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Analgesic Efficacy and Adverse Effects of Meperidine in Managing Postoperative or Labor Pain: A Narrative Review of Randomized Controlled Trials.
Ching Wong, SS, Cheung, CW
Pain physician. 2020;(2):175-201
Abstract
BACKGROUND Meperidine, a synthetic opioid, has a rapid onset and short duration of action. Mounting evidence has challenged meperidine's analgesic benefits, and concerns have been raised about its safety profile. Despite recommendations to restrict the prescription of meperidine, the drug remains frequently used. OBJECTIVES The aim of this study was to evaluate the evidence regarding the efficacy and safety of meperidine for acute postoperative and labor pain. STUDY DESIGN This was a narrative review of the analgesic efficacy and side effects of meperidine compared to other analgesic drugs for acute postoperative and labor pain in adults. SETTING Randomized controlled trials that compared the analgesic efficacy and side effect profile of meperidine versus another analgesic drug in adult patients were evaluated. METHODS A systemized search of randomized controlled trials studying meperidine for acute postoperative or labor pain in the adult patient population from PubMed, Medline, and EMBASE was performed. Included studies reported on different routes of meperidine administration including intramuscular, intravenous, and patient-controlled analgesia in various surgical procedures such as abdominal surgery, Cesarean section, gynecological surgery, orthopedic surgery, cardiothoracic surgery, as well as for labor analgesia. Meperidine's analgesic efficacy and safety profile were compared to other opioids (morphine, tramadol, fentanyl, buprenorphine, nalbuphine, and pentazocine), nonsteroidal anti-inflammatory drugs (ketorolac, diclofenac, and indomethacin), dipyrone, ketamine, and bupivacaine. RESULTS A total of 62 randomized controlled trials published between 1972 and 2018 were reviewed. Meperidine had a similar or inferior analgesic efficacy compared to other analgesics for acute postoperative or labor pain. Meperidine was associated with more sedation and respiratory depression. LIMITATIONS The sample sizes of many clinical studies were small, and therefore probably insufficiently powered to detect differences in uncommon side effects, such as central nervous system toxicity. In addition, some of the included clinical studies were old. CONCLUSION Considering the availability of other effective analgesics with potentially fewer side effects, the use of meperidine for acute postoperative or labor pain should not be recommended. KEY WORDS Acute postoperative pain, adverse effects, labor analgesia, meperidine, pethidine.
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Galantamine-Memantine combination in the treatment of Alzheimer's disease and beyond.
Koola, MM
Psychiatry research. 2020;:113409
Abstract
Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly population worldwide. Despite the major unmet clinical need, no new medications for the treatment of AD have been approved since 2003. Galantamine is an acetylcholinesterase inhibitor that is also a positive allosteric modulator at the α4β2 and α7nACh receptors. Memantine is an N-methyl-d-aspartate receptor modulator/agonist. Both galantamine and memantine are FDA-approved medications for the treatment of AD. The objective of this review is to highlight the potential of the galantamine-memantine combination to conduct randomized controlled trials (RCTs) in AD. Several studies have shown the combination to be effective. Neurodegenerative diseases involve multiple pathologies; therefore, combination treatment appears to be a rational approach. Although underutilized, the galantamine-memantine combination is the standard of care in the treatment of AD. Positive RCTs with the combination with concurrent improvement in symptoms and biomarkers may lead to FDA approval, which may lead to greater utilization of this combination in clinical practice.
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CREDENCE: A silver lining in the dark cloud of diabetic nephropathy.
Hanai, K, Babazono, T
Journal of diabetes investigation. 2020;(3):527-529
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Two Tales: One Story: EMPEROR-Reduced and DAPA-HF.
Verma, S, McGuire, DK, Kosiborod, MN
Circulation. 2020;(23):2201-2204
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Stopping live vaccines after disease eradication may increase mortality.
Aaby, P, Benn, CS
Vaccine. 2020;(1):10-14
Abstract
Several live vaccines may have beneficial non-specific effects (NSEs) reducing mortality more than can be explained by the prevention of the target infection, a phenomenon which has been linked to innate immune training. Most randomised controlled trials (RCTs) of oral polio vaccine (OPV) and measles vaccine (MV) have shown a large reduction in mortality that must have been at least partly nonspecific because it was much larger than the reduction explained by prevention of the target disease. Hence, stopping a live vaccine after disease-eradication could have negative health effects if the potential beneficial NSEs are not considered. We reviewed one eradicated disease, smallpox, and two infections likely to be eradicated in coming decades, polio and measles. No study was made of unintended effects of stopping smallpox vaccination when it happened in 1980. We have subsequently documented in both Guinea-Bissau and Denmark that smallpox-vaccinated individuals continued to have a survival advantage long after smallpox had been eradicated. The few studies which have examined the effect of OPV on survival all suggest strong beneficial NSEs; in RCTs, OPV compared with inactivated polio vaccine (IPV) has been associated with non-specific reductions in morbidity. RCTs, natural experiments and observational studies have found strong beneficial NSEs for MV. Hence, the imminent eradication of polio and the planned stop of OPV in 2024 and the subsequent eradication of measles infection and the possible stop to live MV could have negative effects for child survival. Before live vaccines are phased out, potential unintended effects of stopping these vaccines should be thoroughly studied.
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An appraisal of the SDIR as an estimate of true individual differences in training responsiveness in parallel-arm exercise randomized controlled trials.
Bonafiglia, JT, Brennan, AM, Ross, R, Gurd, BJ
Physiological reports. 2019;(14):e14163
Abstract
Calculating the standard deviation of individual responses (SDIR ) is recommended for estimating the magnitude of individual differences in training responsiveness in parallel-arm exercise randomized controlled trials (RCTs). The purpose of this review article is to discuss potential limitations of parallel-arm exercise RCTs that may confound/complicate the interpretation of the SDIR . To provide context for this discussion, we define the sources of variation that contribute to variability in the observed responses to exercise training and review the assumptions that underlie the interpretation of SDIR as a reflection of true individual differences in training responsiveness. This review also contains two novel analyses: (1) we demonstrate differences in variability in changes in diet and physical activity habits across an intervention period in both exercise and control groups, and (2) we examined participant dropout data from six RCTs and found that significantly (P < 0.001) more participants in control groups (12.8%) dropped out due to dissatisfaction with group assignment compared to exercise groups (3.4%). These novel analyses raise the possibility that the magnitude of within-subject variability may not be equal between exercise and control groups. Overall, this review highlights that potential limitations of parallel-arm exercise RCTs can violate the underlying assumptions of the SDIR and suggests that these limitations should be considered when interpreting the SDIR as an estimate of true individual differences in training responsiveness.
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7.
Ethical Issues in Pragmatic Cluster-Randomized Trials in Dialysis Facilities.
Goldstein, CE, Weijer, C, Taljaard, M, Al-Jaishi, AA, Basile, E, Brehaut, J, Cook, CL, Grimshaw, JM, Lacson, E, Lindsay, C, et al
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2019;(5):659-666
Abstract
A pragmatic cluster-randomized trial (CRT) is a research design that may be used to efficiently test promising interventions that directly inform dialysis care. While the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials provides general ethical guidance for CRTs, the dialysis setting raises additional considerations. In this article, we outline ethical issues raised by pragmatic CRTs in dialysis facilities. These issues may be divided into 7 key domains: justifying the use of cluster randomization, adopting randomly allocated individual-level interventions as a facility standard of care, conducting benefit-harm analyses, gatekeepers and their responsibilities, obtaining informed consent from research participants, patient notification, and including vulnerable participants. We describe existing guidelines relevant to each domain, illustrate how they were considered in the Time to Reduce Mortality in End-Stage Renal Disease (TiME) trial (a prototypical pragmatic hemodialysis CRT), and highlight remaining areas of uncertainty. The following is the first step in an interdisciplinary mixed-methods research project to guide the design and conduct of pragmatic CRTs in dialysis facilities. Subsequent work will expand on these concepts and when possible, argue for a preferred solution.
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8.
Hidradenitis Suppurativa: A Systematic Review and Meta-analysis of Therapeutic Interventions.
Tchero, H, Herlin, C, Bekara, F, Fluieraru, S, Teot, L
Indian journal of dermatology, venereology and leprology. 2019;(3):248-257
Abstract
Hidradenitis suppurativa is a chronic inflammatory condition that affects skin regions bearing apocrine glands. Although hidradenitis suppurativa is difficult to treat and cure, the currently available treatments are directed toward managing the lesions and associated symptoms. This review presents an evidence-based outline of the available treatment options. We searched four electronic databases and extracted data from retrieved studies for qualitative or quantitative analysis. Meta-analysis was conducted using the comprehensive meta-analysis software to generate pooled standardized mean differences or risk ratios. Numerous medical treatments are available for hidradenitis suppurativa such as antibiotics, retinoids, antiandrogens, immunosuppressive and anti-inflammatory agents and radiotherapy for early lesions. Adalimumab, an anti-tumor necrosis factor antibody, was superior to placebo in reducing Sartorius score (standardized mean difference = -0.32, confidence interval [-0.46, -0.18], P < 0.0001) and pain (risk ratio = 1.42, confidence interval [1.07, 1.9], P = 0.02), when given weekly (not every other week). Combination therapies (such as antibiotics and hyperbaric oxygen therapy) have been tested, which have shown promising results that are yet to be confirmed. Based on the quality of evidence, the most recommended treatments for hidradenitis suppurativa include adalimumab and laser therapy. Surgery (either by simple excision or complete local excision followed by skin graft) is the first choice for intractable disease presenting in the late stages. However, the evidence on most of these treatments is deficient and further randomized trials are needed to establish the most efficient therapies for hidradenitis suppurativa management.
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9.
Trials and Tribulations of CETP Inhibitors.
Tall, AR, Rader, DJ
Circulation research. 2018;(1):106-112
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Abstract
The development of CETP (cholesteryl ester transfer protein) inhibitors has had a long and difficult course with 3 compounds failing in phase III clinical trials. Finally, the REVEAL (Randomized Evaluation of the Effects of Anacetrapib through Lipid modification) trial has shown that the CETP inhibitor anacetrapib decreased coronary heart disease when added to statin therapy. Although the result is different to earlier studies, this is likely related to the size and duration of the trial. The benefit of anacetrapib seems to be largely explained by lowering of non-HDL-C (high-density lipoprotein cholesterol), rather than increases in HDL-C. Although the magnitude of benefit for coronary heart disease appeared to be moderate, in part this may have reflected aspects of the trial design. Anacetrapib treatment was associated with a small increase in blood pressure, but was devoid of major side effects and was also associated with a small reduction in diabetes mellitus. Treatment with CETP inhibitors, either alone or in combination with statins, could provide another option for patients with coronary disease who require further reduction in LDL (low-density lipoprotein) and non-HDL-C.
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Assessment of omega-3 carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: Rationale and design of the STRENGTH trial.
Nicholls, SJ, Lincoff, AM, Bash, D, Ballantyne, CM, Barter, PJ, Davidson, MH, Kastelein, JJP, Koenig, W, McGuire, DK, Mozaffarian, D, et al
Clinical cardiology. 2018;(10):1281-1288
Abstract
It is uncertain whether omega-3 fatty acids are beneficial in statin-treated patients. Epanova is a mix of omega-3 free fatty acids, not requiring co-ingestion with food, which can lower triglycerides by up to 31%. STRENGTH will examine whether Epanova 4 g daily reduces the rate of cardiovascular events in statin-treated patients with hypertriglyceridemia and low levels of HDL-C at high risk for developing cardiovascular events. STRENGTH is a randomized, double-blind, placebo-controlled trial. Patients had a triglyceride level ≥ 180 to <500 mg/dL and HDL-C < 42 mg/dL (men) or < 47 mg/dL (women) in the presence of either (1) established atherosclerotic cardiovascular disease, (2) diabetes with one additional risk factor, or (3) were other high-risk primary prevention patients, based on age and risk factor assessment. Patients should be treated with a statin, for >4 weeks, and have LDL-C < 100 mg/dL, but were also eligible if LDL-C was ≥100 mg/dL while on maximum tolerated statin therapy. The study will extend from October 30, 2014 to October 30, 2019. 13 086 patients were randomized to Epanova 4 g or placebo daily in addition to standard medical therapy. The primary efficacy outcome is time to first event of cardiovascular death, myocardial infarction, stroke, coronary revascularization or hospitalization for unstable angina. The trial will continue until 1600 patients reach the primary endpoint, with a median duration of therapy of 3 years. STRENGTH will determine whether Epanova 4 g daily will reduce cardiovascular events in statin-treated high-risk patients with hypertriglyceridemia and low HDL-C levels.