A Short Screening Tool to Identify Victims of Child Sex Trafficking in the Health Care Setting

Objectives The aim of this study was to describe characteristics of commercial sexual exploitation of children/child sex trafficking (CSEC/CST) victims and to develop a screening tool to identify victims among a high-risk adolescent population. Methods In this cross-sectional study, patients aged 12 to 18 years who presented to 1 of 3 metropolitan pediatric emergency departments or 1 child protection clinic and who were identified as victims of CSEC/CST were compared with similar-aged patients with allegations of acute sexual assault/sexual abuse (ASA) without evidence of CSEC/CST. The 2 groups were compared on variables related to medical and reproductive history, high-risk behavior, mental health symptoms, and injury history. After univariate analysis, a subset of candidate variables was subjected to multivariable logistic regression to identify an optimum set of 5 to 7 screening items. Results Of 108 study participants, 25 comprised the CSEC/CST group, and 83 comprised the ASA group. Average (SD) age was 15.4 (1.8) years for CSEC/CST patients and 14.8 (1.6) years for ASA patients; 100% of the CSEC/CST and 95% of the ASA patients were female. The 2 groups differed significantly on 16 variables involving reproductive history, high-risk behavior, sexually transmitted infections, and previous experience with violence. A 6-item screen was constructed, and a cutoff score of 2 positive answers had a sensitivity of 92%, specificity of 73%, positive predictive value of 51%, and negative predictive value of 97%. Conclusions Adolescent CSEC/CST victims differ from ASA victims without evidence of CSEC/CST across several domains. A 6-item screen effectively identifies CSEC/CST victims in a high-risk adolescent population.

http://ift.tt/2Ed31FB

Human Immunodeficiency Virus Risk Factors and Beliefs Reported by Families Presenting to a Pediatric Emergency Department

Objectives Adolescents are at greater risk for acquiring human immunodeficiency virus (HIV) due to increased risk behaviors. Parental influence is known to reduce adolescent risk behaviors. We compared HIV risk behaviors reported by adolescents to parents' perception of adolescent risky behavior engagement. We also examined participants' knowledge of HIV transmission and testing preferences. Methods Participants included English-speaking adolescents and parents presenting to a pediatric emergency department. Participants were interviewed separately in private. Modeled after existing instruments, "adolescent" and "parent" questionnaires included multiple choices items, Likert-type scales, and standard yes/no and true/false options. Data were analyzed using a κ statistic and observed agreement to measure discordance between adolescent and parent responses. Results Participants included 126 adolescents and 110 parents. Many adolescents reported ever having sex (61%), of which 32% reported always practicing safe sex. Comparative analysis revealed low agreement between adolescents' risk behaviors and parents' perception of risk behavior engagement by youth. Discordance concerning tobacco use was greatest (κ = 0.13), followed by drug use (κ = 0.19) and ever having sex (κ= 0.19), and alcohol use (κ= 0.22). There was also poor agreement regarding HIV transmission knowledge (ie, oral sex; κ = 0.16). Participants shared strong agreement regarding parental support for adolescent interest in HIV testing (95.5%). Conclusions Parents are mostly unaware of adolescents' broad risk behaviors. Participants' knowledge of HIV transmission is limited. Adolescents and parents shared strong agreement regarding HIV testing preferences. Multidimensional HIV prevention strategies aiming to decrease adolescent risk behaviors, increase parental involvement, and improve adolescent and parental knowledge of HIV transmission are needed.

http://ift.tt/2CpYm2R

CME Review Article

No abstract available

http://ift.tt/2CSIoPv

Dexamethasone Compared to Prednisone for the Treatment of Children With Acute Asthma Exacerbations

Systemic corticosteroids are recommended in clinical practice guidelines for the treatment of acute asthma exacerbation based on evidence demonstrating reduced hospitalizations and improved outcomes after administration in the emergency department. Although prednisone and related oral preparations have been recommended previously, researchers have assessed dexamethasone as an alternative based on its longer biologic half-life and improved palatability. Systematic reviews of multiple small trials and 2 larger trials have found no difference in revisits to the emergency department compared to prednisone for dexamethasone given either as an intramuscular injection or orally. Studies of oral administration have found reduced emesis for dexamethasone compared to prednisone both in the emergency department and for a second oral dose, typically given 24 to 48 hours later. Studies assessing a single dose of dexamethasone have found equivalent improvement at follow-up but with some evidence of increased symptoms and increased need for additional corticosteroids compared to multiple doses of prednisone. Future research could further assess dexamethasone dose, formulation, and frequency and measure other related adverse effects such as behavior change. Consideration of baseline differences within the heterogeneous population of children requiring acute care for asthma may also guide the design of an optimal dexamethasone regimen.

http://ift.tt/2F6c1hc

Epidemiology of the Critically Ill Child in the Resuscitation Bay

Background Children account for approximately 33 million annual emergency department (ED) visits in the United States. The spectrum and frequency of children with a critical illness presenting to an ED has not been previously analyzed. Objective The purpose of this study was to examine the range of critical illness presenting to a tertiary Children's Hospital ED. Methods This study was a retrospective chart review of all pediatric patients requiring immediate care in the medical resuscitation bay during a 25-month period from August 2005 to September 2007. Data are from a single center, academic, tertiary care pediatric hospital. A log of all patients requiring immediate care is kept in the medical resuscitation bay. Patients recorded in the log for a period of 25 consecutive months were reviewed for type of critical illness, frequency of critical illness, mode of arrival, and outcome. Trauma patients were excluded. Results There were approximately 45,000 pediatric visits per year with a total of 87,766 patients seen during the study period. There were 249 pediatric patients who required care in the medical resuscitation bay during the reviewed period. Complete data were obtained from 242 subjects' charts. Patients requiring immediate care accounted for 0.28% of all the visits. Conclusions This study documents the infrequent need for pediatric critical care in the ED of a nonacademic tertiary children's hospital in the United States and reinforces the need to provide protocols, mock codes, and simulation labs in preparation for critically ill children.

http://ift.tt/2CCuVKX

Pediatric Exposures to Bombina Toads Reported to Poison Centers

Objectives Fire-bellied toads (genus Bombina) secrete toxins from their skin that may cause problems to humans, particularly if they get in the eye. This study aimed to describe pediatric exposures to fire-bellied toads reported to a large poison center system. Methods Cases were fire-bellied toad exposures among patients aged 13 years or younger reported to Texas poison centers during 2000–2014. The distribution by various demographic and clinical factors was determined. Results Of 20 total exposures, the mean patient age was 5.8 years (range, 2–13 years); 70% of the patients were boys. The exposure route was ocular (70%), dermal (55%), and ingestion (20%). Eighty-five percent of the exposures occurred at the patient's own residence. Sixty percent of the patients were managed onsite, and 40% were already at or en route to a health care facility. The medical outcome was as follows: minor effects (45%), moderate effects (5%), and not followed but judged to have minimal clinical effects (50%). The most common reported symptoms were ocular irritation/pain (65%), dermal irritation/pain (30%), and red eye (20%). Decontamination by dilution/irrigation/wash was reported in 95% of the patients. Conclusions Few pediatric exposures to fire-bellied toads were reported. Those that were reported were most likely to involve ocular followed by dermal routes. The exposures tended not to be serious and could be managed outside of a health care facility.

http://ift.tt/2CTPAuZ

Gastric Perforation After a Dog Attack

Dog bites are a major cause of injury, especially in the pediatric population. Common anatomic sites of dog bites on children are the peripheries and the head and neck. The torso is reportedly injured less frequently, and only 2 cases of intra-abdominal injury secondary to dog bites have been reported. We recently encountered a 3-year-old boy presenting with peritonitis who had sustained multiple dog bites to his trunk and upper limbs. Emergency laparotomy was performed. Surgical findings revealed penetration of the peritoneum and single perforation of the anterior gastric wall with multiple tooth marks; thus, the gastric perforation was debrided and repaired. After receiving rabies prophylaxis and amoxicillin-clavulanate, the patient had an uneventful postoperative course. The principles of management of dog bites include debridement of wounds and use of prophylactic antibiotics. Because rabies is always fatal, postexposure prophylaxis should be considered in appropriate cases. Dog bites can be life-threatening, and prevention is the best approach to solve this problem. Clinicians need to be aware that some dog bites can be devastating and should be familiar with the principles of managing these wounds.

http://ift.tt/2m3U5uV

Improving Pediatric Preparedness in Critical Access Hospital Emergency Departments: Impact of a Longitudinal In Situ Simulation Program

Objectives Critical access hospitals (CAH) see few pediatric patients. Many of these hospitals do not have access to physicians with pediatric training. We sought to evaluate the impact of an in situ pediatric simulation program in the CAH emergency department setting on care team performance during resuscitation scenarios. Methods Five CAHs conducted 6 high-fidelity pediatric simulations over a 12-month period. Team performance was evaluated using a validated 35-item checklist representing commonly expected resuscitation team interventions. Checklists were scored by assigning zero point for "yes" and 1 point for "no". A lower final score meant more items on the list had been completed. The Kruskal-Wallis rank test was used to assess for differences in average scores among institutions. A linear mixed effects model with a random institution intercept was used to examine trends in average scores over time. P

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Improving Time to Antibiotics for Pediatric Oncology Patients With Suspected Infections: An Emergency Department–Based Quality Improvement Intervention

Objective Studies in pediatric patients with fever and neutropenia demonstrate that shorter time to antibiotics is associated with a decrease in pediatric intensive care unit admissions and in-hospital mortality. In 2012, a 2-phase quality improvement intervention was implemented in a pediatric emergency department (ED) to improve care for this high-risk patient population. The objective was to determine if the introduction of (1) a rapid absolute neutrophil count (ANC) test and (2) a standardized prearrival process decreased time to antibiotics for febrile hematology/oncology(heme/onc) patients presenting to the ED. Methods The rapid ANC test introduced in February 2012 decreased turn-around-times in the laboratory from 60 to 10 minutes. The standardization of the prearrival communication between the heme/onc team and ED was implemented in August 2012 as part of a clinical standard work pathway for heme/onc patients who presented to the ED with fever and possible neutropenia. Time from arrival to the ED to administration of first antibiotic was measured. Data from January 2011 to December 2013 were analyzed using statistical process control. Results Seven hundred eighteen encounters for 327 patients were included. After the rapid ANC test, the proportion of patients who received antibiotics within 60 minutes of arrival increased from 47% to 60%. There was further improvement to 69% with implementation of the clinical standard work pathway. Mean time to antibiotics decreased from 83 to 65 minutes (21% decrease). Conclusion This 2-phase quality improvement intervention increased the proportion of patients who received antibiotics within 60 minutes of arrival to the ED. Similar processes may be implemented in other pediatric EDs to improve timeliness of antibiotic administration.

http://ift.tt/2CJWGVk

Children Covered by Medicaid/State Children's Health Insurance Program More Likely to Use Emergency Departments for Food Allergies

Background Food allergies (FAs) occur in 4% to 8% of children in the United States, and emergency department (ED) visits account for up to 20% of their costs. In 2010, the National Institute of Allergy and Infectious Diseases established diagnostic criteria and management practices for FAs, and recognition and treatment of FAs for pediatric ED practitioners has been described. Objective This study identified trends and factors related to ED visits for pediatric FAs in the United States from 2001 to 2010. It was hypothesized that FAs increased and that differences existed in ED utilization based on age, insurance status, and geography. Low concordance with treatment guidelines for FAs was expected. Methods Multivariate logistic regression, using National Hospital Ambulatory Medical Care Survey data, estimated factors associated with ED visits and treatment of FAs and nonspecific allergic reactions. Trends and treatment patters used weighted frequencies to account for the complex 4-stage probability survey design. Results An estimated 239,303 (95% confidence interval [CI], 180,322–298,284) children visited the ED for FAs, demonstrating a significant rate increase during the period (53.08, P

http://ift.tt/2CB8qGe

Point-of-Care Ultrasound Identification of Internal Jugular Vein Thrombosis in Newly Diagnosed Lymphoma

Abstract We present a case of a child who presented with neck swelling and was ultimately diagnosed with lymphoma after an internal jugular vein thrombosis was discovered by point-of-care ultrasound. The use of point-of-care ultrasound enabled thrombus detection, which prompted further evaluation and treatment.

http://ift.tt/2CzMRWE

Instruments to Identify Commercially Sexually Exploited Children: Feasibility of Use in an Emergency Department Setting

Objective This review examines the screening instruments that are in existence today to identify commercially sexually exploited children. The instruments are compared and evaluated for their feasibility of use in an emergency department setting. Methods Four electronic databases were searched to identify screening instruments that assessed solely for commercial sexual exploitation. Search terms included "commercially sexually exploited children," "CSEC," "domestic minor sex trafficking," "DMST," "juvenile sex trafficking," and "JST." Those terms were then searched in combination with each of the following: "tools," "instruments," "screening," "policies," "procedures," "data collection," "evidence," and "validity." Results Six screening instruments were found to meet the inclusion criteria. Variation among instruments included number of questions, ease of administration, information sources, scoring methods, and training information provided. Two instruments were determined to be highly feasible for use in the emergency department setting, those being the Asian Health Services and Banteay Srei's CSEC Screening Protocol and Greenbaum et al's CSEC/child sex trafficking 6-item screening tool. Conclusions A current dearth of screening instruments was confirmed. It is recommended that additional screening instruments be created to include developmentally appropriate instruments for preadolescent children. Numerous positive features were identified within the instruments in this review and are suggested for use in future screening instruments, including succinctness, a simple format, easy administration, training materials, sample questions, multiple information sources, designation of questions requiring mandatory reporting, a straightforward scoring system, and an algorithm format.

http://ift.tt/2BuUmgE

Pediatric Lawnmower Injuries

Objective The aim of this study was to evaluate demographics, characteristics, and mechanisms of injuries caused by lawnmowers in children. Methods Chart review from 1990 to 2010 at a level I pediatric trauma center identified patients younger than 18 years with lawnmower injuries. Demographics and characteristics of the injuries were analyzed by descriptive statistical analysis. Results The study identified 88 subjects, with 80% males and 42% of the subjects younger than 5 years. When the lawnmower type was specified, riding lawnmowers caused the majority of injuries (72%). The most common mechanism of injury was related to slipping under lawnmower/being run over (51%). The most common injuries were lacerations (36%), fractures (27%), and amputations (22%); lower extremities were injured more frequently than other body areas (62%). The majority of patients (76%) required hospitalization with a mean length of stay (LOS) of 9.7 days and a mean number of procedures of 4. Complications included 6 infections, 1 tissue necrosis, and 1 death from hemorrhagic shock. Riding-lawnmower injuries were associated with younger children (P

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CME Review Article

No abstract available

http://ift.tt/2CzdT0m

Trauma Arrest and Spinal Injury in a 3-Year-Old Girl

Abstract Management of an acutely injured pediatric patient with multiple traumas is a common challenge facing clinicians in pediatric emergency care. Blunt trauma is more common in the pediatric population with motor vehicle accidents being the most common cause of injury. Spinal injury, especially in young children, is only seen in 1% to 2% of cases and can be lethal. It is incumbent upon clinicians to be able to meet the challenges of patient management including airway management, providing hemodynamic support, and addressing potentially reversible causes of arrest while recognizing presenting symptoms of spinal injury. This case presents a child in trauma arrest after a motor vehicle crash requiring advanced interventions, diagnostics, and support. Her clinical course is described and reveals a complete distraction of the cervical and thoracic spine. This case illustrates pathology and management along with the importance of proper management and interventions by pediatric emergency clinicians to manage the patient and attempt to maximize the patient's outcome.

http://ift.tt/2CzQ2O0

Carotid Artery Dissection With Associated Territory Stroke After a Minor Head Trauma in a Healthy 4-Month-Old Child

Abstract Internal carotid artery (ICA) dissections with associated stroke are rare events in infants. The usual pathomechanisms include direct trauma to the artery, blunt intraoral trauma, or child abuse. We describe the case of a 4-month-old male patient with ICA dissection and associated middle cerebral artery territory infarction associated with hyperextension/hyperrotation after a minor head injury. Upon treatment with anticoagulants, the patient showed significant improvement of the left-sided hemiparesis. Hemorrhagic transformation that presented shortly after middle cerebral artery infarction did not further increase under heparin treatment and prevented further embolism. In conclusion, hyperextension and/or hyperrotation in minor head trauma is a possible pathomechanism for ICA dissection in infants. However, the scenario is extremely rare, and to our best knowledge, this is the first report describing it. In our patient, anticoagulation did not worsen hemorrhagic transformation.

http://ift.tt/2CByNvD

Skull Bone/Calvarial Infarction and Spontaneous Epidural Hematoma as Cause of Severe Headache in the Emergency Department

No abstract available

http://ift.tt/2CByUHz

Gastrostomy Tubes: Care and Feeding

Abstract Parents often bring their children to the emergency department for adverse events with their child's gastrostomy tube or button. This review will discuss the possible complications and the methods to handle them.

http://ift.tt/2CByT6t

Pediatric Emergency Medicine: Legal Briefs

No abstract available

http://ift.tt/2D1RI3R

Bloodstream Infections in Patients With Intestinal Failure Presenting to a Pediatric Emergency Department With Fever and a Central Line

Objective Previous small studies have found a high occurrence of bloodstream infections (BSIs) in patients with intestinal failure, and these rates are higher than reported rates in other pediatric populations with central lines. The primary study objective was to describe the occurrence of BSIs in patients with intestinal failure who present to the pediatric emergency department (ED) with fever. Methods This 5-year retrospective chart review included febrile patients with intestinal failure and central lines who presented to the Children's Hospital of Pittsburgh ED between 2006 and 2011. Each febrile episode was analyzed at the visit level. Results During the study, 72 patients with 519 febrile episodes were identified. Central blood cultures were obtained in 93% (480/519) of episodes and 69% (330/480) were positive. Of all BSIs, 38% (124/330) were polymicrobial, 32% (105/330) were a single gram-positive organism, 25% (84/330) were a single gram-negative organism, and 5% (17/330) were a single fungal organism. Of the bacterial pathogens, 48% (223/460) were gram-negative. Overall, 60% were enteric organisms. Conclusions Pediatric patients with intestinal failure and central lines have a high occurrence of BSIs with 69% of cultures positive in this study of ED febrile episodes. In contrast to reports in other populations with central lines, BSI occurrence in patients with intestinal failure and fever is higher and larger proportions are gram-negative and enteric organisms. For these patients, we recommend central and peripheral blood cultures, empiric broad spectrum antibiotics targeting gram-negative and enteric organisms, and hospital admission.

http://ift.tt/2D2z1Nq

Brain atrophy measures in preclinical and manifest spinocerebellar ataxia type 2

Abstract

Objective

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited neurodegenerative disease mainly affecting the cerebellum and brainstem. In this Cuban-German research collaboration, we aimed to characterize atrophy patterns and associations with clinical measures in preclinical and manifest SCA2.

Methods

In this study, 16 nonmanifest SCA2 mutation carriers, 26 manifest patients with SCA2, and 18 healthy control subjects underwent magnetic resonance imaging, as well as genetic and clinical characterization including assessment of ataxia (Scale for the Assessment and Rating of Ataxia) and saccade velocity in Cuba were enrolled. Semiautomated quantitative volumetry of the cerebellum and brainstem, subdivided into the medulla oblongata, the pontine brainstem, and mesencephalon was performed. Additionally, the anteroposterior diameter of the pontine brainstem was measured.

Results

Analysis of volumetric data revealed degeneration of the cerebellum and brainstem, in particular of pontine volumes and the anteroposterior diameter of the pons, in both manifest SCA2 patients and individuals at risk for SCA2 compared to controls. Comparing patients with nonataxic preclinical SCA2 mutation carriers, we found more pronounced reductions of the pontine brainstem and cerebellum in manifest SCA2. Volumetric data further showed associations with CAG repeat length and predicted age of onset in preclinical SCA2 individuals, and by trend with ataxia signs in patients. Although saccade velocity was associated with reduction in the pontine brainstem in preclinical and manifest SCA2, reduced ability to suppress interfering stimuli measured by the Stroop task was related to cerebellar volume loss in patients.

Interpretation

Preclinical SCA2 mutation carriers exhibit brain abnormalities, which could be targeted as surrogate parameters for disease progression and in future preventive trials.

http://ift.tt/2CzWDYE

Can therapeutic drug monitoring increase the safety of Imatinib in GIST patients?

Abstract

Imatinib at 400 mg daily is the standard treatment for patients affected with CML and GIST. The intervariability in plasma concentration is very significant. In many reports, a good therapeutic effect is attributed to an adequate concentration of Imatinib. However, few studies have been conducted to investigate the association between plasma concentration and side effects. Besides, no upper concentration limit of Imatinib plasma concentration detection has been established. The correlation of Imatinib trough concentrations (C_min) with adverse effects (AEs) was described here. Plasma samples were obtained from patients after 3 months treatment with Imatinib (steady state, n = 122). Liquid chromatography/ tandem mass spectrometry was used to determine the concentration of Imatinib and its metabolite NDI. The incidence of myelosuppression was increased significantly with the increased Imatinib trough plasma concentration. The plasma level of Imatinib and NDI in patients who developed myelosuppression are 1698.3 ± 598.6 ng/mL and 242.1 ng/mL, respectively, which were significantly higher than those in patients who did not (1327.2 ± 623.4 ng/mL, P = 1.75 × 10^-4; 206.3 ng/mL, P = 0.006). Estimated exposure thresholds of Imatinib and NDI were 1451.6 ng/mL with ROC_AUC (95%CI) of 0.693 (0.597–0.789) and 207.1 ng/mL with ROC_AUC (95%CI) of 0.646 (0.546–0.745), respectively. Multivariate regression confirmed the correlation of Imatinib C_min with myelosuppression. Other side effects such as fluid retention and rash were not found to be correlated with Imatinib concentrations. These results suggest that trough concentration of Imatinib should be taken into consideration to increase the safety of Imatinib therapy in GIST patients.

Since Imatinib is usually administered for a prolonged period, rational management of its side effects is of great importance. Few studies have been conducted to investigate the association between plasma concentration and side effects. In this study, Imatinib-induced myelosuppression was found to be correlated significantly with Imatinib concentration, and the estimated exposure threshold for myelosuppression was 1451.6 ng/mL with ROCAUC (95% CI) of 0.693 (0.597–0.789).

http://ift.tt/2CP2FZG

Dr. Martin Citardi Recognized with AAO-HNS Distinguished Service Award

Martin J. Citardi, MD, professor and chair of the Department of Otorhinolaryngology-Head and Neck Surgery at UTHealth's McGovern Medical School,... Read the full article...

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Three-Dimensional Cellular Arrangement in Epithelial Ovarian Cancer Cell Lines TOV-21G and SKOV-3 is Associated with Apoptosis-Related miRNA Expression Modulation

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, and the lack of chemoresistance biomarkers contributes to the poor prognosis. Cancer stem cells (CSC) have been investigated in EOC to understand its relationship with chemoresistance and recurrence. In this context, in vitro cultivation-models are important tools for CSC studies. MicroRNAs (miRNAs) play key roles in cancer, CSC regulation and apoptosis. Thus, this study aims to evaluate the tumorsphere model as CSC-enrichment method in EOC studies and investigate apoptosis-related miRNAs in tumorspheres-derived EOC cell lines. TOV-21G and SKOV-3 were cultured in monolayer and tumorspheres. Genetic profiles of cell lines were obtained using COSMIC database. CD24/CD44/CD146/CD177 and ALDH1 markers were evaluated in cell lines and tumorspheres-derived by flow cytometry. Eleven miRNAs were selected by in silico analysis for qPCR analysis. According to COSMIC, TOV-21G and SKOV-3 have eight and nine cancer-related mutations, respectively. TOV-21G showed a CD44^+/high/CD24^−/low/CD117^−/low/CD146^−/low/ALDH1^low profile in both culture models; thus, no significant difference between cultivation models was identified. SKOV-3 showed a CD44^+/high/CD24^+/high/ CD117^−/low/CD146^−/low/ALDH1^low profile in both culture models, although the tumorsphere model showed a significant increase in CD24^+/high subpopulation (ovarian CSC-like). Among eleven miRNAs, we observed differences in miRNA expression between culture models. MiR-26a was overexpressed in TOV-21G tumorspheres, albeit downregulated in SKOV-3 tumorspheres. MiR-125b-5p, miR-17-5p and miR-221 was downregulated in tumorsphere model in both cell lines. Given that tumorsphere-derived SKOV-3 had a higher ratio of CD24^+/high cells, we suggest that miR-26a, miR-125b-5p, miR-17-5p and miR-221 downregulation could be related to poor EOC prognosis.

http://ift.tt/2D1XQck

Possible redundant data in the network meta-analysis of pharmacological therapies for opioid-induced constipation

We read with great interest the recent systematic review and network meta-analysis by Sridharan and Sivaramakrishnan, (1) which synthesised data from 23 separate articles reporting randomised controlled trials (RCTs) of pharmacological therapies for opioid-induced constipation (OIC). After pooling and analysing the results from these articles, the authors concluded that subcutaneous methylnaltrexone performed better than other medications for OIC.

http://ift.tt/2COnowR

C-Cbl and Cbl-b expression in skull base chordomas is associated with tumor progression and poor prognosis

Chordomas are rare, locally aggressive malignancies that are often difficult to eradicate. Surgery and radiotherapy are the first-line treatments, but the probability of local recurrence is high. According to our previous research, c-Cbl and Cbl-b have been linked to tumor progression and poor prognosis of glioma. However, their role in skull base chordomas is unclear. To clarify this issue, in the present study we analyzed the expression of c-Cbl and Cbl-b in relation to the clinicopathological features and clinical outcome of skull base chordomas patients (n=70).

http://ift.tt/2qBmxtA

Atypical multivacuolated lipoblasts and atypical mitoses are not compatible with the diagnosis of spindle cell/pleomorphic lipoma

We have read with great interest the recent papers of Michal et al [1,2], describing lipoblasts (including multivacuolated lipoblasts in some cases) and (atypical) mitotic figures in pleomorphic lipomas. We agree with the authors that lipoblasts can be observed in spindle cell/pleomorphic lipomas. In the spindle cell/pleomorphic lipoma chapter of the recent WHO Classification of Tumours of Soft Tissue and Bone, fourth edition, it is stated that "although fat cells typically lack atypia, some spindle cell/pleomorphic lipomas contain atypical adipocytes and lipoblasts, showing morphologically overlap with atypical lipomatous tumours" [3].

http://ift.tt/2m7AsTl

Differentiating Breast Carcinoma with Signet-Ring Features from Gastrointestinal Signet-Ring Carcinoma: Assessment of Immunohistochemical Markers

Signet-ring morphology is recognized throughout the gastrointestinal tract. However, this pattern may be observed in other primary sites giving rise to diagnostic challenges in the work-up of metastases. Relatively newer immunohistochemical markers have not been evaluated in this context. We assessed expression patterns of several common immunohistochemical markers in tumors with signet-ring morphology to delineate a pragmatic approach to this differential diagnosis. Primary breast and gastrointestinal carcinomas showing signet-ring features were reviewed.

http://ift.tt/2qzAVCG

Spiral enteroscopy-assisted ERCP in bariatric length Roux-en-Y anatomy: a large single-center series and review of the literature (with video)

Deep enteroscopy-assisted ERCP (DEA-ERCP) in post-bariatric Roux-en-Y (RY) anatomy is challenging. Laparoscopy-assisted ERCP (LA-ERCP) or EUS-directed transgastric ERCP (EDGE) are technically easier and faster, but are more invasive and morbid procedures. Therefore, we have used DEA-ERCP as our first-line approach, reserving EDGE and LA-ERCP for cases in which adjunctive techniques that cannot be performed through an enteroscope are required (eg, EUS-FNA, SO manometry), or DEA-ERCP failures. The two main methods for DEA-ERCP are balloon- and spirus-assisted.

http://ift.tt/2F8DjDI

Clinical outcome of endoscopic mucosal resection of sporadic, nonampullary duodenal adenoma: a 10-year retrospective

Sporadic non-ampullary duodenal adenomas (SNADAs), although uncommon, pose clinical challenges. Because SNADAs have malignant potential, endoscopic or surgical resection is generally recommended. Endoscopic mucosal resection (EMR) is increasingly used for resection of SNADAs, but large-scale data on natural history after EMR are scarce. In this study, we aimed to evaluate the clinical outcome of EMR for SNADAs and the natural history after EMR from a large single-operator experience with dedicated follow-up.

http://ift.tt/2EhXiP8

The impact of wire caliber on ERCP outcomes: a multicenter randomized controlled trial of 0.025-inch and 0.035-inch guidewires

Wire-guided biliary cannulation has been demonstrated to improve cannulation rates and reduce post-ERCP pancreatitis (PEP), but the impact of wire caliber has not been studied. This study compares successful cannulation rates and ERCP adverse events using a 0.025-inch and 0.035-inch guidewire.

http://ift.tt/2F8CniC

Combination of Albumin-Bilrubin Grade and Platelet to Predict Compensated Patient with Hepatocellular Carcinoma Who Do Not Require Endoscopic Screening for Esophageal Varices

s & Aims: There is no consensus for screening high-risk esophageal varices (HRV) in patients with hepatocellular carcinoma (HCC). Here, we aimed to investigate the prevalence and risk factors of HRV in HCC patients and to assess the combination of albumin-bilirubin grade and platelet count (ALBI-PLT score) for predicting compensated patients who do not need unnecessary endoscopic screening for HRV.

http://ift.tt/2EhXf5U

Temporal trends in postcolonoscopy colorectal cancer rates in screen-eligible persons: a population-based study

Colorectal cancers (CRCs) diagnosed between 6 and 36 months after colonoscopy, termed postcolonoscopy CRCs (PCCRCs), arise primarily due to missed or inadequately treated neoplasms during colonoscopy. Quality indicators and technological advances have been introduced to colonoscopy practice that should have reduced the PCCRC rate over time. We assessed temporal trends in the population rate of PCCRC as a measure of changing colonoscopy quality.

http://ift.tt/2F8UXqL

Intraosseous Vascular Access Is Associated With Lower Survival and Neurologic Recovery Among Patients With Out-of-Hospital Cardiac Arrest

We seek to determine the effect of intraosseous over intravenous vascular access on outcomes after out-of-hospital cardiac arrest.

http://ift.tt/2EfUiT5

What Does It Take to Change an Editor’s Mind? Identifying Minimally Important Difference Thresholds for Peer Reviewer Rating Scores of Scientific Articles

We define a minimally important difference for the Likert-type scores frequently used in scientific peer review (similar to existing minimally important differences for scores in clinical medicine). The magnitude of score change required to change editorial decisions has not been studied, to our knowledge.

http://ift.tt/2F9MaFe

High-Velocity Nasal Insufflation in the Treatment of Respiratory Failure: A Randomized Clinical Trial

We compare high-velocity nasal insufflation, a form of high-flow nasal cannula, with noninvasive positive-pressure ventilation in the treatment of undifferentiated respiratory failure with respect to therapy failure, as indicated by requirement for endotracheal intubation or cross over to the alternative therapy.

http://ift.tt/2Eeyzen

Acute HIV Discovered During Routine HIV Screening With HIV Antigen-Antibody Combination Tests in 9 US Emergency Departments

Newer combination HIV antigen-antibody tests allow detection of HIV sooner after infection than previous antibody-only immunoassays because, in addition to HIV-1 and -2 antibodies, they detect the HIV-1 p24 antigen, which appears before antibodies develop. We determine the yield of screening with HIV antigen-antibody tests and clinical presentations for new diagnoses of acute and established HIV infection across US emergency departments (EDs).

http://ift.tt/2F8yCK2

The role of tryptophan metabolism in postpartum depression

Abstract

The Postpartum depression (PPD) is the most common postpartum psychiatric disorder, afflicting approximately 10%–20% of new mothers. Clinical symptoms of the PPD include depressive disorder, agitation, insomnia, anxiety and confusion, resulting in an increase in suicidal tendencies, thereby having significant impacts on the puerpera, newborn and their family. A growing body of data indicate a role for alterations in tryptophan metabolism in the PPD. The metabolism of tryptophan produces an array of crucial factors that can differentially regulate key physiological processes linked to the PPD. Importantly, an increase in stress hormones and immune-inflammatory activity drives tryptophan to the production of neuroregulatory kynurenine pathway products and away from the serotonin and melatonin pathways. This links the PPD to other disorders of depressed mood, which are classically associated with decreased serotonin and melatonin, coupled to increases in kynurenine pathway products. Several kynurenine pathway products, such as kynurenic acid and quinolinic acid, can have neuroregulatory effects, with consequences pathological underpinnings of the PPD. The current article reviews the role of alterations in tryptophan metabolism in the PPD.

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Prognostic Value of High-Sensitivity Versus Conventional Cardiac Troponin T Assays Among Patients With Type 2 Diabetes Mellitus Undergoing Maintenance Hemodialysis

Mortality is high among patients undergoing hemodialysis for whom cardiac troponin concentration is a strong predictor of outcome. Modern troponin assays allow measurement of very low concentrations.

http://ift.tt/2D1qDO1

Early Tissue Effects of Stereotactic Body Radiotherapy in Spinal Metastases

Stereotactic body radiotherapy (SBRT) is a highly effective and potentially ablative treatment for complex spinal metastases. Recent literature suggests radio-biologic effects of SBRT expanding beyond the traditional concept of DNA-damage. Anti-tumor immunity, vascular damage leading to tumor necrosis and increased rates of tumor apoptosis are implied, yet in-human evidence remains scarce. This study reports unique pathologic confirmation of SBRT-induced biologic effects within spinal metastases treated with pre-operative SBRT.

http://ift.tt/2Cy6LRJ

High prevalence of ESBL-Producing E. coli in private and shared latrines in an informal urban settlement in Dar es Salaam, Tanzania

Data about the burden of extended-spectrum beta-lactamase (ESBL)-producing microorganisms in Africa are limited. Our study aimed to estimate the prevalence of human faecal ESBL carriage in the community of an ...

http://ift.tt/2CJhpbI

Isolation, Culture, and Differentiation of Bone Marrow Stromal Cells and Osteoclast Progenitors from Mice

In this article, we present methods to isolate and differentiate bone marrow stromal cells and hematopoietic stem cells from mouse long bones. Two different protocols are presented yielding different cell populations suitable for expansion and differentiation into osteoblasts, adipocytes, and osteoclasts.

http://ift.tt/2Cz6qOR

Second Harmonic Generation Signals in Rabbit Sclera As a Tool for Evaluation of Therapeutic Tissue Cross-linking (TXL) for Myopia

This protocol describes techniques for evaluating chemical cross-linking of the rabbit sclera using second harmonic generation imaging and differential scanning calorimetry.

http://ift.tt/2qBsRkC

Gastritis staging in the endoscopic follow-up for the secondary prevention of gastric cancer: a 5-year prospective study of 1755 patients

Objective

Operative link on gastritis assessment (OLGA) staging for gastritis ranks the risk for gastric cancer (GC) in progressive stages (0–IV). This prospective study aimed at quantifying the cancer risk associated with each gastritis stage.

Design

A cohort of 1755 consecutive patients with dyspepsia underwent initial (T-0) oesophagogastroduodenoscopy with mapped gastric biopsies, OLGA staging and assessment of Helicobacter pylori infection. Patients were followed for 55 months (median); patients with stages II III and IV underwent a second endoscopy/restaging (T-1), and those with stages 0 and I were followed clinically and through in-depth clinical and record checking. Endpoints were OLGA stage at T-1 and development of gastric epithelial neoplasia.

Results

At T-0, 77.6% of patients had stage 0, 14.4% stage I, 5.1% stage II, 2.1% stage III and 0.85% stage IV. H. pylori infection was detected in 603 patients at T-0 and successfully eradicated in 602 of them; 220 had a documented history of H. pylori eradication; and 932 were H. pylori naïve-negative. Incident neoplastic lesions (prevalence=0.4%; low-grade intraepithelial neoplasia (IEN)=4; high-grade IEN=1; GC=2) developed exclusively in patients with stages III–IV. The risk for epithelial neoplasia was null in patients at stages 0, I and II (95% CI 0 to 0.4), 36.5 per 1000 person-years in patients at stage III (95% CI 13.7 to 97.4) and 63.1 per 1000 person-years in patients at stage IV (95% CI 20.3 to 195.6).

Conclusions

This prospective study confirms that OLGA staging reliably predicts the risk for development of gastric epithelial neoplasia. Although no neoplastic lesions arose in H. pylori-naïve patients, the H. pylori eradication in subjects with advanced stages (III–IV) did not abolish the risk for neoplastic progression.

http://ift.tt/2Eg7EPn

Efficacy of endoscopic screening for esophageal cancer in China (ESECC): design and preliminary results of a population-based randomised controlled trial

Objective

Description of the design and preliminary results of baseline recruitment and screening in the endoscopic screening for esophageal cancer in China (ESECC), the first randomised controlled trial (RCT) assessing efficacy and cost-effectiveness of endoscopic screening for esophageal squamous cell carcinoma (ESCC).

Design

ESECC trial is a cluster RCT, and 668 villages in rural Hua County, Henan Province, a high-incidence area of ESCC in China, were randomised into two arms at a ratio of 1:1. Screening arm participants were screened by Lugol chromoendoscopy; no screening was performed in the control arm. ESCC-specific and all-cause mortality, incidence of advanced ESCC and cost-effectiveness of screening will be evaluated in the next 10-year follow-up. Here, we report the performance of baseline recruitment and randomisation, prevalence of upper GI lesions and risk factors for ESCC.

Results

A total of 17 151 and 16 797 participants were enrolled in screening and control arms from January 2012 to September 2016. The truncated prevalence (aged 45–69 years) of oesophageal and overall upper GI high-grade lesions was 744.0/100 000 and 902.0/100 000. 69.9% of the 113 patients with high-grade oesophageal lesions were of early stage. Risk factors for severe oesophageal dysplasia and more severe lesions in this population included higher age, family history of ESCC, lower body mass index, eating rapidly and frequent ingestion of leftovers.

Conclusion

This ESECC trial met the predesigned recruitment and randomisation requirements. Age, family history, undernutrition and unhealthy dietary habits increased the risk for high-grade oesophageal lesions in this high-risk population.

Trail registration number

NCT01688908; Pre-results.

http://ift.tt/2F8WFbR

Long-term effects of thyroxine-induced hyperthyroidism on the histological attributes of the oviduct in broiler breeder hens

Abstract

A 4-week-long administration of extra thyroxine (T₄) in broiler breeder hens was recommended to lower the cold-induced ascites incidence in the progeny chicks. A hypothesis was tested that the long-term-induced hyperthyroidism might influence the histological traits of oviducts in the exposed hens. A total of 70 47-week-old Cobb 500 breeder hens were randomly allotted to two treatment groups (5 replicates of 7 hens each), including the control (CON) and hyperthyroid (HYPER). Thyroxine (T₄) was orally administered to the HYPER group (0.3 mg/bird day⁻¹) for 100 successive days; whereas the CON group received the drinking water only throughout the trial. At 64 weeks of age, two birds per replicate were cervically dislocated and their oviducts were removed for histological sectioning and staining. Results showed that secretory cells were detected in the anterior infundibulum and the number of secretory cells in the hyperthyroid hens was smaller than that of the control group. Thyroxine-treated hens recorded a decreased number of tubular glands in the magnum as compared to that of the control hens. The circular muscle layer of isthmus showed a more regular arrangement in the control in comparison with the T₄-treated hens. Additionally, the number of uterine tubular glands in the hyperthyroid group was lower than that of the counterparts. A decline in the vaginal epithelial thickness in the hyperthyroid hens was also recorded as compared to the control birds. Overall, the long-term administration of thyroxine was associated with considerable impacts on different parts of the oviduct. The question as to what extent the long-term maternal hyperthyroidism might affect the basal metabolic rate, egg production, fertility rate, duration of fertility, hatchability, and the chick quality remains open to make a final decision on exploitation of this preventative treatment to diminish the ascites incidence in progeny chicks.

http://ift.tt/2qtyGka

Is Ki67 still a powerful ally in predicting the clinical benefit of anthracyclines for the adjuvant treatment of early breast cancer?

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A Cunning Foe

(See pages 156—7 for the Answer to the Photo Quiz.)

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Cover

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News

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In the Literature

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A Cunning Foe

(See pages 154–5 for the Photo Quiz.)

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The Critical Importance of Sampling Fraction to Inferences of Mycobacterium tuberculosis Transmission

To the Editor—In the study by Manson et al [1], whole-genome sequencing was performed on 223 Mycobacterium tuberculosis isolates from the Tiruvallur and Madurai districts of India. They subsequently examined local strain diversity and mutations associated with phenotypic drug resistance in these regions. In this important study, the authors show that lists of published resistance mutations (including [2–4]) have lower positive predictive values for phenotypic resistance in this context; lineages 1 and 3 predominate in India [1], but these published mutations were largely identified using strains from different M. tuberculosis lineages. This highlights a key obstacle to the implementation of genomics for resistance prediction in India and potentially other endemic regions with diverse lineages of M. tuberculosis. By extension, this study emphasizes the critical need to collect strains and categorize the mutations circulating in these regions to better inform such predictions.

http://ift.tt/2m5k460

Reply to Lee and Howden

To the Editor—We thank Dr Lee and Prof Howden for their letter and for giving us an opportunity to better articulate our interpretation of findings, especially with respect to transmission of Mycobacterium tuberculosis among patients within 2 southern Indian districts. Based on analysis of single nucleotide polymorphism (SNP) differences between 223 M. tuberculosis strains from 196 patients within the Thiruvallur and Madurai districts of Tamil Nadu, we report recent intradistrict, but no recent interdistrict, transmission of strains among patients. In drawing these conclusions, we limited our interpretation to the data available to us, which showed that the closest SNP distance between M. tuberculosis isolated from patients in different districts was 85 SNPs, which is substantially higher than the very small numbers of SNPs (as few as 0) observed when comparing isolates from patients treated in the same district and treatment center.

http://ift.tt/2qtoica

In- and Out-of-hospital Mortality Associated with Seasonal and Pandemic Influenza and Respiratory Syncytial Virus in South Africa, 2009–2013

Abstract

Background

Estimates of influenza- and respiratory syncytial virus (RSV)-associated mortality burden are important to guide policy for control. Data are limited on the contribution of out-of-hospital deaths to this mortality.

Methods

We modeled excess mortality attributable to influenza and RSV infection by applying regression models to weekly deaths from national vital statistics from 2009 through 2013, using influenza and RSV laboratory surveillance data as covariates. We fitted separate models for in- and out-of-hospital deaths.

Results

There were 509791 average annual deaths in South Africa, of which 44% (95% confidence interval [CI] 43%–45%) occurred out-of-hospital. Seasonal influenza and RSV all-cause mortality rates were 23.0 (95% CI 11.0–30.6) and 13.2 (95% CI 6.4–33.8) per 100000 population annually (2.3% [95%CI 2.3%–2.4%] and 1.3% [95% CI 1.2%–1.4%] of all deaths respectively). The peak mortality rate was in individuals aged ≥75 years (386.0; 95% CI 176.5–466.3) for influenza and in infants (143.4; 95% CI 0–194.8) for RSV. Overall, 63% (95% CI 62%–-65%) of seasonal influenza and 48% (95% CI 47%–49%) of RSV-associated deaths occurred out-of-hospital. Among children aged <5 years, RSV-associated deaths were more likely to occur in-hospital, whereas influenza-associated deaths were more likely to occur out-of-hospital. The mortality rate was 6.7 (95% CI 6.4–33.8) in the first influenza A(H1N1)pdm09 wave in 2009 and 20.9 (95% CI 6.4–33.8) in the second wave in 2011, with 30% (95% CI 29%–32%) of A(H1N1)pdm09-associated deaths in 2009 occurring out-of-hospital.

Discussion

More than 45% of seasonal influenza- and RSV-associated deaths occur out-of-hospital in South Africa. These data suggest that hospital-based studies may substantially underestimate mortality burden.

http://ift.tt/2m5fV1Y

Call for Action: Invasive Fungal Infections Associated With Ibrutinib and Other Small Molecule Kinase Inhibitors Targeting Immune Signaling Pathways

Abstract

Opportunistic infections caused by Pneumocystis jirovecii, Cryptococcus neoformans, and ubiquitous airborne filamentous fungi have been recently reported in patients with hematological cancers historically considered at low risk for invasive fungal infections (IFIs), after receipt of the Bruton tyrosine kinase inhibitor ibrutinib. The spectrum and severity of IFIs often observed in these patients implies the presence of a complex immunodeficiency that may not be solely attributed to mere inhibition of Bruton tyrosine kinase. In view of the surge in development of small molecule kinase inhibitors for treatment of malignant and autoimmune diseases, it is possible that there would be an emergence of IFIs associated with the effects of these molecules on the immune system. Preclinical assessment of the immunosuppressive effects of kinase inhibitors and human studies aimed at improving patient risk stratification for development of IFIs could lead to prevention, earlier diagnosis, and better outcomes in affected patients.

http://ift.tt/2qBz54g

The Effect of Female Sex on Hepatitis C Incidence Among People Who Inject Drugs: Results From the International Multicohort InC3 Collaborative

Abstract

Background

The objective of this study was to assess differences in hepatitis C virus (HCV) incidence by sex in people who inject drugs (PWID), using a large international multicohort set of pooled biological and behavioral data from prospective observational studies of incident human immunodeficiency virus (HIV) and HCV infections in high-risk cohorts (the InC3 Collaborative).

Methods

HCV infection date was estimated based on a hierarchy of successive serological (anti-HCV), virological (HCV RNA), and clinical (symptoms and/or liver function tests) data. We used a Cox proportional hazards model to calculate the crude and adjusted female to male (F:M) hazard ratio (HR) for HCV incidence using biological sex as the main exposure.

Results

A total of 1868 PWID were observed over 3994 person-years of observation (PYO). Unadjusted F:M HR was 1.38 (95% confidence interval [CI], 1.15–1.65) and remained significant after adjusting for behavioral and demographic risk factors (1.39 [95% CI, 1.12–1.72]). Although syringe and equipment sharing were associated with the highest HCV incidence rate in women (41.62 and 36.83 PYO, respectively), we found no sex differences attributed to these risk factors.

Conclusions

Our findings indicate that women who inject drugs may be at greater risk of HCV acquisition than men, independent of demographic characteristics and risk behaviors. Multiple factors, including biological (hormonal), social network, and differential access to prevention services, may contribute to increased HCV susceptibility in women who inject drugs.

http://ift.tt/2m4sASK

Machine Learning for Healthcare: On the Verge of a Major Shift in Healthcare Epidemiology

Abstract

The increasing availability of electronic health data presents a major opportunity in healthcare for both discovery and practical applications to improve healthcare. However, for healthcare epidemiologists to best use these data, computational techniques that can handle large complex datasets are required. Machine learning (ML), the study of tools and methods for identifying patterns in data, can help. The appropriate application of ML to these data promises to transform patient risk stratification broadly in the field of medicine and especially in infectious diseases. This, in turn, could lead to targeted interventions that reduce the spread of healthcare-associated pathogens. In this review, we begin with an introduction to the basics of ML. We then move on to discuss how ML can transform healthcare epidemiology, providing examples of successful applications. Finally, we present special considerations for those healthcare epidemiologists who want to use and apply ML.

http://ift.tt/2qtofgu

Improvement in Diagnosis of Histoplasma Meningitis by Combined Testing for Histoplasma Antigen and Immunoglobulin G and Immunoglobulin M Anti-Histoplasma Antibody in Cerebrospinal Fluid

Abstract

Background

Central nervous system (CNS) histoplasmosis is a life-threatening condition and represents a diagnostic and therapeutic challenge. Isolation of Histoplasma capsulatum from cerebrospinal fluid (CSF) or brain tissue is diagnostic; however, culture is insensitive and slow growth may result in significant treatment delay. We performed a retrospective multicenter study to evaluate the sensitivity and specificity of a new anti-Histoplasma antibody enzyme immunoassay (EIA) for the detection of IgG and IgM antibody in the CSF for diagnosis of CNS histoplasmosis, the primary objective of the study. The secondary objective was to determine the effect of improvements in the Histoplasma galactomannan antigen detection EIA on the diagnosis of Histoplasma meningitis.

Methods

Residual CSF specimens from patients with Histoplasma meningitis and controls were tested for Histoplasma antigen and anti-Histoplasma immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody using assays developed at MiraVista Diagnostics.

Results

A total of 50 cases and 157 controls were evaluated. Fifty percent of patients with CNS histoplasmosis were immunocompromised, 14% had other medical conditions, and 36% were healthy. Histoplasma antigen was detected in CSF in 78% of cases and the specificity was 97%. Anti-Histoplasma IgG or IgM antibody was detected in 82% of cases and the specificity was 93%. The sensitivity of detection of antibody by currently available serologic testing including immunodiffusion and complement fixation was 51% and the specificity was 96%. Testing for both CSF antigen and antibody by EIA was the most sensitive approach, detecting 98% of cases.

Conclusions

Testing CSF for anti-Histoplasma IgG and IgM antibody complements antigen detection and improves the sensitivity for diagnosis of Histoplasma meningitis.

http://ift.tt/2m5TTvP

Relationship Between Viremia and Specific Organ Damage in Ebola Patients: A Cohort Study

Abstract

Background

Pathogenesis of Ebola virus disease remains poorly understood. We used concomitant determination of routine laboratory biomarkers and Ebola viremia to explore the potential role of viral replication in specific organ damage.

Methods

We recruited patients with detectable Ebola viremia admitted to the EMERGENCY Organizzazione Non Governativa Organizzazione Non Lucrativa di Utilità Sociale (ONG ONLUS) Ebola Treatment Center in Sierra Leone. Repeated measure of Ebola viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), activated prothrombin time (aPTT), international normalized ratio (INR), creatinine, and blood urea nitrogen (BUN) were recorded. Patients were followed up from admission until death or discharge.

Results

One hundred patients (49 survivors and 51 nonsurvivors) were included in the analysis. Unadjusted analysis to compare survivors and nonsurvivors provided evidence that all biomarkers were significantly above the normal range and that the extent of these abnormalities was generally higher in nonsurvivors than in survivors. Multivariable mixed-effects models provided strong evidence for a biological gradient (suggestive of a direct role in organ damage) between the viremia levels and either ALT, AST, CPK LDH, aPTT, and INR. In contrast, no direct linear association was found between viremia and either creatinine, BUN, or bilirubin.

Conclusions

This study provides evidence to support that Ebola virus may have a direct role in muscular damage and imbalance of the coagulation system. We did not find strong evidence suggestive of a direct role of Ebola virus in kidney damage. The role of the virus in liver damage remains unclear, but our evidence suggests that acute severe liver injury is not a typical feature of Ebola virus disease.

http://ift.tt/2qyl9bd

Disability Among Ebola Survivors and Their Close Contacts in Sierra Leone: A Retrospective Case-Controlled Cohort Study

Abstract

Ebola survivors (21/27 [77.8%]) suffered more disability than their close contacts (6/54 [11.1%]) (adjusted odds ratio, 23.5 [95% confidence interval, 6.5–85.7]; P < .001) when measured by the Washington Group Disability Extended Questionnaire. Major limitations in vision, mobility, cognition, and affect were observed in survivors 1 year following the 2014–2016 Ebola outbreak, highlighting the need for long-term rehabilitation.

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A Novel Human Pegivirus, HPgV-2 (HHpgV-1), Is Tightly Associated With Hepatitis C Virus (HCV) Infection and HCV/Human Immunodeficiency Virus Type 1 Coinfection

Abstract

Background

Human pegivirus type 2 (HPgV-2) is a novel blood-borne human pegivirus that mainly infects hepatitis C virus (HCV)–infected subjects. We have investigated the prevalence of HPgV-2 in China, its association with HCV and human immunodeficiency virus type 1 (HIV-1), and the impact on HCV viral load and liver damage.

Methods

A cross-sectional study was conducted with both blood donors and HCV- and HIV-1–infected patients in Guangzhou, China. All subjects were screened for anti-HPgV-2 and HPgV-2 RNA. Demographic and clinical information were obtained from electronic medical records.

Results

We tested 8198 serum or plasma samples. Only 0.15% (6/4017) of healthy blood donors were positive for anti-HPgV-2 and negative for HPgV-2 RNA. No HPgV-2 viremia was detected in hepatitis B virus– or HIV-1–monoinfected individuals. The relatively high frequency of HPgV-2 infection was observed in 1.23% (30/2440) and 0.29% (7/2440) of HCV-infected persons by serological assay and reverse-transcription polymerase chain reaction, respectively. Furthermore, anti-HPgV-2 and HPgV-2 RNA were detected in 8.91% (18/202) and 3.47% (7/202), respectively, of HCV/HIV-1–coinfected subjects. HPgV-2 persistent infection was documented in about 30% of anti-HPgV-2–positive individuals. In addition, HPgV-2 infection may not affect HCV-related liver injury and HCV viral load.

Conclusions

Our results indicate the rarity of HPgV-2 infection in the general population and tight association with HCV, in particular with HCV/HIV-1 coinfection. HPgV-2 appears not to worsen HCV-related liver damage. Our study provides new findings about the association of HPgV-2 and HCV/HIV-1 and the impact of HPgV-2 infection on HCV replication and pathogenesis.

http://ift.tt/2qyrC5Y

Higher Mortality Despite Early Antiretroviral Therapy in Human Immunodeficiency Virus and Hepatitis B Virus (HBV)–Coinfected Patients With High HBV Replication

Abstract

Background

In human immunodeficiency virus (HIV)–infected patients, hepatitis B virus (HBV) coinfection increases the risk of disease progression. Tenofovir plus emtricitabine/lamivudine (TDF/XTC)–based antiretroviral therapy (ART), which suppresses HIV and HBV replication, has the potential for decreasing this risk. Here, we analyze the association between HBV replication, early ART, and mortality in West African adults.

Methods

The Temprano randomized controlled trial assessed the benefits of immediately initiating vs deferring ART in HIV-infected adults with high CD4 counts. After trial completion, participants continued follow-up in a posttrial phase. We analyzed the association between HBV status, immediate ART, and mortality over the entire trial and posttrial follow-up using multivariable Cox proportional hazards regression.

Results

A total of 2052 HIV-infected adults (median baseline CD4 count, 464 cells/μL) were followed for 9394 person-years. At baseline, 1862 (91%) were HIV monoinfected and 190 (9%) HIV/HBV coinfected. Of the latter, 135 (71%) had plasma HBV DNA <2000 IU/mL and 55 (29%) HBV DNA ≥2000 IU/mL. The 60-month probability of death was 11.8% (95% confidence interval [CI], 5.4%–24.5%) in coinfected patients with HBV DNA ≥2000 IU/mL; 4.4% (95% CI, 1.9%–10.4%) in coinfected patients with HBV DNA <2000 IU/mL; and 4.2% (95% CI, 3.3%–5.4%) in HIV-monoinfected patients. Adjusting for ART strategy (immediate vs deferred), the hazard ratio of death was 2.74 (95% CI, 1.26–5.97) in coinfected patients with HBV DNA ≥2000 IU/mL and 0.90 (95% CI, .36–2.24) in coinfected patients with HBV DNA <2000 IU/mL compared to HIV-monoinfected patients. There was no interaction between ART strategy and HBV status for mortality.

Conclusions

African HIV/HBV-coinfected adults with high HBV replication remain at heightened risk of mortality in the early ART era. Further studies are needed to assess interventions combined with early ART to decrease mortality in this population.

Clinical Trials Registration

NCT00495651

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Epidemiology, Clinical Features, and Outcome of Infective Endocarditis due to Abiotrophia Species and Granulicatella Species: Report of 76 Cases, 2000–2015

Abstract

Background

Infective endocarditis (IE) caused by Abiotrophia (ABI) and Granulicatella (GRA) species is poorly studied. This work aims to describe and compare the main features of ABI and GRA IE.

Methods

We performed a retrospective study of 12 IE institutional cases of GRA or ABI and of 64 cases published in the literature (overall, 38 ABI and 38 GRA IE cases).

Results

ABI/GRA IE represented 1.51% of IE cases in our institution between 2000 and 2015, compared to 0.88% of HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella)–related IE and 16.62% of Viridans group streptococci (VGS) IE. Institutional ABI/GRA IE case characteristics were comparable to that of VGS, but periannular complications were more frequent (P = .008). Congenital heart disease was reported in 4 (10.5%) ABI and in 11 (28.9%) GRA cases (P = .04). Mitral valve was more frequently involved in ABI than in GRA (P < .001). Patient sex, prosthetic IE, aortic involvement, penicillin susceptibility, and surgical treatment were comparable between the genera. New-onset heart failure was the most frequent complication without genera differences (P = .21). Five (13.2%) ABI patients and 2 (5.3%) GRA patients died (P = .23). Factors associated with higher mortality were age (P = .02) and new-onset heart failure (P = .02). The genus (GRA vs ABI) was not associated with higher mortality (P = .23).

Conclusions

GRA/ABI IE was more prevalent than HACEK IE and approximately one-tenth as prevalent as VGS; periannular complications were more frequent. GRA and ABI genera IE presented similar clinical features and outcomes. Overall mortality was low, and related to age and development of heart failure.

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Cost Drivers of a Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Phase 3 Clinical Trial

Abstract

Background

Studies indicate that the prevalence of multidrug-resistant infections, including hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), has been rising. There are many challenges associated with these disease conditions and the ability to develop new treatments. Additionally, HABP/VABP clinical trials are very costly to conduct given their complex protocol designs and the difficulty in recruiting and retaining patients.

Methods

With input from clinicians, representatives from industry, and the US Food and Drug Administration, we conducted a study to (1) evaluate the drivers of HABP/VABP phase 3 direct and indirect clinical trial costs; (2) to identify opportunities to lower these costs; and (3) to compare (1) and (2) to endocrine and oncology clinical trials. Benchmark data were gathered from proprietary and commercial databases and used to create a model that calculates the fully loaded (direct and indirect) cost of typical phase 3 HABP/VABP endocrine and oncology clinical trials.

Results

Results indicate that the cost per patient for a 200-site, 1000-patient phase 3 HABP/VABP study is $89600 per patient. The cost of screen failures and screen failure rates are the main cost drivers.

Conclusions

Results indicate that biopharmaceutical companies and regulatory agencies should consider strategies to improve screening and recruitment to decrease HABP/VABP clinical trial costs.

http://ift.tt/2m40zuI

Reply to Gupta-Wright et al

We thank Gupta-Wright et al for their insightful comments on our article and enthusiastically echo many of their points [1, 2]. Indeed, we share their concern regarding the difficulty of ruling out tuberculosis coinfection among patients with confirmed disseminated nontuberculous mycobacterial (NTM) infection who have a positive Determine TB-LAM lateral flow assay (LF-LAM) result. For that reason, in our high-burden tuberculosis setting, it is our policy to always err on the side of initially treating such patients for both infections while continuing to search for definitive evidence of tuberculosis coinfection.

http://ift.tt/2qAuNde

Urinary Lipoarabinomannan Detection and Disseminated Nontuberculous Mycobacterial Disease

To the Editor—We read with interest Nel and colleagues' article, "Does disseminated nontuberculous mycobacterial disease cause false-positive Determine TB-LAM lateral flow assay results? A retrospective review" [1]. The authors present an important finding relevant to clinicians who manage patients with advanced human immunodeficiency virus (HIV). Although we agree that disseminated nontuberculous mycobacterial (NTM) disease needs to be considered in patients with positive Determine TB-LAM lateral flow assay (LF-LAM) results, we urge that the implications for clinical practice be considered in the context of what is known about the relative incidence of tuberculosis and NTM disease in high HIV burden settings. Disseminated NTM disease is almost exclusively observed in patients with extreme immunosuppression (median CD4 count consistently <50 cells/μL, often <10 cells/μL) [2], has always been uncommon in HIV-infected patients in Africa, and has become more rare in the era of combination antiretroviral therapy (ART).

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Aspiring paramedics, nurses, doctors join new year of EMS training program

By Emma Discher The Advocate BATON ROUGE, La. — Aaron Bogan is only a freshman at Denham Springs High School, but he already knows he wants to pursue a medical career. In order to solidify his future plans, Bogan is considering becoming one of the newest certified first responders in Baton Rouge through the Emergency Medical Services Explorer program. Since 1983, the program, organized under the ...

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A case of Shewanella algae endocarditis: an emerging pathogen with a diverse clinical spectrum

Shewanella algae is a rare pathogen related to water exposure in temperate climates. It is commonly associated with skin and soft tissue infections, peritonitis and bacteraemia. We report the first-ever case of S. algae infective endocarditis in a patient with previous splenectomy and explore the difficulties in treatment as well as highlight the importance of this organism as an emerging pathogen.

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Management of homozygous familial hypercholesterolaemia in two brothers

Homozygous familial hypercholesterolaemia (HoFH) is a rare, genetic disorder of abnormally high levels of low-density lipoprotein cholesterol (LDL-C) requiring aggressive interventions to retard the evolution of atherosclerotic cardiovascular disease. We treated two brothers (ages 46 years and 47 years) with HoFH with statins, lipoproteinapheresis (LA) and the microsomal triglyceride transfer protein inhibitor lomitapide. Both brothers carried the p.Thr434Arg homozygous LDLR mutation and had childhood total cholesterol levels >700 mg/dL. Inter-LA LDL-C levels remained high; therefore, they were given escalating doses of oral lomitapide (5–10 mg/day). One brother was able to maintain LDL-C levels <70 mg/dL and stop LA. Lomitapide was well tolerated, with only an episode of headache requiring dose reduction from 40 mg/day to 20 mg/day in one patient. In two HoFH cases, lomitapide was an effective and well-tolerated adjunct therapy. Lomitapide doses required to maintain LDL-C goal levels appear to be lower in clinical practice than in clinical trials.

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Colovesical fistula: a rare complication after renal transplantation

Colovesical fistula per se is a rare condition and most commonly occurs secondary to diverticular disease in normal patients. Colovesical fistula in the setting of post-renal transplantation is even rarer and very few cases have been reported in literature. Patients with autosomal-dominant polycystic kidney disease (ADPKD) are predisposed to diverticulosis and hence are at a higher risk for fistula formation. Herein, we report a case of colovesical fistula in a renal allograft recipient with ADPKD in the absence of diverticulosis. The patient was successfully operated and is stable with no complications at 1-year follow-up.

http://ift.tt/2m6l5dR

Successful management of a 24-year-old pregnant woman with necrotising fasciitis of the forearm

A 24-year-old woman who was 24 weeks pregnant presented to the emergency department with septic shock and an elbow wound that had become infected. She sustained an injury to the tip of the right elbow on a light switch 4 days prior. In the space of 1 day, she developed a necrotising soft tissue infection, which was rapidly spread to the forearm with florid sepsis. Her initial serum C reactive protein was 392 mg/L, and white cell count was 32x10⁹/L. The patient was treated promptly with aggressive surgical debridement and broad-spectrum antibiotics. An early multidisciplinary approach including orthopaedic surgeons, anaesthetics, intensive care, obstetrics, microbiologists and paediatrics was taken. Ultimately, both mother and child had an excellent outcome, the former of whom only had minimal soft tissue resection and primary wound closure. Emphasis is made on first treating the mother as the patient and priority.

http://ift.tt/2qus5pS

Mycophenolate mofetil treatment in a patient with recurrent lymphocytic hypophysitis

Lymphocytic hypophysitis (LHP) is a relatively rare disease characterised by lymphocytic infiltration of the pituitary gland, resulting in pituitary dysfunction. LHP is generally responsive to corticosteroid therapy, but cases with recurrence require clinicians to select second-line therapy. We report here the case of a 58-year-old patient with LHP who developed panhypopituitarism and bitemporal hemianopia. He responded to prednisolone 40 mg/day but relapsed during tapering. The prednisolone dose was increased again and mycophenolate mofetil (MMF) was added. Thereafter, over the course of 1 year, prednisolone was tapered to 8 mg/day without relapse. Because of the rarity of LHP, there are no standard treatment protocols that support the choice of a specific immunosuppressive drug. MMF was effective for recurrent LHP in our case. Further accumulation of cases is needed to establish the standard treatment for this disease.

http://ift.tt/2m53Rhc

Ureteral intramural metastatic deposit of prostate cancer with ureteric obstruction

True metastatic ureteric lesions are exceptionally rare when sourced from any primary tumour. Primary prostatic cancer metastasis to the ureter is understandably even more atypical with very few cases reported in current literature. True intramural ureteric metastatic disease deposited from prostate cancer is an even rarer occurrence. We present a case of a man in his mid-60s with left-sided hydronephrosis in the setting of biochemical recurrence of Gleason 9 prostate cancer. Initially misdiagnosed as obstruction secondary to mass effect from a large trigonal lesion, subsequent investigation revealed solid intramural metastatic deposit of prostate primary tumour in the distal ureter. We detail current hypotheses regarding the subsequent pathophysiology of the disease and its common clinical presentations. Our case highlights that prostatic metastasis should be considered as a differential in coexisting prostate cancer and ureteric obstruction despite its low incidence.

http://ift.tt/2qx6LA2

Guillain-Barre syndrome with exaggerated pleocytosis and anti-GM1 ganglioside antibodies

An 81-year-old man presented with fever, confusion and rapidly-progressive flaccid tetraparesis. Clinical presentation and neurophysiology were consistent with a severe axonal polyneuropathy. Anti-GM1 and Campylobacter serology were both positive, consistent with postinfectious axonal-variant Guillain-Barré syndrome (GBS). GBS is characterised by albuminocytological dissociation, where an elevated protein and acellular cerebrospinal fluid are typical. However, in this case, CSF analysis revealed an exaggerated pleocytosis (72 white blood cells (WBC)/mm³). No source of central nervous system infection or inflammation was identified despite thorough investigation. The patient was treated with intravenous immunoglobulin and intensive rehabilitation.

Albuminocytological dissociation classically distinguishes GBS from infective causes of flaccid weakness (eg, enteroviruses, flaviviruses and HIV). Diagnostic criteria frequently cite a pleocytosis of <50 WBC/mm³ as required in the diagnosis of GBS. However, this case demonstrates that pleocytosis exceeding this level can occur in the presence of convincing evidence of GBS and without demonstrable neurotropic infection.

http://ift.tt/2m6yy5J

Neonatal small left colon syndrome (NSLCS): Rare but important complication in an infant of diabetic mother

Description

A female infant born at 35+6 weeks by caesarean section to a mother with poorly controlled type 1 diabetes was admitted to the neonatal unit due to hypoglycaemia. Birth weight was 3.2 kg (91–98th centile). On day 1, the baby required a glucose load of 10 mg/kg/min to maintain normoglycaemia. By day 2, her blood sugar levels stabilised, feeds were started and intravenous fluids were weaned. With the introduction of feeds, she had milky vomits and abdominal distension. Feeds were stopped and an abdominal X-ray showed a dilated transverse colon with an abrupt transition zone at splenic flexure (figure 1, arrow indicates transition zone). Symptoms resolved after passage of a large, thick plug of mucus and meconium that resembled an intestinal cast (figure 2). 

Figure 1

Patient's plain abdominal X-ray. There is a dilated transverse colon and calibre change at the splenic flexure indicates...

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Trichosporon asahii septic thrombophlebitis following lower extremity amputation in an immunocompetent host

A 59-year-old man with a history of peripheral vascular disease status post femoral popliteal bypass presented with critical limb ischaemia of the left leg. An arterial Doppler ultrasound showed an occluded graft requiring an above knee amputation. Five days after surgery, the patient developed fever, leucocytosis, significant stump swelling and pain, and serosanguinous discharge from his wound. Wound swab cultures from the stump grew Trichosporon asahii. A venous Doppler ultrasound revealed extensive thrombosis of the left lower extremity. Biopsy of the left thigh muscle showed necrotic thrombus with fungal hyphae in the clotted blood vessel. The left femoral vein was subsequently resected, and the excised venous tissue also grew T. asahii. The patient was successfully treated with voriconazole based on antifungal susceptibilities. This case describes an invasive fungal infection in the absence of typical immunosuppressive conditions commonly associated with Trichosporon spp. It also illustrates the role of a combination of antimicrobial and surgical management in achieving cure.

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Laparoscopic Versus Open Liver Resection for Colorectal Liver Metastases—Which Is a More Suitable Standard Practice?

No abstract available

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Using Confidential Clinical Data Registries for Public Reporting and Pay for Performance

No abstract available

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Corrigendum

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http://ift.tt/2Cz5UA6

Mechanism of recipient cell-dependent differences in exosome uptake

Abstract

Background

Exosomes, small-membrane vesicles, are secreted by cells and include several types of proteins and nucleic acids. Exosomes transfer cellular information derived from donor cells and are involved in various physiological and pathological events, such as organ-specific metastasis. Elucidating the exosome uptake mechanisms is important for understanding the progression processes of organ-specific metastasis. However, whether the exosomes secreted by the donor cells are selectively or non-selectively incorporated into the recipient cells is unknown.

Methods

In this study, three human carcinoma cell lines, A549 (lung), HCT116 and COLO205 (colon), were used. The exosome isolation efficiency was compared between three methods: ultracentrifugation, ExoQuick-TC and Total Exosome Isolation kits. Recipient cells were treated with Pitstop 2, an inhibitor of clathrin-dependent endocytosis, or genistein, an inhibitor of caveolae-dependent endocytosis, and then incubated with DiO-labeled exosomes.

Results

Among the three methods examined, ultracentrifugation was the most efficient and reproducible. Exosomes derived from a donor cell line are incorporated into the three cell lines, but the exosome uptake capability was different depending on the recipient cell type and did not depend on the donor cell type. Exosome uptake in COLO205 was inhibited by Pitstop 2 and genistein. Exosome uptake in HCT116 was inhibited by Pitstop 2, but not genistein, while that in A549 cells was not inhibited by these inhibitors. Taken together, these results suggest that the exosomes secreted by donor cells are non-selectively incorporated into recipient cells and that the exosome uptake mechanism is different depending on the recipient cells.

Conclusions

Different recipient cells' exosome uptake capabilities may be involved in organ-specific metastasis.

http://ift.tt/2qB8kwW

Gene-expression signature regulated by the KEAP1-NRF2-CUL3 axis is associated with a poor prognosis in head and neck squamous cell cancer

Abstract

Background

NRF2 is the key regulator of oxidative stress in normal cells and aberrant expression of the NRF2 pathway due to genetic alterations in the KEAP1 (Kelch-like ECH-associated protein 1)-NRF2 (nuclear factor erythroid 2 like 2)-CUL3 (cullin 3) axis leads to tumorigenesis and drug resistance in many cancers including head and neck squamous cell cancer (HNSCC). The main goal of this study was to identify specific genes regulated by the KEAP1-NRF2-CUL3 axis in HNSCC patients, to assess the prognostic value of this gene signature in different cohorts, and to reveal potential biomarkers.

Methods

RNA-Seq V2 level 3 data from 279 tumor samples along with 37 adjacent normal samples from patients enrolled in the The Cancer Genome Atlas (TCGA)-HNSCC study were used to identify upregulated genes using two methods (altered KEAP1-NRF2-CUL3 versus normal, and altered KEAP1-NRF2-CUL3 versus wild-type). We then used a new approach to identify the combined gene signature by integrating both datasets and subsequently tested this signature in 4 independent HNSCC datasets to assess its prognostic value. In addition, functional annotation using the DAVID v6.8 database and protein-protein interaction (PPI) analysis using the STRING v10 database were performed on the signature.

Results

A signature composed of a subset of 17 genes regulated by the KEAP1-NRF2-CUL3 axis was identified by overlapping both the upregulated genes of altered versus normal (251 genes) and altered versus wild-type (25 genes) datasets. We showed that increased expression was significantly associated with poor survival in 4 independent HNSCC datasets, including the TCGA-HNSCC dataset. Furthermore, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and PPI analysis revealed that most of the genes in this signature are associated with drug metabolism and glutathione metabolic pathways.

Conclusions

Altogether, our study emphasizes the discovery of a gene signature regulated by the KEAP1-NRF2-CUL3 axis which is strongly associated with tumorigenesis and drug resistance in HNSCC. This 17-gene signature provides potential biomarkers and therapeutic targets for HNSCC cases in which the NRF2 pathway is activated.

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Stromal CD10 expression in breast cancer correlates with tumor invasion and cancer stem cell phenotype

Abstract

Background

Previous investigations have indicated that CD10 is associated with biological aggressivity in human cancers, but the use of this marker for diagnosis and prognosis is more complex. The aim of this study was to evaluate the expression of CD10 in breast cancer and its association with the clinicopathological features. In addition, we investigated whether a relationship exists between CD10 expression and cancer stem cells.

Methods

CD10 expression was examined by the immunohistochemistry in a series of 133 invasive breast carcinoma cases. Results were correlated to several clinicopathological parameters. Cancer stem cell phenotype was assessed by the immunohistochemical analysis of CD44 and ALDH1.

Results

Significant CD10 expression was found in the fusiform stromal cells in 19.5% of the cases and in the neoplastic cells in 7% of the cases. The stromal CD10 positivity was more frequently found in tumors with lymph node metastasis (p = 0.01) and a high histological grade (p = 0.01). However, CD10 expression by the neoplastic cells correlates with a high histological grade (p = 0.03) and the absence of estrogen (p = 0.002) as well as progesterone (p = 0.001) receptor expression.

We also found that CD10 expression by the stromal cells, but not by the neoplastic cells, correlates significantly with the expression of cancer stem cell markers (CD44+/ALDH1+) (p = 0.002).

Conclusion

These findings support the role of the stromal CD10 expression in breast cancer progression and dissemination, and suggest a relationship with cancer stem cells.

http://ift.tt/2qvwTv3

A train the trainer program for healthcare professionals tasked with providing psychosocial support to breast cancer survivors

Abstract

Background

The objective of this study is to develop, implement, and evaluate a training program for healthcare providers to improve ability to provide psychosocial support to breast cancer survivors in Korea.

Methods

Based on a needs assessment survey and in-depth interviews with breast cancer survivors, a multidisciplinary team developed two-day intensive training program as well as education materials and counseling notes. Participants' overall satisfaction was evaluated after the training.

Results

The training program included a total of 16 lectures held over the course of seven sessions. Forty-one nurses and 3 social workers participated in the training program. Mean age was 37.5(± 6.4) years, and on average, they had 11.1 (± 5.6) years of experience. Participants' overall satisfaction was good as following: program contents (4.04), trainee guidebook (3.82), location and environment (4.10), and program organization (4.19). Among the participants, 31 (70.4%) received certification after submitting real consultation cases after the training.

Conclusion

Two day intensive training can provide a comprehensive and coordinated education to healthcare professionals for implementing survivorship care with an emphasis on psychosocial support. Furthermore, the program should resume as a periodic continuing education course for healthcare providers. Similar education for graduate students in oncology nursing would be beneficial.

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Incidence of bone metastases in patients with solid tumors: analysis of oncology electronic medical records in the United States

Abstract

Background

Bone metastases commonly occur in conjunction with solid tumors, and are associated with serious bone complications. Population-based estimates of bone metastasis incidence are limited, often based on autopsy data, and may not reflect current treatment patterns.

Methods

Electronic medical records (OSCER, Oncology Services Comprehensive Electronic Records, 569,000 patients, 52 US cancer centers) were used to identify patients ≥18 years with a solid tumor diagnosis recorded between 1/1/2004 and 12/31/2013, excluding patients with hematologic tumors or multiple primaries. Each patient's index date was set to the date of his or her first solid tumor diagnosis in the selection period. Kaplan-Meier analyses were used to quantify the cumulative incidence of bone metastasis with follow-up for each patient from the index date to the earliest of the following events: last clinic visit in the OSCER database, occurrence of a new primary tumor or bone metastasis, end of study (12/31/2014). Incidence estimates and associated 95% confidence intervals (CI) are provided for up to 10 years of follow-up for all tumor types combined and stratified by tumor type and stage at diagnosis.

Results

Among 382,733 study patients (mean age 64 years; mean follow-up 940 days), breast (36%), lung (16), and colorectal (12%) tumors were most common. Mean time to bone metastasis was 400 days (1.1 years). Cumulative incidence of bone metastasis was 2.9% (2.9–3.0) at 30 days, 4.8% (4.7–4.8) at one year, 5.6% (5.5–5.6) at two years, 6.9% (6.8–7.0) at five years, and 8.4% (8.3–8.5) at ten years. Incidence varied substantially by tumor type with prostate cancer patients at highest risk (18% – 29%) followed by lung, renal or breast cancer. Cumulative incidence of bone metastasis increased by stage at diagnosis, with markedly higher incidence among patients diagnosed at Stage IV of whom11% had bone metastases diagnosed within 30 days.

Conclusions

These estimates of bone metastasis incidence represent the experience of a population with longer follow-up than previously published, and represent experience in the recent treatment landscape. Underestimation is possible given reliance on coded diagnoses but the clinical detail available in electronic medical records contributes to the accuracy of these estimates.

http://ift.tt/2qywKHa

Relationship between the extent of resection and the survival of patients with low-grade gliomas: a systematic review and meta-analysis

Abstract

Background

Surgical resection is necessary to conduct a pathological biopsy and to achieve a reduction of intracranial pressure in low-grade gliomas patients. This study aimed to determine whether a greater extent of resection would increase the overall 5-year and 10-year survival of patients with low-grade gliomas.

Methods

The studies addressing relationship between the extent of resection and the prognosis of low-grade gliomas updated until March 2017 were systematically searched in two databases (Pubmed and EMBASE). The relationships among categorical variables were analyzed using an odds ratio (OR) and a95% confidence interval (CI). Significance was established using CIs at a level of 95% or P < 0.05. Funnel plot was used to detect the publication bias.

Results

Twenty articles (a total of 2128 patients) were identified. The meta-analysis showed that the 5-year (Odds ratio (OR), 3.90;95% Confidence Interval (CI), 2.79~5.45; P < 0.01; Z = 7.95) and 10-year OS (OR, 7.91; 95%CI, 5.12~12.22; P < 0.01; Z = 9.33) associated with gross total resection (GTR) were higher than those associated with subtotal resection (STR). Similarly, as compared with biopsy(BX), the 5-year and 10-year OS were higher after either GTR (5-year: OR, 5.43; 95%CI, 3.57~8.26; P < 0.01; Z = Z = 7.9; 10-year: OR, 10.17; 95%CI, 4.02~25.71; P < 0.00001; Z = 4.9) or STR (5-year: OR, 2.59; 95%CI, 1.81~ − 3.71; P < 0.00001; Z = 5.19; 10-year: OR, 2.21; 95%CI, 1.164.25; P = 0.02; Z = 2.39).

Conclusions

Our research found that a greater extent of resection could significantly increase the OS of patients with low-grade gliomas.

http://ift.tt/2m6RVvv

A multicentre survey of the antibiotic susceptibility of clinical Bacteroides species from Hungary

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Risk factors, outcomes and genotypes of carbapenem-nonsusceptible Klebsiella pneumoniae bloodstream infection: a three-year retrospective study in a large tertiary hospital in Northern China

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http://ift.tt/2m4M7m6

Changes in the microbiological epidemiology of febrile neutropenia in autologous stem cell transplant recipients

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http://ift.tt/2qCLTrd

Goldmann tonometry tear film error and partial correction with a shaped applanation surface

http://ift.tt/2qB02oI

Prognostic factors in Chinese patients with prostate cancer receiving primary androgen deprivation therapy: validation of Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score and impacts of pre-existing obesity and diabetes mellitus

Abstract

Purpose

Our aim was to determine the prognostic factors in Chinese patients with prostate cancer receiving primary androgen deprivation therapy (PADT), validate the Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score, and investigate the impacts of pre-existing obesity and diabetes mellitus (DM).

Methods

The study enrolled Chinese patients diagnosed with prostatic adenocarcinoma and treated with bilateral orchiectomy as PADT at Huashan Hospital, Fudan University (Shanghai, China), from January 2003 to December 2015. The overall survival (OS) and prognostic value of J-CAPRA score, pre-existing obesity, DM, and various clinicopathological variables were analyzed.

Results

Of the 435 patients enrolled, 174 (40.0%) deaths occurred during follow-up; 3- and 5-year OS were 74.0 and 58.9%, respectively. Multivariate analysis identified that higher Gleason score and metastasis were both correlated with worse OS and that higher J-CAPRA score was correlated with worse OS [hazard ratio (HR) 1.110, 95% confidence interval (CI) 1.035–1.190, P = 0.003). Different risk categories based on J-CAPRA score showed good stratification in OS (log-rank P = 0.015). In subgroup analysis, pre-existing obesity as a protective factor in younger patients (age ≤ 65, HR 0.271, 95% CI 0.075–0.980, P = 0.046) and pre-existing DM as a risk factor in older patients (> 75, HR 1.854, 95% CI 1.026–3.351, P = 0.041) for OS were recognized, and the prediction accuracy of J-CAPRA was elevated after incorporating pre-existing obesity and DM.

Conclusions

The J-CAPRA score presented with good OS differentiation among Chinese patients under PADT. Younger patients (age ≤ 65) had better OS with pre-existing obesity, while older patients (age > 75) had worse OS with pre-existing DM.

http://ift.tt/2CIeShY

Modulation of lateral and longitudinal interdimeric interactions in microtubule models by Laulimalide and Peloruside A association. A molecular modeling approach on the mechanism of microtubule stabilizing agents

Abstract

Laulimalide (LAU) and Peloruside A (PLA) are non-taxane microtubule stabilizing agents with promising antimitotic properties. These ligands promote the assembly of microtubules (MTs) by targeting a unique binding site on β-tubulin. The X-ray structure for LAU/PLA-tubulin association was recently elucidated but little information is available regarding the role of these ligands as modulators of interdimeric interactions across MTs. Herein we report the use of Molecular Dynamics (MD), Principal Component Analysis (PCA), MM/GBSA binding free energy calculations, and computational Alanine Scanning Mutagenesis (ASM) to examine effect of LAU/PLA association on lateral and longitudinal contacts between tubulin dimers in reduced MT models. MD and PCA results revealed that LAU/PLA exerts a strong restriction of lateral and longitudinal interdimeric motions, thus enabling the stabilization of the MT lattice. Besides structural effects, LAU/PLA induces a substantial strengthening of longitudinal interdimeric interactions, whereas lateral contacts are less affected by these ligands, as revealed by MM/GBSA and ASM calculations. These results are valuable to increase understanding about the molecular features involved in MT stabilization by LAU/PLA, and to design novel compounds capable of emulating the mode of action of these ligands.

This article is protected by copyright. All rights reserved.

MD simulations revealed that Laulimalide and Peloruside A association induce a strong restriction in the lateral and longitudinal interdimeric motion between tubulin dimers in reduced microtubule models, which can be related to the stabilization of the microtubule lattice. According to MM/GBSA calculations, Laulimalide and Peloruside A strengthen the longitudinal interdimeric association, whereas lateral interactions are less affected by these ligands.

http://ift.tt/2m37vbp

Clinical characteristics and mutation analysis of five Chinese patients with maple syrup urine disease

Abstract

Maple syrup urine disease (MSUD) is an autosomal recessive disorder affecting branched-chain amino acids (BCAAs) metabolism and caused by a defect in the thiamine-dependent enzyme branched chain α-ketoacid dehydrogenase (BCKD) with subsequent accumulation of BCAAs and corresponding branched-chain keto acids (BCKAs) metabolites. Presently, at least 4 genes of BCKDHA, BCKDHB, DLD and DBT have been reported to cause MSUD. Furthermore, more than 265 mutations have been identified as the cause across different populations worldwide. Some studies have reported the data of gene mutations in Chinese people with MSUD. In this study, we present clinical characteristics and mutational analyses in five Chinese Han child with MSUD, which had been screened out by tandem mass spectrometry detection of amino acids in blood samples. High-throughput sequencing, Sanger sequence and real-time qualitative PCR were performed to detect and verify the genetic mutations. Six different novel genetic variants were validated in BCKDHB gene and BCKDHA gene, including c.523 T > C, c.659delA, c.550delT, c.863G > A and two gross deletions. Interestingly, 3 cases had identical mutation of BCKDHB gene (c.659delA). We predicted the pathogenicity and analyzed the clinical characteristics. The identification of these mutations in this study further expands the mutation spectrum of MSUD and contributes to prenatal molecular diagnosis of MSUD.

http://ift.tt/2m4ob2e

Changing Versus Protecting the Status Quo: Why Men and Women Engage in Different Types of Action on Behalf of Women

Abstract

We investigate women's and men's willingness to engage in action on behalf of women, and we identify two distinct categories of behavior: action that aims to challenge gender inequality (feminist action) and action that aims to protect women from violence (protective action). Three online studies were conducted. For each study, a U.S. community sample was recruited. In Study 1 (n = 602), women reported greater intentions to engage in feminist action than men did. Men, however, were just as willing as women to participate in protective action. In Study 2 (n = 726), we replicated these gender differences and found that protective action was positively predicted by benevolent sexism among men. In Study 3 (N = 582), we investigated why women reported greater intentions to engage in feminist action compared to men. We found that women were more aware of gender inequality, which was associated with identification as a feminist, and through this, intentions to engage in feminist action. Awareness of gender inequality also predicted intentions to engage in protective action among women. Men, however, were less aware of gender inequality, which was associated with the belief that feminist action leads to women having more rights than men do and subsequently greater willingness to participate in protective action. Our results can assist social policymakers and activists to develop appropriate campaigns for gender equality if their goal is to challenge, rather than protect women from, the status quo.

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Response to ‘Aprepitant and fosaprepitant decrease the effectiveness of hormonal contraceptives’

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Comment on “Use of antibiotics during pregnancy and the risk of major congenital malformations: a population based cohort study” by Muanda et al.

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Fatal prescription charts

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Migrant perinatal depression study: a prospective cohort study of perinatal depression on the Thai-Myanmar border

Purpose

Perinatal depression is a significant contributor to maternal morbidity. Migrant women in resource-poor settings may be at increased risk, yet little research has been conducted in low-income and middle-income settings. This prospective cohort study of migrant women on the Thai-Myanmar border aims to establish prevalence of perinatal depression, identify risk factors for perinatal depression and examine associations with infant outcomes.

Participants

Participating women are labour migrants and refugees living on the Thai-Myanmar border. A total of 568 women were recruited in their first trimester of pregnancy and are being followed up to 1-year postpartum.

Findings to date

At baseline, women in our study had a median age of 25 years, the predominant ethnicity was Sgaw Karen (48.9%), agriculture was the main employment sector (39.2%) and educational attainment was low with a median of 4 years of education. In the first trimester of pregnancy, a quarter (25.8%; 95% CI 22.3 to 29.5) of all women were depressed as diagnosed by the Structured Clinical Interview for the Diagnosis of DSM-IV Disorders.

Future plans

Follow-up is ongoing and expected to continue until January 2018. The prevalence of depression at later stages of pregnancy and during the first postpartum year will be identified, and associations between depression status and demographic, social, migration-related, medical, obstetric and infant factors will be quantified.

Trial registration number

NCT02790905.

http://ift.tt/2AB36kw

Comparative efficacy and tolerability of new-generation antidepressants for major depressive disorder in children and adolescents: protocol of an individual patient data meta-analysis

Introduction

Although previous conventional meta-analyses and network meta-analyses have provided some important findings about pharmacological treatments for children and adolescents with depressive disorders in the past decades, several questions still remain unsolved by the aggregate data from those meta-analyses. Individual participant data meta-analysis (IPD-MA) enables exploration of the impacts of individual characteristics on treatment effects, allowing matching of treatments to specific subgroups of patients. We will perform an IPD-MA to assess the efficacy and tolerability of new-generation antidepressants for major depressive disorder in children and adolescents.

Methods and analysis

We will systematically search for all double-blind randomised controlled trials (RCTs) that have compared any new-generation antidepressant with placebo for the acute treatment of major depressive disorder in children and adolescents, in the following databases: PubMed, EMBASE, the Cochrane Library, PsycINFO, Web of Science, CINAHL, LILACS and ProQuest Dissertations. We will contact all corresponding authors of included RCTs and ask for their cooperation in this project by providing individual participant data from the original trials. The primary outcomes will include efficacy, measured as the mean change of depression symptoms by Children's Depression Rating Scale Revised (CDRS-R), and tolerability, measured as the proportion of patients who withdrew from the trials early due to adverse effects. The secondary outcomes will include response rates, remission rates, deterioration rate, all-cause discontinuation, suicidal-related outcomes and global functioning outcome. Using the raw de-identified study data, we will use mixed-effects logistic and linear regression models to perform the IPD-MAs. The risk of bias of included studies will be assessed using the Cochrane risk of bias tool. We will also detect the publication bias and effects of non-participation of eligible studies.

Dissemination

Ethical approval is not required given that informed consent has already been obtained from the patients by the trial investigators before the included trials were conducted. This study may have considerable implications for practice and help improve patient care.

PROSPERO registration number

CRD42016051657.

http://ift.tt/2qtyQYR