Understanding the Burden of Tuberculosis Among American Indians/Alaska Natives in the U.S.: A Validation Study

Objective

We validated cases of active tuberculosis (TB) recorded in the Indian Health Service (IHS) National Patient Information Reporting System (NPIRS) and evaluated the completeness of TB case reporting from IHS facilities to state health departments.

Methods

We reviewed the medical records of American Indian/Alaska Native (AI/AN) patients at IHS health facilities who were classified as having active TB using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes from 2006 to 2009 for clinical and laboratory evidence of TB disease. Individuals were reclassified as having active TB disease; recent latent TB infection (LTBI); past positive tuberculin skin test (TST) only; or as having no evidence of TB, LTBI, or a past positive TST. We compared validated active TB cases with corresponding state records to determine if they were reported.

Results

The study included 596 patients with active TB as per ICD-9-CM codes. Based on chart review, 111 (18.6%) had active TB; 156 (26.2%) had LTBI; 104 (17.4%) had a past positive TST; and 221 (37.1%) had no evidence of TB disease, LTBI, or a past positive TST. Of the 111 confirmed cases of active TB, 89 (80.2%) resided in participating states; 81 of 89 (91.2%) were verified as reported TB cases.

Conclusions

ICD-9-CM codes for active TB disease in the IHS NPIRS do not accurately reflect the burden of TB among AI/ANs. Most confirmed active TB cases in the IHS health system were reported to the state; the national TB surveillance system may accurately represent the burden of TB in the AI/AN population.Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis (M. tuberculosis) complex. Treatment for active TB disease requires months of combination drug therapy. Left untreated, TB can result in substantial morbidity and occasionally death. Although the number of TB cases in the United States has steadily declined during the past two decades, TB remains a major health concern within many subgroups, including American Indians/Alaska Natives (AI/ANs). The TB case rate among AI/ANs is estimated at 5.6 per 100,000 population, notably higher than the national average of 3.4 cases per 100,000 population.¹Surveillance of active TB disease is an important component of monitoring and controlling the spread of TB. Currently, annual rates of TB in the U.S. are calculated by the Centers for Disease Control and Prevention (CDC) National Tuberculosis Surveillance System (NTSS).¹ The NTSS is an electronic database that relies on the collaboration of state and local health departments; each person diagnosed with TB disease is verified as an incident case of TB and reported using a standard TB case form. The criteria for TB disease surveillance are based on a laboratory case definition, clinical case definition, or provider diagnosis.^1,2 The laboratory case definition requires isolation of M. tuberculosis complex in culture or detection of M. tuberculosis complex nucleic acids by amplification testing or demonstration of acid-fast bacilli in a clinical specimen when a culture cannot be obtained. The clinical case definition requires (1) a positive tuberculin skin test (TST), (2) signs and symptoms compatible with TB, (3) treatment with at least two anti-TB medications, and (4) a completed diagnostic evaluation. A provider diagnosis is used when the clinical presentation is consistent with TB but the criteria to meet laboratory or clinical case definitions are not met.The Indian Health Service (IHS), an agency of the U.S. Department of Health and Human Services, provides comprehensive health-care services through IHS, Tribal, and Urban Indian facilities (collectively referred to hereafter as IHS) to eligible AI/AN people who are members of 566 federally recognized Tribes. IHS provides care for approximately 2.1 million (62%) of the nation''s estimated 3.4 million AI/ANs.³ The IHS maintains a national database, the National Patient Information Reporting System (NPIRS).⁴ Within NPIRS, diseases and conditions are coded according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM).⁵ In addition, IHS is in the process of implementing an electronic health record (EHR) system.⁶ Electronic data collected by IHS have the potential to serve as a resource to better understand the burden and monitor trends of TB disease within the AI/AN population; yet, the accuracy of NPIRS for identifying people with TB disease has not been previously established. Several previous studies in other U.S. populations have cited wide variability (0%–77%) in the positive predictive value (PPV) of ICD-9-CM diagnostic codes for active TB disease.^7–13CDC provides guidance for IHS providers to report all nationally notifiable diseases, including TB, to local and state authorites.^1,2 However, there are no explicit mechanisms for IHS to report cases of TB directly to the NTSS, and the extent to which IHS facilities collaborate with local authorities on case reporting is not well understood.We validated active cases of TB disease within the AI/AN population by reviewing the medical charts of individuals assigned an active TB disease ICD-9-CM code in the inpatient and outpatient NPIRS visit data from 2006 to 2009 to determine the completeness of reporting TB disease by examining whether validated TB cases from IHS facilities were reported to state health departments.     

Genetic feedback for psychiatric conditions: Where are we now and where are we going

Genome‐wide association studies are rapidly advancing our understanding of the genetic architecture of complex disorders, including many psychiatric conditions such as major depression, schizophrenia, and substance use disorders. One common goal of genome‐wide association studies is to use findings for enhanced clinical prediction in the future, which can aid in identifying at‐risk individuals to enable more effective prevention screening and treatment strategies. In order to achieve this goal, we first need to gain a better understanding of the issues surrounding the return of complex genetic results. In this article, we summarize the current literature on: (a) genetic literacy in the general population, (b) the public's interest in receiving genetic test results for psychiatric conditions, (c) how individuals react to and interpret their genotypic information for specific psychiatric conditions, and (d) gaps in our knowledge that will be critical to address as we move toward returning genotypic information for psychiatric conditions in both research and clinical settings. By reviewing extant studies, we aim to increase awareness of the potential benefits and consequences of returning genotypic information for psychiatric conditions.     

Activity of PD-1 blockade with nivolumab among patients with recurrent atypical/anaplastic meningioma: phase II trial results

BackgroundProgrammed death ligand 1 (PD-L1) contributes to tumor immunosuppression and is upregulated in aggressive meningiomas. We performed a phase II study of nivolumab, a programmed death 1 (PD-1) blocking antibody among patients with grade ≥2 meningioma that recurred after surgery and radiation therapy.MethodsTwenty-five patients received nivolumab (240 mg biweekly) until progression, voluntary withdrawal, unacceptable toxicity, or death. Tumor mutational burden (TMB) and quantification of tumor-infiltrating lymphocytes (TIL) were evaluated as potential immunocorrelative biomarkers. Change in neurologic function was prospectively assessed using the Neurologic Assessment in Neuro-Oncology (NANO) scale.ResultsEnrolled patients had multiple recurrences including ≥3 prior surgeries and ≥2 prior courses of radiation in 60% and 72%, respectively. Nivolumab was well tolerated with no unexpected adverse events. Six-month progression-free survival (PFS-6) rate was 42.4% (95% CI: 22.8, 60.7) and the median OS was 30.9 months (95% CI: 17.6, NA). One patient achieved radiographic response (ongoing at 4.5 years). TMB was >10/Mb in 2 of 15 profiled tumors (13.3%). Baseline TIL density was low but increased posttreatment in 3 patients including both patients with elevated TMB. Most patients who achieved PFS-6 maintained neurologic function prior to progression as assessed by NANO.ConclusionNivolumab was well tolerated but failed to improve PFS-6, although a subset of patients appeared to derive benefit. Low levels of TMB and TIL density were typically observed. NANO assessment of neurologic function contributed to outcome assessment. Future studies may consider rationally designed combinatorial regimens.     

Use of esmolol after failure of standard cardiopulmonary resuscitation to treat patients with refractory ventricular fibrillation

Introduction

We compare the outcomes for patients who received esmolol to those who did not receive esmolol during refractory ventricular fibrillation (RVF) in the emergency department (ED).

Methods

A retrospective investigation in an urban academic ED of patients between January 2011 and January 2014 of patients with out-of-hospital or ED cardiac arrest (CA) with an initial rhythm of ventricular fibrillation (VF) or ventricular tachycardia (VT) who received at least three defibrillation attempts, 300 mg of amiodarone, and 3 mg of adrenaline, and who remained in CA upon ED arrival. Patients who received esmolol during CA were compared to those who did not.

Results

90 patients had CA with an initial rhythm of VF or VT; 65 patients were excluded, leaving 25 for analysis. Six patients received esmolol during cardiac arrest, and nineteen did not. All patients had ventricular dysrhythmias refractory to many defibrillation attempts, including defibrillation after administration of standard ACLS medications. Most received high doses of adrenaline, amiodarone, and sodium bicarbonate. Comparing the patients that received esmolol to those that did not: 67% and 42% had temporary return of spontaneous circulation (ROSC); 67% and 32% had sustained ROSC; 66% and 32% survived to intensive care unit admission; 50% and 16% survived to hospital discharge; and 50% and 11% survived to discharge with a favorable neurologic outcome, respectively.

Conclusion

Beta-blockade should be considered in patients with RVF in the ED prior to cessation of resuscitative efforts.     

Amygdala damage affects event‐related potentials for fearful faces at specific time windows

The amygdala is known to influence processing of threat‐related stimuli in distant brain regions, including visual cortex. The time‐course of these distant influences is unknown, although this information is important for resolving debates over likely pathways mediating an apparent rapidity in emotional processing. To address this, we recorded event‐related potentials (ERPs) to seen fearful face expressions, in preoperative patients with medial temporal lobe epilepsy who had varying degrees of amygdala pathology, plus healthy volunteers. We found that amygdala damage diminished ERPs for fearful versus neutral faces within the P1 time‐range, ∼100–150 ms, and for a later component at ∼500–600 ms. Individual severity of amygdala damage determined the magnitude of both these effects, consistent with a causal amygdala role. By contrast, amygdala damage did not affect explicit perception of fearful expressions nor a distinct emotional ERP effect at 150–250 ms. These results demonstrate two distinct time‐points at which the amygdala influences fear processing. The data also demonstrate that while not all aspects of expression processing are disrupted by amygdala damage, there is a crucial impact on an early P1 component. These findings are consistent with the existence of multiple processing stages or routes for fearful faces that vary in their dependence on amygdala function. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Quantum Monte Carlo computations of phase stability,equations of state,and elasticity of high-pressure silica

Silica (SiO₂) is an abundant component of the Earth whose crystalline polymorphs play key roles in its structure and dynamics. First principle density functional theory (DFT) methods have often been used to accurately predict properties of silicates, but fundamental failures occur. Such failures occur even in silica, the simplest silicate, and understanding pure silica is a prerequisite to understanding the rocky part of the Earth. Here, we study silica with quantum Monte Carlo (QMC), which until now was not computationally possible for such complex materials, and find that QMC overcomes the failures of DFT. QMC is a benchmark method that does not rely on density functionals but rather explicitly treats the electrons and their interactions via a stochastic solution of Schrödinger’s equation. Using ground-state QMC plus phonons within the quasiharmonic approximation of density functional perturbation theory, we obtain the thermal pressure and equations of state of silica phases up to Earth’s core–mantle boundary. Our results provide the best constrained equations of state and phase boundaries available for silica. QMC indicates a transition to the dense α-PbO₂ structure above the core-insulating D” layer, but the absence of a seismic signature suggests the transition does not contribute significantly to global seismic discontinuities in the lower mantle. However, the transition could still provide seismic signals from deeply subducted oceanic crust. We also find an accurate shear elastic constant for stishovite and its geophysically important softening with pressure.     

A prospective cohort study of cancer incidence following the diagnosis of Parkinson's disease.

BACKGROUND: Prior studies suggest a decreased risk of cancer among patients with Parkinson's disease (PD). METHODS: Matched cohort analysis among the 22,071 participants in the Physician's Health Study. A total of 487 incident cases of PD without preceding cancer were identified by self-report. Each PD case was matched by age to a reference participant who was alive and cancer free at the time of PD diagnosis. Both cohorts were followed for incident cancer. We used proportional hazards models to calculate adjusted relative risks (RR) for cancer. RESULTS: A total of 121 cancers were confirmed during a median follow-up of 5.2 years (PD) and 5.9 years (reference). Those with PD developed less cancer (11.0% versus 14.0%), with an adjusted RR of 0.85 [95% confidence interval (95% CI), 0.59-1.22]. Reduced risk was present for smoking-related cancers such as lung (RR, 0.32), colorectal (RR, 0.54), and bladder (RR, 0.68), as well as for most non-smoking-related cancers such as prostate cancer (RR, 0.74). In contrast, PD patients were at significantly increased risk (RR, 6.15; 95% CI, 1.77-21.37) for melanoma. PD patients who smoked were at reduced risk for smoking-related cancer (RR, 0.33; 95% CI, 0.12-0.92), whereas nonsmokers with PD were at increased risk (RR, 1.80; 95% CI, 0.60-5.39). This interaction was statistically significant (P(interaction) = 0.02). CONCLUSIONS: Our results suggest a decreased incidence of most cancers in patients with PD. PD patients had a significantly increased risk of malignant melanoma, a finding consistent with prior studies. We confirmed an interaction between smoking and the relationship of PD to smoking-related cancer that may fit the pattern of a gene-environment interaction.     

Early sonographic diagnosis of body stalk anomaly

Ultrasonographic features of a fetus at 18 weeks of gestation suggesting a body stalk anomaly are presented. These included a large abdominal anterior wall defect in apparent continuity with the placenta, severe kyphoscoliosis of the lower spine, the absence of one kidney, and a very short umbilical cord with only one umbilical artery. The amniotic fluid was reduced and the fetus was almost immobile at short-interval ultrasound examinations. The pregnancy was terminated and autopsy of the fetus showed abnormalities compatible with maldevelopment of both cephalic and caudal embryonic folds.     

Prism adaptation can improve contralesional tactile perception in neglect

The authors show that prismatic adaptation can reduce tactile inattention in stroke patients with unilateral neglect. Four patients with visuospatial neglect and tactile extinction underwent 10-minute application of 20 degrees right-shifting prismatic lenses during pointing. This improved contralesional tactile perception in all patients, even for a task requiring no exploration or spatial motor responses. This finding suggests a potential role for prismatic adaptation in the rehabilitation of multiple sensory modalities in patients with neglect.