The dictated operative note: important but is it being taught?
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Data Collection↗
Biomedical subjects
R A Moore
Publications and source records attributed to R A Moore.
The role of Mucodyne in reducing the need for surgery in patients with persistent otitis media with effusion.
UNLABELLED: A recent meta-analysis suggested a possible beneficial effect of carboxymethylcysteine (Mucodyne) in resolving otitis media with effusion (OME), but the methodology in several of the included trials was flawed. A double-blind randomised controlled trial (RCT) involving 163 patients (78 randomised to Mucodyne and 85 to placebo) was therefore performed. MAIN OUTCOME MEASURE: operative intervention or not. Of the 28 patients with resolved OME, 17 were in the Mucodyne group and 11 in the placebo group. Although it appeared that patients treated with Mucodyne were 1.68 times more likely to undergo resolution of OME than patients receiving placebo, this did not reach statistical significance. [Risk ratio of 1.68 (95% C.I., 0.74-3.37)]. chi2 test (df = 162) = 2.24 (P = 0.134). The absolute risk difference in the study was 8.5% (95% C.I., -3-20). We cannot exclude the possibility that Mucodyne is as beneficial as a 20% additional resolution of OME, or as harmful as a 3% decrease in the resolution of OME.
Carbocysteine↗
Five easy pieces on evidence-based medicine (2).
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Double-Blind Method↗
Single-dose ketorolac and pethidine in acute postoperative pain: systematic review with meta-analysis.
For a systematic review of postoperative analgesic efficacy and adverse effects of single doses, injected or oral, of pethidine and ketorolac compared with placebo, we sought published randomized studies in moderate to severe postoperative pain. Information on summed pain intensity or pain relief outcomes over 4-6 h was extracted and converted to dichotomous information to produce the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief. Minor and major adverse effect data were extracted and summarized. For pethidine 100 mg i.m., eight randomized, controlled studies met the inclusion criteria, with 203 patients given pethidine and 161 placebo. The NNT to produce at least 50% pain relief was 2.9 (95% confidence interval 2.3-3.9). At this dose, pethidine produced significantly more drowsiness and dizziness than placebo, with numbers-needed-to-harm (NNH) of 2.9 (2.2-4.4) and 7.2 (4.8-14), respectively. For ketorolac, 14 reports met the inclusion criteria (six i.m. and eight oral). Most i.m. information (176 patients) was available for the 30 mg dose, which had an NNT of 3.4 (2.5-4.9). Most oral information was available for the 10 mg dose, which had an NNT of 2.6 (2.3-3.1). Oral ketorolac 10 mg was consistently at least as effective as ketorolac 30 mg i.m. Only with oral ketorolac 10 mg were there significantly more adverse effects than with placebo, with an NNH for any adverse effect of 7.3 (4.7-17).
Acute Disease↗
HSV-1 amplicon vectors are a highly efficient gene delivery system for skeletal muscle myoblasts and myotubes.
Analysis of RyR1 structure function in muscle cells is made difficult by the low (<5%) transfection efficiencies of myoblasts or myotubes using calcium phosphate or cationic lipid techniques. We inserted the full-length 15.3-kb RyR1 cDNA into a herpes simplex virus type 1 (HSV-1) amplicon vector, pHSVPrPUC between the ori/IE 4/5 promoter sequence and the HSV-1 DNA cleavage/packaging signal (pac). pHSVGN and pHSVGRyR1, two amplicons that expressed green fluorescent protein, were used for fluorescence-activated cell sorter analysis of transduction efficiency. All amplicons were packaged into HSV-1 virus particles using a helper virus-free packaging system and yielded 10(6) transducing vector units/ml. HSVRyR1, HSVGRyR1, and HSVGN virions efficiently transduced mouse myoblasts and myotubes, expressing the desired product in 70-90% of the cells at multiplicity of infection 5. The transduced cells appeared healthy and RyR1 produced by this method was targeted properly and restored skeletal excitation-contraction coupling in dyspedic myotubes. The myotubes produced sufficient protein to allow single-channel analyses from as few as 10 100-mm dishes. In most cases this method could preclude the need for permanent transfectants for the study of RyR1 structure function.
Animals↗
Women's knowledge of, and attitudes to, contraceptive effectiveness and adverse health effects.
Our objectives were to determine women's knowledge of the effectiveness of different contraceptive methods and the risks of thrombosis with use of hormonal contraceptives, and their attitudes regarding the acceptability of bleeding irregularities and weight change. An additional aim was to determine what information women want to be given about contraceptives. In order to satisfy the study objectives, a series of semi-structured focus groups was conducted with women of differing life-stage and background from Oxford. Quantitative data were collected using a structured questionnaire. Qualitative data were collected through discussion with group members. Forty-five women attended four focus groups. Women were segregated into the following groups: professional working mothers; non-professional mothers; young, unmarried professional women; and undergraduate students. Women tended to overestimate the risks and underestimate the effectiveness of hormonal contraceptives. They were resistant to interference with their bleeding patterns and weight.
Adolescent↗
Naturally occurring, nonregressing canine oral papillomavirus infection: host immunity, virus characterization, and experimental infection.
Papillomaviruses occasionally cause severe, nonregressing or recurrent infections in their human and animal hosts. The mechanisms underlying these atypical infections are not known. Canine oral papillomavirus (COPV) typically regresses spontaneously and is an important model of mucosal human papillomavirus infections. A severe, naturally occurring, nonregressing COPV infection provided an opportunity to investigate some aspects of viral pathogenicity and host immunity. In this case, the papillomas proved refractory to surgical and medical treatments, including autogenous vaccination and vaccination with capsid (L1) virus-like particles. High levels of induced anti-L1 antibodies appeared to have no effect on the infection. The papillomas spread to oesophageal mucosa, perioral haired skin, and remote cutaneous sites. Isolation of COPV from the animal and sequencing of several regions of the viral genome showed no differences to the COPV prototype. Experimental infection of beagle dogs with this viral isolate resulted in the uncomplicated development and regression of oral warts within the usual period, indicating that the virus was not an unusual pathogenic variant. These findings support the hypothesis that the recurrent lesions seen in some human papillomavirus infections, such as recurrent laryngeal papillomatosis, are associated with specific defects in host immunity rather than variations in viral pathogenicity.
Animals↗
Injected morphine in postoperative pain: a quantitative systematic review.
This systematic review of single-dose, placebo-controlled, randomized trials assessed pain relief from subcutaneous, intramuscular or intravenous morphine compared with placebo in postoperative pain. Pain relief or pain intensity difference over 4 to 6 hours was extracted and converted into the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and the number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief. In 15 trials, comparing intramuscular morphine 10 mg (486 patients) with placebo (460 patients) morphine had an NNT of 2.9 (95% confidence interval 2.6-3.6). This meant that one of every three patients with moderate or severe postoperative pain treated with 10 mg intramuscular morphine had at least 50% pain relief, and would not have achieved this had they been given placebo. Minor adverse effects were more common with morphine (34%) than with placebo (23%) (relative risk 1.49 [1.09-2.04]), but drug related study withdrawal was rare (1.2% overall) and no different from placebo.
Analgesics, Opioid↗
Reporting of adverse effects in clinical trials should be improved: lessons from acute postoperative pain.
We assessed the quality of assessment and reporting of adverse effects in randomized, double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain. Reports were identified by systematic searching of a number of bibliographic databases (e.g., MEDLINE). Information on adverse effect assessment, severity and reporting, patient withdrawals, and anesthetic used was extracted. Compliance with former guidelines for adverse effect reporting was noted. Fifty-two studies were included; two made no mention of adverse effects. No method of assessment was given in 19 studies. Twenty trials failed to report the type of anesthetic used, eight made no mention of patient withdrawals, and nine did not state the severity of reported adverse effects. Only two studies described the method of assessment of adverse effect severity. When all adverse effect data were pooled, significantly more adverse effects were reported with active treatment than with placebo. For individual adverse effects, there was no difference between active (acetaminophen 1000 mg or ibuprofen 400 mg) and placebo; the exception was significantly more somnolence/drowsiness with ibuprofen 400 mg. Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain. All studies published after 1994 complied with former guidelines for adverse effect reporting. Different methods of assessing adverse effects produce different reported incidence: patient diaries yielded significantly more adverse effects than other forms of assessment. We recommend guidelines for reporting adverse effect information in clinical trials.
Acetaminophen↗
Current studies on the pathogenesis of melioidosis.
Burkholderia pseudomallei is a major cause of bacterial septicemias in many parts of the world, particularly Thailand; the known geographic range of the organism appears to be enlarging as awareness of the organism and the disease it causes--melioidosis--increases. B. pseudomallei is intrinsically resistant to most antibiotics, and our knowledge of B. pseudomallei pathogenesis is lacking. Thus, the long-term objective of our research is to define at a molecular level the pathogenesis by combining genetic, immunologic, and biochemical approaches with animal model studies. Basic studies on B. pseudomallei pathogenesis are acutely needed to provide a knowledge base to rationally design new modes of therapy directed against this organism.
Animals↗
Cost-effectiveness of ondansetron for postoperative nausea and vomiting.
The decision as to whether prophylaxis against postoperative nausea and vomiting is better than treatment of established postoperative nausea and vomiting could be made on the basis of cost-effectiveness. The cost-effectiveness of ondansetron was calculated using data from published quantitative systematic reviews of randomised trials. Milligrams of ondansetron required to achieve a desired endpoint were chosen as a cost unit. Modelling was based on a cohort of 1000 patients, and examined control event rates (i.e. incidence of postoperative nausea and vomiting without prophylaxis) of between 10 and 90%. In a sensitivity analysis, cost-effectiveness of recommended intravenous doses (4 mg for treatment and prophylaxis) was compared with minimal effective doses as shown by meta-analysis (1 mg for treatment, 8 mg for prophylaxis). Fewer patients experience any postoperative nausea and vomiting symptoms with prophylaxis compared with treatment. But prophylaxis is only marginally more effective than treatment, and treatment of established postoperative nausea and vomiting with effective doses (i.e. 1 or 4 mg) is more cost-effective and safer than prophylaxis with effective doses (i.e. 4 or 8 mg). Reasons for this are the selective treatment of patients who actually need treatment, the high success rate with a lowest dose tested (1 mg) in established postoperative nausea and vomiting, and the disappointing antinausea effect of prophylactic ondansetron even at an eight-fold higher dose.
Antiemetics↗
Young men's knowledge of testicular cancer and testicular self-examination: a lost opportunity?
Testicular cancer remains the most commonly occurring cancer in young men (aged 20-45 years) and recent trends suggest an increase throughout the western world. Whilst testicular cancer is highly treatable late diagnosis resulting in poorer treatment outcomes remains a problem. Testicular self-examination (TSE) a procedure whereby young men can routinely systematically examine their testicles has been advocated as a particularly effective health education intervention. This study aimed to establish the knowledge of testicular cancer and prevalence of TSE practice amongst young men. A descriptive survey approach using a 16-item self-report questionnaire was administered to a convenience sample of 203 male undergraduate and postgraduate students at the University of Huddersfield. Results indicated that the majority of the respondents were either uninformed or misinformed about the risks and symptoms of testicular cancer although 78% indicated an interest in accessing information. Only 32% had prior knowledge of TSE, 22% practiced TSE, and worryingly only a single respondent was able to recognize the correct procedure and indicated he regularly practiced TSE. Sixty-eight per cent indicated that TSE should be a part of general health assessments for men. Although some critics of TSE argue the cost of teaching TSE outweighs the benefits in terms of early diagnosis this study suggests that young men may be willing to participate in an aspect of personal health surveillance. If this is the case then low cost strategies to increase impact on the target audience should be considered.
Adolescent↗
Efflux-mediated aminoglycoside and macrolide resistance in Burkholderia pseudomallei.
Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to a wide range of antimicrobial agents including beta-lactams, aminoglycosides, macrolides, and polymyxins. We used Tn5-OT182 to mutagenize B. pseudomallei to identify the genes involved in aminoglycoside resistance. We report here on the identification of AmrAB-OprA, a multidrug efflux system in B. pseudomallei which is specific for both aminoglycoside and macrolide antibiotics. We isolated two transposon mutants, RM101 and RM102, which had 8- to 128-fold increases in their susceptibilities to the aminoglycosides streptomycin, gentamicin, neomycin, tobramycin, kanamycin, and spectinomycin. In addition, both mutants, in contrast to the parent, were susceptible to the macrolides erythromycin and clarithromycin but not to the lincosamide clindamycin. Sequencing of the DNA flanking the transposon insertions revealed a putative operon consisting of a resistance, nodulation, division-type transporter, a membrane fusion protein, an outer membrane protein, and a divergently transcribed regulatorprotein. Consistent with the presence of an efflux system, both mutants accumulated [3H] dihydro streptomycin, whereas the parent strain did not. We constructed an amr deletion strain, B. pseudomallei DD503, which was hypersusceptible to aminoglycosides and macrolides and which was used successfully in allelic exchange experiments. These results suggest that an efflux system is a major contributor to the inherent high-level aminoglycoside and macrolide resistance found in B. pseudomallei.
Animals↗
Current perspectives in evidence-based laboratory medicine.
This review examines some of the current perspectives in evidence-based laboratory medicine. From evidence-based medicine, which has concentrated mainly on treatments, we have learned that systematic reviews of the literature are the major way of producing high-quality evidence. This is because systematic reviews search all the literature, apply quality standards to ensure that only the best evidence is available, and aggregate a sufficient weight of information to inform on both the direction of a result (that a treatment works) and the magnitude of the result (how good the treatment is). In laboratory medicine, we have few systematic reviews. Even those we do have give little insight into features of studies which provide the closest view of the 'truth'. It may well be that current studies of laboratory tests are just not good enough. Often, they are too limited in scope, too small, and choose inappropriate patient populations. In the future, comprehensive, prospective and large studies should examine patient demographics and clinical history, as well as laboratory findings. This will better predict those features that are most closely associated with the correct diagnosis in a particular clinical situation. Clinical decision rules combining all available data will be the best way forward.
Clinical Laboratory Techniques↗
Livial: a review of clinical studies.
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Affective Symptoms↗
When placebo controlled trials are essential and equivalence trials are inadequate.
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Antiemetics↗
A transgenic myogenic cell line lacking ryanodine receptor protein for homologous expression studies: reconstitution of Ry1R protein and function.
CCS embryonic stem (ES) cells possessing two mutant alleles (ry1r-/ry1r-) for the skeletal muscle ryanodine receptor (RyR) have been produced and injected subcutaneously into severely compromised immunodeficient mice to produce teratocarcinomas in which Ry1R expression is absent. Several primary fibroblast cell lines were isolated and subcloned from one of these tumors that contain the knockout mutation in both alleles and exhibit a doubling time of 18-24 h, are not contact growth inhibited, do not exhibit drastic morphological change upon serum reduction, and possess the normal complement of chromosomes. Four of these fibroblast clones were infected with a retrovirus containing the cDNA encoding myoD and a puromycin selection marker. Several (1-2 microg/ml) puromycin-resistant subclones from each initial cell line were expanded and examined for their ability to express myoD and to form multinucleated myotubes that express desmin and myosin upon removal of mitogens. One of these clones (1B5 cells) was selected on this basis for further study. These cells, upon withdrawal of mitogens for 5-7 d, were shown by Western blot analysis to express key triadic proteins, including skeletal triadin, calsequestrin, FK506-binding protein, 12 kD, sarco(endo)plasmic reticulum calcium-ATPase1, and dihydropyridine receptors. Neither RyR isoform protein, Ry1R (skeletal), Ry2R (cardiac), nor Ry3R (brain), were detected in differentiated 1B5 cells. Measurements of intracellular Ca2+ by ratio fluorescence imaging of fura-2-loaded cells revealed that differentiated 1B5 cells exhibited no responses to K+ (40 mM) depolarization, ryanodine (50-500 microM), or caffeine (20-100 mM). Transient transfection of the 1B5 cells with the full-length rabbit Ry1R cDNA restored the expected responses to K+ depolarization, caffeine, and ryanodine. Depolarization-induced Ca2+ release was independent of extracellular Ca2+, consistent with skeletal-type excitation-contraction coupling. Wild-type Ry1R expressed in 1B5 cells were reconstituted into bilayer lipid membranes and found to be indistinguishable from channels reconstituted from rabbit sarcoplasmic reticulum with respect to unitary conductance, open dwell times, and responses to ryanodine and ruthenium red. The 1B5 cell line provides a powerful and easily managed homologous expression system in which to study how Ry1R structure relates to function.
Animals↗
Phantom-limb pain.
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Amputation, Surgical↗