Long-term effects of cranial irradiation and intrathecal chemotherapy in treatment of childhood leukemia: a MEG study of power spectrum and correlated cognitive dysfunction

<p>Abstract</p> <p>Background</p> <p>Prophylaxis to prevent relapses in the central nervous system after childhood acute lymphoblastic leukemia (ALL) used to consist of both intrathecal chemotherapy (CT) and cranial irradiation (CRT). CRT was mostly abolished in the eighties because of its neurotoxicity, and replaced with more intensive intrathecal CT. In this study, a group of survivors treated with CRT before 1983 and another group treated without CRT thereafter are investigated 20–25 years later, giving a much stronger perspective on long-term quality of life than previous studies. The outcomes will help to better understand these groups’ current needs and will aid in anticipating late effects of prophylactic CRT that is currently applied for other diseases. This study evaluates oscillatory neuronal activity in these long-term survivors. Power spectrum deviations are hypothesized to correlate with cognitive dysfunction.</p> <p>Methods</p> <p>Resting state eyes-closed magnetoencephalography (MEG) recordings were obtained from 14 ALL survivors treated with CT + CRT, 18 treated with CT alone and 35 controls. Relative spectral power was calculated in the δ, θ, α1, α2, β and γ frequency bands. The Amsterdam Neuropsychological Tasks (ANT) program was used to assess cognition in the executive functions domain. MEG data and ANT scores were correlated.</p> <p>Results</p> <p>In the CT + CRT group, relative θ power was slightly increased (p = 0.069) and α2 power was significantly decreased (p = 0.006). The CT + CRT group performed worse on various cognitive tests. A deficiency in visuomotor accuracy, especially of the right hand, could be clearly associated with the deviating regional θ and α2 powers (0.471 < r < 0.697). A significant association between decreased regional α2 power and less attentional fluctuations was found for CT + CRT patients as well as controls (0.078 < r < 0.666). Patients treated with CT alone displayed a power spectrum similar to controls, except for a significantly increased level of left frontal α2 power (p = 0.030).</p> <p>Conclusions</p> <p>The tendency towards global slowing of brain oscillatory activity, together with the fact that dementia has been reported as a late effect of CRT and the neuropsychological deficiencies currently present, suggest that the irradiated brain might be aging faster and could be at risk for early‐onset dementia. The CT group showed no signs of early aging.</p

Feasibility of continuous monitoring of vital signs in surgical patients on a general ward: an observational cohort study

Objective To determine feasibility, in terms of acceptability and system fidelity, of continuous vital signs monitoring in abdominal surgery patients on a general ward.Design Observational cohort study.Setting Tertiary teaching hospital.Participants Postoperative abdominal surgical patients (n=30) and nurses (n=23).Interventions Patients were continuously monitored with the SensiumVitals wearable device until discharge in addition to usual care, which is intermittent Modified Early Warning Score measurements. Heart rate, respiratory rate and axillary temperature were monitored every 2 min. Values and trends were visualised and alerts sent to the nurses.Outcomes System fidelity was measured by analysis of the monitoring data. Acceptability by patients and nurses was assessed using questionnaires.Results Thirty patients were monitored for a median duration of 81 hours (IQR 47–143) per patient, resulting in 115 217 measurements per parameter. In total, 19% (n=21 311) of heart rate, 51% (n=59 184) of respiratory rate and 9% of temperature measurements showed artefacts (n=10 269). The system algorithm sent 972 alerts (median alert rate of 4.5 per patient per day), of which 90.3% (n=878) were system alerts and 9.7% (n=94) were vital sign alerts. 35% (n=33) of vital sign alerts were true positives. 93% (n=25) of patients rated the patch as comfortable, 67% (n=18) felt safer and 89% (n=24) would like to wear it next time in the hospital. Nurses were neutral about usefulness, with a median score of 3.5 (IQR 3.1–4) on a 7-point Likert scale, ease of use 3.7 (IQR 3.2–4.8) and satisfaction 3.7 (IQR 3.2–4.8), but agreed on ease of learning at 5.0 (IQR 4.0–5.8). Neutral scores were mostly related to the perceived limited fidelity of the system.Conclusions Continuous monitoring of vital signs with a wearable device was well accepted by patients. Nurses’ ratings were highly variable, resulting in on average neutral attitude towards remote monitoring. Our results suggest it is feasible to monitor vital signs continuously on general wards, although acceptability of the device among nurses needs further improvement

The effect of steroids in patients undergoing cardiopulmonary bypass: an individual patient meta-analysis of two randomized trials

Objective: Steroids suppress the inflammatory response to cardiopulmonary bypass, but the impact on death at 30 days, myocardial infarction or injury, stroke, renal failure, respiratory failure, new atrial fibrillation, transfusion requirement, infection, and length of intensive care unit (ICU) and hospital stays are uncertain. Design: Patient-level data meta-analysis of 2 randomized trials. Setting: Eighty-eight cardiac surgical centers in 19 countries. Participants: A total of 11,989 participants, from the Steroids in Cardiac Surgery trial and the Dexamethasone in Cardiac Surgery study, undergoing cardiac surgery with the use of cardiopulmonary bypass. Interventions: Participants were randomly assigned to steroid or placebo. Measures and Main Results: Outcomes assessed were mortality at 30 days, myocardial infarction or injury, stroke, renal failure, respiratory failure, new atrial fibrillation, transfusion requirement, infection, and length of ICU and hospital stays. There was no significant difference in death at 30 days between the steroid and placebo groups (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.72-1.07). Myocardial infarction did not differ significantly (OR, 1.17; 95% CI, 0.93-1.47); however, myocardial injury was higher in the steroid group (OR, 1.25; 95% CI, 1.12-1.40). There were no significant differences for the outcomes of stroke, renal failure, new atrial fibrillation, or transfusion. Steroids significantly reduced respiratory failure (OR, 0.83; 95% CI, 0.75-0.99), infection (OR, 0.80; 95% CI, 0.72-0.89), and length of ICU (p < 0.001) and hospital stays (p = 0.006). Conclusions: This patient-level meta-analysis does not support the routine use of steroids in cardiac surgery. Steroid administration did not decrease the risk of death, myocardial infarction, stroke, renal failure, new atrial fibrillation, or transfusion. Steroids increased the risk of myocardial injury in both the Steroids in Cardiac Surgery and Dexamethasone in Cardiac Surgery trials. Finally, steroids lowered the risk of respiratory failure and infection, and reduced length of ICU and hospital stay

Substance use in individuals with mild to borderline intellectual disability:A comparison between self-report, collateral-report and biomarker analysis

Background and aims Individuals with mild or borderline intellectual disability (MBID) are at risk of substance use (SU). At present, it is unclear which strategy is the best for assessing SU in individuals with MBID. This study compares three strategies, namely self-report, collateral-report, and biomarker analysis. Methods and procedures In a sample of 112 participants with MBID from six Dutch facilities providing care to individuals with intellectual disabilities, willingness to participate, SU rates, and agreement between the three strategies were explored. The Substance use and misuse in Intellectual Disability − Questionnaire (SumID-Q; self-report) assesses lifetime use, use in the previous month, and recent use of tobacco, alcohol, cannabis, and stimulants. The Substance use and misuse in Intellectual Disability − Collateral-report questionnaire (SumID-CR; collateral-report) assesses staff members' report of participants' SU over the same reference periods as the SumID-Q. Biomarkers for SU, such as cotinine (metabolite of nicotine), ethanol, tetrahydrocannabinol (THC), and its metabolite THCCOOH, benzoylecgonine (metabolite of cocaine), and amphetamines were assessed in urine, hair, and sweat patches. Results Willingness to provide biomarker samples was significantly lower compared to willingness to complete the SumID-Q (p < 0.001). Most participants reported smoking, drinking alcohol, and using cannabis at least once in their lives, and about a fifth had ever used stimulants. Collateralreported lifetime use was significantly lower. However, self-reported past month and recent SU rates did not differ significantly from the rates from collateral-reports or biomarkers, with the exception of lower alcohol use rates found in biomarker analysis. The agreement between self-report and biomarker analysis was substantial (kappas 0.60–0.89), except for alcohol use (kappa 0.06). Disagreement between SumID-Q and biomarkers concerned mainly over-reporting of the SumID-Q. The agreement between SumID-CR and biomarker analysis was moderate to substantial (kappas 0.48 − 0.88), again with the exception of alcohol (kappa 0.02). Conclusions and implications In this study, the three strategies that were used to assess SU in individuals with MBID differed significantly in participation rates, but not in SU rates. Several explanations for the better-than-expected performance of self- and collateral-reports are presented. We conclude that for individuals with MBID, self-report combined with collateralreport can be used to assess current SU, and this combination may contribute to collaborative, early intervention efforts to reduce SU and its related harms in this vulnerable group

Towards a Multiplex Cereal Traceability Tool Using Padlock Probe Ligation on Genomic DNA

Current EU regulations on the protection of products with certain characteristics (geographical indications and designations of origin) aim to ensure fair competition for producers and increased consumers' trust. Within the European integrated research project TRACE analytical methods are being developed to allow the maintenance of specific regulations for PGIs (products of protected geographical indication) and PDOs (products of designated origin). An example within the project is the PGI wheat variety Farro della Garfagnana. Aim of the research was to develop amethod to establish the purity of Farro della Garfagnana DNA in in complex cereal mixtures. The combined approach of padlock probe ligation and multiplex microarray detection can identify possible admixtures. One undesired 'contaminant' for Farro della Garfagnana is common bread wheat (Triticum aestivum), containing the BBAuAuDD genome. Since Farro harbours the BBAuAu genome, absence of the D-genome rules out the presence of bread wheat. The current detection limit of this multimethod is at least 2.5 % bread wheat in Farro.JRC.DDG.D.2-Reference material

A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients

Abstract Background Nivolumab is administered in a weight-based or fixed-flat dosing regimen. For patients with non-small cell lung cancer (NSCLC), a potential exposure-response relationship has recently been reported and may argue against the current dosing strategies. The primary objectives were to determine nivolumab pharmacokinetics (PK) and to assess the relationship between drug clearance and clinical outcome in NSCLC, melanoma, and renal cell cancer (RCC). Methods In this prospective observational cohort study, individual estimates of nivolumab clearance and the impact of baseline covariates were determined using a population-PK model. Clearance was related to best overall response (RECISTv1.1), and stratified by tumor type. Results Two-hundred-twenty-one patients with metastatic cancer receiving nivolumab-monotherapy were included of whom 1,715 plasma samples were analyzed. Three baseline parameters had a significant effect on drug clearance and were internally validated in the population-PK model: gender, BSA, and serum albumin. Women had 22% lower clearance compared to men, while the threshold of BSA and albumin that led to &gt; 20% increase of clearance was &gt; 2.2m2 an

Enhancement opportunities in operating room utilization; with a statistical appendix

Item does not contain fulltextBACKGROUND: The purpose of this study was to assess the direct and indirect relationships between first-case tardiness (or "late start"), turnover time, underused operating room (OR) time, and raw utilization, as well as to determine which indicator had the most negative impact on OR utilization to identify improvement potential. Furthermore, we studied the indirect relationships of the three indicators of "nonoperative" time on OR utilization, to recognize possible "trickle down" effects during the day. MATERIALS AND METHODS: (Multiple) linear regression analysis and mediation effect analysis were applied to a data set from all eight University Medical Centers in the Netherlands. This data set consisted of 190,071 OR days (on which 623,871 surgical cases were performed). Results : Underused OR time at the end of the day had the strongest influence on raw utilization, followed by late start and turnover time. The relationships between the three "nonoperative" time indicators were negligible. The impact of the partial indirect effects of "nonoperative" time indicators on raw utilization were statistically significant, but relatively small. The "trickle down" effect that late start can cause resulting in an increased delay as the day progresses, was not supported by our results. CONCLUSIONS: The study findings clearly suggest that OR utilization can be improved by focusing on the reduction of underused OR time at the end of the day. Improving the prediction of total procedure time, improving OR scheduling by, for example, altering the sequencing of operations, changing patient cancellation policies, and flexible staffing of ORs adjusted to patient needs, are means to reduce "nonoperative" time