Worthwhile Effect Research Articles

Implementing MICRO‐HOPE in primary care with extra nurse support

AbstractAn audit of work to implement the MICRO‐HOPE study findings in a UK rural practice is presented. Seventy‐three out of an eligible group of 142 who fitted the HOPE trial criteria were not taking an ACE inhibitor. Of these, 60 were invited to a special clinic session with a visiting nurse to provide an opportunity to offer ACE inhibitor treatment and follow‐up. The average age of males (n=29) and females (n=31) was 70.7 (SD 9.9) and 70.1 (SD 8.9) respectively. The mean HbA1c of the invited group was 7.64% (CI 7.33–7.95%) and mean blood pressure was 138/75mmHg (CI 134–143/73–77mmHg).Thirty‐five (58%) patients attended and 20 (33%) started taking ramipril as a result of the intervention. In the interim, three had been started on treatment by a hospital. At 12 weeks, 14 (23%) were still on treatment from the practice. Only two (10%) achieved the target dosage of 10mg ramipril daily. Six patients (30%) had side‐effects and stopped ramipril treatment. The total cost of the intervention was £3200.The nurse‐led intervention increased the appropriate ACE inhibitor usage among people with type 2 diabetes from 49% to 59% over three months. The proportion of patients on either an ACE inhibitors or angiotensin II‐receptor antagonists rose from a baseline of 56% to 65% at six months.For a brief intervention, this was a worthwhile effect. This audit shows that increasing ACE inhibitor use is resource intensive but its small scale may exaggerate the effect size. Clarity is needed around the issue of any ‘class effect’ for ACE inhibitors and how patients will cope with the increasing burden of medication. Copyright © 2003 John Wiley & Sons, Ltd.

Application of the headspace CO2 method (ISO 14 593) to the assessment of the ultimate biodegradability of surfactants: results of a calibration exercise.

In the recent review of the control of marketing surfactants used in detergents, the EU decided to increase the severity of the testing procedure by using the criterion of ultimate biodegradability (mineralization) rather than primary biodegradation (removal of the parent molecule) to ensure that possible harmful organic metabolites do not reach the environment. The relatively new ISO headspace CO2 test, considered to be an improvement on the OECD 301B (Sturm CO2) test was chosen. The method was subjected to a ring test by 11 laboratories using one of each of four classes of surfactants plus a poorly degradable reference surfactant; all laboratories satisfactorily applied the method. The necessary addition of silica gel to the medium containing the cationic surfactant, known as a class to be more inhibitory than other classes, was confirmed as a technique for avoiding inhibition of the inoculum. The biodegradability of the surfactants was in general agreement with results reported in the literature and the often reported variable values of % inorganic carbon (IC) produced of the theoretical was found. The anionic and cationic surfactants were readily biodegradable (%IC > 60), the non-ionic surfactant was well below the pass value, while the amphoteric was borderline. The IC production by the blank controls, one of the validity criteria, was about 0.3 mg C/100 ml test medium, equivalent to 3 mg C/l, as recommended in the ISO text. Mild conditions of pre-exposure of the inoculum to the test surfactant did not produce consistent worthwhile effects on either the percentage biodegradation or on its variability.

Predicting Intentions Versus Predicting Behaviors: Domestic Violence Prevention From a Theory of Reasoned Action Perspective

A central assumption of many models of human behavior is that intention to perform a behavior is highly predictive of actual behavior. This article presents evidence that belies this notion. Based on a survey of 1250 Philadelphia adults, a clear and consistent pattern emerged suggesting that beliefs related to domestic violence correlate with intentions to act with respect to domestic violence but rarely correlate with reported actions (e.g., talking to the abused woman). Numerous methodological and substantive explanations for this finding are offered with emphasis placed on the complexity of the context in which an action to prevent a domestic violence incident occurs. We conclude by arguing that despite the small, insignificant relationships between beliefs and behaviors found, worthwhile aggregate effects on behavior might still exist, thus reaffirming the role of communication campaign efforts.

Influence of the bystander effect on HSV-tk/GCV gene therapy. A review.

Despite the development of new therapeutic strategies, cancer remains incurable in most patients with advanced disease. A recent potential improvement in therapeutic strategies is the concept of suicide gene therapy. After transfection with a suicide gene, cells can convert a harmless prodrug into its toxic metabolite, resulting in selective elimination of these cells. One of the most frequently studied therapeutic strategies is based on transfection with the herpes simplex virus thymidine kinase gene (HSV-tk), followed by ganciclovir administration. Despite promising results in vitro and in vivo, the antitumor effect in clinical trials remains poor, due to very low transfection efficiency. However, high percentages of transfected cells are not mandatory for complete eradication of a tumor in vivo. Transfected tumor cells appear to be capable of inducing the death of neighboring untransfected cells. This cell kill is called the "bystander effect". Various attempts have been made to increase this effect. A substantial bystander effect could overcome the limitations of low transfection efficiency and result in an enhanced and possibly clinically worthwhile antitumor effect in patients. This review is focused on the HSV-tk/GCV system and gives an overview of current knowledge on the bystander effect in vitro and in vivo. In addition, theories concerning its mechanisms and possible approaches to augment this effect are discussed. Finally, we give an overview of clinical trials using suicide gene therapy.

Somatostatin or octreotide for acute bleeding oesophageal varices.

Somatostatin and its derivative, octreotide, are often used for emergency treatment of bleeding oesophageal varices in patients with cirrhosis of the liver. The placebo controlled trials have shown varying results, however, and their power has been quite low. An updated systematic review of a previously published meta-analysis was therefore performed. To study whether somatostatin or octreotide improve survival or reduce the number of blood transfusions in patients with suspected or verified acute or recently bleeding oesophageal varices. MEDLINE and The Cochrane Library are searched every three months. Reference lists of articles and authors. All randomised trials comparing somatostatin or octreotide with placebo or no treatment in patients suspected of acute bleeding from oesophageal varices. The effect variables extracted were: mortality, number of blood transfusions, number with balloon tamponade, number with initial haemostasis and number with rebleeding. Intention to treat analyses were conducted; a random effects analysis was preferred if there was significant heterogeneity between the trials (p<0.10). The meta-analysis comprised 820 patients. The active drugs had no effect on survival; a total of 91 patients died in the experimental groups vs 85 patients in the control groups (odds ratio 1.04, 95% confidence interval (CI) 0.74 to 1.46). The number of transfusions was less with drugs, the difference between experimental and control therapy was 1.2 units of blood products saved per patient (95% CI 0. 8 to 1.6). There were no significant differences in use of balloon tamponade (odds ratio 0.59, 95% CI 0.21 to 1.70), number of patients failing initial haemostasis (odds ratio 0.66, 95% CI 0.32 to 1.37) or number with rebleeding (odds ratio 0.73, 95% CI 0.30 to 1.79). It should be noted, however, that the trials were heterogeneous with respect to these secondary variables. The effect corresponded to one unit of blood saved per patient. This effect is small and treatment with these drugs in acute bleeding oesophageal varices is therefore of doubtful value. This does not suggest a need for further studies. On the other hand, the confidence interval for the effect on mortality was wide. Hence, a large placebo controlled trial is needed if one wishes to rule out the possibility that a worthwhile effect on mortality may have been overlooked.

Muscle stretching for treatment and prevention of contracture in people with spinal cord injury.

Contracture, or reduced joint mobility, is a common and disabling sequel of spinal cord injury. The primary intervention for the treatment and prevention of contracture is regular stretch to soft tissues. While the rationale for this intervention appears sound, the effectiveness of stretching has not been verified with well designed clinical trials. One recent randomised trial suggests there is no clinically worthwhile effect from a typical stretch protocol applied to spinal cord injured patients. Despite the negative results of this first trial, we argue that therapists should continue administering stretch for the treatment and prevention of contracture until the results of further studies emerge. To maximise the probability of attaining a clinically worthwhile effect, we suggest that therapists stretch soft tissues for long periods (at least 20 min, and perhaps for as long as 12 h a day). Practical suggestions are given on how to readily provide spinal cord injured patients with sustained stretch to key joints and muscle groups. Stretch is most likely to be effective if started before the onset of contracture. Soft tissues most at risk should be targeted, particularly if contracture is likely to impose functionally important limitations.

Screening for breast cancer with mammography.

Mammographic screening for breast cancer is controversial, as reflected in greatly varying national policies. To assess the effect of screening for breast cancer with mammography on mortality and morbidity. MEDLINE (16 May 2000), The Cochrane Breast Cancer Group's trial register (24 Jan 2000) and reference lists. Letters, abstracts and unpublished trials. Authors were contacted. Randomised trials comparing mammographic screening with no mammographic screening. Data were extracted by both authors independently. Seven completed and eligible trials involving half a million women were identified. The two best trials provided medium-quality data and, when combined, yield a relative risk for overall mortality of 1.00 (95% CI 0.96-1.05) after 13 years. However, the trials are underpowered for all-cause mortality, and confidence intervals include a possible worthwhile effect as well as a possible detrimental effect. If data from all eligible trials (excluding flawed studies) are considered then the relative risk for overall mortality after 13 years is 1.01 (95% CI 0.99-1.03). The best trials failed to show a significant reduction in breast cancer mortality with a relative risk of 0.97 (95% CI 0.82-1.14). If data from all eligible trials (excluding flawed studies) are considered then the relative risk for breast cancer mortality after 13 years is 0.80 (95% CI 0.71-0.89). However, breast cancer mortality is considered to be an unreliable outcome and biased in favour of screening. Flaws are due to differential exclusion of women with breast cancer from analysis and differential misclassification of cause of death. The currently available reliable evidence does not show a survival benefit of mass screening for breast cancer (and the evidence is inconclusive for breast cancer mortality). Women, clinicians and policy makers should consider these findings carefully when they decide whether or not to attend or support screening programs.

Two-year outcome of ventilation tubes in a randomized controlled trial of persistent childhood otitis media with effusion

Introduction. Resolving the conflict between commissioners and providers of treatment in otitis media with effusion requires a cost-effectiveness trial in which the outcomes reflect health gain for the whole child. TARGET (Trial of Alternative Regimens of Glue Ear Treatment) is an MRC-funded randomized controlled trial of surgical management (bilateral ventilation tubes with and without adjuvant adenoidectomy) versus non-surgical management in children aged between 3.25 and 6.75 years. Methods. The entry criterion was bilateral otitis media (OME) associated with a pure-tone average (PTA) >20 dB HL in the better hearing ear, documented as persistent over a 12-week watchful waiting period. The watchful waiting period of 12 weeks is supported as appropriate for routine practice, because 48% of children meeting the criterion at their first visit showed sufficient resolution to no longer satisfy the entry criterion. Certain groups of children were not randomized because of overriding parental or doctor concern, or because the parents refused participation or randomization. These groups did not differ significantly on any of the variables likely to affect the outcome. Some children with a PTA >40 dB HL were excluded from randomization but were fully followed-up following surgery. Results were found to be largely similar to those for the randomized children with this degree of hearing impairment. Of the 370 randomized children, 124 had bilateral Shephard ventilation tubes inserted under a general anaesthetic within 6 weeks, 127 had similar surgery but with the addition of adenoidectomy, and 119 had non-surgical management. Following randomization, all children were followed up 3, 6, 12, 18 and 24 months later. This paper presents an initial analysis, on an intention-to-treat basis, of the outcomes in the children having ventilation tubes alone against the non-surgically managed children. The adjuvant effect of adenoidectomy will be reported subsequently. Results. The average effect of management, summarized over the first and both years, for the hearing, the reported hearing difficulty, the parental report of the child's behaviour, the child's general health and the parental report of quality of family life are shown in Tables 2, 3, 4, 5 and 6 respectively. The differences in the effect between ventilation tubes and non-surgical management were all significant (P < 0.05) except when indicated by NS (not significant). The effect of surgery is reported both as a difference and as a proportion of the standard deviation in the sample prior to randomization. Using the latter scale, a difference of 0.33 SD is a modest but worthwhile effect, 0.66 SD a substantial effect, 1.00 SD a large effect, and 1.33 SD a very large effect. Table 2. Average effect of management on hearing loss (HL) Mean dB HL over 1 year 2 years The mean HL at randomization was 32.7 dB HL (SD 6.1). Ventilation tubes 17.6 18.5 No surgery 23.4 21.8 Difference 5.8 3.3 Size of effect 0.9 SD 0.6 SD Table 3. Average effect of management on reported hearing difficulty Mean score over 1 year 2 years The mean score at randomization was 10.4 (SD 3.2). Ventilation tubes 4.6 4.9 No surgery 8.1 7.8 Difference 3.5 2.9 Size of effect 1.3 SD 1.3 SD Table 4. Average effect of management on behaviour Mean score over 1 year 2 years The disease effect of otitis media (OME) on behaviour was 0.67 SD. The mean score at randomization was 13.2 (SD 5.7). Ventilation tubes 10.5 9.7 No surgery 12.2 12.0 Difference 1.7 2.3 Size of effect 0.3 SD 0.6 SD Table 5. Average effect of management on general health Mean score over 1 year 2 years The disease effect of otitis media (OME) on general health was 0.68 SD. The mean score at randomization was 1.2 (SD 0.8). Ventilation tubes 0.8 0.9 No surgery 1.0 1.0 Difference 0.2 0.1 Size of effect 0.4 NS Table 6. Average effect of management on quality of life (QOL) Mean QOL over 1 year 2 years The disease effect of otitis media (OME) on QOL was 1.01 SD. The mean QOL at randomization was 16.1 (SD 4.4). Ventilation tubes 18.5 18.9 No surgery 17.6 18.3 Difference 0.9 0.6 Size of effect 0.4 SD NS Conclusions. The substantial beneficial effect of ventilation tubes on the hearing in children with bilateral, persistent OME has been confirmed up to 2 years. This is mirrored by a substantial and significant improvement in behaviour. There is a modest but significant improvement in general health and parental quality of life up to 1 year. There is a potential additional effect on these outcomes of adenoidectomy which will be subsequently reported.

Outcome measures in acute stroke trials: a systematic review and some recommendations to improve practice.

There is little consistency in the measurement of outcome in acute stroke trials, and this may complicate interpretation of the results and reduce the likelihood of detecting worthwhile drug effects. This study aims to investigate empirically the measures used to date and to give recommendations for future studies. A systematic review of all published randomized studies of acute stroke drug intervention was undertaken, and the measures used were recorded. Fifty-one studies involving 57 214 subjects were identified. These studies used 14 different measures of impairment, 11 different measures of activity, 1 measure of "quality of life," and 8 miscellaneous other measures. Timing of outcome assessments varied from 1 week to 1 year, with the modal time being 3 months. Many studies used ordinal measures but dichotomized results for analysis. Of the 51 studies included in the review, only 21 demonstrated benefit with the defined primary outcome measure. In several studies, however, post hoc analysis using varied outcome measures or varied cut points for dichotomizing outcomes resulted in positive results, whereas the primary study analysis failed to do so. There is no consensus on the level of outcome to be used, the method of measurement to be used, or the most appropriate timing of the assessment. It is recommended that future studies should include extended/instrumental activities and advanced mobility as components of the primary outcome measure, with outcome assessment being undertaken at 6 months. New initiatives in developing stroke-specific outcomes may address some of the current problems in the assessment of stroke outcomes

Selective decontamination of the digestive tract — current national practice

The use of selective decontamination of the digestive tract (SDD) in the intensive care setting was first reported in 19841 and, since then, has been the subject of many further studies. Two large meta-analyses have been conducted2 3 and have suggested that, used alone, the topical element of SDD reduces the incidence of nosocomial respiratory tract infections (NRTIs), but has no impact on mortality. When the systemic element is added, however, not only are NRTIs prevented, but mortality is also reduced. It was estimated that either six2, or five3 patients had to be treated to prevent one NRTI and 23 to prevent one death. This would appear to be a worthwhile effect and one which, in terms of supporting evidence, compares favourably with some interventions used commonly in clinical practice. Despite this, there is an impression that SDD is very little used in this country and this study sought to explore this. In September 1998, a questionnaire was sent to the directors of all general intensive care units (ICUs) in the UK and Ireland (n = 289). In addition to basic information about the unit, it asked whether SDD was in routine use, if so whether both topical and systemic elements were used, and whether it was used on all or selected cases. If SDD was not routinely used, it asked for the reasons. A telephone follow-up of non-responders was undertaken. Responses were obtained from 222 ICUs (77%). Of these, 66 were in teaching and 156 in non-teaching hospitals. A total of 213 units (96%) never used SDD. The nine units that did use it (six teaching, three non-teaching) did so only in selected cases. The commonest reason for selective use was major trauma, but liver failure, liver transplants, long-stay patients, burns and oesophageal perforation were also cited. Of the nine units using SDD, all but one used combined topical and systemic antibiotics. A lack of evidence of efficacy was the commonest reason for non-use (184 units) but concerns were also expressed about costs and cost-effectiveness (47 units) and the development of resistant organisms (35 units). Unusually for intensive care practice, SDD represents a treatment for which there is reasonable evidence of efficacy and yet one which, paradoxically, is rarely used. It is particularly interesting that the lack of such evidence is most commonly cited as the reason for non-use. The potential for producing resistant organisms and the issue of cost-effectiveness are, as yet, unquantified and may prove to be more valid reasons.

Integrated learning systems in the classroom

The main focus for this paper is an overview and critique of an extensive series of empirical evaluations of Integrated Learning Systems (ILS) in UK classrooms which took place between 1994 and 1998. The main purpose of the investigations was to determine if the use of ILS was effective in producing worthwhile gains in basic numeracy and literacy. Findings from three phases of research offered evidence relevant to this question. The safest conclusion is that the investigations failed to find any convincing evidence for gains. Though ‘safe’, this conclusion masks some highly significant differences between the findings of the three phases. One produced evidence of statistically significant, positive and educationally worthwhile effects. A second generated relatively neutral findings; a mixture of small positive and equally small negative effects, while a third led to the conclusion that is was “difficult to find anything but an apparently negative effect on achievement”. A consideration of the nature and implications of these different findings forms the main content of this paper. The findings are assessed from three perspectives. The first explores issues concerning research methodology with a view to identifying minimal rules of “good practice” in empirical evaluations of the impact of computers on educational achievement. The second considers the findings from a more theoretical perspective; exploring the case that conceptual analysis can also provide a source of converging evidence in evaluations of the educational impact of technology. Finally, the paper cites evidence from observational data to explore the thesis that any impact of ICT on pupils’ learning will not be understood without attention to the way in which the technology is assimilated into teaching and learning practices. We argue that, even in relation to systems designed to support individualised, automated teaching, there are sound theoretical reasons to expect that any long-term and cumulative effects on performance will be mediated and influenced by classroom practice. Finally, implications of this argument for developing principles of design based on the “system–learner–teacher” triangle are explored.

SPORT PERFORMANCE ENHANCEMENT: DESIGN AND ANALYSIS OF RESEARCH

SPORT PERFORMANCE ENHANCEMENT: DESIGN AND ANALYSIS OF RESEARCH

Assessing whether to perform a confirmatory randomized clinical trial.

A confirmatory randomized clinical trial is a trial that is aimed at assessing whether a treatment effect observed in a previous randomized trial (or trials) is real and important. There is often considerable disagreement about the need for such confirmatory trials. Our aim is to provide a general statistical framework for evaluating whether a confirmatory trial is warranted in a particular situation. The results of two clinical trials are considered: 1) a Cancer and Leukemia Group B trial comparing induction chemotherapy plus radiotherapy with radiotherapy alone in the treatment of patients with locally advanced non-small-cell lung cancer and 2) a North Central Cancer Treatment Group trial comparing surgery plus adjuvant chemotherapy with surgery alone in the treatment of patients with advanced colon cancer. In our analysis, we argue that differences in the interpretation of results from a randomized trial are based on differences in prior beliefs about the efficacy of the treatment(s) under study. We believe that a major factor in the decision to perform a confirmatory trial is prior skepticism about the clinical worth of the treatment in question. Both the level of prior skepticism and the minimum treatment effect deemed clinically worthwhile require subjective judgment. We develop a Bayesian framework to allow differences in interpretation to be examined systematically and the need for a confirmatory trial to be assessed. Our model allows the addition of prior belief (specified in the form of a prior distribution of treatment effect) to the results of a trial to yield a posterior distribution. The interpretation of trial results is based on the posterior distribution and will vary as the prior distribution (i.e., the prior belief) varies. To aid in the interpretation of trial results, we also advocate the specification of a minimum clinically worthwhile treatment effect at the start of a trial. Our approach acknowledges that a number of different prior beliefs are possible, giving rise to a range of interpretations of results from a clinical trial. This approach provides a formal and systematic basis for considering both the range of likely opinions and the subsequent decision to be made with regard to the need for a confirmatory trial. We recommend that this approach be considered in the discussion of future confirmatory randomized clinical trials.

Toward More Research on Effective Practices with Gifted Students in General-Education Settings

A lack of efficacy research related to effective practices for gifted students in the general-education setting exists in the literature. Future research efforts in this area need to begin by clearly defining worthwhile effects to study. These worthwhile effects relate to what we want our gifted students to accomplish in both the short and long term. Once these effects are defined, we recommend that researchers identify the important critical attributes of the desired practices, include ways of determining if the practice is actually implemented in the classroom, and use technically adequate measures and procedures to gather data.

The Epidemiological Association between Blood Pressure and Stroke: Implications for Primary and Secondary Prevention

Data from prospective observational studies indicate that usual levels of blood pressure are directly and continuously related to the risk of stroke. The strength of this association has been substantially underestimated by many previous analyses that have not taken account of the "regression dilution bias;" correction for this increases by about 60% the strength of the association between blood pressure levels and stroke risk. From corrected analyses it is apparent that a difference in usual blood pressure levels of just 9/5 mmHg would ultimately confer about a one-third difference in stroke risk. The associations between blood pressure and stroke risk are of similar size in hypertensives and in normotensives. Moreover, because most strokes occur in normotensives, the stroke avoidance that is likely to be conferred by a downward shift in population blood pressure is actually greater in normotensives than hypertensives. For large populations in which stroke is common, a relatively small change in the average adult blood pressure could have large effects on stroke mortality and morbidity. In China, for example, a decline of 9/5mmHg in the average adult blood pressure might be expected to prevent about 400, 000 deaths from stroke each year; more than three quarters of the deaths prevented would have occurred in normotensive individuals. For individuals, the benefits of blood pressure reduction are likely to be greatest in those at highest risk of stroke. It is possible that blood pressure reduction among either hypertensives or normotensives with a history of cerebrovascular disease could confer particularly worthwhile effects. This hypothesis requires investigation in a large-scale randomised trial. (Hypertens Res 1994; 17: Suppl. I S23-S32)

Feasibility of Alternative Grass Silage Systems: Part 2, Economic Assessment

Three novel silage making technologies described in Part 1, mat making, dewatering and absorbents, were tested in simulations over a 10-year period of grass growth, silage conservation and feeding to a dairy herd, using a whole-system forage conservation model. The novel technologies were compared with a conventional system using a mower-conditioner and a precision chop harvester. Simulation results showed that mat making improved profitability by as much as £2400 per year on a 40 ha, 100 cow farm. About £600 gain was due to reduced field losses, another £600 was attributed to improved digestibility and £1200 was due to the replacement of the forage harvester by a lower-cost mat harvester. Optimization of mat making suggested mowing only in the morning so that most mats reached 25 to 30% dry matter in the afternoon and could be ensiled on the same day the forage was mowed. The benefits of dewatering, in terms of reducing purchased supplemental feedstuffs because the juice and fibre could be fed separately, amounted to £1000 per year. However, this was too small a saving to cover the extra cost of equipment and chemicals to separate and preserve the juice. The use of absorbents was also not economic if applied in sufficient quantities to have any worthwhile effect on effluent production. Of the three technologies considered, only mat making offered the prospect of an economically acceptable means of reducing effluent production from unwilted silage.

Meta-analysis of second-line antirheumatic drugs: sample size bias and uncertain benefit

Placebo controlled trials of methotrexate, auranofin, penicillamine, azathioprine, sulphasalazine, gold sodium thiomalate and chloroquines were subjected to meta-analysis. The difference between drugs and placebo in the erythrocyte sedimentation rate was 8.8 mm/hr [95% confidence interval (CI), 6.4–11.3]. In multiple linear regression analyses, with the physician's global evaluation and relative change in joint tenderness count as outcome variables, a substantial sample size bias was demonstrated. The effect decreased with increasing sample size. The risk of dropping out from any cause was larger on drug than on placebo (odds ratio, 1.17; CI, 0.99–1.38). No evidence of a worthwhile effect on radiological changes was found. Of the 3439 patients, 4 went into complete remission on drug. We conclude that the benefit of second-line drugs is uncertain.

Hexetidine mouthrinse in the management of minor aphthous ulceration and as an adjunct to oral hygiene

A number of compounds have been used in the management of recurrent oral ulceration, including antimicrobials. This was a double-blind placebo-controlled cross-over study to assess the value of a 0.1% hexetidine mouthwash in the management of minor aphthous ulceration and as an adjunct to oral hygiene. Forty patients with a catalogued history of ulceration took part. Patients were randomly allocated to active/placebo or vice versa order of mouthwashes, which were used as 15 ml volumes three times a day. Treatment periods were 6 weeks with a 3 week washout. During each period patients kept daily records of the number, site, and duration of ulcers, together with pain scores. Plaque and gingivitis were scored at baseline and end of treatment periods. Thirty-eight patients completed the study, with no significant treatment differences between active and placebo rinses on any ulcer parameter. Additionally, the hexetidine rinse provided no significant benefit to oral hygiene or gingival health. However, there was a significant period effect, with considerable ulcer improvements during the second period, irrespective of treatment. In conclusion, the hexetidine rinse appeared to offer no benefits to these patients, but professional supervision of ulcer treatment does appear to result in a worthwhile placebo effect.

Management of Gilles de la Tourette Syndrome Using Sulpiride

One hundred and fourteen patients with Gilles de la Tourette syndrome have been reviewed. Sixty-three were managed using sulpiride, and worthwhile beneficial effects occurred in 59%. Our experience with sulpiride compared to other drug treatments is discussed. The main adverse side effects of sulpiride treatment were sustained drowsiness and, possibly, depression. Tardive dyskinesia was not reported in our cohort.

A Statistical Approach for Calculating the Minimum Number of Animals Needed in Research

Statistical significance and practical importance are not equivalent concepts. Statistical significance refers to the probability that random chance alone is responsible for the observed difference between treatment groups. In contrast, practical importance refers to the usefulness of the observed difference (i.e., is the difference big enough to matter?). With massive numbers of animals, it sometimes is possible to show that trivial differences are statistically significant—but if the difference is trivial, it has little relevance to the overall study. Similarly, if only a very limited number of animals is used, it might not be possible to show that a clinically meaningful difference is statistically significant—and a worthwhile effect might be missed. It is unethical to use either too many or too few animals in research. Using many more animals than needed is an abuse of our privilege to use animals and a waste of research monies. It also is wrong to use so few animals that either a reliable answer cannot be obtained or the smallest important effect cannot be observed; in this case, all the animals and monies are wasted. This article will not present formulas for sample size calculations. Rather, the article will provide an understanding of the issues underlying those calculations, including actual elements of sample size calculations, assessment of the kind of data, whether the purpose of analysis is description or comparison, common sample size mistakes, and ways to decrease the sample size. These issues will be addressed by using examples frequently encountered by animal research investigators. How investigators' decisions regarding these issues affect the number of animals needed will be highlighted.