The utility of exome sequencing in diagnosing pediatric neurodevelopmental disorders in a highly consanguineous population.

Exome sequencing (ES) has been utilized in diagnosing children with neurodevelopmental manifestations, this study aimed to investigate the utility of ES in children within a highly consanguineous population that presented with neurodevelopmental complaints. A retrospective chart review was performed for 405 children with neurodevelopmental complaints who have had ES and were evaluated in multiple centers in the United Arab Emirates over a four-year period. Within the cohort of 405 children, consanguinity was reported in 35% (144/405). The primary clinical presentations were developmental delay/cognitive impairment, distinctive facial features, hypotonia, seizures, and weakness. The diagnostic yield was 57% (231/405). Novel variants were identified in 54% (125/231) of positive cases. Within the positive cases, specific treatment was available in 6% (13/231) and copy number variants (CNV) were reported in 3% (8/231) of cases. In eight children, variants in genes that have not yet been linked to human disease that could potentially be the cause of the observed phenotype "candidate genes" were identified. ES was utilized effectively within this cohort with a high diagnostic yield and through the identification of novel gene variants, CNVs, candidate genes and secondary findings as well as the alteration of the treatment plan in cases where treatment was available.

The Diagnostic Value of Whole-Exome Sequencing in a Spectrum of Rare Neurological Disorders Associated with Cerebellar Atrophy.

Several neurological disorders, neurodevelopmental disorders, and neurodegenerative disorders have a genetic element with various clinical presentations ranging from mild to severe presentation. Neurological disorders are rare multifactorial disorders characterized by dysfunction and degeneration of synapses, neurons, and glial cells which are essential for movement, coordination, muscle strength, sensation, and cognition. The cerebellum might be involved at any time, either during development and maturation or later in life. Herein, we describe a spectrum of NDDs and NDs in seven patients from six Egyptian families. The core clinical and radiological features of our patients included dysmorphic features, neurodevelopmental delay or regression, gait abnormalities, skeletal deformities, visual impairment, seizures, and cerebellar atrophy. Previously unreported clinical phenotypic findings were recorded. Whole-exome sequencing (WES) was performed followed by an in silico analysis of the detected genetic variants' effect on the protein structure. Three novel variants were identified in three genes MFSD8, AGTPBP1, and APTX, and other previously reported three variants have been detected in "TPP1, AGTPBP1, and PCDHGC4" genes. In this cohort, we described the detailed unique phenotypic characteristics given the identified genetic profile in patients with neurological "neurodevelopmental disorders and neurodegenerative disorders" disorders associated with cerebellar atrophy, hence expanding the mutational spectrum of such disorders.

Sialic acid and anti-ganglioside M1 antibodies are invaluable biomarkers correlated with the severity of autism spectrum disorder.

BACKGROUND: Autism spectrum disorders (ASD) are devastating neurodevelopmental disorders that showed global increased prevalence. They are characterized by impairment of social communication and stereotyped patterns. OBJECTIVE: This study aimed at measuring the levels of total sialic acid (SA) and anti-ganglioside M1 (anti- GM1) IgG antibodies as essential biomarkers in a cohort of children with ASD to identify their diagnostic yield as well as their correlation with the severity of autistic behaviors. METHODS: The demographic characteristics, anthropometric measurements, and clinical data were recorded. The levels of total plasma SA and serum anti-GM1 IgG antibodies levels were measured in 100 children with ASD and 100 healthy controls. The severity of ASD-related symptoms was assessed by using the Childhood Autism Rating Scale (CARS). RESULTS: Children with ASD had significantly higher levels of both SA and anti-GM1 antibodies than healthy controls (p < 0.001). SA showed a statistically significant moderate diagnostic performance while anti-GM1 antibody showed a statistically significant high diagnostic in differentiating severe from mild to moderate autism. Moreover, both SA and anti-GM1 antibodies levels were significantly correlated to the severity of ASD symptoms (p < 0.001). CONCLUSION: The significantly increased levels of SA and anti-GM1 antibodies in children with ASD and their correlation with autism-related symptoms suggest their possible etiopathogenic role in autism as one of the pediatric autoimmune neuropsychiatric disorders. However, further large-scale studies are still needed to explore their possible bidirectional relationship as biomarkers for autism.

Medical leadership training varies substantially between UK medical schools: Report of the leadership in undergraduate medical education national survey (LUMENS).

BACKGROUND: Doctors are increasingly expected to demonstrate medical leadership and management (MLM) skills. The Faculty of Medical Leadership and Management (FMLM) has published an indicative undergraduate curriculum to guide the development of MLM content at UK medical schools. METHOD: Students from 30 medical schools were surveyed to determine their understanding of MLM teaching at their school. Timetables for 21 schools were searched for MLM-related keywords. Student-reported teaching and timetabled teaching were coded according to predefined themes. Aggregated demographic and postgraduate performance data were obtained through collaboration with the Medical Student Investigators Collaborative (msico.org). RESULTS: Whilst 88% of medical students see MLM teaching as relevant, only 18% believe it is well integrated into their curriculum. MLM content represented ∼2% of timetabled teaching in each 5-year undergraduate medical course. Most of this teaching was dedicated to teamwork, performance/reflection and communication skills. There was minimal association between how much of a topic students believed they were taught, and how much they were actually taught. We found no association between the volume of MLM teaching and performance in postgraduate examinations, trainee career destinations or fitness to practice referrals. CONCLUSION: Our findings demonstrate limited and variable teaching of MLM content. Delivery was independent of broader teaching and assessment factors.

Clinical and survival differences during separate COVID-19 surges: Investigating the impact of the Sars-CoV-2 alpha variant in critical care patients.

A number of studies have highlighted physiological data from the first surge in critically unwell Covid-19 patients but there is a paucity of data describing emerging variants of SARS-CoV-2, such as B.1.1.7. We compared ventilatory parameters, biochemical and physiological data and mortality between the first and second COVID-19 surges in the United Kingdom, where distinct variants of SARS-CoV-2 were the dominant stain. We performed a retrospective cohort study investigating critically unwell patients admitted with COVID-19 across three tertiary regional ICUs in London, UK. Of 1782 adult ICU patients screened, 330 intubated and ventilated patients diagnosed with COVID-19 were included. In the second wave where B.1.1.7 variant was the dominant strain, patients were had increased severity of ARDS whilst compliance was greater (p<0.05) and d-dimer lower. The 28-day mortality was not statistically significant (1st wave: 42.2% vs 2nd wave: 39.8%). However, when adjusted for key covariates, the hazard ratio for 28-day mortality in those patients with B.1.1.7 was 3.79 (CI 1.04-13.8; p = 0.043) compared to the original strain. During the second surge in the UK, where the COVID-19 variant B.1.1.7 was most prevalent, significantly more patients presented to critical care with severe ARDS. Furthermore, mortality risk was significantly greater in our ICU population during the second wave of the pandemic in those patients with B.1.1.7. As ICUs are experiencing further waves (particularly by the delta (B.1.617.2) variant), we highlight the urgent need for prospective studies describing immunological and pathophysiological differences across novel emerging variants.

Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study.

BACKGROUND: Considering the expanding industrial applications of carbon nanotubes (CNTs), safety assessment of these materials is far less than needed. Very few long-term in vivo studies have been carried out. This is the first 2-year in vivo study to assess the effects of double walled carbon nanotubes (DWCNTs) in the lung and pleura of rats after pulmonary exposure. METHODS: Rats were divided into six groups: untreated, Vehicle, 3 DWCNT groups (0.12 mg/rat, 0.25 mg/rat and 0.5 mg/rat), and MWCNT-7 (0.5 mg/rat). The test materials were administrated by intratracheal-intrapulmonary spraying (TIPS) every other day for 15 days. Rats were observed without further treatment until sacrifice. RESULTS: DWCNT were biopersistent in the rat lung and induced marked pulmonary inflammation with a significant increase in macrophage count and levels of the chemotactic cytokines CCL2 and CCL3. In addition, the 0.5 mg DWCNT treated rats had significantly higher pulmonary collagen deposition compared to the vehicle controls. The development of carcinomas in the lungs of rats treated with 0.5 mg DWCNT (4/24) was not quite statistically higher (p = 0.0502) than the vehicle control group (0/25), however, the overall incidence of lung tumor development, bronchiolo-alveolar adenoma and bronchiolo-alveolar carcinoma combined, in the lungs of rats treated with 0.5 mg DWCNT (7/24) was statistically higher (p < 0.05) than the vehicle control group (1/25). Notably, two of the rats treated with DWCNT, one in the 0.25 mg group and one in the 0.5 mg group, developed pleural mesotheliomas. However, both of these lesions developed in the visceral pleura, and unlike the rats administered MWCNT-7, rats administered DWCNT did not have elevated levels of HMGB1 in their pleural lavage fluids. This indicates that the mechanism by which the mesotheliomas that developed in the DWCNT treated rats is not relevant to humans. CONCLUSIONS: Our results demonstrate that the DWCNT fibers we tested are biopersistent in the rat lung and induce chronic inflammation. Rats treated with 0.5 mg DWCNT developed pleural fibrosis and lung tumors. These findings demonstrate that the possibility that at least some types of DWCNTs are fibrogenic and tumorigenic cannot be ignored.

Clinical profile, treatment modalities, and outcomes in patients with infantile spasms: A retrospective study from the United Arab of Emirates (UAE).

BACKGROUND: Infantile spasms (IS) are an epileptic encephalopathy where the prognosis is generally poor, with most patients exhibiting psychomotor retardation or intractable epilepsy. However, it is claimed that early and aggressive treatment is related to better response rate and outcome, especially in patients with idiopathic IS. OBJECTIVE: To investigate different treatment modalities and outcomes in patients with IS attending a pediatric neurology clinic at a specialized neurology center in Abu Dhabi, United Arab Emirates. METHODS: Retrospective chart review was done for detailed history, demographic data, etiology, neuro-diagnostic workup, treatment modalities, and the outcomes for all patients diagnosed with IS from September 2014 to September 2019. RESULTS: Three treatment modalities were identified as 1st line- Prednisolone United Kingdom Infantile Spasms Study (UKISS) (N = 15, 46.8%), Anti-Seizure Medications (ASMs) (N = 12, 37.5%), and Vigabatrin (N = 5, 15.6%). The complete response rate to Vigabatrin as a 1st line treatment showed the highest statistical significance (X2 = 7.34, p = 0.007). Patients with idiopathic IS showed a comparable response to treatment to those with symptomatic IS. Additional response to 2nd line treatment with Prednisolone UKISS protocol (25%) and Vigabatrin (15%) was noted in patients who showed partial or no response to the 1st line treatment. None of our patients received Adrenocorticotropic Hormone as treatment. All patients with desirable final outcomes were with idiopathic IS and none were symptomatic. CONCLUSION: More than a third of our patients showed poor treatment response whenever they were not offered treatment according to the current available protocols. This indicates an urgent need for having a unified treatment protocol that takes into consideration the availability of medications, professional expertise as well as diagnostic workup outside major tertiary care centers in our region.

Rectus sheath catheter analgesia versus standard care following major abdominal surgery: An observational study of 911 patients.

BACKGROUND: It is unknown whether rectus sheath catheter (RSC) continuous infusion of local anaesthetic is superior to standard post-operative opiate analgesia following major abdominal surgery. Previous audit in our Trust had suggested RSC was very effective and reduced opiate analgesia use. We aimed to see if this was maintained as the technique became more widespread comparing clinical outcomes and post-operative opiate analgesia requirements between patients who had RSCs and those that did not following major abdominal surgery over a 32-month period. METHODS: A retrospective observational study investigated patients who had major abdominal surgery at a single centre in the UK between January 2018 and August 2020. Placement of RSCs was at the discretion of the surgical team according to their own personal choice. All patients having the procedure in both an elective and non-elective setting have been included in this study, including patients requiring higher level care after emergency surgery. Clinical outcomes and post-operative opiate analgesia requirements (oral and intravenous) were analysed using multivariate logistic regression models adjusting for American Association of Anesthesiologists (ASA) grade and type of surgery (emergency vs elective and open vs laparoscopic). RESULTS: There were 911 patients; 276/911 (30.3%) RSC and 635/911 (69.7%) non-RSC. Median age was 64 (52-74) years; 51.6% were male. In the adjusted models, RSC was associated with a reduced likelihood of serious complications (OR 0.49 (95% CI 0.33, 0.72); p < 0.001) and lower length of stay in ICU (OR 0.95 (95% CI 0.91, 0.99); p = 0.029). RSC was not associated with reduced post-operative opiate analgesia use. There were 3/276 (1.1%) adverse events following RSC placement during the period of data collection. CONCLUSIONS: Clinical outcomes may be superior for patients following major abdominal surgery when RSCs are placed for post-operative analgesia but uncertainty remains. This paper highlights the difficulty with retrospective non-selected data in answering this question. High quality prospective randomised data are required to determine the effects on clinical outcomes and post-operative opiate analgesia requirements.

Sudden unexpected death in epilepsy: A pilot study on neurologists' knowledge and experience in the Eastern Mediterranean region.

Background- Sudden unexpected death in epilepsy (SUDEP) is an important concern in patients with epilepsy who are otherwise healthy. Current knowledge of SUDEP and attitudes of neurologists in the Eastern Mediterranean Region (EMR) towards discussing SUDEP with their patients remain unknown. Objective- We aimed at assessing knowledge, attitudes and factors affecting SUDEP discussion practices of neurologists practicing in the EMR. Methodology- An electronic and paper-based survey was sent to 350 neurologists practicing in the EMR. They were questioned about the frequency, timing, and factors affecting their willingness to initiate SUDEP discussion. We also included questions about perceived patient reactions towards SUDEP discussions and neurologists' preferred way to provide SUDEP information to their patients. Results- We received 132 responses from the 350 surveys sent out (response rate 37.7%). Our results showed that only 1.5% of the neurologists discussed SUDEP with "most" of their patients and their caregivers while 55.3% "rarely" or "never" discussed it. Factors such as additional epilepsy training and more years of clinical experience did not significantly affect the frequency of SUDEP discussion (p = 0.329, p = 0.728). A significant negative association between the number of patients seen per year and the frequency of SUDEP discussion was seen (P= 0.046). Based on their selection of known risk factors, 81% of neurologists were considered as having insufficient knowledge of SUDEP. The top three perceived reactions by the neurologists on SUDEP discussion were distress (74.2%), anxiety (70.5%) and depression (65.9%). Most neurologists initiated SUDEP discussion by themselves and preferred brochures/pamphlets, websites and training sessions to provide SUDEP information. Conclusion- Neurologists in the EMR rarely discuss SUDEP, and have limited knowledge about its risk factors. Upon discussing SUDEP, they overwhelmingly receive negative reactions but not always. Based on our findings, we believe an unintended knowledge gap exists on part of the neurologists. This, coupled with a lack of trained epilepsy nurses and patient education material in regional languages can also be attributed to poor SUDEP discussion practices in the EMR.

Effects of oral bovine lactoferrin on a mouse model of inflammation associated colon cancer.

Patients with ulcerative colitis or colonic Crohn's disease have a significantly increased risk of developing colorectal cancer. Bovine lactoferrin (bLF) reportedly inhibited the development of colon cancer in rats and mice, and in a placebo controlled trial, ingestion of bLF inhibited the growth of intestinal polyps. In addition, in a case study, a patient with Crohn's disease was reported to have remained in remission for over 7 years while ingesting 1 g of bLF daily. Thus, bLF has an inhibitory effect on colon carcinogenesis, and it may also promote remission of Crohn's disease. The purpose of this study was to investigate the effects of bLF in a mouse model of colorectal cancer related to irritable bowel disease (IBD). The mice were divided into 4 groups: (i) no treatment; (ii) treated with bLF only; (iii) treated with azoxymethane plus dextran sulfate sodium (AOM + DSS); and (iv) treated with AOM + DSS + bLF. AOM was used to initiate intestinal cancer, and DSS was used to induce IBD-like inflammation in the intestine of the C57BL/6 mice. At the end of the study, the mice treated with AOM + DSS + bLF had a better fecal score, fewer lesions in the colon, and less weight loss than the mice treated with AOM + DSS without bLF. However, there were no statistically significant differences between the two groups with respect to tumor burden.

A Crosstalk Between Brachypodium Root Exudates, Organic Acids, and Bacillus velezensis B26, a Growth Promoting Bacterium.

Plant growth-promoting rhizobacteria (PGPR) are associated with plant roots and use organic compounds that are secreted from root exudates as food and energy source. Root exudates can chemoattract and help bacteria to colonize the surface of plant roots by inducing chemotactic responses of rhizospheric bacteria. In this study, we show that root colonization of Brachypodium distachyon by Bacillus velezensis strain B26 depends on several factors. These include root exudates, organic acids, and their biosynthetic genes, chemotaxis, biofilm formation and the induction of biofilm encoding genes. Analysis of root exudates by GC-MS identified five intermediates of the TCA cycle; malic, fumaric, citric, succinic, oxaloacetic acids, and were subsequently evaluated. The strongest chemotactic responses were induced by malic, succinic, citric, and fumaric acids. In comparison, the biofilm formation was induced by all organic acids with maximal induction by citric acid. Relative to the control, the individual organic acids, succinic and citric acids activated the epsD gene related to EPS biofilm, and also the genes encoding membrane protein (yqXM) and hydrophobin component (bslA) of the biofilm of strain B26. Whereas epsA and epsB genes were highly induced genes by succinic acid. Similarly, concentrated exudates released from inoculated roots after 48 h post-inoculation also induced all biofilm-associated genes. The addition of strain B26 to wild type and to icdh mutant line led to a slight induction but not biologically significant relative to their respective controls. Thus, B26 has no effect on the expression of the ICDH gene, both in the wild type and the mutant backgrounds. Our results indicate that root exudates and individual organic acids play an important role in selective recruitment and colonization of PGPR and inducing biofilm. The current study increases the understanding of molecular mechanisms behind biofilm induction by organic acids.

Comparative carcinogenicity study of a thick, straight-type and a thin, tangled-type multi-walled carbon nanotube administered by intra-tracheal instillation in the rat.

BACKGROUND: Multi-walled carbon nanotubes can be divided into two general subtypes: tangled and straight. MWCNT-N (60 nm in diameter) and MWCNT-7 (80-90 nm in diameter) are straight-type MWCNTs, and similarly to asbestos, both are carcinogenic to the lung and pleura when administered to rats via the airway. Injection of straight-type MWCNTs into the peritoneal cavity also induces the development of mesothelioma, however, injection of tangled-type MWCNTs into the peritoneal cavity does not induce carcinogenesis. To investigate these effects in the lung we conducted a 2-year comparative study of the potential carcinogenicities of a straight-type MWCNT, MWCNT-A (approximately 150 nm in diameter), and a tangled-type MWCNT, MWCNT-B (7.4 nm in diameter) after administration into the rat lung. Crocidolite asbestos was used as the reference material, and rats administered vehicle were used as the controls. Test materials were administered by intra-Tracheal Intra-Pulmonary Spraying (TIPS) once a week over a 7 week period (8 administrations from day 1 to day 50), followed by a 2-year observation period without further treatment. Rats were administered total doses of 0.5 or 1.0 mg MWCNT-A and MWCNT-B or 1.0 mg asbestos. RESULTS: There was no difference in survival between any of the groups. The rats administered MWCNT-A or asbestos did not have a significant increase in bronchiolo-alveolar hyperplasia or tumors in the lung. However, the rats administered MWCNT-B did have significantly elevated incidences of bronchiolo-alveolar hyperplasia and tumors in the lung: the incidence of bronchiolo-alveolar hyperplasia was 0/20, 6/20, and 9/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively, and the incidence of adenoma and adenocarcinoma combined was 1/19, 5/20, and 7/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively. Malignant pleural mesothelioma was not induced in any of the groups. CONCLUSIONS: The results of this initial study indicate that tangled-type MWCNT-B is carcinogenic to the rat lung when administered via the airway, and that straight-type MWCNT-A did not have higher carcinogenic potential in the rat lung than tangled-type MWCNT-B.

Organic acids and root exudates of Brachypodium distachyon: effects on chemotaxis and biofilm formation of endophytic bacteria.

Root colonization by plant-growth-promoting bacteria could not be useful without the beneficial properties of the bacterium itself. Thus, it is necessary to evaluate the bacterial capacity to form biofilms and establish a successful interaction with the plant roots. We assessed the ability of growth-promoting bacterial strains to form biofilm and display chemotactic behaviour in response to organic acids and (or) root exudates of the model plant Brachypodium distachyon. This assessment was based on the evaluation of single strains of bacteria and a multispecies consortium. The strains coexisted together and formed biofilm under biotic (living root) and abiotic (glass) surfaces. Citric acid stimulated biofilm formation in all individual strains, indicating a strong chemotactic behaviour towards organic acids. Recognizing that the transition from single strains of bacteria to a "multicellular" system would not happen without the presence of adhesion, the alginate and exopolysaccharide (EPS) contents were evaluated. The EPS amounts were comparable in single strains and consortium forms. Alginate production increased 160% in the consortium subjected to drought stress (10% PEG). These findings demonstrated that (i) bacteria-bacteria interaction is the hub of various factors that would not only affect their relation but also could indirectly affect the balanced plant-microbe relation and (ii) root exudates could be very selective in recruiting a highly qualified multispecies consortium.

Role of allopurinol and febuxostat in the amelioration of dextran-induced colitis in rats.

Ulcerative colitis is a chronic auto-inflammatory disorder confined to the colorectal region. It is challenging to find an absolute treatment and current therapy aims to ameliorate symptoms, decrease relapses and prevent prognosis of colorectal cancer. In the present study, we investigated the possible action of xanthine oxidase inhibitors in murine colitis model by measuring different indicative parameters and comparing the results to those of the reference sulfasalazine. Also, we compared the effects of combining sulfasalazine and allopurinol to each drug alone. Dextran Sodium Sulfate (DSS) is used in this study to induce ulcerative colitis in male wistar rats as it is known to be the closest model that mimics human ulcerative colitis. Allopurinol was given prior to colitis induction by four days and febuxostat for six days before induction with DSS (5% w/v) and continue to give them concomitantly during the induction.Il-1ß, malondialdehyde, reduced glutathione (GSH), xanthine oxidase, and superoxide dismutase were measured in colonic tissue. We also measured concentrations of IL-1ß, Il-6 and uric acid in serum. Allopurinol dose-dependently ameliorated biochemical injuries. Febuxostat has shown better results than allopurinol and sulfasalazine, and this is the first study to demonstrate this.

A qualitative inquiry into the barriers and facilitators to achieving home death.

OBJECTIVES: To explore the barriers and facilitators to patients achieving death at home. METHODS: In-depth, semistructured interviews with end-of-life care experts were conducted to develop an insight into the barriers and facilitators to achieving death at home. Thirty-three interviews were conducted compromising of a mixture of face-to-face and tele interviews. Experts included healthcare professionals working in the community, hospital and policy/academic settings. Thematic analysis was undertaken on interview transcripts. RESULTS: Three overarching themes, further divided into a total of 12 subthemes were identified. The three themes were 'managing people', 'education' and 'planning'. The 'managing people' theme included subthemes of patient preferences and family influences; the 'education' theme encompassed knowledge and training, perceptions of death and communication and the 'planning' theme contained seven subthemes including 'coordination', 'resources' and 'cost'. CONCLUSIONS: Multiple barriers and facilitators to achieving death at home were identified in this study. Of particular significance was the identification of the fear and stigma associated with death among doctors, patients and their families serving as a barrier to home death, not previously identified in the literature. Additionally, the importance of social networks and resource provision were highlighted as key in influencing patient death at home.

MWCNT-7 administered to the lung by intratracheal instillation induces development of pleural mesothelioma in F344 rats.

Multi-walled carbon nanotube-7 (MWCNT-7) fibers are biopersistent and have a structure similar to asbestos. MWCNT-7 has been shown to induce malignant mesothelioma when administered by intrascrotal or intraperitoneal injection in rats and mice, and an inhalation study demonstrated that rats exposed to respirable MWCNT-7 developed lung tumors. MWCNT-N, which is similar to MWCNT-7, was shown to induce both lung tumors and malignant mesothelioma in rats when administered by trans-tracheal intrapulmonary spraying (TIPS). The present study was performed to investigate the carcinogenicity of MWCNT-7 when administered by the TIPS method. Ten-week-old male F344/Crj rats were divided into 3 groups and administered 0.5 mL vehicle, 0.250 µg/mL MWCNT-7 or 0.250 µg/mL crocidolite once a week for 12 weeks (total doses of 1.5 mg/rat) and then observed for up to 104 weeks. Rats in the MWCNT-7 group began to die from pathologies associated with the development of malignant mesothelioma 35 weeks after the final TIPS administration. Overall, the incidence of malignant mesothelioma in the MWCNT-7 group was significantly higher than in the vehicle or crocidolite groups.

Can Medical Students Lead Effective Quality Improvement Initiatives? A Systematic Review.

Quality improvement project (QUIP) concepts are becoming embedded into medical school curricula, with many students now expected to conduct a QUIP as part of their progression. This study aimed to assess whether student-led QUIPs can be effective and sustainable. A systematic literature search was conducted using 5 databases: MEDLINE, Embase, Ovid, CINAHL, and PsycINFO. The authors searched for articles published between January 28, 1978, and January 28, 2018. In all, 3965 articles were identified through database searching, and an additional 9 articles through hand searches. After screening and full-text analysis, 12 articles were included. Greater than 50% of QUIPs described a statistically significant improvement in the primary outcome. However, effective student-led QUIPs were not necessarily sustainable, with a mean final audit at 4.4 months. Medical students have the potential to produce effective QUIPs. There now needs to be a structured approach to give medical students the freedom to test and validate more unique interventions.

Barriers and facilitators influencing death at home: A meta-ethnography.

BACKGROUND: In many countries, achieving a home death represents a successful outcome from both a patient welfare and commissioning viewpoint. Significant variation exists in the proportion of home deaths achieved internationally, with many countries unable to meet the wishes of a large number of patients. This review builds on previous literature investigating factors influencing home death, synthesising qualitative research to supplement evidence that quantitative research in this field may have been unable to reach. AIM: To identify and understand the barriers and facilitators influencing death at home. DESIGN: Meta-ethnography. DATA SOURCES: The review adhered to the PRISMA guidelines. A systematic literature search was conducted using five databases: PubMed, EMBASE, Ovid, CINAHL and PsycINFO. Databases were searched from 2006 to 2016. Empirical, UK-based qualitative studies were included for analysis. RESULTS: A total of 38 articles were included for analysis. Seven overarching barriers were identified: lack of knowledge, skills and support among informal carers and healthcare professionals; informal carer and family burden; recognising death; inadequacy of processes such as advance care planning and discharge; as well as inherent patient difficulties, either due to the condition or social circumstances. Four overarching facilitators were observed: support for patients and healthcare professionals, skilled staff, coordination and effective communication. CONCLUSION: Future policies and clinical practice should develop measures to empower informal carers as well as emphasise earlier commencement of advance care planning. Best practice discharge should be recommended in addition to addressing remaining inequity to enable non-cancer patients greater access to palliative care services.

A direct comparison of porcine (Strattice™) and bovine (Surgimend™) acellular dermal matrices in implant-based immediate breast reconstruction.

INTRODUCTION: Acellular dermal matrix (ADM) assisted implant-based breast reconstruction (IBBR) has grown in popularity over traditional submuscular techniques. Numerous human, bovine or porcine derived ADMs are available with the type used varying considerably worldwide. Yet, comparative evidence for the efficacy of different ADMs particularly xenogenic is limited. This study directly compares early outcomes of porcine (Strattice™) and bovine (Surgimend™) ADMs in IBBR. METHOD: Retrospective study of sequential experience of immediate IBBR using Strattice or Surgimend ADM. Data was collected for patients undergoing ADM assisted IBBR after prophylactic or therapeutic mastectomy in Cambridge (October 2011-March 2016). Patient demographics, adjuvant and neoadjuvant therapies, operative details, postoperative management and outcomes were analysed. KEY RESULTS: Total of 81 patients underwent IBBR with ADM; 38 bilateral and 43 unilateral (n = 119 breasts). Strattice was used in 30 breasts (25%) and Surgimend in 89 (75%). Analysis of patient specific variables showed statistical significance only for higher mastectomy weight in the Strattice group (367.1 ± 159.3 g versus 296.3 ± 133.4 g; P = 0.0379). Strattice was associated with higher rates of skin erythema post-operatively (16.7% versus 4.5%; P = 0.044). Analysed per woman or per breast, there was no statistically significant difference in rates of haematoma, infection, wound dehiscence, skin necrosis or seroma, although there was a trend towards more complications with Strattice. CONCLUSION: This study found significantly higher rates of skin erythema and a trend towards higher complication rates with Strattice in IBBR. Randomised controlled trials comparing different ADM outcomes are needed to inform best practice.