Impact of Prehospital Pain Management on Emergency Department Management of Injured Children.

OBJECTIVE: Provision of analgesia for injured children is challenging for Emergency Medical Services (EMS) clinicians. Little is known about the effect of prehospital analgesia on emergency department (ED) care. We aimed to determine the impact of prehospital pain interventions on initial ED pain scale scores, timing and dosing of ED analgesia for injured patients transported by EMS. METHODS: This is a planned, secondary analysis of a prospective multicenter cohort of children with actual or suspected injuries transported to one of 11 PECARN-affiliated EDs from July 2019-April 2020. Using Wilcoxon rank sum for continuous variables and chi-square testing for categorical variables, we compared the change in EMS-to-ED pain scores and timing and dosing of ED-administered opioid analgesia in those who did and those who did not receive prehospital pain interventions. RESULTS: We enrolled 474 children with complete prehospital and ED pain management data. Prehospital interventions were performed on 262/474 (55%) of injured children and a total of 88 patients (19%) received prehospital opioids. Children who received prehospital opioids with or without adjunctive non-pharmacologic pain management experienced a greater reduction in pain severity and were more likely to receive ED opioids in higher doses earlier and throughout their ED care. Non-pharmacologic pain interventions alone did not impact ED care. CONCLUSIONS: We demonstrate that prehospital opioid analgesia is associated with both a significant reduction in pain severity at ED arrival and the administration of higher doses of opioid analgesia earlier and throughout ED care.

Morning surge in blood pressure using a random-effects multiple-component cosinor model.

Blood pressure (BP) fluctuates throughout the day. The pattern it follows represents one of the most important circadian rhythms in the human body. For example, morning BP surge has been suggested as a potential risk factor for cardiovascular events occurring in the morning, but the accurate quantification of this phenomenon remains a challenge. Here, we outline a novel method to quantify morning surge. We demonstrate how the most commonly used method to model 24-hour BP, the single cosinor approach, can be extended to a multiple-component cosinor random-effects model. We outline how this model can be used to obtain a measure of morning BP surge by obtaining derivatives of the model fit. The model is compared with a functional principal component analysis that determines the main components of variability in the data. Data from the Mitchelstown Study, a population-based study of Irish adults (n = 2047), were used where a subsample (1207) underwent 24-hour ambulatory blood pressure monitoring. We demonstrate that our 2-component model provided a significant improvement in fit compared with a single model and a similar fit to a more complex model captured by b-splines using functional principal component analysis. The estimate of the average maximum slope was 2.857 mmHg/30 min (bootstrap estimates; 95% CI: 2.855-2.858 mmHg/30 min). Simulation results allowed us to quantify the between-individual SD in maximum slopes, which was 1.02 mmHg/30 min. By obtaining derivatives we have demonstrated a novel approach to quantify morning BP surge and its variation between individuals. This is the first demonstration of cosinor approach to obtain a measure of morning surge.

Short-term genetic consequences of habitat loss and fragmentation for the neotropical palm Oenocarpus bataua.

Habitat loss and fragmentation may impact animal-mediated dispersal of seed and pollen, and a key question is how the genetic attributes of plant populations respond to these changes. Theory predicts that genetic diversity may be less sensitive to such disruptions in the short term, whereas inbreeding and genetic structure may respond more strongly. However, results from studies to date vary in relation to species, context and the parameter being assessed, triggering calls for more empirical studies, especially from the tropics, where plant-animal dispersal mutualisms are both disproportionately common and at risk. We compared the genetic characteristics of adults and recruits in a long-lived palm Oenocarpus bataua in a recently fragmented landscape (<2 generations) in northwest Ecuador using a suite of 10 polymorphic microsatellite markers. We sampled individuals from six forest fragments and one nearby continuous forest. Our goal was to assess short-term consequences of fragmentation, with a focus on how well empirical data from this system follow theoretical expectations. Mostly congruent with predictions, we found stronger genetic differentiation and fine-scale spatial genetic structure among recruits in fragments compared with recruits in continuous forest, but we did not record differences in genetic diversity or inbreeding, nor did we record any differences between adults in fragments and adults in continuous forest. Our findings suggest that genetic characteristics of populations vary in their sensitivity to change in response to habitat loss and fragmentation, and that fine-scale spatial genetic structure may be a particularly useful indicator of genetic change in recently fragmented landscapes.

Epistatic interactions of AKT1 on human medial temporal lobe biology and pharmacogenetic implications.

AKT1 controls important processes in medial temporal lobe (MTL) development and plasticity, but the impact of human genetic variation in AKT1 on these processes is not known in healthy or disease states. Here, we report that an AKT1 variant (rs1130233) previously associated with AKT1 protein expression, prefrontal function and schizophrenia, affects human MTL structure and memory function. Further, supporting AKT1's role in transducing hippocampal neuroplasticity and dopaminergic processes, we found epistasis with functional polymorphisms in BDNF and COMT--genes also implicated in MTL biology related to AKT1. Consistent with prior predictions that these biologic processes relate to schizophrenia, we found epistasis between the same AKT1, BDNF and COMT functional variants on schizophrenia risk, and pharmacogenetic interactions of AKT1 with the effects on cognition and brain volume measures by AKT1 activators in common clinical use--lithium and sodium valproate. Our findings suggest that AKT1 affects risk for schizophrenia and accompanying cognitive deficits, at least in part through specific genetic interactions related to brain neuroplasticity and development, and that these AKT1 effects may be pharmacologically modulated in patients.

Prediction of outcome of early ER+ breast cancer is improved using a biomarker panel, which includes Ki-67 and p53.

BACKGROUND: The aim of this study is to determine whether immunohistochemical (IHC) assessment of Ki67 and p53 improves prognostication of oestrogen receptor-positive (ER+) breast cancer after breast-conserving therapy (BCT). In all, 498 patients with invasive breast cancer from a randomised trial of BCT with or without tumour bed radiation boost were assessed using IHC. METHODS: The ER+ tumours were classified as 'luminal A' (LA): ER+ and/or PR+, Ki-67 low, p53-, HER2- or 'luminal B' (LB): ER+ and/or PR+and/or Ki-67 high and/or p53+ and/or HER2+. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ispilateral breast tumour recurrence (IBTR), locoregional recurrence (LRR), distant metastasis-free survival (DMFS) and breast cancer-specific survival (BCSS). RESULTS: In all, 73 patients previously LA were re-classified as LB: a greater than four-fold increase (4.6-19.3%) compared with ER, PR, HER2 alone. In multivariate analysis, the LB signature independently predicted LRR (hazard ratio (HR) 3.612, 95% CI 1.555-8.340, P=0.003), DMFS (HR 3.023, 95% CI 1.501-6.087, P=0.002) and BCSS (HR 3.617, 95% CI 1.629-8.031, P=0.002) but not IBTR. CONCLUSION: The prognostic evaluation of ER+ breast cancer is improved using a marker panel, which includes Ki-67 and p53. This may help better define a group of poor prognosis ER+ patients with a greater probability of failure with endocrine therapy.

CT colonography and transient bacteraemia: implications for antibiotic prophylaxis.

OBJECTIVES: To determine the prevalence of transient bacteraemia after CT colonography (CTC). METHODS: Blood cultures were obtained at 5, 10 and 15 min after CTC from 100 consecutive consenting patients. Blood samples were cultured in both aerobic and anaerobic media and positive blood culture samples were analysed by a microbiologist. RESULTS: Blood culture samples were positive for growth in sixteen patients. All positive blood culture samples were confirmed skin contaminants. There were no cases of significant bacteraemia. The estimated significant bacteraemia rate as a result of CTC is 0-3.7%, based on 95% confidence intervals around extreme results using Wilson's score method. CONCLUSIONS: American Heart Association and National Institute for Clinical Excellence guidelines advise that antibiotic prophylaxis before lower gastrointestinal endoscopy is not indicated in patients with at risk cardiac lesions (ARCL) as the risk of a transient bacteraemia leading to infective endocarditis is low. These data show that the prevalence of transient bacteraemia after CTC is also low. It follows that patients with ARCL do not require antibiotic prophylaxis before CTC.

[Medical students as members of the health care team]. / Los estudiantes de medicina como parte del equipo de salud.

BACKGROUND: Teaching hospitals include both undergraduate and postgraduate students, but the role of medical students in the health care team has not been clearly established. AIM: To know the opinion of different professionals about the role of medical students and how this opinion may have an influence in medical education. MATERIAL AND METHODS: A qualitative method was used, asking open questions to focus groups of physicians, nurses and midwives, technicians and undergraduate medical students of 4th and 5th grade. RESULTS: Physicians believe that medical students have no special role in the health care team, nurses think that they may help in communication with patients, and technicians (nurses's aids) value their companionship and closeness with patients. Medical students recognize that their main function is to learn but they are aware that they do help patients. They suggest increasing their integration with other students of other health related careers. CONCLUSIONS: Although medical students are usually not seen as part of the health care team, they may fulfill a role with patients during their clinical learning practice. This would improve the quality of their training and the multidisciplinary work of the health care team.

Response of Ips confusus to synthetic sex pheromones in nature.

The first flight response of bark beetles to synthetic sex pheromones under natural conditions is reported. Two insect species predaceous on this bark beetle also responded. The synthetic compounds delivered in an airstream from a substrate of Carbowax 20M on Chromosorb A appear to elicit the same response as the natural attractant from male-infested bolts of ponderosa pine elicits.

Brevicomin: principal sex attractant in the frass of the female western pine beetle.

The principal component of the sex attractant produced by the female western pine beetle (Dendrotonus brevicomis) is exo-7-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]octane; the trivial name brevicomin is suggested.

Western pine beetle: specificity among enantiomers of male and female components of an attractant pheromone.

The flight response of both sexes of Dendroctonus brevicomis to the mixture of myrcene, racemic frontalin, and (1R,5S,7R)-(+)-exo-brevicomin and to the mixture of myrcene, (1S,5R)-(-)-frontalin and racemic exo-brevicomin was significantly greater than the response to the same mixtures in which the antipodes were substituted. The flight response to these two mixtures was also greater than the response to the ternary mixture of myrcene, racemic frontalin, and racemic exo-brevicomin (MFE). The walking response of both sexes to the mixture of myrcene, racemic frontalin, and (+)-exo-brevicomin was not different from the response to MFE. Substitution of the antipode lowered the response when compared to that of MFE. When evaporated with ponderosa pine turpentine, (-)-frontalin was active in the field while its antipode was not.

Frequency and histopathologic basis of hepatic surface nodularity in patients with fulminant hepatic failure.

PURPOSE: To determine the frequency and histopathologic basis of hepatic surface nodularity at imaging in patients with fulminant hepatic failure. MATERIALS AND METHODS: The committee on human research approved this HIPAA-compliant study and waived written informed consent. Thirty-five consecutive patients [24 female [mean age, 38 years +/- 19 (standard deviation); range, 1-67 years] and 11 male [mean age, 29 years +/- 22; range, 2-61 years]] with a mean age of 35 years +/- 20 (range, 1-67 years) who underwent liver transplantation for fulminant hepatic failure at our institution during a 5-year period were retrospectively identified. Pretransplant ultrasonographic (n = 38; three patients each had two studies) and computed tomographic (n = 2) studies were retrospectively and independently reviewed for hepatic surface nodularity. Liver explant histopathologic findings (n = 33; slides unavailable in two patients) were reviewed for cirrhosis and for the combination of alternating foci of confluent regenerative nodules and necrosis. Differences among patients with nodular versus smooth liver surfaces in the proportion with the two histopathologic findings were compared with Fisher exact test. Differences in illness duration and maximum liver biochemical indices were compared with Mann-Whitney Rank Sum test. RESULTS: Fifteen of 35 patients (43%) demonstrated hepatic surface nodularity at pretransplant imaging, none of whom had cirrhosis at histopathologic examination. One patient with a smooth liver surface had cirrhosis. Compared with those who had a smooth liver surface, patients with hepatic surface nodularity had a significantly greater proportion with the histopathologic finding of a combination of alternating foci of confluent regenerative nodules and necrosis (12 of 14 vs one of 19, P < .001), longer illness duration (31 days +/- 32 vs 13 days +/- 13, P = .029), and lower maximum liver biochemical indices. CONCLUSION: Hepatic surface nodularity is commonly seen at imaging in fulminant hepatic failure and usually reflects a combination of alternating foci of confluent regenerative nodules and necrosis; this is important because an erroneous radiologic diagnosis of cirrhosis in this setting could adversely affect transplantation status.

Mid-Upper Arm Circumference (MUAC) shows strong geographical variations in children with edema: results from 2277 surveys in 55 countries.

BACKGROUND: Severe acute malnutrition (SAM) is defined by a mid-upper arm circumference (MUAC) less than 115 mm or a weight-for-height z-score (WHZ) less than - 3 but also by the presence of bilateral pitting edema, also known as kwashiorkor or edematous malnutrition. Although edematous malnutrition is a life threatening condition, it has not been prioritized in recent research and has been neglected in global health initiatives. METHODS: Two thousand two hundred and seventy-seven survey datasets were collected, and the age, sex, weight, height, MUAC and the presence or absence of edema were analyzed for more than 1.7 million children of 6-59 months from 55 countries, covering the period of 1992 to 2015. RESULTS: During the last 10 years, the prevalence of nutritional edema was estimated at less than 1% in most of the countries where data were available. Some countries in Central and South Africa, as well as Haiti in the Caribbean, reported higher prevalence, and Yemen, Zimbabwe and the Democratic Republic of Congo reported prevalence between 1 and 2%. Surveys from a significant number of countries in Africa indicated that more than a third of SAM cases defined by MUAC < 115 mm had edema, including Malawi, Rwanda, Zambia, Togo and Cameroon. Children with edema were consistently shown across various analyses to have a significantly lower median MUAC than children without edema. However, the MUAC distribution had a large spread, with many children with edema having a MUAC > 115 mm, and this varied widely between countries, with median MUAC in edematous children ranging from 102 mm (Mali) to 162 mm (Sri Lanka). The proportion of SAM children with edema was found to be higher for older children. CONCLUSIONS: This study provides the most recent geographical distribution of nutritional edema and demonstrates that edema is a common manifestation of SAM, mainly occurring in Central Africa. The associated nutritional status, as assessed by MUAC, shows strong variation among children with edema. A more systematic and standardized system is required to collect data on edema in order to facilitate prevention, screening, referral and treatment of edematous malnutrition.

A pilot randomised comparison of dexamethasone 96 mg vs 16 mg per day for malignant spinal-cord compression treated by radiotherapy: TROG 01.05 Superdex study.

AIM: To test the viability of a full-scale randomised comparison of two steroid doses given with radiotherapy for malignant spinal-cord compression (MSCC), to test Internet randomisation and to compare different functional outcome measures. MATERIALS AND METHODS: A log of screened patients at eight recruiting centres was maintained. Patients were randomised via the Superdex website to either 96 mg or 16 mg daily of dexamethasone. Radiotherapy treatment was 30 Gy in 10 fractions. Outcomes assessed used ambulation, Barthel Index ambulation, Functional Independence Measure (FIM) ambulation and Functional Improvement Score (FIS) at 1 month. RESULTS: One hundred and thirty-one patients were screened. Ninety-three (71%) were ineligible, 65% of these were because duration of prior steroid use was greater than 12 h, failure to meet strict definition of magnetic resonance imaging, defined MSCC, multi-level disease or previous spinal-cord compression treatment. Twenty of the 38 eligible patients were randomised, including seven outside standard office hours. There was a high rate of serious adverse events (n = 9), but only one was considered likely to be related to study medication. At baseline, 75% were ambulant, 70% had FIM ambulation scores greater than 5 and 50% had Barthel Index ambulation scores greater than 2. At day 28, including all randomised patients (by scoring four dead patients as non-ambulant), ambulation scores by the various definitions were 60%, 45% and 40%, respectively. For the 16 patients evaluable at day 28, the mean FIS was -1.4. Median survival was 69 days and 1-year survival 13%. CONCLUSION: Web randomisation was successful; however, the high ineligibility rate precludes a full-scale dexamethasone dose trial in Australia. Choice of measure of ambulation has potentially significant effects on outcomes and implications for the design of any future MSCC trials. Referral delays are of concern.

Identification of differentially expressed genes in pancreatic cancer cells using cDNA microarray.

To identify new diagnostic markers and drug targets for pancreatic cancer, we compared the gene expression patterns of pancreatic cancer cell lines growing in tissue culture with those of normal pancreas using cDNA microarray analysis. Fluorescently (cyanine 5) labeled cDNA probes, made individually from mRNA samples of nine pancreatic cell lines, were each combined with fluorescently (cyanine 3) labeled universal reference mRNA. The mixed probes of each sample were then hybridized with 5760 cDNA arrays (5289 unique cDNA sequences) printed on individual microscope slides. Fluorescently (cyanine 5) labeled normal pancreas mRNA was also compared with the same universal reference mRNA reference pool. The expression ratios of neoplastic versus normal pancreas cells were then calculated by multiplying the ratio of cancer versus the universal reference mRNA and the ratio of the universal reference mRNA cell versus normal pancreas. For 5289 different genes interrogated by the arrays, 30 of them showed an expression ratio 2 SD from the mean in at least three of the nine pancreatic cell lines studied. To confirm the expression profiles of these genes, quantitative reverse transcription-PCR and Northern blot were carried out for 25 of the overexpressed genes. To verify the overexpression in patient samples, two of the overexpressed genes, c-Myc and Rad51, were selected to undergo analysis by reverse transcription-PCR in frozen tumor tissues and by immunostaining in paraffin-embedded tissue section microarrays. The results of these experiments are in agreement with the microarray data. Potential up-regulated targets of note from this study include urokinase-type plasminogen activator receptor, serine/threonine kinase 15, thioredoxin reductase, and CDC28 protein kinase 2, as well as several others.

July 2004: 40-year-old man with headaches and dyspnea.

A 40-year-old man had a 6-week history of severe frontal headaches and dry cough. Chest x-ray showed hilar adenopathy with bilateral parenchymal infiltrates. A diagnosis of atypical pneumonia was made. Four weeks later he was admitted with persistent headache. Infectious screen was negative. Brain MR post contrast, revealed cerebellar enhancement and swelling with moderate tonsillar herniation; findings which precluded the performance of a lumbar puncture. High resolution CT thorax confirmed hilar abnormalities; shown by microscopy to represent non caseating granulomata. A presumptive diagnosis of sarcoidosis was reached. Despite an initial symptomatic improvement his headache persisted. Repeat MRI, eleven days after admission, showed reduced cerebellar enhancement and swelling with no change in the degree of tonsillar herniation. He deteriorated acutely and died two weeks after admission. Autopsy revealed cerebral oedema with tonsillar herniation secondary to cryptococcal meningitis variety neoformans. There was no evidence of neurosarcoid. Active and inactive sarcoid was identified in the lungs and hilar nodes with no evidence of systemic sarcoid. Focal evidence of cryptococcal pneumonitis was present in the lung as a necrotic focus. A strong index of clinical suspicion is necessary to diagnose the rare association of cryptococcus complicating sarcoidosis.

Inhalation aromatherapy during radiotherapy: results of a placebo-controlled double-blind randomized trial.

PURPOSE: To determine whether the inhalation of aromatherapy during radiotherapy reduces anxiety. PATIENTS AND METHODS: Three hundred thirteen patients undergoing radiotherapy were randomly assigned to receive either carrier oil with fractionated oils, carrier oil only, or pure essential oils of lavender, bergamot, and cedarwood administered by inhalation concurrently with radiation treatment. Patients underwent assessment by the Hospital Anxiety and Depression Scale (HADS) and the Somatic and Psychological Health Report (SPHERE) at baseline and at treatment completion. RESULTS: There were no significant differences in HADS depression or SPHERE scores between the randomly assigned groups. However, HADS anxiety scores were significantly lower at treatment completion in the carrier oil only group compared with either of the fragrant arms (P =.04). CONCLUSION: Aromatherapy, as administered in this study, is not beneficial.

Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease.

A new class of potent, selective, nonsteroidal inhibitors of aromatase have been discovered. The most potent member of this series is fadrozole hydrochloride, CGS 16949 A, 4-(5,6,7,8-tetrahydroimidazo[1,5-alpha]pyridin-5-yl)benzonitrile monohydrochloride, 26a. In addition, the 6,7-dihydropyrrolo[1,2-c]imidazole (21a) and the 6,7,8,9-tetrahydroimidazo[1,5-alpha]azepine (21b) analogues were synthesized and evaluated. CGS 16949 A's ability to selectively inhibit aromatase (IC50 = 4.5 nM) over other cytochrome P-450 enzymes and suppress estrogen production when administered orally make it a suitable candidate to test the potential of an aromatase inhibitor in estrogen-dependent diseases including breast cancer.

Angiotensin converting enzyme inhibitors: 1-glutarylindoline-2-carboxylic acids derivatives.

The preparation of a series of 1-glutarylindoline-2(S)-carboxylic acid derivatives, 6a-v and 21a-c, is described. The above compounds were tested for inhibition of angiotensin converting enzyme. The structure-activity relationship of the series is also discussed. Compound 6u, the most potent member of the series, had an in vitro IC50 of 4.8 X 10(-9) M. Compound 6v, an ethyl ester of 6u, lowered blood pressure 70 mm in spontaneous hypertensive rats at an oral dose of 30 mg/kg.

Imidazo[1,5-a]pyridines: a new class of thromboxane A2 synthetase inhibitors.

The synthesis and structure-activity profile of a new class of potent and highly specific thromboxane A2 synthetase inhibitors is described. The most potent member of this series in vitro is determined to be imidazo[1,5-a]-pyridine-5-hexanoic acid (9).