Risk Of False Positive Diagnosis Research Articles

Knowledge, Attitudes, and Practices of Moroccan Community Rheumatologists' Regarding the Management of Non-radiographic Axial Spondyloarthritis: A National Cross-Sectional Study.

Introduction Non-radiographic axial spondyloarthritis (nr-axSpA) is within the spectrum of axial spondyloarthritis (axSpA). The emergence of the nr-axSpA concept, defined by the absence of significant erosive damage to the sacroiliac joints, has prompted numerous initiatives aimed at enhancing the early detection and management of this condition. The aim of the study was to assess the knowledge, attitudes, and practices related to the diagnosis and management of nr-axSpA by rheumatologists in Morocco. Methods We conducted a cross-sectional online survey among the rheumatologist community in Morocco. Rheumatologists received via e-mail a structured Google Forms (Google Inc., Mountainview, CA) questionnaire divided into four sections: sociodemographic data of rheumatologists, knowledge, attitudes, and practices related to the diagnosis and treatment management of nr-axSpA. Results A total of 110 rheumatologists (mean age of 44±13 years, 77.3% females, median professional experience of 12 years (4, 75; 26.25 years)) participated in the survey (response rate of 25%). Most responders reported a diagnosis delay issue in spondyloarthritis(SpA) (93.6%); 70.9% of rheumatologists incorrectly regarded the 2009 Assessment of Spondyloarthritis International Society (ASAS) classification criteria for axSpA as diagnostic criteria. Rheumatologists' awareness of recommended magnetic resonance imaging (MRI) sequences for detecting sacroiliac joint inflammation and structural changes in SpA varied significantly, from 69.1% to 14.5%. Their knowledge of additional subchondral edema cases in these joints, beyond SpA, ranged from 48.2% to 87.3%. Almost all rheumatologists believed that the use of sacroiliac MRI would contribute to the early diagnosis of axSpA (97.3%) but could also lead to false positive diagnoses, according to 47.3% of rheumatologists; 73.6% believed that incorrectly using the 2009 ASAS classification criteria as diagnostic criteria in nr-axSpA could also result in false-positive diagnoses. In their practice, 2009 ASAS classification criteria were used as diagnostic criteria in axSpA by 39.1% of rheumatologists. Of the total participants, 91.8% indicated that they approach nr-axSpA similarly to radiographic axial spondyloarthritis, with disparities in recommendations of biological therapies. Conclusion Our survey provides insight into the current status of nr-axSpA management among Moroccan rheumatologists. It also addresses concerns regarding the risk of false positive diagnoses when using the 2009 ASAS classification criteria for axSpA as diagnostic criteria by rheumatologists and the potential risk of misdiagnosis associated with excessive reliance on MRI, despite its utility for early diagnosis.

Outcomes Based on CNS Disease Status in Pediatric Acute Myeloid Leukemia and the Role of Peripheral Blood Contamination in Diagnostic Lumbar Punctures; A Report from the Children's Oncology Group Studies AAML0531 and AAML1031

The diagnosis and treatment of CNS leukemia in AML differs between pediatric and adult oncology. Adult AML patients generally receive no prophylactic intrathecal (IT) treatment. Here we evaluate an approach utilized on 2 recent Children's Oncology Group (COG) clinical trials for pediatric AML which included CNS prophylaxis and a low threshold to initiate CNS leukemia directed therapy.A total of 2119 patients with de novo AML were evaluable from COG trials AAML0531 and AAML1031. Patients with FLT3/ITD on AAML1031 are excluded as that cohort remains eligible for ongoing accrual. The median (range) follow-up time was 7.1 (0 - 10.5) years for AAML0531 and 2.5 (0 - 5.7) years for AAML1031. All patients received IT cytarabine once with each induction and intensification cycle (except for one of the intensification cycles with high dose cytarabine). An LP to determine CNS status was performed at start of induction therapy. CNS positive (CNSpos) leukemia was treated with twice weekly IT cytarabine until 2 negative CSF samples were obtained (minimum 4 and maximum 6 ITs). CNSpos was defined similarly on both trials (Table 1). In order to understand the role of traumatic LP in CNS status and outcomes, CNS status in this analysis was further classified according to criteria used for ALL (Table 1). Comparing the ALL criteria to the AML CNS definition, CNS1 patients are CNS negative (CNSneg) and CNS3 patients are CNSpos, however among patients with CNS2 by ALL criteria, the AML CNS definition does not take into account the number of CSF WBCs in an atraumatic LP and also uses a higher CSF RBC number (100 versus 10) to require use of the Steinherz/Bleyer algorithm.The rate of CNS relapse (isolated CNS and combined CNS and bone marrow) was evaluated separately on each trial since the protocols differed in number of chemotherapy courses and SCT allocation. On AAML0531, the 5 year CNS relapse rate was lower for CNS1 (4.5 ± 1.7%) compared to CNS2 (9.1 ± 4.5%) or CNS3 (17.7 ±9.4%), P<0.001. This finding was replicated in the AAML1031 outcomes; CNS relapse rates were 4.9 ± 1.8% (CNS1), 11.7 ± 5.0% (CNS2) and 19.3 ±8.8% (CNS3), P<0.001. Patients who were CNSpos had a higher 5 year CNS relapse rate on both studies (CNSpos 13.2 ± 5.1% vs. CNSneg 4.9 ± 1.7% on AAML0531, P<0.001; CNSpos 12.9 ± 4.3 % vs. CNSneg 5.6 ± 1.8% on AAML1031, P<0.001). Event free survival (combined AAML0531 and AAML1031) differed by CNS category (CNS1 51.2%, CNS2 43.5%, CNS3 37.7%, P<0.001) and AML CNS group (CNSneg 41.2%, CNSpos 49.9%, P<0.001), but overall survival did not differ significantly.We evaluated the role of peripheral blood contamination. For patients with CSF RBC ≥100, the majority of patients were classified by ALL criteria as CNS2 or CNS3, and the rate of CNS3 disease increased approximately two fold compared to those with CSF RBC <100 (Fig 1a). When considering the COG AML definition, CNSpos rate was substantially higher among those with CSF RBC 10-99 (41%) compared to those with CSF RBC <10 (24%) or RBC ≥100 (27%; Fig 1b). This difference is likely due to the presence of peripheral blood blasts without “correction” for this blood contamination because the Steinherz/Bleyer algorithm was not used to determine CNSpos when CSF RBC <100.The median blood WBC count was significantly lower in patients with CNS1 (14,650; 95% CI 13,200-15,900) compared to CNS2 (46,200; 95% CI 40,500-53,700) or CNS3 (32,400; 95% CI 21,900-43,500). Further, when this analysis was restricted to patients with an atraumatic tap (CSF RBC <10), those with CNS1 still had significantly lower WBC compared to those with CNS2 or CNS3 (median WBC [95% CI]: CNS1 15,100 [13,400-16,800]; CNS2 53,700 [45,800-62,000]; CNS3 35,500 [21,000-50,100]). This suggests that the biologic drivers resulting in leukocytosis may also increase the risk of CNS leukemia.This analysis demonstrates that CNS disease in AML is associated with a higher CNS relapse risk but caution must be used in interpreting disease status at diagnosis. Due to the worse prognosis associated with CNS disease, we advocate continued use of diagnostic lumbar punctures and intensified treatment for pediatric patients with CNS disease. However, we also speculate that deferring the initial diagnostic lumbar puncture until clearance of peripheral blasts (which usually occurs by day 5-8 of induction) may minimize the risk of false positive diagnosis of CNS disease resulting from high peripheral WBC and blast contamination of CSF samples. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

ICD-11: changes in the diagnostic criteria of substance dependence

HintergrundIn der ICD(International Classification of Diseases)-11 ändern sich die Kriterien für die Diagnose der Substanzabhängigkeit.Ziel der Arbeit (Fragestellung)Erörterung der Vor- und Nachteile der neu verfassten Diagnosekriterien.Material und MethodenDiskussion unter Berücksichtigung neurobiologischer, sozialer und klinischer Forschungsergebnisse.ErgebnisseIm ICD-11 werden wie bisher Abhängigkeitserkrankungen und schädlicher Gebrauch unterschieden. Zur Diagnose der Abhängigkeit werden die ehemals 6 Diagnosekriterien in 3 Paaren gebündelt, von denen künftig 2 erfüllt sein müssen. Innerhalb der Paare genügt ein erfülltes Kriterium, damit das Paar als bejaht gilt. Unter Bezugnahme wissenschaftlicher Erkenntnisse im Suchtbereich zeigen sich Vor- und Nachteile. Hierbei könnte sich die Spezifität der Diagnosestellung gegenüber dem ICD-10 verschlechtern, da pro Paar nur ein Kriterium erfüllt sein muss und somit die Möglichkeit besteht, dass nicht problematisches Konsumverhalten inkorrekt pathologisiert und falsch diagnostiziert wird. Das erscheint als problematisch, da die Definition des ICD-10 „Anhaltender Konsum trotz eindeutiger schädlicher Folgen“, im ICD-11 weiter gefasst wird als „Oft fortgeführter Konsum trotz Auftreten von Problemen“. Dies könnte dazu führen, dass das Kriterium einfach deshalb erfüllt wird, weil der Konsum einer Substanz in einem bestimmten Land illegal ist. In der bisher größten multinationalen Studie in 10 Ländern zur Konkordanz der Diagnosesysteme wurde unter Verwendung der ICD-11 die Alkoholabhängigkeit ca. 10 % häufiger gestellt als mittels ICD-10.SchlussfolgerungIn der ICD-11 werden die Diagnosen der Substanzabhängig und des Missbrauchs als klinisch sinnvolle Syndrome aufrechterhalten. Ob die diagnostischen Neuerungen in der Praxis hilfreich sind oder beispielsweise negative soziale Auswirkungen für die Betroffenen im Sinne unangemessener Pathologisierung mit sich bringen, ist systematisch zu prüfen.

Observational study to compare histologically confirmed benign and malignant papillary neoplasm with demographic parameters and features of neoplasm

Papillary lesions of the breast encompass a wide spectrum of benign and malignant entities. Cytological interpretation of these is difficult and they top the list of conditions with a risk of false-positive diagnosis. Understanding the correlation of histologically confirmed benign and malignant papillary neoplasm with demographic parameters and features of neoplasm will help to distinguish the different lesions. To compare histologically confirmed benign and malignant papillary neoplasm with demographic parameters and features of neoplasm A retrospective study was performed from January 2010 to December 2015 in the cytology section, Department of Pathology of a tertiary care and referral hospital including patients diagnosed as papillary lesion on FNAC. Histopathological follow-up was available for total 44 cases. A total of 44 breast aspirates and their corresponding histology were reviewed. Majority of the patients with benign and malignant neoplasm had age between 41-50 years (33%) and 51-60 years. All patients with benign neoplasm were women whereas among patients with malignant neoplasm 12 were women and one was a man. Benign papilloma, 36.3% cases showed cellular smear, followed by 27.2% showed moderate cellularity. Malignant papillary lesions, cases showed both cellular and moderate cellularity. Papillary carcinoma is an infrequent histologic subtype of breast carcinoma. Cytological diagnosis of the lesion is difficult due to overlap with benign entity and other mimics.

Machine Learning Approach towards Mammographic Breast Density Measurement for Breast Cancer Risk Prediction: An Overview

“Mammographic breast density” is significant biomarker which has strong association with the occurrence of breast cancer. Generally, in dense breast the tissues of breast cancer get hidden and hence the sensitivity of mammogram reduces significantly. It also increases the risk of false positive diagnosis in computer detection system. Development in the cutting-edge technology has the ability to improve the breast density measurement standards, and lead to early prediction of breast cancer by overcoming the restriction of subjective analysis of breast density measurement. In spite of development of different techniques for automatic breast density measurement, very few tools are practically available for breast cancer risk prediction. Basic objective behind this article is to provide an organized overview of selective research articles having specific application of machine learning approach for mammographic breast density measurement. We have selected research articles which follows the pipe-line of image processing with machine learning. Accuracy and computational complexity of selected methods are highlighted in order to decide the best possible future guidelines of research in this area. Hence the modification in preprocessing algorithms to remove pectoral muscle, refining of segmentation as well as feature extraction algorithms in terms of computational complexity and accuracy, selection of more accurate machine learning algorithm can make a positive impact on accuracy enhancement of breast density measurement.

How common is real repeated implantation failure? An indirect estimate of the prevalence.

What is the real prevalence of repeated implantation failure (RIF) and what reliable estimates can be given on the risk of false-positive diagnosis after two or three failed IVF attempts. A recent theoretical model suggested that commonly used definitions (two or three failed IVF attempts in good-prognosis couples) may expose couples to substantial odds of overdiagnosis and overtreatment. This model, however, was theoretical and based on unproven assumptions that the pregnancy rate in the non-RIF population was 30% and the prevalence of RIF was 10%. In the present study, we applied this model to real data to distinguish the real prevalence of RIF and to provide more reliable estimates on the risk of false-positive diagnosis after two or three failed IVF attempts. To this aim, we retrospectively selected 1221 good-prognosis couples and evaluated pregnancy rates up to the third cycle. The clinical pregnancy rate at first, second and third IVF cycle was 52%, 41% and 28%, respectively. A pregnancy rate of 61% was extrapolated in the non-RIF population and 15% among women who had experienced RIF. Therefore, the rate of false-positive diagnoses of RIF after two, three and six failed cycles would be 46%, 25%, and 2%, respectively. Our analyses show that estimated prevalence of RIF is 15%. The frequently used definition of RIF based on three failed attempts (but not two) in good-prognosis couples seems justified. Physicians, however, should bear in mind that couples may be inappropriately labelled with this condition in one out of four cases.

Reducing the risk of misdiagnosis of indirect ELISA by normalizing serum-specific background noise: The example of detecting anti-FGFR3 autoantibodies

Indirect enzyme-linked immunosorbent assay (ELISA) is an important diagnostic method as it enables the quantification of the presence of autoantibodies in human blood sera. However, unspecific binding of antibodies to the solid phase causes considerable serum-specific background noise (SSBN), involving the risk of false positive diagnosis. Therefore, we present a simple and concise, yet obvious proof-of-principle of a recently suggested normalization method. The method is based on subtracting SSBN by using non-coated ELISA wells as a control for each serum-of-interest. We performed ELISA to quantify anti-fibroblast growth factor receptor 3 (FGFR3) antibody levels in three positive controls (two anti-FGFR3-positive patients and a rabbit antiserum against FGFR3) and 58 negative controls (healthy blood donors). In all subjects, we found considerable unspecific reactivity which strongly varied among subjects. The conventional normalization method was not able to balance this strong SSBN, as demonstrated by 2/58 false positive healthy controls and one FGFR3-positive patient that was hidden in the noise (false negative). SSBN normalization reduced the frequency of false-positives to 0/58. Further, all three anti-FGFR3-positive sera were successfully detected and even doubled their z-score used to determine positivity. Albeit occupying more space on the ELISA plate, we strongly recommend considering this normalization method when working with blood sera. To better put the idea across to the community, we depict the SSBN issue and its solution in a graphic scheme. We conclude that SSBN normalization increases the sensitivity and specificity of indirect ELISA and thereby reduces the risk of false positive and false negative diagnosis. © 2019. Licensed under the Creative Commons [CC BY-NC 4.0 licence, https://doi.org/10.1016/j.jim.2019.01.004].

Benign Nodule Shrinkage: A Diagnosis not to be Missed

Thyroid nodules presenting ultrasonographic (US) findings suspicious for malignancy should undergo fine-needle aspiration and further cytologic analysis according to the Bethesda 2010 classification. Benign necrotic thyroid nodules may also harbor suspicious US features as follows: ill-defined margins, taller than wide aspect, strong hypoechogenicity, high stiffness index on elastography examination, and reported worrisome cytologic or histologic alterations. We report the case of a benign thyroid nodule showing shrinkage over time and harboring malignant US features. Fine-needle aspiration cytology examination showed necrosis and no malignant cells. Precise Doppler US analysis of the nodule and its evolution over time may limit the risk of false-positive diagnosis of thyroid malignancy.

Ciliated muconodular papillary tumor of the lung: The risk of false-positive diagnosis in frozen section

Ciliated muconodular papillary tumor (CMPT) is newly-defined low-grade malignant tumor, characterized as papillary tumor consisting of ciliated columnar, goblet, and basal cells. We present one case of pulmonary peripheral neoplasm misdiagnosed as mucinous adenocarcinoma. Pathologic findings showed, centrally, cystic papillary growth consisting of ciliated columnar, goblet, and basal cells, and peripherally, some tumor cells spread along the adjacent alveolar walls, in a lepidic fashion, and floating in pool of mucin. Tumor cells had bland nuclei, and no mitotic activity was observed. This had been initially misdiagnosed as mucinous adenocarcinoma in frozen section. We reviewed previous articles as well as permanent and frozen slides. In conclusion, in order to reduce the possibility of false positives, it is important to be aware that CMPT is a rare form of peripheral mucin-producing tumor with characteristic histologic findings.

(18)F-FDG Uptake at the Surgical Margin after Hepatic Resection: Patterns of Uptake and Differential Diagnosis.

To evaluate the patterns of (18)F-FDG uptake at the surgical margin after hepatectomy to identify features that may differentiate benign and malignant uptake. Patients who had undergone a PET/CT after hepatectomy were identified. Delay between resection and PET/CT, presence of uptake at the surgical margin, pattern of uptake, and maximal standardized value were recorded. The PET/CT findings were correlated with contrast-enhanced CT or MRI. There were 26 patients with increased 18F-FDG uptake; uptake was diffuse in seven and focal in 19. Diffuse uptake was due to inflammation in all cases. Focal uptake was due to recurrence in 12 and inflammation in seven cases. Defining a focal pattern only as a positive for malignancy yielded 100% sensitivity, 87% specificity, 37% false positive rate. As expected, SUVmax was significantly higher for recurrence than inflammation, but did overlap. Contrast-enhanced CT allowed differentiation between malignant and benign uptake in all cases. F-FDG uptake after hepatectomy does not equate to recurrence and yields a high false positive rate. Diffuse uptake did not require additional evaluation in our sample. Focal uptake, however, may be due to recurrence; differentiating benign and malignant nodular uptake relies on optimal contrast-enhanced CT or MRI. • Marginal uptake exposes patients to the risk of false positive diagnosis of recurrence. • Benign and malignant patterns of marginal uptake overlap. • Diffuse marginal uptake in our experience, has a high chance to be inflammatory. • Focal marginal uptake can be due to recurrent tumour or inflammation. • Contrast-enhanced CT or MR allows the differentiation between benign and malignant uptake.

Fixed ratio or lower limit of normal as cut-off value for FEV1/VC: An outcome study

There is no consensus on the appropriate cut-off level for the ratio between forced expiratory volume and vital capacity (FEV(1)/VC) for the diagnosis of chronic obstructive pulmonary disease (COPD). Application of a fixed ratio of 0.7 carries the risk of false positive diagnoses in elderly subjects and false negative diagnoses in younger subjects. The use of the lower limit of normal (LLN) of an individually predicted value should eliminate this problem. There is insufficient information about the outcome of elderly subjects with an FEV(1)/VC < 0.7 but above the LLN. We report lung function (spirometry and lung clearance index, LCI), mortality and risk of cardiac events in relation to FEV(1)/VC in a population-based sample of men examined at age 55 years. We stratified subjects as having FEV(1)/VC ≥ 0.7 (N), <0.7 but > LLN (FR+) and <0.7 and <LLN (FR+LLN+). Hazard ratio for death was 1, 1.33 (0.94-1.9) and 1.71 (1.3-2.2), respectively, when adjusted for smoking and a number of cardiovascular risk factors. In contrast, there was no increase in the corrected hazard ratio for cardiac events. FEV(1) progressively declined and LCI increased from N to FR+ and FR+LLN+. Subjects with FEV(1)/VC ratio below 0.7 but above the lower limit of normal form an intermediate group with respect to lung function impairment and mortality rates. Careful evaluation of patient history and extended lung function testing may be warranted in subjects with FEV(1)/VC < 0.7 but above the lower limit of normal.

Diagnostic Accuracy of Computed Tomography in Patients with Suspected Abdominal Aortic Aneurysm Rupture

This study was planned to evaluate the accuracy of computed tomography angiography (CTA) for suspected rupture of abdominal aortic aneurysm (AAA). Retrospective, observational study. A total of 97 patients who underwent open aneurysm repair for suspected rupture of AAA. The accuracy of preoperative and post hoc evaluation of CTA scans was evaluated by using the intra-operative findings as reference. At surgery, 58 patients were found to have a ruptured aneurysm. Interpretation of CTA findings at admission resulted in one false-negative and two false-positive diagnoses of aneurysm rupture as observed at surgery (sensitivity 98.3%, specificity 94.9%, positive predictive value 96.6%, negative predictive value 97.4%). Post hoc, blinded review of CTA findings resulted in one false-negative and three false-positive diagnoses of aneurysm rupture (sensitivity 98.3%, specificity 92.3%, positive predictive value 95.0%, negative predictive value 97.3%). Agreement between initial and post hoc assessment of CTA-findings was statistically significant (kappa 0.978, p < 0.0001). CTA is highly accurate in the diagnosis of suspected rupture of AAA. The risk of false-positive diagnosis is very low and it is not likely to affect the correct analysis of the results of comparative studies on endovascular versus open repair of ruptured AAA.

Comparative study of the cognitive performance of Greek Australian and Greek national elderly: Implications for neuropsychological practice

In the area of dementia diagnosis and assessment of cognitive functioning of elderly culturally and linguistically diverse individuals (CALDI) little is known about cognitive test performance differences between migrants and peers from their country of origin. This study investigated whether community dwelling elderly Greek Australian (GA) performance on tests of cognition was comparable to that of elderly Greek national ‘normal’ individuals without a diagnosis of dementia (Gn). Based on available cross-cultural literature it was hypothesised that GA would obtain lower scores on the Cambridge Cognitive Examination of the Elderly and the Mini-Mental Status Examination compared to Gn due to issues relating to the migrant experience such as acculturation, reduced language fluency and proficiency. The results of the current study supported the hypothesis arguing for caution when interpreting CALDI performance on tests that have not been normed in that particular group because there may be a greater risk of false-positive diagnoses.

NQO1 Expression in Pancreatic Cancer and Its Potential Use as a Biomarker

Pancreatic ductal adenocarcinoma (PDA) is rarely curable due to regional/metastatic spread at diagnosis. Identification of molecular markers may enhance diagnosis and early detection of PDA. The 2-electron reductase, NAD(P)H:quinone oxidoreductase (NQO1) has been found to be overexpressed in many solid tumors including PDA, and may be a useful clinically relevant diagnostic marker of malignancy. For this study, we used 37 surgical resection cases: 24 PDAs and 13 benign pancreatic tissue specimens. An additional 16 specimens from pancreatic endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) were included as a pilot series. NQO1 was detected by avidin-biotin based immunohistochemical and immunocytochemical methods. Both staining intensity and proportion of NQO1 positive tumor cells were scored. Moderate to strong (2 to 3+) staining for NQO1 was detected in 22/24 (92%) surgically resected PDAs, 9/9 (100%) EUS-FNAs with malignant diagnoses, one cytologically atypical but not diagnostic for malignancy EUS-FNA, and 1/6 (17%) EUS-FNAs initially diagnosed as negative for malignancy. Subsequent histologic assessment confirmed malignancy in all 9 cytologically positive EUS-FNAs and in the atypical case. The NQO1 positive case initially diagnosed as negative for malignancy showed no evidence of carcinoma on subsequent tissue biopsy. NQO1 staining was also observed in some benign ducts/cells; however, correlation of NQO1 expression with cellular morphology assessment minimizes the risk of false positive diagnosis. NQO1 is consistently overexpressed in PDA. Although NQO1 is observed in some benign tissue components, this marker may be a clinically useful diagnostic adjunct for detection of PDA, independent of tumor grade/stage.

Improved prenatal diagnosis of the congenital nephrotic syndrome of the Finnish type based on DNA analysis

Haplotype analysis and alpha-fetoprotein quantitation comprise a prenatal diagnosis of congenital nephrosis. Congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessive disease characterized by massive proteinuria and nephrotic syndrome from birth. Prenatal diagnosis of CNF has previously been based on the quantitation of alpha-fetoprotein (AFP) in the amniotic fluid and maternal serum, but an increased AFP is not specific for the disease. We have recently localized the CNF gene to the chromosome 19q13.1 region and observed a strong linkage disequilibrium to the genetic markers D19S610, D19S608, D19S224 and D19S220 in this chromosomal area. Four main CNF-haplotypes have been observed in Finnish kindreds. In the present study, linkage and haplotype analyses have been applied to prenatal diagnosis of six families with a history of CNF. The results diminish the risk of false positive diagnosis and abortions of healthy fetuses in families at risk.

Does routine ultrasound scanning improve outcome in pregnancy? Meta-analysis of various outcome measures.

To evaluate the effectiveness of routine ultrasound scanning in pregnancy by a meta-analysis of various outcome measures. Meta-analysis of randomised controlled trials evaluating the effect of routine ultrasound scanning on perinatal mortality and morbidity. Live birth rate (that is, live births per pregnancy) is included as a measure of pregnancy outcome in addition to the conventional perinatal mortality. 15,935 pregnancies (7992 in which routine ultrasound scanning was used and 7943 controls with selective scanning) from four randomised controlled trials. Perinatal mortality, live birth rate, rate of miscarriage, Apgar score < 7 at 1 minute, and number of induced labours. The live birth rate was identical in both screening and control groups (odds ratio = 0.99; 95% confidence interval 0.88 to 1.12) although the perinatal mortality was significantly lower in the group who had routine ultrasonography (0.64, 0.43 to 0.97). Differences in perinatal morbidity between the two groups as measured by the proportion of newborn babies with Apgar score < 7 at 1 minute were not significant (1.05; 0.93 to 1.19). Routine ultrasound scanning does not improve the outcome of pregnancy in terms of an increased number of live births or of reduced perinatal morbidity. Routine ultrasound scanning may be effective and useful as a screening for malformation. Its use for this purpose, however, should be made explicit and take into account the risk of false positive diagnosis in addition to ethical issues.

13 - Screening for Ovarian Cancer

This chapter has stressed the urgent need for a screening test for the early detection of ovarian cancer. Real-time, mechanical sector ultrasonography is non-invasive, rapid, painless and has no harmful effects. It can be used to determine ovarian morphology and measure ovarian volume quickly in 99.4 per cent of post-menopausal women. Used correctly, with a precise knowledge of the pelvic anatomy and with proper training in methodology, the risk of false positive diagnoses of ovarian enlargement is small. The incidence of ovarian abnormality diagnosed by ultrasound in this series was 3 per cent. The ovarian neoplasms included clear-cell carcinoma, and serous and mucinous cystadenomas. However, ultrasound appearances of ovarian neoplasms bore little, if any, correlation with the histological diagnosis. Thus, we believe that real-time mechanical sector ultrasonography is reliable in the detection of ovarian neoplasms but the diagnosis can be made only by histological examination. The potential of this technique as a screening test for the early detection of ovarian cancer warrants further evaluation.

Influence of spatulation time upon the radio‐graphic homogeneity of Adaptic Radiopaque® fillings

1)Twelve test cavities were filled with Adaptic Radiopaque by the author, varying the spatulation times form 5 s to 60 s at 5-s intervals but using the same mixing technique. Fillings spatulated for less than 20 s appeared inhomogeneous on radiograph. 2)Twenty-eight dentists produced 84 test fillings determining themselves their spatulation time and applying their own mixing technique. Spatulation times varied from 10 to 55 s. The fillings were radiographed under standardized conditions. Twenty-five were classified as radiographically homogeneous, 35 as partly inhomogeneous, and 24 as inhomogeneous. Short spatulation times were correlated with a high frequency of inhomogeneous fillings. Only 15% of fillings spatulated for less than 30 s were radiographically homogeneous. The observed inhomogeneities imply a risk of false positive diagnoses of secondary carious lesions.