Risk of Bias and Quality of Reporting in Colon and Rectal Cancer Systematic Reviews Cited by National Comprehensive Cancer Network Guidelines.

INTRODUCTION: Given the changing landscape of colorectal cancer, systematic reviews are likely to play a key role in advancing the understanding of prevention, diagnosis, and treatment. METHODS: We conducted a cross-sectional investigation of the risk of bias and reporting quality of systematic reviews referenced by colon and rectal cancer National Comprehensive Cancer Network (NCCN) guidelines. We used two widely accepted tools: Risk of Bias in Systematic reviews (ROBIS) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Using ROBIS, only 3 (4.8%) systematic reviews were judged with low risk of bias, 35 (55.6%) systematic reviews were judged with unclear risk of bias, and 25 (39.7%) systematic reviews were judged with high risk of bias. Across all systematic reviews, the individual bias domains at the highest risk of bias were domains 1 (protocol and eligibility criteria) and 2 (methods to identify and select studies). Across all studies, the median adherence to PRISMA was 74.1% (IQR 69.2-80.0%), corresponding to approximately 20 of 27 items. CONCLUSIONS: Systematic reviews cited in NCCN guidelines for colon and rectal cancer are frequently at unclear or high risk of bias and do not report key systematic review items that are important for the critical appraisal of results.

Comparison of conference abstracts and full-text publications of randomized controlled trials presented at four consecutive World Congresses of Pain: Reporting quality and agreement of results.

BACKGROUND: Conference abstracts are a potential source of new and relevant information about randomized controlled trials (RCTs). However, their dependability is questionable. The objectives of this study were to quantify the agreement between results of RCTs reported in abstracts presented at the four most recent World Congresses on Pain (WCP) and their corresponding full publications, and to analyse the completeness of reporting in those abstracts. METHODS: To identify RCTs, we screened all abstracts presented at four WCPs from 2008 to 2014. Two independent authors identified corresponding full-text reports published through August 2016. Data about the main outcomes in each abstract and full publication were extracted, including the outcome domains and numerical results reported. We reported discordance between abstracts and full texts. We evaluated abstracts against the CONSORT for Abstracts checklist. RESULTS: Approximately half of the 614 included abstracts had been fully published. Among the 306 abstract/publication pairs, eight pairs were not evaluable, and in the remaining 298 we found some form of discordance in 31% of the cases; the majority of discordances were quantitative, i.e. numerical results were different in the two locations, but with the same direction of effect. In the abstract-publication pairs where the abstract presented only preliminary/interim results, 79% had some form of discordance, mostly quantitative. CONCLUSIONS: The reporting quality of the 614 abstracts was suboptimal; the median adherence across all domains for all abstracts was 26%. In conclusion, conference abstracts of pain research are often not necessarily dependable information. Authors should be required to report abstracts according to reporting guidelines. SIGNIFICANCE: Abstracts of RCTs addressing pain are not often dependable information sources; half of them are not published, their reporting quality is suboptimal. When published, 30% of abstracts-full text pairs have discordant results, with 78% discordance when abstracts present preliminary results.

The use of systematic reviews to justify anaesthesiology trials: A meta-epidemiological study.

AIMS: New randomized clinical trials (RCTs) should be initiated if previous systematic reviews (SRs) indicate that new trials are needed. We analysed whether RCTs published in anaesthesiology journals mentioned previous SRs as a rationale for conducting trial and for discussing results. METHODS: This was a meta-epidemiological, descriptive cross-sectional study. We analysed RCTs published in the seven first-quartile anaesthesiology journals between 2014 and 2016. We studied text and bibliography of the RCTs to assess whether the authors made a reference to previous SRs when justifying the need for their own clinical trial and discussing the results. RESULTS: In the 622 studied RCTs 126 (20%) mentioned verbatim or cited one or more SRs as justification for conducting a trial, most commonly in introduction of a manuscript. Almost half of the included RCTs (44%) did not cite a single systematic review. There was no significant difference between the years in the number of explicitly mentioned SRs as justification for conducting a trial (F = 0.540, p = 0.583). Trials citing, mentioning or explicitly using SRs as a justification were published in journals with significantly higher impact factor and included significantly higher number of participants, while there was no difference in using SRs in trials in terms of funding type, type of intervention or positive versus negative results. CONCLUSIONS: Trialists should use evidence from existing SRs for planning a trial, while ethics committees, peer-reviewers and editors should require authors to provide evidence that a new trial is indeed necessary. SIGNIFICANCE: Since less than a fifth of trials published in high-impact journals in the field of anaesthesiology explicitly mention previous systematic review as a justification for conducting the trial, authors, ethics committees, editors and peer-reviewers need to increase their awareness of the need for proper justification regarding the necessity for a new trial.

Sharing of prescription analgesics amongst patients in family practice: Frequency and associated factors.

OBJECTIVE: To analyse the frequency of nonrecreational prescription analgesic sharing, associated factors and differences between lenders and borrowers. METHODS: A cross-sectional study was conducted in 10 outpatient family medicine practices in Croatia amongst 1000 patients to whom their physicians have prescribed analgesics at least once in their lives. A questionnaire was used to collect data about patients' pain intensity, prescription analgesic sharing habits, factors associated with this behaviour, perception of risks associated with the conduct and demographic data. Logistic regression was conducted to analyse independent factors associated with lending and borrowing prescription analgesics. RESULTS: We found that 61% of patients in family medicine practices engage in sharing prescription analgesics, whether it was lending (42%) and/or borrowing (54%). Independent predictors of lending prescription analgesics were as follows: history of sharing prescription medication other than analgesics, providing information regarding the medication alongside the prescription medication itself, not reading package insert that accompanies medication, subjective perception of personal health and decreased awareness of personal harm associated with prescription analgesic sharing. Independent predictors of prescription analgesic borrowing were as follows: younger age, communicating details regarding the medication that was given, scanning of package insert accompanying the medication, biased subjective perception of personal health and perceiving alternative medicine as a safer option over conventional medicine. CONCLUSIONS: Sharing prescription analgesics is highly prevalent amongst patients in family medicine. Healthcare providers should remain alert by routinely questioning patients regarding such behaviours. Preventive interventions should be conceived and established. SIGNIFICANCE: Sharing of prescription analgesics is a highly prevalent behaviour amongst pain patients, and there exist independent factors associated with such conduct. This information can be useful in the design of interventions aimed at mitigating analgesic sharing behaviour in the future.

The effects of intraganglionic injection of calcium/calmodulin-dependent protein kinase II inhibitors on pain-related behavior in diabetic neuropathy.

Calcium/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the transmission of nociceptive input in diabetic neuropathy. The aim of this study was to test whether intraganglionic (i.g.) injection of CaMKII inhibitors may alleviate pain-related behavior in diabetic rats. Diabetes was induced in Sprague-Dawley rats using 55 mg/kg streptozotocin intraperitoneally. Two weeks after diabetes induction, CaMKII inhibitors myristoil-AIP and KN93 were injected directly into the right L5 dorsal root ganglion (DRG). Behavioral testing with mechanical and thermal stimuli was performed before induction of diabetes, the day preceding the injection, as well as 2 and 24h after the i.g. injection. The expression of total CaMKII and its alpha isoform in DRG neurons was analyzed using immunohistochemistry. CaMKII inhibitors attenuated pain-related behavior in a modality-specific fashion. Attenuation of nociceptive behavior was accompanied with a corresponding decrease of CaMKII alpha expression in DRG neurons on the side of injection. A significant decrease of CaMKII alpha expression was seen in small- and medium-sized neurons. In conclusion, our study provides evidence that CaMKII inhibitors are potential pharmacological agents that should be further explored for treatment of diabetic neuropathy symptoms.

Attenuation of pain-related behaviour evoked by carrageenan injection through blockade of neuropeptide Y Y1 and Y2 receptors.

BACKGROUND: It is well known that neuropeptide Y (NPY) participates in the modulation of chronic pain, but its exact role has not yet been fully explained. In this study, we explored whether targeted delivery of NPY and its antagonists into dorsal root ganglion (DRG) modulates pain-related behaviour in rats with experimentally induced inflammatory nociception. METHODS: Inflammatory nociception was induced by intraplantar carrageenan injection. Immediately after carrageenan injection, NPY or its antagonists were injected directly into DRG. Behavioural testing was performed on the day preceding the carrageenan injection and four times (5 h after, on the first, fifth and eighth days) following the injection. Immunohistochemical analysis was performed 8 days following the surgery. RESULTS: Our results showed that NPY, applied directly to DRG, induced cold allodynia in carrageenan inflammatory pain model. NPY in carrageenan-injected rats did not additionally exacerbate activation of satellite cells in DRG and astrocytes in dorsal horn caused by intraplantar carrageenan injection. However, application of NPY Y1 and Y2 antagonists directly into DRG reversed carrageenan proalgesic effects and reduced gliosis in DRG and dorsal horn. CONCLUSION: These findings indicate an important link between pain-related behaviour and neuroimmune actions of NPY Y1 and Y2 receptors.