Updated systematic review and meta‐analysis of the predictive value of serum biomarkers in the assessment and management of fever during neutropenia in children with cancer

Routinely measurable biomarkers as predictors for adverse outcomes in febrile neutropenia could improve management through risk stratification. This systematic review assesses the predictive role of biomarkers in identifying events such as bacteraemia, clinically documented infections, microbiologically documented infection, severe sepsis requiring intensive care or high dependency care and death. This review collates 8319 episodes from 4843 patients. C‐reactive protein (CRP), interleukin (IL)‐6, IL‐8 and procalcitonin (PCT) consistently predict bacteraemia and severe sepsis; other outcomes have highly heterogeneous results. Performance of the biomarkers at admission using different thresholds demonstrates that PCT > 0.5 ng/mL offers the best compromise between sensitivity and specificity: sensitivity 0.67 (confidence interval [CI] 0.53‐0.79) specificity 0.73 (CI 0.66‐0.77). Seventeen studies describe the use of serial biomarkers, with PCT having the greatest discriminatory role. Biomarkers, potentially with serial measurements, may predict adverse outcomes in paediatric febrile neutropenia and their role in risk stratification is promising.     

Personality predicts activity in reward and emotional regions associated with humor

Previous research and theory suggest that two stable personality dimensions, extroversion and neuroticism, differentially influence emotional reactivity to a variety of pleasurable phenomena. Here, we use event-related functional MRI to address the putative neural and behavioral associations between humor appreciation and the personality dimensions of introversion-extroversion and emotional stability-neuroticism. Our analysis showed extroversion to positively correlate with humor-driven blood oxygenation level-dependent signal in discrete regions of the right orbital frontal cortex, ventrolateral prefrontal cortex, and bilateral temporal cortices. Introversion correlated with increased activation in several regions, most prominently the bilateral amygdala. Although neuroticism did not positively correlate with any whole-brain activation, emotional stability (i.e., the inverse of neuroticism) correlated with increased activation in the mesocortical-mesolimbic reward circuitry encompassing the right orbital frontal cortex, caudate, and nucleus accumbens. Our findings tie together existing neurobiological studies of humor appreciation and are compatible with the notion that personality style plays a fundamental role in the neurobiological systems subserving humor appreciation.     

Local expression of tumor necrosis factor-alpha and interleukin-4 mRNA in different types of warts

The natural history of warts shows considerable variations between individuals, ranging from spontaneous regression to prolonged persistence. The level of cytokines participate in the immune response to human papilloma virus. This work investigates local expression of T-helper1 (Th1)/ T-helper2 (Th2)/ cytokines in a trial to disclose the different immunological mechanisms affecting the natural history of warts. A total of thirty patients suffering from different types (common, plane, plantar and anogenital) of viral warts were included. An excision biopsy was used to assess tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4) expression. Local expression of TNF-alpha (Th1) and IL-4 (Th2) in wart tissue was determined using in-situ hybridization technique. The cytokines probes used in this assay detect messenger RNA (mRNA) in wart tissue. Local expression of TNF-alpha mRNA was higher in viral wart patients compared to healthy control (P < 0.01), while local expression of IL-4 was not significantly higher in patients compared to control (P > 0.05). Statistical analysis was done to determine whether variations in cytokine mRNA expression depend on wart location or clinical types. In conclusion, immunoreactivity to warts is likely to be associated with a predominant Th-1 or mixed Th-1/ Th-2 cytokine mRNA expression profile. However, it does not appear to be a simple causal relationship between expression of a Th-1 pattern and clearance.     

Dental student perception and assessment of their clinical knowledge in educating patients about preventive dentistry

In today's dental school curricula, an increasing amount of time is dedicated to technological advances, and preventive dentistry topics may not be adequately addressed. Freshman (D1) students participated in a new Introduction to Preventive Dentistry course, which consisted of didactic lectures, active learning breakout sessions and case‐based studies. The goal of this study was to determine if D1 dental students completing the course had a better knowledge and comfort level with basic preventive dentistry concepts and caries risk assessment than the upcoming graduating senior dental students. Following the completion of the course, D1 students were administered a survey that assessed their comfort level describing preventive dentistry topics to patients. This was immediately followed by an unannounced examination over the same topics. Senior (D4) students, who had not taken a formal course, reported statistically significant higher comfort levels than D1 students. However, the D4s scored significantly lower in all of the examination areas than the D1 students. Higher scores in D1s may have been due to recent exposure to the course material. However, the basic nature of the content‐specific questions should be easily answered by novice practitioners educating their patients on oral disease prevention. As the current data shows lower content‐specific scores of basic preventive dentistry knowledge amongst graduating D4 students, this may indicate a need for more guidance and education of students during the patient care. This study showed that implementation of a formalised course for D1 students can successfully ameliorate deficiencies in knowledge of preventive dentistry topics.     

Rationing critical care beds: a systematic review

OBJECTIVE: Rationing critical care beds occurs daily in the hospital setting. The objective of this systematic review was to examine the impact of rationing intensive care unit beds on the process and outcomes of care. DATA SOURCE: We searched MEDLINE (1966-2003), CINAHL (1982-2003), Ovid Healthstar (1975-2003), EMBASE (1980-2003), Scisearch (1980-2003), the Cochrane Library, PUBMED related articles, personal files, abstract proceedings, and reference lists. STUDY SELECTION: We included studies of seriously ill patients considered for admission to an intensive care unit bed during periods of reduced availability. We had no restriction on study design. Studies were excluded if rationing was performed using a scoring system or protocol and if cost-effectiveness was the only outcome. DATA EXTRACTION: In duplicate and independently, we performed data abstraction and quality assessment. DATA SYNTHESIS: We included ten observational studies. Hospital mortality rate was increased in patients refused intensive care unit admission vs. those admitted (odds ratio, 3.04; 95% confidence interval, 1.49-6.17). Factors associated with both intensive care unit bed refusal and increased mortality rate were increased age, severity of illness, and medical diagnosis. When intensive care unit beds were reduced, admitted patients were sicker, were less often admitted primarily for monitoring, and had a shorter intensive care unit length of stay, without other observed adverse effects. CONCLUSIONS: These studies suggest that patients who are perceived not to benefit from critical care are more often refused intensive care unit admission; refusal is associated with an increased risk of hospital death. During times of decreased critical bed availability, several factors, including age, illness severity, and medical diagnosis, are used to triage patients, although their relative importance is uncertain. Critical care bed rationing requires further investigation.     

Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes

Low-risk myelodysplastic syndrome (MDS) with normal cytogenetics accounts for approximately 50% of MDS patients. There are no pathognomonic markers in these cases and the diagnosis rests on cytomorphologic abnormalities in bone marrow and/or peripheral blood. Affymetrix high-resolution single-nucleotide polymorphism (SNP) genotyping microarrays allow detection of cytogenetically cryptic genomic aberrations. We have studied 119 low-risk MDS patients (refractory anemia [RA] = 22; refractory cytopenia with multilineage dysplasia [RCMD] = 51; refractory anemia with ringed sideroblasts [RARS] = 12; refractory cytopenia with multilineage dysplasia with ringed sideroblasts [RCMD-RS] = 12; 5q- syndrome = 16; refractory anemia with excess blasts [RAEB] = 6) using SNP microarrays to seek chromosomal markers undetected by conventional cytogenetics. Loss of heterozygosity (LOH) detected by 50K arrays was verified using 250K and 500K arrays. We demonstrate the presence of uniparental disomy (UPD) in 46%, deletions in 10%, and amplifications in 8% of cases. Copy number (CN) changes were acquired, whereas UPDs were also detected in constitutional DNA. UPD on 4q was identified in 25% of RARS, 12% of RCMD with normal cytogenetics, 17% of RAEB, and 6% of 5q- syndrome cases. Univariate analysis showed deletions (P = .04) and International Prognostic Scoring System (IPSS; P < .001) scores correlated with overall survival; however, on multivariate analysis only IPSS scores retained prognostic significance (P < .001). We show, for the first time, that SNP microarray analysis in low-risk MDS patients reveals hitherto unrecognized UPD and CN changes that may allow stratification of these patients for early therapeutic interventions.