bluuebunny/crossref_metadata_2025 huggingface dataset:
Monocytopenia in clozapine-induced agranulocytosis: insights into pathophysiology and treatment
Authors: Patel Rajvi , Lima Ateaya , Burke Christopher , Hoffman Mark
Published: January 2019

A 26-year-old man with history of schizophrenia was admitted for neutropaenia. He was started on clozapine 3 months prior to admission. As a result he had weekly monitoring of his blood counts and on day of admission was noted to have an absolute neutrophil count (ANC) of 450 cells/μL. He was admitted for clozapine-induced agranulocytosis. Clozapine was held and the patient was started on granulocyte colony-stimulating factor (G-CSF) filgrastim and received two doses without any signs of ANC recovery. On further review, it was noted that the absolute monocyte count (AMC) was also low and tracked with the trend of ANC. We then theorised that the impact of clozapine was on a haematopoietic precursor (colony-forming unit granulocyte-macrophage, CFU-GM) which gives rise to both monocytic and myeloid lineages. Therefore, sargramostim GM-CSF was started. After two doses, the ANC and AMC started trending up and by the third dose, both counts had fully recovered. He was discharged from the hospital and there are no plans to rechallenge with clozapine. Thus, we demonstrate a case of monocytopenia accompanying clozapine-induced agranulocytosis with successful use of GM-CSF. At least in this case, the target of the clozapine injury appears to be the CFU-GM, explaining the rapid and full response to GM-CSF after lack of response to G-CSF.
Rare case of bladder chondroma causing lower urinary tract symptoms
Authors: Ngweso Simeon , Mukhtar Saheel , Forrest Cindy , Mander Julian
Published: January 2019

An extraosseous or soft tissue chondroma is a rare, benign cartilaginous tumour characterised by the formation of mature hyaline cartilage. The majority of osseous chondromas are located within the medullary cavity of long bones. Soft tissue chondromas are extremely rare with only five cases affecting the bladder being reported in the literature. Soft tissue chondroma of the bladder is a rare cause of lower urinary tract symptoms and abdominopelvic pain. All reported cases of soft tissue chondromas of the bladder have occurred in women in their fifth to seventh decades of life. We describe the case of a 65-year-old woman diagnosed with a soft tissue chondroma of her bladder while being investigated for lower urinary tract symptoms.
Focal myositis and contracture secondary to amiodarone extravasation from a peripheral cannula
Authors: Ledingham David , Cordato Dennis
Published: January 2019

A 63-year-old man underwent cardioversion of atrial fibrillation with intravenous amiodarone through an antecubital fossa cannula. Mid-infusion, the cannula tissued. He developed immediate pain and swelling. At 3 weeks, he continued to have significant pain and had developed a fixed flexion deformity. MRI demonstrated focal myositis of the biceps and brachialis muscles. Treatment included physiotherapy and plastic surgery but sadly in spite of this, the patient has had minimal symptomatic improvement at 1 year. Amiodarone extravasation is well recognised to cause local injection site reactions. Involvement of deeper tissues is rare. To our knowledge, this is only the second description of a consequent focal myositis in the literature.
Physiotherapist-delivered stress inoculation training integrated with exercise versus physiotherapy exercise alone for acute whiplash-associated disorder (StressModex): a randomised controlled trial of a combined psychological/physical intervention
Authors: Sterling Michele , Smeets Rob , Keijzers Gerben , Warren Jacelle , Kenardy Justin
Published: January 2019

Objective

There are few effective treatments for acute whiplash-associated disorders (WAD). Early symptoms of postinjury stress predict poor recovery. This randomised controlled trial (StressModex) investigated whether physiotherapist-led stress inoculation training integrated with exercise is more effective than exercise alone for people with acute WAD.

Methods

108 participants (<4 weeks) at risk of poor recovery (moderate pain-related disability and hyperarousal symptoms) were randomly assigned by concealed allocation to either physiotherapist-led stress inoculation training and guideline-based exercise (n=53) or guideline-based exercise alone (n=55). Both interventions comprised 10 sessions over 6 weeks. Participants were assessed at 6 weeks and at 6 and 12 months postrandomisation. Analysis was by intention to treat using linear mixed models.

Results

The combined stress inoculation training and exercise intervention was more effective than exercise alone for the primary outcome of pain-related disability at all follow-up points. At 6 weeks, the treatment effect on the 0–100 Neck Disability Index was (mean difference) −10 (95% CI −15.5 to −4.48), at 6 months was −7.8 (95% CI −13.8 to −1.8) and at 12 months was −10.1 (95% CI −16.3 to −4.0). A significant benefit of the stress inoculation and exercise intervention over exercise alone was also found for some secondary outcomes.

Conclusion

A physiotherapist-led intervention of stress inoculation training and exercise resulted in clinically relevant improvements in disability compared with exercise alone—the most commonly recommended treatment for acute WAD. This contributes to the case for physiotherapists to deliver an early psychological intervention to patients with acute WAD who are otherwise at high risk of a poor outcome.

Trial registration number

ACTRN12614001036606.
Exercise-induced laryngeal obstruction in athletes treated with inspiratory muscle training
Authors: Sandnes Astrid , Andersen Tiina , Clemm Hege Havstad , Hilland Magnus , Vollsæter Maria , Heimdal John-Helge , Eide Geir Egil , Halvorsen Thomas , Røksund Ola Drange
Published: January 2019

Background

Exercise-induced laryngeal obstruction (EILO) is common in athletes and presents with dyspnoea, chest tightness, inspiratory stridor and sometimes panic reactions. The evidence for conservative treatment is weak, but case reports suggest effects from inspiratory muscle training (IMT). We aimed to explore effects from IMT used in athletes with EILO.

Method

Twenty-eight athletes, mean age 16.4 years, diagnosed with EILO at our clinic, participated in a 6-week treatment programme, using a resistive flow-dependent IMT device (Respifit S). Four athletes competed at international level, 13 at national and 11 at regional levels. Video-recorded continuous transnasal flexible laryngoscopy was performed from rest to peak exercise (continuous laryngoscopy exercise (CLE) test) and scored before and 2–4 weeks after the training period. Ergospirometric variables were obtained from this CLE set-up. Lung function was measured according to guidelines. Symptom scores and demographic variables were obtained from a questionnaire.

Results

After the treatment period, symptoms had decreased in 22/28 (79%) participants. Mean overall CLE score had improved after treatment (p<0.001), with the scores becoming normal in five athletes but worse in two. Most of the improvement was explained by changes at the glottic laryngeal level (p=0.009). Ergospirometric variables revealed significantly higher peak minute ventilation explained by higher tidal volumes and were otherwise unchanged.

Conclusion

This explorative study underlines the heterogeneous treatment response of EILO and suggests that IMT may become an efficient conservative treatment tool in subgroups, possibly contributing to better control of the vocal folds. The signals from this study should be tested in future controlled interventional studies.
Evaluation of a simulation-based Risk Management and Communication Masterclass to reduce the risk of complaints, medicolegal and dentolegal claims
Authors: Jolly John , Bowie Paul , Dawson Lauren , Heslington Lorna , Dinwoodie Mark
Published: January 2019

Objectives

To understand clinicians’ experiences, learning and professional impacts following participation in a Risk Management and Communication Masterclass (RMCM) designed and delivered by Medical Protection Society. To identify the course’s strengths and areas for enhancement.

Design

Mixed method study including semistructured telephone interviews. Interviews were conducted between October and December 2017, 6–30 months after course participation. Data were subjected to a thematic analysis. Quantitative analysis of participants’ feedback ratings (n=486) on RMCMs delivered between December 2014 and May 2017 was also undertaken.

Setting

RMCMs were delivered to Doctors and Dentists based in the UK and Ireland and South Africa. Participants: A sample of 12 volunteer doctors (Obstetricians/Gynaecologists, Orthopaedic/Spinal Surgeons, General Surgeons, Paediatricians, General Practitioners) and dentists chosen to represent different clinical specialities accepted the invitation to participate.

Results

Study participants reported examples of person-centred communication skills such as empathy, shared-decision making and managing patient expectations in their workplaces following participation in the RMCM. Many clinicians gave examples describing how they used the communication models they learned when back at work. They also demonstrated a better understanding of the motivations for patients to complain or claim. RMCM course participants’ high feedback ratings provided further evidence that the course was valuable and met learning objectives.

Conclusions

It may prove difficult to demonstrate quantitatively that liability improves as a direct result of risk management and communications training. Our results on other dimensions (reactions, learning, behaviour change and impact) suggest that the RMCM has a positive and durable effect based on participant feedback.
British society of gastroenterology Endoscopy Quality Improvement Programme (EQIP): overview and progress
Authors: Rees Colin J , Koo Sara , Anderson John , McAlindon Mark , Veitch Andrew M , Morris Allan John , Bhandari Pradeep , East James E , Webster George , Oppong Kofi W , Penman Ian D
Published: January 2019

High quality gastrointestinal (GI) endoscopy improves patient care. Raising standards in endoscopy improves diagnostic accuracy, management of pathology and ultimately improves outcomes. Historical identification of significant variation in colonoscopy quality led to the development of the Joint Advisory Group (JAG) on GI Endoscopy, the Global Rating Scale (GRS), JAG Endoscopy Training System (JETS) training and certification. These measures led to major improvements in UK endoscopy but significant variation in practice still exists. To improve quality further the British Society of Gastroenterology Endoscopy Quality Improvement (EQIP) has been established with the aim of raising quality and reducing variation in the quality of UK endoscopy. A multifaceted approach to quality improvement (QI) will be undertaken and is described in this manuscript. Upper GI EQIP will support adoption of standards alongside regional upskilling courses. Lower GI EQIP will focus on supporting endoscopists to achieve current standards alongside approaches to reducing postcolonoscopy colorectal cancer rates. Endoscopic retrograde cholangiopancreatography EQIP will adopt a regional approach of using local data to support network-based QI. Newer areas of endoscopy practice such as small bowel endoscopy and endoscopic ultrasound will focus on identifying key performance indicators as well as standardising training and accreditation pathways. EQIP will also support QI in management of GI bleeding as well as standardising the approach to new techniques and technologies. Where evidence is lacking, approaches to gather new evidence and support the translation into clinical practice will be supported.
What every endoscopist should know about decontamination
Authors: Griffiths Helen , Dwyer Laura
Published: January 2019

Carbapenemase-resistant Enterobacteriaceae (CRE) has been implicated in an alarming increase in the incidence of endoscopy-associated infections and deaths worldwide. Public Health England acknowledges that the rapid spread of CRE bacteria poses an increasing threat to public health and modern medicine here in the UK. As endoscopists, we assume that the endoscope we are handed has been appropriately decontaminated, but how many of us can honestly say that we understand the process and the pathway by which the instruments we use are reprocessed? Do we understand the associated risks if the pathway fails and our part in supporting the teams responsible for this critical role? Successful decontamination of endoscopes is everyone’s business, and this article outlines what every endoscopist should know about decontamination.
Developmental origins of endometriosis: a Swedish cohort study
Authors: Gao Menghan , Allebeck Peter , Mishra Gita D , Koupil Ilona
Published: January 2019

Background

Endometriosis is a chronic condition affecting women of reproductive age and is associated with multiple health burdens. Yet, findings regarding its ‘developmental origins’ are inconsistent. We aimed to investigate the associations of birth characteristics with endometriosis. We also explored potential mediation by adult social and reproductive factors.

Methods

This cohort study consisted of 3406 women born in Uppsala, Sweden, between 1933 and 1972. We used data from archived birth records and endometriosis diagnoses at ages 15–50 recorded in the national patient registers. Socioeconomic and reproductive characteristics were obtained from routine registers. HRs were estimated from Cox regression.

Results

During the follow-up, 111 women have been diagnosed with endometriosis, and most cases are external endometriosis (ie, outside the uterus, n=91). Lower standardised birth weight for gestational age was associated with increased rate of endometriosis (HR 1.35 per standard deviation decrease; 95% CI 1.08 to 1.67). This increased rate was also detected among women with fewer number of live births (HR 2.38; 95% CI 1.40 to 4.07 for one child vs ≥2 children; HR 6.09; 95% CI 3.88 to 9.57 for no child vs ≥2 children) and diagnosed infertility problem (HR 2.00; 95% CI 1.10 to 3.61) prior to endometriosis diagnosis. All the observed associations were stronger for external endometriosis. However, no evidence was found that number of births was the mediator of the inverse association between standardised birth weight and endometriosis.

Conclusion

This study supports the developmental origins theory and suggests that exposure to growth restriction during the fetal period is associated with increased risk of endometriosis during reproductive years.
Clinical spectrum and pleiotropic nature ofCDH1germline mutations
Authors: Figueiredo Joana , Melo Soraia , Carneiro Patrícia , Moreira Ana Margarida , Fernandes Maria Sofia , Ribeiro Ana Sofia , Guilford Parry , Paredes Joana , Seruca Raquel
Published: January 2019

CDH1encodes E-cadherin, a key protein in adherens junctions. Given that E-cadherin is involved in major cellular processes such as embryogenesis and maintenance of tissue architecture, it is no surprise that deleterious effects arise from its loss of function. E-cadherin is recognised as a tumour suppressor gene, and it is well established thatCDH1genetic alterations cause diffuse gastric cancer and lobular breast cancer—the foremost manifestations of the hereditary diffuse gastric cancer syndrome. However, in the last decade, evidence has emerged demonstrating thatCDH1mutations can be associated with lobular breast cancer and/or several congenital abnormalities, without any personal or family history of diffuse gastric cancer. To date, no genotype–phenotype correlations have been observed. Remarkably, there are reports of mutations affecting the same nucleotide but inducing distinct clinical outcomes. In this review, we bring together a comprehensive analysis ofCDH1-associated disorders and germline alterations found in each trait, providing important insights into the biological mechanisms underlying E-cadherin’s pleiotropic effects. Ultimately, this knowledge will impact genetic counselling and will be relevant to the assessment of risk of cancer development or congenital malformations inCDH1mutation carriers.
Suicide in Parkinson’s disease
Authors: Shepard Melissa Deanna , Perepezko Kate , Broen Martijn P G , Hinkle Jared Thomas , Butala Ankur , Mills Kelly A , Nanavati Julie , Fischer Nicole Mercado , Nestadt Paul , Pontone Gregory
Published: January 2019

Persons with Parkinson’s disease (PwP) have many known risk factors for suicide and suicidal ideation (SI). Despite this, there is limited understanding of suicidality in this population. We conducted a systematic review to synthesise the available literature on suicidality in PwP and highlight areas for potential intervention and further research. We identified 116 articles discussing SI, suicidal behaviours, suicide attempts and/or fatal suicide in PwP. These articles describe prevalence, suicide methods, risk factors for suicide and SI and treatment of suicidality. In this review, we summarise the current literature and provide suggestions for how clinicians can identify and treat PwP who are at risk for suicide, for example, through aggressive treatment of depression and improved screening for access to lethal means.
Can Death Cafés resuscitate morale in hospitals?
Authors: Hammer Rachel , Ravindran Nithya , Nielsen Nathan
Published: January 2019

Death Cafés are non-profit social franchises that arise spontaneously in communities to serve as informal forums for discussing death. There is a great need within the medical community for the kind of conversation that Death Cafés foster: open, unstructured, spontaneous, genuine and interdisciplinary dialogue. Burnout in healthcare, with symptoms of exhaustion, depersonalisation and decreased efficacy, is a global crisis, with alarming estimates suggesting one in three practicing physicians experience burnout. While open-forum community-based Death Cafés exist widely, there appears to be no evidence in the literature to suggest that healthcare settings have adapted this model for fostering debriefings among hospital employees. We have started hospital-based Death Cafés in a large, public, urban-centre, Level I Trauma centre in the Gulf South in an effort to study healthcare worker burnout. In this brief commentary, we introduce the concept of hospital-based Death Cafés as distinct from community-based Death Cafés. From our experience, hospital-based Death Cafés are easy to implement, inexpensive, require little planning and yet offer tremendous reward to participants. Should the phenomenon of Death Cafés take off in hospitals as it has in communities internationally, we propose that this intervention be studied for its effect on healthcare worker burnout.
Characterization of strut indentation during mechanical thrombectomy in acute ischemic stroke clot analogs
Authors: Weafer Fiona M , Duffy Sharon , Machado Ines , Gunning Gillian , Mordasini Pasquale , Roche Ellen , McHugh Peter E , Gilvarry Michael
Published: January 2019

Background

Although it is common practice to wait for an ‘embedding time’ during mechanical thrombectomy (MT) to allow strut integration of a stentriever device into an occluding thromboembolic clot, there is a scarcity of evidence demonstrating the value or optimal timing for the wide range of thrombus compositions. This work characterizes the behavior of clot analogs of varying fibrin and cellular compositions subject to indentation forces and embedding times representative of those imparted by a stentriever during MT. The purpose of this study is to quantify the effect of thrombus composition on device strut embedding, and to examine the precise nature of clot integration into a stentriever device at a microstructural level.

Method

Clot analogs with 0% (varying densities), 5%, 40%, and 80% red blood cell (RBC) content were created using ovine blood. Clot indentation behavior during an initial load application (loading phase) followed by a 5-min embedding time (creep phase) was analyzed using a mechanical tester under physiologically relevant conditions. The mechanism of strut integration was examined using micro-computed tomography (µCT) with an EmboTrap MT device (Cerenovus, Galway, Ireland) deployed in each clot type. Microstructural clot characteristics were identified using scanning electron microscopy (SEM).

Results

Compressive clot stiffness measured during the initial loading phase was shown to be lowest in RBC-rich clots, with a corresponding greatest maximum indentation depth. Meanwhile, additional depth achieved during the simulated embedding time was most pronounced in fibrin-rich clots. SEM imaging identified variations in microstructural mechanisms (fibrin stretching vs rupturing) which was dependent on fibrin:cellular content, while µCT analysis demonstrated the mechanism of strut integration was predominantly the formation of surface undulations rather than clot penetration.

Conclusions

Disparities in indentation behavior between clot analogs were attributed to varying microstructural features induced by the cellular:fibrin content. Greater indentation was identified in clots with higher RBC content, but with an increased level of fibrin rupture, suggesting an increased propensity for fragmentation. Additional embedding time improves strut integration, especially in fibrin-rich clots, through the mechanism of fibrin stretching with the majority of additional integration occurring after 3 mins. The level of thrombus incorporation into the EmboTrap MT device (Cerenovus, Galway, Ireland) was primarily influenced by the stentriever design, with increased integration in regions of open architecture.
Bone lead associations with blood lead, kidney function and blood pressure among US, lead-exposed workers in a surveillance programme
Authors: Barry Vaughn , Todd Andrew C , Steenland Kyle
Published: January 2019

Objectives

Bone lead and past blood lead levels may be more strongly associated with current health effects than current blood lead, representing recent exposure. We examined whether current bone lead was correlated with maximum past blood lead and compared how three lead measures predicted current blood pressure (BP) and kidney function among workers with past occupational lead exposure.

Methods

Adult men in a lead surveillance programme residing near New York City were enrolled. Current bone and blood lead, BP and estimated glomerular filtration rate (eGFR) were measured. Maximum past blood lead was obtained from surveillance data. Regression models were used to determine associations of health with different lead measures.

Results

Among 211 participants, median (IQR) bone, maximum past blood and current blood leads were 13.8 (9.4–19.5) µg lead per bone mineral gram, 29.0 (14.0–38.0) µg/dL and 2.5 (1.5–4.4) µg/dL, respectively. Maximum past and current blood lead were significantly associated with current bone lead in adjusted analyses (both p<0.0001), with associations driven by high blood lead. Bone lead was associated with increased continuous systolic BP (coefficient=0.36; 95% CI 0.05 to 0.67; p=0.02); categorical analyses indicated this was driven by the top two bone lead quartiles. Bone lead was non-significantly associated with decreased (worse) eGFR (coefficient=−0.15; 95% CI −0.36 to 0.07; p=0.18).

Conclusions

Bone lead was significantly associated with past maximum and current blood lead. The association between bone and current blood lead was possibly driven by bone lead resorption into blood. Bone lead, but not past or current blood lead, was associated with elevated systolic BP.
IgG4-related diseases: state of the art on clinical practice guidelines
Authors: Iaccarino Luca , Talarico Rosaria , Scirè Carlo Alberto , Amoura Zahir , Burmester Gerd , Doria Andrea , Faiz Karim , Frank Charissa , Hachulla Eric , Hie Miguel , Launay David , Montecucco Carlomaurizio , Monti Sara , Mouthon Luc , Tincani Angela , Toniati Paola , Van Hagen Pieter Martin , Van Vollenhoven Ronald F , Bombardieri Stefano , Mueller-Ladner Ulf , Schneider Matthias , Smith Vanessa , Cutolo Maurizio , Mosca Marta , Alexander Tobias
Published: January 2019

Immunoglobulin G4-related diseases (IgG4-RD) are a group of chronic relapsing–remitting inflammatory conditions, characterised by tissue infiltration with lymphocytes and IgG4-secreting plasma cells, fibrosis and a usually favourable response to steroids.

In this narrative review, we summarise the results of a systematic literature research, which was performed as part of the European Reference Network ReCONNET, aimed at evaluating existing clinical practice guidelines (CPGs) and recommendations in IgG4-RD. From 167 publications initially obtained from a systematic literature search, only one was identified as a systematic multispecialist, evidence-based, consensus guidance statement on diagnosis and treatment of IgG4-RD, which may be recommended for use as CPG in IgG4-RD.

With the recognition of a limited evidence based in this increasingly recognised disease, the group discussion has identified the following unmet needs: lack of shared classification criteria, absence of formal guidelines on diagnosis, no evidence-based therapeutic recommendations and lack of activity and damage indices. Areas of unmet needs include the difficulties in diagnosis, management and monitoring and the scarcity of expert centres.
Cluster-randomised trial of a nurse-led advance care planning session in patients with COPD and their loved ones
Authors: Houben Carmen H M , Spruit Martijn A , Luyten Hans , Pennings Herman-Jan , van den Boogaart Vivian E M , Creemers Jacques P H M , Wesseling Geertjan , Wouters Emiel F M , Janssen Daisy J A
Published: January 2019

Rationale

Advance care planning (ACP) is uncommon in patients with chronic obstructive pulmonary disease (COPD).

Objectives

To assess whether a nurse-led ACP-intervention can improve quality of patient-physician end-of-life care communication in patients with COPD. Furthermore, the influence of an ACP-intervention on symptoms of anxiety and depression in patients and loved ones was studied. Finally, quality of death and dying was assessed in patients who died during 2-year follow-up.

Methods

A multicentre cluster randomised-controlled trial in patients with advanced COPD was performed. The intervention group received an 1.5 hours structured nurse-led ACP-session. Outcomes were: quality of patient-physician end-of-life care communication, prevalence of ACP-discussions 6 months after baseline, symptoms of anxiety and depression in patients and loved ones and quality of death and dying.

Results

165 patients were enrolled (89 intervention; 76 control). The improvement of quality of patient-physician end-of-life care communication was significantly higher in the intervention group compared with the control group (p<0.001). The ACP-intervention was significantly associated with the occurrence of an ACP-discussion with physicians within 6 months (p=0.003). At follow-up, symptoms of anxiety were significantly lower in loved ones in the intervention group compared with the control group (p=0.02). Symptoms of anxiety in patients and symptoms of depression in both patients and loved ones were comparable at follow-up (p>0.05). The quality of death and dying was comparable between both groups (p=0.17).

Conclusion

One nurse-led ACP-intervention session improves patient-physician end-of-life care communication without causing psychosocial distress in both patients and loved ones.
Early specialist palliative care on quality of life for malignant pleural mesothelioma: a randomised controlled trial
Authors: Brims Fraser , Gunatilake Samal , Lawrie Iain , Marshall Laura , Fogg Carole , Qi Cathy , Creech Lorraine , Holtom Nicola , Killick Stephanie , Yung Bernard , Cooper David , Stadon Louise , Cook Peter , Fuller Elizabeth , Walther Julie , Plunkett Claire , Bates Andrew , Mackinlay Carolyn , Tandon Anil , Maskell Nicholas A , Forbes Karen , Rahman Najib M , Gerry Stephen , Chauhan Anoop J
Published: January 2019

Purpose

Malignant pleural mesothelioma (MPM) has a high symptom burden and poor survival. Evidence from other cancer types suggests some benefit in health-related quality of life (HRQoL) with early specialist palliative care (SPC) integrated with oncological services, but the certainty of evidence is low.

Methods

We performed a multicentre, randomised, parallel group controlled trial comparing early referral to SPC versus standard care across 19 hospital sites in the UK and one large site in Western Australia. Participants had newly diagnosed MPM; main carers were additionally recruited. Intervention: review by SPC within 3 weeks of allocation and every 4 weeks throughout the study. HRQoL was assessed at baseline and every 4 weeks with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30. Primary outcome: change in EORTC C30 Global Health Status 12 weeks after randomisation.

Results

Between April 2014 and October 2016, 174 participants were randomised. There was no significant between group difference in HRQoL score at 12 weeks (mean difference 1.8 (95% CI −4.9 to 8.5; p=0.59)). HRQoL did not differ at 24 weeks (mean difference −2.0 (95% CI −8.6 to 4.6; p=0.54)). There was no difference in depression/anxiety scores at 12 weeks or 24 weeks. In carers, there was no difference in HRQoL or mood at 12 weeks or 24 weeks, although there was a consistent preference for care, favouring the intervention arm.

Conclusion

There is no role for routine referral to SPC soon after diagnosis of MPM for patients who are cared for in centres with good access to SPC when required.

Trial registration number

ISRCTN18955704.
Buffering mepivacaine with sodium bicarbonate speeds and potentiates analgesia of median and ulnar nerve blocks performed on horses
Authors: Boone Lindsey , Schumacher John , DeGraves Fred , Cole Robert
Published: January 2019

The objective of this study was to determine if buffering mepivacaine HCL (mepHCl) with sodium bicarbonate (NaHCO3) would significantly decrease the time to onset of analgesia when performing median and ulnar nerve blocks in naturally lame horses. Median and ulnar nerve blocks were performed on the naturally lame limb of nine horses during two separate study periods, with a minimum washout period of three days between study periods. Nerve blocks were performed by administering mepHCl alone or mepHCl mixed with NaHCO3 (nine parts 2 per cent mepHCl to one part 8.4 per cent NaHCO3). Lameness was evaluated objectively using a wireless, inertial, sensor‐based, motion analysis system (Lameness Locator) prior to the high regional nerve block and every five minutes following administration of the nerve block for 75 min. Resolution of lameness occurred earlier and was more profound for horses administered median and ulnar nerve blocks performed with mepHCl and NaHCO3 than when these nerve blocks were performed using only mepHCl.
Genetic analysis of fiber-dimension traits and combined selection for simultaneous improvement of growth and stiffness in lodgepole pine (Pinus contorta)
Authors: Hayatgheibi Haleh , Fries Anders , Kroon Johan , Wu Harry X.
Published: January 2019

Quantitative genetic variation of fiber-dimension traits and their relationship with diameter at breast height (DBH) and solid-wood traits (i.e., density and modulus of elasticity (MOE)) was investigated in lodgepole pine (Pinus contorta Dougl. ex Loud. var. latifolia Engelm.). A total of 823 increment cores were sampled from 207 half-sib families at two independent progeny trials, aged 34–35 years, located in northern Sweden. High-resolution pith-to-bark profiles were obtained for radial fiber width (RFW), tangential fiber width (TFW), fiber wall thickness (FWT), and fiber coarseness (FC) using SilviScan. Heritabilities ranged from 0.29 to 0.74, and inheritance increased with cambial maturity. Estimated age–age genetic correlations indicate that early selection between ages 5 and 8 years is highly efficient. Our results indicate that selection for a 1% increase in DBH or MOE incurs a negligible effect on fiber-dimension traits and maximum genetic gains are reached when DBH and MOE are considered jointly. Moreover, simultaneous improvement of growth and stiffness is achievable when a selection index with 7 to 10 economical weights for MOE relative to 1 for DBH is incorporated. However, the unfavorable relationship between solid-wood traits and pulp and paper related traits suggests that breeding strategies must be implemented to improve wood quality of lodgepole pine for multiple uses.
A perfect fluid model for compact stars
Authors: Estevez-Delgado Gabino , Estevez-Delgado Joaquin , García Nadiezhda Montelongo , Duran Modesto Pineda
Published: January 2019

In the framework of Einstein’s theory of general relativity we present a new interior solution with a perfect fluid; this is constructed from the proposal of a gravitational redshift factor. The geometry is regular and density and pressure are monotonic decreasing functions; furthermore, the sound speed is smaller than the light speed and monotonic increasing. The solution depends on a parameter w ∈ (0, 2.037 550 932 5] related to the compactness of the star u = GM/c2R, the maximum value of which is u = 0.266 085 831 6, which allows for describing compact stars like quark stars or neutron stars. Although there is a diversity of stars for which the model can be used, we only apply this solution to describe the interior of a neutron star PSR J0348+0432. According to the observations, it is known that its mass M = (2.01 ± 0.04)M⊙ and its radius is between 12 062 and 12 957 km, so the value of the compactness is in the range u ∈ [0.224 484 5, 0.250 933 8]. In addition to the decreasing behavior of the mentioned pressure and density functions, the results are consistent with the density value range typical of neutron stars and the maximal central density of the star result to be 1.283 818 × 1018 kg/m3.
Is Adjuvant Chemotherapy Efficient in Colon Cancer with High Microsatellite Instability? A Look Towards the Future
Authors: Schiappacasse Cocio Guido V. , Schiappacasse Enrico D.
Published: January 2019

The high microsatellite instability (MSI-H) is frequently observed in localized colorectal adenocarcinoma. MSI-H is a good prognostic factor in nonmetastatic colon adenocarcinoma. However, MSI-H is not a predictive factor because it is not related with better survival in patients with colon cancer with adjuvant chemotherapy. MSI-H should be a predictive factor because it is associated with a higher expression of enzymes, which are inhibited by cytotoxic agents. Here, we analyze this controversy. We conclude MSI-H is not a predictive factor because the adjuvant therapy based on traditional cytotoxic agents does not act on either immune signaling pathways or BRAF mutation.
Albuminuria Regression and All-Cause Mortality among Insulin-Treated Patients with Type 2 Diabetes: Analysis of a Large UK Primary Care Cohort
Authors: Anyanwagu Uchenna , Donnelly Richard , Idris Iskandar
Published: January 2019

Background: Overt albuminuria (urinary albumin-creatinine ratio [ACR] > 300 mg/g) is an established risk factor for progression of nephropathy and total mortality. However, whether a reduction in ACR translates into a reduction in mortality and/or cardiovascular (CV) events among insulin-treated patients with type 2 diabetes (T2D) in routine practice is currently not known. Methods: We obtained data on a large cohort of insulin users with T2D and nephropathy (baseline ACR ≥300 mg/g) from UK general practices between 2007 and 2014. Their corresponding ACR values after 1year of follow-up were thereafter categorized into: (1) < 300 mg/g (i.e., albuminuria regression) or (2) > 300 mg/g (i.e., nonregression of albuminuria), and the cohort was followed-up for 5 years for all-cause mortality and CV events. Cox proportional hazard models were fitted to estimate the risk of all-cause death. Results: A total of 11,074 patients with insulin-treated T2D met the inclusion criteria. Their mean age was 62.3 (13.6) years; mean HbA1c: 8.7 (1.8) and 53% were male. A total of 682 deaths occurred after a follow-up period of 43,393 person-years with a mortality rate of 16 per 1,000 person-years. Five-year survival was markedly reduced in the group whose proteinuria persisted or progressed (91 vs. 95%; log-rank p value < 0.001). Compared to patients whose ACR levels remained above 300 mg/g, all-cause mortality and CV events were 31 and 27% lower in those whose albuminuria regressed to < 300 mg/g (adjusted hazard ratio [aHR] 0.69; 95% CI 0.52–0.91; p = 0.008 and aHR 0. 73; 95% CI 0.54–0.98; p = 0.041), respectively. Conclusion: In patients with insulin-treated T2D and nephropathy in routine practice, a regression in albuminuria (e.g., via better BP or glycemic control) is associated with a significant reduction in all-cause mortality. Thus, albuminuria is not only simply a risk marker of renal and CV disease but also an independent target for therapy. Albuminuria reduction should be viewed as a goal for renal and CV protection.
POLYMORPHIC PROFILES OF Ganoderma spp. ISOLATES FROM BANYUMAS, CENTRAL JAVA, INDONESIA
Authors: Ratnaningtyas Nuniek Ina , Susanto Agus Hery , Yulia Ana
Published: January 2019

Ganoderma spp. are known as both beneficial and harmful fungi to humans. These are distributed worldwide in sufficiently high diversity. To generate a polymorphic profile and a genetic inter-relationship of several isolates of Ganoderma spp., a study was conducted using the Random Amplified Polymorphic DNA (RAPD) markers on Ganoderma spp. from Banyumas Regency, Central Java, Indonesia. The fruiting bodies of the collected Ganoderma spp. were first morphologically characterized, then analyzed using RAPD with four random primers, i.e., OPC-1, OPC-2, OPC-4, and OPC-5. The results revealed that the four primers generated polymorphic bands of the 10 samples with a polymorphism level of 100%, showing high genetic diversity. The level of genetic similarity ranged between 0.48 and 0.82, indicating moderate similarities among samples. The constructed dendrogram resulted in the grouping of the Ganoderma spp. isolates into three clusters at a similarity coefficient of 0.63, but neither according to geographical locations nor growth substrates.
Unexpected High Prevalence of Cardiovascular Disease Risk Factors and Psychiatric Disease Among Young People With Sudden Cardiac Arrest
Authors: Allan Katherine S. , Morrison Laurie J. , Pinter Arnold , Tu Jack V. , Dorian Paul ,   the Rescu Investigators, Nascimiento Barto , Scales Damon , Ko Dennis , Hutchison Jamie , Dainty Katie , Swartz Richard , Verbeek Richard , Rizoli Sandro , Cheskes Sheldon , Brooks Steven , Lin Steve , Chan Tim
Published: January 2019

Background

It is believed that most sudden cardiac arrests (
SCA
s) in young people occur in previously healthy people with rare risk factors for sudden death. Few studies have investigated large populations with complete ascertainment. Our objective was to use multisource records to identify and classify all out‐of‐hospital cardiac arrests in the Greater Toronto Area (population 6.6 million) in people aged 2 to 45 years from 2009 to 2012.

Methods and Results

Expert reviewers employed a systematic process, with emergency medical services, in‐hospital and coroner records, to adjudicate the cause of death as
SCA
from cardiac or noncardiac causes. We report the adjudicated etiologies, circumstances, triggers, and characteristics of the
SCA
cohort. Of 2937 eligible
out‐of‐hospital cardiac arrest
cases, 608 (20.7%)
SCA
s had an adjudicated etiology of cardiac cause (120 survivors and 488 nonsurvivors). Two thirds of these
SCA
patients had a history of cardiovascular disease, and over 50% had been diagnosed with ≥1 cardiovascular disease risk factor. Moreover, 20.1% of
SCA
s were diagnosed with psychiatric disease and 30% had central nervous system drugs prescribed. Over 30% of
SCA
patients had
central nervous system
active drugs, including drugs of abuse detected postmortem, with opioids and ethanol being detected most frequently. Potentially heritable structural cardiac diseases accounted for only 6.9% of
SCA
events, with acquired cardiac diseases comprising the rest.

Conclusions

The underlying causes of
SCA
, in people aged 2 to 45 years, often occur in those with previously diagnosed cardiovascular diseases, and are associated with contributory factors including prescribed medications, recreational drugs, and a concomitant psychiatric history.
Sex Differences in Outcomes Following Endovascular Treatment for Symptomatic Peripheral Artery Disease: An Analysis From the K‐VIS ELLA Registry
Authors: Choi Ki Hong , Park Taek Kyu , Kim Jihoon , Ko Young‐Guk , Yu Cheol Woong , Yoon Chang‐Hwan , Lee Jae‐Hwan , Min Pil‐Ki , Koh Yoon Seok , Chae In‐Ho , Choi Donghoon , Choi Seung‐Hyuk ,   the K‐VIS Investigators
Published: January 2019

Background

With advances in peripheral artery disease (
PAD
) treatments such as endovascular treatment (
EVT
), personalized patient assessment is important. Data on sex differences in clinical outcome for
PAD
patients undergoing
EVT
have been limited, and studies have produced conflicting results. This study sought to compare midterm clinical outcomes between women and men in a large population of patients with
PAD
undergoing
EVT
.

Methods and Results

The K‐
VIS ELLA
(Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease) registry is a nationwide, multicenter, observational study that includes 3073
PAD
patients undergoing
EVT
. The study population was divided into men (n=2523) and women (n=550). The primary outcome was a composite of death, myocardial infarction, and major amputation; the secondary outcome included major adverse limb events. Women had more comorbidities and more severe and complex target lesions than men. Women showed higher rates of death, myocardial infarction, or major amputation than men (14.8% versus 9.8%, adjusted hazard ratio 1.350, 95%
CI
1.017‐1.792,
P
=0.038), and higher rates of major adverse limb events (19.9% versus 14.5%, adjusted hazard ratio 1.301, 95%
CI
1.014‐1.670,
P
=0.039) and procedural complications (10.2% versus 5.9%,
P
<0.001) based on multivariable analysis. In patients with claudication, the primary outcome incidence was significantly higher in women (hazard ratio 2.088, 95%
CI
1.421‐3.068,
P
<0.001). In contrast, there was no significant difference in primary outcome for patients with critical limb ischemia between the 2 groups (hazard ratio 1.164, 95%
CI
0.800‐1.694,
P
=0.426). A significant interaction (
P
=0.035) between patient presentation and outcome was observed.

Conclusions

In a large population of patients with
PAD
undergoing
EVT
, women had higher rates of death, myocardial infarction, or major amputation than men and higher rates of complex lesions, procedural complications, and limb‐specific adverse events.
Changing Epidemiology of Hypoplastic Left Heart Syndrome: Results of a National Swedish Cohort Study
Authors: Öhman Annika , El‐Segaier Milad , Bergman Gunnar , Hanséus Katarina , Malm Torsten , Nilsson Boris , Pivodic Aldina , Rydberg Annika , Sonesson Sven‐Erik , Mellander Mats
Published: January 2019

Background

Norwood surgery provides a palliative surgical option for hypoplastic left heart syndrome and has been available in Sweden since 1993. The practice of prenatal ultrasound screening was gradually implemented in the same era, resulting in an increased prenatal detection rate. Our primary aims were to study changes in the incidence of live births, prenatal detection rate, and the termination of pregnancies over time. The secondary aims were to study the proportion of live‐borns undergoing surgery and to identify factors that influenced whether surgery was or was not performed.

Methods and Results

Neonates with hypoplastic left heart syndrome with aortic atresia born 1990‐2010 were identified through national databases, surgical files, and medical records. The fetal incidence was estimated from the period when prenatal screening was rudimentary. The study period was divided into the presurgical, early surgical, and late surgical periods. The incidence was calculated as the overall yearly incidence for each time period and sex separately. Factors influencing whether surgery was performed were analyzed using Cox‐logistic regression. The incidence at live birth decreased from 15.4 to 8.4 per 100 000. The prenatal detection rate increased from 27% to 63%, and terminations increased from 19% to 56%. The odds of having surgery was higher in the late period and higher in the group with prenatal diagnosis.

Conclusions

We observed a decrease in incidence of live‐borns with hypoplastic left heart syndrome aortic atresia. There was in increase in prenatal detection rate and an increase in termination of pregnancy. The proportion of live‐borns who underwent surgery increased between time periods.
Racial Differences in the Effect of Granulocyte Macrophage Colony‐Stimulating Factor on Improved Walking Distance in Peripheral Artery Disease: The PROPEL Randomized Clinical Trial
Authors: McDermott Mary M. , Polonsky Tamar S. , Guralnik Jack M. , Ferrucci Luigi , Tian Lu , Zhao Lihui , Stein James , Domanchuk Kathryn , Criqui Michael H. , Taylor Doris A. , Li Lingyu , Kibbe Melina R.
Published: January 2019

Background

The effects of race on response to medical therapy in people with peripheral artery disease (
PAD
) are unknown.

Methods and Results

In the PROPEL (Progenitor Cell Release Plus Exercise to Improve Functional Performance in PAD) Trial,
PAD
participants were randomized to 1 of 4 groups for 6 months: supervised treadmill exercise+granulocyte‐macrophage colony‐stimulating factor (
GM
‐
CSF
) (Group 1), exercise+placebo (Group 2), attention control+
GM
‐
CSF
(Group 3), or attention control+placebo (Group 4). Change in 6‐minute walk distance was measured at 12‐ and 26‐week follow‐up. In these exploratory analyses, groups receiving
GM
‐
CSF
(Groups 1 and 3), placebo (Groups 2 and 4), exercise (Groups 1 and 2), and attention control (Groups 2 and 4) were combined, maximizing statistical power for studying the effects of race on response to interventions. Of 210
PAD
participants, 141 (67%) were black and 64 (30%) were white. Among whites,
GM
‐
CSF
improved 6‐minute walk distance by +22.0 m (95%
CI
: −4.5, +48.5,
P
=0.103) at 12 weeks and +44.4 m (95%
CI
: +6.9, +82.0,
P
=0.020) at 26 weeks, compared with placebo. Among black participants, there was no effect of
GM
‐
CSF
on 6‐minute walk distance at 12‐week (
P
=0.26) or 26‐week (−5.0 m [−27.5, +17.5,
P
=0.66]) follow‐up, compared with placebo. There was an interaction of race on the effect of
GM
‐
CSF
on 6‐minute walk change at 26‐week follow‐up (
P
=0.018). Exercise improved 6‐minute walk distance in black (
P
=0.006) and white (
P
=0.034) participants without interaction.

Conclusions

GM
‐
CSF
improved 6‐minute walk distance in whites with
PAD
but had no effect in black participants. Further study is needed to confirm racial differences in
GM
‐
CSF
efficacy in
PAD
.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01408901.