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Biomedical subjects

Robert G Newcombe

Publications and source records attributed to Robert G Newcombe.

At least 19 recordsLinked to original sources
PubMed2007

Bayesian estimation of false-negative rate in a clinical trial of sentinel node biopsy.

Estimating the false-negative rate is a major issue in evaluating sentinel node biopsy (SNB) for staging cancer. In a large multicentre trial of SNB for intra-operative staging of clinically node-negative breast cancer, two sources of information on the false-negative rate are available.Direct information is available from a preliminary validation phase: all patients underwent SNB followed by axillary nodal clearance or sampling. Of 803 patients with successful sentinel node localization, 19 (2.4 per cent) were classed as false negatives. Indirect information is also available from the randomized phase. Ninety-seven (25.4 per cent) of 382 control patients undergoing axillary clearance had positive axillae. In the experimental group, 94/366 (25.7 per cent) were apparently node positive. Taking a simple difference of these proportions gives a point estimate of -0.3 per cent for the proportion of patients who had positive axillae but were missed by SNB. This estimate is clearly inadmissible. In this situation, a Bayesian analysis yields interpretable point and interval estimates. We consider the single proportion estimate from the validation phase; the difference between independent proportions from the randomized phase, both unconstrained and constrained to non-negativity; and combined information from the two parts of the study. As well as tail-based and highest posterior density interval estimates, we examine three obvious point estimates, the posterior mean, median and mode. Posterior means and medians are similar for the validation and randomized phases separately and combined, all between 2 and 3 per cent, indicating similarity rather than conflict between the two data sources.

Bayes Theorem↗
PubMed2006

A deficiency of the odds ratio as a measure of effect size.

The odds ratio is probably the most widely used measure of association for binary variables. It has many well-recognized advantages and disadvantages vis-à-vis the risk ratio. We demonstrate that for chained or conditional probabilities, odds ratios can behave paradoxically, by failing to show a reinforcement effect that is expressed very clearly when risk ratios are used.

Adolescent↗
PubMed2006

Meta-analyses of studies of 0.2% delmopinol mouth rinse as an adjunct to gingival health and plaque control measures.

BACKGROUND: Delmopinol is a third-generation anti-plaque agent used as a mouthwash to reduce plaque and alleviate gingivitis. OBJECTIVE: To create an overview of the anti-plaque efficacy of 0.2% delmopinol as an adjunct to normal oral hygiene measures by meta-analysis of completed clinical trials. MATERIALS AND METHODS: Eight double-blind, parallel-group studies were identified. Study durations ranged from 8 to 24 weeks. Five studies (n=913) involved supervised rinsing; three studies (n=467) involved unsupervised rinsing. These sets of trials were analysed separately and in combination. Efficacy outcomes comprised modified plaque index, modified gingival index (MGI) and gingival bleeding on probing (BOP). RESULTS: Delmopinol 0.2% was superior to placebo for the reduction of plaque scores in both sets of studies. Effects on MGI and BOP were also better with delmopinol 0.2% than with placebo. In most instances, 95% confidence intervals were wholly in favour of delmopinol. Pooled analysis of all eight studies confirmed statistically significant effects of delmopinol 0.2% compared with placebo (p<0.00001). Delmopinol met the efficacy criteria of the American Dental Association in studies of extended duration. CONCLUSION: Delmopinol 0.2% mouthwash is effective as an adjunct measure for reducing plaque burden and indices of gingivitis, whether or not it is used under supervision.

Dental Plaque↗
PubMed2006

Optimal refresher training intervals for AED and CPR skills: a randomised controlled trial.

AIM: To determine the optimal refresher training interval for lay volunteer responders in the English National Defibrillator Programme who had previously undertaken a conventional 4-h initial class and a first refresher class at 6 months. METHODS: Subjects were randomised to receive either two additional refresher classes at intervals of 7 and 12 months or one additional refresher class after 12 months. RESULTS: Greater skill loss had occurred when the second refresher class was undertaken at 12 compared with 7 months. Skill retention however, was higher in the former group, ultimately resulting in no significant difference in final skill performance. There was no significant difference in performance between subjects attending two versus three refresher classes. On completion of refresher training all subjects were able to deliver countershocks, time to first shock decreased by 17s in both groups, and the proportion of subjects able to perform most skills increased. The execution of several important interventions remained poor, regardless of the total number of classes attended or the interval between them. These included CPR skills, defibrillation pad placement, and pre-shock safety checks. Refresher classes held more frequently and at shorter intervals increased subjects' self-assessed confidence, possibly indicating greater preparedness to use an AED in a real emergency. CONCLUSIONS: This study shows that the ability to deliver countershocks is maintained whether the second refresher class is held at seven or 12 months after the first. To limit skill deterioration between classes, however, refresher training intervals should not exceed 7 months. The quality of instruction given should be monitored carefully. Learning and teaching strategies require review to improve skill acquisition and maintenance.

Cardiopulmonary Resuscitation↗
PubMed2006

Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial.

BACKGROUND: Sentinel lymph node biopsy in women with operable breast cancer is routinely used in some countries for staging the axilla despite limited data from randomized trials on morbidity and mortality outcomes. We conducted a multicenter randomized trial to compare quality-of-life outcomes between patients with clinically node-negative invasive breast cancer who received sentinel lymph node biopsy and patients who received standard axillary treatment. METHODS: The primary outcome measures were arm and shoulder morbidity and quality of life. From November 1999 to October 2003, 1031 patients were randomly assigned to undergo sentinel lymph node biopsy (n = 515) or standard axillary surgery (n = 516). Patients with sentinel lymph node metastases proceeded to delayed axillary clearance or received axillary radiotherapy (depending on the protocol at the treating institution). Intention-to-treat analyses of data at 1, 3, 6, and 12 months after surgery are presented. All statistical tests were two-sided. RESULTS: The relative risks of any lymphedema and sensory loss for the sentinel lymph node biopsy group compared with the standard axillary treatment group at 12 months were 0.37 (95% confidence interval [CI] = 0.23 to 0.60; absolute rates: 5% versus 13%) and 0.37 (95% CI = 0.27 to 0.50; absolute rates: 11% versus 31%), respectively. Drain usage, length of hospital stay, and time to resumption of normal day-to-day activities after surgery were statistically significantly lower in the sentinel lymph node biopsy group (all P < .001), and axillary operative time was reduced (P = .055). Overall patient-recorded quality of life and arm functioning scores were statistically significantly better in the sentinel lymph node biopsy group throughout (all P < or = .003). These benefits were seen with no increase in anxiety levels in the sentinel lymph node biopsy group (P > .05). CONCLUSION: Sentinel lymph node biopsy is associated with reduced arm morbidity and better quality of life than standard axillary treatment and should be the treatment of choice for patients who have early-stage breast cancer with clinically negative nodes.

Arm↗
PubMed2006

Factors affecting failed localisation and false-negative rates of sentinel node biopsy in breast cancer--results of the ALMANAC validation phase.

BACKGROUND: Despite the widespread application of sentinel lymph node biopsy (SLNB) for early stage breast cancer, there is a wide variation in reported test performance characteristics. A major aim of this prospective multicentre validation study was to quantify detection and false-negative rates of SLNB and evaluate factors influencing them. METHODS: Eight-hundred and fourty-two patients with clinically node-negative breast cancer underwent SLNB according to a standardised protocol that used a combination of radiopharmaceutical 99mTc-albumin colloid and Patent Blue V dye. SLNB was followed by standard axillary treatment at the same operation in all patients. RESULTS: Sentinel lymph nodes (SLNs) were identified in 803 (96.1%) of 836 evaluable cases. The median number of SLNs removed per patient was 2 (range 1-9). There were 19 false negatives, resulting in a sensitivity of 263/282 (93.3%) and accuracy 782/803 (97.6%). SLNs were successfully identified by blue dye in 698 (85.6%), by isotope in 698 (85.6%), and by the combination of blue dye and isotope in 782 (96.0%) of 815 patients. Among 276 node positive patients, one or more positive SLNs were identified by blue dye in 251 (90.9%), by isotope in 246 (89.1%) and by the combination of blue dye and gamma probe in 258 (93.5%). Obesity, tumor location other than upper outer quadrant and non-visualisation of SLNs on the pre-operative lymphoscintiscan were significantly associated with failed localisation (p<0.001, p=0.008, p<0.001, respectively). The false-negative rate in patients with grade 3 tumors was 9.6%, compared with 4.7% in those with grade 2 tumors (p=0.022). The false-negative rate in patients who had one SLN harvested was 10.1%, compared with 1.1% in those who had multiple SLNs (three or more) removed (p=0.010). CONCLUSION: SLNB can accurately determine whether axillary metastases are present in patients with early stage breast cancer with clinically negative axillary nodes. Both success and accuracy of SLNB are optimised by the combined use of blue dye and isotope. SLNB success decreases with increasing body mass, tumor location other than the upper outer quadrant and non-visualisation of hot nodes on the pre-operative lymphoscintiscan. This study demonstrates reduction in the predictive value of a negative SLNB in grade 3 tumors.

Adult↗
PubMed2006

Confidence intervals for an effect size measure based on the Mann-Whitney statistic. Part 1: general issues and tail-area-based methods.

For two random variables X and Y, theta = Pr[Y > X] + (1/2)Pr[Y = X] is advocated as a general measure of effect size to characterize the degree of separation of their distributions. It is estimated by U/mn, a generalization of the Mann-Whitney U statistic, derived by dividing U by the product of the two sample sizes. It is equivalent to the area under the receiver operating characteristic curve. It is readily visualized in terms of two Gaussian distributions with appropriately separated peaks. The effect of discretization of a continuous variable is explored. Tail-area-based confidence interval methods are developed which can be applied to very small samples or extreme outcomes.

Confidence Intervals↗
PubMed2006

Confidence intervals for an effect size measure based on the Mann-Whitney statistic. Part 2: asymptotic methods and evaluation.

Several asymptotic confidence interval methods for U/mn, the Mann-Whitney U statistic divided by the product of the two sample sizes, are developed and evaluated alongside published methods. Novel methods derived from Gaussian and beta models perform well, though overall a modification of the Hanley-McNeil approach (method 5 in this evaluation) performed better and is recommended for calculating confidence intervals for U/mn for continuously distributed data.

Confidence Intervals↗
PubMed2006

Injuries in homes with certain built forms.

BACKGROUND: Rates of injuries may occur more frequently in different types of homes. METHODS: Retrospective population-based cohort study utilizing three linked databases: a population register, an architectural assessment of homes in the area, and an emergency department-based injury surveillance system. RESULTS: Over 58,000 homes were classified into 94 different types according to age, size, and built form. Among the 112,248 inhabitants, there were 18,044 emergency department attendances for treatment of an injury suffered in the home. Adjusted odds ratio of injuries for residents of purpose-built apartments was substantially elevated for all injuries (2.07; 95% confidence interval [CI]=1.87-2.30) and poisoning episodes (5.6; 95% CI=3.8-8.3). CONCLUSIONS: Residents of apartment buildings have substantially higher injury rates. Additional research is required to investigate the contribution of environmental hazards and behavioral factors underlying these high rates.

Accidents, Home↗
PubMed2006

Tooth bleaching by different concentrations of carbamide peroxide and hydrogen peroxide whitening strips: an in vitro study.

OBJECTIVE: To investigate the tooth whitening effects of various concentrations of carbamide peroxide (CP) gels and 6% hydrogen peroxide (HP) whitening strips used on an intrinsic, in vitro stain model in a simulated home-applied bleaching protocol. METHOD: Extracted third molars were sectioned and stained to Vita shade C4 using a standardized tea solution. Stained specimens were then bleached with 10, 15, 20, 22, and 30% CP gels applied in custom-made trays for 8-hour sessions for 14 days. A 6% HP whitening strip product was also tested in a regimen of twice-daily 30-minute treatments for 14 days. Shades were assessed at baseline and at 2, 5, 7, 10, and 14 days of treatment using a shade guide (SG) and a shade vision system (SVS), recorded as shade guide unit (SGU) changes from baseline, and CIE L*a*b* recordings using a chromometer. RESULTS: By day 14, all CP treatments resulted in at least 12 SGU improvements by SG and SVS methods: the HP treatment mean was just less than 12 SGU. With the chromometer, the CP improvements ranged from approximately 19 to 28 units and 16 units for the HP whitening strips. Observationally, by SG and SVS, CP treatments achieved the maximum improvement (12-13 SGU) at different time points: day 5 for 30% CP, day 10 for 22% CP, and day 14 for the other three treatments. SG and SVS data were virtually binary, switching from 0 to scores of 9 or above as bleaching progressed. The differences between the six treatments in the mean day to achieve a positive SG or SVS score (9 or more units) approached significance. For each of the SG, SVS, and L*a*b* scores, the dose-response correlation with CP concentration was significant at one or more assessment times. SG and SVS showed extremely strong agreement in detecting change and substantial agreement with L*a*b*. CONCLUSION: This in vitro study supports the limited data available from the very few available randomized controlled clinical trials indicating that CP and HP home-use bleaching systems can achieve considerable tooth whitening outcomes, albeit at different rates, which appear to be concentration dependent. CLINICAL SIGNIFICANCE: There is a clear significant relationship for both concentration and duration of exposure for CP bleaching agents. The final shade change is independent of the concentration of bleaching agent, with time as the dominant variable. Higher concentrations of CP that have not been investigated previously may be a treatment option for esthetic improvement of shade where time is at a premium, but caution must be exercised in view of the possible increased incidence of sensitivity.

Carbamide Peroxide↗
PubMed2005

Post-operative arm morbidity and quality of life. Results of the ALMANAC randomised trial comparing sentinel node biopsy with standard axillary treatment in the management of patients with early breast cancer.

This study is the first large prospective RCT of sentinel node biopsy (SNB) compared with standard axillary treatment (level I-III axillary lymph node dissection or four node sampling), which includes comprehensive and repeated quality of life (QOL) assessments over 18 months. Patients (n = 829) completed the Functional Assessment of Cancer Therapy - Breast (FACT-B+4) and the Spielberger State/Trait Anxiety Inventory (STAI) at baseline (pre-surgery) and at 1, 3, 6, 12, and 18 months post-surgery. There were significant differences between treatment groups favouring the SNB group throughout the 18 months assessment. Patients in the standard treatment group showed a greater decline in Trial Outcome Index (TOI) scores (physical well-being, functional well-being and breast cancer concerns subscales in FACT-B+4) and recovered more slowly than patients in the SNB group (p < 0.01). The change in total FACT-B+4 scores (measuring global QOL) closely resembled the TOI results. 18 months post-surgery approximately twice as many patients in the standard group compared with the SNB group reported substantial arm swelling (14% versus 7%) (p = 0.002) or numbness (19% versus 8.7%) (p < 0.001). Despite the uncertainty about undergoing a relatively new procedure and the possible need for further surgery, there was no evidence of increased anxiety amongst patients randomised to SNB (p > 0.05). For 6 months post-surgery younger patients reported less favourable QOL scores (p < 0.001) and greater levels of anxiety (p < 0.01). In view of the benefits regarding arm functioning and quality of life, the data from this randomised study support the use of SNB in patients with clinically node negative breast cancer.

Adult↗
PubMed2005

Home injuries and built form--methodological issues and developments in database linkage.

BACKGROUND: The aim of this body of research is to determine whether injuries in the home are more common in particular types of housing. Previous home injuries research has tended to focus on behaviours or the provision of safety equipment to families with young children. There has been little consideration of the physical environment. This study reports methodological developments in database linkage and analysis to improve researchers abilities to utilise large administrative and clinical databases to carry out health and health services research. METHODS: The study involved linking a database of home injuries obtained from an emergency department surveillance system with an external survey of all homes in an area and population denominators for home types derived from a health service administrative database. Analysis of injury incidence by housing type was adjusted for potential biases due to deprivation and distance to hospital. For non-injured individuals data confidentiality considerations required the deprivation and distance measures be imputed. The process of randomly imputing these variables and the testing of the validity of this approach is detailed. RESULTS: There were 14,081 first injuries in 112,248 residents living in 54,081 homes over a two-year period. The imputation method worked well with imputed and observed measures in the injured group being very similar. Re-randomisation and a repeated analysis gave identical results to the first analysis. One particular housing type had a substantially elevated odds ratio for injury occurrence, OR = 2.07 (95% CI: 1.87 to 2.30). CONCLUSIONS: The method of data linkage, imputation and statistical analysis used provides a basis for improved analysis of database linkage studies.

Accidents, Home↗
PubMed2005

Role of routine preoperative lymphoscintigraphy in sentinel node biopsy for breast cancer.

Sentinel node biopsy (SNB) is rapidly emerging as the preferred technique for nodal staging in breast cancer. When radioactive colloid is used, a preoperative lymphoscintiscan is obtained to ease sentinel lymph node (SN) identification. This study evaluates whether preoperative lymphoscintigraphy adds diagnostic accuracy to offset the additional time and cost required. 823 breast cancer patients underwent SNB based on lymphoscintigraphy, intraoperative gamma probe detection, and blue dye mapping using 99 mTc-nanocolloid and Patent Blue V injected peritumourally. The SNB was followed by standard axillary treatment at the same operation. Preoperative lymphoscintigraphy was performed around 3 h after the radioisotope injection. Preoperative lymphoscintigraphy revealed SNs in 593 (72%) of the 823 patients imaged. SN visualisation on lymphoscintigraphy was less successful in large tumours and tumours involving the upper outer quadrant of the breast (P=0.046, P<0.001, respectively). Lymphoscintigraphy showed internal mammary sentinel nodes in 9% (62/707) patients. The SN was identified intraoperatively in 98% (581) patients who had SN visualised on preoperative lymphoscintigraphy, with a false-negative rate of 7%. In patients who did not have SN visualised on preoperative lymphoscintigraphy, the SN was identified at operation in 90% (204) patients, with a false-negative rate of 7%. The SN identification rate was significantly higher in patients with SN visualised on preoperative lymphoscintigraphy (P<0.001). SN identification rate intraoperatively using the gamma probe was significantly higher in the SN visualised group compared with the SN non-visualised group (95% vs. 68%; chi square (1 degrees of freedom (df)) P<0.001. There was no statistically significant difference in the false-negative rate and the operative time between the two groups. A mean of 2.3 (standard deviation (SD) 1.3) SNs per patient were removed in patients with SN visualised on preoperative lymphoscintigraphy compared with 1.8 (SD 1.2) in patients with no SN visualised on lymphoscintigraphy (P<0.001). Although SN visualisation on preoperative lymphoscintigraphy significantly improved the intraoperative SN localisation rate, SN was successfully identified in 90% of patients with no SN visualisation on lymphoscintigraphy. Given the time and cost required to perform routine preoperative lymphoscintigraphy, these data suggest that it may not be necessary in all cases. It may be valuable for surgeons in the learning phase to shorten the learning curve and in patients who have increased risk of intraoperative failed localisation (obese or old patients). A negative preoperative lymphoscintiscan predicts the inability to localise with the hand-held gamma probe. Therefore, if the SN is not visualised on lymphoscintigraphy then the addition of intraoperative blue dye is recommended to increase the likelihood of SN identification.

Breast↗
PubMed2005

A randomized trial of nicotine enemas for active ulcerative colitis.

BACKGROUND & AIMS: Ulcerative colitis (UC) is largely a disease of nonsmokers in which transdermal nicotine improves the symptoms but often causes adverse events (AEs). Nicotine enemas cause fewer AEs and were used as supplemental treatment for active UC. METHODS: We treated 104 patients with active UC with either 6-mg nicotine enemas or placebo enemas for 6 weeks in a randomized double-blind study. Patients continued their oral therapy, if any, for UC: 68 patients were taking mesalamine, 15 patients were taking prednisolone, and 12 patients were taking thiopurines during the study. Clinical, sigmoidoscopic, and histologic assessments were made at baseline and at the end of the study and symptoms were recorded daily on a diary card. The primary end point was induction of clinical remission and clinical improvement also was measured by the UC disease activity index. After the study, patients then used nicotine enemas daily for 4 weeks and sigmoidoscopy with a biopsy examination was repeated. AEs and salivary cotinine levels were monitored throughout the study. RESULTS: Clinical remission was achieved in 14 of 52 (27%) patients on active treatment and 14 of 43 (33%) patients on placebo (P = .55). The UC disease activity index improved by 1.45 points in the active group and by 1.65 points for those on placebo (P = .88). Only 1 patient discontinued treatment because of an AE (abdominal pain). In the 47 patients taking mesalamine only, active treatment conferred benefit that was not statistically significant; disease remission occurred in 9 of 25 patients on active therapy and 4 of 21 patients on placebo (P = .20). CONCLUSIONS: Six-milligram nicotine enemas were well tolerated but were not found to be efficacious for active UC.

Adult↗
PubMed2004

The learning curve in sentinel node biopsy: the ALMANAC experience.

Sentinel node biopsy (SNB) is a minimally invasive procedure to stage the axilla in patients with breast cancer. Like any new surgical procedure, it is associated with a learning curve. This article describes the learning curve as part of the ALMANAC trial. The first phase of this trial is a validation phase in which surgeons perform SNB followed by an immediate axillary dissection in a consecutive series of 40 patients with invasive breast cancer. Each surgeon completes a mandatory program of proctored training during this phase. Surgeons who achieve a localization rate of 90% or more and a false-negative rate of 5% or less are eligible to proceed to the randomized phase. All 13 surgeons who completed 40 procedures as part of the validation phase of the ALMANAC trial achieved the set target. This study shows that a standardized training program allows surgeons to achieve a satisfactory localization rate and an acceptable false-negative rate after 40 SNBs.

Adult↗