Use of the Capability, Opportunity and Motivation Behaviour model (COM-B) to Understand Interventions to Support Physical Activity Behaviour in People with Stroke: An Overview of Reviews.

OBJECTIVE: Physical activity in people with stroke remains low despite considerable research. This overview aimed to provide high-level synthesis and aid clinical decision-making. The Capability, Opportunity, Motivation-Behaviour (COM-B) model was used to classify interventions to understand which components improve physical activity behaviour in people with stroke. DATA SOURCES: CINAHL, Cochrane Database, MEDLINE, PEDro, PsychINFO, SPORTDiscus. REVIEW METHODS: A systematic search was conducted (November 2023) to identify reviews of interventions to improve physical activity in people with stroke. Results were screened and assessed for eligibility. Participant characteristics, intervention classification using COM-B, and effect of intervention were extracted. Quality was assessed using AMSTAR2, and Corrected Cover Analysis for study overlap. Narrative synthesis was used to understand components of interventions to improve physical activity behaviour. RESULTS: 1801 references were screened and 29 full-text references assessed for eligibility. Twenty reviews were included. Quality ranged from critically low (n = 3) to high (n = 10). Study overlap calculated using corrected cover area indicated slight overlap (0.028) and minimal reporting bias.The majority of participants were mobile with mild stroke and community dwelling. Twenty-three interventions were classified using COM-B. Three of twelve interventions classified to one aspect of the COM-B were effective. Fourteen of sixteen effective interventions combined at least two COM-B elements, ten of these combined capability and motivation. CONCLUSION: Interventions including at least two elements of the COM-B are most likely to improve physical activity in mobile stroke survivors. Further research is needed to understand physical activity behaviour in those with moderate to severe stroke.

Is there evidence for a relationship between cognitive impairment and fatigue after acquired brain injury: a systematic review and meta-analysis.

PURPOSE: Fatigue is a major symptom of ABI. Greater fatigue is associated with cognitive impairment. Our aim was to systematically review, describe and analyse the literature on the extent of this relationship. METHODS: Five databases were searched from inception. Studies were included where: participants had a defined clinical diagnosis of ABI which included TBI, stroke or subarachnoid haemorrhage; a fatigue measure was included; at least one objective cognitive measure was used. Three reviewers individually identified studies and determined quality using the Quality Assessment Tool for Observational Cohort and Cross-sectional Studies. RESULTS: Sixteen of the 412 identified studies, investigating the relationship between cognitive dysfunction and fatigue, comprising a total of 1,745 participants, were included. Quality ranged from fair to good. Meta-analysis found fatigue was significantly associated with an overall pattern of cognitive slowing on tasks of sustained attention. A narrative synthesis found weak associations with fatigue and information processing, attention, memory and executive function. CONCLUSION: Analysis found sustained attentional performance had stronger associations with fatigue after ABI. Whereas, weak associations were found between fatigue and information processing, attention and to some extent memory and executive function. More focused research on specific cognitive domains is needed to understand the mechanisms of fatigue.

Cognitive dysfunction is associated with higher fatigue levels after stroke, traumatic brain injury or subarachnoid haemorrhage.Management of cognitive dysfunction may improve fatigue and participation in meaningful activities after stroke, traumatic brain injury or subarachnoid haemorrhage.Intervention strategies that reduce cognitive load during everyday activities (e.g., grading the burden on attentional resources), may potentially be effective in managing post-ABI fatigue.Agreement on core measures could facilitate integration of findings into clinical practice.

Topical analgesics for acute and chronic pain in adults - an overview of Cochrane Reviews.

BACKGROUND: Topical analgesic drugs are used for a variety of painful conditions. Some are acute, typically strains or sprains, tendinopathy, or muscle aches. Others are chronic, typically osteoarthritis of hand or knee, or neuropathic pain. OBJECTIVES: To provide an overview of the analgesic efficacy and associated adverse events of topical analgesics (primarily nonsteroidal anti-inflammatory drugs (NSAIDs), salicylate rubefacients, capsaicin, and lidocaine) applied to intact skin for the treatment of acute and chronic pain in adults. METHODS: We identified systematic reviews in acute and chronic pain published to February 2017 in the Cochrane Database of Systematic Reviews (the Cochrane Library). The primary outcome was at least 50% pain relief (participant-reported) at an appropriate duration. We extracted the number needed to treat for one additional beneficial outcome (NNT) for efficacy outcomes for each topical analgesic or formulation, and the number needed to treat for one additional harmful outcome (NNH) for adverse events. We also extracted information on withdrawals due to lack of efficacy or adverse events, systemic and local adverse events, and serious adverse events. We required information from at least 200 participants, in at least two studies. We judged that there was potential for publication bias if the addition of four studies of typical size (400 participants) with zero effect increased NNT compared with placebo to 10 (minimal clinical utility). We extracted GRADE assessment in the original papers, and made our own GRADE assessment. MAIN RESULTS: Thirteen Cochrane Reviews (206 studies with around 30,700 participants) assessed the efficacy and harms from a range of topical analgesics applied to intact skin in a number of acute and chronic painful conditions. Reviews were overseen by several Review Groups, and concentrated on evidence comparing topical analgesic with topical placebo; comparisons of topical and oral analgesics were rare.For at least 50% pain relief, we considered evidence was moderate or high quality for several therapies, based on the underlying quality of studies and susceptibility to publication bias.In acute musculoskeletal pain (strains and sprains) with assessment at about seven days, therapies were diclofenac Emulgel (78% Emulgel, 20% placebo; 2 studies, 314 participants, NNT 1.8 (95% confidence interval 1.5 to 2.1)), ketoprofen gel (72% ketoprofen, 33% placebo, 5 studies, 348 participants, NNT 2.5 (2.0 to 3.4)), piroxicam gel (70% piroxicam, 47% placebo, 3 studies, 522 participants, NNT 4.4 (3.2 to 6.9)), diclofenac Flector plaster (63% Flector, 41% placebo, 4 studies, 1030 participants, NNT 4.7 (3.7 to 6.5)), and diclofenac other plaster (88% diclofenac plaster, 57% placebo, 3 studies, 474 participants, NNT 3.2 (2.6 to 4.2)).In chronic musculoskeletal pain (mainly hand and knee osteoarthritis) therapies were topical diclofenac preparations for less than six weeks (43% diclofenac, 23% placebo, 5 studies, 732 participants, NNT 5.0 (3.7 to 7.4)), ketoprofen over 6 to 12 weeks (63% ketoprofen, 48% placebo, 4 studies, 2573 participants, NNT 6.9 (5.4 to 9.3)), and topical diclofenac preparations over 6 to 12 weeks (60% diclofenac, 50% placebo, 4 studies, 2343 participants, NNT 9.8 (7.1 to 16)). In postherpetic neuralgia, topical high-concentration capsaicin had moderate-quality evidence of limited efficacy (33% capsaicin, 24% placebo, 2 studies, 571 participants, NNT 11 (6.1 to 62)).We judged evidence of efficacy for other therapies as low or very low quality. Limited evidence of efficacy, potentially subject to publication bias, existed for topical preparations of ibuprofen gels and creams, unspecified diclofenac formulations and diclofenac gel other than Emulgel, indomethacin, and ketoprofen plaster in acute pain conditions, and for salicylate rubefacients for chronic pain conditions. Evidence for other interventions (other topical NSAIDs, topical salicylate in acute pain conditions, low concentration capsaicin, lidocaine, clonidine for neuropathic pain, and herbal remedies for any condition) was very low quality and typically limited to single studies or comparisons with sparse data.We assessed the evidence on withdrawals as moderate or very low quality, because of small numbers of events. In chronic pain conditions lack of efficacy withdrawals were lower with topical diclofenac (6%) than placebo (9%) (11 studies, 3455 participants, number needed to treat to prevent (NNTp) 26, moderate-quality evidence), and topical salicylate (2% vs 7% for placebo) (5 studies, 501 participants, NNTp 21, very low-quality evidence). Adverse event withdrawals were higher with topical capsaicin low-concentration (15%) than placebo (3%) (4 studies, 477 participants, NNH 8, very low-quality evidence), topical salicylate (5% vs 1% for placebo) (7 studies, 735 participants, NNH 26, very low-quality evidence), and topical diclofenac (5% vs 4% for placebo) (12 studies, 3552 participants, NNH 51, very low-quality evidence).In acute pain, systemic or local adverse event rates with topical NSAIDs (4.3%) were no greater than with topical placebo (4.6%) (42 studies, 6740 participants, high quality evidence). In chronic pain local adverse events with topical capsaicin low concentration (63%) were higher than topical placebo (5 studies, 557 participants, number needed to treat for harm (NNH) 2.6), high quality evidence. Moderate-quality evidence indicated more local adverse events than placebo in chronic pain conditions with topical diclofenac (NNH 16) and local pain with topical capsaicin high-concentration (NNH 16). There was moderate-quality evidence of no additional local adverse events with topical ketoprofen over topical placebo in chronic pain. Serious adverse events were rare (very low-quality evidence).GRADE assessments of moderate or low quality in some of the reviews were considered by us to be very low because of small numbers of participants and events. AUTHORS' CONCLUSIONS: There is good evidence that some formulations of topical diclofenac and ketoprofen are useful in acute pain conditions such as sprains or strains, with low (good) NNT values. There is a strong message that the exact formulation used is critically important in acute conditions, and that might also apply to other pain conditions. In chronic musculoskeletal conditions with assessments over 6 to 12 weeks, topical diclofenac and ketoprofen had limited efficacy in hand and knee osteoarthritis, as did topical high-concentration capsaicin in postherpetic neuralgia. Though NNTs were higher, this still indicates that a small proportion of people had good pain relief.Use of GRADE in Cochrane Reviews with small numbers of participants and events requires attention.

Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults.

BACKGROUND: This review is an update of "Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults" last updated in Issue 4, 2009. Ketoprofen is a non-selective nonsteroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. This review is one of a series on oral analgesics for acute postoperative pain. Individual reviews have been brought together in two overviews to provide information about the relative efficacy and harm of the different interventions. OBJECTIVES: To assess the efficacy and safety of single dose oral ketoprofen and oral dexketoprofen compared with placebo for acute postoperative pain, using methods that permit comparison with other analgesics evaluated in the same way, and criteria of efficacy recommended by an in-depth study at the individual patient level. SEARCH METHODS: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from 2009 to 28 March 2017. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries. SELECTION CRITERIA: Randomised, double-blind, placebo-controlled trials of single dose orally administered ketoprofen or dexketoprofen in adults with moderate to severe acute postoperative pain. DATA COLLECTION AND ANALYSIS: Two review authors independently considered studies for inclusion in the review, examined issues of study quality and potential bias, and extracted data. For dichotomous outcomes, we calculated risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH) with 95% confidence intervals (CI) for ketoprofen and dexketoprofen, compared with placebo, where there were sufficient data. We collected information on the number of participants with at least 50% of the maximum possible pain relief over six hours, the median time to use of rescue medication, and the proportion of participants requiring rescue medication. We also collected information on adverse events and withdrawals. We assessed the quality of the evidence using GRADE, and created 'Summary of findings' tables. MAIN RESULTS: This updated review included 24 studies; six additional studies added 1001 participants involved in comparisons of ketoprofen or dexketoprofen and placebo, with a 12% increase in participants taking ketoprofen and a 65% increase for dexketoprofen. Most participants (70%) were women. Dental studies typically involved young participants (mean age 20 to 30 years); other types of surgery involved older participants (mean age 37 to 68 years). Overall, we judged the studies at high risk of bias only for small size, which can lead to an overestimation of benefit.Ketoprofen doses ranged between 6.5 mg and 150 mg. The proportion of participants achieving at least 50% pain relief over six hours with the usual ketoprofen oral dose of 50 mg was 57%, compared to 23% with placebo, giving an NNT of 2.9 (95% CI 2.4 to 3.7) (RR 2.5, 95% CI 2.0 to 3.1; 594 participants; 8 studies; high quality evidence). Efficacy was significantly better in dental studies (NNT 1.8) than other surgery (NNT 4.2). The proportion of participants using rescue medication within six hours was lower with ketoprofen (32%) than with placebo (75%), giving a number needed to treat to prevent use of rescue medication (NNTp) of 2.3 (95% CI 1.8 to 3.1); 263 participants; 4 studies; high quality evidence). Median time to remedication estimates were poorly reported. Reports of any adverse event were similar with ketoprofen (18%) and placebo (11%) (RR 1.6, 95% CI 0.98 to 2.8; 342 participants; 5 studies; high quality evidence). No study reported any serious adverse events (very low quality evidence).Dexketoprofen doses ranged between 5 mg and 100 mg. The proportion of participants achieving at least 50% pain relief over six hours with the usual dexketoprofen oral dose of 20 mg or 25 mg was 52%, compared to 27% with placebo, giving an NNT of 4.1 (95% CI 3.3 to 5.2) (RR 2.0, 95% CI 1.6 to 2.2; 1177 participants; 8 studies; high quality evidence). Efficacy was significantly better in dental studies (NNT 2.7) than other surgery (NNT 5.7). The proportion of participants using rescue medication within six hours was lower with dexketoprofen (47%) than placebo (69%), giving an NNTp of 4.7 (95% CI 3.3 to 8.0); 445 participants; 5 studies; high quality evidence). Median time to remedication estimates were poorly reported. Reports of any adverse event were similar with dexketoprofen (14%) and placebo (10%) (RR 1.4, 95% CI 0.89 to 2.2; 536 participants, 6 studies; high quality evidence). No study reported any serious adverse events (very low quality evidence). AUTHORS' CONCLUSIONS: Ketoprofen at doses of 25 mg to 100 mg is an effective analgesic in moderate to severe acute postoperative pain with an NNT for at least 50% pain relief of 2.9 with a 50 mg dose. This is similar to that of commonly used NSAIDs such as ibuprofen (NNT 2.5 for 400 mg dose) and diclofenac (NNT 2.7 for 50 mg dose). Dexketoprofen is also effective with an NNT of 4.1 in the dose range 10 mg to 25 mg. Differential efficacy between dental surgery and other types of surgery seen for both drugs is unusual. Both drugs were well tolerated in single doses.

Oxycodone for pain in fibromyalgia in adults.

BACKGROUND: This review replaces part of an earlier review that evaluated oxycodone for both neuropathic pain and fibromyalgia, which has now been split into separate reviews for the two conditions. This review will consider pain in fibromyalgia only.Opioid drugs are commonly used to treat fibromyalgia, but they may not be beneficial for people with this condition. Most reviews have examined all opioids together. This review sought evidence specifically for oxycodone, at any dose, and by any route of administration. OBJECTIVES: To assess the analgesic efficacy and adverse events of oxycodone for treating pain in fibromyalgia in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE for randomised controlled trials from inception to 25 July 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries. SELECTION CRITERIA: We planned to include randomised, double-blind trials of eight weeks' duration or longer, comparing oxycodone (alone or in fixed-dose combination with naloxone) with placebo or another active treatment. We did not include observational studies. DATA COLLECTION AND ANALYSIS: The plan was for two independent review authors to extract data and assess trial quality and potential bias. Where pooled analysis was possible, we planned to use dichotomous data to calculate risk ratio and numbers needed to treat for one additional event, using standard methods. MAIN RESULTS: No study satisfied the inclusion criteria. Effects of interventions were not assessed as there were no included studies. We have only very low quality evidence and are very uncertain about estimates of benefit and harm. AUTHORS' CONCLUSIONS: There is no randomised trial evidence to support or refute the suggestion that oxycodone, alone or in combination with naloxone, reduces pain in fibromyalgia.

Oxycodone for neuropathic pain in adults.

BACKGROUND: This is an update of an earlier review that considered both neuropathic pain and fibromyalgia (Issue 6, 2014), which has now been split into separate reviews for the two conditions. This review considers neuropathic pain only.Opioid drugs, including oxycodone, are commonly used to treat neuropathic pain, and are considered effective by some professionals. Most reviews have examined all opioids together. This review sought evidence specifically for oxycodone, at any dose, and by any route of administration. Separate reviews consider other opioids. OBJECTIVES: To assess the analgesic efficacy and adverse events of oxycodone for chronic neuropathic pain in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from inception to 6 November 2013 for the original review and from January 2013 to 21 December 2015 for this update. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries. This update differs from the earlier review in that we have included studies using oxycodone in combination with naloxone, and oxycodone used as add-on treatment to stable, but inadequate, treatment with another class of drug. SELECTION CRITERIA: We included randomised, double-blind studies of two weeks' duration or longer, comparing any dose or formulation of oxycodone with placebo or another active treatment in chronic neuropathic pain. DATA COLLECTION AND ANALYSIS: Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. Where pooled analysis was possible, we used dichotomous data to calculate risk ratio and numbers needed to treat for one additional event, using standard methods.We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table. MAIN RESULTS: The updated searches identified one additional published study, and one clinical trial registry report. We included five studies reporting on 687 participants; 637 had painful diabetic neuropathy and 50 had postherpetic neuralgia. Two studies used a cross-over design and three used a parallel group design; all studies used a placebo comparator, although one study used an active placebo (benztropine). Modified-release oxycodone (oxycodone MR) was titrated to effect and tolerability. One study used a fixed dose combination of oxycodone MR and naloxone. Two studies added oxycodone therapy to ongoing, stable treatment with either pregabalin or gabapentin. All studies had one or more sources of potential major bias.No study reported the proportion of participants experiencing 'substantial benefit' (at least 50% pain relief or who were very much improved). Three studies (537 participants) in painful diabetic neuropathy reported outcomes equivalent to 'moderate benefit' (at least 30% pain relief or who were much or very much improved), which was experienced by 44% of participants with oxycodone and 27% with placebo (number needed to treat for one additional beneficial outcome (NNT) 5.7).All studies reported group mean pain scores at the end of treatment. Three studies reported a greater pain intensity reduction and better patient satisfaction with oxycodone MR alone than with placebo. There was a similar result in the study adding oxycodone MR to stable, ongoing gabapentin, but adding oxycodone MR plus naloxone to stable, ongoing pregabalin did not show any additional effect.More participants experienced adverse events with oxycodone MR alone (86%) than with placebo (63%); the number needed to treat for an additional harmful outcome (NNH) was 4.3. Serious adverse events (oxycodone 3.4%, placebo 7.0%) and adverse event withdrawals (oxycodone 11%, placebo 6.4%) were not significantly different between groups. Withdrawals due to lack of efficacy were less frequent with oxycodone MR (1.1%) than placebo (11%), with a number needed to treat to prevent one withdrawal of 10. The add-on studies reported similar results.We downgraded the quality of the evidence to very low for all outcomes, due to limitations in the study methods, heterogeneity in the pain condition and study methods, and sparse data. AUTHORS' CONCLUSIONS: There was only very low quality evidence that oxycodone (as oxycodone MR) is of value in the treatment of painful diabetic neuropathy or postherpetic neuralgia. There was no evidence for other neuropathic pain conditions. Adverse events typical of opioids appeared to be common.

Hydromorphone for neuropathic pain in adults.

BACKGROUND: Opioid drugs, including hydromorphone, are commonly used to treat neuropathic pain, and are considered effective by some professionals. Most reviews have examined all opioids together. This review sought evidence specifically for hydromorphone, at any dose, and by any route of administration. Other opioids are considered in separate reviews.This review is part of an update of a previous review, Hydromorphone for acute and chronic pain that was withdrawn in 2013 because it needed updating and splitting to be more specific for different pain conditions. This review focuses only on neuropathic pain. OBJECTIVES: To assess the analgesic efficacy of hydromorphone for chronic neuropathic pain in adults, and the adverse events associated with its use in clinical trials. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), via the CRSO; MEDLINE via Ovid; and EMBASE via Ovid from inception to 17 November 2015, together with reference lists of retrieved papers and reviews, and two online study registries. SELECTION CRITERIA: We included randomised, double-blind studies of two weeks' duration or longer, comparing hydromorphone (at any dose, by any route of administration, or in any formulation) with placebo or another active treatment in chronic neuropathic pain. DATA COLLECTION AND ANALYSIS: Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS: Searches identified seven publications relating to four studies. We excluded three studies. One post hoc (secondary) analysis of a study published in four reports assessed the efficacy of hydromorphone in neuropathic pain, satisfied our inclusion criteria, and was included in the review. The single included study had an enriched enrolment, randomised withdrawal design with 94 participants who were successfully switched from oral morphine to oral hydromorphone extended release (about 60% of those enrolled). These participants were then randomised to continuing hydromorphone for 12 weeks or tapering down the hydromorphone dose to placebo. The methodological quality of the study was generally good, but we judged the risk of bias for incomplete outcome data as unclear, and for study size as high.Since we identified only one study for inclusion, we were unable to carry out any analyses. The included study did not report any of our prespecified primary outcomes, which relate to the number of participants achieving moderate or substantial levels of pain relief. It did report a slightly larger increase in average pain intensity for placebo in the randomised withdrawal phase than for continuing with hydromorphone. It also reported the number of participants who withdrew due to lack of efficacy in the randomised withdrawal phase, which may be an indicator of efficacy. However, in addition to using an enriched enrolment, randomised withdrawal study design, there was an unusual choice of imputation methods for withdrawals (about 50% of participants); the evidence was of very low quality and inadequate to make a judgement on efficacy. Adverse events occurred in about half of participants with hydromorphone, the most common being constipation and nausea. A similar proportion of participants experienced adverse events with placebo, the most common being opioid withdrawal syndrome (very low quality evidence). Most adverse events were mild or moderate in intensity. One in eight participants withdrew while taking hydromorphone during the conversion and titration phase, despite participants being opioid-tolerant (very low quality evidence).We downgraded the quality of the evidence to very low because there was only one study with few participants, it did not report clinically useful efficacy outcomes, and it was a post hoc analysis. AUTHORS' CONCLUSIONS: There was insufficient evidence to support or refute the suggestion that hydromorphone has any efficacy in any neuropathic pain condition.

Topical NSAIDs for acute musculoskeletal pain in adults.

BACKGROUND: Use of topical NSAIDs to treat acute musculoskeletal conditions has become widely accepted because they can provide pain relief without associated systemic adverse events. This review is an update of 'Topical NSAIDs for acute pain in adults' originally published in Issue 6, 2010. OBJECTIVES: To determine the efficacy and safety of topically applied NSAIDs in acute musculoskeletal pain in adults. SEARCH METHODS: We searched the Cochrane Register of Studies Online, MEDLINE, and EMBASE to February 2015. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers websites. For the earlier review, we also searched our own in-house database and contacted manufacturers. SELECTION CRITERIA: We included randomised, double-blind, active or placebo (inert carrier)-controlled trials in which treatments were administered to adults with acute pain resulting from strains, sprains or sports or overuse-type injuries (twisted ankle, for instance). There had to be at least 10 participants in each treatment arm, with application of treatment at least once daily. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, and extracted data. We used numbers of participants achieving each outcome to calculate the risk ratio and numbers needed to treat for an additional beneficial outcome (NNT) or additional harmful outcome (NNH) compared with placebo or other active treatment. We reported 95% confidence intervals (CI). We were particularly interested to compare different formulations (gel, cream, plaster) of individual NSAIDs. MAIN RESULTS: For this update we added 14 new included studies (3489 participants), and excluded four studies. We also identified 20 additional reports of completed or ongoing studies that have not been published in full. The earlier review included 47 studies.This update included 61 studies. Most compared topical NSAIDs in the form of a gel, spray, or cream with a similar topical placebo; 5311 participants were treated with a topical NSAID, 3470 with placebo, and 220 with an oral NSAID. This was a 63% increase in the number of included participants over the previous version of this review. We also identified a number of studies in clinical trial registries with unavailable results amounting to about 5900 participants for efficacy and 5300 for adverse events.Formulations of topical diclofenac, ibuprofen, ketoprofen, piroxicam, and indomethacin demonstrated significantly higher rates of clinical success (more participants with at least 50% pain relief) than matching topical placebo (moderate or high quality data). Benzydamine did not. Three drug and formulation combinations had NNTs for clinical success below 4. For diclofenac, the Emulgel® formulation had the lowest NNT of 1.8 (95% CI 1.5 to 2.1) in two studies using at least 50% pain intensity reduction as the outcome. Diclofenac plasters other than Flector® also had a low NNT of 3.2 (2.6 to 4.2) based on good or excellent responses in some studies. Ketoprofen gel had an NNT of 2.5 (2.0 to 3.4), from five studies in the 1980s, some with less well defined outcomes. Ibuprofen gel had an NNT of 3.9 (2.7 to 6.7) from two studies with outcomes of marked improvement or complete remission. All other drug and formulation combinations had NNT values above 4, indicating lesser efficacy.There were insufficient data to compare reliably individual topical NSAIDs with each other or the same oral NSAID.Local skin reactions were generally mild and transient, and did not differ from placebo (high quality data). There were very few systemic adverse events (high quality data) or withdrawals due to adverse events (low quality data). AUTHORS' CONCLUSIONS: Topical NSAIDs provided good levels of pain relief in acute conditions such as sprains, strains and overuse injuries, probably similar to that provided by oral NSAIDs. Gel formulations of diclofenac (as Emugel®), ibuprofen, and ketoprofen, and some diclofenac patches, provided the best effects. Adverse events were usually minimal.Since the last version of this review, the new included studies have provided additional information. In particular, information on topical diclofenac is greatly expanded. The present review supports the previous review in concluding that topical NSAIDs are effective in providing pain relief, and goes further to demonstrate that certain formulations, mainly gel formulations of diclofenac, ibuprofen, and ketoprofen, provide the best results. Large amounts of unpublished data have been identified, and this could influence results in updates of this review.

Treating chronic non-cancer pain in older people--more questions than answers?

There is little evidence specifically relating to drug treatments for pain in older people, but much can be extrapolated from what we already know. The evidence about drug treatments for chronic non-cancer pain is changing, driven by major improvements in understanding of clinical trial analysis and by the adoption of patient-centered outcomes of proven economic benefit. There is clear evidence of lack of useful effect, or insufficient evidence of effect for a number of commonly used drugs, including paracetamol, topical rubefacients, low concentration topical capsaicin, and for strong opioids in chronic non-cancer pain. In musculoskeletal pain there is evidence of efficacy for NSAIDs, tramadol, and tapentadol, and in neuropathic pain for duloxetine, pregabalin, and gabapentin, with weak evidence for amitriptyline. The new perspective is of drugs that work well in a minority of patients, but hardly at all in the remainder. The goal of treatment is large reductions in pain, by 50% or more. This outcome, and only this outcome, is associated with large benefits in terms of improved sleep, reduced depression, and large gains in function and quality of life. It is not possible to predict which patient will benefit from which drug, but early success or failure appears to be predictive of long-term success or failure. The emphasis is on stopping treatments that do not work and switching to other drugs in the same or different class, so that any potential future risk of treatment is balanced by very large and immediate benefit.

Oxycodone for neuropathic pain and fibromyalgia in adults.

BACKGROUND: This review is one of a series on drugs used to treat neuropathic pain and fibromyalgia. These conditions are estimated to affect 3 to 10% of adults, and are difficult to treat. Although they probably have different aetiologies, neuropathic pain and fibromyalgia can respond to the same therapies. There have been substantial changes in the standards of evidence considered necessary for assessment of interventions to treat chronic pain, to provide data that are more robust and clinically relevant. Oxycodone is a strong opioid agonist widely used to manage severe pain; this review assesses evidence for oxycodone using current standards of evidence designed to reduce bias. OBJECTIVES: To assess the analgesic efficacy and adverse events of oxycodone for chronic neuropathic pain and fibromyalgia. SEARCH METHODS: On 6 November 2013, we searched CENTRAL, MEDLINE and EMBASE databases. We reviewed the bibliographies of all included studies and of reviews, and also searched two clinical trial databases, ClinicalTrials.gov and the World Health Organisation (WHO) International Clinical Trials Registry Platform, to identify additional published or unpublished data. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with double-blind assessment of participant outcomes following two weeks of treatment or longer (although the emphasis of the review was on studies of eight weeks or longer) that used a placebo or active comparator. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted efficacy and adverse event data, examined issues of study quality, and assessed risk of bias. We performed analysis using three tiers of evidence. First tier evidence was derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, eight to 12 weeks duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that was considered very likely to be biased or used outcomes of limited clinical utility, or both. MAIN RESULTS: We included three studies with 254 participants; 204 had painful diabetic neuropathy and 50 postherpetic neuralgia. Study size ranged from 45 to 159 participants. Two studies used a cross-over design and one a parallel group design; study duration was four or six weeks. Controlled release oxycodone (oxycodone CR) was used in all three studies, with doses titrated up to a maximum of between 60 and 120 mg daily; mean doses achieved ranged between 37 and 45 mg daily. All studies used a placebo comparator, although in one study, an active placebo (benztropine) was used. All studies had one or more sources of potential major bias.No study reported the proportion of participants experiencing at least 50% pain relief or who were very much improved, while one reported the proportion with at least 30% pain relief, two reported at least moderate pain relief, and one reported the number of participants who considered treatment to be moderately effective. No study provided first or second tier evidence for an efficacy outcome. Third tier evidence indicated greater pain intensity reduction and better patient satisfaction with oxycodone than with placebo in all three studies, but such evidence was derived mainly from group mean data, with last observation carried forward (LOCF) imputation or completer analysis, in small studies lasting less than eight weeks (very low quality evidence).Adverse events were more common with oxycodone CR than with placebo. At least one adverse event was experienced by 86% of participants taking oxycodone CR and 63% taking placebo, and the number needed to treat for an additional harmful effect (NNH) was 4.3. The effect of oxycodone on serious adverse events reported was uncertain in comparison with placebo (oxycodone 3.4% versus placebo: 7.0%; RR 0.48 (95% confidence interval (CI) 0.18 to 1.23; very low quality evidence); one death was reported with oxycodone CR, but was not attributed to treatment. Adverse event withdrawals did not differ significantly between groups, occurring in 11% of participants with oxycodone CR and 6.4% with placebo (RR 1.69 (0.83 to 3.43); very low quality evidence). Withdrawals due to lack of efficacy were less frequent with oxycodone CR (1.1%) than placebo (11%), with an NNT to prevent one withdrawal of 10 (RR 0.12 (0.03 to 0.45); very low quality evidence).We found no relevant studies in chronic neuropathic pain conditions other than painful diabetic neuropathy or postherpetic neuralgia, or in fibromyalgia. AUTHORS' CONCLUSIONS: No convincing, unbiased evidence suggests that oxycodone (as oxycodone CR) is of value in treating people with painful diabetic neuropathy or postherpetic neuralgia. There is no evidence at all for other neuropathic pain conditions, or for fibromyalgia. Adverse events typical of opioids appear to be common.

Meta-analysis of efficacy and safety of intravenous ferric carboxymaltose (Ferinject) from clinical trial reports and published trial data.

BACKGROUND: Recommendations given for intravenous iron treatment are typically not supported by a high level of evidence. This meta-analysis addressed this by summarising the available date from clinical trials of ferric carboxymaltose using clinical trial reports and published reports. METHODS: Clinical trial reports were supplemented by electronic literature searches comparing ferric carboxymaltose with active comparators or placebo. Various outcomes were sought for efficacy (attainment of normal haemoglobin (Hb), increase of Hb by a defined amount, for example), together with measures of harm, including serious adverse events and deaths. RESULTS: Fourteen studies were identified with 2,348 randomised patients exposed to ferric carboxymaltose, 832 to oral iron, 762 to placebo, and 384 to intravenous iron sucrose. Additional data were available from cohort studies. Intravenous ferric carboxymaltose was given up to the calculated iron deficit (up to 1,000 mg in one week) for iron deficiency anaemia secondary to chronic kidney disease, blood loss in obstetric and gynaecological conditions, gastrointestinal disease, and other conditions like heart failure. The most common comparator was oral iron, and trials lasted 1 to 24 weeks. Intravenous ferric carboxymaltose improved mean Hb, serum ferritin, and transferrin saturation levels; the mean end-of-trial increase over oral iron was, for Hb 4.8 (95% confidence interval 3.3 to 6.3) g/L, for ferritin 163 (153 to 173) µg/L, and for transferrin saturation 5.3% (3.7 to 6.8%). Ferric carboxymaltose was significantly better than comparator in achievement of target Hb increase (number needed to treat (NNT) 6.8; 5.3 to 9.7) and target Hb NNT (5.9; 4.7 to 8.1). Serious adverse events and deaths were similar in incidence in ferric carboxymaltose and comparators; rates of constipation, diarrhoea, and nausea or vomiting were lower than with oral iron. CONCLUSIONS: This review examined the available trials of intravenous ferric carboxymaltose using details from published papers and unpublished clinical trial reports. It increases the evidence available to support recommendations given for intravenous iron treatment, but there are limited trial data comparing different intravenous iron preparations.

Is there an association between low dose aspirin and anemia (without overt bleeding)? Narrative review.

BACKGROUND: Overt bleeding associated with low dose aspirin (LDA) is well-recognized, little attention is given to the possibility of association between LDA and occult bleeding, although this is known to occur in healthy volunteers. LDA is used increasingly in primary and secondary prevention of a number of medical conditions, many of which are common in older people, as is anemia. Anemia in older people is associated with adverse outcomes including disability, morbidity and mortality. The purpose of this study was to review the evidence that LDA might cause anemia without overt bleeding. METHODS: An extensive narrative review was carried out. Electronic searching (including database links) and reference lists of reports were used to identify studies reporting on use of aspirin ≤325 mg/day and anemia or change in hemoglobin (Hb) without overt bleeding. Data were extracted from reports of trials, adverse drug reactions (ADRs) and prevalence studies of adults aged ≥18 years, published since 1980. RESULTS: There are few relevant data, with considerable heterogeneity among trial designs, duration, and patient characteristics in studies of LDA. In five randomised trials (n = 5879) in (mostly secondary) prevention, the majority of patients were men without peptic ulcer disease aged 50-70 years and no consistent association between LDA and change in Hb was found. In two smaller studies (n = 609) of primary prevention in healthy patients aged ≥70 years, there was a small but statistically significant fall in Hb with LDA. Observational studies, and data from trials in which use of LDA was not a primary focus of the study, were inconclusive. CONCLUSIONS: It is not clear whether there is an association between LDA and anemia in the absence of overt bleeding, but there may be an association between LDA and fall in Hb in (a subset of) older patients. The available evidence has significant limitations, which are discussed; studies including more older patients, and publication of individual patient data, would help clarify this important matter.

Single dose oral oxycodone and oxycodone plus paracetamol (acetaminophen) for acute postoperative pain in adults.

BACKGROUND: Oxycodone is a strong opioid agonist used to treat severe pain. It is commonly combined with milder analgesics such as paracetamol. This review updates a previous review that concluded, based on limited data, that all doses of oxycodone exceeding 5 mg, with or without paracetamol, provided analgesia in postoperative pain, but with increased incidence of adverse events compared with placebo. Additional new studies provide more reliable estimates of efficacy and harm. OBJECTIVES: To assess efficacy, duration of action, and associated adverse events of single dose oral oxycodone, with or without paracetamol, in acute postoperative pain in adults. SEARCH STRATEGY: Cochrane CENTRAL, MEDLINE, EMBASE and Oxford Pain Relief Database, searched in May 2009. SELECTION CRITERIA: Randomised, double blind, placebo-controlled trials of single dose orally administered oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants remedicating over specified time periods, and time-to-use of rescue medication, were sought as additional measures of efficacy. Adverse events and withdrawals information was collected. MAIN RESULTS: This updated review includes 20 studies, with 2641 participants. For oxycodone 15 mg alone compared with placebo, the NNT for at least 50% pain relief was 4.6 (95% Confidence Interval 2.9 to 11). For oxycodone 10 mg plus paracetamol 650 mg, the NNT was 2.7 (2.4 to 3.1). A dose response was demonstrated for this outcome with combination therapy. Duration of effect was 10 hours with oxycodone 10 mg plus paracetamol 650 mg, and 4 hours with half that dose. Fewer participants needed rescue medication over 6 hours at the higher dose. Adverse events occurred more frequently with combination therapy than placebo, but were generally described as mild to moderate in severity and rarely led to withdrawal. AUTHORS' CONCLUSIONS: Single dose oxycodone is an effective analgesic in acute postoperative pain at doses over 5 mg; oxycodone is two to three times stronger than codeine. Efficacy increases when combined with paracetamol. Oxycodone 10 mg plus paracetamol 650 mg provides good analgesia to half of those treated, comparable to commonly used non-steroidal anti-inflammatory drugs, with the benefit of longer duration of action.

Duloxetine for painful diabetic neuropathy and fibromyalgia pain: systematic review of randomised trials.

BACKGROUND: Duloxetine hydrochloride is a reuptake inhibitor of 5-hydroxytryptamine and norepinephrine used to treat depression, generalized anxiety disorder, neuropathic pain, and stress incontinence in women. We investigated the efficacy of duloxetine in painful diabetic neuropathy and fibromyalgia to allow comparison with other antidepressants. METHODS: We searched PubMed, EMBASE (via Ovid), and Cochrane CENTRAL up to June 2008 for randomised controlled trials using duloxetine to treat neuropathic pain. RESULTS: We identified six trials with 1,696 patients: 1,510 were treated with duloxetine and 706 with placebo. All patients had established baseline pain of at least moderate severity. Trial duration was 12 to 13 weeks. Three trials enrolled patients with painful diabetic neuropathy (PDN) and three enrolled patients with fibromyalgia. The number needed to treat (NNT) for at least 50% pain relief at 12 to 13 weeks with duloxetine 60 mg versus placebo (1,211 patients in the total comparison) was 5.8 (95% CI 4.5 to 8.4), and for duloxetine 120 mg (1,410 patients) was 5.7 (4.5 to 5.7). There was no difference in NNTs between PDN and fibromyalgia. With all doses of duloxetine combined (20/60/120 mg) there were fewer withdrawals for lack of efficacy than with placebo (number needed to treat to prevent one withdrawal 20 (13 to 42)), but more withdrawals due to adverse events (number needed to harm (NNH) 15 (11 to 25)). Nausea, somnolence, constipation, and reduced appetite were all more common with duloxetine than placebo (NNH values 6.3, 11, 11, and 18 respectively). The results for duloxetine are compared with published data for other antidepressants in neuropathic pain. CONCLUSION: Duloxetine is equally effective for the treatment of PDN and fibromyalgia, judged by the outcome of at least 50% pain relief over 12 weeks, and is well tolerated. The NNT of 6 for 50% pain relief suggests that this is likely to be a useful drug in these difficult-to-treat conditions, where typically only a minority of patients respond. Comparing duloxetine with antidepressants for pain relief in DPN shows inadequacies in the evidence for efficacy of antidepressants, which are currently recommended in PDN care pathways.

Prevalence of anaemia in older persons: systematic review.

BACKGROUND: Ageing populations will impact on healthcare provision, especially since extra years are not necessarily spent in good health. It is important to identify and understand the significance of common medical problems in older people. Anaemia may be one such problem. We report on the prevalence of anaemia in cohorts of elderly people in the general population. The presence of anaemia is associated with a worse prognosis for both morbidity and mortality. METHODS: Electronic searching and reference lists of published reports were used to identify studies that reported on prevalence of anaemia in cohorts of at least 100 individuals predominantly aged 65 years and over living in developed countries, together with criteria used to define anaemia. Studies of anaemia prevalence in specific disease groups or published before 1980 were excluded. Prevalence data for the entire cohort, for men and women separately and for different age bands were extracted. RESULTS: Forty-five studies contributed data. Thirty-four studies (n = 85,409) used WHO criteria to define anaemia. The weighted mean prevalence was 17% (3-50%) overall, and 12% (3-25%) in studies based in the community (27, n = 69,975), 47% (31-50%) in nursing homes (3, n = 1481), and 40% (40-72%) in hospital admissions (4, n = 13,953). Anaemia prevalence increased with age, was slightly higher in men than women, and was higher in black people than white. Most individuals classified as anaemic using WHO criteria were only mildly anaemic. CONCLUSION: Anaemia, as defined by WHO criteria, is common in older people living in the community and particularly common in nursing home residents and hospital admissions. Predicted demographic changes underline the need to understand more about anaemia in older people.