The impact and burden of chronic pain in the workplace: a qualitative systematic review.

BACKGROUND: Chronic pain (CP) poses a diverse and substantial burden for employees, employers, and society. The deleterious consequences of CP in the workplace are frequently underestimated. OBJECTIVE: To estimate the burden of CP in the European workplace. METHODS: A systematic review following PRISMA statement guidelines was conducted to identify studies reporting work-related outcomes for people with CP. EMBASE, MEDLINE, EconLit, and Cochrane Library databases were searched up to 18th August 2010. RESULTS: We identified 91 observational studies. Few were specifically designed to investigate the association between CP, productivity, and employment. The focus for this review was studies clearly reporting outcomes relating to the burden of CP on employment status (n = 37), sickness absence (absenteeism, n = 47), and loss of productivity because of reduced ability at work (presenteeism, n = 8). CONCLUSION: The body of evidence identified from the systematic review indicates that CP has a substantial negative impact on work-related outcomes, supporting the importance of interventions to reduce the burden of CP. Well-designed prospective studies specifically assessing the direct consequences of CP on employment are needed to confirm these findings.

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

BACKGROUND: Ketoprofen is a non-selective non-steroidal 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. OBJECTIVES: To assess efficacy, duration of action, and associated adverse events of single dose oral ketoprofen and dexketoprofen in acute postoperative pain in adults. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to August 2009. SELECTION CRITERIA: Randomised, double blind, placebo-controlled trials of single dose orally administered ketoprofen and dexketoprofen 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 using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. MAIN RESULTS: Fourteen studies compared ketoprofen (968 participants) at mainly 25 mg and 50 mg with placebo (520 participants). Seven studies compared dexketoprofen (681 participants) at mainly 10 mg to 25 mg with placebo (289 participants). Studies were of adequate reporting quality, and participants had pain following dental, orthopaedic, obstetric, gynaecological and general surgery. There was considerable clinical heterogeneity between studies in dental and other types of surgery, particularly bunionectomy, which limited analysis.Ketoprofen at doses between 12.5 mg and 100 mg produced NNTs for at least 50% pain relief over 4 to 6 hours of 2.4 to 3.3. For dental studies only there was a trend to more efficacy at higher doses, with NNT decreasing from 2.4 at 12.5 mg to 1.6 at 100 mg. Dexketoprofen at doses of 10/12.5 mg and 20/25 mg produced NNTs for at least 50% pain relief over 4 to 6 hours of 3.2 and 3.6, with no obvious dose response. Significantly fewer participants used rescue medication with ketoprofen and dexketoprofen than placebo. The median time to remedication was about 5 hours with ketoprofen and 4 hours with dexketoprofen. The expected equivalent efficacy with a half dose of dexketoprofen compared to ketoprofen was not demonstrated.Adverse events were uncommon with both drugs, and not significantly different from placebo. 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 3.3 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 at 50 mg dose). Duration of action is about 5 hours. Dexketoprofen is also effective with NNTs of 3.2 to 3.6 in the dose range 10 mg to 25 mg. Both drugs were well tolerated in single doses.

Systematic review of dexketoprofen in acute and chronic pain.

BACKGROUND: Dexketoprofen, an NSAID used in the management of acute and chronic pains, is licensed in several countries but has not previously been the subjected of a systematic review. We used published and unpublished information from randomised clinical trials (RCTs) of dexketoprofen in painful conditions to assess evidence on efficacy and harm. METHODS: PubMed and Cochrane Central were searched for RCTs of dexketoprofen for pain of any aetiology. Reference lists of retrieved articles and reviews were also searched. Menarini Group produced copies of published and unpublished studies (clinical trial reports). Data were abstracted into a standard form. For studies reporting results of single dose administration, the number of patients with at least 50% pain relief was derived and used to calculate the relative benefit (RB) and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief compared with placebo. RESULTS: Thirty-five trials were found in acute pain and chronic pain; 6,380 patients were included, 3,381 receiving dexketoprofen. Information from 16 trials (almost half the total patients) was obtained from clinical trial reports from previously unpublished trials or abstracts. Almost all of the trials were of short duration in acute conditions or recent onset pain.All 12 randomised trials that compared dexketoprofen (any dose) with placebo found dexketoprofen to be statistically superior. Five trials in postoperative pain yielded NNTs for 12.5 mg dexketoprofen of 3.5 (2.7 to 4.9), 25 mg dexketoprofen of 3.0 (2.4 to 3.9), and 50 mg dexketoprofen of 2.1 (1.5 to 3.5). In 29/30 active comparator trials, dexketoprofen at the dose used was at least equivalent in efficacy to comparator drugs. Adverse event withdrawal rates were low in postoperative pain and somewhat higher in trials of longer duration; no serious adverse events were reported. CONCLUSION: Dexketoprofen was at least as effective as other NSAIDs and paracetamol/opioid combinations. While adverse event withdrawal was not different between dexketoprofen and comparator analgesics, the different conditions and comparators studies precluded any formal analysis. Exposure was limited, and no conclusions could be drawn about safety in terms of serious adverse events like gastrointestinal bleeding or cardiovascular events.

Single dose oral celecoxib for acute postoperative pain in adults.

BACKGROUND: This is an update of a review published in The Cochrane Library, Issue 1, 2003. Celecoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor prescribed for the relief of chronic pain in osteoarthritis and rheumatoid arthritis. Celecoxib is believed to be associated with fewer upper gastrointestinal adverse effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). Its effectiveness in acute pain was demonstrated in the earlier review. Additional studies have now been published for the 400 mg dose, and this updated review provides more robust estimates of efficacy and harm. OBJECTIVES: To assess analgesic efficacy and adverse effects of a single oral dose of celecoxib for moderate to severe postoperative pain. SEARCH STRATEGY: Cochrane CENTRAL, MEDLINE, EMBASE, and the Oxford Pain Database. Most recent search: July 2008. SELECTION CRITERIA: Randomised controlled trials (RCTs) of adults prescribed any dose of oral celecoxib or placebo for acute postoperative pain were included. DATA COLLECTION AND ANALYSIS: Eight studies (1380 participants) met the inclusion criteria. Studies were assessed for quality and data extracted by two review authors. Summed pain relief (TOTPAR) or pain intensity difference (SPID) was converted into dichotomous information yielding the number of participants with at least 50% pain relief over four to six hours, and used to calculate the relative benefit (RB) and number-needed-to-treat-to-benefit (NNT) for one patient to achieve at least 50% pain relief with celecoxib who would not have done so with placebo. Information on use of rescue medication was used to calculate the proportion of participants requiring rescue medication and the weighted mean (WM) of the median time to use. MAIN RESULTS: The NNT for celecoxib 200 mg and 400 mg compared with placebo for at least 50% pain relief over four to six hours was 4.2 (CI 3.4 to 5.6) and 2.5 (2.2 to 2.9) respectively. The WM of the median time to use of rescue medication was 6.6 hours with celecoxib 200 mg, 8.4 with celecoxib 400 mg, and 2.3 hours with placebo. The WM proportion of participants requiring rescue medication over 24 hours was 74% with celecoxib 200 mg, 63% for celecoxib 400 mg, and 91% for placebo. The NNT to prevent one patient using rescue medication was 4.8 (3.5 to 7.7) and 3.5 (2.9 to 4.6) for celecoxib 200 mg and 400 mg respectively. One serious adverse event probably related to celecoxib was reported by the trialists. AUTHORS' CONCLUSIONS: Single dose oral celecoxib is an effective means of postoperative pain relief. The 400 mg dose has similar efficacy to ibuprofen 400 mg.

Bias from industry trial funding? A framework, a suggested approach, and a negative result.

Bias from funding sources of trials would threaten their validity. Meta-analyses of high quality acute pain and migraine trials were used to explore the hypothesis that industry funding of clinical trials produced more favourable results than non-profit sponsorship. Analyses were planned to evaluate whether industry-sponsored trials had different results from trials funded by academic or other non-profit sources, but of 176 trials, only two were supported by non-profit sources, while 31 provided no statement of support. An alternative method is proposed within industry-sponsored trials, looking at conflicting industry interests for the same drug, used either as test or comparator treatment. Fifty-three trials used an analgesic as test and 90 as comparator, allowing comparisons to be made for aspirin 600/650 mg, ibuprofen 400 mg, paracetamol (acetaminophen) 1000 mg, rofecoxib 50 mg and sumatriptan 50 and 100 mg. Only for sumatriptan 50 and 100 mg, with the outcome of headache response at 2 h, was there any significant difference between the drug used as a test or as a comparator. The direction was for higher (worse) NNTs with sumatriptan as comparator. Investigating potential industry bias through the funding source of trials is unlikely to be adequate because of a dearth of trials funded by non-profit organisations. We propose a method based on potential conflict of interest within industry-sponsored trials. Using this method, established clinical trial results in acute pain and migraine appear to be unbiased.

Outcomes in acute pain trials: systematic review of what was reported?

Single-dose clinical trial methods for evaluating analgesics have been used successfully for over 50 years. The aims of this review were to examine which pain measurement scales have been used in high quality acute pain trials, to investigate other common measurements or characteristics, to confirm that different scales used by standard methods give the same estimate of analgesic effect, to investigate remedication methodologies and the potential of 'time to remedication' as a standard outcome. Published reports of randomised, double blind, placebo-controlled trials, investigating at least 20 adult patients (10 patients per treatment arm) experiencing moderate or severe pain using at least one standard pain intensity or pain relief scale were sought. Key design features, outputs and outcomes were catalogued for each report. The main outcomes reported were misleading, detailing only the mean values of data with a demonstrably skewed distribution. After 50 years, the reporting of results from acute pain trials warrants a fresh look. Possible improvements include reporting the number of patients with certain levels of pain relief, or the actual number (percentage) of patients with a certain level of pain relief at a certain time, or more useful information on remedication from trials of at least 12 h duration. Most useful would be all three. Further exploration would only be possible from analysis at the individual patient level.

Pain and analgesic response after third molar extraction and other postsurgical pain.

There is uncertainty over whether the patient group in which acute pain studies are conducted (pain model) has any influence on the estimate of analgesic efficacy. Data from four recently updated systematic reviews of aspirin 600/650 mg, paracetamol 600/650 mg, paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model. Area under the pain relief versus time curve equivalent to at least 50% maximum pain relief over 6 h was used as the outcome measure. Event rates with treatment and placebo, and relative benefit (RB) and number needed to treat (NNT) were used as outputs from the meta-analyses. The event rate with placebo was systematically statistically lower for dental than postsurgical pain for all four treatments. Event rates with analgesics, RB and NNT were infrequently different between the pain models. Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven, and, on balance, no major difference is likely.

Oral valdecoxib and injected parecoxib for acute postoperative pain: a quantitative systematic review.

BACKGROUND: Clinical trials suggest that cyclo-oxygenase-2 specific inhibitors (coxibs) are an effective treatment for acute postoperative pain. The aims of this systematic review were to examine the evidence for oral valdecoxib and injected parecoxib, and quantify efficacy and adverse effects. METHODS: Information from randomized, double-blind studies in acute postoperative pain was sought. The area under the pain relief versus time curve over four to six hours was dichotomized using validated equations to derive the proportion of patients with treatment and placebo with at least 50% pain relief over four to six hours and calculate the number-needed-to-treat (NNT). Information on duration of analgesia and adverse events was also collected. RESULTS: The NNT for one patient to experience at least 50% relief over six hours following a single oral dose of valdecoxib 20 mg and 40 mg was 1.7 (1.4 to 2.0) and 1.6 (1.4 to 1.8) respectively. The NNT for one patient to have at least 50% relief over four to six hours with parecoxib 20 mg IV and 40 mg IV was 3.0 (2.3 to 4.1) and 2.3 (2.0 to 2.6) respectively. Mean time to remedication (weighted by trial size) was >24 hours with valdecoxib 40 mg, 8.7 hours with parecoxib 40 mg IV and 1.7 to 1.8 hours with placebo. There were no statistical differences between treatment and placebo for any adverse effect. CONCLUSION: Both oral valdecoxib and injected parecoxib are effective treatments for acute postoperative pain.

Ibuprofen 400 mg is effective in women, and women are well represented in trials.

BACKGROUND: A recent article in the New Scientist argued that women were under-represented in clinical trials which, until now, had masked the finding that ibuprofen 400 mg was ineffective in women. METHODS: Meta-analysis of randomised, double-blind placebo-controlled trials of ibuprofen 400 mg in acute pain, and use of individual patient information were planned to test the hypothesis that ibuprofen is ineffective in women. For each trial the proportion of women participating, the number of patients with at least 50% pain relief and the overall event rate for ibuprofen 400 mg and placebo was calculated. For each patient percentage pain relief was calculated, and the numbers of women and men achieving at least 50% pain relief used to calculate number-needed-to-treat (NNT) for ibuprofen 400 mg compared to placebo. RESULTS: Thirty-seven included trials had 3,577 patients, 67% of whom were women. The proportion with at least 50% pain relief was unaffected by how many women were included. In an analysis of 678 individual patients the proportion of women and men with at least 50% pain relief was the same, NNT 3.4 (2.6 to 4.6) and 2.5 (2.0 to 3.3) respectively. CONCLUSION: There is no clinically meaningful difference in the efficacy of ibuprofen 400 mg between men and women experiencing moderate to severe postoperative pain and women were well represented.

Single-dose rofecoxib for acute postoperative pain in adults: a quantitative systematic review.

BACKGROUND: Rofecoxib is a cyclo-oxygenase 2 selective inhibitor. This systematic review of rofecoxib in acute pain examined studies in adults of analgesic efficacy over six hours, the amount and quality of the evidence on extended duration of analgesia, and the quality and quantity of evidence on adverse events. METHODS: Cochrane Library (issue 4, 2001), Biological Abstracts (March 2002), MEDLINE (March 2002) and PubMed (March 2002) were searched using rofecoxib as a free text term. The area under the pain relief versus time curve was dichotomized using validated equations to derive the proportion of patients on rofecoxib 50 mg or placebo with at least 50% pain relief over six hours. This was used to calculate the number needed to treat for at least 50% pain relief over six hours for rofecoxib compared with placebo. Information on duration of analgesia and adverse events was also collected. RESULTS: Five included trials investigated 1,118 patients, of whom 211 received placebo and 464 received rofecoxib 50 mg. The NNT for rofecoxib 50 mg was 2.3 (95% confidence interval 2.0 to 2.6). The weighted mean remedication time was 1.9 hours for placebo (126 patients), 7.4 hours for ibuprofen 400 mg (97 patients) and 13.6 hours for rofecoxib 50 mg (322 patients). CONCLUSION: Rofecoxib at 2-4 times the standard daily dose for chronic pain is an effective single dose oral analgesic in acute pain. Limitations in trial reporting constrain conclusions about longer duration of analgesia and adverse event profile.