Chemogenetic inhibition reveals midline thalamic nuclei and thalamo- accumbens projections mediate cocaine-seeking in rats

Abstract

Drug addiction is a chronic disease that is shaped by alterations in neuronal function within the cortical-basal ganglia-thalamic circuit. However, our understanding of how this circuit regulates drug-seeking remains incomplete, and relapse rates remain high. The midline thalamic nuclei are an integral component of the cortical-basal ganglia-thalamic circuit and are poised to mediate addiction behaviors, including relapse. It is surprising that little research has examined the contribution of midline thalamic nuclei and their efferent projections in relapse. To address this, we expressed inhibitory, G_i/o- coupled DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) in a subset of the midline thalamic nuclei or in midline thalamic nuclei neurons projecting to either the nucleus accumbens or the amygdala. We examined the effect of transiently decreasing activity of these neuronal populations on cue-induced and cocaine-primed reinstatement of cocaine-seeking. Reducing activity of midline thalamic nuclei neurons attenuated both cue-induced and cocaine-primed reinstatement, but had no effect on cue-induced reinstatement of sucrose-seeking or locomotor activity. Interestingly, attenuating activity of efferent projections from the anterior portion of midline thalamic nuclei to the nucleus accumbens blocked cocaine-primed reinstatement but enhanced cue-induced reinstatement. Decreasing activity of efferent projections from either the posterior midline thalamic nuclei to the nucleus accumbens or the midline thalamic nuclei to amygdala had no effect. These results reveal a novel contribution of subsets of midline thalamic nuclei neurons in drug-seeking behaviors, and suggest that modulation of midline thalamic nuclei activity may be a promising therapeutic target for preventing relapse.

This article is protected by copyright. All rights reserved.

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Endogenous endophthalmitis and osteomyelitis associated with interleukin 17 inhibitor treatment for psoriasis in a patient with diabetes

A 64-year-old man with type 2 diabetes mellitus and plaque psoriasis presented to the emergency room with 3 days of progressive right eye pain and decreased vision. After extensive workup and multidisciplinary team effort, the patient was diagnosed with and treated for unilateral endogenous methicillin-sensitive Staphylococcus aureus endophthalmitis, bacteraemia and osteomyelitis of the foot. The patient had been started on the interleukin 17 (IL-17) inhibitor secukinumab for his treatment-resistant plaque psoriasis 4 weeks prior to presentation. After treatment, his final vision was light perception and the foot infection resolved without sequelae. To our knowledge, this is the first reported case of both endogenous endophthalmitis and osteomyelitis associated with an IL-17 inhibitor.

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An elusive ciliopathy: Joubert syndrome

The police brought a 65-year-old female patient to the EADU after being found 'roaming the streets' in an apparent state of confusion. This was her third admission under the same circumstances during the last 3 years. Neurological examination revealed (1) cognitive impairment, (2) oculomotor apraxia, (3) abnormal cancellation of vestibular ocular reflex, (4) mild ataxia and (5) mild hypotonia. Renal function was abnormal and liver function was normal. No retinal disturbance was found. The head CT on admission was normal for stroke and the lumbar puncture was negative for encephalitis. Her brain MRI showed 'molar tooth sign', suggestive of Joubert syndrome, which was confirmed by genetic testing showing anomalous NPHP1 gene

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Clinical neurophysiology of prolonged disorders of consciousness: from diagnostic stimulation to therapeutic neuromodulation

The philosopher David Chalmers (1995) defined the quest for the ultimate theory of consciousness as the "hard problem" of science. For the clinician, the "hard problem" is probing consciousness in non-communicating patients lying in the vegetative state (VS) or in the minimally conscious state (MCS), the most severe conditions along the spectrum of prolonged disorders of consciousness (DoC) from acquired brain injury (Young, 1998). By definition, VS patients exhibit signs of wakefulness but no signs of awareness (non-responsive; Jennett and Plum, 1972), whereas MCS patients show signs of wakefulness and fluctuating signs of awareness (responsive; Giacino et al, 2002), with behavioural interactions of lower (MCS-) or higher (MCS+) level of complexity (Bruno et al, 2011).

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Practical considerations for large-scale gut microbiome studies

Abstract

First insights on the human gut microbiome have been gained from medium-sized, cross-sectional studies. However, given the modest portion of explained variance of currently identified covariates and the small effect size of gut microbiota modulation strategies, upscaling seems essential for further discovery and characterisation of the multiple influencing factors and their relative contribution. In order to guide future research projects and standardisation efforts, we here review currently applied collection and preservation methods for gut microbiome research. We discuss aspects such as sample quality, applicable omics techniques, user experience and time and cost efficiency. In addition, we evaluate the protocols of a large-scale microbiome cohort initiative, the Flemish Gut Flora Project, to give an idea of perspectives, and pitfalls of large-scale faecal sampling studies. Although cryopreservation can be regarded as the gold standard, freezing protocols generally require more resources due to cold chain management. However, here we show that much can be gained from an optimised transport chain and sample aliquoting before freezing. Other protocols can be useful as long as they preserve the microbial signature of a sample such that relevant conclusions can be drawn regarding the research question, and the obtained data are stable and reproducible over time.

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Lifestyles in transition: evolution and natural history of the genus Lactobacillus

Abstract

Lactobacillus species are found in nutrient-rich habitats associated with food, feed, plants, animals and humans. Due to their economic importance, the metabolism, genetics and phylogeny of lactobacilli have been extensively studied. However, past research primarily examined lactobacilli in experimental settings abstracted from any natural history, and the ecological context in which these bacteria exist and evolve has received less attention. In this review, we synthesize phylogenetic, genomic and metabolic metadata of the Lactobacillus genus with findings from fine-scale phylogenetic and functional analyses of representative species to elucidate the evolution and natural history of its members. The available evidence indicates a high level of niche conservatism within the well-supported phylogenetic groups within the genus, with lifestyles ranging from free-living to strictly symbiotic. The findings are consistent with a model in which host-adapted Lactobacillus lineages evolved from free-living ancestors, with present-day species displaying substantial variations in terms of the reliance on environmental niches and the degree of host specificity. This model can provide a framework for the elucidation of the natural and evolutionary history of Lactobacillus species and valuable information to improve the use of this important genus in industrial and therapeutic applications.

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Commentary on: “Influence of OATP1B1 Function on the Disposition of Sorafenib-β-D-Glucuronide”

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New cell block containing agarose for cytopathological diagnosis of tumor samples

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Urinary tract involvement of mantle cell lymphoma diagnosed by urine cytology

Abstract

Urinary tract lymphoma is unusual, with the kidney being the most commonly reported site of involvement. Urinary bladder involvement by lymphoma is rare. Mantle cell lymphoma (MCL) is a relatively uncommon type of lymphoma. Herein, we report a case of MCL of the urinary bladder diagnosed by urine cytology, with confirmatory immunocytochemical stains, which has not previously been reported in the literature.

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Collagen balls on ThinPrep cervical cytology

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Monthly News Roundup - June 2017

New Fluoroquinolone Baxdela Approved for Certain Skin Infections Roughly 3 million patients are hospitalized each year in the U.S. with acute bacterial skin and skin structure infections (ABSSSIs), some of which may be difficult-to-treat and...

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Physician Burnout: The Hidden Health Care Crisis

Physician burnout is an under recognized and under reported problem. Characterized by a state of mental exhaustion, depersonalization, and a decreased sense of personal accomplishment, burnout may affect over 60% of family practice providers and at least one-third of gastroenterologists. Some studies have shown that younger physicians, those performing high risk procedures, and those experiencing work-life conflicts are at greatest risk. If unrecognized, the costs to the physician and to the health care system can be enormous, as physician burnout is associated with increased rates of depression, alcohol and drug abuse, divorce, suicide, medical errors, difficult relationships with co-workers, and patient dissatisfaction, as well as physician attrition.

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AGA Institute Series: Focus on Enhancing High-Value Care When does assessment for bile duct stones need to be performed prior to cholecystectomy for calculus gallbladder disease?

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Exploration of Two Training Paradigms Using Forced Induced Weight Shifting With the Tethered Pelvic Assist Device to Reduce Asymmetry in Individuals After Stroke: Case Reports.

Many robotic devices in rehabilitation incorporate an assist-as-needed haptic guidance paradigm to promote training. This error reduction model, while beneficial for skill acquisition, could be detrimental for long-term retention. Error augmentation (EA) models have been explored as alternatives. A robotic Tethered Pelvic Assist Device has been developed to study force application to the pelvis on gait and was used here to induce weight shift onto the paretic (error reduction) or nonparetic (error augmentation) limb during treadmill training. The purpose of these case reports is to examine effects of training with these two paradigms to reduce load force asymmetry during gait in two individuals after stroke (>6 mos). Participants presented with baseline gait asymmetry, although independent community ambulators. Participants underwent 1-hr trainings for 3 days using either the error reduction or error augmentation model. Outcomes included the Borg rating of perceived exertion scale for treatment tolerance and measures of force and stance symmetry. Both participants tolerated training. Force symmetry (measured on treadmill) improved from pretraining to posttraining (36.58% and 14.64% gains), however, with limited transfer to overground gait measures (stance symmetry gains of 9.74% and 16.21%). Training with the Tethered Pelvic Assist Device device proved feasible to improve force symmetry on the treadmill irrespective of training model. Future work should consider methods to increase transfer to overground gait. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Unwarranted claims of drug efficacy in pharmaceutical sales visits: Are drugs approved on the basis of surrogate outcomes promoted appropriately?

Abstract

Aim

This study compares physicians' recall of the claims of benefits on cardiovascular disease and diabetes made by pharmaceutical sales representatives for drugs approved on the basis of a surrogate outcome, i.e., an off-label claim, versus those approved on the basis of a serious morbidity or mortality (clinical) outcome.

Methods

Physicians in primary care practices in Montreal, Vancouver, Sacramento and Toulouse who saw sales representatives as part of their usual practice and served a non-referral population were contacted in blocks of 25 from a randomized list of all physicians practicing in the relevant metropolitan area. We compared how frequently physicians reported that sales reps made claims of serious morbidity or mortality (clinically meaningful) benefit for drugs approved on the basis of surrogate outcomes versus drugs approved on the basis of clinical outcomes.

Results

There were 448 promotions for 58 unique brand name drugs. Claims of clinically meaningful benefit were reported in 156 (45%) of the 347 promotions for surrogate outcome drugs, constituting unwarranted efficacy claims, i.e., off-label promotion. Claims of clinical benefit were reported in 72 of the 101 promotions (71%) for drugs approved on the basis of clinical outcomes, adjusted OR=0.3 (95% CI 0.2, 0.6), p<0.001.

Conclusions

Claims of efficacy made in sales visit promotions for drugs approved only on the basis of surrogate outcomes extended beyond the regulator-approved efficacy information for the product in almost half of promotions. Unapproved claims of drug efficacy constitute a form of off-label promotion and merit greater attention from regulators.

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A Randomized Controlled Trial on the Effect of a Double Check on the Detection of Medication Errors

The use of a double check by 2 nurses has been advocated as a key error-prevention strategy. This study aims to determine how often a double check is used for high-alert medications and whether it increases error detection.

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Variance in the Efficacy of Brief Interventions to Reduce Hazardous and Harmful Alcohol Consumption Between Injury and Noninjury Patients in Emergency Departments: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

We adopt a comparative framework to measure the extent to which variance in the efficacy of alcohol brief interventions to reduce hazardous and harmful drinking at less than or equal to 5-, 6-, and 12-month follow-up in emergency department settings can be determined by differences between study populations (targeted injury and noninjury specific).

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Expert Consensus Guidelines for Stocking of Antidotes in Hospitals That Provide Emergency Care

We provide recommendations for stocking of antidotes used in emergency departments (EDs). An expert panel representing diverse perspectives (clinical pharmacology, medical toxicology, critical care medicine, hematology/oncology, hospital pharmacy, emergency medicine, emergency medical services, pediatric emergency medicine, pediatric critical care medicine, poison centers, hospital administration, and public health) was formed to create recommendations for antidote stocking. Using a standardized summary of the medical literature, the primary reviewer for each antidote proposed guidelines for antidote stocking to the full panel.

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Low Accuracy of Positive qSOFA Criteria for Predicting 28-Day Mortality in Critically Ill Septic Patients During the Early Period After Emergency Department Presentation

We determine the diagnostic performance of positive Quick Sequential Organ Failure Assessment (qSOFA) scores for predicting 28-day mortality among critically ill septic patients during the early period after emergency department (ED) presentation.

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Is Bedside Ultrasonography Rapid and Accurate for Confirmation of Central Venous Catheter Position and Exclusion of Pneumothorax Compared With Chest Radiograph?

The authors identified 15 articles (13 full studies and 2 abstracts) reporting 1,553 central venous catheter insertions (subclavian or internal jugular) among 1,511 patients and included 1,469 central venous catheter insertions with 258 cases of catheter malposition in the meta-analysis. No studies demonstrated low risk of bias, with 9 studies demonstrating high risk of bias because of inconsistent data reporting. Ten studies reported central venous catheter malposition and pneumothorax, whereas 5 reported only central venous catheter malposition.

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Immunotherapy of Prostate Cancer: Facts and Hopes

In the last few years immunotherapy has become an important cancer treatment modality and while the principles of immunotherapy evolved over many decades, the FDA approvals of sipuleucel-T and ipilimumab began a new wave in immuno-oncology. Despite the current enthusiasm, it is unlikely that any of the immunotherapeutics alone can dramatically change prostate cancer outcomes, but combination strategies are more promising and provide a reason for optimism. Several completed and ongoing studies have shown that the combination of cancer vaccines or checkpoint inhibitors with different immunotherapeutic agents, hormonal therapy (enzalutamide), radiation therapy (radium 223), DNA-damaging agents (olaparib), or chemotherapy (docetaxel) can enhance immune responses and induce more dramatic, long-lasting clinical responses without significant toxicity. The goal of prostate cancer immunotherapy does not have to be complete eradication of advanced disease, but rather the return to an immunologic equilibrium with an indolent disease state. In addition to determining the optimal combination of treatment regimens, efforts are also ongoing to discover biomarkers of immune response. With such concerted efforts, the future of immunotherapy in prostate cancer looks brighter than ever.

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Reply

In our recent study, "Efficacy of Intravenous and Endotracheal Epinephrine during Neonatal Cardiopulmonary Resuscitation in the Delivery Room,"1 we raise concerns that the currently recommended dosing recommendations for both intravenous and endotracheal (ET) epinephrine frequently needed to be repeated before return of spontaneous circulation (ROSC) is achieved. We also demonstrated that the vast majority of infants who achieved ROSC did so after receiving an intravenous (IV) dose of epinephrine even if prior ET doses were provided.

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Detecting Pharmaceuticals in the Red Blood Cell Inventory of a Hospital Blood Bank

We tested 220 red blood cell units for the presence of pharmaceuticals; 15 units (6.8%) were confirmed to contain low concentrations of opiates, benzodiazepines, stimulants, or barbiturates. Further study is needed to determine whether these drugs, which are not prohibited in donated blood by current Food and Drug Administration standards, could mediate adverse reactions in children.

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Evaluation of Neonatal Lung Volume Growth by Pulmonary Magnetic Resonance Imaging in Patients with Congenital Diaphragmatic Hernia

To evaluate postnatal lung volume in infants with congenital diaphragmatic hernia (CDH) and determine if a compensatory increase in lung volume occurs during the postnatal period.

http://ift.tt/2t6ShUS

The Microbiome and Biomarkers for Necrotizing Enterocolitis: Are We Any Closer to Prediction?

The past decade has seen a substantial increase in interest for biomarkers across a spectrum of disease states, fueled by emerging "omics" technologies. Biomarkers hold the promise of early detection and diagnosis, prognostication of disease severity, and new insights into disease mechanisms. Necrotizing enterocolitis (NEC) has been a prime target, with its high mortality, burden of morbidity in infants born preterm, and unpredictable onset.1,2 This review focuses on recent advances in NEC biomarker research, including the use of gut microbiome patterns of infants born preterm, and the application of new proteomic and metabolomic technology.

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Prevalence of Hypoalbuminemia and Elevated Bilirubin/Albumin Ratios in a Large Cohort of Infants in the Neonatal Intensive Care Unit

To provide descriptive data on serum albumin levels and the bilirubin to albumin (B/A) ratio in neonates admitted to the neonatal intensive care unit, assess the effect of gestational and chronological age on serum albumin and the B/A ratio, and evaluate the association between extreme values and mortality.

http://ift.tt/2smPOIV

The Relationship between High Flow Nasal Cannula Flow Rate and Effort of Breathing in Children

To use an objective metric of effort of breathing to determine optimal high flow nasal cannula (HFNC) flow rates in children <3 years of age.

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Scrofula

An 8-year-old boy presented with the complaint of swelling over the left side of the neck over the last 6 weeks. The swelling was gradually progressive and painless; it ruptured with thick purulent discharge 2 days before presentation. There was no history of fever, cough, or weight loss. His father had pulmonary tuberculosis and was currently receiving therapy. On examination, the patient had an ulcerative lesion of 3.2 × 2.1 cm with undermined edges and a necrotic base with surrounding induration (Figure, A).

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Sulfasalazine-Induced Crystalluria Causing Severe Acute Kidney Injury

Sulfasalazine is an anti-inflammatory agent commonly used in the treatment of autoimmune conditions such as inflammatory bowel disease and rheumatoid arthritis. Sulfasalazine is converted by gut bacteria into sulfapyridine and the clinically active metabolite 5-aminosalicylic acid (5-ASA), and its efficacy is proportional to the 5-ASA concentration within the intestinal lumen. Renal complications are commonly reported for the chemically similar 5-ASA derivative mesalamine, but are not well-known side effects of sulfasalazine therapy.

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Comparative Genomics of Two Sequential Candida glabrate Clinical Isolates

Candida glabrate is an important fungal pathogen which develops rapidly antifungal resistance in treated patients. It is known that azole treatments lead to antifungal resistance in this fungal species and that multidrug efflux transporters are involved in this process. Specific mutations in the transcriptional regulator PDR1 result in upregulation of the transporters. In addition, we showed that the PDR1 mutations can contribute to enhance virulence in animal models. We were interested in this study to compare genomes of two specific C. glabrate related isolates, one of which was azole-susceptible (DSY562) while the other was azole-resistant (DSY565). DSY565 contained a PDR1 mutation (L280F) and was isolated after a time lapse of 50 days of azole therapy. We expected that genome comparisons between both isolates could reveal additional mutations reflecting host adaptation or even additional resistance mechanisms. The PacbBio technology used here yielded 14 major contigs (sizes 0.18 Mb-1.6 Mb) and mitochondrial genomes from both DSY562 and DSY565 isolates that were highly similar to each other. Comparisons of the clinical genomes with the published CBS138 genome indicated important genome rearrangements, but not between the clinical strains. Among unique features, several retrotransposons were identified in the genomes of the investigated clinical isolates. DSY562 and DSY565 contained each a large set of adhesin-like genes (101 and 107, respectively), which exceed by far the number of reported adhesins (66) in the CBS138 genome. Comparison between DSY562 and DSY565 yielded 17 non-synonymous SNPs (among which the expected PDR1 mutation) as well as small size indels in coding regions (11) but mainly in adhesin-like genes. The genomes were containing a DNA mismatch repair allele of MSH2 known to be involved in the so-called hypermutator phenotype of this yeast species and the number of accumulated mutations between both clinical isolates is consistent with the presence of a MSH2 defect. In conclusion, this study is the first to compare genomes of C. glabrate sequential clinical isolates using the PacBio technology as an approach. The genomes of these isolates taken in the same patient at two different time points were exhibiting limited variations, even if submitted to the host pressure.

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Gene2Function: An Integrated Online Resource for Gene Function Discovery

One of the most powerful ways to develop hypotheses regarding biological functions of conserved genes in a given species, such as in humans, is to first look at what is known about function in another species. Model organism databases (MODs) and other resources are rich with functional information but difficult to mine. Gene2Function (G2F) addresses a broad need by integrating information about conserved genes in a single online resource.

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Fine Mapping, Transcriptome Analysis, and Marker Development for Y2, the Gene that Conditions Beta-Carotene Accumulation in Carrot (Daucus carota L.)

Domesticated carrots, Daucus carota subsp. sativus, are the richest source of beta-carotene in the US diet, which when consumed is converted into vitamin A, an essential component of eye health and immunity. The Y₂ locus plays a significant role in beta-carotene accumulation in carrot roots, but a candidate gene has not been identified. To advance our understanding of this locus, the genetic basis of beta-carotene accumulation was explored by utilizing an advanced mapping population, transcriptome analysis, and nucleotide diversity in diverse carrot accessions with varying levels of beta-carotene. A single large effect Quantitative Trait Locus (QTL) on the distal arm of chromosome 7 overlapped with the previously identified beta-carotene accumulation QTL, Y₂. Fine mapping efforts reduced the genomic region of interest to 650 kb including 72 genes. Transcriptome analysis within this fine mapped region identified four genes differentially expressed at two developmental time points and 13 genes differentially expressed at one time point. These differentially expressed genes included transcription factors and genes involved in light signaling and carotenoid flux, including a member of the Di19 gene family involved in Arabidopsis photomorphogenesis, and a homolog of the bHLH36 transcription factor involved in maize carotenoid metabolism. Analysis of nucleotide diversity in 25 resequenced carrot accessions revealed a drastic decrease in diversity of this fine-mapped region in orange cultivated accessions as compared to white and yellow cultivated and to white wild samples. The results presented in this study provide a foundation to identify and characterize the gene underlying beta-carotene accumulation in carrot.

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Mitochondrial genomic backgrounds affect nuclear DNA methylation and gene expression

Mitochondrial DNA (mtDNA) mutations and polymorphisms contribute to many complex diseases, including cancer. Using a unique mouse model that contains nuclear DNA (nDNA) from one mouse strain and homoplasmic mitochondrial haplotypes from different mouse strain(s) - designated Mitochondrial Nuclear Exchange (MNX) - we show that mtDNA can alter mammary tumor metastasis. Since retrograde and anterograde communication exist between the nuclear and mitochondrial genomes, we hypothesized that there are differential mtDNA-driven changes in nDNA expression and DNA methylation. Genome-wide nDNA methylation and gene expression were measured in harvested brain tissue from paired wild-type and MNX mice. Selective differential DNA methylation and gene expression were observed between strains having identical nDNA, but different mtDNA. These observations provide insights into how mtDNA might alter epigenetic regulation and thereby contribute to the pathogenesis of metastasis.

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Overview of Cancer Stem Cells and Stemness for Community Oncologists

Abstract

Advances in cancer research in the past have led to an evolving understanding of cancer pathogenesis and the development of novel drugs that significantly improve patient outcomes. However, many patients still encounter treatment resistance, recurrence, or metastasis and eventually die from progressing disease. Experimental evidence indicates that a subpopulation of cancer cells, called cancer stem cells (CSCs), possess "stemness" properties similar to normal stem cells, including self-renewal, differentiation, and proliferative potential. These stemness properties are lost during differentiation and are governed by pathways such as STAT3, NANOG, NOTCH, WNT, and HEDGEHOG, which are highly dysregulated in CSCs due to genetic and epigenetic changes. Promising results have been observed in preclinical models targeting these CSCs through the disruption of stemness pathways in combination with current treatment modalities. This has led to anti-CSC–based clinical trials in multiple stages of development. In this review, we discuss the role of CSCs and stemness pathways in cancer treatment and how they relate to clinical observations. Because CSCs and the stemness pathways governing them may explain the negative clinical outcomes observed during treatment, it is important for oncologists to understand how they contribute to cancer progression and how they may be targeted to improve patient outcomes.

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Population Pharmacokinetics of Human Antithrombin Concentrate in Pediatric Patients

Abstract

Aims

Antithrombin is increasingly used in pediatric patients, yet there are few age-specific pharmacokinetic data to guide dosing. We aim to describe the pharmacokinetic profile of human (plasma-derived) antithrombin concentrate in pediatric patients.

Methods

A retrospective review of 5 years of patients < 19 years of age admitted to our institution who received antithrombin concentrate, were not on mechanical circulatory support and had baseline (pre-dose) and post-dose plasma antithrombin activity levels available for analysis, was performed. Demographic and laboratory variables, antithrombin dosing information and use of continuous infusion unfractionated heparin were collected. Population pharmacokinetic analysis was performed with bootstrap analysis. The model developed was tested against a validation dataset from a cohort of similar patients and predictive value was calculated.

Results

A total 184 patients met study criteria (male 46.7%, median age (years) 0.35 (IQR 0.07-3.9). A median of 2 antithrombin doses (IQR1-4) were given to patients (Dose of 46.3+13.6 units/kg) with median of 3 (IQR 2-7) post-dose levels per patient. Continuous infusion unfractionated heparin was administered in 87.5% of patients at a mean dose of 34.1+22.7 units/kg/hour. A one compartment exponential error model best fit the data, and significant covariates included allometrically scaled weight on clearance and volume of distribution, unfractionated heparin dose on clearance, and baseline antithrombin activity level on volume of distribution. The model resulted in a median -1.75% prediction error (IQR -11.75% - 6.5%) when applied to the validation dataset (n=30).

Conclusions

Antithrombin pharmacokinetics are significantly influenced by concurrent use of unfractionated heparin and baseline anthrombin activity.

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In-Vivo Patellar Motion Under a Dynamic Weight-Bearing Condition in Individuals With Patellofemoral Pain Syndrome: Erratum

No abstract available

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Comparison Between Single and Combined Clinical Postural Stability Tests in Individuals With and Without Chronic Ankle Instability

Objective: To determine if a single or/and combined clinical tests match group membership based on self-reported ankle function. Design: Cross-sectional. Setting: Biomechanics Laboratory. Participants: From participants, 58 meeting inclusion/exclusion criteria were divided into a chronic ankle instability (CAI) group (n = 25) who reported ≤25 on the Cumberland Ankle Instability Tool (CAIT) and a history of moderate–severe ankle sprain(s) and a control group (n = 33) who reported ≥29 on the CAIT and no history of ankle sprain(s). Interventions: Participants completed the following clinical tests: Foot Lift Test (FLT), the Star Excursion Balance Test (SEBT), the Single-Leg Hop Test (SLHT), and the Time in Balance Test (TIB) in a randomized order. A linear regression model was applied to determine measures that matched ankle group membership. Main Outcome Measures: The mean of SEBT reach distance was normalized to percentage leg length. The mean of number of errors in the FLT was recorded. The SLHT and TIB were reported as time in seconds, and the means were calculated. Results: The most parsimonious combination of tests (SLHT and SEBT) resulted in correctly matching 70.69% (41/58) of participants into groups, which was significantly better than chance. The multiple correlation coefficients (R value) for combining the SLHT and SEBT was 0.39. Conclusions: Using SLHT and SEBT resulted in improved recognition of participants designated into the CAI or control groups. Self-report perception of ankle function provides limited information for clinicians and researchers. Using multiple clinical function tests may be more helpful in determining deficits and intervention effectiveness.

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Does Acupressure Hit the Mark? A Three-Arm Randomized Placebo-Controlled Trial of Acupressure for Pain and Anxiety Relief in Athletes With Acute Musculoskeletal Sports Injuries

Objectives: Injuries are a common consequence of sports and recreational activity. The optimal management of symptoms is a crucial element of sports injury management. Acupressure has previously been shown to effectively decrease symptoms of musculoskeletal injury, thus may be considered a potentially useful intervention in the management of sport-related injuries. Therefore, this study was conducted to examine the effectiveness of acupressure in decreasing pain and anxiety in acutely injured athletes. Design: A prospective 3-arm randomized placebo-controlled trial. Setting: A sports injury clinic, Dunedin, New Zealand. Patients: Seventy-nine athletes who sustained a sport-related musculoskeletal injury on the day. Intervention: Three minutes of either acupressure, sham acupressure, or no acupressure. Main Outcome Measures: The primary outcomes of pain and anxiety intensity were measured before and immediately after the intervention on a 100-mm visual analog scale (VAS). Pain and anxiety relief, satisfaction with treatment, willingness to repeat a similar treatment, and belief in the effect of acupressure were secondary outcomes measured on Likert scales after the intervention. Results: The acupressure group reported 11 mm less pain (95% CI: 5-17) on average than the sham acupressure group, and 9 mm less (95% CI: 3-16) than the control group as a result of the intervention (P

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Triple Fracture of the Intra-Articular Second Metacarpal Head, Intra-Articular Fourth Metacarpal Base, and Ulnar Styloid of An Ice Hockey Player: A Case Report

Abstract: We present a case of simultaneous ipsilateral fractures at the intra-articular second metacarpal head, intra-articular fourth metacarpal base, and ulnar styloid. These fractures were caused by the peculiar condition of a blow to the fist during an ice hockey game; the hand was struck while it was gripping a stick. The specific combination of these fractures has not been previously reported in the literature. In this incident, axial compression force was transmitted from the second and fourth metacarpal heads while skipping the third metacarpal head to the ulnar side of the wrist via the carpometacarpal joints and carpal bones. Because each fracture exhibited only slight displacement, we used conservative treatment with good outcomes.

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Impact of a Short-Term Water Abstinence on Airway Hyperresponsiveness in Elite Swimmers

Objective: To investigate the effect of a swimming break on airway hyperresponsiveness (AHR) and to evaluate perception of bronchoconstriction-related symptoms after methacholine challenge testing (MCT). Design: Observational, controlled study. Setting: University department. Participants: Overall, 25 healthy, elite, competitive swimmers aged ≥14 years from the local Olympic training center and 25 healthy control subjects. Independent Variable: Duration of water abstinence. Main Outcome Measures: Primary outcome measures were a positive MCT with a provocation dose (PD) and the perception score of bronchoconstriction-related symptoms at visit 1 (V1, training period) and visit 2 (V2, after swimming break). Results: In the study, 13 swimmers (52%) and 10 control subjects (40%) showed AHR. The PD did not differ significantly between V1 and V2 in the swimmers (P = 0.81) or in the control subjects (P = 0.74). No correlation of fraction of exhaled nitric oxide with the PD could be established in both the groups (swimmers: P = 0.97; controls: P = 0.99). The majority of swimmers with AHR were asymptomatic, and only minimal differences in perception of bronchoconstriction-related symptoms between swimmers and control subjects were observed (P = 0.23). Conclusions: A swimming break of 25 ± 8 days does not seem sufficient to significantly reduce AHR in elite swimmers. Thus, relevant and systematic effects of short-term water abstinence on AHR seem unlikely. Because the majority of swimmers remain asymptomatic, AHR may escape routine screening examinations. The impact of AHR on athletic performance and the long-term clinical consequences remain to be clarified.

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Reliability and Practicality of the Core Score: Four Dynamic Core Stability Tests Performed in a Physician Office Setting

Objective: Pilot study to determine the practicality and inter-rater reliability of the "Core Score," a composite measure of 4 clinical core stability tests. Design: Repeated measures. Setting: Academic hospital physician clinic. Participants: 23 healthy volunteers with mean age of 32 years (12 females, 11 males). Assessment of Variables: All subjects performed 4 core stability maneuvers under direct observation from 3 independent physicians in sequence. Main Outcome Measures: Inter-rater reliability and time necessary to perform examination. Results: The Core Score scale is 0 to 12, with 12 reflecting the best core stability. The mean composite score of all 4 tests for all subjects was 9.54 (SD, 1.897; range, 4-12). The intraclass correlation coefficients (ICC 1,1) for inter-rater reliability for the composite Core Score and 4 individual tests were 0.68 (Core Score), 0.14 (single-leg squat), 0.40 (supine bridge), 0.69 (side bridge), and 0.46 (prone bridge). The time required for a single examiner to assess a given subject's core stability in all 4 maneuvers averaged 4 minutes (range, 2-6 minutes). Conclusions: Even without specialized equipment, a clinically practical and moderately reliable measure of core stability may be possible. Further research is necessary to optimize this measure for clinical application. Clinical Relevance: Despite the known value of core stability to athletes and patients with low back pain, there is currently no reliable and practical means for rating core stability in a typical office-based practice. This pilot study provides a starting point for future reliability research on clinical core stability assessments.

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A Comparison of Clinical Outcome Between Athletes and Nonathletes Undergoing Hip Arthroscopy for Femoroacetabular Impingement

Objective: To compare the clinical outcome of arthroscopic surgery for femoroacetabular impingement (FAI) between athlete and nonathlete patients. Design: Retrospective case-control study. Level of Evidence III. Patients and Methods: Seventy-four patients who underwent arthroscopic FAI correction from March 2009 to April 2012 were enrolled in this study. The patients were divided into 2 groups, according to their sports participation (47 in the athlete group and 27 in the nonathlete group). Main Outcome Measures: We reviewed clinical and radiographic data for all patients, up to a minimum of 2 years after surgery. We used analysis of covariance to compare the mean patient reported outcome scores including modified Harris hip score (MHHS) and the nonarthritis hip score (NAHS) preoperatively, at 6, 12, and 24 months after surgery. Results: The mean age at the time of surgery in the athlete group was significantly lower than that in the nonathlete group. Although there was no significant difference in preoperative MHHS and NAHS, the mean NAHS at 6, 12, and 24 months postoperatively and the mean MHHS at 24 months postoperatively in athletes were significantly higher than that in nonathletes (P

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An Unusual Cause of Headache and Fatigue in a Division 1 Collegiate Athlete

Abstract: Variegate porphyria (VP) is an autosomal dominant disorder of porphyrin metabolism. We report a case of a 21-year-old male collegiate athlete who complained of recurrent headache and fatigue. Extensive testing after initial presentation failed to identify a cause. Months later, his grandmother was diagnosed with VP after being hospitalized; hence, he was tested. He was positive for a heterozygous missense mutation, R168H, in one protoporphyrinogen oxidase allele. This case highlights a rare disorder of heme synthesis that should be considered in the differential diagnosis of exertional fatigue and headaches in athletes. When other more common causes of fatigue and/or headache are unable to be identified, a more focused history and examination may lead to a more unusual but crucial diagnosis. To our knowledge, there are no reported cases of this condition in Division I collegiate athletes.

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Arthroscopic Shoulder Surgery in Female Professional Tennis Players: Ability and Timing to Return to Play

Objective: To assess the outcome and time to return to previous level of competitive play after shoulder surgery in professional tennis players. Design: Retrospective case series. Setting: Tertiary academic centre. Patients and Interventions: The records of all female tennis players on the Women's Tennis Association (WTA) professional circuit between January 2008 and June 2010 were reviewed to identify players who underwent shoulder surgery on their dominant (serving) shoulder. Main Outcome Measures: Primary outcomes were the ability and time to return to professional play and if they were able to return to their previous level of function as determined by singles ranking. Preoperative and postoperative singles rankings were used to determine rate and completeness of return to preoperative function. Results: During the study period, 8 professional women tennis players from the WTA tour underwent shoulder surgery on their dominant arm. Indications included rotator cuff debridement or repair, labral reconstruction for instability or superior labral anterior posterior lesion, and neurolysis of the suprascapular nerve. Seven players (88%) returned to professional play. The mean time to return to play was 7 months after surgery. However, only 25% (2 of 8) players achieved their preinjury singles rank or better by 18 months postoperatively. In total, 4 players returned to their preinjury singles ranking, with their peak singles ranking being attained at a mean of 2.4 years postoperatively. Conclusions: In professional female tennis players, a high return to play rate after arthroscopic shoulder surgery is associated with a prolonged and often incomplete return to previous level of performance. Thus, counseling the patient to this fact is important to manage expectations. Level Of Evidence: Level IV—Case Series.

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Comparison of Different Physical Activity Measurement Methods in Adults Aged 45 to 64 Years Under Free-Living Conditions

Objective: To compare physical activity (PA) measured by 4 methods in adults under free-living conditions in relation to selected demographic and anthropometric variables. Design: Cohort study. Setting: Department of Sports Medicine. Participants: Clinically healthy men (81) and women (69) aged 45 to 64 years. Interventions: Physical activity monitoring for 7 consecutive days under free-living conditions by pedometer (P) and accelerometer (A) simultaneously and PA questionnaires: International Physical Activity Questionnaire (IPAQ) and Seven-Day Physical Activity Questionnaire Recall (SDPAR) completed after the 7-day PA. Main Outcome Measures: Comparison of PA measured by pedometer, IPAQ, and SDPAR with accelerometer with regard to age, body mass, gender, and obesity type. Results: Total energy expenditure (EE) by IPAQ was higher than A (P

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The Efficacy of Sustained Heat Treatment on Delayed-Onset Muscle Soreness

Objective: To assess the impact of heat applied for 8 hours immediately after or 24 hours after exercise on delayed-onset muscle soreness (DOMS) in large skeletal muscle groups measured by subjective and objective means. Design: Cross-sectional repeated measure design study. Setting: Research laboratory. Subjects: Three groups of 20 subjects, age range 20 to 40 years. Intervention: Squats were conducted in three 5-minute bouts to initiate DOMS; 3 minutes of rest separated the bouts. One group had heat applied immediately after exercise, and a second group had heat applied 24 hours after exercise. A third group was the control group where no heat was applied. Main Outcome Measures: Visual analog pain scales, muscle strength of quads, range of motion of quads, stiffness of quads (Continuous Passive Motion machine), algometer to measure quadriceps soreness, and blood myoglobin. Results: The most significant outcome was a reduction in soreness in the group that had low-temperature heat wraps applied immediately after exercise (P

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Can a Repeated Sprint Ability Test Help Clear a Previously Injured Soccer Player for Fully Functional Return to Activity? A Pilot Study

Objective: To investigate the effects of fatigue induced by a repeated sprint ability (RSA) test on the neuromuscular responses of soccer players with a recent history of lower limb injuries (CH) and a matched control group in good fitness condition (GH). Design: This was a case–control study. Participants: Nine CH and 9 GH. Independent Variable: Allocation to CH or GH. Main Outcome Measures: Each player was assessed for blood lactate concentration and jumping performance [squat jump (SJ) and countermovement jump (CMJ)] before/after RSA. Post-RSA rate of perceived exertion (RPE) was obtained. Receiver operating characteristic analysis was performed to calculate RSA sensitivity and specificity in distinguishing between CH and GH. Intraclass correlation coefficient was used to assess reliability. Results: No baseline differences were found for any variable. ΔSJ before/after RSA was −14 ± 2% and −5 ± 2% in CH and GH, respectively (P

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Delayed Onset Vascular Stiffening Induced by Eccentric Resistance Exercise and Downhill Running

Objectives: Eccentric exercise induces muscle stiffening and soreness as well as unfavorable changes in macrovascular function. We tested the hypothesis that systemic eccentric exercise could evoke greater arterial stiffening than local eccentric resistance exercise. Design and Intervention: Twenty healthy young men were randomly assigned into either the downhill running (DR) and the eccentric resistance exercise (RE) group followed by a crossover design with an exercise and sham control trial. Main Outcome Measures: Carotid–femoral pulse wave velocity (cfPWV), central hemodynamic measures, and biomarkers were obtained. Results: Muscle soreness and plasma creatine kinase concentrations increased similarly after exercise in both groups. The cfPWV increased significantly at 48 hours post-exercise in both groups and remained elevated at 72 hours in DR. C-reactive protein (CRP) was elevated at 24 and 48 hours in DR, and 48 hours in RE. The increases in cfPWV were associated with the corresponding elevations in CRP in DR (r = 0.70, P

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Cancers of the Esophagus and Stomach: Potential Mechanisms Behind the Beneficial Influence of Physical Activity

Objective: To compare findings from several recent meta-analyses showing a reduced risk of gastric and esophageal cancers in physically active individuals, to assess the magnitude of this benefit, and to seek information on potential underlying mechanisms. Data Sources: A comprehensive search of Ovid/Medline from 1996 to February 2016, using the terms physical activity or exercise or training and esophageal or gastric cancer, and supplementing the articles identified by material from references lists and personal files. Main Results: Moderate-to-vigorous physical activity is associated with a 20% to 30% reduction in the risk of gastroesophageal adenocarcinomas, with a significant dose/response relationship. Benefit is greater in women than in men, and greater for noncardia than for cardia or esophageal tumors. Mechanisms could include a reduction of visceral fat (with a lesser production of cancer promoting hormones and reduced gastroesophageal reflux) and/or a lesser likelihood of smoking and excessive alcohol consumption. Physical activity does not protect against Helicobacter pylori infections or gastric ulceration, but mechanisms related to the impact of exercise on immune function, antioxidant mechanisms, and gastroesophageal reflux remain to be explored. Conclusions: Regular, moderate-to-vigorous physical activity is associated with a clinically significant reduction in the risk of gastroesophageal adenocarcinomas, but mechanisms are as yet unclear, and a causal relationship remains to be proven.

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Factors Influencing the Underreporting of Concussion in Sports: A Qualitative Study of Minor Hockey Participants

Objective: The present study is to identify factors contributing to underreporting of concussion in adolescent athletes. Design: Qualitative interviews. Setting: Participants were interviewed in an office environment. Participants: Interviews were conducted with 31 minor hockey players, 10 parents, 6 coaches, 4 trainers, 2 managers, and one game official. Players were 13 to 15 year old. With selective sampling, an inductive approach of analyzing the interviews was undertaken and themes were identified and analyzed. Assessment of Risk Factors: Underreporting is a complex phenomenon. A number of risk factors related to hockey culture, players, reference others, and rules of play were assessed. Main Outcome Measures: Reasons not reporting concussion is accepted in minor hockey. Results: Aspects of hockey culture such as an overemphasis on winning games and upheld misperceptions about the risks associated with concussion were identified as relevant to the underreporting of concussions. Various factors relevant to the underreporting of concussions include player's motivation to win, group membership dynamics such as a player's role as the team's "enforcer," coaches' own motivation to win to further their own opportunities in the sport, and parents' personal financial interest or alternative agenda in terms of time commitments and their child's future career prospects. Conclusions: Our findings indicate that underreporting of concussion among those players interviewed appears to be prevalent and associated with misconceptions about injury risk, and a culture that both reinforces and encourages underreporting with tacit or overt complicity of parents and coaches. Our findings support the need to alter the culture of violence and tough play in hockey by education, rule changes, economic measures, and changes in governance of the sport. Interviewing more stakeholders and policy makers would shed light on such potential interventions.

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Exercise-Associated Hyponatremia in a Lactating Female

Abstract: A 37-year-old woman presented to the emergency department with severe headache, which quickly progressed to altered mental status and seizure activity in hospital. Her initial serum sodium concentration ([Na+]) was 126 mmol/L. In the 24 hours before admission, she exercised vigorously for 120 minutes (interval training plus yoga) and also consumed more than 4 liters of fluid during that time to both stay hydrated and facilitate milk production because she was actively nursing 2 children. Her serum [Na+] and altered mental status corrected slowly over the next 48 hours with furosemide, hypertonic saline, and fluid restriction. This case is unique because it discusses the possible pathogenic role that lactation-induced oxytocin release may have on sustained antidiuresis and dilutional exercise-associated hyponatremia (EAH). This would be the first report documenting EAH in a lactating woman, which may highlight an underrecognized risk factor for physically active women who are concurrently breast-feeding.

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Baseline Performance and Psychometric Properties of the Child Sport Concussion Assessment Tool 3 (Child-SCAT3) in 5- to 13-year-old Athletes

Objective: To determine the normative, baseline performance and psychometric properties of the Child Sport Concussion Assessment Tool 3 (Child-SCAT3) in 5- to 13-year-old athletes. Design: Cross-sectional study. Setting: Practice fields. Participants: Contact sport athletes (N = 155) 5 to 13 years old. Independent Variables: Age, gender, verbal intellectual functioning (receptive vocabulary). Main Outcome Measures: Child-SCAT3: self-reported and parent-reported symptoms, cognitive performance (child form of the Standardized Assessment of Concussion; SAC-C), and balance (modified Balance Error Scoring System, mBESS-C; tandem gait). A subset of the sample repeated the Child-SCAT3 at another date. Some subjects also completed the Adult-SCAT3 version of the symptom checklist and mBESS. Results: Small-to-medium-sized effects of age were observed on all Child-SCAT3 components. Effects of gender and receptive vocabulary were observed on select components of the SCAT3. Younger age and lower receptive vocabulary were independently associated with greater symptom endorsement, yet parents rated higher symptom burden for older children. Internal consistency reliability and stability of symptom ratings was good to excellent. Stability was more modest for SAC-C and tandem gait scores and very poor for mBESS-C scores, perhaps due to restricted variance. Inter-rater reliability (self-rated vs parent-rated symptoms) was fair. Conclusions: The Child-SCAT3 self-report symptom checklist may be inappropriate to administer to younger school-aged children. Some of the age effects observed warrant use of demographically appropriate norms in Child-SCAT3 interpretation. The findings can provide guidance for clinicians assessing children of varying ages and point to directions for further development of refined approaches for pediatric concussion assessment.

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A Case Report of Traumatic Partial Extensor Carpi Ulnaris Subluxation in an Elite Hockey Player With Review of the Literature

Abstract: In this article, we present a unique case of traumatic partial recurrent extensor carpi ulnaris (ECU) subluxation in an elite hockey player. To the best of our knowledge, this is the only report of partial ECU subluxation due to a split in the ECU tendon presented in the literature. This case illustrates the importance of proper diagnosis and treatment of such a lesion. We also emphasize that dynamic ultrasound is an excellent and cost-effective imaging modality that can help with the diagnosis of partial ECU subluxation. Finally, surgical treatment for failed conservative management showed excellent results in an elite athlete.

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Epidemiology of Chest, Rib, Thoracic Spine, and Abdomen Injuries Among United States High School Athletes, 2005/06 to 2013/14

Objective: Describe chest and abdominal injury epidemiology among US high school athletes. Design: Retrospective analysis of longitudinal surveillance data. Setting: Injury data from 2005/06 to 2013/14 academic years were collected using an internet-based surveillance system. Participants: A large sample of US high schools. Assessment of Risk Factors: Injuries sustained as a function of sport. Main Outcome Measures: Chest, rib, thoracic spine, and abdominal injuries sustained during high school athletic events. Results: Overall 1487 chest, rib, thoracic spine, and abdominal injuries occurred during 30 415 179 athletic exposures (AEs); an injury rate of 4.9 injuries per 100 000 AEs. Over half (56.8%) of injured athletes were evaluated by another medical provider in addition to the athletic trainer, and 34 injuries (2.3%) required surgery. Diagnostic techniques, including x-ray, magnetic resonance imaging or computed tomography were used in 729 (49.0%) injuries. The injury rate was higher in boys' (6.8) than girls' (2.0) sports [rate ratio (RR), 3.43; 95% CI, 3.04-4.10]. Football (47.7%) accounted for the highest proportion of injuries followed by wrestling (18.5%), boys' soccer (4.6%), and girls' soccer (3.7%). The rate of injury was higher in competition than practice, (RR, 2.86; 95% CI, 2.59-3.23). Only 57.7% of injured athletes were able to return to play within 1 week. Conclusions: Chest and abdominal injuries in high school sports although relatively rare, can result in loss of playing time and frequently prompt medical evaluation. Thus, they present a physical and economic burden. To optimize prevention, further studies can focus on subgroup risk factor identification to drive development of targeted prevention strategies.

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Nationwide Implementation of the FIFA 11+ Injury Prevention Program in Canadian Youth Soccer

No abstract available

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A case of neuropsychiatric lupus Erythematosus characterized by the Owl’s eye sign: a case report

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disorder characterized by multiple affected systems. More than half of SLE patients will suffer from neuropsychiatric lupus erythematosus (NPSLE...

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Ethnic differences in the +405 and −460 vascular endothelial growth factor polymorphisms and peripheral neuropathy in patients with diabetes residing in a North London, community in the United Kingdom

There are marked ethnic differences in the susceptibility to the long-term diabetic vascular complications including sensory neuropathy. The vascular endothelial growth factor (VEGF) +405 (C/G) and −460 (T/C) ...

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Thrombocytopenia induced by dabigatran: two case reports

Vitamin K inhibitors (e.g. warfarin) and indirect thrombin inhibitors (e.g. heparin) are widely used to prevent thromboembolic disorders (e.g. myocardial infarction, venous thromboembolism, and stroke). These ...

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Long-term and late treatment consequences: endocrine and metabolic effects.

Purpose of review: Cancer therapies often result in the 'late effect of cancer treatment' whereby secondary health complications emerge years after radiotherapy and chemotherapy. This review focuses on endocrine and metabolic consequences in adult cancer survivors as late treatment effects. Recent findings: Endocrine and metabolic disorders are among the most common late effects. Endocrine disorders include hypopituitarism, which leads to growth hormone deficiency, hypogonadism, adrenal insufficiency and hypothyroidism and related clinical manifestations. Hypogonadism in particular is associated with a wide range of health complications requiring input from the like of endocrine and fertility specialists. Immune checkpoint inhibitors are novel anticancer agents, some of which are uniquely associated with hypophysitis which requires early recognition and management, including steroid replacement. Metabolic syndrome, a significant risk for cardiovascular disease, is highly prevalent. Although the effects of cranial irradiation on the hypothalamic-pituitary system are more apparent, the relationship between chemotherapy and endocrine/metabolic disorders remains to be elucidated. There exist published guidelines for monitoring endocrine and cardiometabolic risk in cancer survivors, but the extent of monitoring appears insufficient. Summary: Regular monitoring and early management of endocrine/metabolic disorders is required to prevent the elevated rates of health complications after cancer treatment, and thereby improve cancer survivorship. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Unmasking chronic breathlessness.

No abstract available

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Palliative care and interstitial lung disease.

Purpose of review: The palliative care needs of people with interstitial lung disease (ILD) have recently been highlighted by the National Institute for Health and Care Excellence. All people with progressive ILD should receive best supportive care to improve symptom control and quality of life and where possible this should be evidence based. Recent findings: Deaths from ILD are increasing and deaths in hospital are more common compared to home. People with ILD experience a wide range of symptoms including breathlessness and cough. People living with ILD often suffer unmet physical and psychological needs throughout the disease journey. Few appropriately validated outcome measures exist for ILD which has hampered research on the longitudinal experience of symptoms and quality of life and the evaluation of interventions. Recent recommendations from the National Institute of Clinical Excellence promote the use of a new palliative care needs assessment tool. Use of a tool in busy respiratory clinics may help to highlight those requiring specialist input. Summary: Further research into the role of opioids, oxygen and neuromodulatory agents in symptom management are needed. In addition, exploration of breathlessness and case conference interventions in transitioning patients from the hospital to community settings is a priority. Further work is needed to identify a core set of validated ILD-specific patient-reported outcome measures for the robust evaluation of interventions. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Quantitative Disease Progression Model of Alpha-1 Proteinase Inhibitor Therapy on CT Lung Density in Patients with Alpha-1 Antitrypsin Deficiency

Summary

Aims

Early-onset emphysema attributed to alpha-1 antitrypsin deficiency (AATD) is frequently overlooked and undertreated. RAPID-RCT/RAPID-OLE, the largest clinical trials of purified human alpha-1 proteinase inhibitor (A₁-PI; 60 mg/kg/wk) therapy completed to date, demonstrated for the first time that A₁-PI is clinically effective in slowing lung tissue loss in AATD. A post-hoc pharmacometric analysis was undertaken to further explore dose, exposure and response.

Methods

A disease progression model was constructed, utilizing observed A₁-PI exposure and lung density decline rates (measured by computed tomography) from RAPID-RCT/RAPID-OLE, to predict effects of population variability and higher doses on A₁-PI exposure and clinical response. Dose-exposure and exposure-response relationships were characterized using nonlinear and linear mixed effects models, respectively. The dose-exposure model predicts summary exposures and not individual concentration kinetics; covariates included baseline serum A₁-PI, forced expiratory volume in one second and body weight. The exposure-response model relates A₁-PI exposure to lung density decline rate at varying exposure levels.

Results

60 mg/kg/wk achieved trough serum levels >11 μM (putative 'protective threshold') in ≥98% patients. Dose-exposure-response simulations revealed increasing separation between A₁-PI and placebo in the proportions of patients achieving higher reductions in lung density decline rate; improvements in decline rates ≥0.5 g/L/yr occurred more often in patients receiving A₁-PI: 63% vs. 12%.

Conclusion

Weight-based A₁-PI dosing reliably raises serum levels above the 11 μM threshold. However, our exposure-response simulations question whether this is the maximal, clinically effective threshold for A₁-PI therapy in AATD. The model suggested higher doses of A₁-PI would yield greater clinical effects.

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The Impact of Serum Potassium-Influencing Antihypertensive Drugs on the Risk of Out-of-Hospital Cardiac Arrest: A Case Control Study

Abstract

Background

Sudden cardiac arrest (SCA) is a complex multifactorial event and most commonly caused by ventricular tachycardia/ fibrillation (VT/ VF). Some antihypertensive drugs could induce hypokalaemia or hyperkalaemia that may increase susceptibility to VT/VF and SCA.

Objective

To assess the association between different classes of antihypertensive drugs classified according to their potential impact on serum potassium levels and the occurrence of out-of-hospital cardiac arrest (OHCA) based on VT/VF.

Methods

A case-control study was performed among current users of antihypertensive drugs. Cases were OHCA victims with electrocardiogram documented VT/VF drawn from the AmsteRdam REsuscitation STudies (ARREST) registry, and controls were non-OHCA individuals from the PHARMO database. Antihypertensive drugs were classified into: (1) antihypertensives with neutral effect on serum potassium levels; (2) hypokalaemia-inducing antihypertensives; (3) hyperkalaemia-inducing antihypertensives; (4) combination of antihypertensives with hypo- and hyperkalaemic effects.

Results

We included 1,345 cases and 4,145 controls. The risk of OHCA was significantly increased among users of hypokalaemia-inducing antihypertensives (adjusted OR 1.39; 95%CI [1.10-1.76]) and among users of a combination of antihypertensives with hypo- and hyperkalaemic effects (adjusted OR 1.42; 95%CI [1.17-1.72]) versus users of antihypertensives with neutral effect. There was no difference in OHCA risk between users of hyperkalaemia-inducing antihypertensives versus users of antihypertensive drugs with neutral effect (adjusted OR 1.15; 95%CI [0.95-1.40]).

Conclusion

The risk of OHCA is significantly increased in patients who were current users of hypokalaemia-inducing antihypertensives and patients using a combination of antihypertensives with hypo- and hyperkalaemic effects.

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Workplace violence against physicians in Turkeys emergency departments: a cross-sectional survey

Objective

We aimed to determine the prevalence of violence directed at emergency department (ED) physicians in Turkey and confirm the factors influencing such violence.

Design

Cross-sectional survey study.

Setting

Country of Turkey.

Participants

Physicians currently practising in EDs in Turkey.

Main outcome measures

The prevalence of violence directed at physicians and factors that may influence it, such as physicians' personal characteristics, ED characteristics and physicians' opinions regarding the causes of and suggested methods of preventing violence.

Results

A total of 713 physicians participated. Of these, 78.1% reported being subjected to violence in the past year and 65.9% reported more than one such incident. Being subjected to violence was related to age (p=0.008), working in an ED with a high patient admission rate (p=0.018), current position (p<0.001), working outside regular work hours (p<0.001), working in a state hospital (p<0.001) and level of experience (p<0.001). Gender, type of patient typically seen, region and patient waiting period did not influence subjection to violence. The present safety precautions against violence do not appear to influence the prevalence of violence.

Conclusions

Our results indicated that ED physicians' experience of violence is related to personal characteristics such as age and level of expertise, and hospital and ED characteristics such as high patient admission rates. Presently, no measures taken to reduce this violence have been proven effective.

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Heart Failure in Epidermolysis Bullosa

M.T. Villarroel Salcedo
Actas Dermosifiliogr.2017;108:498

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Mycosis Fungoides in Pediatric Patients: A Diagnostic Challenge

Rosa Izu Belloso
Actas Dermosifiliogr.2017;108:499

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Eosinophils as a Warning Sign

E. Rodríguez-Díaz
Actas Dermosifiliogr.2017;108:499-500

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Antimicrobial Photodynamic Therapy: An Unexplored New Field

J. Romaní
Actas Dermosifiliogr.2017;108:500

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Considerations on Subgroup Analyses in Clinical Trials

P. Coto-Segura
Actas Dermosifiliogr.2017;108:501

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Psoriasis and Psychiatric Disorders: The Next Frontier

J.M. Carrascosa, F. Ballesca
Actas Dermosifiliogr.2017;108:502-5

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Psoriasis and Nonalcoholic Fatty Liver Disease

J.M. Carrascosa, C. Bonanad, E. Dauden, R. Botella, A. Olveira-Martín
Actas Dermosifiliogr.2017;108:506-14

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Angiogenesis in Dermatology – Insights of Molecular Mechanisms and Latest Developments

N.A. Richarz, A. Boada, J.M. Carrascosa
Actas Dermosifiliogr.2017;108:515-23

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Hair-follicle Transplant Into Chronic Ulcers: A New Graft Concept

M.L. Martínez Martínez, E. Escario Travesedo, F. Jiménez Acosta
Actas Dermosifiliogr.2017;108:524-31

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Follicular Unit Extraction for Hair Transplantation: An Update

F. Jiménez-Acosta, I. Ponce-Rodríguez
Actas Dermosifiliogr.2017;108:532-7

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Causes and Cures of Skin Diseases in the Work of Hildegard of Bingen

J. Romaní, M. Romaní
Actas Dermosifiliogr.2017;108:538-43

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Cardiomyopathy in Patients With Hereditary Bullous Epidermolysis

A. Batalla, A. Vicente, J. Bartrons, F. Prada, C. Fortuny, M.A. González-Enseñat
Actas Dermosifiliogr.2017;108:544-9

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Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis: Subgroup analysis of Latin American patients in the phase 3 randomized UNCOVER-3 study

F. Valenzuela, C. de la Cruz Fernandez, R.L. Galimberti, S. Gürbüz, M. McKean-Matthews, L. Goncalves, R. Romiti
Actas Dermosifiliogr.2017;108:550-63

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Mycosis Fungoides: Experience in a Pediatric Hospital

A.B. Cervini, A.N. Torres-Huamani, C. Sanchez-La-Rosa, L. Galluzzo, V. Solernou, J. Digiorge, P. Rubio
Actas Dermosifiliogr.2017;108:564-70

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Pediatric Allergic Contact Dermatitis: Clinical and Epidemiological Study in a Tertiary Hospital

J.M. Ortiz Salvador, A. Esteve Martínez, D. Subiabre Ferrer, A.M. Victoria Martínez, J. de la Cuadra Oyanguren, V. Zaragoza Ninet
Actas Dermosifiliogr.2017;108:571-8

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Eosinophilic Dermatosis of Hematologic Malignancy

S. Lucas-Truyols, B. Rodrigo-Nicolás, C. Lloret-Ruiz, E. Quecedo-Estébanez
Actas Dermosifiliogr.2017;108:e39-44

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Photodynamic Therapy With Methylene Blue for Skin Ulcers Infected With Pseudomonas aeruginosa and Fusarium spp.

C. Aspiroz, M. Sevil, C. Toyas, Y. Gilaberte
Actas Dermosifiliogr.2017;108:e45-8

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Multiple Papules on Both Hands

A. Panés-Rodríguez, A. Jaka-Moreno, I. Arias-Camisón Montero, A. Tuneu-Valls
Actas Dermosifiliogr.2017;108:579-80

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Nodule on the External Ear

S. Heras-González, L. Aspe-Unanue, R. González-Pérez
Actas Dermosifiliogr.2017;108:581-2

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RF-Itraconazole Pulse Therapy for Seborrheic Dermatitis: A Treatment Approach to Consider

V. Fatsini-Blanch, M.I. Martínez-González, S. Heras-González, A. de Quintana-Sancho
Actas Dermosifiliogr.2017;108:583-4

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Peculiar Clinical Presentation of Coxsackievirus B4 Infection: Neonatal Restrictive Cardiomyopathy

AJP Rep 2017; 07: e124-e126
DOI: 10.1055/s-0037-1601352

Introduction Restrictive cardiomyopathy in fetuses and neonates is extremely rare and has a poor outcome. Its etiology in neonates is elusive: metabolic diseases (e.g., Gaucher, Hurler syndrome), neuromuscular disorders (e.g., muscular dystrophies, myofibrillar myopathies), or rare presentation of genetic syndromes (e.g., Coffin–Lowry syndrome) account for a minority of the cases, the majority remaining idiopathic. Case Study We report the case of a 17-day-old male infant presenting cardiogenic shock following a restrictive dysfunction of the left ventricle. Postmortem investigations revealed coxsackievirus B4 myocarditis with histological lesions limited to the left heart. However, polymerase chain reaction (PCR) for coxsackievirus B4 was positive in the left as well as in the right ventricular samples. Conclusion In conclusion, coxsackievirus myocarditis is a cause of restrictive cardiomyopathy, and its diagnosis should involve PCR screening as a more sensitive technique.
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Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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Embracing model-based designs for dose-finding trials

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KIBRA attains oncogenic activity by repressing RASSF1A

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A combined biomarker panel shows improved sensitivity for the early detection of ovarian cancer allowing the identification of the most aggressive type II tumours

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LIM kinase 1 interacts with myosin-9 and alpha-actinin-4 and promotes colorectal cancer progression

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Kinase-driven metabolic signalling as a predictor of response to carboplatin–paclitaxel adjuvant treatment in advanced ovarian cancers

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Harmonisation of biobanking standards in endometrial cancer research

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Geriatric assessment is superior to oncologists’ clinical judgement in identifying frailty

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World Congress Integrative Medicine & Health 2017: part three

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World Congress Integrative Medicine & Health 2017: Part one

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World Congress Integrative Medicine & Health 2017: part two

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Anti-diabetic effect of black ginseng extract by augmentation of AMPK protein activity and upregulation of GLUT2 and GLUT4 expression in db/db mice

Black ginseng (Panax ginseng C. A. Meyer), three to nine times-steamed and dried ginseng, has biological and pharmacological activities. In this study, the anti-diabetic effects of the black ginseng ethanol extra...

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Hypoglycaemic activity of Mathurameha, a Thai traditional herbal formula aqueous extract, and its effect on biochemical profiles of streptozotocin-nicotinamide-induced diabetic rats

The Thai traditional herbal formula–Mathurameha, consisting of 26 medicinal plants, has been used as an alternative and complementary medicine for diabetes treatment in Wangnamyen Hospital, Thailand. To provid...

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A practical examination of RNA isolation methods for European pear (Pyrus communis)

With the goal of identifying fast, reliable, and broadly applicable RNA isolation methods in European pear fruit for downstream transcriptome analysis, we evaluated several commercially available kit-based RNA...

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Paramedics stop to mow lawn for 98-year-old woman

By EMS1 Staff WACO, Texas — Paramedics took over lawn duties for a 98-year-old woman when they saw her working in 90-degree weather. KWTX reported that the crew was in between calls when they spotted Margaret Durham, 98, mowing her lawn. She appeared to be overheated; the paramedics got out of the ambulance and finished the job for her. "She's elderly and looked exhausted," paramedic ...

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Retired paramedic creates group for responders with PTSD

By EMS1 Staff SIOUX FALLS, S.D. — A retired paramedic created a group to help EMS providers cope with PTSD. KDLT reported that Kent Meyer, who was a paramedic for 14 years, hopes to help first responders deal with PTSD that is caused by the job. "It's not just a job, it's who you are, it's a part of you," Meyer said. "I felt alone, I felt all alone." Meyer ...

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Cover

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Mechanisms governing inflammasome activation, assembly and pyroptosis induction

Abstract

Inflammasomes are multimeric protein complexes that regulate inflammatory responses and pyroptotic cell death to exert host defense against microbes. Intracellular pattern-recognition receptors such as nucleotide-binding domain and leucine-rich repeat receptors (NLRs) and absent in melanoma 2 like receptors (ALRs) assemble the inflammasome complexes in response to pathogens and danger or altered-self signals in the cell. Inflammasome sensors, in association with an adaptor protein—apoptosis-associated speck-like protein containing a caspase-activation and -recruitment domain (ASC)—activate inflammatory caspase-1 to enable the release of inflammatory cytokines and induce cell death, conferring host defense against pathogens. Beyond infectious diseases, the importance of inflammasomes is implicated in a variety of clinical conditions such as auto-inflammatory diseases, neuro-degeneration and metabolic disorders and the development of cancers. Understanding inflammasome activation and its molecular regulation can unveil therapeutic targets for controlling inflammasome-mediated disorders. In this review, we describe recent advances in inflammasome biology and discuss its activation, structural insights into inflammasome assembly and mechanisms for the execution of pyroptosis.

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In This Issue

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Integrity of immunoglobulin variable regions is supported by GANP during AID-induced somatic hypermutation in germinal center B cells

Abstract

Immunoglobulin affinity maturation depends on somatic hypermutation (SHM) in immunoglobulin variable (IgV) regions initiated by activation-induced cytidine deaminase (AID). AID induces transition mutations by C→U deamination on both strands, causing C:G→T:A. Error-prone repairs of U by base excision and mismatch repairs (MMRs) create transversion mutations at C/G and mutations at A/T sites. In Neuberger's model, it remained to be clarified how transition/transversion repair is regulated. We investigate the role of AID-interacting GANP (germinal center-associated nuclear protein) in the IgV SHM profile. GANP enhances transition mutation of the non-transcribed strand G and reduces mutation at A, restricted to GYW of the AID hotspot motif. It reduces DNA polymerase η hotspot mutations associated with MMRs followed by uracil-DNA glycosylase. Mutation comparison between IgV complementary and framework regions (FWRs) by Bayesian statistical estimation demonstrates that GANP supports the preservation of IgV FWR genomic sequences. GANP works to maintain antibody structure by reducing drastic changes in the IgV FWR in affinity maturation.

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Outstanding Merit Award for 2016

The article 'Guanosine and its modified derivatives are endogenous ligands for TLR7' (doi: 10.1093/intimm/dxv062), by Takuma Shibata et al., has been given the Outstanding Merit Award for 2016; that is, it has been selected by the Editor-in-Chief as the best paper published last year in the journal. The full text of the article is available for free online (http://ift.tt/2tpLkkG) but it is summarized here.

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Activation of group 2 innate lymphoid cells exacerbates and confers corticosteroid resistance to mouse nasal type 2 inflammation

Abstract

Both T_h2 cells and group 2 innate lymphoid cells (ILC2s) contribute to allergic diseases. However, their exact role and relationship in nasal allergic disorders are unclear. In this study, we investigated the cooperation of T_h2 cells and ILC2s in a mouse model of nasal allergic disorder. To differentially activate T_h2 cells and/or ILC2s in nasal mucosa, mice were intra-nasally administered ovalbumin (OVA) antigen, papain, an ILC2-activator, or both for 2 weeks. Epithelial thickness and number of eosinophils in the nasal mucosa were evaluated at 24 h after the final challenge. Intra-nasal administration of OVA and papain preferentially activated T_h2 cells and ILC2s, respectively, in the nose. Both OVA and papain increased the nasal epithelial thickness and number of eosinophils, and their coadministration significantly enhanced the symptoms. Although T-/B-cell-deficient mice showed severely decreased nasal symptoms induced by OVA or OVA-plus-papain, the mice still showed slight papain-induced nasal symptoms. In ILC2-deficient mice, OVA-plus-papain-induced nasal symptoms were suppressed to the same level as OVA-alone. Similarly, IL-33- and ST2-deficient mice showed decreased OVA-plus-papain-induced nasal symptoms. IL-5 induced eosinophilia only, but IL-13 contributed to both nasal epithelial thickening and eosinophilia induced by OVA-plus-papain. Dexamethasone ameliorated OVA-alone-induced nasal epithelial thickening. However, OVA-plus-papain-induced nasal epithelial thickening was only partially controlled by dexamethasone. These results demonstrate that IL-33/ST2-pathway-mediated ILC2 activation exacerbated T_h2-cell-induced nasal inflammation by producing IL-13. Although T_h2-cell-alone-induced nasal inflammation was controlled by corticosteroid treatment, the activation of ILC2s conferred treatment resistance. Therefore, ILC2s and their activators could be therapeutic targets for treatment-refractory nasal allergic disorders.

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Table of Contents

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Corrigendum

Dissecting the formation, structure and barrier function of the stratum corneum

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Long-term survival of the mouse ES cell-derived mast cell, MEDMC-BRC6, in mast cell-deficient Kit W-sh/W-sh mice

Abstract

Mast cells (MCs) play pivotal roles in allergic reactions and the host defense against microbial infection through the IgE-dependent and IgE-independent signaling pathways. MC lines that can be analyzed both in vitro and in vivo would be useful for the study of MC-dependent immune responses. Here, we investigated the functional characteristics of a mouse embryonic stem cell-derived MC-like cell line, MEDMC-BRC6. The cell line expressed FcεRI and c-Kit and showed degranulation and production of inflammatory cytokines and chemokines, including TNF-α, IL-6 and MCP-1, upon cross-linking FcεRI with IgE. These cytokines and chemokines were also produced by the cell line by stimulation of TLR2 and TLR4. MEDMC-BRC6 survived in the peritoneal cavity and the ear skin for at least 6 months after the transfer into genetically compatible MC-deficient Kit^W-sh/W-sh mice, in which systemic anaphylaxis was successfully induced. Thus, MEDMC-BRC6 cells represent a potent tool for investigating the functions of MCs in vitro and in vivo.

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Thyroid neoplasia risk is increased nearly 30 years after the Chernobyl accident

Abstract

To evaluate risk of thyroid neoplasia nearly 30 years following exposure to radioactive iodine (I-131) from the 1986 Chernobyl nuclear accident, we conducted a fifth cycle of thyroid screening of the Ukrainian-American (UkrAm) cohort during 2012-2015, following four previous screening cycles started in 1998. We identified 47 thyroid cancers (TC) and 33 follicular adenomas (FA) among 10,073 individuals who were <18 years at the time of the accident and had a mean I-131 dose of 0.62 Gy. We found a significant I-131 dose response for both TC and FA, with an excess odd ratio per Gy of 1.36 (95% CI: 0.39 to 4.15) and 2.03 (95% CI: 0.55 to 6.69), respectively. The excess risk of malignant and benign thyroid neoplasia persists nearly three decades after exposure and underscores the importance of continued follow-up of this cohort to characterize long-term pattern of I-131 risk. This article is protected by copyright. All rights reserved.

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Impact of extending screening mammography to older women: Information to support informed choices

ABSTRACT

From 2013 through 2017, the Australian national breast cancer screening program is gradually inviting women aged 70-74 years to attend screening, following a policy decision to extend invitations to older women. We estimate the benefits and harms of the new package of biennial screening from age 50-74 compared to the previous programme of screening from age 50-69. Using a Markov model, we applied estimates of the relative risk reduction for breast cancer mortality and the risk of overdiagnosis from the Independent UK Panel on Breast Cancer Screening review to Australian breast cancer incidence and mortality data. We estimated screening specific outcomes (recalls for further imaging, biopsies, false positive and interval cancer rates) from data published by BreastScreen Australia. Compared to stopping at age 69, screening 1000 women to age 74 is likely to avert one more breast cancer death, with an additional 78 women receiving a false positive result and another 28 women diagnosed with breast cancer, of whom eight will be overdiagnosed and overtreated. The extra five years of screening results in approximately seven more overdiagnosed cancers to avert one more breast cancer death. Thus extending screening mammography in Australia to older women results in a less favourable harm to benefit ratio than stopping at age 69. Supporting informed decision making for this age group should be a public health priority. This article is protected by copyright. All rights reserved.

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Hypertension-induced synapse loss and impairment in synaptic plasticity in the mouse hippocampus mimics the aging phenotype: implications for the pathogenesis of vascular cognitive impairment

Abstract

Strong epidemiological and experimental evidence indicates that hypertension has detrimental effects on the cerebral microcirculation and thereby promotes accelerated brain aging. Hypertension is an independent risk factor for both vascular cognitive impairment (VCI) and Alzheimer's disease (AD). However, the pathophysiological link between hypertension-induced cerebromicrovascular injury (e.g., blood–brain barrier disruption, increased microvascular oxidative stress, and inflammation) and cognitive decline remains elusive. The present study was designed to characterize neuronal functional and morphological alterations induced by chronic hypertension and compare them to those induced by aging. To achieve that goal, we induced hypertension in young C57BL/6 mice by chronic (4 weeks) infusion of angiotensin II. We found that long-term potentiation (LTP) of performant path synapses following high-frequency stimulation of afferent fibers was decreased in hippocampal slices obtained from hypertensive mice, mimicking the aging phenotype. Hypertension and advanced age were associated with comparable decline in synaptic density in the stratum radiatum of the mouse hippocampus. Hypertension, similar to aging, was associated with changes in mRNA expression of several genes involved in regulation of neuronal function, including down-regulation of Bdnf, Homer1, and Dlg4, which may have a role in impaired synaptic plasticity. Collectively, hypertension impairs synaptic plasticity, reduces synaptic density, and promotes dysregulation of genes involved in synaptic function in the mouse hippocampus mimicking the aging phenotype. These hypertension-induced neuronal alterations may impair establishment of memories in the hippocampus and contribute to the pathogenesis and clinical manifestation of both vascular cognitive impairment (VCI) and Alzheimer's disease (AD).

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New Methods to Study Gustatory Coding

We present three new methods to study gustatory coding. Using a simple animal, the moth Manduca sexta (Manduca), we describe a dissection protocol, the use of extracellular tetrodes to record the activity of multiple gustatory receptor neurons, and a system for delivering and monitoring precisely timed pulses of tastants.

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Introducing DAVE: Online Analysis Tools for the Genomic Data Commons

NCI has released an online, open-access cancer research resource for the Genomic Data Commons called the Data Analysis, Visualization, and Exploration Tools, or DAVE.

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EM Nerd-The Case of the Failed Assumptions

Whether you are aware of it our not, three major assumptions are present when employing any diagnostic strategy in the Emergency Department. First, that the diagnostic test in question will identify a group of patients at risk of a poor outcome due to an otherwise undiagnosed process. Second, there is an effective therapeutic intervention that […]

EMCrit by Rory Spiegel.

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Using Press Ganey Provider Feedback To Improve Patient Satisfaction: A Pilot Randomized Controlled Trial

Abstract

Study Objective

To conduct a pilot randomized controlled trial to assess the feasibility, logistics and potential effect of monthly provider funnel plot feedback reports from Press Ganey data and semi-annual face-to-face coaching sessions to improve patient satisfaction scores.

Methods

This was a pilot randomized controlled trial of 25 emergency medicine faculty providers in one urban academic emergency department. We enrolled full-time clinical faculty with at least 12 months of baseline Press Ganey data, who anticipated working in the ED for at least 12 additional months. Providers were randomized into intervention or control groups in a 1:1 ratio. The intervention group had an initial 20-minute meeting to introduce the funnel plot feedback tool and standardized feedback on their baseline Press Ganey scores, then received a monthly email with their individualized funnel plot depicting cumulative Press Ganey scores (compared to their baseline score and the average score of all providers) for 12 months. The primary outcome was the difference in Press Ganey "Doctor-Overall" scores between treatment groups at 12 months. We used a weighted analysis of covariance model to analyze the study groups, accounting for variation in the number of surveys by provider and baseline scores.

Results

Of 37 eligible faculty, we enrolled 25 providers, 13 of whom were randomized to the intervention group and 12 to the control group. During the study period, there were 815 Press Ganey surveys returned, ranging from 4 to 71 surveys per provider. For the standardized overall doctor score over 12 months (primary outcome), there was no difference between the intervention and control groups (difference 1.3 points, 95% confidence interval -2.4 – 5.9, p = .47). Similarly, there was no difference between groups when evaluating the four categories of doctor-specific patient satisfaction scores from the Press Ganey survey (all p > 0.05).

Conclusions

In this pilot trial of monthly provider funnel plot Press Ganey feedback reports, there was no difference in patient satisfaction scores between the intervention and control groups after 12 months. While this study was not powered to detect outcome differences, we demonstrate the feasibility, logistics, and effect sizes that could be used to inform future definitive trials.

This article is protected by copyright. All rights reserved.

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Accuracy of Computed Tomography Imaging Criteria in the Diagnosis of Adult Open Globe Injuries by Neuroradiology and Ophthalmology

Abstract

Objective

To evaluate the sensitivity and specificity of computed tomography (CT) diagnosis of open globes; determine which imaging factors are most predictive of open globe injuries; and evaluate the agreement between neuroradiologist and ophthalmologist readers for diagnosis of open and closed globes.

Methods

This study was a retrospective cohort study. Patients who presented to Memorial Hermann—Texas Medical Center with suspicion for open globes were reviewed. One neuroradiologist and 2 ophthalmologists masked to clinical information reviewed CT images for signs concerning for open globe including change in globe contour, anterior chamber deformation, intraocular air, vitreous hemorrhage, subretinal fluid indicating retinal or choroidal detachment, dislocated or absent lens, intraocular foreign body, and orbital fracture. Using the clinically or surgically confirmed globe status as the true globe status, sensitivity, specificity, and agreement (kappa) were calculated and used to investigate which imaging factors are most predictive of open globe injuries.

Results

One hundred fourteen patients were included: 35 patients with open globes and 79 patients with closed globes. Specificity was greater than 97% for each reader, and sensitivity ranged from 51 to 77% among readers. The imaging characteristics most consistently used to predict an open globe injury were change in globe contour and vitreous hemorrhage (sensitivity: 43% to 57% and specificity > 98%). The agreement of impression of open globe between the neuroradiologist and ophthalmologists was good and excellent between ophthalmologists.

Conclusions

CT imaging is not absolute, and the sensitivity is still inadequate to be fully relied upon. The CT imaging findings most predictive of an open globe injury were change in globe contour and vitreous hemorrhage. Clinical exam or surgical exploration remains the most important component in evaluating for a suspected open globe, with CT imaging as an adjunct.

This article is protected by copyright. All rights reserved.

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Production of Chemicals by Klebsiella pneumoniae Using Bamboo Hydrolysate as Feedstock

Bamboo powder was pretreated with NaOH and enzymatically hydrolyzed. The hydrolysate of bamboo was used as the feedstock for 2,3-butanediol, R-acetoin, 2-ketogluconic acid, and xylonic acid production by Klebsiella pneumoniae.

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Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism

Subclinical hypothyroidism is defined as an elevated serum thyrotropin level and a serum free thyroxine level within the reference range. Between 8% and 18% of adults 65 years of age or older have these biochemical features, and the prevalence is higher among women than among men. Subclinical…

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Mammalian Cell Encapsulation in Alginate Beads Using a Simple Stirred Vessel

This video and manuscript describe an emulsion-based method to encapsulate mammalian cells in 0.5% to 10% alginate beads which can be produced in large batches using a simple stirred vessel. The encapsulated cells can be cultured in vitro or transplanted for cellular therapy applications.

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Assessment of gender and age effects on serum and hair trace element levels in children with autism spectrum disorder

Abstract

The primary objective of the present study was to investigate the levels of essential trace elements in hair and serum in children with autism spectrum disorder (ASD) and investigate the age and gender effects. Children with ASD were characterized by significantly higher levels of copper (Cu) (+8%), iron (Fe) (+5%), and selenium (Se) (+13%) levels in hair and only 8% higher serum Cu levels. After stratification for gender, ASD boys were characterized by significantly increased hair Cu (+ 25%), Fe (+ 25%), and Se (+ 9%) levels, whereas in girls only Se content was elevated (+ 15%). Boys and girls suffering from ASD were characterized by significantly higher serum manganese (Mn) (+20%) and Cu (+18%) as compared to the control values, respectively. In the group of younger children (2–5 years), no significant group difference in hair trace element levels was detected, whereas serum Cu levels were significantly higher (+7%). In turn, the serum concentration of Se in ASD children was 11% lower than that in neurotypical children. In the group of older children with ASD (6–10 years), hair Fe and Se levels were 21% and 16% higher, whereas in serum only Cu levels were increased (+12%) as compared to the controls. Correlation analysis also revealed a different relationship between serum and hair trace element levels with respect to gender and age. Therefore, it is highly recommended to assess several bioindicative matrices for critical evaluation of trace element status in patients with ASD in order to develop adequate personalized nutritional correction.

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SSADH deficiency in an Italian family: a novel ALDH5A1 gene mutation affecting the succinic semialdehyde substrate binding site

Abstract

SSADH deficiency (SSADHD) is a rare autosomal recessively inherited metabolic disorder. It is associated with mutations of ALDH5A1 gene, coding for the homotetrameric enzyme SSADH. This enzyme is involved in γ-aminobutyric acid (GABA) catabolism, since it oxidizes succinic semialdehyde (SSA) to succinate. Mutations in ALDH5A1 gene result in the abnormal accumulation of γ-hydroxybutyrate (GHB), which is pathognomonic of SSADHD. In the present report, diagnosis of SSADHD in a three-month-old female was achieved by detection of high levels of GHB in urine. Sequence analysis of ALDH5A1 gene showed that the patient was a compound heterozygote for c.1226G > A (p.G409D) and the novel missense mutation, c.1498G > C (p.V500 L). By ALDH5A1 gene expression in transiently transfected HEK293 cells and enzyme activity assays, we demonstrate that the p.V500 L mutation, despite being conservative, produces complete loss of enzyme activity. In silico protein modelling analysis and evaluation of tetramer destabilizing energies suggest that structural impairment and partial occlusion of the access channel to the active site affect enzyme activity. These findings add further knowledge on the missense mutations associated with SSADHD and the molecular mechanisms underlying the loss of the enzyme activity.

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