Epidural Corticosteroid Injections for Sciatica: An Abridged Cochrane Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic with meta-analysis OBJECTIVES.: The aim of this study was to investigate the efficacy and safety of epidural corticosteroid injections compared with placebo injection in reducing leg pain and disability in patients with sciatica. SUMMARY OF BACKGROUND DATA: Conservative treatments, including pharmacological and nonpharmacological treatments, are typically the first treatment options for sciatica but the evidence to support their use is limited. The overall quality of evidence found by previous systematic reviews varies between moderate and high, which suggests that future trials may change the conclusions. New placebo-controlled randomized trials have been published recently which highlights the importance of an updated systematic review. METHODS: The searches were performed without language restrictions in the following databases from 2012 to 25 September 2019: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PubMed, Embase, CINAHL, PsycINFO, International Pharmaceutical Abstracts, and trial registers. We included placebo-controlled randomized trials investigating epidural corticosteroid injections in patients with sciatica. The primary outcomes were leg pain intensity and disability. The secondary outcomes were adverse events, overall pain, and back pain intensity. We grouped similar trials according to outcome measures and their respective follow-up time points. Short-term follow-up (>2 weeks but ≤3 months) was considered the primary follow-up time point due to the expected mechanism of action of epidural corticosteroid injection. Weighted mean differences (MDs) and risk ratios (RRs) with their respective 95% confidence intervals (CIs) were estimated. We assessed the overall quality of evidence using the GRADE approach and conducted the analyses using random effects. RESULTS: We included 25 clinical trials (from 29 publications) providing data for a total of 2470 participants with sciatica, an increase of six trials when compared to the previous review. Epidural corticosteroid injections were probably more effective than placebo in reducing short-term leg pain (MD -4.93, 95% CI -8.77 to -1.09 on a 0-100 scale), short-term disability (MD -4.18, 95% CI: -6.04 to -2.17 on a 0-100 scale) and may be slightly more effective in reducing short-term overall pain (MD -9.35, 95% CI -14.05 to -4.65 on a 0-100 scale). There were mostly minor adverse events (i.e., without hospitalization) after epidural corticosteroid injections and placebo injections without difference between groups (RR 1.14, 95% CI: 0.91-1.42). The quality of evidence was at best moderate mostly due to problems with trial design and inconsistency. CONCLUSION: A review of 25 placebo-controlled trials provides moderate-quality evidence that epidural corticosteroid injections are effective, although the effects are small and short-term. There is uncertainty on safety due to very low-quality evidence. LEVEL OF EVIDENCE: 1.

Non-prescription sales of antimicrobial agents at community pharmacies in developing countries: a systematic review.

Antimicrobial resistance (AMR) is a global challenge. Developing countries are more vulnerable to the consequences of AMR than developed nations because of complex issues pertaining to the nature of their healthcare systems. Inappropriate antimicrobial drug use and the unrestricted availability of antimicrobial agents in community pharmacies in developing countries can contribute to the emergence of resistant microbes. The aim of this systematic review was to explore the availability of antimicrobial agents without a doctor's prescription in developing countries and to investigate factors that contribute to inappropriate antimicrobial supply in developing countries. The EMBASE, MEDLINE and International Pharmaceutical Abstracts databases were searched for articles published between 1980 and November 2017 describing studies using simulated client (or pseudo-patient) methodology in community pharmacies supplying non-prescription antimicrobial agents. Overall, 50 studies were included in this systematic review. All of the studies involved supply of one or more antimicrobials without a prescription. These studies involved using a hypothetical case presentation or direct product request by a simulated client. The review found non-prescription supply of antimicrobials as reported in 28 developing countries across Asia, Africa, South America, Europe and Middle Eastern regions. Contributing factors for non-prescription antimicrobial supply were poor national medicines regulations, limited availability of qualified pharmacists, commercial pressure on pharmacy staff, consumer demand, inappropriate prescribing practices and lack of awareness of AMR.

Pilot study of milrinone for low systemic blood flow in very preterm infants.

OBJECTIVES: To examine the hemodynamic effects of milrinone given prophylactically to very preterm infants at high risk of low superior vena cava (SVC) flow and to investigate the preliminary efficacy and safety of an optimal dose. STUDY DESIGN: This was a prospective, open-label study in two stages. The first involved dose escalation in two cohorts. Milrinone infusions of 0.25 microg/kg per minute (n = 8) and then 0.5 microg/kg per minute (n = 11) were administered from 3 to 24 hours of age. Population pharmacokinetic modeling was used to develop an optimized dose regimen. Ten infants then were loaded with 0.75 microg/kg per minute for 3 hours, followed by 0.2 microg/kg per minute maintenance until 18 hours of age. Infants were monitored for blood pressure, serial echocardiograms, and blood milrinone levels. The primary outcome was maintenance of SVC flow greater than 45 mL/kg per minute through the first 24 hours. RESULTS: Low SVC flow developed in 36% of babies at both 0.25 microg/kg per minute and 0.5 microg/kg per minute of milrinone. Blood levels on these two regimens were slow to reach the target range and accumulated above this range by 24 hours. At 0.75 to 0.2 microg/kg per minute, no infant had SVC flow below 45 mL/kg per minute, compared with 61% in historic control subjects. Four infants needed an additional inotrope to support blood pressure. Blood levels were within the target range in 9 of 10 babies. CONCLUSIONS: We used population pharmacokinetic modeling to develop an optimal dosing regimen for milrinone. The efficacy and safety in this novel preventative approach to circulatory support is encouraging but inconclusive. We do not recommend the use of milrinone in preterm infants outside a research setting.