bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficiency of the logistic regression and cox proportional hazards models in longitudinal studies
Authors: Annesi Isabella , Moreau Thierry , Lellouch Joseph
Published: April 2007

Both logistic regression and Cox proportional hazards models are used widely in longitudinal epidemiologic studies for analysing the relationship between several risk factors and a time‐related dichotomous event. The two models yield similar estimates of regression coefficients in studies with short follow‐up and low incidence of event occurrence. Further, with just one dichotomous covariate and identical censoring times for all subjects, the asymptotic relative efficiency of the two models is very close to 1 unless the duration of follow‐up is extended. We generalize this result to several qualitative or quantitative covariates. This was motivated by the analysis of mortality data from a study where all subjects are followed up during the same fixed period without loss except by death. Logistic and Cox models were applied to these data. Similar results were obtained for the two models in shorter periods of follow‐up of five years or less, but not in longer periods of ten years or more, where the survival rate was lower.
A cautionary note on the use of autoregressive models in analysis of longitudinal data
Authors: Stanek Edward J. , Shetterley Susan S. , Allen Lindsay H. , Pelto Gretel H. , Chavez Adolfo
Published: April 2007

Rosner et al. presented a simple, easily implemented modelling method for retaining time order relationships in analyses of longitudinal data when successive measures are correlated. Evaluation of time order is particularly useful in epidemiologic studies concerned with exposure to potentially toxic substances and subsequent outcome, but may also have use in more traditional growth studies that relate intake to subsequent development. The analysis allows for unequally spaced measures and missing data. The estimation method permits varying numbers of observations per subject and, with measures equally spaced, one can fit the model with use of ordinary least squares regression software. We report on a potential false association that can result when both exposure and outcome are related to time. We illustrate this problem with a small scale simulation and example. We also note a more serious problem with Rosner's approach in interpreting parameters. Although the model may be useful for prediction, parameters depend on the autocorrelation and are not readily interpretable. We recommend alternative modelling strategies be used when autocorrelation of errors is suspected.
Single‐stage cluster sampling with a telescopic respondent rule: A variation motivated by a survey of dementia in elderly residents of Shanghai
Authors: Levy Paul S. , Yu Elena S. H. , Liu William T. , Wong Siu‐Chi , Zhang Ming‐Yuan , Wang Zheng‐Yu , Katzman Robert
Published: April 2007

In this report, we consider the situation in which one wishes to identify a cohort of a specified number of individuals within each of several domains for future follow‐up studies based on a single‐stage cluster sampling design. We develop sample size formulae relevant to this situation and introduce a variation of single‐stage cluster sampling that seems more suitable in this situation than is ordinary single‐stage cluster sampling. The basis for this variation is the concept that the definition of eligible respondents is not the same for all clusters. The use of this modified respondent rule (which we call telescopic) enables one to meet specified sample sizes in all domains of interest without the need to sample extra individuals in some domains. We used a version of this sampling design successfully in the field with a survey of elderly persons conducted in Shanghai, People's Republic of China.
Cost and efficiency in clinical trials: The U.S. physicians' health study
Authors: Buring Julie E. , Hennekens Charles H.
Published: April 2007

The U.S. Physicians' Health Study, a primary prevention trial of low‐dose aspirin in the reduction of cardiovascular disease and of beta‐carotene in lowering cancer risk, implemented a number of design strategies to decrease costs and increase efficiency. These included the choice of physicians as the study population, use of a factorial design, implementation of a pre‐randomization run‐in phase, and the collection of pre‐randomization blood specimens. The use of these strategies enabled us to enroll 22,071 subjects and maintain high compliance and long‐term follow‐up at a fraction of the usual cost of large‐scale trials of primary prevention.
Sickle cell anaemia trial
Authors: Gaston Marilyn Hughes , Verter Joel
Published: April 2007

The major cause of death in sickle cell anaemia is from infection, especially infection caused by Streptococcus pneumoniae. Meningitis, pneumonia and septicaemia caused by this organism are the primary types of infection leading to death. Children under three years of age are at highest risk. We have known for over twenty years that approximately 30 per cent of the infants born with sickle cell anaemia will become infected in the first three years of life and one‐third can be expected to die from the infection. These data were the reason that we conducted the Prophylactic Penicillin Study (PROPS), a trial to investigate the effectiveness of oral prophylactic penicillin in preventing severe infection due to S. pneumoniae.

This investigation was a very efficient, cost effective study because of its timeliness and its conduct within the framework of an ongoing study. Moreover, the question being answered was simple and focused with up‐to‐date data that permitted accurate estimates of sample size and incidence.
Factorial and reciprocal control designs
Authors: Byar David P.
Published: April 2007

The basic principles of factorial designs are briefly reviewed and estimating equations for a 23 factorial design are presented in order to show how easily the basic idea of the 2 × 2 factorial design generalizes to higher dimensions. Fractional factorial designs are explained and advocated for situations in which the number of experimental groups might otherwise become unmanageably large or costly. Actual examples of use in medical settings are presented for both a 23 full factorial and a half‐fractional 24 design. A new class of designs called reciprocal control designs is proposed for certain disease screening studies. An example is provided by a study designed to screen for lung, colorectal, and prostate cancers.
The role of internal pilot studies in increasing the efficiency of clinical trials
Authors: Wittes Janet , Brittain Erica
Published: April 2007

Investigators often design clinical trials without knowing precisely the values of such necessary parameters as the variances or the event rates in the control group. In order to determine reasonable values for such parameters, they may design a small pilot study external to the main trial. In this paper we propose designs, which we term internal pilot studies, that designate a portion of the main trial as a pilot phase. At the end of the internal pilot study, the investigators recompute preselected parameters and recalculate required sample size. The study then proceeds with the modifications dictated by the internal pilot. Final analyses of the results incorporate all data, disregarding the fact that part of the data came from a pilot phase. As one example of this type of design, we consider a study to compare two normally distributed means. By simulation, we show a numerical example for which the effect of the procedure on the α‐level is negligible, but the potential gain in power considerable. We urge considering a similar approach for a number of types of endpoints.
An examination of the efficiency of some quality assurance methods commonly employed in clinical trials
Authors: Neaton James D. , Duchene Alain G. , Svendsen Kenneth H. , Wentworth Deborah
Published: April 2007

The cost and efficiency of training clinical centre staff and of duplicate data entry in clinical trials is reviewed. Training is an essential component of quality assurance programmes and it is usually carried out at regular intervals in long‐term clinical trials. Initial training of staff and regular retraining is important to assure standardization and it can lead to reduced trial costs. Interim training for new staff and for remedial purposes is less efficient than regularly scheduled training sessions. Regional centres for training and the use of computer aided instruction are two ways such interim training can be made more efficient and standardized. Duplicate data entry or verification can result in a substantial reduction in data entry errors depending on the nature of the data being keyed. Selective verification should especially be considered for important fields for which consistency checks cannot be performed, that are alphabetic or that are several characters in length. Quality assurance procedures should be implemented to monitor data entry accuracy in clinical trials.
Efficient use of endpoints in clinical trials: A clinical perspective
Authors: Terrin Michael L.
Published: April 2007

Efficiencies in the use of endpoints in clinical trials are hard won, not easy. They depend upon the shifting of study resources among clinical centres and central units, as well as between numbers of participants and the costs of the endpoint measurement. Costs of endpoint measurement and evaluation do not tell the whole story; nor do costs multiplied by the total number of patients to be recruited; other costs generated by a particular endpoint must also be taken into account. Each clinical trial must be considered separately for the efficient use of endpoints.
The applicability of results of streamlined trials to clinical practice: The myocarditis treatment trial
Authors: O'connell John B. , Mason Jay W.
Published: April 2007

The application of the results of clinical trials to medical practice depends in part upon the understanding and acceptance of study results by the practising physician. Involving non‐academic practitioners as investigators in streamlined trials is an effective means to increase enrolment and minimize cost. Streamlining data collection to accommodate the needs of the practitioner, however, decreases the amount of scientifically and clinically relevant data that are collected. More important, biased enrolment is more likely in this setting. Modifications in organization and design of the Myocarditis Treatment Trial form an example of streamlining an ongoing clinical trial to enhance enrolment.
Hypothesis versus significance testing for controlled clinical trials: A dialogue
Authors: Salsburg David
Published: April 2007

The mathematical formulations of Neyman‐Pearson hypothesis testing and the Fisherian concept of significance tests are examined as alternative ways of applying statistical models to data from clinical trials.
A sequential phase II/III trial for binary outcomes
Authors: Storer Barry E.
Published: April 2007

This paper describes a simple two‐stage design for randomized clinical trials with a binary outcome. An early stopping criterion applies to results in the experimental arm only and seeks to evaluate that arm with respect to some external standard of efficacy. Stopping rules are similar to those commonly used in phase II designs. This design has no adverse impact on the overall type I error rate, though one must increase sample size to accommodate a modest loss in power.
The choice of a balanced allocation method for a clinical trial in otitis media with effusion
Authors: Zielhuis G. A. , Straatman H. , Van 'T Hof‐Grootenboer A. E. , Van Lier H. J. J. , Rach G. H. , Van Den Broek P.
Published: April 2007

We review the choice of treatment allocation procedures in a specific small clinical trial of the effect of tympanostomy tubes on language development in patients with otitis media with effusion. The options for balanced allocation available at the planning stage are discussed. A clearly favourable method could not be identified. A simulation study was performed, and its results demonstrated least imbalance with the variance method. In practice this method produced considerable imbalance on relevant prognostic factors.
Bias in the one‐step method for pooling study results
Authors: Greenland Sander , Salvan Alberto
Published: April 2007

The one‐step (Peto) method for obtaining pooled effect estimates can yield extremely biased results when applied to unbalanced data. Even for balanced studies, the one‐step estimate may incorporate an unacceptable degree of bias. In place of the one‐step estimate, we recommend use of ordinary Mantel‐Haenszel, weighted least squares, or maximum likelihood estimates whenever the total number of events is adequate for such methods. If the total number of events is small, we recommend exact methods.
Predicting response to treatment: Differentiating active‐factor and non‐specific effects
Authors: Young Michael A. , Fogg Louis F.
Published: April 2007

An important step in providing treatment is prediction of which treatments will be effective for which patients. Common methods for prediction of efficacy, however, are inconsistent with the assumptions of the standard placebo‐control paradigm for establishment of efficacy. This is because in prediction of the observed response, one ignores the distinction between response attributable to non‐specific factors and that attributable to active‐treatment factors. This paper presents a paradigm for the use of log‐linear analysis that allows for the development of predictive methods that take into account this distinction. An example with simulated data demonstrates how, if this distinction is ignored, one can reach misleading conclusions and make non‐optimal treatment decisions as a result of an inaccurate cost ‐ benefit analysis of the treatment.
Optimal choice of prognostic variables with an application to cardiac monitoring using M‐mode echocardiography
Authors: Puterman Martin L. , Schumacher Peter , Sandor George G. S.
Published: April 2007

This paper provides a methodology for the optimal choice of a subset from a large number of interrelated diagnostic variables. We use predetermined abnormal ranges for each measurement and code subjects as abnormal or normal on this basis. We present a procedure to determine the smallest subset of measurements that identifies any subject abnormal on at least one measurement. We formulate and solve the problem using integer programming. We then apply this methodology to study the use of M‐mode echocardiography to determine potentially cardiotoxic side effects of chemotherapy and compare its performance to several multivariate methods. Extensions and modifications are discussed.
The proportionate mortality ratio and its relationship with measures of mortality
Authors: Hansen Eva Stottrup
Published: April 2007

Under certain circumstances a proportionate mortality ratio (PMR) equals the cause‐specific standardized mortality ratio (SMR) divided by the overall SMR. In this paper, the relationship between PMR and SMR is derived stepwise with focus on the conditions that must be fulfilled for each step of the derivation to be valid. It appears essential that the following conditions be fulfilled: (1) the compared populations are closed throughout the period of study; (2) all deaths (or a representative sample) in the compared populations are included in the analysis; (3) every dead person is assigned to exactly the same exposure category that he or she would have been assigned to in a follow‐up study; and (4) possible diagnostic misclassification is not exposure‐dependent. Furthermore, for dead people within the comparison group, the relative frequency of the cause of death of interest must be constant over age. In view of this it is recommended that PMR studies of occupational mortality are designed to cover only a short period; to use data from national or regional death certificate registries only; to be restricted to lifetime occupations; to make use of a hand‐picked comparison group that has had the same access to medical care and diagnosis as the index group; and to restrict the PMR analysis to age‐at‐death strata in which the relative frequency of the studied cause of death is constant in the comparison group of deceased persons.
An application of the LFP survival model to smoking cessation data
Authors: Koehler Kenneth J. , McGovern Paul G.
Published: April 2007

We use a limited failure population (LFP) model based on the Weibull distribution to model the times from initial abstinence to return to smoking for subjects enrolled in programmes to help them stop smoking. The model contains a third parameter that corresponds to the proportion of subjects who permanently abstain from smoking. The data are subject to both right and interval censoring. Furthermore, subjects receive treatment in groups, and individuals in the same group may provide correlated outcomes. Use of a maximum likelihood estimation procedure which assumes independent outcomes provides reasonable parameter estimates, but the corresponding standard errors tend to be too small, which results in tests with inflated type I error levels and confidence intervals that tend to be too narrow. We use a bootstrap procedure to obtain more reasonable values for the standard errors and to construct confidence intervals that more nearly achieve the stated coverage probabilities.
Estimation of risk ratios in case‐base studies with competing risks
Authors: Flanders W. Dana , Dersimonian Rebecca , Rhodes Philip
Published: April 2007

The case‐base study is a recently developed modification of the case‐control design that leads to risk ratio estimates. Currently available methods for the analysis of case‐base studies lead to estimates of the unconditional risk ratio which may be misleading if censoring occurs. In this manuscript, we describe an approach for the analysis of case‐base studies that yields conditional risk ratio estimates which remain valid in the presence of censoring. The approach we propose for estimating risk ratios and their standard errors involves a non‐iterative procedure.
Murphy's law of limiting dilution cloning
Authors: Staszewski Robert
Published: April 2007

Conventional practice and literature on limiting dilution cloning address the irrelevant problem of selection of a single progenitor from a uniform population, and provide optimistic estimates of monoclonality for interesting cultures and subcultures. Any cell line established via these estimates is suspect and may be polyclonally metastable. Cultures derived by limiting dilution of the progenitors of independently Poisson distributed populations obey a counterintuitive relation with the characteristics of a Murphy's law: the probability that an interesting culture is monotypic or monoclonal is less than that of a random non‐sterile culture, decreases for increasingly rare interesting cultures, and is bounded below by the probability of sterility. A priori and empiric a posteriori estimates of the probability that interesting subcultures are monotypic or monoclonal are derived consistent with this principle.
Biplots in biomedical research
Authors: Gabriel K. Ruben , Odoroff Charles L.
Published: April 2007

The biplot is a graphical display of multivariate data. A number of examples from biomedical research illustrate its use. Biplots allow for inspection of data preliminary to formal analysis, and can follow an analysis by the graphical inspection of residuals. The simplicity and intuitive appeal of these displays is stressed. An appendix indicates their method of construction and the software for producing them.
Must clinical trials be large? The interpretation of p‐values and the combination of test results
Authors: Barnard G. A.
Published: April 2007

The notion that small, well planned clinical trials may not be worth undertaking is shown to arise from an overemphasis on just one way of interpreting P‐values. Alternative forms of P and other interpretations are put forward. Attention is drawn to some aspects of the theory of hypothesis testing which seem less well known than they should be.
Some historical and methodological developments in early clinical trials at the national institutes of health
Authors: Greenhouse Samuel W.
Published: April 2007

This paper reviews five randomized clinical trials with unusual design or analysis features from institutes other than the National Cancer Institute or the National Heart, Lung and Blood Institute. These are: a Cooperative Study of Retrolental Fibroplasia sponsored by the National Institute of Neurological Diseases and Blindness; the Diabetic Retinopathy Study sponsored by the National Eye Institute; the University Group Diabetes Program sponsored by the National Institute of Arthritis and Metabolic Diseases; a Clinical Trial of the Extracranial to Intracranial Arterial Anastomosis (EC/IC bypass) by the National Institute of Neurological and Communicative Disorders and Stroke; and the Clinical Trial of Hereditary Angioedema by the National Institute of Allergy and Infectious Diseases.
Estimating correlation between alternative measures of disease progression in a longitudinal study
Authors: Schluchter Mark D.
Published: April 2007

A primary outcome variable in longitudinal studies is often the rate of change of a continuous measurement over time. Examples include the one‐second forced expiratory volume (FEV1) in pulmonary studies or glomerular filtration rate (GFR) in renal studies. An individual patient's least‐squares estimate of slope obtained from a linear regression is an imprecise measure of the true slope for that patient, and correlations involving the estimated slopes will be biased due to this measurement error. This paper presents methods for estimating the true correlation between these imprecise slope estimates, or between slope estimates and other variables measured with error. In addition to providing a simple consistent estimator of the correlation, we show how the maximum likelihood estimate of the correlation coefficient and a 100(1 — α) per cent confidence interval can be obtained. An example estimating the correlation between GFR and inverse serum creatinine slopes in patients with chronic renal disease is given.
Prognostic scores for detecting a high risk group: Estimating the sensitivity when applied to new data
Authors: Phillips Andrew N. , Thompson Simon G. , Pocock Stuart J.
Published: April 2007

The sensitivity of a prognostic scoring system will tend to be exaggerated if the scoring system is both derived and validated on the same data. This paper provides, by analogy to regression with error in an explanatory variable, an intuitive basis for the methodological results of Copas which seek to estimate the degree of such exaggeration. There was good agreement between Copas' results and those achieved in a series of cross‐validation exercises where logistic regression models predicting the risk of ischaemic heart disease were derived using data from the prospective British Regional Heart Study. When truly important variables were included, the exaggeration of the sensitivity increased as the number of cases of disease available decreased. It is concluded that Copas' method, which is easy to implement in practice, may be helpful in realistically anticipating the extent of such exaggeration, and that it can be usefully employed before pursuing a scoring system on newly collected data.
Variation in heart disease mortality across census tracts as a function of overdispersion and social class mixture
Authors: Jarjoura David , Logue Everett
Published: April 2007

Variation in heart disease (HD) mortality rates across census tracts is greater than expected given binomial error and available explanatory variables. We extended an extra‐binomial variation model for rates standardized by the direct method. The overdispersion parameter accounted for 36 per cent of the observed variation in standardized rates. Ignoring overdispersion resulted in a change in an estimate of the effect of social class on HD mortality and substantial underestimation of the error of the estimates of such effects. Ecologic regression on the proportional mixture of social classes within tracts provided an appealing approach to the problem of estimating fixed effects with aggregated data.
The graphical representation of clinical trials with particular reference to measurements over time
Authors: Senn S. J. , Auclair P. , Johnson Samuel
Published: April 2007

Clinical trials are frequently analysed as if they were surveys when they are in fact experiments. In particular the experimental basis of clinical trials is rarely reflected in the graphs which are used to illustrate them. Proposals are made, and illustrated by example, as to how appropriate figures may be devised, both for parallel‐group designs and for crossover trials, to illustrate the experimental nature of clinical trials with measurements over time.

It is incident to physicians, I am afraid, beyond all men, to mistake subsequence for consequence.
Quantifying misclassification bias in cohort studies of vaccine efficacy
Authors: Farrington Conor Patrick
Published: April 2007

A simple mathematical model is presented to quantify the bias due to misclassification in prospective cohort studies of vaccine efficacy. Limitations of methods based on quantifying misclassification in 2 × 2 tables are discussed. The model is applied to data from three examples of the design and analysis of studies of pertussis vaccine efficacy.
Adjusting for misselection using subsampling in epidemiological studies
Authors: Blettner Maria , Becher Heiko
Published: April 2007

In epidemiological research it is sometimes necessary to conduct a case‐control study in a part of the population which is not exposed to certain risk factors. Such a study design may be useful to investigate the risk related to a weak carcinogen in presence of other strong risk factors. It may happen that some individuals are wrongly included in the study group due to misreporting of the true exposure status. This misselection may cause biased odds ratio estimates of the factors of interest. It is therefore recommended that an evaluation study to validate the selection procedure is undertaken. We propose a two‐stage sample design, consisting of a case‐control study and a validation study in a subsample. Misselection rates in cases and control for different exposure groups may be estimated in the subsample and used to correct the odds ratio estimation from the first stage. It is shown how the total sample size should be attributed to the case‐control sample and to the second‐stage sample in order to give an unbiased estimate with minimal variance. The allocation is shown to be dependent on a number of parameters which is illustrated numerically and graphically. Efficiency considerations are also addressed.
Test statistics and sample size formulae for comparative binomial trials with null hypothesis of non‐zero risk difference or non‐unity relative risk
Authors: Farrington Conor P. , Manning Godfrey
Published: April 2007

When it is required to establish a materially significant difference between two treatments, or, alternatively, to show that two treatments are equivalent, standard test statistics and sample size formulae based on a null hypothesis of no difference no longer apply. This paper reviews some of the test statistics and sample size formulae proposed for comparative binomial trials when the null hypothesis is of a specified non‐zero difference or non‐unity relative risk. Methods based on restricted maximum likelihood estimation are recommended and applied to studies of pertussis vaccine.
Statistical methods for determining risk factors of chronic otitis media with effusion
Authors: Le Chap T. , Lindgren Bruce R.
Published: April 2007

We use logistic regression with paired Bernouilli outcomes to analyse data on subjects who have either one or two organs (e.g. ears) each of which may develop disease. In this model, subject‐specific covariates are related to the probability of developing disease. The proposed method is applied to determine risk factors for chronic otitis media with effusion.
Sample size estimation for comparing two or more treatment groups in clinical trials
Authors: Day Simon J. , Graham David F.
Published: April 2007

Methods for estimating required sample size for comparing two population means have been published. Most involve the use of complicated formulae and tables. These methods are limited to comparing two groups. Although techniques exist to determine sample sizes for comparing more than two groups, they are intrinsically far more complicated. A simple linear nomogram is proposed as a solution to these problems, and its use is illustrated with examples of parallel group, ordered parallel group and factorial designs.
Methodological pitfalls in the analysis of contraceptive failure
Authors: Trussell James
Published: April 2007

Although the literature on contraceptive failure is vast and is expanding rapidly, our understanding of the relative efficacy of methods is quite limited because of defects in the research design and in the analytical tools used by investigators. Errors in the literature range from simple arithmetical mistakes to outright fraud. In many studies the proportion of the original sample lost to follow‐up is so large that the published results have little meaning. Investigators do not routinely use life table techniques to control for duration of exposure; many employ the Pearl index, which suffers from the same problem as does the crude death rate as a measure of mortality. Investigators routinely calculate ‘method’ failure rates by eliminating ‘user’ failures from the numerator (pregnancies) but fail to eliminate ‘imperfect’ use from the denominator (exposure); as a consequence, these ‘method’ rates are biased downward. This paper explores these and other common biases that snare investigators and establishes methodological guidelines for future research.
Epidemiologic oversight of the medical care provided to medicare beneficiaries
Authors: Krakauer Henry , Bailey R. Clifton
Published: April 2007

The Health Care Financing Administration is charged by law with the assurance of the quality of the medical care rendered to Medicare beneficiaries, a function carried out through the Peer Review Organizations. To guide and support this activity, a programme of epidemiologic surveillance of the health of such persons has been devised and is being implemented. Its focus is on the objective measures of health‐mortality, morbidity, disability and expenditures for health care. Its principal components are analyses of trends in those measures over time and of their variations among geographic areas, as problem‐finding techniques, and evaluations of the comparative effectiveness of strategies of management of patients, as problem‐solving tools. Examples of the feasibility and utility of this strategy include an evaluation of the longitudinal impact of administrative changes undertaken in 1983‐1984, the assessment of variations in patient mortality rates among hospitals, the characterization of the management of patients with ischemic heart disease, and a demonstration of a methodology for the observational evaluation of revascularization in various types of patients hospitalized for acute myocardial infarction. The objectives of the programme are the improvement of review of medical practices as carried out by the Peer Review Organizations, assistance to clinicians in the management of patients, and guidance to planners in the allocation of resources.
Empirical evaluation of statistical models for counts or rates
Authors: Wolfe Robert A. , Petroni Gina R. , McLaughlin Catherine G. , McMahon Laurence F.
Published: April 2007

We consider methods for selecting the joint specification of the mean and variance functions in statistical models for rates or counts. Based on analyses of diagnosis‐specific hospital discharge rates in Michigan, we show that a Poisson model with an extra variance component for the systematic variation is superior to several other probability models with regard to specification of the error structure. Further, the deviance residual appears superior to the Pearson residual. The proper specification of such variation is crucial for many types of analyses, such as identification of outliers and regression analyses designed to explain the systematic component of the variation.
Comparison of the proportions of affected relatives of cases and controls: Analysis and minimum sample size formula
Authors: Commenges Daniel , Letenneur Luc
Published: April 2007

The problem of familial aggregation has frequently been approached by comparing the proportion of affected relatives of index cases with the proportion of affected relatives of index controls. This type of study has an analogy with the case‐control design and is frequently analysed as if it was one. It is however an essentially different design which may involve dependent observations. We show that conventional tests for comparing proportions of affected subjects are still valid with this design; we give a formula for computing the minimum sample size required to detect a given degree of aggregation measured by the intracluster correlation coefficient, which can be estimated very simply by the difference in proportions of affected relatives in the two groups.
Fatigue load computation of wind turbine gearboxes by coupled finite element, multi‐body system and aerodynamic analysis
Authors: Heege Andreas , Betran Jaume , Radovcic Yvan
Published: April 2007

The main concern of the present publication is the computation of dynamic loads of wind turbine power trains, with particular emphasis on planetary gearbox loads. The applied mathematical approach relies on a non‐linear finite element method, which is extended by multi‐body system functionalities, and aerodynamics based on the blade element momentum theory. Copyright © 2007 John Wiley & Sons, Ltd.
Gas chromatographic determination of tocopherols and sterols in soya sludges and residues — an improved method
Authors: Nelson J. P. , Milun A. J. , Fisher H. D.
Published: April 2007

An improved method is described for determining the tocopherol and sterol content of soya sludges and residues. Samples are saponified and the extracted unsaponifiables are derivatized prior to gas chromatography to eliminate interferences. Data are presented to demonstrate the improvements realized.
A New Technique of Hepatic Segmentectomy by Selective Portal Venous Occlusion Using a Balloon Catheter through a Branch of the Superior Mesenteric Vein
Authors: Ou Jin‐Rui , Chen Wei , Lau Wan‐Yee
Published: April 2007

Background

We describe a new technique of segment‐based liver resection by inserting a 6 French balloon catheter into the portal vein via a branch of the superior mesenteric vein.

Materials and Methods

The catheter was guided into the relevant portal branch supplying the liver segment that contained the tumor. Injection of methylene blue through the catheter delineated the liver segment(s) to be resected. This operation was carried out on 48 patients with a 0% in‐hospital mortality.

Results

The 5‐year overall survival was 52.1% and the 5‐year disease‐free survival was 20.8%.

Conclusions

Our experience showed this technique to be a viable alternative for anatomical liver segmentectomy.
Can Nipple‐sparing Mastectomy and Immediate Breast Reconstruction with Modified Extended Latissimus Dorsi Muscular Flap Improve the Cosmetic and Functional Outcome among Patients with Breast Carcinoma?
Authors: Denewer Adel , Farouk Omar
Published: April 2007

Background

Nipple–areola complex (NAC) preservation is a new revolution in breast cancer surgery and breast reconstruction, if reliability and safety are considered. The latissimus dorsi muscular flap is a versatile flap that is gaining renewed popularity for immediate breast reconstruction with development of modifications. We are introducing nipple‐sparing mastectomy (NSM) for Egyptian patients with breast carcinoma and reporting our results with a new modification of the extended latissimus dorsi muscular flap.

Methods

Between July 2005 and August 2006; forty‐one patients with stage I to III breast carcinoma had NSM and immediate breast reconstruction. We performed a new modification to the extended latissimus dorsi muscular flap that allowed us to obtain enough autologous tissue to reconstruct the breast without implant or back incision. The postoperative aesthetic results with specific view of the preserved NAC were evaluated.

Results

We applied both an objective and subjective aesthetic result to our monitoring. Aesthetic grading results of breast reconstruction were as follows: excellent in 31, good in 6, fair in 2, poor in 2. Both reconstructed breast and donor site complications were minor. Patients are followed for a median follow‐up of 7.9 months (range: 4–11 months). In this short period of follow‐up, no local recurrence or distant failure has been observed.

Conclusions

Nipple‐sparing mastectomy with immediate breast reconstruction using modified extended latissimus dorsi muscular flap allows single‐stage, totally autologous reconstruction with a satisfactory aesthetic result, low morbidity, and good quality of life.
Transferrin hypoglycosylation in hereditary fructose intolerance: Using the clues and avoiding the pitfalls
Authors: Adamowicz M. , Płoski R. , Rokicki D. , Morava E. , Giżewska M. , Mierzewska H. , Pollak A. , Lefeber D. J. , Wevers R. A. , Pronicka E.
Published: April 2007

Hereditary fructose intolerance (HFI) is caused by a deficiency of aldolase B due to mutations of the ALDOB gene. The disease poses diagnostic problems because of unspecific clinical manifestations. We report three cases of HFI all of whom had a chronic disease with neurological, nephrological or gastroenterological symptoms, whereas nutritional fructose intolerance, the pathognomonic sign of HFI, was apparent only in retrospect. In all patients a hypoglycosylated pattern of transferrin isoforms was found but was misinterpreted as a sign of CDG Ix. The correct diagnosis was achieved with marked delay (26, 36 and 24 months, respectively) by sequencing of the ALDOB gene two common mutations were identified on both alleles or on one (A150P/A175D, A150P/− and A150P/A175D). The diagnosis was further supported by normalization of transferrin isoforms on a fructose‐free diet. Data available in two patients showed that following the fructose restriction the type I pattern of carbohydrate‐deficient transferrin detectable on fructose‐containing diet disappeared after 3–4 weeks. These cases illustrate that in the first years of life HFI may show misleading variability in clinical presentation and that protein glycosylation analysis such as transferrin isofocusing may give important diagnostic clues. However, care should be taken not to misinterpret the abnormal results as CDG Ix as well as to remember that a normal profile does not exclude HFI due to the possibility of spontaneous fructose restriction in the diet. The presented data also emphasize the usefulness of ALDOB mutation screening for diagnosis of HFI.
Therapeutic concepts in succinate semialdehyde dehydrogenase (SSADH; ALDH5a1) deficiency (γ‐hydroxybutyric aciduria). Hypotheses evolved from 25 years of patient evaluation, studies inAldh5a1−/−mice and characterization of γ‐hydroxybutyric acid pharmacology
Authors: Knerr I. , Pearl P. L. , Bottiglieri T. , Carter Snead O. , Jakobs C. , Gibson K. M.
Published: April 2007

We overview the pathophysiological bases, clinical approaches and potential therapeutic options for succinate semialdehyde dehydrogenase (SSADH; EC1.2.1.24) deficiency (γ‐hydroxybutyric aciduria, OMIM 271980, 610045) in relation to studies on SSADH gene‐deleted mice, outcome data developed from 25 years of patient evaluation, and characterization of γ‐hydroxybutyric acid (GHB) pharmacology in different species. The clinical picture of this disorder encompasses a wide spectrum of neurological and psychiatric dysfunction, such as psychomotor retardation, delayed speech development, epileptic seizures and behavioural disturbances, emphasizing the multifactorial pathophysiology of SSADH deficiency. The murine SSADH−/−(e.g.Aldh5a1−/−) mouse model suffers from epileptic seizures and succumbs to early lethality.Aldh5a1−/−mice accumulate GHB and γ‐aminobutyric acid (GABA) in the central nervous system, exhibit alterations of amino acids such as glutamine (Gln), alanine (Ala) and arginine (Arg), and manifest disturbances in other systems including dopamine, neurosteroids and antioxidant status. Therapeutic concepts in patients with SSADH deficiency and preclinical therapeutic experiments are discussed in light of data collected from research inAldh5a1−/−mice and animal studies of GHB pharmacology; these studies are the foundation for novel working approaches, including pharmacological and dietary trials, which are presented for future evaluation in this disease.
Effect of population density of compatible neighbours on inbreeding level within a Primula sieboldii population
Authors: Kitamoto N. , Ueno S. , Tsumura Y. , Washitani I. , Ohsawa R.
Published: April 2007

We investigated the effect of population density of compatible neighbours on inbreeding level of Primula sieboldii, a heterostylous clonal herb. Pollinator availability, seed set, selfing rate, diversity of pollen donors, and fitness of progenies were compared between less and more isolated genets, which differed in the number of compatible opposite‐morph genets within 20 m, the range at which most pollen flow occurred. Although pollinator availability did not differ between the two groups, seed set and diversity of pollen donors in more isolated genets were significantly lower than in less isolated genets. Additionally, the mean selfing rates of less and more isolated genets were 1.3 and 36.7%, respectively, and the mean leaf area of the self‐fertilized seedlings was 70 to 40% smaller than that of outcrossed seedlings of the same mother genet. Due to this large inbreeding depression, it is unlikely that self‐fertilized seedlings could successfully establish in natural habitats and hence the inbreeding level in the next generation around the more isolated genet would not increase rapidly. However, the possibility of mating between full‐sibs would increase because the diversity of pollen donors was low and both pollen and seed dispersal were spatially restricted. Thus the inbreeding level of the next generations would gradually increase around the more isolated genets owing to biparental inbreeding. This study suggested that the population density of compatible neighbours has a critical impact on the future inbreeding level within P. sieboldii populations.
Intra-articular Corticosteroid Injection for the Treatment of Idiopathic Adhesive Capsulitis of the Shoulder
Authors: Marx Robert G. , Malizia Robert W. , Kenter Keith , Wickiewicz Thomas L. , Hannafin Jo A.
Published: April 2007

Treatment for idiopathic adhesive capsulitis or frozen shoulder of the shoulder is controversial. The hypothesis of the study is that intra-articular corticosteroid injection in the early stages of idiopathic adhesive capsulitis will lead to a razpid resolution of stiffness and symptoms. This is a retrospective cohort study of only patients with stage 1 or stage 2 adhesive capsulitis. The diagnosis was made by history and physical examination and only when other causes of pain and motion loss were eliminated. Stage 1 adhesive capsulitis was defined as significant improvement in pain and normalization of motion following intra-articular injection. Stage 2 included patients who had significant improvement in pain and partial improvement in motion following injection. Seven patients with stage 1 and 53 patients with stage 2 comprised the baseline cohort. The mean age was 52 years (range: 30 to 78); 46 patients were female and nine patients had diabetes mellitus. Patients completed a physical examination as well as a shoulder rating questionnaire for symptoms and disability. Criteria for resolution were defined as forward flexion and external rotation to within 15° of the contralateral side and internal rotation to within three spinal levels of the contralateral side. Forty-four of the patients out of 60 met the criteria for recovery at a mean of 6.7 months. The mode and median time to recovery was 3 months. The mean score at final follow-up for 41 patients using the shoulder-rating questionnaire of L'Insalata was 90 (range 52–100). The mean time to recovery for the stage 1 patients was 6 weeks (range: 2 weeks to 3 months), and it was 7 months for stage 2 patients (range: 2 weeks to 2 years). Glenohumeral corticosteroid injection for early adhesive capsulitis may have allowed patients to recover motion at a median time of 3 months. In many cases, the patients had improvement prior to the 3-month mark; however, that was the routine time for follow-up. Patients with stage 1 disease tended to resolve more rapidly than stage 2 patients. Prompt recognition of stage 1 and stage 2 idiopathic adhesive capsulitis and early injection of corticosteroid with local anesthesia may be both diagnostic and therapeutic.
Familiärer Darmkrebs
Authors: Friedl W. , Propping P.
Published: April 2007

Bis zu 5% der Fälle von erblichem Darmkrebs beruhen auf einer monogen erblichen Veranlagung. Hierzu gehören das erbliche kolorektale Karzinom ohne Polyposis (Lynch-Syndrom, HNPCC) mit 2–3% und die adenomatösen Polyposissyndrome (familiäre adenomatöse Polyposis, FAP- und MUTYH-assoziierte Polyposis, MAP) mit etwa 1% der Fälle. Hamartomatöse Polyposissyndrome (familiäre juvenile Polyposis, Peutz-Jeghers- und Cowden-Syndrom), die ebenfalls mit einem erhöhten Darmkrebsrisiko einhergehen, sind weitaus seltener. Für die genannten Tumorsyndrome ist die genetische Grundlage weitgehend bekannt. Die Identifizierung der ursächlichen Keimbahnmutation in den entsprechenden DNA-Reparatur-Genen (z. B. bei HNPCC und MAP) oder in Tumorsuppressorgenen (bei der FAP und den hamartomatösen Polyposissyndromen) ermöglicht die Sicherung der Diagnose bei den Erkrankten und die prädiktive Diagnostik bei deren gesunden Familienangehörigen. Im Hinblick auf eine gezielte und sinnvolle molekulargenetische Diagnostik sollte der einweisende Kliniker dem Untersucher eine möglichst detaillierte Beschreibung des Krankheitsbilds mitgeben. Die zusätzlich erhobene Familienanamnese kann weitere Hinweise auf den vorliegenden Gendefekt liefern. Da HNPCC klinisch im Einzelfall schwer von sporadischen Krebsfällen unterschieden werden kann, wird eine Untersuchung des Tumorgewebes auf Vorliegen eines DNA-Reparaturdefekts der Mutationsanalyse in einer Blutprobe vorgeschaltet. Bei den Polyposissyndromen erfolgt die Mutationsanalyse direkt in der Blutprobe, nach sorgfältiger klinischer Einordnung (insbesondere histologische Klassifizierung und Anzahl der Polypen).
A randomised controlled study of reflexology for the management of chronic low back pain
Authors: Poole Helen , Glenn Sheila , Murphy Peter
Published: April 2007

The use of complementary and alternative medicine (CAM) for the management of chronic low back pain (CLBP) continues to rise. However, questions regarding the efficacy of many CAM therapies for CLBP remain unresolved. The present study investigated the effectiveness of reflexology for CLBP. A pragmatic randomised controlled trial was conducted. N=243 patients were randomised to one of three groups: reflexology, relaxation, or non‐intervention (usual care). All completed a questionnaire booklet before and after the treatment phase, and at six months follow up. This measured their general health status, pain, functioning, coping strategies and mood. After adjusting for pre‐treatment scores repeated measures ANCOVA found no significant differences between the groups pre and post treatment on the primary outcome measures of pain and functioning. There was a main effect of pain reduction, irrespective of group. Trends in the data illustrated the pain reduction was greatest in the reflexology group. Thus, the current study does not indicate that adding reflexology to usual GP care for the management of CLBP is any more effective than usual GP care alone.