Respiratory sinus arrhythmia (RSA) has been traditionally defined as the high-frequency component of heart-rate fluctuations (HRF) synchronous with the respiratory movements (RM), i.e., the frequency of RSA corresponds to the respiration rate. It can be shown that at defined relations of mean heart and respiration rate some essential effects must be taken into consideration in studies using RSA parameters. The relevance of these effects is shown and a new strategy of RSA quantification demanded, at least in neonates. The diagnostic importance, physiological background and future application of the low-frequency components of the neonatal HRF are reviewed on the basis of our own results. Nonrespiratory cardiovascular HRF cannot always be detected in the neonate by power spectral analysis. Movement-related HRF have a potential diagnostic importance per se, but may also artefactually disturb the quantification of other HRF components. Long-term trends can be used to describe sleep-state related trends and their disturbances.

Arrhythmia, Sinus↗

PubMedDate not supplied

Economic impact of introducing propentofylline for the treatment of dementia in Sweden.

The purpose of this study was to estimate the impact of the introduction of propentofylline, a glial-cell modulator with neuroprotective properties, on the costs of dementia care in Sweden. To estimate the clinical effects of propentofylline treatment on dementia, we conducted a meta-analysis of four double-masked, placebo-controlled, randomized clinical trials and a simulation in a cohort of 57,000 patients with Alzheimer's disease (AD) or vascular dementia (VaD). This cohort represented the fraction of the total AD and VaD population in Sweden with mild-to-moderate disease, the target population for propentofylline treatment. The rate of progression of dementia was expressed in terms of the annual rate of change in score on the Mini-Mental State Examination (MMSE). The costs of care were estimated on the basis of a prospective population-based study. A regression model was used to quantify the costs of dementia care as a function of MMSE score. The estimates obtained were used to calculate and compare the costs of dementia care until death, with or without propentofylline treatment. The sensitivity of the results to a variety of model assumptions was also assessed. The total gross cost for 9 years under the current treatment strategy was SEK (Swedish kronor) 168.06 billion. Including propentofylline in the treatment strategy yielded net savings of SEK 0.8 billion, since the savings in the cost of patient care outweighed the drug acquisition costs. Over 9 years, this saving represents 3.8% of the costs of dementia care in the target population (MMSE score, 15-25 points) and 0.5% of the costs in the total AD and VaD population. The annual savings per patient ranged from SEK 5517 to 6387 during the first 4 years of propentofylline treatment. If an extended neuroprotective effect of propentofylline is assumed, savings increase to SEK 1.6 billion, equivalent to 7.6% of total care costs in the target population and 1.0% in the total population. Savings increase to SEK 14.6 billion if the extended neuro-protective effect is assumed to be effective in an extended target population (MMSE score, 0-25 points) without increased survival. In the sensitivity analysis, most scenarios yielded benefits in favor of propentofylline treatment. The clinical effects of propentofylline translate into meaningful economic effects. The drug acquisition costs are more than offset by the savings achieved in the cost of care. The inclusion of a broader range of outcomes may increase these savings.

Aged↗

PubMedDate not supplied

A 12-month, randomized, placebo-controlled trial of propentofylline (HWA 285) in patients with dementia according to DSM III-R. The European Propentofylline Study Group.

Alzheimer's disease (AD) and vascular dementia (VaD) share several features such as overactivation of microglial cells, damage induced by free radicals, glutamate and calcium overload. Propentofylline (HWA 285) has shown beneficial effects on all of these common elements, thus favouring its use in both subtypes of dementia. In a multinational, randomized, 12-month, double-blind, parallel-group study 260 out-patients with mild to moderate AD or VaD received 300 mg propentofylline (n = 129) or placebo (n = 131) three times daily 1 h before meals. The efficacy was tested at four independent rater levels (physician, psychologist, relative and patient) with assessments covering three major domains of dementia (global function, cognitive function and activities of daily living). After 12 months, the total patient population showed statistically significant treatment differences in favour of propentofylline for the global measures of dementia (Gottfries-Bråne-Steen scale, GBS, p = 0.001; Clinical Global Impressions, CGI, item I: p = 0.004, item II: p = 0.072) as well as for the cognitive measures (Syndrome Short Test, SKT, p = 0.002) and Mini-Mental State Examination (p = 0.001). The activities of daily living also showed a significant treatment difference in favour of propentofylline (p = 0.002). No significant treatment differences were found for rating scales performed by the patients. At month 12, VaD patients showed treatment differences in favour of propentofylline for the GBS total score (p = 0.006), CGI item I (p = 0.004), GGI item II (p = 0.044) and SKT (p = 0.028). Treatment differences for AD patients were all in favour of propentofylline and reached statistical significance for the SKT (p = 0.018). Propentofylline showed a good safety profile with respect to adverse events, vital signs, ECG and laboratory changes.

Activities of Daily Living↗