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Πέμπτη 28 Ιουνίου 2018

The correct use of noninferiority trials

With great interest, we read the report by Paniagua et al that 2 doses of dexamethasone were noninferior to a 5-day course of prednisone to treat children of asthma exacerbation.1 They conducted a randomized noninferiority controlled trial comparing the scores for persistent symptoms and quality of life at day 7 of illness.

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Skin-to-skin care cannot be blamed for increase in suffocation deaths

We read with interest the report by Bass et al1; however, we believe the data presented are insufficient to support the authors' conclusions that an increase in suffocation deaths is due, in part, to skin-to-skin care (SSC) and resultant sudden unexpected perinatal collapse.

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Use of a Pediatric Syncope Unit Improves Diagnosis and Lowers Costs: A Hospital-Based Experience

To assess the effect of a dedicated pediatric syncope unit on the diagnostic and therapeutic management of children with suspected syncope. We also evaluated the effectiveness of the pediatric syncope unit model in decreasing unnecessary tests and hospitalizations, minimizing social costs, and improving diagnostic yield.

https://ift.tt/2KuvHku

Oxygen Treatment for Immature Infants beyond the Delivery Room: Lessons from Randomized Studies

Without supplemental oxygen, extremely preterm infants often have low arterial oxygen tension (PaO2) or arterial oxygen saturation (SaO2) compared with older children. Until recently, oxygen was administered to these infants in the early weeks after birth, with little evidence to balance the risks and benefits. Five large randomized controlled trials of lower (85%-89%) vs higher (91%-95%) pulse oximeter saturation (SpO2) targets with masking of group allocation now provide high quality evidence to guide practice and serve as a baseline for future research.

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Reply

We appreciate the opportunity to respond to the comments of Drs Bartick and Feldman-Winter concerning our recent publication on trends in newborn sudden unexpected infant deaths (SUID). They state that we concluded "an increase in suffocation deaths is due in part to skin-to-skin care (SSC) and resultant sudden unexpected postnatal collapse (SUPC)." We actually noted that the decrease in SUID that occurred in the postneonatal period before 2002 did not occur in neonates and that SUPC may have contributed to that outcome.

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Spuriously Low Serum Bicarbonate Levels in Patients With Hyperlipidemia: A Report of 4 Cases

Four patients were recently seen at our institution presenting with severe hypobicarbonatemia and elevated anion gap on serum specimens processed by an autoanalyzer using enzymatic reactions. Arterial blood gas values in each case revealed no significant acid-base disturbance and a marked discordance between arterial blood gas calculated bicarbonate levels and those reported on the basic metabolic panel. All patients had profound hyperlipidemia (triglycerides > 3,500mg/L), and ultracentrifugation of one patient's serum corrected the discordance.

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Development and evaluation of percentile distribution of body weight by gestational week as a tool for gestational weight management: a retrospective study based on hospital routine data

Objectives

This study aimed to construct and validate smoothed gestational weight centile curves based on preconception weight status for Chinese pregnant women.

Design

A retrospective study based on hospital routine data

Setting

Hospital prenatal care.

Population

A cohort of pregnant Chinese women with preconception and gestational body weights without maternal or neonatal complications (sample 1, n=2992), and a non-selective independent sample (sample 2, n=7420), were selected from hospital routine data for curve construction and validation.

Study design

Smoothed body weight centile curves for each gestational week were constructed using the LMS method in sample 1. Validation in sample 2 included analysis of agreement between predicted weight at the 38th week and observed values using the Bland–Altman Index. Predictions were also compared with international curves.

Results

Smoothed centile curves of gestational weight for the three preconception body mass index groups showed a similar non-linear increasing trend. The differences between predicted body weights and observed values were 0.66±1.58 kg, 0.14±1.61 kg and –0.54±2.06 kg in the underweight, normal weight and overweight groups, respectively. Bland-Altman Index values were 5.2%, 5.6% and 4.7% in the underweight, normal weight and overweight groups, respectively, with limits of agreement of –2.4~3.8 kg, –3.0~3.3 kg and –4.4~3.4 kg, respectively. These limits of agreement were narrower than those of available international curves.

Conclusion

Body weight percentiles for gestational weeks 0–42 were proposed for underweight, normal weight or overweight Chinese women. These curves could constitute a useful tool for individualised gestational weight management by predicting body weight at a later gestation phase.



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Continuity of care with doctors--a matter of life and death? A systematic review of continuity of care and mortality

Objective

Continuity of care is a long-standing feature of healthcare, especially of general practice. It is associated with increased patient satisfaction, increased take-up of health promotion, greater adherence to medical advice and decreased use of hospital services. This review aims to examine whether there is a relationship between the receipt of continuity of doctor care and mortality.

Design

Systematic review without meta-analysis.

Data sources

MEDLINE, Embase and the Web of Science, from 1996 to 2017.

Eligibility criteria for selecting studies

Peer-reviewed primary research articles, published in English which reported measured continuity of care received by patients from any kind of doctor, in any setting, in any country, related to measured mortality of those patients.

Results

Of the 726 articles identified in searches, 22 fulfilled the eligibility criteria. The studies were all cohort or cross-sectional and most adjusted for multiple potential confounding factors. These studies came from nine countries with very different cultures and health systems. We found such heterogeneity of continuity and mortality measurement methods and time frames that it was not possible to combine the results of studies. However, 18 (81.8%) high-quality studies reported statistically significant reductions in mortality, with increased continuity of care. 16 of these were with all-cause mortality. Three others showed no association and one demonstrated mixed results. These significant protective effects occurred with both generalist and specialist doctors.

Conclusions

This first systematic review reveals that increased continuity of care by doctors is associated with lower mortality rates. Although all the evidence is observational, patients across cultural boundaries appear to benefit from continuity of care with both generalist and specialist doctors. Many of these articles called for continuity to be given a higher priority in healthcare planning. Despite substantial, successive, technical advances in medicine, interpersonal factors remain important.

PROSPERO registration number

CRD42016042091.



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Correction: Experiences of older people dying in nursing homes: a narrative systematic review of qualitative studies

Greenwood N, Menzies-Gow E, Nilsson D, et al. Experiences of older people dying in nursing homes: a narrative systematic review of qualitative studies. BMJ Open 2018; 8(6):e021285. doi: 10.1136/bmjopen-2017-021285.

There is an error in the references. Reference number 17 is cited as:

Fleming J, Farquhar M, Brayne C, et al. Death and the oldest old: attitudes and preferences for end-of-life care--Qualitative research within a population-based cohort study. PLoS One 2016;11:e0150686. doi:10.1371/journal.pone.0150686

However, the correct reference is:

Fleming J, Calloway R, Perrels A, et al. Dying comfortably in very old age with or without dementia in different care settings – a representative "older old" population study. BMC Geriatr 201717:222. doi:10.1186/s12877-017-0605-2



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De novo variants in GABRA2 and GABRA5 alter receptor function and contribute to early-onset epilepsy

Abstract
GABAA receptors are ligand-gated anion channels that are important regulators of neuronal inhibition. Mutations in several genes encoding receptor subunits have been identified in patients with various types of epilepsy, ranging from mild febrile seizures to severe epileptic encephalopathy. Using whole-genome sequencing, we identified a novel de novo missense variant in GABRA5 (c.880G > C, p.V294L) in a patient with severe early-onset epilepsy and developmental delay. Targeted resequencing of 279 additional epilepsy patients identified 19 rare variants from nine GABAA receptor genes, including a novel de novo missense variant in GABRA2 (c.875C > A, p.T292K) and a recurrent missense variant in GABRB3 (c.902C > T, p.P301L). Patients with the GABRA2 and GABRB3 variants also presented with severe epilepsy and developmental delay. We evaluated the effects of the GABRA5, GABRA2 and GABRB3 missense variants on receptor function using whole-cell patch-clamp recordings from human embryonic kidney 293T cells expressing appropriate α, β and γ subunits. The GABRA5 p.V294L variant produced receptors that were 10-times more sensitive to GABA but had reduced maximal GABA-evoked current due to increased receptor desensitization. The GABRA2 p.T292K variant reduced channel expression and produced mutant channels that were tonically open, even in the absence of GABA. Receptors containing the GABRB3 p.P301L variant were less sensitive to GABA and produced less GABA-evoked current. These results provide the first functional evidence that de novo variants in the GABRA5 and GABRA2 genes contribute to early-onset epilepsy and developmental delay, and demonstrate that epilepsy can result from reduced neuronal inhibition via a wide range of alterations in GABAA receptor function.

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CHP1 reduction ameliorates spinal muscular atrophy pathology by restoring calcineurin activity and endocytosis

Abstract
Autosomal recessive spinal muscular atrophy (SMA), the leading genetic cause of infant lethality, is caused by homozygous loss of the survival motor neuron 1 (SMN1) gene. SMA disease severity inversely correlates with the number of SMN2 copies, which in contrast to SMN1, mainly produce aberrantly spliced transcripts. Recently, the first SMA therapy based on antisense oligonucleotides correcting SMN2 splicing, namely SPINRAZATM, has been approved. Nevertheless, in type I SMA-affected individuals—representing 60% of SMA patients—the elevated SMN level may still be insufficient to restore motor neuron function lifelong. Plastin 3 (PLS3) and neurocalcin delta (NCALD) are two SMN-independent protective modifiers identified in humans and proved to be effective across various SMA animal models. Both PLS3 overexpression and NCALD downregulation protect against SMA by restoring impaired endocytosis; however, the exact mechanism of this protection is largely unknown. Here, we identified calcineurin-like EF-hand protein 1 (CHP1) as a novel PLS3 interacting protein using a yeast-two-hybrid screen. Co-immunoprecipitation and pull-down assays confirmed a direct interaction between CHP1 and PLS3. Although CHP1 is ubiquitously present, it is particularly abundant in the central nervous system and at SMA-relevant sites including motor neuron growth cones and neuromuscular junctions. Strikingly, we found elevated CHP1 levels in SMA mice. Congruently, CHP1 downregulation restored impaired axonal growth in Smn-depleted NSC34 motor neuron-like cells, SMA zebrafish and primary murine SMA motor neurons. Most importantly, subcutaneous injection of low-dose SMN antisense oligonucleotide in pre-symptomatic mice doubled the survival rate of severely-affected SMA mice, while additional CHP1 reduction by genetic modification prolonged survival further by 1.6-fold. Moreover, CHP1 reduction further ameliorated SMA disease hallmarks including electrophysiological defects, smaller neuromuscular junction size, impaired maturity of neuromuscular junctions and smaller muscle fibre size compared to low-dose SMN antisense oligonucleotide alone. In NSC34 cells, Chp1 knockdown tripled macropinocytosis whereas clathrin-mediated endocytosis remained unaffected. Importantly, Chp1 knockdown restored macropinocytosis in Smn-depleted cells by elevating calcineurin phosphatase activity. CHP1 is an inhibitor of calcineurin, which collectively dephosphorylates proteins involved in endocytosis, and is therefore crucial in synaptic vesicle endocytosis. Indeed, we found marked hyperphosphorylation of dynamin 1 in SMA motor neurons, which was restored to control level by the heterozygous Chp1 mutant allele. Taken together, we show that CHP1 is a novel SMA modifier that directly interacts with PLS3, and that CHP1 reduction ameliorates SMA pathology by counteracting impaired endocytosis. Most importantly, we demonstrate that CHP1 reduction is a promising SMN-independent therapeutic target for a combinatorial SMA therapy.

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RAD Sequencing and a Hybrid Antarctic Fur Seal Genome Assembly Reveal Rapidly Decaying Linkage Disequilibrium, Global Population Structure and Evidence for Inbreeding

Recent advances in high throughput sequencing have transformed the study of wild organisms by facilitating the generation of high quality genome assemblies and dense genetic marker datasets. These resources have the potential to significantly advance our understanding of diverse phenomena at the level of species, populations and individuals, ranging from patterns of synteny through rates of linkage disequilibrium (LD) decay and population structure to individual inbreeding. Consequently, we used PacBio sequencing to refine an existing Antarctic fur seal (Arctocephalus gazella) genome assembly and genotyped 83 individuals from six populations using restriction site associated DNA (RAD) sequencing. The resulting hybrid genome comprised 6,169 scaffolds with an N50 of 6.21 Mb and provided clear evidence for the conservation of large chromosomal segments between the fur seal and dog (Canis lupus familiaris). Focusing on the most extensively sampled population of South Georgia, we found that LD decayed rapidly, reaching the background level by around 400 kb, consistent with other vertebrates but at odds with the notion that fur seals experienced a strong historical bottleneck. We also found evidence for population structuring, with four main Antarctic island groups being resolved. Finally, appreciable variance in individual inbreeding could be detected, reflecting the strong polygyny and site fidelity of the species. Overall, our study contributes important resources for future genomic studies of fur seals and other pinnipeds while also providing a clear example of how high throughput sequencing can generate diverse biological insights at multiple levels of organisation.



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Genetic Analysis of Signal Generation by the Rgt2 Glucose Sensor of Saccharomyces cerevisiae

The yeast S. cerevisiae senses glucose through Snf3 and Rgt2, transmembrane proteins that generate an intracellular signal in response to glucose that leads to inhibition of the Rgt1 transcriptional repressor and consequently to derepression of HXT genes encoding glucose transporters. Snf3 and Rgt2 are thought to be glucose receptors because they are similar to glucose transporters. In contrast to glucose transporters, they have unusually long C-terminal tails that bind to Mth1 and Std1, paralogous proteins that regulate function of the Rgt1 transcription factor. We show that the C-terminal tail of Rgt2 is not responsible for its inability to transport glucose. To gain insight into how the glucose sensors generate an intracellular signal, we identified RGT2 mutations that cause constitutive signal generation. Most of the mutations alter evolutionarily-conserved amino acids in the transmembrane spanning regions of Rgt2 that are predicted to be involved in maintaining an outward-facing conformation or to be in the substrate binding site. Our analysis of these mutations suggests they cause Rgt2 to adopt inward-facing or occluded conformations that generate the glucose signal. These results support the idea that Rgt2 and Snf3 are glucose receptors that signal in response to binding of extracellular glucose and inform the basis of their signaling.



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High Serum Fractalkine is Associated with Lower Trabecular Bone Score in Premenopausal Women with Graves’ Disease

Horm Metab Res
DOI: 10.1055/a-0633-2814

Chemokine CX3CL1 (fractalkine) may be an important factor linking thyroid status and bone remodeling, through tetrac, a derivative of thyroxine. This study explores the relationship between serum fractalkine levels and parameters of thyroid status and bone in premenopausal women with Graves' disease (GD) in comparison to healthy controls. This cross-sectional study included three premenopausal female groups: active GD; cured GD, and healthy age-, gender-, and BMI-matched controls. Measurement of serum fractalkine levels (Quantikine® ELISA), total amino-terminal peptide of procollagen type 1 (P1NP), CTx, thyroid hormones, BMD and trabecular bone score (TBS) were performed in all study subjects. Sixty women (21, 16, and 23 in active GD, cured GD, and healthy control groups, respectively) were included. Serum fractalkine levels were higher (p<0.05) in active and cured GD subjects compared to healthy controls (mean 0.7±0.14; 0.93±0.15, and 0.48±0.13 ng/ml, respectively). Lumbar spine BMD was lowest in the cured GD group in comparison to active GD and control group subjects (0.926±0.03; 1.016±0.03; 1.051±0.03 g/cm2; p<0.05, respectively). TBS was lower (p<0.05) in both GD groups than controls being lowest in those with active GD (1.395±0.02; 1.402±0.02, 1.469±0.02, respectively). Serum fractalkine concentration was positively correlated with fT4, and negatively correlated with TBS values. GD in pre-menopausal females is associated with increased serum fractalkine concentration and decreased TBS. Fractalkine may be a currently unappreciated link between hyperthyroidism and bone; further research into this possibility is needed.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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Penicillin Allergy Linked to MRSA, C. Difficile Risk

THURSDAY, June 28, 2018 -- There is a correlation for documented penicillin allergy with increased risk of methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile, which is mediated by increased use of β-lactam alternative...

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New Rules May Constrain Docs' Ability to Treat Chronic Pain

THURSDAY, June 28, 2018 -- New laws and regulations designed to limit the use of prescription narcotics may further constrain doctors' ability to treat patients, according to an article published online May 30 in Medical Economics. Physicians and...

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Nurse Preceptors Must Balance Teaching, Patient Care

THURSDAY, June 28, 2018 -- Caring for deteriorating patients while precepting novice nurses requires a balancing of teaching and patient care roles, according to a study published online June 19 in the Journal of Clinical Nursing. Carol Della Ratta,...

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Variation in Quality of Trials for Atrial Fibrillation, Flutter

THURSDAY, June 28, 2018 -- The quality of atrial fibrillation/atrial flutter (AF/AFL) trials is variable, and trials often rely on recurrence as the primary endpoint, according to a review published online June 27 in JACC: Clinical...

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FDA Approves Continuous Glucose Monitoring System

THURSDAY, June 28, 2018 -- The Eversense Continuous Glucose Monitoring (CGM) system, which has a fully implantable sensor to detect glucose, has been approved by the U.S. Food and Drug Administration for use in people age 18 years and older with...

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Molecular Profiling of Pancreatic Cancer Patients: Initial Results from the Know Your Tumor Initiative

Purpose: To broaden access to and implementation of precision medicine in the care of pancreatic cancer patients, the Know Your Tumor (KYT) program was initiated using a turn-key precision medicine system. Patients undergo commercially available multi-omic profiling to determine molecularly rationalized clinical trials and off-label therapies. Experimental Design: Tumor samples were obtained for 640 patients from 287 academic and community practices covering 44 states. CAP/CLIA-accredited laboratories were used for genomic, proteomic and phosphoprotein-based molecular profiling. Results: Tumor samples were adequate for next-generation sequencing in 96% and immunohistochemistry in 91% of patients. A tumor board reviewed the results for every patient and found actionable genomic alterations in 50% of patients (with 27% highly actionable) and actionable proteomic alterations (excluding chemopredictive markers) in 5%. Actionable alterations commonly found were in DNA repair genes (BRCA1/2 or ATM mutations, 8.4%) and cell cycle genes (CCND1/2/3 or CDK4/6 alterations, 8.1%). A subset of samples was assessed for actionable phosphoprotein markers. Among patients with highly actionable biomarkers, those who received matched therapy (n=17) had a significantly longer median progression-free survival (PFS) than those who received unmatched therapy (n=18; PFS = 4.1 vs. 1.9 months; HR: 0.47; 95% CI: 0.24-0.94; adjusted P-value = 0.03). Conclusions: A comprehensive precision medicine system can be implemented in community and academic settings, with highly actionable findings observed in over 25% of pancreatic cancers. Patients whose tumors have highly actionable alterations and receive matched therapy demonstrated significantly increased PFS. Our findings support further prospective evaluation of precision oncology in pancreatic cancer.



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STAG2 Is a Biomarker for Prediction of Recurrence and Progression in Papillary Non-Muscle-Invasive Bladder Cancer

Purpose: Most bladder cancers are early-stage tumors known as papillary non–muscle-invasive bladder cancer (NMIBC). After resection, up to 70% of NMIBCs recur locally, and up to 20% of these recurrences progress to muscle invasion. There is an unmet need for additional biomarkers for stratifying tumors based on their risk of recurrence and progression. We previously identified STAG2 as among the most commonly mutated genes in NMIBC and provided initial evidence in a pilot cohort that STAG2-mutant tumors recurred less frequently than STAG2 wild-type tumors. Here, we report a STAG2 biomarker validation study using two independent cohorts of clinically annotated papillary NMIBC tumors from the United States and Europe.

Experimental Design: The value of STAG2 immunostaining for prediction of recurrence was initially evaluated in a cohort of 82 patients with papillary NMIBC ("Georgetown cohort"). Next, the value of STAG2 immunostaining for prediction of progression to muscle invasion was evaluated in a progressor-enriched cohort of 253 patients with papillary NMIBC ("Aarhus cohort").

Results: In the Georgetown cohort, 52% of NMIBC tumors with intact STAG2 expression recurred, whereas 25% of STAG2-deficient tumors recurred (P = 0.02). Multivariable analysis identified intact STAG2 expression as an independent predictor of recurrence (HR = 2.4; P = 0.05). In the progressor-enriched Aarhus cohort, 38% of tumors with intact STAG2 expression progressed within 5 years, versus 16% of STAG2-deficient tumors (P < 0.01). Multivariable analysis identified intact STAG2 expression as an independent predictor of progression (HR = 1.86; P = 0.05).

Conclusions: STAG2 IHC is a simple, binary, new assay for risk stratification in papillary NMIBC. Clin Cancer Res; 1–9. ©2018 AACR.



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Prevalence of needle stick injury and its associated factors among nurses working in public hospitals of Dessie town, Northeast Ethiopia, 2016

Nurses are exposed to dangerous and deadly blood borne pathogens through contaminated needle stick injuries. This study was designed to assess prevalence of needle stick injury and its associated factors among...

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Identification of cyclic hexapeptides natural products with inhibitory potency against Mycobacterium tuberculosis

Our aim was to identify natural products with anti-tubercular activity.

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Second month sputum smear as a predictor of tuberculosis treatment outcomes in Brazil

The value of sputum smear microscopy (SSM) after 2 months of treatment in the management of pulmonary tuberculosis is controversial. We analysed second month-SSM conversion as a predictor of treatment success ...

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Tuberculosis co-infection and its associated factors among People living with HIV/AIDS attending antiretroviral therapy clinic in southern Ethiopia: a facility based retrospective study

The study aimed to determine the prevalence and identify determinants of TB among People living with HIV/AIDS (PLWHAs) through reviewing and analyzing patient case files from the anti-retro viral treatment (AR...

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Chondroid lipoma of the neck: a case report

Chondroid lipoma, first described in 1993 by Meis and Enzinger, is a very rare lipomatous tumor. Because it is a benign tumor, it does not require radiotherapy, chemotherapy, or extensive resection. However, h...

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Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012

Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012

Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012, Published online: 29 June 2018; doi:10.1038/s41416-018-0131-9

Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012

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Integrative analysis of oncogenic fusion genes and their functional impact in colorectal cancer

Integrative analysis of oncogenic fusion genes and their functional impact in colorectal cancer

Integrative analysis of oncogenic fusion genes and their functional impact in colorectal cancer, Published online: 29 June 2018; doi:10.1038/s41416-018-0153-3

Integrative analysis of oncogenic fusion genes and their functional impact in colorectal cancer

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A randomised phase II study of second-line XELIRI regimen versus irinotecan monotherapy in advanced biliary tract cancer patients progressed on gemcitabine and cisplatin

A randomised phase II study of second-line XELIRI regimen versus irinotecan monotherapy in advanced biliary tract cancer patients progressed on gemcitabine and cisplatin

A randomised phase II study of second-line XELIRI regimen versus irinotecan monotherapy in advanced biliary tract cancer patients progressed on gemcitabine and cisplatin, Published online: 29 June 2018; doi:10.1038/s41416-018-0138-2

A randomised phase II study of second-line XELIRI regimen versus irinotecan monotherapy in advanced biliary tract cancer patients progressed on gemcitabine and cisplatin

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Characterisation of tumour microvessel density during progression of high-grade serous ovarian cancer: clinico-pathological impact (an OCTIPS Consortium study).

Characterisation of tumour microvessel density during progression of high-grade serous ovarian cancer: clinico-pathological impact (an OCTIPS Consortium study).

Characterisation of tumour microvessel density during progression of high-grade serous ovarian cancer: clinico-pathological impact (an OCTIPS Consortium study)., Published online: 29 June 2018; doi:10.1038/s41416-018-0157-z

Characterisation of tumour microvessel density during progression of high-grade serous ovarian cancer: clinico-pathological impact (an OCTIPS Consortium study).

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Prophylactic Hypogastric Artery Ligation during Placenta Percreta Surgery: A Retrospective Cohort Study

AJP Rep 2018; 08: e142-e145
DOI: 10.1055/s-0038-1666793

Objective To evaluate if prophylactic hypogastric artery ligation (HAL) decreases surgical blood loss and blood products transfused. Study Design This is a retrospective cohort study comparing patients with placenta percreta undergoing prophylactic HAL at the time of cesarean hysterectomy versus those who did not. Data were presented as means ± standard deviations, proportions, or medians with interquartile ranges. Demographic and clinical data were compared in the groups using Student's t-test for normally distributed data or the Mann–Whitney U test for nonnormally distributed data. Fisher's exact test was used for proportions and categorical variables. Data are reported as significant where p was <0.05. Results There were 26 patients included in the control group with no HAL and 11 patients included in the study group. Estimated blood loss for the study group was 1,000 mL versus 800 mL in the control. Units of PRCBs transfused were 4.5 units in the study group versus 2 units for the control group. None of these measures were found to be statistically significant. Conclusion Our data suggest there was no benefit in the use of prophylactic HAL in decreasing surgical blood loss or amount of blood products transfused in patients who had a cesarean hysterectomy performed for placenta percreta. Précis Prophylactic HAL does not decrease blood loss during surgery for placenta percreta.
[...]

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Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text



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Microcirculatory Impairment Is Associated With Multiple Organ Dysfunction Following Traumatic Hemorrhagic Shock: The MICROSHOCK Study

Objectives: To assess the relationship between microcirculatory perfusion and multiple organ dysfunction syndrome in patients following traumatic hemorrhagic shock. Design: Multicenter prospective longitudinal observational study. Setting: Three U.K. major trauma centers. Patients: Fifty-eight intubated and ventilated patients with traumatic hemorrhagic shock. Interventions: Sublingual incident dark field microscopy was performed within 12 hours of ICU admission (D0) and repeated 24 and 48 hours later. Cardiac output was assessed using oesophageal Doppler. Multiple organ dysfunction syndrome was defined as Serial Organ Failure Assessment score greater than or equal to 6 at day 7 post injury. Measurements and Main Results: Data from 58 patients were analyzed. Patients had a mean age of 43 ± 19 years, Injury Severity Score of 29 ± 14, and initial lactate of 7.3 ± 6.1 mmol/L and received 6 U (interquartile range, 4–11 U) of packed RBCs during initial resuscitation. Compared with patients without multiple organ dysfunction syndrome at day 7, patients with multiple organ dysfunction syndrome had lower D0 perfused vessel density (11.2 ± 1.8 and 8.6 ± 1.8 mm/mm2; p

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Evaluation of Effect of Probiotics on Cytokine Levels in Critically Ill Children With Severe Sepsis: A Double-Blind, Placebo-Controlled Trial

Objectives: To evaluate the effect of probiotics on cytokines in children with severe sepsis. Design: Randomized, double-blind, placebo-controlled trial. Setting: ICU of a tertiary care teaching hospital in North India. Patients: Children 3 months to 12 years old with severe sepsis. Interventions: Enrolled children were randomized to probiotic (n = 50) and placebo (n = 50) groups. Probiotic group received VSL#3 (VSL Pharmaceuticals, Towson, MD) (Lactobacillus paracasei, L. plantarum, L. acidophilus, L. delbrueckii, Bifidobacterium longum, B. breve, B. infantis, Streptococcus salivarius; maltose; and silicon dioxide), and placebo group received maltose and silicon dioxide. Dose was 1 sachet twice daily for 7 days. Blood was collected on days 1 and 7 for estimation of interleukin-6, interleukin-12p70, interleukin-17, tumor necrosis factor-α, interleukin-10, and transforming growth factor -β1. "Primary outcome": Change in cytokine levels in probiotic and placebo groups from day 1 to 7. "Secondary outcomes": Sequential Organ Failure Assessment score, healthcare-associated infections, ICU stay, and mortality. Measurements and Main Results: On day 7, probiotic group had significantly lower levels of proinflammatory cytokines (interleukin-6 [80 vs 186 pg/mL, p = 0.001]; interleukin-12p70 [44 vs 79 pg/mL, p = 0.001]; interleukin-17 [217 vs 293 pg/mL, p = 0.01]; and tumor necrosis factor-α [192 vs 348 pg/mL, p = 0.01]) and higher levels of antiinflammatory cytokines (interleukin-10 [320 vs 240 pg/mL, p = 0.02] and TGF-β1 [311 vs 221 ng/mL, p = 0.01]) than placebo group. From day 1 to 7, probiotic group showed significant decrease in proinflammatory cytokines (interleukin-6 [196–80 pg/mL, p = 0.001]; interleukin-12p70 [71–44 pg/mL, p = 0.01]; interleukin-17 [258–217 pg/mL, p = 0.01]; and tumor necrosis factor-α [347–192 pg/mL, p = 0.001]) and increase in antiinflammatory cytokines (interleukin-10 [198–320 pg/mL, p = 0.001] and TGF-β1 [216–311 ng/mL, p = 0.001]) as compared to placebo group. Sequential Organ Failure Assessment score on day 7 was significantly less in probiotic group (1 vs 3). There was a nonsignificant trend toward lower incidence of HCAIs (14% vs 20%) and duration of ICU stay (6.5 vs 9 d) in probiotic group. Mortality was similar in two groups. Conclusions: Probiotics supplementation for 7 days resulted in significant decrease in proinflammatory and increase in antiinflammatory cytokines in children with severe sepsis. This work was performed at Department of Pediatrics, Advanced Pediatrics Centre, Department of Immunopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by Department of Pediatrics for buying enzyme-linked immunosorbent assay kits of cytokines. There was no relation between authors or the institution with VSL pharmaceuticals except the fact that VSL pharmaceuticals provided probiotics and placebo packed in identical sachets. Dr. Angurana received other support and assistance from departmental funds. Dr. Bansal disclosed that the drug and placebo used in this study were provided by the company. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Arun Bansal, MD, MAMS, FCCM, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India 160012. E-mail: drarunbansal@gmail.com Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2ICmXUb

Use of a Novel, Electronic Health Record–Centered, Interprofessional ICU Rounding Simulation to Understand Latent Safety Issues

Objectives: The electronic health record is a primary source of information for all professional groups participating in ICU rounds. We previously demonstrated that, individually, all professional groups involved in rounds have significant blind spots in recognition of patient safety issues in the electronic health record. However, it is unclear how team dynamics impacts identification and verbalization of viewed data. Therefore, we created an ICU rounding simulation to assess how the interprofessional team recognized and reported data and its impact on decision-making. Design: Each member of the ICU team reviewed a simulated ICU chart in the electronic health record which contained embedded patient safety issues. The team conducted simulated rounds according to the ICU's existing rounding script and was assessed for recognition of safety issues. Setting: Academic medical center. Subjects: ICU residents, nurses, and pharmacists. Intervention: None. Measurements and Main Results: Twenty-eight teams recognized 68.6% of safety issues with only 50% teams having the primary diagnosis in their differential. Individually, interns, nurses, and pharmacists recognized 30.4%, 15.6%, and 19.6% of safety items, respectively. However, there was a negative correlation between the intern's performance and the nurse's or the pharmacist's performance within a given team. The wide variance in recognition of data resulted in wide variance in orders. Overall, there were 21.8 orders requested and 21.6 orders placed per case resulting in 3.6 order entry inconsistencies/case. Between the two cases, there were 145 distinct orders place with 43% being unique to a specific team and only 2% placed by all teams. Conclusions: Although significant blind spots exist in the interprofessional team's ability to recognize safety issues in the electronic health record, the inclusion of other professional groups does serve as a partial safety net to improve recognition. Electronic health record–based, ICU rounding simulations can serve as a test-bed for innovations in ICU rounding structure and data collection. This work was performed at Oregon Health and Science University, Portland, OR. Supported, in part, by Agency for Healthcare Research and Quality R01HS023793. Drs. Bordley's, McGrath's, Nguyen's, and Gold's institutions received funding from the Agency for Healthcare Research and Quality (AHRQ) and American Association of Medical Colleges (AAMC) and Donaghue Foundation. Drs. Bordley and McGrath received support for article research from the AHRQ and AAMC. Drs. Mulanax's and Mohan's institutions received funding from AAMC and AHRQ r01HS23793. Dr. Gold received support for article research from the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: goldje@ohsu.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2tDxz0F

Survival of Patients With Vancomycin-Resistant Enterococcus faecium Bacteremia Treated With Conventional or High Doses of Daptomycin or Linezolid Is Associated With the Rate of Bacterial Clearance

Objectives: Vancomycin-resistant enterococci are important pathogens for healthcare-associated infections. Although linezolid is bacteriostatic and daptomycin is rapidly bactericidal against vancomycin-resistant enterococci in vitro, it is not clear whether they differ in their effect on bacterial clearance in patients with vancomycin-resistant enterococci bloodstream infections. Design: Prospective observational study. Setting: Two university hospitals and research laboratory. Patients: Patients with vancomycin-resistant enterococci bloodstream infection proven by blood cultures were prospectively enrolled from January 2010 to July 2015. Interventions: Sequential blood samples were collected. Real-time quantitative polymerase chain reaction was used to monitor bacterial loads. Measurements and Main Results: One hundred eight patients with vancomycin-resistant enterococci bloodstream infection were enrolled. Quantitative polymerase chain reaction assays were performed on 465 blood isolates. We found this method to be closely correlated with colony-forming units and more sensitive than culture. Sixty-three patients (58.3%) received "conventional dose" daptomycin (6–9 mg/kg), 15 (13.9%) received high-dose daptomycin (≥ 9 mg/kg), and 30 (27.8%) were treated with linezolid (600 mg every 12 hr) as sole agents. The initial mean bacterial load was 1.03 log10 copies/mL and unrelated to survival. Survivors had a more rapid early bacterial clearance than nonsurvivors (Δ log10 copies/mL/d; –0.16 vs 0.31; p = 0.02). Multivariable logistic regression showed that a slower early bacterial clearance independently predicted increased mortality (odds ratio, 3.21; 95% CI, 1.03–10.02; p = 0.045). Conventional dose daptomycin was associated with a significantly slower rate of bacterial clearance than high-dose daptomycin (Δ log10 copies/mL/d; –0.04 vs –0.41; p

https://ift.tt/2IxtgbL

Cerebral Concussion Primes the Lungs for Subsequent Neutrophil-Mediated Injury

Objectives: Mild traumatic brain injury in the form of concussion is extremely common, and the potential effects on pulmonary priming have been underestimated. The aim of this study was to characterize the pulmonary response following mild traumatic brain injury and assess the pulmonary susceptibility to lung injury after a subsequent innocuous pulmonary insult. Design: Experimental in vivo study. Setting: University research laboratory. Subjects: Male CD1 mice. Interventions: We developed a model of concussive traumatic brain injury in mice followed by pulmonary acid microaspiration. To assess the dependent role of neutrophils in mediating pulmonary injury, we specifically depleted neutrophils. Measurements and Main Results: Lateral fluid percussion to the brain resulted in neuronal damage and neutrophil infiltration as well as extensive pulmonary interstitial neutrophil accumulation but no alveolar injury. Following subsequent innocuous acid microaspiration, augmented alveolar neutrophil influx led to the development of pulmonary hemorrhage that was reduced following neutrophil depletion. Conclusions: This model shows for the first time that innocuous acid microaspiration is sufficient to induce neutrophil-mediated lung injury following mild concussion and that the extracranial effects of mild traumatic brain injury have been underestimated. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Drs. Andrews, Rhodes, and Dhaliwal conceived the project. Drs. Humphries, Rhodes, and Dhaliwal designed the experiments. Dr. Humphries, Dr. O'Neill, and Ms. Scholefield performed experiments. Drs. Dorward and Rhodes provided methods. Drs. Mackinnon, Rossi, Haslett, Andrews, and Rhodes provided guidance and edited the article. Drs. Humphries and Dhaliwal wrote the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported mainly by a U.K. Medical Research Council (MRC) PhD Studentship to Dr. Humphries. Also supported by the MRC (MR/K013386/1 [Drs. Rossi and Haslett]) and the Wellcome Trust WT096497 (Dr. Dorward). Dr. Dorward received support for article research from Wellcome Trust/Charity Open Access Fund. Drs. Humphries and Haslett received support for article research from Research Councils UK (RCUK). Dr. Dorward's institution received funding from Wellcome Trust. Dr. Haslett's institution received funding from Medical Research Council studentship. Drs. Haslett and Dhaliwal received funding from Edinburgh Molecular Imaging. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Duncan C. Humphries or Kevin Dhaliwal, MRC Centre for Inflammation Research, University of Edinburgh, 47 Little France Crescent, Edinburgh, United Kingdom. E-mail: Duncan.Humphries@ed.ac.uk; Kev.Dhaliwal@ed.ac.uk Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2N7L3tC

Diabetes and Glucose Dysregulation and Transition to Delirium in ICU Patients

Objectives: To investigate whether diabetes and glucose dysregulation (hyperglycemia and/or hypoglycemia) are associated with ICU delirium. Design: Prospective cohort study. Setting: Thirty-two–bed mixed intensive care in a tertiary care center. Patients: Critically ill patients admitted to the ICU with transitions of mental status from awake and nondelirious to delirious or remaining awake and nondelirious on the next day. Patients admitted because of a neurologic illness were excluded. Interventions: None. Measurements and Main Results: The study population consisted of 2,745 patients with 1,720 transitions from awake and nondelirious to delirious and 11,421 nontransitions remaining awake and nondelirious. Generalized mixed effects models with logit link function were performed to study the association between diabetes mellitus, glucose dysregulation, and delirium, adjusting for potential confounders. Diabetes was not associated with delirium (odds ratio adjusted, 0.93; 95% CI, 0.73–1.18). In all patients, the occurrence of hyperglycemia (odds ratio adjusted, 1.35; 95% CI, 1.15–1.59) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.65; 95% CI, 1.12–2.28) compared with normoglycemia were associated with transition to delirium. Hypoglycemia was not associated with transition to delirium (odds ratio adjusted, 1.86; 95% CI, 0.73–3.71). In patients without diabetes, the occurrence of hyperglycemia (odds ratio adjusted, 1.41; 95% CI, 1.16–1.68) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.87; 95% CI, 1.07–2.89) were associated with transition to delirium. In patients with diabetes, glucose dysregulation was not associated with ICU delirium. Conclusions: Diabetes mellitus was not associated with the development of ICU delirium. For hypoglycemia, only a nonsignificant odds ratio for ICU delirium could be noted. Hyperglycemia and the occurrence of hyperglycemia and hypoglycemia on the same day were associated with ICU delirium but only in patients without diabetes. Our study supports the institution of measures to prevent glucose dysregulation in nondiabetic ICU patients and contributes to the understanding of the determinants of delirium. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: k.vankeulen@zha.nl Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2IEpywS

The Impact of Heart Rate Response During 48-Hour Rewarming Phase of Therapeutic Hypothermia on Neurologic Outcomes in Out-of-Hospital Cardiac Arrest Patients

Objectives: Bradycardia during therapeutic hypothermia has been reported to be a predictor of favorable neurologic outcomes in out-of-hospital cardiac arrests. However, bradycardia occurrence rate may be influenced by the target body temperature. During therapeutic hypothermia, as part of the normal physiologic response, heart rate decreases in the cooling phase and increases during the rewarming phase. We hypothesized that increased heart rate during the rewarming phase is another predictor of favorable neurologic outcomes. To address this hypothesis, the study aimed to examine the association between heart rate response during the rewarming phase and neurologic outcomes in patients having return of spontaneous circulation after out-of-hospital cardiac arrest. Design: A secondary analysis of the Japanese Population-based Utstein style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia registry, which was a multicenter prospective cohort study. Setting: Fourteen hospitals throughout Japan. Patients: Patients suffering from out-of-hospital cardiac arrest who received therapeutic hypothermia after the return of spontaneous circulation from 2005 to 2011. Intervention: None. Measurements and Main Results: This study enrolled 452 out-of-hospital cardiac arrest patients, of which 354 were analyzed, and 80.2% survived to hospital discharge, of which 57.3% had a good neurologic outcome. Heart rate response was calculated using heart rate data recorded during therapeutic hypothermia in the abovementioned registry. Heart rate response in the rewarming phase (heart rate response-rewarming) was calculated as follows: (heart rate [post rewarming]–heart rate [pre rewarming])/heart rate (pre rewarming) × 100. The primary outcome was an unfavorable neurologic outcome at hospital discharge, that is, a Cerebral Performance Category of 3–5. Multivariable logistic regression analysis was performed to determine the association between heart rate response-rewarming and unfavorable neurologic outcomes. Multivariable logistic regression analysis showed that heart rate response-rewarming was independently associated with unfavorable outcomes (odds ratio [per 10% change], 0.86; 95% CI, 0.78–0.96; p = 0.004). Conclusions: Increased heart rate in the approximately 48-hour rewarming phase during therapeutic hypothermia was significantly associated with and was an independent predictor of favorable neurologic outcomes during out-of-hospital cardiac arrest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by Cardiovascular Disease grant H19-Shinkin-03 (a study related to the establishment of a prehospital system in acute myocardial infarction and stroke), Ministry of Health, Labour and Welfare of Japan. Dr. Tahara disclosed work for hire. Dr. Yasuga disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: hifumitoru@gmail.com Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2tCuo9k

Impact of Very Early Physical Therapy During Septic Shock on Skeletal Muscle: A Randomized Controlled Trial

Objectives: As the catabolic state induced by septic shock together with the physical inactivity of patients lead to the rapid loss of muscle mass and impaired function, the purpose of this study was to test whether an early physical therapy during the onset of septic shock regulates catabolic signals and preserves skeletal muscle mass. Design: Randomized controlled trial. Setting: Tertiary mixed ICU. Patients: Adult patients admitted for septic shock within the first 72 hours. Interventions: Patients were assigned randomly into two groups. The control group benefited from manual mobilization once a day. The intervention group had twice daily sessions of both manual mobilization and 30-minute passive/active cycling therapy. Measurements and Main Results: Skeletal muscle biopsies and electrophysiology testing were performed at day 1 and day 7. Muscle biopsies were analyzed for histology and molecular components of signaling pathways regulating protein synthesis and degradation as well as inflammation markers. Hemodynamic values and patient perception were collected during each session. Twenty-one patients were included. Three died before the second muscle biopsy. Ten patients in the control and eight in the intervention group were analyzed. Markers of the catabolic ubiquitin-proteasome pathway, muscle atrophy F-box and muscle ring finger-1 messenger RNA, were reduced at day 7 only in the intervention group, but without difference between groups (muscle atrophy F-box: –7.3% ± 138.4% in control vs –56.4% ± 37.4% in intervention group; p = 0.23 and muscle ring finger-1: –30.8% ± 66.9% in control vs –62.7% ± 45.5% in intervention group; p = 0.15). Muscle fiber cross-sectional area (µm2) was preserved by exercise (–25.8% ± 21.6% in control vs 12.4% ± 22.5% in intervention group; p = 0.005). Molecular regulations suggest that the excessive activation of autophagy due to septic shock was lower in the intervention group, without being suppressed. Markers of anabolism and inflammation were not modified by the intervention, which was well tolerated by the patients. Conclusions: Early physical therapy during the first week of septic shock is safe and preserves muscle fiber cross-sectional area. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. This work was performed at ICU, Saint Luc university hospital, Université catholique de Louvain (UCL), Brussels, Belgium. Clinical trial registered with www.clinicaltrials.gov (NCT01787045). Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by funds from the "Department of Critical Care Medicine of Saint Luc University Hospital." During study inclusions, the ICU received a lending from RECK-Technik GmbH & Co. (KG, 88422 Betzenweiler, Germany) of the motorized cycling device MOTOmed Viva2 with MOTOmed sam2 training analysis program. Drs. Hickman and Laterre disclosed that, during study inclusions, the ICU received a lending from RECK-Technik GmbH & Co. (KG, 88422 Betzenweiler, Germany) of the motorized cycling device MOTOmed Viva2 with MOTOmed sam2 training analysis program (the company RECK-Technik GmbH & Co had no role in the study design, conduction of the study, analyses, and article preparation). The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Pierre-François Laterre, MD, ICU, Department of Critical Care Medicine, Saint Luc University Hospital, Université catholique de Louvain (UCL), Avenue Hippocrate 10, 1200 Brussels, Belgium. E-mail: pierre-francois.laterre@uclouvain.be Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2Kvj0T5

Increasing Evidence-Based Interventions in Patients with Acute Infections in a Resource-Limited Setting: A Before-and-After Feasibility Trial in Gitwe, Rwanda

Objective: To evaluate whether a focused education program and implementation of a treatment bundle increases the rate of early evidence-based interventions in patients with acute infections. Design: Single-center, prospective, before-and-after feasibility trial. Setting: Emergency department of a sub-Saharan African district hospital. Patients: Patients > 28 days of life admitted to the study hospital for an acute infection. Interventions: The trial had three phases (each of four months). Interventions took place during the second (educational program followed by implementation of the treatment bundle) and third (provision of resources to implement treatment bundle) phases. Measurements and Main Results: Demographic, clinical, and laboratory data were collected at study enrollment; 24, 48, and 72 hours after hospital admission; and at discharge. A total of 1,594 patients were enrolled (pre-intervention, n = 661; intervention I, n = 531; intervention II, n = 402). The rate of early evidence-based interventions per patient during Intervention Phase I was greater than during the pre-intervention phase (74 ± 17 vs. 79 ± 15%, p

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Surviving Sepsis Campaign: Research Priorities for Sepsis and Septic Shock

Objective: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock. Design: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations. Methods: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (Supplemental Table 1, Supplemental Digital Content 2, https://ift.tt/2tDxpX7) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science. Results: The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: 1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; 2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; 3) should rapid diagnostic tests be implemented in clinical practice?; 4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; 5) what are the predictors of sepsis long-term morbidity and mortality?; and 6) what information identifies organ dysfunction? Conclusions: While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock. This article is being simultaneously published in Critical Care Medicine and Intensive Care Medicine in the August issue of both journals. Craig M. Coopersmith and Daniel De Backer are co-chairs of the committee who contributed equally to the final manuscript. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Surviving Sepsis Research Subgroup Heads: Clifford Deutschman (basic/translational science), Ricard Ferrer (administration/epidemiology), Ishaq Lat (fluids and vasoactive agents), Flavia R. Machado (post-intensive care unit), Greg S. Martin (adjunctive therapy), Ignacio Martin-Loeches (infection), Mark E. Nunnally (scoring/identification) Conflicts of Interest: Dr. DeBacker is immediate past president of the European Society of Intensive Care Medicine and has received consulting fees from Edwards Lifesciences, Fresenius Kabi, and Grifols. Dr. Deutschman is a consultant for Enlivix Therapeutix LTD. Dr. Ferrer Roca received honoraria from Toray, MSD, Pfizer and Grifols. Dr. Martin serves on a medical advisory board for Edwards Lifesciences and Grifols. Dr. Antonelli is president of the European Society of Intensive Care Medicine and received honoraria from Pfizer, Toray, Orion, and Air liquid. Dr. Evans is the current co-chair of the Surviving Sepsis Campaign guidelines committee. Dr. Kesecioglu is president-elect of the European Society of Intensive Care Medicine and has received honorarium from Xenios AG. Professor Rhodes is the current co-chair of the Surviving Sepsis Campaign guidelines committee. For information regarding this article, Email: ddebacke@ulb.ac.be Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2IEpux8

Peer Support in Critical Care: A Systematic Review

Objectives: Identifying solutions to improve recovery after critical illness is a pressing problem. We systematically evaluated studies of peer support as a potential intervention to improve recovery in critical care populations and synthesized elements important to peer support model design. Data Sources: A systematic search of Medical Literature Analysis and Retrieval System Online, Cumulative Index to Nursing and Allied Health Literature, PsychINFO, and Excertpa Medica Database was undertaken May 2017. Prospective Register of Systematic Reviews identification number: CRD42017070174. Study Selection: Two independent reviewers assessed titles and abstracts against study eligibility criteria. Studies were included where 1) patients and families had experienced critical illness and 2) patients and families had participated in a peer support intervention. Discrepancies were resolved by consensus and a third independent reviewer adjudicated as necessary. Data Extraction: Two independent reviewers assessed study quality with the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool, and data were synthesized according to the Preferred Reporting Items for Systematic Reviews guidelines and interventions summarized using the Template for Intervention Description and Replication Checklist. Data Synthesis: Two-thousand nine-hundred thirty-two studies were screened. Eight were included, comprising 192 family members and 92 patients including adults (with cardiac surgery, acute myocardial infarction, trauma), pediatrics, and neonates. The most common peer support model of the eight studies was an in-person, facilitated group for families that occurred during the patients' ICU admission. Peer support reduced psychologic morbidity and improved social support and self-efficacy in two studies; in both cases, peer support was via an individual peer-to-peer model. In the remaining studies, it was difficult to determine the outcomes of peer support as the reporting and quality of studies was low. Conclusions: Peer support appeared to reduce psychologic morbidity and increase social support. The evidence for peer support in critically ill populations is limited. There is a need for well-designed and rigorously reported research into this complex intervention. This study does not necessarily represent the views of the U.S. government or Department of Veterans Affairs. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Dr. Haines' institution received funding from the Society of Critical Care Medicine (SCCM) and Western Health, and he received funding from Western Health. Dr. Hopkins' institution received funding from Intermountain Research and Medical Foundation Grant to study family outcomes after critical illness. Dr. McPeake's institution received funding from SCCM. Dr. Quasim's institution received funding from a Health Foundation dissemination grant, Health Foundation Scaling Up grant, SCCM Thrive Grant for Peer support collaborative, and SCCM Thrive, ICU follow-up clinic collaborative. Dr. Iwashyna disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Kimberley.haines@wh.org.au Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2Kww4aI

Human–Computer Interaction in Face Matching

Cognitive Science, EarlyView.


https://ift.tt/2IAPrh6

Translating the ICAP Theory of Cognitive Engagement Into Practice

Cognitive Science, EarlyView.


https://ift.tt/2KvlJ25

“Girls Are as Good as Boys at Math” Implies That Boys Are Probably Better: A Study of Expressions of Gender Equality

Cognitive Science, EarlyView.


https://ift.tt/2IAj3ey

A 12-week evaluation of annatto tocotrienol supplementation for postmenopausal women: safety, quality of life, body composition, physical activity, and nutrient intake

Evidence suggests that tocotrienols may benefit bone health in osteopenic women. However, their safety in this population has never been investigated. This study was to evaluate the safety of a 12-week supplem...

https://ift.tt/2KkHpip

TDP-43 as a potential biomarker for amyotrophic lateral sclerosis: a systematic review and meta-analysis

Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) are incurable, progressive and fatal neurodegenerative diseases with patients variably affected clinically by motor, behavior, and cognitiv...

https://ift.tt/2KuBsvf

Autoantibodies against neuronal surface proteins in spontaneous subarachnoid and intracerebral haemorrhage

Brain autoimmunity has been reported in patients with preceding infection of the central nervous system by herpesviridae. It has been hypothesized that neuronal damage releasing antigens might trigger secondary i...

https://ift.tt/2N8Qk46

A randomised phase II study of second-line XELIRI regimen versus irinotecan monotherapy in advanced biliary tract cancer patients progressed on gemcitabine and cisplatin



https://ift.tt/2tIXova

Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012



https://ift.tt/2lEHVIY

Integrative analysis of oncogenic fusion genes and their functional impact in colorectal cancer



https://ift.tt/2tOSBIV

Characterisation of tumour microvessel density during progression of high-grade serous ovarian cancer: clinico-pathological impact (an OCTIPS Consortium study).



https://ift.tt/2lG6WUc

Vonoprazan-based triple therapy is non-inferior to susceptibility-guided proton pump inhibitor-based triple therapy for Helicobacter pylori eradication

All Helicobacter pylori-infected patients are recommended for eradication with an appropriate regimen in each geographic area. The choice of the therapy is somewhat dependent on the antimicrobial susceptibility. ...

https://ift.tt/2tBRwos

Cytomegalovirus infection and outcome in immunocompetent patients in the intensive care unit: a systematic review and meta-analysis

Cytomegalovirus (CMV) infection is common in immunocompetent patients in intensive care units (ICUs). However, whether CMV infection or CMV reactivation contributes to mortality of immunocompetent patients rem...

https://ift.tt/2yYhqYO

Bacille Calmette-Guérin (BCG) spondylitis with adjacent mycotic aortic aneurysm after intravesical BCG therapy: a case report and literature review

Although intravesical bacille Calmette-Guérin (BCG) therapy is accepted as an effective treatment for bladder cancer, serious complications may occur in rare cases. To date, only 4 cases have been reported in ...

https://ift.tt/2Nab23k

Uptake of hepatitis B vaccination and its determinants among health care workers in a tertiary health facility in Enugu, South-East, Nigeria

Hepatitis B vaccination is the most effective method of prevention for hepatitis B virus infection. It is a major public health problem in Nigeria, and health workers are at increased risk. This study determin...

https://ift.tt/2tLr4YI

New Guidelines Increase Melanoma Staging Reproducibility

THURSDAY, June 28, 2018 -- Greater reproducibility and higher concordance are seen for melanoma staging with the American Joint Committee on Cancer (AJCC) classification of cancer staging, the AJCC Cancer Staging Manual, 8th edition (AJCC 8), which...

https://ift.tt/2lCx2Ye

Combination of LABA + Inhaled Glucocorticoid Safe in Asthma

THURSDAY, June 28, 2018 -- Compared to treatment with an inhaled glucocorticoid alone, combination therapy with a long-acting β2-agonist (LABA) and an inhaled glucocorticoid is not associated with a significantly higher risk of serious...

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Health Care Technology Impacts Younger Patient Satisfaction

THURSDAY, June 28, 2018 -- Health care communication technology is a determinant of patient satisfaction in younger patients, according to a report published by Black Book Market Research LLC. Black Book collected over 57,000 viewpoints on...

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Midlife Fitness Linked to Lower Risk of Depression, CVD Death

THURSDAY, June 28, 2018 -- Midlife fitness is associated with reduced risk of depression in later life and with reductions in the risk of cardiovascular disease (CVD) mortality and CVD mortality after later-life depression, according to a study...

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USPSTF Favors Osteoporosis Screening to Prevent Fracture

THURSDAY, June 28, 2018 -- The U.S. Preventive Services Task Force (USPSTF) recommends screening for osteoporosis to prevent fractures for women aged ≥65 years and for postmenopausal women aged <65 years at increased risk of osteoporosis. These...

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Enzalutamide Improves Outcomes for Aggressive Prostate Cancer

THURSDAY, June 28, 2018 -- Enzalutamide treatment can significantly lower risk of metastasis or death in men with rapidly advancing, castration-resistant prostate cancer, according to a phase 3 study published online June 28 in the New England...

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Radiomic Model Approach for Characterizing Nodules Promising

THURSDAY, June 28, 2018 -- A radiomic low-dose computed tomography (LDCT)-based approach is promising for indeterminate screen-detected nodule characterization, according to a study published online May 14 in PLOS One. Tobias Peikert, M.D., from the...

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Genetic Risk, Lifestyle Predict CVD, Diabetes Independently

THURSDAY, June 28, 2018 -- Genetic risk and lifestyle are independent predictors of incident cardiovascular disease and diabetes, according to a study published online June 27 in JAMA Cardiology. M. Abdullah Said, from the University of Groningen in...

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FDA Approves Epidiolex for Severe Forms of Epilepsy

THURSDAY, June 28, 2018 -- The U.S. Food and Drug Administration has approved Epidiolex (cannabidiol) oral solution for treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome for patients age 2 years and older. The rare,...

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Prenatal Pediatric Visit Recommended for Expectant Families

THURSDAY, June 28, 2018 -- All expectant families should have a pediatric prenatal visit, according to a clinical report published online June 25 in Pediatrics. Michael Yogman, M.D., from Harvard Medical School in Boston, and colleagues from the...

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In Situ Measurement and Correlation of Cell Density and Light Emission of Bioluminescent Bacteria

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Bioluminescent bacteria regulate light production through a variety of mechanisms, such as quorum sensing. This novel method allows the in situ investigation of bioluminescence and the correlation of light emission to cell density. An artificial bioluminescent Escherichia coli system allows the characterization of lux operons, Lux proteins, and their interplay.

https://ift.tt/2Kuu9DG

Optogenetics Identification of a Neuronal Type with a Glass Optrode in Awake Mice

This work introduces a method to perform an optogenetic single-unit recording reliably from an awake mouse using a custom-made glass optrode.

https://ift.tt/2KqVczI

Quantitative positron emission tomography–guided magnetic resonance imaging postprocessing in magnetic resonance imaging–negative epilepsies

Epilepsia, EarlyView.


https://ift.tt/2lIqozO

Murine Oropharyngeal Aspiration Model of Ventilator-associated and Hospital-acquired Bacterial Pneumonia

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Infectious pneumonia is among the most common infections in human. An appropriate in vivo model is critical for understanding disease pathogenesis and testing the efficacy of novel therapeutics. With this murine oropharyngeal aspiration pneumonia model, one can examine the pathogenesis and new treatments against these deadly infections.

https://ift.tt/2N4kWDI

Impact of fluid challenge increase in cardiac output on the relationship between systemic and cerebral hemodynamics in severe sepsis compared to brain injury and controls

Cognitive dysfunction and delirium after ICU are frequent and may partially result from brain ischemia episodes. We hypothesized that systemic inflammation (severe sepsis or septic shock) modifies the control ...

https://ift.tt/2lDXVLg

Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions

DNA regulatory elements, such as enhancers, control gene expression by physically contacting target gene promoters, often through long-range chromosomal interactions spanning large genomic distances. Promoter Capture Hi-C (PCHi-C) identifies significant interactions between promoters and distal regions, enabling the assignment of potential regulatory sequences to their target genes.

https://ift.tt/2KrZmre

EMCrit Podcast – Acid Base Ep. 7 – Bicarb Updates, Quantitative Approach, and Prof. David Story

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Bicar-ICU changes my practice with bicarb infusions and let's end the great lactate debate on EMCrit 227:

EMCrit Project by Scott Weingart.



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Liver chemoembolization of hepatocellular carcinoma using TANDEM® microspheres

Future Oncology, Ahead of Print.


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Genomic ERBB2/ERBB3 mutations promote PD-L1-mediated immune escape in gallbladder cancer: a whole-exome sequencing analysis

Objectives

Patients with gallbladder carcinoma (GBC) lack effective treatment methods largely due to the inadequacy of both molecular characterisation and potential therapeutic targets. We previously uncovered a spectrum of genomic alterations and identified recurrent mutations in the ErbB pathway in GBC. Here, we aimed to study recurrent mutations of genes and pathways in a larger cohort of patients with GBC and investigate the potential mechanisms and clinical significance of these mutations.

Design

We performed whole-exome sequencing (WES) in 157 patients with GBC. Functional experiments were applied in GBC cell lines to explore the oncogenic roles of ERBB2/ERBB3 hotspot mutations, their correlation with PD-L1 expression and the underlying mechanisms. ERBB inhibitors and a PD-L1 blocker were used to evaluate the anticancer activities in co-culture systems in vitro and in vivo.

Results

WES identified ERBB2 and ERBB3 mutations at a frequency of 7%–8% in the expanded cohort, and patients with ERBB2/ERBB3 mutations exhibited poorer prognoses. A set of in vitro and in vivo experiments revealed increased proliferation/migration on ERBB2/ERBB3 mutation. Ectopic expression of ERBB2/ERBB3 mutants upregulated PD-L1 expression in GBC cells, effectively suppressed normal T-cell-mediated cytotoxicity in vitro through activation of the PI3K/Akt signalling pathway and contributed to the growth and progression of GBC in vivo. Treatment with an ERBB2/ERBB3 inhibitor or a PD-L1 monoclonal antibody reversed these immunosuppressive effects, and combined therapy revealed promising therapeutic activities.

Conclusions

ERBB2/ERBB3 mutations may serve as useful biomarkers in identifying patients who are sensitive to ERBB2/ERBB3 inhibitors and PD-L1 monoclonal antibody treatment.

Trial registration number

NCT 02442414;Pre-results.



https://ift.tt/2lIXBLs

Experimental Methods for Spin- and Angle-Resolved Photoemission Spectroscopy Combined with Polarization-Variable Laser

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Here, we combine polarization-variable 7-eV laser with spin- and angle-resolved photoemission technique to visualize the spin-orbital coupling effect in solid states.

https://ift.tt/2tNvi1U

Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment

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We describe a method to significantly enhance orthotopic engraftment of lung cancer cells into the murine lungs by pre-conditioning the airways with injury. This approach may also be applied to study stromal interactions within the lung microenvironment, metastatic dissemination, lung cancer co-morbidities, and to more efficiently generate patient derived xenografts.

https://ift.tt/2tCU6up

A safer presentation of intravenous paracetamol is available



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A retrospective and observational analysis of harmful excipients in medicines for hospitalised neonates in Latvia

Background

Medicines used in neonates contain different excipients, which may not be safe in this age group.

Objective

To analyse the frequency at which hospitalised neonates are exposed to harmful excipients (HEs) and to identify substitution possibilities for medicines containing HEs.

Materials and methods

Retrospective, observational study at a university paediatric hospital from 1 September 2015 till 29 February 2016. All hospitalised neonates who received a prescription for medicines containing an HE were included. Neonates were divided into four groups according to gestational age (<28 weeks; 28 to <32 weeks; 32 to <37 weeks and ≥37 weeks). The following excipients were analysed: parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride. Excipients were identified from the Summaries of Product Characteristics.

Results

296 (102(34.5%) preterm) neonates included in the study received 1472 prescriptions for 106 medicines. The most often used formulations were intravenous (48/106; 45.3%) and oral solid formulations (20; 18.9%). The total number of different excipients was 169. In total, 29/106 (27.4%) medicines contained at least one HE. In total 82/102 (80.4%) preterm and 118/194 (60.8%) term neonates received medications with at least one HE. Substitution was possible for 9/29 (31.0%) HE-containing medicines.

Conclusions

Use of HEs can be reduced by using HE-free products available on the European market. However, medicine substitution was possible in only a small number of cases. Therefore the main focus should be on information and education of the hospital specialists about HEs used in medicines and their adverse reactions.



https://ift.tt/2yQhQQC

Why shared-care arrangements for prescribing in attention deficit hyperactivity disorder may not be accepted

Objectives

To investigate the reasons for the failure of uptake of shared-care arrangements for prescribing in attention deficit hyperactivity disorder.

Methods

A questionnaire was sent to 140 randomly selected general practitioners (GPs) in our local commissioning group area, and semistructured interviews were carried out with five GPs.

Results

Thirty-five questionnaires were returned, giving a response rate of 25%. The results indicate multifactorial reasons for failure to accept shared care. Three main factors were identified, namely GP concerns about the robustness of the diagnosis, lack of availability or uptake of non-pharmacological treatments and a perception that secondary-care physical monitoring was inconsistent.

Conclusions

Our recommendations for facilitating uptake of shared-care partnerships include improving documentation on how the decision to initiate medication is made, enhancing access to and communicating use of non-pharmacological treatments and ensuring communication of the results of physical monitoring and follow-up.



https://ift.tt/2N7QFUL

Factors associated with patient satisfaction in an outpatient hospital pharmacy

Objective

To analyse the factors leading to greater satisfaction among patients attending the outpatient hospital pharmacy (OPh).

Methods

A cross-sectional study was conducted of patients attending the OPh of a 1250-bed university hospital. A self-administered questionnaire for measuring outpatients' satisfaction was developed. Global satisfaction was measured on a scale of 1 to 10. Indices of perceived quality for accessibility, interpersonal professional–patient relationship and the convenience of the process were modelled through a principal component analysis using varimax rotation. The relationship between the principal components and overall satisfaction was evaluated using regression analysis.

Results

A questionnaire-based survey was conducted between May and June 2015. A total of 509 valid responses (86.9% response rate) were collected from the OPh. The overall satisfaction score was 7.81 (95% CI 7.59 to 8.04). The principal component analysis produced two components that explained 62.1% of the variance. The first component (CP1) contained questions related to the adequacy of the resources and services. The second component (CP2) contained questions about interpersonal professional–patient relationship. An additional unit in the CP2 was associated with a 3.23 increased risk of having higher satisfaction scores, while an increase of an additional unit in CP1 was associated with a 1.93 increased risk of having higher satisfaction scores.

Conclusions

Our study shows that the factor which predicts the satisfaction of patients who come to the OPh is the quality of care provided by pharmacists—in particular, information provided, resolution of doubts, personal attention and time devoted to the patient.



https://ift.tt/2yXGVJM

Physicochemical stability of oxycodone-ketamine solutions in polypropylene syringe and polyvinyl chloride bag for patient-controlled analgesia use

Objectives

The study evaluated the stability of three combinations of oxycodone and ketamine diluted in normal saline (NS) after storage for 7 days at 23°C and exposed to light.

Methods

The stability of three mixtures of oxycodone and ketamine (oxycodone 0.4 mg/mL+ketamine 40 mg/mL, oxycodone 10 mg/mL+ketamine 0.1 mg/mL and oxycodone 10 mg/mL+ketamine 40 mg/mL) in NS stored in a polypropylene syringe and a polyvinyl chloride (PVC) bag was studied. The physical characteristics, including pH, colour and precipitation, were evaluated. The samples were analysed in triplicate by a stability-indicating high-performance liquid chromatography method.

Results

There was no significant change in the pH values of any solution. No precipitation or change in colour was observed. All formulations maintained more than 95% of the initial concentration of each drug on day 7. No trace of degradation products was detected.

Conclusions

Ketamine (0.1–40 mg/mL) combined with oxycodone (0.4–10 mg/mL) is physically compatible and chemically stable for 7 days when diluted with NS, packaged in polypropylene syringe or PVC bag and stored at 23°C.



https://ift.tt/2N5DDa8

Prescription of antibiotics in Riga and Vilnius tertiary childrens hospitals

Objectives

The aim of this study was to compare the use of antibiotics among hospitalised children in Riga (Latvia) and in Vilnius (Lithuania) at two tertiary paediatric centres.

Methods

A point prevalence survey (PPS) was conducted using validated and standardised Antibiotic Resistance and Prescribing in European Children (ARPEC) project methodology during November 2012. All inpatients less than 18 years old were included in the study. All data were recorded for patients with active antimicrobial prescriptions at 8 am on the day of the survey. Data were entered into the ARPEC-webPPS programme and were validated online for accuracy.

Results

The proportion of patients receiving antimicrobial therapy was statistically different: 128 (37.0%) patients in Riga and 83 (26.3%) in Vilnius. The most common age group in Riga and Vilnius was 1–5 years. The most commonly used antibiotic classes for the treatment and prophylaxis of infection were third-generation cephalosporins (38; 25.5% prescriptions) in Riga and second-generation cephalosporins (16; 19.8%) in Vilnius. Parenteral use of antimicrobials was higher in Riga than in Vilnius: 111 (74.5%) prescriptions to paediatric patients in Riga and 45 (55.6%) prescriptions in Vilnius.

Conclusions

The PPS identified differences in antibiotic use in both hospitals and problem areas for improvement: high use of third-generation cephalosporins for paediatric patients (in Riga) and predominant use of parenteral antibiotics. Further collaboration between both centres is needed because sharing audit data and antimicrobial stewardship initiatives may encourage further changes in practice at both institutions.



https://ift.tt/2tO8yik

Commission: communication on the future of digital health



https://ift.tt/2N6vy5a

Evaluation of antibiotic prescribing for adult inpatients at Sultan Qaboos University Hospital, Sultanate of Oman

Objective

Little is known into the prudent use of antibiotics in hospitals in Oman. This study is to evaluate antibiotic prescribing by measuring the overall compliance with the local antibiotic prescribing guidelines.

Methods

An observational study involving 366 patients' admission episodes as determined by power analysis on patients (≥18 years) on oral and/or parenteral antibiotic during admission, in the period of 10 weeks (1 February–15 April, 2014). The adapted audit tool of the Barking, Havering and Redbridge University Hospitals NHS Trust was used for this study. Analyses were performed using descriptive statistics. Main outcome measures: antibiotic prescribing compliance with the local guidelines as well as the overall restricted antibiotic policy adherence at Sultan Qaboos University Hospital (SQUH).

Results

The number of prescribed and audited antibiotics totalled 825, compliance with local guidelines was suboptimal at 63% (n=520), and of 211 restricted antibiotics prescribed, the overall adherence to restricted antibiotic policy was inadequate at 46% (n=98). The majority of the antibiotics prescribed were broad spectrum at 90% (n=739), mainly penicillins at 31% (n=256) and cephalosporins at 17% (n=139).

Conclusion

The study has provided valuable baseline details of antibiotic prescribing patterns in SQUH. The diagnosis was documented in 89% (n=327) of the admission episodes. However, the compliance with SQUH antibiotic prescribing guidelines was suboptimal, and the overall compliance with SQUH restricted antibiotic guidelines was in 46% of the prescriptions. Further studies are required to address the reasons behind the non-compliance with local guidelines.



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Crystal ball gazing



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Stability and compatibility of ondansetron with haloperidol in parenteral admixtures

Background

The chemical stability of coadministered ondansetron (OND) and haloperidol (HAL) in parenteral admixtures has not been described yet.

Objective

The aim of the present work is to study the chemical stability and the compatibility of OND and HAL admixtures.

Methods

Normal saline solution and dextrose were used to prepare the admixture solutions of the drugs; the materials of the containers were the original plastic bags of the diluents and the stability was studied at 20°C. Compatibility was studied by visual inspection of no colour change and turbidity or precipitation appearance. The concentration of the drugs was studied by ultraviolet detection high-performance liquid chromatography. The method was validated following the Food and Drug Administration and European Medicines Agency guidelines, and the assay enables the measurement of both drugs with a linear calibration curve (r=0.999) over the concentration range 10–100 µg/mL, with acceptable values of linearity, precision and accuracy. Darunavir was used as internal standard.

Results

Most of the admixtures have an adequate concentration until 24 hours(less than 10% of loss). 25% of the samples show a higher loss at 24 hours, and the chemical stability of these samples is 12 hours.

Conclusions

The stability and compatibility of OND and HAL in the coadministered admixtures in Viaflo plastic bags with normal saline or dextrose are suggested at 12 hours.



https://ift.tt/2yNPXbS

What do laypeople consider 'medication and are they aware of modulators of a drugs effects?

Objectives

Healthcare providers expect patients to be responsible partners during drug treatment, who know potential risks impeding drug effects and are able to accurately report prescribed and non-prescribed medication. This presumes that they have the same understanding of the term 'medication' as healthcare providers. We assessed which products laypeople label as medication and which modulators of drug effects they know.

Methods

People visiting the otorhinolaryngology outpatient clinic at a university hospital were invited to anonymously complete a questionnaire assessing which products out of 23 listed examples are medications and valuing 12 modulators potentially influencing drug effects.

Results

Among 94 participants, 86 (91.5%) identified on average 14.4±3.3 (62.6%) of the products and 79 (84.0%) identified 6.7±2.0 (55.5%) of the modulators correctly. Women performed better than men (p<0.01). Regular medication intake, education level and age did not influence the results.

Conclusions

Laypeople are at risk of misclassifying medications and modulators of drug effects.



https://ift.tt/2N7QoBd

Oral anticancer medicines in acute oncology; recognition by non-specialist clinicians and risk reduction measures

Objective

This study investigated the awareness of non-oncology specialist medical staff about commonly used oral anticancer medicines (OAMs).

Methods

Interviews conducted with a range of non-oncology specialist doctors.

Results

The recognition of OAMs was poor by all grades of doctors, with capecitabine being the only drug recognised by more than half the doctors (26 of 40; 65%). Consultant medical staff scored significantly better than most junior grades of staff.

Conclusions

A barrier to safe patient care appears to be the initial identification of OAMs on acute admission. Once a drug had been identified as an OAM, doctors are aware that they should not prescribe it and should contact the acute oncology service for advice. A range of measures has been introduced to improve the identification of OAMs by doctors.



https://ift.tt/2yNPFBO

Progression of systemic lupus erythematosus associated with propofol administration: a case report

Propofol is a sedative-hypnotic agent used as a general anaesthetic with a good safety profile. However, the potential risk for patients with systemic lupuserythematosus (SLE) receiving propofol remains unclear. We report the case of a patient who received an intravenous infusion of propofol for painless gastroscopy which exacerbated acute SLE despite no history of allergies. The adverse effect might be because propofol increased T helper cells and trigged the induction of B cell differentiation and plasmablast formation, which further promoted the secretion of auto-antibodies. This case shows that propofol can exacerbate SLE symptoms in some patients and highlights the importance of identifying potential immune-related factors before propofol administration, especially in patients with autoimmune diseases. It is important to be aware of and differentiate this uncommon and non-specific SLE manifestation from a myriad of disorders presenting with a primary digestive disorder in the outpatient clinic.



https://ift.tt/2N7PEvV

Feasibility of a multidisciplinary approach for medical review among elderly patients in four Italian long-term nursing homes

Objectives

To establish the feasibility and the specific tasks of a multidisciplinary team approach for medical review in four nursing homes for the elderly in Italy.

Methods

Prospective study conducted between November 2012 and September 2013. Review of therapies was performed by seven clinical pharmacists and four nurses using composite criteria for drug discrepancy evaluation with subsequent submission to 31 physicians.

Results

The rate of prevalence of drug discrepancies recorded for 2556 medications reviewed in 333 patients was 34.1% (871/2556). Of these, only 35.5% (309/871) were accepted by clinicians. The highest clinician acceptance rates were observed for drug substitutions (91.3%, 211/231) and dosing regimen modifications (96.4%, 53/55). A significant decrease in the mean number of medications prescribed per patient (from 7.7±2.8 to 7.3±2.7, p<0.05) was observed.

Conclusions

Interventions aimed at improving interactions between pharmacists and physicians and awareness among physicians of major pharmacological interactions should be encouraged.



https://ift.tt/2yNPoPi

2017 EAHP Statements survey results are online



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Building for better bones: evaluation of a clinical pathway in the secondary prevention of osteoporotic fractures

Objective

Osteoporosis is a common disease that is underdiagnosed and undertreated. A multidisciplinary intervention may improve the identification and treatment of osteoporosis and may consequently prevent secondary fractures.

Method

Retrospective, single-centre study comparing attitude to screening and treatment of patients admitted to the orthopaedic unit of the general hospital AZ Sint-Jan Brugge-Oostende AV (Belgium) before and after the implementation of a clinical pathway.

Results

A total of 172 patients (86 before and 86 after) were included in this study. The implementation of the pathway resulted in an increase in bone mineral density tests performed, an increment in the number of referrals to a specialist in the field of osteoporosis, and an increase in prevention and treatment of osteoporosis.

Conclusion

The implementation of a clinical pathway coordinated and evaluated by a clinical pharmacist improved the identification, referral and treatment of osteoporosis in patients hospitalised due to low-impact fractures.



https://ift.tt/2tLFAQk

Junior doctors communication with hospital pharmacists about prescribing



https://ift.tt/2tDNUlI

Abiraterone-Olaparib Combo Aids Men with mCRPC [News in Brief]

HRR deficiency isn't factor in therapeutic response to antiandrogen and PARP inhibitor in metastatic castrate-resistant prostate cancer.



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Tailoring the deep brain stimulation indications in Parkinson’s disease



https://ift.tt/2yPI065

There is no benefit in the use of postnatal intravenous immunoglobulin for the prevention of relapses of multiple sclerosis: findings from a systematic review and meta-analysis

ABSTRACT Multiple sclerosis (MS) is a complex autoimmune and neurodegenerative disease of the central nervous system. Since MS affects mostly fertile women, pregnancy issues often arise in daily practice. The present study assessed the use of postpartum intravenous immunoglobulin (IVIG) in MS. Methods The authors individually searched for records using PubMed, Medline, EMBASE, Cochrane, SciELO, LILACS, and Google Scholar, using the terms "multiple sclerosis" OR "MS" AND "pregnancy" OR "gestation" OR "partum" OR "post-partum" OR "puerperium" AND "immunoglobulin". Results The initial search returned 321 papers. There were 11 eligible articles selected for the review. In total, 380 patients had received post-natal IVIG to reduce the number of postpartum relapses. The unadjusted number needed to treat was 6.3 for the quantitative and 5.8 for the qualitative analyses. Conclusion The therapeutic effect of IVIG for prevention of postnatal relapses in MS could not clearly be established in this meta-analysis.


RESUMO Esclerose múltipla (EM) é uma complexa doença autoimune e neurodegenerativa do sistema nervoso central. Uma vez que EM afeta principalmente mulheres em idade fértil, assuntos relacionados à gravidez frequentemente surgem na prática diária. O presente estudo avaliou o uso pós-parto de imunoglobulina (IVIG) na EM. Métodos Os autores individualmente pesquisaram as bases de dados PubMed, Medline, EMBASE, Cochrane, SciELO, LILACS, e Google Scholar usando os termos "multiple sclerosis" OR "MS" AND "pregnancy" OR "gestation" OR "partum" OR "post-partum" OR "puerperium" AND "immunoglobulin". Resultados A pesquisa inicial retornou 321 artigos. Havia 11 artigos elegíveis para a revisão. No total, havia relato de 380 pacientes que receberam IVIG após a gravidez visando reduzir o número de surtos. O número necessário para tratar não ajustado foi 6,3 para análise quantitativa e 5,8 para análise qualitativa. Conclusão O efeito terapêutico da IVIG para prevenção dos surtos pós-parto na EM não pôde ser claramente estabelecida nesta meta-análise.

https://ift.tt/2lFnThy

Prevalence of obesity among stroke patients in five Brazilian cities: a cross-sectional study

ABSTRACT Objective There is gap in knowledge about obesity prevalence in stroke patients from low- and middle-income countries. Therefore, we aimed to measure the prevalence of overweight and obesity status among patients with incident stroke in Brazil. Methods In a cross-sectional study, we measured the body mass index (BMI) of ischemic and hemorrhagic stroke patients. The sample was extracted in 2016, from the cities of Sobral (CE), Sertãozinho (SP), Campo Grande (MS), Joinville (SC) and Canoas (RS). Results In 1,255 patients with first-ever strokes, 64% (95% CI, 62–67) were overweight and 26% (95%CI, 24–29) were obese. The obesity prevalence ranged from 15% (95%CI, 9–23) in Sobral to 31% (95%CI, 18–45) in Sertãozinho. Physical inactivity ranged from 53% (95%CI, 43-63) in Sobral to 80% (95%CI, 73–85) in Canoas. Conclusions The number of overweight patients with incident stroke is higher than the number of patients with stroke and normal BMI. Although similar to other findings in high-income countries, we urgently need better policies for obesity prevention.


RESUMO Objetivo Há uma lacuna de conhecimento sobre a prevalência de obesidade em pacientes com AVC (acidente vascular cerebral) de países de baixa e média renda. Portanto, objetivamos medir a prevalência de sobrepeso e obesidade entre pacientes com AVC no Brasil. Métodos Em um estudo transversal, medimos o índice de massa corporal (IMC) em pacientes com AVC isquêmico e hemorrágico. A amostra foi extraída em 2016, nas cidades de Sobral (CE), Sertãozinho (SP), Campo Grande (MS), Joinville (SC) e Canoas (RS). Resultados Entre 1255 casos de AVC, 64% (95%CI, 62–67) apresentavam sobrepeso e 26% (95%CI, 24–29) obesidade. A prevalência de obesidade variou de 15% (95%CI, 9–23) em Sobral a 31% (95%CI, 18–45) em Sertãozinho. Conclusões A quantidade de pacientes com AVC e IMC anormal é maior do que a de pacientes com AVC e IMC normal. Embora esta prevalência seja similar às de países de alta renda, precisamos urgentemente de melhores políticas de prevenção da obesidade. Atividade física deveria ser parte da prescrição médica.

https://ift.tt/2tN65ov

Neurosyphilis and ocular syphilis clinical and cerebrospinal fluid characteristics: a case series

ABSTRACT Background During the first decade of this century, a significant increase in the incidence of syphilis was documented. Objective To study clinical and laboratory characteristics of central nervous system and ocular syphilis. Methods A retrospective case series of 13 patients with a clinical and laboratory diagnosis of neurosyphilis and/or ocular syphilis who had been admitted to the Neurology and Neuro-ophthalmology Service of the Hospital de Clínicas, Federal University of Paraná. Results Nine patients had a diagnosis of neurosyphilis and two of them also had ocular syphilis. Four patients had a diagnosis of ocular syphilis alone. Among the patients with a diagnosis of neurosyphilis, six had symptomatic syphilitic meningitis, of whom one manifested as cranial nerve palsy alone, one as cranial nerve palsy plus ocular syphilis, two as transverse myelitis (syphilitic meningomyelitis), one as meningitis worsening the patient's myasthenia gravis symptoms and one as meningitis plus ocular syphilis. Additionally, we diagnosed three patients with meningovascular neurosyphilis. In the univariate analysis, patients without ocular syphilis showed greater levels of total protein and white blood cells in the cerebrospinal fluid than patients with ocular syphilis. Conclusion This Brazilian case series of patients with neurosyphilis and ocular syphilis highlights the wide variability of this disease. A high degree of diagnostic suspicion is necessary when facing neurological and ocular symptoms for rapid diagnosis and appropriate management of patients.


RESUMO Introdução Na primeira década deste século observou-se um aumento significativo da incidência de sífilis no mundo. Objetivo Estudar características clínicas e laboratoriais da sífilis no Sistema Nervoso Central e da sífilis ocular. Métodos Estudou-se, retrospectivamente, uma série de treze casos com diagnóstico clínico e laboratorial de neurossífilis e/ou sífilis ocular, admitidos aos Serviços de Neurologia ou Neuroftalmologia do Hospital de Clínicas da Universidade Federal do Paraná. Resultados Nove pacientes tiveram diagnóstico de neurosífilis e dois destes apresentaram concomitantemente sífilis ocular. Quatro pacientes tiveram somente o diagnóstico de sífilis ocular. Dos pacientes com diagnóstico de neurosífilis, seis apresentaram meningite sifilítica sintomática, dentre os quais um se apresentou com paralisia isolada de par craniano, um com paralisia de par craniano associada sífilis ocular, dois com mielite transversa (manifestação de meningomielite), um com meningite que agravou sintomas de Miastenia Gravis e um com meningite isolada associada a sífilis ocular. Houve 3 casos de neurosífilis meningovascular. Na análise univariada, pacientes sem manifestações oculares de sífilis apresentaram maiores níveis proteína total e leucócitos do que os pacientes com sífilis ocular. Conclusão Essa série brasileira de casos de pacientes com neurosífilis e sífilis ocular destaca a alta variabilidade clínica desta doença. Alto grau de suspeição diagnóstica é necessário quando em frente a sintomas neurológicos e oculares para rápido diagnóstico e adequado manejo dos pacientes.

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Performances on the Timed Up and Go Test and subtasks between fallers and non-fallers in older adults with cognitive impairment

ABSTRACT This work aimed to compare performances on the Timed Up and Go (TUG) test and its subtasks between faller and non-faller older adults with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). A prospective study was conducted, with 38 older adults with MCI and 37 with mild AD. Participants underwent an assessment at baseline (the TUG and its subtasks using the Qualisys ProReflex system) and the monitoring of falls at the six-month follow up. After six months, 52.6% participants with MCI and 51.3% with AD fell. In accordance with specific subtasks, total performance on the TUG distinguished fallers from non-fallers with AD, fallers from non-fallers with MCI and non-fallers with MCI from non-fallers with AD. Although no other difference was found in total performances, non-fallers with MCI and fallers with AD differed on the walking forward, turn and turn-to-sit subtasks; and fallers with MCI and non-fallers with AD differed on the turn-to-sit subtask.


RESUMO O objetivo deste trabalho foi comparar o desempenho do Timed up and go test (TUG) e suas subtarefas entre idosos caidores e não caidores com comprometimento cognitivo leve (CCL) e doença de Alzheimer (DA) leve. Um estudo prospectivo foi conduzido, com 38 idosos com CCL e 37 com DA leve. Foi realizada uma avaliação inicial (TUG e subtarefas por meio do sistema Qualisys Pro Reflex) e um monitoramento de quedas por 6 meses. Após 6 meses, 52.6% pessoas com CCL e 51.3% com DA caíram. Em concordância com subtarefas específicas, a performance total do TUG distinguiu caidores de não caidores com DA, caidores de não caidores com CCL e não caidores com CCL de não caidores com DA. Embora nenhuma outra diferença foi encontrada na performance total do TUG, não caidores com CCL e caidores com DA apresentaram diferenças nas performances das subtarefas marcha ida, retornar e virar-se para sentar; e caidores com CCL e não caidores com DA diferiram na subtarefa virar-se para sentar.

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