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R A Moore

Publications and source records attributed to R A Moore.

At least 55 records · Page 3Linked to original sources
PubMed2001

Pain and systematic reviews.

There is a huge medical literature, with very large amounts of information. Some of that information is useful, some not. The task is to distil the information, apply quality filters, and place it into context so that we can use the knowledge we have with wisdom. The process of systematically reviewing the literature helps us generate solid, unbiased knowledge. Using appropriate tools, like numbers needed to treat (NNT), we can provide a solid basis to allow practitioners and their patients to make the best, and best informed, choices about their care.

Evidence-Based Medicine↗
PubMed2001

Nitric oxide synthase as a marker in colorectal carcinoma.

Elevated inducible nitric oxide synthase (iNOS) activity has been found in 60 per cent of colon adenomas and 20 to 50 per cent of adenocarcinomas. We postulated that high levels of iNOS may increase the invasive and metastatic potential of colon carcinoma and could be indicative of survival potential. Data were reviewed for 52 patients with colorectal carcinoma diagnosed in 1991 and 1992. Specimens were stained for iNOS and catalogued as low-activity staining (LAS) or high-activity staining (HAS) on the basis of visual evaluation by three pathologists. Thirty patients were LAS and 22 HAS. Age, sex, preoperative carcinoembryonic antigen, tumor and nodal status, and American Joint Committee on Cancer staging were not different between groups. Forty-six per cent of the HAS group remained alive after 5 years versus 71 per cent in the LAS group. Survival was significantly lower and metastatic status significantly higher in the HAS group. Results indicated that iNOS activity may be a prognostic indicator of long-term survival potential after treatment for colon cancer. In addition results suggested that metastasis was greater in colon carcinoma specimens that maintain an activated iNOS and that these cells clinically react more aggressively. Conclusions are tempered by the fact that results were based on a limited sample size.

Adult↗
PubMed2000

Colonoscopy in octogenarians and older patients.

INTRODUCTION: Colonoscopy in the elderly has been considered by many to be risky because of mechanical bowel preparation and dehydration, electrolyte disturbances, conscious sedation, and hypoxic complications. We hypothesized that colonoscopy in octogenarians and older patients is a safe procedure. MATERIALS AND METHODS: A retrospective review of 803 patients who underwent colonoscopy from January 1997 to October 1997 was performed. The patients were grouped by age: group A (17-49 years) had 166 patients (20%); group B (50-79 years) had 534 patients (67%); and group C (80 years and older) had 103 patients (13%). Results were considered significant at p value less than 0.05 unless otherwise noted. RESULTS: Blood in the stool (84%) and history of colonic vascular disease (5.8%) were the most common indication in group C (84%). Colonoscopy was used in group A (18%) more often than in the other groups to rule out inflammatory bowel disease. History of colon polyps was a more common indication in group B (20%) than in the other groups. Group A had a significantly higher incidence of normal examinations (84%) and diagnosis of inflammatory bowel disease (14%). Group B had a higher incidence of polyps than the other groups. Group C had the highest incidence of vascular disease (15%). Diverticular disease and carcinoma were more common in groups B (37%) and C (52%). The amount of sedation in the groups did not significantly differ. Completion of the colonoscopy to the cecum or anastomotic sites did not differ among the groups (p > 0.05), nor did complication rates among groups (p > 0.05). CONCLUSIONS: Colonoscopy is safe in octogenarians and older patients. Age does not, by itself, confer an increased risk to the procedure.

Adolescent↗
PubMed2000

Are the pneumococcal polysaccharide vaccines effective? Meta-analysis of the prospective trials.

The objective was to review the evidence of effectiveness of the polyvalent polysaccharide pneumococcal vaccine from prospective properly randomised controlled trials comparing pneumococcal vaccines with placebo in subjects who are immunocompetent and those likely to have an impaired immune system. Databases searched included the Cochrane Library, (issue 2, 2000), MEDLINE (1966-August 2000), PubMed (to August 2000) and EMBASE ( to August 2000). Reference lists of reports and reviews were also searched. To be included in the analysis, a study had to have been a prospective randomised comparison of a polysaccharide pneumococcal vaccine (any valency) and to have a placebo or no treatment comparison group. Papers had to report important clinical outcomes, such as rates of pneumonia, pneumococcal pneumonia, lower respiratory tract infections, pneumonia deaths or bacteraemia. Serological outcomes were not sought. Thirteen randomised comparisons with over 45,000 subjects were identified in an extensive literature review. Eight studies had a quality score of 3 or more on a scale of 1 to 5. In three comparisons with 21,152 immunocompetent subjects (South African gold miners, New Guinea highlanders) pneumococcal vaccination was effective in reducing the incidence of all-cause pneumonia (relative risk 0.56, 95% confidence interval 0.47 to 0.66), pneumococcal pneumonia (0.16; 0.11 to 0.23), pneumonia deaths (0.70; 0.50 to 0.96) and bacteraemia (0.18; 0.09 to 0.34). In ten comparisons in over 24,000 people who were elderly or likely to have impaired immune systems, pneumococcal vaccination was without effect for any outcome. Present guidelines recommend pneumococcal vaccination for "high-risk" groups. There is no evidence from randomised trials that this is of any benefit.

Bacteremia↗
PubMed2000

Importance of radiation therapy for breast cancer patients treated with high-dose chemotherapy and stem cell transplant.

PURPOSE: To determine local-regional failure rates in breast cancer patients treated with surgery and high-dose chemotherapy with stem cell transplant and to relate local-regional failure to the use and timing of radiation treatment. METHODS AND MATERIALS: We retrospectively reviewed the records of 165 breast cancer patients treated on institutional protocols with surgery and high-dose chemotherapy with stem cell transplant. All patients had either Stage III disease, 10 or more positive axillary lymph nodes, or 4 or more positive axillary lymph nodes following neoadjuvant chemotherapy. Twelve patients had inflammatory breast cancer. Thirteen patients treated with breast preservation and 5 patients who died from toxicity within 30 days of transplant were excluded from the analyses of local-regional recurrences. In the remaining 147 patients, 108 were treated with adjuvant radiation and 39 were not. The disease stage distribution for these two groups was comparable. The median follow-up for surviving patients was 35 months. RESULTS: The 3- and 5-year actuarial disease-free survival (DFS) for the entire group was 60% and 51%, respectively. The 5-year rates of freedom from isolated local-regional recurrence were 95% in the patients treated with adjuvant radiation and 86% in the patients who did not receive radiation (p = 0.014, log rank comparison). The 5-year rates of any local-regional recurrence as a first event (isolated recurrences plus those with simultaneous local-regional and distant recurrences) were 92% versus 82%, respectively for patients whose treatment did and did not include radiation (p = 0.038). We could not demonstrate a correlation of the timing of radiation with the risk of local-regional recurrence. CONCLUSIONS: These data indicate that high-dose chemotherapy does not negate the importance of radiation in optimizing local-regional control in patients with high-risk breast cancer. Given the results of recent randomized trials studying postmastectomy radiation, which show that improving local-regional control improves overall survival (OS), we believe that all breast cancer patients with high-risk primary breast cancer who are treated with high-dose chemotherapy with stem cell transplant should receive radiation as a component of their treatment.

Adult↗
PubMed2000

Single dose dextropropoxyphene, alone and with paracetamol (acetaminophen), for postoperative pain.

BACKGROUND: Patient surveys have shown that postoperative pain is often not managed well, and there is a need to assess the efficacy and safety of commonly used analgesics as newer treatments become available. Dextropropoxyphene is one example of an opioid analgesic in current use, and is widely prescribed for pain relief in combination with paracetamol under names such as Co-proxamol and Distalgesic. OBJECTIVES: To determine the analgesic efficacy and adverse effects of single dose oral Dextropropoxyphene alone and in combination with paracetamol (acetaminophen) for moderate to severe postoperative pain. SEARCH STRATEGY: Published reports were identified from: Medline (1966 - November 1996), Biological Abstracts (1985 - 1996), Embase (1980 - 1996), the Cochrane Library (Issue 4 1996), and the Oxford Pain Relief Database (1954 - 1994). Additional studies were identified from the reference lists of retrieved reports. Date of the most recent searches: July 1998. SELECTION CRITERIA: The inclusion criteria used were: full journal publication, postoperative pain, postoperative oral administration, adult patients, baseline pain of moderate to severe intensity, double-blind design, and random allocation to treatment groups which included dextropropoxyphene and placebo or a combination of dextropropoxyphene plus paracetamol and placebo. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers, and trials were quality scored. Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield 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. MAIN RESULTS: Six trials (440 patients) compared dextropropoxyphene with placebo and five (963 patients) compared dextropropoxyphene plus paracetamol 650 mg with placebo. For a single dose of dextropropoxyphene 65 mg in postoperative pain the NNT for at least 50% pain relief was 7.7 (95% confidence interval 4.6 to 22) when compared with placebo over 4-6 hours. For the equivalent dose of dextropropoxyphene combined with paracetamol 650 mg the NNT was 4.4 (3.5 to 5.6) when compared with placebo. These results were compared with those for other analgesics obtained from equivalent systematic reviews. Pooled data showed increased incidence of central nervous system adverse effects for dextropropoxyphene plus paracetamol compared with placebo. REVIEWER'S CONCLUSIONS: The combination of dextropropoxyphene 65 mg with paracetamol 650 mg shows similar efficacy to tramadol 100 mg for single dose studies in postoperative pain but with a lower incidence of adverse effects. The same dose of paracetamol combined with 60 mg codeine appears more effective but, with the slight overlap in the 95% confidence intervals, this conclusion is not robust. Adverse effects of both combinations were similar. Ibuprofen 400 mg has a lower (better) NNT than both dextropropoxyphene 65 mg plus paracetamol 650 mg and tramadol 100 mg.

Acetaminophen↗
PubMed2000

Single dose oral ibuprofen and diclofenac for postoperative pain.

BACKGROUND: Ibuprofen and diclofenac are two widely used non-steroidal anti-inflammatory (NSAID) analgesics. It is therefore important to know which drug should be recommended for postoperative pain relief. This review seeks to compare the relative efficacy of the two drugs, and also considers the issues of safety and cost. OBJECTIVES: To assess the analgesic efficacy of ibuprofen and diclofenac in single oral doses for moderate to severe postoperative pain. SEARCH STRATEGY: Randomised trials were identified by searching Medline (1966 to December 1996), Embase (1980 to January 1997), the Cochrane Library (Issue 3 1996), Biological Abstracts (January 1985 to December 1996) and the Oxford Pain Relief Database (1950 to 1994). Date of the most recent searches: July 1998. SELECTION CRITERIA: The inclusion criteria used were: full journal publication, postoperative pain, postoperative oral administration, adult patients, baseline pain of moderate to severe intensity, double-blind design, and random allocation to treatment groups which compared either ibuprofen or diclofenac with placebo. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers, and trials were quality scored. Summed pain relief or pain intensity difference over four to six hours was extracted, and converted into dichotomous information yielding the number of patients with at least 50% pain relief. This was then used to calculate the relative benefit and the number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief. MAIN RESULTS: Thirty-four trials compared ibuprofen and placebo (3,591 patients), six compared diclofenac with placebo (840 patients) and there were two direct comparisons of diclofenac 50 mg and ibuprofen 400 mg (130 patients). In postoperative pain the NNTs for ibuprofen 200 mg were 3.3 (95% confidence interval 2.8 to 4.0) compared with placebo, for ibuprofen 400 mg 2.7 (2.5 to 3.0), for ibuprofen 600 mg 2.4 (1.9 to 3.3), for diclofenac 50 mg 2.3 (2.0 to 2.7) and for diclofenac 100 mg 1.8 (1.5 to 2.1). Direct comparisons of diclofenac 50 mg with ibuprofen 400 mg showed no significant difference between the two. REVIEWER'S CONCLUSIONS: Both drugs work well. Choosing between them is an issue of dose, safety and cost.

Analgesics, Non-Narcotic↗
PubMed2000

Radiotherapy for the palliation of painful bone metastases.

BACKGROUND: Radiotherapy is used commonly to provide pain relief for painful bone metastases, and there is a perception that of the three-quarters of patients who achieve pain relief, half of these stay free from pain. However, the precise contribution from radiotherapy may be unclear because of difficulties in assessing the numbers of people achieving relief, the extent of relief and its duration, and the influence of other contemporaneous interventions, such as analgesics. OBJECTIVES: To assess pain relief from: 1. localised bone metastases achieved by radiotherapy, comparing the efficacy of different fractionation schedules 2. more generalised metastatic disease achieved by radiotherapy or radioisotopes. SEARCH STRATEGY: Studies were identified by searching Medline (1966 to August 1998), Embase (1980 to 1998), the Cochrane Library (1998 Issue 3) and the Oxford Pain Relief Database (1950 to 1994). SELECTION CRITERIA: The inclusion criteria used were: full journal publication, patients with pain due to bone metastases, and random allocation to a radiotherapeutic intervention (either external irradiation or administration of radioisotopes). DATA COLLECTION AND ANALYSIS: The number of patients achieving complete pain relief and at least 50% at one month were compared with an assumed natural history of 1 in 100 patients achieving pain relief without treatment to obtain the number-needed-to-treat (NNT). Summed pain relief or pain intensity difference over four to six hours was extracted, converted into dichotomous information yielding the number of patients with at least 50% pain relief, and used to calculate the relative benefit and the NNT for one patient to achieve at least 50% pain relief. MAIN RESULTS: Twenty trials reported on 43 different radiotherapy fractionation schedules and eight studies of radioisotopes. Radiotherapy produced complete pain relief at one month in 395/1580 (25%) patients, and at least 50% relief in 788/1933 (41%) patients at some time during the trials. There were no differences in the proportions of patients achieving these outcomes between single or multiple fraction schedules. The number-needed-to-treat (NNT) to achieve complete relief at one month (compared with an assumed natural history of 1 in 100 patients whose pain resolved without treatment) was 4.2 (95% CI 3.7-4.7). No pooled estimates of speed of onset of relief, or of its duration, could be obtained. In the largest trial (759 patients) 52% of those who had complete relief had achieved it within four weeks, and the median duration of complete relief was 12 weeks. For more generalised disease, radioisotopes produced similar analgesic results to external irradiation. Adverse effect reporting was poor. There were no obvious differences between the various fractionation schedules in the incidence of nausea and vomiting, diarrhoea or pathological fractures. REVIEWER'S CONCLUSIONS: Radiotherapy is clearly effective at reducing pain from painful bone metastases. There was no evidence of any difference in efficacy between different fractionation schedules, nor indeed of a dose-response with total dose of radiation. For treatment of generalised bone pain both hemibody irradiation and radioisotopes can reduce the number of painful new sites.

Bone Neoplasms↗
PubMed2000

Single dose oral aspirin for acute pain.

BACKGROUND: Aspirin has been known to be an effective analgesic for many years and is commonly used throughout the world for many different pain conditions. It is important for both prescribers and patients to have the best possible information about the efficacy and safety of analgesics, and this need is reflected in patient surveys which show that postoperative pain is often poorly managed. We also need to benchmark relative efficacy and safety of current analgesics so that we can compare them with new analgesics. OBJECTIVES: To quantitatively assess the analgesic efficacy and adverse effects of a single-dose of aspirin in acute pain of moderate to severe intensity. SEARCH STRATEGY: Randomised trials were identified by searching Medline (1966 to March 1998), Embase (1980 to January 1998), the Cochrane Library (Issue 1,1998) and the Oxford Pain Relief Database (1950 to 1994). SELECTION CRITERIA: The inclusion criteria used were: full journal publication, postoperative pain or a mixture of postoperative and acute trauma pain, oral administration, adult patients, baseline pain of moderate to severe intensity, double-blind design, and random allocation to treatment groups which compared aspirin with placebo. DATA COLLECTION AND ANALYSIS: Summed pain relief or pain intensity difference over four to six hours was extracted, and converted into dichotomous information yielding the number of patients with at least 50% pain relief. This was then used to calculate the relative benefit and the number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief. MAIN RESULTS: Seventy-two randomised single-dose trials met our inclusion criteria, with 3253 patients given aspirin, and 3297 placebo. Significant benefit of aspirin over placebo was shown for aspirin 600/650 mg, 1000 mg and 1200 mg, NNTs for at least 50% pain relief of 4.4 (4.0 to 4.9), 4.0 (3.2 to 5.4) and 2.4 (1.9 to 3.2) respectively. Single-dose aspirin 600/650 mg produced significantly more drowsiness and gastric irritation than placebo, with a number-needed-to-harm (NNH) of 28 (19 to 52) and 38 (22 to 174) respectively. Type of pain model, pain measurement, sample size, quality of study design, and study duration had no significant impact on the results. REVIEWER'S CONCLUSIONS: Aspirin is an effective analgesic for acute pain of moderate to severe intensity with a clear dose-response. Drowsiness and gastric irritation were seen as significant adverse effects even though the studies were single-dose. The pain relief achieved with aspirin was very similar milligram for milligram to that seen with paracetamol.

Acute Disease↗
PubMed2000

Single dose dihydrocodeine for acute postoperative pain.

BACKGROUND: Dihydrocodeine is a synthetic opioid analgesic developed in the early 1900s. Its structure and pharmacokinetics are similar to that of codeine and it is used for the treatment of postoperative pain or as an antitussive. It is becoming increasingly important to assess the relative efficacy and harm caused by different treatments. Relative efficacy can be determined when an analgesic is compared with control under similar clinical circumstances. OBJECTIVES: To quantitatively assess the analgesic efficacy and adverse effects of single-dose dihydrocodeine compared with placebo in randomised trials in moderate to severe postoperative pain. SEARCH STRATEGY: Published reports were identified from a variety of electronic databases including Medline, Biological Abstracts, Embase, the Cochrane Library and the Oxford Pain Relief Database. Additional studies were identified from the reference lists of retrieved reports. SELECTION CRITERIA: The following inclusion criteria were used: full journal publication, clinical trial, random allocation of patients to treatment groups, double blind design, adult patients, pain of moderate to severe intensity at baseline, postoperative administration of study drugs, treatment arms which included dihydrocodeine and placebo and either oral or injected (intramuscular or intravenous) administration of study drugs. DATA COLLECTION AND ANALYSIS: Data collection and analysis: Summed pain intensity and pain relief data over 4-6 hours were extracted and converted into dichotomous information to yield the number of patients obtaining at least 50% pain relief. This was used to calculate relative benefit and number-needed-to-treat for one patient to obtain at least 50% pain relief. Single-dose adverse effect data were collected and used to calculate relative risk and number-needed-to-harm. MAIN RESULTS: Fifty-two reports were identified as possible randomised trials which assessed dihydrocodeine in postoperative pain. Four reports met the inclusion criteria; all assessed oral dihydrocodeine. Three reports (194 patients) compared dihydrocodeine with placebo and one (120 patients) compared dihydrocodeine (30 mg or 60 mg) with ibuprofen 400 mg. For a single dose of dihydrocodeine 30 mg in moderate to severe postoperative pain the NNT for at least 50% pain relief was 8.1 (95% confidence interval 4.1 to 540) when compared with placebo over a period of 4-6 hours. Pooled data showed significantly more patients to have reported adverse effects with dihydrocodeine 30 mg than with placebo. When compared to ibuprofen 400 mg both dihydrocodeine 30 mg and 60 mg were significantly inferior. REVIEWER'S CONCLUSIONS: A single 30 mg dose of dihydrocodeine is not sufficient to provide adequate pain relief in postoperative pain. Statistical superiority of ibuprofen 400 mg over dihydrocodeine (30 mg or 60 mg) was shown.

Acute Disease↗
PubMed2000

Single dose piroxicam for acute postoperative pain.

BACKGROUND: Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties, and is used mainly for treating rheumatic disorders. Some drugs have been directly compared against each other within a trial setting to determine their relative efficacies, whereas other have not. It is possible, however, to compare analgesics indirectly by examining the effectiveness of each drug against placebo when used in similar clinical situations. OBJECTIVES: To determine the analgesic efficacy and adverse effects of single-dose piroxicam compared with placebo in moderate to severe postoperative pain. To compare the effects of piroxicam with other analgesics. SEARCH STRATEGY: Published reports were identified from systematic searching of Medline, Biological Abstracts, Embase, The Cochrane Library and the Oxford Pain Relief Database. Additional studies were identified from the reference lists of retrieved reports. SELECTION CRITERIA: The following inclusion criteria were used: full journal publication, randomised placebo controlled trial, double-blind design, adult patients, postoperative pain of moderate to severe intensity at the baseline assessment, postoperative administration of oral or intramuscular piroxicam. DATA COLLECTION AND ANALYSIS: Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients obtaining at least 50% pain relief. This was used to calculate estimates of relative benefit and number-needed-to-treat for one patient to obtain at least 50% pain relief. Information was collected on adverse effects and estimates of relative risk and number-needed-to-harm were calculated. MAIN RESULTS: Three trials (141 patients) compared oral piroxicam 20 mg with placebo and one (15 patients) compared oral piroxicam 40 mg with placebo. For single doses of piroxicam 20 mg and 40 mg the respective numbers-needed-to-treat for at least 50% pain relief were 2.7 (2.1 to 3.8) [95% confidence interval] and 1.9 (1.2 to 4.3) [95% confidence interval] compared with placebo over 4-6 hours in moderate to severe postoperative pain. The reported incidence of adverse effects was no higher with piroxicam (20 mg or 40 mg) than with placebo. REVIEWER'S CONCLUSIONS: Piroxicam appears to be of similar efficacy to other non-steroidal anti-inflammatory drugs (NSAIDs) and intramuscular morphine 10 mg when used as a single oral dose in the treatment of moderate to severe postoperative pain.

Acute Disease↗
PubMed2000

Single dose oxycodone and oxycodone plus paracetamol (acetominophen) for acute postoperative pain.

BACKGROUND: Oxycodone is a strong opioid agonist which is useful for the management of severe pain. It is becoming increasingly important to assess the relative efficacy and harm caused by different treatments. This can be determined when an analgesic is compared with control under similar clinical circumstances. OBJECTIVES: To quantitatively assess the analgesic efficacy and adverse effects of single-dose oxycodone and oxycodone plus paracetamol in randomised trials in acute postoperative pain. SEARCH STRATEGY: Published reports were identified from Medline, Biological Abstracts, Embase, the Cochrane Library and the Oxford Pain Relief Database. Additional studies were identified from the reference lists of retrieved reports. SELECTION CRITERIA: The inclusion criteria were: full journal publication, clinical trial, random allocation of adult patients to treatment groups, double blind design, moderate to severe baseline pain, postoperative administration of study drugs, treatment arms which included oxycodone or oxycodone plus paracetamol and placebo (or active control for which comparable efficacy data exist), and oral, intramuscular or intravenous administration of study drugs. DATA COLLECTION AND ANALYSIS: Summed pain intensity and pain relief data over 4-6 hours were extracted and converted into dichotomous information yielding the number of patients obtaining at least 50% pain relief. Estimates of relative benefit and number-needed-to-treat were calculated. Single-dose adverse effect data were collected. MAIN RESULTS: Seventy-seven reports were identified. Seven reports met the inclusion criteria; all assessed oral oxycodone. For efficacy, a significant benefit of active drug over placebo was shown for all doses of oxycodone and oxycodone plus paracetamol, except oxycodone 5 mg. For adverse effects, the number of patients reporting adverse effects was extracted for each dose of active drug versus placebo. When these data were pooled for the individual doses significantly more adverse effects with active drug than with placebo were shown for all doses, except oxycodone 5 mg and its combination with paracetamol 325 mg. This was also shown for drowsiness/somnolence. Significantly more nausea, vomiting and dizziness/lightheadedness were reported with oxycodone 10 mg plus paracetamol (650 mg and 1000 mg) than with placebo. REVIEWER'S CONCLUSIONS: Single-dose oral oxycodone, with or without paracetamol, appears to be of comparable efficacy to intramuscular morphine and non-steroidal anti-inflammatory drugs. Central nervous system adverse effects were common.

Acetaminophen↗
PubMed2000

Divergent functional properties of ryanodine receptor types 1 and 3 expressed in a myogenic cell line.

Of the three known ryanodine receptor (RyR) isoforms expressed in muscle, RyR1 and RyR2 have well-defined roles in contraction. However, studies on mammalian RyR3 have been difficult because of low expression levels relative to RyR1 or RyR2. Using the herpes simplex virus 1 (HSV-1) helper-free amplicon system, we expressed either RyR1 or RyR3 in 1B5 RyR-deficient myotubes. Western blot analysis revealed that RyR1- or RyR3-transduced cells expressed the appropriate RyR isoform of the correct molecular mass. Although RyR1 channels exhibited the expected unitary conductance for Cs(+) in bilayer lipid membranes, 74 of 88 RyR3 channels exhibited pronounced subconductance behavior. Western blot analysis with an FKBP12/12.6-selective antibody reveals that differences in gating behavior exhibited by RyR1 and RyR3 may be, in part, the result of lower affinity of RyR3 for FKBP12. In calcium imaging studies, RyR1 restored skeletal-type excitation-contraction coupling, whereas RyR3 did not. Although RyR3-expressing myotubes were more sensitive to caffeine than those expressing RyR1, they were much less sensitive to 4-chloro-m-cresol (CMC). In RyR1-expressing cells, regenerative calcium oscillations were observed in response to caffeine and CMC but were never seen in RyR3-expressing 1B5 cells. In [(3)H]ryanodine binding studies, only RyR1 exhibited sensitivity to CMC, but both RyR isoforms responded to caffeine. These functional differences between RyR1 and RyR3 expressed in a mammalian muscle context may reflect differences in association with accessory proteins, especially FKBP12, as well as structural differences in modulator binding sites.

Animals↗
PubMed2000

Teasing apart quality and validity in systematic reviews: an example from acupuncture trials in chronic neck and back pain.

The objectives of the study were (1) to carry out a systematic review to assess the analgesic efficacy and the adverse effects of acupuncture compared with placebo for back and neck pain and (2) to develop a new tool, the Oxford Pain Validity Scale (OPVS), to measure validity of findings from randomized controlled trials (RCTs), and to enable ranking of trial findings according to validity within qualitative reviews. Published RCTs (of acupuncture at both traditional and non-traditional points) were identified from systematic searching of bibliographic databases (e.g. MEDLINE) and reference lists of retrieved reports. Pain outcome data were extracted with preference given to standardized outcomes such as pain intensity. Information on adverse effects was also extracted. All included trials were scored using a five-item 0-16 point validity scale (OPVS). The individual RCTs were ranked according to their OPVS score to enable more weight to be placed on the trials of greater validity when drawing an overall conclusion about the efficacy of acupuncture for relieving neck and back pain. Statistical analyses were carried out on the OPVS scores to assess the relationship between trial finding (positive or negative) and validity. Thirteen RCTs met the inclusion criteria. Five trials concluded that acupuncture was effective, and eight concluded that it was not effective for relieving back or neck pain. There was no obvious difference between the findings of trials using traditional and non-traditional points. Using the new OPVS scale, the validity scores of the included trials ranged from 4 to 14. There was no significant relationship between OPVS score and trial finding (positive versus negative). Authors' conclusions did not always agree with their data. We drew our own conclusions (positive/negative) based on the data presented in the reports. Re-analysis using our conclusions showed a significant relationship between OPVS score and trial finding, with higher validity scores associated with negative findings. OPVS is a useful tool for assessing the validity of trials in qualitative reviews. With acupuncture for chronic back and neck pain, we found that the most valid trials tended to be negative. There is no convincing evidence for the analgesic efficacy of acupuncture for back or neck pain.

Acupuncture Therapy↗
PubMed2000

Quantitative estimation of rare adverse events which follow a biological progression: a new model applied to chronic NSAID use.

Randomised controlled trials (RCTs) alone are unlikely to provide reliable estimates of the incidence of rare events because of their limited size. Cohort, case control, and other observational studies have large numbers but are vulnerable to various kinds of bias. Wanting to estimate the risk of death from bleeding or perforated gastroduodenal ulcers with chronic usage of non-steroidal anti-inflammatory drugs (NSAIDs) with greater precision, we developed a model to quantify the frequency of rare adverse events which follow a biological progression. The model combined data from both RCTs and observational studies. We searched systematically for any report of chronic (>/=2 months) use of NSAIDs which gave information on gastroduodenal ulcer, bleed or perforation, death due to these complications, or progression from one level of harm to the next. Fifteen RCTs (19364 patients exposed to NSAIDs for 2-60 months), three cohort studies (215076 patients redeeming a NSAID prescription over a 3-12 month period), six case-control studies (2957 cases) and 20 case series (7406), and case reports (4447) were analysed. In RCTs the incidence of bleeding or perforation in 6822 patients exposed to NSAIDs was 0.69%; two deaths occurred. Of 11040 patients with bleeding or perforation with or without NSAID exposure across all reports, 6-16% (average 12%) died; the risk was lowest in RCTs and highest in case reports. Death from bleeding or perforation in all controls not exposed to NSAIDs occurred in 18 out of 849489 (0.002%). From these numbers we calculated the number-needed-to-treat for one patient to die due to gastroduodenal complications with chronic (>/=2 months) NSAIDs as 1/((0.69x¿6-16%, average 12%¿)-0.002%))=909-2500 (average 1220). On average 1 in 1200 patients taking NSAIDs for at least 2 months will die from gastroduodenal complications who would not have died had they not taken NSAIDs. This extrapolates to about 2000 deaths each year in the UK.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Antidepressants and anticonvulsants for diabetic neuropathy and postherpetic neuralgia: a quantitative systematic review.

To determine the relative efficacy and adverse effects of antidepressants and anticonvulsants in the treatment of diabetic neuroapathy and postherpetic neuralgia, published reports were identified from a variety of electronic databases, including Medline, EMBASE, the Cochrane Library and the Oxford Pain Relief Database, and from two previously published reviews. Additional studies were identified from the reference lists of retrieved reports. The relative benefit (RB) and number-needed-to-treat (NNT) for one patient to achieve at least 50 % pain relief was calculated from available dichotomous data, as was the relative risk (RR) and number-needed-to-harm (NH) for minor adverse effects and drug related study withdrawal. In diabetic neuropathy, 16 reports compared antidepressants with placebo (491 patient episodes) and three compared anticonvulsants with placebo (321). The NNT for at least 50 % pain relief with antidepressants was 3.4 (95 % confidence interval 2.6-4. 7) and with anticonvulsants 2. 7 (2. 2-3. 8). In postherpetic neuralgia, three reports compared antidepressants with placebo (145 patient episodes) and one compared anticonvulsants with placebo (225), giving an NNT with antidepressants of 2.1 (1. 7-3) and with anticonvulsants 3.2 (2.4-5). There was little difference in the incidence of minor adverse effects with either antidepressants or anticonvulsants compared with placebo, with 1VH (minor) values of about 3. For drug-related study withdrawal, antidepressants had an NNH (major) of 17 (11-43) compared with placebo, whereas with anticonvulsants there was no significant difference from placebo. Antidepressants and anticonvulsants had the same efficacy and incidence of minor adverse effects in these tzoo neuropathic pain conditions. There was no evidence that selective serotonin reuptake inhibitors (SSRIs) were better than older antidepressants, and no evidence that gabapentin was better than older anticonvulsants. In these trials patients were more likely to stop taking antidepressants than anticonvulsants because of adverse effects.

Anticonvulsants↗