Trial of atorvastatin for the primary prevention of cardiovascular events in patients with rheumatoid arthritis (TRACE RA): A multicenter, randomized, placebo controlled trial (2019)

Type of publication:
Journal article

Author(s):
Kitas GD, Nightingale P, Armitage J, Sattar N, Belch JJF, Symmons DPM; TRACE RA consortium.

Collaborators (137) Kitas G, Belch J, Symmons D, Williams H, Vasishta S, Storey R, Nightingale P, Bruce I, Durrington P, McInnes I, Nightingale P, Sattar N, Situnayake D, Struthers A, Lowe G, Armitage J, Fox K, Haskard D, Dore C, Bosworth A, Kitas G, Belch J, Symmons D, Williams H, Frenneaux M, Edwards C, Emberson J, Bax D, Cobbe S, Stott D, Sturrock R, Macfarlane P, Klocke R, Pullar T, Knight S, Rowe I, Kumar P, Goodson N, Mulherin D, Brzeski M, Gardiner P, Situnayake D, Walker D, Callaghan R, Allen M, McCarey D, George E, Deighton C, Kirkham B, Teh LS, Luqmani R, Chakravarty K, Nixon J, Richards S, Scott D, Woolf T, Prouse P, Packham J, Davies M, DeLord D, O’Neill T, Pande I, Harvie J, Watts R, Rankin E, Papasavvas G, Emery P, Sinha A, Dasgupta B, Bruce I, Creamer P, Zoma A, Walsh D, Van-Laar J, *Capps N, Cairns A, Marguerie C, Kumar N, Abernethy R, Lillicrap M, Ralston S, Makadsi R, Hopkinson N, Tan S, Akil M, Ahmad Y, Adler M, Bukhari M, Sanders P, Roussou E, Binymin K, Hassan A, Hughes R, O’Reilly D, Sainsbury P, Richmond R, Malgorzata M, Nisar M, McEntergart A, Roy D, Marks J, Batley M, McKenna F, Irani M, Harris H, Smyth A, Tunn E, Young A, Thomas J, Hall F, Marshall T, Rao C, Baburaj K, Dixey J, Gendi N, Birrell F, Chelliah G, Teh LS, Morgan A, Fishman D, Knights S, Coady D, Makadsi R, Smith B, Harrison B, Walker D, Siebert S, Chan A, Putchakayala K, Al-Ansari A, Gough A, Naz S, Kumar N, Pyne D, Mahmud T, Patel Y, Isdale A.

Citation:
Arthritis Rheumatol. 2019 Apr 15. doi: 10.1002/art.40892. [Epub ahead of print]

Abstract:
OBJECTIVE:

Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVE in RA patients.

METHODS:

Randomized, double-blind, placebo-controlled trial designed for 80% power at p<0.05 to detect a 32% CVE risk reduction based on an estimated 1.8% per annum (pa) event rate. Patients aged >50 years or with RA duration >10 years; without clinical atherosclerosis, diabetes, or myopathy; received atorvastatin 40mg daily or matching placebo. Primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary/tertiary endpoints included plasma lipids and safety.

RESULTS:

3002 patients (mean age 61 years, 74% female) were followed for a median 2.51 years (IQR 1.90-3.49) [7,827 patient-years] – early termination was due to lower than expected event rate (0.77% pa). Among patients allocated atorvastatin 24/1504 (1.6%) had a primary endpoint, compared with 36/1498 (2.4%) on placebo (hazard ratio 0.66, 95%CI 0.39-1.11, p=0.115); adjusted hazard ratio (0.60, 95%CI 0.32-1.15, p=0.127). At trial end, patients on atorvastatin had 0.77±0.04 mmol/L lower LDL-cholesterol compared to placebo (p<0.0001); CRP (mg/L) was also significantly lower on atorvastatin than placebo (2.59 (0.94-6.08) vs. 3.60 (1.47-7.49) – p<0.0001). CVE risk reduction per mmol/L LDLc reduction was 42% (95%CI -14%-70%). Adverse events in the atorvastatin (298 (19.8%)) and placebo (292 (19.5%)) groups were similar.

CONCLUSION:

Atorvastatin 40mg daily was safe and resulted in significantly greater reduction of LDLc than placebo in patients with RA. The 40% (adjusted) CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta-analysis of statin effects in other populations.

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Parent experiences with paediatric allergy pathways in the West Midlands: A qualitative study (2019)

Type of publication:
Journal article

Author(s):
Diwakar, Lavanya; Cummins, Carole; Hackett, Scott; *Rees, Martyn; *Charles, Lynette; Kerrigan, Caroline; Creed, Helen; Roberts, Tracy

Citation:
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology; Mar 2019; vol. 49 (no. 3); p. 357-365

Abstract:
BACKGROUND The prevalence, severity and complexity of allergic diseases have been increasing steadily in the United Kingdom over the last few decades. Primary care physicians are often not adequately trained in allergy management while specialist services for allergy are scarce and heterogeneous. Services, therefore, have been unable to meet the rising demand. This is particularly true for paediatric allergy services in the United Kingdom.OBJECTIVE To understand parent experiences with paediatric allergy pathways in the West Midlands (WM) region of the United Kingdom.METHODS Parents of children aged between 0 and 16 years from the WM region were recruited opportunistically until thematic saturation was achieved. Eighteen semi-structured
interviews were carried out and transcribed verbatim. Data were analysed on NVivo software using the framework method. Themes were identified from the transcripts as well as from existing
literature.RESULTS Parents highlighted numerous issues related to allergy services in the region including difficulties with being taken seriously by their physicians, problems with accessing health care and issues with information and the need for additional supportive care for allergies.CONCLUSIONS AND CLINICAL RELEVANCE Primary care for children with allergies in the WM is disparate. Parents experience difficulties in accessing primary and secondary care services and also obtaining timely and appropriate information regarding their child’s allergies. Most parents were happy to be reviewed by either specialist nurses or by consultants in the hospital. Improving accessibility and availability of reliable information as well as provision of additional services (such as psychologists and dietetics) were highlighted by parents as being important to allergy services in the region. These findings can help inform future planning and commissioning of allergy services.

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Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study) (2019)

Type of publication:
Journal article

Author(s):
Schmidinger, Manuela; Bamias, Aristotelis; Procopio, Giuseppe; Hawkins, Robert; Sanchez, Angel Rodriguez; Vázquez, Sergio; *Srihari, Narayanan; Kalofonos, Haralabos; Bono, Petri; Pisal, Chaitali Babanrao; Hirschberg, Yulia; Dezzani, Luca; Ahmad, Qasim; Jonasch, Eric

Citation:
The oncologist; Mar 2019 [epub ahead of print]

Abstract:
BACKGROUND Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC).SUBJECTS, MATERIALS, AND METHODS Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared
characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups.RESULTS Six hundred fifty-seven patients were enrolled and received ≥1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2-12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE
(85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups.CONCLUSION PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. IMPLICATIONS FOR PRACTICE PRINCIPAL is the largest (n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authors’ knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are
treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months.

Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception (2019)

Type of publication:
Journal article

Author(s):
Dhillon-Smith, Rima K; Middleton, Lee J; Sunner, Kirandeep K; Cheed, Versha; Baker, Krys; Farrell-Carver, Samantha; Bender-Atik, Ruth; Agrawal, Rina; Bhatia, Kalsang; Edi-Osagie, Edmond; Ghobara, Tarek; Gupta, Pratima; Jurkovic, Davor; Khalaf, Yacoub; MacLean, Marjory; McCabe, Christopher; Mulbagal, Khashia; Nunes, Natalie; Overton, Caroline; Quenby, Siobhan; Rai, Raj; Raine-Fenning, Nick; Robinson, Lynne; Ross, Jackie; *Sizer, Andrew; Small, Rachel; Tan, Alex; *Underwood, Martyn; Kilby, Mark D; Boelaert, Kristien; Daniels, Jane; Thangaratinam, Shakila; Chan, Shiao Y; Coomarasamy, Arri

Citation:
The New England journal of medicine 2019; 380:1316-1325

Abstract:
BACKGROUND Thyroid peroxidase antibodies are associated with an increased risk of miscarriage and preterm birth, even when thyroid function is normal. Small trials indicate that the use of levothyroxine could reduce the incidence of such adverse outcomes.METHODS We conducted a double-blind, placebo-controlled trial to investigate whether levothyroxine treatment would increase live-birth rates among euthyroid women who had thyroid peroxidase antibodies and a history of miscarriage or infertility. A total of 19,585 women from 49 hospitals in the United Kingdom underwent testing for thyroid peroxidase antibodies and thyroid function. We randomly assigned 952 women to receive either 50 μg once daily of levothyroxine (476 women) or placebo (476 women) before conception through the end of pregnancy. The primary outcome was live birth after at least 34 weeks of gestation.RESULTS The follow-up rate for the primary outcome was 98.7% (940 of 952 women). A total of 266 of 470 women in the levothyroxine group (56.6%) and 274 of 470 women in the placebo group (58.3%) became pregnant. The live-birth rate was 37.4% (176 of 470 women) in the levothyroxine group and 37.9% (178 of 470 women) in the placebo group (relative risk, 0.97; 95% confidence interval [CI], 0.83 to 1.14, P = 0.74; absolute difference, -0.4 percentage points; 95% CI, -6.6 to 5.8). There were no significant between group differences in other pregnancy outcomes, including pregnancy loss or preterm birth, or in neonatal
outcomes. Serious adverse events occurred in 5.9% of women in the levothyroxine group and 3.8% in the placebo group (P = 0.14).CONCLUSIONS The use of levothyroxine in euthyroid women with thyroid peroxidase antibodies did not result in a higher rate of live births than placebo. (Funded by the United Kingdom National Institute for Health Research; TABLET Current Controlled Trials number, ISRCTN15948785.).

Kikuchi-Fujimoto Disease and Prognostic Implications (2019)

Type of publication:
Journal article

Author(s):
*Salamat, Sebastian; *Chan, Jacquline; *Jolly, Karan; *Powell, George; *Harrison, Katherine; *Ahanger, Sajad; *Hari, Churunal

Citation:
Head and neck pathology; Mar 2019

Abstract:
Abstract Kikuchi-Fujimoto disease (KFD) is a rare cause of lymphadenitis seen mostly in Asian populations (Kikuchi in Nippon Ketsueki Gakkai Zasshi 35:379-80, 1972). First described in 1972, KFD is a benign and self-limiting disease characterised by lymphadenopathy, mild fever, fatigue, and leukopenia (Fujimoto in Naika 30:920-7, 1972; Lin et al. in Otolaryngol Head Neck Surg 128(5): 650-3, 2003). We present a case of a 38-year-old woman with a 6-week history of cervical lymphadenopathy. Her ultrasound scan and fine needle aspiration cytology results were inconclusive. Excisional biopsy of the lymph node confirmed presence of KFD. The aetiology of KFD is unknown; however, there is strong association with systemic lupus erythematosus (SLE). Kucukardali reported 9% of European KFD patients and 28% of East Asian patients had concomitant SLE (Kucukardali et al. in Clin Rheumatol 26(1):50-4, 2007). We describe a follow-up algorithm for newly diagnosed KFD cases, based on the current literature. KFD is a rare cause of cervical lymphadenopathy. It is associated with increased risk of developing SLE, therefore early diagnosis and long-term follow-up are recommended.

Effectiveness of Intra-Gastric Balloon as a Bridge to Definitive Surgery in the Super Obese (2019)

Type of publication:
Journal article

Author(s):
Ball, William; Raza, Syed Soulat; Loy, John; *Riera, Manel; *Pattar, Jayaprakash; *Adjepong, Samuel; *Rink, James

Citation:
Obesity surgery; Feb 2019

Abstract:
BACKGROUND British National guidelines (NICE) recommend bariatric surgery for patients with a body mass index (BMI) > 40 kg/m2, or BMI > 35 kg/m2 with any comorbidities of the metabolic syndrome. Intra-gastric balloons (IGB) can be used in super obese patients as a first step, before definitive surgery. AIMS Quantify
weight loss 6 months after IGB placement, measure progression to definitive surgery and identify complications.METHODSData collected retrospectively on 50 patients. Forty-six proposed for definitive bariatric surgery, four patients excluded. Analysis performed using SPSS v23.0. RESULTS Median weight decreased from 165.5 to 155 kg (range 78 to 212, p < 0.01), BMI from 57.4 to 52.15 (range 32.9 to 70.5, p < 0.01), percentage excess weight loss (%EWL) was 12.9% (range – 3.3 to 64.66%, p < 0.01) and BMI reduction was 4.25 kg/m2 (range – 1.3 to 13.9, p < 0.01). Twenty-nine out of 46 patients (63%) progressed to definitive bariatric surgery. Ten out of 46 patients (21.7%) had complications requiring readmission. Seven of these patients required early balloon removal and six failed to progress to definitive surgery. Six patients had a second balloon placement, their actual weight loss was less successful, with some regaining weight. DISCUSSION IGB is useful to aid weight loss prior to definitive bariatric surgery. Results from first balloon placement are encouraging and comparable with other studies “as reported by Genco et al. (Int J of Obes 30:129-133, 2006).” Readmission due to nausea, vomiting, dehydration and poor compliance may be associated with poor weight loss and failure to progress to definitive surgery. Second balloon placements were less successful. CONCLUSION IGB as bridging therapy is a safe and useful adjunct. Sequential IGBs do not seem to provide additional benefit.