bluuebunny/crossref_metadata_2025 huggingface dataset:
Medication and employment
Authors: Swales Caroline , McDowall Peter
Published: April 2019

Medication allows many people with long-term health conditions to pursue productive employment when they would otherwise be unable to work safely and effectively. However, both short-term and long-term pharmacological treatments can have implications for work. The number of medications taken by individuals has increased; the risk of harm increasing with polypharmacy. The Internet has transformed communications, and practitioners have greater accessibility to updated clinical data with increased communication between specialists. But easier access to data on medication and health conditions for employees has both positive and negative influences. High-profile road traffic fatalities have raised public concerns about the potential adverse effects of medication and of employees not reporting or managing conditions effectively. Occupational health professionals are not regular prescribers. However, they can help to monitor safe use of medications, by observing and recording compliance and adverse effects in relation to workplace health and safety. Greater involvement in employees’ medication management, with onward communication of problems to treating physicians, is required to enable occupational health to participate in medicines optimization.
Musculoskeletal conditions, part 3: disorders of upper and lower limbs
Authors: Valanejad Sam , Blackburn Julia , Walker-Bone Karen
Published: April 2019

Occupational activities can result in certain musculoskeletal disorders due to prolonged repetitiveness, inappropriate ergonomic settings, physical hardship, and acute injuries. These disorders comprise a major portion of sickness absence, presenteeism, and referrals to occupational health services with a significant burden on the economy. Some of these disorders are more common in the ageing workforce, and some can become complicated by the expanding epidemy of obesity. An occupational health practitioner is required to have evidence-based knowledge about these disorders in terms of occupational aetiology, preventative or attenuating measures at workplaces, medical and surgical therapeutic interventions, and relevant rehabilitation processes. This chapter covers most of the common work-related musculoskeletal disorders affecting upper and lower limbs with emphasis on their work implications that can assist occupational health practitioners with providing appropriate recommendations for employers and employees.
Epilepsy
Authors: Brown Ian , Prevett Martin C.
Published: April 2019

This chapter on epilepsy reviews the epidemiology of epilepsy, including the classification of seizure types, causes of epilepsy, risks of seizure recurrence, and chances of remission, and examines the responsibility of the occupational health professional and sensible employee restrictions. It reviews primary and secondary prevention of epilepsy in the workplace and the impact of alcohol and drugs. It also considers the effect of antiepileptic drugs and other co-morbidities on work performance and special work problems, including disclosure of epilepsy, accidents, absence records, and employment practice. The chapter ends with a review of the medical services available, opportunities for sheltered work, and epilepsy support organizations, along with a brief discussion on relevant legislation and the driving licence regulations.
Cardiovascular diseases
Authors: Bono Joseph De , Zhou Anli Yue
Published: April 2019

Cardiovascular diseases are one of the leading causes of morbidity and mortality in the UK. Cardiovascular diseases can affect those in employment and can limit working capacity. Multiple considerations should be taken into account when assessing return to work, including psychosocial factors. This chapter provides a comprehensive and up-to-date evidence-based overview of common cardiovascular diseases such as coronary heart disease, valvular disease, congenital heart disease, hypertension, syncope, and implantable cardiac devices including pacemakers (with a special section on implantable devices and electromagnetic fields). Topics of interest also covered within this chapter include travel, firefighters, stress, shift working, hazardous substances, hot conditions, and driving.
Dermatological disorders
Authors: Sayed Hanaa , English John
Published: April 2019

The skin acts as a protective barrier against a number of hazards within our environment. These hazards can be chemical (e.g. acids, alkalis, solvents, or oils), biological, (e.g. bacteria, plant allergens, or raw food), or physical (e.g. ultraviolet light or mechanical shearing forces). Occupational skin diseases are significant, with irritant contact dermatitis being the commonest. Pre-existing skin diseases and occupational skin diseases have implications for employment, where legal considerations are relevant. When workers are exposed to hazardous substances at work, employers have a duty under the Control of Substances Hazardous to Health regulations. When severe, occupational skin diseases may warrant workplace adjustments or redeployment.
Hearing and vestibular disorders
Authors: Eyears Julian , Hutson Kristian
Published: April 2019

Hearing and vestibular disorders are prevalent in working populations and may heavily impact a worker’s ability to perform and work safely. It is frequently incumbent on the occupational health professional to assess the extent and impact of these disorders on the workplace. This is optimally executed by careful examination and assessment and using a knowledge of the conditions and treatment options. The employer may also be requested to perform a risk assessment in the workplace. The occupational health professional should have a good understanding of noise-induced hearing loss and audiometry programmes. They should also be able to assess and advise about the impact of hearing loss in the workplace and may also be required to manage a health surveillance programme.
Hidden impairments
Authors: Adamou Marios , Hobson John
Published: April 2019

This chapter on hidden impairments considers the neurodevelopmental disorders including autism spectrum disorders and attention deficit hyperactivity disorder and their impact on employment and how occupational health (OH) professionals can provide appropriate advice on fitness to work. These chronic disorders have a combined prevalence of up to 6%, are highly co-morbid, and commonly present with specific learning disabilities such as dyspraxia, dyslexia, and dyscalculia. As the term implies, they are often missed by clinicians and are costly to society. With equality legislation and increasing diagnosis of neurodevelopmental disorders, OH professionals should be aware of the functional impact of these conditions and the behavioural and cognitive challenges to performance at work so they can best support the individual and advise the employer. The chapter provides guidance on how work can be designed and organized to enable people with neurodevelopmental disorders to obtain and retain suitable employment and to benefit from work.
Epidemiology and biostatistics
Authors: Damani Nizam
Published: April 2019

This section includes a chapter on basic epidemiology and biostatistics as applied to healthcare-associated infections (HAIs). The epidemiology section summarizes various types of studies and outlines the advantages and disadvantages of case–control and cohort studies. It describes the incidence and prevalence rate and how to calculate the most common HAIs. Practical advice is also given on how to avoid bias and confounders. The chapter describes basic concepts in biostatistics and tests of statistical significance used in investigating an outbreak. It also provides guidance on how to calculate the sensitivity and specificity of the test and describes how to interpret confidence intervals and statistical process charts.
Control of multidrug-resistant microorganisms
Authors: Damani Nizam
Published: April 2019

This chapter discusses the burden and impact of antimicrobial resistant (AMR) bacteria on human health. It describes the types of antibiotic resistance, and the various factors which are responsible for promoting the emergence and spread of multidrug-resistant organisms (MDROs) in the healthcare facility. The chapter provides advice on how to successfully implement an antibiotic stewardship programme in hospital and strategies to promote prudent antibiotic prescribing. The role and responsibilities of the antimicrobial management team is also discussed. It provides a summary and characteristic of most commonly encountered MRDOs in a healthcare facility and provide practical advice on how to prevent and control the spread of methicillin-resistant Staph. aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended-spectrum beta-lactamases (ESBLs), carbapenem-resistant Enterobacteriaceae (CRE), and multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii.
Support services
Authors: Damani Nizam
Published: April 2019

This section discusses the role of hospital support services in the prevention and control of infection. It examines the role and responsibilities of the occupational health department which include pre-employment assessment and provision of guidance on how to manage healthcare workers who are exposed and/or infected with various communicable diseases and multidrug-resistant pathogens. It outlines the importance of infections spread by contaminated environment and provides practical advice on the environmental cleaning. Advice on the management of clinical waste, kitchen and catering services, linen and laundry services, and pest control is also provided.
Assessment and Staging of Care for People with Dementia
Authors: Semrau Maya , Burns Alistair , Lobo Antonio , Olde Rikkert Marcel , Robert Philippe , Schepens Mirjam , Stoppe Gabriela , Sartorius Norman
Published: April 2019

Assessment and Staging of Care for Dementia: The IDEAL schedule and its user manual gives a detailed overview of the International Schedule for the Integrated Assessment and Staging of Care for Dementia (IDEAL schedule) and provides all information that is needed when learning how to use the schedule and when using it. This includes details on the aims of the schedule; a description of how the schedule was developed and tested; instructions on how to use the schedule; the IDEAL schedule itself; the glossary of terms used in the schedule; and suggestions about the interventions that are recommended for consideration at different stages of severity of dementia. The book also includes four case histories, which are recommended for use when training in the use of the schedule.
How was the IDEAL schedule developed and tested?
Authors: Semrau Maya , Burns Alistair , Lobo Antonio , Rikkert Marcel Olde , Robert Philippe , Schepens Mirjam , Stoppe Gabriela , Sartorius Norman
Published: April 2019

This chapter provides information on how the International Schedule for the Integrated Assessment and Staging of Care for Dementia (IDEAL schedule) was developed and tested. It includes information on the three developmental stages of the IDEAL schedule: 1) a series of focus groups, which involved convening stakeholders who were engaged in the process of care for people with dementia to assess the need for a new dementia staging schedule, and to identify the ideal design, necessary items, and characteristics for such a staging schedule; 2) a pilot study with the draft schedule and using case histories to assess inter-rater reliability of assessments obtained using the schedule; and 3) a large-scale cross-country field study to test the schedule’s inter-rater reliability when used to assess patients in clinical practice. Information about the feasibility/acceptability and validity testing of the IDEAL schedule is also included in this chapter.
Introduction to the causes of cardiovascular disease and type 2 diabetes mellitus, South Asians, and the structure and approach of this book
Authors: Bhopal Raj S.
Published: April 2019

Coronary heart disease (CHD) and stroke, collectively cardiovascular disease (CVD), are caused by narrowing and blockage of the arteries supplying the heart and brain, respectively. In type 2 diabetes (DM2) insulin is insufficient to maintain normal blood glucose. Until the 1980s, CHD, stroke, and DM2 were seen as problems of the modern lifestyles of rich countries. South Asians should have been protected, e.g. by less smoking, more vegetarianism, and lower levels of obesity. However, the contrary was true and South Asians have high susceptibility to these diseases. The established causes cannot account for the susceptibility. For example, obesity tends to be lower in South Asians than in European origin people but DM2, though caused by obesity, is about three times commoner. About ten major groups of explanations have been published. The aim of this book is to produce a synthesis of the causal explanations to guide prevention, clinical care, and research.
Other risk factors and explanations
Authors: Bhopal Raj S.
Published: April 2019

As is usual with medical and scientific puzzles, there have been numerous creative ideas to explain South Asians’ susceptibility to diabetes, CHD, and stroke that have not been developed into either fully articulated hypotheses or have rarely or never been included in hypothesis testing or evaluation studies. These include thyroid dysfunction, lactose intolerance, vitamin B12 and folate deficiency, infection, and chronic inflammation. Vitamin D deficiency has been studied intensively recently in relation to chronic disease including some work on South Asians. Cardiovascular anatomy and physiology has been explored in observational and though these explanations have little theoretical foundation but they need some consideration.
Implications for health policy, public health, health care, and research
Authors: Bhopal Raj S.
Published: April 2019

Achieving internationally agreed prevention strategies is extremely difficult and doing so for South Asians, specifically, is tougher still. Most guidance is centred on individual level behaviour change. The challenge is to produce focused, low cost, effective actions, underpinned by clear, simple, and accurate explanations of the causes of the phenomenon. The key messages are that the high risk of CVD and DM2 in urbanizing South Asians is not inevitable. It is not innate or genetic. Similarly, the risks are unlikely to be acquired in utero, birth, or infancy, and programmed in a fixed way. Rather, exposure to risk factors in childhood, adolescence, and most particularly in adulthood is the key. In addition to the established causes we need to research additional factors especially those identified as novel in Chapter 9. National legislation and policy that alters environments to reduce exposure to risk factors and increase exposure to protective factors is essential.
Incidence and epidemiology
Authors: Moiemen Naiem , Allouni Ammar
Published: April 2019

Burns is a global injury with devastating outcomes. Over 95% of burns occurs in low-income countries. The incidence is particularly significant in vulnerable groups. Scalds are the commonest injuries in toddlers, followed by contact burns while flame burns are less than 10%. The commonest injury in preschool children is scald followed by contact then flame burns. Flame burns are the commonest in older children over the age of 9 years. The incidence of burns in the elderly is rising especially in high-income countries as the life expectancy increases, however the outcome in this group is still unsatisfactory. Non-accidental burns of children, elderly and vulnerable adults require collaborative managements between different agencies to insure safeguarding vulnerable patients. Although health and legislations has dramatically reduced the number of burns injuries in fire disasters, terrorist attacks has become the commonest source of mass casualties.
The burns management pathway I: assessing and transferring patients with an acute burn injury
Authors: Shokrollahi Kayvan , Yao Susie
Published: April 2019

The initial management of patients with an acute burn injury is often undertaken by individuals with relatively little experience in this area. To optimize outcomes and minimize the risk of long-term sequelae, clinicians should understand the key steps in initial management and safe transfer of these patients to a specialist burns unit. These include safely extricating patients and providing prompt first aid at scene; rapidly and accurately assessing them at the nearest emergency department or trauma centre; appropriately managing their airway and oxygenation; obtaining intravenous access and initiating fluid resuscitation; assessing burn extent and depth and considering the potential need for escharotomies; providing analgesia and appropriate tetanus prophylaxis; and covering and warming the patient while temporarily dressing their burns. Once these measures are taken, any patient with a burn injury may be discussed with a specialist burns unit for advice. If deemed necessary and accepted, they should be promptly transferred to a burns unit with an appropriate escort. Prior to transfer, a systematic re-assessment should be undertaken, and any required treatments should be continued during the transfer. Copies of all referral information and the results of initial assessments and investigations should be sent with the patient to ensure a robust handover process.
Assessment of burn surface area
Authors: Pritchard-Jones Rowan , Shokrollahi Kayvan
Published: April 2019

Assessment of total body surface area of a burn injured patient is a crucial step in managing burn injury. The chapter describes a number of techniques from using the size of the patient’s palm as an estimate of 1% to the gold standard Lund and Browder Chart. Key caveats are explained, copies of the charts included as well as the use of the CE certified app Mersey Burns.
Fluid resuscitation in burns
Authors: Pritchard-Jones Rowan , Seaton Chris , Shokrollahi Kayvan
Published: April 2019

This chapter guides the reader through the phases of resuscitating a burn-injured patient and monitoring response. It explains when to resuscitate, the reasons fluids are important in the care of burn injured patients and describes the use of both the Parkland Formula and Muir and Barclay Protocol. The chapter further describes how to monitor and respond to the patients changing physiology during fluid resuscitation, and how to identify and respond to myoglobinuria.
Escharotomies
Authors: Norbury William B.
Published: April 2019

Following a significant thermal or electrical injury, tissues beneath the skin swell through fluid loss into the interstitial space. The increase in extravascular fluid together with the inelastic nature of the overlying burned skin compound to increase pressure within the affected limb. This increase in pressure can compromise the vascular supply distally in an affected limb or increase ventilatory pressures in those with circumferential burns of the chest and abdomen. This chapter will give guidance on when and how to perform escharotomies; however, the final decision is usually based on experience and clinical judgment. Figures illustrate detail markings and techniques for escharotomies and fasciotomies of the upper limb, lower limb, chest and abdomen.
Anaesthesia: preoperative management of patients with acute burns
Authors: Woodson Lee C.
Published: April 2019

Major burn injuries affect every organ system and present challenges for every aspect of perioperative anaesthetic care. Although anaesthetists possess skills and experience that match the needs of these critically ill patients, perioperative decisions require consideration of unique pathophysiological changes associated with large burns along with knowledge of predictable technical challenges. Careful preoperative evaluation and preparation is critical. Initial care of patients with inhalation injury may involve management of difficult airways including bronchoscopic examination. Preoperative evaluation requires understanding of fluid resuscitation of burns. Adequate planning for perioperative care also depends on close preoperative communication with ICU staff and surgeons. Intraoperative care should be compatible with ICU course and goals, while anaesthetic choices such as monitors, vascular access and blood products are determined by the surgical plan. Impaired thermoregulation in burn patients requires attention to equipment and conditions in the operative theatre.
Principles of burn reconstruction
Authors: Warbrick-Smith James , Potokar Tom S
Published: April 2019

Burn reconstruction continues until either the maximal functional and aesthetic outcome has been achieved, or the patient and surgeon feel no further intervention is warranted. Communication with the patient about the limitations of outcome is vital. This chapter discusses the process of assessment of burn reconstruction and timing considerations.
Remote assessment of burns
Authors: Pope-Jones Sophie , Dickson William
Published: April 2019

More than 90% of burns can be managed as outpatients by non-specialists e.g. emergency departments, minor injury units and general practice. Outpatient management in supportive home environments aims to reduce unnecessary admissions and improve cost effectiveness without compromising quality of care. This chapter discusses the definition of minor burns, assessment and selection of patients for outpatient management, treatment options, complications, when to admit and typical follow up arrangements. However, since research into burn injuries has largely focused on burns requiring inpatient resuscitation, high level evidence on which to base robust recommendations is limited. This chapter, therefore, summarizes the authors’ practice, widely accepted practice and existing evidence for consideration and does not constitute dogmatic recommendations.
Cost of burn care
Authors: Allouni Ammar , Moiemen Naiem
Published: April 2019

Modern information and communication technologies such as the Internet and Smart phones are revolutionizing how individuals communicate, seek and exchange information. Telemedicine is a subspecialty of medicine that utilizes some of these Information technologies to enable and deliver healthcare at a geographical distance. It is a constantly evolving science as it incorporates new advancements in technology and responds and adapts to changing health needs and variabilities in different societies. Burns are a relatively common injury requiring specialist care to enable the best outcome. In the UK there are relatively few specialized burns units and burns expertise is therefore often not easily attainable due to geographical difficulties. This chapter endeavours to describe current Burns care provision in the UK and how Telemedicine can be used in the assessment and management of burns patients. Telemedicine is explored in terms of modes, cost-effectiveness, and potential medicolegal and ethical issues.
Non-accidental injury (NAI) in children
Authors: Molajo Adeyinka , Shokrollahi Kayvan
Published: April 2019

This chapter explores the topic of non-accidental injury burns in children. It is important to consider the possibility of non-accidental injury and recognize injury patterns. The chapter gives a concise overview of the patient and parent characteristics, assessment of such patients and differential diagnoses to consider in the process of managing children in these situations. Patterns of injury in non-accidental burns are described.
Desquamating skin disorders
Authors: Hindocha Sandip , Shokrollahi Kayvan
Published: April 2019

Exfoliating skin disorders or exfoliative and necrotizing disease of the skin form an important part for all those managing acute dermatological and plastic surgery emergencies; including the burns surgeon. It is imperative that such conditions are evaluated in a burns text as these patients should be managed on a burns unit with allied professional input. This chapter focuses on the classification, aetiology, and management of such disorders. Management includes initial assessment and suggested surgical approach. In addition scoring and prognostic indicators are referenced to allow the reader application of knowledge in clinical practice.
Frostbite
Authors: Tadiparth Sujatha , Shokrollahi Kayvan
Published: April 2019

Frostbite is the damage sustained by tissues when exposed to temperatures below their freezing point (<0°C). Extremities such as fingers, toes, nose and ears are most commonly affected. A number of extrinsic and intrinsic factors predispose to frostbite. The severity of frostbite can be classified into four degrees. Tissue injury occurs firstly, by direct cell damage and death from the formation of intracellular ice crystals and secondly, by vascular insufficiency and tissue ischaemia which result from vasoconstriction, endothelial injury and thromboembolism. Treatment is focused on gentle rewarming in a warm circulating bath (40–41°C). Tissues should be allowed to demarcate with rewarming and then surgical debridement or amputation performed if necrotic tissue is present. Tissue plasminogen activator can lead to rapid clearance of vascular thromboses, restore arterial perfusion and improve tissue salvage. Long-term sequelae can result including, cold hypersensitivity, sensory deficits, chronic pain, heterotropic calcification, and pigmentary changes.
Face transplantation
Authors: Sinha Indranil , Vyas Raj M. , Pomahac Bohdan
Published: April 2019

Facial composite tissue allotransplantation is an emerging field which offers the potentially restore facial form and function, even following the most severe traumatic injuries. This benefit must be carefully weighed against the need to lifelong immunosuppression, associated infection risks, and possible rejection. Patients must be carefully screened for medical and psychiatric issues prior to the procedure. However, in the well-selected patient, this procedure can be transformative. Uniformly, patients self-report a dramatic improvement post transplantation. In addition, return of sensation in the transplanted allograft occurs in 3–6 months, although return of motor function takes longer and remains incomplete. Ultimately, facial composite tissue transplantation is a powerful technique in the properly selected patient.
Pain management
Authors: Yancey William L , Meyer Walter J. , Woodson Lee C. , Przkora Rene
Published: April 2019

Treatment of pain in the burn patient presents a unique set of challenges. The pathology of pain with these injuries, while consistent at its most basic level, varies considerably with factors such as the burn severity and the stage of treatment/healing. The experience of pain shows similar variation. The assessment of pain and recognition of contributing factors such as anxiety and depression require vigilance and persistence, especially among paediatric populations. Multiple techniques for the measurement of pain in patients have been evaluated and are suitable for routine use. A multimodal approach to the treatment of pain should be employed, including pharmacological, surgical, non-pharmacological, and psychological therapies.
Burn care drug formulary
Authors: Barton Greg
Published: April 2019

This chapter contains an overview of the medication commonly prescribed in the burns patient ranging from initial management with fluids and sedation for those patients requiring intubation through analgesia and drugs that modify catabolism to the management of distressing symptoms such as itch in the rehabilitation phase.
Prognostic significance of human telomerase reverse transcriptase promoter region mutations C228T and C250T for overall survival in spinal chordomas
Authors: Bettegowda Chetan , Yip Stephen , Jiang Bowen , Wang Wei-Lien , Clarke Michelle J , Lazary Aron , Gambarotti Marco , Zhang Ming , Sciubba Daniel M , Wolinsky Jean-Paul , Goodwin C Rory , McCarthy Edward , Germscheid Niccole M , Sahgal Arjun , Gokaslan Ziya L , Boriani Stefano , Varga Peter Pal , Fisher Charles G , Rhines Laurence D
Published: April 2019

Background

Spinal chordomas, a subtype of primary spinal column malignancies (PSCM), are rare tumors with poor prognosis, and we have limited understanding of the molecular drivers of neoplasia.

Methods

Study design was a retrospective review of prospectively collected data with cross-sectional survival. Archived paraffin embedded pathologic specimens were collected for 133 patients from 6 centers within Europe and North America between 1987 and 2012. Tumor DNA was extracted and the human telomerase reverse transcriptase (hTERT) promoter was sequenced. The hTERT mutational status was correlated with overall survival (OS) and time to first local recurrence.

Results

Ninety-two chordomas, 26 chondrosarcomas, 7 osteosarcomas, 3 Ewing’s sarcomas, and 5 other malignant spinal tumors were analyzed. Median OS following surgery was 5.8 years (95% CI: 4.6 to 6.9) and median time to first local recurrence was 3.9 years (95% CI: 2.5 to 6.7). Eight chordomas, 2 chondrosarcomas, 1 Ewing’s sarcoma, and 1 other malignant spinal tumor harbored either a C228T or C250T mutation in the hTERT promoter. In the overall cohort, all patients with hTERT mutation were alive at 10 years postoperative with a median OS of 5.1 years (95% CI: 4.5 to 6.6) (P = 0.03). hTERT promoter mutation was observed in 8.7% of spinal chordomas, and 100% of chordoma patients harboring the mutation were alive at 10 years postoperative compared with 67% patients without the mutation (P = 0.05).

Conclusions

We report for the first time that hTERT promoter mutations C228T and C250T are present in approximately 8.7% of spinal chordomas. The presence of hTERT mutations conferred a survival benefit and could potentially be a valuable positive prognostic molecular marker in spinal chordomas.
Molecular grouping and outcomes of young children with newly diagnosed ependymoma treated on the multi-institutional SJYC07 trial
Authors: Upadhyaya Santhosh A , Robinson Giles W , Onar-Thomas Arzu , Orr Brent A , Billups Catherine A , Bowers Daniel C , Bendel Anne E , Hassall Tim , Crawford John R , Partap Sonia , Fisher Paul G , Tatevossian Ruth G , Seah Tiffany , Qaddoumi Ibrahim A , Vinitsky Anna , Armstrong Gregory T , Sabin Noah D , Tinkle Christopher L , Klimo Paul , Indelicato Danny J , Boop Frederick A , Merchant Thomas E , Ellison David W , Gajjar Amar
Published: April 2019

Background

This report documents the clinical characteristics, molecular grouping, and outcome of young children with ependymoma treated prospectively on a clinical trial.

Methods

Fifty-four children (aged ≤3 y) with newly diagnosed ependymoma were treated on the St Jude Young Children 07 (SJYC07) trial with maximal safe surgical resection, 4 cycles of systemic chemotherapy, consolidation therapy using focal conformal radiation therapy (RT) (5-mm clinical target volume), and 6 months of oral maintenance chemotherapy. Molecular groups were determined by tumor DNA methylation using Infinium Methylation EPIC BeadChip and profiled on the German Cancer Research Center/Molecular Neuropathology 2.0 classifier.

Results

One of the 54 study patients had metastases (cerebrospinal fluid positive) at diagnosis. Gross or near-total resection was achieved in 48 (89%) patients prior to RT. At a median follow-up of 4.4 years (range, 0.2–10.3 y), 4-year progression-free survival (PFS) was 75.1% ± 7.2%, and overall survival was 92.6% ± 4.4%. The molecular groups showed no significant difference in PFS (4-year estimates: posterior fossa ependymoma group A [PF-EPN-A; 42/54], 71.2% ± 8.3%; supratentorial ependymoma positive for v-rel avian reticuloendotheliosis viral oncogene homolog A [ST-EPN-RELA; 8/54], 83.3% ± 17.0%; and supratentorial ependymoma positive for Yes-associated protein [4/54], 100%, P = 0.22). Subtotal resection prior to RT was associated with an inferior PFS compared with gross or near-total resection (4-year PFS: 41.7% ± 22.5% vs 79.0% ± 7.1%, P = 0.024), as was PF-EPN-A group with 1q gain (P = 0.05). Histopathologic grading was not associated with outcomes (classic vs anaplastic; P = 0.89).

Conclusions

In this prospectively treated cohort of young children with ependymoma, ST-EPN-RELA tumors had a more favorable outcome than reported from retrospective data. Histologic grade did not impact outcome. PF-EPN-A with 1q gain and subtotal resection were associated with inferior outcomes.
Prolonging the Reduction of Nicotine Self-Administration in Rats by Coadministering Chronic Nicotine With Amitifadine, a Triple Monoamine Reuptake Inhibitor With CYP2B6 Inhibitory Actions
Authors: Levin Edward D , Wells Corinne , Slade Susan , Lee Michelle , McKinney Anthony A , Rose Jed E , Rezvani Amir H
Published: April 2019

Introduction

Existing treatments can aid tobacco smoking cessation, but they have low efficacy. Because there is a network of neural systems involved in tobacco addiction, combination treatments may provide greater efficacy. Chronic nicotine and amitifadine have each been shown to significantly reduce nicotine self-administration in rats. This study was conducted to determine if the combination of chronic nicotine with amitifadine, a triple monoamine reuptake inhibitor with CYP2B inhibitory effects, would reduce nicotine self-administration to a greater extent than either alone or placebo.

Methods

This study tested the combination of nicotine plus amitifadine in young adult female Sprague-Dawley rats self-administering nicotine (0.03 mg/kg/infusion). This combination was compared with each treatment alone and the vehicle during continuing nicotine self-administration as well as during resumption of self-administration after a week of enforced abstinence, modeling a quit attempt. Finally, we studied the residual effects of these therapies after discontinuation of treatment.

Results

Treatment with either chronic nicotine or amitifadine alone significantly reduced nicotine self-administration relative to controls. The combination of the treatments significantly enhanced this effect. After treatment withdrawal, all of the groups showed increases in nicotine self-administration, but only the combined treatment group remained significantly below control rates of nicotine self-administration.

Conclusions

This study showed the promise of amitifadine as a possible new treatment for smoking cessation and suggested that amitifadine is more effective when given with chronic nicotine. The improved efficacy of the amitifadine and nicotine combination may be potentiated by amitifadine’s inhibitory effects on CYP2B, which slows nicotine metabolism.

Implications

This study replicated the effects that chronic nicotine or chronic amitifadine, a triple reuptake inhibitor, significantly reduces nicotine self-administration in rats. It extends those findings by showing that the combination of chronic nicotine plus amitifadine causes significantly greater reduction in nicotine self-administration than either drug treatment alone. The combination of chronic amitifadine and chronic nicotine also causes a persistent significant reduction in nicotine self-administration after the end of treatment. The amitifadine and nicotine treatment should be assessed in humans to determine whether this combination provides greater efficacy in smoking cessation than transdermal nicotine treatment alone.
A SIMULATION STUDY OF DEPOSITION PARAMETERS FOR 129I DISCHARGED FROM THE ROKKASHO REPROCESSING PLANT
Authors: Abe Koichi , Hasegawa Hidenao , Akata Naofumi , Kakiuchi Hideki , Chiang Jing-Hsien , Suwa Hiroji , Hisamatsu Shun’ichi
Published: April 2019

The first commercial spent nuclear fuel reprocessing plant at Rokkasho in Japan discharged 129I from actual spent nuclear fuel into the atmosphere during its test operation from 2006 to 2008. Previously, we measured monthly atmospheric concentrations of gaseous and particulate 129I and atmospheric deposition rates of 129I from the campus of our institute, which is 2.6 km east of the main stack of the plant. In this study, we simulated the atmospheric concentrations and deposition rates of 129I using a combination of the Fifth-Generation Penn State/NCAR Mesoscale Model and the improved CG-MATHEW/ADPIC models, Version 5.0. Here, we report on the optimised deposition parameters of 129I used to simulate the measured values using 129I atmospheric discharge rates from the main stack.
The R2R3 MYB transcription factor MYB189 negatively regulates secondary cell wall biosynthesis in Populus
Authors: Jiao Bo , Zhao Xin , Lu Wanxiang , Guo Li , Luo Keming
Published: April 2019

Secondary cell wall (SCW) biosynthesis during wood formation in trees is controlled by a multilevel regulatory network that coordinates the expression of substantial genes. However, few transcription factors involved in the negative regulation of secondary wall biosynthesis have been characterized in tree species. In this study, we isolated an R2R3 MYB transcription factor MYB189 from Populus trichocarpa, which is expressed predominantly in secondary vascular tissues, especially in the xylem. A novel repression motif was identified in the C-terminal region of MYB189, which indicates this factor was a transcriptional repressor. Overexpression (OE) of MYB189 in Arabidopsis and poplar resulted in a significant reduction in the contents of lignin, cellulose and hemicelluloses. Vascular development in stems of MYB189 OE lines was markedly inhibited, leading to a dramatic decrease in SCW thickness of xylem fibers. Gene expression analyses showed that most of the structural genes involved in the biosynthesis of lignin, cellulose and xylans were significantly downregulated in MYB189-overexpressing poplars compared with the wild-type control. Chromatin immunoprecipitation-quantitative real-time polymerase chain reaction and transient expression assays revealed that MYB189 could directly bind to the promoters of secondary wall biosynthetic genes to repress their expression. Together, these data suggest that MYB189 acts as a repressor to regulate SCW biosynthesis in poplar.
DNMT1 and DNMT3B genetic polymorphisms affect the clinical course and outcome of melanoma patients
Authors: Maric Helena , Supic Gordana , Kandolf-Sekulovic Lidija , Maric Veljko , Mijuskovic Zeljko , Radevic Tatjana , Rajovic Milica , Magic Zvonko
Published: April 2019

The aberrant DNA methylation plays a critical role in a number of different malignancies, including melanoma. DNA methylation is catalyzed by DNA methyltransferases (DNMTs), involved in methylation maintenance (DNMT1) and de novo DNA methylation (DNMT3A and DNMT3B). The current study investigated the association of genetic variants in the DNMT1 and DNMT3B with the clinicopathologic features and the clinical course of melanoma patients. In the present study, DNMT1 (rs2228612, rs2228611, and rs2114724) and DNMT3B (rs406193 and rs2424932) polymorphisms were examined in 123 melanoma patients. Single nucleotide polymorphisms were assessed using TaqMan SNPs Genotyping Assays according to the manufacturer’s protocols. The carriers of the variant genotype of DNMT1 rs2228612 had poorer overall survival and recurrence-free survival, (P = 0.000 and 0.000, respectively), and an increased risk for adverse outcome [hazard ratio (HR) = 6.620, 95% confidence interval (CI): 2.214–19.791, P = 0.001]. DNMT1 rs2228612 was also associated with ulceration (P = 0.045), nodal status (P = 0.030), progression (P = 0. 007), and stage of disease (P = 0.003). Univariate analysis indicated that tumor-infiltrating lymphocytes could be a marker of good prognosis in melanoma patients (HR = 0.323, 95% CI: 0.127–0.855, P = 0.025), whereas the genotype distribution of the DNMT3B rs406193 polymorphism correlated significantly with the presence of tumor-infiltrating lymphocytes (P = 0.012). The multivariate analysis showed that the DNMT1 rs2228612 polymorphism (HR = 12.126, 95% CI: 2.345–62.715, P = 0.003) is an independent predictor of poor overall survival in melanoma patients. As expected, disease progression was also found to be an independent prognostic factor in melanoma patients (HR = 37.888, 95% CI: 3.615–397.062, P = 0.002). DNMT1 rs2228612 was found to be an independent predictor of poor overall survival in melanoma patients. DNMTs polymorphisms could serve as a potential target for novel therapeutic approaches.
Reconsideration of the Anterior Surgical Plane of Total Mesorectal Excision for Rectal Cancer
Authors: Fang Jiafeng , Zheng Zongheng , Wei Hongbo
Published: April 2019

INTRODUCTION:

Previous studies on total mesorectal excision suggested dissection anterior to Denonvilliers’ fascia, which might lead to intraoperative pelvic autonomic nerves injury and a high incidence of urogenital dysfunction.

TECHNIQUE:

We dissected 4 cases of cadavers, mainly focusing on anatomy of Denonvilliers’ fascia, to study the relationship between Denonvilliers’ fascia and rectum. In practice, instead of dissection 1 cm above peritoneal reflection, dissection of the peritoneum was performed at the lowest level of peritoneal reflection during laparoscopic resection for mid-low rectal cancer.

RESULTS:

The cadaveric study revealed that there were loose tissues between Denonvilliers’ fascia and rectal specimen, thus a surgical plane posterior to Denonvilliers’ fascia did exist. During laparoscopic resection for mid-low rectal cancer, some loose reticulate structures between Denonvilliers’ fascia and proper fascia of rectum would present after dissection of peritoneum at the lowest level of peritoneal reflection. Then dissection within the surgical plane posterior to Denonvilliers’ fascia became easy and feasible. In this plane, both the pelvic nerves and postoperative urogenital function could be well protected by Denonvilliers’ fascia.

CONCLUSIONS:

The anterior surgical plane for total mesorectal excision should be reconsidered, and dissection posterior to Denonvilliers’ fascia is feasible and practicable for patients without risk of positive anterior circumferential resection margin.
A NOVEL SURGICAL TECHNIQUE FOR RESCUING A DISLOCATED ACCOMMODATIVE INTRAOCULAR LENS (CRYSTALENS)
Authors: Mantopoulos Dimosthenis , Prenner Jonathan L. , Wheatley H. Matthew
Published: April 2019

Purpose:

To describe a novel surgical technique for rescuing a dislocated “in-the-bag” accommodative intraocular lens (Crystalens; Bausch and Lomb Inc, Rochester NY) and report its postoperative outcome.

Methods:

Interventional case report. An 82-year-old patient with history of pseudoexfoliation syndrome presented with a posteriorly dislocated “in-the-bag” Crystalens intraocular lens. A pars plana vitrectomy was performed. The Crystalens intraocular lens was rescued, and scleral sulcus fixated using prolene suture.

Results:

No intraoperative or postoperative complications were noted. The preoperative visual acuity was 6/200. The vision improved to 20/30, 8 weeks after the surgery.

Conclusion:

Rescuing, instead of exchanging, a Crystalens intraocular lens might be a safe alternative in patients with a dislocated “in-the-bag” Crystalens intraocular lens.
SEGMENTAL DIFFUSE VASCULAR LEAKAGE: A FLUORESCEIN ANGIOGRAPHIC FINDING IN PATIENTS WITH VON HIPPEL–LINDAU DISEASE
Authors: Deák Gábor Gy , Pulido Jose S. , Jampol Lee M.
Published: April 2019

Purpose:

To describe a novel fluorescein angiographic finding in patients with von Hippel–Lindau disease.

Methods:

Retrospective case series of patients diagnosed with retinal capillary hemangioblastoma (RCH) in the setting of von Hippel–Lindau.

Results:

We identified six eyes of three patients with von Hippel–Lindau and leaky retinal vessels. All eyes showed segmental diffuse vascular leakage (SDVL) that was seen in the late phase of the angiogram and that originated from third order and more peripheral retinal veins and adjacent capillaries. These vessels did not drain from the RCHs. Segmental diffuse vascular leakage was mainly seen in the mid and far periphery. In some cases, it was located near the RCHs, while in other cases, it was remote. Segmental diffuse vascular leakage was also seen in one eye without RCHs. On follow-up, the extent and intensity of segmental diffuse vascular leakage did not change after the RCHs were treated with laser or cryotherapy.

Conclusion:

Diffuse vascular leakage from retinal venules around and away from RCHs in patients with von Hippel–Lindau disease is seen, but the clinical and prognostic importance of this finding is uncertain.
The Outcome of Scleral Lens Fitting for Keratoconus With Resolved Corneal Hydrops
Authors: Kreps Elke O. , Claerhout Ilse , Koppen Carina
Published: April 2019

Purpose:

To investigate the success and failure of scleral lens fitting in patients with keratoconus with resolved hydrops.

Methods:

Retrospective case series of patients with keratoconus who attended the Ophthalmology Department at Antwerp University Hospital, Belgium, and developed acute hydrops between January 1, 2015, and June 30, 2018. The exclusion criteria included amblyopia, mental retardation, and insufficient follow-up.

Results:

Of the 25 patients with keratoconus with acute hydrops, 14 patients (16 eyes) were included in this study. Median age was 31 years (range 19–52 years). Before hydrops, the median maximum keratometry value of affected eyes was 81.3 D (range 66.3–108.3 D). Acute hydrops was managed medically in 5 eyes (31.3%), by observation in 5 eyes (31.3%), by application of bandage contact lens in 1 eye (6.3%), and compression corneal sutures in 5 eyes (31.3%). Contact lens fitting after hydrops was not necessary for 2 patients (2 eyes; 12.5%) because of excellent vision in the fellow eye. Of the remaining patients, 11 (68.8%) were successfully fitted with mini-scleral lenses, with a median visual acuity of 0.7 (0.5–0.9; decimal Snellen). Three patients (3 eyes; 18.8%) proceeded to graft surgery because of limited visual acuity with scleral lenses (n = 2) or persistent edema (n = 1).

Conclusions:

Scleral lenses are effective for providing satisfactory visual acuity after corneal hydrops in keratoconus. A scleral lens trial is advised before listing patients for graft surgery.
Bilateral Congenital Corneal Opacities as an Early-Onset Ocular Feature of Kabuki Syndrome
Authors: Lin Po-An , Tseng Sung-Huei , Lai I-Wen , Huang Yi-Hsun
Published: April 2019

Purpose:

Kabuki syndrome (KS) is a rare congenital disorder characterized by multiple systemic anomalies and unique facial characteristics. Here, we present the first case, to the best of our knowledge, of bilateral congenital corneal opacities as an early-onset ocular manifestation of KS associated with a KMT2D gene mutation.

Methods:

The proband is a girl. At birth, bilateral corneal opacities, short fifth fingers, patent ductus arteriosus, absence of the uvula, and an ectopic kidney on the right side were noted. Ophthalmic examinations revealed vascularized, nonhomogeneous opacities in both corneas; to prevent deprivation amblyopia, bilateral corneal transplantations were performed.

Results:

At 1 year and 10 months of age, she was referred by a general practitioner to our pediatric endocrinologist for failure to thrive. Genetic analysis at that age revealed the presence of a KMT2D gene mutation, and the patient was diagnosed with KS.

Conclusions:

The clinical diagnosis of KS is challenging because the most remarkable facial features are not evident until early childhood. In this case, bilateral congenital corneal opacities were identified as an early-onset ocular manifestation of KS. KS should be considered as a differential diagnosis in patients with bilateral congenital corneal opacities.