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Background: Recent clinical trials and guideline updates have highlighted the efficacy and safety of sodium-glucose cotransporter-2 inhibitor (SGLT2i) use in patients with type 2 diabetes (T2D) and comorbidities including atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or heart failure (HF). Objective: This study assesses the rates of guideline-based prescribing of SGLT2i in patients with T2D and one or more of the following comorbidities: ASCVD, CKD, or HF, prior to and after the 2022 American Diabetes Association (ADA) guideline publication within the Atrius Health clinical pharmacy, internal medicine, and specialty medicine departments. Methods: This is a retrospective chart review of data from the electronic medical record. Patients with the aforementioned criteria were included if they were managed by either the clinical pharmacy department, internal medicine, or specialty medicine departments. Patients were excluded if they did not have any of the comorbidities listed or a form of diabetes other than T2D. Results: Of the 10,631 patients enrolled, 354 (3.3%) were initiated on an SGLT2i during the study. The average number of SGLT2i initiations prior to the 2022 ADA guideline publication was five prescription starts per week. After the guideline publication initiation increased to seven prescription starts per week. Secondary outcomes showed the majority of SGLT2i prescriptions were started in the internal medicine department, followed by cardiology and nephrology. Conclusion: Overall utilization rates of SGLT2i are low but increased after the 2022 ADA guidelines were published. These results suggest opportunities to optimize the use of SGLT2i in this patient population. [ABSTRACT FROM AUTHOR]

The Cochrane Library of Systematic Reviews is published monthly online (http://www.thecochranelibrary.com). The library currently contains 7332 complete reviews and 2520 protocols for reviews in production. In addition, there are citations of 1,055,253 randomized controlled trials and 15,764 cited papers in the Cochrane Methodology Register. The Health Technology Assessment database contains some 17,000 citations. The impact factor of the Cochrane Library stands at 6.1. This report attempted to identify all relevant reviews published in the 2 months to May 31, 2017. Eight reviews have been identified that have potential relevance for practitioners in pain and palliative medicine. Readers are encouraged to access the full report for any articles of interest, as only a brief commentary is provided. [ABSTRACT FROM AUTHOR]

Opioids are the foundation of standard analgesic regimens for moderate to severe pain due to life-threatening illnesses such as cancer, and are increasingly employed in chronic noncancer pain of the same severity. Opioids are frequently used for long periods in these populations, sometimes for years. However, side effects are common and may reduce quality of life, or become life threatening, and frequently cause patients to discontinue opioid therapy. Successful opioid therapy dictates that benefits of analgesia outweigh safety concerns. The mechanisms, incidence, and treatment or prevention of commonly reported side effects in chronic pain populations are reviewed, employing best available evidence along with empiric practice. General management strategies include switching opioids ("opioid rotation"), discontinuation of concurrent medications that exacerbate side effects, and symptomatic treatment. In addition, recently recognized adverse events that occur alter long-term opioid therapy are discussed. High-quality evidence is lacking for the treatment of most side effects, and the true incidence, underlying mechanisms, and clinical implications of long-term responses to opioid therapy are not yet fully understood. [ABSTRACT FROM AUTHOR]

Context. Opioid-induced bowel dysfunction (OBD) is characterized by constipation, incomplete evacuation, bloating, and increased gastric reflux. OBD occurs both acutely and chronically, in multiple disease states, resulting in increased morbidity and reduced quality of life. Objective. To compare the efficacy and safety of traditional and peripherally active opioid antagonists vs conventional interventions for OBD. Design. We searched MEDLINE, the Cochrane Central Register of Controlled Trials and EMBASE. Additional reports were identified from the reference lists of retrieved articles. Study Selection. Studies were included if they were randomized controlled trials that investigated the efficacy of mu-opioid antagonists for OBD. Data Extraction. Data were extracted by two independent investigators and included demographic variables, diagnoses, interventions, efficacy, and adverse events. Results of Data Synthesis. Twenty-two articles met inclusion criteria and provided data on 2,352 opioid antagonist-treated patients. The opioid antagonist investigated was alvimopan (eight studies), methylnaltrexone (six), naloxone (seven), and nalbuphine (one). Meta-analysis demonstrated that methylnaltrexone and alvimopan are efficacious in reversing opioid-induced increased gastrointestinal transit time and constipation, and that alvimopan is safe and efficacious in treating postoperative ileus. The incidence of adverse events with opioid antagonists was similar to placebo and generally reported as mild-to-moderate. Conclusions. Insufficient evidence exists for the safety or efficacy of naloxone or nalbuphine in the treatment of OBD. Long-term efficacy and safety of any of the opioid antagonists is unknown, as is the incidence or nature of rare adverse events. Alvimopan and methylnaltrexone both show promise in treating OBD, but further data will be required to fully assess their place in therapy. [ABSTRACT FROM AUTHOR]

Summary: Background: Patients may control postoperative pain by self-administration of intravenous opioids using devices designed for this purpose (patient controlled analgesia or PCA). Two previous meta-analyses found patients preferred PCA versus conventional analgesia but disclosed no differences in analgesic consumption or length of postoperative hospital stay. Results were equivocal regarding differences in pain intensity or relief between groups. We performed an updated and expanded analysis to fully explore differences between PCA and conventional analgesia. Methods: Randomized controlled trials (RCTs) were identified from MEDLINE, the Cochrane Central Register of Controlled Trials and EMBASE. RCTs that compared PCA without a continuous background infusion versus conventional parenteral analgesia and that employed pain intensity as an outcome were selected. Meta-analyses were performed of outcomes that included analgesic efficacy, analgesic consumption, patient satisfaction, length of stay and side effects. Results: PCA provides better pain control and greater patient satisfaction than conventional parenteral analgesia. Patients using PCA consume higher amounts of opioids than controls, and have a higher incidence of pruritus, but a similar incidence of other side effects. There is no difference in the length of stay. Conclusions: This review provides evidence that PCA is an efficacious alternative to conventional systemic analgesia for postoperative pain control. [Copyright &y& Elsevier]

Purpose. The pharmacotherapy and assessment of postoperative pain in general pharmacy practice settings are reviewed. Summary. Numerous factors related to all levels of society and the health care system contribute to suboptimal treatment of postoperative pain, despite awareness of this challenge for at least the past 30 years and the availability of potent analgesics and tools to help clinicians care for persons with postoperative pain. The consequences of acute pain include clinical, economic, and patient-reported outcomes; thus, improving the treatment of postoperative pain has the potential to improve health care from a broad perspective. Opioids remain the cornerstone of treatment of postoperative pain. Multimodal analgesia also has the potential to improve the pharmacotherapy of postoperative pain. In addition to the appropriate use of drugs, it is important that clinicians be comfortable with equianalgesic dosage conversion, helping ensure that analgesic-related adverse effects are minimal, assessing pain and function, and incorporating this information into patient care. Conclusion. Providing optimal management of postoperative pain is a vital goal for all health care providers. There is substantial potential for pharmacists to help meet this goal. [ABSTRACT FROM AUTHOR]

Purpose. The pharmacotherapy and assessment of postoperative pain in general pharmacy practice settings are reviewed. Summary. Numerous factors related to all levels of society and the health care system contribute to suboptimal treatment of postoperative pain, despite awareness of this challenge for at least the past 30 years and the availability of potent analgesics and tools to help clinicians care for persons with postoperative pain. The consequences of acute pain include clinical, economic, and patient-reported outcomes; thus, improving the treatment of postoperative pain has the potential to improve health care from a broad perspective. Opioids remain the cornerstone of treatment of postoperative pain. Multimodal analgesia also has the potential to improve the pharmacotherapy of postoperative pain. In addition to the appropriate use of drugs, it is important that clinicians be comfortable with equianalgesic dosage conversion, helping ensure that analgesic-related adverse effects are minimal, assessing pain and function, and incorporating this information into patient care. Conclusion. Providing optimal management of postoperative pain is a vital goal for all health care providers. There is substantial potential for pharmacists to help meet this goal. [ABSTRACT FROM AUTHOR]

Context In the United States, an estimated 2 million persons have neuropathic pain that is often resistant to therapy. The use of opioids for neuropathic pain remains controversial, in part because studies have been small, have yielded equivocal results, and have not established the long-term risk-benefit ratio of this treatment. Objective To assess the efficacy and safety of opioid agonists for the treatment of neuropathic pain based on published randomized controlled trials (RCTs). Data Sources We searched MEDLINE (1966 to December 2004) and the Cochrane Central Register of Controlled Trials (fourth quarter, 2004) for articles in any language, along with reference lists of reviews and retrieved articles, using a combination of 9 search terms for RCTs with 32 terms for opioids and 15 terms for neuropathic pain. Study Selection Trials were included in which opioid agonists were given to treat central or peripheral neuropathic pain of any etiology, pain was assessed using validated instruments, and adverse events were reported. Studies in which drugs other than opioid agonists were combined with opioids or opioids were administered epidurally or intrathecally were excluded. Data Extraction Data were extracted by 2 independent investigators and included demographic variables, diagnoses, interventions, efficacy, and adverse effects. Data Synthesis Twenty-two articles met inclusion criteria and were classified as short-term (less than 24 hours; n = 14) or intermediate-term (median = 28 days; range = 8-56 days; n = 8) trials. The short-term trials had contradictory results. In contrast, all 8 intermediate-term trials demonstrated opioid efficacy for spontaneous neuropathic pain. A fixed-effects model meta-analysis of 6 intermediate-term studies showed mean posttreatment visual analog scale scores of pain intensity after opioids to be 14 units lower on a scale from 0 to 100 than after placebo (95% confidence interval [CI], -18 to -10; P<.001). According to number needed to harm (NNH), the most common adverse event was nausea (NNH, 3.6; 95% CI, 2.9-4.8), followed by constipation (NNH, 4.6; 95% CI, 3.4-7.1), drowsiness (NNH, 5.3; 95% CI, 3.7-8.3), vomiting (NNH, 6.2; 95% CI, 4.6-11.1), and dizziness (NNH, 6.7; 95% CI, 4.8-10.0). Conclusions Short-term studies provide only equivocal evidence regarding the efficacy of opioids in reducing the intensity of neuropathic pain. Intermediate-term studies demonstrate significant efficacy of opioids over placebo for neuropathic pain, which is likely to be clinically important. Reported adverse events of opioids are common but not life-threatening. Further RCTs are needed to establish their long-term efficacy, safety (including addiction potential), and effects on quality of life. [ABSTRACT FROM AUTHOR]

Summary: Postoperative pain and functioning after hospital discharge has been incompletely described. The purpose of this pilot prospective cohort study was to describe postoperative pain, health-related quality of life, and functioning 1 month after participants left the hospital. Participants underwent radical prostatectomy (RP), total hip replacement (THR), or total knee replacement (TKR), and completed the SF-36 and questions from the Treatment Outcomes of Pain Survey (TOPS) 4 weeks after leaving the hospital to go home. Participants’ SF-36 scale scores were compared to US norms. Thirty persons participated in this study, 15 following RP, 8 after TKR, and 7 after THR. Participants’ mean SF-36 scale scores in each surgical group were lower than US norms for physical functioning, physical roles, bodily pain, vitality and social functioning, and also on the emotional roles and mental health scales for the RP and TKR groups. Postoperative pain interfered with participants’ ability to participate in desired activities (42.9% RP, 28.6% THR, 100% TKR), ability to sleep (21.4% RP, 71.4% THR, 75% TKR), and with normal sexual functioning (50% RP, 28.6% THR, 25% TKR). During the first month after surgery, postoperative pain contributed to diminished health-related quality of life and interfered with activities considered important to patients. [Copyright &y& Elsevier]

Abstract: Persistent postsurgical pain (PPSP) is common after breast and thoracic surgeries. Understanding which risk factors consistently contribute to PPSP will allow clinicians to apply preventive strategies, as they emerge, to high-risk patients. The objective of this work was to systematically review and meta-analyze the literature on risk factors of PPSP after breast and thoracic surgeries. A systematic literature search using Ovid Medline, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Embase, PsycINFO, and Scopus databases was conducted. Study screening with inclusion and exclusion criteria, data extraction, and risk of bias assessment was performed independently by 2 authors. The data for each surgical group were analyzed separately and meta-analyzed where possible. The literature search yielded 5584 articles, and data from 126 breast surgery and 143 thoracic surgery articles were considered for meta-analysis. In breast surgery, younger age, higher body mass index, anxiety, depression, diabetes, smoking, preoperative pain, moderate to severe acute postoperative pain, reoperation, radiotherapy, and axillary lymph node dissection were the main factors associated with higher risk of PPSP. In thoracic surgery, younger age, female sex, hypertension, preoperative pain, moderate to severe acute postoperative pain, surgical approach, major procedure, and wound complications were associated with PPSP. This systematic review demonstrated certain consistent risk factors of PPSP after breast and thoracic surgeries, as well as identified research gaps. Understanding the factors that increase susceptibility to PPSP can help selectively allocate resources to optimize perioperative care in high-risk patients and help develop targeted, risk-stratified interventions for PPSP prevention. [ABSTRACT FROM AUTHOR]

The aims of this review were to systematically identify the current evidence base of placebo (or "sham") randomised controlled trials (RCTs) of spinal cord stimulation (SCS) for neuropathic pain and to undertake a meta-analysis to investigate the effectiveness of SCS when compared with a placebo comparator arm. Electronic databases were searched from inception until January 2019 for RCTs of SCS using a placebo/sham control. Searches identified 8 eligible placebo-controlled randomised trials of SCS for neuropathic pain. Meta-analysis shows a statistically significant reduction in pain intensity during the active stimulation treatment periods compared with the control treatment periods, pooled mean difference -1.15 (95% confidence interval -1.75 to -0.55, P = 0.001) on a 10-point scale. Exploratory study-level subgroup analysis suggests a larger treatment effect in RCTs using a placebo control (defined as studies where the device was inactive and at least one of the study procedures was different between the arms) than a sham control (defined as all study procedures being equal between arms including SCS device behaviour). Our findings demonstrate limited evidence that SCS is effective in reducing pain intensity when compared with a placebo intervention. Our analyses suggest that the magnitude of treatment effect varies across trials and, in part, depends on the quality of patient blinding and minimisation of carryover effects. Improved reporting and further methodological research is needed into placebo and blinding approaches in SCS trials. Furthermore, we introduce a differentiation between placebo and sham concepts that may be generalisable to trials evaluating surgical or medical procedures. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Inconsistencies in Opioid Equianalgesic Ratios: Clinical and Research Implications," by C. L. O'Bryant in a 2008 issue.

Abstract: The interest and the rationale for meaningful engagement of patients as partners in clinical trials of pain treatments has been increasing. No specific guidance on patient engagement for pain research studies currently exists; thus, the goal of this narrative review was to provide a historical perspective and a current evaluation of the literature on engaging patients as partners in clinical studies in general and in pain-related studies more specifically. We described how regulatory and funding agencies have developed approaches to incorporate input from patients and patient partners in their decision-making processes. We provided an overview on key practices of patient recruitment and engagement as partners in clinical research and highlighted the perceived benefits and challenges of such partnerships. We summarized factors that can facilitate or hinder meaningful patient engagement in clinical trials of pain treatments and outlined gaps that future research should address to optimize patient-centered clinical research. [ABSTRACT FROM AUTHOR]

Background and Aims: Prospective trial registration can increase research integrity. This Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) review was designed to compare the primary outcomes (PO) reported in registries with associated publications for opioid use disorder (OUD) clinical trials.Design: The World Health Organization's International Clinical Trials Registry Platform (ICTRP) was searched for completed trials (2010 through 2019). Associated publications were identified and paired with trial registry data based on the publication date.Measurements: Reviewers independently rated the occurrence of discrepancies between the POs in the registry compared to the publication. An analysis of prospective versus retrospective registration was also completed.Findings: One-hundred and forty trials were identified in the search, and 43 registry-publication pairs evaluated. Only 34 of the 43 pairs could be examined for discrepancies because nine did not report a PO in registry and publication. Of the 34 pairs, only four met rigorous criteria for prospective trial registration and had an exact match of POs. In contrast, the majority of the 34 trials, or 80%, had inconsistent POs (e.g., registered secondary outcomes published as primary; the timing of PO not specified) and/or were retrospectively registered.Conclusions: Many clinical trials focused on OUD have not met the standards of trial registration, such as consistent reporting of POs and prospective registration. Failure to properly register trial characteristics undermines the validity of research findings and can delay the development of life-saving treatments. Recommendations for improving prospective trial reporting practices are provided. [ABSTRACT FROM AUTHOR]

The article focuses on prevalence of comorbid chronic pain conditions among patients with temporomandibular disorders.

Abstract: Pragmatic randomised clinical trials aim to directly inform clinical or health policy decision making. Here, we systematically review methods and design of pragmatic trials of pain therapies to examine methods, identify common challenges, and areas for improvement. Seven databases were searched for pragmatic randomised controlled clinical trials that assessed pain treatment in a clinical population of adults reporting pain. All screening steps and data extractions were performed twice. Data were synthesised descriptively, and correlation analyses between prespecified trial features and PRECIS-2 (PRagmatic-Explanatory Continuum Indicator Summary 2) ratings and attrition were performed. Protocol registration: PROSPERO-ID CRD42020178954. Of 57 included trials, only 21% assessed pharmacological interventions, the remainder physical, surgical, psychological, or self-management pain therapies. Three-quarters of the trials were comparative effectiveness designs, often conducted in multiple centres (median: 5; Q1/3: 1, 9.25) and with a median sample size of 234 patients at randomization (Q1/3: 135.5; 363.5). Although most trials recruited patients with chronic pain, reporting of pain duration was poor and not well described. Reporting was comprehensive for most general items, while often deficient for specific pragmatic aspects. Average ratings for pragmatism were highest for treatment adherence flexibility and clinical relevance of outcome measures. They were lowest for patient recruitment methods and extent of follow-up measurements and appointments. Current practice in pragmatic trials of pain treatments can be improved in areas such as patient recruitment and reporting of methods, analysis, and interpretation of data. These improvements will facilitate translatability to other real-world settings-the purpose of pragmatic trials. [ABSTRACT FROM AUTHOR]

Objectives: Spinal cord stimulation (SCS) is a recognized treatment for chronic pain. This systematic review aims to assess economic evaluations of SCS for the management of all chronic pain conditions, summarize key findings, and assess the quality of studies to inform healthcare resource allocation decisions and future research.Methods: Economic evaluations were identified by searching general medical and economic databases complemented with screening of reference lists of identified studies. No restrictions on language or treatment comparators were applied. Relevant data were extracted. The quality of included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist.Results: Fourteen studies met the inclusion criteria and were judged to be of acceptable quality. Economic evaluations assessed SCS for the management of refractory angina pectoris, failed back surgery syndrome (FBSS), complex regional pain syndrome (CRPS), diabetic peripheral neuropathy (DPN), and peripheral arterial disease. Model-based studies typically applied a 2-stage model, i.e. decision tree followed by Markov model. Time horizon varied from 1 year to lifetime. Cost-effectiveness ranged widely from dominant (SCS cost-saving and more effective) to incremental cost-effectiveness ratio of >£100,000 per quality-adjusted life-year. Cost-effectiveness appeared to depend on the time horizon, choice of comparator, and indication. Ten of the studies indicated SCS as cost-saving or cost-effective compared with the alternative strategies.Conclusion: The results consistently suggest that SCS is cost-effective when considering a long-term time horizon, particularly for the management of FBSS and CRPS. Further studies are needed to assess the cost-effectiveness of SCS for ischemic pain and DPN. [ABSTRACT FROM AUTHOR]

Multiple recent pharmacological clinical trials in neuropathic pain have failed to show beneficial effect of drugs with previously demonstrated efficacy, and estimates of drug efficacy seems to have decreased with accumulation of newer trials. However, this has not been systematically assessed. Here, we analyze time-dependent changes in estimated treatment effect size in pharmacological trials together with factors that may contribute to decreases in estimated effect size. This study is a secondary analysis of data from a previous published NeuPSIG systematic review and meta-analysis, updated to include studies published up till March 2017. We included double-blind, randomized, placebo-controlled trials examining the effect of drugs for which we had made strong or weak recommendations for use in neuropathic pain in the previously published review. As the primary outcome, we used an aggregated number needed to treat for 50% pain reduction (alternatively 30% pain reduction or moderate pain relief). Analyses involved 128 trials. Number needed to treat values increased from around 2 to 4 in trials published between 1982 and 1999 to much higher (less effective) values in studies published from 2010 onwards. Several factors that changed over time, such as larger study size, longer study duration, and more studies reporting 50% or 30% pain reduction, correlated with the decrease in estimated drug effect sizes. This suggests that issues related to the design, outcomes, and reporting have contributed to changes in the estimation of treatment effects. These factors are important to consider in design and interpretation of individual study data and in systematic reviews and meta-analyses. [ABSTRACT FROM AUTHOR]

Summary Background New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis. Methods Between April, 2013, and January, 2014, NeuPSIG of the International Association for the Study of Pain did a systematic review and meta-analysis of randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January, 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies. We used number needed to treat (NNT) for 50% pain relief as a primary measure and assessed publication bias; NNT was calculated with the fixed-effects Mantel-Haenszel method. Findings 229 studies were included in the meta-analysis. Analysis of publication bias suggested a 10% overstatement of treatment effects. Studies published in peer-reviewed journals reported greater effects than did unpublished studies ( r 2 9·3%, p=0·009). Trial outcomes were generally modest: in particular, combined NNTs were 6·4 (95% CI 5·2–8·4) for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine (nine of 14 studies); 7·7 (6·5–9·4) for pregabalin; 7·2 (5·9–9·21) for gabapentin, including gabapentin extended release and enacarbil; and 10·6 (7·4–19·0) for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A, and undetermined for lidocaine patches. Based on GRADE, final quality of evidence was moderate or high for all treatments apart from lidocaine patches; tolerability and safety, and values and preferences were higher for topical drugs; and cost was lower for tricyclic antidepressants and tramadol. These findings permitted a strong recommendation for use and proposal as first-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only. Interpretation Our results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain. Inadequate response to drug treatments constitutes a substantial unmet need in patients with neuropathic pain. Modest efficacy, large placebo responses, heterogeneous diagnostic criteria, and poor phenotypic profiling probably account for moderate trial outcomes and should be taken into account in future studies. Funding NeuPSIG of the International Association for the Study of Pain. [ABSTRACT FROM AUTHOR]

Abstract: Study Objective: To assess platelet function and safety following single-dose administration of a novel formulation of intravenous (IV) diclofenac sodium (Dyloject) 37.5 mg versus oral diclofenac 50 mg, IV ketorolac 30 mg, and oral acetylsalicylic acid (ASA) 325 mg. Design: Open-label, randomized, single-dose, 4-treatment crossover study. Setting: Clinical research unit. Patients: 30 healthy, ASA physical status I adult men. Interventions: Subjects were randomized to one of 6 treatment sequences that included 4 single-dose treatments. Study drug administration occurred on Days 1, 3, 5, and 7. Measurements: Platelet count, closure time as measured by platelet function analyzer (PFA-100), prothrombin time (PT), activated partial thromboplastin time (aPTT), and plasma concentrations of the study drugs were obtained over 24 hours after each treatment. The primary endpoint was the area under the curve for PFA collagen-epinephrine (CEPI) closure time difference from 0-6 hours post-drug administration (AUC0-6h). Secondary endpoints included the maximum change from baseline in PFA CEPI closure time. Main Results: AUC0-6h (mean ± SD) for CEPI closure time difference was significantly smaller after IV diclofenac 37.5 mg (249 ± 216 sec.hrs) than after ketorolac [and ASA (950 ± 287 sec.hrs and 834 ± 237 sec.hrs, respectively); P ≤ 0.0001 for both] but not after the oral diclofenac control (286 ± 265 sec.hrs; P = 0.40). Similarly, the maximum change from baseline in PFA CEPI closure time was lower after IV diclofenac than after ketorolac or ASA across all time intervals examined. There were no significant changes in PT or aPTT at any time point with any treatment. There was a low frequency of adverse events. Conclusions: Acetylsalicylic acid and ketorolac both substantially disrupted platelet function in contrast to IV diclofenac 37.5 mg or oral diclofenac 50 mg control. Diclofenac, with its balanced COX-1 and COX-2 inhibitory profile, may pose less risk of postoperative bleeding than nonsteroidal antiinflammatory drugs (NSAIDs) such as ketorolac and ASA, which predominantly inhibit COX-1. [Copyright &y& Elsevier]

Introduction. Parenteral opioids are the standard of care for treating moderate to severe postsurgical pain. This randomized, double-blind, dose-ranging study compared the safety and efficacy of intranasal (IN) morphine with intravenous (IV) morphine and placebo. Methods. In total, 187 postbunionectomy patients with moderate to severe pain were randomized to receive IN morphine 3.75 mg, 7.5 mg, 15 mg, or 30 mg, IV morphine 7.5 mg, or placebo in the single-dose phase and IN morphine 7.5 mg or 15 mg thereafter. The primary outcome was a dose–response assessment for total pain relief based upon visual analog scales. Secondary endpoints included pain intensity, pain relief, patient global evaluation, and time to rescue medication. Safety assessments included adverse events and nasal examination. Results. A statistically significant linear dose response was observed over the IN morphine dose range for 4-hour total pain relief. Patients reported statistically significant pain relief and pain intensity differences following IV morphine and IN morphine at doses of 7.5 mg and greater within 30 minutes postdose, compared with placebo. Median times to rescue medication were 124 and 140 minutes for IN morphine 7.5 mg and 15 mg dosage groups, respectively, and 130 minutes for IV morphine. Local adverse events associated with IN morphine were transient and mostly mild (bad taste, nasal congestion, throat irritation, and sneezing). Systemic adverse events, regardless of route of administration, were dose-related and consistent with expected opioid effects. Conclusions. By multiple measures of pain intensity and pain relief, IN morphine provides sustained analgesia in postsurgical patients and thus may offer a safe and less invasive alternative to IV morphine. [ABSTRACT FROM AUTHOR]