Parents' Experiences of Pediatric Palliative Care and the Impact on Long-Term Parental Grief

ContextApproximately 25% of children diagnosed with cancer eventually die. Losing a child puts parents at increased risk for developing psychological problems.ObjectivesTo explore parents' perceptions of the interaction with health care professionals (communication, continuity of care, and parental involvement) and symptom management during the pediatric palliative phase, and to investigate the influence on long-term grief in parents who lost a child to cancer.MethodsA total of 89 parents of 57 children who died of cancer between 2000 and 2004 participated in this retrospective cross-sectional study by completing a set of questionnaires measuring grief (Inventory of Traumatic Grief), parents' perceptions of the interaction with health care professionals (communication, continuity of care, and parental involvement), and symptom management during the palliative phase. Care was assessed on a five point Likert scale (1 = disagree and 5 = agree).ResultsParents highly rated communication (4.6 ± 0.6), continuity of care (4.3 ± 0.6), and parental involvement (4.6 ± 0.7) during the palliative phase. Parents' most often reported physical and psychological symptoms of their child during the palliative phase were fatigue (75%), pain (74%), anxiety to be alone (52%), and anger (48%). Higher ratings of parents on communication (β = −9.08, P = 0.03) and continuity of care (β = −11.74, P = 0.01) were associated with lower levels of long-term parental grief. The severity of the child's dyspnea (β = 2.96, P = 0.05), anxiety to be alone (β = 4.52, P < 0.01), anxiety about the future (β = 5.02, P < 0.01), anger (β = 4.90, P < 0.01), and uncontrolled pain (β = 6.60, P < 0.01) were associated with higher levels of long-term parental grief. Multivariate models combining the interaction with health care professionals and symptom management showed a significant influence of both aspects on long-term parental grief.ConclusionBoth interaction with health care professionals, especially communication and continuity of care, and symptom management in children dying of cancer are associated with long-term parental grief levels.     

Soluble receptor for advanced glycation end products (sRAGE) in plasma and synovial fluid is inversely associated with disease severity of knee osteoarthritis

Objectives:The aim of this study was to measure soluble receptor for advanced glycation end products (sRAGE) in plasma and synovial fluid of knee osteoarthritis (OA) patients and to determine the correlation between sRAGE levels and disease severity.Design and methods:Thirty-six OA patients and 15 healthy controls were enrolled in this study. OA grading was performed using the Kellgren–Lawrence classification. sRAGE levels in plasma and synovial fluid were analyzed by enzyme-linked immunosorbent assay.Results:Plasma sRAGE levels were significantly lower in OA patients than in healthy controls (P = 0.01). sRAGE levels in plasma were remarkably higher with regard to paired synovial fluid (P = 0.001). Additionally, sRAGE concentrations in plasma and synovial fluid showed significant inverse correlation with disease severity (r = ?0.65, P < 0.001 and r = ?0.55, P = 0.001, respectively). Further analysis showed that there was a strong positive correlation between plasma and synovial sRAGE concentration (r = 0.81, P < 0.001).Conclusions:sRAGE levels were significantly lower in OA patients compared with controls, and sRAGE levels in plasma and synovial fluid also decreased significantly as the disease severity increased. Accordingly, sRAGE levels could be used as a biochemical marker for assessing the severity and progression of knee OA.     

CYP11B2 gene haplotypes independently and in concurrence with aldosterone and aldosterone to renin ratio increase the risk of hypertension

ObjectivesAldosterone synthase produces aldosterone, which regulates electrolytes and thereby blood pressure. Polymorphisms in aldosterone-synthase gene (CYP11B2) may associate with heterogeneous aldosterone production and hypertension. Hence, we investigated ? 344T/C, Iw/Ic polymorphisms of CYP11B2, plasma renin activity (PRA) and aldosterone concentration (PAC).Design and methodsConsecutive ethnically-matched 450 hypertensive patients and 360 controls were screened by PCR-RFLP for genotypes and haplotypes; PRA and PAC were measured.ResultsThe Iw/Ic polymorphism distribution differed significantly between the two groups (LRT χ² = 15.8, df = 2, P = 0.000). The mutant allele-Ic and genotype-Ic/Ic were overrepresented in patients (35% versus 27% and 13% versus 7%). Overrepresentation of T-Ic haplotype in patients was identified as risk haplotype (P = 0.000). Patients had significantly higher PAC and aldosterone-to-renin ratio (ARR; P  = 0.000), which was Ic-allele dependent.ConclusionsThe haplotype T-Ic associated with hypertension susceptibility. Correlation between Ic-allele and raised ARR likely serve in hypertension management.     

Measurement of oxidized lipoprotein (a) in patients with acute coronary syndromes and stable coronary artery disease by 2 ELISAs: Using different capture antibody against oxidized lipoprotein (a) or oxidized LDL

ObjectiveTo evaluate clinical value of oxidized lipoprotein(a) [ox-Lp(a)] levels.Design and methodsOx-Lp(a) were measured by 2 ELISAs using antibodies against ox-Lp(a) [ox-Lp(a)1] or oxidized low-density lipoprotein [ox-Lp(a)2], and studied in 161 acute coronary syndromes (ACS) patients, 114 stable coronary artery disease (CAD) and 100 control subjects.ResultsOx-Lp(a)1 was found related with ox-Lp(a)2 (r = 0.864, P = 0.000). Controlling for plasma lipids, Lp(a) and clinical characteristics, odds ratios of ox-Lp(a)1 on ACS and stable CAD were 5.06 (95% confidence interval 1.82–14.04) and 2.20 (0.78–6.22); those of ox-Lp(a)2 were 3.37 (1.07–10.63) and 1.35 (0.41–4.48), respectively. Receiver-operating characteristic curve analysis confirmed that performances of ox-Lp(a)1 were significantly superior to those for ox-Lp(a)2 in ACS (area: 0.803 vs. 0.723, P < 0.001) and stable CAD (area: 0.670 vs. 0.607, P < 0.01).ConclusionOx-Lp(a) levels using antibodies against ox-Lp(a) may represent a better risk marker than those using antibodies against oxidized low-density lipoprotein for ACS and stable CAD.     

Paraoxonase activity in athletes with depleted iron stores and iron-deficient erythropoiesis

ObjectiveThe aim of this study was to evaluate how conditions that precede anaemia (iron store depletion and iron-deficient erythropoiesis) affect human serum paraoxonase PON1 activity.Design and methodsBased on haemoglobin, transferrin saturation and serum ferritin values 119 athletes were divided into three groups: with iron depletion, with deficient erythropoiesis and controls. The following parameters were measured: paraoxonase activity towards paraoxon (POase) and diazoxon (DZOase), lipid hydroperoxides (LOOH), the pro-oxidant-antioxidant balance (PAB), red blood cells (RBC) and lipid status.ResultsSignificant differences were found between athletes with different stages of iron deficiency and controls with respect to PON 1 activity and oxidative stress status parameters (Wilks' Lambda = 0.712, F = 5.241, p < 0.001, η² = 0.156). There was no significant difference between the PON1 192 Q and R polymorphism distribution in the two groups of athletes with different stages of iron deficiency and controls (χ² = 1.086; p = 0.896). PON1 activity was positively correlated with RBCs, haemoglobin, transferrin saturation (p < 0.001) and ferritin (p = 0.037) and negatively correlated with LOOH (p = 0.044) in all three study groups.ConclusionsDeficient erythropoiesis in athletes contributes to impaired PON1 activity. In contrast, iron depletion, regardless of increased oxidative stress, does not affect PON1 activity.     

Common genetic polymorphisms in pre-microRNAs were associated with increased risk of dilated cardiomyopathy

BackgroundCommon single nucleotide polymorphisms (SNPs) in pre-microRNAs may change their property through altering microRNAs (miRNAs) expression and/or maturation, resulting diverse functional consequences. We conducted a pilot study to test whether SNPs in pre-microRNAs were associated with dilated cardiomyopathy (DCM).MethodsGenotypes of 3 SNPs in pre-miRNAs (has-mir-196a2 rs11614913 C/T, hsa-mir-499 rs3746444 A/G, hsa-mir-146a rs2910164 C/G) in 221 DCM patients and 321 control subjects were determined with the use of PCR-restriction fragment length polymorphism (RFLP) assay.ResultsSignificantly increased DCM risks were found to be associated with variant allele of has-mir-196a2 rs11614913 C/T (T allele) and hsa-mir-499 rs3746444 A/G (G allele) (P < 0.0001, OR = 1.730, 95% CI = 1.345–2.227, and P < 0.0001, OR = 1.794, 95% CI = 1.350–2.385, respectively). We found that increased DCM risk was statistically significantly associated with these 2 SNPs in a dominant model (P = 0.0001 and P < 0.0001 for rs11614913 and rs3746444, respectively). No association between DCM risk and hsa-mir-146a rs2910164 C/G was observed (P = 0.451, OR = 1.102, 95% CI = 0.856–1.418).ConclusionsBoth the has-mir-196a2 rs11614913 C/T and hsa-mir-499 rs3746444 A/G, but not hsa-mir-146a rs2910164 C/G, are associated with a significantly increased risk of DCM, indicating that common genetic polymorphisms in pre-microRNAs are associated with DCM.     

Validation of a simple screening test for elementary visuo-spatial perception deficit

ObjectiveThe reliability and validity of a screening test for a deficit in elementary visuo-spatial perception (EVSP) were evaluated.MethodThis prospective study collected performance from 210 typically developing individuals and evaluated the internal consistency of the EVSP screening test. Test–retest reliability was examined with 25 individuals. Validity also involved retrospective clinical data collected from 223 non-typically developing children coming to the hospital for outpatient consultation. Since EVSP matures through childhood, we standardized the EVSP screening test scores by age category and performed Pearson correlations with standardized clinical tests scores.ResultsTest–retest reliability (intraclass correlation coefficient = 0.76) and internal consistency (Cronbach's alpha = 0.76) were satisfactory. Construct validity included correlation with the subtests of the Wechsler Intelligence Scale IV (WISC-IV) involving visuo-spatial analysis (Matrix Reasoning and Block Design, P < 0.01; Symbol Search and Coding, P < 0.05) and was reinforced by the expected non-correlation between the Verbal Comprehension Index and EVSP scoring class. The EVSP scoring class was correlated with Manual dexterity of the M-ABC (P < 0.05) and the Working Memory Index (P < 0.05) of the WISC-IV including the subtest Arithmetic (P < 0.01).ConclusionThis screening test is reliable and valid to evaluate EVSP before more complex cognitive or motor assessment.     

High density lipoprotein-anionic peptide factor effect on reverse cholesterol transport in type 2 diabetic patients with and without coronary artery disease

ObjectivesTo verify if HDL3 Anionic Peptide Factor (HDL3-APF) is as an apolipoprotein that promotes the reverse cholesterol transport.Design and methodsWe investigated a possible association between plasma HDL3-APF concentration, cholesterol efflux from Fu5AH cells and cholesteryl ester transfer protein (CETP) activity in type 2 diabetic patients with coronary artery disease (CAD) (n = 36), those without CAD (n = 20), and 37 healthy subjects.ResultsPlasma APF concentrations were decreased in diabetics with CAD compared to controls (p < 0.01). Cellular cholesterol efflux was decreased in diabetics without and with CAD, (p < 0.01 and p < 0.001 respectively). CETP activity was significantly elevated in all patient groups. Multiple linear regression analysis shows that cholesterol efflux was independently and positively related only to APF concentrations in controls.ConclusionsAPF is likely to be a key independent factor for promoting cellular cholesterol efflux in healthy subjects. However this association is altered in type 2 diabetes.     

Clinical significance of Stratifin,ERα and PR promoter methylation in tumor and serum DNA in Indian breast cancer patients

Objectives:The objective of this study was to determine the concordance of promoter methylation of stratifin, ERα and PR in tumor and circulating DNA in breast cancer patients and their association with clinicopathological parameters and disease prognosis.Design and methods:Methylation specific PCR were carried out to investigate the promoter methylation status of stratifin, ERα and PR in tumor and circulating DNA in 100 breast cancer patients in a prospective study. The effect of promoter methylation on protein expression was evaluated by immunohistochemistry.Results:Significant association was observed between promoter methylation of stratifin in tumors (61%) and paired sera (56%) (r = 0.78; p ≤ 0.001). Loss of stratifin expression was observed in 47% tumors and was associated with poor overall survival (p = 0.05). Significant correlation was observed between methylation status of ERα with PRB (p < 0.0001, OR = 20.8, 95% CI = 7.4–58.0) and stratifin (p = 0.003, OR = 2.0, 95% CI = 0.8–4.4).Conclusion:This study underscores the potential utility of serum DNA methylation of these genes as surrogate for tumor DNA methylation as a promising tool for cancer diagnosis.     

Soluble urokinase-type plasminogen activator receptor forms in plasma as markers of atherosclerotic plaque vulnerability

Objectives:To test if circulating forms of the soluble urokinase-type plasminogen activator receptor (suPAR) are potential biomarkers of plaque vulnerability.Design and methods:Plasma concentrations of suPAR(I–III), suPAR(II–III) and uPAR(I) were measured by time-resolved fluorescence immunoassays in Caucasian patients operated for symptomatic carotid atherosclerosis (n = 255). Local suPAR release from plaques into the circulation was assessed in plasma passing retrogradely over the plaque in the carotid artery, collected during surgery (n = 7).Results:The suPAR(I–III) (P = 0.03) and suPAR(II–III) (P = 0.006) concentrations were higher after ischemic strokes and transient ischemic attacks, i.e., clinical subgroups associated with poorer prognosis and a less stable plaque phenotype, than after amaurosis fugax. Slightly elevated suPAR(I–III) levels were found in plasma from the carotid lesion. However, refuting the hypothesis, the concentrations of the suPAR forms were not higher in patients with short intervals between clinical event and blood sampling compared with those with long intervals. Age, inflammatory markers and diabetes were confounding factors independently associated with suPAR forms.Conclusion:Circulating suPAR forms are probably not useful biomarkers of atherosclerotic plaque vulnerability.     

VEGF-A gene promoter polymorphisms and microvascular complications in patients with essential hypertension

ObjectivesWe investigated the possible involvement of vascular endothelial growth factor (VEGF-A) gene promoter polymorphisms in essential hypertension (EH).Design and methods1225 bp of the VEGF-A gene promoter were screened for polymorphisms using PCR amplification and direct DNA sequence analysis in 62 EH and 62 normotensive (HS) individuals. Circulating VEGF-A levels were determined by immunoassay.Results?152G/A (p = 0.009) and ?116G/A (p = 0.016) polymorphisms were correlated to hypertension (p < 0.05). Median platelet VEGF-A load in EH was 2.10 fg/plt. Patients with microvascular complications (MC) had higher platelet VEGF-A load than those without (p = 0.005). Multivariate analyses showed that ?116 A allele was an independent predictor of microalbuminuria (p = 0.014) and increased platelet VEGF-A load (p = 0.009) in EH. Platelet VEGF-A load independently predicted MC (p = 0.049) in addition to ?116G/A polymorphism (p = 0.035).ConclusionsAbnormal regulation of VEGF-A due to polymorphism at position ?116 might represent a genetic factor for increased VEGF-A production and MC in EH.     

The role of knee joint moments and knee impairments on self-reported knee pain during gait in patients with knee osteoarthritis

BackgroundThe association between high mechanical knee joint loading during gait with onset and progression of knee osteoarthritis has been extensively studied. However, less attention has been given to risk factors related to increased pain during gait. The purpose of this study was to evaluate knee joint moments and clinical characteristics that may be associated with gait-related knee pain in patients with knee osteoarthritis.MethodsSixty-seven participants with knee osteoarthritis were stratified into three groups of no pain (n = 18), mild pain (n = 27), or moderate/severe pain (n = 22) based on their self-reported symptoms during gait. All participants underwent three-dimensional gait analysis. Quadriceps strength, knee extension range of motion, radiographic knee alignment and self-reported measures of global pain and function were also quantified.FindingsThe moderate/severe pain group demonstrated worse global pain (P < 0.01) and physical function scores (P < 0.01) compared to the no pain and the mild pain groups. The moderate/severe pain group also walked with greater knee flexion moments during the midstance phase of gait compared to the no pain group (P = 0.02). Additionally, the moderate/severe pain group demonstrated greater varus knee malalignment (P = 0.009), which was associated with higher weight acceptance peak knee adduction moments (P = 0.003) and worse global pain (P = 0.003) and physical function scores (P = 0.006).InterpretationGreater knee flexion moment is present during the midstance phase of gait in patients with knee osteoarthritis and moderate/severe pain during gait. Additionally, greater varus malalignment may be a sign of increased global knee joint dysfunction that can influence many activities of daily living beyond gait.     

Multi-center evaluation of a commercial Kit for tacrolimus determination by LC/MS/MS

ObjectivesA multi-center evaluation (3 sites) of the LC/MS/MS MassTrak? tacrolimus Immunosuppressants Kit (Kit) was undertaken.Design and methodsTen aspects of the analytical performance of the Kit were investigated based on FDA and CLSI guidelines.ResultsThe linear analytical range of the procedure was between 0.68 and 31.7 ng/mL. Within-run and total imprecision were < 6% and < 8% (n = 240), respectively. Recoveries of tacrolimus added to clinical samples that contained between 5 and 10 ng/mL of tacrolimus before addition were 99, 102 and 105% at 5.0, 10 and 20 ng/mL, respectively. Comparison of in-house and Kit procedures in samples from liver (n = 50–58) or kidney (n = 50 or 51) transplant recipients yielded method mean biases between ? 2.0 and + 10.7% at 5 and 15 ng/mL.ConclusionsThis evaluation indicates that the Kit is suitable for the monitoring of tacrolimus in kidney and liver transplant recipients.     

Video laryngoscopy versus direct laryngoscopy for tracheal intubation during in-hospital cardiopulmonary resuscitation

AimTracheal intubation during cardiopulmonary resuscitation (CPR) is a high-risk procedure. Here, we investigated the efficacy of video laryngoscopy for tracheal intubation during CPR.MethodsData regarding tracheal intubation during CPR from in-hospital cardiac arrests occurring between January 2011 and December 2013 (n = 229) were prospectively collected and retrospectively analyzed.ResultsThe initial laryngoscopy method was video laryngoscopy in 121 patients (52.8%) and direct laryngoscopy in 108 patients (47.2%). The rate of successful intubation at the first attempt was higher with video laryngoscopy (71.9%; 87/121) than with direct laryngoscopy (52.8%; 57/108; p = 0.003). The rate of success at the first attempt was higher for experienced (73.0%; 84/115) than inexperienced operators, including residents (52.6%; 60/114; p = 0.001). Mortality at day 28 after CPR was not significantly different between patients with successful tracheal intubation at the first attempt and without (68.1% [98/144] vs. 67.1% [57/85]; p = 0.876). In multivariate logistic regression analysis, a predicted difficult airway (odds ratio [95% confidence interval] = 0.22 [0.10–0.49]; p < 0.001), intubation by an experienced operator (2.63 [1.42–4.87]; p = 0.002), and use of video laryngoscopy rather than direct laryngoscopy (2.42 [1.30–4.45]; p = 0.005) were independently associated with a successful tracheal intubation at the first attempt.ConclusionUse of video laryngoscopy during CPR from in-hospital cardiac arrest is independently associated with successful tracheal intubation at the first attempt.     

Long-term high-intensity interval training associated with lifestyle modifications improves QT dispersion parameters in metabolic syndrome patients

BackgroundQT dispersion (QTd) is a marker of myocardial electrical instability, and is increased in metabolic syndrome (MetS). Moderate intensity continuous exercise (MICE) training was shown to improve QTd in MetS patients.ObjectivesTo describe long-term effects of MICE and high-intensity interval exercise training (HIIT) on QTd parameters in MetS.MethodsSixty-five MetS patients (53 ± 9 years) were assigned to either a MICE (60% of peak power output [PPO]), or a HIIT program (alternating phases of 15–30 s at 80% of PPO interspersed by passive recovery phases of equal duration), twice weekly during 9 months. Ventricular repolarization indices (QT dispersion = QTd, standard deviation of QT = sdQT, relative dispersion of QT = rdQT, QT corrected dispersion = QTcd), metabolic, anthropometric and exercise parameters were measured before and after the intervention.ResultsNo adverse events were noted during exercise. QTd decreased significantly in both groups (51 vs 56 ms in MICE, P < 0.05; 34 vs 38 ms in HIIT, P < 0.05). Changes in QTd were correlated with changes in maximal heart rate (r = ?0.69, P < 0.0001) and in heart rate recovery (r = ?0.49, P < 0.01) in the HIIT group only. When compared to MICE, HIIT training induced a greater decrease in weight, BMI and waist circumference. Exercise capacity significantly improved by 0.82 and 1.25 METs in MICE and HIIT groups respectively (P < 0.0001). Lipid parameters also improved to the same degree in both groups.ConclusionIn MetS, long-term HIIT and MICE training led to comparable effects on ventricular repolarization indices, and HIIT might be associated with greater improvements in certain cardiometabolic risk factors.     

The effects of gait retraining in runners with patellofemoral pain: A randomized trial

BackgroundRunning popularity has increased resulting in a concomitant increase in running-related injuries with patellofemoral pain most commonly reported. The purpose of this study was to determine whether gait retraining by modifying footstrike patterns from rearfoot strike to forefoot strike reduces patellofemoral pain and improves associated biomechanical measures, and whether the modification influences risk of ankle injuries.MethodsSixteen subjects (n = 16) were randomly placed in the control (n = 8) or experimental (n = 8) group. The experimental group performed eight gait retraining running sessions over two weeks where footstrike pattern was switched from rearfoot strike to forefoot strike, while the control group performed running sessions with no intervention. Variables were recorded pre-, post-, and one-month post-running trials.FindingsKnee pain was significantly reduced post-retraining (P < 0.05; effect size = 0.294) and one-month follow-up (P < 0.05; effect size = 0.294). Knee abduction was significantly improved post-retraining (P < 0.05; effect size = 0.291) and one-month follow-up (P < 0.05; effect size = 0.291). Ankle flexion was significantly different post-retraining (P < 0.05; effect size = 0.547), as well as ankle range of motion post-retraining (P < 0.05; effect size = 0.425) and one-month follow-up (P < 0.05; effect size = 0.425).InterpretationFindings suggest running with a forefoot strike pattern leads to reduced knee pain, and should be considered a possible strategy for management of patellofemoral pain in recreational runners.This trial is registered at the US National Institutes of Health (clinicaltrials.gov) #NCT02567123.     

New factors that affect quality of life in patients with aphasia

BackgroundAphasia severity is known to affect quality of life (QoL) in stroke patients, as is mood disorders, functional limitations, limitations on activities of daily life, economic status and level of education. However, communication limitation or fatigue has not been explored in this specific population.ObjectiveWe aimed to investigate whether these factors were associated with QoL in patients with aphasia after stroke.MethodsPatients with aphasia were included from April 2014 to November 2017 after a first stroke and were followed for 2 years post-stroke. QoL was assessed at follow-up by the French Sickness Impact Profile 65 (SIP-65). We explored predictors such as mood disorders, communication impairment, fatigue, limitations on activities of daily life, and aphasia severity in addition to socio-demographic factors.ResultsWe included 32 individuals (22 men; mean age 60.7 [SD 16.6] years) with aphasia after a first stroke. Poor QoL as assessed by the SIP-65 was significantly associated (Pearson correlations) with increased severity of aphasia initially (P = 0.008) and at follow-up (P = 0.01); increased communication activity limitations at follow-up (P < 0.001); increased limitations on activities of daily life at baseline (P = 0.008) and follow-up (P < 0.001); increased fatigue at follow-up (P = 0.001); and increased depression symptoms at follow-up (P = 0.001). On multivariable analysis, QoL was associated with communication activity limitations, limitations on activities of daily life, fatigue and depression, explaining more than 75% of the variance (linear regression R² = 0.756, P < 0.001). The relative importance in predicting the variance was 32% for limitations on activities of daily life, 21% fatigue, 23% depression and 24% communication activity limitations.ConclusionAphasia severity, mood disorders and functional limitations may have a negative effect on QoL in patients with aphasia. Also, for the first time, we show that fatigue has an important impact on QoL in this population. Specific management of this symptom might be beneficial and should be explored in future studies.