Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.

Chronic pain is a major source of morbidity for which there are limited effective treatments. Palmitoylethanolamide (PEA), a naturally occurring fatty acid amide, has demonstrated utility in the treatment of neuropathic and inflammatory pain. Emerging reports have supported a possible role for its use in the treatment of chronic pain, although this remains controversial. We undertook a systematic review and meta-analysis to examine the efficacy of PEA as an analgesic agent for chronic pain. A systematic literature search was performed, using the databases MEDLINE and Web of Science, to identify double-blind randomized controlled trials comparing PEA to placebo or active comparators in the treatment of chronic pain. All articles were independently screened by two reviewers. The primary outcome was pain intensity scores, for which a meta-analysis was undertaken using a random effects statistical model. Secondary outcomes including quality of life, functional status, and side effects are represented in a narrative synthesis. Our literature search identified 253 unique articles, of which 11 were ultimately included in the narrative synthesis and meta-analysis. Collectively, these articles described a combined sample size of 774 patients. PEA was found to reduce pain scores relative to comparators in a pooled estimate, with a standard mean difference of 1.68 (95% CI 1.05 to 2.31, p = 0.00001). Several studies reported additional benefits of PEA for quality of life and functional status, and no major side effects were attributed to PEA in any study. The results of this systematic review and meta-analysis suggest that PEA is an effective and well-tolerated treatment for chronic pain. Further study is warranted to determine the optimal dosing and administration parameters of PEA for analgesic effects in the context of chronic pain.

The Effect of Smoking Cessation on Acute Pain: A Systematic Review.

Smoking is a known risk factor for developing various pain-related disorders. However, acute pain often triggers the craving for cigarette consumption, resulting in a positive feedback mechanism. In addition, there is evidence of decreased pain tolerance during the early stages of abstinence. Therefore, in this study, we aimed to investigate whether a period of decreased pain tolerance and increased pain intensity occurs during smoking cessation. A systematic literature search was conducted through PubMed and Web of Science databases for controlled studies investigating the influence of smoking cessation on acute (defined as pain presentation of < 3 months) and postoperative pain. The outcomes of interest included pain perception threshold, pain tolerance, pain intensity, and postoperative opioid requirements. The search strategy yielded 1478 studies, of which 13 clinical studies met our inclusion criteria. The included studies collectively represented data from 1721 participants from four countries. Of these, 43.3% of the included individuals were females. The mean age of the included subjects was 44.2 ± 8.2 years. The duration of smoking cessation varied considerably. The shortest duration was 2 h; others investigated the effect after more than 1 month of smoking cessation. Smokers had a history of 14.6 ± 9.9 years of nicotine abuse. The mean number of daily smoked cigarettes was 17.5 ± 10.3. Most studies examined in this systematic review show a negative influence of smoking cessation on acute pain. However, the affected pain modalities, the duration of the altered pain perception, and whether male and female smokers are equally affected could not be ascertained due to high heterogeneity and few available studies.

Perpetuation of Retracted Publications Using the Example of the Scott S. Reuben Case: Incidences, Reasons and Possible Improvements.

In 2009, Scott S. Reuben was convicted of fabricating data, which lead to 25 of his publications being retracted. Although it is clear that the perpetuation of retracted articles negatively effects the appraisal of evidence, the extent to which retracted literature is cited had not previously been investigated. In this study, to better understand the perpetuation of discredited research, we examine the number of citations of Reuben's articles within 5 years of their retraction. Citations of Reuben's retracted articles were assessed using the Web of Science Core Collection (Thomson Reuters, NY). All citing articles were screened to discriminate between articles in which Reuben's work was quoted as retracted, and articles in which his data was wrongly cited without any note of the retraction status. Twenty of Reuben's publications had been cited 274 times between 2009 and 1024. In 2014, 45 % of the retracted articles had been cited at least once. In only 25.8 % of citing articles was it clearly stated that Reuben's work had been retracted. Annual citations decreased from 108 in 2009 to 18 in 2014; however, the percentage of publications correctly indicating the retraction status also declined. The percentage of citations in top-25 %-journals, as well as the percentage of citations in journals from Reuben's research area, declined sharply after 2009. Our data show that even 5 years after their retraction, nearly half of Reuben's articles are still being quoted and the retraction status is correctly mentioned in only one quarter of the citations.

Fentanyl for the treatment of tumor-related breakthrough pain.

BACKGROUND: Breakthrough cancer pain (BTCP) is common among cancer patients and markedly lowers their quality of life. The treatment for BTCP episodes that is recommended in current guidelines involves extended-release formulations in combination with rapid-onset and short-acting opioids. In the past few years, several new preparations of fentanyl, an opioid with a very rapid onset, have been approved for this indication. Treating physicians need to be aware of the clinical differences between the newer fentanyl preparations and immediate-release opioids. METHODS: We searched the PubMed and Embase databases for randomized controlled trials (RCTs) of fentanyl for buccal, sublingual or intranasal administration in comparison with other opioids or a different fentanyl preparation for the treatment of BTCP. RESULTS: In 6 trials of buccal, sublingual or intranasal fentanyl versus oral immediate-release opioids for the treatment of BTCP episodes, the use of fentanyl was associated with significantly less intense pain. In particular, fentanyl more often lowered the intensity of pain by at least 33% (range between studies: 13% to 57%) or by at least 50% (range between studies: 9% to 38%) within 15 minutes. Please change to "versus" if you agree.] Dose titration should begin at the lowest dose. When one fentanyl preparation is exchanged for another, the effective dose will probably differ. CONCLUSION: The newer fentanyl preparations extend the treatment options for BTCP. They relieve pain within a short time better than conventional, immediate-release oral opioids do and may therefore be very helpful for patients with suddenly arising, intense, and short-lasting BTCP episodes. Further comparative trials are urgently needed.