Delirium occurs frequently in adults undergoing hematopoietic cell transplantation, with significant associated morbidity. Little is known about the burden of delirium in children in the ...peri-transplant period. This study was designed to determine delirium rates, define risk factors (demographic and treatment related), and establish feasibility of multi-institutional bedside screening for delirium in children undergoing hematopoietic cell transplant.
This is a multi-institutional point prevalence study. All subjects were prospectively screened for delirium twice daily using the Cornell Assessment of Pediatric Delirium over a 10-day period. De-identified data, including basic demographics and daily characteristics, were extracted from the electronic medical record.
Eleven North American institutions were included, 106 children were enrolled, and 883 hospital days were captured. Delirium screening was successfully completed on more than 98% of the study days. Forty-eight children (45%) developed delirium over the course of the 10-day study. Children were diagnosed with delirium on 161/883 study days, for an overall delirium rate of 18% per day. Higher delirium rates were noted in children <5 years old (aOR 0.41 for children over 5 years), and in association with specific medications (melatonin, steroids, and tacrolimus).
Delirium was a frequent occurrence in our study cohort, with identifiable risk factors. Delirium screening is highly feasible in the pediatric hematopoietic cell transplant patient population. A large-scale prospective longitudinal study following children throughout their transplant course is urgently needed to fully describe the epidemiology of pediatric delirium, explore the effects of delirium on patient outcomes, and establish guidelines to prevent and treat delirium in the peri-transplant period.
Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive androgen-independent prostate cancer. We compared docetaxel plus estramustine with mitoxantrone plus ...prednisone in men with metastatic, hormone-independent prostate cancer.
We randomly assigned 770 men to one of two treatments, each given in 21-day cycles: 280 mg of estramustine three times daily on days 1 through 5, 60 mg of docetaxel per square meter of body-surface area on day 2, and 60 mg of dexamethasone in three divided doses before docetaxel, or 12 mg of mitoxantrone per square meter on day 1 plus 5 mg of prednisone twice daily. The primary end point was overall survival; secondary end points were progression-free survival, objective response rates, and post-treatment declines of at least 50 percent in serum prostate-specific antigen (PSA) levels.
Of 674 eligible patients, 338 were assigned to receive docetaxel and estramustine and 336 to receive mitoxantrone and prednisone. In an intention-to-treat analysis, the median overall survival was longer in the group given docetaxel and estramustine than in the group given mitoxantrone and prednisone (17.5 months vs. 15.6 months, P=0.02 by the log-rank test), and the corresponding hazard ratio for death was 0.80 (95 percent confidence interval, 0.67 to 0.97). The median time to progression was 6.3 months in the group given docetaxel and estramustine and 3.2 months in the group given mitoxantrone and prednisone (P<0.001 by the log-rank test). PSA declines of at least 50 percent occurred in 50 percent and 27 percent of patients, respectively (P<0.001), and objective tumor responses were observed in 17 percent and 11 percent of patients with bidimensionally measurable disease, respectively (P=0.30). Grade 3 or 4 neutropenic fevers (P=0.01), nausea and vomiting (P<0.001), and cardiovascular events (P=0.001) were more common among patients receiving docetaxel and estramustine than among those receiving mitoxantrone and prednisone. Pain relief was similar in both groups.
The improvement in median survival of nearly two months with docetaxel and estramustine, as compared with mitoxantrone and prednisone, provides support for this approach in men with metastatic, androgen-independent prostate cancer.
Energy metabolism and insulin action follow a diurnal rhythm. It is therefore important that investigations into dysregulation of these pathways are relevant to the physiology of this diurnal rhythm.
...We examined glucose uptake, markers of insulin action, and the phosphorylation of insulin signaling intermediates in muscle of chow and high fat, high sucrose (HFHS) diet-fed rats over the normal diurnal cycle.
HFHS animals displayed hyperinsulinemia but had reduced systemic glucose disposal and lower muscle glucose uptake during the feeding period. Analysis of gene expression, enzyme activity, protein abundance and phosphorylation revealed a clear diurnal regulation of substrate oxidation pathways with no difference in Akt signaling in muscle. Transfection of a constitutively active Akt2 into the muscle of HFHS rats did not rescue diet-induced reductions in insulin-stimulated glucose uptake.
These studies suggest that reduced glucose uptake in muscle during the diurnal cycle induced by short-term HFHS-feeding is not the result of reduced insulin signaling.
•Investigating metabolism in rodents over the diurnal cycle more accurately models normal animal physiology.•Diurnal regulation of substrate oxidation is altered in muscle of HFHS-fed rats.•There is a disconnect between glucose uptake and canonical insulin signaling in muscle.•Activation of Akt2 does not rescue diet-induced reductions in insulin-stimulated glucose uptake in muscle.
Previous studies have suggested that frailty among older adults with cancer is associated with a variety of negative outcomes, including greater chemotherapy toxicity and worse survival. However, ...results often do not include patient-reported outcomes, such as quality of life (QOL). The objective of this study was to evaluate frailty prior to receipt of moderately- or highly-emetogenic chemotherapy and acute changes in QOL in patients at least 65 years of age. It was hypothesized that frail patients would report greater declines in QOL.
Participants completed questionnaires before receiving their first infusion and again five days later. A 59-item deficit accumulation index score was created at baseline using a modified Rockwood frailty index. QOL was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G). The relationship between baseline frailty and QOL was evaluated using a dichotomized deficit accumulation index (frail vs. robust) in repeated measures ANOVA.
Study participants (n = 151) had a mean age of 72 (SD = 4.5) and 62% were female. Nearly half (42%) were frail at baseline. Frail participants reported worse QOL at baseline compared to robust participants. Frail patients reported smaller declines in overall and physical (p < 0.0001) and emotional (p = 0.006) QOL from baseline to five days after receiving chemotherapy. At five days, frail participants reported better emotional and physical QOL compared to robust participants.
Contrary to expectations, frail patients reported smaller declines in QOL compared to robust patients using a deficit accumulation index. These results can be used to help educate frail patients on what to expect during treatment.
Influxes of migrant women of childbearing age to receiving countries have made their perinatal health status a key priority for many governments. The international research collaboration
Reproductive ...Outcomes And Migration (ROAM) reviewed published studies to assess whether migrants in western industrialised countries have consistently poorer perinatal health than receiving-country women. A systematic review of literature from Medline, Health Star, Embase and PsychInfo from 1995 to 2008 included studies of migrant women/infants related to pregnancy or birth. Studies were excluded if there was no cross-border movement or comparison group or if the receiving country was not western and industrialised. Studies were assessed for quality, analysed descriptively and meta-analysed when possible. We identified 133 reports (>20,000,000 migrants), only 23 of which could be meta-analysed. Migrants were described primarily by geographic origin; other relevant aspects (e.g., time in country, language fluency) were rarely studied. Migrants' results for preterm birth, low birthweight and health-promoting behaviour were as good or better as those for receiving-country women in ≥50% of all studies. Meta-analyses found that Asian, North African and sub-Saharan African migrants were at greater risk of feto-infant mortality than ‘majority’ receiving populations, and Asian and sub-Saharan African migrants at greater risk of preterm birth. The migration literature is extensive, but the heterogeneity of the study designs and definitions of migrants limits the conclusions that can be drawn. Research that uses clear, specific migrant definitions, adjusts for relevant risk factors and includes other aspects of migrant experience is needed to confirm and understand these associations.
Children at risk for early reading difficulties were identified on entry into kindergarten, and half of these children received small-group intervention two to three times a week during their ...kindergarten year. The other half received whatever remedial assistance was offered by their home schools. These children were again assessed at the beginning of first grade, and those who continued to have difficulties in reading received either one-to-one daily tutoring offered by project teachers from the beginning to the end of first grade or whatever remedial assistance was offered by their home schools over the same time period. All target children were periodically assessed through the end of third grade. Results suggest that either kindergarten intervention alone or kindergarten intervention combined with first-grade intervention are both useful vehicles for preventing early and long-term reading difficulties in most at-risk children.
Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for ...virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias.
To assess the disease-stabilizing activity of carboxyaminoimidazole (CAI) in patients with metastatic renal cell cancer (RCC) using a randomized discontinuation trial (RDT) design.
Recruited patients ...had a performance status of 0 to 2, minimal neuropathy or cerebellar dysfunction, measurable disease, and normal organ function. Treatment with 250 mg/d CAI was initiated in all patients and continued until disease progression in those with an objective response. Protocol treatment was discontinued for unacceptable toxicity or progressive disease; patients with stable disease at the 16-week evaluation point were randomly assigned in a double-blind manner to continued CAI or placebo. The primary end point was the stable disease rate in the randomized groups.
A total of 368 patients were accrued and received therapy. Ninety percent had a performance status of 0 or 1, 80% underwent a prior nephrectomy, and 41% had received no prior systemic therapy. Serious or life-threatening toxicity was experienced by 34%, with asthenia (15%) and neuropsychiatric difficulties (7%) being most common. At the randomization point, 51% of patients had progressed, 30% withdrew, 1% experienced a partial response, and 17% had stable disease and were randomly assigned. A Bayesian futility analysis utilizing the first 49 randomly assigned patients suggested that the probability of demonstrating a higher stable disease rate in the experimental group was less than 9% even under the most optimistic a priori assumptions, and further trial accrual was halted.
CAI is inactive in RCC. The RDT design should be further explored for evaluating activity of putative disease stabilizing agents.
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