Excellent Prognosis of Patients With Invasive Lung Adenocarcinomas During Surgery Misdiagnosed as Atypical Adenomatous Hyperplasia, Adenocarcinoma In Situ, or Minimally Invasive Adenocarcinoma by Frozen Section.

BACKGROUND: Our previous study revealed that intraoperative frozen section (FS) analysis could differentiate invasive lung adenocarcinoma (LUAD) accurately from preinvasive lesions. However, few articles have analyzed the clinical impact of FS errors such as underestimation of invasive adenocarcinomas (IACs), and whether complementary therapy is needed remains controversial. RESEARCH QUESTION: What is the prognosis of patients undergoing limited resection for invasive LUAD misdiagnosed as atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), or minimally invasive adenocarcinoma (MIA) by intraoperative FS analysis? STUDY DESIGN AND METHODS: From 2012 through 2018, data on 3031 patients undergoing sublobar resection of AAH, AIS, or MIA diagnosed by FS analysis were collected. The concordance rate between FS analysis and final pathologic results was evaluated. To assess the clinical significance of a discrepancy between FS and final pathologic results, patients with final pathologic results of IAC were identified for prognostic evaluation. RESULTS: When AAH, AIS, and MIA were classified together as a group, the overall concordance rate between FS and final pathologic results was 93.7%, and 192 patients (6.3%) received an upgraded diagnosis from the final pathologic results. Misdiagnosed IACs consisted of 94 patients (48.9%) with lepidic-predominant adenocarcinoma, 77 patients (40.1%) with acinar predominant adenocarcinoma, 19 patients (9.9%) with papillary predominant adenocarcinoma, one patient with solid predominant adenocarcinoma, and one patient with invasive mucinous adenocarcinoma. Among these patients, no positive N1 or N2 lymph node findings were observed. Moreover, the 5-year recurrence-free survival was still 100%, although the final pathologic results turned out to be IAC. INTERPRETATION: Patients undergoing limited resection of invasive LUAD misdiagnosed as AAH, AIS, or MIA by FS analysis showed excellent prognoses. Sublobar resection guided by FS diagnosis would be adequate for these underestimated cases of invasive LUAD.

Common alternative diagnoses among a pediatric hospital-based cohort evaluated for tuberculosis in Karachi, Pakistan: The need for facilitated referral in tuberculosis clinics.

BACKGROUND: Children evaluated for tuberculosis (TB) are often diagnosed with miscellaneous conditions that mimic TB. Knowledge of differentials informs policy on service provision through liaison with referral centers offering definitive diagnosis and treatment for common alternative disorders. METHODS: We reviewed medical records of children who were offered diagnostic testing for TB (culture or Xpert MTB/RIF) at a tertiary care hospital in Karachi, Pakistan to identify common alternative diagnoses among children who are evaluated for TB. RESULTS: From January 2014 to December 2015, of 126 culture or Xpert MTB/RIF negative children presenting with chronic symptoms, 31 were diagnosed and treated for TB based on clinical criteria (5 of 48 children with pulmonary and 26 of 78 with extrapulmonary presentations; 10.4% and 33.3%, respectively). Among remaining 95 patients, common alternative diagnoses to pulmonary TB (n = 43) were bacterial pneumonia or empyema (60.5%, n = 25) and underlying bronchiectasis (20.9%, n = 9). Among 52 extrapulmonary presentations, the most common alternative diagnoses were lymphoproliferative disorders (n = 11, 21.1%), bacterial infections (n = 11, 21.1%), and autoimmune disorders (n = 9, 17.3%). Of note, five children were diagnosed with underlying primary immunodeficiencies (9.6%). Children with alternative disorders were treated for TB in 25 of 95 cases (26.3%). Although 77.8% (n = 98) children were followed up at the facility, 15.9% (n = 20) were lost to follow-up. CONCLUSIONS: Pediatric TB mimics many disorders that primary level centers are not equipped to diagnose or manage, leading to suboptimal outcomes. Knowledge of common alternative diagnoses is essential to inform facilitated referral for common mimicking disorders in children.

Macrolide-resistant Mycoplasma genitalium infections in Cuban patients: an underestimated health problem.

BACKGROUND: The increasing prevalence of macrolide resistant Mycoplasma genitalium is a major concern worldwide. In Cuba, several cases of clinical treatment failure with 1 g single dose and extended azithromycin regimen have been detected and the aim of the present investigation was to retrospectively determine the prevalence of macrolide-resistance mediating mutations (MRMM) in M. genitalium-positive samples conserved at the Cuban National Reference Laboratory of Mycoplasma Research between 2009 and 2016. METHODS: A total of 280 positive DNA extracts were analysed by a 5' nuclease assay for detection of M. genitalium MRMM. Ten urogenital specimens from patients with azithromycin treatment failure and MRMM were inoculated in Vero cell to obtain the isolates for subsequent determination of antimicrobial susceptibility. RESULTS: The overall prevalence of MRMM was 32%. No MRMM was detected in samples collected between 2009 and 2013 but since 2014 a dramatic increase to 90% (95% CI, 76-96%) in 2016 was seen. Three new M. genitalium isolates were isolated in Vero cell cultures and confirmed phenotypic resistance to macrolides in a cell-culture assisted susceptibility test. Preliminary observations suggest that combination therapy with levofloxacin and doxycycline may represent an affordable option for treatment of macrolide resistant M. genitalium infections. CONCLUSIONS: This investigation showed the rapid emergence and high prevalence of MRMM in M. genitalium-infected patients in Cuba and confirmed the phenotypic resistance in isolates carrying MRMM. We suggest that Cuban guidelines for sexually transmitted infections are modified to include testing for M. genitalium and detection of MRMM in patients with failure of syndromic treatment, to ensure that in these cases, the treatment will be guided by etiologic diagnosis.

Obstacles to diagnosis and treatment of Lyme disease in the USA: a qualitative study.

OBJECTIVE: For many individuals with Lyme disease, prompt treatment leads to rapid resolution of infection. However, severe complications can occur if treatment is delayed. Our objective was to identify themes around belated diagnosis or treatment of Lyme disease using the General Model of Total Patient Delay (GMTPD). DESIGN: We conducted a qualitative interview study using indepth telephone interviews. SETTING: Participants were patients from a large, integrated health system in the state of Pennsylvania, USA. PARTICIPANTS: There were 26 participants. Participants had to have a diagnosis of Lyme disease between 2014 and 2017 and a positive IgG western blot. We used a stratified purposeful sampling design to identify patients with and without late Lyme disease manifestations. To ensure variation in care experiences, we oversampled patients diagnosed outside of primary care. OUTCOME MEASURES: We asked participants about their experience from first Lyme disease symptoms to treatment. We applied an iterative coding process to identify key themes and then synthesised codes into higher order codes representing the GMTPD stages: appraisal delay (symptom to recognition of illness); illness delay (inferring illness to deciding to seek help); behavioural delay (deciding to seek help to the act of seeking help); scheduling delay (seeking help to attending an appointment); and treatment delay (attending appointment to treatment). RESULTS: Appraisal delay themes included symptom misattribution, intermittent symptoms and misperceptions about the necessity of a bull's-eye rash. Health insurance status was a driver of illness and behavioural delays. Scheduling delay was not noted by participants, in part, because 10 of the 26 patients went to urgent care or emergency department settings. Misdiagnoses were more common in these settings, contributing to treatment delay. CONCLUSION: Our study identified potentially modifiable risk factors for belated treatment. Targeting these risk factors may minimise time to treatment and reduce the occurrence of preventable complications.

Are health care provider organizations ready to tackle diagnostic error? A survey of Leapfrog-participating hospitals.

BACKGROUND: A 2015 National Academy of Medicine report on improving diagnosis in health care made recommendations for direct action by hospitals and health systems. Little is known about how health care provider organizations are addressing diagnostic safety/quality. METHODS: This study is an anonymous online survey of safety professionals from US hospitals and health systems in July-August 2016. The survey was sent to those attending a Leapfrog Group webinar on misdiagnosis (n=188). The instrument was focused on knowledge, attitudes, and capability to address diagnostic errors at the institutional level. RESULTS: Overall, 61 (32%) responded, including community hospitals (42%), integrated health networks (25%), and academic centers (21%). Awareness was high, but commitment and capability were low (31% of leaders understand the problem; 28% have sufficient safety resources; and 25% have made diagnosis a top institutional safety priority). Ongoing efforts to improve diagnostic safety were sparse and mostly included root cause analysis and peer review feedback around diagnostic errors. The top three barriers to addressing diagnostic error were lack of awareness of the problem, lack of measures of diagnostic accuracy and error, and lack of feedback on diagnostic performance. The top two tools viewed as critically important for locally tackling the problem were routine feedback on diagnostic performance and culture change to emphasize diagnostic safety. CONCLUSIONS: Although hospitals and health systems appear to be aware of diagnostic errors as a major safety imperative, most organizations (even those that appear to be making a strong commitment to patient safety) are not yet doing much to improve diagnosis. Going forward, efforts to activate health care organizations will be essential to improving diagnostic safety.

Local allergic rhinitis to pollens is underdiagnosed in young patients.

BACKGROUND: Local allergic rhinitis (LAR) has been observed in patients without atopy. However, LAR is still underdiagnosed in patients with perennial or seasonal nasal symptoms. OBJECTIVE: The aim of this study was to determine the prevalence of LAR in young patients with a previous diagnosis of nonallergic rhinitis or suspicion of allergy. METHODS: A total of 121 patients, ages 12-18 years old, with confirmed nonallergic rhinitis and typical seasonal nasal symptoms were examined. Skin-prick tests; serum and nasal specific immunoglobulin E (IgE) measurements; and nasal provocation tests by using grass (Phleum partense), Artemisia, and birch pollens were performed. A control group of age-matched patients with a diagnosis of seasonal allergic rhinitis underwent the same procedures as the test group. RESULTS: LAR to grass pollen (P. partense), Artemisia, and birch was confirmed in 17 (16.6%), 6 (5.9%), and 9 (8.9%) of patients, respectively. Polyvalent allergy was established in 21 subjects (20.8%): grass and Artemisia, 11 patients (10.9%); and grass and birch, 10 patients (9.9%). The remaining 48 patients (47.5%) were diagnosed with nonallergic rhinitis. The results of the nasal provocation tests and the concentrations of nasal IgE were similar among the analyzed groups. Furthermore, the concentration of nasal IgE increased faster in patients with LAR than in patients with allergic rhinitis; however, this difference was not statistically significant. CONCLUSION: LAR is a serious problem in young patients; however, its significance is still unappreciated.

Discordance of histopathologic parameters in cutaneous melanoma: Clinical implications.

BACKGROUND: Histopathologic analysis remains the gold standard for the diagnosis of melanoma, however previous studies have shown a substantial rate of interobserver variability in the evaluation of melanocytic lesions. OBJECTIVE: We sought to evaluate discordance in the histopathological diagnosis and microstaging parameters of melanoma and subsequent impact on clinical management. METHODS: This was a retrospective review of 588 cases of cutaneous melanoma and melanoma in situ from January 2009 to December 2014 that were referred to Emory University Hospital, Atlanta, GA, for treatment. Per institutional policy, all outside melanoma biopsy specimens were reviewed internally. Outside and institutional reports were compared. RESULTS: Disagreement between outside and internal reports resulted in a change in American Joint Committee on Cancer pathologic stage in 114/588 (19%) cases, resulting in a change in management based on National Comprehensive Cancer Network guidelines in 105/588 (18%) cases. LIMITATIONS: Given the retrospective nature of data collection and the bias of a tertiary care referral center, cases in this study may not be representative of all melanoma diagnoses. CONCLUSION: These findings confirm consistent subjectivity in the histopathologic interpretation of melanoma. This study emphasizes that a review of the primary biopsy specimen may lead to significant changes in tumor classification, resulting in meaningful changes in clinical management.

Performance of ACR Lung-RADS in a clinical CT lung screening program.

PURPOSE: The aim of this study was to assess the effect of applying ACR Lung-RADS in a clinical CT lung screening program on the frequency of positive and false-negative findings. METHODS: Consecutive, clinical CT lung screening examinations performed from January 2012 through May 2014 were retroactively reclassified using the new ACR Lung-RADS structured reporting system. All examinations had initially been interpreted by radiologists credentialed in structured CT lung screening reporting following the National Comprehensive Cancer Network's Clinical Practice Guidelines in Oncology: Lung Cancer Screening (version 1.2012), which incorporated positive thresholds modeled after those in the National Lung Screening Trial. The positive rate, number of false-negative findings, and positive predictive value were recalculated using the ACR Lung-RADS-specific positive solid/part-solid nodule diameter threshold of 6 mm and nonsolid (ground-glass) threshold of 2 cm. False negatives were defined as cases reclassified as benign under ACR Lung-RADS that were diagnosed with malignancies within 12 months of the baseline examination. RESULTS: A total of 2,180 high-risk patients underwent baseline CT lung screening during the study interval; no clinical follow-up was available in 577 patients (26%). ACR Lung-RADS reduced the overall positive rate from 27.6% to 10.6%. No false negatives were present in the 152 patients with >12-month follow-up reclassified as benign. Applying ACR Lung-RADS increased the positive predictive value for diagnosed malignancy in 1,603 patients with follow-up from 6.9% to 17.3%. CONCLUSIONS: The application of ACR Lung-RADS increased the positive predictive value in our CT lung screening cohort by a factor of 2.5, to 17.3%, without increasing the number of examinations with false-negative results.

Prevalence of unrecognized benign paroxysmal positional vertigo in older patients.

Dizziness is a relatively common complaint which occurs more often with increasing age. Benign paroxysmal positional vertigo (BPPV) is an important cause which can easily be treated but is frequently not recognized by professionals. The aim of this study was to assess the prevalence of unrecognized BPPV in older patients. Patients ≥70 years of age (n = 989) indicated whether they experienced dizziness, and if so whether the symptoms were typical for BPPV. If affirmed, a diagnostic maneuver was performed. Positive patients were treated at once. All suspected patients completed quality of life questionnaires and were followed for 3 and 6 months. Positive BPPV patients were compared with negative (but suspected) patients. Almost one quarter of the patients (226 patients, 23 %) suffered from dizziness, among whom 101 were suspected of BPPV. Less than half (n = 45) underwent the diagnostic maneuver, of whom 13 (29 %) were positive for BPPV. At follow-up, one patient developed BPPV, leading to a total of 14 positive patients (overall prevalence 1.4 %). BPPV positive patients did not differ from BPPV negative patients. Among a large group of older patients, one quarter experiences dizziness, and 1.4 % has definite BPPV.

Evaluation of the interval cancer rate and its determinants on the Girona Health Region's early breast cancer detection program.

BACKGROUND: The main aim of this study is to estimate the rate of false negative and true IC on the Program for the Early Detection of Breast Cancer (PEDBC) run by the Girona Health Region (GHR) and compare the clinicopathological characteristics of these tumors with those detected within the same program. METHODS: A retrospective cohort study including all women participating on the Girona PEDBC between 2000 and 2006, with negative mammography screening. The IC included are those detected between the first and second round of screening and between the second and third round. RESULTS: We identified a total of 43 IC, representing an incidence rate of 0.70 cases per 1,000 screened women. Of the 43 probable IC, we were able to classify a total of 22 (51.2%) cases. Of these 22 cases, 54.5% were classified as true interval tumors, 13.6% false negatives, 18.2% occult tumors and the remaining 13.6% minimal sign.We found significant differences in some clinicopathological characteristics of the IC comparing with the tumors detected within the program during the same period. CONCLUSIONS: The IC rate for the PEDBC is within the expected parameters, with a high proportion of cases of true interval cancers (54.5%) and a low proportion of false negatives (13.6%). The results show that the proportional incidence of IC is within the limits set by European Guidelines. Furthermore, it has been confirmed that IC display more aggressive clinicopathological characteristics than screening breast cancers.

Electronic health record-based triggers to detect potential delays in cancer diagnosis.

BACKGROUND: Delayed diagnosis of cancer can lead to patient harm, and strategies are needed to proactively and efficiently detect such delays in care. We aimed to develop and evaluate 'trigger' algorithms to electronically flag medical records of patients with potential delays in prostate and colorectal cancer (CRC) diagnosis. METHODS: We mined retrospective data from two large integrated health systems with comprehensive electronic health records (EHR) to iteratively develop triggers. Data mining algorithms identified all patient records with specific demographics and a lack of appropriate and timely follow-up actions on four diagnostic clues that were newly documented in the EHR: abnormal prostate-specific antigen (PSA), positive faecal occult blood test (FOBT), iron-deficiency anaemia (IDA), and haematochezia. Triggers subsequently excluded patients not needing follow-up (eg, terminal illness) or who had already received appropriate and timely care. Each of the four final triggers was applied to a test cohort, and chart reviews of randomly selected records identified by the triggers were used to calculate positive predictive values (PPV). RESULTS: The PSA trigger was applied to records of 292 587 patients seen between 1 January 2009 and 31 December 2009, and the CRC triggers were applied to 291 773 patients seen between 1 March 2009 and 28 February 2010. Overall, 1564 trigger positive patients were identified (426 PSA, 355 FOBT, 610 IDA and 173 haematochezia). Record reviews revealed PPVs of 70.2%, 66.7%, 67.5%, and 58.3% for the PSA, FOBT, IDA and haematochezia triggers, respectively. Use of all four triggers at the study sites could detect an estimated 1048 instances of delayed or missed follow-up of abnormal findings annually and 47 high-grade cancers. CONCLUSIONS: EHR-based triggers can be used successfully to flag patient records lacking follow-up of abnormal clinical findings suspicious for cancer.

Random effects models for assessing diagnostic accuracy of traditional Chinese doctors in absence of a gold standard.

Two common problems in assessing the accuracy of traditional Chinese medicine (TCM) doctors in detecting a particular symptom are the unknown true symptom status and the ordinal-scale of the symptom status. Wang et al. (Biostatistics 2011; DOI: 10.1093/biostatistics/kxq075) proposed a nonparametric maximum likelihood method for estimating the accuracy of different TCM doctors without a gold standard when the true symptom status is measured on an ordinal-scale. A key assumption of their work is that the diagnosis results are independent conditional on the gold standard. This assumption can be violated in many practical situations.In this paper, we propose a random effects modeling approach that extends their method to incorporate dependence structure among different tests or doctors. The proposed method is illustrated on a real data set from TCM, which contains the diagnostic results from five doctors for the same patients regarding symptoms related to Chills disease. The same data set was analyzed by Wang et al. under the conditional independence assumption. In addition, we also discuss an ad hoc test for the model fitting and a likelihood ratio test on the random effects.

Randomized study of the effect of topical anesthesia on tuberculin skin test reaction size in children.

Tuberculin skin test (TST) application in children can be eased by topical anesthesia, but no study has determined whether lidocaine-prilocaine mixture application modifies TST skin reactions. We compared TST performed with and without topical anesthesia in 46 children (range, 0.4-15.9 years), and found that topical lidocaine-prilocaine did not affect the TST size reaction. Topical lidocaine-prilocaine can be used for TST.

[Dynamic evaluation of the effects of quality management]. / Dynamische Evaluierung der Effekte von Qualitätsmanagement.

PURPOSE: Evaluation of the effects of quality management over time at a radiology department. MATERIALS AND METHODS: Data concerning the performance of the department, entered on a monthly basis, will be compared with entries in the error report system on the basis of time series analysis (regression models taking seasons and auto-correlation effects into account). The observation period consists of 46 homogeneous monthly time pulses. RESULTS: Effects of the suggestions and the total number of reports in the quality assurance system on the performance of the department can be observed with a two-month delay. This association is statistically highly significant (p < 0.01) and, because of the procedures used, not attributable to general developmental trends, seasonal fluctuations or autoregressive processes. CONCLUSION: Evaluation of quality assurance measures is a well justified demand and should be based on the analysis of data collected from quality assurance systems operating on a continuous basis over a long period of time. The analysis of data from a radiology department shows that quality assurance is reflected in the performance of the department.

Rates of new or missed colorectal cancers after colonoscopy and their risk factors: a population-based analysis.

BACKGROUND & AIMS: The rate of new or missed colorectal cancer (CRC) after colonoscopy and their risk factors in usual practice are unknown. Our objective was to evaluate the rate and risk factors in a population-based study. METHODS: We analyzed data from the Canadian Institute for Health Information, the Ontario Health Insurance Program, and Ontario Cancer Registry for all patients (> or =20 years of age) with a new diagnosis of right-sided, transverse, splenic flexure/descending, rectal or sigmoid CRC in Ontario from April 1, 1997 to March 31, 2002, who had a colonoscopy within the 3 years before their diagnosis. Patients with new or missed cancers were those whose most recent colonoscopy was 6 to 36 months before diagnosis. We examined characteristics that might be risk factors for new or missed CRC. RESULTS: We identified a diagnosis of CRC in 3288 (right sided), 777 (transverse), 710 (splenic flexure/descending), and 7712 (rectal or sigmoid) patients. The rates of new or missed cancers were 5.9%, 5.5%, 2.1%, and 2.3%, respectively. Independent risk factors for these cancers in men and women were older age; diverticular disease; right-sided or transverse CRC; colonoscopy by an internist or family physician; and colonoscopy in an office. CONCLUSIONS: Because having an office colonoscopy and certain patient, procedure, and physician characteristics are independent risk factors for new or missed CRC, physicians must inform patients of the small risk (2% to 6%) of these cancers after colonoscopy. The influence of type of physician and setting on the accuracy of colonoscopy, potentially modifiable risk factors, warrants further study.

Discrepancias entre el diagnóstico clínico y el anatomopatológico en un Servicio de Cuidados Intensivos Polivalente / Discrepancies between clinical and pathological diagnosis in a Polyvalent Intensive Care Service

Objetivos. Analizar la frecuencia y espectro de las patologías más relevantes encontradas en el estudio necrópsico. Valorar la asociación entre estancia en la Unidad de Cuidados Intensivos (UCI) inferior a 24 horas y la tasa de errores diagnósticos. Material y métodos. Estudio retrospectivo observacional durante un período de 46 meses en una UCI polivalente. Las diferencias entre el diagnóstico clínico y anatomopatológico se establecieron en función de la clasificación de Goldman. Resultados. Se realizaron 85 autopsias de un total de 520 exitus (16,3%). Cinco pacientes fueron excluidos por información incompleta. De los 80 casos, encontramos 30 pacientes con errores mayores, 21 con repercusión terapéutica y pronóstica, y 9 en los que la estrategia terapéutica no se hubiera modificado. El diagnóstico más frecuentemente encontrado en el error tipo I fue la infección bacteriana seguida de la patología cardiovascular. La tasa de errores mayores con repercusión terapéutica fue superior en los pacientes con una estancia en UCI inferior a 24 horas (40% frente a 21%; p < 0,05). Conclusiones. La autopsia continúa siendo una herramienta útil para evaluar la calidad del diagnóstico clínico. Los errores diagnósticos con repercusión terapéutica son las infecciones bacterianas y la patología cardiovascular. Los pacientes con una estancia en la UCI inferior a 24 horas presentan una tasa mayor de errores diagnósticos tipo I

Objectives. Analyze the frequency and spectrum of the most relevant diseases found in the necropsic study. Assess the association between stay in Intensive Care Unit (ICU) less than 24 hours and rate of diagnostic errors. Material and methods. Retrospective, observational study during a 46 month period in a polyvalent ICU. The differences between the clinical and pathological diagnoses were established based on Goldman's classification. Results. A total of 85 autopsies out of 520 exitus (16.3%) were done. Five patients were excluded due to incomplete information. Of the 80 cases, we found 30 patients with major errors, 21 with therapeutic and prognostic repercussion, 9 in which the therapeutic strategy had not been modified. The most frequently found diagnosis in type I error was bacterial infection followed by cardiovascular disease. Major error rate with therapeutic repercussion was superior in patients with a stay in the ICU less than 24 hours (40% vs 21%; p < 0.05). Conclusions. Autopsy continues to be a useful tool to assess quality of clinical diagnosis. The diagnostic errors with therapeutic repercussion are bacterial infections and cardiovascular disease. Patients with a stay less than 24 hours have a higher rate of type I diagnostic errors