Getting wound care right: evaluation of a week of intensive teaching on wound care for undergraduate nursing students.

INTRODUCTION: Tissue viability skills are essential for nurses, but education on this in undergraduate programmes can be inadequate. After approval of the Future Nurse curriculum in 2019, a small team of staff at the University of Salford developed a Getting Wound Care Right week to improve students' knowledge and clinical skills. METHODS: To evaluate the week, the 250 students who had participated in all activities were invited 6 months after the week to contribute a 250-word reflection for a case series. The aim of this was to understand the impact of the week on participants' knowledge, skills and confidence in caring for patients with wounds and whether it had sparked interest in further learning. RESULTS: Four students contributed reflections, which were overwhelmingly positive. They described the knowledge attained, which included that on anatomy and physiology of the skin and wound healing, evidence-based assessment, treatment and management of wounds, and the impact of wounds on patients' quality of life. Skills gained included those in categorisation of wounds, wound assessment and pressure redistribution when seated. Responses on the impact on clinical practice focused on the importance of multidisciplinary working within wound care, seating provision for pressure ulcer prevention and management, and dressing selection. Negative comments related to students realising that clinical practice could be improved rather than indications that the format is ineffective or inappropriate. Limitations of the evaluation included the small number of participants and a lack of responses from every field of practice. CONCLUSIONS: The Getting Wound Care Right week format is a viable approach to meeting Future Nurse curriculum requirements. The approach could be enhanced by a greater emphasis on the relevance of wound care teaching to children and young people's nursing students. The week improved students' clinical confidence on placements when caring for patients with wounds. Further robust evaluation of the module is needed to confirm the findings of this initial evaluation.

Reduced C9orf72 expression exacerbates polyGR toxicity in patient iPSC-derived motor neurons and a Type I protein arginine methyltransferase inhibitor reduces that toxicity.

Introduction: Intronic repeat expansions in the C9orf72 gene are the most frequent known single genetic causes of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These repeat expansions are believed to result in both loss-of-function and toxic gain-of-function. Gain-of-function results in the production of toxic arginine-rich dipeptide repeat proteins (DPRs), namely polyGR and polyPR. Small-molecule inhibition of Type I protein arginine methyltransferases (PRMTs) has been shown to protect against toxicity resulting from polyGR and polyPR challenge in NSC-34 cells and primary mouse-derived spinal neurons, but the effect in human motor neurons (MNs) has not yet been explored. Methods: To study this, we generated a panel of C9orf72 homozygous and hemizygous knockout iPSCs to examine the contribution of C9orf72 loss-of-function toward disease pathogenesis. We differentiated these iPSCs into spinal motor neurons (sMNs). Results: We found that reduced levels of C9orf72 exacerbate polyGR15 toxicity in a dose-dependent manner. Type I PRMT inhibition was able to partially rescue polyGR15 toxicity in both wild-type and C9orf72-expanded sMNs. Discussion: This study explores the interplay of loss-of-function and gain-of-function toxicity in C9orf72 ALS. It also implicates type I PRMT inhibitors as a possible modulator of polyGR toxicity.

Early Versus Postoperative Chemical Thromboprophylaxis Is Associated with Increased Bleeding Risk Following Abdominal Visceral Resections: a Multicenter Cohort Study.

BACKGROUND: Abdominal visceral resections incur relatively higher rates of postoperative bleeding and venous thromboembolism (VTE). While guidelines recommend the use of perioperative chemical thromboprophylaxis, the most appropriate time for its initiation is unknown. Here, we investigated whether early (before skin closure) versus postoperative commencement of chemoprophylaxis affected VTE and bleeding rates following abdominal visceral resection. METHODS: Retrospective review of all elective abdominal visceral resections undertaken between January 1, 2018, and June 30, 2019, across four tertiary-referral hospitals. Major bleeding was defined as the need for blood transfusion, reintervention, or > 20 g/L fall in hemoglobin from baseline. Clinical VTE was defined as imaging-proven symptomatic disease < 30 days post-surgery. RESULTS: A total of 945 cases were analyzed. Chemoprophylaxis was given early in 265 (28.0%) patients and postoperatively in 680 (72.0%) patients. Mean chemoprophylaxis exposure doses were similar between the two groups. Clinical VTE developed in 14 (1.5%) patients and was unrelated to chemoprophylaxis timing. Postoperative bleeding occurred in 71 (7.5%) patients, with 57 (80.3%) major bleeds, requiring blood transfusion in 48 (67.6%) cases and reintervention in 31 (43.7%) cases. Bleeding extended length-of-stay (median (IQR), 12 (7-27) versus 7 (5-11) days, p < 0.001). Importantly, compared to postoperative chemoprophylaxis, early administration significantly increased the risk of bleeding (10.6% versus 6.3%, RR 1.45, 95% CI 1.05-1.93, p = 0.038) and independently predicted its occurrence. CONCLUSIONS: The risk of bleeding following elective abdominal visceral resections is substantial and is higher than the risk of clinical VTE. Compared with early chemoprophylaxis, postoperative initiation reduces bleeding risk without an increased risk of clinical VTE.

Hypothesis and Theory: Roles of Arginine Methylation in C9orf72-Mediated ALS and FTD.

Hexanucleotide repeat expansion (G4C2n) mutations in the gene C9ORF72 account for approximately 30% of familial cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), as well as approximately 7% of sporadic cases of ALS. G4C2n mutations are known to result in the production of five species of dipeptide repeat proteins (DRPs) through non-canonical translation processes. Arginine-enriched dipeptide repeat proteins, glycine-arginine (polyGR), and proline-arginine (polyPR) have been demonstrated to be cytotoxic and deleterious in multiple experimental systems. Recently, we and others have implicated methylation of polyGR/polyPR arginine residues in disease processes related to G4C2n mutation-mediated neurodegeneration. We previously reported that inhibition of asymmetric dimethylation (ADMe) of arginine residues is protective in cell-based models of polyGR/polyPR cytotoxicity. These results are consistent with the idea that PRMT-mediated arginine methylation in the context of polyGR/polyPR exposure is harmful. However, it remains unclear why. Here we discuss the influence of arginine methylation on diverse cellular processes including liquid-liquid phase separation, chromatin remodeling, transcription, RNA processing, and RNA-binding protein localization, and we consider how methylation of polyGR/polyPR may disrupt processes essential for normal cellular function and survival.

Type I PRMT Inhibition Protects Against C9ORF72 Arginine-Rich Dipeptide Repeat Toxicity.

Repeat expansion mutations in the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat-associated non-AUG translation of this expansion produces dipeptide repeat proteins (DRPs). The arginine containing DRPs, polyGR and polyPR, are consistently reported to be the most toxic. Here we demonstrated that small molecule inhibition of type I protein arginine methyltransferases (PRMT) protects against polyGR and polyPR toxicity. Furthermore, our findings suggest that asymmetric dimethylation of polyGR and polyPR by Type I PRMTs plays important roles in their cytotoxicity.

Variations in practice of thromboprophylaxis across general surgical subspecialties: a multicentre (PROTECTinG) study of elective major surgeries.

BACKGROUND: Despite guidelines recommending perioperative thromboprophylaxis for patients undergoing general surgery, we have observed significant variations in its practice. This may compromise patient safety. Here, we quantify the heterogeneity of perioperative thromboprophylaxis across all major general surgical operations, and place them in relation to their risk of bleeding and venous thromboembolism. METHODS: Retrospective review of all elective major general surgeries performed between 1 January 2018 and 30 June 2019 across seven Victorian hospitals was conducted. RESULTS: A total of 5912 patients who underwent 6628 procedures were reviewed. Significant heterogeneity was found in the use of chemoprophylaxis, timing of its initiation, type of anticoagulant administered and application of extended chemoprophylaxis. These variations were observed within the same procedure, and between different surgeries and subspecialties. Contrastingly, there was minimal heterogeneity with the use of mechanical thromboprophylaxis. Oesophago-gastric, liver and colorectal cancer resections had the highest thromboembolic risk. Breast, oesophago-gastric, liver, pancreas and colon cancer resections had the highest bleeding risk. CONCLUSION: Perioperative chemoprophylaxis across general surgery is highly variable. This study has highlighted key areas of variance. Our findings also enable surgeons to compare their practices, and provide baseline data to inform future efforts towards optimizing thromboprophylaxis for general surgical patients.

Pre-operative and intra-operative chemical thromboprophylaxis increases bleeding risk following elective cholecystectomy: a multicentre (PROTECTinG) study.

BACKGROUND: Cholecystectomy is commonly performed in general surgery. Despite guidelines recommending chemical thromboprophylaxis in the perioperative period, the most appropriate time for its initiation is unknown. Here, we investigated whether timing of chemoprophylaxis affected venous thromboembolism (VTE) and bleeding rates post-cholecystectomy. METHODS: Retrospective review of all elective cholecystectomies performed between 1 January 2018 and 30 June 2019, across seven Victorian hospitals. Clinical VTE was defined as imaging-proven symptomatic disease within 30 days of surgery. Major bleeding was defined as the need for blood transfusion, surgical intervention or >20 g/L fall in haemoglobin from baseline. RESULTS: A total of 1744 cases were reviewed. Chemoprophylaxis was given early (pre- or intra-operatively), post-operatively or not given in 847 (48.6%), 573 (32.9%) and 324 (18.6%) patients, respectively. This varied significantly between surgeons, fellows, trainees and institutions. Clinical VTE occurred in 5 (0.3%) patients and was not associated with chemoprophylaxis timing. Bleeding occurred in 42 (2.4%) patients. Of this, half were major events, requiring surgical control in 5 (11.9%) patients and blood transfusion in 9 (21.4%) patients. Bleeding also extended length of stay (mean (SD), 3.1 (4.0) versus 1.4 (2.2) days, P < 0.001). One bleeding-related mortality was recorded. Importantly, when compared with post-operative (risk ratio 1.46, 95% confidence interval 1.21-1.62) and no (RR 1.23, 95% CI 1.03-1.35) chemoprophylaxis, early usage significantly increased bleeding risk and independently predicted its occurrence. CONCLUSIONS: Perioperative chemoprophylaxis is variable among patients undergoing elective cholecystectomy. The rate of clinical VTE post-cholecystectomy is low. Early chemoprophylaxis increases bleeding risk without an appreciable additional protection from VTE.

Reducing unnecessary neonatal testing in infants of mothers with thyroid disease.

AIM: To examine the numbers of asymptomatic infants <8 weeks who had appropriate thyroid function tests (TFTs) in addition to the newborn screening test, because of maternal thyroid disease, before and after the implementation of an updated institutional guideline and staff education. METHODS: A medical record audit of infants <8 weeks born at a metropolitan teaching hospital, who had TFTs between 1 July 2017 and 31 October 2017 was performed as part of a quality improvement project. Records were reviewed to determine the indication for testing and whether this complied with the current 2011 institutional guideline. A multidisciplinary staff education package was developed to coincide with the publication of an updated guideline in August 2018. Staff education and resources were provided throughout July 2018. A post-intervention audit was repeated between 1 August 2018 and 1 December 2018, assessing compliance with the 2018 guideline. RESULTS: In the baseline period, 40 of 457 infants born had TFTs performed, of which 26 of 40 (65%) were for maternal thyroid disease. Of these 10 of 26 (38%) met the 2011 criteria for testing; 1 of 26 (4%) met the updated 2018 criteria. In the post-intervention period, 14 of 412 infants born had TFTs of which 5 of 14 (36%) were tested due to maternal thyroid disease and all were compliant with the new guideline. CONCLUSIONS: Baseline audit revealed unnecessary neonatal thyroid function testing of healthy babies. Implementation of an updated guideline and a brief, targeted education package successfully increased awareness of the updated recommendations, reduced unnecessary testing and led to improved practice.

Abatacept in Early Diffuse Cutaneous Systemic Sclerosis: Results of a Phase II Investigator-Initiated, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: T cells play a key role in the pathogenesis of early systemic sclerosis. This study was undertaken to assess the safety and efficacy of abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc). METHODS: In this 12-month, randomized, double-blind, placebo-controlled trial, participants were randomized 1:1 to receive either subcutaneous abatacept 125 mg or matching placebo, stratified by duration of dcSSc. Escape therapy was allowed at 6 months for worsening disease. The coprimary end points were change in the modified Rodnan skin thickness score (MRSS) compared to baseline and safety over 12 months. Differences in longitudinal outcomes were assessed according to treatment using linear mixed models, with outcomes censored after initiation of escape therapy. Skin tissue obtained from participants at baseline was classified into intrinsic gene expression subsets. RESULTS: Among 88 participants, the adjusted mean change in the MRSS at 12 months was -6.24 units for those receiving abatacept and -4.49 units for those receiving placebo, with an adjusted mean treatment difference of -1.75 units (P = 0.28). Outcomes for 2 secondary measures (Health Assessment Questionnaire disability index and a composite measure) were clinically and statistically significantly better with abatacept. The proportion of subjects in whom escape therapy was needed was higher in the placebo group relative to the abatacept group (36% versus 16%). In the inflammatory and normal-like skin gene expression subsets, decline in the MRSS over 12 months was clinically and significantly greater in the abatacept group versus the placebo group (P < 0.001 and P = 0.03, respectively). In the abatacept group, adverse events occurred in 35 participants versus 40 participants in the placebo group, including 2 deaths and 1 death, respectively. CONCLUSION: In this phase II trial, abatacept was well-tolerated, but change in the MRSS was not statistically significant. Secondary outcome measures, including gene expression subsets, showed evidence in support of abatacept. These data should be confirmed in a phase III trial.

Primary Neurons and Differentiated NSC-34 Cells Are More Susceptible to Arginine-Rich ALS Dipeptide Repeat Protein-Associated Toxicity than Non-Differentiated NSC-34 and CHO Cells.

A repeat expansion mutation in the C9orf72 gene is the most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In this study, using multiple cell-based assay systems, we reveal both increased dipeptide repeat protein (DRP) toxicity in primary neurons and in differentiated neuronal cell lines. Using flow cytometry and confocal laser scanning microscopy of cells treated with fluorescein isothiocyanate (FITC)-labeled DRPs, we confirm that poly-glycine-arginine (GR) and poly-proline-arginine (PR) DRPs entered cells more readily than poly-glycine-proline (GP) and poly-proline-alanine (PA) DRPs. Our findings suggest that the toxicity of C9-DRPs may be influenced by properties associated with differentiated and aging motor neurons. Further, our findings provide sensitive cell-based assay systems to test phenotypic rescue ability of potential interventions.

The Scleroderma Patient-Centered Intervention Network Cohort: baseline clinical features and comparison with other large scleroderma cohorts.

Objectives: The Scleroderma Patient-centered Intervention Network (SPIN) Cohort is a web-based cohort designed to collect patient-reported outcomes at regular intervals as a framework for conducting trials of psychosocial, educational, self-management and rehabilitation interventions for patients with SSc. The aim of this study was to present baseline demographic, medical and patient-reported outcome data of the SPIN Cohort and to compare it with other large SSc cohorts. Methods: Descriptive statistics were used to summarize SPIN Cohort characteristics; these were compared with published data of the European Scleroderma Trials and Research (EUSTAR) and Canadian Scleroderma Research Group (CSRG) cohorts. Results: Demographic, organ involvement and antibody profile data for SPIN (N = 1125) were generally comparable with that of the EUSTAR (N = 7319) and CSRG (N = 1390) cohorts. There was a high proportion of women and White patients in all cohorts, though relative proportions differed. Scl70 antibody frequency was highest in EUSTAR, somewhat lower in SPIN, and lowest in CSRG, consistent with the higher proportion of interstitial lung disease among dcSSc patients in SPIN compared with in CSRG (48.5 vs 40.3%). RNA polymerase III antibody frequency was highest in SPIN and remarkably lower in EUSTAR (21.1 vs 2.4%), in line with the higher prevalence of SSc renal crisis (4.5 vs 2.1%) in SPIN. Conclusion: Although there are some differences, the SPIN Cohort is broadly comparable with other large prevalent SSc cohorts, increasing confidence that insights gained from the SPIN Cohort should be generalizable, although it should be noted that all three cohorts include primarily White participants.

Ultrasonography-detected subclinical inflammation in patients with hand osteoarthritis and established rheumatoid arthritis: a comparison between two different pathologies using the same ultrasound examination protocol.

OBJECTIVES: A recent review of ultrasound (US) studies in osteoarthritis (OA) showed very limited data about hand OA. Previous US studies in patients with OA described a degree of overlap between the US appearance of rheumatoid arthritis (RA) and OA joints. The present study aimed to assess the US features of subclinical inflammation in RA and hand OA, using the same US examination protocol. METHODS: A retrospective, cohort study compared patients with established RA (n = 224) and hand OA (n = 73), with respect to several demographic, clinical, laboratory and US parameters. We used a 22-hand joint US examination protocol (wrists, metacarpophalangeal and proximal interphalangeal joints bilaterally - Outcome Measures in Rheumatology Clinical Trials [OMERACT] scoring system) for all patients. RESULTS: Subclinical joint inflammation in the context of equivocal clinical examination was found in 9.6% of OA patients compared with 46.4% of RA patients (p = 0.0001), despite the fact that there was no significant difference between the degree of chronic joint swelling (synovial hypertrophy grades 2 and 3; p = 0.75 and p = 0.11, respectively). The presence of osteophytes was more common in patients with hand OA, as expected (p = 0.0001). CONCLUSIONS: Our study findings reflected differences between the incidence and characteristics of subclinical inflammation in patients with RA and OA, which could be helpful in patients with an equivocal clinical examination or history of both diseases. Almost one in 10 patients with hand OA had active synovitis, while almost one in two patients with RA had uncontrolled inflammation in at least one joint.

A curious case of cholestasis: oral terbinafine associated with cholestatic jaundice and subsequent erythema nodosum.

Terbinafine is a commonly prescribed antifungal agent used in the treatment of trichophytic onychomycosis and chronic cutaneous mycosis that are resistant to other treatments. This case report highlights a rarely documented but important adverse hepatic reaction that was caused by the use of oral terbinafine. A woman in her thirties presented with a 3-week history of jaundice, malaise, itching, nausea, decreased appetite, weight loss, dark orange urine and intermittent non-radiating epigastric pain. She had recently finished a 3-week course of oral terbinafine for a fungal nail infection. Liver biopsy findings were consistent with chronic active hepatitis secondary to a drug reaction. A few days after initial presentation, the patient developed erythema nodosum. Delayed development of erythema nodosum secondary to terbinafine could not be excluded.

Chronic fatigue syndrome in adolescents: a follow-up study.

OBJECTIVES: To compare the frequency of persistent symptoms up to 8 years after illness onset in adolescents diagnosed as having chronic fatigue syndrome, idiopathic chronic fatigue, and unexplained fatigue for less than 6 months, and to determine if hospital admission is associated with outcome. DESIGN: A cohort study using questionnaire follow-up. SETTING: A tertiary referral hospital. PATIENTS: Consecutive adolescents referred for assessment of persistent fatigue were identified and retrospectively divided into 3 groups according to the diagnostic criteria for chronic fatigue syndrome and idiopathic chronic fatigue. INTERVENTION: A questionnaire was designed and administered by telephone at a mean of 4.57 years after the initial examination. MAIN OUTCOME MEASURE: The persistence of self-reported symptoms was compared with respect to patient group and admission. RESULTS: Outcome data were obtained for 34 (69%) of the 49 eligible subjects. Twenty-five percent of the chronic fatigue syndrome group showed near to complete improvement, 31% showed partial improvement, and 44% showed no improvement. The idiopathic chronic fatigue group had near to complete recovery in 50%, partial in 10%, and no improvement in 40%. Those with unexplained fatigue for less than 6 months had all recovered. There was no difference between the outcome of the subjects admitted to the hospital and those managed as outpatients. CONCLUSIONS: Adolescents with less than 6 months of fatigue have a good outcome. Unexplained fatigue lasting more than 6 months has a similar outcome regardless of the presence of minor criteria for chronic fatigue syndrome.