We describe factors associated with immunosuppression compliance after kidney transplantation and examine relationships between compliance with allograft outcomes and costs. Medicare claims for ...immunosuppression in 15 525 renal transplant recipients with at least 1 year of graft function were used to calculate compliance as medication possession ratio. Compliance was categorized by quartiles as poor, fair, good and excellent. We modeled adjusted associations of clinical factors with the likelihood of persistent compliance by multiple logistic regressions (aOR), and estimated associations of compliance with subsequent graft and patient survival with Cox proportional hazards (aHR). Adolescent recipients aged 19–24 years were more likely to be persistently noncompliant compared to patients aged 24–44 years (aOR 1.49 1.06–2.10). Poor (aHR 1.80 1.52–2.13) and fair (aHR 1.631.37–1.93) compliant recipients were associated with increased risks of allograft loss compared to the excellent compliant recipients. Persistent low compliance was associated with a $12 840 increase in individual 3‐year medical costs. Immunosuppression medication possession ratios indicative of less than the highest quartile of compliance predicted increased risk of graft loss and elevated costs. These findings suggest that interventions to improve medication compliance among kidney transplant recipients should emphasize the benefits of maximal compliance, rather than discourage low compliance.
In this study of US Medicare claims, patient non‐compliance with immunosuppresion medications not only increased the risk of graft failure and death, but was also associated with an average increase in health care costs of almost $13,000.
Simultaneous heart–kidney transplantation (SHK) remains uncommon in the US. We examined outcomes of SHK compared to heart transplant alone (HTA) and deceased donor kidney transplant (DDKT).
Data from ...OPTN/UNOS heart and kidney data bases were used to identify 16 710 HTA, 263 SHK transplants and 68 833 DDK transplants between 1998 and 2007. Outcomes included patient survival (PS), acute cardiac and renal rejection and renal graft survival (rGS).
The adjusted risk of death was 44% lower with SHK compared to HTA. Over half of SHK were performed in cases where pretransplant dialysis was not initiated. In these cases, there was no significant difference in the risk of death between SHK and HTA (HR 1.01; 95% CI 0.67–1.50).
Recipients of SHK had worse 1‐year rGS and PS and had a higher relative risk of overall renal graft loss compared to DDKT recipients. One‐year rates of cardiac (14.5%) and renal (6.5%) rejection were lower in SHK compared to HTA and DDKT, respectively.
Recipients of SHK had a lower adjusted risk of death compared to HTA recipients, particularly in patients who required pretransplant dialysis. These data suggest that SHK should be considered in heart transplant candidates with renal failure requiring dialysis, whereas the utility of SHK in cases of renal failure not requiring dialysis warrants further study.
Simultaneous heart kidney transplant was associated with superior patient survival compared to heart transplant only, but with similar overall renal allograft survival and superior functional renal graft survival compared deceased donor kidney only transplant.
We describe factors associated with poor compliance and dose reductions and examine the relative impact of compliance, dose reduction and discontinuation on graft outcome.
Medicare claims for MMF in ...7062 deceased donor renal recipients with at least 1 year of graft function were used to calculate compliance and dose reductions. Compliance was modeled using medication possession ratio to define quartiles for poor, low, medium and high compliance. The relative impact of compliance, dose reduction and discontinuation on graft outcome was assessed with Cox proportional hazards.
Pediatric (Age 0–18, Odds ratio = 1.71, 95% CI 1.11–2.63, p = 0.014) and adolescent recipients (19–24, 1.57, 1.23–2.00, p < 0.001) were more likely poorly compliant compared to adults age 25–44. Poor compliance was also associated with physical limitations, hypertension, delayed graft function, rejection, infection and GI conditions. Poor (1.43, 1.11–1.84, p = 0.005) and low (1.46, 1.13–1.88, p = 0.004) compliance was associated with an increased hazard of graft loss as was >50% dose reduction (1.69, 1.15–2.50, p = 0.008) and discontinuation (8.34, 6.85–10.2, p < 0.001).
Medication possession ratios lower than the 3‐year mean were associated with an increased risk of graft loss. These results may indicate that interventions to improve compliance among kidney transplant recipients should strive for high rather than discourage low compliance.
Poor immunosuppression compliance as measured using the frequency of prescription filling was associated with increased risk of kidney allograft loss. See also editorial by Abbott in this issue on page 2647.
Stat3 is a member of the Janus-activated kinase/STAT signalling pathway. It normally resides in the cytoplasm and can be activated through phosphorylation. Activated Stat3 (p-Stat3) translocates to ...the nucleus to activate the transcription of several molecules involved in cell survival and proliferation. The constitutive activation of Stat3 has been shown in various types of malignancies, and its expression has been reported to indicate a poor prognosis. However, the correlation between the constitutive activation of Stat3 and the prognosis of cervical cancer patients has not been reported.
The immunohistochemical analysis of p-Stat3 expression was performed on tissues from 125 cervical squamous-cell carcinoma patients who underwent extended hysterectomy and pelvic lymphadenectomy, and the association of p-Stat3 expression with several clinicopathological factors and survival was investigated.
Positive p-Stat3 expression was observed in 71 of 125 (56.8%) cases and was significantly correlated with lymph node metastasis, lymph vascular space invasion, and large tumour diameter (>4 cm) by Fisher's exact test. Kaplan-Meier survival analysis showed that p-Stat3 expression was statistically indicative of a poor prognosis for overall survival (P=0.006) and disease-free survival (P=0.010) by log-rank test.
These data showed that p-Stat3 expression in cervical cancer acts as a predictor of poor prognosis.
We have cited more than 23 studies showing that de novo development of anti-HLA antibodies is associated with increased acute and chronic rejection and decreased graft survival in kidney, heart, ...lung, liver, and corneal transplants. Antibodies to both HLA class I and class II antigens seem to be detrimental. Antibodies of the IgG isotype and possibly the IgM isotype were clinically relevant. Most studies showed that donor-specific antibodies were associated with rejection and graft loss. Therefore, HLA antibodies provide a clinical readout for patient alloreactivity that may have the ability to distinguish graft dysfunction due to immunologic and nonimmunologic causes. Antibody may act as a critical trigger for rejection of allografts and may serve as an early indicator of a slowly smoldering chronic rejection that is not manifested at a given time by biochemical measures such as serum creatinine levels. The effectiveness of various drugs on chronic rejection should be evaluable by their effects on HLA antibody production. We predict that recently developed ELISA and flow cytometry techniques using purified HLA antigen will increase the clinical relevance of posttransplantation HLA antibody monitoring by (1) allowing the detection of low levels of donor antibody; (2) easily distinguishing the isotype and target (HLA class I or class II) of the antibodies; and (3) correlating the antibody with specific graft pathology.
Parkinson's disease is a neurodegenerative disorder characterized pathologically by the loss of nigrostriatal dopamine neurons that project from the substantia nigra in the midbrain to the putamen ...and caudate nuclei, leading to the clinical features of bradykinesia, rigidity, and rest tremor. Oxidative stress from oxidized dopamine and related compounds may contribute to the degeneration characteristic of this disease.
To investigate a possible role of the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4) in protection from oxidative stress, we investigated GPX4 expression in postmortem human brain tissue from individuals with and without Parkinson's disease. In both control and Parkinson's samples, GPX4 was found in dopaminergic nigral neurons colocalized with neuromelanin. Overall GPX4 was significantly reduced in substantia nigra in Parkinson's vs. control subjects, but was increased relative to the cell density of surviving nigral cells. In putamen, GPX4 was concentrated within dystrophic dopaminergic axons in Parkinson's subjects, although overall levels of GPX4 were not significantly different compared to control putamen.
This study demonstrates an up-regulation of GPX4 in neurons of substantia nigra and association of this protein with dystrophic axons in striatum of Parkinson's brain, indicating a possible neuroprotective role. Additionally, our findings suggest this enzyme may contribute to the production of neuromelanin.
Multiple sclerosis (MS) is a central nervous system disease associated with irreversible progression of disability, which imposes a substantial socioeconomic onus. The objective of this study was to ...determine the economic impact of multiple sclerosis from the Brazilian household and healthcare system perspectives. Secondary objectives were to assess the impact of fatigue on daily living and health-related quality of life (HRQL) of MS patients.
This is a cross-sectional study in which Brazilian eligible patients attending eight major MS specialized sites answered an interview capturing data on demographics, disease characteristics and severity, comorbidities, resource utilization, fatigue, utilities and health-related quality of life from November/2011 to May/2012 . Costs were assessed considering a prevalence-based approach within 1 year of resource consumption and were estimated by multiplying the amount used by the corresponding unit cost. Patients were classified as having mild, moderate or severe disability according to the Expanded Disability Status Scale (EDSS).
In total, 210 patients who met eligibility criteria were included, 40 % had mild, 43 % moderate and 16 % severe disability; disability level was missing for 1 %. The average total direct cost per year was USD 19,012.32 (SD = 10,465.96), and no statistically significant differences were not observed according to MS disability level (p = 0.398). The use of disease modifying therapies (DMTs) corresponded to the majority of direct expenditures, especially among those patients with lower levels of disability, representing around 90 % of total costs for mild and moderate MS patients. It was also observed that expenses with medical (except DMTs) and non-medical resources are higher among patients with more severe disease. Worsening disability also had an important influence on health-related quality of life and self-perceived impact of fatigue on daily living.
Our data demonstrates the significant economic impact of MS on both Brazilian household and health system, in terms of DMTs and other disease management costs. When patients move upwards on the disease severity scale, costs with health resources other than drugs are significantly increased.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims
Patient‐performed lung ultrasound (LUS) in a heart failure (HF) telemedicine model may be used to monitor worsening pulmonary oedema and to titrate therapy, potentially reducing HF admission. ...The aim of the study was to assess the feasibility of training HF patients to perform a LUS self‐exam in a telemedicine model.
Methods and results
A pilot study was conducted at a public hospital involving subjects with a history of HF. After a 15 min training session involving a tutorial video, subjects performed a four‐zone LUS using a handheld ultrasound. Exams were saved on a remote server and independently reviewed by two LUS experts. Studies were determined interpretable according to a strict definition: the presence of an intercostal space, and the presence of A‐lines, B‐lines, or both. Subjects also answered a questionnaire to gather feedback and assess self‐efficacy. The median age of 44 subjects was 53 years (range, 36–64). Thirty (68%) were male. Last educational level attained was high school or below for 31 subjects (70%), and one‐third used Spanish as their preferred language. One hundred fifty of 175 lung zones (85%) were interpretable, with expert agreement of 87% and a kappa of 0.49. 98% of subjects reported that they could perform this LUS self‐exam at home.
Conclusions
This pilot study reports that training HF patients to perform a LUS self‐exam is feasible, with reported high self‐efficacy. This supports further investigation into a telemedicine model using LUS to reduce emergency department visits and hospitalizations associated with HF.
We investigated graft and patient survival implications of simultaneous pancreas kidney (SPK) transplant from old donors. Data describing patients with type 1 diabetes mellitus listed for an SPK ...transplant from 1994 to 2005 were drawn from Organ Procurement and Transplant Network registries. Allograft survival, patient survival and long‐term survival expectations among SPK recipients from young (age <45 years) and old (age ≥45 years) donors were modeled by multivariate regression. We also examined predictors of reduced early access to young donor transplants. Of 16 496 eligible SPK candidates, 8850 patients (53.6%) received an SPK transplant and 776 (8.8%) of these transplants were from old donors. Reasonable 5‐year, death‐censored kidney (77.8 %) and pancreas (71.3%) survivals were achieved with old donors. SPK transplantation from both young and old donors predicted lower mortality compared to continued waiting. An additional expected wait of 1.5 years for a young donor equalized long‐term survival expectations to that achieved with use of old donors. Early allocation of young donor transplants declined in the more recent era and varied by region, candidate age, blood type and sensitization. We conclude that old SPK donors should be considered for patients with decreased access to young donor transplants. Prospective evaluation of this practice is needed.
This retrospective study of UNOS data suggests that older simultaneous pancreas kidney transplant donors offer reasonable organ‐specific graft survivals and an important patient survival benefit compared to long‐term waiting, arguing for consideration of older donors in candidates with decreased access to standard transplants.
This study determined the local equivalence ratio of a CH
4/air mixture in a laminar premixed flame using spark-induced breakdown spectroscopy (SIBS) with a fiber-coupled intensified charge coupled ...device (ICCD) spectrometer. Spectrally resolved emission spectra of plasma generated by a spark plug were investigated for their potential to measure local fuel concentrations in a premixed mixture. The influence of key parameters, such as the camera gate timing and spark energy, on the intensity of radical emission was illustrated. The intensity ratio of CN/NH had a greater sensitivity to the equivalence ratio than did that of CN/OH, and the local equivalence ratio could be obtained with high resolution by measuring the local intensity ratios of CN/NH. Moreover, a spark-plug sensor with an optical fiber was developed for application in spark-ignition engines. The atomic emission intensity during the breakdown and arc phases of spark discharge could be obtained using the fiber-optic spark-plug sensor. The H
α/O intensity showed better linearity than the CN/NH intensity ratio in lean mixtures. The results presented here confirm the use of SIBS as a diagnostic tool for spark-ignition engines.
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