Cost effectiveness of a new combined immunosuppressive and antiviral regimen on the one-year follow-up of kidney transplant patients.

Background: Medical prescription after organ transplant must prevent both rejection and infectious complications. We assessed the 1-year effectiveness and cost of introducing a new combined regimen in kidney transplantation. Methods: Patients transplanted from January 2000 to March 2003 (Period 1) were compared to patients transplanted from April 2003 to July 2005 (Period 2). In period 1, patients were treated with Basiliximab, Cyclosporin, steroids and Mycophenolate (MMF) or Azathioprine. Prophylaxis with Valacyclovir was prescribed only in CMV D+/R- patients. In period 2, immunosuppressive drugs were Basiliximab, Tacrolimus, steroids and MMF. A 3-month universal CMV prophylaxis with Valganciclovir was used. Medical charts of outpatient visits allowed identifying drug, laboratory and radiological tests use, and hospital information system causes of hospitalisation and length of stay (LOS) over the first year after transplant. Patients with incomplete costs data were excluded. Results: 53 patients were analysed in period 1, and 60 in period 2. CMV serostatus patterns were not significantly different between the 2 periods. Over 12 months, acute rejection decreased from 22 patients (42%) in period 1 to 4 patients (7%) in period 2 (p<0.001), and CMV infection from 25 patients (47%) to 9 patients (15%, p<0.001). Average total rehospitalisation LOS decreased from 28±19 to 20±11 days (p<0.007). Average outpatient visits decreased from 49±10 to 39±8 (p<0.001). Average immunosuppression and CMV prophylaxis costs increased from US$ 18,362±6,546 to 24,637±5,457 (p<0.001), while average graft rejection costs decreased form US$ 4,135±9,164 to 585±2,850 (p=0.005), and average CMV treatment costs from US$ 2,043±5,545 to 91±293 (p=0.008). Average outpatient visits costs decreased from US$ 7,619±1,549 to 6,074±1,043 (p<0.001), and other hospital costs from US$ 3,801±6,519 to 1,196±3,146 (p=0.007). Altogether, average 1-year treatment costs decreased from US$ 35,961±14,916 to 32,584±6,211 (p=0.115). Cost-effectiveness ratios to avoid graft rejection and CMV infection decreased from US$ 61,482±9,292 to 34,911± 1,639 (p=0.006) and US$ 68,070±11,122 to 39,899±2,650 (p=0.015), respectively. Conclusion: The new combined regimen administered in period 2 was significantly more effective. Its additional cost was more than offset by savings linked with complications avoidance.

Sibling competition and the risk of falling out of the nest

In birds, sibling competition encompasses several activities, one of which is jostling for position, that is, competing for the location in the nest where parents predictably deliver food items. We hypothesized that nestlings that compete by jostling for position may fall out of the nest either accidentally or because siblings push each other to reduce brood size. This hypothesis predicts that in a competitive environment needy nestlings trade-off the benefit of being fed against the cost of falling out of the nest. As a first attempt to evaluate this hypothesis, we experimentally manipulated the number of young per brood in the colonial Alpine swift, Apus melba. Nestlings fell out of their colony more frequently when reared in enlarged than in reduced broods. Because brood size manipulation affects not only the number of young per nest but also their body condition, we analysed an extended data set to disentangle these two factors. This analysis showed that, independently of brood size, nestlings in poor condition and those reared in broods where sibling differed markedly in weight were more likely to disappear from the colony. Nestling disappearance also occurred predominantly in nests close to the colony entrances. Although nestling swifts can wander in the colony and become adopted in neighbouring nests, we found no evidence that wandering per se increased the risk of falling out of the colony. Our study therefore highlights a novel cost of scramble competition.

Cost-effectiveness analysis of a European primary-care physician training in smoking cessation counseling.

BACKGROUND: Physician training in smoking cessation counseling has been shown to be effective as a means to increase quit success. We assessed the cost-effectiveness ratio of a smoking cessation counseling training programme. Its effectiveness was previously demonstrated in a cluster randomized, control trial performed in two Swiss university outpatients clinics, in which residents were randomized to receive training in smoking interventions or a control educational intervention. DESIGN AND METHODS: We used a Markov simulation model for effectiveness analysis. This model incorporates the intervention efficacy, the natural quit rate, and the lifetime probability of relapse after 1-year abstinence. We used previously published results in addition to hospital service and outpatient clinic cost data. The time horizon was 1 year, and we opted for a third-party payer perspective. RESULTS: The incremental cost of the intervention amounted to US$2.58 per consultation by a smoker, translating into a cost per life-year saved of US$25.4 for men and 35.2 for women. One-way sensitivity analyses yielded a range of US$4.0-107.1 in men and US$9.7-148.6 in women. Variations in the quit rate of the control intervention, the length of training effectiveness, and the discount rate yielded moderately large effects on the outcome. Variations in the natural cessation rate, the lifetime probability of relapse, the cost of physician training, the counseling time, the cost per hour of physician time, and the cost of the booklets had little effect on the cost-effectiveness ratio. CONCLUSIONS: Training residents in smoking cessation counseling is a very cost-effective intervention and may be more efficient than currently accepted tobacco control interventions.

Cost-effectiveness analysis of immune-modulating nutritional support for gastrointestinal cancer patients.

BACKGROUND & AIM: Immune-modulating nutritional formula containing arginine, omega-3 fatty acids and nucleotides has been demonstrated to decrease complications and length of stay in surgical patients. This study aims at assessing the impact of immune-modulating formula on hospital costs in gastrointestinal cancer surgical patients in Switzerland. METHOD: Based on a previously published meta-analysis, the relative risks of overall and infectious complications with immune-modulating versus standard nutrition formula were computed. Swiss hospital costs of patients undergoing gastrointestinal cancer surgery were retrieved. A method was developed to compute the patients' severity level, not taking into account the complications from the surgery. Incremental costs of complications were computed for both treatment groups, and sensitivity analyses were carried out. RESULTS: Relative risk of complications with pre-, peri- and post-operative use of immune-modulating formula was 0.69 (95%CI 0.58-0.83), 0.62 (95%CI 0.53-0.73) and 0.73 (95%CI 0.35-0.96) respectively. The estimated average contribution of complications to the cost of stay was CHF 14,949 (euro10,901) per patient (95%CI 10,712-19,186), independently of case's severity. Based on this cost, immune-modulating nutritional support decreased costs of hospital stay by CHF 1638 to CHF 2488 per patient (euro1195-euro1814). Net hospital savings were present for baseline complications rates as low as 5%. CONCLUSION: Immune-modulating nutritional solution is a cost-saving intervention in gastrointestinal cancer patients. The additional cost of immune-modulating formula are more than offset by savings associated with decreased treatment of complications.

Cost-utility analysis of a three-month exercise programme vs usual care following multidisciplinary rehabilitation for chronic low back pain.

OBJECTIVE: To assess the cost-utility of an exercise programme vs usual care after functional multidisciplinary rehabilitation in patients with chronic low back pain. DESIGN: Cost-utility analysis alongside a randomized controlled trial. SUBJECTS/PATIENTS: A total of 105 patients with chronic low back pain. METHODS: Chronic low back pain patients completing a 3-week functional multidisciplinary rehabilitation were randomized to either a 3-month exercise programme (n = 56) or usual care (n = 49). The exercise programme consisted of 24 training sessions during 12 weeks. At the end of functional multidisciplinary rehabilitation and at 1-year follow-up quality of life was measured with the SF-36 questionnaire, converted into utilities and transformed into quality--adjusted life years. Direct and indirect monthly costs were measured using cost diaries. The incremental cost-effectiveness ratio was calculated as the incremental cost of the exercise programme divided by the difference in quality-adjusted life years between both groups. RESULTS: Quality of life improved significantly at 1-year follow-up in both groups. Similarly, both groups significantly reduced total monthly costs over time. No significant difference was observed between groups. The incremental cost-effectiveness ratio was 79,270 euros. CONCLUSION: Adding an exercise programme after functional multidisciplinary rehabilitation compared with usual care does not offer significant long-term benefits in quality of life and direct and indirect costs.

Influence of the world's most challenging mountain ultra-marathon on energy cost and running mechanics

PURPOSE: To examine the effects of the world's most challenging mountain ultra-marathon (Tor des Géants(®) 2012) on the energy cost of three types of locomotion (cycling, level and uphill running) and running kinematics. METHODS: Before (pre-) and immediately after (post-) the competition, a group of ten male experienced ultra-marathon runners performed in random order three submaximal 4-min exercise trials: cycling at a power of 1.5 W kg(-1) body mass; level running at 9 km h(-1) and uphill running at 6 km h(-1) at an inclination of +15 % on a motorized treadmill. Two video cameras recorded running mechanics at different sampling rates. RESULTS: Between pre- and post-, the uphill-running energy cost decreased by 13.8 % (P = 0.004); no change was noted in the energy cost of level running or cycling (NS). There was an increase in contact time (+10.3 %, P = 0.019) and duty factor (+8.1 %, P = 0.001) and a decrease in swing time (-6.4 %, P = 0.008) in the uphill-running condition. CONCLUSION: After this extreme mountain ultra-marathon, the subjects modified only their uphill-running patterns for a more economical step mechanics.

An outcome and cost analysis of anal fistula plug insertion vs endorectal advancement flap for complex anal fistulae.

AIM: The study aimed to compare the rate of success and cost of anal fistula plug (AFP) insertion and endorectal advancement flap (ERAF) for anal fistula. METHOD: Patients receiving an AFP or ERAF for a complex single fistula tract, defined as involving more than a third of the longitudinal length of of the anal sphincter, were registered in a prospective database. A regression analysis was performed of factors predicting recurrence and contributing to cost. RESULTS: Seventy-one patients (AFP 31, ERAF 40) were analysed. Twelve (39%) recurrences occurred in the AFP and 17 (43%) in the ERAF group (P = 1.00). The median length of stay was 1.23 and 2.0 days (P < 0.001), respectively, and the mean cost of treatment was euro5439 ± euro2629 and euro7957 ± euro5905 (P = 0.021), respectively. On multivariable analysis, postoperative complications, underlying inflammatory bowel disease and fistula recurring after previous treatment were independent predictors of de novo recurrence. It also showed that length of hospital stay ≤ 1 day to be the most significant independent contributor to lower cost (P = 0.023). CONCLUSION: Anal fistula plug and ERAF were equally effective in treating fistula-in-ano, but AFP has a mean cost saving of euro2518 per procedure compared with ERAF. The higher cost for ERAF is due to a longer median length of stay.

Life span and reproductive cost explain interspecific variation in the optimal onset of reproduction.

Fitness can be profoundly influenced by the age at first reproduction (AFR), but to date the AFR-fitness relationship only has been investigated intraspecifically. Here, we investigated the relationship between AFR and average lifetime reproductive success (LRS) across 34 bird species. We assessed differences in the deviation of the Optimal AFR (i.e., the species-specific AFR associated with the highest LRS) from the age at sexual maturity, considering potential effects of life history as well as social and ecological factors. Most individuals adopted the species-specific Optimal AFR and both the mean and Optimal AFR of species correlated positively with life span. Interspecific deviations of the Optimal AFR were associated with indices reflecting a change in LRS or survival as a function of AFR: a delayed AFR was beneficial in species where early AFR was associated with a decrease in subsequent survival or reproductive output. Overall, our results suggest that a delayed onset of reproduction beyond maturity is an optimal strategy explained by a long life span and costs of early reproduction. By providing the first empirical confirmations of key predictions of life-history theory across species, this study contributes to a better understanding of life-history evolution.

Objective analysis of gait coordination for total knee arthroplasty outcome

Introduction: Coordination is a strategy chosen by the central nervous system to control the movements and maintain stability during gait. Coordinated multi-joint movements require a complex interaction between nervous outputs, biomechanical constraints, and pro-prioception. Quantitatively understanding and modeling gait coordination still remain a challenge. Surgeons lack a way to model and appreciate the coordination of patients before and after surgery of the lower limbs. Patients alter their gait patterns and their kinematic synergies when they walk faster or slower than normal speed to maintain their stability and minimize the energy cost of locomotion. The goal of this study was to provide a dynamical system approach to quantitatively describe human gait coordination and apply it to patients before and after total knee arthroplasty. Methods: A new method of quantitative analysis of interjoint coordination during gait was designed, providing a general model to capture the whole dynamics and showing the kinematic synergies at various walking speeds. The proposed model imposed a relationship among lower limb joint angles (hips and knees) to parameterize the dynamics of locomotion of each individual. An integration of different analysis tools such as Harmonic analysis, Principal Component Analysis, and Artificial Neural Network helped overcome high-dimensionality, temporal dependence, and non-linear relationships of the gait patterns. Ten patients were studied using an ambulatory gait device (Physilog®). Each participant was asked to perform two walking trials of 30m long at 3 different speeds and to complete an EQ-5D questionnaire, a WOMAC and Knee Society Score. Lower limbs rotations were measured by four miniature angular rate sensors mounted respectively, on each shank and thigh. The outcomes of the eight patients undergoing total knee arthroplasty, recorded pre-operatively and post-operatively at 6 weeks, 3 months, 6 months and 1 year were compared to 2 age-matched healthy subjects. Results: The new method provided coordination scores at various walking speeds, ranged between 0 and 10. It determined the overall coordination of the lower limbs as well as the contribution of each joint to the total coordination. The difference between the pre-operative and post-operative coordination values were correlated with the improvements of the subjective outcome scores. Although the study group was small, the results showed a new way to objectively quantify gait coordination of patients undergoing total knee arthroplasty, using only portable body-fixed sensors. Conclusion: A new method for objective gait coordination analysis has been developed with very encouraging results regarding the objective outcome of lower limb surgery.

Psychosocial care for the caregivers of primary malignant brain tumor patients.

Despite clinical experience that suggests a high burden of care among relatives of individuals with a primary malignant brain tumor (PMBT), little is known about their actual needs. In this study, the caregivers' personal experiences, quality of life, burden of care, and psychological well-being were examined. Fifty-nine percent did not receive any financial aid for home care, 33% had increased risk for psychosomatic problems, 45% had anxiety, and 33% increased depression levels. The caregiver's quality of life was most strongly affected by the burden of care (p < .001) and the patient's mental state (p < .03). To improve the situation, empathetic professionals and an early implementation of palliative care and social work are required.

Influence of climate on the presence of colour polymorphism in two montane reptile species.

The coloration of ectotherms plays an important role in thermoregulation processes. Dark individuals should heat up faster and be able to reach a higher body temperature than light individuals and should therefore have benefits in cool areas. In central Europe, montane local populations of adder (Vipera berus) and asp viper (Vipera aspis) exhibit a varying proportion of melanistic individuals. We tested whether the presence of melanistic V. aspis and V. berus could be explained by climatic conditions. We measured the climatic niche position and breadth of monomorphic (including strictly patterned individuals) and polymorphic local populations, calculated their niche overlap and tested for niche equivalency and similarity. In accordance with expectations, niche overlap between polymorphic local populations of both species is high, and even higher than that of polymorphic versus monomorphic montane local populations of V. aspis, suggesting a predominant role of melanism in determining the niche of ectothermic vertebrates. However, unexpectedly, the niche of polymorphic local populations of both species is narrower than that of monomorphic ones, indicating that colour polymorphism does not always enable the exploitation of a greater variability of resources, at least at the intraspecific level. Overall, our results suggest that melanism might be present only when the thermoregulatory benefit is higher than the cost of predation.

Role of penicillin-binding proteins in Streptococcus gordonii

Résumé Streptococcus gordonii est une bactérie colonisatrice naturelle de la cavité buccale de l'homme. Bien que normalement commensale, elle peut causer des infections graves, telles que des bactériémies ou des endocardites infectieuses. La pénicilline étant un des traitements privilégiés dans de tels cas, l'augmentation rapide et globale des résistances à cet antibiotique devient inquiétante. L'étude de la physiologie et des bases génétiques de ces résistances chez S. gordonii s'avère donc importante. Les cibles moléculaires privilégiées de la pénicilline G et des β-lactames sont les penicilllin-binding proteins (PBPs). Ces enzymes associées à la membrane ont pour rôle de catalyser les réactions de transpeptidation et de transglycosylation, qui constituent les dernières étapes de la biosynthèse du peptidoglycan (PG). Elles sont définies comme classe A ou B selon leur capacité d'assurer soit les deux réactions, soit uniquement la transpeptidation. Les β-lactames inhibent le domaine transpeptidase de toutes les PBPs, entraînant l'inhibition de la synthèse du PG, l'inhibition de la croissance, et finalement la mort cellulaire. Chez les streptocoques, les PBPs sont aussi les premiers déterminants de la résistance à la pénicilline. De plus, elles sont impliquées dans la morphologie bactérienne, en raison de leur rôle crucial dans la formation du PG. Le but de ce travail était de caractériser les PBPs de S. gordonii et d'étudier leurs fonctions dans la vie végétative de la bactérie ainsi que durant le développement de la résistance à la pénicilline. Premièrement, des mutants auxquels il manque une ou deux PBP(s) ont été construits. Leur étude - au niveau physiologique, biochimique et morphologique - a montré le caractère essentiel ou dispensable de chaque protéine, ainsi que certaines de leurs fonctions potentielles. Deuxièmement, des mutants résistants à la pénicilline ont été générés. Leur caractérisation a montré l'importance des mutations dans les PBPs ainsi que dans d'autres gènes encore inconnus, de même que le rôle crucial des PBPs de classe A dans le développement de la résistance à la pénicilline. Des expériences supplémentaires sur des isolats résistants ont aussi prouvé que la résistance a un coût en terme de fitness, coût que S. gordonii parvient à compenser par des mécanismes d'adaptation. Finalement, les promoteurs des gènes des PBPs ont été déterminés et leur expression a été étudiée grâce au gène de luciférase. Il a ainsi été montré que la résistance à la pénicilline entraîne non seulement des altérations au niveau des protéines, mais aussi au niveau de la régulation des gènes. De plus, la pénicilline génère directement des modifications dans l'expression de PBPs spécifiques. Summary Streptococcus gordonii is a normal inhabitant of the human oral cavity and a pioneer colonizer of teeth. Although usually considered as a commensal, this organism can cause life-threatening infections such as bacteraemia or endocarditis. Since penicillin is one of the preferential treatments for such pathologies, the rapid and general increase of antibiotic resistance in the overall population becomes an issue. Thus, studying the physiologic and genetic bases of such a resistance in S. gordonii is of interest. The primary molecular targets of penicillin G and other β-lactams are the so called penicillin-binding proteins (PBPs). These are membrane-associated proteins that catalyze the last steps in peptidoglycan (PG) biosynthesis, namely transpeptidation and transglycosylation. Depending on their capacity to catalyze either reactions or only transpeptidation, they are considered as class A or class B PBPs, respectively. β-lactam antibiotics inhibit the transpeptidase domain of both of these classes of enzymes, resulting in inhibition of PG assembly, inhibition of bacterial growth, and ultimately leading to cell death. In streptococci, PBPs are also the primary determinants of penicillin-resistance. Moreover, because of their crucial role in PG formation, they are implicated in fundamental aspects of cell morphology. The goal of this work was thus to characterize S. gordonii PBPs and to explore their functions in terms of vegetative life and penicillin-resistance development. First, single and double PBP-inactivated mutants were generated and their effect on the bacterial physiology, cell wall biochemistry and ultrastructural morphology was assessed. This demonstrated the essentiality or dispensability of each protein for bacterial life. Second, penicillin-resistant mutants were generated by cyclic exposure to increasing concentrations of the drug. Characterization of these mutants pointed out the importance of both PBP and non-PBP mutations, as well as the crucial role of the class A PBPs in the development of penicillin-resistance. Further experiments on resistant isolates demonstrated the fitness cost of this resistance, but also the capacity of S. gordonii to adapt and regain the fitness of the wild-type. Finally, the promoters of PBP genes were determined and their expression was monitored using luciferase fusions. This showed that penicillin-resistance, in addition to modifications at the level of the protein, also triggered genetic alterations. Moreover, penicillin itself generated modifications in the expression of specific PBPs.

Computed tomography angiography vs 3 T black-blood cardiovascular magnetic resonance for identification of symptomatic carotid plaques.

BACKGROUND: The purpose of this prospective study was to perform a head-to-head comparison of the two methods most frequently used for evaluation of carotid plaque characteristics: Multi-detector Computed Tomography Angiography (MDCTA) and black-blood 3 T-cardiovascular magnetic resonance (bb-CMR) with respect to their ability to identify symptomatic carotid plaques. METHODS: 22 stroke unit patients with unilateral symptomatic carotid disease and >50% stenosis by duplex ultrasound underwent MDCTA and bb-CMR (TOF, pre- and post-contrast fsT1w-, and fsT2w- sequences) within 15 days of symptom onset. Both symptomatic and contralateral asymptomatic sides were evaluated. By bb-CMR, plaque morphology, composition and prevalence of complicated AHA type VI lesions (AHA-LT6) were evaluated. By MDCTA, plaque type (non-calcified, mixed, calcified), plaque density in HU and presence of ulceration and/or thrombus were evaluated. Sensitivity (SE), specificity (SP), positive and negative predictive value (PPV, NPV) were calculated using a 2-by-2-table. RESULTS: To distinguish between symptomatic and asymptomatic plaques AHA-LT6 was the best CMR variable and presence / absence of plaque ulceration was the best CT variable, resulting in a SE, SP, PPV and NPV of 80%, 80%, 80% and 80% for AHA-LT6 as assessed by bb-CMR and 40%, 95%, 89% and 61% for plaque ulceration as assessed by MDCTA. The combined SE, SP, PPV and NPV of bb-CMR and MDCTA was 85%, 75%, 77% and 83%, respectively. CONCLUSIONS: Bb-CMR is superior to MDCTA at identifying symptomatic carotid plaques, while MDCTA offers high specificity at the cost of low sensitivity. Results were only slightly improved over bb-CMR alone when combining both techniques.

Rôle de l'inactivité physique dans l'étiologie de l'obésité [The role of physical inactivity in the etiology of obesity].

The activity-related energy expenditure mainly depends upon body weight, the type, intensity and duration of the exercise as well as the mechanical efficiency with which the subjects perform the work. Controversy still exist about the role of hypoactivity in the aetiology of obesity both in adolescence and adulthood. A number of experimental studies based on indirect assessment of physical activity (such as pedometers, accelerometers, cinematography and heart rate) have demonstrated a significant reduction in spontaneous physical activity in certain obese groups as compared to lean matched controls. On the other hand, direct measurements of energy expenditure (by indirect calorimetry) have shown a linear relationship between body weight and 24-hour (or activity-related) energy expenditure. It therefore appears that despite the greater placidity characterising some grossly obese subjects, the absolute rate of energy expenditure - particularly in weight bearing activities - is not lower than in lean subjects, since the hypoactivity does not fully compensate for the greater gross energy cost of a given activity.

Rapid diagnostic tests for the home-based management of malaria, in a high-transmission area.

Rapid diagnostic tests (RDT) are sometimes recommended to improve the home-based management of malaria. The accuracy of an RDT for the detection of clinical malaria and the presence of malarial parasites has recently been evaluated in a high-transmission area of southern Mali. During the same study, the cost-effectiveness of a 'test-and-treat' strategy for the home-based management of malaria (based on an artemisinin-combination therapy) was compared with that of a 'treat-all' strategy. Overall, 301 patients, of all ages, each of whom had been considered a presumptive case of uncomplicated malaria by a village healthworker, were checked with a commercial RDT (Paracheck-Pf). The sensitivity, specificity, and positive and negative predictive values of this test, compared with the results of microscopy and two different definitions of clinical malaria, were then determined. The RDT was found to be 82.9% sensitive (with a 95% confidence interval of 78.0%-87.1%) and 78.9% (63.9%-89.7%) specific compared with the detection of parasites by microscopy. In the detection of clinical malaria, it was 95.2% (91.3%-97.6%) sensitive and 57.4% (48.2%-66.2%) specific compared with a general practitioner's diagnosis of the disease, and 100.0% (94.5%-100.0%) sensitive but only 30.2% (24.8%-36.2%) specific when compared against the fulfillment of the World Health Organization's (2003) research criteria for uncomplicated malaria. Among children aged 0-5 years, the cost of the 'test-and-treat' strategy, per episode, was about twice that of the 'treat-all' (U.S.$1.0. v. U.S.$0.5). In older subjects, however, the two strategies were equally costly (approximately U.S.$2/episode). In conclusion, for children aged 0-5 years in a high-transmission area of sub-Saharan Africa, use of the RDT was not cost-effective compared with the presumptive treatment of malaria with an ACT. In older patients, use of the RDT did not reduce costs. The question remains whether either of the strategies investigated can be made affordable for the affected population.