[Opioids in chronic noncancer pain-are opioids different? A systematic review and meta-analysis of efficacy, tolerability and safety in randomized head-to-head comparisons of opioids of at least four week's duration]. / Opioide bei chronischen nicht-tumorbedingten Schmerzen - gibt es Unterschiede? Systematische Übersicht und Metaanalyse der Wirksamkeit, Verträglichkeit und Sicherheit in randomisierten Direktvergleichen von Opioiden über mindestens 4 Wochen.

BACKGROUND: We updated a systematic review on the comparative efficacy, tolerability and safety of opioids and of their routes of application in chronic noncancer pain (CNCP). METHODS: We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as the reference sections of original studies and systematic reviews of randomized controlled trials (RCTs) of opioids in CNCP. We included randomized head-to-head comparisons of opioids (opioid of the sponsor of the study versus standard opioid) of at least 4 week's duration. Using a random effects model, absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. The quality of evidence was rated by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: We included 13 RCTs with 6748 participants. Median study duration was 15 weeks (range 4-56 weeks). Hydromorphone, morphine, oxymorphone and tapentadol were compared to oxycodone; fentanyl to morphine and buprenorphine to tramadol. In pooled analysis, there were no significant differences between the two groups of opioids in terms of mean pain reduction (low-quality evidence), the patient global impression to be much or very much improved outcome (low-quality evidence), physical function (very low-quality evidence), serious adverse events (moderate-quality evidence) or mortality (moderate-quality evidence). There was no significant difference between transdermal and oral application of opioids in terms of mean pain reduction, physical function, serious adverse events, mortality (all low-quality evidence) or dropout due to adverse events (very low-quality). CONCLUSION: Pooled head-to-head comparisons of opioids (opioid of the sponsor of the study versus standard opioid) provide no rational for preferring one opioid and/or administration route over another in the therapy of patients with CNCP. The English full-text version of this article is freely available at SpringerLink (under "Supplemental").

[Opioids in chronic noncancer pain-are opioids superior to nonopioid analgesics? A systematic review and meta-analysis of efficacy, tolerability and safety in randomized head-to-head comparisons of opioids versus nonopioid analgesics of at least four week's duration]. / Opioide bei chronischen nicht-tumorbedingten Schmerzen - sind sie Nichtopioidanalgetika überlegen? Systematische Übersicht und Metaanalyse der Wirksamkeit, Verträglichkeit und Sicherheit in randomisierten Direktvergleichen von Opioiden und Nichtopioidanalgetika über mindestens 4 Wochen.

BACKGROUND: Some leading German pain medicine experts postulate that there is a type of chronic non-cancer pain (CNCP) with an opioid requirement. We tested whether opioids are superior to nonopioid analgesics in the management of CNCP in studies of at least 4 week's duration. METHODS: We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as the reference sections of original studies and systematic reviews of randomised controlled trials (RCTs) of opioids in CNCP. We included double-blind RTCs comparing opioids to nonopioid analgesics of at least 4 week's duration. Relative risks differences (RD) of categorical data and standardized mean differences (SMD) of continuous variables were calculated using a random effects model. RESULTS: We included 10 RCTs with 3046 participants. Median study duration was 6 weeks (range 4-12 weeks). Five studies compared tramadol with nonsteroidal anti-inflammatory drugs (NSAIDs) in osteoarthritis pain and one trial compared tramadol to flupirtine in low back pain. Morphine was compared to antidepressants (two studies), an anticonvulsant (one study) and an antiarrhythmic (one study) in different neuropathic pain syndromes. There was no significant difference between opioids and nonopioid analgesics in pain reduction (SMD 0.03 [95 % confidence interval, CI - 0.18, 0.24]; p = 0.76). Nonopioid analgesics were superior to opioids in improving physical function (SMD 0.17 [95 % CI 0.02, 0.32]; p = 0.03). Patients dropped out due to adverse events more frequently with opioids than with nonopioid analgesics (RD 0.09 [95 % CI 0.06, 0.13]; p < 0.0001). There was no significant difference between opioids and nonopioid analgesics in terms of serious adverse events or dropout rates due to lack of efficacy. CONCLUSION: Nonopioid analgesics are superior to opioids in terms of improvement of physical function and tolerability in short-term (4-12 weeks) therapy of neuropathic, low back and osteoarthritis pain. Our results do not support the concept of an"opioid-requiring" CNCP. The English full-text version of this article is freely available at SpringerLink (under "Supplemental").

[Erratum to: Opioids for chronic non-tumor-related pain--are not opioid analgesics superior? Systematic Review and Meta-analysis of Efficacy, tolerability and safety in randomized direct comparison of opioids and non-opioid analgesia for at least 4 weeks]. / Erratum zu: Opioide bei chronischen nicht-tumorbedingten Schmerzen - sind sie Nichtopioidanalgetika überlegen? Systematische Übersicht und Metaanalyse der Wirksamkeit, Verträglichkeit und Sicherheit in randomisierten Direktvergleichen von Opioiden und Nichtopioidanalgetika über mindestens 4 Wochen.

Fig. 1 is slightly flawed as shown (the last line is missing). We enter the picture again correctly.

[Opioids in chronic low back pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration]. / Opioide bei chronischem Kreuzschmerz. Systematische Übersicht und Metaanalyse der Wirksamkeit, Verträglichkeit und Sicherheit in randomisierten, placebokontrollierten Studien über mindestens 4 Wochen.

BACKGROUND: The efficacy and safety of opioid therapy in chronic low back pain (CLBP) is under debate. We updated a recent systematic review on the efficacy and safety of opioids in CLBP. METHODS: We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as reference sections of original studies and systematic reviews of randomized controlled trials (RCTs) of opioids in CLBP. We included double-blind randomized placebo-controlled studies of at least 4 weeks duration. Using a random effects model, absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. RESULTS: We included 12 RCTs with 17 treatment arms and 4375 participants. Median study duration was 12 (4-16) weeks. Of the 17 treatment arms, seven (41.2 %) used oxycodone; four (23.6 %) tramadol; buprenorphine and oxymorphone were each used in two (11.8 %) and hydromorphone and tapentadol each in one (5.8 %). The results for studies with parallel/cross-over design were as follows (with 95 % confidence interval, CI): opioids were superior to placebo in reducing pain intensity (SMD - 0.29 [- 0.37, - 0.21], p < 0.0001; six studies with 2896 participants). Opioids were superior to placebo in 50 % pain reduction (RD 0.05 [0.01, 0.10], p = 0.01; two studies with 1492 participants; number needed to benefit (NNTB) 19 [95 % CI 10-107]). Opioids were not superior to placebo in reports of much or very much improved pain (RD 0.16 [- 0.01, 0.34], p = 0.07; two studies with 1153 participants). Opioids were superior to placebo in improving physical functioning (SMD - 0.22 [- 0.31, - 0.12], p < 0.0001; four studies with 1895 participants). Patients dropped out less frequently with opioids than with placebo due to lack of efficacy (RD - 0.10 [- 0.16, - 0.04], p = 0.001; five studies with 3168 participants; NNTB 10 [8-13]). Patients dropped out more frequently with opioids than with placebo due to adverse events (RD 0.12 [0.05, 0.19], p = 0.0007; six studies with 2910 participants; number needed to harm (NNTH) 7 [95 % CI 6-8]). There was no significant difference between opioids and placebo in terms of the frequency of serious adverse events or deaths. CONCLUSION: Opioids were superior to placebo in terms of efficacy and inferior in terms of tolerability. Opioids and placebo did not differ in terms of safety during the study period. The conclusion on the safety of opioids compared to placebo is limited by the low number of serious adverse events and deaths. Short-term and intermediate-term opioid therapy may be considered in selected CLBP patients. The English full-text version of this article is freely available at SpringerLink (under "Supplemental").

[Methodology of the development of the updated LONTS guidelines for long-term administration of opioids in noncancer pain]. / Methodenreport der aktualisierten Leitlinie "Langzeitanwendung von Opioiden bei nicht-tumorbedingten Schmerzen - LONTS".

BACKGROUND: The update of the German S3 guidelines on long-term opioid therapy of chronic noncancer pain (CNCP), the"LONTS" (AWMF registration number 145/003) was scheduled for May 2014. METHODS: The guidelines were developed by 25 scientific societies and two patient self-help organizations under the coordination of the German Pain Society and the Association of the Scientific Medical Societies in Germany (AWMF). RESULTS: A systematic literature search was performed in the CENTRAL, MEDLINE and Scopus databases from October 2008 to October 2013. Meta-analyses of randomized controlled trials (RCT) of opioids in CNPC of study duration ≥ 4 weeks were conducted. Levels of evidence were assigned according to the Oxford Centre for Evidence-Based Medicine version 2009 classification system. The formulation and strength of recommendations was established in a multistep formalized consensus procedure, in accordance with AWFM rules and standards. The guidelines were reviewed by three scientific societies not involved in their development and were approved by the executive boards of the societies that were engaged in development of the guidelines. CONCLUSION: The guidelines will be published in several forms: complete and short scientific versions, as well as clinical practice and patient versions.

[Opioids in chronic osteoarthritis pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration]. / Opioide bei chronischem Arthroseschmerz. Systematische Übersicht und Metaanalyse der Wirksamkeit, Verträglichkeit und Sicherheit in randomisierten, placebokontrollierten Studien über mindestens 4 Wochen.

BACKGROUND: The efficacy, tolerability and safety of opioid therapy in chronic osteoarthritis (OA) pain is under debate. We updated a Cochrane systematic review on the efficacy and safety of opioids in chronic OA pain published in 2009. METHODS: We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as reference sections of original studies and systematic reviews of randomized controlled trials (RCTs) of opioids in chronic osteoarthritis (OA) pain. We included double-blind randomized placebo-controlled studies lasting ≥ 4 weeks. Using a random effects model, absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. RESULTS: We included 20 RCTs with 33 treatment arms and 8545 participants. Median study duration was 12 (4-24) weeks. Oxycodone and tramadol were each tested in six studies; buprenorphine, hydromorphone, morphine and tapentadol each in two studies and codeine, fentanyl and oxymorphone in one study each. Results are reported with 95 % confidence intervals (CIs). Opioids were superior to placebo in reducing pain intensity (SMD - 0.22 [- 0.28, - 0.17], p < 0.00001; 16 studies with 6743 participants). Opioids were not superior to placebo in 50 % pain reduction (RD - 0.00 [- 0.07, 0.07], p = 0.96; two studies with 2684 participants). Opioids were superior to placebo in terms of reports of much or very much global improvement (RD 0.13 [0.05, 0.21], p = 0.002; three studies with 2251 participants). Opioids were superior to placebo in improving physical functioning (SMD - 0.22 [- 0.28, - 0.17], p < 0.00001; 14 studies with 5887 participants). Patients dropped out more frequently with opioids than with placebo (RD 0.17 [0.14, 0.21], p < 0.00001; 15 studies with 6834 participants; number needed to harm 5 [4-6]. There was no significant difference between opioids and placebo in the frequency of serious adverse events (SAE) or deaths over the respective observation periods. CONCLUSION: Opioids were superior to placebo in terms of efficacy and inferior in terms of tolerability. The effect sizes of average reduction in pain intensity and physical disability were small. Opioids and placebo did not differ in terms of safety. The conclusion on the safety of opioids compared to placebo is limited by the low number of SAE and deaths. Short-term opioid therapy may be considered in selected chronic OA pain patients. No current evidence-based guideline recommends opioids as first-line treatment option for chronic OA pain. To provide superior evidence for future treatment guidelines, RCTs must directly compare existing pharmacological and nonpharmacological therapies and administer these in various combinations and sequences. The English full-text version of this article is freely available at SpringerLink (under "Supplemental").

[Opioids in chronic neuropathic pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration]. / Opioide bei chronischem neuropathischem Schmerz. Systematische Übersicht und Metaanalyse der Wirksamkeit, Verträglichkeit und Sicherheit in randomisierten, placebokontrollierten Studien über mindestens 4 Wochen.

BACKGROUND: The efficacy and safety of opioid therapy in chronic neuropathic pain (CNP) is under debate. We updated a recent Cochrane systematic review on the efficacy, tolerability and safety of opioids in CNP. METHODS: We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as the reference sections of original studies and systematic reviews of randomized controlled trials (RCTs) of opioids in CNP. We included double-blind randomized placebo-controlled studies of at least 4 weeks duration. Using a random effects model, absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. RESULTS: We included 12 RCTs with 1192 participants. The included diagnostic entities were painful diabetic neuropathy (four studies), postherpetic neuralgia (three studies), mixed polyneuropathic pain (two studies), and lumbar root, spinal cord injury and postamputation pain (one study each). Mean study duration was 6 (4-12) weeks. Four studies tested morphine, three studies tramadol, two studies oxycodone and one study tapentadol. These are the pooled results of studies with a parallel or cross-over design: opioids were superior to placebo in reducing pain intensity (SMD - 0.64 [95 % confidence interval, CI - 0.81, - 0.46], p < 0.0001; 11 studies with 1040 participants). Opioids were not superior to placebo in 50 % pain reduction (RD 0.16 [95 % CI - 0.04, 0.35], p = 0.11; one study with 93 participants). Opioids were not superior to placebo in reports of much or very much improved pain (RD 0.17 [95 % CI - 0.01, 0.36], p = 0.07; one study with 53 participants). Opioids were superior to placebo in improving physical functioning (SMD - 0.28 [95 % CI - 0.43, - 0.13], p < 0.0001; seven studies with 680 participants). Patients dropped out less frequently due to lack of efficacy with opioids than with placebo (RD - 0.07 [95 % CI - 0.13, - 0.02], p = 0.008; six studies with 656 participants). Patients dropped out due to adverse events more frequently with opioids than with placebo (RD 0.08 [95 % CI 0.05, 0.12], p < 0.0001; ten studies with 1018 participants; number needed to harm 11 [95 % CI 8-17]). There was no significant difference between opioids and placebo in terms of the frequency of serious adverse events (SAE) or deaths. CONCLUSION: In short-term studies (4-12 weeks) in CNP, opioids were superior to placebo in terms of efficacy and inferior in terms of tolerability. Opioids and placebo did not differ in terms of safety. The conclusion relating to the safety of opioids compared to placebo in CNP is limited by the low number of SAE and deaths. Short-term opioid therapy may be considered in selected CNP patients. The English full-text version of this article is freely available at SpringerLink (under "Supplementary Material").

[Erratum to: Opioids in chronic low back pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration]. / Erratum zu: Opioide bei chronischem Kreuzschmerz. Systematische Übersicht und Metaanalyse der Wirksamkeit, Verträglichkeit und Sicherheit in randomisierten, placebokontrollierten Studien über mindestens 4 Wochen.

In Infobox 1 (Excluded with reason), p. 9, two reference numbers are missing. Item 2 (Gordon et al.): [34] Item 4 (Yarlas et al.): All data published by [39]

[Erratum to: Methodology of the development of the updated LONTS guidelines for long-term administration of opioids in noncancer pain]. / Erratum zu: Methodenreport der aktualisierten Leitlinie "Langzeitanwendung von Opioiden bei nicht-tumorbedingten Schmerzen - LONTS".

In the sentence "For dichotomous variables, the threshold for 'appreciable benefit' or 'appreciable harm' was set at a relative risk reduction (RRR) or relative risk increase (RRI) ≥ 10 % [5]" the relative risk increase (RRI) is not ≥10 %, but ≥ 25 %.

Efficacy, acceptability and safety of Internet-delivered psychological therapies for fibromyalgia syndrome: A systematic review and meta-analysis of randomized controlled trials.

This systematic review aimed at evaluating the efficacy, acceptability and safety of Internet-based psychological therapies (IPTs) in fibromyalgia syndrome (FMS). Clinicaltrials.gov, Cochrane Library, MEDLINE, PsycINFO and SCOPUS were searched from inception to January 2018. Randomized controlled trials (RCTs) comparing IPTs with controls were analysed. Primary outcomes were ≥50% pain relief, disability, negative mood, acceptability and safety at end of therapy and at 6-month follow up. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD) with 95% confidence intervals (CI). Six RCTs using different types of Internet-based cognitive-behavioural therapies [ICBTs] (acceptance-based; exposure-based; traditional) with 493 patients were included. At the end of treatment, ICBTs were superior to controls (waiting list, attention control, treatment as usual) in reducing negative mood (SMD -0.51 [95% CI -0.87 to -0.15]) (moderate quality evidence) and disability (SMD -0.56 [95% CI -1.00 to -0.13]) (moderate quality evidence). There were no statistically significant differences between ICBTs and controls in pain relief of 50% or greater (RD 0.09 [95% CI -0.02 to 0.20] (moderate quality evidence) and acceptability (moderate quality evidence). No data on safety and any outcomes at long-term follow-up compared to controls were found. The data available did not allow statistical comparisons between unguided and guided ICBTs and of ICBTs versus traditional face-to-face therapies. ICBTs provided a clinically relevant benefit over control interventions in reducing negative mood and disability at the end of treatment. SIGNIFICANCE: Internet-delivered cognitive behavioural therapies provided a clinically relevant benefit in reducing negative mood and disability in patients with FMS at the end of treatment if compared to waiting list, treatment as usual and attention controls.

Efficacy, acceptability and safety of cognitive behavioural therapies in fibromyalgia syndrome - A systematic review and meta-analysis of randomized controlled trials.

This updated systematic review aimed at evaluating the efficacy, acceptability and safety of cognitive behavioural therapies (CBTs) in fibromyalgia syndrome (FMS). Clinicaltrials.gov, Cochrane Library, MEDLINE, PsycINFO and SCOPUS were searched from September 2013 to May 2017. Randomized controlled trials (RCTs) comparing CBTs with controls were analysed. Primary outcomes were ≥50% pain relief, ≥20% improvement of health-related quality of life (HRQoL), negative mood, fatigue, disability, acceptability and safety at end of therapy and at 6 months follow-up. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD) with 95% confidence intervals (CI). 29 RCTs with 2509 subjects were included. CBTs were superior to controls (waiting list, attention control, treatment as usual, other active non-pharmacological therapies) in pain relief of 50% or greater (RD 0.05 [95% CI 0.02-0.07] (high-quality evidence), improvement of HRQoL of 20% or greater (RD 0.13 [95% CI 0.00-0.26], (moderate quality evidence), and in reducing negative mood (SMD -0.43 [95% CI -0.62 to -0.24]) (high-quality evidence), disability (SMD -0.30 [95% CI -0.52 to -0.08]) (high-quality evidence) and fatigue (SMD - 0-27 [95% CI -0.50 to -0.03]) (high-quality evidence). There were no statistically significant differences between CBTs and controls in acceptability and safety (high-quality evidence). The update did not change the major findings of the previous review. CBTs provided a clinically relevant benefit over control interventions in reducing some key symptoms of FMS and disability at the end of treatment. SIGNIFICANCE: This updated systematic review with meta-analysis on cognitive behavioural therapies (CBTs) including acceptance-based CBTs endorse the efficacy and tolerability of CBTs in reducing key symptoms and disability in FMS in the short- and long-term if compared to waiting list, treatment as usual, attention controls and active non-pharmacological therapies. CBTs did not differ in efficacy except superiority for coping with pain and tolerability from recommended drug therapy (pregabalin and/or duloxetine).

[Effectiveness of autologous blood donation in coronary surgery--a retrospective analysis]. / Die Effektivität der Eigenblutspende in der Koronarchirurgie--eine retrospektive Analyse.

OBJECTIVE: This study was performed to evaluate whether autologous blood donation prior to coronary artery bypass graft surgery (cabg) reduces homologous blood requirements and the risk of homologous blood transfusion. METHODS: Within a period of 18 months, 633 patients undergoing cabg surgery were retrospectively included into the study. Non-donors were included if preoperative haemoglobin concentration exceeded 12.5 g%. RESULTS: According to demographic data, risk scores of patients who donated blood (n = 201) were lower. More patients of this group received left internal mammary bypass grafts (63% vs. 51%; p = 0.047). Nevertheless, blood loss did not differ between donors and non-donors. Prior to blood donation, haemoglobin-concentration was significantly higher in male donors (n = 177) compared to female donors (n = 24) (15 +/- 1.2 vs. 13.8 +/- 1 g%; P < 0.001). Compared to female donors, male patients donated significantly more blood units. The risk of homologous blood donation was significantly lower in male donors than in male non-donors (no homologous transfusion: 20% vs. 42%; P < 0.0001; Odds Ratio: 0.34; 95% confidence-interval: 0.23-0.52). Accordingly, homologous blood requirements were lower in male donors (0.9 +/- 3.4 vs. 1.6 +/- 3.6 blood units; P = 0.02). Between female donors and non-donors neither the number of patients treated with homologous blood (no homologous transfusion: 29% vs. 33%, P = 1; odds ratio: 1.17; 95% confidence-interval: 0.4-3.4), nor the mean number of transfused homologous blood units (1.8 +/- 1.6 vs. 1.9 +/- 2.4; P = 0.83) was different. Reactions during blood donation requiring treatment (bradycardia, hypotension, angina, arrhythmias) occurred more often in female patients (5/24 vs. 9/177; P = 0.015). CONCLUSION: In our study, autologous blood donation significantly decreased the risk of homologous transfusion and homologous blood requirements in male cabg patients. We were not able to prove the efficacy of autologous blood donation in female cabg patients. Due to the small sample size of our investigation, further prospective studies are necessary to answer the question whether patients with low blood volume, body weight and body height scheduled for cabg surgery should be excluded from autologous blood donation.