Burden of serious harms from diagnostic error in the USA.

BACKGROUND: Diagnostic errors cause substantial preventable harms worldwide, but rigorous estimates for total burden are lacking. We previously estimated diagnostic error and serious harm rates for key dangerous diseases in major disease categories and validated plausible ranges using clinical experts. OBJECTIVE: We sought to estimate the annual US burden of serious misdiagnosis-related harms (permanent morbidity, mortality) by combining prior results with rigorous estimates of disease incidence. METHODS: Cross-sectional analysis of US-based nationally representative observational data. We estimated annual incident vascular events and infections from 21.5 million (M) sampled US hospital discharges (2012-2014). Annual new cancers were taken from US-based registries (2014). Years were selected for coding consistency with prior literature. Disease-specific incidences for 15 major vascular events, infections and cancers ('Big Three' categories) were multiplied by literature-based rates to derive diagnostic errors and serious harms. We calculated uncertainty estimates using Monte Carlo simulations. Validity checks included sensitivity analyses and comparison with prior published estimates. RESULTS: Annual US incidence was 6.0 M vascular events, 6.2 M infections and 1.5 M cancers. Per 'Big Three' dangerous disease case, weighted mean error and serious harm rates were 11.1% and 4.4%, respectively. Extrapolating to all diseases (including non-'Big Three' dangerous disease categories), we estimated total serious harms annually in the USA to be 795 000 (plausible range 598 000-1 023 000). Sensitivity analyses using more conservative assumptions estimated 549 000 serious harms. Results were compatible with setting-specific serious harm estimates from inpatient, emergency department and ambulatory care. The 15 dangerous diseases accounted for 50.7% of total serious harms and the top 5 (stroke, sepsis, pneumonia, venous thromboembolism and lung cancer) accounted for 38.7%. CONCLUSION: An estimated 795 000 Americans become permanently disabled or die annually across care settings because dangerous diseases are misdiagnosed. Just 15 diseases account for about half of all serious harms, so the problem may be more tractable than previously imagined.

COVID-19 clinical outcomes by patient disability status: A retrospective cohort study.

BACKGROUND: People with disabilities might experience worse clinical outcomes of SARS-CoV-2 infection, but evidence is limited. OBJECTIVE: To investigate if people with disabilities requiring assistance are more likely to experience severe COVID-19 or death. METHODS: Data from the Johns Hopkins COVID-19 Precision Medicine Analytics Platform Registry (JH-CROWN) included 6494 adult patients diagnosed with COVID-19 and admitted between March 4, 2020-October 29, 2021. Severe COVID-19 and death were defined using the occurrence and timing of clinical events. Assistive needs due to disabilities were reported by patients or their proxies upon admission. Multivariable-adjusted Cox proportional hazards models were used to examine the associations between disability status and severe COVID-19 or death. Primary models adjusted for demographics and secondary models additionally adjusted for clinical covariates. RESULTS: In this clinical cohort (47-73 years, 49% female, 39% Black), patients with disabilities requiring assistance had 1.35 times (95% confidence interval [CI]:1.01, 1.81) the hazard of severe COVID-19 among patients <65 years, but not among those ≥65 years, equating to an additional 17.5 severe COVID-19 cases (95% CI:7.7, 28.2) per 100 patients. A lower risk of mortality was found among patients <65 years, but this finding was not robust due to the small number of deaths. CONCLUSIONS: People with disabilities requiring assistance aged <65 years are more likely to develop severe COVID-19. Although our study is limited by using a medical model of disability, these analyses intend to further our understanding of COVID-19 outcomes among people with disabilities. Also, standardized disability data collection within electronic health records is needed.

Rate of diagnostic errors and serious misdiagnosis-related harms for major vascular events, infections, and cancers: toward a national incidence estimate using the "Big Three".

BACKGROUND: Missed vascular events, infections, and cancers account for ~75% of serious harms from diagnostic errors. Just 15 diseases from these "Big Three" categories account for nearly half of all serious misdiagnosis-related harms in malpractice claims. As part of a larger project estimating total US burden of serious misdiagnosis-related harms, we performed a focused literature review to measure diagnostic error and harm rates for these 15 conditions. METHODS: We searched PubMed, Google, and cited references. For errors, we selected high-quality, modern, US-based studies, if available, and best available evidence otherwise. For harms, we used literature-based estimates of the generic (disease-agnostic) rate of serious harms (morbidity/mortality) per diagnostic error and applied claims-based severity weights to construct disease-specific rates. Results were validated via expert review and comparison to prior literature that used different methods. We used Monte Carlo analysis to construct probabilistic plausible ranges (PPRs) around estimates. RESULTS: Rates for the 15 diseases were drawn from 28 published studies representing 91,755 patients. Diagnostic error (false negative) rates ranged from 2.2% (myocardial infarction) to 62.1% (spinal abscess), with a median of 13.6% [interquartile range (IQR) 9.2-24.7] and an aggregate mean of 9.7% (PPR 8.2-12.3). Serious misdiagnosis-related harm rates per incident disease case ranged from 1.2% (myocardial infarction) to 35.6% (spinal abscess), with a median of 5.5% (IQR 4.6-13.6) and an aggregate mean of 5.2% (PPR 4.5-6.7). Rates were considered face valid by domain experts and consistent with prior literature reports. CONCLUSIONS: Diagnostic improvement initiatives should focus on dangerous conditions with higher diagnostic error and misdiagnosis-related harm rates.

Long-term Persistence of Oral HPV Over 7 Years of Follow-up.

BACKGROUND: Human papillomavirus-related oropharyngeal cancer (HPV-OPC) incidence is increasing, but the natural history of the precursor-oral HPV-has not been well described. METHODS: This observational cohort study of people living with HIV and at-risk HIV uninfected people evaluated participants semiannually using 30-second oral rinse and gargle specimens over 7 years. Initially, 447 participants were followed for 4 years as part of the Persistent Oral Papillomavirus Study, and a subset of 128 who showed persistent infections at the last Persistent Oral Papillomavirus Study visit had an additional visit, as part of the Men and Women Understanding Throat HPV Study, on average 2.5 years later. Extracted DNA from oral rinse and gargle specimens was amplified using polymerase chain reaction and type specification of 13 oncogenic HPV types. Risk factors for oncogenic oral HPV clearance were evaluated using Cox models. RESULTS: The majority of oncogenic oral HPV infections cleared quickly, with a median time to clearance of 1.4 years (interquartile range = 0.5-3.9 years). After 7 years of follow-up, 97% of incident and 71% of prevalent infections had cleared. Lower HPV-16 viral load was statistically significantly associated with clearance (per 10-fold decrease in copy number: adjusted hazard ratio [aHR] = 2.51, 95% confidence interval [CI] = 1.20 to 5.26; P = .01). Adjusted analyses showed that oncogenic oral HPV clearance was lower among prevalent than incident-detected infections (aHR = 0.44, 95% CI = 0.35 to 0.55), among men than women (aHR = 0.74, 95% CI = 0.60 to 0.91), for older participants (aHR per 10 years increasing age = 0.81, 95% CI = 0.74 to 0.89), and among people living with HIV (aHR = 0.76, 95% CI = 0.60 to 0.95). One participant who had oral HPV-16 consistently detected at 10 study visits over 4.5 years was subsequently diagnosed with HPV-OPC. CONCLUSIONS: This prospective study of oncogenic oral HPV infection is the longest and largest quantification of oral HPV-16 infections to date.

Serious misdiagnosis-related harms in malpractice claims: The "Big Three" - vascular events, infections, and cancers.

Background Diagnostic errors cause substantial preventable harm, but national estimates vary widely from 40,000 to 4 million annually. This cross-sectional analysis of a large medical malpractice claims database was the first phase of a three-phase project to estimate the US burden of serious misdiagnosis-related harms. Methods We sought to identify diseases accounting for the majority of serious misdiagnosis-related harms (morbidity/mortality). Diagnostic error cases were identified from Controlled Risk Insurance Company (CRICO)'s Comparative Benchmarking System (CBS) database (2006-2015), representing 28.7% of all US malpractice claims. Diseases were grouped according to the Agency for Healthcare Research and Quality (AHRQ) Clinical Classifications Software (CCS) that aggregates the International Classification of Diseases diagnostic codes into clinically sensible groupings. We analyzed vascular events, infections, and cancers (the "Big Three"), including frequency, severity, and settings. High-severity (serious) harms were defined by scores of 6-9 (serious, permanent disability, or death) on the National Association of Insurance Commissioners (NAIC) Severity of Injury Scale. Results From 55,377 closed claims, we analyzed 11,592 diagnostic error cases [median age 49, interquartile range (IQR) 36-60; 51.7% female]. These included 7379 with high-severity harms (53.0% death). The Big Three diseases accounted for 74.1% of high-severity cases (vascular events 22.8%, infections 13.5%, and cancers 37.8%). In aggregate, the top five from each category (n = 15 diseases) accounted for 47.1% of high-severity cases. The most frequent disease in each category, respectively, was stroke, sepsis, and lung cancer. Causes were disproportionately clinical judgment factors (85.7%) across categories (range 82.0-88.8%). Conclusions The Big Three diseases account for about three-fourths of serious misdiagnosis-related harms. Initial efforts to improve diagnosis should focus on vascular events, infections, and cancers.

Evaluating the Utility and Prevalence of HPV Biomarkers in Oral Rinses and Serology for HPV-related Oropharyngeal Cancer.

Performance of commercially available human papillomavirus (HPV) assays (approved for cervical HPV detection) is unknown for detecting HPV-related oropharyngeal cancer (HPV-OPC). Assays for detection of HPV DNA [ELISA (DEIA) and Cobas], and RNA (Aptima) in oral rinse samples, and serum HPV oncogene antibodies were evaluated. Sensitivity and specificity of each test was explored among HPV-OPC cases and controls. Biomarker prevalence was evaluated among 294 "at-risk" people (screening) and 133 "high-risk" people [known to previously have oral oncogenic HPV (oncHPV) DNA and/or HPV16 E6/E7 antibodies detected]. HPV16 E6 antibodies had the best overall test performance with sensitivity of 88%, compared with oral HPV16 DNA sensitivity of 51% by DEIA and 43% by Cobas (each P < 0.001). Specificity was comparable in each of these tests (≥98%). When positivity for any oncHPV type was compared with HPV16 for the same test, sensitivity was comparable (60% vs. 51%, 40% vs. 43%, and 92% vs. 88% for DEIA, Cobas, and E6 antibodies, respectively), but specificity was reduced (93%-97%). Aptima had poor sensitivity (23%). Sensitivity decreased when cotesting HPV16 oral rinse DNA and E6 antibodies (37%-48%), or multiple E antibodies (69%-72%). HPV16 DNA were detected in ∼2% of the at-risk by either DEIA or Cobas and up to 15% of the high-risk population. HPV16 E6 seroprevalence was 2.3% and 2.4% in the at-risk and high-risk populations, respectively. Oral rinse HPV testing had moderate-to-poor sensitivity for HPV-OPC, suggesting many true positives would be missed in a potential screening scenario. HPV16 E6 serum antibody was the most promising biomarker evaluated.

Health Care Expenditures of Medicare Beneficiaries with Normal Pressure Hydrocephalus.

BACKGROUND: Normal pressure hydrocephalus (NPH) is an underdiagnosed and undertreated condition affecting the elderly population and with costs associated with its surgical management reported to be less than those associated with conservative management. OBJECTIVE: To determine if the rate of diagnosis of NPH has improved over the last decade, the rate of treatment has increased, and if surgical treatment costs and socioeconomic factors related to receipt of treatment have changed over time compared with conservative therapy. METHODS: A retrospective study based on data from a nationally representative random sample of 2,378,637 Medicare beneficiaries (2006-2010) was performed. Shunt surgery, shunt revision, replacement, and removal were analyzed as independent variables. RESULTS: A total of 2321 patients with NPH were included, with 580 (24.99%) receiving a first shunt procedure. The adjusted effect of the procedure is that total 5-year expenditures are $11,676 more per patient (P < 0.001) than expenditures associated with nonsurgical management. Shunt revision ($22,715, P < 0.01) and/or replacement ($46,607, P < 0.001) add significantly to 5-year expenditures. Socioeconomic factors including African American race (P = 0.006); age 75-79 years (P = 0.024), 80-84 years (P < 0.001), and ≥85 years (P < 0.001); and Medicaid (P < 0.001) have significant negative associations with shunt surgery. CONCLUSIONS: There was a 1.66-fold increase in the rate of diagnosis of NPH, from 0.12% in 1999 to 0.2% in 2008. The total costs per surgical patient rose by approximately 145% to 160% comparing 2001 and 2010. This increase was mainly due to hospital (by 167% to 168%) and home health costs (by 118% to 148%). Providing appropriate care across the socioeconomic spectrum warrants further study and requires identifying the factors that limit access to care.

Preventive Care Delivery to Young Children With Sickle Cell Disease.

Preventive services can reduce the morbidity of sickle cell disease (SCD) in children but are delivered unreliably. We conducted a retrospective cohort study of children aged 2 to 5 years with SCD, evaluating each child for 14 months and expecting that he/she should receive ≥75% of days covered by antibiotic prophylaxis, ≥1 influenza immunization, and ≥1 transcranial Doppler ultrasound (TCD). We used logistic regression to quantify the relationship between ambulatory generalist and hematologist visits and preventive services delivery. Of 266 children meeting the inclusion criteria, 30% consistently filled prophylactic antibiotic prescriptions. Having ≥2 generalist, non-well child care visits or ≥2 hematologist visits was associated with more reliable antibiotic prophylaxis. Forty-one percent of children received ≥1 influenza immunizations. Children with ≥2 hematologist visits were most likely to be immunized (62% vs. 35% among children without a hematologist visit). Only 25% of children received ≥1 TCD. Children most likely to receive a TCD (42%) were those with ≥2 hematologist visits. One in 20 children received all 3 preventive services. Preventive services delivery to young children with SCD was inconsistent but associated with multiple visits to ambulatory providers. Better connecting children with SCD to hematologists and strengthening preventive care delivery by generalists are both essential.

Ambulatory care connections of Medicaid-insured children with sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) requires coordinated ambulatory care from generalists and hematologists. We examined when children with SCD establish ambulatory care connections, whether these connections are maintained, and how these connections are used before and after hospitalizations. PROCEDURE: We conducted a retrospective cohort study of Medicaid-insured Maryland children with SCD from 2002 to 2008. For children enrolled from birth, time to first, second, and third generalist and first hematologist visits was plotted. For all children, we analyzed ambulatory visits by age group, by emergency department (ED) and hospital use, and before and after hospitalizations. RESULTS: The overall study cohort comprised 851 children; 178 provided data from birth. Ambulatory care connections to generalists were made rapidly; connections to hematologists occurred more slowly, if at all (38% of children had not seen a hematologist by age 2 years). Visits with generalists decreased as patients aged, as did visits with hematologists (54% of children in the 12-17 year age group had no hematology visits in 2 years). Children with higher numbers of ED visits or hospitalizations also had higher numbers of ambulatory visits (generalist and hematologist). Most children had visits with neither generalists nor hematologists in the 30 days before and after hospitalizations. CONCLUSIONS: Medicaid-insured children with SCD rapidly connect with generalists after birth; connections to hematologists occur more slowly. The observation that connections to generalists and hematologists diminish with time and are infrequently used around hospitalizations suggests that the ambulatory care of many Medicaid-insured children with SCD may be inadequate.