Endovenous laser ablation therapy in children: applications and outcomes

BACKGROUND: Endovenous laser ablation is well recognized as the first-line treatment for superficial venous reflux with varicose veins in adults. It is not widely reported and is not an established practice in pediatric patients. OBJECTIVE: To illustrate a variety of pediatric venous conditions in which endovenous laser ablation can be utilized and to demonstrate its feasibility and safety in children. MATERIALS AND METHODS: We conducted a retrospective review of endovenous laser ablation procedures performed between January 2007 and July 2014 at two large pediatric institutions. RESULTS: We included 35 patients (17 males) who underwent endovenous laser ablation to 43 veins. Median age at first treatment was 14 years (range: 3-18 years). Median weight was 56 kg (range: 19-97 kg). Underlying diagnoses were common venous malformation (15), Klippel-Trenaunay syndrome (8), superficial venous reflux with varicose veins (5), verrucous hemangioma-related phlebectasia (4), venous varix (2) and arteriovenous fistula (1). The most common aim of treatment was to facilitate sclerotherapy. Thirty-four patients had treatment in the lower limbs and one patient in an upper limb. Ten of the veins treated with endovenous laser ablation had an additional procedure performed to close the vein. Complications attributable to endovenous laser ablation occurred in two patients (6%). One patient experienced post-procedural pain and one patient developed a temporary sensory nerve injury. Median clinical follow-up was 13 months (range: 28 days-5.7 years). The aim of the treatment was achieved in 29 of the 35 (83%) patients. CONCLUSION: Endovenous laser ablation is technically feasible and safe in children. It can be used in the management of a range of pediatric venous diseases with good outcomes

Arterial Recanalization for Access for Arterial Intervention in Children: Techniques and Outcomes

PURPOSE: To assess technical success of arterial recanalization in children requiring repeated arterial access and intervention. MATERIALS AND METHODS: Over 14 years, 41 attempts to cross 30 arterial occlusions were made in 22 patients (13 male, 9 female). Median patient age was 12 months (15 days-14 years), and weight was 7.6 kg (3.0-77.3 kg). Techniques and outcomes were recorded. RESULTS: Twenty-five of 41 (61%) attempts at crossing an arterial occlusion were successful. Nineteen of 30 (63%) first attempts to cross occlusions were successful, and 6 of 11 (55%) repeat attempts were successful. The occluded segments were combinations of common femoral artery (n = 4), external iliac artery (n = 36), common iliac artery (n = 11), and aorta (n = 1). Complications occurred in 5 of 41(12%) attempts: 3 minor complications (hematoma, extravasation, and transient leg ischemia) and 2 major complications (rupture and thrombosis). CONCLUSIONS: Arterial access by recanalization of occluded segments is technically feasible in children, with a low complication rate

Quality and readability of online patient information regarding sclerotherapy for venous malformations

BACKGROUND: Patients often use the internet as a source of information about their condition and treatments. However, this information is unregulated and varies in quality. OBJECTIVE: To evaluate the readability and quality of online information for pediatric and adult patients and caregivers regarding sclerotherapy for venous malformations. MATERIALS AND METHODS: “Venous malformation sclerotherapy” was entered into Google, and results were reviewed until 20 sites that satisfied predefined inclusion criteria were identified. Scientific and non-patient-focused web pages were excluded. Readability was assessed using the Flesch Reading Ease Score and American Medical Association reading difficulty recommendations and quality was assessed using Journal of the American Medical Association standards and assessing if the site displayed HONcode (Health on the Net Code) certification. Assessment of the breadth of relevant information was made using a predefined checklist. RESULTS: Forty-nine search engine results were reviewed before 20 sites were identified for analysis. Average Flesch Reading Ease Score was 44 (range: 24.2–70.1), representing a “fairly difficult” reading level. None of the sites had a Flesch Reading Ease Score meeting the American Medical Association recommendation of 80-90. Only one site met all four Journal of the American Medical Association quality criteria (average: 2.1). None of the sites displayed a HONcode seal. The information most frequently found was: sclerotherapy is performed by radiologists, multiple treatments may be needed and surgery is an alternative treatment. CONCLUSION: Online information regarding sclerotherapy for venous malformations is heterogeneous in quality and breadth of information, and does not meet readability recommendations for patient information. Radiologists should be aware of and account for this when meeting patients

Meaning behind measurement : self-comparisons affect responses to health related quality of life questionnaires

Purpose The subjective nature of quality of life is particularly pertinent to the domain of health-related quality of life (HRQOL) research. The extent to which participants’ responses are affected by subjective information and personal reference frames is unknown. This study investigated how an elderly population living with a chronic metabolic bone disorder evaluated self-reported quality of life. Methods Participants (n = 1,331) in a multi-centre randomised controlled trial for the treatment of Paget’s disease completed annual HRQOL questionnaires, including the SF-36, EQ-5D and HAQ. Supplementary questions were added to reveal implicit reference frames used when making HRQOL evaluations. Twenty-one participants (11 male, 10 female, aged 59–91 years) were interviewed retrospectively about their responses to the supplementary questions, using cognitive interviewing techniques and semi-structured topic guides. Results The interviews revealed that participants used complex and interconnected reference frames to promote response shift when making quality of life evaluations. The choice of reference frame often reflected external factors unrelated to individual health. Many participants also stated that they were unclear whether to report general or disease-related HRQOL. Conclusions It is important, especially in clinical trials, to provide instructions clarifying whether ‘quality of life’ refers to disease-related HRQOL. Information on selfcomparison reference frames is necessary for the interpretation of responses to questions about HRQOL.The Chief Scientist Office of the Scottish Government Health Directorates, The PRISM funding bodies (the Arthritis Research Campaign, the National Association for the Relief of Paget’s disease and the Alliance for Better Bone Health)Peer reviewedAuthor final versio

Sub-luminous type Ia supernovae from the mergers of equal-mass white dwarfs with M~0.9 M_sun

Type Ia supernovae (SNe Ia) are thought to result from thermonuclear explosions of carbon-oxygen white dwarf stars. Existing models generally explain the observed properties, with the exception of the sub-luminous 1991-bg-like supernovae. It has long been suspected that the merger of two white dwarfs could give rise to a type Ia event, but hitherto simulations have failed to produce an explosion. Here we report a simulation of the merger of two equal-mass white dwarfs that leads to an underluminous explosion, though at the expense of requiring a single common-envelope phase, and component masses of ~0.9 M_sun. The light curve is too broad, but the synthesized spectra, red colour and low expansion velocities are all close to what is observed for sub-luminous 1991bg-like events. While mass ratios can be slightly less than one and still produce an underluminous event, the masses have to be in the range 0.83-0.9 M_sun.Comment: Accepted to Natur

Statistical analysis plan for the ‘Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage’ (TICH-2) trial

Rationale Aside from blood pressure lowering, treatment options for intracerebral haemorrhage remain limited and a proportion of patients will undergo early haematoma expansion with resultant significant morbidity and mortality. Tranexamic acid (TXA), an anti-fibrinolytic drug, has been shown to significantly reduce mortality in patients, who are bleeding following trauma, when given rapidly. TICH-2 is testing whether TXA is effective at improving outcome in spontaneous intracerebral haemorrhage (SICH). Methods and design TICH-2 is a pragmatic, phase III, prospective, double-blind, randomised placebo-controlled trial. Two thousand adult (aged ≥ 18 years) patients with an acute SICH, within 8 h of stroke onset, will be randomised to receive TXA or the placebo control. The primary outcome is ordinal shift of modified Rankin Scale score at day 90. Analyses will be performed using intention-to-treat. Results This paper and its attached appendices describe the statistical analysis plan (SAP) for the trial and were developed and published prior to database lock and unblinding to treatment allocation. The SAP includes details of analyses to be undertaken and unpopulated tables which will be reported in the primary and key secondary publications. The database will be locked in early 2018, ready for publication of the results later in the same year. Discussion The SAP details the analyses that will be done to avoid bias arising from prior knowledge of the study findings. The trial will determine whether TXA can improve outcome after SICH, which currently has no definitive therapy. Trial registration ISRCTN registry, ID: ISRCTN93732214. Registered on 17 January 2013

Alcohol consumption and lifetime change in cognitive ability:a gene × environment interaction study

Studies of the effect of alcohol consumption on cognitive ability are often confounded. One approach to avoid confounding is the Mendelian randomization design. Here, we used such a design to test the hypothesis that a genetic score for alcohol processing capacity moderates the association between alcohol consumption and lifetime change in cognitive ability. Members of the Lothian Birth Cohort 1936 completed the same test of intelligence at age 11 and 70 years. They were assessed for recent alcohol consumption in later life and genotyped for a set of four single-nucleotide polymorphisms in three alcohol dehydrogenase genes. These variants were unrelated to late-life cognition or to socioeconomic status. We found a significant gene × alcohol consumption interaction on lifetime cognitive change (p = 0.007). Individuals with higher genetic ability to process alcohol showed relative improvements in cognitive ability with more consumption, whereas those with low processing capacity showed a negative relationship between cognitive change and alcohol consumption with more consumption. The effect of alcohol consumption on cognitive change may thus depend on genetic differences in the ability to metabolize alcohol

Abnormal expression of p27kip1 protein in levator ani muscle of aging women with pelvic floor disorders – a relationship to the cellular differentiation and degeneration

BACKGROUND: Pelvic floor disorders affect almost 50% of aging women. An important role in the pelvic floor support belongs to the levator ani muscle. The p27/kip1 (p27) protein, multifunctional cyclin-dependent kinase inhibitor, shows changing expression in differentiating skeletal muscle cells during development, and relatively high levels of p27 RNA were detected in the normal human skeletal muscles. METHODS: Biopsy samples of levator ani muscle were obtained from 22 symptomatic patients with stress urinary incontinence, pelvic organ prolapse, and overlaps (age range 38–74), and nine asymptomatic women (age 31–49). Cryostat sections were investigated for p27 protein expression and type I (slow twitch) and type II (fast twitch) fibers. RESULTS: All fibers exhibited strong plasma membrane (and nuclear) p27 protein expression. cytoplasmic p27 expression was virtually absent in asymptomatic women. In perimenopausal symptomatic patients (ages 38–55), muscle fibers showed hypertrophy and moderate cytoplasmic p27 staining accompanied by diminution of type II fibers. Older symptomatic patients (ages 57–74) showed cytoplasmic p27 overexpression accompanied by shrinking, cytoplasmic vacuolization and fragmentation of muscle cells. The plasma membrane and cytoplasmic p27 expression was not unique to the muscle cells. Under certain circumstances, it was also detected in other cell types (epithelium of ectocervix and luteal cells). CONCLUSIONS: This is the first report on the unusual (plasma membrane and cytoplasmic) expression of p27 protein in normal and abnormal human striated muscle cells in vivo. Our data indicate that pelvic floor disorders are in perimenopausal patients associated with an appearance of moderate cytoplasmic p27 expression, accompanying hypertrophy and transition of type II into type I fibers. The patients in advanced postmenopause show shrinking and fragmentation of muscle fibers associated with strong cytoplasmic p27 expression

Balancing the dilution and oddity effects: Decisions depend on body size

Background Grouping behaviour, common across the animal kingdom, is known to reduce an individual's risk of predation; particularly through dilution of individual risk and predator confusion (predator inability to single out an individual for attack). Theory predicts greater risk of predation to individuals more conspicuous to predators by difference in appearance from the group (the ‘oddity’ effect). Thus, animals should choose group mates close in appearance to themselves (eg. similar size), whilst also choosing a large group. Methodology and Principal Findings We used the Trinidadian guppy (Poecilia reticulata), a well known model species of group-living freshwater fish, in a series of binary choice trials investigating the outcome of conflict between preferences for large and phenotypically matched groups along a predation risk gradient. We found body-size dependent differences in the resultant social decisions. Large fish preferred shoaling with size-matched individuals, while small fish demonstrated no preference. There was a trend towards reduced preferences for the matched shoal under increased predation risk. Small fish were more active than large fish, moving between shoals more frequently. Activity levels increased as predation risk decreased. We found no effect of unmatched shoal size on preferences or activity. Conclusions and Significance Our results suggest that predation risk and individual body size act together to influence shoaling decisions. Oddity was more important for large than small fish, reducing in importance at higher predation risks. Dilution was potentially of limited importance at these shoal sizes. Activity levels may relate to how much sampling of each shoal was needed by the test fish during decision making. Predation pressure may select for better decision makers to survive to larger size, or that older, larger fish have learned to make shoaling decisions more efficiently, and this, combined with their size relative to shoal-mates, and attractiveness as prey items influences shoaling decisions