bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling the impact of detecting and treating ductal carcinoma in situ in a breast screening programme
Authors: McCann Jenny , Treasure Peter , Duffy Stephen 
Published: August 2004

Objectives: Screening has substantially increased the detection of carcinoma in situ of the breast (CIS). Opinions vary as to whether this constitutes over-diagnosis or an opportunity to interrupt breast cancer's natural history. In England, incidence of invasive cancer and CIS increased in women of screening age (50–64 years), leading to a subsequent deficit in invasive incidence in women aged 65–69 years immediately beyond the invited age range. We aimed to model underlying incidence of invasive cancer and CIS expected in the absence of screening, and to quantify the likely relative contributions of their early detection to the observed reduction in invasive cancer in women of postscreening age. Setting: UK NHS breast screening programme in England. Methods: Poisson regression modelling was used to establish the underlying incidence of invasive and in situ cancers in the absence of screening. We then estimated age- and year-specific excess detection rates attributable to screening. Applying these to population figures we estimated conservatively the relative contributions of early diagnosis of CIS and invasive cancer at 50–64 years of age to the subsequent deficit in invasive cancer in women beyond invitation age (65–69 years), for screening early in the programme and at steady state. Results: Our model estimated a 1.6% annual increase in incidence, giving an estimated deficit of 4.22 invasive cancers per 10,000 women aged 65–69 years in 1996. Carcinoma in situ contributed 13–17% to the deficit, assuming a mean six year lead time and 75–100% progression to invasive cancer. At steady state, with current screening performance and with lead times of 3–4 years (invasive cancer) and 6–9 years (CIS), invasive incidence might be reduced by 5–6 cancers per 10,000 women aged 65–69 years in 2010 (15–20% of underlying incidence), CIS contributing 20–40%. Discussion: The longer lead time associated with CIS attenuates the impact its early detection has on subsequent invasive incidence. At steady state screening, its detection contributes significantly to the deficit in invasive incidence. Our results suggest that, cancer for cancer, there may be just as much benefit in detecting and treating a case of CIS as there is in treating a case of invasive cancer.
Screening for physical and psychological illness in the British Armed Forces: III: The value of a questionnaire to assist a Medical Officer to decide who needs help
Authors: Rona RJ , Hooper R , Jones M , French C , Wessely S 
Published: August 2004

Objectives: To estimate the positive and negative predictive values (PPVT and NPVT), sensitivity and specificity of a full and abridged screening questionnaire of physical and psychological health, using primary care doctors' (medical officers [MOs]) assessments as to whether the servicemen needed medical help as a gold standard. Methods: From a tri-service random sample of those who completed a questionnaire, all 'screen-positive' and an equal random sample of 'screen-negative' were selected to attend their medical centre. MOs were aware that the screening was aimed at detecting psychological illness, but were blind as to the 'screen-positivity' of any serviceman. The MO completed a questionnaire that asked whether the patient needed medical help and whether s/he was previously aware of this need. Results: 314 subjects were available for analysis. The PPVT was 47% (95% confidence interval [CI] 36–59%) for the full questionnaire and 48% (95% CI 36–60%) for the abridged questionnaire. Of those 'screen-positive' subjects whom the MO rated as needing help, one third had problems already known to the MO, regardless of the length of the questionnaire. The sensitivity and specificity of the full and abridge questionnaires were 43% and 74%, and 36% and 83% respectively. The PPVT did not vary greatly between health dimensions nor did selection of servicemen with very high scores. Conclusions: The use of MOs as a gold standard is important because of their central role in initiating the management of any condition uncovered by a screening programme. Using MOs as a gold standard, the validity of the screening questionnaires for physical and psychological health in the military was mediocre.
A cluster-randomised trial of screening for language disorders in toddlers
Authors: de Koning HJ , de Ridder-Sluiter JG , van Agt HME , Reep-van den Bergh CMM , van der Stege HA , Korfage IJ , Polder JJ , van der Maas PJ 
Published: August 2004

Objective: To assess the screening performance of a specific language-screening instrument at 18 and 24 months of age and to assess its effect on the early detection and prognosis of language delay. Design: Child health care physicians were randomised to the intervention group, in which specific language screening was conducted twice (at age 18 months and 24 months), or to the control group (usual care). The specific screening instrument consisted of a uniform set of questions for the parents and test elements for the child, with scaled scores to assess responses. Setting: Child health care in the Netherlands and referral of screen-positive children. Subjects: 5734 children in the intervention group and 4621 in the control group. Main outcome measures: Test characteristics and disorders at 24 months, and confirmed diagnoses of a language disorder before 36 months in both groups. Gold standard based on reports of parents, specialists and expert panel. Prognosis estimated from two diagnostic language development performance scores at 36 months (in questionnaire). Results: In the intervention group, 3147 of the 5734 children (55%) were screened with the specific screening instrument and 73 of the screened children (2.3%) were screen-positive. Of the screen-positive children, 41 (55%) had confirmed language delay (diagnostic assessment and/or reported treatment). The estimated sensitivity of the test ranged between 24–52% depending on the severity of language disorders. The prevalence of language disorders in three-year olds was estimated to be 2.4–5.3%. In the intervention group, 1.25–2 times more children with language delay had been diagnosed before 36 months. The assessment of language development at 36 months showed no statistically significant differences between the intervention and the control groups. Conclusions: The inclusion of a specific language-screening instrument in child health centre activities resulted in the earlier detection of children with language delay. Short-term health benefits could not be demonstrated. Large-scale introduction cannot be recommended on the basis of this information alone.
Surgical intervention in screen-detected patients versus symptomatic patients with breast cancer
Authors: Dillon MF , Hill ADK , Quinn CM , O'Doherty A , Crown J , Fleming FJ , McDermott EW , O'Higgins N 
Published: August 2004

Objectives: The impact of population-based screening for breast cancer on the rate of breast-conserving surgery has not been established. We sought to evaluate whether surgical intervention in patients with screen-detected breast cancer differed from those with clinically detected tumours. Settings: St Vincent's University Hospital and the BreastCheck Merrion Unit, part of the Irish National Breast Screening Programme, were the setting for the study. Methods: A total of 902 patients referred for surgery to St Vincent's University Hospital over a four-year period (2000–2003) were studied. Patients with breast cancers detected during the prevalent round of screening (n=325) were compared with patients presenting with symptomatic disease (n=577). The operative procedure, nature of axillary surgery and histopathological findings were recorded in each case. Results: There was an increase in breast-conserving therapy in the screened population compared with symptomatic cases (68% screened versus 53% symptomatic; p<0.0001), with a corresponding reduction in axillary clearance rates (65% screened versus 81% symptomatic; p<0.0001). Nodal positivity was similar following correction for size in all tumours >1 cm, regardless of method of detection. Sentinel node biopsy was successfully undertaken in 39% of tumours <2 cm (T1 tumours) in the screening population. Conclusions: The screened population was statistically more likely to have breast-conserving therapy than the symptomatic group. Sentinel node biopsy has evolved into an acceptable alternative to axillary clearance in T1 cancers, particularly in screen-detected cases.
Screening for physical and psychological illness in the British Armed Forces: II: Barriers to screening – learning from the opinions of Service personnel
Authors: French C , Rona RJ , Jones M , Wessely S 
Published: August 2004

Objective: To identify any potential barriers to the effectiveness of a military health screening programme based on the beliefs of British Service personnel. Methods: As part of a pilot evaluation of the suitability of a new health screening questionnaire for the British Armed Forces, 73 men and women from the three Services, of various ranks and age, underwent a semi-structured interview after completing a screening questionnaire. Participants were asked about the veracity of their answers and their views regarding a screening questionnaire. Afterwards questionnaires were sent to 4496 randomly selected personnel from the three Services, which validated the main emerging themes. A constant comparative method of analysis was used to identify and categorise all ideas presented. Results: The main barriers to health screening were lack of trust, perceived low quality of healthcare, and perceived lack of concern within the institution about work environments and home life. The central issue was 'confidence' in military health care provision. Screening was considered worthwhile, but many confided that they would not honestly answer some items in the questionnaire. Lack of trust in medical confidentiality, stigmatisation and fears that the process would jeopardise career prospects were stressed. Many Service personnel admitted to seeking medical help outside the Armed Forces. Conclusions: Concerns raised by Service personnel may endanger the value of a screening programme and the provision of health services. Greater emphasis needs to be placed upon gaining the confidence of those targeted for health screening.
APC resistance: What have we learned since 1993? / APC-Resistenz: Was haben wir seit 1993 hinzugelernt?
Authors: Dahlbäck B. 
Published: August 2004

Abstract
APC resistance, defined as a poor anticoagulant
response to activated protein C (APC), was described in
February 1993 as a novel and important inherited risk
factor of thrombosis. An avalanche of research activities
was triggered that during the past eleven years has elucidated
not only the molecular mechanisms of APC resistance,
but also general pathogenetic mechanisms of
thrombosis. In 1994, factor V (FV) was identified as the
factor associated with APC resistance, and a point mutation
in the FV gene (Arg506Gln or FV Leiden) was found
to be the genetic cause of APC resistance. This mutation
eliminates one of three APC-cleavage sites in FV, which
not only results in impaired APCmediated degradation
of FVa, but surprisingly also of FVIIIa. The dual effects of
FV Leiden were explained by the discovery of a novel
property of FV, namely that FV has the potential to
express anticoagulant activity in addition to being a procoagulant
protein. As an anticoagulant, FV functions as
an APC cofactor in synergy with protein S in the regulation
of FVIIIa in the tenase complex. Studies of APC
resistance and FV Leiden performed in many laboratories
world-wide have given insights into clinical, epidemiological as well as molecular details. This review focuses on what we have learned since 1993 about the molecular mechanisms of APC resistance and the involvement of FV in the regulation of blood coagulation by the anticoagulant protein C system.
Das SARS-assoziierte Coronavirus – Die erste Pandemie des 21. Jahrhunderts / The SARS-associated coronavirus – The first pandemic of the 21st century
Authors: Berger A. , Drosten C. , Doerr H. W. , Preiser W. 
Published: August 2004

Abstract
The severe acute respiratory syndrome (SARS) first
occurred in southern China at the end of 2002 and has
caused more than 8000 illnesses in total with over 700
fatalities as of end of August 2003. A unique collaborative
effort, led by the World Health Organization (WHO) and
uniting several laboratories from around the world,
allowed the identification of the causative agent within
only one month. It is a hitherto unknown novel coronavirus
(provisionally termed SARS-associated coronavirus
or SARS-CoV) that fulfills Kochs postulates. The virus is
easily propagated in cell culture (under suitable highsecurity
laboratory conditions) which should facilitate further
studies into its stability as well as the development
of antivirally active substances and vaccines.
Although diagnostic laboratory tests, particularly for
the detection of viral nucleic acid and virusspecific antibodies,
were quickly available, the case definition for
SARS continues to be based on clinical and epidemiological
criteria. In view of the threat of a (seasonal) recurrence
of the infection it is urgently necessary to evaluate
and to further improve the available laboratory methods.
SARS is a good example of how rapidly an infectious
disease may spread through international travel activities;
but it also demonstrates the importance of a wellcoordinated
international cooperation in such a case.
Through the use of the latest advances together with
more traditional laboratory methods and the constant
exchange of (interim) results, patient samples and reagents,
an unprecedented collaborative effort soon
achieved a breakthrough. This should provide encouragement
in the struggle against other novel infectious
agents.
Testicular tumor markers: Corner-stones in the management of malignant
germ cell tumors / Hoden-Tumor-marker: Eckpfeiler in der Behandlung maligner Keimzelltumoren
Authors: Albrecht W. , Santis M. De , Dossenbach-Glaninger A. 
Published: August 2004

Abstract
Management of testicular tumor patients without marker
assessment is unacceptable in these days. Markers are
included in the TNM scheme since 1997 in form of the S
classification. The combination of AFP, hCG, LDH and
PLAP shows high specificity and sensitivity, in contrast
to most tumor markers in other malignancies.
While preoperative markers are usually available, it is
less common to monitor the immediate postoperative
course. Still there are patients with the first control of
tumor markers four weeks after surgery. In patients
showing normal markers after four weeks, one may have
missed a prolonged marker decline, such overlooking
remaining tumor tissue which could have been treated
more easily if detected in time, and not as late as metastases
can be identified by imaging alone. If markers have
not normalized after four weeks, there is a substantial
delay in starting adjuvant treatment with a probable
decreased chance for cure of the disease.
Furthermore, tumor markers are important for classifying
the risk of primary metastatic disease as well as for
evaluation of response to chemotherapy. Marker normalization
is a prerequisite for successful post-chemotherapy
surgery. During follow-up, rising markers are able
to identify relapsing tumors at an earlier stage than imaging
techniques alone.
Gesamt-Genom-Microarray-Analyse und Target-Validierung mittels qPCR / Whole genome microarray analysis and target validation by using qPCR
Authors: Klein H.-G. , Gorinevski D. , Hörmann J. , Marschall C. , Mayer K. , Vanetti M. 
Published: August 2004

Abstract
In modern pharmaceutical research, microarrays for the
analysis of differential gene expression are some of the
most valuable tools for the characterization of novel
compounds and their biological activity. Moreover, basic
clinical research in medicine has benefited tremendously
from this rapid development leading to the discovery of
new pathophysiological concepts for numerous diseases
and to an increased significance for molecular genetic
approaches by the characterization of molecular signatures
(synonymous for gene expression profile, gene profiling,
expression profiling) of diseases or diseased
tissues. Extensive data already exist particularly in oncology,
where gene profiling has been brought into patient
care. For the clinical application of innovative diagnostic
procedures, the quest for disease prognosis as well as
optimized therapies usually have the highest priority. Particularly
in this field, gene expression profiling could help
to improve and supplement phenotypic diagnostics and
classical laboratory analytics. It is foreseeable that the
analysis of a limited number of diagnostically relevant targets
and their quantitative measurement by real-time
PCR, a reliable technique for this kind of analyses, would
suffice. For the identification of diagnostically relevant
targets, the research community currently has access to
a number of whole-genome arrays or topic-specific
arrays, which provide information about the up- or down-regulation
of transcripts. These techniques are primarily
based upon hybridization of mRNA or cDNA to capture
probes and the semi-quantitative measurement of the
signal intensity. This article demonstrates the workflow
required when setting up a gene expression laboratory
for routine analytics in biomedical research and
diagnostics.
The history, advantages and limitations of point-of-care testing for blood glucose / Geschichte, Vorteile und Grenzen des Point-of-Care-Testing im Bereich der Blutzuckerkontrolle
Authors: Nichols J.H. 
Published: August 2004

Abstract
Glucose testing has evolved from primitive urine tasting
and chemical tests to sophisticated enzymatic and biosensor
technologies with computerized data recording
capabilities. Glucose monitoring will become more
important in the future, as the incidence of diabetes
increases. Current meters allow for the rapid analysis of
small amounts of blood in a variety of healthcare settings,
but suffer from the instability and common interferences
of their enzyme-based technologies. Although
the performance of glucose meters is not yet as accurate
as laboratory methods, glucose meters provide a reasonable
estimate to base insulin management and trend
glucose control. Glucose self-management delays the
onset of diabetic complications and intensive monitoring
of surgical inpatients improves patient outcome. Future
research promises to develop less invasive and more
continuous monitoring methods. While there is currently
no cure for diabetes, the advent of glucose meters and
monitoring technologies has provided new insights into
the nature of the disease and made diabetes a more
manageable disorder.
Online-Qualitätssicherung patientennaher Sofortdiagnostik (Point-of-Care-Testing) unter Nutzung des Kommunikations-Systems des Krankenhauses / Online quality assurance of point-of-care testing by using the hospital information system
Authors: Messner B. , Frick G. , Blobner M. , Albrecht K. , Schade T. , Luppa P. B. 
Published: August 2004

Abstract
The new guidelines of the German Bundesärztekammer
for quality assurance of quantitative laboratory analyses
(RiliBÄK), enacted on 01.01.2002, also have impacts on
point-of-care testing (POCT) in clinical settings. The University
Hospital Klinikum rechts der Isar has realized an
online-quality assurance scheme of all decentralized
POCT by using the hospital information system. All blood
gas and glucose POC systems were successively linked
to the core laboratory. There, all internal quality assurance
data are validated and documented by the use of
two central servers with appropriate software tools. The
quality control records are maintained electronically for
five years. The supervising POC manager also responds
to out-of-control situations by giving hints to the testing
personnel for remedial action. Additionally, online-transmitted
individual patient test results are transformed into
cumulative reports and re-transferred to the clinics by the
same network. External quality control is solely performed
by the core laboratory. Our new online-quality
assurance scheme already led to a more economic use
of POCT.
The laboratory responsibility in stopping the allergic march / Die Rolle des Labors beim Unterbrechen des allergischen Marsches
Authors: Menheere P. P. C. A. 
Published: August 2004

Abstract
Nowadays, it is generally accepted that allergic disease
of childhood develops into serious health problems in
adults. Allergy starts with mild forms of atopic dermatitis,
poorly differentiated gastrointestinal disease or recurrent
wheezing, mostly caused by food allergens. Later in
childhood the importance of food allergens diminishes,
but the inhalant allergens become more important and
are responsible for bronchial asthma, allergic rhinitis or
conjunctivitis. Finally, in adulthood, allergic asthma is the
cause of irreversible changes of pulmonary tissue, reducing
lung capacity and function. This progressive development
of allergic disease in children causing minor (or
sometimes even major) discomfort into irreversible
changes of lung or skin tissue with consequently compromised
functionality, is called the allergic march. Early
recognition and correct intervention can modify this process.
All allergic patients may benefit from different kinds
of therapy that are available nowadays. It is important,
that the consulted physician is aware of the relation
between possible future healthcare problems and actual
allergic disease. Since allergy is of increasing complexity,
the physician is not able anymore to survey the complete
discipline. During the diagnostic phase, the physician
asks without exception for laboratory confirmation of the
allergy and for determination of the involved allergens.
Clinical chemists trained in allergy are seeing much more
demands for diagnosis of allergy. Furthermore, they are
aware of cross reactions and seasonal changes of exposure.
The clinical chemist should interpret the results and
he should advise the physician by proposing therapies
that might stop or even avoid progressive development.
The use of expert systems is beneficial in providing a tool
to combine the patient's information and history and the
results of allergy testing into a report of results containing
an interpretation and advice about possible therapies.
Close cooperation between the physician and the clinical
chemist is necessary to stop the allergic march.