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Biomedical subjects

R A Moore

Publications and source records attributed to R A Moore.

At least 109 records · Page 6Linked to original sources
PubMed1997

Efficacy, dose-response, and safety of ondansetron in prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized placebo-controlled trials.

OBJECTIVE: The authors reviewed efficacy and safety data for ondansetron for preventing postoperative nausea and vomiting (PONV). METHODS: Systematically searched, randomized, controlled trials (obtained through MEDLINE, EMBASE, Biological Abstracts, manufacturer's database, manual searching of journals, and article reference lists) were analyzed. Relevant end points were prevention of early PONV (within 6 h after surgery) and late PONV (within 48 h) and adverse effects. Relative benefit and number-needed-to-treat were calculated. The number-needed-to-treat indicated how many patients had to be exposed to ondansetron to prevent PONV in one of them who would have vomited or been nauseated had he or she received placebo. RESULTS: Fifty-three trials were found that had data from 7,177 patients receiving 24 different ondansetron regimens and from 5,712 controls receiving placebo or no treatment. Average early and late PONV incidences without ondansetron were 40% and 60%, respectively. There was a dose response for oral and intravenous ondansetron. Best number-needed-to-treat to prevent PONV with the best documented regimens was between 5 and 6. This was achieved with an intravenous dose of 8 mg and an oral dose of 16 mg. Antivomiting efficacy was consistently better than antinausea efficacy. Efficacy in children was poorly documented. Ondansetron significantly increased the risk for elevated liver enzymes (number-needed-to-harm was 31) and headache (number-needed-to-harm was 36). CONCLUSIONS: If the risk of PONV is very high, for every 100 patients receiving an adequate dose of ondansetron 20 patients will not vomit who would have vomited had they received placebo. The antinausea effect is less pronounced. Of these 100, three will have elevated liver enzymes and three will have a headache who would not have had these adverse effects without the drug.

Antiemetics↗
PubMed1997

Systematic review of outpatient services for chronic pain control.

AIM OF REPORT. This report reviews the evidence about the effectiveness of treatments for chronic pain. While treatment of chronic pain is usually seen as an integrated service, this report concentrates on the individual interventions that constitute the service. HOW THE RESEARCH WAS CONDUCTED. Searches of databases and journals identified over 15,000 randomised studies with pain as an outcome, and many more which were not randomised. Over 150 systematic reviews relevant to chronic pain treatment were identified and their quality assessed using a simple scoring system. Systematic reviews conducted for this report were based mainly on randomised trials. The number needed to treat (NNT) was chosen as the output for the report. NNTs of 2-4 indicate effective treatments. Because NNT is treatment-specific it overcomes problems associated with highly variable placebo or control event rates in pain trials. Such variability is predominantly due to the limited numbers of patients in the clinical trials. Dichotomous outcome measures are important in synthesising information from many studies, and in deriving NNTs. Methods have been developed which allow mean information on pain relief and intensity to be converted reliably into the simple dichotomous outcome of at least 50% pain relief. RESEARCH FINDINGS. PHYSICAL INTERVENTIONS. Transcutaneous electrical nerve stimulation (TENS) has been shown not to be effective in postoperative and labour pain. In chronic pain, there is evidence that TENS effectiveness increases slowly, and that large doses need to be used. There is lack of evidence for the effectiveness of TENS in chronic pain. There is a lack of evidence for the effectiveness of relaxation. Intravenous systemic regional blockade with guanethidine has been shown to be without effect. Epidural corticosteroids are effective in the short term for back pain and sciatica. Injections of corticosteroids in or around shoulder joints for shoulder pain have been shown not to be effective. There is a lack of evidence supporting spinal cord stimulators. Case series are of poor quality and do not provide evidence of effectiveness, although at least 50% pain relief at 5 years is reported in over 50% of patients. PHARMACOLOGICAL INTERVENTIONS. Minor analgesics are important in chronic pain. NNTs were calculated for analgesics given orally for moderate or severe acute postoperative pain. The NNTs found ranged from 17 (poor) for codeine, 60 mg, to 2.5 (good) for ibuprofen, 400 mg. Anticonvulsant and antidepressant drugs are prescribed for neuropathic pains like diabetic neuropathy. NNTs are of the order of 2.5, showing them to be effective treatments. However, there are too few studies with too few patients to determine which is the best drug. Minor adverse events are common, and major adverse events occur in about 1 in 20 patients. There are no studies comparing antidepressants and anticonvulsants directly. Systemic local anaesthetic-type drugs have been shown to be effective in nerve injury pain but there is little or no evidence to support their use in migraine or cancer-related pain. Topical NSAIDs (for example, gels, creams) are effective in rheumatological conditions with an overall NNT of 3. There are too few studies to determine which is the best agent. Topical NSAIDs have few adverse events; most importantly they are without the major gastrointestinal adverse events found with oral NSAIDs, which might make them an important choice for some patients with peripheral arthritis. (ABSTRACT TRUNCATED)

Ambulatory Care↗
PubMed1996

Condyloma acuminata in infants and children. A survey of colon and rectal surgeons.

PURPOSE: Condyloma acuminata are anogenital warts caused by a human papillomavirus. Human papillomavirus is a tissue-specific, site-specific, double-stranded DNA virus, which is capable of inducing high-grade genital intraepithelial neoplasia and malignancy. The incidence of anogenital warts in the pediatric age group is rising, and sexual abuse has been implicated as a potential cause. METHODS: Accumulated data from separate questionnaires sent to practicing colorectal surgeons who are members of The American Society of Colon and Rectal Surgeons and fellows in colon and rectal training programs have been analyzed. RESULTS: Thirty percent of those polled responded to our survey. Of the respondents, 93 percent see less than two pediatric cases per year. Seventy-two percent stated that tissue specimens would be sent routinely for histopathologic identification. Although 73 percent of surgeons consider anogenital warts a potentially sexually transmitted disease, only 26 percent reported screening for other sexually transmitted diseases. A diagnostic and therapeutic protocol is followed by 19 percent of respondents. Patient follow-up varied from six months (43 percent) to lifelong examinations (3 percent). Sixty-four percent of respondents agreed that a diagnostic and therapeutic protocol based on current knowledge would be beneficial. CONCLUSION: We conclude that colon and rectal surgeons have a low exposure to anogenital warts in infants and children. Furthermore, we believe that a diagnostic and therapeutic protocol based on the current literature would be helpful.

Aftercare↗
PubMed1996

Assessing the quality of reports of randomized clinical trials: is blinding necessary?

It has been suggested that the quality of clinical trials should be assessed by blinded raters to limit the risk of introducing bias into meta-analyses and systematic reviews, and into the peer-review process. There is very little evidence in the literature to substantiate this. This study describes the development of an instrument to assess the quality of reports of randomized clinical trials (RCTs) in pain research and its use to determine the effect of rater blinding on the assessments of quality. A multidisciplinary panel of six judges produced an initial version of the instrument. Fourteen raters from three different backgrounds assessed the quality of 36 research reports in pain research, selected from three different samples. Seven were allocated randomly to perform the assessments under blind conditions. The final version of the instrument included three items. These items were scored consistently by all the raters regardless of background and could discriminate between reports from the different samples. Blind assessments produced significantly lower and more consistent scores than open assessments. The implications of this finding for systematic reviews, meta-analytic research and the peer-review process are discussed.

Double-Blind Method↗
PubMed1996

Ibuprofen compared with ibuprofen plus caffeine after third molar surgery.

OBJECTIVES: To compare the relative merits of single doses of ibuprofen and ibuprofen plus caffeine in the treatment of pain after third molar removal. DESIGN: Randomised, double-blind, placebo-controlled, single-dose parallel-group comparison of placebo, ibuprofen 200 and 400 mg with ibuprofen 200 mg plus 50, 100 or 200 mg of caffeine. SUBJECTS: 161 patients undergoing lower third molar removal. RESULTS: All active treatments produced significant analgesia and mood elevation compared with placebo. There was no significant difference in the effects of 200 and 400 mg of ibuprofen. Adding caffeine to 200 mg ibuprofen produced significantly more analgesic effect at 45 and 60 min than ibuprofen 200 mg alone. Ten patients reported 11 adverse effects, none in the highest caffeine dose group. CONCLUSIONS: Caffeine increased the analgesic effect of ibuprofen 200 mg, through an earlier onset of analgesic effect. This was achieved in this single dose context without problematic adverse effects.

Adult↗
PubMed1996

Morphine and morphine-6-glucuronide plasma concentrations and effect in cancer pain.

The relationships between plasma morphine and metabolite (M3G and M6G) concentrations and analgesic efficacy were investigated in an open study of 39 cancer pain patients receiving chronic oral morphine therapy with either morphine sulfate solution or controlled-release morphine tablets. There were no differences in morphine, metabolite kinetics, or analgesic efficacy between equivalent doses of conventional or controlled-release formulations. The increase in morphine plasma concentration after a dose (1 hr for normal release, 2 hr for controlled release) was correlated significantly with the dose of morphine (r = 0.914, P < 0.001). There was a significant reduction in pain intensity (P < 0.05) and increase in pain relief (P < 0.001) after the dose of morphine administration, when compared with the predose score. One-half of the patients had mild and tolerable adverse effects. Patients were classified by mean pain relief between doses as having optimal, moderate, or poor pain control. No simple relationship was found between morphine plasma concentration and pain control. Morphine plus M6G concentrations in the "optimal control" group (751.2 +/- 194 nmol/L), however, were more than twice those found in the "moderate control" group (276.9 +/- 41.9 nmol/L) (P < 0.05), and no patient in the moderate control group had a morphine plus M6G concentration greater than 405 nmol/L. These results support the importance of M6G in morphine analgesia. For these hospitalized patients, there appeared to be a therapeutic range of morphine plus M6G plasma concentrations for optimal pain control with a lower limit of 400 nmol/L predose.

Adult↗
PubMed1996

A systematic review of antidepressants in neuropathic pain.

The objective of this study was to review the effectiveness and safety of antidepressants in neuropathic pain. In a systematic review of randomised controlled trials, the main outcomes were global judgements, pain relief or fall in pain intensity which approximated to more than 50% pain relief, and information about minor and major adverse effects. Dichotomous data for effectiveness and adverse effects were analysed using odds ratio and number needed-to-treat (NNT) methods. Twenty-one placebo-controlled treatments in 17 randomised controlled trials were included, involving 10 antidepressants. In six of 13 diabetic neuropathy studies the odds ratios showed significant benefit compared with placebo. The combined odds ratio was 3.6 (95% CI 2.5-5.2), with a NNT for benefit of 3 (2.4-4). In two of three postherpetic neuralgia studies the odds ratios showed significant benefit, and the combined odds ratio was 6.8 (3.5-14.3), with a NNT of 2.3 (1.7-3.3). In two atypical facial pain studies the combined odds ratio for benefit was 4.1 (2.3-7.5), with a NNT of 2.8 (2-4.7). Only one of three central pain studies had analysable dichotomous data. The NNT point estimate was 1.7. Comparisons of tricyclic antidepressants did not show any significant difference between them; they were significantly more effective than benzodiazepines in the three comparisons available. Paroxetine and mianserin were less effective than imipramine. For 11 of the 21 placebo-controlled treatments there was dichotomous information on minor adverse effects; combining across pain syndromes the NNT for minor (noted in published report) adverse effects was 3.7 (2.9-5.2). Information on major (drug-related study withdrawal) adverse effects was available from 19 reports; combining across pain syndromes the NNT for major adverse effects was 22 (13.5-58). Antidepressants are effective in relieving neuropathic pain. Compared with placebo, of 100 patients with neuropathic pain who are given antidepressants, 30 will obtain more than 50% pain relief, 30 will have minor adverse reactions and four will have to stop treatment because of major adverse effects. With very similar results for anticonvulsants it is still unclear which drug class should be first choice. Treatment would be improved if we could harness the dramatic improvement seen on placebo in some of the trials.

Antidepressive Agents↗
PubMed1996

Demonstrating effectiveness--the concept of numbers-needed-to-treat.

When assessing a health-care intervention the main question is--does it work? Often, a more difficult question needs to be answered--how well does it work? Systematic reviews and meta-analyses help to provide answers to both questions. Too often though, the results are expressed in a way that leaves the reader asking, 'what is the result?' Numbers-needed-to-treat is a simple method for conveying the answers. It can be applied to any chosen clinical outcome with dichotomous data, and the results can be understood by doctor, patient and the public. This paper discusses the concept of numbers-needed-to-treat and gives worked examples using trials in H. pylori eradication and lowering of serum cholesterol.

Helicobacter Infections↗
PubMed1995

Cyclosporine-induced worsening of hepatic dysfunction in a patient with Crohn's disease and enterocutaneous fistula.

Cyclosporine recently has become part of the treatment regimen for patients with refractory inflammatory bowel disease, though it is still considered investigational for that purpose. However, little attention has been given to the potential hepatotoxicity associated with cyclosporine administration. This can be especially significant in patients with preexisting abnormalities of liver function, including those induced by total parenteral nutrition.

Adult↗
PubMed1995

Nucleotide sequence of the gyrA gene and characterization of ciprofloxacin-resistant mutants of Helicobacter pylori.

PCR was used to amplify a 238-bp region from Helicobacter pylori which corresponded to the quinolone resistance-determining region in Escherichia coli. The gyrA gene of H. pylori was cloned and sequenced. An open reading frame of 2,478 nucleotides coded for a polypeptide of 826 amino acids with a calculated molecular mass of 92,508 Da. The amino acid sequence showed an overall 52% identity with other bacterial gyrA genes but was most closely related to the gyrA subunit of Campylobacter jejuni (76.5% identity). Sequencing of the amplification product from ciprofloxacin-resistant mutants of H. pylori revealed four classes of mutations with substitutions at amino acid 87 (Asn-->Lys), amino acid 88 (Ala-->Val), and amino acid 91 (Asp-->Gly, -->Asn, or -->Tyr) and a double substitution at amino acids 91 and 97 (Ala-->Val). Ciprofloxacin-susceptible strains of H. pylori could be transformed to ciprofloxacin resistance by using the amplified fragment from resistant strains as donor DNA. Of the 11 ciprofloxacin-resistant mutants examined, only one did not have an alteration within the quinolone resistance-determining region, suggesting that, in H. pylori, resistance to quinolones is primarily a result of alterations in gyrA.

Amino Acid Sequence↗
PubMed1995

Metronidazole uptake in Helicobacter pylori.

Currently, the mechanism of metronidazole resistance is not understood in Helicobacter pylori. We have looked at uptake of metronidazole into a sensitive and a resistant strain of H. pylori. Both strains displayed rapid uptake of [14C]metronidazole, although the resistant strain accumulated the drug at a slower rate and to a lesser amount than the sensitive strain. Uptake was inhibited by KCN and carbonyl cyanide m-chlorophenyl-hydrazone (CCCP) but not by sodium arsenate. Thin-layer chromatography analysis of lysed cell supernatants showed that metronidazole was metabolized in both strains. A variety of related imidazole compounds inhibited metronidazole uptake, consistent with a common transport system for this group of antibiotics. Our data do not support an absence of uptake or metabolism as a cause of resistance in the strain examined.

Biological Transport, Active↗
PubMed1994

Comparative QSAR studies of two series of 1,4-dihydropyridines as slow calcium channel blockers.

Quantitative structure activity analysis was applied to two series of dihydropyridine (DHP) calcium channel blocking agents. One series of compounds was composed of DHPs substituted in the 4-position with an ortho or meta nitro substituted phenyl ring. The second group consisted of DHPs substituted at the 4-position with a novel thieno [3,2-c] pyridine ring. Both series consisted of compounds with unsymmetrical ester substitutions on the dihydropyridine ring. The antihypertensive activity of the compounds were determined in a spontaneously hypertensive rat model. Regression analysis indicated the antihypertensive activity of an i.v. dose correlated with the calculated octanol/water coefficent (clogP). Regression analysis did not find correlation with the in vitro potency and the clogP values.

Animals↗
PubMed1993

Categorization of clinical isolates of Helicobacter pylori on the basis of restriction digest analyses of polymerase chain reaction-amplified ureC genes.

Restriction endonuclease analyses of a 1.1-kb polymerase chain reaction-amplified portion of the ureC gene from Helicobacter pylori were used to group or to differentiate 21 clinical isolates. Isolates were placed into 4 groups after HindIII digestion alone, and placement was expanded into 15 groups after isolates were digested with AluI and PvuI.

Bacterial Typing Techniques↗