Analysis of 23 364 patient-generated, physician-reviewed malpractice claims from a non-tort, blame-free, national patient insurance system: lessons learned from Sweden.

CONTEXT: In Sweden, patient malpractice claims are handled administratively and compensated if an independent physician review confirms patient injury resulting from medical error. Full access to all malpractice claims and hospital discharge data for the country provided a unique opportunity to assess the validity of patient claims as indicators of medical error and patient injury. OBJECTIVE: To determine: (1) the percentage of patient malpractice claims validated by independent physician review, (2) actual malpractice claims rates (claims frequency / clinical volume) and (3) differences between Swedish and other national malpractice claims rates. DESIGN, SETTING AND MATERIAL: Swedish national malpractice claims and hospital discharge data were combined, and malpractice claims rates were determined by county, hospital, hospital department, surgical procedure, patient age and sex and compared with published studies on medical error and malpractice. RESULTS: From 1997 to 2004, there were 23 364 inpatient malpractice claims filed by Swedish patients treated at hospitals reporting 11 514 798 discharges. The overall claims rate, 0.20%, was stable over the period of study and was similar to that found in other tort and administrative compensation systems. Over this 8-year period, 49.5% (range 47.0-52.6%) of filed claims were judged valid and eligible for compensation. Claims rates varied significantly across hospitals; surgical specialties accounted for 46% of discharges, but 88% of claims. There were also large differences in claims rates for procedures. CONCLUSIONS: Patient-generated malpractice claims, as collected in the Swedish malpractice insurance system and adjusted for clinical volumes, have a high validity, as assessed by standardised physician review, and provide unique new information on malpractice risks, preventable medical errors and patient injuries. Systematic collection and analysis of patient-generated quality of care complaints should be encouraged, regardless of the malpractice compensation system in use.

Analysis of 23 364 patient-generated, physician-reviewed malpractice claims from a non-tort, blame-free, national patient insurance system: lessons learned from Sweden.

CONTEXT: In Sweden, patient malpractice claims are handled administratively and compensated if an independent physician review confirms patient injury resulting from medical error. Full access to all malpractice claims and hospital discharge data for the country provided a unique opportunity to assess the validity of patient claims as indicators of medical error and patient injury. OBJECTIVE: To determine: (1) the percentage of patient malpractice claims validated by independent physician review, (2) actual malpractice claims rates (claims frequency / clinical volume) and (3) differences between Swedish and other national malpractice claims rates. Design, setting and material: Swedish national malpractice claims and hospital discharge data were combined, and malpractice claims rates were determined by county, hospital, hospital department, surgical procedure, patient age and sex and compared with published studies on medical error and malpractice. RESULTS: From 1997 to 2004, there were 23 364 inpatient malpractice claims filed by Swedish patients treated at hospitals reporting 11 514 798 discharges. The overall claims rate, 0.20%, was stable over the period of study and was similar to that found in other tort and administrative compensation systems. Over this 8-year period, 49.5% (range 47.0-52.6%) of filed claims were judged valid and eligible for compensation. Claims rates varied significantly across hospitals; surgical specialties accounted for 46% of discharges, but 88% of claims. There were also large differences in claims rates for procedures. CONCLUSIONS: Patient-generated malpractice claims, as collected in the Swedish malpractice insurance system and adjusted for clinical volumes, have a high validity, as assessed by standardised physician review, and provide unique new information on malpractice risks, preventable medical errors and patient injuries. Systematic collection and analysis of patient-generated quality of care complaints should be encouraged, regardless of the malpractice compensation system in use.

Charting the possible impact of national guidelines on the management of rheumatoid arthritis.

OBJECTIVE: To identify temporal trends in the prescription of disease-modifying antirheumatic drugs (DMARDs) in patients with early rheumatoid arthritis (RA). METHODS: Using data from the Swedish RA register (n = 2,584), we analysed the proportion of RA patients prescribed DMARDs at their first consultation between 1997 and 2001. Statistical process control (SPC) was used to chart and analyse major changes in prescription behaviour, while more traditional time series analysis methods (i.e. regression) were used to corroborate the nature of any trend. RESULTS: The SPC method identified an upward shift in the prescription of DMARDs in July 1998 and a change in the process by October 1998. Time series analysis confirmed an increasing trend in DMARD prescription over the period as a whole and the trend was statistically significant (p

Inotropic and chronotropic effects of isoprenaline in rats exposed to 30 bar.

Inotropic and chronotropic responses to the beta-agonist, isoprenaline (ISO) were studied with a transducer located in the left ventricle and a catheter placed in the left femoral artery in anesthetized rats at 1 and 30 bar. The hemodynamic control values were equal in both series. During ISO infusion the chronotropy increased equally (34%) at 1 and 30 bar. The inotropy increased by 38% during ISO infusion at 1 bar (Series 1). Increased inotropy (44%), and unchanged chronotropy were found during compression to 30 bar (Series 2). The ISO evoked inotropic responses in absolute values were greater at 30 bar than at 1 bar. Nevertheless, an equal relative (%) increase in inotropy was found during ISO infusion at 30 bar compared to 1 bar. The cardiac oxygen consumption was estimated to be 65% higher at 30 bar during ISO infusion compared to that at 1 bar.

Cardiovascular changes in anesthetized rats during exposure to 30 bar.

The effect of exposure to 30 bar (PHe = 29.0 bar, PN2 = 0.8 bar, PO2 = 0.2 bar) on left ventricular pressure, cardiac contractility, heart rate (HR), and arterial pressure was studied in anesthetized rats. During compression there was a progressive increase in maximal left ventricular pressure (LVPmax), maximal velocity of LVP rise (+ dP/dtmax) and fall (- dP/dtmax), systolic pressure (APsys), and pulse pressure (delta AP). The greatest increase in contractility per bar was found between 1 and 5 bar. Immediately after 30 bar was reached, LVPmax (19%), + dP/dtmax (60%), and - dP/dtmax (22%). APsys (19%), and delta AP (43%) were significantly increased from predive values, with an additional increase detected for all these variables after 60 min at 30 bar. An increase in estimated oxygen consumption (work load) of the heart was also found during compression to and at 30 bar. No changes in HR, mean arterial pressure, and end-diastolic pressure were observed during the high-pressure exposure, indicating that the inotropic changes were not due to changes in peripheral hemodynamics.

Increased cardiac contractility in rats exposed to 5 bar.

The left ventricular pressure, arterial blood pressure and heart rate were studied in three series of pentobarbital-anaesthetized rats exposed to 5-bar normoxic (PO2 = 0.2 bar) environments: nitrogen-oxygen (15 and 60 min) and helium-oxygen (15 min). The maximal left ventricular pressure (LVP max) and the maximal velocities of LVP rise (+ dP/dt max) and fall (- dP/dt) were significantly (P less than 0.01) increased immediately after reaching normoxic 5 bar (He, 13-28%; N2, 13-23%) and during the exposure at 5 bar (He, 22-44%; N2, 13-18%). The pulse pressure increased significantly (He, 50-62%; N2, 30-34%; P less than 0.01) during the hyperbaric exposure. No changes in heart rate or end-diastolic and mean arterial pressure were detected. The present findings indicate an enhanced cardiac contractility (+ dP/dt max) at 5 bar, with the greatest increase found when He was used as inert gas. The increased contractility was of significant duration (at least 60 min), and was not completely reversed until 5-10 min after decompression.

Positive inotropic effect on the rat atrial myocardium compressed to 5, 10 and 30 bar.

The contractile activity of spontaneously beating auricular preparations from the rat was studied during and after pressure exposure to 5, 10 and 30 bar in three series of experiments (compression and decompression rate: 1 bar min-1). The preparations were mounted in an organ bath within a pressure chamber and perfused with oxygenated preheated Krebs-Henseleit solution (37 degrees C, pH = 7.45) containing alpha-, beta- and muscarinic-receptor blockers and blockers of the neuronal and extraneuronal uptake mechanisms. No change in chronotropy of the cardiac preparations were observed during or after exposures to the pressures tested. Significant increase in cardiac contractility (20-40%, P less than 0.01) described by the peak tension (Tmax), the maximal velocity of tension rise (T'max) and fall (T'min) were apparent at 5 and 10 bar. Further significant elevations (60-80%, P less than 0.05) in Tmax, T'max and T'min were detected during exposure to 30 bar. The cardiac contractility increased rapidly with pressure, was approximately unchanged during stable elevated pressures at 5, 10 and 30 bar, but was maintained above control values 15 min after completed decompression. Since no change in chronotropy and loading of the preparations occurred, it is concluded that the increased contractility is due to a positive inotropy generated by the hydrostatic pressure. Furthermore, it is indicated that this positive inotropy is not related to adrenoceptor activation since the effect was achieved in the presence of alpha-, and beta-adrenoceptor blockade.

Functional alpha-adrenoceptors in human atrial preparations in the presence of beta-receptor blockade.

Inotropic effects via cardiac alpha-adrenoceptors were studied in electrically driven auricular strips (1 Hz, 37 degrees C) from patients treated with beta-blockers for months prior to open heart surgery. Marked alpha-mediated positive inotropic effects were demonstrated with adrenaline (A), noradrenaline (NA) and phenylephrine (PHE) in the presence of beta-blocker and with blockers of the muscarinic receptor and of the neuronal and extraneuronal uptake mechanisms for the catecholamines. In the presence of approximately 10(-6) M propranolol the maximal effects as well as the potencies (pD2-values) for A and NA were not significantly different while higher than for PHE. The alpha 1-blocker, prazosin (10(-6) M), markedly reduced the pD2-values but not the intrinsic activities (alpha-values) for A, NA and PHE in the beta-blocked preparations. Methoxamine, however, induced negative inotropic responses at normal and low frequencies (1, 0.5 and 0.1 Hz) of stimulation, suggestive of non-specific, cardiodepressant effects. Other agonists with alpha-effects in other types of tissue (oxymethazoline, xylomethazoline and clonidine) were without effects on the force and velocity of contraction in the auricular strips under the present experimental conditions. The results show alpha 1-type of adrenoceptor-induced inotropic effects for A, NA and PHE during beta-blockade in human auricular strips, indicating that cardiac alpha 1-receptors may have clinical importance by increasing the inotropy of the human myocardium treated with beta-blocking agents.

Activation of cardiac beta 2 adrenoceptors in the human heart.

Comparative pharmacologic studies have indicated that the cardiac beta 2 adrenoceptors of vertebrate species are "adrenaline" receptors; i.e., the distribution of beta 2 receptors in the heart seems to be related to the amounts of adrenaline in the sympathetic nerves and in the circulation, and the beta 2 receptors seem to be stimulated mainly by adrenaline. In the human right atrium the order of potency for the agonists and the blocking agents indicate a relatively high proportion of active beta 2 receptors. These findings are in agreement with radioligand binding studies demonstrating up to 50% beta 2 receptors in myocardial membrane preparations. The pharmacologic studies thus add support to the assumption that these beta 2 receptors are functionally active and not merely experimental oddities. It is hypothesized that in normal situations the beta 2-receptor effects are additive to the beta 1 effects. However, during acute stress situations the large amounts of released adrenaline are assumed to increase markedly both inotropy and chronotropy in the heart via beta 2 receptors. It is postulated that only unselective beta blockers can abolish all beta-receptor effects in the heart during stress reactions with profound catecholamine stimulation.

Functional beta 1- and beta 2-adrenoceptors in the human myocardium.

Functional beta-adrenoceptor populations in the human heart were studied in vitro in electrically-paced strips of the right auricular and ventricular myocardium. The relative potency of selected agonists in producing inotropic responses (Tmax, T'max) in the presence of blockers for neuronal and extraneuronal uptakes was found to be as follows: isoprenaline greater than noradrenaline = adrenaline = salbutamol greater than dobutamine. Prenalterol had a negative inotropic effect in these preparations. The selective beta 1-(practolol) and beta 2-(H 35/25) blockers reduced inotropic responses to adrenaline (Tmax, T'max) and noradrenaline (T'max) in the auricular strips. These results indicate the participation of beta 2-adrenoceptors in inotropic responses in the human auricular and ventricular myocardium. For comparison, inotropic responses of electrically-paced rat myocardium to beta-adrenergic agonists in the presence of blockers for neuronal and extraneuronal uptakes were likewise studied. The relative potencies for Tmax were: noradrenaline = adrenaline greater than prenalterol greater than dobutamine = salbutamol. Given the high relative potency of salbutamol in the human myocardial strips (analogous to that previous shown in the beta 2-dominated atria of the frog and trout) and the low relative potency of salbutamol in the rat tissue, these findings indicate a greater population of functionally active beta 2-adrenoceptors in the human than in the rat myocardium.

Functional alpha 1-adrenoceptors in the rat heart during beta-receptor blockade.

In absence of beta-receptor blocking agents, alpha-adrenergic inotropic effects could be demonstrated in the rat myocardium for the synthetic alpha-agonists phenylephrine and methoxamine, but not for the naturally occurring catecholamines, adrenaline and noradrenaline. Other synthetic alpha-agonists were without effects. In the presence of the beta-receptor blocking agent, propranolol or timolol, marked alpha-effects were demonstrated for adrenaline and noradrenaline in both the right and left atria and the right ventricle. The results indicate that alpha-receptors may be functionally important in the beta-blocked myocardium.

Absence of calcium paradox in the cardiac ventricle of the Atlantic hagfish (Myxine glutinosa).

Spontaneously beating strips of the cardiac ventricle of the cyclostome Myxine glutinosa were characterized with respect to dependence on extracellular calcium for the cardiac contractility at 8 degrees C. The force developing (Tmax) was reduced by 20-50% when exposed to calcium-free medium (+/- 10(-3)M EDTA) for 15-60 min. Return to normal Myxine Ringer (4.5 mM Ca2+) resulted in 120-130% recovery to Tmax without change in resting tension. These experiments show that the heart of this primitive vertebrate, analogous to that of other poikilotherms, does not display the "Ca-paradox" phenomenon. Being relatively insensitive to changes in extracellular Ca2+ the Myxine myocardium differs from that in most poikilotherms in other respects, e.g. in the mechanisms regulating beat to beat changes in intracellular Ca2+.

Comparative aspects of adrenergic receptors in the hearts of lower vertebrates.

The cardiac adrenoceptors of lower vertebrates were characterized in atrial preparations. Adrenaline (A) potentiated the force and frequency of contraction in the spontaneously beating atria of the frog, trout and flounder and in electrically paced atrial strips from the shark. The inotropic responses of A were most pronounced at the lower temperatures for the frog and trout, while A enhanced frequency to a greater extent at higher temperatures in the frog atria. Atrial alpha-receptors activated by A at 8 degrees C could not be detected in any of the species under study. The apparent affinities for the inotropic and chronotropic responses of agonist in the frog (15 degrees C) and trout (8 degrees C) atria were: Iso greater than Sal greater than or equal to A greater than NA. A cocaine-sensitive uptake for A and NA was apparent in these atria, consistent with sympathetic innervation. The affinities for the catecholamines in the flounder and shark atria were not increased by cocaine, in accordance with absence of sympathetic innervation of the atria in these species. These atria were also insensitive to corticosterone. The affinities for A and NA were on the other hand higher in the sympathetically non-innervated atria of the flounder than in the innervated atria of the frog and trout. The apparent orders of relative affinities for agonists were Iso greater than A = NA greater than Sal for the flounder, and of the relative potencies Iso = A greater than NA greater than Sal for the shark atrium. The results are consistent with the hypothesis that catecholamines enhance cardiac performance in lower vertebrates chiefly via "adrenaline" receptors which resemble the beta 2-type of mammalian adrenoceptors in many respects. Unlike that in mammals, cardiac adrenaline receptors in the frog and trout are activated by the sympathetic neurotransmitter ("innervated" receptors). On the other hand, the adrenaline receptors of the flounder and shark are responding to the circulating catecholamines ("humoral" receptors). However, the flounder atrium, with equal affinities for A and NA, appears as an exception to the rule by having a mixed population of humoral beta 1- and beta 2-adrenoceptors, indicating a role for circulating NA in cardiac regulation in this species.