Objectives:Stroke and TIA are recognized complications of acute herpes zoster (HZ). In this study, we evaluated HZ as a risk factor for cerebrovascular disease (stroke and TIA) and myocardial infarction (MI) in a UK population cohort.Methods:A retrospective cohort of 106,601 HZ cases and 213,202 controls matched for age, sex, and general practice was identified from the THIN (The Health Improvement Network) general practice database. Cox proportional hazard models were used to examine the risks of stroke, TIA, and MI in cases and controls, adjusted for vascular risk factors, including body mass index >30 kg/m2, smoking, cholesterol >6.2 mmol/L, hypertension, diabetes, ischemic heart disease, atrial fibrillation, intermittent arterial claudication, carotid stenosis, and valvular heart disease, up to 24 years (median 6.3 years) after HZ occurrence.Results:Risk factors for vascular disease were significantly increased in cases of HZ compared with controls. Adjusted hazard ratios (AHRs) for TIA and MI but not stroke were increased in all patients with HZ (AHR [95% confidence interval]: 1.15 [1.09–1.21] and 1.10 [1.05–1.16], respectively). However, stroke, TIA, and MI were increased in cases whose HZ occurred when they were younger than 40 years (AHR [95% confidence interval]: 1.74 [1.13–2.66], 2.42 [1.34–4.36], 1.49 [1.04–2.15], respectively). Subjects younger than 40 years were significantly less likely to be asked about vascular risk factors than were older patients (p < 0.001).Conclusion:HZ is an independent risk factor for vascular disease in the UK population, particularly for stroke, TIA, and MI in subjects affected before the age of 40 years. In older subjects, better ascertainment of vascular risk factors and earlier intervention may explain the reduction in risk of stroke after the occurrence of HZ.
Objective: To compare the relative efficacy of ustekinumab (UST) vs. other therapies for 1-year response and remission rates in patients with moderate-severe UC. Methods: Randomized controlled trials reporting induction and maintenance efficacy of anti-TNFs (infliximab [IFX], adalimumab [ADA], golimumab [GOL]), vedolizumab (VDZ), tofacitinib (TOF) or UST were identified through a systematic literature review (SLR). Analyses were conducted for clinical response, clinical remission and endoscopic-mucosal healing for populations with and without failure of prior biologics (non-biologic failure [NBF]; biologic failure [BF]). Maintenance data from trials with re-randomized response designs were recalculated to correspond to treat-through arms. Bayesian network meta-analyses (NMA) were conducted to obtain posterior distribution probabilities for UST to perform better than comparators. Results: Six trials included NBF patients and four included BF patients. In NBF patients, UST as a 1year regimen showed higher probabilities of clinical response, remission and endoscopic-mucosal healing vs. all treatments: Bayesian probabilities of UST being better than active therapies ranged from 91% (VDZ) to 100% (ADA) for response; 82% (VDZ) to 99% (ADA) for remission and 82% (IFX) to 100% (ADA and GOL) for endoscopic-mucosal healing. In BF patients, UST was the most effective treatment (Q8W dose); however, effect sizes were smaller than in the NBF population. Conclusions: Results indicate a higher likelihood of response, remission and endoscopic-mucosal healing at 1 year with UST vs. comparators in the NBF population. In BF patients, a higher likelihood of response to UST vs. the most comparators was also observed, although results were more uncertain.
Objectives: To assess the relative efficacy of canagliflozin, a sodium glucose cotransporter 2 inhibitor (SGLT2) as add-on to insulin +/-oral antihyperglycaemic drugs for the treatment of T2DM compared to dipeptidyl peptidase-4 inhibitors (DPP-4s), glucagon-like peptide-1 receptor agonists (GLP-1s), sulphonylureas, pioglitazone, and other SGLT2 inhibitors, using Bayesian NMA methods. MethOds: A systematic literature review was conducted according to NICE guidelines and available data on HbA1c, weight and systolic blood pressure (SBP) were extracted. Networks were based on treatment-and dose-specific nodes, except for sulphonylureas where doses were combined. Selection of fixed versus random effects was based on the deviance information criterion. Results were interpreted based on absolute differences and Bayesian probabilities for treatments to perform better than others (P), where P≤ 30% indicated a smaller effect and P≥ 70% a larger effect. Results: Eighteen trials reported results at 26 +/-4 weeks. HbA1c reductions were highest for liraglutide 1.8mg, pioglitazone 45mg and glibenclamide. Canagliflozin 300mg had greater HbA1c reductions than all remaining comparators, except for exenatide where the reduction was similar. Canagliflozin 100mg had a greater reduction than dapagliflozin 5mg, vildagliptin, saxagliptin and lixisenatide and a similar reduction versus DPP-4s, glimepiride, lixisenatide, pioglitazone 30mg, metformin and dapagliflozin 10mg. Both dosages of canagliflozin were associated with greater weight loss than DPP-4s, glibenclamide, pioglitazone 30mg and dapagliflozin (Δ = -2.13 to -3.45kg; Δ = -7.61 to -8.25kg; Δ = -3.34 to -3.95kg; Δ = -0.44 to -1.73kg, respectively). Weight reductions were highest for liraglutide 1.8mg and exenatide 10μ g. Both dosages of canagliflozin had higher SBP reductions than dapagliflozin and saxagliptin; at least similar reductions were estimated versus exenatide 10μ g. cOnclusiOns:These results suggest that canagliflozin is a valuable treatment option as add-on to insulin therapy, as it provides not only similar or better glucose lowering than many other options, but also weight loss.
Objectives To compare work absenteeism and short-term disability among adults with psoriasis or psoriatic arthritis (PsA), versus controls in the USA. Methods Adults eligible for work absenteeism and/or short-term disability benefits between 1/1/2009 and 4/30/2020 were screened in the IBM® MarketScan® Commercial and Health and Productivity Management Databases. The following groups were defined: (1) psoriasis: ≥ 2 psoriasis diagnoses ≥ 30 days apart and no PsA diagnoses; (2) PsA: ≥ 2 PsA diagnoses ≥ 30 days apart; (3) control: absence of psoriasis and PsA diagnoses. Controls were matched to psoriasis and PsA patients based on age, gender, index year, and comorbidities. Non-recreational work absences and sick leaves were evaluated in absentee-eligible patients, and short-term disability was evaluated in short-term disability-eligible patients. Costs (in 2019 USD) associated with each type of work absence were evaluated. Results 4261 psoriasis and 616 PsA absentee-eligible and 25,213 psoriasis and 3480 PsA short-term disability-eligible patients were matched to controls. Average non-recreational work absence costs were $1681, $1657, and $1217 for the PsA, psoriasis, and control group, respectively. Compared with psoriasis patients and controls, more PsA patients had sick leaves after 1 year (56.2% versus 55.6% and 41.5%, p < 0.0001). Similarly, short-term disability was more frequent in PsA patients than psoriasis patients and controls at year one (8.8% versus 5.6% and 4.7%, p < 0.0001) and corresponding costs were higher ($605, $406, and $335 on average, p < 0.0001). Conclusion Annual work absenteeism and short-term disability were consistently greater among patients with PsA and psoriasis than controls, highlighting the substantial economic burden of psoriatic disease. Key points• Patients with PsA had greater short-term disability compared with patients with psoriasis and patients with neither psoriasis nor PsA.• Patients with PsA and patients with psoriasis incurred greater non-recreational work absences and sick leaves than patients with neither psoriasis nor PsA.
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