bluuebunny/crossref_metadata_2025 huggingface dataset:
Interim analysis of continuous long‐term endpoints in clinical trials with longitudinal outcomes
Authors: Galbraith Sally , Marschner Ian C.
Published: May 2003

This paper discusses interim analysis for clinical trials where the primary endpoint is observed at a specific long‐term follow‐up time, but where repeated measures of the same outcome are also taken at earlier times. Methods are considered for improving the efficiency with which the long‐term treatment difference is estimated, making use of information from shorter‐term follow‐up times. This approach to interim analysis has previously been studied for binary endpoints assessed at two time points during follow‐up. Here we adapt and extend this methodology to include continuous endpoints assessed at an arbitrary number of follow‐up times, making use of methods for analysing multivariate normal data subject to monotone missingness and unstructured mean and covariance relationships. The magnitude of efficiency gains obtained by using short‐term measurements is considered, as well as how these gains depend on the number and timing of the short‐term measurements. Sequential analysis of treatment differences is discussed, including the extent to which efficiency gains translate into reductions in the expected duration of a sequentially monitored trial. The methods are illustrated on a data set involving a placebo‐controlled comparison of longitudinal cholesterol measurements. Copyright © 2003 John Wiley & Sons, Ltd.
Microarrays, pattern recognition and exploratory data analysis
Authors: Mertens Bart J. A.
Published: May 2003

We explore the application of principal component based approaches to pattern recognition in microarray analysis. A comparative assessment is presented, based on predictive evaluation, following a review of some key methodology. On the basis of these results, we select principal component based linear discrimination for a further in‐depth analysis. We are particularly interested in studying the use of principal component decomposition for the evaluation of the condition of estimation of the pooled covariance matrix. The results are used to give some guidance as to how principal components may be used as a data exploratory tool in the analysis of microarray data. Opportunities for further development are outlined as well as implications for wider statistical modelling of microarray data. Copyright © 2003 John Wiley & Sons, Ltd.
Likelihood‐based confidence intervals for a log‐normal mean
Authors: Wu Jianrong , Wong A. C. M. , Jiang Guoyong
Published: May 2003

To construct a confidence interval for the mean of a log‐normal distribution in small samples, we propose likelihood‐based approaches – the signed log‐likelihood ratio and modified signed log‐likelihood ratio methods. Extensive Monte Carlo simulation results show the advantages of the modified signed log‐likelihood ratio method over the signed log‐likelihood ratio method and other methods. In particular, the modified signed log‐likelihood ratio method produces a confidence interval with a nearly exact coverage probability and highly accurate and symmetric error probabilities even for extremely small sample sizes. We then apply the methods to two sets of real‐life data. Copyright © 2003 John Wiley & Sons, Ltd.
Estimates, power and sample size calculations for two‐sample ordinal outcomes under before–after study designs
Authors: Strickland Pamela A. Ohman , Lu Shou‐En
Published: May 2003

Sample size calculations are given for comparing two groups of subjects, typically referring to active and non‐active intervention groups, on an ordinal outcome in experiments where the subjects are measured before and after intervention. These calculations apply to log‐odds models with random intercepts, treatment, time and treatment‐by‐time interaction terms, the latter being the term of interest. The assumed forms of the odds ratios are flexible, allowing for proportional odds, adjacent categories, or other conditional models for ordinal responses. Simulations studies show that, for given sample sizes, the nominal and actual powers of the proposed test are similar. Copyright © 2003 John Wiley & Sons, Ltd.
A modified large‐sample approach to approximate interval estimation for a particular intraclass correlation coefficient
Authors: Cappelleri Joseph C. , Ting Naitee
Published: May 2003

We consider the problem of constructing a confidence interval for the intraclass correlation coefficient in an interrater reliability study when both raters and subjects are random effects in a two‐way random effects model. A simulation study is conducted to investigate and compare the interval coverage per cents of three methods of approximation: (i) Satterthwaite's two moments, the standard approach; (ii) modified three moments, a newer approach; and (iii) modified large sample, the newest approach for this particular problem. One‐sided lower and two‐sided bounds are examined. For the two‐moment approach, coverage of confidence intervals can be understated for not only one‐sided bounds but also two‐sided bounds. Coverage of confidence intervals for the modified large‐sample approach is either correct or conservative and provides narrower two‐sided widths than the modified three‐moment approach, which can understate coverage on one‐sided and two‐sided bounds for two or three raters. The competing methods are illustrated with data from a reliability study of four raters evaluating the number of decayed, missing, and filled surfaces in the permanent teeth of ten subjects. Overall, the modified large‐sample approach provides the most satisfactory performance of the three methods. Copyright © 2003 John Wiley & Sons, Ltd.
Age‐conditional probabilities of developing cancer
Authors: Fay Michael P. , Pfeiffer Ruth , Cronin Kathleen A. , Le Chenxiong , Feuer Eric J.
Published: May 2003

We propose an estimator of the probability of developing a disease in a given age range, conditional on never having developed the disease prior to the beginning of the age range. Our estimator improves the one described by Wun, Merrill and Feuer ( Lifetime Data Analysis 1998; 4, 169–186) that is currently used by the U.S. National Cancer Institute for the SEER Cancer Statistics Review. Both estimators use cross‐sectional disease rates and provide an interpretation of these rates in terms of the age‐conditional probability of developing disease in a hypothetical cohort. The difficulty of this problem is that rates are not available per person‐years alive and disease free, but only per person‐years alive. Wun et al. used ad hoc methods to handle this problem which did not properly account for competing risks, did not provide a measure of variability, and only allowed age ranges using prespecified 5‐year age intervals. Here we solve the problem under a unified competing risks framework, which allows the calculation of the age‐conditional probabilities for any age range. We generalize gamma confidence intervals to apply to our new statistic. Although our new method provides estimates which are numerically similar to that of Wun et al., this paper provides a comprehensive theoretical basis for estimation and inference about the age‐conditional probability of developing a disease. Published in 2003 by John Wiley & Sons, Ltd.
A maximum likelihood approach for estimating the QT correction factor using mixed effects model
Authors: Shah Amrik , Hajian Gerald
Published: May 2003

Assessment of QT interval prolongation is often used for assessing the cardiac safety of a new drug. However, the correction of the QT interval for varying heart rates has potential bias due to various different correction factors. This article proposes a maximum likelihood (ML) approach for calculating the appropriate individual correction factor using the data. The data come from a study with 24 subjects participating in a 10 day multiple dose (NEW RX) placebo‐controlled cross‐over trial with repeat ECGs obtained at baseline and at day 10. ML techniques were used to fit a random‐effects model to observed QT and HR values for estimating the pooled and individual correction factors. QTc values using four correction factors (Bazett, Friderecia, pooled and individual) were investigated. The relative performance of the various correction factors are given in terms of variability and graphical techniques. The pooled correction factor was estimated to be 0.292 and the individual correction factors ranged from 0.19 to 0.41. The assessment of the treatment effect on QTc yielded inconsistent results. Bazett's factor indicated prolongation (6.55±1.20), Friderecia's factor indicated no change, while the pooled (‐2.92±0.94) and individual (‐2.82±1.00) factors showed a significant decrease. Graphical examination of individual QTc data showed a significant advantage in the use of individual correction factors versus Bazett's factor both in terms of sensitivity as well as reduction in bias. Use of individual correction factors is advocated for the assessment of possible drug‐induced QTc prolongation. Copyright © 2003 John Wiley & Sons, Ltd.
Interval estimates of the probability of toxicity at the maximum tolerated dose for small samples
Authors: Natarajan Loki , O'Quigley John
Published: May 2003

Following on from the work of O'Quigley et al., we investigate the performance of interval estimates of the probability of toxicity following completion of a phase I clinical trial. Our particular focus is on very small sample sizes, not uncommon in phase I studies. Specifically, we study the situations for which the sample sizes are 12 or 16. Simulations are used to show that the coverage of the confidence intervals, even for very modest sample sizes, are close to nominal in most cases. Averaged over the range of situations considered, coverage rates are accurate for both sample sizes of 12 and 16. As for the larger sample size of 20, studied previously, it is possible to obtain further, albeit modest, improvements via the use of the Cornish–Fisher inversion. Copyright © 2003 John Wiley & Sons, Ltd.
Robustness of sample size re‐estimation procedure in clinical trials (arbitrary populations)
Authors: Govindarajulu Z.
Published: May 2003

In clinical trials, one of the main questions that is being asked is how many additional observations, if any, are needed beyond those originally planned. In a two‐treatment double‐blind clinical experiment, one is interested in testing the null hypothesis of equality of the means against one‐sided alternative when the common variance σ2 is unknown. We wish to determine the required total sample size when the error probabilities αand βare specified at a predetermined alternative. Shih provided a two‐stage procedure which is an extension of Stein's one‐sample procedure, assuming normal response. He estimates σ2 by the method of maximum likelihood via the EM algorithm and carries out a simulation study in order to evaluate the effective level of significance and the power. The author proposed a closed‐form estimator for σ2 and showed analytically that the difference between the effective and nominal levels of significance is negligible and that the power exceeds 1‐β when the initial sample size is large. Here we consider responses from arbitrary distributions in which the mean and the variance are not functionally related and show that when the initial sample size is large, the conclusions drawn previously by the author still hold. The effective coverage probability of a fixed‐width interval is also evaluated. Proofs of certain assertions are deferred to the Appendix. Copyright © 2003 John Wiley & Sons, Ltd.
Positive solutions of critical semilinear elliptic equations on non-contractible planar domains
Authors: Struwe Michael
Published: May 2003

For semilinear elliptic equations of critical exponential growth we establish the existence of positive solutions to the Dirichlet problem on suitable non-contractible domains.
Universality for conformally invariant intersection exponents
Authors: Lawler Gregory F. , Werner Wendelin
Published: May 2003

Abstract. We construct a class of conformally invariant measures on sets (or paths) and we study the critical exponents called intersection exponents associated to these measures. We show that these exponents exist and that they correspond to intersection exponents between planar Brownian motions. More precisely, using the definitions and results of our paper [27], we show that any set defined under such a conformal invariant measure behaves exactly as a pack (containing maybe a non-integer number) of Brownian motions as far as all intersection exponents are concerned. We show how conjectures about exponents for two-dimensional self-avoiding walks and critical percolation clusters can be reinterpreted in terms of conjectures on Brownian exponents.
A note on trilinear forms for reducible representations and Beilinson's conjectures
Authors: Harris Michael , Scholl Anthony J.
Published: May 2003

We extend Prasad's results on the existence of trilinear forms on representations of GL2 of a local field, by permitting one or more of the representations to be reducible principal series, with infinite-dimensional irreducible quotient. We apply this in a global setting to compute (unconditionally) the dimensions of the subspaces of motivic cohomology of the product of two modular curves constructed by Beilinson.
Characterization of optimal shapes and masses through Monge-Kantorovich equation
Authors: Bouchitté Guy , Buttazzo Giuseppe
Published: May 2003

We study some problems of optimal distribution of masses, and we show that they can be characterized by a suitable Monge-Kantorovich equation. In the case of scalar state functions, we show the equivalence with a mass transport problem, emphasizing its geometrical approach through geodesics. The case of elasticity, where the state function is vector valued, is also considered. In both cases some examples are presented.
Excision in entire cyclic cohomology
Authors: Meyer Ralf
Published: May 2003

We prove that entire and periodic cyclic cohomology satisfy excision for extensions of bornological algebras with a bounded linear section. That is, for such an extension we obtain a six term exact sequence in cohomology.
The Creation of a Religious Centre: Christianisation in the Diocese of Liège
in the Carolingian Period
Authors: TADA SATOSHI
Published: May 2003

The bishops of Liège became concerned with Christianisation throughout the whole diocese in the Carolingian period. This study examines the concrete measures that they took. The field chosen is the Ardennes region in the south of the diocese, where they reorganised the abbey of St-Hubert as a religious centre. The bishops reformed the community and offered it economic support. They also encouraged the cult of St Hubert and introduced the new custom of annual processions. This approach throws light on the pastoral situation in a way that their episcopal capitularies cannot.
The Martyrs' Memorial at Oxford
Authors: ATHERSTONE ANDREW
Published: May 2003

The Martyrs' Memorial at Oxford is usually interpreted as an anti-Tractarian statement provoked by the publication of R. H. Froude's notorious Remains. This paper argues, however, that the monument's anti-Catholic nature has been overlooked, largely as a result of interpreting the scheme in the light of subsequent developments. Much of the original polemic surrounding the project was directed exclusively against Roman Catholicism and it won support from a wide theological spectrum within the Church of England. The heated debate over the wording of the inscription is examined, as is the question of whether the memorial should take the form of a Martyrs' Church or a Martyrs' Monument.
The Rise and Fall of the Catholic University College, Kensington, 1868–1882
Authors: HORWOOD TOM
Published: May 2003

Cardinal Manning's Catholic University project was a spectacular failure. Financial mismanagement by Thomas John Capel, the Rector, as well as gossip surrounding his personal life, undermined confidence in him and the college. The Jesuits opposed the scheme as it rivalled their own plans. Despite a Vatican ban, the Jesuits, some influential converts, old Catholic families and sympathetic bishops continued to press for Catholic higher education at Oxford, for social reasons and because they preferred the classical education to Manning's scientific syllabus. The project revealed the tensions and divisions caused by Manning's vision of future Catholic engagement in late Victorian society.
The Suppression of Lutheran Heretics in England, 1526–1529
Authors: D'ALTON CRAIG W.
Published: May 2003

This article examines responses to the spread of Lutheranism and related heresies in England during the final years of the ascendancy of Cardinal Thomas Wolsey. It demonstrates that the preferred method for dealing with scholars and others toying with the New Learning was to attempt to convince them of the error of their ways rather than to punish them. The small number of Lutheran heresy trials in the 1520s is shown to be evidence not of a ‘soft’ approach to the growing problem of Lutheran infiltration, but of a successful policy of humanist reform.
Developmental dynamics in L1 and L2 acquisition: Processability Theory and generative entrenchment
Authors: PIENEMANN MANFRED
Published: May 2003

This paper has two major objectives: (1) to summarise Processability Theory, a processing-oriented approach to explaining language development and (2) to utilise this theory in the comparison of development in LI and L2 acquisition. Proponents of the Fundamental Difference Hypothesis (between L1 and L2) assume that L1 development can be explained with reference to Universal Grammar (UG) which, in their view, is inaccessible to L2 learners. Instead, they claim that a second language develops on the basis of language processing strategies.

I will show that the fundamentally different developmental paths inherent in first and second language acquisition can both be explained on the basis of the same language processing mechanics (as specified in Processability Theory). I will demonstrate that the developmental differences between L1 and L2 are caused by the qualitatively different early structural hypotheses which propagate through the acquisition process. The concept of “propagation of structural features” will be viewed as “generative entrenchment,” a logical-mathematical concept, which has proved to be highly productive in examining other kinds of developmental processes.
What's in a process? Explaining development in language acquisition
Authors: BIALYSTOK ELLEN
Published: May 2003

The tension between considering language acquisition to be a process of learning or a process of development is the visible surface of a theoretical iceberg. The difference between learning and development is neither simple nor self-evident, yet the implications that follow from a commitment to one or the other are considerable. Development is usually construed as an unfolding, the impassive evolution of “being.” Children develop physically, cognitively, emotionally almost in spite of themselves; they may not develop to their full potential, and they may require massive environmental support, but even in cases of benign neglect, children will normally become taller, smarter, and more stable. Learning implies a measure of control and responsibility. It depends on experience and on the availability of resources: conceptual, social, intellectual, and so on.
On Processability Theory and second language acquisition
Authors: CARROLL SUSANNE E.
Published: May 2003

Responding to an invitation to comment on Pienemann's paper leaves me on the horns of a dilemma: I think the approach is novel and shows how future second language acquisition (SLA) research can be done. However, it is difficult to judge from the paper what the exact contribution of the theory is to be.
Does the formulator know its LFG?
Authors: DE BOT KEES
Published: May 2003

A problem when reacting to a contribution as rich and as highly interesting as Pienemann's paper,
is that it is much easier to react to what's not in it than to what is. An example is the relation
between the theory proposed and the way linguistic knowledge is acquired: “[Processability theory]
… is not designed to contribute anything to the question of the innate or learnt origin of
linguistic knowledge or the inferential processes by which linguistic input is converted into linguistic
knowledge.” It is not easy to interpret the full consequences of the model if we are not to take
into account the inferential processes by which the learner adds new information to his/her system.
Maybe here the dividing lines are drawn too strictly: if the hypothesis space of the learner is restricted
by the procedures that can be applied, one wonders at what level in the cognitive system these restrictions
are located. Does the conceptualizer already know what the system is capable of doing, or is it uninformed
(as follows from a strict interpretation of Levelt's proposal of an incremental system without
feedforward)? In the latter case, this would mean that the learners/speakers would still try to express
their communicative intentions and only later on in the process would things go wrong, for example,
because the S-procedure cannot be carried out.
Semantic-informational and formal processing principles in Processability Theory
Authors: HULSTIJN JAN
Published: May 2003

Let me begin my comments on Pienemann's keynote paper by expressing my admiration for the scholar who has developed Processability Theory (PT) over a period of some fifteen years with great determination and perseverance. What in earlier publications (e.g. Pienemann, 1985, 1987) appeared to me to be a rather disparate set of principles aiming to account for a limited set of empirical data (the well known sequence of five word orders of the ZISA study), has now evolved into a coherent theory which meets the demands of falsifiability, as PT's claims are formulated in sufficient detail to allow SLA researchers to put them to empirical test. PT comprises a number of principles of great generality, accounting, in principle, for the acquisition of any structure in any language, thereby exceeding the limits of the ZISA data of natural German L2 acquisition. As such, it is to be hoped that PT will have a healthy influence on the field of SLA research, as this field, in the last few years, has perhaps been dominated too much by the issue of whether L2 learners have access to Universal Grammar.
Comparing and explaining the trajectories of first and second language acquisition: in search of the right mix of psychological and linguistic factors
Authors: KEMPEN GERARD
Published: May 2003

When you compare the behavior of two different age groups which are trying to master the
same sensori-motor or cognitive skill, you are likely to discover varying learning routes:
different stages, different intervals between stages, or even different orderings of stages.
Such heterogeneous learning trajectories may be caused by at least six different types of factors:

(1) Initial state: the kinds and levels of skills the learners have available at the onset of the learning episode.

(2) Learning mechanisms: rule-based, inductive, connectionist, parameter setting, and so on.

(3) Input and feedback characteristics: learning stimuli, information about success and failure.

(4) Information processing mechanisms: capacity limitations, attentional biases, response preferences.

(5) Energetic variables: motivation, emotional reactions.

(6) Final state: the fine-structure of kinds and levels of subskills at the end of the learning episode.

This applies to language acquisition as well. First and second language learners probably differ on all six factors. Nevertheless, the debate between advocates and opponents of the Fundamental Difference Hypothesis concerning L1 and L2 acquisition have looked almost exclusively at the first two factors. Those who believe that L1 learners have access to Universal Grammar whereas L2 learners rely on language processing strategies, postulate different learning mechanisms (UG parameter setting in L1, more general inductive strategies in L2 learning). Pienemann opposes this view and, based on his Processability Theory, argues that L1 and L2 learners start out from different initial states: they come to the grammar learning task with different structural hypotheses (SOV versus SVO as basic word order of German).
How to slice the cake?
Authors: MUYSKEN PIETER
Published: May 2003

Manfred Pienemann offers an interesting, fair-minded, and systematic account of the role of processability constraints in explaining language development. Thus he opens up a wide field of research in the area of the interaction of grammatical knowledge and processing constraints, and Pienemann should be applauded for this kick-off. In my view, this field should be explored in a non-partisan manner. Rather than pushing either grammar or processing at the expense of the other, we should be looking at the division of labour between different mental capacities, and at potential sites of overlap, conflict, and convergence. L2 development is crucial in this research, because it may show how much can be accomplished with non-grammatical processing. I will limit myself here to a number of disjointed remarks on some directions for research.
On the “wrong-headedness” of generative entrenchment
Authors: SCHWARTZ BONNIE D.
Published: May 2003

The main thesis Pienemann puts forward is that while L1 acquisition and L2 acquisition of a particular language (e.g. German) exhibit non-parallel paths of development, such a difference does not entail that the processing resources claimed to be responsible for transitioning from one stage to the next are any different in the two situations. The cause of the difference in routes, he suggests, is the difference in departure points. In the German case at hand, L1 acquirers begin with an SOV grammar, while L2 acquisition, according to Pienemann, starts off SVO (“canonical order”). “Generative entrenchment” of SVO is what makes the ensuing development distinct from that of L1 German: “once a decision has been made and a new structure has been added, it is very costly, if not impossible, for the developmental process to move to a different developmental path.” I think there's something very right about this general picture – but also that part of it is “wrong-headed.”
A focus on processing
Authors: PIENEMANN MANFRED
Published: May 2003

Given that my paper touched upon many aspects of L1 an L2 acquisition, it is not surprising that the commentaries have raised a diverse range of issues. Nevertheless, one should not lose sight of the fact that the paper has a tightly defined focus, namely to delineate the influence of language processing factors and developmental dynamics on developmental trajectories in L1 and L2 acquisition, and this is done in a very explicit manner. As Carroll rightly puts it in her commentary, this “[e]xplicitness allows us to formulate questions which could otherwise not be asked.”
Interlingual homograph recognition: Effects of task demands and language intermixing
Authors: DIJKSTRA TON , VAN JAARSVELD HENK , BRINKE SJOERD TEN
Published: May 2003

A series of three lexical decision experiments showed that interlingual homographs may be recognized faster than, slower than, or as fast as monolingual control words depending on task requirements and language intermixing. In Experiment 1, Dutch bilingual participants performed an English lexical decision task including English/Dutch homographs, cognates, and purely English control words. Reaction times to interlingual homographs were unaffected by the frequency of the Dutch reading and did not differ from monolingual controls. In contrast, cognates were recognized faster than controls. In Experiment 2, Dutch participants again performed an English lexical decision task on homographs, but, apart from nonwords, Dutch words were included which required a “no” reaction. Strong inhibition effects were obtained which depended on the relative frequency difference of the two readings of the homograph. These turned into frequency-dependent facilitation effects in Experiment 3, where participants performed a general lexical decision task, responding “yes” if a word of either language was presented. It is argued that bilingual word recognition models can only account for the series of experiments if they explain how lexical processing is affected by task demands and stimulus list composition.
Attitudes toward psychiatry among students entering medical school
Authors: Malhi G. S. , Parker G. B. , Parker K. , Carr V. J. , Kirkby K. C. , Yellowlees P. , Boyce P. , Tonge B.
Published: May 2003

Objective:  To survey the attitudes of Australian medical students to determine their views about the relative attractiveness of psychiatry as a career compared with other specialities, and against findings from a North American study.

Method:  We surveyed 655 first‐year medical students attending six Australian Universities.

Results:  Responses indicated that Australian medical students view psychiatry as distinctly less ‘attractive’ than other career options, as reported in the North American sample. In comparison with other disciplines, psychiatry was regarded as more interesting and intellectually challenging, but also as lacking a scientific foundation, not being enjoyable and failing to draw on training experiences.

Conclusion:  Our findings suggest that psychiatry has an image problem that is widespread, reflecting community perceptions and the specialist interests of medical students on recruitment. If psychiatry is to improve its ‘attractiveness’ as a career option, identified image problems need to be corrected and medical student selection processes re‐considered.
A follow‐up study of juvenile obsessive–compulsive disorder from India
Authors: Janardhan Reddy Y. C. , Srinath S. , Prakash H. M. , Girimaji S. C. , Sheshadri S. P. , Khanna S. , Subbakrishna D. K.
Published: May 2003

Objective:  To study the long‐term course and outcome of juvenile obsessive–compulsive disorder (OCD).

Method:  Two to 9‐year follow‐up of largely self‐referred, drug‐naïve subjects (n = 58) by employing catch‐up longitudinal design.

Results:  The mean follow‐up period was 5 years. Nearly three‐fourth of the sample was adequately treated with medications. Only 21% of the subjects had clinical OCD at follow‐up and 48% were in true remission (no OCD and not on treatment). Earlier age‐at‐onset was associated with better course and outcome.

Conclusion:  Juvenile OCD has favorable outcome. Our findings are applicable to psychiatric hospital settings in India and perhaps to the general psychiatric settings in the Western countries. Whether the better outcome in this sample is the result of differing clinical characteristics or because of true cross‐cultural variation in the course needs further exploration. It is speculated that early onset OCD could be a subtype of juvenile OCD with better outcome.
A case study of an extremely violent serial rapist with borderline personality disorder in remission
Authors: Martens W. H. J.
Published: May 2003

Objective:  To provide evidence that some borderline patients with poor prognosis can obtain complete remission.

Method:  Case of a violent rapist with borderline personality disorder in remission is reported. An attempt was made to reveal the mechanism of recovery in this forensic patient who initially was assessed as psychotherapeutically untreatable.

Results:  Psychotherapeutic effects and favourable psychosocial factors such as successful college graduation, increased social–emotional capacities and valuable new relationships did also play a very important role in this remission process.

Conclusion:  Controlled studies are necessary to elucidate the mechanism of recovery among criminal patients with borderline personality disorder in order to provide adequate treatment programmes and to construct more reliable prediction methods for prognosis and reoffending.
Shared decision making in psychiatry
Authors: Hamann J. , Leucht S. , Kissling W.
Published: May 2003

Objective: In other medical fields, ‘shared decision making’ (a strategy for including patients in therapeutic decision processes) has been studied for several years now. This survey presents the potential of shared decision making for psychiatry.

Method: Literature search.

Results: Research in other medical fields shows that shared decision making positively influences patients’ satisfaction as well as health outcomes. The application of shared decision making to psychiatry is still in the initial stage.

Conclusion: Evidence that shared decision making can be successfully practiced in psychiatry would contribute to an improved inclusion of psychiatric patients in therapeutic decisions and thereby help to implement basic rights of a group of patients who have not sufficiently benefited from consumer empowerment in other medical fields.
Can presence or absence of periodontal pathogens distinguish between subjects with chronic and aggressive periodontitis? A systematic review
Authors: Mombelli Andrea , Casagni Federico , Madianos Phoebus N.
Published: May 2003

Objectives:  The purpose of this study was to determine to what extent the presence or absence of periodontal pathogens can distinguish between subjects with chronic and aggressive periodontitis.

Material and Methods:  A systematic review of cross sectional and longitudinal studies providing microbiological data both from patients with chronic periodontitis (ChP) and aggressive periodontitis (AgP) at a subject level. Strict inclusion criteria were applied. The presence or absence of five microorganisms was selected as primary study parameters: Actinobacillus actinomycetemcomitans (AA), Porphyromonas gingivalis (PG), Prevotella intermedia (PI), Bacteroides forsythus (BF), and Campylobacter rectus (CR).

Results:  The presence or absence of AA could be evaluated in 11 papers. In seven papers the presence or absence of PG could be analysed. Subject specific data on PI were available from six studies. Two studies could be used regarding the presence or absence of BF, and two regarding CR. Sensitivity and specificity of every microbiological test were individually calculated for each selected study, assuming that the clinical diagnosis of AgP or ChP was the true status the tests attempted to detect. AgP was considered to be the condition of interest and ChP was considered equivalent to ‘non‐AgP’. Receiver Operator Characteristic (ROC) diagrams were constructed using these data. ROC diagrams indicated the limited discriminatory ability of all of the test parameters to identify subjects with AgP. An additional assessment showed that the highly leukotoxic variant of AA was uniquely associated with patients suffering from aggressive periodontitis. However, in a high proportion of patients diagnosed with AgP the presence of this variant could not be detected.

Conclusion:  The presence or absence of AA, PG, PI, BF or CR could not discriminate between subjects with AgP from those with ChP.
A systematic review of the effect of anti‐infective therapy in the treatment of peri‐implantitis
Authors: Klinge Björn , Gustafsson Anders , Berglundh Tord
Published: May 2003

The aim of this systematic review was to assess the treatment of peri‐implantitis with special emphasis on the role of anti‐infective therapy. No randomized controlled clinical trial was available for analysis. Of 145 peri‐implant studies initially screened, 21 studies (six human and 15 animal studies) were analysed regarding the outcome of treatment of peri‐implantitis. A multitude of treatment regimens, including anti‐infective therapy, was reported. The antibiotic regimens varied between studies. No standardized medication protocol was used. Type of antibiotic, dosage, duration and time for initiation of antibiotic treatment were different for all studies, but details were not always reported. A non‐medicated control group was reported in one animal experiment only. The outcomes following anti‐infective treatment of peri‐implantitis are highly variable. The evidence for a consistent and clinically relevant advantage using antibiotics can be questioned in this context. There are to date no data available to support specific treatment protocols. It is suggested that randomized human controlled clinical trials for the treatment of peri‐implantitis be initiated.
A systematic review of the survival of implants in bone sites augmented with barrier membranes (guided bone regeneration) in partially edentulous patients
Authors: Hämmerle Christoph H. F. , Jung Ronald E. , Feloutzis Andreas
Published: May 2003

The aim of the present systematic review was to assess the survival of implants in regenerated bone applying the method of guided bone regeneration (GBR) compared with the survival of implants in non‐regenerated bone. Studies to be included in this review needed to provide at least 12‐month results following prosthetic reconstruction of titanium implants in bone regenerated by GBR with or without membrane supporting materials. The outcome measures were implant survival described as presence of implant, implant success (according to the criteria in the respective study), absence of clinical implant mobility, absence of implant fracture, absence of progressive peri‐implant crestal bone loss as assessed on radiographs without clinical signs of peri‐implant infection, absence of peri‐implant infection with suppuration. A MEDLINE search and a hand search of relevant scientific journals were conducted including studies from the year 1990 to May 2001. A total of 11 studies could be identified fulfilling the inclusion criteria. All studies except two had the characteristics of case series or cross‐sectional surveys. The two different studies had both test and control implants included in their analysis and qualified as controlled clinical trials. Cumulative success or survival rates, respectively, for implants in regenerated bone ranged from 100% after 5 years to 79.4% after 5 years of function. Regarding survival data, no significant differences were found in the controlled clinical trials between implants in regenerated compared to implants in non‐regenerated bone. Within the limits of this systematic review characterized by second and third levels of evidence, the following conclusions can be drawn: The survival rate of implants placed into sites with regenerated/augmented bone using barrier membranes varied between 79% and 100% with the majority of studies indicating more than 90% after at least one year of function. The survival rates obtained in the present systematic review are similar to those generally reported for implants placed conventionally into sites without the need for bone augmentation.
A guide to systematic reviews
Authors: Needleman Ian G.
Published: May 2003

Systematic reviews have become widely used for evaluating evidence across all fields of biomedicine. The objective of a systematic review is to provide a comprehensive and contemporary appraisal of research using transparent methods whilst aiming to minimize bias. In essence, research methodology is employed in the conduct of the review. Such reviews are therefore fundamentally different from traditional ‘narrative’ review articles in their purpose and in their potential to aid clinical decision‐making. This paper is a guide to the rationale and nature of systematic reviews and will provide a background to understanding their use in clinical practice.
Is periodontitis associated with an increased risk of coronary heart disease and preterm and/or low birth weight births?
Authors: Madianos Phoebus N. , Bobetsis Georgios A. , Kinane Denis F.
Published: May 2003

The objective of this systematic review was to determine whether periodontal disease is associated with an increased risk for coronary heart disease (CHD) and preterm and/or low birth weight deliveries (PLBW). A literature search was performed to identify cross‐sectional, case‐control, and cohort studies as well as clinical trials addressing different aspects of periodontal disease (clinical, microbial, immunological) and clinical outcomes of CHD or PLBW. The periodontitis–CHD association was evaluated in eight cohort, four case‐control‐ and four cross‐sectional studies. Meta‐analysis was not performed due to the extensive heterogeneity of the studies, particularly with regard to periodontitis measures, which varied from full mouth probing assessments to questionnaires. Percentage‐wise, 50% of the cohort studies (4/8), 75% of the case‐control studies (3/4) and 50% of the cross‐sectional studies (2/4) reported a significant association between clinical measures of periodontitis and CHD (excess risk ranged from 0 to 3.3‐fold). The periodontitis–PLBW association was evaluated in one cohort and two case‐control studies. The cohort study as well as one of the two case‐control studies reported a significant association between periodontitis and PLBW (odds ratios 4.4–7.9). From two additional case‐control studies microbiological data could be extracted. Bacteroides forsythus was found to be associated with PLBW in both studies. In conclusion, the evidence linking periodontitis with an increased risk for CHD and PLBW is limited. There is a clear need for new, well designed observational and intervention studies to confirm the thus far observed associations, explore the validity of the associations in diverse populations, establish whether they are causal in nature and determine potential benefits of periodontal intervention in reducing the risk for these conditions.
A systematic review of efficacy of machine‐driven and manual subgingival debridement in the treatment of chronic periodontitis
Authors: Tunkel J. , Heinecke A. , Flemmig T. F.
Published: May 2003

Objectives:  The purpose of this systematic review was to determine the efficacy of machine‐driven compared with manual subgingival debridement in the treatment of periodontitis.

Background:  Mechanical debridement of the periodontal pocket plays a pivotal role in the treatment of periodontitis.

Methods:  A literature search for controlled clinical trials with at least 6 months' follow‐up comparing machine‐driven instruments with hand instruments for the treatment of chronic periodontitis was performed up to April 2001. Screening of titles and abstracts as well as data extraction was conducted independently by two reviewers (J.T. & T.F.F.). As primary outcome variable, the prevention of tooth loss was used; secondary outcome variables were the prevention of disease progression, the resolution of anatomical defects and the resolution of gingival inflammation. Efficiency was assessed by mean time needed to treat one tooth.

Results:  From a total of 419 abstracts, 27 articles were included for the review. The weighted kappa score for agreement between the two reviewers was 0.77, 95% CI: 0.65–0.89, indicating substantial agreement. No study reported on the selected primary outcome variables. Using clinical attachment gain, probing pocket depth reduction or bleeding on probing reduction as outcome variables, there appeared to be no differences between ultrasonic/sonic and manual debridement. No major differences in the frequency or severity of adverse effects were found. However no meta‐analysis could be performed on any of the previously mentioned parameters. Ultrasonic/sonic debridement was found to take significantly less time, i.e. 36.6%, than debridement using hand instruments (P = 0.0002, 95% CI of the standardized effect estimate: 0.39–1.37, heterogeneity P = 0.77).

Conclusions:  With respect to clinical outcome measures, the available data do not indicate a difference between ultrasonic/sonic and manual debridement in the treatment of chronic periodontitis for single‐rooted teeth; however, the evidence for this is not very strong. In addition, ultrasonic/sonic subgingival debridement requires less time than hand instrumentation. Further research is needed to assess the efficacy of machine‐driven debridement on multirooted teeth and clinical outcome variables having tangible benefit to the patients should be used.
A systematic review of the  effect of surgical debridement vs.  non‐surgical debridement for the treatment of chronic periodontitis
Authors: Heitz‐Mayfield L. J. A. , Trombelli L. , Heitz F. , Needleman I. , Moles D.
Published: May 2003

Objective:  To systematically review the evidence of effectiveness of surgical vs. non‐surgical therapy for the treatment of chronic periodontal disease.

Methods:  A search was conducted for randomized controlled trials of at least 12 months duration comparing surgical with non‐surgical treatment of chronic periodontal disease. Data sources included the National Library of Medicine computerised bibliographic database MEDLINE, and the Cochrane Oral Health Group (COHG) Specialist Trials Register. Screening, data abstraction and quality assessment were conducted independently by multiple reviewers (L.H., F.H., L.T.). The primary outcome measures evaluated were gain in clinical attachment level (CAL) and reduction in probing pocket depth (PPD).

Results:  The search provided 589 abstracts of which six randomized controlled trials were included. Meta‐analysis evaluation of these studies indicated that 12 months following treatment, surgical therapy resulted in 0.6 mm more PPD reduction (WMD 0.58 mm; 95% CI 0.38, 0.79) and 0.2 mm more CAL gain (WMD 0.19 mm; 95% CI 0.04, 0.35) than non‐surgical therapy in deep pockets (>6 mm). In 4–6 mm pockets scaling and root planing resulted in 0.4 mm more attachment gain (WMD −0.37 mm; 95% CI −0.49, −0.26) and 0.4 mm less probing depth reduction (WMD 0.35 mm; 95% CI 0.23, 0.47) than surgical therapy. In shallow pockets (1–3 mm) non‐surgical therapy resulted in 0.5 mm less attachment loss (WMD −0.51 mm; 95% CI −0.74, −0.29) than surgical therapy.

Conclusions:  Both scaling and root planing alone and scaling and root planing combined with flap procedure are effective methods for the treatment of chronic periodontitis in terms of attachment level gain and reduction in gingival inflammation. In the treatment of deep pockets open flap debridement results in greater PPD reduction and clinical attachment gain.