Volume 8, Issue 2

The concept that disease rooted principally in chronic aberrant constitutive and reactive activation of mast cells (MCs), without the gross MC neoplasia in mastocytosis, first emerged in the 1980s, but only in the last decade has recognition of “mast cell activation syndrome” (MCAS) grown significantly. Two principal proposals for diagnostic criteria have emerged. One, originally published in 2012, is labeled by its authors as a “consensus” (re-termed here as “consensus-1”). Another sizable contingent of investigators and practitioners favor a different approach (originally published in 2011, newly termed here as “consensus-2”), resembling “consensus-1” in some respects but differing in others, leading to substantial differences between these proposals in the numbers of patients qualifying for diagnosis (and thus treatment). Overdiagnosis by “consensus-2” criteria has potential to be problematic, but underdiagnosis by “consensus-1” criteria seems the far larger problem given (1) increasing appreciation that MCAS is prevalent (up to 17% of the general population), and (2) most MCAS patients, regardless of illness duration prior to diagnosis, can eventually identify treatment yielding sustained improvement. We analyze these proposals (and others) and suggest that, until careful research provides more definitive answers, diagnosis by either proposal is valid, reasonable, and helpful.

Despite the breadth of patient safety initiatives, physicians talking about their mistakes to other physicians is a difficult thing to do. This difficulty may be exacerbated by a limited exposure to how to analyze and discuss mistakes and respond in a productive way. At the University of Virginia, we recognized the importance of understanding cognitive biases for residents in both their clinical and personal professional development. We re-designed our resident led morbidity and mortality (M&M) conference using a model that integrates dual-process theory and metacognition to promote informed reflection and analysis of cognitive diagnostic errors. We believe that structuring M&M in this way builds a culture that encourages reflection together to learn our most difficult diagnostic errors and to engage in where our thought processes went wrong. In slowly building this culture, we hope to inoculate residents with the habits of mind that can best protect them from harmful biases in their clinical reasoning while instilling a culture of self-reflection.

Reflective practice is essential for the ongoing maturation of clinicians and requires regular self-evaluation in association with ongoing mentoring and feedback. Currently, most resident physicians do not have access to educational experiences that fulfill these needs. We present a novel model for structured one-on-one longitudinal coaching using the principles of deliberate practice to improve diagnostic skills. This is an easily implementable educational model that can be replicated in residencies across the country to improve clinical reasoning. Skills learned through this program have the potential not only to bolster the academic approach to patients but to also directly improve the clinical assessment and care of patients under the trainee’s care.

Objectives Explicit education on diagnostic reasoning is underrepresented relative to the burden of diagnostic errors. Medical educators report curricular time is a major barrier to implementing new curricula. The authors propose using concise student-identified educational opportunities -- differential diagnosis and summary statement writing -- to justify curriculum development in diagnostic reasoning. Methods Eighteen clerkship and 235 preclinical medical students participated in a 1 h computerized case presentation and facilitated discussion. Students were surveyed on their attitudes toward the case. Results All 18 (100% response) clerkship students and 121 of the 235 preclinical students completed the survey. Students felt the module was effective and relevant. They proposed medical schools consider longitudinal computerized case presentations as an educational strategy. Conclusions A computerized case presentation is a concise instructional strategy to teach critical points in diagnosis to clerkship and preclinical medical students.

Objectives Little is known about how physician diagnostic thinking unfolds over time when evaluating patients. We designed a case-based simulation to understand how physicians reason, create differential diagnoses, and employ strategies to achieve a correct diagnosis. Methods Between June 2017 and August 2018, hospital medicine physicians at two academic medical centers were presented a standardized case of a patient presenting with chest pain who was ultimately diagnosed with herpes zoster using an interview format. Case information was presented in predetermined aliquots where participants were then asked to think-aloud, describing their thoughts and differential diagnoses given the data available. At the conclusion of the interview, participants were asked questions about their diagnostic process. Interviews were recorded, transcribed, and content analysis was conducted to identify key themes related to the diagnostic thinking process. Results Sixteen hospital medicine physicians (nine men, seven women) participated in interviews and four obtained the correct final diagnosis (one man, three women). Participants had an average of nine years of experience. Overall, substantial heterogeneity in both the differential diagnoses and clinical reasoning among participants was observed. Those achieving the correct diagnosis utilized systems-based or anatomic approaches when forming their initial differential diagnoses, rather than focusing on life-threatening diagnoses alone. Evidence of cognitive bias was common; those with the correct diagnosis more often applied debiasing strategies than those with the incorrect final diagnosis. Conclusions Heterogeneity in diagnostic evaluation appears to be common and may indicate faulty data processing. Structured approaches and debiasing strategies appear helpful in promoting diagnostic accuracy.

Objectives Diagnostic error is a serious public health problem. Measuring diagnostic performance remains elusive. We sought to measure misdiagnosis-related harms following missed acute myocardial infarctions (AMI) in the emergency department (ED) using the symptom-disease pair analysis of diagnostic error (SPADE) method. Methods Retrospective administrative data analysis (2009–2017) from a single, integrated health system using International Classification of Diseases (ICD) coded discharge diagnoses. We looked back 30 days from AMI hospitalizations for antecedent ED treat-and-release visits to identify symptoms linked to probable missed AMI (observed > expected). We then looked forward from these ED discharge diagnoses to identify symptom-disease pair misdiagnosis-related harms (AMI hospitalizations within 30-days, representing diagnostic adverse events). Results A total of 44,473 AMI hospitalizations were associated with 2,874 treat-and-release ED visits in the prior 30 days. The top plausibly-related ED discharge diagnoses were “chest pain” and “dyspnea” with excess treat-and-release visit rates of 9.8% (95% CI 8.5–11.2%) and 3.4% (95% CI 2.7–4.2%), respectively. These represented 574 probable missed AMIs resulting in hospitalization (adverse event rate per AMI 1.3%, 95% CI 1.2–1.4%). Looking forward, 325,088 chest pain or dyspnea ED discharges were followed by 508 AMI hospitalizations (adverse event rate per symptom discharge 0.2%, 95% CI 0.1–0.2%). Conclusions The SPADE method precisely quantifies misdiagnosis-related harms from missed AMIs using administrative data. This approach could facilitate future assessment of diagnostic performance across health systems. These results correspond to ∼10,000 potentially-preventable harms annually in the US. However, relatively low error and adverse event rates may pose challenges to reducing harms for this ED symptom-disease pair.

Objectives The National Academy of Medicine identified diagnostic error as a pressing public health concern and defined failure to effectively communicate the diagnosis to patients as a diagnostic error. Leveraging Patient’s Experience to improve Diagnosis (LEAPED) is a new program for measuring patient-reported diagnostic error. As a first step, we sought to assess the feasibility of using LEAPED after emergency department (ED) discharge. Methods We deployed LEAPED using a cohort design at three EDs within one academic health system. We enrolled 59 patients after ED discharge and queried them about their health status and understanding of the explanation for their health problems at 2-weeks, 1-month, and 3-months. We measured response rates and demographic/clinical predictors of patient uptake of LEAPED. Results Of those enrolled (n=59), 90% (n=53) responded to the 2-week post-ED discharge questionnaire (1 and 3-month ongoing). Of the six non-responders, one died and three were hospitalized at two weeks. The average age was 50 years (SD 16) and 64% were female; 53% were white and 41% were black. Over a fifth (23%) reported they were not given an explanation of their health problem on leaving the ED, and of those, a fourth (25%) did not have an understanding of what next steps to take after leaving the ED. Conclusions Patient uptake of LEAPED was high, suggesting that patient-report may be a feasible method of evaluating the effectiveness of diagnostic communication to patients though further testing in a broader patient population is essential. Future research should determine if LEAPED yields important insights into the quality and safety of diagnostic care.

Background Timely diagnosis of pediatric sepsis remains elusive. We estimated the risk of potentially missed pediatric sepsis in US emergency departments (EDs) and determined factors associated with its occurrence. Methods In a retrospective study of linked inpatient and ED records from four states using administrative data (excluding 40% with missing identifiers), we identified children admitted with severe sepsis and/or septic shock who had at least one ED treat-and-release visit in the 7 days prior to sepsis admission. An expert panel rated the likelihood of each ED visit being related to subsequent sepsis admission. We used multivariable regression to identify associations with potentially missed sepsis. Results Of 1945 patients admitted with severe sepsis/septic shock, 158 [8.1%; 95% confidence interval (CI), 6.9%–9.4%] had potentially missed sepsis during an antecedent treat-and-release ED visit. The odds of potentially missed sepsis were lower for each additional comorbid chronic condition [odds ratio (OR), 0.86; 95% CI, 0.80–0.92] and higher in California (OR, 2.26; 95% CI, 1.34–3.82), Florida (OR, 3.33; 95% CI, 1.95–5.70), and Massachusetts (OR, 2.87; 95% CI, 1.35–6.09), compared to New York. Conclusions Administrative data can be used to screen large populations for potentially missed sepsis and identify cases that warrant detailed record review.

Objectives The occurrence of head computed tomography (HCT) at emergency department (ED) visit for non-specific neurological symptoms has been associated with increased subsequent stroke risk and may be a marker of diagnostic error. We evaluate whether HCT occurrence among ED headache patients is associated with increased subsequent cerebrovascular disease risk. Methods We conducted a retrospective cohort study of consecutive adult patients with headache who were discharged home from the ED (ED treat-and-release visit) at one multicenter institution. Patients with headache were defined as those with primary ICD-9/10-CM discharge diagnoses codes for benign headache from 9/1/2013-9/1/2018. The primary outcome of cerebrovascular disease hospitalization was identified using ICD-9/10-CM codes and confirmed via chart review. We matched headache patients who had a HCT (exposed) to those who did not have a HCT (unexposed) in the ED in a one-to-one fashion using propensity score methods. Results Among the 28,121 adult patients with ED treat-and-release headache visit, 45.6% (n=12,811) underwent HCT. A total of 0.4% (n=111) had a cerebrovascular hospitalization within 365 days of index visit. Using propensity score matching, 80.4% (n=10,296) of exposed patients were matched to unexposed. Exposed patients had increased risk of cerebrovascular hospitalization at 365 days (RR: 1.65: 95% CI: 1.18–2.31) and 180 days (RR: 1.62; 95% CI: 1.06–2.49); risk of cerebrovascular hospitalization was not increased at 90 or 30 days. Conclusions Having a HCT performed at ED treat-and-release headache visit is associated with increased risk of subsequent cerebrovascular disease. Future work to improve cerebrovascular disease prevention strategies in this subset of headache patients is warranted.

Background Pediatric abdominal pain is challenging to diagnose and often results in unscheduled return visits to the emergency department. External pressures and diagnostic momentum can impair physicians from thoughtful reflection on the differential diagnosis (DDx). We implemented a diagnostic time-out intervention and created a scoring tool to improve the quality and documentation rates of DDx. The specific aim of this quality improvement (QI) project was to increase the frequency of resident and attending physician documentation of DDx in pediatric patients admitted with abdominal pain by 25% over 6 months. Methods We reviewed a total of 165 patients admitted to the general pediatrics service at one institution. Sixty-four history and physical (H&P) notes were reviewed during the baseline period, July–December 2017; 101 charts were reviewed post-intervention, January–June 2018. Medical teams were tasked to perform a diagnostic time-out on all patients during the study period. Metrics tracked monthly included percentage of H&Ps with a ‘complete’ DDx and quality scores (Qs) using our Differential Diagnosis Scoring Rubric. Results At baseline, 43 (67%) resident notes and 49 (77%) attending notes documented a ‘complete’ DDx. Post-intervention, 59 (58%) resident notes and 69 (68%) attending notes met this criteria. Mean Qs, pre- to post-intervention, for resident-documented differential diagnoses increased slightly (2.41–2.47, p = 0.73), but attending-documented DDx did not improve (2.85–2.82, p = 0.88). Conclusions We demonstrated a marginal improvement in the quality of resident-documented DDx. Expansion of diagnoses considered within a DDx may contribute to higher diagnostic accuracy.

Objectives Using case review to determine whether a patient experienced a delayed diagnosis is challenging. Measurement would be more accurate if case reviewers had access to multi-expert consensus on grading the likelihood of delayed diagnosis. Our objective was to use expert consensus to create a guide for objectively grading the likelihood of delayed diagnosis of appendicitis, new-onset diabetic ketoacidosis (DKA), and sepsis. Methods Case vignettes were constructed for each condition. In each vignette, a patient has the condition and had a previous emergency department (ED) visit within 7 days. Condition-specific multi-specialty expert Delphi panels reviewed the case vignettes and graded the likelihood of a delayed diagnosis on a five-point scale. Delayed diagnosis was defined as the condition being present during the previous ED visit. Consensus was defined as ≥75% agreement. In each Delphi round, panelists were given the scores from the previous round and asked to rescore. A case scoring guide was created from the consensus scores. Results Eighteen expert panelists participated. Consensus was achieved within three Delphi rounds for all appendicitis and sepsis vignettes. We reached consensus on 23/30 (77%) DKA vignettes. A case review guide was created from the consensus scores. Conclusions Multi-specialty expert reviewers can agree on the likelihood of a delayed diagnosis for cases of appendicitis and sepsis, and for most cases of DKA. We created a guide that can be used by researchers and quality improvement specialists to allow for objective case review to determine when delayed diagnoses have occurred for appendicitis, DKA, and sepsis.

Background The number of websites providing laboratory test information is increasing fast, although the accuracy of reported resources is sometimes questionable. The aim of this study was to assess the quality of online retrievable information by Google Search engine. Methods Considering urinalysis, cholesterol and prostate-specific antigen (PSA) as keywords, the Google Search engine was queried. Using Google Trends, users’ search trends (interest over time) were evaluated in a 5-year period. The first three or 10 retrieved hits were analysed in blind by two reviewers and classified according to the type of owner or publisher and for the quality of the reported Web content. Results The interest over time constantly increased for all the three considered tests. Most of the Web content owners were editorial and/or publishing groups (mean percentage 35.5% and 30.0% for the first three and 10 hits, respectively). Public and health agencies and scientific societies are less represented. Among the first three and 10 hits, cited sources were found to vary from 26.0% to 46.7% of Web page results, whilst for cholesterol, 60% of the retrieved Web contents reported only authors’ signatures. Conclusions Our findings confirm those obtained in other studies in the literature, demonstrating that online Web searches can lead patients to inadequately written or reviewed health information.

Background This study aimed to investigate whether the temperature of distilled water used for reconstituting lyophilized routine internal quality control (IQC) material may influence the process of validation of analytical sessions of routine hemostasis testing. Methods Routine hemostasis testing was performed for 10 consecutive days using two levels of IQC materials dissolved using distilled water at three different temperatures (2–4°C, 22–24°C and 36–38°C). The tests assayed comprised prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FBG), antithrombin (AT), protein C (PC), protein S (PS) and D-dimer (D-Dimer HS 500), using the same ACL TOP 700 hemostasis instrument. Results Overall, 50% (i.e. 7/14) IQC measurements displayed statistically significant bias when lyophilized material was dissolved with distilled water at 3–5°C compared to 22–24°C, and in two instances (level I for both PT and D-dimer) the bias was higher than the quality specifications. Concerning lyophilized material dissolved with distilled water at 36–38°C, 21% (3/14) IQC values displayed a statistically significant bias compared to 22–24°C, and in one instance (level 2 for PT) the bias was higher than the quality specifications. Conclusions The results of this study show that water temperature, as used to dissolve lyophilized IQC material, may represent an important pre-analytical variable in routine hemostasis testing, especially cold temperatures. Laboratory professionals are encouraged to standardize water temperature, preferably between 22 and 24°C, before reconstituting lyophilized IQC materials used to validate routine hemostasis testing.

Background Diagnosis of hematolymphoid neoplasm (HLN) requires different technologies which are performed on a patient basis instead of per protocol. We hypothesize that integration of hematimetric and cytological analysis along with multiparametric flow cytometry (MFC) provides a framework to evaluate peripheral blood (PB) samples from Primary Care. Methods Samples from patients with persistent (>3 months) lymphocytosis (>5 × 10 9 /L) and/or monocytosis (>10 9 /L) or the presence of atypical and/or blast cells upon the smear review were analyzed by MFC concurrent to cytological analysis. MFC studies were carried out following standardized procedures. Results In a 3-year period, smear review and MFC were performed simultaneously in 350 samples, demonstrating HLN in 194 cases (55.4%). In 156 cases, reactive cell populations were found. The combination of age, absolute lymphocyte count (ALC), hemoglobin and platelets provided the best correlation with MFC for the presence of a chronic lymphoproliferative disorder (CLPD) in lymphocytosis [area under the curve (AUC) 0.891, p < 0.05]. A model evaluating the probability of CLPD has been proposed and validated in an independent cohort. Conclusions A strategy to perform MFC studies following standardized procedures has proven to be useful to evaluate samples from patients in Primary Care centers for HLN diagnosis or reactive conditions, providing a sensitive and rapid clinical orientation and avoiding unnecessary consultations in routine clinical practice. The probability for the presence of CLPD in PB can be calculated and help guide decision-making regarding further testing.

Background Gram-negative lipopolysaccharides are potent inducers of inflammation and have been shown to be present in patients with end-stage kidney disease. There are a variety of different manufacturers and assay types to quantify endotoxin levels; however, there is no standard methodology to demonstrate its presence in plasma. Methods A control group consisting of haemodialysis and non-kidney disease was selected. Five sets of experiments were conducted to try and ascertain the best platform for plasma endotoxin testing. This included: testing of blank tubes; the effects of freezing, thawing and storage on recovery; the effect of different buffers; use of an endpoint assay and comparison of turbidimetric vs. chromogenic kinetic assays. Results No endotoxin was detected in the blood collection tubes. Freezing and thawing per se did not affect spike recovery rates. However, the sequencing of sample dilution relative to freezing had a significant effect on endotoxin recovery. Buffers increased spike recovery at all levels of dilution. No endotoxin was demonstrated with either the turbidimetric or chromogenic kinetic assay at two different dilutions in the haemodialysis controls. The endpoint assay at a 1:5 dilution did not achieve a valid standard curve. Conclusions The findings of our study suggest that, when testing plasma samples, either a turbidimetric or chromogenic assay may be used and should be diluted with appropriate buffers to achieve optimal recovery. Studies looking to quantify the presence of plasma endotoxin need to internally validate their assays and specify their validation findings in their results.

Objectives In the laboratory medicine segment, benchmarking is the process in which institutions seek to compare with the macro environment (performance comparison and best practices with different laboratories) and improve their results based on quality indicators. The literature has highlighted the vulnerability of the pre-analytical phase in terms of risks and failures and the use of interlaboratory comparison as an opportunity to define a strategic performance benchmark aligned with the laboratory medicine sector, which has been a promising strategy to ensure continuous improvement, identifying within the pre-analytical process the critical activities to guarantee patient safety. In this context, this paper aims to present the three-year experience (2016–2018) of the Benchmarking Program and Laboratory Indicators – in Portuguese, Programa de Benchmarking e Indicadores Laboratoriais (PBIL) – with emphasis on pre-analytical indicators and their comparison against literature references and other programs of benchmarking in the area of laboratory medicine. PBIL is organized by the Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC/ML) in conjunction with Controllab and coordinated by a Brazilian group with representatives from different countries. Methods The data presented in this paper involving the performance results of 180 laboratories with active participation. Results are presented in percentage (%, boxplot graphical in quartiles) and Sigma metric, recognized as the metric that best indicates the magnitude of failures in a process. The Pareto Chart was used to facilitate ordering and to identify the main errors in the pre-analytical phase. The Radar Chart was made available in this work for the purpose of comparing the results obtained in Sigma by the PBIL and IFCC Working Group Laboratory Errors and Patient Safety (WG LEPS). Results In the study period, just over 80% of the pre-analytical failures are related to Blood culture contamination (hospital-based and non-hospital-based laboratories), Recollect and Non-registered exams, with failure rates of 2.70, 1.05 and 0.63%, respectively. The performance of the PBIL program participants was in line with the literature references, and allowed to identify benchmarks in the laboratory medicine market, target of PBIL, with best practices were observed for some indicators. Conclusions The results of the program demonstrate the importance of an ongoing program comparative performance-monitoring program for setting more robust goals and consequently reducing laboratory process failures. Even with these promising premises and results, the contextualized analysis of the program indicators, point to a still significant number of failures in our market, with possibilities for improvement in order aiming to ensure more robust and effective processes.

Objectives This study aimed to disclose the importance of nipple discharge (ND) and the accuracy of its economic and fast cytological interpretation. Methods All ND cytology cases for Saudi patients done between 2004 and 2013 were retrieved from the Pathology e-system. Only cases that have subsequent tissue diagnoses were included in this study (n = 228). Age and bloody nature of the ND were both tested for association with a higher chance of carcinoma. Diagnostic accuracy of ND cytology was calculated twice, including and excluding the “atypical” cases. Results Specificity and positive predictive value were 100% for ND cytology in both cases. Sensitivity (34.6%; 52.9%), negative predictive value (93.15 %; 96.1%), false-negative rate (65.4%; 47.1%), accuracy rate (93.4%; 96.2%), when atypical cases were included and excluded; respectively. Only 10.5% of the patients complaining from nipple discharge had breast cancer. For those who had cancer, nipple discharge cytology was positive and showed the cancer cells in only 37.5%, while the rest were false negative. Bloody ND disclosed a significant association with malignancy (p < 0.001), but the association was statistically not significant for old age (p = 0.062). Conclusions The prospect of having breast cancer with the presentation of ND is low, and it can be missed by studying the ND cytology alone in a high proportion of cases. Excluding the atypical category did not make a significant improvement in the test’s accuracy.