In this two-part series on sources of bias in studies of diagnostic test performance, we outline common errors and optimal conditions during three study phases: patient selection, interpretation of the index test and disease verification by a gold standard. Here in part 1, biases associated with suboptimal participant selection are discussed through the lens of partial verification bias and spectrum bias, both of which increase the proportion of participants who are the 'sickest of the sick' or the 'wellest of the well.' Especially through retrospective methodology, partial verification introduces bias by including patients who are test positive by a gold standard, since patients with a positive index test are more likely to go on to further gold standard testing. Spectrum bias is frequently introduced through case-control design, dropping of indeterminate results or convenience sampling. After reading part 1, the informed clinician should be better able to judge the quality of a diagnostic test study, its inherent limitations and whether its results could be generalisable to their practice. Part 2 will describe how interpretation of the index test and disease verification by a gold standard can contribute to diagnostic test bias.

Multiple pitfalls can occur with the conduct and analysis of a study of diagnostic tests, resulting in biased accuracy. Our conceptual model includes three stages: patient selection, interpretation of the index test and disease verification. In part 2, we focus on (1) Interpretation bias (or workup bias): where the classification of an indeterminate index test result can bias the accuracy of a test or how lack of blinding can bias a subjective test result, and (2) Disease verification bias: where the index test result is incorporated into the gold standard or when the gold standard is applied only to a select population as the gold standard is an invasive test. In an example with age-adjusted D-dimer for pulmonary embolism, differential verification bias was a limitation due to the use of two gold standards-CT for a high-risk population and follow-up for symptoms in a low-risk population. However, there are circumstances when certain choices in study design are unavoidable, and result in biased test characteristics. In this case, the informed reader will better judge the quality of a study by recognising the potential biases and limitations by being methodical in their approach to understanding the methods, and in turn, better apply studies of diagnostic tests into their clinical practice.

Clozapine is an atypical antipsychotic drug prescribed for treatment-resistant schizophrenia. The risk of adverse hematologic, cardiovascular, and neurologic effects has tempered its use, and reports of overdoses remain rare. We report a case of accidental acute clozapine intoxication in a clozapine-naïve patient, who presented with symptoms mimicking acute stroke and later developed status epilepticus. Clozapine intoxication is a rare presentation in the emergency department with potential for iatrogenic harm if not correctly identified.

Objective

Routine CT for patients with acute flank pain has not been shown to improve patient outcomes, and it may unnecessarily expose patients to radiation and increased costs. As preliminary steps toward the development of a guideline for selective CT, we sought to determine the prevalence of clinically important outcomes in patients with acute flank pain and derive preliminary decision rules.

Methods

We analyzed data from a randomized trial of CT vs. ultrasonography for patients with acute flank pain from 15 EDs between October 2011 and February 2013. Clinically important outcomes were defined as inpatient admission for ureteral stones and alternative diagnoses. Clinically important stones were defined as stones requiring urologic intervention. We sought to derive highly sensitive decision rules for both outcomes.

Results

Of 2759 participants, 236 (8.6%) had a clinically important outcome and 143 (5.2%) had a clinically important stone. A CDR including anemia (hemoglobin <13.2g/dl), WBC count >11000/μl, age>42years, and the absence of CVAT had a sensitivity of 97.9% (95% CI 94.8-99.2%) and specificity of 18.7% (95% 17.2-20.2%) for clinically important outcome. A CDR including hydronephrosis, prior history of stone, and WBC count <8300/μl had a sensitivity of 98.6% (95% CI 94.5-99.7%) and specificity of 26.0% (95% 24.2-27.7%) for clinically important stone.

Conclusions

We determined the prevalence of clinically important outcomes in patients with acute flank pain, and derived preliminary high sensitivity CDRs that predict them. Validation of CDRs with similar test characteristics would require prospective enrollment of 2100 patients.

Abstract Objective. Emergency medical services (EMS) "superusers" -those who use EMS services at extremely high rates -have not been well characterized. Recent interest in the small group of individuals who account for a disproportionate share of health-care expenditures has led to research on frequent users of emergency departments and other health services, but little research has been done regarding those who use EMS services. To inform policy and intervention implementation, we undertook a descriptive analysis of EMS superusers in a large urban community. In this paper we compare EMS superusers to low, moderate, and high users to characterize factors contributing to EMS use. We also estimate the financial impact of EMS superusers. Methods. We conducted a retrospective cross-sectional study based on 1 year of data from an urban EMS system. Data for all EMS encounters with patients age ≥18 years were extracted from electronic records generated on scene by paramedics. We identified demographic and clinical variables associated with levels of EMS use. EMS users were characterized by the annual number of EMS encounters: low (1), moderate (2-4), high (5-14), and superusers (≥15). In addition, we performed a financial analysis using San Francisco Fire Department (SFFD) 2009 charge and reimbursement data. Results. A total of 31,462 adults generated 43,559 EMS ambulance encounters, which resulted in 39,107 transports (a 90% transport rate). Encounters for general medical reasons were common among moderate and high users and less frequent among superusers and low users, while alcohol use was exponentially correlated with encounter frequency. Superusers were significantly younger than moderate EMS users, and more likely to be male. The superuser group created a significantly higher financial burden/person than any other group, comprising 0.3% of the study population, but over 6% of annual EMS charges and reimbursements. Conclusions. In this retrospective study, adult EMS "superusers" emerged as a distinct, predominantly male population and their EMS encounters were associated with alcohol use. Continued analysis of this unique, high-cost, and frequently transported population will likely illuminate specific intervention strategies.

Statements about building walls, deportation and denying services to undocumented immigrants made during President Trump's presidential campaign and presidency may induce fear in Latino populations and create barriers to their health care access. To assess how these statements relate to undocumented Latino immigrants' (UDLI) and Latino legal residents/citizens' (LLRC) perceptions of safety and their presentations for emergency care, we conducted surveys of adult patients at three county emergency departments (EDs) in California from June 2017 to December 2018. Of 1,684 patients approached, 1,337 (79.4%) agreed to participate: 34.3% UDLI, 36.9% LLRC, and 29.8% non-Latino legal residents/citizens (NLRC). The vast majority of UDLI (95%), LLRC (94%) and NLRC (85%) had heard statements about immigrants. Most UDLI (89%), LLRC (88%) and NLRC (87%) either thought that these measures were being enacted now or will be enacted in the future. Most UDLI and half of LLRC reported that these statements made them feel unsafe living in the US, 75% (95% CI 70-80%) and 51% (95% CI 47-56%), respectively. More UDLI reported that these statements made them afraid to come to the ED (24%, 95% CI 20-28%) vs LLRC (4.4%, 95% CI 3-7%) and NLRC (3.5%, 95% CI 2-6%); 55% of UDLI with this fear stated it caused them to delay coming to the ED (median delay 2-3 days). The vast majority of patients in our California EDs have heard statements during the 2016 presidential campaign or from President Trump about measures against undocumented immigrants, which have induced worry and safety concerns in both UDLI and LLRC patients. Exposure to these statements was also associated with fear of accessing emergency care in some UDLIs. Given California's sanctuary state status, these safety concerns and ED access fears may be greater in a nationwide population of Latinos.