Lyme disease overdiagnosis in a large healthcare system: a population-based, retrospective study.

OBJECTIVES: To evaluate the impact of false-positive IgM immunoblots on Lyme disease treatment and case reporting in a large healthcare system. METHODS: We obtained the results of all Lyme disease serological tests ordered at U.S. Air Force healthcare facilities in the USA between January 2013 and December 2017. We conducted chart reviews to adjudicate positive IgM immunoblots (from two-tier and independent testing) as true positives or false positives using established criteria, and we assessed whether these cases were reported to the U.S. Department of Defense surveillance system. RESULTS: Of the 18 410 serum tests (17 058 immunoassays and 1352 immunoblots) performed on 15 928 unique individuals, 249/1352 (18.4%) IgM immunoblots were positive. After excluding repeat tests, insufficiently documented cases, and participants with a history of Lyme disease, 212 positive IgM immunoblot cases were assessed. A total of 113/212 (53.3%) were determined to be false positives. Antibiotics were prescribed for Lyme disease for 97/99 (98.0%) participants with a true-positive test and 91/113 (80.5%) participants with a false-positive test. The number of false-positive cases reported to the surveillance system was identical to the number of unreported true-positive cases (n = 44). CONCLUSIONS: Lyme disease serological tests were overused in a large healthcare system, and positive results were frequently misinterpreted, leading to misdiagnosis and widespread antibiotic misuse. Underreporting of true-positive cases was offset by overreporting of false-positive cases, suggesting that the discrepancy between the reported incidence and true incidence of Lyme disease may not be as significant as previously assumed.

Hypermanganesemia due to mutations in SLC39A14: further insights into Mn deposition in the central nervous system.

BACKGROUND: The SLC39A14, SLC30A10 and SLC39A8 are considered to be key genes involved in manganese (Mn) homeostasis in humans. Mn levels in plasma and urine are useful tools for early recognition of these disorders. We aimed to explore further biomarkers of Mn deposition in the central nervous system in two siblings presenting with acute dystonia and hypermanganesemia due to mutations in SLC39A14. These biomarkers may help clinicians to establish faster and accurate diagnosis and to monitor disease progression after chelation therapy is administered. RESULTS: A customized gene panel for movement disorders revealed a novel missense variant (c.311G > T; p.Ser104Ile) in SLC39A14 gene in two siblings presenting at the age of 10 months with acute dystonia and motor regression. Mn concentrations were analyzed using inductively coupled mass spectrometry in plasma and cerebrospinal fluid, disclosing elevated Mn levels in the index case compared to control patients. Surprisingly, Mn values were 3-fold higher in CSF than in plasma. We quantified the pallidal index, defined as the ratio between the signal intensity in the globus pallidus and the subcortical frontal white matter in axial T1-weighted MRI, and found significantly higher values in the SLC39A14 patient than in controls. These values increased over a period of 10 years, suggesting the relentless pallidal accumulation of Mn. Following genetic confirmation, a trial with the Mn chelator Na2CaEDTA led to a reduction in plasma Mn, zinc and selenium levels. However, parents reported worsening of cervical dystonia, irritability and sleep difficulties and chelation therapy was discontinued. CONCLUSIONS: Our study expands the very few descriptions of patients with SLC39A14 mutations. We report for the first time the elevation of Mn in CSF of SLC39A14 mutated patients, supporting the hypothesis that brain is an important organ of Mn deposition in SLC39A14-related disease. The pallidal index is an indirect and non-invasive method that can be used to rate disease progression on follow-up MRIs. Finally, we propose that patients with inherited defects of manganese transport should be initially treated with low doses of Na2CaEDTA followed by gradual dose escalation, together with a close monitoring of blood trace elements in order to avoid side effects.

Neighborhood environment and risk of ischemic stroke: the brain attack surveillance in Corpus Christi (BASIC) Project.

The authors explored whether neighborhood-level characteristics are associated with ischemic stroke and whether the association differs by ethnicity, age, and gender. Using data from the Brain Attack Surveillance in Corpus Christi Project (January 2000-June 2003), they identified cases of ischemic stroke (n = 1,247) from both hospital and out-of-hospital sources. Census tracts served as proxies for neighborhoods, and neighborhood socioeconomic status scores were constructed from census variables (higher scores represented less disadvantage). In Poisson regression analyses comparing the 90th percentile of neighborhood score with the 10th, the relative risk of stroke was 0.49 (95% confidence interval (CI): 0.41, 0.58). After adjustment for age, gender, and ethnicity, this association was attenuated (relative risk (RR) = 0.79, 95% CI: 0.63, 1.00). There was no ethnic difference in the association of score with stroke (p for interaction = 0.79). Significant effect modification was found for age (p for interaction < 0.001) and gender (p for interaction = 0.04), with increasing scores being protective against stroke in men and younger persons. Associations were attenuated after adjustment for education (men: RR = 0.77, 95% CI: 0.55, 1.07; persons aged <65 years: RR = 0.65, 95% CI: 0.41, 1.02). Neighborhood characteristics may influence stroke risk in certain gender and age groups. Mechanisms for these associations should be examined.