False negatives of screening in large-scale population / 上海预防医学

ObjectiveTo explore the changing trend of negative predictive value and number of false negatives in screening tests under the condition of low infection rate of infectious diseases. MethodsAssuming that the population is 20 million， to calculate the negative predictive value， numbers of true negatives and false negatives of the combination of different sensitivity （75.0%， 80.0%， 85.0%， 90.0%， 95.0%， 99.0%） and specificity （90.0%， 95.0%， 99.0%， 99.9%） when the disease infection rate of the population is 0.10%， 1.0% and 5.0% respectively. ResultsWhen the population infection rate is 0.1%， with the screening test sensitivity ≥75.0% and specificity ≥90.0%， the number of true negatives in 20 million people is about 17.98‒19.96 million. When the sensitivity is 75.0%， the negative predictive value is 99.972%‒99.975%， and the number of false negatives is 5 000； When the sensitivity increases to 99.0%， the negative predictive value is 99.999%， and the number of false negatives decreases to 200. When the population infection rate is 1.0%， a screening test with sensitivity ≥75.0% and specificity ≥90.0% can detect about 17.82‒19.78 million true negatives in 20 million population. When the sensitivity is 75.0%， the negative predictive value is 99.720%‒99.748%， and the number of false negatives is 50 000； When the sensitivity increases to 99.0%， the negative predictive value increases to 99.990%， and the number of false negatives decreases to 2 000. When the population infection rate is 5.0%， with sensitivity ≥75.0% and specificity ≥90.0%， the number of true negatives in 20 million people is about 17.10‒18.98 million； when the sensitivity is 75.0%， the negative predictive value is 98.559%‒98.700%， and the number of false negatives can reach 250 000； When the sensitivity is 99.0%， the negative predictive value increases to 99.942%‒99.947%， and the number of false negatives decreases to 10 000. The lower the infection rate of the population， the fewer false negatives will appear in the screening. ConclusionThe number of false negatives in large-scale screenings increases exponentially with the increase of infection rate. Screenings should be carried out as early as possible in a pandemic of infectious diseases， so as to control the spread of the pandemic as soon as possible.

Atrial fibrillation diagnosis algorithm based on improved convolutional neural network / 生物医学工程学杂志

Atrial fibrillation (AF) is a common arrhythmia, which can lead to thrombosis and increase the risk of a stroke or even death. In order to meet the need for a low false-negative rate (FNR) of the screening test in clinical application, a convolutional neural network with a low false-negative rate (LFNR-CNN) was proposed. Regularization coefficients were added to the cross-entropy loss function which could make the cost of positive and negative samples different, and the penalty for false negatives could be increased during network training. The inter-patient clinical database of 21 077 patients (CD-21077) collected from the large general hospital was used to verify the effectiveness of the proposed method. For the convolutional neural network (CNN) with the same structure, the improved loss function could reduce the FNR from 2.22% to 0.97% compared with the traditional cross-entropy loss function. The selected regularization coefficient could increase the sensitivity (SE) from 97.78% to 98.35%, and the accuracy (ACC) was 96.62%, which was an increase from 96.49%. The proposed algorithm can reduce the FNR without losing ACC, and reduce the possibility of missed diagnosis to avoid missing the best treatment period. Meanwhile, it provides a universal loss function for the clinical auxiliary diagnosis of other diseases.

The adequate number of lymph node dissection in pancreatic cancer radical surgery based on nodal staging score(with four-center cohort validation) / 中国实用外科杂志

OBJECTIVE: To estimate the number of lymph nodes(LNs)needed to be examined for adequate LN staging via nodal staging score(NSS).METHODS: A model was fitted based on 3989 pN + patients with resected primary pancreatic adenocarcinoma in the Surveillance,Epidemiology and End RESULTS:(SEER)database.The number of nodes to examine to achieve an N SS of 90% was used as the optimal number.The results were validated in node negative patients from the SEER cohort(2583 patients)and a local multicenter cohort(93 patients).RESULTS: Tumor size is a determinant for the extent of lymphadenectomy.According to the tumor size<2 cm and ≥2 cm,15 and 20 LNs would need to be examined to achieve90% confidence in a pN0 patient.As a result of missing node-positive case,the prevalence of nodepositive was adjusted from 60.7% to 71.0%.In the survival analysis,more LNs examined was shown to be correlated with better prognosis in patients with tumor ≥2 cm.CONCLUSION: The minimum number of LNs for adequate staging depends on the tumor size.The estimation provides a practical standard for evaluating the extent of LN yield for surgeons.

Formulation and evaluation on Sysmex XN9000 blood cell analyzer re-examination criteria in ISO15189 accredited laboratory / 国际检验医学杂志

Objective To establish the re-examination criteria of the Sysmex XN-9000 automatic blood cell analyzer pipeline suitable for this laboratory for ensuring the accuracy of detection results .Methods A total of 2250 whole blood samples were se-lected from inpatients ,outpatients and subjects undergoing physical examination .The Sysmex XN-9000 blood cell analyzer was a-dopted to conduct the detection .With the manual microscopic examination as the golden standard ,26 items of re-examination criteria were performed the verification and evaluation .The positive predicting value ,negative predicting value ,false positive rate ,false neg-ative rate and re-examination rate were performed by the statistics .Results In compariing the instrument alarm information with the microscopic examination results ,the positive predicting value was 91 .59% ,the negative predicting value was 98 .64% ,the false positive rate was 2 .09% ,the false negative rate was 1 .02% and the re-examination rate was 24 .84% .Conclusion The formulated re-examination criteria of the Sysmex XN-9000 blood cell analyzer is in accord with the characteristics of our laboratory ,which in-creases the detection efficiency ,prevents the missing detection and false detection and has clinical guidance significance .

Application of brainstem auditory evoked potentials in diagnosis of brain death / 中国中西医结合急救杂志

Objective To evaluate the diagnostic validity of application of brainstem auditory evoked potential (BAEP) as an ancillary test in patients with brain death.Methods A prospective observational study was conducted. Adult patients (≥ 18 years) with brain death were consecutively admitted to the Department of Intensive Care Unit (ICU) of Beijing Tiantan Hospital Affiliated to Capital Medical University from July 2015 to June 2017, and they further underwent BAEP monitoring. The following findings: absence of all waveforms at bilateral sides, absence of all waveforms except wave-Ⅰonly present at bilateral orunilateral side were set as the positive criteria of BAEP for the diagnosis of brain death, and its diagnostic sensitivity (SEN), positive predictive value (PPV) and false negative rate (FNR) were further assessed.Results A total of 47 patients were enrolled in the study, and the 43 complete BAEP results were analyzed. The SEN, PPV and FNR of the above 3 types of diagnostic criteria (absence of all waveforms, and unilateral or bilateral presence of wave-Ⅰ only) were 100% [95% confidence interval (95%CI) 90-100], 100% (95%CI 89-100), and 0% (95%CI 0-9), respectively.Conclusion As an ancillary test, BAEP has extremely high validity for the diagnosis of patients with brain death, thus it should be used more extensively in clinical practice.

Feasibility of sentinel lymph node biopsy in breast cancer patients following neoadjuvant chemotherapy: A systematic analysis / 第二军医大学学报

Objective To evaluate whether sentinel lymph node biopsy(SLNB)can be used in breast cancer patients following neoadjuvant chemotherapy (NCT) by systematically reviewing the published literatures. Methods The databases CBM, PubMed, Medline and Embase were searched using "breast cancer", "neoadjuvant chemotherapy" and "sentinel lymph node biopsy" as free words and MeSH terms for related literatures. The papers were selected strictly in accordance with the inclusion and exclusion criteria. The studies were divided into axillary lymph node-negative group and axillary lymph node-positive group according to the status of axillary lymph node before NCT. The data of the included researches were extracted and were then merged using STATA to estimate the identification rate and false-negative rate of SLNB in this setting. Results Forty-one studies were identified which involving a total of 5 848 patients. Lymph node-negative group contained 2 050 patients, and 1 891 of them were successfully detected in more than one sentinel lymph node, with the detecting rate and the false-negative rate being 0.94 (95% CI = 0.92-0.96) and 0.07 (95% CI = 0.04-0.10), respectively. Lymph node-positive group contained 3 798 patients, and 3 059 of them were successfully detected in more than one sentinel lymph node, with the detecting rate and false-negative rate being 0.87 (95% CI = 0.84-0.90) and 0.13 (95% CI = 0.11-0.16), respectively. Conclusion SLNB is reliable for women with lymph node-negative breast cancer receiving neoadjuvant chemotherapy. But it is not recommended for those with lymph node-positive breast cancer.

Analysis of the diagnosis value of B ultrasound for uterine endometrial polyps / 中国医学装备

Objective: To observe the accuracy rate, false negative rate of B ultrasound examination in the diagnosis of endometrial polyps and discuss the diagnosis value. Methods:Selected 80 cases of patients with endometrial polyps treated in the hospital from 2013 January-2013 year in June as the research object and they were confirmed by pathological examination, mean age (43.9±11.2) years old, they were examined by B ultrasound examination before and after menstruation, then analyze sensitivity, specific degrees of B Ultrasound performance combining with pathological examination and the survey of satisfaction for patients. Results:the patients before and after the menstrual endometrium showed different degrees of thickening, ranging from 1.2-2.4 cm, the probe showed ligulate, papillary substance not uniform, single, multiple echo;after analysis 73 cases were diagnosed as endometrial polyp, the correct diagnostic rate was 91.2%and the false negative rate was 8.8%. 76 cases (95%) were satisfactory for the simplicity, low cost, accurate diagnosis. Conclusion:B ultrasound examination in the diagnosis of endometrial polyps has high correct rate and is noninvasive, safe, and is easily accepted by patients, so it has important clinical value.

Value of doppler ultrasound hook-wire-guided suspicious node biopsy in early breast cancer / 中华内分泌外科杂志

Objective To explore ideal surgical axillary management of early breast cancer,and to determine the feasibility of reducing false negative rate of sentinel lymph node biopsy(SLNB)by combination of axillary suspicious lymph node biopsy and SLNB.Methods From Jan.2008 to Oct.2009,42 consecutive cases with early breast cancer were enrolled.All patients underwent suspicious node hook-wire location by doppler ultrasonography before operation.SLNB and suspicious lymph node biopsy were performed during operation.Complete axillary nodes dissection(ALND)or level II dissection would be conducted according to the biopsy result.The difference of node status prediction between SLNB and SLNB with axillary suspicious lymph node biopsy and was compared.Results All the 42 cases successfully underwent SLNB (100%).There were 2 false negatives occurred in SLNB,resulting in false negative rate of 11%,sensitivity of 88.9%and accuracy of 95.2%in predicting axillary nodes status.By contrast,SLNB with axillary suspicious node biopsy showed a false-negative rate of 0%,sensitivity of 100%,and accuracy of 100%.Conclusions Compared to SLNB in early breast cancer,combination of suspicious node biopsy and SLAB has a tendency of reducing false negative rate.However,Because of the limited samples,the difference has no statistical significance(P=0.2500).

How Many Sentinel Lymph Nodes Are Enough for Accurate Axillary Staging in T1-2 Breast Cancer? / 한국유방암학회지

PURPOSE: During a sentinel lymph node biopsy (SLNB) for breast cancer, the appropriate number of sentinel lymph nodes (SLNs) to be removed for accurate axillary staging is still controversial. We hypothesized that there might be an optimal threshold number of SLNs. We investigated how many SLNs should be removed to achieve an acceptable accuracy and ensure minimal morbidity. METHODS: We reviewed data of 328 patients with invasive breast cancer who underwent SLNB followed by complete level I and II axillary dissection between January 2004 and December 2005. The false negative rate (FNR) and accuracy of SLNB according to the number of removed SLNs were evaluated. RESULTS: The mean number of SLNs removed was 3.0 (range, 1-14), and that of total retrieved axillary lymph nodes was 17.5 (range, 10-40). In total, 111 (33.8%) patients had positive nodes on the permanent pathological report. Among them, 12 patients had negative SLNs; thus, the overall FNR of SLNB was 10.8% (12/111) and the accuracy was 96.3% (316/328). The FNR was 26.6% for a single SLN, 8.0% for two, and 11.1% for three. In cases where four or more SLNs were removed, the FNR decreased to 0% and accuracy reached 100%. CONCLUSION: Our data suggest that a SLNB should not only remove one or two of the hottest node(s) when other hot nodes exist. We also suggest that four might be an optimal threshold number of SLNs to be removed and that removal of more than four SLNs does not improve axillary staging accuracy.

The Number of Removed Lymph Nodes for an Acceptable False Negative Rate in Sentinel Lymph Node Biopsy for Breast Cancer / 한국유방암학회지

PURPOSE: This study was performed to find the adequate number of removed lymph nodes to achieve an acceptable false-negative rate when performing sentinel lymph node biopsy for breast cancer. METHODS: A total of 179 sentinel node biopsies combined with conventional axillary lymph node dissection for breast cancer were performed between November 2003 and June 2007. RESULTS: The overall identification rate of sentinel lymph node and the false negative rate of the biopsy were 95.0% and 8.1%, respectively. Yet the false negative rate of the biopsy was lowered as the number of the removed nodes was increased. Especially, the false negative rate was 0% when more than 4 lymph nodes were removed. CONCLUSION: We recommend that four lymph nodes should be removed to obtain accurate results in sentinel node biopsy for breast cancer.

False-negative results of conventional Papanicolaou cervical cytology in women with cervical conization / 부인종양

OBJECTIVE: The conventional Papanicolaou smear seems to be more accurate for detecting a high-grade squamous intraepithelial lesion (HSIL) than a low-grade squamous intraepithelial lesion (LSIL). The purpose of this study was to investigate false-negative results of conventional Pap smear cytology in women with cervical conization. METHODS: This study was performed in Gynecologic Oncology Clinic of the Department of Obstetrics and Gynecology at Dankook University Medical Center from July 1, 1994 to December 31, 2004. 260 women from age 22 to 75 years had undergone conventional Papanicolaou cervical cytologic test and cervical conization. Conization was performed using ncold-knife cone' method or nlarge electrosurgical excision procedure (LEEP) cone' method. The cervical cytology were studied in comparison with histology of conization specimens. RESULTS: Of the 260 histologic diagnoses, there were 41 (15.8%) diagnoses of chronic cervicitis, 8 (3.1%) of CIN 1, 18 (6.9%) of CIN 2, 150 (57.7%) of CIN 3, 38 (14.6%) of SCC, 2 (0.8%) of AIS, 1 (0.4%) of ACC, and 2 (0.8%) of ASC. Pap cytology showed sensitivity of 97.9-98.2%, specificity of 4.9-6.7%, and false-negative rate of 1.8-2.2% according to the variables. CONCLUSION: Significantly false-negative rate of Pap cytology in women with conization was very low. And so, conventional Pap cytology is still clinically efficient for screening high-grade cervical lesions with adequate sampling technique.

Result of Sentinel Lymph Node Biopsy Using Radioisotope in Clinically Lymph Node Negative Breast Cancer / 한국유방암학회지

PURPOSE: Sentinel lymph node biopsy (SLNB) has been developed to accurately assess the axillary lymph node status accurately without having to remove most of the axillary contents in node negative early breast cancer patients. The aims of this study were to evaluate the accuracy, the false negative rate and the advantage of additional axillary sampling for SLNB with using radioisotope. METHODS: Between December 2003 and June 2005, we carried out SLNB for 574 breast cancer patients who were diagnosed and had operation at Asan Medical Center. For detection of the sentinel lymph node (SLN), radioisotope was injected into the periareolar area on the operating day, breast scintigraphy was performed and finally the biopsy was done using a gamma-detection probe in the operating room. If the SLN turned out to be positive for metastatic malignancy according to the frozen section histology, then additional axillary lymph nodes (LN) dissection was performed. But, if it was free of metastasis, then only axillary node sampling (n< or =5) or no further treatment was done. RESULTS: The mean number of resected SLNs was 2.67+/-0.98 (1-7) and the mean number of total LN was 8.5+/-5.0 (1-38). The SLN was detected 82.8% of the time on lymphoscintigraphy and 98.4% of the time with the gamma probe. Axillary metastasis was founded in 118 cases (20.9%). The accuracy was 98.2%, and the false negative rate was 7.89%. For the SLN positive cases, there were 73/78 cases (93.6%) of 1st SLN metastasis, there were 75/78 cases (93.6%) of 1st and 2nd SLN metastasis, and 75/78 (93.6%) of 1st to 3rd SLN metastasis. The false negative rate of the alternative frozen section was 40% and that of the full frozen section was 24.1%. The difference was statistically significant. CONCLUSION: SLNB using (99m)Tc-antimony trisulfide colloid (0.5 mCi) showed a high detection rate and a low false negative rate. The false negative rate was decreased by using full section H&E staining and at least 3 SLNs showed the exact LN status. Even if the SLN was free of metastasis, additional sampling may decrease the false negative rate.

Interval Breast Cancers: Comparisons with Screen Detected Cancers

PURPOSE: Although the screening with a mammography has been shown to reduce breast cancer mortality, it has limitations relating to its sensitivity and efficacy. Interval cancers are those that become symptomatic, and are detected between screening examinations. The success of a screening program in reducing the rate of mortality due to breast cancer relies on keeping the number of interval cancers at a minimum. This study was performed to review the mammographic features of interval cancers, and to compare their clinicopathological factors with those cancers detected by screening. METHODS: Of the 881 women who had operations for breast cancer performed between 1995 and 1999, we retrospectively analyzed the medical records and mammograms of 57 who received at least a mammogram before the diagnosis of their breast cancer. These patients were divided into an interval cancer group, who had symptoms, and a screen detected cancer group, who had not. The factors compared included the clinical, radiographic, histopathological, and immunohistochemical features. RESULTS: Interval cancers were more likely to have masses, than microcalcifications, in their mammographic features, and were more likely to be invasive and at a higher stage according to their histopathological features. The false negative rate was 48% for the screen detected cancers, and 35% for the interval cancers (P=0.414). HRT users had the higher false negative rate of 51.6% than the 26.9% for the nonuser (P=0.103). CONCLUSION: The interval cancers were found to be different from the screen detected cancers in terms of their radiological and pathological features. The standardization of screen interval, and additional magnification mammography, or ultrasonography may contribute to reduce false negative rates of mammography.

False negative cytology in cervical smears: An evaluation of 186 cases of squamous intraepithelial lesion and squamous cell carcinoma, hitologically confirmed / 대한산부인과학회잡지

OBJECTIVE: To estimate false-negative rate of cervical smears in histologically confirmed squamous intraepithelial lesion and squamous cell carcinoma METHOD: From 1993 to 1998, total 186 cases of cervical smear performed within 1 year before histological confirmation squamous intraepithelial lesion and squamous cell carcinoma, were reviewed and the false negative rate of the each group was analyzed. RESULTS: 1. Histologic diagnosis of 186 cases includes 8 cases of low grade SIL, 87 cases of high grade SIL, 91 cases of squamous cell carcinoma. 2. Overall false negative rate was 18.8% (35/186). False negative rate of LSIL was higher (50%; 4/8) compared with the other two groups. (HSIL:23% ;20/87, SCC:12.1% ;11/91) 3. 18 of 35 false negative cases were reviewed. 8 cases(44.4%) were sampling error and 10 cases(55.6%) were interpretation error. 4. Estimated overall sampling error was 8-9% ; interpretation error 10-11%. CONCLUSION: Reducing the false negative rate of cervical smears, especially in cervical intraepithelial neoplasia lesion is important to save the patients from invasive cervical cancer. Further studies on the causes of false negatives and the efforts to eliminate these barriers are actually needed.

False Negative Rate of Cervical Cytology Using the Autopap 300 QC System in Rescreening Modality / 대한부인종양콜포스코피학회잡지

OBJECTIVES: To estimate false-negative rate of cervical smears using Autopap 300 QC system in rescreening modality. METHODS: From September 1997 to December 1997, Total 26,983 cervical smears were obtained and 18,592 cervical smears were rescreened by Autopap 300 QC system with 10% review rate. The 274 cases of total 26,983 cervieal smears were confirmed histologically by colposcopic biopsy, cone biopsy and hysterectomy. The 274 cases of cervical smears, which obtained prior to pathologic diagnosis made, were evaluated based on cyto-histologic correlation and then the false negative rate were estimated. The cervical smears were reviewed, researching for the cause of false negative. RESULTS: (1) Histologic diagnosis of 274 cases include 65 cases of Low SIL, 173 cases of High SIL, 29 cases of SCC, 2 cases of adenocarcinoma in situ, and 5 cases of invasive adenocarcinoma. (2) The false negative rate were 3% (9/274). Those were 6.2%(4/65) of LSIL, 2.3% (4/173) Of HSIL, none of SCC and AIS, and 20%(5/1) of invasive adenocarcinoma. (3) The false negative cases were reviewed. The 6 cases were sampling enor and 3 cases were screening error. CONCLUSION: Using AutoPap 300 QC system in rescreening modality, The false negative rate of cervical smears were decreased, compared with our previous study.

Accuracy of Cervical Pap Smear / 대한부인종양콜포스코피학회잡지

BACKGROUND: Carcinoma of the uterine cervix is a theoretically preventable disease because its precursor lesions can be detected by cervical Papanicolau smears and appropriately treated, Although cervical cytology screening programmes have resulted in the redution of cervical cancer incidence and mortality, Pap smear have been subjected to intense scrutiny and criticism in recent years. The focus of criticism has been the false-negative Pap smear, and the false-negative Pap smear is the major quality issue currently facing the physicians. To reduce the false-negative rate of Pap smear, it is essential to improve the accuracy of Pap smear. But false-negative rate of Pap smear has been reported variously. OBJECTIVE: This study was undertaken to evaluate accuracy of Pap smear by study false-negative and false-positive rate of Pap smear and to determine whether false-negative and false-positive rate had any correlations with clinical factors. STUDY DESIGN: The study population was comprised of 346 women, who were undertaken gynecologic operation at the Department of Obstetrics & Gynecology at Hanyang University hospital between March, 1997 and April, 1998. All patients were taken Pap smear before operation. In 93 women of these, preoperative diagnosis were cervical intraepithelial neoplasia and carcinoma in situ of uterine cervix, and in 253 women of these, preoperative diagnosis were benign disease as uterine myoma or adenomyosis, etc. All of their surgical specimen were examined. Pap smear, pathology, medical charts of all patients were reviewed retrospectively, and false-negative rate and false-positive rate were calculated. Clinical factors that associated with false-negative and false-positive rate were evaluated. Fishers exact test and Pearson chi-square test were used of statistical analysis, RESULTS: False-negative rate of Pap smear was 7.2%, false-positive rate was 4.6%, corresponding rate with histology was 88.2%. Sensitivity and specificity of PAP smear were 87.0% and 97.0% respctively. According to gross finding of uterine cervix, erosion was 46.6% in cervical intraepithelial neoplasia, 67.8% in carcinoma in situ, 66.6% in microinvasive carcinoma of uterine cervix and 55.3% of 103 erosion findings was cervical intraepithelial neoplasia, carcinoma in situ or microinvasive carcinoma. 23.1% of cervical lesion were normal gross finding. Menopause was associated with false-negative rate and previous vaginal infection history, previous cervical minor operation, delivery mode, contraception method, pelvic inflammatory disease history, vaginal bleeding at Pap smear and gross finding of cerbix were not associated. There were no clinical factors that were associated with false-positive rate. CONCLUSION: Compared with other reports, false-negative rate(7.2%) and false-positive rate(4.6%) of Pap smear was lower and corresponding rate(88.2%) was higher in Hanyand university hospital. Because of higher false-negative rate in menopausal women, it need more careful to take and interpretate Pap smear in these group.

Reliability Indexes of Automated Perimetric Tests

The "reliability" of a subject's automated perimetric result is generally assessed by three measures: fixation loss, false positive and false negative rates. These reliability indicies were examined for 237 glaucomatous and ocular hypertensive eyes who for the first time underwent visual field testing (central 30-2 test on Humphrey visual field analyzer. Allergan Humphrey). Of the examination results, 11% of subjects were considered unreliable with the use of the manufacturer's reliability criteria. 71% of the unreliable results were due to failure to meet the criterion for fixation loss. The rest 29% were due to high false negative rates. After given reinstruction and more attention to fixation loss throughout the test by the technician, second visual field test was performed. On second examination, 82% of fixation loss and 71% of false negative rate was reduced.