Characteristics of retracted publications related to pain research: a systematic review.

ABSTRACT: Retraction is a mechanism for correcting the scientific record and alerts readers when a study contains unreliable or flawed data. Such data may arise from error or research misconduct. Studies examining the landscape of retracted publications provide insight into the extent of unreliable data and its effect on a medical discipline. We aimed to explore the extent and characteristics of retracted publications in pain research. We searched the EMBASE, PubMed, CINAHL, PsycINFO, and Retraction Watch databases to December 31, 2022. We included retracted articles that (1) investigated mechanisms of painful conditions, (2) tested treatments that aimed to reduce pain, or (3) measured pain as an outcome. Descriptive statistics were used to summarise the included data. We included 389 pain articles published between 1993 and 2022 and retracted between 1996 and 2022. There was a significant upward trend in the number of retracted pain articles over time. Sixty-six percent of articles were retracted for reasons relating to misconduct. The median (interquartile range) time from article publication to retraction was 2 years (0.7-4.3). The time to retraction differed by reason for retraction, with data problems, comprising data falsification, duplication, and plagiarism, resulting in the longest interval (3 [1.2-5.2] years). Further investigations of retracted pain articles, including exploration of their fate postretraction, are necessary to determine the impact of unreliable data on pain research.

Perspectives on Participation in Clinical Trials Among Individuals With Pain, Depression, and/or Anxiety: An ACTTION Scoping Review.

For individuals experiencing pain, the decision to engage in clinical trials may be influenced by a number of factors including current and past care, illness severity, physical functioning, financial stress, and caregiver support. Co-occurring depression and anxiety may add to these challenges. The aim of this scoping review was to describe perspectives about clinical trial participation, including recruitment and retention among individuals with pain and pain comorbidities, including depression and/or anxiety. We searched PubMed, CINAHL, PsycINFO, and Cochrane CENTRAL databases. Study features, sample demographics, perspectives, barriers and/or motivations were collected and described. A total of 35 assessments were included in this scoping review with 24 focused on individuals with pain (24/35, 68.6%), 9 on individuals with depression and/or anxiety (9/35, 25.7%), and 2 on individuals with pain and co-occurring depression/anxiety (2/35, 5.7%). Barriers among participants with pain and those with depression included: research team's communication of information, fear of interventional risks, distrust (only among respondents with pain), too many procedures, fear of inadequate treatment, disease-life stressors, and embarrassment with study procedures (more commonly reported in participants with depression). Facilitators in both groups included: altruism and supportive staff, better access to care, and the ability to have outcome feedback (more commonly among individuals with depression). Individuals with pain and depression experience challenges that affect trial recruitment and retention. Engaging individuals with pain within research planning may assist in addressing these barriers and the needs of individuals affected by pain and/or depression. PERSPECTIVE: This review highlights the need to address barriers and facilitators to participation in clinical trials, including the need for an assessment of perspectives from underserved or marginalized populations.

A comparison of registered and published primary outcomes in clinical trials of opioid use disorder: ACTTION review and recommendations.

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.

The prevalence of comorbid chronic pain conditions among patients with temporomandibular disorders: A systematic review.

BACKGROUND: This systematic review was designed to evaluate the presence of comorbid conditions among patients with temporomandibular disorders (TMDs). TYPES OF STUDIES REVIEWED: The authors reviewed studies that reported the prevalence or incidence of chronic pain conditions or psychiatric disorders (anxiety, mood, personality disorders) among patients with any type of TMD. The authors calculated sample size-weighted prevalence estimates when data were reported in 2 or more studies for the same comorbid condition. RESULTS: A total of 9 prevalence studies and no incidence studies were eligible for review; 8 of the studies examined chronic pain comorbidities. Weighted estimates showed high prevalence of pain comorbidities across studies, including current chronic back pain (66%), myofascial syndrome (50%), chronic stomach pain (50%), chronic migraine headache (40%), irritable bowel syndrome (19%), and fibromyalgia (14%). A single study examined psychiatric disorders and found that current depression was the most prevalent disorder identified (17.5%). CONCLUSIONS AND PRACTICAL IMPLICATIONS: There is a high prevalence of comorbid chronic pain conditions among patients with TMDs, with more than 50% of patients reporting chronic back pain, myofascial syndrome, and chronic stomach pain. Psychiatric disorders among patients with different types of TMDs were studied less commonly in this pain population. Knowledge of the distribution of these and other comorbid disease conditions among patients with different types of TMDs can help dentists and other health care providers to identify personalized treatment strategies, including the coordination of care across medical specialties.

Single-dose intravenous ibuprofen for acute postoperative pain in adults.

BACKGROUND: Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, may reduce the incidence and severity of opioid-induced adverse events (AEs). OBJECTIVES: To assess the analgesic efficacy and adverse effects of single-dose intravenous (IV) ibuprofen, compared with placebo or an active comparator, for moderate-to-severe postoperative pain in adults. SEARCH METHODS: We searched the following databases without language restrictions: CENTRAL, MEDLINE, Embase and LILACS on 10 June 2021. We checked clinical trials registers and reference lists of retrieved articles for additional studies. SELECTION CRITERIA: We included randomized trials that compared a single postoperative dose of intravenous (IV) ibuprofen with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for review inclusion, assessed risk of bias, and extracted data. Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a 4- and 6-hour period. Our secondary outcomes were time to, and number of participants using rescue medication; withdrawals due to lack of efficacy, adverse events (AEs), and for any other cause; and number of participants reporting or experiencing any AE, serious AEs (SAEs), and specific NSAID-related or opioid-related AEs. We were not able to carry out any planned meta-analysis. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: Only one study met our inclusion criteria, involving 201 total participants, mostly female (mean age 42 years), undergoing primary, unilateral, distal, first metatarsal bunionectomy (with osteotomy and internal fixation). Ibuprofen 300 mg, placebo or acetaminophen 1000 mg was administered intravenously to participants reporting moderate pain intensity the day after surgery. Since we identified only one study for inclusion, we did not perform any quantitative analyses. The study was at low risk of bias for most domains. We downgraded the certainty of the evidence due to serious study limitations, indirectness and imprecision. Ibuprofen versus placebo Findings of the single study found that at both the 4-hour and 6-hour assessment period, the proportion of participants with at least 50% pain relief was 32% (24/76) for those assigned to ibuprofen and 22% (11/50) for those assigned to placebo. These findings produced a risk ratio (RR) of 1.44 (95% confidence interval (CI) 0.77 to 2.66 versus placebo for at least 50% of maximum pain relief over the 4-hour and 6-hour period (very low-certainty evidence). Median time to rescue medication was 101 minutes for ibuprofen and 71 minutes for placebo (1 study, 126 participants; very low-certainty evidence). The number of participants using rescue medication was not reported within the included study. During the study (1 study, 126 participants), 58/76 (76%) of participants assigned to ibuprofen and 39/50 (78%) assigned to placebo reported or experienced any adverse event (AE), (RR 0.98, 95% CI 0.81 to 1.19; low-certainty evidence). No serious AEs (SAEs) were experienced (1 study, 126 participants; very low-certainty evidence). Ibuprofen versus active comparators Ibuprofen (300 mg) was similar to the active comparator, IV acetaminophen (1000 mg) at 4 hours and 6 hours (1 study, 126 participants). For those assigned to active control (acetaminophen), the proportion of participants with at least 50% pain relief was 35% (26/75) at 4 hours and 31% (23/75) at 6 hours. At 4 hours, these findings produced a RR of 0.91 (95% CI 0.58 to 1.43; very low-certainty evidence) versus active comparator (acetaminophen). At 6 hours, these findings produced a RR of 1.03 (95% CI 0.64 to 1.66; very low-certainty evidence) versus active comparator (acetaminophen). Median time to rescue medication was 101 minutes for ibuprofen and 125 minutes for the active comparator, acetaminophen (1 study, 151 participants; very low-certainty evidence). The number of participants using rescue medication was not reported within the included study. During the study, 8/76 (76%) of participants assigned to ibuprofen and 45/75 (60%) assigned to active control (acetaminophen) reported or experienced any AE, (RR 1.27, 95% CI 1.02 to 1.59; very low-certainty evidence). No SAEs were experienced (1 study, 151 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: There is insufficient evidence to support or refute the suggestion that IV ibuprofen is effective and safe for acute postoperative pain in adults.

Single-dose intravenous ketorolac for acute postoperative pain in adults.

BACKGROUND: Postoperative pain is common and may be severe. Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, may reduce the incidence and severity of opioid-induced adverse events (AEs). OBJECTIVES: To assess the analgesic efficacy and adverse effects of single-dose intravenous ketorolac, compared with placebo or an active comparator, for moderate to severe postoperative pain in adults. SEARCH METHODS: We searched the following databases without language restrictions: CENTRAL, MEDLINE, Embase and LILACS on 20 April 2020. We checked clinical trials registers and reference lists of retrieved articles for additional studies. SELECTION CRITERIA: Randomized double-blind trials that compared a single postoperative dose of intravenous ketorolac with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.  Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a four- and six-hour period. Our secondary outcomes were time to and number of participants using rescue medication; withdrawals due to lack of efficacy, adverse events (AEs), and for any other cause; and number of participants experiencing any AE, serious AEs (SAEs), and NSAID-related or opioid-related AEs. For subgroup analysis, we planned to analyze different doses of parenteral ketorolac separately and to analyze results based on the type of surgery performed. We assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 12 studies, involving 1905 participants undergoing various surgeries (pelvic/abdominal, dental, and orthopedic), with 17 to 83 participants receiving intravenous ketorolac in each study. Mean study population ages ranged from 22.5 years to 67.4 years. Most studies administered a dose of ketorolac of 30 mg; one study assessed 15 mg, and another administered 60 mg. Most studies had an unclear risk of bias for some domains, particularly allocation concealment and blinding, and a high risk of bias due to small sample size. The overall certainty of evidence for each outcome ranged from very low to moderate. Reasons for downgrading certainty included serious study limitations, inconsistency and imprecision. Ketorolac versus placebo Very low-certainty evidence from eight studies (658 participants) suggests that ketorolac results in a large increase in the number of participants achieving at least 50% pain relief over four hours compared to placebo, but the evidence is very uncertain (risk ratio (RR) 2.81, 95% confidence interval (CI) 1.80 to 4.37). The number needed to treat for one additional participant to benefit (NNTB) was 2.4 (95% CI 1.8 to 3.7). Low-certainty evidence from 10 studies (914 participants) demonstrates that ketorolac may result in a large increase in the number of participants achieving at least 50% pain relief over six hours compared to placebo (RR 3.26, 95% CI 1.93 to 5.51). The NNTB was 2.5 (95% CI 1.9 to 3.7). Among secondary outcomes, for time to rescue medication, moderate-certainty evidence comparing intravenous ketorolac versus placebo demonstrated a mean median of 271 minutes for ketorolac versus 104 minutes for placebo (6 studies, 633 participants). For the number of participants using rescue medication, very low-certainty evidence from five studies (417 participants) compared ketorolac with placebo. The RR was 0.60 (95% CI 0.36 to 1.00), that is, it did not demonstrate a difference between groups. Ketorolac probably results in a slight increase in total adverse event rates compared with placebo (74% versus 65%; 8 studies, 810 participants; RR 1.09, 95% CI 1.00 to 1.19; number needed to treat for an additional harmful event (NNTH) 16.7, 95% CI 8.3 to infinite, moderate-certainty evidence). Serious AEs were rare. Low-certainty evidence from eight studies (703 participants) did not demonstrate a difference in rates between ketorolac and placebo (RR 0.62, 95% CI 0.13 to 3.03). Ketorolac versus NSAIDs  Ketorolac was compared to parecoxib in four studies and diclofenac in two studies. For our primary outcome, over both four and six hours there was no evidence of a difference between intravenous ketorolac and another NSAID (low-certainty and moderate-certainty evidence, respectively). Over four hours, four studies (337 participants) produced an RR of 1.04 (95% CI 0.89 to 1.21) and over six hours, six studies (603 participants) produced an RR of 1.06 (95% CI 0.95 to 1.19). For time to rescue medication, low-certainty evidence from four studies (427 participants) suggested that participants receiving ketorolac waited an extra 35 minutes (mean median 331 minutes versus 296 minutes). For the number of participants using rescue medication, very low-certainty evidence from three studies (260 participants) compared ketorolac with another NSAID. The RR was 0.90 (95% CI 0.58 to 1.40), that is, there may be little or no difference between groups.   Ketorolac probably results in a slight increase in total adverse event rates compared with another NSAID (76% versus 68%, 5 studies, 516 participants; RR 1.11, 95% CI 1.00 to 1.23; NNTH 12.5, 95% CI 6.7 to infinite, moderate-certainty evidence). Serious AEs were rare. Low-certainty evidence from five studies (530 participants) did not demonstrate a difference in rates between ketorolac and another NSAID (RR 3.18, 95% CI 0.13 to 76.99). Only one of the five studies reported a single serious AE. AUTHORS' CONCLUSIONS: The amount and certainty of evidence for the use of intravenous ketorolac as a treatment for postoperative pain varies across efficacy and safety outcomes and amongst comparators, from very low to moderate. The available evidence indicates that postoperative intravenous ketorolac administration may offer substantial pain relief for most patients, but further research may impact this estimate. Adverse events appear to occur at a slightly higher rate in comparison to placebo and to other NSAIDs. Insufficient information is available to assess whether intravenous ketorolac has a different rate of gastrointestinal or surgical-site bleeding, renal dysfunction, or cardiovascular events versus other NSAIDs. There was a lack of studies in cardiovascular surgeries and in elderly populations who may be at increased risk for adverse events.

The Prevalence of Psychiatric and Chronic Pain Comorbidities in Fibromyalgia: an ACTTION systematic review.

Fibromyalgia (FM) is a chronic widespread pain condition that overlaps with multiple comorbid health conditions and contributes to considerable patient distress. The aim of this review was to provide a systematic overview of psychiatric and chronic pain comorbidities among patients diagnosed with FM and to inform the development of recommendations for the design of clinical trials. Thirty-one, cross-sectional, clinical epidemiology studies that evaluated patients diagnosed with FM were included for review. None of the reviewed studies reported on the incidence of these comorbidities. Sample size-weighted prevalence estimates were calculated when prevalence data were reported in 2 or more studies for the same comorbid condition. The most prevalent comorbidity across all studies reviewed was depression/major depressive disorder (MDD) with over half of the patients included having this diagnosis in their lifetime (weighted prevalence up to 63%). In addition, nearly one-third of FM patients examined had current or lifetime bipolar disorder, panic disorder, or post-traumatic stress disorder. Less common psychiatric disorders reported included generalized anxiety disorder, obsessive compulsive disorder, and specific phobias (agoraphobia, social phobia). There were fewer studies that examined chronic pain comorbidities among FM patients, but when evaluated, prevalence was also high ranging from 39% to 76% (i.e., chronic tension-type or migraine headache, irritable bowel syndrome, myofascial pain syndrome, and temporomandibular disorders). The results of the review suggest that depression and chronic pain conditions involving head/jaw pain and IBS were elevated among FM patients compared to other conditions in the clinic-based studies. In contrast, anxiety-related disorders were much less common. Addressing the presence of these comorbid health conditions in clinical trials of treatments for FM would increase the generalizability and real-world applicability of FM research.

Single-dose intravenous diclofenac for acute postoperative pain in adults.

BACKGROUND: Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, reduces the incidence and severity of opioid-induced adverse events (AEs). OBJECTIVES: To assess the analgesic efficacy and adverse effects of single-dose intravenous diclofenac, compared with placebo or an active comparator, for moderate to severe postoperative pain in adults. SEARCH METHODS: We searched the following databases without language restrictions: the Cochrane Central Register of Controlled Trials (Cochrane Register of Studies Online), MEDLINE, and Embase on 22 May 2018. We checked clinical trials registers and reference lists of retrieved articles for additional studies. SELECTION CRITERIA: We included randomized trials that compared a single postoperative dose of intravenous diclofenac with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for review inclusion, assessed risk of bias, and extracted data.Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a four- and six-hour period.Our secondary outcomes were time to, and number of participants using rescue medication; withdrawals due to lack of efficacy, AEs, and for any cause; and number of participants experiencing any AE, serious AEs (SAEs), and NSAID-related AEs. We performed a post hoc analysis of opioid-related AEs, to enable indirect comparisons with other analyses of postoperative analgesics.For subgroup analysis, we planned to analyze different doses and formulations of parenteral diclofenac separately.We assessed the overall quality of the evidence for each outcome using GRADE and created two 'Summary of findings' tables. MAIN RESULTS: We included eight studies, involving 1756 participants undergoing various surgeries (dental, mixed minor, abdominal, and orthopedic), with 20 to 175 participants receiving intravenous diclofenac in each study. Mean study population ages ranged from 24.5 years to 54.5 years. Intravenous diclofenac doses varied among and within studies, ranging from 3.75 mg to 75 mg. Five studies assessed newer formulations of parenteral diclofenac that could be administered as an undiluted intravenous bolus. Most studies had an unclear risk of bias for several domains and a high risk of bias due to small sample size. The overall quality of evidence for each outcome was generally low for reasons including unclear risk of bias in studies, imprecision, and low event numbers.Primary outcomeThree studies (277 participants) produced a number needed to treat for an additional beneficial outcome (NNTB) for at least 50% of maximum pain relief versus placebo of 2.4 (95% confidence interval (CI) 1.9 to 3.1) over four hours (low-quality evidence). Four studies (436 participants) produced an NNTB of 3.8 versus placebo (95% CI 2.9 to 5.9) over six hours (low-quality evidence). No studies provided data for the comparison of intravenous diclofenac with another NSAID over four hours. At six hours there was no difference between intravenous diclofenac and another NSAID (low-quality evidence).Secondary outcomesFor secondary efficacy outcomes, intravenous diclofenac was generally superior to placebo and similar to other NSAIDs.For time to rescue medication, comparison of intravenous diclofenac versus placebo demonstrated a median of 226 minutes for diclofenac versus 80 minutes for placebo (5 studies, 542 participants, low-quality evidence). There were insufficient data for pooled analysis for comparisons of diclofenac with another NSAID (very low-quality evidence).For the number of participants using rescue medication, two studies (235 participants) compared diclofenac with placebo. The number needed to treat to prevent one additional harmful event (NNTp) (here, the need for rescue medication) compared with placebo was 3.0 (2.2 to 4.5, low-quality evidence). The comparison of diclofenac with another NSAID included only one study (98 participants). The NNTp was 4.5 (2.5 to 33) for ketorolac versus diclofenac (very low-quality evidence).The numbers of participants withdrawing were generally low and inconsistently reported (very low-quality evidence). Participant withdrawals were: 6% (8/140) diclofenac versus 5% (7/128) placebo, and 9% (8/87) diclofenac versus 7% (6/82) another NSAID for lack of efficacy; 2% (4/211) diclofenac versus 0% (0/198) placebo, and 3% (4/138) diclofenac versus 2% (2/129) another NSAID due to AEs; and 11% (21/191) diclofenac versus 17% (30/179) placebo, and 18% (21/118) diclofenac versus 15% (17/111) another NSAID for any cause.Overall adverse event rates were similar between intravenous diclofenac and placebo (71% in both groups, 2 studies, 296 participants) and between intravenous diclofenac and another NSAID (55% and 58%, respectively, 2 studies, 265 participants) (low-quality evidence for both comparisons). Serious and specific AEs were rare, preventing meta-analysis.There were sufficient data for a dose-effect analysis for our primary outcome for only one alternative dose, 18.75 mg. Analysis of the highest dose employed in each study demonstrated a relative benefit compared with placebo of 1.9 (1.4 to 2.4), whereas for the group receiving 18.75 mg, the relative benefit versus placebo was 1.6 (1.2 to 2.1, 2 studies). Compared to another NSAID, the high-dose analysis demonstrated a relative benefit of 0.9 (0.8 to 1.1), for the group receiving 18.75 mg, the relative benefit was 0.78 (0.65 to 0.93). For direct comparison of high dose versus 18.75 mg, the proportion of participants with at least 50% pain relief was 66% (90/137) for the high-dose arm versus 57% (77/135) in the low-dose arm. There were insufficient data for subgroup meta-analysis of different diclofenac formulations. AUTHORS' CONCLUSIONS: The amount and quality of evidence for the use of intravenous diclofenac as a treatment for postoperative pain is low. The available evidence indicates that postoperative intravenous diclofenac administration offers good pain relief for the majority of patients, but further research may impact this estimate. Adverse events appear to occur at a similar rate to other NSAIDs. Insufficient information is available to assess whether intravenous diclofenac has a different rate of bleeding, renal dysfunction, or cardiovascular events versus other NSAIDs. There was insufficient information to evaluate the efficacy and safety of newer versus traditional formulations of intravenous diclofenac. There was a lack of studies in major and cardiovascular surgeries and in elderly populations, which may be at increased risk for adverse events.

Methadone for neuropathic pain in adults.

BACKGROUND: This review replaces an earlier review, "Methadone for chronic non-cancer pain in adults". This review serves to update the original and includes only studies of neuropathic pain. Methadone belongs to a class of analgesics known as opioids, that are considered the cornerstone of therapy for moderate-to-severe postsurgical pain and pain due to life-threatening illnesses; however, their use in neuropathic pain is controversial. Methadone has many characteristics that differentiate it from other opioids, which suggests that it may have a different efficacy and safety profile. OBJECTIVES: To assess the analgesic efficacy and adverse events of methadone for chronic neuropathic pain in adults. SEARCH METHODS: We searched the following databases: CENTRAL (CRSO), MEDLINE (Ovid), and Embase (Ovid), and two clinical trial registries. We also searched the reference lists of retrieved articles. The date of the most recent search was 30 November 2016. SELECTION CRITERIA: We included randomised, double-blind studies of two weeks' duration or longer, comparing methadone (in any dose, administered by any route, and in any formulation) with placebo or another active treatment in chronic neuropathic pain. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. There were insufficient data to perform pooled analyses. We assessed the overall quality of the evidence for each outcome using GRADE and created a 'Summary of findings' table. MAIN RESULTS: We included three studies, involving 105 participants. All were cross-over studies, one involving 19 participants with diverse neuropathic pain syndromes, the other two involving 86 participants with postherpetic neuralgia. Study phases ranged from 20 days to approximately eight weeks. All administered methadone orally, in doses ranging from 10 mg to 80 mg daily. Comparators were primarily placebo, but one study also included morphine and tricyclic antidepressants.The included studies had several limitations related to risk of bias, particularly incomplete reporting, selective outcome reporting, and small sample sizes.There were very limited data for our primary outcomes of participants with at least 30% or at least 50% pain relief. Two studies reported that 11/29 participants receiving methadone achieved 30% pain relief versus 7/29 participants receiving placebo. Only one study presented data in a manner that allowed us to calculate the number of participants with at least 50% pain relief. None of the 19 participants achieved a 50% reduction in pain intensity, either when receiving methadone or when receiving placebo. No study provided data for our other primary outcomes of Patient Global Impression of Change scale (PGIC) much or very much improved (equivalent to at least 30% pain relief) and PGIC very much improved (equivalent to at least 50% pain relief).For secondary efficacy outcomes, one study reported maximum and mean pain intensity and pain relief, and reported statistically significant improvements versus placebo for all outcomes with 20 mg daily doses of methadone, but not with 10 mg daily doses. The second study reported differences in pain reduction between methadone (n = 26) and morphine (n = 38) and found morphine to be statistically superior. The third study reported the number of responders (variously defined) for several pain and functional outcomes and found methadone to be statistically superior to placebo for the outcomes of categorical pain intensity and evoked pain. In the two studies that reported data, 0/29 participants withdrew due to lack of efficacy, whereas 4/29 participants withdrew due to adverse events while taking methadone versus 3/29 while taking placebo.One study reported incidences for several individual adverse events, but found a statistically significant increased incidence for methadone over placebo for only one event, dizziness. The other studies did not report data in a manner that enabled us to analyze adverse events. There were no serious adverse events or deaths reported.We assessed the quality of the evidence as very low for all efficacy and safety outcomes using GRADE, primarily because of the heterogeneity of study designs and populations, short durations, cross-over methodology, and few participants and events. AUTHORS' CONCLUSIONS: The three studies provide very limited, very low quality evidence of the efficacy and safety of methadone for chronic neuropathic pain, and there were too few data for pooled analysis of efficacy or harm, or to have confidence in the results of the individual studies. No conclusions can be made regarding differences in efficacy or safety between methadone and placebo, other opioids, or other treatments.

Single dose intravenous paracetamol or intravenous propacetamol for postoperative pain.

BACKGROUND: This is an updated version of the original Cochrane review published in Issue 10, 2011. Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the treatment of acute pain. It may be administered orally, rectally, or intravenously. The efficacy and safety of intravenous (IV) formulations of paracetamol, IV paracetamol, and IV propacetamol (a prodrug that is metabolized to paracetamol), compared with placebo and other analgesics, is unclear. OBJECTIVES: To assess the efficacy and safety of IV formulations of paracetamol for the treatment of postoperative pain in both adults and children. SEARCH METHODS: We ran the search for the previous review in May 2010. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE (May 2010 to 16 February 2016), EMBASE (May 2010 to 16 February 2016), LILACS (2010 to 2016), a clinical trials registry, and reference lists of reviews for randomized controlled trials (RCTs) in any language and we retrieved articles. SELECTION CRITERIA: Randomized, double-blind, placebo- or active-controlled single dose clinical trials of IV paracetamol or IV propacetamol for acute postoperative pain in adults or children. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, which included demographic variables, type of surgery, interventions, efficacy, and adverse events. We contacted study authors for additional information. We graded each included study for methodological quality by assessing risk of bias and employed the GRADE approach to assess the overall quality of the evidence. MAIN RESULTS: We included 75 studies (36 from the original review and 39 from our updated review) enrolling a total of 7200 participants.Among primary outcomes, 36% of participants receiving IV paracetamol/propacetamol experienced at least 50% pain relief over four hours compared with 16% of those receiving placebo (number needed to treat to benefit (NNT) = 5; 95% confidence interval (CI) 3.7 to 5.6, high quality evidence). The proportion of participants in IV paracetamol/propacetamol groups experiencing at least 50% pain relief diminished over six hours, as reflected in a higher NNT of 6 (4.6 to 7.1, moderate quality evidence). Mean pain intensity at four hours was similar when comparing IV paracetamol and placebo, but was seven points lower on a 0 to 100 visual analog scale (0 = no pain, 100 = worst pain imaginable, 95% CI -9 to -6, low quality evidence) in those receiving paracetamol at six hours.For secondary outcomes, participants receiving IV paracetamol/propacetamol required 26% less opioid over four hours and 16% less over six hours (moderate quality evidence) than those receiving placebo. However, this did not translate to a clinically meaningful reduction in opioid-induced adverse events.Meta-analysis of efficacy comparisons between IV paracetamol/propacetamol and active comparators (e.g., opioids or nonsteroidal anti-inflammatory drugs) were either not statistically significant, not clinically significant, or both.Adverse events occurred at similar rates with IV paracetamol or IV propacetamol and placebo. However, pain on infusion occurred more frequently in those receiving IV propacetamol versus placebo (23% versus 1%). Meta-analysis did not demonstrate clinically meaningful differences between IV paracetamol/propacetamol and active comparators for any adverse event. AUTHORS' CONCLUSIONS: Since the last version of this review, we have found 39 new studies providing additional information. Most included studies evaluated adults only. We reanalyzed the data but the results did not substantially alter any of our previously published conclusions. This review provides high quality evidence that a single dose of either IV paracetamol or IV propacetamol provides around four hours of effective analgesia for about 36% of patients with acute postoperative pain. Low to very low quality evidence demonstrates that both formulations are associated with few adverse events, although patients receiving IV propacetamol have a higher incidence of pain on infusion than both placebo and IV paracetamol.

Survey Evaluation of Pharmacy Practice Involving Deaf Patients.

INTRODUCTION: For a patient who is deaf, providing patient care can be more difficult due to communication barriers. This study was conducted in order to better understand pharmacists' current means of communicating with deaf patients as well as investigating pharmacists' knowledge of their legal responsibility to these patients. METHODS: Surveys were used to gather information from pharmacists and were distributed in areas with a large population of deaf patients. RESULTS: Of the 73 pharmacists who completed surveys, 50 (68.5%) of them interact with at least 1 to 5 deaf patients monthly. Pharmacists responded that accessibility of interpreters is the most significant barrier to communication and providing written material is the method most used to communicate with deaf patients. None of the 73 pharmacists who completed the survey felt that they have a legal obligation to provide and pay for an interpreter. CONCLUSION: When interacting with a deaf patient, pharmacists may experience communication barriers. Pharmacists should strive to appropriately communicate with the deaf as well as familiarize themselves with legal obligations to this patient population.

Patient controlled opioid analgesia versus non-patient controlled opioid analgesia for postoperative pain.

BACKGROUND: This is an updated version of the original Cochrane review published in Issue 4, 2006. Patients may control postoperative pain by self administration of intravenous opioids using devices designed for this purpose (patient controlled analgesia or PCA). A 1992 meta-analysis by Ballantyne et al found a strong patient preference for PCA over non-patient controlled analgesia, but disclosed no differences in analgesic consumption or length of postoperative hospital stay. Although Ballantyne's meta-analysis found that PCA did have a small but statistically significant benefit upon pain intensity, a 2001 review by Walder et al did not find statistically significant differences in pain intensity or pain relief between PCA and groups treated with non-patient controlled analgesia. OBJECTIVES: To evaluate the efficacy and safety of patient controlled intravenous opioid analgesia (termed PCA in this review) versus non-patient controlled opioid analgesia of as-needed opioid analgesia for postoperative pain relief. SEARCH METHODS: We ran the search for the previous review in November 2004. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 12), MEDLINE (1966 to 28 January 2015), and EMBASE (1980 to 28 January 2015) for randomized controlled trials (RCTs) in any language, and reference lists of reviews and retrieved articles. SELECTION CRITERIA: We selected RCTs that assessed pain intensity as a primary or secondary outcome. These studies compared PCA without a continuous background infusion with non-patient controlled opioid analgesic regimens. We excluded studies that explicitly stated they involved patients with chronic pain. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, which included demographic variables, type of surgery, interventions, efficacy, and adverse events. We graded each included study for methodological quality by assessing risk of bias and employed the GRADE approach to assess the overall quality of the evidence. We performed meta-analysis of outcomes that included pain intensity assessed by a 0 to 100 visual analog scale (VAS), opioid consumption, patient satisfaction, length of stay, and adverse events. MAIN RESULTS: Forty-nine studies with 1725 participants receiving PCA and 1687 participants assigned to a control group met the inclusion criteria. The original review included 55 studies with 2023 patients receiving PCA and 1838 patients assigned to a control group. There were fewer included studies in our updated review due to the revised exclusion criteria. For the primary outcome, participants receiving PCA had lower VAS pain intensity scores versus non-patient controlled analgesia over most time intervals, e.g., scores over 0 to 24 hours were nine points lower (95% confidence interval (CI) -13 to -5, moderate quality evidence) and over 0 to 48 hours were 10 points lower (95% CI -12 to -7, low quality evidence). Among the secondary outcomes, participants were more satisfied with PCA (81% versus 61%, P value = 0.002) and consumed higher amounts of opioids than controls (0 to 24 hours, 7 mg more of intravenous morphine equivalents, 95% CI 1 mg to 13 mg). Those receiving PCA had a higher incidence of pruritus (15% versus 8%, P value = 0.01) but had a similar incidence of other adverse events. There was no difference in the length of hospital stay. AUTHORS' CONCLUSIONS: Since the last version of this review, we have found new studies providing additional information. We reanalyzed the data but the results did not substantially alter any of our previously published conclusions. This review provides moderate to low quality evidence that PCA is an efficacious alternative to non-patient controlled systemic analgesia for postoperative pain control.

Interferons as therapeutic agents for infectious diseases.

This article explains the rationale for development of interferons as therapeutic agents, and describes commercial products available today. It also provides a summary of studies that have been performed with interferons for use as exogenous biological response modifiers in viral infections. Overall, the best data exist for treatment of viral hepatitis B and C, for which interferons are a cornerstone of therapy. Although infections with human papillomavirus and common cold viruses sometimes respond favorably to interferons, their outcomes are far from ideal. Finally, the role of interferons as vaccine adjuvants is still being explored but could be promising.

Current therapies for chronic hepatitis C.

Hepatitis C virus affects more than 180 million people worldwide and as many as 4 million people in the United States. Given that most patients are asymptomatic until late in the disease progression, diagnostic screening and evaluation should be performed in patients who display high-risk behaviors associated with acquisition of hepatitis C. Chronic hepatitis C is associated with cirrhosis, hepatic failure, and death; therefore, treatment is aimed at reducing these complications, as well as improving quality of life and minimizing adverse effects. The American Association for the Study of Liver Diseases Practice Guidelines on the Diagnosis, Management, and Treatment of Hepatitis C represent the gold standard for guidance on the management of hepatitis C. Standard treatment for hepatitis C is peginterferon alpha in combination with ribavirin. Currently, two pegylated interferon products are approved by the U.S. Food and Drug Administration for the treatment of hepatitis C. The duration of therapy with peginterferon and ribavirin is dictated by viral genotype and virologic response. Additional therapies are under investigation for treatment of chronic hepatitis C and show early promise of comparative efficacy and fewer adverse effects. Special considerations in certain populations, including patients coinfected with human immunodeficiency virus, those with end-stage renal disease, injection drug users, pregnant women, and pediatric patients, should guide treatment decisions.