A single centre, open label, pilot study evaluating the effect of intra-articular hyaluronic acid injection on pain and functionality when injected into the ankle (tibio-talar and sub-talar) joint in patients with haemophilic arthropathy.

AIMS: Ankle arthropathy commonly affects persons with haemophilia (PWH). Joint damage causes loss of movement, pain and reduced function. Current treatments are limited. Viscosupplementation has been used to treat other patient groups with joint damage. Viscosupplements serve to augment or act as a substitute for synovial fluid and may ameliorate the effects of cartilage loss by cushioning joints and reducing pain. This study evaluated intra-articular Ostenil Plus™ (HA) for ankle arthropathy in PWH. Reduction in pain was the primary outcome. METHODS: A single centre open label pilot study. PWH and significant ankle arthropathy, according to MRI scores, were recruited. Participants received intra-articular HA injections at baseline and 6 months. Follow up assessments were completed three-monthly for 1 year. Pain was assessed by the Visual Analogue Scale (VAS). Participant perceptions of overall changes to pain, function and quality of life were sought. RESULTS: Twenty-four participants were recruited, three withdrew. Twenty-six joints were injected. Twenty participants had severe haemophilia. Mean age 35 years. Participants reported significant reduction in pain over the study. VAS baseline: 5.62; 6 month 3.92; 12-month 3.42, P < .0001. Joint function improved together with ankle HJHS. No change was seen for EQ-5D-5L. Sixteen participants reported reductions in ankle pain and stiffness and greater confidence in undertaking physical activities. No significant adverse reactions were reported. CONCLUSION: Ostenil Plus™ treatment improves pain, function and patient perception of functional ability in PWH and ankle arthropathy. This study supports the use of HA as a safe treatment in PWH.

Immediate post-procedural functional assessment of percutaneous coronary intervention: current evidence and future directions.

Percutaneous coronary intervention (PCI) guided by coronary physiology provides symptomatic benefit and improves patient outcomes. Nevertheless, over one-fourth of patients still experience recurrent angina or major adverse cardiac events following the index procedure. Coronary angiography, the current workhorse for evaluating PCI efficacy, has limited ability to identify suboptimal PCI results. Accumulating evidence supports the usefulness of immediate post-procedural functional assessment. This review discusses the incidence and possible mechanisms behind a suboptimal physiology immediately after PCI. Furthermore, we summarize the current evidence base supporting the usefulness of immediate post-PCI functional assessment for evaluating PCI effectiveness, guiding PCI optimization, and predicting clinical outcomes. Multiple observational studies and post hoc analyses of datasets from randomized trials demonstrated that higher post-PCI functional results are associated with better clinical outcomes as well as a reduced rate of residual angina and repeat revascularization. As such, post-PCI functional assessment is anticipated to impact patient management, secondary prevention, and resource utilization. Pre-PCI physiological guidance has been shown to improve clinical outcomes and reduce health care costs. Whether similar benefits can be achieved using post-PCI physiological assessment requires evaluation in randomized clinical outcome trials.

Ticagrelor alone vs. ticagrelor plus aspirin following percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: TWILIGHT-ACS.

AIMS: The aim of this study was to determine the effect of ticagrelor monotherapy on clinically relevant bleeding and major ischaemic events in relation to clinical presentation with and without non-ST elevation acute coronary syndromes (NSTE-ACS) among patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS AND RESULTS: We conducted a pre-specified subgroup analysis of The Ticagrelor With Aspirin or Alone in High Risk Patients After Coronary Intervention (TWILIGHT) trial, which enrolled 9006 patients with high-risk features undergoing PCI with DES. After 3 months of dual antiplatelet therapy (DAPT) with ticagrelor plus aspirin, 7119 adherent and event-free patients were randomized in a double-blind manner to ticagrelor plus placebo versus ticagrelor plus aspirin for 12 months. The primary outcome was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding while the composite of all-cause death, myocardial infarction (MI), or stroke was the key secondary outcome. Among patients with NSTE-ACS (n = 4614), ticagrelor monotherapy reduced BARC 2, 3, or 5 bleeding by 53% [3.6% vs. 7.6%; hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.36-0.61; P < 0.001) and in stable patients (n = 2503) by 24% (4.8% vs. 6.2%; HR 0.76; 95% CI 0.54-1.06; P = 0.11; nominal Pint = 0.03). Rates of all-cause death, MI, or stroke among those with (4.3% vs. 4.4%; HR 0.97; 95% CI 0.74-1.28; P = 0.84) and without (3.1% vs. 3.2%; HR 0.96; 95% CI 0.61-1.49; P = 0.85) NSTE-ACS were similar between treatment arms irrespective of clinical presentation (Pint = 0.96). CONCLUSION: Among patients with or without NSTE-ACS who have completed an initial 3-month course of DAPT following PCI with DES, ticagrelor monotherapy reduced clinically meaningful bleeding events without increasing ischaemic risk as compared with ticagrelor plus aspirin. The benefits of ticagrelor monotherapy with respect to bleeding events were more pronounced in patients with NSTE-ACS. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02270242.

Early low-dose rituximab for active thyroid eye disease: An effective and well-tolerated treatment.

BACKGROUND: Thyroid eye disease (TED) is an autoimmune inflammatory disease that can be disfiguring and potentially sight threatening. Suppression of inflammation in active disease can reduce the risk of visual loss and limit long-term sequelae. Current management involves inflammation suppression using glucocorticoids. The aim of this study was to evaluate the efficacy of early disease intervention with targeted immunomodulatory therapy to alter disease course. This paper reports the efficacy of low-dose rituximab in reducing clinical activity in TED in a small population. METHODS: A retrospective audit of consecutive patients with active TED managed primarily with a 100 mg rituximab infusion. Further glucocorticoid or steroid-sparing agents were prescribed if clinically indicated. Clinical activity score, VISA overall severity score and Oxford Quality of Life score were recorded at each visit as well as TSH receptor antibody levels (TRAb), B cell subsets and adverse reactions. RESULTS: Twelve patients had mean follow-up of 6.3 months. Clinical activity scores significantly decreased (mean score 5.08 to 1.58; P < 0.001), VISA overall severity scores reduced by 50% from 12 to 6, P < 0.001 and the mean cumulative dose of IV methylprednisolone was 2.3 g. 100 mg rituximab induced significant CD19+ B cell depletion (n = 8, P < 0.001). There was no significant reduction in serum TRAb (n = 8, P = 0.06). A transient infusion-related rash was the only adverse effect, n = 4. QoL scores did not differ markedly before and after treatment. CONCLUSION: Low-dose rituximab is an efficacious, well-tolerated and safe treatment for active TED; reducing disease activity and allowing reduced administration of systemic steroid.

Early use of steroid-sparing agents in the inactivation of moderate-to-severe active thyroid eye disease: a step-down approach.

OBJECTIVES: The current first-line treatment for management of active thyroid eye disease (TED) is high-dose intravenous corticosteroids, which have the potential for serious adverse effects. Our aim was to evaluate the effect of steroid-sparing agents (SSAs) in patients with moderate-to-severe active TED, using methotrexate as first-line. METHODS: Presented is a retrospective, four-year, single-centre, consecutive case series of patients with moderate-to-severe TED treated using the Oxford protocol. Treatment modality, disease activity, and adverse effects are reported at presentation, 6- and 12-month follow-up. RESULTS: 104 consecutive TED patients treated by the Oxford TED team were reviewed. 24 patients with moderate-to-severe active disease were identified (mean age 46.8 years;12 female) with a mean pretreatment VISA inflammatory index score of 5.5/10 (SD = 1.98; range 1-9). Intravenous methyl-prednisolone (IVMP) and an SSA was commenced in all patients. Mean total steroid dose was 2.72 g (SD = 1.4;1.0-6.9). 38% of patients (n = 9) received ≤1.5 g of IVMP. Only two patients required >4.5 g of IVMP equating to the EUGOGO treatment protocol dose for this patient group. There was significant improvement in inflammatory index score both at the intermediate review (mean score 2.7; SD = 2.8; P < 0.001; mean follow up 25.2 weeks) and at one year or last follow-up (mean score 1.4; SD = 1.5; P < 0.001; mean follow up 48.0 weeks). No serious or long-term adverse effects were reported. CONCLUSION: This study suggests that the initiation of an SSA, using methotrexate as first-line, with limited adjuvant IVMP is an effective and safe treatment for moderate-to-severely active TED, resulting in a significant reduction in both disease activity and total steroid load.

A simple care bundle to reduce unplanned admission rate for day case pediatric circumcision.

BACKGROUND: An electronic review of unplanned day case admission rates in our hospital demonstrated an average annual rate for pediatric circumcision of 2%-3% in recent years with high levels of perioperative strong opiate use. This lay above target unplanned admission rates (<2%) set out by the Royal College of Anaesthetists for day case surgery. A targeted quality improvement initiative was undertaken to improve patient flow through the pediatric day case surgery unit for elective circumcision. Among the reasons for unplanned admission, factors modifiable by the anesthetist (pain, postoperative nausea and vomiting, somnolence) are significant contributors. METHODS: A prospective audit was undertaken over a 3-month period. Our practice was compared with evidence-based analgesic and antiemetic interventions in accordance the Association of Paediatric Anaesthetists of Great Britain and Ireland. Perioperative strong opiate administration rates occurred in 44% of cases. Four strategic interventions were selected based on quality of evidence, ease of implementation, and low cost: selection of higher concentration local anesthetic use for penile blocks, intravenous dexamethasone, and preoperative paracetamol combined with maximum dose nonsteroidal anti-inflammatory. RESULTS: The audit was duplicated a year later demonstrating a significant increase in application of these interventions with a parallel fall in strong opiate use from 44% to 9% and an unprecedented zero unplanned admission rate in our unit for 10 months in a row after implementation. CONCLUSION: Regular scrutiny of patient electronic data helps identify high impact areas for audit and intervention. Unplanned admission in pediatric day case surgery is an area amenable to such targeted intervention.

Comparison of Three Different Hepatitis C Virus Genotyping Methods: 5'NCR PCR-RFLP, Core Type-Specific PCR, and NS5b Sequencing in a Tertiary Care Hospital in South India.

BACKGROUND: Based on genetic heterogeneity, hepatitis C virus (HCV) is classified into seven major genotypes and 64 subtypes. In spite of the sequence heterogeneity, all genotypes share an identical complement of colinear genes within the large open reading frame. The genetic interrelationships between these genes are consistent among genotypes. Due to this property, complete sequencing of the HCV genome is not required. HCV genotypes along with subtypes are critical for planning antiviral therapy. Certain genotypes are also associated with higher progression to liver cirrhosis. METHODS: In this study, 100 blood samples were collected from individuals who came for routine HCV genotype identification. These samples were used for the comparison of two different genotyping methods (5'NCR PCR-RFLP and HCV core type-specific PCR) with NS5b sequencing. RESULTS: Of the 100 samples genotyped using 5'NCR PCR-RFLP and HCV core type-specific PCR, 90% (κ = 0.913, P < 0.00) and 96% (κ = 0.794, P < 0.00) correlated with NS5b sequencing, respectively. Sixty percent and 75% of discordant samples by 5'NCR PCR-RFLP and HCV core type-specific PCR, respectively, belonged to genotype 6. All the HCV genotype 1 subtypes were classified accurately by both the methods. CONCLUSION: This study shows that the 5'NCR-based PCR-RFLP and the HCV core type-specific PCR-based assays correctly identified HCV genotypes except genotype 6 from this region. Direct sequencing of the HCV core region was able to identify all the genotype 6 from this region and serves as an alternative to NS5b sequencing.

Gene-expression profiling of calves 6 and 9 months after inoculation with Mycobacterium avium subspecies paratuberculosis.

Early detection of Johne's disease (JD) caused by Mycobacterium avium subspecies paratuberculosis (MAP) is essential to reduce transmission; consequently, new diagnostic techniques and approaches to detect MAP or markers of early MAP infection are being explored. The objective was to identify biomarkers associated with MAP infection at 6 and 9 months after oral inoculation. Therefore, gene expression analysis was done using whole blood cells obtained from MAP-infected calves. All MAP-inoculated calves had a cell-mediated immune response (IFN-γ) to Johnin PPD specific antigens, and 60% had an antibody response to MAP antigens. Gene expression analysis at 6 months after inoculation revealed downregulation of chemoattractants, namely neutrophil beta-defensin-9 like peptide (BNBD9-Like), S100 calcium binding protein A9 (s100A9) and G protein coupled receptor 77 (GPR77) or C5a anaphylatoxin chemotactic receptor (C5a2). Furthermore, BOLA/MHC-1 intracellular antigen presentation gene was downregulated 9 months after inoculation. In parallel, qPCR experiments to evaluate the robustness of some differentially expressed genes revealed consistent downregulation of BOLA/MHC-I, BNBD9-Like and upregulation of CD46 at 3, 6, 9, 12, and 15 months after inoculation. In conclusion, measuring the expression of these genes has potential for implementation in a diagnostic tool for the early detection of MAP infection.

Dacryoadenitis associated with linear scleroderma en coup de sabre: A case report and review of literature.

Dacryoadenitis in the setting of linear scleroderma en coup de sabre (LScs) is an association that has not previously been described in the scientific literature. The purpose of this case report is to describe the co-existence of LScs and chronic dacryoadenitis and how it was managed. We report the case of a 42-year-old woman who presented with a 4-month history of left upper eyelid swelling with radiological enlargement of the left lacrimal gland on orbital CT and MRI imaging. Clinical examination revealed a left erythematous, swollen upper eyelid with lateral conjunctival injection and a palpable left lacrimal gland. An ipsilateral band-like cutaneous depression in the fronto-temporal region was also noted, which extended to the ipsilateral upper eyelid and brow. Serology revealed nucleolar antinuclear antibodies. A further incisional biopsy of the lacrimal gland confirmed chronic inflammatory changes and fibrous tissue. Based on both the histological and clinical findings, a diagnosis of dacryoadenitis in association with LScs was made. Oral methotrexate was commenced. The patient responded well with less frequent episodes of eyelid swelling and reduced periocular pain. This case describes for the first time, the ophthalmological manifestation of chronic dacryoadenitis in association with linear scleroderma en coup de sabre.

Brugada syndrome.

As a clinical entity the Brugada syndrome has existed since 1992 and has been associated with a high risk of sudden cardiac death predominately in younger males. Patients can present with symptoms (ie syncope, palpitations, aborted sudden cardiac death) and asymptomatically. Its three characteristic electrocardiographic patterns can occur both spontaneously or after provocation with sodium channel-blocking agents. Risk stratification and the need for treatment depend on the patient's symptoms, electrocardiography, family history, and electrophysiological inducibility to discern if treatment by implantable cardioverter defibrillator, the only effective treatment to date, is appropriate. This review focuses on Brugada syndrome and various aspects of the disease including proposed mechanisms, epidemiology, clinical presentations, genetics, diagnosis, risk stratification, and treatment options.