Study of η and η' Photoproduction at MAMI.

The reactions γp→ηp and γp→η^{'}p are measured from their thresholds up to the center-of-mass energy W=1.96 GeV with the tagged-photon facilities at the Mainz Microtron, MAMI. Differential cross sections are obtained with unprecedented statistical accuracy, providing fine energy binning and full production-angle coverage. A strong cusp is observed in the total cross section for η photoproduction at the energies in the vicinity of the η^{'} threshold, W=1896 MeV (E_{γ}=1447 MeV). Within the framework of a revised ηMAID isobar model, the cusp, in connection with a steep rise of the η^{'} total cross section from its threshold, can only be explained by a strong coupling of the poorly known N(1895)1/2^{-} state to both ηp and η^{'}p. Including the new high-accuracy results in the ηMAID fit to available η and η^{'} photoproduction data allows the determination of the N(1895)1/2^{-} properties.

A systematic review and meta-analysis of ketamine for the prevention of persistent post-surgical pain.

While post-operative pain routinely resolves, persistent post-surgical pain (PPSP) is common in certain surgeries; it causes disability, lowers quality of life and has economic consequences. The objectives of this systematic review and meta-analysis were to evaluate the effectiveness of ketamine in reducing the prevalence and severity of PPSP and to assess safety associated with its use. We searched the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE through December 2012 for articles in any language. We included randomized, controlled trials in adults in which ketamine was administered perioperatively via any route. Seventeen studies, the majority of which administered ketamine intravenously, met all inclusion criteria. The overall risk of developing PPSP was not significantly reduced at any time point in the ketamine group vs. placebo, nor did comparisons of pain severity scores reach statistical significance. Sensitivity analysis of exclusively intravenous ketamine studies included in this meta-analysis demonstrated statistically significant reductions in risk of developing PPSP at 3 and 6 months (P = 0.01 and P = 0.04, respectively). Adverse event rates were similar between ketamine and placebo groups. The study data from our review are heterogeneous and demonstrate efficacy of intravenously administered ketamine only in comparison with placebo. Highly variable timing and dosing of ketamine in these studies suggest that no unifying effective regimen has emerged. Future research should focus on clinically relevant outcomes, should stratify patients with pre-existing pain and possible central sensitization and should enroll sufficiently large numbers to account for loss to follow-up in long-term studies.

Single-dose intravenous paracetamol or propacetamol for prevention or treatment of postoperative pain: a systematic review and meta-analysis.

Paracetamol is the most commonly prescribed analgesic for the treatment of acute pain. The efficacy and safety of i.v. formulations of paracetamol is unclear. We performed a systematic search (multiple databases, bibliographies, any language, to May 2010) for single-dose, randomized, controlled clinical trials of propacetamol or i.v. paracetamol for acute postoperative pain in adults or children. Thirty-six studies involving 3896 patients were included. For the primary outcome, 37% of patients (240/367) receiving propacetamol or i.v. paracetamol experienced at least 50% pain relief over 4 h compared with 16% (68/527) receiving placebo (number needed to treat=4.0; 95% confidence interval, 3.5-4.8). The proportion of patients in propacetamol or i.v. paracetamol groups experiencing at least 50% pain relief diminished over 6 h. Patients receiving propacetamol or paracetamol required 30% less opioid over 4 h and 16% less opioid over 6 h than those receiving placebo. However, this did not translate to a reduction in opioid-induced adverse events (AEs). Similar comparisons between propacetamol or i.v. paracetamol and active comparators were either not statistically significant, not clinically significant, or both. AEs occurred at similar rates with propacetamol or i.v. paracetamol and placebo. However, pain on infusion occurred more frequently in those receiving propacetamol compared with placebo (23% vs 1%). A single dose of either propacetamol or i.v. paracetamol provides around 4 h of effective analgesia for about 37% of patients with acute postoperative pain. Both formulations are associated with few AEs, although patients receiving propacetamol have a higher incidence of pain on infusion.

Mu-opioid antagonists for opioid-induced bowel dysfunction.

BACKGROUND: Opioid-induced bowel dysfunction (OBD) is characterized by constipation, incomplete evacuation, bloating, and increased gastric reflux. OBD occurs both acutely and chronically, in multiple disease states, resulting in increased morbidity and reduced quality of life. OBJECTIVES: To compare the efficacy and safety of traditional and peripherally active opioid antagonists versus conventional interventions for OBD. SEARCH STRATEGY: We searched MEDLINE, the Cochrane Central Register of Controlled Trials and EMBASE in January 2007. Additional reports were identified from the reference lists of retrieved papers. SELECTION CRITERIA: Studies were included if they were randomized controlled trials that investigated the efficacy of mu-opioid antagonists for OBD. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent review authors and included demographic variables, diagnoses, interventions, efficacy, and adverse events. MAIN RESULTS: Twenty-three studies met inclusion criteria and provided data on 2871 opioid antagonist-treated patients. The opioid antagonists investigated were alvimopan (nine studies), methylnaltrexone (six), naloxone (seven), and nalbuphine (one). Meta-analysis demonstrated that methylnaltrexone and alvimopan were better than placebo in reversing opioid-induced increased gastrointestinal transit time and constipation, and that alvimopan appears to be safe and efficacious in treating postoperative ileus. The incidence of adverse events with opioid antagonists was similar to placebo and generally reported as mild-to-moderate. AUTHORS' CONCLUSIONS: Insufficient evidence exists for the safety or efficacy of naloxone or nalbuphine in the treatment of OBD. Long-term efficacy and safety of any of the opioid antagonists is unknown, as is the incidence or nature of rare adverse events. Alvimopan and methylnaltrexone both show promise in treating OBD, but further data will be required to fully assess their place in therapy.

Patient controlled opioid analgesia versus conventional opioid analgesia for postoperative pain.

BACKGROUND: Patients may control postoperative pain by self-administration of intravenous opioids using devices designed for this purpose (patient controlled analgesia or PCA). A 1992 meta-analysis by Ballantyne found a strong patient preference for PCA over conventional analgesia but disclosed no differences in analgesic consumption or length of postoperative hospital stay. Although Ballantyne's meta-analysis found that PCA did have a small but statistically significant benefit upon pain intensity, Walder's review in 2001 did not find a significant differences in pain intensity and pain relief between PCA and conventionally treated groups. OBJECTIVES: To evaluate the efficacy of PCA versus conventional analgesia (such as a nurse administering an analgesic upon a patient's request) for postoperative pain control. SEARCH STRATEGY: Randomized controlled trials (RCTs) were identified from the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2004, Issue 3), MEDLINE (1966 to 2004), and EMBASE (1994 to 2004). Additional reports were identified from the reference lists of retrieved papers. SELECTION CRITERIA: RCTs of PCA versus conventional analgesia that employed pain intensity as a primary or secondary outcome were selected. These trials included RCTs that compared PCA without a continuous background infusion versus conventional parenteral analgesic regimens. Studies that explicitly stated they involved patients with chronic pain were excluded. DATA COLLECTION AND ANALYSIS: Trials were scored using the Oxford Quality Scale. Meta-analyses were performed of outcomes that included analgesic efficacy assessed by a Visual Analog Scale (VAS), analgesic consumption, patient satisfaction, length of stay and adverse effects. A sufficient number of the retrieved trials reported these parameters to permit meta-analyses. MAIN RESULTS: Fifty-five studies with 2023 patients receiving PCA and 1838 patients assigned to a control group met inclusion criteria. PCA provided better pain control and greater patient satisfaction than conventional parenteral 'as-needed' analgesia. Patients using PCA consumed higher amounts of opioids than the controls and had a higher incidence of pruritus (itching) but had a similar incidence of other adverse effects. There was no difference in the length of hospital stay. AUTHORS' CONCLUSIONS: This review provides evidence that PCA is an efficacious alternative to conventional systemic analgesia for postoperative pain control.

Opioids for neuropathic pain.

BACKGROUND: The use of opioids for neuropathic pain remains controversial. Studies have been small, have yielded equivocal results, and have not established the long-term risk-benefit ratio of this treatment. OBJECTIVES: To assess the efficacy and safety of opioid agonists for the treatment of neuropathic pain. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (2nd Quarter 2005), MEDLINE (1966 to June 2005), and EMBASE (1980 to 2005 Week 27) for articles in any language, and reference lists of reviews and retrieved articles. SELECTION CRITERIA: Trials were included in which opioid agonists were given to treat central or peripheral neuropathic pain of any etiology, pain was assessed using validated instruments, and adverse events were reported. Studies in which drugs other than opioid agonists were combined with opioids or opioids were administered epidurally or intrathecally were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent investigators and included demographic variables, diagnoses, interventions, efficacy, and adverse effects. MAIN RESULTS: Twenty-three trials met the inclusion criteria and were classified as short-term (less than 24 hours; n = 14) or intermediate-term (median = 28 days; range = eight to 70 days; n = 9). The short-term trials had contradictory results. In contrast all nine intermediate-term trials demonstrated opioid efficacy for spontaneous neuropathic pain. Meta-analysis of seven intermediate-term studies showed mean post-treatment visual analog scale scores of pain intensity after opioids to be 13 points lower on a scale from zero to 100 than after placebo (95% confidence interval -16 to -9; P < 0.00001). The most common adverse events were nausea (33% opioid versus 9% control: number needed to treat to harm (NNH) 4.2) and constipation (33% opioid versus 10% control: NNH 4.2), followed by drowsiness (29% opioid versus 12% control: NNH 6.2), dizziness (21% opioid versus 6% control: NNH 7.1), and vomiting (15% opioid versus 3% control: NNH 8.3). Where reported, 23 (11%) of 212 participants withdrew because of adverse events during opioid therapy versus nine (4%) of 202 receiving placebo. AUTHORS' CONCLUSIONS: Short-term studies provide only equivocal evidence regarding the efficacy of opioids in reducing the intensity of neuropathic pain, whereas intermediate-term studies demonstrate significant efficacy of opioids over placebo, which is likely to be clinically important. Reported adverse events of opioids are common but not life threatening. Further randomized controlled trials are needed to establish long-term efficacy, safety (including addiction potential), and effects on quality of life.

Systemic administration of local anesthetic agents to relieve neuropathic pain.

BACKGROUND: Lidocaine, mexiletine, tocainide, and flecainide are local anesthetics which give an analgesic effect when administered orally or parenterally. Early reports described the use of intravenous lidocaine or procaine to relieve cancer and postoperative pain (Keats 1951; Gilbert 1951; De Clive-Lowe 1958; Bartlett 1961). Interest reappeared decades later when patient series and clinical trials reported that parenteral lidocaine and its oral analogs tocainide, mexiletine, and flecainide relieved neuropathic pain in some patients (Boas 1982; Lindblom 1984; Petersen 1986; Dunlop 1988; Bach 1990; Awerbuch 1990). With the recent publication of clinical trials with high quality standards, we have reviewed the use of systemic lidocaine and its oral analogs in neuropathic pain to update our knowledge, to measure their benefit and harm, and to better define their role in therapy. OBJECTIVES: To evaluate pain relief and adverse effect rates between systemic local anesthetic-type drugs and other control interventions. SEARCH STRATEGY: We searched MEDLINE (1966 through 15 May 2004), EMBASE (January 1980 to December 2002), Cancer Lit (through 15 December 2002), Cochrane Central Register of Controlled Trials (2nd Quarter, 2004), System for Information on Grey Literature in Europe (SIGLE), and LILACS, from January 1966 through March 2001. We also hand searched conference proceedings, textbooks, original articles and reviews. SELECTION CRITERIA: We included trials with random allocation, that were double blinded, with a parallel or crossover design. The control intervention was a placebo or an analgesic drug for neuropathic pain from any cause. DATA COLLECTION AND ANALYSIS: We collected efficacy and safety data from all published and unpublished trials. We calculated combined effect sizes using continuous and binary data for pain relief and adverse effects as primary and secondary outcome measurements, respectively. MAIN RESULTS: Thirty-two controlled clinical trials met the selection criteria; two were duplicate articles. The treatment drugs were intravenous lidocaine (16 trials), mexiletine (12 trials), lidocaine plus mexiletine sequentially (one trial), and tocainide (one trial). Twenty-one trials were crossover studies, and nine were parallel. Lidocaine and mexiletine were superior to placebo [weighted mean difference (WMD) = -11; 95% CI: -15 to -7; P <0.00001], and limited data showed no difference in efficacy (WMD = -0.6; 95% CI: -7 to 6), or adverse effects versus carbamazepine, amantadine, gabapentin or morphine. In these trials, systemic local anesthetics were safe, with no deaths or life-threatening toxicities. Sensitivity analysis identified data distribution in three trials as a probable source of heterogeneity. There was no publication bias. AUTHORS' CONCLUSIONS: Lidocaine and oral analogs were safe drugs in controlled clinical trials for neuropathic pain, were better than placebo, and were as effective as other analgesics. Future trials should enroll specific diseases and test novel lidocaine analogs with better toxicity profiles. More emphasis is necessary on outcomes measuring patient satisfaction to assess if statistically significant pain relief is clinically meaningful.

NSAIDS or paracetamol, alone or combined with opioids, for cancer pain.

BACKGROUND: NSAIDs are widely applied to treat cancer pain and are frequently combined with opioids in combination preparations for this purpose. However, it is unclear which agent is most clinically efficacious for relieving cancer-related pain, or even what may be the additional benefit of combining an NSAID with an opioid in this setting. OBJECTIVES: To assess the effects of NSAIDs, alone or combined with opioids, for the treatment of cancer pain. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Issue 2, 2002), MEDLINE (January 1966 to March 2003), EMBASE (January 1980 to December 2001), LILACS (January 1984 to December 2001) and reference list of articles. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials that compared NSAID versus placebo; NSAID versus NSAID; NSAID versus NSAID plus opioid; opioid versus opioid plus NSAID; or NSAID versus opioid. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse event information was collected from trials. Where there was disagreement between reviewers, the opinion of an additional reviewer was sought to resolve the issue. MAIN RESULTS: Forty-two trials involving 3084 patients were included. Clinical heterogeneity of study methods and outcomes precluded meta-analyses and only supported a qualitative systematic review. Seven of eight papers that compared NSAID with placebo demonstrated superior efficacy of NSAID with no difference in side effects. Thirteen papers compared one NSAID with another; four reported increased efficacy of one NSAID over another. Four different studies found that one NSAID had fewer side effects than one or more others. Twenty-three studies compared NSAIDs and opioids in combination or alone with NSAID/opioid combinations. Thirteen out of 14 studies found no difference, or low clinical difference, when combining an NSAID plus an opioid versus either drug alone. Comparisons between various NSAID/opioid combinations were inconclusive. Nine studies assessed the association between dose and efficacy and safety. Four papers demonstrated increased efficacy with increased dose, but no dose-dependent increase in side effects within the dose ranges studied. Study duration ranged from single dose studies performed over six hours to crossover studies lasting six weeks; however the majority of studies were of less than seven days duration. AUTHORS' CONCLUSIONS: Based upon limited data, NSAIDs appear to be more effective than placebo for cancer pain; clear evidence to support superior safety or efficacy of one NSAID over another is lacking; and trials of combinations of an NSAID with an opioid have disclosed either no difference (4 out of 14 papers), a statistically insignificant trend towards superiority (1 out of 14 papers), or at most a slight but statistically significant advantage (9 out of 14 papers), compared with either single entity. The short duration of studies undermines generalization of their findings on efficacy and safety of NSAIDs for cancer pain.

Adverse reaction to extra-amniotic prostaglandin E2.

An immediate and severe reaction to prostaglandin E2 (PGE2), given by the extra-amniotic route to induce the abortion of a hydatidiform mole, is reported.

A histological study of normal vulval skin from infancy to old age.

A number of histological parameters in clinically normal skin from the vulva throughout the female life span were studied. These are compared and evaluated to establish a base line to assist with the interpretation of diseased vulval skin.