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.

Right coronary artery flow velocity and volume assessment with spiral K-space sampled breathhold velocity-encoded MRI at 3 tesla: accuracy and reproducibility.

PURPOSE: To evaluate accuracy and reproducibility of flow velocity and volume measurements in a phantom and in human coronary arteries using breathhold velocity-encoded (VE) MRI with spiral k-space sampling at 3 Tesla. MATERIALS AND METHODS: Flow velocity assessment was performed using VE MRI with spiral k-space sampling. Accuracy of VE MRI was tested in vitro at five constant flow rates. Reproducibility was investigated in 19 healthy subjects (mean age 25.4 +/- 1.2 years, 11 men) by repeated acquisition in the right coronary artery (RCA). RESULTS: MRI-measured flow rates correlated strongly with volumetric collection (Pearson correlation r = 0.99; P < 0.01). Due to limited sample resolution, VE MRI overestimated the flow rate by 47% on average when nonconstricted region-of-interest segmentation was used. Using constricted region-of-interest segmentation with lumen size equal to ground-truth luminal size, less than 13% error in flow rate was found. In vivo RCA flow velocity assessment was successful in 82% of the applied studies. High interscan, intra- and inter-observer agreement was found for almost all indices describing coronary flow velocity. Reproducibility for repeated acquisitions varied by less than 16% for peak velocity values and by less than 24% for flow volumes. CONCLUSION: 3T breathhold VE MRI with spiral k-space sampling enables accurate and reproducible assessment of RCA flow velocity.

Incidence and risk factors for Contegra graft infection following right ventricular outflow tract reconstruction: long-term results.

OBJECTIVES: The aim of this study was to evaluate the risk factors associated with Contegra graft (Medtronic Minneapolis, MN, USA) infection after reconstruction of the right ventricular outflow tract. METHODS: One hundred and six Contegra grafts were implanted between April 1999 and April 2010 for the Ross procedure (n = 46), isolated pulmonary valve replacement (n = 32), tetralogy of Fallot (n = 24), double-outlet right ventricle (n = 7), troncus arteriosus (n = 4), switch operation (n = 1) and redo of pulmonary valve replacement (n = 2). The median age of the patients was 13 years (range 0-54 years). A follow-up was completed in all cases with a median duration of 7.6 years (range 1.7-12.7 years). RESULTS: There were 3 cases of in-hospital mortality. The survival rate during 7 years was 95.7%. Despite the lifelong endocarditis prophylaxis, Contegra graft infection was diagnosed in 12 (11.3%) patients at a median time of 4.4 years (ranging from 0.4 to 8.7 years). Univariate analysis of preoperative, perioperative and postoperative variables was performed and the following risk factors for time to infection were identified: female gender with a hazard ratio (HR) of 0.19 (P = 0.042), systemic-to-pulmonary shunt (HR 6.46, P < 0.01), hypothermia (HR 0.79, P = 0.014), postoperative renal insufficiency (HR 11.97, P = 0.015) and implantation of permanent pacemaker during hospitalization (HR 5.29, P = 0.075). In 2 cases, conservative therapy was successful and, in 10 patients, replacement of the infected valve was performed. The Contegra graft was replaced by a homograft in 2 cases and by a new Contegra graft in 8 cases. Cox's proportional hazard model indicated that time to graft infection was significantly associated with tetralogy of Fallot (HR 0.06, P = 0.01), systemic-to-pulmonary shunt (HR 64.71, P < 0.01) and hypothermia (HR 0.77, P < 0.01). CONCLUSION: Contegra graft infection affected 11.3% of cases in our cohort, and thus may be considered as a frequent entity that can be predicted by both intraoperative and early postoperative factors. After the diagnosis of infection associated with the Contegra graft was confirmed, surgical treatment was the therapy of choice.

Parallel Research, Multiple Intellectual Property Right Protection Instruments, and the Correlation among R&D Projects, September 2005

The choice of a research path in attacking scientific and technological problems is a significant component of firms’ R&D strategy. One of the findings of the patent races literature is that, in a competitive market setting, firms’ noncooperative choices of research projects display an excessive degree of correlation, as compared to the socially optimal level. The paper revisits this question in a context in which firms have access to trade secrets, in addition to patents, to assert intellectual property rights (IPR) over their discoveries. We find that the availability of multiple IPR protection instruments can move the paths chosen by firms engaged in an R&D race toward the social optimum.

Transhepatic ipsilateral right portal vein embolization extended to segment IV: improving hypertrophy and resection outcomes with spherical particles and coils.

PURPOSE: To analyze outcomes after right portal vein embolization extended to segment IV (right PVE + IV) before extended right hepatectomy, including liver hypertrophy, resection rates, and complications after embolization and resection, and to assess differences in outcomes with two different particulate embolic agents. MATERIALS AND METHODS: Between 1998 and 2004, transhepatic ipsilateral right PVE + IV with particles and coils was performed in 44 patients with malignant hepatobiliary disease, including metastases (n = 24), biliary cancer (n = 14), and hepatocellular carcinoma (n = 6). Right PVE + IV was considered if the future liver remnant (FLR; segments II/III with or without I) was less than 25% of the total estimated liver volume (TELV). Tris-acryl microspheres (100-700 microm; n = 21) or polyvinyl alcohol (PVA) particles (355-1,000 microm; n = 23) were administered in a stepwise fashion. Smaller particles were used to occlude distal branches, followed by larger particles to occlude proximal branches until near-complete stasis. Coils were then placed in secondary portal branches. Computed tomographic volumetry was performed before and 3-4 weeks after right PVE + IV to assess FLR hypertrophy. Liver volumes and postembolization and postoperative outcomes were measured. RESULTS: After right PVE + IV with PVA particles, FLR volume increased 45.5% +/- 40.9% and FLR/TELV ratio increased 6.9% +/- 5.6%. After right PVE + IV with tris-acryl microspheres, FLR volume increased 69.0% +/- 30.7% and FLR/TELV ratio increased 9.7% +/- 3.3%. Differences in FLR volume (P = .0011), FLR/TELV ratio (P = .027), and resection rates (P = .02) were statistically significant. Seventy-one percent of patients underwent extended right hepatectomy (86% after receiving tris-acryl microspheres, 57% after receiving PVA). Thirteen patients (29%) did not undergo resection (extrahepatic spread [n = 9], inadequate hypertrophy [n = 3], other reasons [n = 1]). No patient developed postembolization syndrome or progressive liver insufficiency after embolization or resection. One death after resection occurred as a result of sepsis and hemorrhage. Median hospital stays were 1 day after right PVE + IV and 7 days after resection. CONCLUSION: Transhepatic ipsilateral right PVE + IV with use of particles and coils is a safe, effective method for inducing contralateral hypertrophy before extended right hepatectomy. Embolization with small spherical particles provides improved hypertrophy and resection rates compared with larger, nonspherical particles.

Quality of life transformations before and after kidney transplantation: A prospective qualitative study.

The aim of this IRB-approved study was to analyze prospectively quality of life (QOL) and psychological changes in 30 ESRD patients before and after kidney transplantation (KT). Semi-structured interviews were conducted after inclusion on the waiting list (A). Follow-up interviews were performed 6 months later with patients still awaiting KT (B6, n= 15), and with transplant recipients 6, 12 and 24 months after KT (C6, n=15; C12, n=15; C24, n=14). Qualitative thematic analysis was performed. A: All patients reported loss of freedom, 87% tried to maintain normality; 57% modified medical directives. All mentioned emotional fragility, negative thoughts (43%), and suicidal thoughts (20%) related to loss of QOL from dialysis (D), and professional tension (26%). B6: 40% reported no change compared to baseline, while 60% mentioned increase of illness intrusiveness, 46% D side effects, 40% communication problems, and 33% concerns about the waiting list handling. Fear of emotional breakdown (40%), couple problems (47%), and worsened professional difficulties (20%) were reported. C6: All patients reported recovery of QOL and concerns about acute rejection. 73% were anxious about laboratory results. 93% felt dependent on immunosuppressants (IS), 47% reported difficulties coping with their regimen, and 47% were concerned about side effects; 67% had resumed work, but medical constraints led 40% to professional stigmatization. C12: All enjoyed good QOL. Adherence to IS was mandatory (100%). All were aware of the limited long-term graft survival and 47% anxious about a possible return to D. 60% underlined positive life value; 47% resumed a full time job; 40% were on social security. C24: Good QOL was underlined (86%). Patients stated they would prefer re-TX to resuming D (71%). Post-TX health problems were mentioned (64%); increase of creatinine levels induced fear (36%). 79% complained about side effects. 64% reported changes in life values. This study reveals positive QOL and psychological transformations after KT, which are associated with positive changes related to graft survival and freedom from D. Psychological follow-up should be offered to patients who face relapsing ESRD or post-TX co-morbidities.

Not the right job but a secure one : over-education and temporary employment in France, Italy and Spain

Resorting to four waves of the European Community Household Panel, this research explores the association between temporary employment and the likelihood of being over-educated. Such an association has been largely ignored by the literature explaining over-education, more inclined to attribute such a mismatch to the system of education. Selecting three similarly standarised and stratified systems of education (France, Italy and Spain) and controlling for many other variables likely to affect over-education, like gender, age, tenure, job change, firm size or sector, the paper demonstrates that such an association between temporary employment and over-education exists. Being a stepping stone towards a more stable and adjusted position in the labour market, holding a temporary employment may be associated to a higher likelihood of being over-educated. Such an association is more likely in Italy and France. Yet, the opposite sign prevails where permanent employment becomes such a valuable asset as to make individuals trade human capital by employment security. This is the case of Spain.

Frequency and impact of autosomal dominant polycystic kidney disease in the Seychelles (Indian Ocean).

BACKGROUND: As little such data is available in African populations, we investigated the prevalence of ADPKD and the impact of the disease in the Seychelles islands, where approximately 65% of the population is of African descent and 30% of Caucasian or mixed descent. METHODS: Prevalent cases were identified over a 3-year period by requesting all the doctors in the country (most of them are employed within a national health system) to refer all presumed or confirmed cases and by systematically examining the family members of all confirmed cases. The diagnosis was based on standard criteria including ultrasonographic findings and family history. RESULTS: Forty-two cases were identified in this population of 74,331 inhabitants, a total prevalence (per 100,000 total population) of 57 (95% CI, 41-76). All but one of the cases were of Caucasian descent so that the prevalence rates of the disease in the populations of Black and Caucasian descents were respectively 2 (0-11) and 184 (132-249). The prevalence rates of the gene(s) carriers were estimated to be 75 (45-117) in the total population respectively 6 (0-33) and 236 (140-372) in the Black and Caucasian populations. Haplotype analysis in 58 cases from three families showed a common DNA fragment in all affected individuals. Cases had significantly higher blood pressure compared to the general population and 21% had serum creatinine higher than 120 mumol/l. Among the established pedigrees, mean age of death between 1960 and 1995 (haemodialysis was introduced in 1992) was younger in subjects with than those without ADPKD (50.5 vs 67.7 years; P < 0.001). CONCLUSIONS: In the Seychelles, ADPKD clusters in the Caucasian population (possibly a founder effect), is rare in individuals of black descent, and is associated with substantial clinical and survival impact.

Bicarbonate de sodium pour ralentir la progression de la maladie rénale chronique [Sodium bicarbonate to slow the progression of chronic kidney disease].

Metabolic acidosis is a prevalent complication in moderate and late stages of chronic kidney disease (CKD). It is established that the correction of metabolic acidosis may improve metabolic bone disorders and protein degradation in the skeletal muscle, two characteristic complications of patients with advanced CKD. In the last 18 months, three randomized controlled trials have drawn the attention on a novel indication to correct metabolic acidosis in these patients, i.e., halting CKD progression. These data show that sodium bicarbonate, a cheap and easily manageable treatment, may delay the progression of CKD and the need of a renal replacement therapy such as dialysis or kidney transplantation.

Right Hepatectomy in Patients over 70 Years of Age: An Analysis of Liver Function and Outcome.

BACKGROUND: As a consequence of the increase in life expectancy, hepatobiliary surgeons have to deal with an emerging aged population. We aimed to analyze the liver function and outcome after right hepatectomy (RH) in patients over 70 years of age. METHODS: From January 2006 to December 2009, we prospectively collected data of 207 consecutive elective hepatectomies. In patients who had RH, cardiac risk was assessed by a dedicated preoperative workup. Liver failure (LF) was defined by the "fifty-fifty" criteria at postoperative day 5 (POD) and morbidity by the Clavien-Dindo classification. Liver function tests (LFTs) and short-term outcome were retrospectively analyzed in patients over (elderly group, EG) and younger (young group, YG) than 70 years of age. RESULTS: Eighty-seven consecutive RH were performed during the study period. Indication for surgery included 90 % malignancy in 47 % of patients requiring preoperative chemotherapy. ASA grade > 2 (44 vs. 16 %, p = 0.027), ischemic heart disease (17 vs. 5 %, p = 0.076), and preoperative cardiac failure (26 vs. 2 %, p < 0.001) were more frequent in the EG (n = 23) than in the YG (n = 64). Both groups were similar regarding rates of normal liver parenchyma, chemotherapy and intraoperative parameters. The overall morbidity rates were comparable, but the serious complication (grades III-V) rate was relatively higher in the EG (39 vs. 25 %, p = 0.199), particularly in patients with diabetes mellitus (100 vs. 29 %, p = 0.04) and those who had additional nonhepatic surgery (67 vs. 35 %, p = 0.110) and transfusions (44 vs. 30 %, p = 0.523). The 90-day mortality rate was similar (9 % in the EG vs. 3 % in the YG, p = 0.28) and was related to heart failure in the EG. LFTs showed a similar trend from POD 1 to 8, and patients ≥70 years of age had no liver failure. CONCLUSIONS: Age ≥70 years alone is not a contraindication to RH. However, major morbidity is particularly higher in the elderly with diabetes. This high-risk group should be closely monitored in the postoperative course. Liver function is not altered in the elderly patient after RH.

Young people, parents and radical right voting: The case of the Swiss People's Party

It is commonly found that young people tend to adopt the political party choice of their parents. However, far less is known about the applicability of this theory when investigating radical right support. Using the Swiss Household panel data (1999e2007), this study empirically identifies the relationship between parents' preference for the Swiss radical right party SVP and their attitudes toward immigrants and the EU, and their offspring's preference for the SVP. Disaggregating fathers' and mothers' influence reveals that in particular, mothers' SVP support plays a role in SVP support among young people, even after controlling for educational similarities. We also demonstrate that girls are more likely to be influenced by their mothers than are boys. Furthermore, parents' negative attitudes toward the EU exert a positive influence on their children's radical right voting, independent of their voting pattern.

Is a Combined School/Public Library Right for Your Community?

This document is intended to assist Iowa communities in making informed decisions on combining school and public library services. It provides decision-makers with a means of assessing the feasibility of establishing a combined library and, if the decision is made to proceed, with a Planning Guide that addresses the many areas of library operations that need to be considered if the combined library is to be successful. Alternatives to combining libraries exist. Contracted services provide one such option. There are many areas where school and public libraries can and should collaborate in order to provide better service to the community. These alternatives are also outlined in this document.

La dénervation rénale unilatérale et le système kallikréine-bradykinine rénal chez le rat [Unilateral renal denervation and the renal kallikrein-bradykinin system in the rat].

AIM: The antihypertensive effect of renal denervation in hypertensive patients is partially explained by increased tubular natriuresis. To study the possible contribution of the kallikrein-kinin system (KKS) to this natriuretic effect in rats, we measured kallikrein activity (KA) and bradykinin concentrations (BK) in plasma and tissues. METHODS: To measure KA, we adapted and validated an enzymatic assay that cleaves para-nitroaniline (pNA) from the tripeptide H-D-Pro-Phe-Arg-pNA. The coefficients of variation (CV) within- and between-assays were less than 8% for plasma and tissue KA (plasma n=6 and 13; tissue n=4). Linear results for serially diluted samples confirmed the assay specificity. Tissue BK determinations were based on an established assay for plasma BK: tissue was homogenized and kinins extracted in ethanol, and BK was isolated by high-performance (HPLC) liquid chromatography and quantitated by radioimmunassay. Within- and between-assay CV for plasma BK were 18% (n=8 and n=35, respectively) and for BK in various tissues less than 16% (n=5-8). RESULTS: In male Wistar rats (n=3), plasma BK was 8.2±6.6 fmol/mL (mean±SD), and tissue BK (fmol/g) in 14 tested organs varied between brain (14±3) and submaxillary gland (521±315). Six days after left-sided unilateral renal denervation, left renal tissue BK (89±9) was not different from right renal BK (75±23). Similarly, KA was comparable in the two kidneys (left 18.0±1.5, right 15.8±1.4μkat/g). CONCLUSION: Any possible effect of unilateral renal denervation on the kidney's KKS would have to be bilateral.