Prevalence, Incidence and Treatment Patterns of Prurigo Nodularis in England: A Retrospective Database Analysis.

BACKGROUND: Prurigo nodularis (PN) is a pruritic skin disease characterised by multiple, intensely itchy skin nodules in symmetrically distributed areas of the extremities. There are very limited studies on the epidemiology and treatment pathways for PN, especially moderate-to-severe PN, from England. OBJECTIVES: To assess the epidemiology and treatment pathways of mild and moderate-to-severe PN in England. METHODS: This retrospective cohort study used data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) in England. Adult patients (≥18 years) with a PN specific diagnosis code any time between 1 April 2007 and 1 March 2019 (patient identification period) were selected. Patients were included if their first PN diagnostic code (index diagnosis date, IDD) was recorded during the identification period, with data available 6 months pre- and ≥12 months post-IDD. Patients were classified into moderate-to-severe PN (MSPN) or mild PN (MiPN) based on the presence or absence of a prescription record, post IDD, for either a systemic immunosuppressant or a gabapentinoid. Patients with MSPN and MiPN were matched 1:1 for age, gender and IDD. Prevalence and incidence were calculated for each year from 2007 to 2019. Drugs prescribed post IDD were analysed. RESULTS: A total of 8,933 patients (MSPN: 2,498 patients; MiPN: 6,539 patients) were included for the study; 2,462 patients each with MiPN and MSPN were included for the comparative analysis. Atopic dermatitis, asthma and eosinophilic oesophagitis were significantly higher (all p<0.001) in patients with MSPN (vs MiPN). The prevalence of overall PN cases increased during the study period. The incidence rate also showed a similar trend. The rates of prescription of potent and super potent topical corticosteroids (TCS), topical calcineurin inhibitors, first- and second- generation antihistamines, oral and injectable systemic corticosteroid, methotrexate, antidepressants and tacrolimus were significantly higher (all p <0.001) in patients with MSPN (vs MiPN). CONCLUSIONS: The epidemiology of PN was consistent with other European studies. Patients with MSPN received a significantly higher number of prescriptions for potent TCS and systemic drugs, as compared with milder patients.

A Systematic Literature Review of Psychological Interventions for Adults with Type 1 Diabetes.

INTRODUCTION: The psychological burden of type 1 diabetes mellitus (T1DM) is considerable. The condition affects the daily lives of adults living with T1DM (ALWT1DM) in many ways. International guidelines highlight the importance of providing psychological support to ALWT1DM to improve health outcomes and well-being. METHODS: We conducted a systematic literature review of randomised controlled trials (RCTs) to identify the evidence on the impact of psychological interventions on glycaemic control and psychological outcomes in ALWT1DM. Literature searches of Medline, Embase, Cochrane Central Register of Controlled Trials, PsycInfo, and the grey literature were performed to identify relevant RCTs, published in English, from 2001 onward. Fourteen RCTs of ten psychological interventions in ALWT1DM were eligible and included in the qualitative synthesis. The studies varied considerably in terms of duration, target population, endpoints, and efficacy. RESULTS: Overall, psychological interventions did not perform significantly better than control treatments in improving glycaemic control, although selected patient groups did report benefits from some psychological intervention types, such as cognitive behavioural therapy. Although most of the psychological interventions produced small, nonsignificant improvements in self-reported patient functioning, some treatments were effective in reducing diabetes distress and improving mental health, even if no impact on glycaemic control was observed. DISCUSSION: Current guidelines for the treatment of T1DM recommend access to psychological services; however, there is a paucity of high-quality evidence from clinical trials on the effectiveness or preferred structure of psychological support. There is a clear need for more rigorous, large-scale, international research to address the efficacy of psychological interventions in ALWT1DM.

A multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin compared with standard therapy for the treatment of transverse myelitis in adults and children (STRIVE).

BACKGROUND: Transverse myelitis (TM) is an immune-mediated disorder of the spinal cord that affects adults and children and that causes motor, sensory and autonomic dysfunction. There is a prolonged recovery phase, which may continue for many years. Neuromyelitis optica (NMO) is an uncommon relapsing inflammatory central nervous system condition in which TM can be the first presenting symptom. As TM and NMO affect many patients in the prime of their working life, the disorder can impose a significant demand on health resources. There are currently no robust controlled trials in children or adults to inform the optimal treatment of TM. However, treatment with intravenous immunoglobulin (IVIG) is being effectively used in the management of a range of neurological conditions. Although other interventions such as plasma exchange (PLEX) in addition to intravenous (IV) methylprednisolone therapy can be beneficial in TM, PLEX is costly and technically challenging to deliver in the acute setting. IVIG is more readily accessible and less costly. OBJECTIVE: To evaluate whether additional and early treatment with IVIG is of extra benefit in TM compared with standard therapy with IV steroids. DESIGN: A multicentre, single-blind, parallel-group randomised controlled trial of IVIG compared with standard therapy for the treatment of TM in adults and children. PARTICIPANTS: Patients aged ≥ 1 year diagnosed with either acute first-onset TM or first presentation of NMO. Target recruitment was 170 participants (85 participants per arm). INTERVENTIONS: Participants were randomised 1 : 1 to treatment with IV methylprednisolone only or treatment with IV methylprednisolone plus 2 g/kg of IVIG in divided doses within 5 days of the first commencement of steroid therapy. MAIN OUTCOME MEASURES: Primary outcome measure - American Spinal Injury Association (ASIA) Impairment Scale at 6 months post randomisation, with a good outcome defined by a two-grade change. Secondary and tertiary outcome measures - ASIA motor and sensory scales, Expanded Disability Status Scale, health outcome, quality of life, Client Service Receipt Inventory and International Spinal Cord Injury Pain, Bladder and Bowel Basic Data Sets. RESULTS: In total, 26 participants were screened and two were randomised into the study. With the limited sample size, treatment effect could not be determined. However, we identified barriers to accrual that included strict inclusion criteria, the short enrolment window, challenges associated with the use of the ASIA Impairment Scale as an outcome measure and estimation of the incidence of TM. CONCLUSIONS: The study did not reach the end point and the effect of IVIG in TM/NMO could not be determined. Investigators should be aware of the potential challenges associated with carrying out a rare disease trial with a short enrolment window. The study question is one that still necessitates investigation. Preliminary work to ameliorate the effect of the barriers encountered in this study is vital. TRIAL REGISTRATION: EudraCT 2014-002335-34, ClinicalTrials.gov NCT02398994 and Current Controlled Trials ISRCTN12127581. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 31. See the NIHR Journals Library website for further project information. Funding was also received from Biotest AG, Germany (supply of IVIG) and the Transverse Myelitis Society (excess research cost to facilitate study initiation).

Host-microbiome interactions in human type 2 diabetes following prebiotic fibre (galacto-oligosaccharide) intake.

Aberrant microbiota composition and function have been linked to several pathologies, including type 2 diabetes. In animal models, prebiotics induce favourable changes in the intestinal microbiota, intestinal permeability (IP) and endotoxaemia, which are linked to concurrent improvement in glucose tolerance. This is the first study to investigate the link between IP, glucose tolerance and intestinal bacteria in human type 2 diabetes. In all, twenty-nine men with well-controlled type 2 diabetes were randomised to a prebiotic (galacto-oligosaccharide mixture) or placebo (maltodextrin) supplement (5·5 g/d for 12 weeks). Intestinal microbial community structure, IP, endotoxaemia, inflammatory markers and glucose tolerance were assessed at baseline and post intervention. IP was estimated by the urinary recovery of oral 51Cr-EDTA and glucose tolerance by insulin-modified intravenous glucose tolerance test. Intestinal microbial community analysis was performed by high-throughput next-generation sequencing of 16S rRNA amplicons and quantitative PCR. Prebiotic fibre supplementation had no significant effects on clinical outcomes or bacterial abundances compared with placebo; however, changes in the bacterial family Veillonellaceae correlated inversely with changes in glucose response and IL-6 levels (r -0·90, P=0·042 for both) following prebiotic intake. The absence of significant changes to the microbial community structure at a prebiotic dosage/length of supplementation shown to be effective in healthy individuals is an important finding. We propose that concurrent metformin treatment and the high heterogeneity of human type 2 diabetes may have played a significant role. The current study does not provide evidence for the role of prebiotics in the treatment of type 2 diabetes.

Genotypic relatedness and characterization of Staphylococcus pseudintermedius associated with post-operative surgical infections in dogs.

Staphylococcus pseudintermedius is a commensal organism of dogs that can also be implicated in surgical site infections (SSIs) in dogs. Particularly with the recent emergence and spread of the ST71-t02-SCCmecII-III multidrug-resistant S. pseudintermedius clonal lineage (MDRSP), it is important to understand the clonal diversity of S. pseudintermedius in SSIs in dogs. The study reported here investigated the genotypic relatedness of 124 S. pseudintermedius isolates from the surgical wounds of 90 dogs admitted to a referral practice in the UK. This study also aimed to understand whether MDRSP is better adapted to survival and persistence in different environments compared with other S. pseudintermedius. Whilst no individual S. pseudintermedius clonal type was primarily responsible for S. pseudintermedius-associated SSIs in dogs, we found that MDRSP was the most represented clonal type among the isolates studied. However, we observed no difference in the level of biofilm production, susceptibility to biocides or carriage of specific virulence determinants between MDRSP and other S. pseudintermedius isolates studied. Interestingly, in the competitive fitness study, MDRSP did not outcompete any member of the other S. pseudintermedius isolates studied in each environment. Our data suggest that the determinants that promote S. pseudintermedius-associated SSIs in dogs are distributed among S. pseudintermedius as a species and are not restricted to a few clonal types. They also provide evidence to support the suggestion that MDRSP is not better adapted to survival or persistence in different environments and is no more virulent than other S. pseudintermedius isolates.

Design and application of a loop-mediated isothermal amplification assay for the rapid detection of Staphylococcus pseudintermedius.

Staphylococcus pseudintermedius is a commensal and opportunistic pathogen of dogs. It is mainly implicated in canine pyoderma, as well as other suppurative conditions of dogs. Although bacterial culture is routinely used for clinical diagnosis, molecular methods are required to accurately identify and differentiate S. pseudintermedius from other members of the Staphylococcus intermedius group. These methods, owing largely to their cost, are not easy to implement in nonspecialized laboratories or veterinary practices. In the current study, loop-mediated isothermal amplification (LAMP), a novel isothermal nucleic acid amplification procedure, was employed to develop a rapid, specific, and sensitive S. pseudintermedius assay. Different detection strategies, including the use of a lateral flow device, were evaluated. The assay was evaluated for cross-reactivity against 30 different bacterial species and validated on a panel of 108 S. pseudintermedius isolates, originating from different dog breeds and locations within the United Kingdom. The assay was specific, showing no cross-reactivity during in silico and in vitro testing. When tested using DNA extracts prepared directly from 35 clinical surgical site swabs, the assay could detect S. pseudintermedius in less than 15 min, with a diagnostic sensitivity of 94.6%, superior to that of a polymerase chain reaction method. The LAMP assay also had an analytical sensitivity in the order of 10(1) gene copies, and the amplified products were readily detected using a lateral flow device. The LAMP assay described in the present study is simple and rapid, opening up the possibility of its use as a diagnostic tool within veterinary practices.