Equity in the finance of health care: some further international comparisons.

This paper presents further international comparisons of progressivity of health care financing systems. The paper builds on the work of Wagstaff et al. [Wagstaff, A., van Doorslaer E., et al., 1992. Equity in the finance of health care: some international comparisons, Journal of Health Economics 11, pp. 361-387] but extends it in a number of directions: we modify the methodology used there and achieve a higher degree of cross-country comparability in variable definitions; we update and extend the cross-section of countries; and we present evidence on trends in financing mixes and progressivity.     

Noise in the signal-averaged electrocardiogram and accuracy for identification of patients with sustained monomorphic ventricular tachycardia after myocardial infarction

Late potentials are detected at various noise levels in clinicalstudies. The aim of this study was, in a case-control design,to assess the effect of residual noise level on the identificationof patients with sustained monomorphic ventncular tachycardiaafter myocardial infarction. Electrocardiograms from 16 patientswith prior myocardial infarction and documented sustained monomorphicventricular tachycardia and 41 patients with prior myocardialinfarction and without ventncular tachycardia, were analysedby two signal averaging procedures to noise level 0·2and 0·4 µV Standard time domain parameters weremeasured. Two definitions of late potential were analysed: (1)if any two of the following criteria were present (signal-averagedQRS duration >120 ms, late potential duration >40 ms,and root-mean-square voltage of the terminal 40 ms of the filteredQRS <25µV); or (2) if the signal-averaged QRS duration120 ms. Overall the signal-averaged electrocardiogram performedbetter at noise level 0·4µV compared to noise level0·2µV with respect to identification of patientswith or without ventricular tachycardia after myocordial infarction.Reducing noise level from 0·4 to 0·2 µVincreased the sensitivity, but the consequence was a substantialdecrease in specificity. Our data indicate that when a highsensitivity is the goal, the definition based only on signal-averagedQRS duration 120 ms should be applied; sensitivity was 88% andspecificity 59% at noise level 0·4 µV. If a highspecificity is the goal, the definition should be based on thedefinition with two abnormal parameters; sensitivity was 69%and specificity 68% at noise level 0·4µV.     

Steady-state kinetics of imipramine in patients

Steady-state plasma level kinetics were studied in 76 patients given imipramine (IP) 150 to 225 mg/day for 2–5 weeks. IP was given in three divided doses at 8.00 a.m., 1.00 p.m. and 5.00 p.m. Plasma concentrations of IP and its active metabolite desipramine (DMI) were determined by quantitative in situ thin-layer chromatography. The plasma levels of IP and DMI showed pronounced flucutations throughout the day with a ratio of about 2 between highest and lowest level. Patients with steady-state levels of IP and/or DMI below 50 g/l reached this within 1 week of treatment. Patients with higher steady-state levels reached steady-state concentrations within 2–3 weeks. There were some intraindividual fluctuations in plasma levels from week to week after steady state had been reached (coefficient of variation: 10–20%). Interindividually, the steady-state levels corrected to a dose of 3.5 mg/kg per day varied considerably: IP: 6–356 g/l, DMI: 24–659 g/l and IP+DMI: 58–809 g/l. The steady-state plasma levels showed a skew distribution that became normal by logarithmic transformation. The IP/DMI ratio ranged from 0.07 to 5.5 with a median value of 0.47. Compared to data from amitriptyline treated patients the IP/DMI ratios had significantly lower median value and larger variation than the corresponding plasma level ratios of amitriptyline/nortriptyline. Several statistically significant differences in steady-state levels between age groups were found. For IP: Women aged 30–39 had lower levels than women aged 20–29, 40–49, and 50–59, and men aged 50–59 and 60–65; men aged 30–39 had lower levels than men aged 60–65. For DMI: Women aged 30–39 had lower levels than women aged 50–59.     

Muscular Performance and Fatigue in Primary Hyperparathyroidism

The purpose of this study was to evaluate changes in muscular strength and endurance, work capacity, and subjective fatigue following surgical treatment of primary hyperparathyroidism (pHPT), and to assess whether changes in muscular function were due to changes in activation of the muscles. A prospective consecutive study design was used, and patients surgically treated for nontoxic goiter served as controls. Nineteen female patients with mild to moderate pHPT and 20 controls were included. Maximal isometric handgrip and quadriceps strength, quadriceps endurance (intermittent stimulation), and quadriceps activation (superimposed twitch technique) were used for evaluation of muscular function. All patients were operated on successfully. Knee extension strength increased by 17 ± 17% (mean ± SD; p= 0.0004) in the patients, whereas no change was observed in the controls. The relative strength increase correlated positively to patient age at operation (r= 0.52, p= 0.02). Handgrip strength, quadriceps endurance, and general work capacity did not change in any group after operation. Subjective fatigue was preoperatively higher in patients than in controls (p= 0.01), and decreased postoperatively to the level of controls. In conclusion, women with pHPT increase knee extension force after parathyroidectomy as a result of increased force generation capacity of the muscle. If change in physical performance is a determinant for change in subjective fatigue in pHPT after operation, then change in strength of the quadriceps muscle seems to be of primary importance, whereas handgrip strength, muscular endurance, and work capacity do not seem to be important. The cause of the increasing strength benefit with increasing age at operation as found in this study needs further investigation.     

Inhibition of hyperacute transplant rejection by soluble proteins with the functional domains of CD46 and FcgammaRII

BACKGROUND: Recombinant soluble forms of complement regulatory molecules, including the human complement regulatory protein CD46 (rsCD46), have been shown to inhibit hyperacute transplant rejection (HAR) and protect against complement-mediated inflammatory tissue damage. Similarly, recombinant soluble forms of the immunoglobulin receptor FcgammaRII (rsFcgammaRII) can attenuate antibody-mediated inflammatory responses. We have produced and tested the function of novel recombinant chimeric proteins that incorporate the functional domains of both CD46 (membrane cofactor protein, MCP) and the low affinity human IgG receptor FcgammaRII (CD32). METHODS: Two recombinant soluble chimeric proteins (CD46:FcR and FcR:CD46) were designed and produced using a human cell expression system. Their ability to protect cells against complement-mediated lysis (through the CD46 domain) and bind human IgG (through the Fc receptor domain) was assessed in vitro. They were also tested in vivo in the rat reverse passive Arthus reaction and a murine model of hyperacute cardiac transplant rejection. RESULTS: In vitro, the functional domains of the chimeric proteins each retained their activity. In vivo, the serum half-life of the recombinant chimeric proteins in mice was more than either rsCD46 or rsFcgammaRII. In the rat reverse passive Arthus reaction, intradermal injection of each recombinant protein substantially reduced inflammatory skin edema (>50%) and polymorphonuclear neutrophil infiltration (>90%). In the hyperacute rejection model, i.v. treatment with FcR:CD46 prevented complement-mediated rejection, macroscopic bruising, edema, and thrombosis more effectively than rsCD46. CONCLUSIONS: CD46/FcgammaRII bifunctional proteins have an improved ability to control complement-mediated hyperacute graft rejection and have therapeutic potential in other conditions involving antibody-mediated inflammation.     

Coamplification of DDX1 correlates with an improved survival probability in children with MYCN-amplified human neuroblastoma.

PURPOSE: Amplification of the MYCN oncogene at chromosome 2p24-25 identifies an aggressive subtype of human neuroblastoma with a poor clinical outcome. Differences in amplicon structure and coamplification of genes telomeric and centromeric to the MYCN oncogene have previously been described. A relevant role of gene coamplification for neuroblastoma pathogenesis remains elusive. PATIENTS AND METHODS: We analyzed 98 primary neuroblastoma tumors with MYCN amplification for coamplification of seven additional genes at chromosome 2p24-25 (DDX1, NAG, NSE1, LPIN1, EST-AA581763, SMC6, and SDC1). Two semiquantitative multiplex polymerase chain reactions were used to obtain the amplification status of the target genes in relation to a reference gene on chromosome 2q (Inhibin-beta-b). Furthermore, mRNA expression pattern of coamplified genes in a subset of tumors was analyzed. RESULTS: Our results show that the frequency of gene coamplification on 2p24-25 in neuroblastoma is correlated directly to the physical distance to MYCN. Coamplification is correlated to an upregulated gene expression for DDX1 and NAG. Coamplification of the DDX1 gene within 400kb telomeric to MYCN identifies a subgroup of advanced stage neuroblastoma tumors with a more favorable outcome (P =.027, log-rank test). A high expression level of DDX1 is associated with a trend towards a better survival probability (P =.058, log-rank test). CONCLUSION: Our results indicate that DDX1 coamplification correlates with a better prognosis and improved patient survival in MYCN-amplified neurobastoma.     

Safety and efficacy of drospirenone used in a continuous combination with 17beta-estradiol for prevention of postmenopausal osteoporosis.

OBJECTIVE: To evaluate the combination of 17beta-estradiol and continuous drospirenone for the prevention of postmenopausal osteoporosis. METHODS: A total of 180 (75%) healthy postmenopausal women aged 45-65 years completed a 2-year prospective study. Bone mineral density (BMD) at lumbar spine, hip and total body as well as endometrial thickness, markers of bone turnover and serum lipids were measured regularly. Treatment groups were given placebo or 1 mg 17beta-estradiol combined with 1, 2 or 3 mg drospirenone daily. RESULTS: BMD at the lumbar spine, hip and total body increased by 7, 4 and 3%, respectively, in all hormone groups versus placebo (all p < 0.001). Bone markers all decreased accordingly (serum osteocalcin 52%, serum bone specific alkaline phosphatase 36%, serum CrossLaps 67% and urinary CrossLaps 75% from baseline; all p < 0.001). Total cholesterol and low-density lipoprotein cholesterol decreased by 8% and 13%, respectively (both p < 0.001). High-density lipoprotein cholesterol and triglycerides remained unchanged. No significant dose-related effects were found. Endometrial thickness increased by 1.2 mm only in the 1-mg drospirenone group (p < 0.01 versus placebo). CONCLUSION: The combination of 17beta-estradiol and drospirenone has a positive effect on BMD and a potentially beneficial effect on lipids. Although endometrial thickness increased slightly, the safety of the endometrium was assured, as no cases of hyperplasia or cancer occurred.