Routine repeat head CT may not be necessary for patients with mild TBI.

Background:Routine repeat cranial CT (RHCT) is standard of care for CT-verified traumatic brain injury (TBI). Despite mixed evidence, those with mild TBI are subject to radiation and expense from serial CT scans. Thus, we investigated the necessity and utility of RHCT for patients with mild TBI. We hypothesized that repeat head CT in these patients would not alter patient care or outcomes. Methods:We retrospectively studied patients suffering from mild TBI (Glasgow Coma Scale (GCS) score 13-15) and treated at the R Adams Cowley Shock Trauma Center from November 2014 through January 2015. The primary outcome was the need for surgical intervention. Outcomes were compared using paired Student's t-test, and stratified by injury on initial CT, GCS change, demographics, and presenting vital signs (mean ± SD). Results:Eighty-five patients met inclusion criteria with an average initial GCS score=14.6±0.57. Our center sees about 2800 patients with TBI per year, or about 230 per month. This includes patients with concussions. This sample represents about 30% of patients with TBI seen during the study period. Ten patients required operation (four based on initial CT and others for worsening GCS, headaches, large unresolving injury). There was progression of injury on repeat CT scan in only two patients that required operation, and this accompanied clinical deterioration. The mean brain Abbreviated Injury Scale (AIS) score was 4.8±0.3 for surgical patients on initial CT scan compared with 3.4±0.6 (P<0.001) for non-surgical patients. Initial CT subdural hematoma size was 1.1±0.6 cm for surgical patients compared with 0.49±0.3 cm (P=0.05) for non-surgical patients. There was no significant difference between intervention groups in terms of other intracranial injuries, demographics, vital signs, or change in GCS. Overall, 75 patients that did not require surgical intervention received RHCT. At $340 per CT,$51 000 was spent on unnecessary imaging ($367 000/year, extrapolated). Discussion:In an environment of increased scrutiny on healthcare expenditures, it is necessary to question dogma and eliminate unnecessary cost. Our data questions the use of routine repeat head CT scans in every patient with anatomic TBI and suggests that clinically stable patients with small injury can simply be followed clinically. Level of evidence:Level III

An ELISA-based procedure for assaying proteins in digests of human leukocytes and cell lines, using specifically selected peptides and appropriate antibodies

BACKGROUND: We describe the application of an ELISA-based assay (the Peptidomatrix) that can be used to simultaneously identify and quantitate a number of proteins in biological samples. The biological sample (blood component, biopsy, culture or other) is first lysed to release all the proteins, without any additional separation. The denatured proteins in the sample are then digested in bulk with the desired proteolytic enzyme(s). The peptides in the digest are then assayed by appropriate antibodies, using a competition ELISA protocol. RESULTS: As an example of its use, the present paper applies the Peptidomatrix to the assay of four membrane proteins MDR1 (P-glycoprotein or ABCB1), MRP1 (ABCC1), BCRP/MXR (ABCG2) and the alpha subunit of the Na, K_ATPase (ATP1A1), present in a number of cell lines and in human lymphocytes. We show that we can detect and quantitate these proteins, using a series of peptide-antibody pairs, and that we can differentiate between cell lines or cell preparations that express the target proteins and those that do not. CONCLUSION: We have devised a simple, ELISA-based proteomics assay that enables the quantitation of designated proteins in a cell or tissue sample, and that can be used in any laboratory, with minimal specialized equipment

Piloting a mental health training programme for community health workers in South Africa: an exploration of changes in knowledge, confidence and attitudes

Background There is a shortage of trained mental health workers in spite of the significant contribution of psychiatric disorders to the global disease burden. Task shifting, through the delegation of health care tasks to less specialised health workers such as community health workers (CHWs), is a promising approach to address the human resource shortage. CHWs in the Western Cape province of South Africa provide comprehensive chronic support which includes that for mental illness, but have thus far not received standardized mental health training. It is unknown whether a structured mental health training programme would be acceptable and feasible, and result improved knowledge, confidence and attitudes amongst CHWs. Methods We developed and piloted a mental health training programme for CHWs, in line with the UNESCO guidelines; the WHO Mental Health Gap Action Programme and the South African National framework for CHW training. In our quasi-experimental (before-after) cohort intervention study we measured outcomes at the start and end of training included: 1) Mental health knowledge, measured through the use of case vignettes and the Mental Health Knowledge Schedule; 2) confidence, measured with the Mental Health Nurse Clinical Confidence Scale; and 3) attitudes, measured with the Community Attitudes towards the Mentally Ill Scale. Knowledge measures were repeated 3 months later. Acceptability data were obtained from daily evaluation questionnaires and a training evaluation questionnaire, while feasibility was measured by participant attendance at training sessions. Results Fifty-eight CHWs received the training, with most (n = 56, 97.0%) attending at least 7 of the 8 sessions. Most participants (n = 29, 63.04%) demonstrated significant improvement in knowledge, which was sustained at 3-months. There was significant improvement in confidence, along with changes in attitude, indicating improved benevolence, reduced social restrictiveness, and increased tolerance to rehabilitation of the mentally ill in the community but there was no change in authoritarian attitudes. The training was acceptable and feasible. Conclusions Mental health training was successful in improving knowledge, confidence and attitudes amongst trained CHWs. The training was acceptable and feasible. Further controlled studies are required to evaluate the impact of such training on patient health outcomes. Trial registration PACTR PACTR201610001834198 , Registered 26 October 2016

Development of the EORTC QLQ-CAX24, a questionnaire for cancer patients with cachexia

Context Cachexia is commonly found in cancer patients and has profound consequences; yet there is only one questionnaire that examines the patient's perspective. Objective To report a rigorously developed module for patient self-reported impact of cancer cachexia. Methods Module development followed published guidelines. Patients from across the cancer cachexia trajectory were included. In Phase 1, health-related quality of life (HRQOL) issues were generated from a literature review and interviews with patients in four countries. The issues were revised based on patient and health care professional (HCP) input. In Phase 2, questionnaire items were formulated and translated into the languages required for Phase 3, the pilot phase, in which patients from eight countries scored the relevance and importance of each item, and provided qualitative feedback. Results A total of 39 patients and 12 HCPs took part in Phase 1. The literature review produced 68 HRQOL issues, with 22 new issues arising from the patient interviews. After patient and HCP input, 44 issues were formulated into questionnaire items in Phase 2. One hundred ten patients took part in Phase 3. One item was reworded, and 20 items were deleted as a consequence of patient feedback. Conclusions The QLQ-CAX24 is a cancer cachexia-specific questionnaire, comprising 24 items, for HRQOL assessment in clinical trials and practice. It contains five multi-item scales (food aversion, eating and weight-loss worry, eating difficulties, loss of control, and physical decline) and four single items

Whole Blood Interferon-Gamma Responses to Mycobacterium tuberculosis Antigens in Young Household Contacts of Persons with Tuberculosis in Uganda

Due to immunologic immaturity, IFN-gamma-producing T cell responses may be decreased in young children compared to adults, thus we hypothesized that IFN-gamma responses to mycobacterial antigens in household contacts exposed to Mycobacterium tuberculosis (Mtb) would be impaired in young children relative to adults. The objective of this study was to compare whole blood IFN-gamma production in response to mycobacterial antigens between children and adults in Uganda.We studied household contacts of persons with culture-positive pulmonary tuberculosis (TB) enrolled in a cohort study conducted in Kampala, Uganda. Whole blood IFN-gamma production in response to Mtb culture-filtrate antigens was measured by ELISA and compared between infants (<2 years old, n = 80), young children (2 <5 years old, n = 216), older children (5 <15 years old, n = 443) and adults (> or =15 years old, n = 528). We evaluated the relationship between IFN-gamma responses and the tuberculin skin test (TST), and between IFN-gamma responses and epidemiologic factors that reflect exposure to Mtb, and the effect of prior BCG vaccination on IFN-gamma responses. Young household contacts demonstrated robust IFN-gamma responses comparable to those of adults that were associated with TST and known risk factors for infection. There was no effect of prior BCG immunization on the IFN-gamma response.Young children in a TB endemic setting can mount robust IFN-gamma responses generally comparable to those of adults, and as in adults, these responses correlated with the TST and known epidemiologic risk factors for Mtb infection

Search for supersymmetry in events with b-quark jets and missing transverse energy in pp collisions at 7 TeV

Results are presented from a search for physics beyond the standard model based on events with large missing transverse energy, at least three jets, and at least one, two, or three b-quark jets. The study is performed using a sample of proton-proton collision data collected at sqrt(s) = 7 TeV with the CMS detector at the LHC in 2011. The integrated luminosity of the sample is 4.98 inverse femtobarns. The observed number of events is found to be consistent with the standard model expectation, which is evaluated using control samples in the data. The results are used to constrain cross sections for the production of supersymmetric particles decaying to b-quark-enriched final states in the context of simplified model spectra.Comment: Submitted to Physical Review

A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC).

BACKGROUND: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation's sTBI Management Guidelines, as they were not evidence-based. METHODS: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists' decision tendencies were the focus of recommendations. RESULTS: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination. CONCLUSIONS: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management

Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids

We report here the design, development and performance of a novel formulation of liposome- encapsulated glucocorticoids (GCs). A highly efficient (>90%) and stable GC encapsulation was obtained based on a transmembrane calcium acetate gradient driving the active accumulation of an amphipathic weak acid GC pro-drug into the intraliposome aqueous compartment, where it forms a GC-calcium precipitate. We demonstrate fabrication principles that derive from the physicochemical properties of the GC and the liposomal lipids, which play a crucial role in GC release rate and kinetics. These principles allow fabrication of formulations that exhibit either a fast, second-order (t1/2 ∼1 h), or a slow, zero-order release rate (t1/2 ∼ 50 h) kinetics. A high therapeutic efficacy was found in murine models of experimental autoimmune encephalomyelitis (EAE) and hematological malignancies