Rapid switching from levetiracetam to brivaracetam in pharmaco-resistant epilepsy in people with and without intellectual disabilities: a naturalistic case control study.

BACKGROUND: Approximately one quarter of people with an intellectual disability (PwID) have epilepsy of whom nearly three-quarters are pharmaco-resistant. There are higher reported neuropsychiatric side-effects to anti-seizure medication (ASM) in this group. Levetiracetam (LEV) is a first-line ASM with a stronger association with neuropsychiatric symptoms for PwID than other ASMs. Brivaracetam (BRV) is a newer ASM. Recent studies suggest a beneficial effect of swapping people who experience neuropsychiatric events with LEV to BRV. However, there is limited evidence of this for PwID. This evaluation analyses real world outcomes of LEV to BRV swap for PwID compared to those without ID. METHODS: We performed a multicentre, retrospective review of clinical records. Demographic, clinical characteristics and reported adverse events of patients switched from LEV to BRV (2016-2020) were recorded at 3 months pre and 6- and 12-month post-BRV initiation. Outcomes were compared between PwID and those without and summarised using cross-tabulations and logistic regression models. A Bonferroni correction was applied. RESULTS: Of 77 participants, 46 had ID and 52% had a past psychiatric illness. 71% participants switched overnight from LEV to BRV. Seizure reduction of > 50% was seen in 40% patients. Psychiatric illness history was predictive of having neuropsychiatric side-effects with LEV but not BRV (p = 0.001). There was no significant difference for any primary outcomes between PwID versus without ID. CONCLUSIONS: Switching from LEV to BRV appears as well tolerated and efficacious in PwID as those without ID with over 90% still on BRV after 12 months.

Indicators for the evaluation of musculoskeletal trauma systems: A scoping review and Delphi study.

BACKGROUND: Trauma is a leading cause of mortality and morbidity, disproportionately affecting low- and middle-income countries. Musculoskeletal trauma results in the majority of post-traumatic morbidity and disability globally. The literature has reported many performance indicators relating to trauma care, but few specific to musculoskeletal injuries. STUDY OBJECTIVES: The purpose of this study was to establish a practical list of performance indicators to evaluate and monitor the quality and equity of musculoskeletal trauma care delivery in health systems worldwide. METHODS: A scoping review was performed that identified performance indicators related to musculoskeletal trauma care. Indicators were organized by phase of care (general, prevention, pre-hospital, hospital, post-hospital) within a modified Donabedian model (structure, process, outcome, equity). A panel of 21 experts representing 45 countries was assembled to identify priority indicators utilizing a modified Delphi approach. RESULTS: The scoping review identified 1,206 articles and 114 underwent full text review. We included 95 articles which reported 498 unique performance indicators. Most indicators related to the hospital phase of care (n = 303, 60%) and structural characteristics (n = 221, 44%). Mortality (n = 50 articles) and presence of trauma registries (n = 16 articles) were the most frequently reported indicators. After 3 rounds of surveys our panel reached consensus on a parsimonious list of priority performance indicators. These focused on access to trauma care; processes and key resources for polytrauma triage, patient stabilization, and hemorrhage control; reduction and immobilization of fractures and dislocations; and management of compartment syndrome and open fractures. CONCLUSIONS: The literature has reported many performance indicators relating to trauma care, but few specific to musculoskeletal injuries. To create quality and equitable trauma systems, musculoskeletal care must be incorporated into development plans with continuous monitoring and improvement. The performance indicators identified by our expert panel and organized in a modified Donabedian model can serve as a method for evaluating musculoskeletal trauma care.

A narrative review of the epidemiology and economics of chronic wounds.

Chronic wounds have a debilitating effect on the quality of life of many individuals, and the large economic impact on health system budgets warrants greater attention in policy making and condition management than is currently evident. The aim of this narrative review is to summarize the nature and extent of the chronic wound problem that confronts health systems across the world. The first section is used to highlight the underlying epidemiology relating to chronic wounds, while the second explores the economic costs associated with them and the relative efficiency of measures designed to manage them.

Wound healing: potential therapeutic options.

This review highlights the range of therapeutic options available to clinicians treating difficult-to-heal wounds. While certain treatments are established in daily clinical practice, most therapeutic interventions lack robust and rigorous data regarding their efficacy, which would help to determine when, and for whom, they should be used. The purpose of this review is to give a broad overview of the available interventions, with a brief summary of the evidence base for each intervention.

The Baltic Sea: An ecosystem with multiple stressors.

This introductory chapter to our Environment International VSI does not need an abstract and therefore we just include our recommendations below in order to proceed with the resubmission. Future work should examine waterbirds as food web sentinels of multiple stressors as well as Baltic Sea food web dynamics of hazardous substances and how climate change may modify it. Also, future work should aim at further extending the new frameworks developed within BALTHEALTH for energy and contaminant transfer at the population level (Desforges et al., 2018, Cervin et al., 2020/this issue Silva et al., 2020/this issue) and their long term effects on Baltic Sea top predators, such as harbour porpoises, grey seals ringed seals, and white-tailed eagles. Likewise, the risk evaluation conducted for PCB in connection with mercury on Arctic wildlife (Dietz et al., 2019, not a BONUS BALTHEALTH product) could be planned for Baltic Sea molluscs, fish, bird and marine mammals in the future. Finally, future efforts could include stressors not covered by the BONUS BALTHEALTH project, such as food web fluxes, overexploitation, bycatches, eutrophication and underwater noise.

Design and testing of communication materials for a breastfeeding social media marketing campaign: Breastfeed4Ghana.

Breastfeed4Ghana was a social media-based campaign implemented to address identified gaps in the protection, promotion, and support of breastfeeding in Ghana. This paper describes the process of campaign materials development and testing to ensure their cultural and content appropriateness. The 60 campaign materials, each consisting of an image and text message, underwent a process of creation, testing, revision, and finalization. Existing research evidence and infant and young child feeding communication tools that were culturally relevant for Ghana were used to develop the materials. All materials were tested and finalized through an iterative process that incorporated input from six focus group discussions (FGDs) with mothers, and content and technical experts. The materials were revised to ensure scientific accuracy, understandability, and cultural appropriateness of the messages, as well as alignment of the messages with the images. Finalized materials were reviewed and approved by the Ghana Food and Drugs Authority. Analysis for this paper involved summarizing and categorizing the types and sources of input as well as the research team's responses to the input received. The 60 campaign materials received a total of 132 inputs. Most inputs came from FGDs (78.4%); and most inputs were on the campaign material images. The evidence-informed process of materials creation, use of multiple input sources, and a broad-based iterative process allowed the creation of 60 evidence-based and culturally appropriate materials for a breastfeeding social media campaign in Ghana. This paper could serve as a guide for other social media campaign efforts looking to develop culturally appropriate materials.

Guidelines on suicide amongst anaesthetists 2019.

Anaesthetists are thought to be at increased risk of suicide amongst the medical profession. The aims of the following guidelines are: increase awareness of suicide and associated vulnerabilities, risk factors and precipitants; to emphasise safe ways to respond to individuals in distress, both for them and for colleagues working alongside them; and to support individuals, departments and organisations in coping with a suicide.

Depression prevalence in Type 2 diabetes is not related to diabetes-depression symptom overlap but is related to symptom dimensions within patient self-report measures: a meta-analysis.

AIM: Depression is common in Type 2 diabetes, yet rates vary. Overlap between symptoms of depression and diabetes may account for this variability in depression prevalence rates. We examined to what extent depression prevalence was a function of the proportion of depression-diabetes symptom overlap (items within symptom dimensions) and sample characteristics. METHODS: Electronic and hand searching of published and unpublished works identified 147 eligible papers. Of 3656 screened, 147 studies (149 samples, N = 17-229 047, mean sample age 25.4-82.8 years, with 152 prevalence estimates), using 24 validated depression questionnaires were selected. Sample size, publication type, sample type, gender, age, BMI, HbA1c , depression questionnaire and prevalence rates were extracted. RESULTS: Prevalence rates ranged from 1.8% to 88% (mean = 28.30%) and were higher in younger samples, samples with higher mean HbA1c and clinic samples. Diabetes-depression symptom overlap did not affect prevalence. A higher proportion of anhedonia, cognition, cognitive, negative affect and sleep disturbance symptoms, and a lower proportion of somatic symptoms were consistently associated with higher depression prevalence. CONCLUSIONS: The lack of an overall effect of diabetes-depression symptom overlap might suggest that assessment of depression in Type 2 diabetes is generally not confounded by co-occuring symptoms. However, questionnaires with proportionally more or fewer items measuring other symptom categories were associated with higher estimates of depression prevalence. Depression measures that focus on the cardinal symptoms of depression (e.g. negative affect and cognition), limiting symptoms associated with increasing diabetes symptomatology (e.g. sleep disturbance, cognitive) may most accurately diagnose depression.

Development and validation of a gene expression test to identify hard-to-heal chronic venous leg ulcers.

BACKGROUND: Chronic venous leg ulcers pose a significant burden to healthcare systems, and predicting wound healing is challenging. The aim of this study was to develop a genetic test to evaluate the propensity of a chronic ulcer to heal. METHODS: Sequential refinement and testing of a gene expression signature was conducted using three distinct cohorts of human wound tissue. The expression of candidate genes was screened using a cohort of acute and chronic wound tissue and normal skin with quantitative transcript analysis. Genes showing significant expression differences were combined and examined, using receiver operating characteristic (ROC) curve analysis, in a controlled prospective study of patients with venous leg ulcers. A refined gene signature was evaluated using a prospective, blinded study of consecutive patients with venous ulcers. RESULTS: The initial gene signature, comprising 25 genes, could identify the outcome (healing versus non-healing) of chronic venous leg ulcers (area under the curve (AUC) 0·84, 95 per cent c.i. 0·73 to 0·94). Subsequent refinement resulted in a final 14-gene signature (WD14), which performed equally well (AUC 0·88, 0·80 to 0·97). When examined in a prospective blinded study, the WD14 signature could also identify wounds likely to demonstrate signs of healing (AUC 0·73, 0·62 to 0·84). CONCLUSION: A gene signature can identify people with chronic venous leg ulcers that are unlikely to heal.

Comparative Biology of Cycad Pollen, Seed and Tissue - A Plant Conservation Perspective.

Cycads are the most endangered of plant groups based on IUCN Red List assessments; all are in Appendix I or II of CITES, about 40% are within biodiversity 'hotspots,' and the call for action to improve their protection is long-standing. We contend that progress in this direction will not be made until there is better understanding of cycad pollen, seed and tissue biology, which at the moment is limited to relatively few (<10%) species. We review what is known about germplasm (seed and pollen) storage and germination, together with recent developments in the application of contemporary technologies to tissues, such as isotype labelling, biomolecular markers and tissue culture. Whilst progress is being made, we conclude that an acceleration of comparative studies is needed to facilitate the integration of in situ and ex situ conservation programmes to better safeguard endangered cycads.

Response rate to a single dose of vinblastine administered to dogs with treatment-naive multicentric lymphoma.

Vincristine is included in vincristine, cyclophosphamide, doxorubicin and prednisone (CHOP) chemotherapy protocols, which are the gold-standard treatment for high-grade canine lymphoma. Vincristine can result in relatively high rates of gastrointestinal toxicity, whereas vinblastine is generally well tolerated and thus may represent an under-utilized and minimally toxic alternative to vincristine. Our objective was to determine the response rate and toxicity associated with a single dose of vinblastine administered to dogs with treatment-naïve, intermediate to large-cell, multicentric lymphoma. Twenty client-owned dogs were enrolled with signed owner consent. A Simon's minimax, phase II, two-stage trial was performed to test the efficacy of vinblastine administered at 2 mg/m2 IV followed by a pilot trial of vinblastine at 2.5 mg/m2 . No dogs were administered concurrent steroids or other chemotherapy. One out of 14 dogs receiving vinblastine at 2 mg/m2 demonstrated a partial response. Three out of five dogs demonstrated a partial response to vinblastine at 2.5 mg/m2 . Gastrointestinal toxicity was infrequent and low grade for both groups. The majority of dogs (80%) in the 2.5 mg/m2 dosing group developed neutropenia 1-week post administration. Vinblastine was well tolerated but minimally efficacious at a dose of 2 mg/m2 IV in dogs with treatment-naive, multicentric lymphoma. Because of poor response rates, treatment at this dose is not recommended. A small subset of dogs administered 2.5 mg/m2 had significantly improved response rates (P = 0.04), suggesting that higher doses may have improved efficacy, although further research is indicated to confirm these preliminary findings.

Alginate Encapsulation to Enhance Biopreservation Scope and Success: A Multidisciplinary Review of Current Ideas and Applications in Cryopreservation and Non-Freezing Storage.

BACKGROUND: The development of encapsulation technologies has played an important role in improving cryopreservation outcomes for many cell and tissue types over the past 20 years. Alginate encapsulation cryopreservation (AECryo) has been incorporated into a range of applications in biotechnology, species conservation and clinical therapies, using cells from many different phyla, including higher plants, animal and human cells. This review describes the background to the origins of AECryo, the development of AECryo in higher plant tissues, broadening to current applications in algal conservation, the roles for AECryo in preserving phytodiversity, fungal species and in animal and human cells. OBJECTIVE: The main aims are to provide information resources on AECryo in different areas of biology and to stimulate new ideas for wider applications and future improvement. The translation of this useful biopreservation strategy into new opportunities for cell cryopreservation and storage at non-freezing temperatures are also discussed.

Multiple sclerosis: long-term outcomes in ethnic minorities. Analysis of a UK population-based registry.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is most frequent in Caucasian populations. However, studies of MS in other ethnic groups may offer unique insights into genetic and environmental influences on the disease, and data on long-term outcomes in these patients is limited. In this work clinical features and time to disability milestones were investigated in ethnic minority (EM) patients with MS in a UK population and comparisons were made to a Caucasian cohort from the same region. METHODS: In all, 1949 MS patients (1866 Caucasian, 83 EM) were identified from a regional disease registry. Cox proportional hazards regression was used to analyse the time to Expanded Disability Status Scale (EDSS) 3.0, 4.0 and 6.0. RESULTS: Ethnic minority patients were younger at disease onset (28.6 years vs. 32.8 years, P = 0.001), and primary progressive MS was less common (EM 4.8%, Caucasian 11.6%, P = 0.03). After correction for clinical variables, ethnicity was associated with time to EDSS 3.0 [EM: hazard ratio (HR) 1.75, P < 0.0001] and 4.0 (HR 1.46, P = 0.03), but not 6.0 (HR 1.5, P = 0.05). CONCLUSIONS: Ethnic minority patients reach early levels of fixed disability more rapidly than Caucasian patients, but this effect diminishes at later stages of the disease. This has implications for clinical management of these patients.

Levels of wound calprotectin and other inflammatory biomarkers aid in deciding which patients with a diabetic foot ulcer need antibiotic therapy (INDUCE study).

AIMS: Deciding if a diabetic foot ulcer is infected in a community setting is challenging without validated point-of-care tests. Four inflammatory biomarkers were investigated to develop a composite algorithm for mildly infected diabetic foot ulcers: venous white cell count, C-reactive protein (CRP) and procalcitonin, and a novel wound exudate calprotectin assay. Calprotectin is a marker of neutrophilic inflammation. METHODS: In a prospective study, people with uninfected or mildly infected diabetic foot ulcers who had not received oral antibiotics in the preceding 2 weeks were recruited from community podiatry clinics for measurement of inflammatory biomarkers. Antibiotic prescribing decisions were based on clinicians' baseline assessments and participants were reviewed 1 week later; ulcer infection was defined by clinicians' overall impression from their two assessments. RESULTS: Some 363 potential participants were screened, of whom 67 were recruited, 29 with mildly infected diabetic foot ulcers and 38 with no infection. One participant withdrew early in each group. Ulcer area was 1.32 cm2 [interquartile range (IQR) 0.32-3.61 cm2 ] in infected ulcers and 0.22 cm2 (IQR 0.09-1.46 cm2 ) in uninfected ulcers. Baseline CRP for mild infection was 9.00 mg/ml and 6.00 mg/ml for uninfected ulcers; most procalcitonin levels were undetectable. Median calprotectin level in infected diabetic foot ulcers was 1437 ng/ml and 879 ng/ml in uninfected diabetic foot ulcers. Area under the receiver operating characteristic curve for a composite algorithm incorporating calprotectin, CRP, white cell count and ulcer area was 0.68 (95% confidence intervals 0.52-0.82), sensitivity 0.64, specificity 0.81. CONCLUSIONS: A composite algorithm including CRP, calprotectin, white cell count and ulcer area may help to distinguish uninfected from mildly infected diabetic foot ulcers. Venous procalcitonin is unhelpful for mild diabetic foot ulcer infection.

Defining sepsis on the wards: results of a multi-centre point-prevalence study comparing two sepsis definitions.

Our aim was to prospectively determine the predictive capabilities of SEPSIS-1 and SEPSIS-3 definitions in the emergency departments and general wards. Patients with National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled over a 24-h period in 13 Welsh hospitals. The primary outcome measure was mortality within 30 days. Out of the 5422 patients screened, 431 fulfilled inclusion criteria and 380 (88%) were recruited. Using the SEPSIS-1 definition, 212 patients had sepsis. When using the SEPSIS-3 definitions with Sequential Organ Failure Assessment (SOFA) score ≥ 2, there were 272 septic patients, whereas with quickSOFA score ≥ 2, 50 patients were identified. For the prediction of primary outcome, SEPSIS-1 criteria had a sensitivity (95%CI) of 65% (54-75%) and specificity of 47% (41-53%); SEPSIS-3 criteria had a sensitivity of 86% (76-92%) and specificity of 32% (27-38%). SEPSIS-3 and SEPSIS-1 definitions were associated with a hazard ratio (95%CI) 2.7 (1.5-5.6) and 1.6 (1.3-2.5), respectively. Scoring system discrimination evaluated by receiver operating characteristic curves was highest for Sequential Organ Failure Assessment score (0.69 (95%CI 0.63-0.76)), followed by NEWS (0.58 (0.51-0.66)) (p < 0.001). Systemic inflammatory response syndrome criteria (0.55 (0.49-0.61)) and quickSOFA score (0.56 (0.49-0.64)) could not predict outcome. The SEPSIS-3 definition identified patients with the highest risk. Sequential Organ Failure Assessment score and NEWS were better predictors of poor outcome. The Sequential Organ Failure Assessment score appeared to be the best tool for identifying patients with high risk of death and sepsis-induced organ dysfunction.

Viscoelastometry guided fresh frozen plasma infusion for postpartum haemorrhage: OBS2, an observational study.

BACKGROUND: Postpartum haemorrhage (PPH) can be exacerbated by haemostatic failure. Based on data from trauma studies, empirical infusions of fresh frozen plasma (FFP) are often given during severe PPH if coagulation tests are unavailable. This study observed a cohort of women with moderate/severe PPH in whom FFP infusion was guided by the use of viscoelastometric point-of-care testing (VE-POCT) and clinical assessment. METHODS: Women were enrolled into this observational study when blood loss was measured or suspected to be about 1000 mL. If Fibtem A5 determined by Rotem ® thromboelastometry remained >15 mm, or bleeding stopped, FFP was withheld. If Fibtem A5 was ≤15 mm and bleeding ongoing, women were randomized into an interventional study as previously reported. Clinical and laboratory outcomes were recorded. RESULTS: The study recruited 605 women and 98% had FFP withheld. The median (25 th -75 th centile) total blood loss was 1500 (1300-2000) mL with 300 (50-545) mL occurring after enrolment. Total blood loss was >2500 mL in 40/605 (6.6%) women. RBCs were transfused in 141/605 (23.3%) patients and 11 (1.8%) received ≥4 units. At least one invasive procedure was performed in 283/605 (46.8%) women. Level 3 care was required for 10/605 (1.7%) women. No women developed clinically significant haemostatic impairment. CONCLUSIONS: Restrictive use of FFP guided by clinical assessment of bleeding and VE-POCT is feasible and did not result in clinically significant haemostatic impairment. Studies should compare the clinical and cost effectiveness of empirical FFP infusions, according to current guidelines, with targeted use of FFP based on VE-POCT. CLINICAL TRIAL REGISTRATION: ISRCTN46295339 ( http://www.isrctn.com/ISRCTN46295339 ) (accessed July 24, 2017), EudraCT 2012-005511-11 ( https://www.clinicaltrialsregister.eu/ctr-search?query=2011-005511-11 ) (accessed July 24, 2017).

Antarctic seals: Molecular biomarkers as indicators for pollutant exposure, health effects and diet.

Weddell (Leptonychotes weddellii), Ross (Ommatophoca rossii) and crabeater seals (Lobodon carcinophaga) are phocid seals with a circumpolar distribution around Antarctica. As long-lived and large top predators, they bioaccumulate contaminants and are considered as sentinels of ecosystem health. Antarctic seals are increasingly exposed to climate change, pollution, shipping and fisheries. To reveal and understand possible anthropogenic impacts on their immune and health status, this study investigates sensitive biomarkers of the xenobiotic metabolism and immune system in relation to mercury (Hg) burden. Gene-transcription studies using minimally-invasive blood samples are useful to monitor physiological processes in wildlife that can be related to different stressors. Blood samples of 72 wild-caught seals (Weddell n=33; Ross n=12; crabeater n=27) in the Amundsen and Ross Seas in 2008-2011 were investigated. Copy numbers per µl mRNA transcription of xenobiotic biomarkers (aryl hydrocarbon receptor (AHR)), aryl hydrocarbon receptor nuclear translocator (ARNT) and peroxisome proliferator-activated receptor (PPARα) and immune relevant cell mediators (cytokines interleukin-2 (IL-2), interleukin-10 (IL-10) and heat-shock-protein 70 (HSP70)) were measured using reference genes Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide (YWHAZ) and ribosomal protein L4 (RPL4) by real time RT-qPCR. Hg concentration was analysed in fur. Hg concentration increased with body weight and standard length in all species. Crabeater seals showed a lower Hg concentration than Ross and Weddell seals. Species-specific differences in gene-transcription were found between all species with highest levels of AHR, ARNT and PPARα in crabeater seals. Ross seals showed highest IL-10 and HSP70 transcription, while HSP70 was exceptionally low in crabeater seals. Between Hg and HSP70 a clear negative relationship was found in all species. The species-specific, age and sex-dependent gene-transcription probably reflect dietary habits, pollutant exposure and immune status.

New horizons in the understanding of the causes and management of diabetic foot disease: report from the 2017 Diabetes UK Annual Professional Conference Symposium.

Diabetes-related foot disease remains a common problem. For wounds, classic teaching recommends the treatment of any infection, offloading the wound and ensuring a good blood supply, as well as ensuring that the other modifiable risk factors are addressed and optimized. There remain, however, several questions about these and other aspects of the care of diabetes-related foot disease. Some of these questions are addressed in the present report; in particular, the impact of newer technologies in the identification of any organisms present in a wound, as well as the use of novel approaches to treat infections. The use of new remote sensing technology to identify people at risk of developing foot ulceration is also considered, in an attempt to allow early intervention and prevention of foot ulcers. The psychological impact of foot disease is often overlooked, but with an increasing number of publications on the subject, the cause-and-effect role that psychology plays in foot disease, such as ulcers and Charcot neuroarthropathy, is considered. Finally, because of heterogeneity in diabetic foot studies, comparing results is difficult. A recently published document focusing on ensuring a standardized way of reporting foot disease trials is discussed.

Optimization of Water Content for the Cryopreservation Of Allium sativum In Vitro Cultures by Encapsulation-Dehydration.

BACKGROUND: There is a general requirement to determine and correlate water content to viability for the standardization of conservation protocols to facilitate effective cryostorage of plant germplasm. OBJECTIVE: This study examined water content as a critical factor to optimize the cryostorage of Allium sativum. MATERIALS AND METHODS: Stem discs were excised from post-harvest, stored bulbs prior to cryopreservation by encapsulation-dehydration and water content was determined gravimetrically. RESULTS: Survival of cryopreserved stem discs was 42.5 %, with 22.5 % exhibiting shoot regrowth following 6 h desiccation. Gravimetric data demonstrated a correlation between water content corresponding with survival / regrowth from desiccated, cryopreserved stem discs. For encapsulated stem discs a 25 % residual moisture and corresponding water content of 0.36 g H2O g-1 d.wt correlated with maximal survival following ~6.5 h of desiccation. CONCLUSION: The data concurs with the literature suggesting the formation of a stable vitrified state and a 'window' for optimal survival and regrowth that is between 6 - 10 h desiccation. Further studies using differential scanning calorimetry (DSC) are suggested to substantiate these findings.