Unmasking Verbal Defensiveness: The Role of Psychological Threat in Sentence Completion Tests.

Shedding light on the validity of sentence completion test (SCT) verbal defensiveness as an index of defensive behavior, the current two-part study examined the relationship between psychological threat and verbal defensiveness among military security and mission-critical team candidates using SCTs. Our study showed that as the threatening nature of SCT stems increased, defensive responses also increased, substantiating the link between psychological threat and defensive behavior. In addition, expert ratings of stem content revealed moderately strong relationships with defensive responses across two different SCTs, irrespective of their structural characteristics. In contrast to previous studies using total verbal defensiveness scores, we examined specific defensive response types and their associations with stem threat ratings, finding that omissions, denial, and comments about the test were linked to stem threat levels. Lastly, our study extends the application of the SCT verbal defensiveness index beyond specialized personnel selection, finding no significant differences in verbal defensiveness based on gender or military status. Overall, these findings contribute to a comprehensive understanding of defensive behavior and its contextual variations.

Anemia has a negative impact on self-rated health in kidney transplant recipients with well-functioning grafts: findings from an 8-year follow-up study.

PURPOSE: Anemia is a predictor of mortality and of self-rated health (SRH). However, studies on the relationship between SRH and changes in hemoglobin (Hb) value over time stratified by chronic kidney disease (CKD) stages are lacking. The aim is to explore whether a change in Hb-value over time associates with SRH at up to 8-year follow-up, stratified for CKD stages. METHODS: A prospective study with a baseline measurement between the 3rd and 12th month after KT was performed on 337 consecutive patients. Demographic and clinical data were retrieved from medical records. CKD stages were estimated using the CKD-EPI formula and divided into two groups: CKD1-2 and CKD3-5. Generalized estimating equations (GEE) were performed to identify associations of SRH at follow-up in both CKD groups. RESULTS: Male gender, new-onset diabetes mellitus after KT (NODAT), a decrease in estimated glomerular filtration rate (eGFR) and Hb-value over time contributed significantly to the GEE model on SRH at follow-up in CKD1-2. For SRH at follow-up in CKD3-5, older age, male gender and chronic renal allograft dysfunction (CRAD) contributed significantly to the GEE model. CONCLUSIONS: At up to 8-year follow-up, male gender, NODAT, a decrease in eGFR and Hb-value over time are associated with poorer SRH in CKD1-2. In such patients, we suggest monitoring slight deteriorations in eGFR and Hb-values. In CKD3-5, higher age, male gender and higher presence of CRAD are associated with poorer SRH at up to 8-year follow-up. In these patients, adequate treatment would slow down CRAD progression.

Risk factors associated with efficacy outcomes in kidney transplantation: analysis of a contemporary cohort of patients from the A2309 trial.

A multivariate analysis of risk factors for a composite endpoint of treated biopsy proven acute rejection (BPAR), graft loss, death, or loss to follow-up was undertaken in a cohort of 833 de novo kidney transplants from an international trial (A2309). Patients were randomized to everolimus (trough concentration 3-8 ng/mL or 6-12 ng/mL) with reduced cyclosporine or to mycophenolic acid (MPA) with standard cyclosporine. Cox proportional hazard modeling, incorporating a range of recipient, donor, and transplant variables, showed that treatment group (i.e., randomization to either everolimus 3-8 ng/mL or 6-12 ng/mL vs. MPA) showed no significant association with risk of the composite efficacy endpoint at either month 12 or month 24 (significance level 0.05). At month 12, Cox proportional hazard modeling showed that black race (hazard ratio (HR) 1.68; 95% confidence interval (CI) 1.08, 2.60; p=0.021), increasing donor age in years (HR 1.01; 95% CI 1.00, 1.03; p=0.022), and delayed graft function (DGF; yes vs. no, HR 2.75; 95% CI 1.82, 4.16; p< 0.001) predicted higher risk of the composite endpoint; female gender (female vs. male HR 0.67; 95% CI 0.48, 0.93; p=0.017), and < 3 HLA mismatches (HR 0.70; 95% CI 0.50, 0.99; p=0.049) were associated with reduced risk. At month 24, increasing recipient age in years (HR 0.99; 95% CI 0.98, 0.99; p=0.028), black recipient race (HR 1.62; 95% CI 1.09, 2.42; p=0.018), increasing donor age in years (HR 1.01; 95% CI 1.00, 1.02; p=0.008) and delayed graft function (DGF) (HR 2.60; 95% CI 1.78, 3.82; p<0.001) were predictive of risk. These findings show that, independently from type of immunosuppression, organ quality (expressed by DGF), donor age and recipient age, race and gender appear to be the main determinants of efficacy within 2 years after kidney transplantation.

Adherence in patients in the first year after kidney transplantation and its impact on graft loss and mortality: a cross-sectional and prospective study.

AIMS: To explore the predictive value of adherence to their immunosuppressive medication in kidney transplant recipients in the first year after kidney transplantation as a determinant of graft loss and mortality up to 12 years (prospective analysis) and its association with sociodemographic and medical factors and social support (cross-sectional analysis). BACKGROUND: Poor adherence to their immunosuppressive medication in kidney transplant recipients remains the leading preventable cause of poor patient outcomes. DESIGN: Prospective and cross-sectional study. METHODS: At baseline, 325 patients 3-12 months posttransplantation were invited to participate. Adherence was assessed using collateral reports - a combination of patients' self-evaluation and an estimate by their nephrologist. The patients provided sociodemographic and medical data and completed the End-Stage Renal Disease Symptom Checklist and Multidimensional scale of perceived social support. At follow-up (average 7·1 years), data on patients and graft survival were obtained. All data were collected from 2002-2013. Multinomial regression analysis and Cox regression were performed. RESULTS: A total of 297 patients (48·1 (12·8) years, 61·6% men) agreed to participate (response rate 91·4%); 67·4% were considered as fully adherent. Poor adherence was associated with higher risk of graft loss and mortality over 12 years. Female sex, higher education, higher perceived side effects of corticosteroids, better perceived cardiac and renal function and higher perceived family social support in the first year posttransplantation were associated with full adherence to immunosuppressive treatment. CONCLUSIONS: Patients with poor adherence to the immunosuppressive medication in the first year after kidney transplantation showed increased likelihood of graft loss and death over 12 years compared with the adherent patients.

Impact of BioFire® Blood Culture Identification (BCID) panels on antibiotic management of bacteremia due to select organisms.

The purpose of this study was to assess changes in time to optimal therapy (TTOT) for bacteremia due to select organisms after implementation of the BioFire® FilmArray® blood culture identification panels at two community teaching hospitals. TTOT (days) was similar in Pre-BCID compared to BCID1 and BCID2 [(2.48 vs. 2.65, p=0.10); (2.48 vs. 2.37, p=0.27)]. There were no significant differences in time to effective antimicrobial therapy between groups. However, there were significantly more therapy changes and appropriate carbapenem use within 24 hours of the Gram stain result for gram-negative organisms in the BCID2 arm compared to the Pre-BCID arm. Additionally, a significant reduction in the duration of vancomycin for gram-positive organisms was noted in the BCID2 arm compared to the Pre-BCID arm. These findings suggest that the incorporation of the BCID2 panel resulted in changes in prescribing practices, leading to more appropriate antimicrobial utilization in a subset of patients.

Impact of rapid blood culture identification PCR panel on optimal antibiotic use in methicillin-susceptible Staphylococcus aureus bacteremia.

Rapid identification of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia may optimize antibiotic use and clinical outcomes. The study objective was to assess the impact of the BioFire® blood culture identification (BCID) polymerase chain reaction (PCR) panel on antibiotic use and clinical outcomes in patients with MSSA bacteremia. This was a retrospective chart review of adult inpatients with MSSA bacteremia during the pre-PCR (June 2018-December 2019) and post-PCR (June 2020-December 2021) implementation periods. The primary endpoint was the difference between the pre-PCR and post-PCR groups in time to optimal MSSA antibiotic therapy (oxacillin or cefazolin). Secondary endpoints included duration of anti-MRSA antibiotic use, in-hospital mortality, hospital and ICU lengths of stay, duration of bacteremia, and 30-day MSSA-related and all-cause readmissions. Two hundred patients were included in the study (100 per group). Median time to optimal therapy was reduced by 19.9 hours in the post-PCR group (49 vs 29.1 hours, respectively, P < 0.001). PCR implementation was associated with significant reductions in the initiation of empiric anti-MRSA antibiotic therapy (98% vs 84%, P = 0.001), duration of empiric anti-MRSA antibiotic use (44.2 vs 20.9 hours, P < 0.001), and duration of bacteremia (68.6 vs 47.3 hours, P = 0.015). No significant differences in length of stay, in-hospital mortality, or 30-day MSSA-related or all-cause readmissions were observed. In patients with MSSA bacteremia, BCID PCR panel implementation decreased time to optimal MSSA antibiotic therapy, duration of bacteremia, and duration of empiric anti-MRSA antibiotic therapy. IMPORTANCE: In this retrospective study of 200 patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, the implementation of the BioFire® blood culture identification polymerase chain reaction (PCR) panel was associated with a decreased time to optimal MSSA antibiotic therapy and shorter durations of empiric anti-MRSA antibiotic therapy and bacteremia. The findings demonstrate the significant role of rapid PCR testing and routine stewardship review in optimizing antimicrobial therapy and management of MSSA bacteremia.

Self-rated health predicts mortality and graft loss after kidney transplantation: a 10-year follow-up study.

BACKGROUND: This study explored whether self-rated health (SRH) shortly after kidney transplantation (KT) predicts mortality and graft loss at up to 10 years' follow-up. METHODS: A total of 276 patients shortly after successful KT were interviewed. SRH was measured using the first item of the SF-36 questionnaire and divided into three tertiles: poor, average and excellent health. Clinical data were retrieved from medical records. Cox regression was used to identify whether different levels of SRH predicted mortality and graft loss in transplant recipients. The observation period was up to 10 years. RESULTS: Poor SRH (HR 11.1, p < 0.001), average SRH (HR 4.21, p < 0.05), estimated glomerular filtration rate (HR 0.26, p < 0.05) and age (HR 1.04, p < 0.05) were significantly associated with mortality. Similarly, poor SRH (HR 6.4, p < 0.001), average SRH (HR 3.6, p < 0.05), new-onset diabetes mellitus after KT (HR 3.3, p < 0.05) and chronic renal allograft dysfunction (HR 3.7, p < 0.00) were significantly associated with graft loss. CONCLUSION: Poor SRH shortly after transplantation indicates an increased risk of mortality and graft loss at up to 10 years' follow-up. SRH could be an inexpensive and reliable indicator for starting diagnostic and/or treatment strategies. The usefulness of SRH compared to other global clinical measures predicting mortality and graft loss should also be studied.

Factors associated with self-rated health after kidney transplantation: a prospective study.

BACKGROUND: This prospective study explores and compares the relationship between patients' self-rated health (SRH) after kidney transplantation (KT) at different follow-up periods and its medical and nonmedical predictors over time. METHODS: Patients (n = 128) who completed a questionnaire (the SRH question of the SF-36 and the End-Stage Renal Disease Symptom Checklist - Transplantation Module) were enrolled. Clinical data were retrieved from medical files. The sample was stratified into early (n = 89) and late (n = 39) cohorts according to time since KT at baseline. Linear regression was used to identify predictors of SRH at follow-up. RESULTS: In both cohorts, a change in glomerular filtration rate (GFR) over time remained a predictor of SRH; in the early cohort, age was an additional predictor; in the late cohort, a change in transplantation-associated psychological distress over time and the number of late acute rejection episodes during the observation period were additional predictors. CONCLUSIONS: Improvement in GFR over time predicted better SRH at each period after KT. Decreased transplantation-associated psychological distress and fewer late acute rejection episodes seemed to predict better SRH at a later follow-up period. Despite these observations, higher SRH was associated with better clinical outcomes.

Optical Coherence Tomography of the Coronary Arteries.

Intravascular imaging, particularly optical coherence tomography, has brought significant improvement in diagnostic and therapeutical approaches to coronary artery disease and has offered superior high-resolution visualization of coronary arteries. The ability to obtain images of intramural and transmural coronary structures allows the study of the process of atherosclerosis, effect of therapies, mechanism of acute coronary syndrome and stent failure, and performance of new devices and enables the interventional cardiologist to optimize the effect of percutaneous coronary intervention. In this review, we provide the summary of the latest published data on clinical use of optical coherence tomography as well as practical algorithm for optical coherence tomography-guided percutaneous coronary intervention for daily interventional practice.

Long-term changes after carotid stenting assessed by intravascular ultrasound and near-infrared spectroscopy.

BACKGROUND: Long-term effect of carotid stenting (CAS) on the stabilization of the plaque is almost unrecognized. Vascular healing and remodeling might seal the atherosclerotic plaque with neointimal hyperplasia decreasing the vulnerability. We aimed to assess long-term change in the lipid signal, stent and luminal dimensions and restenosis after CAS with the intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) imaging. METHODS: We performed follow-up angiography and NIRS-IVUS imaging of 58 carotid stents in 52 patients. Median time from CAS to the follow-up examination was 31 months (range, 5-56). The lipid signal of the stented segment was calculated from a NIRS-derived chemogram (a spectroscopic map) as the lipid core burden index (LCBI, a dimensionless number from 0 to 1,000). Planimetric and volumetric measurements from IVUS were performed to assess change in minimal stent area (MSA), minimal luminal area (MLA), stent and luminal volume, late stent expansion and percentage in-stent restenosis (ISR) volume. RESULTS: During the follow-up period, the mean (±SD) LCBI significantly decreased from 32±56 to 17±27 (P=0.002). The mean stent volume significantly increased from 717±302 to 1,019±429 mm3 (P<0.001) with mean stent expansion 43%±24%. The mean luminal volume increased from 717±302 to 760±359 mm3 (P=0.025) due to ISR encroaching 26%±15% of the stent volume. CONCLUSIONS: Lipid signal decreased during the follow-up period suggesting stabilization of the plaque. Late stent expansion was balanced with neointimal hyperplasia. TRIAL REGISTRATION: The trial is registered under clinicaltrials.gov NCT03141580.

Long-term survival of carotid stenting patients with regard to single- or double-vessel carotid artery disease: a propensity score matching analysis.

INTRODUCTION: There is lack of long-term data outside of controlled clinical trials in carotid artery stenting (CAS). In this study, we compared the short-term outcome, long-term survival, and rate of re-interventions for restenosis in patients after CAS, related to the extent of carotid atherosclerosis classified as single-vessel (unilateral) or double-vessel (bilateral) carotid artery disease. MATERIAL AND METHODS: We retrospectively evaluated 599 patients with significant carotid artery stenosis, who underwent 763 CAS procedures, and used the propensity score to match 226 pairs (452 patients) in the single- or double-vessel carotid disease. RESULTS: There was no significant difference in the occurrence of in-hospital major adverse events (3.5% vs. 3.1% of patients in the double-vessel carotid group vs. the single-vessel carotid group; p = 1) The mean follow-up was 6.1 ±4.0 years, and a total of 181 (40%) deaths occurred during 2759 patient-years, which translates into 7.8 and 5.3 deaths per 100 patient-years in the double-vessel carotid group and the single-vessel carotid group, respectively (p < 0.01). The survival in the double-vessel carotid group vs. the single-vessel carotid group at 10 years was 46% (95% CI: 38-54%) vs. 55% (95% CI: 47-63%) (p < 0.01). Twenty-four (11%) patients and 6 (3%) patients underwent re-interventions for restenosis in the double-vessel and the single-vessel carotid disease group, respectively (p < 0.01). CONCLUSIONS: Patients with CAS and significant double-vessel carotid artery disease had similar peri-procedural risk, but had a worse long-term survival, and a higher rate of re-interventions for restenosis compared to the single-vessel carotid artery disease patients.

Enhanced Fast-VESTAL for Magnetoencephalography Source Imaging: From Theory to Clinical Application in Epilepsy.

A novel magnetoencephalography source imaging approach called Fast Vector-based Spatio-Temporal Analysis (Fast-VESTAL) has been successfully applied in creating source images from evoked and resting-state data from both healthy subjects and individuals with neurological and/or psychiatric disorders, but its reconstructed source images may show false-positive activations, especially under low signal-to-noise ratio conditions. Here, to effectively reduce false-positive artifacts, we introduced an enhanced Fast-VESTAL (eFast-VESTAL) approach that adopts generalized second-order cone programming. We compared the spatiotemporal characteristics of the eFast-VESTAL approach to those of the popular distributed source approaches (e.g., the minimum L2-norm/ mixed-norm methods) using computer simulations and auditory experiments. More importantly, we applied eFast-VESTAL to the presurgical evaluation of epilepsy. Our results demonstrated that eFast-VESTAL exhibited a lower dipole localization error and/or a higher correlation coefficient (CC) between the estimated source time series and ground truth under various conditions of source waveforms. Experimentally, eFast-VESTAL displayed more focal activation maps and a higher CC between the raw and predicted sensor data in response to auditory stimulation. Notably, eFast-VESTAL was the most accurate method for noninvasively detecting the epileptic zones determined using more invasive stereo-electroencephalography in the comparison.

Differences in perceived health status between kidney transplant recipients and dialyzed patients are based mainly on the selection process.

Kidney transplantation offers longer survival, less morbidity and lower costs than dialysis. It is also believed to improve quality of life. The aim of this study was to compare prospectively the perceived health status (PHS) of dialyzed patients on a waiting list with kidney transplant recipients after transplantation, matched for age, gender and comorbidity. The sample consisted of 93 dialyzed patients on a waiting list for deceased-donor kidney transplantation and 87 incident transplant recipients. A total of 62 dialyzed patients were matched for age, gender and comorbidity with 62 transplant recipients. PHS was measured using the SF-36 questionnaire. Data from baseline and after 12 months were compared between the groups. Patients on dialysis had worse physical (49 +/- 21) and mental (59 +/- 18) PHS than transplant recipients (56 +/- 21 and 64 +/- 18, p < or = 0.05), but when matched pairs were compared, no differences in PHS were found. After 12 months, PHS did not change significantly in either group. The PHS of patients after kidney transplantation is better than that of those on dialysis. However, this fact is significantly influenced by the selection procedure, as only some dialyzed patients are put onto the waiting list while others were actually transplanted. The differences disappear with matching.

Impact of personality and psychological distress on health-related quality of life in kidney transplant recipients.

Health-related quality of life (HRQoL) has become an important outcome in the evaluation of kidney transplantation (KT). Although the medical and sociodemographic predictors of HRQoL in patients after KT are well known, there is still a lack of knowledge about the psychological factors involved. This study focuses on the role of personality and actual psychological distress in predicting HRQoL after KT. Sociodemographic (gender, age, education, average income), medical (glomerular filtration, serum albumin, number of co-morbid diseases) and psychological data (neuroticism, extroversion, psychological distress) were collected from 177 (60.5% male subjects; 48 +/- 12.1 years) kidney transplant recipients, and physical and mental HRQoL were measured using the SF-36. A univariate general linear model analysis was performed. Higher physical HRQoL was associated with younger age, higher education and income, a low number of co-morbid diseases, lower neuroticism and distress. Higher mental HRQoL was associated with higher education and income, longer time from KT, higher extroversion, lower neuroticism and distress. In both physical and mental HRQoL, actual distress was the best predictor, even when controlled for neuroticism. These results confirm the importance of psychological distress in patients and its impact on their HRQoL after KT and can be applied in intervention programs focused on increasing HRQoL.

Posttransplant Anemia as a Prognostic Factor of Mortality in Kidney-Transplant Recipients.

Background. Findings on the association between posttransplant anemia (PTA) and mortality in posttransplant patients are scarce. This study explored whether PTA shortly after kidney transplantation (KT) predicts mortality at up to 10 years' follow-up, stratified for chronic kidney disease (CKD) stages. Methods. PTA was divided into 3 categories according to the hemoglobin (Hb) value: severe (Hb < 10 g/dl), mild (10.0 g/dl ≤ Hb < 11.9 g/dl), or no PTA (Hb ≥ 12 g/dl). CKD stages were estimated using the CKD-EPI formula and divided into 2 groups: CKD1-2 and CKD3-5. Cox regression, stratified according to CKD, was performed to identify whether different categories of PTA predicted mortality in KT recipients. Results. Age, being female, and both mild and severe PTA contributed significantly to the Cox regression model on mortality in CKD1-2. In the Cox regression model for mortality in CKD3-5, age and severe PTA contributed significantly to this model. Conclusion. PTA shortly after KT increased the risk of mortality at up to 10 years' follow-up. Even mild PTA is associated with a 6-fold higher risk of mortality and severe PTA with a 10-fold higher risk of mortality in CKD1-2. Clinical evaluation and treatment of anemia might reduce the higher risk of mortality in patients with PTA in early stages of CKD after KT.

Predictors of perceived health status in patients after kidney transplantation.

BACKGROUND: Patients after kidney transplantation have decreased mortality, morbidity and better quality of life compared to people on dialysis. Major efforts are being directed towards research into graft and patient survival. Research into quality of life is less intensive. The aim of this study was to explore the predictors of perceived health status (PHS) in kidney transplant recipients. METHODS: Out of 218 patients after kidney transplantation 138 participated in the study. Linear regression analysis was performed to predict PHS, measured with the SF-36 questionnaire, in three age categories (<40, 40-59, >or=60 years). Independent variables included social support (measured with the Social Support List Discrepancies questionnaire), sociodemographic and medical variables, side effects and compliance. RESULTS: Predictors of better PHS in patients<40 years were better social support (P

Clinical experience of conversion from cyclosporine to tacrolimus prolonged-release in stabilized kidney transplant patients.

BACKGROUND AND AIMS: The CONCERTO study results showing the beneficial effects of conversion from cyclosporine to tacrolimus prolonged-release (tacrolimus PR) in stabilised patients after kidney transplantation, were first published in 2011. This communication describes our first experience of conversion from cyclosporine to tacrolimus PR in stabilised kidney transplant patients. The aim was to determine whether it could be used in routine clinical practice in the Czech and Slovak Republics. METHODS: Evaluation was carried out at five transplantation centres in the Czech Republic and Slovakia. In all participating Centres, the drug conversion was conducted according to the ICH/GCP guidelines. A total of 104 patients stabilised after kidney transplantation were converted from maintenance therapy with cyclosporine to treatment with tacrolimus PR. The data were collected 26 weeks after the switch. The primary endpoint was change in kidney graft function measured from the estimated glomerular filtration rate (GFR). The effect of conversion on blood pressure, metabolic parameters and cosmetic changes was also recorded. Special attention was paid to the safety and tolerability of treatment with tacrolimus PR. RESULTS: GFR increased after six months by 10 % (P = 0.040). In addition a significant decrease in serum creatinine and triglycerides level was found together with major reduction in the incidence and severity of gingival hyperplasia and hirsutism. 3% of patients developed new onset of diabetes mellitus. Otherwise, the switch was very well-tolerated, without serious adverse events or acute rejections. CONCLUSION: Conversion from cyclosporine to tacrolimus PR was shown to be a safe therapeutic alternative with patient benefits.

Social participation after kidney transplantation as a predictor of graft loss and mortality over 10 years: a longitudinal study.

BACKGROUND: Social participation is considered to be an objective parameter for evaluating the success of transplantation. This study explores the association between posttransplant factors (kidney function, perceived side effects of immunosuppressive treatment, comorbidity, physical and mental health-related quality of life [HRQoL]) and social participation in patients 3 months to 6 years after kidney transplantation (baseline) and their impact on graft loss and mortality for up to 10 years (follow-up). METHODS: At baseline, 331 patients provided their socioeconomic and medical data (comorbidity, kidney function) and completed the end-stage renal disease symptom checklist (perceived side effects), the Short Form Health Survey-36 and the Participation Scale. At follow-up, information on all-cause graft-loss and mortality was noted. Binary logistical regression exploring the effects of the independent variables on social participation and Cox regression analyses determining whether social participation predicted graft loss and mortality were performed. RESULTS: Restrictions in social participation were associated with living alone, poorer kidney function, lower perceived side effects of corticosteroids, higher perceived cardiac and renal dysfunction, higher perceived posttransplantation distress, lower physical HRQoL, and fewer working hours. Restrictions in social participation increased the risk of all-cause graft loss 2.29-fold and the risk of all-cause mortality 11.94-fold during follow-up. Education, kidney function, and comorbidity also increased the risk for poor patient outcome. CONCLUSION: Kidney function, perceived side effects, comorbidities, and HRQoL affect social participation in patients after kidney transplantation. Additionally, social participation has a positive effect on long-term patient outcomes, decreasing the odds of graft loss and mortality over 10 years.

The Effect of Interference on the CD8(+) T Cell Escape Rates in HIV.

In early human immunodeficiency virus (HIV) infection, the virus population escapes from multiple CD8(+) cell responses. The later an escape mutation emerges, the slower it outgrows its competition, i.e., the escape rate is lower. This pattern could indicate that the strength of the CD8(+) cell responses is waning, or that later viral escape mutants carry a larger fitness cost. In this paper, we investigate whether the pattern of decreasing escape rates could also be caused by genetic interference among different escape strains. To this end, we developed a mathematical multi-epitope model of HIV dynamics, which incorporates stochastic effects, recombination, and mutation. We used cumulative linkage disequilibrium measures to quantify the amount of interference. We found that nearly synchronous, similarly strong immune responses in two-locus systems enhance the generation of genetic interference. This effect, combined with a scheme of densely spaced sampling times at the beginning of infection and sparse sampling times later, leads to decreasing successive escape rate estimates, even when there were no selection differences among alleles. These predictions are supported by empirical data from one HIV-infected patient. Thus, interference could explain why later escapes are slower. Considering escape mutations in isolation, neglecting their genetic linkage, conceals the underlying haplotype dynamics and can affect the estimation of the selective pressure exerted by CD8(+) cells. In systems in which multiple escape mutations appear, the occurrence of interference dynamics should be assessed by measuring the linkage between different escape mutations.

Health-related quality of life 3 months after kidney transplantation as a predictor of survival over 10 years: a longitudinal study.

AIM: This study explores the association between kidney function, side effects of immunosuppressive treatment, coping self-efficacy, and physical and mental HRQoL at 3 months (baseline) after kidney transplantation (KT) and their impact on patient and graft survival for up to 10 years (follow-up). METHODS: A group of 151 patients provided at baseline their socioeconomic and medical (CKD-EPI) data and completed the End-Stage Renal Disease Symptom Checklist (perceived side effects), the coping self-efficacy scale, and the SF-36. At follow-up, patients' health status was noted. Univariate GLM exploring the main effects of the independent variables on physical and mental HRQoL was performed; furthermore, Cox regression analyses were performed to determine whether the early posttransplantation factors predicted patient and graft survival. RESULTS: Less severe side effects of immunosuppressive treatment and higher efficacy in stopping unpleasant emotions were associated with both higher physical and mental HRQoL at baseline. Younger age was associated with higher physical HRQoL and older age, and lower efficacy in getting support from family and friend were associated with higher mental HRQoL. Patients reporting higher physical and mental HRQoL at 3 months and with higher age and better kidney function had higher odds of surviving with a functioning graft. CONCLUSION: Older age, higher kidney function, and higher physical and mental HRQoL at baseline significantly improved the odds of graft and patient survival over 10 years. These results show the importance of close monitoring of early posttransplantation HRQoL along with kidney function and reported side effects because of their effect on long-term patient outcomes.