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New statistical software for intralaboratory and interlaboratory quality control in clinical cytology. Validation in a simulation study on clinical samples.

OBJECTIVE: To design a statistical software package to provide automated calculations of normal and weighted and 3 indices. STUDY DESIGN: Prompted by the lack of commonly available software to compute weighted kappa and the nonproportionate workload needed to calculate our 3 variability indices manually, the new statistical software package was designed. To demonstrate the performance of the new CONQUISTADOR software, a simulation study (both intralaboratory and interlaboratory) was designed using 5,000 clinical samples randomly selected from a data file of > or = 200,000 conventional Pap smears and programmed to become "analyzed" by 12 cytologists in 5 imaginary laboratories. RESULTS: A representative set of both complete and partial outputs provided by the software, in Excel format (Microsoft, Redmond, Washington, U.S.A.) are shown to illustrate the different functions of the program. In the interlaboratory mode, the software calculates accuracy indicators (sensitivity, specificity, positive and negative predictive value, and their 95% CI), which are not common features of regular statistical packages; kappa and weighted kappa; and their 95% CI (comparison of single laboratories to all laboratories and pairwise comparisons between single laboratories). The 3 diagnostic variability indices can be computed separately for all samples or for only the positive samples. In the intralaboratory mode, the software calculates the same indices for individual cytologists. CONCLUSION: The CONQUISTADOR statistical package has properties that are useful in monitoring cytologic laboratory quality in both intralaboratory and interlaboratory settings. The software will be distributed by the National Institute of Health, Rome, for the delivery costs only.

Clinical Laboratory Techniques↗

Advances in biomedical image analysis--past, present and future challenges.

Starting from raw data files coding eight bits of gray values per image pixel and identified with no more than eight characters to refer to the patient, the study, and technical parameters of the imaging modality, biomedical imaging has undergone manifold and rapid developments. Today, rather complex protocols such as Digital Imaging and Communications in Medicine (DICOM) are used to handle medical images. Most restrictions to image formation, visualization, storage and transfer have basically been solved and image interpretation now sets the focus of research. Currently, a method-driven modeling approach dominates the field of biomedical image processing, as algorithms for registration, segmentation, classification and measurements are developed on a methodological level. However, a further metamorphosis of paradigms has already started. The future of medical image processing is seen in task-oriented solutions integrated into diagnosis, intervention planning, therapy and follow-up studies. This alteration of paradigms is also reflected in the literature. As German activities are strongly tied to the international research, this change of paradigm is demonstrated by selected papers from the German annual workshop on medical image processing collected in this special issue.

Electronic Data Processing↗

Comparative evaluation of underlying causes of death processed by the Automated Classification of Medical Entities and the Underlying Cause of Death Selection Systems.

INTRODUCTION: The correct identification of the underlying cause of death and its precise assignment to a code from the International Classification of Diseases are important issues to achieve accurate and universally comparable mortality statistics. These factors, among other ones, led to the development of computer software programs in order to automatically identify the underlying cause of death. OBJECTIVE: This work was conceived to compare the underlying causes of death processed respectively by the Automated Classification of Medical Entities (ACME) and the "Sistema de Seleção de Causa Básica de Morte" (SCB) programs. MATERIAL AND METHOD: The comparative evaluation of the underlying causes of death processed respectively by ACME and SCB systems was performed using the input data file for the ACME system that included deaths which occurred in the State of S. Paulo from June to December 1993, totalling 129,104 records of the corresponding death certificates. The differences between underlying causes selected by ACME and SCB systems verified in the month of June, when considered as SCB errors, were used to correct and improve SCB processing logic and its decision tables. RESULTS: The processing of the underlying causes of death by the ACME and SCB systems resulted in 3,278 differences, that were analysed and ascribed to lack of answer to dialogue boxes during processing, to deaths due to human immunodeficiency virus [HIV] disease for which there was no specific provision in any of the systems, to coding and/or keying errors and to actual problems. The detailed analysis of these latter disclosed that the majority of the underlying causes of death processed by the SCB system were correct and that different interpretations were given to the mortality coding rules by each system, that some particular problems could not be explained with the available documentation and that a smaller proportion of problems were identified as SCB errors. CONCLUSION: These results, disclosing a very low and insignificant number of actual problems, guarantees the use of the version of the SCB system for the Ninth Revision of the International Classification of Diseases and assures the continuity of the work which is being undertaken for the Tenth Revision version.

Cause of Death↗

Prescribing potentially inappropriate psychotropic medications to the ambulatory elderly.

BACKGROUND: Psychotropic agents account for 23% to 51% of all inappropriate medications prescribed based on 1991 inappropriate medication criteria for nursing home residents. The criteria were revised to apply to all people older than 65 years. This study used the revised criteria in ambulatory settings to quantify potentially inappropriate prescription of psychotropic agents and identify associated characteristics. METHODS: The 1996 public use data files of the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey were analyzed for inappropriate prescription of psychotropic medications for the elderly in office-based settings and outpatient departments. Disease-independent and disease-dependent criteria were analyzed. RESULTS: Elderly patients were prescribed a psychotropic agent in 8. 7% of all visits, antidepressant and antianxiety agents being the most frequently prescribed medications. Commonly, elderly patients receiving psychotropic agents were female, white, aged between 65 and 74 years, and received health care in a metropolitan area. Potentially inappropriate psychotropic agents were prescribed in 27. 2% of all visits involving a psychotropic agent for the elderly. Disease-independent criteria (eg, antidepressant agents and long-acting benzodiazepines) accounted for most of the potentially inappropriate prescriptions. Factors positively associated with potentially inappropriate prescriptions included older age, "seen before" status, and antidepressant drug class, while enrollment in Medicaid, antipsychotic drug class, living in the Northeast region, and receiving health care in a metropolitan area were negatively associated. CONCLUSIONS: Potentially inappropriate prescription of psychotropic agents is very common for the elderly patient in the ambulatory setting. By focusing on the agents most frequently involved (eg, amitriptyline and long-acting benzodiazepines), provider characteristics (eg, location), and patient characteristics (eg, age), the greatest impact on potentially inappropriate prescribing can be achieved.

Adverse Drug Reaction Reporting Systems↗

Excess mortality due to pneumonia or influenza during influenza seasons among persons with acquired immunodeficiency syndrome.

BACKGROUND: Anecdotal reports suggest that influenza-related morbidity may be high among persons with acquired immunodeficiency syndrome (AIDS), but little information is available concerning the population-level impact of influenza on mortality in persons with AIDS. METHODS: Using the Multiple Cause-of-Death data files, which contain information on all deaths occurring in the United States each year, we calculated the numbers of excess deaths and rates of excess death due to pneumonia or influenza among persons with AIDS aged 13 years and older during the influenza seasons 1991-1992 through 1993-1994. For comparison, numbers of excess deaths and excess death rates were also calculated for several other groups including the general US population aged 13 years and older and the general US population aged 65 years and older. RESULTS: During the 1991-1992, 1992-1993, and 1993-1994 influenza seasons, there were 261, 254, and 191 excess deaths due to pneumonia or influenza in persons with AIDS and excess death rates of 19.74, 15.38, and 10.17 deaths per 10 000 persons, respectively, compared with a summer baseline period. For the same seasons, we observed excess death rates of 1.40, 1.62, and 1.48 for the general US population aged 13 years and older and 8.10, 9.28, and 8.54 for the general US population aged 65 years and older. Thus, persons with AIDS had excess death rates substantially higher than the general US population and similar to, if not somewhat higher than, the general US population aged 65 years and older, a group that is already targeted for annual vaccination. The findings were similar when we compared the preinfluenza season with the influenza season. CONCLUSIONS: Persons with AIDS have significant excess mortality due to pneumonia or influenza during influenza seasons and should be considered a high-risk group that is targeted for the prevention of influenza.

Acquired Immunodeficiency Syndrome↗

Effect of larger ablation zone and transition zone on corneal optical aberrations after photorefractive keratectomy.

OBJECTIVE: To evaluate the effects of photorefractive keratectomy on corneal optical aberrations using a 5.5-mm optical zone and a 7.0-mm transition zone. METHODS: Videokeratographs of 72 eyes from 47 patients treated for low to moderate (1-9 diopters) myopia were obtained at the preoperative and 1-, 3-, 6-, 12-, and 18-month postoperative examinations. The videokeratoscopy data files were used to calculate the wavefront variance of the corneas for small (3-mm) and large (7-mm) pupils using a previously described method. RESULTS: In general, all optical aberrations decreased postoperatively for 3-mm pupils and increased for 7-mm pupils compared with preoperative values. For 3-mm pupils, the 2 common optical aberrations (comalike [S(3)] and spherical-like [S(4)]) decreased postoperatively and never returned to preoperative values. For 7-mm pupils, however, comalike aberrations increased slightly and spherical-like aberrations increased by nearly an order of magnitude during the postoperative period. Similarly, for 3-mm pupils, the higher order S(5) and S(6) aberrations decreased throughout the postoperative period, with S(6) values showing an approximately 23-fold reduction at 12 and 18 months. For 7-mm pupils, S(5) and S(6) aberrations increased slightly, more so for S(5) (approximately 3-fold) than for S(6). Total wavefront aberrations decreased an average of 2.3 times postoperatively for 3-mm pupils, and increased significantly (P<.05) at all postoperative examinations for 7-mm pupils. Opening the pupil from 3 mm to 7 mm before surgery produced a 14-fold increase in total aberrations, whereas this same change produced an average 113-fold increase after photorefractive keratectomy. CONCLUSIONS: Corneal optical aberrations after photorefractive keratectomy with a larger ablation zone and a transition zone are less pronounced and more physiologic than those associated with first-generation (5-mm) ablations with no transition zone. CLINICAL RELEVANCE: Evaluating the postoperative corneal aberration structure will help us devise ways to minimize the wavefront aberrations of the eye through the creation of an ideal corneal first surface, thereby improving visual results for patients undergoing excimer laser ablations for refractive correction.

Adult↗

Costs of posttreatment surveillance for patients with upper aerodigestive tract cancer.

OBJECTIVES: To determine the range of recommended follow-up strategies for patients with upper aerodigestive tract cancer treated with curative intent and to estimate the cost of follow-up. DESIGN: Economic analyses of the costs associated with 31 follow-up strategies (12 generic and 19 site specific) identified from a MEDLINE search of the literature for 1978 to 1997 and a search of major textbooks. Generic strategies are not specific for site or histology and are exclusive of strategies designed for the rare patient, ie, patients who would not be considered average in terms of clinical characteristics. Charge data obtained from the Part B Medicare Annual Data File and the Hospital Outpatient Bill File were used as a proxy for cost. SETTING: Ambulatory care. MAIN OUTCOME MEASURES: Nationwide Medicare-allowed charges and an actual-charge proxy for 5 years of surveillance after treatment for upper aerodigestive tract cancer. RESULTS: Medicare-allowed charges for 5-year follow-up ranged from a low of $739 to a high of $14,079 for the generic and site-specific strategies combined and from $739 to $4646 for the 12 generic strategies alone. When Medicare-allowed charges were converted to a proxy for actual charges using a conversion ratio of 1.62, the range was $1198 to $22,807 for all strategies combined (a 19-fold difference in charges) and $1198 to $7597 for the generic strategies alone (a 5-fold difference in charges). CONCLUSIONS: Charges vary extensively across surveillance strategies, particularly if site-specific strategies are considered, although the potential benefit of more intensive, higher-cost strategies on survival or quality of life has yet to be demonstrated.

Continuity of Patient Care↗

Serotypes of Chlamydia trachomatis and risk for development of cervical squamous cell carcinoma.

CONTEXT: Human papillomavirus (HPV) infection has been established as a cause of cervical cancer. Epidemiologic studies suggest that Chlamydia trachomatis infection also confers increased risk for cervical squamous cell carcinoma (SCC). Whether this risk is serotype-specific is unknown. OBJECTIVE: To study the association between exposure to different C trachomatis serotypes and subsequent development of cervical SCC. DESIGN AND SETTING: Longitudinal, nested case-control study within a cohort of 530 000 women who provided samples to serum banks in Finland, Norway, and Sweden. The data files were linked to respective national cancer registries. SUBJECTS: One hundred twenty-eight women who had developed invasive cervical SCC at least 12 months following serum donation. Each case had 3 matched controls. MAIN OUTCOME MEASURE: Risk for the development of cervical SCC by IgG antibodies to 10 different C trachomatis serotypes, adjusted for antibodies to HPV types 16, 18, and 33 and for serum cotinine levels. RESULTS: Of specific C trachomatis serotypes, serotype G was most strongly associated with SCC (adjusted odds ratio [OR], 6.6; 95% confidence interval [CI], 1. 6-27.0). Other serotypes associated with SCC were I (OR, 3.8; 95% CI, 1.3-11.0) and D (OR, 2.7; 95% CI, 1.3-5.6). Presence of serum IgG antibodies to more than 1 serotype increased the adjusted ORs for SCC (P<.001 for trend). CONCLUSIONS: Chlamydia trachomatis serotype G is most strongly associated with subsequent development of cervical SCC. Increasing numbers of exposures to different C trachomatis serotypes also increases risk. Our results strengthen the evidence that there is a link between past C trachomatis infection and cervical SCC.

Antibodies, Bacterial↗

Overall survival from breast cancer in women pregnant or lactating at or after diagnosis. Auckland Breast Cancer Study Group.

The effect of concurrent or subsequent pregnancy or lactation has been studied in women with breast cancer to determine if these variables influence prognosis. Information was collected from 382 women potentially capable of bearing children, aged less than 45 years, in the Auckland Breast Cancer Study Group data file, a consecutive series of women diagnosed with breast cancer from 1976 to 1985, with a median follow-up of 10.2 years. The prevalence of both pregnancy at diagnosis and lactation at diagnosis was 2.6%. The incidence of pregnancy subsequent to diagnosis was 3.9%. Women pregnant at the time of breast cancer diagnosis had significantly more advanced disease than non-pregnant patients, and there was a similar trend for women lactating at diagnosis. Overall survival in these women was poor compared with the non-pregnant and non-lactating groups; only 2 of 10 pregnant patients and 0 of 10 lactating patients survived more than 12 years. The adverse outcome for women lactating at diagnosis of their breast cancer persisted despite allowance for nodal status, tumour size and age. However, survival was similar between pregnant and non-pregnant patients when these variables were taken into account. No significant differences in survival were found between those women who had pregnancies subsequent to diagnosis of breast cancer and breast cancer patients who did not become pregnant.

Adult↗

Chlamydia trachomatis infection as a risk factor for invasive cervical cancer.

Cervical carcinoma is a sexually transmitted disease most strongly linked with human-papillomavirus (HPV) infection. We conducted a prospective sero-epidemiologic study to evaluate the role of Chlamydia trachomatis infection in the development of cervical carcinoma, with invasive cancer as an end point. A nested case-control study within a cohort of 530000 Nordic women was performed. Linking data files of 3 Nordic serum banks and the cancer registries of Finland, Norway and Sweden identified 182 women with invasive cervical carcinoma diagnosed during a mean follow-up of 5 years after serum sampling. The serum samples of the cases and matched cancer-free controls were analyzed for IgG antibodies to C. trachomatis, C. pneumoniae (a control microbe) and HPV types 16, 18 and 33, as well as for serum cotinine (an indicator of tobacco smoking). Serum antibodies to C. trachomatis were associated with an increased risk for cervical squamous-cell carcinoma (HPV- and smoking-adjusted OR, 2.2; 95% CI, 1.3-3.5). The association remained also after adjustment for smoking both in HPV16-seronegative and -seropositive cases (OR, 3.0; 95% CI, 1.8-5.1; OR, 2.3, 95% CI, 0. 8-7.0 respectively). No such association was found for C. pneumoniae. Our prospective study provides sero-epidemiologic evidence that infection with C. trachomatis confers an increased risk for subsequent development of invasive squamous-cell carcinoma of the uterine cervix.

Adenocarcinoma↗

Deconvolution gas chromatography/mass spectrometry of urinary organic acids--potential for pattern recognition and automated identification of metabolic disorders.

The National Institute of Standards and Technology (NIST) Automated Mass Spectral Deconvolution and Identification System (AMDIS) is applied to a selection of data files obtained from the gas chromatography/mass spectrometry (GC/MS) analysis of urinary organic acids. Mass spectra obtained after deconvolution are compared with a special user library containing both the mass spectra and retention indices of ethoxime-trimethylsilyl (EO-TMS) derivatives of a set of organic acids. Efficient identification of components is achieved and the potential of the procedure for automated diagnosis of inborn errors of metabolism and for related research is demonstrated.

Acyl-CoA Dehydrogenase↗

Quadrat analysis software for the detection of spatial or temporal clustering.

A software program is presented which automates the quadrat analysis procedure for detecting spatial or temporal clustering outlined by Boots and Getis. The software essentially compares observed values within areal or temporal sampling units to those values that would have been obtained were the values distributed randomly. A chi-square test of significance is used to assess whether the values are dispersed in a non-random pattern and a t-test is used to assess whether the values are dispersed in a non-regular pattern. The software requires DOS 3.3 or higher and reads dBase-compatible data files.

Chi-Square Distribution↗

Criticism of a hierarchical model using Bayes factors.

This paper analyses a data file of heart transplant surgeries performed in the United States over a two-year period. A Poisson/gamma exchangeable model is used to learn about the underlying death rates for 94 hospitals. There are concerns about the suitability of this hierarchical model, including the need for a hierarchical structure, the existence of outliers, the choice of prior hyperparameters, the need for a covariate in the model, and the manner in which exchangeability was modelled. Each concern motivates the construction of alternative models and Bayes factors are used to compare the existing model with the alternative models. Graphical displays are used to check the sensitivity of the posterior analysis with respect to model perturbations and plots of Bayes factors are used to criticize these perturbations.

Bayes Theorem↗

Design of a state-based workers' compensation information system.

BACKGROUND: California policy makers have long been hampered by a lack of credible information for use in making legislative or administrative changes to address serious problems in the workers' compensation system. In 1993, the legislature directed the California Division of Workers' Compensation to develop a Workers' Compensation Information System (WCIS). METHODS: An advisory committee developed key questions and identified data sources regarding injury/illness incidence, costs, promptness of benefit delivery, adequacy of benefits, satisfaction with services, and other outcomes. RESULTS: Key data elements were identified, mostly from existing mandated reporting forms for employers and physicians, and from standardized medical billings. Data collection will be carried out using: 1) rapid electronic data interchange (EDI) for a minimum number of data elements; 2) electronic collection of data on medical services for a sample of claims; and 3) surveys to address adequacy of benefits, satisfaction with services, return to work, and other outcomes. A state-based repository will analyze data and provide de-identified public use data files. CONCLUSIONS: The proposed WCIS will provide information to improve the performance and to increase the accountability of all the participants in California's Workers' Compensation system. More importantly, it will provide information which will allow improved quality in the provision of mandated benefits to injured workers.

Benchmarking↗

Comparison of Vindelov et al. and bromodeoxyuridine/DNA double-staining flow cytometry methods for analysis of cell cycle distribution in rat thymocytes.

This study compares the cell cycle distribution in rat thymocytes obtained by means of bromodeoxyuridine (BrdUrd) labeling of S-phase cells and the analysis of the S-phase fraction obtained according to the technique of Vindelov et al. (Cytometry 3:332-338, 1983). The proportion of BrdUrd-labeled cells was analyzed in single cell suspensions of adult rat thymocytes after in vivo injection of BrdUrd and the results then compared with those obtained after measuring the cell DNA contents according to the Vindelov et al. method. The percentage of BrdUrd-positive cells was greater than the S-phase fraction obtained using the Vindelov et al. technique. By contrast, no major differences were observed between the percentage of BrdUrd-positive cells and the S-phase fraction obtained after analyzing the DNA histograms of the same data files with the RFIT mathematical model. The elimination of trypsin treatment used in the Vindelov et al. method did not alter the results, whereas the use of DNA denaturation with 2N HCl was shown to increase the percentage of S-phase rat thymocytes (calculated from DNA histograms) independently of whether trypsin treatment was used or not. However, the value of the S-phase fraction was not as great as that obtained after BrdUrd labeling. Thus when comparing BrdUrd-labeling and the Vindelov et al. technique, important differences in the percentage of S-phase adult rat thymocytes were observed. Selective G0/G1 cell loss during washing and centrifugation steps performed after the DNA denaturation used for BrdUrd detection was the main reason for these differences.

Animals↗

Quantitative DNA ploidy analysis of breast carcinoma: a study of the effects of joint photographer experts group (JPEG) compression on DNA ploidy images.

Telepathology usage in the past has typically been a qualitative procedure rather than a quantitative measurement. DNA ploidy using image analysis has been favorably compared to DNA ploidy analysis by flow cytometry in numerous publications. A step from DNA ploidy analysis using conventional image analysis to DNA ploidy analysis using stored images allows DNA ploidy analysis by image cytometry to become a powerful tool in telepathology. Remote DNA ploidy analysis using stored images has an impact on the field of pathology, as not every hospital or laboratory can afford to perform this type of specialized testing. However, images have large data files and require lengthy transmission times over communication systems to other computers. Joint Photographer Experts Group (JPEG) compression is a computer algorithm that allows the file size of an image to be reduced in order to decrease transmission times to another computer. A study was initiated to investigate the effects of JPEG compression on images of Feulgen stained breast tumor touch preps and the resulting DNA ploidy histograms.

Animals↗

Incidence of pelvic inflammatory disease among women treated for gonorrhea or chlamydia.

BACKGROUND: No estimate exists of the incidence of pelvic inflammatory disease (PID) after the occurrence of a recent bout of sexually transmitted disease (STD). METHODS: We used a computerized data file of prescriptions and medical encounters from the Fallon Community Health Plan to estimate the incidence rate of pelvic inflammatory disease (PID) among women with a recently treated episode of gonorrhea or chlamydia (STD). First we identified women with presumed gonorrhea or chlamydia on the basis of a combination of diagnostic codes for cervicitis, vulvovaginitis or Bartholin's abscess, and a computer record of a prescription for doxycycline. We then followed these women to estimate the incidence rate of PID after their treatment for gonorrhea or chlamydia. We estimated the number of cases of pelvic inflammatory disease in this cohort by selecting all women with an International Classification of Diseases (ICD) code of 614.9 entered for either an outpatient or inpatient diagnosis. RESULTS: We estimated the overall risk of PID to be about 9% during the 1-year period following treatment for gonorrhea or chlamydia, with a steep rise in risk coming within the first 45 days. CONCLUSION: The risk of PID in the year after an episode of treated STD is high, but the highest period of risk is in the first few weeks. The shape of the risk curve indicates that some PID cases may result from treatment-resistant infections, or possibly from untreated reinfections.

Journal Article↗

Descriptive epidemiology of acute liver enzyme abnormalities in the general population of central Massachusetts.

OBJECTIVES: This study quantifies the incidence of liver enzyme abnormalities in the general population of central Massachusetts. METHODS: Computerized data files from a health maintenance organization were used to ascertain potential subjects during the study period of 1 July 1992-30 June 1993. Medical records and laboratory tests results were reviewed to confirm the diagnoses. RESULTS: The incidence rates were 40.6 cases per 100,000 persons per year for drug-associated liver enzyme abnormalities, 39.0 per 100,000 persons per year for liver enzyme abnormalities secondary to biliary pathologies, 25.2 per 100,000 persons per year for liver enzyme abnormalities secondary to mononucleosis, 25.2 per 100,000 persons per year for liver enzyme abnormalities of unknown aetiology, 15.4 per 100,000 persons per year for alcoholic liver enzyme abnormalities, 12.2 per 100,000 persons per year for liver malignancy, and 7.3 per 100,000 persons per year for viral hepatitis (HAV, HBV and HCV). Men were more commonly affected by alcoholic liver enzyme abnormalities and viral hepatitis, with respective incidence rates approximately 5 and 2 times higher than women. Liver enzyme abnormalities secondary to mononucleosis occurred predominantly between the ages of 15-24 years. In contrast, liver diseases secondary to biliary pathologies, liver malignancies and drug-associated liver enzyme abnormalities were found most frequently among the elderly. CONCLUSION: Liver enzyme abnormalities occurred with a higher incidence in this general population than reported previously in selected patients. Drug-associated liver enzyme abnormality was the most common type. The magnitude of drug-associated liver enzyme abnormality could be much higher as an appreciable proportion of the liver cases of unknown aetiology are potentially drug-attributable.

Journal Article↗