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Objective: There has been a growing recognition of the need for better pharmacologic management of chronic pain among older adults. To address this need, the National Institutes of Health Pain Consortium sponsored an "Expert Panel Discussion on the Pharmacological Management of Chronic Pain in Older Adults" conference in September 2010 to identify research gaps and strategies to address them. Specific emphasis was placed on ascertaining gaps regarding use of opioid and nonsteroidal anti-inflammatory medications because of continued uncertainties regarding their risks and benefits., Design: Eighteen panel members provided oral presentations; each was followed by a multidisciplinary panel discussion. Meeting transcripts and panelists' slide presentations were reviewed to identify the gaps and the types of studies and research methods panelists suggested could best address them., Results: Fifteen gaps were identified in the areas of treatment (e.g., uncertainty regarding the long-term safety and efficacy of commonly prescribed analgesics), epidemiology (e.g., lack of knowledge regarding the course of common pain syndromes), and implementation (e.g., limited understanding of optimal strategies to translate evidence-based pain treatments into practice). Analyses of data from electronic health care databases, observational cohort studies, and ongoing cohort studies (augmented with pain and other relevant outcomes measures) were felt to be practical methods for building an age-appropriate evidence base to improve the pharmacologic management of pain in later life., Conclusion: Addressing the gaps presented in the current report was judged by the panel to have substantial potential to improve the health and well-being of older adults with chronic pain., (Wiley Periodicals, Inc.)

New, simple, rapid and precise HPLC-PDA method has been developed and validated for quantification of biomarker myrsinoic acid B in stem bark extracts of Rapanea ferruginea Mez. The method employs a Phenomenex C18 column (250 mm × 4.6mm I.D., 5 μm) with acetonitrile:methanol:water (pH 2.6 with phosphoric acid) at 48:30:22 as mobile phase, at a flow rate of 0.7 mL min(-1) and photo diode array (PDA) detection at 270 nm. The validation data show that the method is specific, accurate, precise and robust. The method was linear, over a range of 5-100.0 μg mL(-1), with a limit of detection of 0.369 μg mL(-1) and limit of quantification of 1.233 μg mL(-1). The method has also shown consistent recoveries (average of 101.3% and 0.12% RSD) of the biomarker, with low intra and inter-day relative standard deviation (1.26% and 1.62%, respectively). The evaluated hydroethanolic extract and dry extract presented MAB values of 63.53 and 36.07 mg g(-1), respectively., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Gabapentin and pregabalin are well established for the treatment of seizures and neuropathic pain. Both drugs are eliminated primarily unchanged by renal excretion. As part of an ongoing research program to improve and expand drug testing methods for compliance monitoring of pain patients, the prevalence and concentrations of gabapentin and pregabalin in urine specimens from chronic pain patients were determined by a validated liquid chromatography-tandem mass spectrometry assay. The study was approved by an Institutional Review Board. A total of 57,542 urine specimens from 231 pain clinics located in 19 states were analyzed over the period of November 24, 2009, through May 2010. The limit of quantitation (LOQ) and upper LOQ of the assays for both drugs were 2.5 and 1000 μg/mL, respectively. Gabapentin was identified in 7013 specimens (12.2% prevalence), and pregabalin was identified in 4799 patients (8.3% prevalence). Generally, gabapentin concentrations were more than twofold higher than pregabalin, consistent with their relative potencies. Interestingly, both drugs were found in specimens from 249 patients, likely representing switching of prescriptions by the prescriber.

Background and Purpose: Certain miscellaneous idiopathic headache disorders, which are regarded as entities, are grouped in Chapter 4 of the International Classification of Headache Disorders. Recent epidemiological research suggests that these headache disorders are underdiagnosed., Objectives: To give expert recommendations for the different drug and non-drug treatment procedures of these different headache disorders based on a literature search and on consensus of an expert panel., Methods: All available medical reference systems were screened for all kinds of clinical studies on these headache disorders. The findings in these studies were evaluated according to the recommendations of the EFNS resulting in level A, B or C recommendations and good practice points., Recommendations: For all headache disorders, acute and prophylactic drug treatment is recommended based on case series and on expert consensus. Furthermore, recommendations for the differential diagnoses are given because these headache disorders can also present with a symptomatic form. The most effective drug for the majority of these headache disorders is indomethacin, mostly applied as long-term or short-term prophylaxis., (© 2011 The Author(s). European Journal of Neurology © 2011 EFNS.)

Palliative care improves the quality and cost-effectiveness of adult and pediatric patient care, and it decreases unwanted hospitalizations and aggressive care at the end of life. National palliative care quality standards and preferred practices can be used for benchmarking by institutions, health care systems, and accrediting bodies. Pain and symptom management and the management of delirium for patients is now possible for the vast majority of patients, even those with advanced disease. However, because of shortages of specialists providing "tertiary" palliative care, significant improvements are needed in generalist-level palliative care among oncologists, intensivists, and specialists caring for patients with advanced cardiac, pulmonary, renal, and hepatic diseases. POLST (Physician Orders for Life-Sustaining Treatment) forms are a major advance in end-of-life care. They enable patients' advance directives to be valid wherever they are cared for (home, hospital, or nursing facility).

Spinal neurotransmission plays an important role in the perception of pain signaling. In the present study, we investigated the spinal anti-nociceptive mechanism of current standard analgesics in mouse models of tactile allodynia induced by intrathecal administration of N-methyl-D-aspartic acid (NMDA), prostaglandin E2 (PGE2), and bicuculline. NMDA-induced allodynia is induced by postsynaptic NMDA receptor activation, while PGE2-induced allodynia is triggered by the enhancement of presynaptic glutamate release via EP1 receptor activation. In contrast, bicuculline induces allodynia by the blockade of gamma-aminobutyric acid (GABA)A receptor-mediated inhibitory system. As the clinically available analgesics, pregabalin (alpha2delta-subunit calcium channel ligand), ziconotide (N-type calcium channel blocker), mexiletine (sodium channel blocker), and duloxetine (serotonin and norepinephrine reuptake inhibitors) were evaluated in these neurochemically-induced allodynia models. Pregabalin almost completely alleviated NMDA-, PGE2-, and bicuculline-induced allodynia. Despite being classified as an agent with a similar molecular target mechanism, ziconotide could only alleviate PGE2-induced allodynia, but not NMDA- or bicuculline-induced allodynia, as did mexiletine and duloxetine. These results taken together suggest that ziconotide, mexiletine, and duloxetine suppress spinal hyperactivity via the presynaptic site mechanism. In contrast, pregabalin could suppress via the downstream step during spinal hyperactivation such as postsynaptic NMDA activation or dysfunction of GABAergic control in addition to presynaptic mechanism. In conclusion, present findings provide implication that the spinal anti-nociceptive mechanistic site of pregabalin is different from that of ziconotide, mexiletine, and duloxetine, and pregabalin could have a broader anti-nociceptive mechanism other than N-type calcium channel blockade., (Copyright 2010 Elsevier B.V. All rights reserved.)

The current study addresses the distribution of low concentrations of excreted drugs in the pain patient population in an effort to establish a more rational set of cutoffs for this cohort. To wit, 19 analytes in approximately 8000 urine specimens from pain patients were measured using liquid chromatography tandem mass spectroscopy (LC-MS/MS) methodology. The lower limits of quantitation for the LC-MS/MS were set as the nominal cutoffs for the determination of positive and negative results. The measured concentrations were compared with the Substance Abuse & Mental Health Services Administration (SAMHSA) nominal immunoassay cutoffs, and a subset of "missed samples" was identified for each of the 19 analytes. This "missed samples" subset contained all samples that measured above the LC MS/MS cutoff for a given analyte but below the SAMHSA immunoassay cutoff. The number of "missed samples" divided by the total number of samples measured positive by the LC-MS/MS method defines the percentage of this population that would have been found falsely negative if a prescreen by immunoassay using SAMHSA cutoffs had been conducted. For example, 69% of the specimens that were positive for hydromorphone by LC-MS/MS would have been falsely scored as negative by immunoassay.

The labeling of over-the-counter (OTC) drugs is critical to their safe and effective use, and certain warnings are meant to be read at the point of purchase (POP). Examples include (i) warnings that alert consumers to the fact that the package is not child-resistant and (ii) warnings that alert consumers to potential product tampering. U.S. law mandates these warnings be "conspicuous" and "prominent" so that it is likely that consumers will read them before leaving the store. Our objective was to quantify the relative prominence and conspicuousness of these warnings. Sixty-one participants reviewed the packages of 5 commercially available analgesics to evaluate the prominence and conspicuousness of these warnings. Evaluated data included (i) the time spent examining the warnings compared with other areas of the label (using a bright pupil eye tracker), (ii) the ability to recall information from the OTCs viewed, and (iii) the legibility of the warnings relative to other elements of the labels (as measured by ASTM D7298-06). Eye-tracking data indicated that warnings were viewed by fewer participants and for less time than other elements of the packages. Recall and legibility data also indicated that the warning statements compared unfavorably with other elements of the labels tested. Evidence presented in this study suggests that 2 required warnings on 5 different OTCs are not prominent or conspicuous when compared with other elements of tested labels.

Traditionally, sedation for gastrointestinal endoscopic procedures was provided by the gastroenterologist. Increasingly, however, complex procedures are being performed on seriously ill patients. As a result, anesthesiologists now are providing anesthesia and sedation in the gastrointestinal endoscopy suite for many of these patients. This article reviews the challenges encountered in this environment and anesthetic techniques that can be used successfully for these procedures.

Background: New legal regulations for the marketing of pharmaceutical products were introduced in 2002 in Switzerland. We investigated whether claims in drug advertisements citing published scientific studies were justified by these studies after the introduction of these new regulations., Methods: In this cross-sectional study, two independent reviewers screened all issues of six major Swiss medical journals published in the year 2005 to identify all drug advertisements for analgesic, gastrointestinal and psychopharmacologic drugs and evaluated all drug advertisements referring to at least one publication. The pharmaceutical claim was rated as being supported, being based on a potentially biased study or not to be supported by the cited study according to pre-specified criteria. We also explored factors likely to be associated with supported advertisement claims., Results: Of 2068 advertisements 577 (28%) promoted analgesic, psychopharmacologic or gastrointestinal drugs. Among them were 323 (56%) advertisements citing at least one reference. After excluding multiple publications of the same drug advertisement and advertisements with non-informative references, there remained 29 unique advertisements with at least one reference to a scientific study. These 29 advertisements contained 78 distinct pairs of claims of analgesic, gastrointestinal and psychopharmacologic drugs and referenced studies. Thirty-seven (47%) claims were supported, 16 (21%) claims were not supported by the corresponding reference, and 25 (32%) claims were based on potentially biased evidence, with no relevant differences between drug groups. Studies with conflict of interest and studies stating industry funding were more likely to support the corresponding claim (RR 1.52, 95% CI 1.07-2.17 and RR 1.50, 95% CI 0.98-2.28) than studies without identified conflict of interest and studies without information on type of funding., Conclusion: Following the introduction of new regulations for drug advertisement in Switzerland, 53% of all assessed pharmaceutical claims published in major medical journals are not supported by the cited referenced studies or based on potentially biased study information. In light of the discrepancy between the new legislation and the endorsement of these regulations, physicians should not trust drug advertisement claims even when they seem to refer to scientific studies.

Background: Patients in a minimally conscious state (MCS) show restricted self or environment awareness but are unable to communicate consistently and reliably. Therefore, better understanding of cerebral noxious processing in these patients is of clinical, therapeutic, and ethical relevance., Methods: We studied brain activation induced by bilateral electrical stimulation of the median nerve in five patients in MCS (aged 18-74 years) compared with 15 controls (19-64 years) and 15 patients (19-75 years) in a persistent vegetative state (PVS) with (15)O-radiolabelled water PET. By way of psychophysiological interaction analysis, we also investigated the functional connectivity of the primary somatosensory cortex (S1) in patients and controls. Patients in MCS were scanned 57 (SD 33) days after admission, and patients in PVS 36 (9) days after admission. Stimulation intensities were 8.6 (SD 6.7) mA in patients in MCS, 7.4 (5.9) mA in controls, and 14.2 (8.7) mA in patients in PVS. Significant results were thresholded at p values of less than 0.05 and corrected for multiple comparisons., Findings: In patients in MCS and in controls, noxious stimulation activated the thalamus, S1, and the secondary somatosensory or insular, frontoparietal, and anterior cingulate cortices (known as the pain matrix). No area was less activated in the patients in MCS than in the controls. All areas of the cortical pain matrix showed greater activation in patients in MCS than in those in PVS. Finally, in contrast with patients in PVS, those in MCS had preserved functional connectivity between S1 and a widespread cortical network that includes the frontoparietal associative cortices., Interpretation: Cerebral correlates of pain processing are found in a similar network in controls and patients in MCS but are much more widespread than in patients in PVS. These findings might be objective evidence of a potential pain perception capacity in patients in MCS, which supports the idea that these patients need analgesic treatment.

Study Design: Best evidence synthesis., Objective: To provide evidence-based guidance to primary care clinicians about how to best assess and treat patients with neck pain., Summary of Background Data: There is a need to translate the results of clinical and epidemiologic studies into meaningful and practical information for clinicians., Methods: Based on best evidence syntheses of published studies on the risk, prognosis, assessment, and management of people with neck pain and its associated disorders, plus additional research projects and focused literature reviews reported in this supplement, the 12-member multidisciplinary Scientific Secretariat of the Neck Pain Task Force followed a 4-step approach to develop practical guidance for clinicians., Results: The Neck Pain Task Force recommends that people seeking care for neck pain should be triaged into 4 groups: Grade I neck pain with no signs of major pathology and no or little interference with daily activities; Grade II neck pain with no signs of major pathology, but interference with daily activities; Grade III neck pain with neurologic signs of nerve compression; Grade IV neck pain with signs of major pathology. In the emergency room after blunt trauma to the neck, triage should be based on the NEXUS criteria or the Canadian C-spine rule. Those with a high risk of fracture should be further investigated with plain radiographs and/or CT-scan. In ambulatory primary care, triage should be based on history and physical examination alone, including screening for red flags and neurologic examination for signs of radiculopathy. Exercises and mobilization have been shown to provide some degree of short-term relief of Grade I or Grade II neck pain after a motor vehicle collision. Exercises, mobilization, manipulation, analgesics, acupuncture, and low-level laser have been shown to provide some degree of short-term relief of Grade I or Grade II neck pain without trauma. Those with confirmed Grade III and severe persistent radicular symptoms might benefit from corticosteroid injections or surgery. Those with confirmed Grade IV neck pain require management specific to the diagnosed pathology., Conclusion: The best available evidence suggests initial assessment for neck pain should focus on triage into 4 grades, and those with common neck pain (Grade I and Grade II) might be offered the listed noninvasive treatments if short-term relief is desired.

Key Points: (1) A large number of treatment options have shown generally moderate efficacy in the treatment of diabetic painful neuropathy.(2) Tricyclic antidepressants are the mainstay of therapy, with anticonvulsants, opioids and serotonin-noradrenaline reuptake inhibitors also having a place.(3) Head-to-head trials of current treatments are needed. Meanwhile, selection of therapeutic agents should be individualised.

Aim: Studies in some countries suggest that cancer pain is often not adequately controlled, but little is known about the situation in Spain. The objective of this study was to identify medical oncologists' perceptions about pain management in their patients., Methods: Two-round Delphi survey of 24 medical oncologists from 22 large, geographically diverse hospitals in Spain. Physicians rated each of 150 statements on a Likert scale (1=strongly disagree; 5=strongly agree). The mean, standard deviation and frequency of replies in three agreement categories were calculated for each item. Statements allowing comparison of oncologists' perceptions of how pain is managed in routine clinical practice with how it should be managed were grouped together and analyzed., Results: The most notable discrepancies between the real and the ideal occurred in the failure to provide written information or to confirm that patients understand what they are told, the lack of comprehensive and systematic evaluation of pain, and the lack of use of non-pharmacological treatments (NPTs) for cancer pain., Conclusions: Medical oncologists need to improve their communication skills, providing patients with both written and verbal information about their disease and the plan for pain management. Pain should be evaluated at each patient visit using validated scales, and greater attention should be paid to the possible use of NPTs.

Introduction: Pain is a major problem in the treatment of patients with cancer. This article reviews studies concerning evaluation of patients with cancer pain treated according to The World Health Organization (WHO) analgesic ladder., Materials and Methods: Systematic search of PUBMED, MEDLINE, EMBASE, LILACS, BDENF, and OVID and a hand search of reference lists and textbooks from 1982 to 2004 were performed., Result: Analgesia was considered adequate in 45 to 100% of patients analyzed in the studies., Conclusion: However, the evidence that they provide is insufficient to grant the effectiveness of the WHO guidelines because a controlled clinical trial of this intervention has never been published.

Objective: To collect data on pain management in paediatric oncology with respect to the WHO ladder approach. SETTING, DESIGN, PATIENTS AND METHODS: Eight German tertiary care paediatric oncology centres prospectively documented all their in-patient pain treatment courses from June 1999 to December 2000. Pain was scored using a 1-6 faces scale., Results: Two hundred and twenty four patients (median age, 9 years; range 0.2-32.1) were enrolled. Three hundred and thirty three pain episodes comprising a total of 2265 treatment days were documented. Pain was mostly therapy associated. The most frequently administered non-opioid analgesics were dipyrone and paracetamol. On WHO step 2, tramadol was almost the only opioid used. During tramadol monotherapy average daily pain scores were lower than with a combination of tramadol and non-opioid analgesics. On WHO step 3, morphine was at least part of the analgesic regimen on most treatment days. Strong opioids were combined with a non-opioid analgesic on 41% of the treatment days. The mean intravenous morphine equivalence dose was 0.034 mg/kg/h. During opioid and non-opioid combination therapy, adverse effects were more frequent, and average pain scored higher than on opioid monotherapy., Conclusions: WHO-guidelines were closely followed in Germany and seem to provide effective analgesia for children with cancer pain. In our patient group there is no evidence that a combination of an opioid with a non-opioid is more effective than opioid therapy alone in in-patient paediatric oncology pain treatment.

Objectives: The original COMFORT scale, including both observational and physiologic items, has been validated for measuring distress in children admitted to a pediatric intensive care unit. However, physiologic variables are influenced by drugs given in the pediatric intensive care unit setting. The objectives of this study were to assess the usefulness of physiologic variables in judgment of sedation and to determine new cutoff points for the COMFORT "behavioral" scale (COMFORT-B), using only observational items., Design: Prospective observational study., Setting: Pediatric intensive care unit in a university hospital., Patients: Seventy-eight patients admitted to the pediatric intensive care unit., Interventions: None., Measurements and Results: COMFORT scores were obtained in this patient group. Similar to the original COMFORT scale validation, the expert opinion of nurses (Nurse Interpretation Score of Sedation) served to determine optimal cutoff scores for the COMFORT-B scale. A total of 843 combined COMFORT and Nurse Interpretation Score of Sedation scores were obtained in 78 patients. Cronbach's alpha for the COMFORT scale was .78, increasing to .84 when the physiologic items, blood pressure and heart rate, were excluded. COMFORT scores were significantly different for the three Nurse Interpretation Score of Sedation categories (Kruskal-Wallis, p < .001). According to the pediatric intensive care unit nurses, undersedation was present in 11% and oversedation in 3% of all observations. Cutoff points for the COMFORT-B scale were /=23 for undersedation. The area in the COMFORT-B score between 11 and 22 does not adequately predict under- or oversedation, pointing to a need for supplemental observation., Conclusions: The COMFORT-B scale is a reliable alternative to the original COMFORT scale. The cutoff points of the COMFORT-B scale in conjunction with the Nurse Interpretation Score of Sedation facilitate the use of sedation algorithms on the pediatric intensive care unit.

Objective: To develop systematically validated quality indicators (QIs) addressing analgesic safety., Methods: A comprehensive literature review of existing quality measures, clinical guidelines, and evidence supporting potential QIs concerning nonselective (traditional) nonsteroidal anti-inflammatory drugs (NSAIDs) and newer cyclooxygenase 2-selective NSAIDs was undertaken. An expert panel then validated or refuted potential indicators utilizing a proven methodology., Results: Eleven potential QIs were proposed. After panel review, 8 were judged to be valid; an additional 10 were proposed by the panel, of which 7 were rated as valid. Quality indicators focused upon informing patients about risk, NSAID choice and gastrointestinal prophylaxis, and side effect monitoring., Conclusion: The 15 validated indicators were combined, where appropriate, to yield 10 validated processes of care indicators for the safe use of NSAIDs. These indicators developed by literature review and finalized by our expert panel process can serve as a basis to compare the quality of analgesic use provided by health care providers and delivery systems.

Intraspinal drug infusion using fully implantable pump and catheter systems is a safe and effective therapy for selected patients with chronic pain. The options for this approach are increasing, as drugs that are commercially available for systemic administration are adapted to this use and other drugs that are in development specifically for intraspinal administration become available. In 2000 a Polyanalgesic Consensus Conference was organized to evaluate the existing literature and develop guidelines for drug selection. The major outcome of this effort, an algorithm for drug selection, was based on the best available evidence at the time. Rapid changes have occurred in the science and practice of intraspinal infusion and a Polyanalgesic Consensus Conference 2003 was organized to pursue the following goals: 1) to review the literature on intraspinal drug infusion since 1999, 2) to revise the 2000 drug-selection algorithm, 3) to develop guidelines for optimizing drug dosage and concentration, 4) to create a process for documenting minimum evidence supporting the use of a drug for intraspinal infusion, and 5) to clarify issues pertaining to compounding of drugs. Based on the best available evidence and expert opinion, consensus recommendations were developed in all these areas. The panel's conclusions may provide a foundation for clinical practice and a rational basis for new research.

Objective: To assess the degree of debilitation and the treatment views of individuals with headache presenting to a community pharmacy., Background: Migraine and chronic daily headache are common poorly managed illnesses. Pharmacists recommend an over-the-counter "headache product" to customers more than 53 000 times daily, thus they are well positioned to help those with headache., Design: Pilot project of 22 self-administered surveys of individuals presenting to a community pharmacy with a complaint of headache., Results: Thirteen persons had Migraine Disability Assessment scores of grade III or grade IV. Of the sample population, a substantial minority (41%) did not believe their headaches could be effectively managed with over-the-counter medications, 72% did not feel over-the-counter agents were safer than prescription products, 96% did not indicate that over-the-counter drugs were more effective than prescription drugs, and 50% disagreed that a physician's evaluation was not necessary. Only half of the population was satisfied with their current therapy, and individuals overwhelmingly (91%) wished they could prevent their headaches., Conclusions: The majority of individuals with headache presenting to a community pharmacy had high levels of morbidity and were in need of education regarding the proper role of over-the-counter medications, the advantages of prescription agents, and the benefits of a physician's referral. These preliminary results indicate that community pharmacies are potentially important locations for identification, education, and referral of individuals with headache.

The committee for quality assurance of the German IASP chapter (DGSS) evaluated all relevant guidelines concerning pain treatment. Quality of guidelines was analysed according to the checklist "Methodical quality of guidelines" by Ollenschläger and the user manual released by the German Medical Centre for Quality Assurance. The guideline for the treatment of back pain released by the German Medical Association was examined as well as the one released by the German Association for physical therapy and rehabilitation, the guideline on cervical and lumbal nerve root compression syndrome of the German Association of Neurosurgeons, the guideline for cancer pain of the Drug Committee of the German Medical Association was compared with the one of the German Interdisciplinary Association for Pain Treatment. The guideline for the treatment of chronic headache and facial pain of the Medical Association was evaluated and the guideline for the treatment of trigeminal neuralgia of the German Association of Neurosurgery and Neurology, also the guideline for the treatment of acute postoperative and posttraumatic pain. All guidelines show deficiencies in different aspects and of different severity. At first there are deficiencies in interdisciplinary formulation of the guidelines and identification and interpretation of evidence of multimodal pain treatment options. The most prominent deficiency is the lack of implementation and application trials or impulses by all author associations. This way all expenditure on releasing guidelines is given away without improving quality of pain treatment. The authors' recommendation is to adjust to guidelines and, if they are working or not, tell the authors and improve interdisciplinary in pain treatment guidelines.

Decisions must be made when assigning analgesics, and such decisions involve comparing efficacy and adverse effects. The rules for assessing efficacy by systematic review and by large clinical trials are becoming clearer all the time. It is known, for instance, that trials that are not randomized, are not double-blind, or are too small will exaggerate efficacy. These rules are relatively easy to apply to drug interventions, although there are glaring exceptions, such as in early intra-articular morphine studies. The rules may also be less easy to apply for analgesics available over-the-counter (OTC) if the drugs have not been studied in trials of high quality or if the OTC-recommended doses are below the doses studied in the trials. When there are at least 500 patients studied in trials of high quality, credible efficacy estimates for effective drugs can be derived; more patients are needed for less effective drugs. The number needed to treat and the number needed to harm can be used to compare the efficacy and safety of a treatment with placebo or with other treatments. A recent meta-analysis comparing the number needed to treat for paracetamol 1000 mg and paracetamol 600-650 mg in moderate to severe postoperative pain indicated that paracetamol 1000 mg is likely to be more effective than lower doses. Large data sets allow investigation into dose response, gender differences, and whether particular drugs work better for particular painful conditions. Purists would argue that databases of patient experience should not be used for these efficacy analyses. The rules on how to collect and use evidence on adverse effects are less clearly formulated than they are for efficacy. For safety at or above therapeutic dose, the rules of evidence-gathering are necessarily different, and randomized trials are rarely an adequate or sufficient source. Databases of patient experience, with all the caveats, may be the most reliable data from which to work.

The purposes of this study were as follows: (1) to compare the attitudes which were considered to be barriers to cancer pain management held by Taiwanese cancer patients and their family caregivers; (2) to determine if these barriers were related to patient hesitancy to take analgesics and/or family caregiver hesitancy to administer analgesics: and (3) to determine if attitudinal barriers by patients and/or family caregivers predicted the adequacy of analgesics that patients used. A total of 159 dyads of oncology outpatients and their primary family caregivers (n = 318) participated in this study. The instruments completed by patients consisted of the Barriers Questionnaire-Taiwan form, the Brief Pain Inventory-Chinese version, the ECOG performance status scale, and a demographic and medication questionnaire. Family caregivers completed the Barriers Questionnaire-Taiwan form and a demographic questionnaire. The data in this study revealed that patients and family caregivers had attitudinal barriers to pain management and these concerns were positively correlated between patients and caregivers. Patient concerns were related to their hesitancy to take analgesics and, similarly, caregiver concerns were related to their hesitancy to administer analgesics. Most importantly, patient and caregiver concerns had an impact on how the patients' pain was managed: (1) patients and their family caregivers with higher levels of concerns used inadequate analgesics as compared to patients using adequate analgesics; (2) family caregiver barriers (concerns) were a significant predictor of inadequate management of cancer pain (after controlling for demographic and disease variables). Therefore, educational interventions for overcoming these barriers for both patients and their family caregivers may have potential for improving the management of cancer pain in Taiwan.

Objective: To determine the safety and efficacy of propofol, after detomidine-butorphanol premedication, for induction and anesthetic maintenance for carotid artery translocation and castration or ovariectomy in goats., Study Design: Case series., Animals: Nine 4-month-old Spanish goats (17.1 +/- 2.6 kg) were used to evaluate propofol anesthesia for carotid artery translocation and castration or ovariectomy., Methods: Goats were premedicated with detomidine (10 micrograms/kg intramuscularly [i.m.]) and butorphanol (0.1 mg/kg i.m.) and induced with an initial bolus of propofol (3 to 4 mg/kg intravenously [i.v.]). If necessary for intubation, additional propofol was given in 5-mg (i.v.) increments. Propofol infusion (0.3 mg/kg/min i.v.) was used to maintain anesthesia, and oxygen was insufflated (5 L/min). The infusion rate was adjusted to maintain an acceptable anesthetic plane as determined by movement, muscle relaxation, ocular signs, response to surgery, and cardiopulmonary responses. Systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures, heart rate (HR), ECG, respiratory rate (RR), SpO2, and rectal temperature (T) were recorded every 5 minutes postinduction; arterial blood gas samples were collected every 15 minutes. Normally distributed data are represented as mean +/- SD; other data are medians (range)., Results: Propofol (4.3 +/- 0.9 mg/kg/min i.v.) produced smooth, rapid (15.2 +/- 6 sec) sternal recumbency. Propofol infusion (0.52 +/- 0.11 mg/kg/min i.v.) maintained anesthesia. Mean anesthesia time was 83 +/- 15 minutes. Muscle relaxation was good; eye signs indicated surgical anesthesia; two goats moved before surgery began; one goat moved twice during laparotomy. Means are reported over the course of the data collection period. Means during the anesthesia for pHa (arterial PH), PaCO2, PaO2, HCO3-, and BE (base excess) ranged from 7.233 +/- 0.067 to 7.319 +/- 0.026, 54.1 +/- 4.6 to 65.3 +/- 12.0 mm Hg, 133.1 +/- 45.4 to 183.8 +/- 75.1 mm Hg, 26.9 +/- 2.6 to 28.2 +/- 2.1 mEq/L, and -0.8 +/- 2.9 to 1.4 +/- 2.2 mEq/L. Means over time for MAP were 53 +/- 12 to 85 +/- 21 mm Hg. Mean HR varied over time from 81 +/- 6 to 91 +/- 11 beats/minute; mean RR, from 9 +/- 8 to 15 +/- 5 breaths/minute; SpO2 from 97 +/- 3% to 98 +/- 3%; mean T, from 36.0 +/- 0.6 degrees C to 39.1 +/- 0.7 degrees C. Over time, SpO2 and SaO2 did not change significantly; HR, RR, T, and PaCO2 decreased significantly; SAP, DAP, MAP, pHa, PaO2, and BE increased significantly. HCO3- concentrations increased significantly, peaking at 45 minutes. Recoveries were smooth and rapid; the time from the end of propofol infusion to extubation was 7.3 +/- 3 minutes, to sternal was 9.2 +/- 5 minutes, and to standing was 17.7 +/- 4 minutes. Median number of attempts to stand was two (range of one to four). Postoperative pain was mild to moderate., Conclusions: Detomidine-butorphanol-propofol provided good anesthesia for carotid artery translocation and neutering in goats., Clinical Relevance: Detomidine-butorphanol-propofol anesthesia with oxygen insufflation may be safely used for surgical intervention in healthy goats.

This paper considers whether a physician is criminally liable for administering a dose of painkillers that hastens a patient's death. The common wisdom is that a version of the doctrine of double effect legally protects the physician. That is, a physician is supposedly acting lawfully so long as the physician's primary purpose is to relieve suffering. This paper suggests that the criminal liability issue is more complex than that. Physician culpability can be based on recklessness, and recklessness hinges on whether a physician has taken an unjustifiable risk of hastening death. The authors identify three conditions of justifiability. Their analysis helps to explain the distinction between euthanasia, which is legally banned, and the use of risky analgesics, which is permitted in limited circumstances.

The key to safe anesthesia of a trauma patient is preoperative stabilization. It minimizes the anesthesia risk and allows proper choices of anesthetic drugs. Adequate monitoring throughout anesthesia allows rapid and adequate therapeutic intervention. Proper control of upper airway and support of physiologic functions will enhance the chances of the patient to survive anesthesia.

Lysine clonixinate (LC), an effective and well tolerated non-morphinic analgesic whose mechanism of action is basically due to the inhibition of cyclo-oxygenase, was assessed with a double-blind randomized dummy design versus paracetamol (P) on 200 patients suffering from pain after minor dental surgery. Patients received according to their needs 1 or 2 tablets of 125 mg lysine clonixinate or 500 mg paracetamol every 8 h during 48 h or until pain relief. Both groups, each composed of 100 patients, were comparable in terms of demographic conditions (t test), initial symptoms (chi-square test), characteristics of the extracted dental pieces, surgical complications and wound treatment (chi-square test). Pain intensity scores and daily average intake of tablets (3.4/day) documented in the patients' diary revealed no statistically significant differences between the two treatments (chi-square test). It was found that spontaneous pain measured using a visual analogue scale (VAS) decreased significantly in both treatment groups at the 24-h control examination. The following values were observed in the LC group: baseline 4.38 +/- 1.7; 24-h * 1.20 +/- 1.4; 48-h * 0.36 +/- 1.2. In the P group the values were: baseline 4.28 +/- 1.6; 24-h * 1.11 +/- 1.4; 48-h * 0.30 +/- 0.7 (*p < 0.05). Other variables like facial swelling and night pain, evaluated on a score from 0 to 4 and symptom presence or absence respectively, showed a similar response.(ABSTRACT TRUNCATED AT 250 WORDS)

Perineal tissue injury and uterine cramping within the first 24-48 hours after vaginal delivery are established models for studying pain relief. In this study, information was gathered from prospective, randomized investigations comparing the safety and efficacy of several oral analgesics. Nonsteroidal antiinflammatory drugs (NSAIDs) have been found consistently to be more useful than a placebo or acetaminophen. As compared with aspirin, the newer NSAIDs had a more delayed onset of action but required fewer doses. Mild analgesics were usually all that was necessary, and a combination with codeine was usually unnecessary. Side effects and breast milk concentrations of the drugs were negligible for this short-term therapy. Although no drug was found to be preferable to the others, aspirin and ibuprofen were the least expensive.