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CMAJ : Canadian Medical Association... May 2006Chronic noncancer pain (CNCP) is a major health problem, for which opioids provide one treatment option. However, evidence is needed about side effects, efficacy, and... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Chronic noncancer pain (CNCP) is a major health problem, for which opioids provide one treatment option. However, evidence is needed about side effects, efficacy, and risk of misuse or addiction.
METHODS
This meta-analysis was carried out with these objectives: to compare the efficacy of opioids for CNCP with other drugs and placebo; to identify types of CNCP that respond better to opioids; and to determine the most common side effects of opioids. We searched MEDLINE, EMBASE, CENTRAL (up to May 2005) and reference lists for randomized controlled trials of any opioid administered by oral or transdermal routes or rectal suppositories for CNCP (defined as pain for longer than 6 mo). Extracted outcomes included pain, function or side effects. Methodological quality was assessed with the Jadad instrument; analyses were conducted with Revman 4.2.7.
RESULTS
Included were 41 randomized trials involving 6019 patients: 80% of the patients had nociceptive pain (osteoarthritis, rheumatoid arthritis or back pain); 12%, neuropathic pain (postherpetic neuralgia, diabetic neuropathy or phantom limb pain); 7%, fibromyalgia; and 1%, mixed pain. The methodological quality of 87% of the studies was high. The opioids studied were classified as weak (tramadol, propoxyphene, codeine) or strong (morphine, oxycodone). Average duration of treatment was 5 (range 1-16) weeks. Dropout rates averaged 33% in the opioid groups and 38% in the placebo groups. Opioids were more effective than placebo for both pain and functional outcomes in patients with nociceptive or neuropathic pain or fibromyalgia. Strong, but not weak, opioids were significantly superior to naproxen and nortriptyline, and only for pain relief. Among the side effects of opioids, only constipation and nausea were clinically and statistically significant.
INTERPRETATION
Weak and strong opioids outperformed placebo for pain and function in all types of CNCP. Other drugs produced better functional outcomes than opioids, whereas for pain relief they were outperformed only by strong opioids. Despite the relative shortness of the trials, more than one-third of the participants abandoned treatment.
Topics: Analgesics, Opioid; Chronic Disease; Humans; Pain; Pain Measurement; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 16717269
DOI: 10.1503/cmaj.051528 -
Clinical Pharmacology and Therapeutics Jul 1975The administration of single oral doses of delta-9-tetrahydrocannabinol (THC) to patients with cancer pain demonstrated a mild analgesic effect. At a dose of 20 mg,... (Clinical Trial)
Clinical Trial
The administration of single oral doses of delta-9-tetrahydrocannabinol (THC) to patients with cancer pain demonstrated a mild analgesic effect. At a dose of 20 mg, however, THC induced side effects that would prohibit its therapeutic use including somnolence, dizziness, ataxia, and blurred vision. Alarming adverse reactions were also observed at this dose. THC, 10 mg, was well tolerated and, despite its sedative effect, may analgesic potential.
Topics: Analgesics; Aspirin; Cannabis; Clinical Trials as Topic; Codeine; Dextropropoxyphene; Dronabinol; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neoplasms; Pain; Palliative Care; Phytotherapy; Placebos
PubMed: 50159
DOI: 10.1002/cpt197518184 -
Indian Journal of Palliative Care 2015
PubMed: 25709176
DOI: 10.4103/0973-1075.150148 -
Annals of the Rheumatic Diseases Feb 1981An articular index was devised for the sequential assessment of patients with osteoarthritis (OA). Forty-eight joint units, chosen to reflect the characteristic pattern... (Clinical Trial)
Clinical Trial
An articular index was devised for the sequential assessment of patients with osteoarthritis (OA). Forty-eight joint units, chosen to reflect the characteristic pattern of the disease, were scored for tenderness on pressure or movement on a 4-point scale. Four observers examined patients to assess inter- and intraobserver error. The index was highly reproducible both within and between observers; intraobserver error was, however, significantly smaller. In a double-blind, cross-over trial the index was sufficiently sensitive to detect a statistically significant difference between the responses of patients with OA to an anti-inflammatory agent and to a simple analgesic. It is likely to be a useful addition to current methods of measurement in osteoarthritis.
Topics: Acetaminophen; Clinical Trials as Topic; Dextropropoxyphene; Double-Blind Method; Drug Combinations; Humans; Joints; Ketoprofen; Osteoarthritis; Reference Values
PubMed: 7008713
DOI: 10.1136/ard.40.1.75 -
American Journal of Public Health Mar 1997Using 1993 data, this study examines the prevalence of presumptively inappropriate prescriptions among residents, aged 65 and older, of board and care homes.
OBJECTIVES
Using 1993 data, this study examines the prevalence of presumptively inappropriate prescriptions among residents, aged 65 and older, of board and care homes.
METHODS
Inappropriate drug prescriptions were identified through the use of established criteria developed for application to older nursing home residents and to community-dwelling elderly. This research used a sample of 2054 elderly residents from 410 facilities in 10 states. Weighted analyses were performed with SUDAAN, which accounted for the complex, multistage sampling design.
RESULTS
Depending on the criterion applied, between 20% and 25% of residents had at least one inappropriate prescription. Propoxyphene, long-acting benzodiazepines, dipyridamole, and amitriptyline were prescribed most frequently. Residents with inappropriate drug prescriptions had more complex drug regimens prescribed on a routine basis.
CONCLUSIONS
The results are a conservative estimate of the extent of inappropriate drug prescribing and utilization in board and care facilities. Increased involvement by pharmacists and physicians in systematic drug utilization review is warranted.
Topics: Aged; Aged, 80 and over; Drug Prescriptions; Drug Utilization; Female; Health Services Misuse; Homes for the Aged; Humans; Logistic Models; Male; Nursing Homes; United States
PubMed: 9096541
DOI: 10.2105/ajph.87.3.404 -
Journal of Pain and Symptom Management Nov 1998Experimental studies have indicated that N-methyl-D-aspartate (NMDA) receptor antagonists may be effective analgesics in a wide variety of chronic pain states. The... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Experimental studies have indicated that N-methyl-D-aspartate (NMDA) receptor antagonists may be effective analgesics in a wide variety of chronic pain states. The mechanism is presumed to be related to decreased firing of dorsal horn neurons after constant repeated C-fiber stimulation. Dextromethorphan (DM), a potent NMDA antagonist with a good safety profile, may be a promising agent for the treatment of persistent pain. An open-label randomized trial was designed to examine the effects of combining DM with NSAIDs, dextropropoxyphene, or morphine in cancer patients with pain. Patients who required a change in the step of the World Health Organization's (WHO) analgesic ladder because of a pain level of 4 or more on a numerical pain scale were randomly allocated to receive DM 30 mg three times a day (30 patients) or conventional treatment (30 patients). There were 20 patients randomized for each step of the analgesic ladder. Pain mechanisms, pain intensity (numerical 0-10 scale), symptoms more frequently present in advanced cancer patients or associated with opioid therapy (graded on a 0-3 scale--not at all, slight, a lot, awful), opioid escalation index, days on opioid treatment, and adverse effects were recorded. After 2 days 75%, 80%, and 100% of patients treated with DM in steps 1, 2, and 3, respectively, required conventional treatment, because adequate pain relief had not been achieved (pain scale > 4). Failure of this treatment was equally observed in neuropathic pain or nociceptive pain syndromes. Four patients treated with DM who did not require the conventional treatment immediately did require this change after some days, due to poor pain control. A highly significant reduction in pain was observed in patients directly treated with the conventional treatment in all the three steps of the analgesic ladder. No significant analgesic effects could be found when DM at this dose was combined with NSAIDs, dextropropoxyphene, or morphine.
Topics: Analgesics, Opioid; Dextromethorphan; Dextropropoxyphene; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Female; Humans; Male; Middle Aged; Morphine; Neoplasms; Pain, Intractable; Palliative Care
PubMed: 9846026
DOI: No ID Found -
BioMed Research International 2014To compare the effects of different anesthesia techniques on tourniquet-related ischemia-reperfusion by measuring the levels of malondialdehyde (MDA), ischemia-modified... (Comparative Study)
Comparative Study Randomized Controlled Trial
PURPOSE
To compare the effects of different anesthesia techniques on tourniquet-related ischemia-reperfusion by measuring the levels of malondialdehyde (MDA), ischemia-modified albumin (IMA) and neuromuscular side effects.
METHODS
Sixty ASAI-II patients undergoing arthroscopic knee surgery were randomised to three groups. In Group S, intrathecal anesthesia was administered using levobupivacaine. Anesthesia was induced and maintained with sevoflurane in Group I and TIVA with propofol in Group T. Blood samples were obtained before the induction of anesthesia (t1), 30 min after tourniquet inflation (t2), immediately before (t3), and 5 min (t4), 15 min (t5), 30 min (t 6), 1 h (t7), 2 h (t8), and 6 h (t9) after tourniquet release.
RESULTS
MDA and IMA levels increased significantly compared with baseline values in Group S at t2-t 9 and t2-t7. MDA levels in Group T and Group I were significantly lower than those in Group S at t2-t8 and t2-t9. IMA levels in Group T were significantly lower than those in Group S at t2-t7. Postoperatively, a temporary 1/5 loss of strength in dorsiflexion of the ankle was observed in 3 patients in Group S and 1 in Group I.
CONCLUSIONS
TIVA with propofol can make a positive contribution in tourniquet-related ischemia-reperfusion.
Topics: Acetaminophen; Adolescent; Adult; Anesthesia, Inhalation; Anesthesia, Intravenous; Anesthesia, Spinal; Anesthetics, Inhalation; Anesthetics, Local; Arthroplasty, Replacement, Knee; Aspirin; Bupivacaine; Chlorpheniramine; Dextropropoxyphene; Drug Combinations; Female; Humans; Levobupivacaine; Male; Malondialdehyde; Methyl Ethers; Middle Aged; Reperfusion Injury; Sevoflurane
PubMed: 24701585
DOI: 10.1155/2014/846570 -
The Cochrane Database of Systematic... Aug 2020Acute soft tissue injuries are common and costly. The best drug treatment for such injuries is not certain, although non-steroidal anti-inflammatory drugs (NSAIDs) are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute soft tissue injuries are common and costly. The best drug treatment for such injuries is not certain, although non-steroidal anti-inflammatory drugs (NSAIDs) are often recommended. There is concern about the use of oral opioids for acute pain leading to dependence. This is an update of a Cochrane Review published in 2015.
OBJECTIVES
To assess the benefits or harms of NSAIDs compared with other oral analgesics for treating acute soft tissue injuries.
SEARCH METHODS
We searched the CENTRAL, 2020 Issue 1, MEDLINE (from 1946), and Embase (from 1980) to January 2020; other databases were searched to February 2019.
SELECTION CRITERIA
We included randomised or quasi-randomised controlled trials involving people with acute soft tissue injury (sprain, strain, or contusion of a joint, ligament, tendon, or muscle occurring within 48 hours of inclusion in the study), and comparing oral NSAIDs versus paracetamol (acetaminophen), opioid, paracetamol plus opioid, or complementary and alternative medicine. The outcomes were pain, swelling, function, adverse effects, and early re-injury.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for eligibility, extracted data, and assessed risk of bias. We assessed the quality of the evidence using GRADE methodology.
MAIN RESULTS
We included 20 studies, with 3305 participants. Three studies included children only. The others included predominantly young adults; approximately 60% were male. Seven studies recruited people with ankle sprains only. Most studies were at low or unclear risk of bias; however, two were at high risk of selection bias, three were at high risk of bias from lack of blinding, and five were at high risk of selective outcome reporting bias. Some evidence relating to pain relief was high certainty. Other evidence was either moderate, low or very low certainty, reflecting study limitations, indirectness, imprecision, or combinations of these. Thus, we are certain or moderately certain about some of the estimates, and uncertain or very uncertain of others. Eleven studies, involving 1853 participants compared NSAIDs with paracetamol. There were no differences between the two groups in pain at one to two hours (1178 participants, 6 studies; high-certainty evidence), at days one to three (1232 participants, 6 studies; high-certainty evidence), and at day seven or later (467 participants, 4 studies; low-certainty evidence). There was little difference between the groups in numbers of participants with minimal swelling at day seven or later (77 participants, 1 study; low-certainty evidence). Very low-certainty evidence from three studies (386 participants) means we are uncertain of the finding of little difference between the two groups in return to function at day seven or later. There was low-certainty evidence from 10 studies (1504 participants) that NSAIDs may slightly increase the risk of gastrointestinal adverse events compared with paracetamol. There was low-certainty evidence from nine studies (1679 participants) of little difference in neurological adverse events between the NSAID and paracetamol groups. Six studies, involving 1212 participants compared NSAIDs with opioids. There was moderate-certainty evidence of no difference between the groups in pain at one hour (1058 participants, 4 studies), and low-certainty evidence for no difference in pain at days four or seven (706 participants, 1 study). There was very low-certainty evidence of no important difference between the groups in swelling (84 participants, 1 study). Participants in the NSAIDs group were more likely to return to function in 7 to 10 days (542 participants, 2 studies; low-certainty evidence). There was moderate-certainty evidence (1143 participants, 5 studies) that NSAIDs were less likely to result in gastrointestinal or neurological adverse events compared with opioids. Four studies, involving 240 participants, compared NSAIDs with the combination of paracetamol and an opioid. The applicability of findings from these studies is in question because the dextropropoxyphene combination analgesic agents used are no longer in general use. Very low-certainty evidence means we are uncertain of the findings of no differences between the two interventions in the numbers with little or no pain at day one (51 participants, 1 study), day three (149 participants, 2 studies), or day seven (138 participants, 2 studies); swelling (230 participants, 3 studies); return to function at day seven (89 participants, 1 study); and the risk of gastrointestinal or neurological adverse events (141 participants, 3 studies). No studies reported re-injury rates. No studies compared NSAIDs with oral complementary and alternative medicines, AUTHORS' CONCLUSIONS: Compared with paracetamol, NSAIDs make no difference to pain at one to two hours and at two to three days, and may make no difference at day seven or beyond. NSAIDs may result in a small increase in gastrointestinal adverse events and may make no difference in neurological adverse events compared with paracetamol. Compared with opioids, NSAIDs probably make no difference to pain at one hour, and may make no difference at days four or seven. NSAIDs probably result in fewer gastrointestinal and neurological adverse effects compared with opioids. The very low-certainly evidence for all outcomes for the NSAIDs versus paracetamol with opioid combination analgesics means we are uncertain of the findings of no differences in pain or adverse effects. The current evidence should not be extrapolated to adults older than 65 years, as this group was not well represented in the studies.
Topics: Acetaminophen; Acute Disease; Administration, Oral; Adult; Analgesics; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Bias; Child; Contusions; Female; Humans; Male; Middle Aged; Pain; Randomized Controlled Trials as Topic; Soft Tissue Injuries; Sprains and Strains; Time-to-Treatment; Young Adult
PubMed: 32797734
DOI: 10.1002/14651858.CD007789.pub3 -
Pain Physician 2010Immunoassay screening is used by pain physicians to determine compliance with controlled substances. Because clinical use of pain medications is different from illicit... (Comparative Study)
Comparative Study
BACKGROUND
Immunoassay screening is used by pain physicians to determine compliance with controlled substances. Because clinical use of pain medications is different from illicit drug use, there is a need to evaluate the level of diagnostic accuracy of this procedure for the pain patient.
OBJECTIVE
To compare the results of automated screening by immunoassay with analysis by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) in identifying pain patients using illicit drugs and pain patients excreting low concentrations of their prescribed medications.
STUDY DESIGN
A diagnostic accuracy study.
METHODS
Urine samples from 4,200 pain patients were tested by immunoassay and LC-MS/MS for the following drugs and metabolites: Amphetamine, Methamphetamine, Alpha-hydroxyalprazolam, Lorazepam, Nordiazepam, Oxazepam, Temazepam, Cannabinoids, Cocaine, Methadone, Methadone Metabolite, Codeine, Hydrocodone, Hydromorphone, Morphine, Propoxyphene, and Norpropoxyphene.
RESULTS
In a number of patients negative immunoassay findings were superseded by positive results on analysis by Mass Spectrometry. These were termed false negative results. The greatest failures were for the benzodiazepines (28%) and for cocaine (50%).
LIMITATIONS
The study was limited by the lack of complete demographics for the cohort and because only one immunoassay diagnostic product was used. It was also limited because not all drugs react the same in the immunoassay.
CONCLUSIONS
We show that in general, immunoassay screening results are accurate, although as shown in this study there are many false negative observations. The use of LC-MS/MS technology significantly decreases the number of false negative results.
Topics: Automation; Benzodiazepines; Chromatography, Liquid; Cocaine; Cohort Studies; False Negative Reactions; Humans; Illicit Drugs; Immunoassay; Medication Adherence; Osmolar Concentration; Pain; Single-Blind Method; Substance Abuse Detection; Tandem Mass Spectrometry
PubMed: 20495592
DOI: No ID Found -
The Journal of General Physiology Feb 1996Voltage-dependent ionic currents were recorded from squid giant fiber lobe neurons using the whole-cell patch-clamp technique. When applied to the bathing solution,...
Voltage-dependent ionic currents were recorded from squid giant fiber lobe neurons using the whole-cell patch-clamp technique. When applied to the bathing solution, methadone was found to block IK, I Na and I Ca. Both I Na and I Ca were reduced without apparent change in kinetics and exhibited IC(50)'s of 50-100 and 250-500 mu M, respectively, at +10 mV. In contrast, IK was reduced in a time-dependent manner that is well fit by a simple model of open channel block (K(D)= 32+/- or 2 mu M, +60 mV, 10 degrees Celsius). The mechanism of I(K) block was examined in detail and involves a direct action of methadone, a tertiary amine, on K channels rather than an opioid receptor-mediated pathway. The kinetics of I(K) block resemble those reported for internally applied long chain quaternary ammonium (QA) compounds; and recovery from I(K) block is QA-like in its slow time course and strong dependence on holding potential. A quaternary derivative of methadone (N-methyl-methadone) only reproduced the effects of methadone on I(K) when included in the pipette solution; this compound was without effect when applied externally. I(K) block thus appears to involve diffusion of methadone into the cytoplasm and occlusion of the open K channel at the internal QA blocking site by the protonated form of the drug. This proposed mode of action is supported by the pH and voltage dependence of block as well as by the observation that high external K+ speeds the rate of drug dissociation. In addition, the effect of methadone on I(K) evoked during prolonged (300 ms) depolarizations suggests that methadone block may interfere with endogenous K+ channel inactivation. The effects of temperature, methadone stereoisomers, and the methadone-like drugs propoxyphene and nor-propoxyphene on IK block were examined. Methadone was also found to block I(K) in GH3 cells and in chick myoblasts.
Topics: Analgesics, Opioid; Animals; Cells, Cultured; Chick Embryo; Decapodiformes; Dextropropoxyphene; Electric Stimulation; Hydrogen-Ion Concentration; Ion Channel Gating; Methadone; Muscle, Skeletal; Neurons; Patch-Clamp Techniques; Pituitary Gland; Potassium Channel Blockers; Rats; Receptors, Opioid, mu; Sensitivity and Specificity; Stereoisomerism; Temperature
PubMed: 8833344
DOI: 10.1085/jgp.107.2.243