The value of the negative predictive values.
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Predictive Value of Tests↗
Biomedical subjects
R G Newcombe
Publications and source records attributed to R G Newcombe.
Improved confidence intervals for the difference between binomial proportions based on paired data.
Existing methods for setting confidence intervals for the difference theta between binomial proportions based on paired data perform inadequately. The asymptotic method can produce limits outside the range of validity. The 'exact' conditional method can yield an interval which is effectively only one-sided. Both these methods also have poor coverage properties. Better methods are described, based on the profile likelihood obtained by conditionally maximizing the proportion of discordant pairs. A refinement (methods 5 and 6) which aligns 1-alpha with an aggregate of tail areas produces appropriate coverage properties. A computationally simpler method based on the score interval for the single proportion also performs well (method 10).
Binomial Distribution↗
Hyperhomocysteinemia after an oral methionine load acutely impairs endothelial function in healthy adults.
BACKGROUND: Elevated plasma homocysteine is a risk factor for arteriosclerosis, but a cause-and-effect relationship remains to be fully established. Endothelial dysfunction, an early event in the atherogenic process, has been shown to be associated with hyperhomocysteinemia in experimental and human studies. To further establish a direct relationship between changes in plasma homocysteine and endothelial dysfunction, we investigated whether moderate hyperhomocysteinemia induced by an oral methionine load would acutely impair flow-mediated endothelium-dependent vasodilatation in healthy adults. METHODS AND RESULTS: Twenty-four healthy volunteers completed a randomized crossover study in which an oral methionine load (0.1 g/kg) was administered on 1 of 2 study days, 7 days apart. At each visit, plasma homocysteine and brachial artery endothelium-dependent and -independent dilatation were measured at baseline and at 4 hours. To further elucidate the temporal relationship between methionine, homocysteine, and endothelial function, an oral methionine load was administered in 10 subjects on a separate visit, and the time courses of plasma methionine, homocysteine, and flow-mediated brachial artery dilatation were measured at baseline and after 1, 2, 3, 4, and 8 hours. After oral methionine, plasma homocysteine increased from 7. 9+/-2.0 micromol/L at baseline to 23.1+/-5.4 micromol/L at 4 hours (P<0.0001, n=24) and was associated with a decrease in flow-mediated brachial artery dilatation from 0.12+/-0.09 to 0.06+/-0.09 mm (P<0. 05). The time course of the impairment of flow-mediated vasodilatation mirrored the time course of the increase in homocysteine concentration. CONCLUSIONS: Oral methionine loading raises plasma homocysteine and impairs flow-mediated endothelium-dependent vasodilatation. This supports the view that homocysteine may promote vascular disease by inducing endothelial dysfunction.
Administration, Oral↗
Intra-observer reliability regarding removal of asymptomatic third molars.
OBJECTIVE: To investigate reliability of practitioners' removal decisions and judgements of risk of pathology associated with asymptomatic third molars. SUBJECTS: 10 oral surgeons and 18 family dentists from South Wales with experience ranging from 5 to 28 years. METHOD: Participants were presented with periapical radiographs of 36 asymptomatic, mandibular third molars and were informed of the age and sex of the patients and the degree of eruption of the third molars. Participants were asked to assess, using visual analogue scales, the likelihood of future pathology if the third molars were left in situ and to indicate if they should be removed or not. To assess intra-observer reliability, the 36 cases were duplicated and presented to the participants on a different occasion, a month later. The same questions were asked as on the first occasion. RESULTS: Significant correlations (Pearsons correlation coefficients) were found between initial and repeat assessments of all measures but there was little agreement about the need for removal (Kappa values: 0.54 for oral surgeons and 0.41 for the family dentists). For every item studied, changes in position on the visual analogue scale of two-thirds or more of the total length occurred from the first to the second assessment. CONCLUSION: Treatment decisions about whether or not to remove asymptomatic third molars were not made on a rational basis. Since similar conclusions were recorded in a previous Swedish study, it is inferred that until further high quality evidence of disease prediction is published, decisions to remove third molars prophylactically cannot be made reliably.
Adult↗
Two-sided confidence intervals for the single proportion: comparison of seven methods.
Simple interval estimate methods for proportions exhibit poor coverage and can produce evidently inappropriate intervals. Criteria appropriate to the evaluation of various proposed methods include: closeness of the achieved coverage probability to its nominal value; whether intervals are located too close to or too distant from the middle of the scale; expected interval width; avoidance of aberrations such as limits outside [0,1] or zero width intervals; and ease of use, whether by tables, software or formulae. Seven methods for the single proportion are evaluated on 96,000 parameter space points. Intervals based on tail areas and the simpler score methods are recommended for use. In each case, methods are available that aim to align either the minimum or the mean coverage with the nominal 1 -alpha.
Confidence Intervals↗
Interval estimation for the difference between independent proportions: comparison of eleven methods.
Several existing unconditional methods for setting confidence intervals for the difference between binomial proportions are evaluated. Computationally simpler methods are prone to a variety of aberrations and poor coverage properties. The closely interrelated methods of Mee and Miettinen and Nurminen perform well but require a computer program. Two new approaches which also avoid aberrations are developed and evaluated. A tail area profile likelihood based method produces the best coverage properties, but is difficult to calculate for large denominators. A method combining Wilson score intervals for the two proportions to be compared also performs well, and is readily implemented irrespective of sample size.
Binomial Distribution↗
Medication errors in paediatric practice: insights from a continuous quality improvement approach.
UNLABELLED: The objective was to assess the incidence and consequences of medication errors, highlight sources of recurrent error and institute changes in practice to prevent their recurrence. Utilising a continuous quality improvement approach, a 2-year prospective cohort study was undertaken using an adverse incident reporting scheme. A multidisciplinary committee analysed medication error reports, classifying them according to type (prescription, supply or administration), severity (serious or not serious) and clinical outcome. Changes in policy and practice were implemented to reduce the frequency of errors. There were 441 reported medication errors in the study period, during which 682 patients were admitted for 5315 inpatient days. Errors were more seven times likely to occur in the intensive care setting. Doctors accounted for 72% of errors and prescription errors doubled when new doctors joined the rotation. Most errors (68%) were detected prior to drug administration. Twenty-four serious medication errors were not detected in advance, but only 4 had overt clinical consequences. Excluding prevented errors and appropriate deviations from prescribed therapy, there were 117 actual medication errors (1/5.8 admissions, or 1/45 inpatient days). During the 2nd year of the scheme, the incidence of all reported errors, administration errors and serious errors fell, but the prescription error rate remained constant. CONCLUSIONS: Medication errors occurred commonly in this study, but adverse consequences were rare. The non-punitive, multidisciplinary approach to medication errors utilised in this study increased staff vigilance, highlighted sources of recurrent error, and led to changes in drug policies and staff training, which resulted in improved patient safety and quality of care.
Cohort Studies↗
A method to measure clinical erosion: the effect of orange juice consumption on erosion of enamel.
OBJECTIVE: Acidic soft drinks are frequently implicated in dental erosion, but there are limited supporting data. Research is problematic due to the insidious nature of erosion and accuracy in assessing tissue loss. The aim of this study was to develop and validate, using a negative control, a model to accurately measure erosion in situ due to a single aetiological agent over a relatively short time period. METHODS: An intra-oral appliance capable of retaining an enamel sample was designed in order to assess the effect of orange juice consumption on enamel. The study was a single centre, randomized, placebo controlled, blind, crossover design. RESULTS: Ten subjects, each consuming 11 of orange juice per day for 15 days, showed significantly more erosion on the enamel specimens than the same subjects consuming 11 of water per day over the same time period, measurements undertaken with surfometry. The same investigation was performed in vitro. Again, orange juice was significantly more erosive; indeed, it was in the order of 10 times that produced in situ. Surface microhardness testing in situ and in vitro demonstrated statistically significant differences between exposed and unexposed areas after orange juice treatment. CONCLUSIONS: Changes produced by water either in situ or in vitro were always well within the baseline measurement parameters (+/- 0.3 micron) set down for the method and hence validated the clinical model in terms of reproducibility and accuracy in measurement. It is concluded that this method has confirmed the erosive potential of orange juice in situ. The method could have many applications to study dental erosion under highly controlled conditions and over realistic time periods.
Adult↗
Clinical comparison and performance perspective of three aligning arch wires.
OBJECTIVES: To clinically evaluate three commonly used orthodontic tooth aligning arch wires: 016 x 022 inch active martensitic medium force nickel titanium, 016 x 022 inch graded force active martensitic nickel titanium, and 0.0155 inch multistrand stainless steel. DESIGN: A prospective randomized clinical trial. DATA SOURCE: Measured serial study casts of dental arches for 112 assigned arch wires from 56 consecutive patients. Analysis based on completed records for 98 arch wires and 51 patients. METHOD: A consecutive sample of 56 patients requiring both upper and lower fixed appliance therapy were randomly allocated two different arch wires from a possible three under trial. Good quality impressions were taken of the dental arches at the designated serial stages of alignment (start, T0; 4 weeks, T4; 8 weeks, T8). The resultant casts were measured on a Reflex Microscope to record the change in individual tooth alignment both in three and two dimensions (horizontal plane only). RESULTS: The measurement error was within acceptable limits (range, 0.05 to 0.09 mm) and showed no significant bias. ANOVA statistical models were fitted to the data to adjust for a number of variables. No significant difference in aligning capability (p > 0.05), in either two or three dimensions, was demonstrated between the three arch wires in the trial. CONCLUSION: Heat activated nickel titanium arch wires failed to demonstrate a better performance than the cheaper multistrand stainless steel wires in this randomized clinical trial. The failure to demonstrate in vivo superiority at the clinical level may be due to the confounding effects of large variations in individual metabolic response. Alternatively, it may be that in routine clinical practice NiTi-type wires are not sufficiently deformed to allow their full superelastic properties to come in to play during initial alignment.
Analysis of Variance↗
Home use oral hygiene product trials; timing of the last brushing before scoring; an assessment of variation.
Home use studies to evaluate oral hygiene products often standardise the time lag between plaque scoring and the previous toothbrushing. Most protocols have favoured an evening before brushing regimen, but the rationale and even the validity of this approach has not been evaluated. In this study, a group of 30 adult subjects participated in a 4-period randomised single-blind crossover evaluation of within-subjects and between-subjects variation in plaque levels after two different brushing times. Thus, on 2 occasions, plaque was scored after an "evening before" brushing and on the other 2 occasions plaque was scored after a "morning before" brushing. As expected, mean plaque levels were lower after morning brushing, but only by 11%. There was little difference for lingual plaque (4%) but a greater difference for buccal plaque (18%). Comparisons for within-subjects variation, which ideally should be low, favoured morning brushing but differences were small and not significant. Comparisons for between subjects variation, which ideally should be high to permit discrimination between high and low plaque formers, also favoured morning brushing but were only significant for lingual plaque. Intraclass correlation coefficients of reliability revealed that overall repeatability was high for both morning and evening regimens; marginally favouring morning brushing. Analyses using all four scores per subject disregarding timing of brushing increased within subjects variation and decreased repeatability, particularly for buccal plaque. In conclusion, the data support the concept of standardising the time between plaque scoring and the previous tooth-brushing. There were no clear statistically significant grounds for preferring one brushing regimen to the other, however the data favoured the morning brushing.
Adult↗
A split-mouth placebo-controlled study to determine the effect of amorphous calcium phosphate in the treatment of dentine hypersensitivity.
Many treatments for dentine hypersensitivity are formulated to directly or indirectly occlude the open dentinal tubules associated with the condition. Combining solutions of calcium chloride and potassium phosphate can result in the precipitation of amorphous calcium phosphate. Such a system applied to exposed dentine could occlude dentinal tubules and reduce sensitivity. The aims of this study using a placebo control were to assess the therapeutic value of amorphous calcium phosphate in dentine hypersensitivity and provide further information on the apparently natural improvement in the condition frequently observed in clinical trials. 38 subjects with dentine hypersensitivity affecting 1 tooth in each left and right sides of the jaws were recruited into this split mouth, randomised, double-blind study. At baseline, sensitivity was scored by the subjects on a 0-10 visual apologue scale after tactile, cool and cold water and evaporative stimulation of the test teeth. Active and control, water, solutions were then applied by a 2nd clinician. After 24 h, subjects returned for rescoring. On days 7 and 14, subjects were again rescored and the treatments reapplied. Further follow-up appointments for rescoring were on days 21, 28, 56 and 84. Plaque scores also were recorded from test teeth at each visit. Overall sensitivity decreased considerably and to a similar degree in test and control teeth with no consistent significant treatment difference. Plaque scores also decreased through the study period. It is concluded that either the amorphous calcium phosphate was without therapeutic effect or the activity was masked by the placebo response in the control teeth.
Administration, Topical↗
Controlled trial of antituberculous chemotherapy in Crohn's disease: a five year follow up study.
BACKGROUND: It has been suggested that Mycobacterium paratuberculosis is the cause of Crohn's disease. In a previous report the immediate effect of two years treatment with antituberculous chemotherapy showed no clinical benefit. AIMS: To assess both the immediate and longer term effect of treatment on the disease. METHODS: Patients were followed for five years from their date of entry to the study. One hundred and thirty patients entered the initial study, and of these 111 (81%) were followed regularly. RESULTS: Overall, there was no evidence of consistent benefit or disadvantage from antituberculous chemotherapy in any of the assessments made, including the number of acute relapses, surgical episodes, hospital admissions, disease activity, blood tests, or medication required for Crohn's disease during the follow up period. CONCLUSION: The absence of any benefit at the end of the initial two year trial period, and during the three year subsequent follow up, fails to support the hypothesis that mycobacteria play an important part in the pathogenesis of Crohn's disease, or that antituberculous chemotherapy may be of benefit.
Antitubercular Agents↗
Pharmacokinetics of nicotine carbomer enemas: a new treatment modality for ulcerative colitis.
BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine. OBJECTIVE: To study the pharmacokinetics of nicotine complexed with a polyacrylic carbomer and administered by enema to eight healthy volunteers and to eight patients with active ulcerative colitis, verified sigmoidoscopically. PATIENTS AND METHODS: All 16 subjects were nonsmokers. The mean age for normal subjects was 33 years; the mean for patients with ulcerative colitis was 60 years. Median stool frequency for patients with ulcerative colitis was four daily. Patients were taking 5-amino salicylic acid compounds and five were taking oral prednisolone (median dose, 12 mg daily). Nicotine, 6 mg, complexed with carbomer 974P, 400 mg, was administered in a 100 ml enema after an overnight fast, with serial blood measurements taken over 8 hours. Serum nicotine and cotinine were measured by gas liquid chromatography. Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase. RESULTS: With the exception of nicotine time to reach peak concentration, which was longer in patients (median of 60 minutes compared with 45 minutes; p < 0.005), other comparisons between normal subjects and patients showed no statistically significant difference, although there was considerable inter-subject variation. Maximum concentration of nicotine, 8.1 +/- 3.5 ng/ml, in the 16 subjects occurred after a median of 60 minutes (range, 30 to 180 minutes); maximum cotinine concentrations of 60.4 +/- 11.5 ng/ml occurred after 4 hours. Side effects in five subjects were mild (four subjects) or moderate (one subject) and included lightheadedness, nausea, and headache; these five subjects were female lifelong nonsmokers of low body weight. CONCLUSION: Because most of the active ingredient of nicotine is converted to continine on the first pass through the liver, substantial concentrations can be achieved at the site of disease with only modest rises in serum nicotine, which are responsible for side effects; cotinine has low pharmacologic activity. Topical administration of nicotine may be useful treatment for distal ulcerative colitis.
Acrylic Resins↗
Characterization of nasal airflow.
Nasal airflow and trans-nasal pressure difference was measured by active anterior rhinomanometry in 24 subjects. An analysis was undertaken to determine the 'goodness of fit' of two models used to characterize nasal airflow, one model by Broms and the other by O'Neill and Tolley. A judicious approach to choice of fit criterion led to the conclusion that the latter model provided a more accurate characterization of nasal airflow. Additionally this model may be useful to quantify alar valve stiffness. A portable computerized system incorporating the use of the model has been developed and is currently in use.
Airway Resistance↗
Reporting of clinical trials in Gut: the CONSORT statement. Consolidated Standards of Reporting Trials.
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Clinical Trials as Topic↗
Benefits and limitations of pathology databases to cancer registries.
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Confidence Intervals↗
Prevalence and depth of artificial caries-like lesions adjacent to cavities prepared in roots and restored with a glass ionomer or a dentin-bonded composite material.
One potential advantage of glass-ionomer materials for the treatment of root caries is their ability to release fluoride and so resist cariogenic attack. A commercially available composite material has also been reported to release fluoride which reduced caries lesions in the tooth tissue adjacent to it. The aim of this study was to assess the effectiveness of a conventional glass-ionomer restoration compared with a dentin-bonded, fluoride-releasing, composite restoration when exposed to a microbial artificial caries system. Artificial caries-like lesions produced in relation to the restorations were examined and classified either as outer (surface) lesions or as wall lesions. A split-unit experimental design allowed for within-tooth comparisons of the 2 experimental restorations at different sites on the root surface. These were either totally within the root surface or positioned at the amelo-cemental junction. Outer lesion depths were significantly (p < 0.001) shallower at all sites adjacent to the glass ionomer when compared with the composite restorations. Wall lesions were significantly (p < 0.01) more prevalent adjacent to the composite material. In addition, the cavity margin position significantly (p < 0.05) affected the incidence of wall lesions, particularly in the composite group. In conclusion, glass ionomer was successful in reducing the caries-like lesion production in the adjacent root surface. This resulted from improved marginal integrity and fluoride release from this material when compared with the composite bonding system used.
Adolescent↗
Sequentially balanced three-squares cross-over designs.
Many cross-over designs with t > or = 2 treatments and periods and n = bt subjects (b an integer > or = 1) which incorporate balance for first-order carry-over effects are already known: single squares with any even value of t and some odd ones also; and sequentially balanced pairs of squares for any odd t > or = 3. We describe the construction of designs with b = 3, for t < or = 5, 7, 9, .... This permits use of sequentially balanced designs for any combination of b > 1 and t, except for b = t = 3, for which no such design exists.
Cross-Over Studies↗