Quantitative relationship of renal blood flow with size and density of glomeruli in rat postnatal ontogenesis

The aim of the study was to find the quantitative relationship of postnatal changes in the glomeruli anatomic structure with the blood flow in kidneys. Kidney development was studied in 4-, 12-, 30-, and 65-day-old Wistar rats. Diameters of glomerulus (Dgl, microm), afferent and efferent arterioles (Daf and Def), and the glomeruli density (Ngl, mm(-3)) were measured posthumously. Volumes of one ((see text of symbol))V gl, microm3) and all glomeruli (see text for symbol)(sigma(see text for symbol)Vgl, mm3/cm3) and the glomeruli arterioles lumen (Saf and Sef, microm2) were calculated. The renal specific blood flow (SBF per unit of kidney weight, KW) was measured by the laser-Doppler flowmeter (in perfusion units, p.u.) under sodium barbamyl narcosis. We have found that, during postnatal growth, glomeruli morphological parameters vary according to the equations: Dgl = 7.1 (see text for symbol) KW0.41, (see text for symbol)V gl = 187 (see text for symbol) KW1.23, Ngl = 5309 (see text for symbol) KW-0.63 (KW, mg and for one kidney), Saf = 1.1 (see text for symbol)V gl 0.35, and Sef = 6.3 (see text for symbol) V gl 0.14. The renal SBF in 4-, 12-, and 65-day-old rats increases according to SBF = 6.7 (see text for symbol) (sigma( see text for symbol)V gl)0.98. The renal SBF calculated per unit of glomeruli volume varies a little with age.     

Multicomponent vaccine VP-4 in the therapy of allergic diseases

In the present study the results of the polycomponent vaccine B[symbol: see text]-4 use for the therapy of patients with bronchial asthma (BA) and latex allergy were generalized. The vaccine was introduced by the nasal-subcutaneous or nasal-oral administration simultaneously with the basic therapy. Te studies were conducted first on limited groups of patients, then in the course of the State Trial with the use of placebo control. Excellent and good effect lasting for 1 year and over was registered in 36 patients (66.7%) out of 54 BA patients receiving the vaccine by the intranasal-subcutaneous method. Immunotherapy produced no positive effect in 13 patients (24.1%). Out of 35 examined patients receiving the vaccine by the intranasal oral method, excellent and good effect was registered in 26 patients (74.2%). No effect was registered in 4 patients (11.4%). In the group of 28 patients receiving placebo simultaneously with the basic therapy positive dynamics in the course of the disease was observed only in 3 patients. Treatment with polycomponent vaccine B[symbol: see text]-4 led to a prolonged (to a year and more) decrease in the frequency and severity of exacerbations, contributed to the prolongation of remissions and to a decrease in the amount of administered medicinal preparations, especially systemic corticosteroids. Immunotherapy ensured the correction of the content of lymphocyte subpopulations with markers CD3, CD4, CD72 and a rise in the titers of antibodies to antigens contained in the preparation. The use of therapeutic polycomponent vaccine B[symbol: see text]-4 for the treatment of patients with latex allergy ensured the state of prolonged remission in this group of patients. On the basis of our investigations we believe that the use of the therapeutic polycomponent vaccine B[symbol: see text]-4 may be included into the basis therapy of allergic diseases.     

Ultrastructure of epithelium and ciliary receptors in the parasitic turbellarian Urastoma cyprinae (Turbellaria, "Prolecithophora") and position of the species within Platyhelminthes

Ultrastructure of the epithelium of adult and juvenile Urastoma cyprinae has been studied. The epithelium of both adult and juvenile worms is cellular, ciliated and bears numerous microvilli. The cytoplasm is rich in large, numerous epitheliosomes of two types--electron-dense and with fibrillated content (fig. 1, a, [symbol: see text]; 2, a-[symbol: see text]). Besides large secrete granules small membrane-bounded vesicles were observed (fig. 2, a-[symbol: see text]). In juvenile worms the dense epitheliosomes are less abundant and the fibrillated content in the second type of granules has a different structure: the fibrils are very thin and more densely packed forming the structures of the less electron density (fig. 3, a, [symbol: see text], [symbol: see text] 1). The membrane-bounded vesicles in the epithelium of juvenile worms were not observed. All types of secrete are ejected by exocytosis (fig. 2, [symbol: see text]; 3, [symbol: see text], [symbol: see text]). The ultrastructure of the epithelium in juvenile U. cyprinae is strongly similar to that in parasitic turbellarian Kronborgia, especially to the epithelium in a male and a larva. The basal lamina consists of tree layers and forms numerous deep infoldings into the epithelium (fig. 1, a; 2, a; 3, a, [symbol: see text], [symbol: see text]). The basement membrane projects deep and numerous invaginations into the epithelium which may almost reach the apical membrane (fig. 1, a; 2, a, [symbol: see text], [symbol: see text]; 3, [symbol: see text]). Mitochondria are large and situated mainly near the projections of the basement membrane (fig. 2, [symbol: see text]-[symbol: see text]; 3, [symbol: see text]). Such ultrastructure implies an intensive process of the transmembrane transfer of the dissolved organic substances from the sea water. The same structures were found in the epithelium of Kronborgia. Uptake of organic compounds through the epithelium in the common ancestors of Urastoma and Kronborgia could be the preadaptation to the endoparasitic mode of life in Fecampiida. The differencies in ultrastructure of epithelium in U. cyprinae from the White Sea and from Mediterranean Sea (Noury-Sra?ri e. a., 1990) may be explained by the differences in the method of fixation or by the parasitizing the another host--the mollusk Mytilus galloprovincialis. The ciliary receptors of five types were revealed in U. cyprinae (fig. 3, e, [symbol: see text]; 4; 5; 6). They differ in the shape and length of the ciliary rootlets and in the content of the nerve processes. All receptors lack of the real collars typical for the receptors of Neodermata. Urastoma is most close to the Neodermata amond parasitic turbellarians studied thus far, and the absence of collars in receptors of this species testifies that the collars are the veritable synapomorphy of the Neodermata. The diversity in the ultrastructure and possible functions of receptors correspond to the complicated adaptations of this species. The modern molecular data as well as the ultrastructural evidence attest that parasitic turbellarians of the genera Urastoma, Genostoma and Ichthyophaga are relatives and cannot be included in any turbellarian order known. Therefore Urastoma, Genostoma and Ichthyophaga have been erected in the separate order Urastomida ord. nov. The diagnosis of the new order is given.     

Immunoprophylaxis of acute respiratory diseases with bacterial multicomponent vaccine VP-4 in children at preschool institutions

The prophylactic action of polycomponent vaccine B[symbol: see text]-4, prepared from the antigens of opportunistic bacteria, on morbidity rate in acute respiratory diseases (ARD) of bacterial and mixed (bacterial and viral) etiology in 121 children aged 2-5 years, attending pre-school institutions was evaluated. For comparison, a group of 118 children of the same age from the same institutions was formed. The vaccine was introduced after the schedule consisting of 3 intranasal and 6-9 oral administrations made at intervals of 3-4 days. The duration of the course of immunization was 26 +/- 4 days. The prophylactic effect of B[symbol: see text]-4 on ARD morbidity was evaluated by the number of ARD cases and their duration per child. The prophylactic effect of B[symbol: see text]-4 on ARD morbidity lasted 14 months (the term of observation) after immunization and was manifested by a decrease in the number and duration of ARD cases after administration of the preparation, also in a group of highly susceptible children.     

Direct cost associated with acquired brain injury in Ontario

ABSTRACT: BACKGROUND: Acquired Brain Injury (ABI) from traumatic and non traumatic causes is a leading cause of disability worldwide yet there is limited research summarizing the health system economic burden associated with ABI. The objective of this study was to determine the direct cost of publicly funded health care services from the initial hospitalization to three years post-injury for individuals with traumatic (TBI) and non-traumatic brain injury (nTBI) in Ontario Canada. METHODS: A population-based cohort of patients discharged from acute hospital with an ABI code in any diagnosis position in 2004 through 2007 in Ontario was identified from administrative data. Publicly funded health care utilization was obtained from several Ontario administrative healthcare databases. Patients were stratified according to traumatic and non-traumatic causes of brain injury and whether or not they were discharged to an inpatient rehabilitation center. Health system costs were calculated across a continuum of institutional and community settings for up to three years after initial discharge. The continuum of settings included acute care emergency departments inpatient rehabilitation (IR) complex continuing care home care services and physician visits. All costs were calculated retrospectively assuming the government payer's perspective. RESULTS: Direct medical costs in an ABI population are substantial with mean cost in the first year post-injury per TBI and nTBI patient being $32132 and $38018 respectively. Among both TBI and nTBI patients those discharged to IR had significantly higher treatment costs than those not discharged to IR across all institutional and community settings. This tendency remained during the entire three-year follow-up period. Annual medical costs of patients hospitalized with a brain injury in Ontario in the first follow-up year were approximately $120.7 million for TBI and $368.7 million for nTBI. Acute care cost accounted for 46-65 % of the total treatment cost in the first year overwhelming all other cost components. CONCLUSIONS: The main finding of this study is that direct medical costs in ABI population are substantial and vary considerably by the injury cause. Although most expenses occur in the first follow-up year ABI patients continue to use variety of medical services in the second and third year with emphasis shifting over time from acute care and inpatient rehabilitation towards homecare physician services and long-term institutional care. More research is needed to capture economic costs for ABI patients not admitted to acute care.     

CO2.- radical induced cleavage of disulfide bonds in proteins. A gamma-ray and pulse radiolysis mechanistic investigation

Disulfide bond reduction by the CO2.- radical was investigated in aponeocarzinostatin, aporiboflavin-binding protein, and bovine immunoglobulin. Protein-bound cysteine free thiols were formed under gamma-ray irradiation in the course of a pH-dependent and protein concentration dependent chain reaction. The chain efficiency increased upon acidification of the medium, with an apparent pKa around 5, and decreased abruptly below pH 3.6. It decreased also at neutral pH as cysteine accumulated. From pulse radiolysis analysis, CO2.- proved able to induce rapid one-electron oxidation of thiols and of tyrosine phenolic groups in addition to one-electron donation to exposed disulfide bonds. The bulk rate constant of CO2.- uptake by the native proteins was 5- to 10-fold faster at pH 3 than at pH 8, and the protonated form of the disulfide radical anion, [symbol: see text], appeared to be the major protein radical species formed under acidic conditions. The main decay path of [symbol: see text] consisted of the rapid formation of a thiyl radical intermediate [symbol: see text] in equilibrium with the closed, cyclic form. The thiyl radical was subsequently reduced to the sulfhydryl level [symbol: see text] on reaction with formate, generating 1 mol of the CO2.- radical, thus propagating the chain reaction. The disulfide radical anion [symbol: see text] at pH 8 decayed through competing intramolecular and/or intermolecular routes including disproportionation, protein-protein cross-linking, electron transfer with tyrosine residues, and reaction with sulfhydryl groups in prereduced systems. Disproportionation and cross-linking were observed with the riboflavin-binding protein solely. Formation of the disulfide radical cation [symbol: see text], phenoxyl radical Tyr-O. disproportionation, and phenoxyl radical induced oxidation of preformed thiol groups should also be taken into consideration to explain the fate of the oxygen-centered phenoxyl radical.     

Effect of melanins from black yeast fungi on cultured human cells. I. Proliferation of keratinocytes and fibroblasts

Results of screening of the influence exerted by yeast black melanin on the proliferation of human skin keratinocytes and embryonic fibroblasts are presented. The optimal concentration of the investigated melanins was found to be within 0.005 and 0.0001 mg/ml. 17 samples of DHN-melanin from black yeast and 2 commercial samples of [symbol: see text]OPA-melanin (natural and synthetic) were investigated. It was established that keratinocyte proliferation was inhibited by 3 black yeast melanin samples; the influence of other 14 samples was the same as in the control. Keratinocyte proliferation was stimulated only by a commercial sample of natural [symbol: see text]OPA-melanin at concentration 0.005 mg/ml. The synthetic melanin at concentrations 0.005 and 0.001 mg/ml inhibited keratinocyte proliferation. Of the 17 investigated black yeast melanin samples, only one sample stimulated fibroblast proliferation at concentration 0.005 mg/ml. Three other samples inhibited the proliferation; of these one sample did it at all used concentrations, and two samples at concentration 0.0001 mg/ml. The rest 13 samples of black yeast DHN-melanins and the synthetic [symbol: see text]OPA-melanin did not differ in either action from the control.     

Structure of the epithelium of the parasitic turbellaria Notenera ivanovi (Turbellaria: Fecampiida)

The ultrastructure of the epithelium in Notentera ivanovi (Turbellaria, Fecampiida) has been studied. Notentera ivanovi lacks the digestive system but has a pad of the epidermal cells on the dorsal side of the body, which seems to be similar to the digestive epidermis on LM. Both the ventral and dorsal epithelium are cellular, ciliated and not insunk (fig. 1, a). The ultrastructure of the ventral and dorsal epithelium is similar in essential features. The cells bear abundant microvilli, cilia and are very rich in mitochondria, but the cytoplasm does not contain lysosomes and shows no other indications of phago- or pinocytosis. The basal membrane of epithelial cells forms deep invaginations (fig. 1, [symbol: see text]), partly with dilations (fig. 1, a; 2, a) containing the lamellated material (3, [symbol: see text]). In the basal part of the cells the numerous Golgi apparatus and rare cysternae of the smooth endoplasmic reticulum were observed (fig. 2, a, [symbol: see text]). The epithelium consists of several types of cells, which differ in the structure of secretory granules. The most abundant type of cells contains the granules with the rough-fibrillated content (fig. 1, a; 2, [symbol: see text]; 3, a). The cells of this type cover most part of the body. In some cells the content of such granules becomes condensed and electron-dense granules appear (fig. 3, a, [symbol: see text]). Another type of cells contains the giant granules with the rough-fibrillated content (fig. 3, [symbol: see text]). Third type of the secret is the granules with the finely fibrillated content which is ejected by exocytosis. The cells of the second and third types form a separate areas of the epithelium of the dorsal side of the body but occasionally were observed in the ventral epithelium too. The epithelium of N. ivanovi differs from that in Kronborgia by the abundance and diversity of secretory contents. The role of the epithelium in the digestion remains conjectural. It seems to be mainly the suckering tissue transporting the low molecular nutrients.     

Seed banks, salmon, and sleeping genes: effective population size in semelparous, age-structured species with fluctuating abundance

Previous studies reached contrasting conclusions regarding how fluctuations in abundance affect Ne in semelparous species with variable age at maturity: that Ne is determined by the arithmetic mean N among the T years within a generation (Ne approximately = T(N)t; monocarpic plants with seed banks) or the harmonic mean (Ne approximately T[symbol: see text]; Pacific salmon). I show that these conclusions arise from different model assumptions rather than inherent differences between the species. Sequentially applying standard, discrete-generation formulas for inbreeding Ne to a series of nominal generations accurately predicts the multigenerational rate of increase in inbreeding. Variability in mean realized reproductive success across years (kt) is the most important factor determining Ne and Ne/N. When abundance is driven by random variation in kt, Ne < or = T[symbol: see text] < T(N)t. With random variation in Nt and constant per capita seed production (C), variation in kt is low and Ne approximately T[symbol: see text]; however, if C varies among years, Ne can be closer to T[symbol: see text]. Because population regulation affects the genetic contribution of entire cohorts of monocarpic perennials, Ne for these species may be more closely approximated by T[symbol: see text] than by T(N)t. With density-dependent compensation, Cov(kt, Nt) < 0, and Ne is further reduced because relatively few breeders make a disproportionate contribution to the next generation.     

Minimum inhibitory concentrations of various antifungal agents against Basidiomycetes clinical isolates]

The basidiomycete yeasts are often isolated from clinical samples. A minimal inhibiting concentrations (MIC) of ten antifungals of different groups--azols, allilamines, polyens etc.--against isolates of Rhodotorula, Cryptococcus [symbol: see text] Trichosporon yeasts genera were estimated. No one of these cultures was sensitive to azoles at concentrations 0-256 mcg/ml. A vitality of cultures after incubation during 10 days with antifungals was investigated. Miramistin was the most potent fungicidal agent against all cultures.     

Are membrane enzymes regulated by the viscosity of the membrane environment?

We have examined the idea that membrane enzymes are regulated by the viscosity of surrounding lipids using data compiled from the literature for the effect of the change in membrane viscosity ([symbol: see text]) at the gel- to liquid-crystal-phase transition on the activities of several enzymes. The analysis was not extended explicitly to the problem of viscosity-dependent regulation of membrane enzymes in liquid-crystalline lipids because of the absence of exact data for values of [symbol: see text] in liquid-crystalline phases of variable composition. For most membrane enzymes studied, energies of activation are discontinuous, while kcat is continuous, at the main-phase transition. We consider that the energy of activation contains terms related to the height of the chemical barrier to reaction and terms due to the mechanical properties of the bilayer, such as the work of expansion during the catalytic cycle and the temperature dependence of [symbol: see text]. We find that the differences in energies of activation, above and below the break points in Arrhenius plots, are orders of magnitude larger than can be accounted for by the above mechanical factors. Thus, discontinuities in energies of activation at the phase transition appear to reflect changes in the chemical barrier to reaction, which is independent of [symbol: see text]. The theorectical analysis indicates too that values of [symbol: see text] for bilayers in the liquid-crystalline phase would have to be several orders of magnitude larger than those for gel phases in order to provide a basis for viscosity-dependent regulation of membrane enzymes in liquid-crystalline phases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative study of the diagnostic value of new cholera eltor bacteriophages ctx+, ctx-, and KhDF-3, 4, and 5

The comparative evaluation of the diagnostic value of new cholera eltor bacteriophages ctx+ and ctx-, as well as monophages X[symbol: see text]-3, 4, 5, demonstrated their high activity and specificity. Using of these bacteriophages epidemic potential of 95% Vibrio cholerae eltor strains ctx+ and 84.5% of V. cholerae eltor stains ctx- was determined. Commercial monophages X[symbol: see text]-3, 4, 5 were inferior to bacteriophages ctx+ and ctx- in their diagnostic value: only 55% of strains having gene ctxAB were found to be epidemically dangerous, i.e. 45% of strains capable of causing the disease were not detected. On the basis of the results obtained in this investigation cholera eltor bacteriophages ctx+ and ctx- were recommended for introduction into practical use, while further production of cholera diagnostic monophages X[symbol: see text]-3, 4, 5 was recommended to be stopped.     

Experimental evaluation of efficacy of Lactobacilli in prophylaxis and treatment of cholera

Investigations on experimental models of cholera ("sealed" mice and suckling rabbits) demonstrated that previous daily oral administration of the ferment culture of Lactobacillus acidophilus BKM B-2020[symbol: see text] in a dose of 3.0 x 10(8) microbial cells/ml daily for 5-7 days prevented to the development of Vibrio cholerae infection. The curative effect observed after 3 administrations of lactobacilli within 48 hours after infection with V. cholerae was registered in 50% of cases. This strain of lactobacilli was found to be suitable for use as the basis component of probiotic, an additional remedy for the prophylaxis and treatment of cholera.     

Rates of DNA sequence evolution are not sex-biased in Drosophila melanogaster and D. simulans

To determine whether male- or female-biased mutation rates have affected the molecular evolution of Drosophila melanogaster and D. simulans, we calculated the male-to-female ratio of germline cell divisions ([symbol: see text]) from germline generation data and the male-to-female ratio of mutation rate ([symbol: see text]) by comparing chromosomal levels of nucleotide divergence. We found that the ratio of germline cell divisions changes from indicating a weak female bias to indicating a weak male bias as the age of reproduction increases. The range of [symbol: see text] values that we observed, however, does not lead us to expect much, if any, difference in mutation rate between the sexes. Silent and intron nucleotide divergence were compared between nine loci on the X chromosome and nine loci on the second and third chromosomes. The average levels of nucleotide divergence were not significantly different across the chromosomes, although both silent and intron sites show a trend toward slightly more divergence on the X. These results indicate a lack of sex- or chromosome-biased molecular evolution in D. melanogaster and D. simulans.      

The in vitro and in vivo resistance of synthetic enkephalin analogs to three enkephalin-hydrolyzing enzymes

The magnitude of the in vitro and in vivo resistance of 3 synthetic enkephalin analogs, [D-Ala2,Met5]-enkephalin (DAME), [D-Ala2,Met5]-enkephalinamide (DAME-NH2) and [D-Ala2,D-Met5]enkephalin (DADME), to 3 enkephalin-hydrolyzing enzymes, amastatin-sensitive aminopeptidase (AsA), phosphoramidon-sensitive endopeptidase-24.11 (PsE) and captopril-sensitive dipeptidyl carboxypeptidase I (CsD), was estimated by comparing the potency of enkephalins in the absence of the peptidase inhibitor (PI) with that in the presence of the PI. The enhancement of the potency of enkephalins in the isolated mouse vas deferens preparation by 3 PIs, amastatin, phosphoramidon, and captopril, indicated that the resistance of enkephalins to AsA, PsE, or CsD was DADME [symbol: see text] DAME-NH2 [symbol: see text] DAME > [Met5]-enkephalin (ME), DADME > DAME-NH2 > DAME [symbol: see text] ME, or DADME [symbol: see text] DAME-NH2 > DAME > ME, respectively. Additionally, the data obtained by the s.c. administration of enkephalin analogs to 10-day-old rats with or without PI, showed that PsE played the most important role in the inactivation of both DAME and DAME-NH2. In addition to PsE, both AsA and CsD, or AsA alone, played the significant role in the inactivation of DAME, or DAME-NH2, respectively. In the inactivation of DADME, AsA alone played the significant role. These results showed that the 3 peptidases all played important roles in the inactivation of enkephalins, and therefore only an analog like DADME, which was quite resistant to the 3 enzymes, was able to produce the effect without PIs after its systemic administration. Since even DADME was not completely resistant to the 3 enzymes; however, its potency was further increased by pretreatment of infant rats with the PIs.     

Cost effectiveness analysis of clinically driven versus routine laboratory monitoring of antiretroviral therapy in Uganda and Zimbabwe

Background

Despite funding constraints for treatment programmes in Africa, the costs and economic consequences of routine laboratory monitoring for efficacy and toxicity of antiretroviral therapy (ART) have rarely been evaluated.

Methods

Cost-effectiveness analysis was conducted in the DART trial (ISRCTN13968779). Adults in Uganda/Zimbabwe starting ART were randomised to clinically-driven monitoring (CDM) or laboratory and clinical monitoring (LCM); individual patient data on healthcare resource utilisation and outcomes were valued with primary economic costs and utilities. Total costs of first/second-line ART, routine 12-weekly CD4 and biochemistry/haematology tests, additional diagnostic investigations, clinic visits, concomitant medications and hospitalisations were considered from the public healthcare sector perspective. A Markov model was used to extrapolate costs and benefits 20 years beyond the trial.

Results

3316 (1660LCM;1656CDM) symptomatic, immunosuppressed ART-naive adults (median (IQR) age 37 (32,42); CD4 86 (31,139) cells/mm³) were followed for median 4.9 years. LCM had a mean 0.112 year (41 days) survival benefit at an additional mean cost of $765 [95%CI:685,845], translating into an adjusted incremental cost of $7386 [3277,dominated] per life-year gained and $7793 [4442,39179] per quality-adjusted life year gained. Routine toxicity tests were prominent cost-drivers and had no benefit. With 12-weekly CD4 monitoring from year 2 on ART, low-cost second-line ART, but without toxicity monitoring, CD4 test costs need to fall below $3.78 to become cost-effective (<3xper-capita GDP, following WHO benchmarks). CD4 monitoring at current costs as undertaken in DART was not cost-effective in the long-term.

Conclusions

There is no rationale for routine toxicity monitoring, which did not affect outcomes and was costly. Even though beneficial, there is little justification for routine 12-weekly CD4 monitoring of ART at current test costs in low-income African countries. CD4 monitoring, restricted to the second year on ART onwards, could be cost-effective with lower cost second-line therapy and development of a cheaper, ideally point-of-care, CD4 test.     

Cost Effectiveness of Cryptococcal Antigen Screening as a Strategy to Prevent HIV-Associated Cryptococcal Meningitis in South Africa

Objectives

Cryptococcal meningitis (CM)-related mortality may be prevented by screening patients for sub-clinical cryptococcal antigenaemia (CRAG) at antiretroviral-therapy (ART) initiation and pre-emptively treating those testing positive. Prior to programmatic implementation in South Africa we performed a cost-effectiveness analysis of alternative preventive strategies for CM.

Design

Cost-effectiveness analysis.

Methods

Using South African data we modelled the cost-effectiveness of four strategies for patients with CD4 cell-counts <100 cells/µl starting ART 1) no screening or prophylaxis (standard of care), 2) universal primary fluconazole prophylaxis, 3) CRAG screening with fluconazole treatment if antigen-positive, 4) CRAG screening with lumbar puncture if antigen-positive and either amphotericin-B for those with CNS disease or fluconazole for those without. Analysis was limited to the first year of ART.

Results

The least costly strategy was CRAG screening followed by high-dose fluconazole treatment of all CRAG-positive individuals. This strategy dominated the standard of care at CRAG prevalence ≥0.6%. Although CRAG screening followed by lumbar puncture in all antigen-positive individuals was the most effective strategy clinically, the incremental benefit of LPs and amphotericin therapy for those with CNS disease was small and additional costs were large (US$158 versus US$51per person year; incremental cost effectiveness ratio(ICER) US$889,267 per life year gained). Both CRAG screening strategies are less costly and more clinically effective than current practice. Primary prophylaxis is more effective than current practice, but relatively cost-ineffective (ICER US$20,495).

Conclusions

CRAG screening would be a cost-effective strategy to prevent CM-related mortality among patients initiating ART in South Africa. These findings provide further justification for programmatic implementation of CRAG screening.     

Cost-Effectiveness of a Specialist Geriatric Medical Intervention for Frail Older People Discharged from Acute Medical Units: Economic Evaluation in a Two-Centre Randomised Controlled Trial (AMIGOS)

BackgroundPoor outcomes and high resource-use are observed for frail older people discharged from acute medical units. A specialist geriatric medical intervention, to facilitate Comprehensive Geriatric Assessment, was developed to reduce the incidence of adverse outcomes and associated high resource-use in this group in the post-discharge period.ObjectiveTo examine the costs and cost-effectiveness of a specialist geriatric medical intervention for frail older people in the 90 days following discharge from an acute medical unit, compared with standard care.MethodsEconomic evaluation was conducted alongside a two-centre randomised controlled trial (AMIGOS). 433 patients (aged 70 or over) at risk of future health problems, discharged from acute medical units within 72 hours of attending hospital, were recruited in two general hospitals in Nottingham and Leicester, UK. Participants were randomised to the intervention, comprising geriatrician assessment in acute units and further specialist management, or to control where patients received no additional intervention over and above standard care. Primary outcome was incremental cost per quality adjusted life year (QALY) gained.ResultsWe undertook cost-effectiveness analysis for 417 patients (intervention: 205). The difference in mean adjusted QALYs gained between groups at 3 months was -0.001 (95% confidence interval [CI]: -0.009, 0.007). Total adjusted secondary and social care costs, including direct costs of the intervention, at 3 months were £4412 (€5624, $6878) and £4110 (€5239, $6408) for the intervention and standard care groups, the incremental cost was £302 (95% CI: 193, 410) [€385, $471]. The intervention was dominated by standard care with probability of 62%, and with 0% probability of cost-effectiveness (at £20,000/QALY threshold).ConclusionsThe specialist geriatric medical intervention for frail older people discharged from acute medical unit was not cost-effective. Further research on designing effective and cost-effective specialist service for frail older people discharged from acute medical units is needed.

Trial Registration

ISRCTN registry ISRCTN21800480 http://www.isrctn.com/ISRCTN21800480