Time-varying risks of infection in patients as they proceed through the phases of 'pre-RA': results from the Scottish Early RA inception cohort.

ObjectiveRheumatoid arthritis (RA) develops after progressing through sequential 'pre-RA' phases. The mechanisms driving progression from one phase to the next remain poorly understood. This study examined the longitudinal rates of community and hospital infections in patients during sequential stages of pre-RA and early arthritis. METHODS: The Scottish Early RA inception cohort recruited patients with newly diagnosed RA. Incidences of infection were determined from community antibiotic prescriptions and serious infections were determined by hospital discharge coding. Dates of diagnosis and symptom onset allowed identification of asymptomatic/symptomatic pre-RA and early arthritis eras to analyse infection rates over time compared with age- and sex-matched controls. RESULTS: The incidence rate ratio (IRR) seen in the period 0-6 months prior to symptom onset was 1.28 (95% CI 1.15 to 1.42). In 'symptomatic pre-RA', the IRR was 1.33 (95% CI 1.18 to 1.49) which persisted into 'early arthritis'. The rate of hospital admissions was numerically greater in 'pre-RA' and significantly greater in 'early arthritis' (IRR 1.82, 95% CI 1.32 to 2.46). CONCLUSION: Antibiotic risk is increased in patients with 'pre-RA' at least 6 months before symptoms develop, and this persists throughout the symptomatic pre-RA phase. Infections may be important in the mechanisms that drive progression to RA or be a manifestation of immune dysfunction (or both). These observations could inform safety and efficacy considerations for interventions in pre-RA to prevent progression. Patients with 'pre-RA' with recurrent antibiotic use may also be an identifiable 'high risk' group that could enrich the study population for intervention studies in pre-RA.

Secondary Prevention Medications Post Coronary Artery Bypass Grafting Surgery-A Literature Review.

Secondary prevention after coronary artery bypass graft (CABG) surgery is imperative in slowing the progression of atherosclerosis in both native and grafted vessels. Aspirin and statins remain the key medications for all patients without significant contraindications. The evidence for dual antiplatelet therapy with clopidogrel is less convincing, but there is hope for newer antiplatelet agents, such as ticagrelor. Meanwhile, ß-blockers and angiotensin converting enzyme inhibitors might only offer benefits to specific sub-groups. Post-CABG patients appear to have different medication needs to the general cardiovascular patient and respond differently. In this review, we cover the drug regimens proposed by recent guidelines and the evidence behind their use. Assessing the evidence behind these recommendations, we find that there is an unmet need in some areas for robust population-specific evidence. We hope that future research will address this gap.

Development of locally relevant clinical guidelines for procedure-related neonatal analgesic practice in Kenya: a systematic review and meta-analysis.

Background Increasing numbers of neonates are undergoing painful procedures in low-income and middle-income countries, with adequate analgesia seldom used. In collaboration with a multi-disciplinary team in Kenya, we aimed to establish the first evidence-based guidelines for the management of routine procedure-related neonatal pain that consider low-resource hospital settings. METHODS: We did a systematic review by searching MEDLINE, Embase, CINAHL, and CENTRAL databases for studies published from Jan 1, 1953, to March 31, 2019. We included data from randomised controlled trials using heart rate, oxygen saturation (SpO2), premature infant pain profile (PIPP) score, neonatal infant pain scale (NIPS) score, neonatal facial coding system score, and douleur aiguë du nouveau-né scale score as pain outcome measures. We excluded studies in which neonates were undergoing circumcision or were intubated, studies from which data were unextractable, or when pain was scored by non-trained individuals. We did a narrative synthesis of all studies, and meta-analysis when data were available from multiple studies comparing the same analgesics and controls and using the same outcome measures. 17 Kenyan health-care professionals formed our clinical guideline development panel, and we used the Grading of Recommendations, Assessment, Development and Evaluation framework and the panel's knowledge of the local health-care context to guide the guideline development process. This study is registered with PROSPERO, CRD42019126620. FINDINGS: Of 2782 studies assessed for eligibility, data from 149 (5%) were analysed, with 80 (3%) of these further contributing to our meta-analysis. We found a high level of certainty for the superiority of breastfeeding over placebo or no intervention (standardised mean differences [SMDs] were -1·40 [95% CI -1·96 to -0·84] in PIPP score and -2·20 [-2·91 to -1·48] in NIPS score), and the superiority of oral sugar solutions over placebo or no intervention (SMDs were -0·38 [-0·61 to -0·16] in heart rate and 0·23 [0·04 to 0·42] in SpO2). We found a moderate level of certainty for the superiority for expressed breastmilk over placebo or no intervention (SMDs were -0·46 [95% CI -0·87 to -0·05] in heart rate and 0·48 [0·20 to 0·75] in SpO2). Therefore, the panel recommended that breastfeeding should be given as first-line analgesic treatment, initiated at least 2 min pre-procedure. Given contextual factors, for neonates who are unable to breastfeed, 1-2 mL of expressed breastmilk should be given as first-line analgesic, or 1-2 mL of oral sugar (≥10% concentration) as second-line analgesic. The panel also recommended parental presence during procedures with adjunctive provision of skin-to-skin care, or non-nutritive sucking when possible. INTERPRETATION: We have generated Kenya's first neonatal analgesic guidelines for routine procedures, which have been adopted by the Kenyan Ministry of Health, and have shown a framework for clinical guideline development that is applicable to other low-income and middle-income health-care settings. FUNDING: Wellcome Trust Research Programme, and the Africa-Oxford Initiative.