Is Conversion of a Failed IPAA to a Continent Ileostomy a Risk Factor for Long-term Failure?

BACKGROUND: A continent ileostomy may be offered to patients in hopes of avoiding permanent ileostomy. Data on the outcomes of continent ileostomy patients with a history of a failed IPAA are limited. OBJECTIVE: This study aimed to assess whether a history of previous failed IPAA had an effect on continent ileostomy survival and the long-term outcomes. DESIGN: This was a retrospective cohort study. SETTINGS: This investigation took place in a high-volume, specialized colorectal surgery department. PATIENTS: Patients who underwent continent ileostomy construction after IPAA failure between 1982 and 2013 were evaluated and compared with patients who have no history of IPAA surgery. MAIN OUTCOME MEASURES: Functional outcomes and long-term complications were compared. RESULTS: A total of 67 patients fulfilled the case-matching criteria and were included in the analysis. Requirement of major (52% vs 61%; p = 0.756) and minor (15% vs 19%; p = 0.492) revisions were comparable between patients who had continent ileostomy after a failed IPAA and those who had continent ileostomy without having a previous restorative procedure. Intubations per day (5 vs 5; p = 0.804) and per night (1 vs 1; p = 0.700) were similar in both groups. Our data show no clear relationship between failure of continent ileostomy and history of failed IPAA (p = 0.638). The most common cause of continent ileostomy failure was enterocutaneous/enteroenteric fistula (n = 14). Six patients died during the study period because of other causes unrelated to continent ileostomy. LIMITATIONS: This study was limited by its retrospective and nonrandomized nature. CONCLUSIONS: Converting a failed IPAA to a continent ileostomy did not worsen continent ileostomy outcomes in this selected group of patients. When a redo IPAA is not feasible, continent ileostomy can be offered as an alternative to conventional end ileostomy in highly motivated patients. See Video Abstract at http://bit.ly/2Mh20Sg.

http://bit.ly/2szMRm2

What Every Colorectal Surgeon Should Know About the American Society of Colon and Rectal Surgeons’ Physician Compensation Survey

No abstract available

http://bit.ly/2MogXlL

Industry-Sponsored Studies and Conflict of Interest

No abstract available

http://bit.ly/2szLWls

Impact of the American Society of Colon and Rectal Surgeons’ Research Foundation Grants on Academic Colorectal Surgeons’ Career Trajectory

No abstract available

http://bit.ly/2MgEQLU

Topical Oxymetazoline for Fecal Incontinence in Patients with Spinal Cord Injury: A Double-Blind Randomized Controlled Crossover Study

BACKGROUND: Topical α-agonists contract the internal anal sphincter muscle; therefore, they may serve as treatment for fecal incontinence. OBJECTIVES: The aim of this study was to investigate the effect of the α-agonist oxymetazoline 1.0% on fecal incontinence in patients with spinal cord injury. DESIGN: This was a double-blind, crossover study. Before randomization, all patients underwent a 1-day, open-label anal manometry and pharmacokinetic study. SETTINGS: The study was conducted at the Department of Internal Medicine, Semmelweis University, Hungary. PATIENTS: Nineteen patients were enrolled into a randomized double-blind, placebo-controlled clinical trial with 2 arms: placebo for 4 weeks followed by oxymetazoline for 4 weeks, or vice versa, with an interval 2-week washout period, in a crossover trial design. Treatment order was randomly assigned, and fecal incontinence was captured with daily diaries. MAIN OUTCOME MEASURES: The primary outcome measured was the number of fecal incontinence episodes in the 8 and 12 hours after drug administration. RESULTS: Resting anal pressure increased in response to oxymetzoline (25.2%). The change in the mean fecal incontinence episodes per month (12 hours post drug application) favored oxymetazoline over placebo: 26.3 (SD ±28.4) versus 36 (SD ±39.8) (p = 0.021). When only nongas episodes were included, the mean number of episodes decreased from 10.1 (+4.3) to 6.3 (±2.1) fecal incontinence episodes per month (p = 0.022). No difference was observed in adverse events between treatment and placebo periods. All pharmacokinetic samples were below the detection limit. LIMITATIONS: The study was limited by the small number of participants. CONCLUSIONS: In this study, oxymetazoline gel presented a clear clinical beneficial effect accompanied by a favorable safety and tolerability profile. Results of the pharmacokinetic analysis indicate that the clinical benefit was mainly due to a local effect of oxymetazoline. Future studies are planned to investigate higher doses of oxymetazoline for this indication. See Video Abstract at http://bit.ly/2MjuUkH.

http://bit.ly/2szMDeG

The American Society of Colon and Rectal Surgeons’ Clinical Practice Guidelines for the Management of Pilonidal Disease

No abstract available

http://bit.ly/2svbwrS

Head-Mounted Mixed-Reality Technology During Robotic-Assisted Transanal Total Mesorectal Excision

INTRODUCTION: Head-mounted mixed-reality technologies may enable advanced intraoperative visualization during visceral surgery. In this technical note, we describe an innovative use of real-time mixed reality during robotic-assisted transanal total mesorectal excision. TECHNIQUE: Video signals from the robotic console and video endoscopic transanal approach were displayed on a virtual monitor using a head-up display. The surgeon, assistant, and a surgical trainee used this technique during abdominal and transanal robotic-assisted total mesorectal excision. We evaluated the feasibility and usability of this approach with the use of validated scales. RESULTS: The technical feasibility of the real-time visualization provided by the current setup was demonstrated for both the robotic and transanal parts of the surgery. The surgeon, assistant, and trainee each used the mixed-reality device for 15, 55, and 35 minutes. All participants handled the device intuitively and reported a high level of comfort during the surgery. The task load was easily manageable (task load index:

http://bit.ly/2MfQsPh

Announcements

No abstract available

http://bit.ly/2Mi8xw2

Expert Commentary on Diagnosis and Management of Parastomal Hernias

No abstract available

http://bit.ly/2szrh12

Assessing the Value of Endoscopy Simulator Modules Designed to Prepare Residents for the Fundamentals of Endoscopic Surgery Examination

BACKGROUND: The Fundamentals of Endoscopic Surgery examination is required for all general surgery residents. The test modules are not available for practice before the examination; however, similar modules are commercially available. OBJECTIVE: This study aims to determine which modules are most valuable for resident training and preparation for the examination by evaluating which correlates best with experience level. DESIGN: This was a single-institution study. SETTING: A virtual reality endoscopy simulator was utilized. PARTICIPANTS: General surgery residents and faculty endoscopists performed endoscopy simulator modules (Endobasket 2, Endobubble 1 and 2, Mucosal Evaluation 2, and Basic Navigation) designed to prepare residents for the Fundamentals of Endoscopic Surgery examination. Residents were assigned into junior and senior groups based on the completion of a dedicated endoscopy rotation. MAIN OUTCOME MEASURES: The primary outcomes measured were the mean time to completion, mean number of balloons popped, and mean number of wall hits for the 3 groups. RESULTS: A total of 21 junior residents, 11 senior residents, and 3 faculty participated. There were significant differences among groups in the mean time to completion for the Endobasket, Endobubble, and Mucosal Evaluation modules. The modules that correlated best with experience level were Endobubble 2 and Mucosal Evaluation 2. For Endobubble 2, juniors were slower than seniors, who were in turn slower than faculty (junior 118.8 ± 20.55 seconds, senior 100.3 ± 11.78 seconds, faculty 87.67 ± 2.848 seconds; p

http://bit.ly/2MfH3qZ

Magnetic Resonance Texture Analysis in Identifying Complete Pathological Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer

BACKGROUND: A certain proportion of patients with locally advanced rectal cancer experience complete response after undergoing neoadjuvant chemoradiotherapy. These patients might be suitable for a conservative "watch and wait" approach, avoiding high-morbidity surgery. Texture analysis is a new modality that can assess heterogeneity in medical images by statistically analyzing gray-level intensities on a pixel-by-pixel basis. This study hypothesizes that texture analysis of magnetic resonance images can identify patients with a complete response. OBJECTIVE: This study aims to determine whether texture analysis of magnetic resonance images as a quantitative imaging biomarker can accurately identify patients with complete response. DESIGN: This is a retrospective diagnostic accuracy study. SETTINGS: This study was conducted at Colchester General Hospital, January 2003 to 2014. PATIENTS: All patients diagnosed with locally advanced rectal cancer who underwent long-course chemoradiotherapy had a posttreatment magnetic resonance scan and underwent surgery are included. INTERVENTION: Texture analysis was extracted from T2-weighted magnetic resonance images of the rectal cancer. MAIN OUTCOME MEASURES: Textural features that are able to identify complete responders were identified by a Mann-Whitney U test. Their diagnostic accuracy in identifying complete responders was determined by the area under the receiver operator characteristics curve. Cutoff values were determined by the Youden index. Pathology was the standard of reference. RESULTS: One hundred fourteen patients with first posttreatment MRI scans (6.2 weeks after completion of neoadjuvant treatment) were included. Sixty-eight patients had a second posttreatment scan (10.4 weeks). With no filtration, mean (p = 0.033), SD (p = 0.048), entropy (p = 0.007), and skewness (p = 0.000) from first posttreatment scans, and SD (p = 0.042), entropy (p = 0.014), mean of positive pixels (p = 0.032), and skewness (p = 0.000) from second posttreatment scans were all able to identify complete response. Area under the curve ranged from 0.750 to 0.88. LIMITATIONS: Texture analysis of MRI is a new modality; therefore, further studies are necessary to standardize the methodology of extraction of texture features, timing of scans, and acquisition parameters. CONCLUSIONS: Texture analysis of MRI is a potentially significant imaging biomarker that can accurately identify patients who have experienced complete response and might be suitable for a nonsurgical approach. (Cinicaltrials.gov:NCT02439086). See Video Abstract at http://bit.ly/2MivYoR.

http://bit.ly/2swdAjt

Partial Stapled Hemorrhoidopexy Versus Circumferential Stapled Hemorrhoidopexy for Grade III to IV Prolapsing Hemorrhoids: A Randomized, Noninferiority Trial

BACKGROUND: Long-term outcomes and efficacy of partial stapled hemorrhoidopexy are not known. OBJECTIVE: The purpose of this study was to compare the long-term clinical efficacy and safety of partial stapled hemorrhoidopexy with circumferential stapled hemorrhoidopexy. DESIGN: This was a parallel group, randomized, noninferiority clinical trial. SETTINGS: The study was conducted at a single academic center. PATIENTS: Patients with grade III/IV hemorrhoids between August 2011 and November 2013 were included. INTERVENTIONS: Three hundred patients were randomly assigned to undergo either partial stapled hemorrhoidopexy (group 1, n = 150) or circumferential stapled hemorrhoidopexy (group 2, n = 150). MAIN OUTCOME MEASURES: The primary outcome was the rate of recurrent prolapse at a median follow-up period of 5 years with a predefined noninferiority margin of 3.75%. Secondary outcomes included incidence and severity of postoperative pain, fecal urgency, anal continence, and the frequency of specific complications, including anorectal stenosis and rectovaginal fistula. RESULTS: The visual analog scores in group 1 were less than those in group 2 (p

http://bit.ly/2stAkAC

Clinical Implications of Pretreatment: Lymphocyte-to-Monocyte Ratio in Patients With Rectal Cancer Receiving Preoperative Chemoradiotherapy

BACKGROUND: Despite advances in local control of rectal cancer, recurrence in distant organs is still one of the main causes of mortality. Prognostic biomarkers would be valuable for the treatment of patients who have rectal cancer. OBJECTIVE: The aim of our study was to investigate the prognostic impact of lymphocyte-to-monocyte ratio in patients with rectal cancer receiving preoperative chemoradiotherapy, and to clarify the clinical significance of lymphocyte-to-monocyte ratio. DESIGN: Prospectively maintained data of patients with rectal cancer were retrospectively evaluated to clarify the clinical relevance of the lymphocyte-to-monocyte ratio. SETTING: This study was conducted at a single expert center. PATIENTS: A total of 119 consecutive patients with rectal cancer through chemoradiotherapy followed by total mesorectal excision at our institute were enrolled in this study. Eight patients were excluded because of a lack of laboratory data, and finally 111 patients were assessed in this study. MAIN OUTCOME MEASURES: The primary outcome measured was the clinical relevance of the lymphocyte-to-monocyte ratio in patients with rectal cancer receiving chemoradiotherapy. RESULTS: Patients with a low pretreatment lymphocyte-to-monocyte ratio showed poor prognosis significantly both in overall survival and disease-free survival of those with rectal cancer receiving chemoradiotherapy. Multivariate analyses showed that low pretreatment lymphocyte-to-monocyte ratio level, presence of pathological lymph node metastasis (ypN(+)), and high pretreatment serum C-reactive protein level were independent prognostic factors of overall survival and disease-free survival. In addition, time-to-event analysis divided into 2 groups by ypN status showed that low pretreatment lymphocyte-to-monocyte ratio was correlated with poor overall survival and disease-free survival not only in group ypN(–) but also in group ypN(+). LIMITATIONS: The present study had several limitations, including that it was a retrospective observational and single institutional study with Japanese patients. CONCLUSIONS: The combination of lymphocyte-to-monocyte ratio and ypN status can be a predictive marker of poor prognosis and recurrence among patients with rectal cancer undergoing preoperative chemoradiotherapy. See Video Abstract at http://bit.ly/2szc1B7.

http://bit.ly/2MgeQjK

Should They Stay or Should They Go? The Utility of C-Reactive Protein in Predicting Readmission and Anastomotic Leak After Colorectal Resection

BACKGROUND: Hospital readmission and anastomotic leak following colorectal resection have a negative impact on patients, surgeons, and the health care system. Novel markers of patients unlikely to experience these complications are of value in avoiding readmission. OBJECTIVE: This study aimed to determine the predictive value of C-reactive protein for readmission and anastomotic leak within 30 days following colorectal resection. DESIGN: This is a retrospective review of a prospectively compiled single-institution database. PATIENTS: From January 1, 2013, to July 20, 2017, consecutive patients undergoing elective colorectal resection with anastomosis without the presence of proximal intestinal stoma, who had C-reactive protein measured on postoperative day 3, were included. MAIN OUTCOME MEASURES: The primary outcome measured was the predictive value of C-reactive protein measured on postoperative day 3 for readmission or anastomotic leak within 30 days after colorectal resection. RESULTS: Of the 752 patients examined, 73 (10%) were readmitted within 30 days of surgery and 17 (2%) had an anastomotic leak. Mean C-reactive protein in patients who neither had an anastomotic leak nor were readmitted (127 ± 77 mg/L) was lower than for patients who were readmitted (157 ± 96 mg/L, p = 0.002) and lower than for patients who had an anastomotic leak (228 ± 123 mg/L, p = 0.0000002). The area under the receiver operating characteristic curve for the diagnostic accuracy of C-reactive protein for readmission was 0.59, with a cutoff value of 145 mg/L, generating a 93% negative predictive value. The area under the curve for the diagnostic accuracy of C-reactive protein for anastomotic leak was 0.76, with a cutoff value of 147 mg/L generating a 99% negative predictive value. LIMITATIONS: This study was limited by its retrospective design and because all patients were treated at a single center. CONCLUSIONS: Patients with a C-reactive protein below 145 mg/L on postoperative day 3 after colorectal resection have a low likelihood of readmission within 30 days, and a very low likelihood of anastomotic leak. See Video Abstract at http://bit.ly/2sxNPiH.

http://bit.ly/2MiE7tI

Lymphovascular Invasion and Perineural Invasion Negatively Impact Overall Survival for Stage II Adenocarcinoma of the Colon

BACKGROUND: Lymphovascular invasion and perineural invasion are histopathological features associated with higher-risk colon cancer. OBJECTIVE: The purpose of this study was to quantify the impact of lymphovascular and perineural invasion on overall survival after diagnosis and to determine the protective effect of adjuvant chemotherapy for early adenocarcinoma with high-risk factors. DESIGN: This was a retrospective database review of the 2010–2014 National Cancer Database for colon cancer. SETTINGS: Individuals diagnosed with invasive adenocarcinoma of the colon (histology code 8140) with primary surgical resection with >12 nodes harvested and no positive nodes on pathological examination were included. PATIENTS: A total of 32,493 patients underwent surgical resection for stage II adenocarcinoma of the colon. INTERVENTIONS: The study involved multivariate Cox regression analysis of the impact of lymphovascular and perineural invasion and adjuvant chemotherapy on overall survival after a diagnosis of stage II adenocarcinoma of the colon. MAIN OUTCOME MEASURES: Survival after a diagnosis of stage II adenocarcinoma of the colon was measured. RESULTS: Five-year survival after diagnosis and surgical resection without adjuvant chemotherapy was lower for patients with lymphovascular (60.0%), perineural (56.9%), and lymphovascular and perineural invasion (55.8%) compared with double-negative disease (66.1%). Log-rank testing confirmed that adjuvant chemotherapy improved 5-year survival after diagnosis for lymphovascular (85.5%), perineural (83.6%), and lymphovascular and perineural invasion (74.3%). After controlling for differences in cohorts, Cox regression analysis showed an increased HR for mortality of 14.0% for lymphovascular (HR = 1.141 (95% CI, 1.060–1.228)), 32.1% for perineural (HR = 1.321 (95% CI, 1.176–1.483)), and 41.0% for lymphovascular and perineural invasion (HR = 1.409 (95% CI, 1.231–1.612)) compared with having neither. Chemotherapy showed a 43% reduction in hazard for mortality (HR = 0.570 (95% CI, 0.513–0.633)). LIMITATIONS: The study was limited by its retrospective review and observational bias. CONCLUSIONS: Lymphovascular and perineural invasion have a detrimental effect on survival after diagnosis of stage II adenocarcinoma of the colon. Chemotherapy may be protective specifically when lymphovascular and perineural invasion are present. See Video Abstract at http://bit.ly/2szrgdu.

http://bit.ly/2MlMjJK

Fully Robotic Resection of a Splenic Flexure Tumor with Intracorporeal Anastomosis

No abstract available

http://bit.ly/2Mi8vEq

Outcomes of Patients with 3rd or Higher Relapsed Classical Hodgkin Lymphoma: Results from the German Hodgkin Study Group

http://bit.ly/2AS1SEm

Novel patterns of response under immunotherapy

Abstract

Novel patterns of response and progression to immunotherapy have been reported that are not observed with conventional cytotoxic or targeted anti-cancer treatments. A major breakthrough with immunotherapy is potential to achieve durable responses in a subset of patients with advanced cancer that can be maintained several years even after stopping treatment. No standardized definition of durable response exists in the literature, and the optimal duration of treatment in case of durable response is not clearly established. However, the majority of patients do not respond to immunotherapy. Initially reported in advanced melanoma patients, pseudoprogression occurs when tumor index lesions regress after initial progression, supporting the concept of treating some patients beyond progression. Overall, reported rates of pseudoprogression never exceed 10%, meaning that the large majority of patients who have a disease progression will not eventually respond to treatment. The decision to pursue treatment beyond progression must therefore only be taken in carefully selected patients with clinical benefit, who did not experience severe toxicities with immunotherapy. Conversely, rapid progressions, called hyperprogressions, were reported by several teams with rates ranging from 4% to 29%. These observations need to be confirmed from randomized trials. It is essential to interrupt treatment in patients with hyperprogression, in order to switch to another potentially active treatment. Finally, some patients experience dissociated responses, with some lesions shrinking and others growing. Local treatment with surgery or radiotherapy for growing lesions may be considered. Several immune specific related response criteria were developed to better capture benefits of immunotherapy. These criteria only address the pseudoprogression pattern of response, and do not capture the other patterns of response such as hyperprogression and dissociated response. The classic RECIST remains a reasonable and meaningful method to assess response to immunotherapy in the clinic.

http://bit.ly/2SZeujT

Contralateral breast irradiation in BRCA-carriers: the conundrum of prophylactic versus early treatment?

http://bit.ly/2ANdMz5

Brentuximab Vedotin and ESHAP is Highly Effective as Second-Line Therapy for Hodgkin Lymphoma Patients (Long-Term Results of a Trial by the Spanish GELTAMO Group)

Abstract

Purpose

In this work, we assessed the efficacy and safety of Brentuximab Vedotin (BV) plus ESHAP [BRESHAP] as second-line therapy for Relapsed/Refractory Hodgkin lymphoma RRHL to improve the results before autologous stem cell transplantation (ASCT).

Patients and Methods

This was a multicenter, open-label, phase I-II trial of patients with RRHL after first-line chemotherapy. Treatment had three 21-day cycles of etoposide, solumedrol, high-dose AraC, and cisplatin. BV was administered at three dose levels (0.9, 1.2 and 1.8 mg/kg) IV on day-1 to 3 + 3 cohorts of patients. Final BV dose was 1.8 mg/kg. Responding patients proceeded to ASCT, followed by three BV courses (1.8 mg/kg, every 21 days). Main endpoints for evaluation were maximum tolerable dose and overall and complete response before ASCT.

Results

66 patients were recruited (median age, 36yr; range, 18-66): 40 were primary refractory, 16 early relapse, and 10 late relapse. There were 39 severe adverse events were reported in 22 patients, most frequently fever (n = 25, 35% neutropenic), including three deaths. Grade 3-4 hematological toxicity presented in 28 cases: neutropenia (n = 21), thrombocytopenia (n = 14), and anemia (n = 7). Grade ≥3-4 extrahematological adverse events (≥5%) were: non-neutropenic fever (n = 13) and hypomagnesaemia (n = 3). 64 patients underwent stem cell mobilization; all collected >2·10e6/Kg CD34+ cells (median, 5.75; range, 2.12-33.4). Overall response before transplant was 91% (CI 84-98%), including 70% complete responses (CR, 95% CI 59-81%). 60 patients were transplanted with no failure engraftments. Post-transplant response was CR in 49 patients (82%, CI 73-91%) and partial responses in six (10%, CI 5-15%). After a mean follow-up of 27 months, the 30-month time to treatment to failure was 74% (95% CI, 68-80%), progression-free survival 71% (95% CI, 65-77%), and overall survival 91% (CI, 84-98%).

Conclusion

BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.

http://bit.ly/2SZsev9

Risk profiling based on p16 and HPV DNA more accurately predicts location of disease relapse in patients with oropharyngeal squamous cell carcinoma

Abstract

Background

In the era of precision medicine and HPV related oropharyngeal squamous cell carcinoma (OPSCC) it is relevant to assess the risk of not only survival, but also the risk of local, regional or distant treatment failure. The UICC 8^th edition uses the surrogate marker p16 to stratify for HPV association but discordance between p16 status and HPV association has been shown. The purpose of this study was to develop a prognostic model to predict the risk of local, regional, and distant metastases and non-cancer-related death for patients with OPSCC, test the prognostic relevance of adding HPV DNA and p16 status, and validate the findings in an independent external dataset.

Patients and methods

Consecutive patients diagnosed with OPSCC and treated with curative radiotherapy with or without cisplatin in eastern Denmark from 2000–2014 were included. Characteristics included age, gender, TNM stage, smoking habits, performance status, and HPV status assessed with p16 and HPV DNA. The information was used to develop a prognostic model for first site of failure with four competing events; recurrence in T-, N- and M-site, and death with no evidence of disease.

Results

Overall 1243 patients were eligible for the analysis. A prognostic model with the four events was developed and externally validated in an independent dataset with a heterogeneously treated patient population from another institution. The individual prognostication from the competing risk analysis is displayed in a user friendly online tool (https://rasmussen.shinyapps.io/OPSCCmodelHPV_p16/). Replacing p16 status with the combined variable HPV/p16 status influenced the HR and patients with HPV-/p16+ had significantly higher HR of M-site recurrence than HPV+/p16+ with a HR = 2.56; CI [1.30; 5.02]; p = 0.006(p = 0.013 in the validation cohort).

Conclusion

Patients with HPV-/p16+ have significantly higher risk of M-site recurrence and could potentially be relevant candidates for clinical trials testing systemic treatments in combination with conventional treatments.

http://bit.ly/2AT4EsQ

News

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Cover

http://bit.ly/2Dhze0T

In the Eye of the Beholder: A Conjunctival Lesion in a Woman With Acute Myelogenous Leukemia

http://bit.ly/2TRwjl0

In the Literature

http://bit.ly/2DhzaOH

Normative growth charts for Shwachman-Diamond syndrome from Italian cohort of 0-8 years old

Objectives

Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder. Its predominant manifestations include exocrine pancreatic insufficiency, bone marrow failure and skeletal abnormalities. Patients frequently present failure to thrive and susceptibility to short stature. Average birth weight is at the 25th percentile; by the first birthday, >50% of patients drop below the third percentile for height and weight.

The study aims at estimating the growth charts for patients affected by SDS in order to give a reference tool helpful for medical care and growth surveillance through the first 8 years of patient's life.

Setting and participants

This retrospective observational study includes 106 patients (64 M) with available information from birth to 8 years, selected among the 122 patients included in the Italian National Registry of SDS and born between 1975 and 2016. Gender, birth date and auxological parameters at repeated assessment times were collected. The General Additive Model for Location Scale and Shape method was applied to build the growth charts. A set of different distributions was used, and the more appropriate were selected in accordance with the smallest Akaike information criterion.

Results

A total of 408 measurements was collected and analysed. The median number of observations per patient amounted to 3, range 1–11. In accordance with the methods described, specific SDS growth charts were built for weight, height and body mass index (BMI), separately for boys and girls.

The 50th and 3rd percentiles of weight and height of the healthy population (WHO standard references) respectively correspond to the 97th and 50th percentiles of the SDS population (SDS specific growth charts), while the difference is less evident for the BMI.

Conclusions

Specific SDS growth charts obtained through our analysis enable a more appropriate classification of patients based on auxological parameters, representing a useful reference tool for evaluating their growth during childhood.

http://bit.ly/2DgAqBE

Towards sustainable healthcare system performance in the 21st century in high-income countries: a protocol for a systematic review of the grey literature

Introduction

There is wide recognition that, if healthcare systems continue along current trajectories, they will become harder to sustain. Ageing populations, accelerating rates of chronic disease, increasing costs, inefficiencies, wasteful spending and low-value care pose significant challenges to healthcare system durability. Sustainable healthcare systems are important to patients, society, policy-makers, public and private funders, the healthcare workforce and researchers. To capture current thinking about improving healthcare system sustainability, we present a protocol for the systematic review of grey literature to capture the current state-of-knowledge and to compliment a review of peer-reviewed literature.

Methods and analysis

The proposed search strategy, based on the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines, includes Google Advanced Search, snowballing techniques and targeted hand searching of websites of lead organisations such as WHO, Organisation for Economic Cooperation and Development, governments, public policy institutes, universities and non-government organisations. Documents will be selected after reviewing document summaries. Included documents will undergo full-text review. The following criteria will be used: grey literature document; English language; published January 2013–March 2018; relevant to the healthcare delivery system; the content has international or national scope in high-income countries. Documents will be assessed for quality, credibility and objectivity using validated checklists. Descriptive data elements will be extracted: identified sustainability threats, definitions of sustainability, attributes of sustainable healthcare systems, solutions for improvement and outcome measures of sustainability. Data will be analysed using novel text-mining methods to identify common concept themes and meanings. This will be triangulated with the more traditional analysis and concept theming by the researchers.

Ethics and dissemination

No primary data will be collected, therefore ethical approval will not be sought. The results will be disseminated in peer-reviewed literature, as conference presentations and as condensed summaries for policy-makers and health system partners.

PROSPERO registration number

CRD42018103076.

http://bit.ly/2DhSNGs

Depressive symptoms in people with vision impairment: a cross-sectional study to identify who is most at risk

Objective

To identify the risk factors for significant depressive symptoms in people with visual impairment in England and Wales to provide information on who is most at risk and to whom support services could be targeted in future.

Design

A cross-sectional study using baseline data from a pragmatic randomised controlled trial.

Setting and participants

990 participants aged 18 or over attending 1 of 14 low-vision rehabilitation primary care optometry-based clinics in South Wales or two hospital clinics in London.

Outcome measure

A score of ≥6 on the Geriatric Depression Scale-15 was classed as clinically significant depressive symptoms.

Results

In a multivariable logistic regression model, significant depressive symptoms were associated with age (adjusted OR (AOR)=0.82, 95% CI: 0.66 to 0.90, p<0.001), ethnicity (AOR non-white compared with white=1.72, 95% CI: 1.05 to 2.81, p=0.031), total number of eye conditions (AOR for two vs one condition=0.98, 95% CI: 0.67 to 1.43; three or more vs one condition=0.34, 95% CI: 0.15 to 0.75, p=0.026), self-reported health (AOR for excellent vs poor=0.01, 95% CI: 0.00 to 0.12; very good vs poor=0.06, 95% CI: 0.03 to 0.13; good vs poor=0.14, 95% CI: 0.08 to 0.24; fair vs poor=0.28, 95% CI: 0.18 to 0.46, p<0.001) and self-reported visual functioning (AOR=1.45, 95% CI: 1.31 to 1.61, p<0.001).

Conclusion

Younger age, a non-white ethnicity, fewer eye conditions and poorer self-reported health and visual function are risk factors for significant depressive symptoms in this population.

Trial registration number

ISRCTN46824140; Pre-results.

http://bit.ly/2TWWGWY

Correction: How do palliative care doctors recognise imminently dying patients? A judgement analysis

White N, Harries P, Harris AJ, et al. How do palliative care doctors recognise imminently dying patients? A judgement analysis. BMJ Open 2018;8:e024996. doi: 10.1136/bmjopen-2018-024996.

This article was previously published with an error.

Fiona Reid and Patrick Stone should be joint last authors.

http://bit.ly/2DhSHP6

Realist evaluation of the role of the Universal Health Coverage Partnership in strengthening policy dialogue for health planning and financing: a protocol

Introduction

In 2011, WHO, the European Union and Luxembourg entered into a collaborative agreement to support policy dialogue for health planning and financing; these were acknowledged as core areas in need of targeted support in countries' quest towards universal health coverage (UHC). Entitled 'Universal Health Coverage Partnership', this intervention is intended to strengthen countries' capacity to develop, negotiate, implement, monitor and evaluate robust and integrated national health policies oriented towards UHC. It is a complex intervention involving a multitude of actors working on a significant number of remarkably diverse activities in different countries.

Methods and analysis

The researchers will conduct a realist evaluation to answer the following question: How, in what contexts, and triggering what mechanisms, does the Partnership support policy dialogue for health planning and financing towards UHC? A qualitative multiple case study will be undertaken in Togo, Liberia, Democratic Republic of Congo, Cape Verde, Burkina Faso and Niger. Three steps will be implemented: (1) formulating context–mechanism–outcome explanatory propositions to guide data collection, based on expert knowledge and theoretical literature; (2) collecting empirical data through semistructured interviews with key informants and observations of key events, and analysing data; (3) specifying the intervention theory.

Ethics and dissemination

The primary target audiences are WHO and its partner countries; international and national stakeholders involved in or supporting policy dialogues in the health sector, especially in low-income countries; and researchers with interest in UHC, policy dialogue, evaluation research and/or realist evaluation.

http://bit.ly/2TWPCcy

Effect of work schedule on prospective antidepressant prescriptions in Sweden: a 2-year sex-stratified analysis using national drug registry data

Introduction

Depression-related mood disorders affect millions of people worldwide and contribute to substantial morbidity and disability, yet little is known about the effects of work scheduling on depression. This study used a large Swedish survey to prospectively examine the effects of work schedule on registry-based antidepressant prescriptions in females and males over a 2-year period.

Methods

The study was based on an approximately representative sample (n=3980 males, 4663 females) of gainfully employed participants in the Swedish Longitudinal Occupational Survey of Health. Sex-stratified analyses were conducted using logistic regression. For exposure, eight categories described work schedule in 2008: 'regular days' (three categories of night work history: none, ≤3 years, 4+ years), 'night shift work', 'regular shift work (no nights)', 'rostered work (no nights)', 'flexible/non-regulated hours' and 'other'. For the primary outcome measure, all prescriptions coded N06A according to the Anatomical Therapeutic Chemical System were obtained from the Swedish National Prescribed Drug Register and dichotomised into 'any' or 'no' prescriptions between 2008 and 2010. Estimates were adjusted for potential sociodemographic, health and work confounders, and for prior depressive symptoms.

Results

In 2008, 22% of females versus 19% of males worked outside of regular daytime schedule. Registered antidepressant prescription rates in the postsurvey period were 11.4% for females versus 5.8% for males. In fully adjusted models, females in 'flexible/non-regulated' schedules showed an increased OR for prospective antidepressant prescriptions (OR=2.01, 95% CI=1.08 to 3.76). In males, odds ratios were most increased in those working 'other' schedules (OR=1.72, 95% CI=0.75 to 3.94) and 'Regular days with four or more years' history of night work' (OR=1.54, 95% CI=0.93 to 2.56).

Conclusions

This study's findings support a relationship between work schedule and prospective antidepressant prescriptions in the Swedish workforce. Future research should continue to assess sex-stratified relationships, using detailed shift work exposure categories and objective registry data where possible.

http://bit.ly/2DhSD1O

Symptoms of post-traumatic stress disorder and depression among Eritrean refugees in Ethiopia: identifying direct, meditating and moderating predictors from path analysis

Objective

This study aimed at testing the significance of mediating and moderating roles of sense of coherence, adaptive coping styles and social support in the relationship between exposure to trauma and psychological symptoms in a refugee population in sub-Saharan Africa.

Methods

A cross-sectional survey design was employed to collect data. The study was carried out in Mai Aini refugee camp in Ethiopia. A total of 562 adult Eritrean refugees aged 18–74 years were selected randomly to screen for depression and post-traumatic stress disorder (PTSD) symptoms and to examine associated factors. Data were collected using the premigration and postmigration living difficulties checklist, Center for Epidemiologic Studies Depression (CES-D) scale, Primary Care PTSD Screener, coping style scale, Sense of Coherence scale and Oslo Social Support scale. Path modelling was used to test the mediation and moderation effects of prespecified factors.

Results

Premigration living difficulties were associated directly with symptoms of PTSD (β=0.09, p<0.05), and associated indirectly with PTSD symptoms in paths through duration of stay in the camp, sense of coherence, postmigration living difficulties, task-oriented coping style and depressive symptoms (β=0.26, p<0.01). Premigration and postmigration living difficulties were associated directly with depressive symptoms with standardised estimate of β=0.35(p<0.001) and β=0.23(p<0.05), respectively. Postmigration living difficulties were associated indirectly with PTSD through paths of sense of coherence, task-oriented coping style and depressive symptoms (β=0.13; p<0.01). Social support moderated the effect of postmigration living difficulties on depressive symptoms (p<0.05). Emotion-oriented coping style moderated the effect of premigration threat for abuse on PTSD (β=–0.18, p<0.001) and depressive (β=–0.12, p<0.01) symptoms, as well as moderating threat to life on PTSD symptoms (β=–0.13, p<0.001).

Conclusions

Sense of coherence and task-oriented coping style showed a partial mediating effect on the association between exposure to trauma and symptoms of PTSD. An emotion-oriented coping style and social support moderated the effect of premigration and postmigration living difficulties, respectively. Fostering social support, task-oriented and emotion-oriented coping styles may be beneficial for these refugees.

http://bit.ly/2TXyGCV

Incidence of hospitalisation for severe complications of influenza virus infection in Japanese patients between 2012 and 2016: a cross-sectional study using routinely collected administrative data

Objective

To calculate the incidence of hospitalisation due to acute respiratory failure, pneumonia, acute respiratory distress syndrome (ARDS), febrile seizures and encephalitis/encephalopathy among influenza-positive patients in Japan, where point-of-care tests are routinely used to diagnose influenza.

Design

A cross-sectional study using routinely collected data.

Setting

Japanese clinics and hospitals between 2012 and 2016.

Participants

Japanese patients aged 0–74 years diagnosed with influenza by a rapid test in employment-related health insurance records.

Primary outcome measures

Incidence of hospitalisation per 100 000 influenza-positive episodes.

Results

We included over 16 million influenza-positive episodes, 1.0% of whom were hospitalised. Of these, 3361 were acute respiratory failure, 27 253 pneumonia, 18 ARDS, 2603 febrile seizure and 159 encephalitis/encephalopathy. The percentage of hospitalisations by age was 2.96% of patients aged 0–1 years, 0.77% aged 2–5, 0.51% aged 6–12, 0.78% aged 13–18, 1.36% aged 19–44, 1.19% aged 45–64, and 2.21% aged 65–74. The incidence of hospitalisations from these five complications combined was highest in influenza-positive patients aged 0–1 years (943 per 100 000) compared with 307 in those aged 2–5 years and 271 in those aged 65–74 years. For pneumonia, the incidence was highest for influenza-positive patients aged 0–5 years and 65 years or more. There were statistically significant decreasing trends over the years in the incidence of all-cause hospitalisations, pneumonia and febrile seizures.

Conclusions

Japanese administrative data revealed that 1.0% of influenza-positive patients aged under 75 years were hospitalised. Male patients had a higher incidence of pulmonary complications and febrile seizures. Children aged 0–5 years and adults aged 65–74 years were at high risk of being admitted to hospital for pneumonia.

http://bit.ly/2DhSATG

Protocol for a feasibility randomised controlled trial of targeted oxygen therapy in mechanically ventilated critically ill patients

Introduction

Oxygen is the most commonly administered drug to mechanically ventilated critically ill adults, yet little is known about the optimum oxygen saturation (SpO₂) target for these patients; the current standard of care is an SpO₂ of 96% or above. Small pilot studies have demonstrated that permissive hypoxaemia (aiming for a lower SpO₂ than normal by using a lower fractional inspired oxygen concentration (FIO₂)) can be achieved in the critically ill and appears to be safe. This approach has not been evaluated in a National Health Service setting. It is possible that permissive hypoxaemia may be beneficial to critically ill patients thus it requires robust evaluation.

Methods and analysis

Targeted OXygen therapY in Critical illness (TOXYC) is a feasibility randomised controlled trial (RCT) to evaluate whether recruiting patients to a study of permissive hypoxaemia is possible in the UK. It will also investigate biological mechanisms that may underlie the links between oxygenation and patient outcomes. Mechanically ventilated patients with respiratory failure will be recruited from critical care units at two sites and randomised (1:1 ratio) to an SpO₂ target of either 88%–92% or ≥96% while intubated with an endotracheal tube. Clinical teams can adjust FIO₂ and ventilator settings as they wish to achieve these targets. Clinical information will be collected before, during and after the intervention and blood samples taken to measure markers of systemic oxidative stress. The primary outcome of this study is feasibility, which will be assessed by recruitment rate, protocol adherence and withdrawal rates. Secondary outcomes will include a comparison of standard critical care outcome measures between the two intervention groups, and the measurement of biomarkers of systemic oxidative stress. The results will be used to calculate a sample size, likely number of sites and overall length of time required for a subsequent large multicentre RCT.

Ethics and dissemination

This study was approved by the London - Harrow Research Ethics Committee on 2 November 2017 (REC Reference 17/LO/1334) and received HRA approval on 13 November 2017. Results from this study will be disseminated in peer-reviewed journals, at medical and scientific meetings, in the NIHR Journals Library and patient information websites.

Trial registration number

NCT03287466; Pre-results.

http://bit.ly/2TVlkqJ

How much emergency department use by vulnerable populations is potentially preventable?: A period prevalence study of linked public hospital data in South Australia

Objectives

To quantify emergency department (ED) presentations by individuals within vulnerable populations compared with other adults and the extent to which these are potentially preventable.

Design

Period prevalence study from 2005-2006 to 2010–2011.

Setting

Person-linked, ED administrative records for public hospitals in South Australia.

Participants

Adults aged 20 or more in South Australia's metropolitan area presenting to ED and categorised as Refugee and Asylum Seeker Countries of birth (RASC); Aboriginal; those aged 75 years or more; or All others.

Main outcome measures

Unadjusted rates of ambulatory care sensitive condition (ACSC), general practitioner (GP)–type presentations and associated direct ED costs among mutually exclusive groups of individuals.

Results

Disparity between RASC and All others was greatest for GP-type presentations (423.7 and 240.1 persons per 1000 population, respectively) with excess costs of $A106 573 (95% CI $A98 775 to $A114 371) per 1000 population. Aboriginal had highest acute ACSC presenter rates (125.8 against 51.6 per 1000 population) with twice the risk of multiple presentations and $A108 701 (95% CI $A374 to $A123 029) per 1000 excess costs. Those aged 75 or more had highest chronic ACSC presenter rates (119.7vs21.1 per 1000), threefold risk of further presentations (incidence rate ratio 3.20, 95% CI 3.14 to 3.26) and excess cost of $A385 (95% CI $A178 160 to $A184 609) per 1000 population.

Conclusions

Vulnerable groups had excess ED presentations for a range of issues potentially better addressed through primary and community healthcare. The observed differences suggest inequities in the uptake of effective primary and community care and represent a source of excess cost to the public hospital system.

http://bit.ly/2DhSyv2

Evaluation of the performance of nucleic acid amplification tests (NAATs) in detection of chlamydia and gonorrhoea infection in vaginal specimens relative to patient infection status: a systematic review

Objective

We evaluated the performance of nucleic acid amplification tests (NAATs) using vaginal specimens in comparison to specimens from the cervix or urine in their ability to detect chlamydia and gonorrhoea infection in women based on patient infection status (PIS).

Design

Systematic review.

Data sources

EMBASE and Ovid MEDLINE databases were searched through 3 October 2017.

Eligibility criteria for selecting studies

We included studies that tested samples from the vagina and ≥1 other site (cervix and/or urine) with ≥2 NAATs for chlamydia and ≥2 NAATs or 1 NAAT and culture for gonorrhoea for each site.

Data extraction and synthesis

Performance is defined as the sensitivity of a NAAT using a specimen site and PIS of the patient. We assessed risk of bias using modified QUADAS-2.

Results

Nine publications met the inclusion criteria (eight for chlamydia; six for gonorrhoea) and were narratively reviewed. Pooled summary estimates were not calculated due to the variable methodology and PIS definitions. Tests performed on vaginal specimens accomplished similar performance to cervical and urine specimens for chlamydia (range of performance estimates: vaginal 65%–100%, cervical 59%–97%, urine 57%–100%) and gonorrhoea (vaginal 64%–100%, cervical 85%–100%, urine 67%–94%). Vaginal specimens were estimated to have a performance >80% for chlamydia and gonorrhoea infections in all but one study.

Conclusions

Performance of the NAATs for chlamydia and gonorrhoea detection using vaginal specimens was similar to that of cervical and urine specimens relative to PIS. As vaginal samples have a higher acceptability and lower cost, the study can support clinical testing guidelines by providing evidence that vaginal samples are a suitable alternative to traditionally used specimens.

http://bit.ly/2TVkFWj

Development and validation protocol for an instrument to measure household water insecurity across cultures and ecologies: the Household Water InSecurity Experiences (HWISE) Scale

Introduction

A wide range of water-related problems contribute to the global burden of disease. Despite the many plausible consequences for health and well-being, there is no validated tool to measure individual- or household-level water insecurity equivalently across varying cultural and ecological settings. Accordingly, we are developing the Household Water Insecurity Experiences (HWISE) Scale to measure household-level water insecurity in multiple contexts.

Methods and analysis

After domain specification and item development, items were assessed for both content and face validity. Retained items are being asked in surveys in 28 sites globally in which water-related problems have been reported (eg, shortages, excess water and issues with quality), with a target of at least 250 participants from each site. Scale development will draw on analytic methods from both classical test and item response theories and include item reduction and factor structure identification. Scale evaluation will entail assessments of reliability, and predictive, convergent, and discriminant validity, as well as the assessment of differentiation between known groups.

Ethics and dissemination

Study activities received necessary ethical approvals from institutional review bodies relevant to each site. We anticipate that the final HWISE Scale will be completed by late 2018 and made available through open-access publication. Associated findings will be disseminated to public health professionals, scientists, practitioners and policymakers through peer-reviewed journals, scientific presentations and meetings with various stakeholders. Measures to quantify household food insecurity have transformed policy, research and humanitarian aid efforts globally, and we expect that an analogous measure for household water insecurity will be similarly impactful.

http://bit.ly/2DhStHK

The economics of physical activity in low-income and middle-income countries: protocol for a systematic review

Introduction

Evidence on the economic costs of physical inactivity and the cost-effectiveness of physical activity interventions in low-income and middle-income countries (LMICs) is sparse, and fragmented where they are available. This is the first review aimed to summarise available evidence on economics of physical activity in LMICs, identify potential target variables for policy, and identify and report gaps in the current knowledge on economics of physical activity in LMICs.

Methods and analysis

Peer-reviewed journal articles of observational, experimental, quasi-experimental and mixed-method studies on economics of physical activity in LMICs will be identified by a search of electronic databases; Scopus, Web of Science and SPORTDiscus. Websites of WHO, the National Institute for Health and Care Excellence international, World Bank and reference lists of included studies will be searched for relevant studies. The study selection process will be a two-stage approach; title and abstract screen for inclusion, followed by a review of selected full-text articles by two independent reviewers. Disagreements will be resolved by consensus and discussion with a third reviewer. Data will be extracted using standardised piloted data extraction forms. Risk of bias will be critically appraised using standard checklists based on study designs. Descriptive synthesis of data is planned. Where relevant, summaries of studies will be classified according to type of economic analysis, country or country category, population, intervention, comparator, outcome and study design. Meta-analysis will be performed where appropriate. This protocol for systematic review is prepared according to the Preferred Reporting Items for Systematic review and Meta-analysis for Protocols –2015 statement.

Ethics and dissemination

Ethical approval is not obtained as original data will not be collected as part of this review. The completed review will be submitted for publication in a peer-reviewed journal and presented at conferences.

PROSPERO registration number

CRD42018099856.

http://bit.ly/2TX98Wp

Study protocol for an open-label, single-arm, multicentre phase II trial to evaluate the efficacy and safety of combined triplet therapy and olanzapine for prevention of carboplatin-induced nausea and vomiting in gynaecological cancer patients

Introduction

Carboplatin (CBDCA) administered at a dosage of 4 mg/mL/min or more area under the blood concentration-time curve (AUC) is considered to be ranked as the highest chemotherapy-induced nausea and vomiting (CINV) risk of the moderately emetogenic chemotherapy agents. The complete response (CR) rate for preventing overall CINV, defined as no emetic episodes and no use of rescue medication, for standard triplet antiemetic therapy (5-HT₃RA, 5-hydroxytryptamine-3 receptor antagonist; NK₁RA, neurokinin-1 receptor antagonist; DEX, dexamethasone) was approximately 60% in gynaecological cancer patients receiving CBDCA-based therapy. Further improvement in antiemetic treatment is needed to optimise care. This trial is to evaluate the efficacy and safety of using 5 mg olanzapine (OLZ) plus standard triplet antiemetic therapy for CINV after AUC ≥4 mg/mL/min CBDCA combination therapy in gynaecological cancer patients.

Methods and analysis

This trial is an open-label, single-arm, multicentre phase II trial. Patients who receive CBDCA (AUC ≥4)-based therapy and have never been administered moderate to high emetogenic chemotherapy will be enrolled. All patients will receive OLZ (5 mg oral administration on days 1–4, after supper) in combination with 5-HT₃RA, NK₁RA and DEX. The primary endpoint is the CR rate during the overall period (0–120 hours). Testing the hypothesis that this regimen can improve CR rate from 60% (null hypothesis) to 75% (alternative hypothesis) with a one-sided type I error of 0.1 and power of 0.8 will require 53 patients. Considering the dropout rate, the target sample size is set at 60.

Ethics and dissemination

The study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals.

Trial registration number

UMIN000031646.

http://bit.ly/2DhSlYM

Assessment of public oral healthcare services in Curitiba, Brazil: a cross-sectional study using the Primary Care Assessment Tool (PCATool)

Objectives

To compare two different models of public oral health in primary care services, a so-called family health strategy (FHS), as opposed to non-FHS services designated as 'conventional' healthcare (CHC), regarding the presence and extent of the attributes of 'good' primary healthcare (PHC). The null hypothesis of this study is that the attributes do not differ between the FHS and CHC.

Design

Cross-sectional.

Setting

Public PHC services in Curitiba, the state capital of Paraná.

Participants

PHC users of the public oral health network (n=900) and dentists active in this municipal network (n=203).

Primary and secondary outcome measures

The Primary Care Assessment Tool (PCATool)-Dentists and PCATool-Users were used to analyse the primary outcomes ('essential' attributes) and secondary outcomes ('derived' attributes) in the PHC.

Results

Overall, the primary care services in oral health were well evaluated, both by users and by dentists, with mean scores ascribed to PHC attributes mostly above the cut-off point (6.6). The exception for users were affiliation (6.36; 95% CI 6.11 to 6.60) and accessibility (5.83; 95% CI 5.78 to 5.89); and for dentists the accessibility (5.80; 95% CI 5.63 to 5.96). When comparing FHS and CHC, there was a superiority of the FHS model, which reached a general mean score of 7.53 (95% CI 7.48 to 7.58) among users and 7.56 (95% CI 7.45 to 7.67) among dentists; on the other hand, the CHC general mean score was of 6.61 (95% CI 6.49 to 6.73) and 6.68 (95% CI 6.56 to 6.80) respectively for users and dentists.

Conclusions

The results reveal a reasonable level of attainment of PHC attributes in the services investigated. Nevertheless, public health managers should make efforts to reduce the difficulties faced by users in accessing dental care. The more positive results achieved by FHS services indicate that the provision of oral healthcare under this strategy should be expanded.

http://bit.ly/2U16M9j

Forecasting and predicting intussusception in children younger than 48 months in Suzhou using a seasonal autoregressive integrated moving average model

Objective

The aims of this study were to highlight some epidemiological aspects of intussusception cases younger than 48 months and to develop a forecasting model for the occurrence of intussusception in children younger than 48 months in Suzhou.

Design

A retrospective study of intussusception cases that occurred between January 2007 and December 2017.

Setting

Retrospective chart reviews of intussusception paediatric patients in a large Children's hospital in South-East China were performed.

Participants

The hospital records of 13 887 intussusception cases in patients younger than 48 months were included in this study.

Interventions

The modelling process was conducted using the appropriate module in SPSS V.23.0.

Methods

The Box-Jenkins approach was used to fit a seasonal autoregressive integrated moving average (ARIMA) model to the monthly recorded intussusception cases in patients younger than 48 months in Suzhou from 2007 to 2016.

Results

Epidemiological analysis revealed that intussusception younger than 48 months was reported continuously throughout the year, with peaks in the late spring and early summer months. The most affected age group was younger than 36 months. The time-series analysis showed that an ARIMA (1,0,1 1,1,1)₁₂ model offered the best fit for surveillance data of intussusception younger than 48 months. This model was used to predict intussusception younger than 48 months for the year 2017, and the fitted data showed considerable agreement with the actual data.

Conclusion

ARIMA models are useful for monitoring intussusception in patients younger than 48 months and provide an estimate of the variability to be expected in future cases in Suzhou. The models are helpful for predicting intussusception cases in Suzhou and could be useful for developing early warning systems. They may also play a key role in early detection, timely treatment and prevention of serious complications in cases of intussusception.

http://bit.ly/2Di72em

Does intake of bread supplemented with wheat germ have a preventive role on cardiovascular disease risk markers in healthy volunteers? A randomised, controlled, crossover trial.

Objective

Intake of whole grains is associated with a reduced risk of cardiovascular disease (CVD). This evidence is also strong for bran alone, but findings about germ are conflicting. Our aim was to elucidate the role of germ in primary prevention of cardiovascular events, and therefore, a staple food was selected for 6 g of germ supplementation. This corresponds to sixfold increase in the global mean consumption of germ, while preserving the sensory proprieties of refined bread which is crucial for consumer's acceptance.

Design

Randomised, double-blinded, crossover, controlled clinical trial with 15-week follow-up comprising a 2-week run-in, two intervention periods of 4 weeks each and a 5-week washout period.

Setting

A single centre in the north of Portugal.

Participants

55 eligible healthy adults (mean age of 34 years and body mass index between 19 and 38 kg/m²) were randomly assigned.

Interventions

The study consisted of two intervention periods including daily intake of refined wheat bread enriched with 6 g of wheat germ and control (non-enriched bread).

Outcomes

Changes in fasting cholesterol and triglycerides, fasting and postprandial glucose, insulin sensitivity and C reactive protein.

Results

We observed no significant effect of daily intake of wheat germ on cholesterol and triglycerides levels, on postprandial glucose response and on insulin sensitivity. Incremental area under curve glucose and homeostasis model assessment for insulin resistance did not change, suggesting that 6 g of wheat germ have no effect on glucose metabolism. No effect was also observed in the subgroup of participants who complied with the protocol (n=47).

Conclusions

The absence of alterations on lipid and glucose profiles suggests that germ up to 6 g/day may have no preventive effect on CVD risk. However, it is important to investigate other food vehicles that can accommodate higher doses of wheat germ in future studies.

Trial registration number

NCT02405507.

http://bit.ly/2TWPA4q

Health-related quality of life and anxiety in the PAN-CAN lung cancer screening cohort

Objectives

The impact of lung cancer screening with low-dose chest CT (LDCT) on participants' anxiety levels and health-related quality of life (HRQoL) is an important consideration in the implementation of such programmes. We aimed to describe changes in anxiety and HRQoL in a high-risk Canadian cohort undergoing LDCT lung cancer screening.

Methods

2537 subjects who had 2% or greater lung cancer risk over 6 years using a risk prediction tool were recruited from eight centres across Canada in the Pan-Canadian Early Detection of Lung Cancer Study (2008–2010). We compared HRQoL and anxiety levels before and after screening of 1237 participants with LDCT (excluding a subset of 1300 participants who also underwent autofluorescence bronchoscopy screening), as well as after investigations performed because of a positive screening examination. The 12-item short-form Physical and Mental Component Scales (SF-12), EQ-5D-3L scores and State Trait Anxiety Inventory-State anxiety were used at each assessment.

Results

Overall, there were no clinically significant differences in HRQoL outcomes between baseline and each of the survey time points following initial screening. No mean change in anxiety in the overall cohort was noted following baseline LDCT, but more participants had clinically significant increase in anxiety versus decrease after baseline screening (increase >minimal clinically important difference (MCID) (n=180) vs decrease >MCID (n=50), p<0.001). This finding persisted but to a lesser degree at the 12 month time point (increase >MCID (n=146) vs decrease >MCID (n=87), p<0.001).

Conclusions

CT screening for lung cancer has no major overall impact on HRQoL among participants, although a minority of participants (number-needed-to-harm=7 after baseline screening and 18 at 1 year) demonstrated clinically significant increased anxiety levels.

Trialregistration number

NCT00751660; Results.

http://bit.ly/2TVlhLz

Cross-sectional study on medicinal products without commercial interest (MPWCI) in the Spanish market

Objective

To confirm that there is a defined group of products to be protected in the Spanish therapeutic arsenal known as 'medicinal products without commercial interest' (MPWCI) and propose the adoption of legal measures aimed at avoiding, or reducing, the lack of supply of said products.

Design

A cross-sectional study of proposed MPWCI based on a survey. The Spanish Agency of Medicines and Medical Devices (AEMPS) was asked for a list of presentations of medicines in order to identify those whose lack could have an impact on welfare.

Setting

A search on the AEMPS website and a survey conducted among 44 companies belonging to Farmaindustria has allowed for the development of a proposal list of presentations that should continue to be marketed in Spain.

Results

Products proposed as MPWCI are old (50% of them have an authorisation of more than 50 years) and are developed by active substances of chemical origin, parenterally administered much more frequently than the rest of the general market (44%vs6.6%, respectively). Unlike oral forms, injectable forms require adequate manufacturing facilities to guarantee the quality and sterility of the product, which naturally increases the cost of the product whose price is low or obsolete. The company experts have not valued the current price revisions as a sufficient enough mechanism to change the consideration of these medicines with respect to the interest on the part of some Marketing Authorisation Holders to maintain their commercialisation.

Conclusions

As shown in the results, an upward revision of prices is necessary to contribute to the permanence of these presentations in the market, although some experts do not consider the current price revisions satisfactory enough to maintain these presentations in the market. Therefore, a specific regulation seems necessary to ensure the continuity on the market of these proposed products.

http://bit.ly/2Dhr0WM

Oral cannabinoids in people living with HIV on effective antiretroviral therapy: CTN PT028--study protocol for a pilot randomised trial to assess safety, tolerability and effect on immune activation

Introduction

Despite antiretroviral therapy (ART), people living with HIV have higher rates of non-infectious chronic diseases. These conditions are driven by relatively high levels of inflammation persisting on ART compared with uninfected individuals. Chronic inflammation also contributes to HIV persistence during ART. Cannabis when taken orally may represent a way to reduce inflammation and strengthen immune responses. Before planning large interventional studies, it is important to ensure that cannabis taken orally is safe and well tolerated in people living with HIV. We propose to conduct a pilot randomised trial to examine the safety and tolerability of cannabis oils containing tetrahydrocannabinol (THC) and cannabidiol (CBD) consumed orally in people living with HIV. We will also measure inflammatory markers, markers of HIV persistence in peripheral blood cells and changes in the gastrointestinal microbiome.

Methods and analysis

Twenty-six people living with HIV having undetectable viral load for at least 3 years will be randomised to receive TN-TC11LM (THC:CBD in 1:1 ratio) or TN-TC19LM (THC:CBD in 1:9 ratio) capsules daily for 12 weeks. Safety and tolerability of these capsules will be assessed through haematological, hepatic and renal blood tests, face-to-face interviews and questionnaires. Proportions of participants without any signs of significant toxicity (grades 0–2 scores on the WHO toxicity scale) and who complete the study, as well as scores on quality of life and mood will be examined using descriptive statistics. The effects on inflammatory markers, markers of peripheral blood reservoir size and effect on the composition of the gastrointestinal microbiome will be assessed before and after study completion.

Ethics and dissemination

This study has been approved by the Research Institute of the McGill University Health Centre. A Data Safety Monitor will review safety information at regular intervals. The final manuscript will be submitted to an open-access journal within 6 months of study completion.

Trial registration number

NCT03550352.

http://bit.ly/2TRrqsa

Symptomatic involvement of the stomach and duodenum as initial presentation of AL amyloidosis

Primary systemic or amyloid light chain (AL) amyloidosis is a multisystem disorder with myriad presentations. Although it can involve the upper gastrointestinal tract in 8% of cases, symptomatic involvement is exceedingly rare. We chronicle here a case of postprandial epigastric pain associated with AL amyloidosis involving the stomach and duodenum. Pathological examination of endoscopic biopsy using Congo red staining confirmed the diagnosis. In order to establish the underlying aetiology of AL amyloidosis, the patient underwent extensive workup. Eventually, she was diagnosed with multiple myeloma based on the standard set of investigations. This paper underscores the importance of clinical suspicion of amyloidosis in patients presenting with non-specific gastrointestinal symptoms and highlights the role of endoscopic biopsy to confirm the amyloid deposition. Since gastrointestinal amyloidosis is a disease with a poor prognosis, early diagnosis and treatment are particularly warranted.

http://bit.ly/2HvAYrN

Overgrowth syndrome in neonates: a rare case series with a review of the literature

We present here two-term neonates presenting with right lower limb hypertrophy, a port-wine stain, acral abnormalities and clubfeet. These neonates had overlapping features of Klippel Trenaunay syndrome and congenital lipomatous overgrowth, vascular malformation, epidermal nevi and scoliosis/skeletal abnormalities. Such overgrowth syndrome has not been previously described in the literature. Both the neonates are doing well and are under regular follow-up.

http://bit.ly/2RRVHKa

Immune thrombocytopenic purpura presenting with spontaneous gingival haemorrhage in pregnancy

Gingival bleeding is a common intraoral finding, typically associated with inflamed tissues and periodontal disease. It is easily provoked by periodontal probing or toothbrushing. Spontaneous gingival bleeding rarely occurs and may be the only sign of systemic bleeding problems such as thrombocytopenia, leukaemia or coagulopathy. In pregnancy, acute onset of thrombocytopenia may occur in systemic disorders such as severe pre-eclampsia, HELLP syndrome (haemolysis, elevated liver enzymes, low platelets) or the acute fatty liver of pregnancy. The diagnosis and management of such conditions may challenge physicians. It requires a systematic approach with a comprehensive history to exclude causes of gingival haemorrhage such as periodontal disease, anticoagulant therapy, maxillofacial trauma, haematological disorders or a bacterial infection. The authors describe a case of immune thrombocytopenic purpura presenting with spontaneous gingival haemorrhage in pregnancy. This case highlights the fact that medical intervention to correct the underlying aberration of haemostasis is necessary for local measures to stop the gingival bleeding successfully.

http://bit.ly/2HgpcRB

Lithium neurotoxicity presenting as dementia with therapeutic serum lithium levels

After 25 years of continuous lithium therapy, a woman with moderate intellectual disability and bipolar disorder developed symptoms suggestive of dementia. In fact, she had developed lithium neurotoxicity, but this was overlooked for 18 months as serial lithium levels were in the therapeutic range.

http://bit.ly/2RZu3uY

Resolution of asthmatic symptoms following successful endoscopic resection of tracheal mucoepidermoid carcinoma

Mucoepidermoid carcinoma (MEC) is a rare tumour of the trachea accounting for up to 0.2% of reported primary lung malignancy. We report a case of a 54-year-old man, ex-smoker, whose presentation mimicked adult onset asthma with cough and wheezing, which did not respond to conventional treatment. He had occasional haemoptysis and weight loss in which CT scan performed for malignancy screening showed a protruding mass in the distal trachea causing endobronchial obstruction. Bronchoscopic intervention was performed to relieve the obstruction that resulted in resolution of asthmatic symptoms. Histological diagnosis confirmed MEC. This case emphasised the importance of a high index of suspicion in an unusual presentation of a common disease and the pivotal role of bronchoscopic intervention in malignant central airway obstruction.

http://bit.ly/2HgpaJt

Solid papillary thyroid carcinoma with Hashimotos thyroiditis: description of a further case with challenging cytological features

Solid papillary thyroid carcinoma (SV-PTC) is a rare variant which is mainly observed in young patients with a history of exposure to ionising radiations. Neoplasms belonging to such category generally carry RET-PTC (REarranged during Transfection- Papillary Thyroid Carcinoma) fusions and seem to have a slightly worse prognosis with respect to classical and follicular variants of papillary thyroid carcinoma (PTC), though consistent prognostic and survival data are scarce. SV-PTC should be differentiated from trabecular-insular poorly differentiated thyroid carcinomas, which occur in a different age group and carry a dismal prognosis. These latter tumours do not show the typical nuclear features of PTC and show tumour necrosis with an high mitotic activity. In this report a further case of SV-PTC is described which was associated to Hashimoto's thyroiditis, a finding never described in the cytological literature up to now for SV-PTC; this association created further differential diagnostic problems. The neoplasm displayed RET-PTC1 fusion.

http://bit.ly/2RYQvnE

Fatal case of necrotising fasciitis due to Vibrio vulnificus in a patient with alcoholic liver disease and diabetes mellitus

Vibrio vulnificus is a halophilic Vibrio found globally. They are thought to be normal microbiome in the estuaries along the coasts associated with seawater and seashells. Infection usually results from consumption of raw oysters or shellfish or exposure of broken skin or open wounds to contaminated salt or brackish water. Clinical manifestations range from gastroenteritis to skin and subcutaneous infection and primary sepsis. Pathogen has the ability to cause infections with significant mortality in high-risk populations, including patients with chronic liver disease, immunodeficiency, diabetes mellitus and iron storage disorders. There is often a lack of clinical suspicion in cases due to Vibrio vulnificus leading to delay in treatment and subsequent mortality. Herein we report a case of necrotising fasciitis in a diabetic patient with alcoholic liver disease caused by Vibrio vulnificus which ended fatally.

http://bit.ly/2Hgp98n

Azygos vein cannulation after catheterisation of the left internal jugular vein in a toddler

Central venous catheterisation is routinely performed in paediatric patients to facilitate therapeutic management when long-term vascular access is needed. Misplacement of the catheter tip in thoracic vessels other than the superior vena cava has been described, along with related complications. Hereby, a case of a 15-month-old child is presented with a fully functional Hickman catheter introduced via the left internal jugular vein. The tip of the catheter was misplaced into the azygos vein. Intraoperative spot fluoroscopic images and anatomical explanations for the course of the catheter are presented. An understanding of the aetiology of the radiological appearance may help to increase recognition of such cases and avoid complications.

http://bit.ly/2RPsmjD

Monomicrobial necrotising soft tissue infection of the hand caused by a Panton-Valentine leukocidin-negative Staphylococcus aureus strain in a 66-year-old patient with diabetes

http://bit.ly/2HgpJTB

Rare presentation of iron deficiency anaemia with cerebral venous sinus thrombosis in a middle-aged woman

This is a case of a female patient presented with a mild headache associated with recurrent episodes of nausea and vomiting, confusion and right-sided hemiparesis, diagnosed of haemorrhagic venous infarction from the thrombosis of left transverse and sigmoid sinus and probably the left vein of Labbe. She had severe microcytic hypochromic anaemia due to iron deficiency, without any other risk factors for cerebral venous thrombosis such as trauma history, infections, coagulation disorders or autoimmune diseases. She had a good prognosis after iron supplementation and anticoagulation therapy.

http://bit.ly/2RTaW5r

Non-traumatic splenic rupture secondary to haemorrhagic infarct in diffuse large B-cell lymphoma

http://bit.ly/2HgpF6j

Paediatric presentation of intracranial haemorrhage due to thrombosis of a developmental venous anomaly

Developmental venous anomalies (DVAs) are the most commonly encountered cerebral malformations. While generally asymptomatic and discovered as incidental findings, there is a small number that can cause intracranial haemorrhage, usually attributed to associated cavernomas; however, venous thrombosis of the draining vein is a rare cause. A 10-year-old woman presented with seizure episodes. Angiographic evaluation revealed a collection of vessels draining into the superior sagittal sinus via the vein of Trolard, concerning for a DVA. The patient improved clinically with supportive care and antiepileptic treatment. Anatomically, DVAs represent dysplasia of primary capillary beds and smaller cerebral veins, resulting in abnormal venous drainage of the affected parenchyma. Several distinguishing radiological findings can help differentiate a DVA from other pathologies. Early radiological identification can help in the initiation of appropriate therapy and prevent incorrect surgical management leading to further neurological demise.

http://bit.ly/2RPsks1

Recurrent case of pregnancy-induced atypical haemolytic uremic syndrome (P-aHUS)

Pregnancy-induced atypical haemolytic uremic syndrome (P-aHUS) is a rare condition characterised by microangiopathic haemolytic anaemia, thrombocytopenia and renal failure. It accounts for approximately 7% of total HUS cases. Here, we present a case of recurrent P-aHUS in a 25-year-old Hispanic woman. Pregnancy was the clear trigger in both instances, and the disease manifested in first week of the postpartum period. Because of her significant obstetric history, a multidisciplinary approach was adopted to monitor her second pregnancy antepartum and post partum. As the patient developed recurrence of P-aHUS 4 days after her delivery, she was immediately administered eculizumab within few hours of disease manifestation. The patient normalised her haematological parameters within 1 week but sustained dialysis-requiring renal failure for a total of 6 weeks. This case highlights the advances as well as the ongoing uncertainties, especially with respect to the use of eculizumab, in this rare but morbid disease.

http://bit.ly/2HgpA2v

Influence of static and dynamic cyclic fatigue tests on the lifespan of four reciprocating systems at different temperatures

Abstract

Aim

To compare the cyclic fatigue resistance of four reciprocating single file systems within artificial stainless steel canals at two temperatures using different kinematics.

Methodology

A total of 240 Instruments, Reciproc Blue, Reciproc, Waveone Gold, Waveone, (60 of each), were tested at room and intracanal temperature using both a static and a dynamic model (n=15) in a stainless‐steel artificial canal with an inner diameter of 1.5 mm, 60° angle of curvature and 5mm radius of curvature until fracture occurred. The time to fracture was measured in seconds using a digital chronometer and data were analyzed using one‐way analysis of variance and Bonferroni tests.

Results

Waveone instruments had significantly less fatigue resistance compared to that of other systems in all conditions (P < 0.05). Comparison of the results from the static and dynamic models at both temperatures revealed that fatigue resistance was significantly increased in the dynamic model for all the instrument systems (P < 0.05). Temperature did not influence the cyclic fatigue resistance results (P > 0.05). There were no significant differences in the mean length of the fractured fragments of the different instruments tested (P > 0.05).

Conclusion

Waveone files had a shorter cyclic fatigue life. The dynamic axial movement extended the cyclic fatigue life, but it did not have any influence on the comparison among the different instruments tested in respect of the static test. Temperature was not found to significantly affect the cyclic fatigue of these nickel‐titanium files.

This article is protected by copyright. All rights reserved.

http://bit.ly/2QT08zS

Classified

ALASKA, New full-time position for a BC/BE Emergency Medicine physician to join a stable, democratic group of 9 physicians. This is a hospital practice based at Fairbanks Memorial Hospital. Annual visits exceed 36,000. Fairbanks Memorial Hospital is a JCAHO accredited 159-bed hospital that is the primary referral center for the 100,000 residents of Alaska's interior. Fairbanks is a truly unique university community with unmatched accessibility to both wilderness recreation and urban culture. We aim to strike a balance between life and medicine, offering excellent compensation and benefits with a 2-year partnership track.

http://bit.ly/2RE9zIQ

Classified 2019 Advertising Rates & Information

Ads and complete payments must be received in writing by the issue's deadline date. These deadlines apply to insertions, cancellations, and changes.

http://bit.ly/2CopIHy

Calendar

▮ Office Orthopedics 3-Day. February 1-3, 2019. Vail, CO. Contact: Holly Canon. Email: hcanon@mer.org. Url: www.mer.org. (12.00)

http://bit.ly/2RBLLFm

Information for Readers

http://bit.ly/2CvdqgV

What's Coming in Annals ● March 2019

http://bit.ly/2Rz7sWv

Editors

http://bit.ly/2CvBPmr

Table of Contents

http://bit.ly/2RBi7QC

Global research highlights

Editor's note: Annals has partnered with a small group of selected journals of international emergency medicine societies to share from each a highlighted research study, as selected monthly by their editors. Our goals are to increase awareness of our readership to research developments in the international emergency medicine literature, promote collaboration among the selected international emergency medicine journals, and support the improvement of emergency medicine world-wide, as described in the WAME statement at http://bit.ly/2dmKsCb.

http://bit.ly/2Cs5QDy

Epinephrine in Out-of-Hospital Cardiac Arrest: Saving Lives or Prolonging Death?

Perkins GD, Ji C, Deakin CD, et al. A randomized trial of epinephrine in out-of-hospital cardiac arrest. N Engl J Med. 2018;379:711-721.

http://bit.ly/2Cvdo8N

Emergency Physicians and Firearms: Effects of Hands-on Training

Emergency department (ED) providers have opportunities to prevent firearm injuries or deaths; ED-based interventions include violence intervention programs and counseling about reducing firearm access to prevent suicide.1 Yet ED providers often do not counsel patients about firearms, in part from knowledge gaps or discomfort discussing firearms. Specific firearm education, including by law enforcement officers, may help providers understand how they help prevent gun violence.

http://bit.ly/2RBjHlg

In reply:

We thank Freedman et al1 for their letter in regard to our randomized trial comparing nausea relief with aromatherapy versus oral ondansetron. We found that patients allocated to arms receiving aromatherapy reported greater nausea reduction at 30 minutes.2 This finding adds to the growing literature demonstrating that aromatherapy has efficacy in treating nausea in the emergency department (ED) setting.3 That said, Freedman et al1 highlight several important study limitations.

http://bit.ly/2CryTXY

Aromatherapy Versus Oral Ondansetron for Antiemetic Therapy Among Adult Emergency Department Patients: A Randomized Controlled Trial

April et al1 conducted an intriguing trial comparing aromatherapy with ondansetron in adult emergency department (ED) patients with nausea. The authors conclude that among ED patients with nausea, aromatherapy provides greater nausea relief than oral ondansetron. It was unexpected to see aromatherapy reported as outperforming a known, potent antiemetic. On close review, we have identified some methodological issues that may have influenced the results and conclusions drawn.

http://bit.ly/2RBjBtU

Woman With Hip Pain

A 42-year-old woman presented to our emergency department (ED) after a high-speed motor vehicle crash. On arrival, the patient was hemodynamically stable but appeared uncomfortable and was complaining of severe left hip pain. On physical examination, the left lower extremity was neurovascularly intact but the left hip was flexed and the left leg was abducted and externally rotated. Given the history and physical examination findings, a radiograph (Figure 1) and computed tomography (CT) scan of the hip (Figure 2) were obtained.

http://bit.ly/2CopHU0

Young Woman With Unilateral Vision Loss

A 38-year-old woman presented with vision loss in her left eye after assault 9 days prior. Visual acuity in the affected eye was 20/400, and the remainder of the ophthalmic and neurologic examination was unremarkable. Bedside ocular ultrasonography was performed (Figure 1). Given the extent of vision loss, ophthalmology was also consulted for further evaluation in the emergency department.

http://bit.ly/2RxlSXc

Young Girl With Torticollis

An 8-year-old girl with no significant medical history presented to the emergency department with 3 days of fever, nontraumatic left-sided neck pain, and sore throat. Physical examination was significant for torticollis, tenderness along the left posterior side of the neck, and bilateral anterior cervical lymphadenopathy. A computed tomography (CT) scan of the neck was obtained (Figures 1 and 2).

http://bit.ly/2Cw02c8

Man With Persistent Rash

A 20-year-old man presented to the emergency department with widespread discrete pruritic rash that started 6 months before. The rash remained persistent, but new lesions continued to appear, and exacerbations were accompanied with swelling and redness of the older lesions, sometimes accompanied by bullae formation. The patient recalled receiving painkillers, including ibuprofen, dipyrone, and naproxen, on a regular basis for headaches. The rash flared several hours after ingestion of the medications.

http://bit.ly/2RBLKkM

Man With Abdominal Pain

A 51-year-old man presented to the emergency department with 8 hours of diffuse abdominal pain. His history was noteworthy for remote prosthetic aortic and tricuspid valve replacements. He had a temperature of 37.2°C (99.0°F), a pulse rate of 120 beats/min, blood pressure of 93/45 mm Hg, and diffuse abdominal tenderness. Initial laboratory test results showed a WBC count of 13,000/mm3 (reference range 4,000 to 10,000/mm3) and a lactate level of 14.8 mmol/L (normal value <1.9 mmol/L). Bedside ultrasonography of the aorta (Figure 1 and Video E1, available online at http://bit.ly/P50aok) revealed shadowing superior to the renal arteries.

http://bit.ly/2CrjKpz

Man With Accidentally Swallowed Dental C+ File

A 32-year-old man presented to the dentist to receive root canal therapy. During the treatment, a C+ file dropped and was accidentally swallowed by the patient. No foreign body was found by emergency gastroscopy that day. The next day, abdominal radiograph showed a cross-shaped high-density shadow in the lower right abdomen (Figure 1, arrow) and the shadow did not move obviously in the radiographic reexaminations during the following 3 days. The patient did not complain of any discomfort. On the fifth day, computed tomography (CT) of the abdomen and pelvis indicated a hyperdense structure located in the ileocecal region (Figures 2 and 3, arrow).

http://bit.ly/2CrGt4X

My Job: A Courtroom Victim Impact Statement

I very distinctly remember walking into the room that day. A few moments earlier, we had stopped resuscitative efforts on a young woman in cardiac arrest. Delivering devastating news to people never gets any easier no matter how many countless times I've done it. I paused in the hallway as I always do to collect my words, compose myself, and take a deep breath. The social worker was sitting in the seat to the right of the door and the mother was on the couch straight ahead of me. I had two choices.

http://bit.ly/2RAmHhZ

Unfolding the Role of Calreticulin in Myeloproliferative Neoplasm Pathogenesis

In 2013, two seminal studies identified gain of function mutations in the Calreticulin (CALR) gene in a subset of JAK2/MPL-negative myeloproliferative neoplasm (MPN) patients. CALR is an endoplasmic reticulum (ER) chaperone protein that normally binds misfolded proteins in the ER and prevents their export to the Golgi and had never previously been reported mutated in cancer or to be associated with hematological disorders. Further investigation determined that mutated CALR is able to achieve oncogenic transformation primarily through constitutive activation of the MPL-JAK-STAT signaling axis. Here we review our current understanding of the role of CALR mutations in MPN pathogenesis and how these insights can lead to innovative therapeutics approaches.

http://bit.ly/2Mg8MYo

CAR T cells targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors

Purpose: Patients with relapsed pediatric solid tumors and CNS malignancies have few therapeutic options and frequently die of their disease. Chimeric antigen receptor (CAR) T cells have shown tremendous success in treating relapsed pediatric acute lymphoblastic leukemia, but this has not yet translated to treating solid tumors. This is partially due to a paucity of differentially expressed cell surface molecules on solid tumors that can be safely targeted. Here, we present B7-H3 (CD276) as a putative target for CAR T cell therapy of pediatric solid tumors, including those arising in the central nervous system. Experimental Design: We developed a novel B7-H3 CAR whose binder is derived from a monoclonal antibody that has been shown to preferentially bind tumor tissues and has been safely used in humans in early phase clinical trials. We tested B7-H3 CAR T cells in a variety of pediatric cancer models. Results: B7-H3 CAR T cells mediate significant anti-tumor activity in vivo, causing regression of established solid tumors in xenograft models including osteosarcoma, medulloblastoma, and Ewing sarcoma. We demonstrate that B7-H3 CAR T cell efficacy is largely dependent upon high surface target antigen density on tumor tissues and that activity is greatly diminished against target cells that express low levels of antigen, thus providing a possible therapeutic window despite low-level normal tissue expression of B7-H3. Conclusions: B7-H3 CAR T cells could represent an exciting therapeutic option for patients with certain lethal relapsed or refractory pediatric malignancies which should be tested in carefully designed clinical trials.

http://bit.ly/2syTUv7

Circulating tumor DNA in advanced anal cancer: a blood biomarker goes viral

Circulating tumor DNA (ctDNA) as a blood-based biomarker for mutation detection is an exciting, highly-sensitive approach in the clinical management of oncology patients. In HPV-associated malignancies like anal cancer, a viral-specific probe can be utilized for ctDNA detection in the majority of patients in order to predict clinical outcomes.

http://bit.ly/2MfX3ZT

Sex Differences Seen in Pursuit of Interventional Cardiology Career

THURSDAY, Jan. 17, 2019 -- Unique factors dissuade female fellows-in-training from pursuing a career in interventional cardiology (IC), according to a study published online Jan. 16 in JACC: Cardiovascular Interventions. Celina M. Yong, M.D., from...

http://bit.ly/2Mh96pV

FDA Approves First Generic Version of Epilepsy Drug Sabril

THURSDAY, Jan. 17, 2019 -- The first generic version of Sabril (vigabatrin) has been approved by the U.S. Food and Drug Administration to prevent complex partial seizures in adults and children aged 10 years and older with epilepsy. "The...

http://bit.ly/2sxyJd9

WHO: Vaccine Hesitancy a Major Global Health Threat

THURSDAY, Jan. 17, 2019 -- Vaccine hesitancy is among the top 10 health threats facing the world in 2019, the World Health Organization says. The movement against vaccinations has taken hold in a number of countries, including the United States. The...

http://bit.ly/2Mfx2Kn

FDA Down to 5 Weeks of Funding to Review New Drug Applications

THURSDAY, Jan. 17, 2019 -- Due to the federal government shutdown, the U.S. Food and Drug Administration has only about five weeks of funding left to review new drug applications, according to Commissioner Scott Gottlieb, M.D. To keep reviewing...

http://bit.ly/2swJY5g

Antibiotics Often Inappropriately Prescribed for Bronchiolitis in ED

THURSDAY, Jan. 17, 2019 -- Most children younger than 2 years with bronchiolitis seen in U.S. emergency departments and prescribed antibiotics have no documented bacterial coinfection, according to a study published online Jan. 17 in the Journal of...

http://bit.ly/2MeYtDS

Prenatal Stimulation of 5-HT 1A Receptors Improves Adaptive Behavior in Prenatally Stressed Rats

Various types of adaptive behavior during the prepubertal period were analyzed in the offspring of rats receiving chronic injections of serotonin (5-HT) reuptake inhibitor fluoxetine, 5-HT_1A receptor agonist buspirone, or their combination starting from gestation day 9 and subjected to immobilization stress from the 15th day of pregnancy until delivery. Prenatal stress increased pain sensitivity, prolonged inflammatory pain response, and increased the levels of anxiety and depression. Chronic administration of drugs acting through 5-HT_1A receptors to pregnant rats improved the studied behavioral parameters in their offspring. Differences in the pain sensitivity were found between the effect of drug combination and each of them separately, and in the level of depression between combined administration and fluoxetine alone.

http://bit.ly/2MfQgPT

A comment on anti-H. pylori therapy and autoimmune diseases

http://bit.ly/2DhsCje

Response to “Hyoscine butylbromide for the management of death rattle: sooner rather than later.”

With great interest we read the article "Hyoscine Butylbromide for the Management of Death Rattle: Sooner Rather Than Later" by Mercadante et al. (1) The authors concluded that the prophylactic use of hyoscine butylbromide, an anticholinergic drug, is an efficient method to prevent death rattle in dying patients with a reduced level of consciousness. The striking study results may be a starting point to change the current practice of treating death rattle.

http://bit.ly/2svoc1X

Necrotic ulcer on the chin

Necrotic ulcer on the chin of a previously healthy 38-year-old woman.

Simonsen S, Winther C, Zachariae C, Skov L.

Int J Dermatol. 2019 Jan 10. doi: 10.1111/ijd.14378. [Epub ahead of print] No abstract available.

PMID:

 

30632142

Persisting ulcer on the chin

Ned Tijdschr Geneeskd  

Meij V1, Kuijpers KC.

Author information

1

St. Antonius Ziekenhuis, Afd. Heelkunde, Nieuwegein, the Netherlands. v.meij@antoniusziekenhuis.nl

Abstract

A 62-year-old woman presented with an ulcerative lesion on the chin. She had not visited tropical regions, but she had been in Cyprus. A skin biopsy revealed coccoid micro-organisms resembling Leishmania. Subsequently a PCR was performed which showed Leishmania donovani and Leishmania infantum complex and the diagnose 'cutaneous leishmaniasis' was confirmed.

PMID: 22129807

Prospective evaluation of ERCP performance in an Italian regional database study

Prospective studies about endoscopic retrograde cholangio-pancreatography (ERCP) in a community setting are rare.

http://bit.ly/2CwzhUT

Lesson from epidemiology of paediatric crohn’s Disease

http://bit.ly/2RB0dgA

Clinical outcomes of endoscopic treatment for gastric epithelial neoplasm in remnant stomach after distal gastrectomy

We aimed to evaluate the feasibility of endoscopic treatment for gastric epithelial neoplasm in the remnant stomach after distal gastrectomy and compared the clinical outcomes by tumor location and endoscopic treatment modality.

http://bit.ly/2CrzBnV

polyRAD: Genotype Calling with Uncertainty from Sequencing Data in Polyploids and Diploids

Low or uneven read depth is a common limitation of genotyping-by-sequencing (GBS) and restriction site-associated DNA sequencing (RAD-seq), resulting in high missing data rates, heterozygotes miscalled as homozygotes, and uncertainty of allele copy number in heterozygous polyploids. Bayesian genotype calling can mitigate these issues, but previously has only been implemented in software that requires a reference genome or uses priors that may be inappropriate for the population. Here we present several novel Bayesian algorithms that estimate genotype posterior probabilities, all of which are implemented in a new R package, polyRAD. Appropriate priors can be specified for mapping populations, populations in Hardy-Weinberg equilibrium, or structured populations, and in each case can be informed by genotypes at linked markers. The polyRAD software imports read depth from several existing pipelines, and outputs continuous or discrete numerical genotypes suitable for analyses such as genome-wide association and genomic prediction.

http://bit.ly/2Rxpkky

Impact of the supine position versus left horizontal position on colonoscopy insertion: a 2-center, randomized controlled trial

Colonoscopy insertion is painful for some patients, constituting one of the main barriers to screening colonoscopy. Few studies have assessed the impact of the supine position (SP) on colonoscopy insertion, especially for unsedated patients. The aim of this randomized controlled trial (RCT) is to clarify this issue.

http://bit.ly/2SVXJWV

Reply

We thank Oakley et al for contributing to the debate on this important contemporary child health and development topic. Like us, they recognize that guidelines should support the best interests of children, and that having conflicting guidelines that are pitted against each other is not helpful.

http://bit.ly/2DgjqLT

Comparison of Initial Pediatric Outpatient Echocardiogram Indications between Community and Academic Practice

To compare the appropriateness and diagnostic yield of initial outpatient transthoracic echocardiography (TTE) between a community pediatric cardiology practice and an academic children's hospital.

http://bit.ly/2TUJd1D

Update on the Native Kidney Biopsy: Core Curriculum 2019

The kidney biopsy is an invaluable tool that has become the gold standard for the diagnosis of pathologic kidney diseases since the early 1950s. Throughout the years, immunohistologic and ultrastructural microscopy techniques have improved and provide more information on the cause and classification of kidney diseases than that available from simple light microscopy alone. Kidney biopsy has become a preferred method to obtain critical information that can be used in conjunction with serologic, urinary, and genetic testing to diagnose a variety of kidney diseases, both acute and chronic.

http://bit.ly/2DioTC9