Developing a new predictor of health expenditure: preliminary results from a primary healthcare setting.

OBJECTIVES: Risk adjustment is a widely used tool for health expenditure prediction and control. Early approaches for estimating health expenditure were based on patient demographic variables alone, whereas more recent models incorporate patient information, such as chronic medical conditions, clinical diagnoses, and self-reported health status. Many studies have investigated the health expenditure predictive capacity of single demographic, morbidity, or health-related quality of life measures, but the best models prove to be those that include them all. The aim of this study was to develop an index that combines measures of perceived health and disease severity and to compare its efficacy in predicting health expenditure with that of the measures taken individually. STUDY DESIGN: This is a linked cross-sectional study. METHODS: In 2009 and 2010, the health-related quality of life questionnaire SF-36 (8 scales, two indices: Physical Component Summary [PCS] and Mental Component Summary [MCS]) was distributed to 886 patients of general practitioners in the Province of Siena, Italy. Severity of diseases was calculated for each patient using the Charlson Index (CH-I) and Cumulative Illness Rating Scale Severity Index (CIRS-SI). Siena Local Health Unit 2012 data on health expenditure were obtained for each patient. Multivariate linear regression was applied to test the performance of severity (CH-I, CIRS-SI) and perceived health (PCS and MCS) measures in predicting health expenditure. The indexes that predicted health expenditure best were then combined in a new tool, and its expenditure predictive capacity was tested. RESULTS: The best health expenditure predictors proved to be PCS and SI (R2 = 0.15 and R2 = 0.17, respectively). When combined in a new index (PCS-SI), better predictive capacity of health expenditure was obtained than with the two single measures separately (R2 = 0.19). CONCLUSIONS: A multidimensional indicator proved to be a better predictor of healthcare expenditure than single health measures.

Dissecting the prognostic signature of patients with astrocytoma isocitrate dehydrogenase-mutant grade 4: a large multicenter, retrospective study.

BACKGROUND: The World Health Organization (WHO) 2021 classification of central nervous system (CNS) tumors classified astrocytoma isocitrate dehydrogenase-mutant (A IDHm) with either microvascular proliferation and/or necrosis or homozygous deletion of CDKN2A/B as CNS grade 4 (CNS WHO G4), introducing a distinct entity and posing new challenges to physicians for appropriate management and prognostication. PATIENTS AND METHODS: We retrospectively collected information about patients diagnosed with A IDHm CNS WHO G4 at three reference neuro-oncological Italian centers and correlated them with survival. RESULTS: A total of 133 patients were included. Patients were young (median age 41 years) and most received post-operative treatment including chemo-radiation (n = 101) and/or temozolomide maintenance (n = 112). With a median follow-up of 51 months, the median overall survival (mOS) was 31.2 months, with a 5-year survival probability of 26%. In the univariate analysis, complete resection (mOS: 40.2 versus 26.3 months, P = 0.03), methyl-guaninemethyltransferase (MGMT) promoter methylation (mOS: 40.7 versus 18 months, P = 0.0136), and absence of telomerase reverse transcriptase (TERT) promoter mutation (mOS: 40.7 versus 18 months, P = 0.0003) correlated with better prognosis. In the multivariate models, lack of TERT promoter mutation [hazard ratio (HR) 0.23, 95% confidence interval (CI) 0.07-0.82, P = 0.024] and MGMT methylation (HR 0.40, 95% CI 0.20-0.81, P = 0.01) remained associated with improved survival. CONCLUSIONS: This is the largest experience in Western countries exploring the prognostic signature of patients with A IDHm CNS G4. Our results show that MGMT promoter methylation and TERT promoter mutation may impact clinical outcomes. This may support physicians in prognostication, clinical management, and design of future studies of this distinct diagnostic entity.

Functional rare males in diploid parthenogenetic Artemia.

Functional males that are produced occasionally in some asexual taxa - called 'rare males' - raise considerable evolutionary interest, as they might be involved in the origin of new parthenogenetic lineages. Diploid parthenogenetic Artemia produce rare males, which may retain the ability to mate with females of related sexual lineages. Here, we (i) describe the frequency of male progeny in populations of diploid parthenogenetic Artemia, (ii) characterize rare males morphologically, (iii) assess their reproductive role, using cross-mating experiments with sexual females of related species from Central Asia and characterize the F1 hybrid offspring viability and (iv) confirm genetically both the identity and functionality of rare males using DNA barcoding and microsatellite loci. Our result suggests that these males may have an evolutionary role through genetic exchange with related sexual species and that diploid parthenogenetic Artemia is a good model system to investigate the evolutionary transitions between sexual species and parthenogenetic strains.

Bactericidal activity of erythromycin in the respiratory system.

In vivo and in vitro studies were carried out to assess tha levels in bronchial mucus of ampicillin, amoxycillin, bacampicillin, cefotaxime and erythromycin, and to compare their minimum bactericidal concentrations and killing rate against hospital strains of Staphylococcus aureus, Streptococcus pyogenes and Haemophilus influenzae. Both the percentage ratios of serum/mucus concentration peaks and of serum/mucus area under the concentration time curve values were higher for erythromycin than for the other antibiotics. Determination of the minimum bactericidal concentrations showed that the bacterial strains were sensitive to small quantities of erythromycin, and the time necessary to sterilize inocula varied from 4 to 16 hours.

[Origin of secretions after denervation of the small intestine in the dog]. / L'origine de la sécrétion après la dénervation de l'intestin grêle de chien.

The origin of the severe diarrhea appearing after intestinal denervation or transplantation was studied on the 3rd and 14th postoperative days in 5 groups of dogs undergoing total or partial denervation. The net movements of water and electrolytes were investigated by employing an experimental model of intestinal perfusion in isolated loops in vivo. The active uptake of phenylalanine and beta-methylglucoside and Na(+)-K(+)-ATPase activity were used for in-vitro evaluation. Bacteriologic and histological specimens were also taken. Following total denervation with anastomosis, a considerable loss of water and electrolytes as well as numerous E. coli were found in the entire small intestine. This net secretion is due to the stagnation of bacteria in the presence of complete denervation and the absence of food since the animals in this group could not eat properly following general anesthesia and surgery. Consequently, peristalsis was not stimulated and bacterial overgrowth occurred. In the group denervation with pseudo-anastomosis, perfusion studies showed a decrease of absorption in the jejunum and minimal but significant secretion in the ileum. A high number of E. coli was also present. Since the mucosa remained intact, nutrition per os was resumed in the immediate postoperative period and excessive water and electrolyte loss was avoided. The high number of bacteria was due to a decrease in intestinal motility since complete denervation was performed. In the denervation group, water and electrolyte movements were identical to those observed in the preceding group but the entire intestine remained sterile.(ABSTRACT TRUNCATED AT 250 WORDS)

Stability of frozen rat plasma containing different antibiotics.

The antibiotic activity was determined at different intervals of time on plasma samples, taken from rats treated with a certain number of commonly used antibiotics, and kept at -20 C up to 8 weeks. The results of the microbiological assays demonstrate that the stability of the antibiotics in the frozen plasma decreases in the following order: oxytetracycline > cephalexin, streptomycin, erythromycin > demeclocycline > ampicillin, amoxycillin > penicillin G, cephaloridine, rolitetracycline, and tetracycline.

Evaluation of pharmacokinetics, bioavailability and dose linearity of diltiazem in healthy volunteers.

The objective of this randomized five-way cross-over study with healthy male volunteers was to determine, one the one hand, the bioavailability and main pharmacokinetic parameters of 4 sustained release diltiazem (Surecaps, CAS 42399-41-7) test preparations with ascending doses (180, 240, 300, 360 mg), administered as single application, versus an immediate release 60 mg diltiazem reference preparation, which was given thrice a day at 8-h intervals. On the other hand, the study also allowed the evaluation of a possible dose linearity of the test substance diltiazem. Plasma concentrations of diltiazem and its major metabolite desacetyl-diltiazem were measured by high pressure liquid chromatography (HPLC) up to 48 h after single dosing of the sustained release preparations as well as after repeated doses of the immediate release formulation. The undesired side effects/concomitant symptoms observed are known to occur after diltiazem administration. For the area under the curve, e.g. calculated from time 0 to the last quantifiable sample (AUC0-Tlast), the study revealed for the parent compound diltiazem mean values of 926.2, 1602.4, 1873.2 and 2415.7 h.ng/ml after administration of the 4 sustained release test preparations, respectively; for the immediate release reference preparation the value was 1007.2 h.ng/ml. Concerning the main metabolite desacetyl-diltiazem the corresponding values for the 4 sustained release formulations were 138.6, 236.9, 280.2 and 345.6 h.ng/ml, respectively. The corresponding value for the immediately release formulation was 127.5 h.ng/ml. Concerning a possible dose linearity of diltiazem, statistical analysis revealed a convincing linear relationship between at least 3 of the 4 sustained release preparations, therefore linearity may be assumed between 240 and 360 mg.(ABSTRACT TRUNCATED AT 250 WORDS)