hand, that walking-induced calf pain is associated with high ISP levels and, on the other, that the risk of CVD in men with calf pain is substantially higher in those with high ISP levels than in those with low levels.

Risk of myocardial infarction in relation to plasma levels of homocysteine and inflammation-sensitive proteins: a long-term nested case-control study.

Several studies have found that the homocysteine plasma level is associated with cardiovascular disease. The authors previously described a relationship between concentrations of fibrinogen and other inflammation-sensitive plasma proteins, namely, alpha1-antitrypsin, ceruloplasmin, haptoglobin, and orosomucoid (alpha1-acid glucoprotein) and the incidence of myocardial infarction (MI). Whether levels of these proteins are related to homocysteine has not been clarified. The aim of this study was to investigate whether a supposed relationship between homocysteine in plasma and the occurrence of MI is modified by these inflammation-sensitive proteins. A nested case-control study was designed, comprising 241 cases of MI, with a mean age of 48 years at baseline, and 241 controls matched for age, month of examination, and duration of follow-up. The mean homocysteine concentration did not differ between cases and controls and there was no association between the baseline homocysteine level and the time lapse before the occurrence of the MI. For the cases, there was no correlation between homocysteine and any of the measured proteins, but for the controls, homocysteine was weakly but significantly negatively correlated to haptoglobin and ceruloplasmin and slightly positively correlated to albumin. For the separated groups of cases and controls there was no association between the number of inflammation-sensitive proteins in the top quartiles and homocysteine concentration. In this population-based, prospective cohort study the occurrence of MI had no relationship to homocysteine baseline plasma level. Furthermore, there was no strong association between homocysteine and the concentrations of any of these inflammation-sensitive proteins.

Multidisciplinary intervention reducing readmissions in medical inpatients: a prospective, non-randomized study.

BACKGROUND: The purpose of this study was to examine whether a multidisciplinary intervention targeting drug-related problems, cognitive impairment, and discharge miscommunication could reduce readmissions in a general hospital population. METHODS: This prospective, non-randomized intervention study was carried out at the department of general internal medicine at a tertiary university hospital. Two hundred medical inpatients living in the community and aged over 60 years were included. Ninety-nine patients received interventions and 101 received standard care. Control/intervention allocation was determined by geographic selection. Interventions consisted of a comprehensive medication review, improved discharge planning, post-discharge telephone follow-up, and liaison with the patient's general practitioner. The main outcome measures recorded were readmissions and hospital nights 12 months after discharge. Separate analyses were made for 12-month survivors and from an intention-to-treat perspective. Comparative analyses were made between groups as well as within groups over time. RESULTS: After 12 months, survivors in the control group had 125 readmissions in total, compared with 58 in the intervention group (Mann-Whitney U test, P = 0.02). For hospital nights, the numbers were 1,228 and 492, respectively (P = 0.009). Yearly admissions had increased from the previous year in the control group from 77 to 125 (Wilcoxon signed-rank test, P = 0.002) and decreased from 75 to 58 in the intervention group (P = 0.25). From the intention-to-treat perspective, the same general pattern was observed but was not significant (1,827 versus 1,008 hospital nights, Mann-Whitney test, P = 0.054). CONCLUSION: A multidisciplinary approach, targeting several different areas, could substantially lower readmissions and hospital costs in a non-terminal general hospital population.

Consequences of orthostatic blood pressure variability in middle-aged men (The Malmö Preventive Project).

OBJECTIVE: To investigate the determinants and consequences of orthostatic hypotension in the middle-aged segment of the general population. METHODS: A population of 5722 men aged 52.6 +/- 3.6 years, previously included in the Malmö Preventive Project (n = 22 444 men), was re-screened after 5.6 +/- 1.0 years and thereafter followed up over a period of 19.6 +/- 5.3 years. RESULTS: At re-screening, 566 (9.9%) participants were found to have orthostatic hypotension according to international consensus criteria, of these 365 (64.5%) demonstrated systolic impairment only. In a multivariate adjusted logistic regression model, age, low BMI, hypertension, increased heart rate, antihypertensive treatment, diabetes and current smoking independently determined orthostatic hypotension, but systolic impairment also showed association with higher pulse pressure and reduced glomerular filtration rate. In a multivariate adjusted Cox proportional hazard model, men with orthostatic hypotension demonstrated a higher risk of incident coronary event, stroke and all-cause mortality than men without orthostatic hypotension. Systolic impairment was a better predictor of all studied endpoints than were the combined criteria of orthostatic hypotension. Moreover, participants with orthostatic hypotension at both baseline and re-screening showed the highest risk of any adverse event (hazard risk 1.76, 95% confidence interval 1.28-2.43, P = 0.001), exceeding the risk predicted by orthostatic hypotension at re-screening only (hazard risk 1.22, 95% confidence interval 1.07-1.38, P = 0.003). CONCLUSION: Orthostatic hypotension may be found in up to 10% of middle-aged men and correlates with well known cardiovascular risk factors such as hypertension, smoking, diabetes and kidney failure. Orthostatic impairment seems to constitute an independent cardiovascular risk factor and may be practically estimated by systolic reaction only. As orthostatic reaction may vary over time, repeated measurements or more accurate diagnostic methods are recommended to identify high-risk patients with persistent orthostatic hypotension.