title: Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff.

text: BACKGROUND In epidemics of highly infectious diseases, such as Ebola Virus Disease (EVD) or SARS, healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Contact precautions by means of personal protective equipment (PPE) can reduce the risk. It is unclear which type of PPE protects best, what is the best way to remove PPE, and how to make sure HCWs use PPE as instructed. OBJECTIVES To evaluate which type or component of full-body PPE and which method of donning or removing (doffing) PPE have the least risk of self-contamination or infection for HCWs, and which training methods most increase compliance with PPE protocols. SEARCH METHODS We searched MEDLINE (PubMed up to 8 January 2016), Cochrane Central Register of Trials (CENTRAL up to 20 January 2016), EMBASE (embase.com up to 8 January 2016), CINAHL (EBSCOhost up to 20 January 2016), and OSH-Update up to 8 January 2016. We also screened reference lists of included trials and relevant reviews, and contacted NGOs and manufacturers of PPE. SELECTION CRITERIA We included all eligible controlled studies that compared the effect of types or components of PPE in HCWs exposed to highly infectious diseases with serious consequences, such as EVD and SARS, on the risk of infection, contamination, or noncompliance with protocols. This included studies that simulated contamination with fluorescent markers or a non-pathogenic virus.We also included studies that compared the effect of various ways of donning or removing PPE, and the effects of various types of training in PPE use on the same outcomes. DATA COLLECTION AND ANALYSIS Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We intended to perform meta-analyses but we did not find sufficiently similar studies to combine their results. MAIN RESULTS We included nine studies with 1200 participants evaluating ten interventions. Of these, eight trials simulated the exposure with a fluorescent marker or virus or bacteria containing fluids. Five studies evaluated different types of PPE against each other but two did not report sufficient data. Another two studies compared different types of donning and doffing and three studies evaluated the effect of different types of training.None of the included studies reported a standardised classification of the protective properties against viral penetration of the PPE, and only one reported the brand of PPE used. None of the studies were conducted with HCWs exposed to EVD but in one study participants were exposed to SARS. Different types of PPE versus each otherIn simulation studies, contamination rates varied from 25% to 100% of participants for all types of PPE. In one study, PPE made of more breathable material did not lead to a statistically significantly different number of spots with contamination but did have greater user satisfaction (Mean Difference (MD) -0.46 (95% Confidence Interval (CI) -0.84 to -0.08, range 1 to 5, very low quality evidence). In another study, gowns protected better than aprons. In yet another study, the use of a powered air-purifying respirator protected better than a now outdated form of PPE. There were no studies on goggles versus face shields, on long- versus short-sleeved gloves, or on the use of taping PPE parts together. Different methods of donning and doffing procedures versus each otherTwo cross-over simulation studies (one RCT, one CCT) compared different methods for donning and doffing against each other. Double gloving led to less contamination compared to single gloving (Relative Risk (RR) 0.36; 95% CI 0.16 to 0.78, very low quality evidence) in one simulation study, but not to more noncompliance with guidance (RR 1.08; 95% CI 0.70 to 1.67, very low quality evidence). Following CDC recommendations for doffing led to less contamination in another study (very low quality evidence). There were no studies on the use of disinfectants while doffing. Different types of training versus each otherIn one study, the use of additional computer simulation led to less errors in doffing (MD -1.2, 95% CI -1.6 to -0.7) and in another study additional spoken instruction led to less errors (MD -0.9, 95% CI -1.4 to -0.4). One retrospective cohort study assessed the effect of active training - defined as face-to-face instruction - versus passive training - defined as folders or videos - on noncompliance with PPE use and on noncompliance with doffing guidance. Active training did not considerably reduce noncompliance in PPE use (Odds Ratio (OR) 0.63; 95% CI 0.31 to 1.30) but reduced noncompliance with doffing procedures (OR 0.45; 95% CI 0.21 to 0.98, very low quality evidence). There were no studies on how to retain the results of training in the long term or on resource use.The quality of the evidence was very low for all comparisons because of high risk of bias in studies, indirectness of evidence, and small numbers of participants. This means that it is likely that the true effect can be substantially different from the one reported here. AUTHORS' CONCLUSIONS We found very low quality evidence that more breathable types of PPE may not lead to more contamination, but may have greater user satisfaction. We also found very low quality evidence that double gloving and CDC doffing guidance appear to decrease the risk of contamination and that more active training in PPE use may reduce PPE and doffing errors more than passive training. However, the data all come from single studies with high risk of bias and we are uncertain about the estimates of effects.We need simulation studies conducted with several dozens of participants, preferably using a non-pathogenic virus, to find out which type and combination of PPE protects best, and what is the best way to remove PPE. We also need randomised controlled studies of the effects of one type of training versus another to find out which training works best in the long term. HCWs exposed to highly infectious diseases should have their use of PPE registered and should be prospectively followed for their risk of infection.


title: Paracardioscopy provides endoscopic visualization of the heart.

text: Paracardioscopy provides totally endoscopic access to the heart via a transabdominal, transdiaphragmatic approach. Structures such as the pulmonary veins, inferior vena cava, left and right atrial appendage, and posterior left atrium can be visualized. Epicardial cardiac procedures, such as ablation procedures for atrial fibrillation, can be successfully performed using this development. This report describes paracardioscopy.


title: Minilaparoscopic cholecystectomy - the new non-visible scars technique. Preliminary report of first series.

text: INTRODUCTION Surgery without scars is the dream of many patients and surgeons as well. It includes many new laparoscopic techniques (LESS, SILS, hybrid NOTES), but data concerning common bile duct (CBD) lesions are unavailable. AIM To establish the new technique of minilaparoscopic cholecystectomy (MCh): non-visible scar intervention without increasing the risk of CBD lesions. MATERIAL AND METHODS Forty consecutive patients with symptomatic gallbladder lithiasis were qualified for elective laparoscopic cholecystectomy (LCh) using one 10/11 mm umbilical port, one 5 mm right suprapubic port and two minilaparoscopic, disposable, no-port graspers. There were 26 women and 14 men, with the mean age 56 (17-72) years and with the average body mass index 28 (18-33) kg/m(2). CO2 Veress 15 mm Hg pneumoperitoneum was performed after transumbilical incision, and the first 10/11 mm port was inserted at the beginning for the 5 mm laparoscope and finally for typical instruments. Next under camera control, a 5 mm trocar was inserted in the right 'bikini line'. To this port the laparoscope was relocated from the umbilicus, and under its control two minilaparoscopic, disposable, non-port graspers were introduced after small, 2 mm skin incisions in the right anterior axillary line and in the right mesogastrium to catch the gallbladder. Next through the umbilical port, using typical instruments, the cystic duct and artery were dissected, clipped and cut. The gallbladder was removed through the umbilical port whole. RESULTS There was no conversion to open cholecystectomy. In 5 cases drainage of the gallbladder lodge was necessary through a 5 mm port in the right bikini line. The time of the intervention ranged from 90 min during the introduction of the new method to 50 min for the last procedures. No postoperative complications were observed, and all patients were discharged at the same time as after conventional LCh. CONCLUSIONS Two-port laparoscopic cholecystectomy performed with two minilaparoscopic no-port graspers does not increase the risk of CBD lesions. It provides an excellent cosmetic effect and is very convenient for the surgeon like typical LCh.


title: How risk communication could have reduced controversy about school closures in Australia during the COVID-19 pandemic.

text: Although there has been consistent evidence indicating that school closures have only limited efficacy in reducing community transmission of coronavirus disease 2019 (COVID-19), the question of whether children should be kept home from school has attracted extensive and often divisive public debate in Australia. In this article we analyse the factors that drove high levels of concern among parents, teachers and the public and led to both demands for school closures in late March 2020, and to many parents' reluctance to return their children to school in May 2020. We discuss how the use of well-established principles of risk communication might have reduced much of this community concern. Then we set out a range of practical suggestions for communication practices that build trust and hence diminish concerns in relation to managing schools over the long term of the COVID-19 pandemic.


docid: bdnwndji

title: The Mental Health Impact of the COVID19 Crisis: The Battle Ahead for Inpatient Survivors.


title: Clinician Mental Health and Well-Being During Global Healthcare Crises: Evidence Learned From Prior Epidemics for COVID-19 Pandemic.

text: Novel coronavirus disease 2019 (COVID-19) is sweeping across the globe, having sickened more than 640,000 people and claimed over 30,000 lives in approximately 202 countries at the time of writing with no sign of slowing down (World Health Organization, 2020). Each time a pandemic or an epidemic disease occurs, such as measles, scarlet fever, HIV/AIDS, Ebola, or the flu of 2013, healthcare professionals are on the front lines, battling diseases and caring for sick and dying patients, even while knowingly putting themselves at risk (Borghese, Di Donato, Ruotolo, & Fiegender, 2020).


title: Diagnosis of Periprosthetic Joint Infection: The Potential of Next-Generation Sequencing.

text: BACKGROUND Next-generation sequencing is a well-established technique for sequencing of DNA and has recently gained attention in many fields of medicine. Our aim was to evaluate the accuracy of next-generation sequencing in identifying the causative organism(s) in patients with periprosthetic joint infection. METHODS In this prospective study, samples were collected from 65 revision arthroplasties (39 knees and 26 hips) and 17 primary arthroplasties (9 hips and 8 knees). Synovial fluid, deep tissue, and swabs were obtained at the time of the surgical procedure and were shipped to the laboratory for next-generation sequencing. Deep-tissue specimens were also sent to the institutional laboratory for culture. Sensitivity and specificity were calculated for next-generation sequencing, using the Musculoskeletal Infection Society (MSIS) definition of periprosthetic joint infection as the standard. RESULTS In 28 revisions, the cases were considered to be infected; cultures were positive in 17 cases (60.7% [95% confidence interval (CI), 40.6% to 78.5%]), and next-generation sequencing was positive in 25 cases (89.3% [95% CI, 71.8% to 97.7%]), with concordance between next-generation sequencing and culture in 15 cases. Among the 11 cases of culture-negative periprosthetic joint infection, next-generation sequencing was able to identify an organism in 9 cases (81.8% [95% CI, 48.2% to 97.7%]). Next-generation sequencing identified microbes in 9 (25.0% [95% CI, 12.1% to 42.2%]) of 36 aseptic revisions with negative cultures and in 6 (35.3% [95% CI, 14.2% to 61.7%]) of 17 primary total joint arthroplasties. Next-generation sequencing detected several organisms in most positive samples. However, in the majority of patients who were infected, 1 or 2 organisms were dominant. CONCLUSIONS Next-generation sequencing may be a useful adjunct in identification of the causative organism(s) in culture-negative periprosthetic joint infection. Our findings suggest that some cases of monomicrobial periprosthetic joint infection may have additional organisms that escape detection when culture is used. Further study is required to determine the clinical implications of isolated organisms in samples from patients who are not thought to be infected. LEVEL OF EVIDENCE Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.


title: The relationship between oxygen uptake kinetics and neuromuscular fatigue in high-intensity cycling exercise.

text: PURPOSE In theory, a slow oxygen uptake ([Formula: see text]) kinetics leads to a greater accumulation of anaerobic by-products, which can, in turn, induce more neuromuscular fatigue. However, the existence of this relationship has never been tested. METHODS After two sessions to measure peak [Formula: see text], peak power output (POpeak), and [Formula: see text] kinetics responses in the unfatigued state (τ [Formula: see text] MOD), 10 healthy young adults performed a 6-min cycling bout at 80% POpeak (INT6-min). [Formula: see text] kinetics responses were also measured during INT6-min. Neuromuscular fatigue was measured isometrically pre- and post-INT6-min (immediately post- and 15-s post-INT6-min) with an innovative cycle ergometer. RESULTS Maximal voluntary contraction (MVC) force, high-frequency doublet amplitude, and the ratio of low- to high-frequency doublet amplitudes decreased by 34 ± 7, 43 ± 11, and 31 ± 13%, respectively (all P < 0.01). A significant Spearman's rank correlation was observed between the change in low-frequency doublet force (ΔDb10) immediately after INT6-min and both τ [Formula: see text] MOD and τ [Formula: see text] INT6-min (ρ = -0.68 and ρ = -0.67, both P < 0.05). When considering the largest responses from the two neuromuscular evaluations post-INT6-min, significant correlations were also found between τ [Formula: see text] MOD and ΔDb10 (ρ = -0.74; P < 0.05) and between τ[Formula: see text] INT6-min and both ΔDb10 and low-frequency fatigue (ρ = -0.70 and ρ = -0.66; both P < 0.05). CONCLUSION The present results suggest that subjects with slow [Formula: see text] kinetics experience more peripheral fatigue, in particular more excitation-contraction coupling failure, likely due to a greater accumulation of protons and/or inorganic phosphates.


title: Epidemiology of H1N1 (2009) influenza among healthcare workers in a tertiary care center in Saudi Arabia: a 6-month surveillance study.

text: BACKGROUND Certain emerging infections, such as severe acute respiratory syndrome and avian influenza, represent a great risk to healthcare workers (HCWs). There are few data about the epidemiology of H1N1 influenza among HCWs. METHODS We conducted a prospective surveillance study for all HCWs at King Abdulaziz Medical City (Riyadh, Saudi Arabia) who were confirmed positive for H1N1 influenza by polymerase chain reaction (PCR) from June 1 through November 30, 2009. RESULTS During 6 months of surveillance, 526 HCWs were confirmed positive for H1N1 influenza. The distribution of these cases showed 2 clear outbreaks: an initial outbreak (peak at early August) and a shorter second wave (peak at end of October). Among all PCR-confirmed cases, the attack rate was significantly higher in clinical HCWs than in nonclinical HCWs (6.0% vs 4.3%; P < .001) and in HCWs in emergency departments than in HCWs in other hospital locations (17.4% vs 5.0%, P < .001). The percentage of HCWs who received regular influenza vaccination was greater for clinical HCWs than for nonclinical HCWs (46.2% vs 24.6%; P < .001). The majority of HCWs with confirmed H1N1 influenza were young (mean age + or - standard deviation, 34.5 + or - 9.5 years), not Saudi (58.4%), female (55.1%), and nurses (36.1%). Approximately 4% of women who were less than 50 years old were pregnant. Reported exposures included contact with a case (41.0%), contact with a sick household member (23.8%), and recent travel history (13.3%). Respiratory symptoms (98.0%), including cough (90.1%), were the most frequently reported symptoms, followed by muscle aches (66.2%), fever (62.5%), headache (57.9%), diarrhea (16.5%), and vomiting (9.8%). None of these HCWs died, and all recovered fully without hospital admission. CONCLUSIONS The results confirm the vulnerability of HCWs, whether clinical or nonclinical, to emerging H1N1 influenza.


title: Nursing Education for Disaster Preparedness and Response.

text: Catastrophic mass casualty events (MCEs), such as pandemic influenza outbreaks, earthquakes, or large-scale terrorism-related events, quickly and suddenly yield thousands of victims whose needs overwhelm local and regional health care systems, personnel, and resources. Such conditions require deploying scarce resources in a manner that is different from the more common multiple casualty event. This article presents issues associated with providing nursing care under MCE circumstances of scarce resources and the educational needs of nurses to prepare them to effectively respond in these emergencies. J Contin Educ Nurs. 2015;46(x):xxx-xxx.


title: Atypical presentation of Middle East respiratory syndrome coronavirus in a Lebanese patient returning from Saudi Arabia.

text: Around 2090 confirmed cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) from 27 countries have been reported to the World Health Organization (WHO) between September 2012 and October 2017, the majority of whom occurring in countries in the Arabian Peninsula, mainly in Saudi Arabia. MERS- CoV can have atypical and misleading presentations resulting in delays in diagnosis and is associated with a high mortality rate especially in elderly patients with multiple comorbidities. Herein, we present the first case of confirmed MERS-CoV infection diagnosed at the American University of Beirut Medical Center (AUBMC) - Lebanon in June 2017 presenting without any respiratory symptoms. This is the second confirmed case of MERS-CoV infection in Lebanon since 2014. The first case presented with a febrile respiratory infection with persistent symptoms despite antibiotic treatment.


title: A reproducible ex vivo model for transanal minimally invasive surgery.

text: BACKGROUND Rectal tumors can be excised through a number of minimally invasive transanal techniques including transanal excision, transanal endoscopic microsurgery, and transanal minimally invasive surgery (TAMIS). Specialty training is often required to master the nuances of these approaches. This study aimed to create a reproducible transanal excision training model that is suited for laparoendoscopic techniques. METHODS Frozen porcine rectum and anus with intact perianal skin were commercially obtained. Thawed specimens were then cut to approximately 20 cm in length. The proximal end of the rectum was then everted and suction applied to the mucosa to create pseudopolyps of various sizes (sessile and pedunculated). Larger pedunculated lesions were made by tying the base of the pseudopolyps with 5-0 monofilament sutures to gather more tissue. Methylene blue dye was injected submucosally into the lesions to simulate tattoos. The proximal rectum was then closed with sutures. The model was suspended in a trainer box by clamping the distal end in a ringed clamp and the proximal end to the box. Transanal excisions using TAMIS were then performed. The procedures were done by trained community colorectal surgeons attending courses on transanal minimally invasive surgery. RESULTS Both partial- and full-thickness excisions of sessile and pedunculated rectal lesions were successfully performed during simulated TAMIS by trained community surgeons learning this laparoendoscopic technique. CONCLUSION Transanal laparoendoscopic procedures to excise rectal tumors can be successfully and reproducibly performed in an ex vivo porcine anorectal model.


title: Erythropoietin in patients with traumatic brain injury and extracranial injury-A post hoc analysis of the erythropoietin traumatic brain injury trial.

text: BACKGROUND Erythropoietin (EPO) may reduce mortality after traumatic brain injury (TBI). Secondary brain injury is exacerbated by multiple trauma, and possibly modifiable by EPO. We hypothesized that EPO decreases mortality more in TBI patients with multiple trauma, than in patients with TBI alone. METHODS A post hoc analysis of the EPO-TBI randomized controlled trial conducted in 2009 to 2014. To evaluate the impact of injuries outside the brain, we calculated an extracranial Injury Severity Score (ISS) that included the same components of the ISS, excluding head and face components. We defined multiple trauma as two injured body regions with an Abbreviated Injury Scale (AIS) score of 3 or higher. Cox regression analyses, allowing for potential differential responses per the presence or absence of extracranial injury defined by these injury scores, were used to assess the effect of EPO on time to mortality. RESULTS Of 603 included patients, the median extracranial ISS was 6 (interquartile range, 1-13) and 258 (43%) had an AIS score of 3 or higher in at least two body regions. On Cox regression, EPO was associated with decreased mortality in patients with greater extracranial ISS (interaction p = 0.048) and weakly associated with differential mortality with multiple trauma (AIS score > 3 or in two regions, interaction p = 0.17). At 6 months in patients with extracranial ISS higher than 6, 10 (6.8%) of 147 EPO-treated patients compared with 26 (17%) of 154 placebo-treated patients died (risk reduction, 10%; 95% confidence interval, 2.9-17%; p = 0.007). CONCLUSION In this post hoc analysis, EPO administration was associated with a potential differential improvement in 6-month mortality in TBI patients with more severe extracranial injury. These findings need confirmation in future clinical and experimental studies. LEVEL OF EVIDENCE Therapeutic study, level III.


Modeling hologenome imbalances in inflammation and cancer.


Research Goals During and Beyond the COVID-19 Pandemic: Reframing Older Adults as Essential and Priceless.


Coronavirus Disease 2019 (COVID-19) and Cardiac Injury.


title: Laparoscopic Partial Sleeve Duodenectomy for the Infra-Ampullary Gastrointestinal Stromal Tumors of the Duodenum.

text: BACKGROUND Although organ-preserving operations are regarded as effective strategies for duodenal gastrointestinal stromal tumors (GISTs), laparoscopic partial sleeve duodenectomy (lap PSD) has not been fully evaluated. The aims of this study were to evaluate the effectiveness and technical feasibility of lap PSD. STUDY DESIGN Between January 2011 and March 2016, we reviewed 13 patients who underwent laparoscopic approach among 22 patients who underwent PSD. PSD for the infra-ampullary lesions was defined as infra-ampullary duodenal resection including the first portion of the jejunum. After resection, all patients underwent reconstruction via side-to-side duodenojejunostomy. RESULTS The total mean operation time was 273 min (range 160-346 min), and estimated mean blood loss was 80 ml (range scanty-200 ml). One patient was converted to open laparotomy because of mesocolonic tumor involvement. The median postoperative hospital stay was 10.5 days (range 4-36 days). There were no postoperative mortalities. Postoperative complications included 2 instances of delayed gastric emptying (DGE), 1 duodenojejunostomy stricture, and 2 intestinal obstructions. No patient was treated with adjuvant therapy. One patient experienced hepatic metastasis 28 months after surgery during a mean follow-up period of 48.6 months. CONCLUSION Lap PSD might be an oncologically effective strategy for duodenal GIST, and the laparoscopic approach is a technically feasible and appealing surgical modality in terms of safety and perioperative results. However, DGE and anastomosis strictures are concerns for postoperative complications, which need to be further investigated.


title: Evaluation of robot-assisted laparoscopic versus open cystectomy and effect of carbon dioxide-pneumoperitoneum on histopathological findings in ureteroenteric anastomoses: results from an experimental randomized porcine study.

text: OBJECTIVE The aim of this study was to investigate the histopathology of ureteroenteric anastomoses (UEAs) after radical cystectomy (RC) with an ileal conduit in a porcine model using different surgical techniques. The study also evaluated the potential anti-inflammatory effect of preoperative carbon dioxide-pneumoperitoneum (CO2P). MATERIALS AND METHODS Forty female Danish Landrace pigs were randomized to four groups: three intervention groups [open surgery ± prior CO2P and robot-assisted laparoscopic cystectomy (RALC)], all subjected to RC and an ileal conduit, and one control group. After euthanization, UEAs were harvested and histopathologically evaluated. RESULTS Five pigs were excluded from the study owing to postoperative complications. Operating room time and clamping of the right and left ureters were significantly longer in the robotic than in the open groups (p < .01). Inflammatory infiltration grade of the left ureter was significantly higher in RALC (p = .032). No statistically significant difference was observed between the open groups receiving prior CO2P or not. CONCLUSIONS Results showed a statistically significant higher inflammatory infiltration grade of the left ureter in RALC, emphasizing the importance of using meticulous techniques when mobilizing the left ureter using the robot. It was not possible to conclude with certainty whether CO2P could constitute an anti-inflammatory agent for local inflammation.


title: Colonic Stool Burden a Useful Surrogate for Slow Transit Constipation as Determined by a Radiopaque Transit Study.

text: OBJECTIVES Plain film abdominal x-ray (AXR) is frequently used in the evaluation of constipation, but studies assessing the association between stool burden on AXR and colonic transit have been limited. We sought to investigate the relationship between colonic stool burden and slow transit constipation, as determined by a radiopaque marker (ROM) transit study. METHODS A retrospective cohort population was assembled, consisting of adult patients with chronic constipation who underwent testing with both a ROM study and anorectal manometry at 2 tertiary care centers over 5 years. Stool burden was graded by 2 independent observers, with colonic transit being assessed by the Hinton method. RESULTS Of 361 patients, 145 (40.3%) had slow transit constipation, and women were more likely than men to have slow transit constipation (42.3% vs 26.5%, P = 0.04). The mean stool burden scores by observer 1 and observer 2 for patients with slow transit constipation were significantly higher than the mean stool burden scores for patients with normal transit constipation (8.1 ± 1.6 vs 6.9 ± 1.9, P < 0.0001; 8.5 ± 1.5 vs 5.8 ± 1.6, P < 0.0001). The Pearson correlation coefficient for the stool burden score and number of remaining ROMs was 0.31 (moderate) for observer 1 (P < 0.0001) and 0.62 (strong) for observer 2 (P < 0.0001), whereas the Pearson correlation coefficient for interrater reliability of the stool burden score was 0.58 (P < 0.0001), indicating a strong correlation. The ideal score cutoff for both observers was 7, with moderate agreement by Cohen's kappa (0.43, P < 0.0001). CONCLUSIONS Stool burden assessment on AXR may be a reliable alternative ROM study in the assessment of colonic transit.


title: Use of Urea Wash ELISA to Distinguish Zika and Dengue Virus Infections.

text: Serologic testing remains crucial for Zika virus diagnosis. We found that urea wash in a Zika virus nonstructural protein 1 IgG ELISA distinguishes secondary dengue virus infection from Zika virus infection with previous dengue (sensitivity 87.5%, specificity 93.8%). This test will aid serodiagnosis, serosurveillance, and monitoring of Zika complications in dengue-endemic regions.


title: Clusters of 2019 coronavirus disease (COVID-19) cases in Chinese tour groups.

text: International travel may facilitate the spread of the novel coronavirus disease (COVID-19). The study describes clusters of COVID-19 cases within Chinese tour groups travelling in Europe January 16-28. We compared characteristics of cases and non-cases to determine transmission dynamics. The index case travelled from Wuhan, China, to Europe on January 16, 2020, and to Shanghai, China, on January 27, 2020, within a tour group (group A). Tour groups with the same outbound flight (group B) or the same tourism venue (group D), and all Chinese passengers on the inbound flight (group C) were investigated. The outbreak involved 11 confirmed cases, 10 suspected cases, and 6 tourists who remained healthy. Group A, involving 7 confirmed cases and 6 suspected cases, consisted of familial transmission followed by propagative transmission. There was less pathogenicity with propagative transmission than with familial transmission. Disease was transmitted in shared outbound flights, shopping venues within Europe, and inbound flight back to China. The novel coronavirus caused clustered cases of COVID-19 in tour groups. When tourism and travel opens up, governments will need to improve screening at airports and consider increased surveillance of tour groups - particularly those with older tour members.


title: Narrative synthesis of psychological and coping responses towards emerging infectious disease outbreaks in the general population: practical considerations for the COVID-19 pandemic.

text: INTRODUCTION Emerging infectious disease outbreaks, such as the present coronavirus disease 2019 (COVID-19) pandemic, often have a psychological impact on the well-being of the general population, including survivors and caregivers. Our study aimed to synthesise extant literature regarding the combined psychological responses and coping methods used by the general population in past outbreaks. METHODS We conducted a narrative synthesis of the published literature over the last two decades with a quality appraisal of included articles that reported both psychological responses and coping strategies within infectious disease outbreaks. RESULTS A total of 144 papers were identified from the search, 24 of which were included in the review. Overall, 18 studies examined the psychosocial responses of the general population towards the severe acute respiratory syndrome epidemic, four studies focused on the Ebola epidemic and two studies covered the H1N1 outbreak. Common themes in psychological responses included anxiety/fears, depression, anger, guilt, grief and loss, post-traumatic stress, and stigmatisation, but also a greater sense of empowerment and compassion towards others. Coping strategies adopted included problem-focused coping (seeking alternatives, self- and other-preservation), seeking social support, avoidance, and positive appraisal of the situation. CONCLUSION Amid the range of psychosocial responses seen in past infectious disease outbreaks, practical considerations for the current COVID-19 pandemic need to focus on the individual in the context of the larger social environment, with an emphasis on raising awareness of the range of possible psychosocial responses, access to psychological help, self- care, empowering self-support groups and sustained engagement with updated, reliable information about the outbreak.


title: Blood Transfusion Requirement and Not Preoperative Anemia Are Associated with Perioperative Complications Following Intracorporeal Robot-Assisted Radical Cystectomy.

text: OBJECTIVES To assess the prevalence of preoperative anemia and the impact of preoperative anemia and blood transfusion requirement on 30- and 90-day complications in a cohort of patients undergoing robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC). PATIENTS AND METHODS IRARC was performed on 166 patients between June 2011 and March 2016. Prospective data were collected for patient demographics, clinical and pathologic characteristics, perioperative variables, transfusion requirements, and hospital length of stay. Thirty- and 90-day complications were classified according to the modified Memorial Sloan Kettering Cancer Center Clavien-Dindo system. RESULTS Preoperative anemia was common (43.4%) and greatest in patients receiving neoadjuvant chemotherapy (48.6%) (p < 0.001). Patients with preoperative anemia were significantly more likely to have an Ileal conduit (p = 0.033), higher cystectomy stage (≥pT3) (p = 0.028), and a lower lymph node yield (p = 0.031). Preoperative anemia was not associated with increased perioperative morbidity but was associated with the requirement for blood transfusion (p = 0.001). Blood transfusion required in 20.4% of patients with intraoperative and postoperative blood transfusion rate was 10.2% and 13.9%, respectively. The 30-day all complication rate and 30-day major complication rate were 55.4% and 15.7%, respectively, while 90-day all complication rate and 90-day major complication rate were 65.7% and 19.3%, respectively. Intraoperative blood transfusion was not associated with increased complications, but postoperative blood transfusion requirement was independently associated with perioperative morbidity: all 30-day complications (p = 0.003), all 90-day complications (p = 0.009), and 90-day major complications (p = 0.004). CONCLUSION The presence of preoperative anemia in patients undergoing iRARC is not associated with increased surgical risk, although preoperative anemic patients were significantly more likely to require blood transfusion. Blood transfusion requirement and specifically postoperative blood transfusion are independently associated with perioperative morbidity and are an important factor for the optimization of postoperative outcomes.


title: How does cellular heparan sulfate function in viral pathogenicity?

text: Heparan sulfate (HS) is ubiquitously expressed on the surfaces and in the extracellular matrix of virtually all cell types, making it an ideal receptor for viral infection. Compared with wild-type viruses, cell culture-adapted laboratory strains exhibit more efficient binding to cellular HS receptors. HS-binding viruses are typically cleared faster from the circulation and cause lower viremia than their non-HS-binding counterparts, suggesting that the HS-binding phenotype is a tissue culture adaptation that lowers virus fitness in vivo. However, when inoculated intracranially, efficient cell attachment through HS binding can contribute to viral neurovirulence. The primary aim of this review is to discuss the roles of HS binding in viral pathogenicity, including peripheral virulence and neurovirulence. Understanding how heparan sulfate functions during virus infection in vivo may prove critical for elucidating the molecular mechanism of viral pathogenesis, and may contribute to the development of therapeutics targeting HS.


How lost lizards and Hurricane Irma are helping me get through coronavirus restrictions.


title: A rabbit osteomyelitis model for the longitudinal assessment of early post-operative implant infections.

text: BACKGROUND Implant infection is one of the most severe complications within the field of orthopaedic surgery, associated with an enormous burden for the healthcare system. During the last decades, attempts have been made to lower the incidence of implant-related infections. In the case of cemented prostheses, the use of antibiotic-containing bone cement can be effective. However, in the case of non-cemented prostheses, osteosynthesis and spinal surgery, local antibacterial prophylaxis is not a standard procedure. For the development of implant coatings with antibacterial properties, there is a need for a reliable animal model to evaluate the preventive capacity of such coatings during a specific period of time. Existing animal models generally present a limited follow-up, with a limited number of outcome parameters and relatively large animal numbers in multiple groups. METHODS To represent an early post-operative implant infection, we established an acute tibial intramedullary nail infection model in rabbits by contamination of the tibial nail with 3.8 × 10⁵ colony forming units of Staphylococcus aureus. Clinical, haematological and radiological parameters for infection were weekly assessed during a 6-week follow-up with post-mortem bacteriological and histological analyses. RESULTS S. aureus implant infection was confirmed by the above parameters. A saline control group did not develop osteomyelitis. By combining the clinical, haematological, radiological, bacteriological and histological data collected during the experimental follow-up, we were able to differentiate between the control and the infected condition and assess the severity of the infection at sequential timepoints in a parameter-dependent fashion. CONCLUSION We herein present an acute early post-operative rabbit implant infection model which, in contrast to previously published models, combines improved in-time insight into the development of an implant osteomyelitis with a relatively low amount of animals.


docid: xgfapcaf

title: Effect of reversible intermittent intra-abdominal vagal nerve blockade on morbid obesity: the ReCharge randomized clinical trial.

text: IMPORTANCE Although conventional bariatric surgery results in weight loss, it does so with potential short-term and long-term morbidity. OBJECTIVE To evaluate the effectiveness and safety of intermittent, reversible vagal nerve blockade therapy for obesity treatment. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, sham-controlled clinical trial involving 239 participants who had a body mass index of 40 to 45 or 35 to 40 and 1 or more obesity-related condition was conducted at 10 sites in the United States and Australia between May and December 2011. The 12-month blinded portion of the 5-year study was completed in January 2013. INTERVENTIONS One hundred sixty-two patients received an active vagal nerve block device and 77 received a sham device. All participants received weight management education. MAIN OUTCOMES AND MEASURES The coprimary efficacy objectives were to determine whether the vagal nerve block was superior in mean percentage excess weight loss to sham by a 10-point margin with at least 55% of patients in the vagal block group achieving a 20% loss and 45% achieving a 25% loss. The primary safety objective was to determine whether the rate of serious adverse events related to device, procedure, or therapy in the vagal block group was less than 15%. RESULTS In the intent-to-treat analysis, the vagal nerve block group had a mean 24.4% excess weight loss (9.2% of their initial body weight loss) vs 15.9% excess weight loss (6.0% initial body weight loss) in the sham group. The mean difference in the percentage of the excess weight loss between groups was 8.5 percentage points (95% CI, 3.1-13.9), which did not meet the 10-point target (P = .71), although weight loss was statistically greater in the vagal nerve block group (P = .002 for treatment difference in a post hoc analysis). At 12 months, 52% of patients in the vagal nerve block group achieved 20% or more excess weight loss and 38% achieved 25% or more excess weight loss vs 32% in the sham group who achieved 20% or more loss and 23% who achieved 25% or more loss. The device, procedure, or therapy-related serious adverse event rate in the vagal nerve block group was 3.7% (95% CI, 1.4%-7.9%), significantly lower than the 15% goal. The adverse events more frequent in the vagal nerve block group were heartburn or dyspepsia and abdominal pain attributed to therapy; all were reported as mild or moderate in severity. CONCLUSION AND RELEVANCE Among patients with morbid obesity, the use of vagal nerve block therapy compared with a sham control device did not meet either of the prespecified coprimary efficacy objectives, although weight loss in the vagal block group was statistically greater than in the sham device group. The treatment was well tolerated, having met the primary safety objective. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01327976.


title: Differences in Morphologic and Hemodynamic Characteristics for "PHASES-Based" Intracranial Aneurysm Locations.

text: BACKGROUND AND PURPOSE Several recent prospective studies have found that unruptured intracranial aneurysms at various anatomic locations have different propensities for future rupture. This study aims to uncover the lack of understanding regarding rupture-prone characteristics, such as morphology and hemodynamic factors, associated with different intracranial aneurysm location. MATERIALS AND METHODS We investigated the characteristics of 311 unruptured aneurysms at our center. Based on the PHASES study, we separated and compared morphologic and hemodynamic characteristics among 3 aneurysm location groups: 1) internal carotid artery; 2) middle cerebral artery; and 3) anterior communicating, posterior communicating, and posterior circulation arteries. RESULTS A mixed model statistical analysis showed that size ratio, low wall shear stress area, and pressure loss coefficient were different between the intracranial aneurysm location groups. In addition, a pair-wise comparison showed that ICA aneurysms had lower size ratios, lower wall shear stress areas, and lower pressure loss coefficients compared with MCA aneurysms and compared with the group of anterior communicating, posterior communicating, and posterior circulation aneurysms. There were no statistical differences between MCA aneurysms and the group of anterior communicating, posterior communicating, and posterior circulation aneurysms for morphologic or hemodynamic characteristics. CONCLUSIONS ICA aneurysms may be subjected to less rupture-prone morphologic and hemodynamic characteristics compared with other locations, which could explain the decreased rupture propensity of intracranial aneurysms at this location.


title: [Gymnastics-sports activities: health benefits in emergency period CoViD-19. How to organize a quick shot.]

text: Regular physical activity grants significant health effects and lowers the risk of premature death for all causes, in particular cardiovascular ones in asymptomatic subjects. Physical activity is useful in the primary and secondary prevention of cardiovascular and lung diseases, metabolic diseases, musculoskeletal diseases, cancer and depression. Recent studies correlate inactivity with chronic low-grade inflammation and obesity, at the origin of chronic non-communicable diseases. The evidence must be taken seriously into consideration in this particular CoViD-19 emergency period and long-term effects of prolonged limitation of sports activity must not be overlooked. Contagion in open places is very difficult and the absolute prohibition of sports activities in open places and the closure of parks are creating discomfort and confusion. Institutions and media are generating the wrong message that active people must be looked at with disapproval. Instead, this habit should be encouraged, in order to protect citizens' and community health, lightening the welfare load for society.


title: Comparison of temperature measurements in esophagus and urinary bladder in comatose patients after cardiac arrest undergoing mild therapeutic hypothermia.

text: BACKGROUND Mild therapeutic hypothermia (MTH) is a recommended method of treatment for comatose out-of-hospital cardiac arrest (OHCA) survivors. However, the proper site of temperature measurement in MTH is still not defined. The aim of this study was to compare temperature measurements in the esophagus and urinary bladder in comatose post-OHCA patients treated with MTH. METHODS This temperature comparison protocol was a part of a prospective, observational, multicenter cohort study. The study population included 36 unconscious patients after resuscitation for OHCA. The patient's core temperature was independently measured every hour during MTH in the urinary bladder and in the esophagus. RESULTS The mean temperature was lower in the esophagus (differences during induction phase: 1.04 ± 0.92ºC, p < 0.0001; stabilization phase: 0.54 ± 0.39ºC, p < 0.0001; rewarming phase: 0.40 ± 0.47ºC, p < 0.0001). Nevertheless, a strong correlation between both sites was found (R² = 0.83, p < 0.001). The decrease in temperature observed in the esophagus during the induction phase was faster when compared with the urinary bladder (1.09 ± 0.71°C/h vs. 0.83 ± 0.41°C/h; p = 0.002). As a consequence, time to reach temperature < 34.0°C was longer when temperature was measured in the urinary bladder (the difference between medians of the time 1.0 [0-1.5] h, p < 0.001). CONCLUSIONS Urinary bladder temperature measurements may lag behind temperature changes measured in the esophagus.Monitoring temperature simultaneously in the esophagus and in the urinary bladder is an accessible and reliable combination, although esophageal measurements seem to better reflect the dynamics of temperature changes, thus it seems to be more appropriate for MTH control. ClinicalTrials.gov Identifier: NCT02611934.


Single port laparoscopic cholecystectomy in adults and children: tools and techniques.


title: Functional cross-talk between distant domains of chikungunya virus non-structural protein 2 is decisive for its RNA-modulating activity.

text: Chikungunya virus (CHIKV) non-structural protein 2 (nsP2) is a multifunctional protein that is considered a master regulator of the viral life cycle and a main viral factor responsible for cytopathic effects and subversion of antiviral defense. The C-terminal part of nsP2 possesses protease activity, whereas the N-terminal part exhibits NTPase and RNA triphosphatase activity and is proposed to have helicase activity. Bioinformatics analysis classified CHIKV nsP2 into helicase superfamily 1. However, the biochemical significance of a coexistence of two functionally unrelated modules in this single protein remains unknown. In this study, recombinant nsP2 demonstrated unwinding of double-stranded RNA in a 5'-3' directionally biased manner and RNA strand annealing activity. Comparative analysis of NTPase and helicase activities of wild type nsP2 with enzymatic capabilities of different truncated or N-terminally extended variants of nsP2 revealed that the C-terminal part of the protein is indispensable for helicase functionality and presumably provides a platform for RNA binding, whereas the N-terminal-most region is apparently involved in obtaining a conformation of nsP2 that allows for its maximal enzymatic activities. The establishment of the protocols for the production of biochemically active CHIKV nsP2 and optimization of the parameters for helicase and NTPase assays are expected to provide the starting point for a further search of possibilities for therapeutic interventions to suppress alphaviral infections.


title: Medicare reimbursement policies and hemodialysis vascular access outcomes: a need for change.

text: In March 2010, the Center for Medicare and Medicaid Services (CMS) convened several clinical technical expert panels (C-TEP) to provide recommendations for improving various aspects of hemodialysis management. One of the C-TEPs was tasked with recommending measures to decrease vascular access-related infections. The members of this C-TEP, who are the authors of this manuscript, concluded unanimously that the single most important measure would be to remove financial and regulatory barriers to timely placement and revision of hemodialysis fistulas and the concurrent avoidance of catheter use. The following position paper outlines the financial barriers to improved vascular access outcomes and our proposals for a future CMS demonstration project.


title: Arthroscopic coronal plane syndesmotic instability has been over-diagnosed.

text: PURPOSE Ankle arthroscopy is widely used for diagnosis of syndesmotic instability, especially in subtle cases. To date, no published article has systematically reviewed the literature in aggregate to understand which instability values should be used intraoperatively. The primary aim was to systematically review the amount of tibiofibular displacement that correlates with syndesmotic instability after a high ankle sprain. A secondary aim is to assess the quality of such research. METHODS Systematic searches of EMBASE (Ovid) and MEDLINE via PubMed, CINAHL, Web of Science, and Google Scholar were used. INCLUSION CRITERIA studies that arthroscopically evaluated the fibular displacement at various stages of syndesmotic ligament injury. Two reviewers independently extracted data and assessed methodological quality using the Anatomical Quality Assessment (AQUA) Tool and methodological index for non-randomized studies (MINORS). RESULTS Eight cadaveric studies and three clinical studies were included for review. All studies reported displacement in the coronal plane, four studies reported in the sagittal plane, and one reported findings in the rotational plane. Four cadaveric studies had a similar experimental set up and the weighted mean associated with instability in the coronal plane could be calculated and was 2.9 mm at the anterior portion of the distal tibiofibular joint and 3.4 mm at the posterior portion. Syndesmotic instability in the sagittal plane is less extensively studied, however available data from a cadaveric study suggests thresholds of 2.2 mm of posterior fibular translation when performing an anterior to posterior hook test and 2.6 mm of anterior fibular translation when performing a posterior to anterior hook test. CONCLUSIONS The results have concluded that the commonly used 2.0 mm threshold value of distal tibiofibular diastasis may lead to overtreatment of syndesmotic instability, and that using threshold values of 2.9 mm measured at the anterior portion of the incisura and 3.4 mm at the posterior portion may represent better cut off values. Given the ready availability of 3 mm probes among standard arthroscopic instrumentation, at the very least surgeons should use 3 mm in lieu of 2 mm probes intraoperatively. LEVEL OF EVIDENCE IV.


title: Continued success of the rapid response radiotherapy program: a review of 2004-2008.

text: PURPOSE To update the clinical activity of the Rapid Response Radiotherapy Program (RRRP). MATERIALS AND METHODS We conducted a retrospective review of our clinic database from January 2004 until July 2008. The number of patients referred to the RRRP, relevant demographic data, diagnosis and treatment dispositions were recorded. Time interval between referral to consultation and consultation to simulation were also calculated. RESULTS During the study period, 3,267 patients were seen in the RRRP. Forty-five percent (1,494) of the patients were new to the clinic. Of the 3,267 patients seen, 1,548 (47.4%) were female and 1,719 (52.6%) were male. The median age was 69.2 years (range, 22-101 years). The most common primary sites were lung (34.2%), breast (21.2%) and prostate (17.0%). The majority of patients were referred for palliative treatment of bone metastases (52.4%) or treatment for brain metastases (20.7%). Of the patients referred, 2,311 (70.5%) patients received palliative radiotherapy. The median duration from referral to consultation was 4 days. The majority (82.3%) of patients were simulated and treated within the first 7 days following consultation. CONCLUSION The number of patients referred to the RRRP from January 2004-July 2008 remains comparable to our previous report (1996-2003). The overall median interval from referral to consultation for the analysed time period was 4 days. Therefore, we are continuing to meet our goal of providing rapid access to palliative radiation treatment for symptomatic cancer patients. Further information relating to progression and advancements within the clinic aimed at improving our patients' quality of life are explored.


title: Surgical management and long-term outcome of umbilical infection in 65 foals (2010-2015).

text: OBJECTIVE To report the short- and long-term outcomes of surgical management of umbilical infection in foals. STUDY DESIGN Retrospective case series. ANIMALS Foals (n = 65). METHODS Medical records (2010-2015) of foals up to 1 month of age, surgically treated for an umbilical infection were reviewed. Short-term (at the time of discharge from hospital) and long-term (1 year after surgery) survival rates were obtained. Clinical variables influencing survival were assessed. Chi-square or Fisher's exact test were used to evaluate the relationship between the data retrieved and outcome. P ≤ .05 was considered statistically significant. RESULTS Sixty-five foals were included in the study, representing 17.2% of all foals admitted to the hospital. Fifty foals were discharged from hospital (77%) and 43 foals (66%) were alive 1 year after surgery. Lower long-term survival rates were associated with: younger age at presentation, septic joints, multiple pathologies, higher creatinine level, higher heart rate, umbilical infection diagnosed at the hospital rather than prior to referral, prolonged hospitalization, longer period between arrival and surgery, and postoperative complications. The most common surgical findings were urachal enlargement followed by right arterial enlargement. CONCLUSION Younger foals with worse systemic condition and concurrent disorders are at higher risk for treatment failure. Early diagnosis improves the outcome. Surgical treatment yields good results and should be considered upon diagnosis, after taking into account the clinical situation. CLINICAL SIGNIFICANCE Based on the results of this study, diagnosis and surgical management of umbilical infection in neonatal foals should be performed as early as possible, and a good outcome can be expected after surgery.


title: Resurgence of Vaccine-Preventable Diseases in the United States: Anesthetic and Critical Care Implications.

text: Vaccine-preventable diseases (VPDs) such as measles and pertussis are becoming more common in the United States. This disturbing trend is driven by several factors, including the antivaccination movement, waning efficacy of certain vaccines, pathogen adaptation, and travel of individuals to and from areas where disease is endemic. The anesthesia-related manifestations of many VPDs involve airway complications, cardiovascular and respiratory compromise, and unusual neurologic and neuromuscular symptoms. In this article, we will review the presentation and management of 9 VPDs most relevant to anesthesiologists, intensivists, and other hospital-based clinicians: measles, mumps, rubella, pertussis, diphtheria, influenza, meningococcal disease, varicella, and poliomyelitis. Because many of the pathogens causing these diseases are spread by respiratory droplets and aerosols, appropriate transmission precautions, personal protective equipment, and immunizations necessary to protect clinicians and prevent nosocomial outbreaks are described.


title: Mapping health communication scholarship: breadth, depth, and agenda of published research in Health Communication.

text: This study analyzed trends and patterns in the 22 years of research published in Health Communication. A content analysis of 642 articles examined the breadth and depth that Health Communication has achieved since its inception. Readers of Health Communication can thus see the history and scope of health communication as defined in the pages of this journal, and juxtapose this historical overview in the backdrop of the current scholarship that appears in the journal. We also identified some notable trends in research for the future development of the journal Health Communication specifically and the health communication discipline in general.


title: Differential diagnosis of acute ocular pain: Teleophthalmology during COVID-19 pandemic - A perspective.

text: Ocular pain is a common complaint which forces the patient to seek immediate medical attention. It is the primeval first response of the body to any severe condition of the eye such as trauma, infections and inflammation. The pain can be due to conditions directly affecting the eye and ocular adnexa; or indirect which would manifest as referred pain from other organ structures such as the central nervous system. Paradoxically, there are several minor and non-sight threatening conditions, which also leads to ocular pain and does not merit urgent hospital visits. In this perspective, we intend to provide guidelines to the practising ophthalmologist for teleconsultation when a patient complains of pain with focus on how to differentiate the various diagnoses that can be managed over teleconsultation and those requiring emergency care in the clinic. These guidelines can decrease unnecessary hospital visits, which is the need of the hour in the pandemic era and also beyond. Patients who are under quarantine and those who are unable to travel would be benefitted, and at the same time, the burden of increased patient load in busy hospital systems can be reduced.


title: Implementation of a clinical pathway for the surgical treatment of colorectal cancer during the COVID-19 pandemic.

text: INTRODUCTION This report summarises the early experience of implementing elective colorectal cancer surgery during the COVID-19 pandemic METHODS: A pathway to minimize the risk of including COVID-19 positive patients for elective surgery was established. Prioritization and additional safety measures were introduced into clinical practice. Minimal-invasive surgery (MIS) was used where appropriate. RESULTS Thirty-eight patients were prioritised, and 23 patients underwent surgery (8 colon, 14 rectal and 1 anal cancer). MIS rate was 78%. There were no major postoperative complications or patients diagnosed with COVID-19. Histopathological outcomes were similar to normal practice. CONCLUSION A safe pathway to offer standard high-quality surgery to colorectal cancer patients during the COVID-19 pandemic is feasible.


Next-Generation Sequencing of Mycobacterium tuberculosis.


title: Detailed Description of Change in Serum Cholesterol Profile with Incremental Weight Loss After Restrictive Bariatric Surgery.

text: INTRODUCTION Dyslipidemia affects up to 75% of morbidly obese individuals and is a key driver of cardiovascular disease. Weight loss is an established strategy to improve metabolic risk, including dyslipidemia. We aimed to determine weight loss goals for resolution of serum lipid abnormalities, by measuring improvements during progressive weight loss in obese individuals. METHODS We performed a prospective cohort study of obese individuals with the metabolic syndrome undergoing adjustable gastric banding. Lipid levels were monitored monthly for 9 months, then three monthly until 24 months. RESULTS There were 101 participants included, age 47.4 ± 10.9 years with body mass index 42.6 ± 5.9 kg/m2. At 24 months, total body weight loss (TBWL) was 18.3 ± 7.9%. This was associated with significant improvements in high-density lipoprotein (HDL) (1.18 vs 1.47, p < 0.001), triglyceride (2.0 vs 1.4, p < 0.001), and total cholesterol to HDL ratio (TC:HDL) (4.6 vs 3.6, p < 0.001). Over this time, progressive and linear improvements in HDL, triglycerides, and TC:HDL were seen with incremental weight loss (observed at 2.5% TBWL intervals). Significant improvements occurred after a threshold weight loss of 7.5-12.5% TBWL was achieved, with odds ratio (OR) 1.48-2.50 for normalization. These odds improved significantly with increasing weight loss (OR 18.2-30.4 with > 25% TBWL). Despite significant weight loss, there was no significant change in low-density lipoprotein (LDL). CONCLUSION Significant improvements in triglycerides, HDL, and TC:HDL occur after 7.5-12.5% TBWL, with ongoing benefit after greater weight loss. LDL needs to be addressed independently, as this was not observed to respond to weight loss alone. TRIAL REGISTRATION NUMBER Australian Clinical Trials Registry (ACTRN12610000049077).


title: Optimization of combined temozolomide and peptide receptor radionuclide therapy (PRRT) in mice after multimodality molecular imaging studies.

text: BACKGROUND Successful treatments of patients with somatostatin receptor (SSTR)-overexpressing neuroendocrine tumours (NET) comprise somatostatin-analogue lutetium-177-labelled octreotate ((177)Lu-TATE) treatment, also referred to as peptide receptor radionuclide therapy (PRRT), and temozolomide (TMZ) treatment. Their combination might result in additive effects. Using MRI and SPECT/CT, we studied tumour characteristics and therapeutic responses after different (combined) administration schemes in a murine tumour model in order to identify the optimal treatment schedule for PRRT plus TMZ. METHODS We performed molecular imaging studies in mice bearing SSTR-expressing H69 (humane small cell lung cancer) tumours after single intravenous (i.v.) administration of 30 MBq (177)Lu-TATE or TMZ (oral 50 mg/kg daily for 14 days). Tumour perfusion was evaluated weekly by dynamic contrast-enhanced MRI (DCE-MRI), whereas tumour uptake of (111)In-octreotide was quantified using SPECT/CT until day 39 after treatment. Based on these results, seven different (177)Lu-octreotate and TMZ combination schemes were evaluated for therapy response, varying the order and time interval of the two therapies and compared with single treatments. RESULTS PRRT and TMZ both resulted in tumour size reduction, accompanied by significant changes in MRI characteristics such as an enhanced tumour perfusion. Moreover, TMZ treatment also resulted in increased uptake of the SST analogue (111)In-octreotide until day 13. In the subsequent therapy study, 90 % of animals receiving (177)Lu-TATE at day 14 after TMZ treatment showed complete response, being the best anti-tumour results among groups. CONCLUSIONS Molecular imaging studies indicated that PRRT after TMZ treatment could induce optimal therapeutic effects because of enhanced tumour uptake of radioactivity after TMZ, which was confirmed by therapy responses. Therefore, clinical translation of TMZ treatment prior to PRRT might increase tumour responses in NET patients as well.


title: Cyclophilin involvement in the replication of hepatitis C virus and other viruses.

text: In recent months, there has been a wealth of promising clinical data suggesting that a more effective treatment regimen, and potentially a cure, for hepatitis C virus (HCV) infection is close at hand. Leading this push are direct-acting antivirals (DAAs), currently comprising inhibitors that target the HCV protease NS3, the viral polymerase NS5B, and the non-structural protein NS5A. In combination with one another, along with the traditional standard-of-care ribavirin and PEGylated-IFNα, these compounds have proven to afford tremendous efficacy to treatment-naíve patients, as well as to prior non-responders. Nevertheless, by targeting viral components, the possibility of selecting for breakthrough and treatment-resistant virus strains remains a concern. Host-targeting antivirals are a distinct class of anti-HCV compounds that is emerging as a complementary set of tools to combat the disease. Cyclophilin (Cyp) inhibitors are one such group in this category. In contrast to DAAs, Cyp inhibitors target a host protein, CypA, and have also demonstrated remarkable antiviral efficiency in clinical trials, without the generation of viral escape mutants. This review serves to summarize the current literature on Cyps and their relation to the HCV viral life cycle, as well as other viruses.


Covid-19: the ethics of clinical research in quarantine.


title: Difficulties arising from the variety of testing schemes used for bovine viral diarrhoea virus (BVDV).

text: Globally, the eradication of bovine viral diarrhoea virus (BVDV) is still in its infancy, but eradication has been, or is being, adopted by several countries or regions. Comparisons between countries' schemes allow others to assess best practice, and aggregating published results from eradication schemes provides greater statistical power when analysing data. Aggregating data requires that results derived from different testing schemes be calibrated against one another. The authors aimed to evaluate whether relationships between published BVDV test results could be created and present the outcome of a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The results are tabulated, providing a summary of papers where there is potential cross-calibration and a summary of the obstacles preventing such data aggregation. Although differences in measuring BVDV present barriers to academic progress, they may also affect progress within individual eradication schemes. The authors examined the time taken to retest following an initial antibody BVDV test in the Scottish eradication scheme. The authors demonstrate that retesting occurred quicker if the initial not negative test was from blood rather than milk samples. Such differences in the response of farmers/veterinarians to tests may be of interest to the design of future schemes.


title: Communication, collaboration and contagion: "virtualisation" of anatomy during COVID-19.

text: COVID-19 has generated a global need for technologies that enable communication, collaboration, education and scientific discourse whilst maintaining physical distance. University closures due to COVID-19 and physical distancing measures disrupt academic activities that previously occurred face-to-face. Restrictions placed on universities due to COVID-19 have precluded most conventional forms of education, assessment, research and scientific discourse. Anatomists now require valid, robust and easy-to-use communication tools to facilitate remote teaching, learning and research. Recent advances in communication, video conferencing and digital technologies may facilitate continuity of teaching and research activities. Examples include highly-interactive video conferencing technology, collaborative tools, social media and networking platforms. In this narrative review, we examine the utility of these technologies in supporting effective communication and professional activities of anatomists during COVID-19 and after. This article is protected by copyright. All rights reserved.


title: Human enterovirus 109 (EV109) in acute paediatric respiratory disease in Hungary.

text: Human enterovirus 109 (EV109) is a recently identified recombinant enterovirus in family Picornaviridae from acute paediatric respiratory illness in Nicaragua. EV109 have not been reported elsewhere. Our aims were the molecular detection and genetic analysis of EV109 from acute childhood respiratory infections in Hungary. Nasopharyngeal aspirates were collected from children under age of 10 years with acute respiratory infections treated in Department of Pulmonology, Kaposi Mór Teaching Hospital, Mosdós, Hungary. Samples were taken from 15 October to 15 May in two respiratory seasons 2005/2006 and 2006/2007. Samples were tested using EV109 specific VP1 primers by RT-PCR method. One (1.1%) of the 92 nasopharyngeal aspirates was positive for EV109 collected from a 2.5-year-old child in January, 2007. The main symptoms were dropping nose, fever (38.1°C), hard cough and wheezing associated with bronchitis and pneumonia. Based upon the VP1 gene region EV109 (L87/HUN/2007, JN900470) has 93% nucleotide identity and identical recombinant pattern to the prototype EV109. This is the first detection of the novel recombinant enterovirus, EV109, in Hungary (in Europe). This study supports the possibility that EV109 is able to cause acute respiratory infections, in addition, it might be plays a part in lower respiratory disease with hospitalization in children.


title: Should Cesarean Scar Defect Be Treated Laparoscopically? A Case Report and Review of the Literature.

text: Several obstetric complications due to inappropriately healed cesarean scar such as placenta accreta, scar dehiscence, and ectopic scar pregnancy are increasingly reported along with rising cesarean rates. Furthermore, many gynecologic conditions, including abnormal uterine bleeding, pelvic pain and infertility, are imputed to deficient cesarean scar healing. Hysteroscopy is the most commonly reported approach for the revision of cesarean scar defects (CSDs). Nevertheless, existing evidence is inadequate to conclude that either hysteroscopy or laparoscopy is effective or superior to each other. Although several management options have been suggested recently, the laparoscopic approach has not been thoroughly scrutinized. We present a case and reviewed the data related to the laparoscopic repair of CSDs and compared the hysteroscopic and laparoscopic management options based on the data from previously published articles. As a result of our analyses, the laparoscopic approach increases uterine wall thickness when compared with the hysteroscopic approach, and both surgical techniques seem to be effective for the resolution of gynecologic symptoms. Hysteroscopic treatment most likely corrects the scar defect but does not strengthen the uterine wall; thus, the potential risk of dehiscence or rupture in subsequent pregnancies does not seem to be improved. Because large uterine defects are known risk factors for scar dehiscence, the repair of the defect to reinforce the myometrial endurance seems to be an appropriate method of treatment.


docid: anhsximm

title: Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis.

text: IMPORTANCE Endovascular thrombectomy with second-generation devices is beneficial for patients with ischemic stroke due to intracranial large-vessel occlusions. Delineation of the association of treatment time with outcomes would help to guide implementation. OBJECTIVE To characterize the period in which endovascular thrombectomy is associated with benefit, and the extent to which treatment delay is related to functional outcomes, mortality, and symptomatic intracranial hemorrhage. DESIGN, SETTING, AND PATIENTS Demographic, clinical, and brain imaging data as well as functional and radiologic outcomes were pooled from randomized phase 3 trials involving stent retrievers or other second-generation devices in a peer-reviewed publication (by July 1, 2016). The identified 5 trials enrolled patients at 89 international sites. EXPOSURES Endovascular thrombectomy plus medical therapy vs medical therapy alone; time to treatment. MAIN OUTCOMES AND MEASURES The primary outcome was degree of disability (mRS range, 0-6; lower scores indicating less disability) at 3 months, analyzed with the common odds ratio (cOR) to detect ordinal shift in the distribution of disability over the range of the mRS; secondary outcomes included functional independence at 3 months, mortality by 3 months, and symptomatic hemorrhagic transformation. RESULTS Among all 1287 patients (endovascular thrombectomy + medical therapy [n = 634]; medical therapy alone [n = 653]) enrolled in the 5 trials (mean age, 66.5 years [SD, 13.1]; women, 47.0%), time from symptom onset to randomization was 196 minutes (IQR, 142 to 267). Among the endovascular group, symptom onset to arterial puncture was 238 minutes (IQR, 180 to 302) and symptom onset to reperfusion was 286 minutes (IQR, 215 to 363). At 90 days, the mean mRS score was 2.9 (95% CI, 2.7 to 3.1) in the endovascular group and 3.6 (95% CI, 3.5 to 3.8) in the medical therapy group. The odds of better disability outcomes at 90 days (mRS scale distribution) with the endovascular group declined with longer time from symptom onset to arterial puncture: cOR at 3 hours, 2.79 (95% CI, 1.96 to 3.98), absolute risk difference (ARD) for lower disability scores, 39.2%; cOR at 6 hours, 1.98 (95% CI, 1.30 to 3.00), ARD, 30.2%; cOR at 8 hours,1.57 (95% CI, 0.86 to 2.88), ARD, 15.7%; retaining statistical significance through 7 hours and 18 minutes. Among 390 patients who achieved substantial reperfusion with endovascular thrombectomy, each 1-hour delay to reperfusion was associated with a less favorable degree of disability (cOR, 0.84 [95% CI, 0.76 to 0.93]; ARD, -6.7%) and less functional independence (OR, 0.81 [95% CI, 0.71 to 0.92], ARD, -5.2% [95% CI, -8.3% to -2.1%]), but no change in mortality (OR, 1.12 [95% CI, 0.93 to 1.34]; ARD, 1.5% [95% CI, -0.9% to 4.2%]). CONCLUSIONS AND RELEVANCE In this individual patient data meta-analysis of patients with large-vessel ischemic stroke, earlier treatment with endovascular thrombectomy + medical therapy compared with medical therapy alone was associated with lower degrees of disability at 3 months. Benefit became nonsignificant after 7.3 hours.


title: Changing epidemiology of respiratory viral infections in hematopoietic cell transplant recipients and solid organ transplant recipients.

text: PURPOSE OF REVIEW New respiratory viruses have been discovered in recent years and new molecular diagnostic assays have been developed that improve our understanding of respiratory virus infections. This article will review the changing epidemiology of these viruses after hematopoietic stem cell and solid organ transplantation. RECENT FINDINGS Respiratory viruses are frequently detected in transplant recipients. A number of viruses have been newly discovered or emerged in the last decade, including human metapneumovirus, human bocavirus, new human coronaviruses and rhinoviruses, human polyomaviruses, and a new 2009 pandemic strain of influenza A/H1N1. The potential for these viruses to cause lower respiratory tract infections after transplantation varies, and is greatest for human metapneumovirus and H1N1 influenza, but appears to be limited for the other new viruses. Acute and long-term complications in hematopoietic and solid organ transplant recipients are active areas of research. SUMMARY Respiratory viral infections are frequently associated with significant morbidity following transplantation and are therefore of great clinical and epidemiologic interest. As new viruses are discovered, and more sensitive diagnostic methods are developed, defining the full impact of emerging respiratory viruses in transplant recipients must be elucidated by well designed clinical studies.


title: Functional replacement of a domain in the rubella virus p150 replicase protein by the virus capsid protein.

text: The rubella virus (RUBV) capsid (C) protein rescues mutants with a lethal deletion between two in-frame NotI sites in the P150 replicase gene, a deletion encompassing nucleotides 1685 to 2192 of the RUBV genome and amino acids (aa) 548 to 717 of P150 (which has a total length of 1,301 aa). The complete domain rescuable by the C protein was mapped to aa 497 to 803 of P150. Introduction of aa 1 to 277 of the C protein (lacking the C-terminal E2 signal sequence) between the NotI sites in the P150 gene in a replicon construct yielded a viable construct that synthesized viral RNA with wild-type kinetics, indicating that C and this region of P150 share a common function. Further genetic analysis revealed that an arginine-rich motif between aa 60 and 68 of the C protein was necessary for the rescue of DeltaNotI deletion mutants and substituted for an arginine-rich motif between aa 731 and 735 of the P150 protein when the C protein was introduced into P150. Possible common functions shared by these arginine-rich motifs include RNA binding and interaction with cell proteins.


title: Ectopeptidases in tumour biology: a review.

text: Cell membrane-bound proteolytic enzymes (ectopeptidases) are integral membrane proteins, orientated asymmetrically with the catalytic site exposed to the extracellular surface, which enables a versatile range of physiological and pathological functions. Ectopeptidases may regulate the release of many growth factors and their receptors into the circulation, as well as activating or inactivating circulating signalling molecules, thereby regulating the availability of ligands for the corresponding receptors. Additionally, many of these ectopeptidases have functions not limited to proteolysis, but are able in themselves to function as receptors, transducing intracellular signals. A versatile range of functions, such as the modulation of cell-signalling, matrix degradation, cell adhesion and migration, which are particularly important for tumour cell growth and dissemination, are attributed largely to the ectopeptidases. Even a minor disruption in the normal proteolytic equilibrium can influence tumor progression, and a range of ectopeptidases, including neutral endopeptidase 24.11, aminopeptidase N, dipeptidyl peptidase IV, angiotensin-converting enzyme, and the disintegrin-metalloproteinases, have been shown to be involved in tumour development and metastasis. The ability to degrade and inactivate peptide hormones and growth factors, with the resultant modulation of the tumour-host interface, may play an important role in the pathogenesis, development or progression of a range of cancers, and the extracellular orientation of the ectopeptidases makes them particularly accessible, and therefore interesting, with regard to therapeutical applications.


title: Radiofrequency is a secure and effective method for pancreatic transection in laparoscopic distal pancreatectomy: results of a randomized, controlled trial in an experimental model.

text: BACKGROUND Postoperative pancreatic fistula (PPF) is the most frequent and serious complication after laparoscopic distal pancreatectomy (LDP). Our goal was to compare the performance, in terms of PPF prevention, and safety of a radiofrequency (RF)-assisted transection device versus a stapler device in a porcine LDP model. METHODS Thirty-two animals were randomly divided into two groups to perform LDP using a RF-assisted device (RF group; n = 16) and stapler device (ST group; n = 16) and necropsied 4 weeks after surgery. The primary endpoint was the incidence of PPF. Secondary endpoints were surgery/transection time, intra/postoperative complications/deaths, postoperative plasmatic amylase and glucose concentration, peritoneal liquid amylase and interleukin 6 (IL-6) concentrations, weight variations, and histopathological changes. RESULTS Two clinical and one biochemical PPF were observed in the ST and RF groups respectively. Peritoneal amylase concentration was significantly higher in the RF group 4 days after surgery, but this difference was no longer present at necropsy. Both groups presented a significant decrease in peritoneal IL-6 concentration during the postoperative follow-up, with no differences between the groups. RF group animals showed a higher postoperative weight gain. In the histopathological exam, all RF group animals showed a common pattern of central coagulative necrosis of the parenchymal surface, surrounded by a thick fibrosis, which sealed main and secondary pancreatic ducts and was not found in ST group. CONCLUSIONS The fibrosis caused by an RF-assisted device can be at least as safe and effective as stapler compression to achieve pancreatic parenchyma sealing in a porcine LDP model.


title: System dynamics modeling as a potentially useful tool in analyzing mitigation strategies to reduce overdose deaths associated with pharmaceutical opioid treatment of chronic pain.

text: OBJECTIVE To illustrate a system-level, simulation-based approach for evaluating mitigation strategies to address the dramatic rise in abuse, addiction, and overdose deaths associated with the use of pharmaceutical opioid analgesics to treat chronic pain. SIMULATED INTERVENTIONS: Making available drug formulations with increased tamper-resistance, prescriber education programs, and programs that reduce rates of medical user-related abuse and addiction. SIMULATED OUTCOME MEASURE: Number of overdose deaths of medical users of pharmaceutical opioid analgesics, including those who abuse or have become addicted. METHODS A demonstration system dynamics model is developed, tested, and used to evaluate the impact of candidate mitigation strategies on the outcome measures. RESULTS Tamper-resistant drug products will likely reduce overdose death rates but may not reduce overall deaths if there is increased prescribing. Prescriber education would likely reduce deaths through a reduction in patient access to pharmaceutical opioid analgesics. CONCLUSIONS The system dynamics approach may have potential for opioid-related policy evaluation. However, metrics must be carefully selected, and trade-offs may be involved. For example, it may be difficult to limit negative outcomes associated with pharmaceutical opioids without adversely affecting chronic pain patients' access to pharmaceutical treatment. Ultimately, a combination of metrics and value judgments will be needed to properly evaluate mitigation strategies.


Scientists call for pandemic investigations to focus on wildlife trade.


title: [Recommendations on extracorporeal life support for critically ill patients with novel coronavirus pneumonia].

text: Along with the sharp increase of confirmed cases novel coronavirus infection, more critically ill cases require extracorporeal membrane oxygenation (ECMO) support. Based on the clinical data of novel coronavirus pneumonia (NCP), as well as the dada from previous clinical studies and the recommendations from the Extracorporeal Life Support Organization (ELSO), the committee board of the Chinese Society of Extracorporeal Life Support (CSECLS) made this recommendations to guide clinical ECMO application in the patients with NCP.


title: Glial cell-line derived neurotrophic factor (GDNF) replacement attenuates motor impairments and nigrostriatal dopamine deficits in 12-month-old mice with a partial deletion of GDNF.

text: Glial cell-line derived neurotrophic factor (GDNF) has been established as a growth factor for the survival and maintenance of dopamine (DA) neurons. In phase I clinical trials, GDNF treatment in Parkinson's disease patients led to improved motor function and GDNF has been found to be down regulated in Parkinson's disease patients. Studies using GDNF heterozygous (Gdnf(+/-)) mice have demonstrated that a partial reduction of GDNF leads to an age-related accelerated decline in nigrostriatal DA system- and motor-function and increased neuro-inflammation and oxidative stress in the substantia nigra (SN). Therefore, the purpose of the current studies was to determine if GDNF replacement restores motor function and functional markers within the nigrostriatal DA system in middle-aged Gdnf(+/-) mice. At 11months of age, male Gdnf(+/-) and wildtype (WT) mice underwent bilateral intra-striatal injections of GDNF (10μg) or vehicle. Locomotor activity was assessed weekly 1-4weeks after treatment. Four weeks after treatment, their brains were processed for analysis of GDNF levels and various DAergic and oxidative stress markers. An intrastriatal injection of GDNF increased motor activity in Gdnf(+/-) mice to levels comparable to WT mice (1week after injection) and this effect was maintained through the 4-week time point. This increase in locomotion was accompanied by a 40% increase in striatal GDNF protein levels and SN GDNF expression in Gdnf(+/-) mice. Additionally, GDNF treatment significantly increased the number of tyrosine hydroxylase (TH)-positive neurons in the SN of middle-aged Gdnf(+/-) mice, but not WT mice, which was coupled with reduced oxidative stress in the SN. These studies further support that long-term changes related to the dysfunction of the nigrostriatal pathway are influenced by GDNF expression and add that this dysfunction appears to be responsive to GDNF treatment. Additionally, these studies suggest that long-term GDNF depletion alters the biological and behavioral responses to GDNF treatment.


title: Viral pneumonia: etiologies and treatment.

text: Viral pathogens are increasingly recognized as a cause of pneumonia, in immunocompetent patients and more commonly among immunocompromised. Viral pneumonia in adults could present as community-acquired pneumonia (CAP), ranging from mild disease to severe disease requiring hospital admission and mechanical ventilation. Moreover, the role of viruses in hospital-acquired pneumonia and ventilator-associated pneumonia as causative agents or as co-pathogens and the effect of virus detection on clinical outcome are being investigated.More than 20 viruses have been linked to CAP. Clinical presentation, laboratory findings, biomarkers, and radiographic patterns are not characteristic to specific viral etiology. Currently, laboratory confirmation is most commonly done by detection of viral nucleic acid by reverse transcription-PCR of respiratory secretions.Apart from the US Food and Drug Administration-approved medications for treatment of influenza pneumonia, the treatment of non-influenza respiratory viruses is limited. Moreover, the evidence supporting the use of available antivirals to treat immunocompromised patients is modest at best. With the widespread use of molecular diagnostics, an aging population, and advancement in cancer therapy, physicians will face a bigger challenge in managing viral respiratory tract infections. Emphasis on infection control measures to prevent the spread of respiratory viruses especially in healthcare settings is extremely important.


title: Impact of age on postoperative outcomes in bariatric surgery.

text: BACKGROUND Age is often related to the increase of perioperative complications and reoperation rates. The authors aimed to determine the influence of age on outcomes of most commonly performed bariatric procedures. METHODS The retrospective study included patients qualified for primary Laparoscopic Sleeve Gastrectomy (LSG) or Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) in two academic hospitals. Patients were divided into two groups: ≥50 (21.2-26.9%) and <50 (57.6-73.1%) years old. Endpoints assessed the influence of patients' age on the perioperative and the one-year postoperative period. RESULTS Operative time was longer in the ≥50-year-old group, but only for LRYGB. There were no differences in the intraoperative adverse events, postoperative morbidity, reoperation and readmission rates between the groups. The risk of port site hernia was increased (OR: 4.23, CI: 1.49-12.06) in the ≥50-year-old group. The mean % of total weight loss 12 months after the bariatric procedure was comparable, but % of excess weight loss and % of excess body mass index loss were lower in the ≥50-year-old group (p = .033 and .032). CONCLUSIONS Bariatric surgery is safe and feasible in patients over 50 years old. The weight loss effect can be worse among patients over 50 years old; nevertheless, the treatment should be considered as effective.


title: Efficacy and unintended consequences of hard-stop alerts in electronic health record systems: a systematic review.

text: Objective Clinical decision support (CDS) hard-stop alerts-those in which the user is either prevented from taking an action altogether or allowed to proceed only with the external override of a third party-are increasingly common but can be problematic. To understand their appropriate application, we asked 3 key questions: (1) To what extent are hard-stop alerts effective in improving patient health and healthcare delivery outcomes? (2) What are the adverse events and unintended consequences of hard-stop alerts? (3) How do hard-stop alerts compare to soft-stop alerts? Methods and Materials Studies evaluating computerized hard-stop alerts in healthcare settings were identified from biomedical and computer science databases, gray literature sites, reference lists, and reviews. Articles were extracted for process outcomes, health outcomes, unintended consequences, user experience, and technical details. Results Of 32 studies, 15 evaluated health outcomes, 16 process outcomes only, 10 user experience, and 4 compared hard and soft stops. Seventy-nine percent showed improvement in health outcomes and 88% in process outcomes. Studies reporting good user experience cited heavy user involvement and iterative design. Eleven studies reported on unintended consequences including avoidance of hard-stopped workflow, increased alert frequency, and delay to care. Hard stops were superior to soft stops in 3 of 4 studies. Conclusions Hard stops can be effective and powerful tools in the CDS armamentarium, but they must be implemented judiciously with continuous user feedback informing rapid, iterative design. Investigators must report on associated health outcomes and unintended consequences when implementing IT solutions to clinical problems.


title: RNA virus population diversity, an optimum for maximal fitness and virulence.

text: The ability of an RNA virus to exist as a population of genetically distinct variants permits the virus to overcome events during infections that would otherwise limit virus multiplication or drive the population to extinction. Viral genetic diversity is created by the ribonucleotide misincorporation frequency of the viral RNA-dependent RNA polymerase (RdRp). We have identified a poliovirus (PV) RdRp derivative (H273R) possessing a mutator phenotype. GMP misincorporation efficiency for H273R RdRp in vitro was increased by 2-3-fold that manifested in a 2-3-fold increase in the diversity of the H273R PV population in cells. Circular sequencing analysis indicated that some mutations were RdRp-independent. Consistent with the population genetics theory, H273R PV was driven to extinction more easily than WT in cell culture. Furthermore, we observed a substantial reduction in H273R PV virulence, measured as the ability to cause paralysis in the cPVR mouse model. Reduced virulence correlated with the inability of H273R PV to sustain replication in tissues/organs in which WT persists. Despite the attenuated phenotype, H273R PV was capable of replicating in mice to levels sufficient to induce a protective immune response, even when the infecting dose used was insufficient to elicit any visual signs of infection. We conclude that optimal RdRp fidelity is a virulence determinant that can be targeted for viral attenuation or antiviral therapies, and we suggest that the RdRp may not be the only source of mutations in a RNA virus genome.


title: Attention-Deficit/Hyperactivity Disorder and Very Preterm/Very Low Birth Weight: A Meta-analysis.

text: CONTEXT Although very preterm (VP), extremely preterm (EP), very low birth weight (VLBW), and extremely low birth weight (ELBW) newborns seem to have a higher risk of later attention-deficit/hyperactivity disorder (ADHD), the magnitude of the risk is not well-defined. OBJECTIVE To systematically review and meta-analyze the risk of VP/VLBW and EP/ELBW individuals to develop a ADHD categorical diagnosis or dimensional symptomatology compared with controls with normal weight and/or birth age. DATA SOURCES We used PsycINFO, Medline, Embase, and Cochrane databases. STUDY SELECTION We selected cross-sectional, prospective, or retrospective studies with no time or language restriction. DATA EXTRACTION Independent reviewers screened and extracted data using predefined standard procedures. RESULTS In 12 studies (N = 1787), researchers relying on a categorical diagnosis showed that both VP/VLBW and EP/ELBW subjects have a higher ADHD risk (odds ratio [OR] = 3.04 higher than controls; 95% confidence interval [CI] 2.19 to 4.21). In subgroup analyses, we demonstrated that the more extreme the cases, the higher the ORs (VP/VLBW: OR = 2.25 [95% CI 1.56 to 3.26]; EP/ELBW: OR = 4.05 [95% CI 2.38 to 6.87]). We drew data from 29 studies (N = 3504) on ADHD symptomatology and found significant associations with inattention (standardized mean difference [SMD] = 1.31, 95% CI 0.66 to 1.96), hyperactivity and impulsivity (SMD = 0.74, 95% CI 0.35 to 1.13), and combined symptoms (SMD = 0.55, 95% CI 0.42 to 0.68) when compared with controls. LIMITATIONS Heterogeneity was significantly high for all analyses involving the 3 ADHD dimensions. CONCLUSIONS With our results, we provide evidence that VP/VLBW subjects have an increased risk of ADHD diagnosis and symptomatology compared with controls, and these findings are even stronger in the EP/ELBW group. Future researchers should address which risk factors related to prematurity or low birth weight lead to ADHD.


title: Etiology and Outcomes of ARDS in a Rural-Urban Fringe Hospital of South India.

text: Objectives. Etiology and outcomes of acute lung injury in tropical countries may be different from those of western nations. We describe the etiology and outcomes of illnesses causing acute lung injury in a rural populace. Study Design. A prospective observational study. Setting. Medical ICU of a teaching hospital in a rural-urban fringe location. Patients. Patients ≥13 years, admitted between December 2011 and May 2013, satisfying AECC criteria for ALI/ARDS. Results. Study had 61 patients; 46 had acute lung injury at admission. Scrub typhus was the commonest cause (7/61) and tropical infections contributed to 26% of total cases. Increasing ARDS severity was associated with older age, higher FiO2 and APACHE/SOFA scores, and longer duration of ventilation. Nonsurvivors were generally older, had shorter duration of illness, a nontropical infection, and higher total WBC counts, required longer duration of ventilation, and had other organ dysfunction and higher mean APACHE scores. The mortality rate of ARDS was 36.6% (22/61) in our study. Conclusion. Tropical infections form a major etiological component of acute lung injury in a developing country like India. Etiology and outcomes of ARDS may vary depending upon the geographic location and seasonal illnesses.


title: Interhemispheric Pathways Are Important for Motor Outcome in Individuals with Chronic and Severe Upper Limb Impairment Post Stroke.

text: Background Severity of arm impairment alone does not explain motor outcomes in people with severe impairment post stroke. Objective Define the contribution of brain biomarkers to upper limb motor outcomes in people with severe arm impairment post stroke. Methods Paretic arm impairment (Fugl-Meyer upper limb, FM-UL) and function (Wolf Motor Function Test rate, WMFT-rate) were measured in 15 individuals with severe (FM-UL ≤ 30/66) and 14 with mild-moderate (FM-UL > 40/66) impairment. Transcranial magnetic stimulation and diffusion weight imaging indexed structure and function of the corticospinal tract and corpus callosum. Separate models of the relationship between possible biomarkers and motor outcomes at a single chronic (≥6 months) time point post stroke were performed. Results Age (ΔR20.365, p = 0.017) and ipsilesional-transcallosal inhibition (ΔR20.182, p = 0.048) explained a 54.7% (p = 0.009) variance in paretic WMFT-rate. Prefrontal corpus callous fractional anisotropy (PF-CC FA) alone explained 49.3% (p = 0.007) variance in FM-UL outcome. The same models did not explain significant variance in mild-moderate stroke. In the severe group, k-means cluster analysis of PF-CC FA distinguished two subgroups, separated by a clinically meaningful and significant difference in motor impairment (p = 0.049) and function (p = 0.006) outcomes. Conclusion Corpus callosum function and structure were identified as possible biomarkers of motor outcome in people with chronic and severe arm impairment.


title: Bidirectional treatment of peritoneal metastasis with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) and systemic chemotherapy: a systematic review.

text: BACKGROUND Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is used in the palliative treatment of peritoneal metastasis. The combination of intraperitoneal and systemic chemotherapy seems rational, and the aim of this systematic review was to compare PIPAC directed monotherapy with a bidirectional treatment approach (PIPAC in combination with systemic chemotherapy). Main outcomes were survival and quality of life. METHODS A systematic literature search in Medline, Embase, Cochrane and the "Pleura and Peritoneum" was conducted and analyzed according to PRISMA guidelines. Studies in English reporting on bidirectional treatment with PIPAC and systemic chemotherapy and published before April 2019 were included. RESULTS Twelve studies with a total of 386 patients were included. None were specifically designed to compare mono- versus bidirectional treatment, but 44% of the patients received bidirectional treatment. This was more frequent in women (non-gynecological cancers) and one-third of the bidirectional treated patients had received no prior chemotherapy. Data from the included studies provided no conclusions regarding survival or quality of life. CONCLUSION Bidirectional treatment with PIPAC and systemic chemotherapy is practised and feasible, and some patients are enrolled having received no prior systemic chemotherapy for their PM. The difficulty in drawing any conclusions based on this systematic review has highlighted the urgent need to improve and standardize reports on PIPAC directed therapy. We have, therefore, constructed a list of items to be considered when reporting on clinical PIPAC research. TRIAL REGISTRATION International Prospective Register of Systematic Reviews, PROSPERO. Registration number: 90352, March 5, 2018.


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title: COVID-19 and the Need for a National Health Information Technology Infrastructure.