Forensic post-mortem CT in children.

Post-mortem computed tomography (PMCT) imaging is gaining popularity and acceptance for use alongside forensic autopsies of children, predominantly to aid in the detection of traumatic injuries. Recent research on this topic has provided a breadth of new information regarding the appropriate usage, imaging guidance, and diagnostic accuracy for the identification of different paediatric pathologies. Additionally, advanced CT imaging techniques, such as PMCT angiography or ventilated PMCT, have been trialled, and post-mortem micro-CT is now being used in specialist centres for the assessment of subtle fractures in extracted bone specimens. Various image post-processing methods (e.g., three-dimensional printing from PMCT imaging data) are being used for the illustration of injuries in the medicolegal setting to a lay audience and provide another avenue for the future of forensic radiology research. In this review, the evidence-based principles and benefits of post-mortem imaging for forensic investigation in childhood deaths are presented, with a particular focus on PMCT and current practices. Variations in forensic imaging strategies around the world, published diagnostic accuracy rates, and expected normal post-mortem imaging findings are discussed, as well as potential future applications and research in this area.

Management of traumatic brain injury in the non-neurosurgical intensive care unit: a narrative review of current evidence.

Each year, approximately 70 million people suffer traumatic brain injury, which has a significant physical, psychosocial and economic impact for patients and their families. It is recommended in the UK that all patients with traumatic brain injury and a Glasgow coma scale ≤ 8 should be transferred to a neurosurgical centre. However, many patients, especially those in whom neurosurgery is not required, are not treated in, nor transferred to, a neurosurgical centre. This review aims to provide clinicians who work in non-neurosurgical centres with a summary of contemporary studies relevant to the critical care management of patients with traumatic brain injury. A targeted literature review was undertaken that included guidelines, systematic reviews, meta-analyses, clinical trials and randomised controlled trials (published in English between 1 January 2017 and 1 July 2022). Studies involving key clinical management strategies published before this time, but which have not been updated or repeated, were also eligible for inclusion. Analysis of the topics identified during the review was then summarised. These included: fundamental critical care management approaches (including ventilation strategies, fluid management, seizure control and osmotherapy); use of processed electroencephalogram monitoring; non-invasive assessment of intracranial pressure; prognostication; and rehabilitation techniques. Through this process, we have formulated practical recommendations to guide clinical practice in non-specialist centres.

Bimekizumab for the treatment of moderate-to-severe plaque psoriasis: efficacy, safety, pharmacokinetics, pharmacodynamics and transcriptomics from a phase IIa, randomized, double-blind multicentre study.

BACKGROUND: Bimekizumab is a monoclonal antibody that selectively inhibits both interleukin (IL)-17A and IL-17F, which is currently under investigation for treatment of moderate-to-severe plaque psoriasis. Maintenance dosing every 4 weeks is well established with IL-17 inhibitors for psoriasis. OBJECTIVES: To investigate the possible dosing interval during bimekizumab maintenance therapy to maintain clear skin, to inform phase III studies. METHODS: Forty-nine patients with moderate-to-severe plaque psoriasis received bimekizumab 320 mg at weeks 0/4, followed at week 16 by bimekizumab 320 mg (n = 17) or placebo (n = 32). Efficacy, safety, pharmacokinetics, immunogenicity and biopsy transcriptomic analyses were assessed to week 28. RESULTS: At week 8, 47% of patients achieved a 100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100), increasing to 57% at week 12 (8 weeks after the second dose) before decreasing. In those who received bimekizumab at week 16, PASI 100 rate increased to comparable peak levels at week 20, but reduced by week 28 to 41% (12 weeks after the third dose). The week 8 transcriptional signature observed in lesional psoriatic skin rapidly normalized to levels consistent with nonlesional skin, resulting in molecular remission. Keratinocyte-related gene products such as CXCL1 (C-X-C motif chemokine ligand 1), IL-8 (encoded by the CXCL8 gene), CCL20 (C-C motif chemokine 20), IL-36γ and IL-17C were profoundly normalized to levels associated with nonlesional skin. CONCLUSIONS: Here, inhibition of IL-17F in addition to IL-17A resulted in rapid, deep clinical responses. Additionally, profound normalization of keratinocyte biology and the psoriatic transcriptome was observed, including normalization of both IL17 and IL23 gene expression by week 8. These data provide evidence to support evaluation of bimekizumab maintenance dosing both every 8 and every 4 weeks in phase III clinical trials.

Alterations in innate immunity and epithelial cell differentiation are the molecular pillars of hidradenitis suppurativa.

BACKGROUND: The large unmet need of hidradenitis suppurativa/acne inversa (HS) therapy requires the elucidation of disease-driving mechanisms and tissue targeting. OBJECTIVE: Robust characterization of the underlying HS mechanisms and detection of the involved skin compartments. METHODS: Hidradenitis suppurativa/acne inversa molecular taxonomy and key signalling pathways were studied by whole transcriptome profiling. Dysregulated genes were detected by comparing lesional and non-lesional skin obtained from female HS patients and matched healthy controls using the Agilent array platform. The differential gene expression was confirmed by quantitative real-time PCR and targeted protein characterization via immunohistochemistry in another set of female patients. HS-involved skin compartments were also recognized by immunohistochemistry. RESULTS: Alterations to key regulatory pathways involving glucocorticoid receptor, atherosclerosis, HIF1α and IL17A signalling as well as inhibition of matrix metalloproteases were detected. From a functional standpoint, cellular assembly, maintenance and movement, haematological system development and function, immune cell trafficking and antimicrobial response were key processes probably being affected in HS. Sixteen genes were found to characterize HS from a molecular standpoint (DEFB4, MMP1, GJB2, PI3, KRT16, MMP9, SERPINB4, SERPINB3, SPRR3, S100A8, S100A9, S100A12, S100A7A (15), KRT6A, TCN1, TMPRSS11D). Among the proteins strongly expressed in HS, calgranulin-A, calgranulin-B and serpin-B4 were detected in the hair root sheath, koebnerisin and connexin-32 in stratum granulosum, transcobalamin-1 in stratum spinosum/hair root sheath, small prolin-rich protein-3 in apocrine sweat gland ducts/sebaceous glands-ducts and matrix metallopeptidase-9 in resident monocytes. CONCLUSION: Our findings highlight a panel of immune-related drivers in HS, which influence innate immunity and cell differentiation in follicular and epidermal keratinocytes as well as skin glands.

Ulcer area reduction at 2 weeks predicts failure to heal by 24 weeks in the venous leg ulcers of patients living alone.

OBJECTIVE: Chronic wounds are costly and affect approximately 1-2% of the population. Venous disease is responsible for about 60% of all chronic leg ulcers and these ulcers can be debilitating, with evidence of a decreased quality of life. Unfortunately, up to 30% of venous leg ulcers (VLUs) fail to heal, despite best practice treatment. This study aimed to identify risk factors associated with delayed healing in participants with VLUs and in particular, whether psychosocial factors play a part in this process. METHOD: A secondary analysis was conducted of a large data set of clinical, wound healing, health, social, economic and psychological data collected in previous prospective studies of participants with VLUs. Generalised linear mixed modelling was used to identify independent predictors of failure to heal after 24 weeks. RESULTS: We recruited 247 participants with 318 VLUs from hospital and community settings. Findings revealed that four early predictors were independently significantly associated with failure to heal by 24 weeks. These were: participants who lived alone (OR 2.3, 95%CI [1.13-4.61], p=0.03); had less than 25% reduction in ulcer area within two weeks of treatment (OR 10.07, 95%CI [4.60-22.19], p<0.001); had higher ulcer severity scores (OR 5.1, 95%CI [2.33-11.88], p=0.001); and participants who were not treated with high level compression therapy (i.e.>30 mmHg) at the time of assessment (OR 4.18, 95% CI [1.95-8.97], p=0.002). CONCLUSION: Identified risk factors offer an opportunity for clinicians to determine realistic outcomes for their patients and to guide decisions on early referral and implementation of tailored adjunctive interventions. Additionally, findings from this study suggest health professionals need to assess and address not only clinical risk factors but also social risk factors, when planning interventions to promote healing.

Widespread correction of central nervous system disease after intracranial gene therapy in a feline model of Sandhoff disease.

Sandhoff disease (SD) is caused by deficiency of N-acetyl-ß-hexosaminidase (Hex) resulting in pathological accumulation of GM2 ganglioside in lysosomes of the central nervous system (CNS) and progressive neurodegeneration. Currently, there is no treatment for SD, which often results in death by the age of five years. Adeno-associated virus (AAV) gene therapy achieved global CNS Hex restoration and widespread normalization of storage in the SD mouse model. Using a similar treatment approach, we sought to translate the outcome in mice to the feline SD model as an important step toward human clinical trials. Sixteen weeks after four intracranial injections of AAVrh8 vectors, Hex activity was restored to above normal levels throughout the entire CNS and in cerebrospinal fluid, despite a humoral immune response to the vector. In accordance with significant normalization of a secondary lysosomal biomarker, ganglioside storage was substantially improved, but not completely cleared. At the study endpoint, 5-month-old AAV-treated SD cats had preserved neurological function and gait compared with untreated animals (humane endpoint, 4.4±0.6 months) demonstrating clinical benefit from AAV treatment. Translation of widespread biochemical disease correction from the mouse to the feline SD model provides optimism for treatment of the larger human CNS with minimal modification of approach.

Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial.

BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH. METHODS: In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin <58 g litre(-1), RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe PPH', defined as a decrease in haemoglobin of >40 g litre(-1), transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death. RESULTS: Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean fibrinogen concentration of 4.5 (sd 1.2) g litre(-1). The intervention group received a mean dose of 26 mg kg(-1) fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected. CONCLUSIONS: We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.

Translation and validation of the Danish version of the postoperative quality of recovery score QoR-15.

BACKGROUND: Patient perceived quality of recovery is an important outcome after surgery and should be measured in clinical trials. Quality of recovery after surgery and general anaesthesia can be measured by the QoR-15. A high score indicates a good recovery and the score ranges from 0 to 150. The aim of this study was to translate the QoR-15 questionnaire into Danish and do a full psychometric evaluation of the Danish version. METHODS: A translation and cultural adaption of the original version of the QoR-15 into a Danish version, the QoR-15D, was performed. After obtaining consent, patients undergoing elective abdominal, orthopaedic or gynaecological surgery under general anaesthesia were included. Patients completed the QoR-15D before surgery and on the first postoperative day. The validity, reliability, responsiveness and clinical feasibility of the QoR-15D were evaluated. RESULTS: One hundred and forty patients returned their pre- and postoperative questionnaire successfully giving a completion rate of 56%. The postoperative QoR-15 score was negatively correlated with duration of surgery (ρ = -0.21, 95% CI: -0.04 to -0.36, P < 0.02) and postoperative stay (ρ = -0.28, 95% CI: -0.12 to -0.43, P < 0.01). Postoperative QoR-15D scores were inversely related to the extent of surgery: minor, intermediate or major (127 ± 22, 106 ± 29 and 96 ± 24, respectively, P < 0.01). Cronbach's alpha and split-half reliability was 0.90 and 0.88. Test-retest reliability was 0.99 (95% CI: 0.94-1.00). Cohen's effect size was 1.13 and the standardized response mean was 0.82. CONCLUSION: The QoR-15D has preserved the validity, excellent reliability, high degree of responsiveness and the clinical feasibility of the original English version.

Risk factors for delayed healing in venous leg ulcers: a review of the literature.

BACKGROUND: Chronic leg ulcers, remaining unhealed after 4-6 weeks, affect 1-3% of the population, with treatment costly and health service resource intensive. Venous disease contributes to approximately 70% of all chronic leg ulcers and these ulcers are often associated with pain, reduced mobility and a decreased quality of life. Despite evidence-based care, 30% of these ulcers are unlikely to heal within a 24-week period and therefore the recognition and identification of risk factors for delayed healing of venous leg ulcers would be beneficial. AIM: To review the available evidence on risk factors for delayed healing of venous leg ulcers. METHODS: A review of the literature in regard to risk factors for delayed healing in venous leg ulcers was conducted from January 2000 to December 2013. Evidence was sourced through searches of relevant databases and websites for resources addressing risk factors for delayed healing in venous leg ulcers specifically. RESULTS: Twenty-seven studies, of mostly low-level evidence (Level III and IV), identified risk factors associated with delayed healing. Risk factors that were consistently identified included: larger ulcer area, longer ulcer duration, a previous history of ulceration, venous abnormalities and lack of high compression. Additional potential predictors with inconsistent or varying evidence to support their influence on delayed healing of venous leg ulcers included: decreased mobility and/or ankle range of movement, poor nutrition and increased age. DISCUSSION: Findings from this review indicate that a number of physiological risk factors are associated with delayed healing in venous leg ulcers and that social and/or psychological risk factors should also be considered and examined further. CONCLUSION: The findings from this review can assist health professionals to identify prognostic indicators or risk factors significantly associated with delayed healing in venous leg ulcers. This will facilitate realistic outcome planning and inform implementation of appropriate early strategies to promote healing.

The role of mobile instrumentation in novel applications of Raman spectroscopy: archaeometry, geosciences, and forensics.

The applications of analytical Raman spectroscopy in the characterisation of materials associated with archaeologically excavated artefacts, forensic investigations of drugs of abuse, security and crime scenes, minerals and rocks and future astrobiological space missions are now well established; however, these applications have emphasised the need for new developments in the area of miniaturised instrumentation which extends the concept and breadth of the analytical requirement to facilitate the provision of data from 'in field' studies. In this respect, the apparently unrelated themes of art and archaeology, forensic science, geological science and astrobiology as covered by this review are unified broadly by the ability to record data nondestructively and without resorting to sampling and the subsequent transfer of samples to the analytical laboratory. In studies of works of art there has long been a requirement for on-site analysis, especially for valuable paintings held under strict museum security and for wall paintings which cannot physically be removed from their setting; similarly, the use of portable Raman spectroscopy in archaeological and geological field work as a first-pass screening device which obviates the necessity of multiple and wasteful specimen collection is high on the wish-list of practicing spectroscopists. As a first-pass screening probe for forensic crime scenes, Raman spectroscopy has proved to be of inestimable value for the early detection of dangerous and prohibited materials such as drugs of abuse, explosives and their chemical precursors, and banned contraband biomaterials such as ivories and animal products; in these applications the advantage of the Raman spectroscopic technique for the recognition of spectral signatures from mixtures of inorganic and organic compounds is paramount and not afforded by other less portable instrumental techniques. Finally, in astrobiological work, these requirements also apply but with the additional prerequisite for system operation remotely - often over distances of several hundred million kilometres - as part of instrumental suites on robotic spacecraft and planetary landers; this necessitates robust and reliable instrumentation for the observation of unique and characteristic spectral features from the planetary geological surface and subsurface which are dependent on the assignment of both biological and geological band signatures.

The perspectives of adults with venous leg ulcers on exercise: an exploratory study.

OBJECTIVE: Exercise has the potential to offer a range of health benefits in addition to improving healing outcomes for people with venous leg ulcers (VLUs). However, despite evidence-based recommendations, most of these individuals do not engage in regular exercise. The aim of this study was to gain an understanding of the perspectives of adults with VLUs, in relation to exercise. METHOD: This was a qualitative design using semi-structured interviews and discussions. Ten participants with venous leg ulceration volunteered to participate. Recruitment was through a specialist wound clinic. Verbatim data were collected by an experienced moderator using a semi-structured guide. Data saturation was reached after three group discussions and two interviews. A random selection of transcripts was sent back to the participants for verification. Thematic content analysis was used to determine major themes and categories. Two transcripts were independently analysed, categories and themes independently developed, cross checked and found comparable. Remaining transcripts were analysed using the developed categories and codes. RESULTS: Regardless of their current exercise routine, participants reported exercising before venous leg ulceration and expressed an interest in either becoming active or maintaining an active lifestyle. Overall, four themes emerged from the findings: i) participant understanding of the relationship between chronic venous insufficiency and exercise patterns; ii) fear of harm impacts upon positive beliefs and attitudes to exercise; iii) perceived factors limit exercise; and iv) structured management facilitates exercise. CONCLUSION: The value of exercise in improving outcomes in VLUs lies in its capacity to promote venous return and reduce the risk of secondary conditions in this population. Despite motivation and interest in being exercise active, people with VLUs report many obstacles. Further exploration of mechanisms that assist this patient population and promote understanding about management of barriers, coupled with promotion of enabling factors, is vital for improving their exercise participation.

Role of recombinant factor VIIa in the clinical management of severe postpartum hemorrhage: consensus among European experts.

OBJECTIVES: There have been significant advances in the medical management of severe postpartum hemorrhage (sPPH) over recent decades, which is reflected in numerous published guidelines. To date, many of the currently available national and international guidelines recommend recombinant factor VIIa (rFVIIa) to be used only at a very late stage in the course of sPPH, as a "last resort", before or after hysterectomy. Based on new safety data, rFVIIa has recently been approved by the European Medicines Agency (EMA) and Swissmedic for use in sPPH, if uterotonics are insufficient to achieve hemostasis, which in fact is significantly earlier in the course of postpartum hemorrhage (PPH). We therefore aimed to develop expert consensus guidance as a step toward standardizing care with the use of rFVIIa for clinicians managing women experiencing life-threatening sPPH. METHODS: The consensus process consisted of one face-to-face meeting with a group of nine experts, including eight obstetrician-gynecologists and a hematologist highly experienced in sPPH care in tertiary care perinatal centers. The panel was representative of multidisciplinary expertise in the European obstetrics community and provided consensus opinion in answer to pre-defined questions around clinical practice with rFVIIa in the management of sPPH. Recommendations have been based on current national and international guidelines, extensive clinical experience, and consensus opinion, as well as the availability of efficacy and new safety data. RESULTS: The expert panel developed 17 consensus statements in response to the 13 pre-defined questions on the use of rFVIIa in the management of sPPH including: available efficacy and safety data and the need for interdisciplinary expertise between obstetricians, anesthesiologists, and hematologists in the management of sPPH. Based on novel data, the experts recommend: (1) earlier administration of rFVIIa in patients with sPPH who do not respond to uterotonic administration to optimize the efficacy of rFVIIa; (2) the importance of hematological parameter prerequisites prior to the administration of rFVIIa to maximize efficacy; and (3) continued evaluation or initiation of further invasive procedures according to standard practice. Furthermore, recommendations on the timing of rFVIIa treatment within the sPPH management algorithm are outlined in a range of specified clinical scenarios and settings, including vaginal delivery, cesarean section, and smaller birthing units before transfer to a tertiary care center. The panel agreed that according to available, and new data, as well as real-world experience, there is no evidence that the use of rFVIIa in patients with sPPH increases the risk of thromboembolism. The authors acknowledge that there is still limited clinical effectiveness data, as well as pharmacoeconomic data, on the use of rFVIIa in sPPH, and recommend further clinical trials and efficacy investigation. CONCLUSIONS: This expert panel provides consensus guidance based on recently available data, clinical experience, and expert opinion, augmented by the recent approval of rFVIIa for use in sPPH by the EMA. These consensus statements are intended to support clinical care for sPPH and may help to provide the impetus and a starting point for updates to existing clinical practice guidelines.

Fewer invited talks by women in evolutionary biology symposia.

Lower visibility of female scientists, compared to male scientists, is a potential reason for the under-representation of women among senior academic ranks. Visibility in the scientific community stems partly from presenting research as an invited speaker at organized meetings. We analysed the sex ratio of presenters at the European Society for Evolutionary Biology (ESEB) Congress 2011, where all abstract submissions were accepted for presentation. Women were under-represented among invited speakers at symposia (15% women) compared to all presenters (46%), regular oral presenters (41%) and plenary speakers (25%). At the ESEB congresses in 2001-2011, 9-23% of invited speakers were women. This under-representation of women is partly attributable to a larger proportion of women, than men, declining invitations: in 2011, 50% of women declined an invitation to speak compared to 26% of men. We expect invited speakers to be scientists from top ranked institutions or authors of recent papers in high-impact journals. Considering all invited speakers (including declined invitations), 23% were women. This was lower than the baseline sex ratios of early-mid career stage scientists, but was similar to senior scientists and authors that have published in high-impact journals. High-quality science by women therefore has low exposure at international meetings, which will constrain Evolutionary Biology from reaching its full potential. We wish to highlight the wider implications of turning down invitations to speak, and encourage conference organizers to implement steps to increase acceptance rates of invited talks.

Novel Phakopsora pachyrhizi extracellular proteins are ideal targets for immunological diagnostic assays.

Phakopsora pachyrhizi, the causal agent of Asian soybean rust (ASR), continues to spread across the southeast and midsouth regions of the United States, necessitating the use of fungicides by producers. Our objective in this research was to identify ASR proteins expressed early during infection for the development of immunodiagnostic assays. We have identified and partially characterized a small gene family encoding extracellular proteins in the P. pachyrhizi urediniospore wall, termed PHEPs (for Phakopsora extracellular protein). Two highly expressed protein family members, PHEP 107 and PHEP 369, were selected as ideal immunodiagnostic targets for antibody development, after we detected PHEPs in plants as early as 3 days postinfection (dpi). Monoclonal antibodies (MAbs; 2E8E5-1 and 3G6H7-3) generated against recombinant PHEP 369 were tested for sensitivity against the recombinant protein and extracts from ASR-infected plants and for specificity against a set of common soybean pathogens. These antibodies should prove applicable in immunodiagnostic assays to detect infected soybeans and to identify ASR spores from sentinel surveillance plots.

Minimizing pharmacodynamic interactions of high doses of lacosamide.

OBJECTIVES: To determine whether pharmacodynamic interactions between high doses of lacosamide (400-800 mg/day) and concomitant sodium channel antiepilepsy drugs (AEDs) can be minimized in patients with drug-resistant partial-onset seizures. MATERIALS AND METHODS: Patients were rapidly initiated with high-dose lacosamide (100 mg/week; increases to 400 to 800 mg/day), while simultaneously tapering concomitant sodium channel AEDs. Seizure frequency and side effects were evaluated at six time points: baseline, titration, 3, 6, 9 and 12 months. RESULTS: Twenty-three patients had a baseline median of 4 seizures/month with persisting partial-onset seizures, despite previous treatment with an average of 6.8 AEDs. Mean decreases in monthly seizure frequency were as follows: 3 months 49.9% (P = 0.011), 6 months 55.4% (P = 0.010), 9 months 60.8% (P = 0.002) and 12 months 58.2% (P = 0.011). Most adverse events were mild CNS-related symptoms and occurred transiently only during titration - there was no significant relationship (χ(2) < 1.5, P > 0.1) between lacosamide dose and the presence of side effects at 3, 6, 9 or 12 months. CONCLUSIONS: Drug-resistant patients rapidly titrated to high doses of lacosamide with simultaneous tapering of traditional sodium channel AEDs had marked reduction in CNS-related adverse events compared with patients treated in three previous pivotal trials that used fixed doses of concomitant AEDs.

Glycerol inhibition of ruminal lipolysis in vitro.

Supplemental glycerol inhibits rumen lipolysis, a prerequisite for rumen biohydrogenation, which is responsible for the saturation of dietary fatty acids consumed by ruminant animals. Feeding excess glycerol, however, adversely affects dry matter digestibility. To more clearly define the effect of supplemental glycerol on rumen lipolysis, mixed populations of ruminal bacteria were incubated with 6 or 20% glycerol (vol/vol). After 48-h anaerobic incubation of mixed culture rumen fluid, rates of free fatty acid production (nmol/mL per h) for the 6 and 20% glycerol-supplemented samples were decreased by 80 and 86%, respectively, compared with rates from nonsupplemented control cultures (12.4±1.0; mean ± SE). Conversely, assay of the prominent ruminal lipase-producing bacteria Anaerovibrio lipolyticus 5S, Butyrivibrio fibrisolvens 49, and Propionibacterium species avidum and acnes revealed no effect of 2 or 10% (vol/vol) added glycerol on lipolytic activity by these organisms. Supplementing glycerol at 6% on a vol/vol basis, equivalent to supplementing glycerol at approximately 8 to 15% of diet dry matter, effectively reduced lipolysis. However, the mechanism of glycerol inhibition of ruminal lipolysis remains to be demonstrated.

Decreased mobility, lack of social support, haemosiderosis and use of antidepressant medications may predict recurrent venous leg ulcers within 12 months of healing: A prospective longitudinal study.

AIM: To identify clinical, medical and psychosocial predictors of venous leg ulcer recurrence within 12 months of healing. METHODS: A multi-site study was conducted in Australia in community and hospital outpatient settings. Adults with venous leg ulcers were recruited within 4 weeks of healing and data were collected on preventative treatments and health, medical, clinical and psychosocial factors. Follow-up data on recurrences were collected every 3 months until ulcer recurrence, or until 12 months after healing pending which occurred first. Factors associated with time to recurrence were analysed using a Cox proportional hazards regression model. DESIGN: Secondary data analysis of a multi-site, prospective longitudinal study to validate a risk assessment tool for recurrence. RESULTS: A sample of 143 participants was recruited (51% male, Mage = 73 years, SD 13.6). Almost half (49.6%) had an ulcer recurrence within 12 months, with a mean time to ulcer recurrence of 37 weeks (SE 1.63, 95% CI 33.7-40.1). Factors measured at the time of healing that were significant independent predictors of recurrence were: prescribed antidepressant medications (p = .035), presence of haemosiderosis (p = .006), decreased mobility (longer sitting times) (p = .007) and lower social support scale scores (p = .002). Participants who wore compression systems providing 20 mmHg or higher for at least 5 days/week were less likely to recur, although not reaching statistical significance (p = .06). CONCLUSION: Results provide evidence that antidepressant medications, haemosiderosis, decreased mobility and lack of social support are risk factors associated with ulcer recurrence; therefore, these variables are modifiable and could guide early intervention.

Incidence of persistent postpartum opioid use by mode of delivery: a 2016 cohort study of Danish women.

BACKGROUND: The use of oral opioids as standard treatment after cesarean delivery has been linked to persistent use in opioid-naïve women in the USA. In Denmark, the use of opioids after cesarean delivery is typically restricted to in-hospital use. The aim of this study was to estimate the incidence of persistent postpartum opioid use in Denmark and compare the incidence by mode of delivery. METHODS: This was a national cohort study of all women giving birth in Denmark in 2016, with one-year follow-up. Data from Danish registries were retrieved and combined using each woman's unique identification number. Persistent use of opioids was defined as ≥3 redeemed opioid prescriptions 31-365 days postpartum. RESULTS: A total of 62 520 births were included in the cohort: 49 859 vaginal deliveries, 5310 intrapartum cesarean deliveries, and 7351 pre-labor cesarean deliveries. For all births, persistent postpartum opioid use occurred in 85 (140 in 100 000) women of whom 36 (42%) had opioid use during pregnancy. The incidence of persistent opioid use was highest in the pre-labor cesarean delivery cohort (n=27; 360 in 100 000) and lowest in the intrapartum cesarean delivery cohort (n=3, 60 in 100 000; P<0.001). Women taking opioids during pregnancy were at increased risk of persistent opioid use (odds ratio 63.3; 95% CI 43.9 to 91.4). CONCLUSIONS: Women giving birth in Denmark, where use of post-discharge opioid treatment is generally restricted, have a low risk of developing persistent use of opioids, with very few women seeking additional analgesic treatment from their general practitioner.