Process Evaluation to Document Crucial Moments in Development of the National Neurological Conditions Surveillance System at the U.S. Centers for Disease Control and Prevention

Background: Neurological conditions or disorders strike roughly 50 million Americans annually but accurate and comprehensive national estimates for many of these conditions are not available. In 2019, Congress provided $5 million to Centers for Disease Control and Prevention (CDC) to establish the National Neurological Conditions Surveillance System (NNCSS). CDC focused initial activities on multiple sclerosis and Parkinson’s disease. Purpose: We conducted a process evaluation to document and understand multifaceted work to implement a new surveillance activity for two neurological conditions. Setting: We conducted this evaluation with government personnel internal to the Center for Surveillance, Epidemiology, and Laboratory Services at the Centers for Disease Control and Prevention in Atlanta, GA. Intervention: A new public health surveillance activity for two neurological conditions, multiple sclerosis and Parkinson’s disease, that uses existing data resources and systems. Research design: The evaluation included interviews with CDC personnel and review of administrative and programmatic information. Data were analyzed and interpreted to identify crucial moments in the first year of funded work on NNCSS. The study revealed that this surveillance activity required diverse contributions and collaboration within the federal government and with non-governmental organizations. The findings can be used to guide work to enhance surveillance for many neurological conditions. Findings: The study revealed that this surveillance activity required diverse contributions and collaboration within the federal government and with non-governmental organizations. While collaboration is a cornerstone of public health practice, it is not always well-documented in planning or implementation of surveillance or other data-related activities. Keywords: program evaluation; surveillance; neurological conditions; neurological disorders; multiple sclerosis; Parkinson’s disease

Geographic Differences in Time to Culture Conversion in Liquid Media: Tuberculosis Trials Consortium Study 28. Culture Conversion Is Delayed in Africa

Tuberculosis Trials Consortium Study 28, was a double blind, randomized, placebo-controlled, phase 2 clinical trial examining smear positive pulmonary Mycobacterium tuberculosis. Over the course of intensive phase therapy, patients from African sites had substantially delayed and lower rates of culture conversion to negative in liquid media compared to non-African patients. We explored potential explanations of this finding.In TBTC Study 28, protocol-correct patients (n = 328) provided spot sputum specimens for M. tuberculosis culture in liquid media, at baseline and weeks 2, 4, 6 and 8 of study therapy. We compared sputum culture conversion for African and non-African patients stratified by four baseline measures of disease severity: AFB smear quantification, extent of disease on chest radiograph, cavity size and the number of days to detection of M. tuberculosis in liquid media using the Kaplan-Meier product-limit method. We evaluated specimen processing and culture procedures used at 29 study laboratories serving 27 sites.African TB patients had more extensive disease at enrollment than non-African patients. However, African patients with the least disease by the 4 measures of disease severity had conversion rates on liquid media that were substantially lower than conversion rates in non-African patients with the greatest extent of disease. HIV infection, smoking and diabetes did not explain delayed conversion in Africa. Some inter-site variation in laboratory processing and culture procedures within accepted practice for clinical diagnostic laboratories was found.Compared with patients from non-African sites, African patients being treated for TB had delayed sputum culture conversion and lower sputum conversion rates in liquid media that were not explained by baseline severity of disease, HIV status, age, smoking, diabetes or race. Further investigation is warranted into whether modest variation in laboratory processes substantially influences the efficacy outcomes of phase 2 TB treatment trials or if other factors (e.g., nutrition, host response) are involved.ClinicalTrials.gov NCT00144417

Assessment of the infectious diseases surveillance system of the Republic of Armenia: an example of surveillance in the Republics of the former Soviet Union

BACKGROUND: Before 1991, the infectious diseases surveillance systems (IDSS) of the former Soviet Union (FSU) were centrally planned in Moscow. The dissolution of the FSU resulted in economic stresses on public health infrastructure. At the request of seven FSU Ministries of Health, we performed assessments of the IDSS designed to guide reform. The assessment of the Armenian infectious diseases surveillance system (AIDSS) is presented here as a prototype. DISCUSSION: We performed qualitative assessments using the Centers for Disease Control and Prevention (CDC) guidelines for evaluating surveillance systems. Until 1996, the AIDSS collected aggregate and case-based data on 64 infectious diseases. It collected information on diseases of low pathogenicity (e.g., pediculosis) and those with no public health intervention (e.g., infectious mononucleosis). The specificity was poor because of the lack of case definitions. Most cases were investigated using a lengthy, non-disease-specific case-report form Armenian public health officials analyzed data descriptively and reported data upward from the local to national level, with little feedback. Information was not shared across vertical programs. Reform should focus on enhancing usefulness, efficiency, and effectiveness by reducing the quantity of data collected and revising reporting procedures and information types; improving the quality, analyses, and use of data at different levels; reducing system operations costs; and improving communications to reporting sources. These recommendations are generalizable to other FSU republics. SUMMARY: The AIDSS was complex and sensitive, yet costly and inefficient. The flexibility, representativeness, and timeliness were good because of a comprehensive health-care system and compulsory reporting. Some data were questionable and some had no utility

Unexpected decline in tuberculosis cases coincident with economic recession -- United States, 2009

<p>Abstract</p> <p>Background</p> <p>Since 1953, through the cooperation of state and local health departments, the U.S. Centers for Disease Control and Prevention (CDC) has collected information on incident cases of tuberculosis (TB) disease in the United States. In 2009, TB case rates declined -11.4%, compared to an average annual -3.8% decline since 2000. The unexpectedly large decline raised concerns that TB cases may have gone unreported. To address the unexpected decline, we examined trends from multiple sources on TB treatment initiation, medication sales, and laboratory and genotyping data on culture-positive TB.</p> <p>Methods</p> <p>We analyzed 142,174 incident TB cases reported to the U. S. National Tuberculosis Surveillance System (NTSS) during January 1, 2000-December 31, 2009; TB control program data from 59 public health reporting areas; self-reported data from 50 CDC-funded public health laboratories; monthly electronic prescription claims for new TB therapy prescriptions; and complete genotyping results available for NTSS cases. Accounting for prior trends using regression and time-series analyses, we calculated the deviation between observed and expected TB cases in 2009 according to patient and clinical characteristics, and assessed at what point in time the deviation occurred.</p> <p>Results</p> <p>The overall deviation in TB cases in 2009 was -7.9%, with -994 fewer cases reported than expected (<it>P </it>< .001). We ruled out evidence of surveillance underreporting since declines were seen in states that used new software for case reporting in 2009 as well as states that did not, and we found no cases unreported to CDC in our examination of over 5400 individual line-listed reports in 11 areas. TB cases decreased substantially among both foreign-born and U.S.-born persons. The unexpected decline began in late 2008 or early 2009, and may have begun to reverse in late 2009. The decline was greater in terms of case counts among foreign-born than U.S.-born persons; among the foreign-born, the declines were greatest in terms of percentage deviation from expected among persons who had been in the United States less than 2 years. Among U.S.-born persons, the declines in percentage deviation from expected were greatest among homeless persons and substance users. Independent information systems (NTSS, TB prescription claims, and public health laboratories) reported similar patterns of declines. Genotyping data did not suggest sudden decreases in recent transmission.</p> <p>Conclusions</p> <p>Our assessments show that the decline in reported TB was not an artifact of changes in surveillance methods; rather, similar declines were found through multiple data sources. While the steady decline of TB cases before 2009 suggests ongoing improvement in TB control, we were not able to identify any substantial change in TB control activities or TB transmission that would account for the abrupt decline in 2009. It is possible that other multiple causes coincident with economic recession in the United States, including decreased immigration and delayed access to medical care, could be related to TB declines. Our findings underscore important needs in addressing health disparities as we move towards TB elimination in the United States.</p

Influence of inhaled nitric oxide on gas exchange during normoxic and hypoxic exercice in highly trained cyclists

Une étude sur les effets de l'inhalation d'oxyde nitrique (20 ppm) sur les échanges gazeux au cours d'un exercice normoxique et hypoxique chez 7 cyclistes entrainés. Evaluation et comparaison de la consommation d'oxygène et du taux de saturation artérielle d'oxyhémoglobine en condition hypoxique et normoxique

Assessment of the infectious diseases surveillance system of the Republic of Armenia: an example of surveillance in the Republics of the former Soviet Union

Abstract Background Before 1991, the infectious diseases surveillance systems (IDSS) of the former Soviet Union (FSU) were centrally planned in Moscow. The dissolution of the FSU resulted in economic stresses on public health infrastructure. At the request of seven FSU Ministries of Health, we performed assessments of the IDSS designed to guide reform. The assessment of the Armenian infectious diseases surveillance system (AIDSS) is presented here as a prototype. Discussion We performed qualitative assessments using the Centers for Disease Control and Prevention (CDC) guidelines for evaluating surveillance systems. Until 1996, the AIDSS collected aggregate and case-based data on 64 infectious diseases. It collected information on diseases of low pathogenicity (e.g., pediculosis) and those with no public health intervention (e.g., infectious mononucleosis). The specificity was poor because of the lack of case definitions. Most cases were investigated using a lengthy, non-disease-specific case-report form Armenian public health officials analyzed data descriptively and reported data upward from the local to national level, with little feedback. Information was not shared across vertical programs. Reform should focus on enhancing usefulness, efficiency, and effectiveness by reducing the quantity of data collected and revising reporting procedures and information types; improving the quality, analyses, and use of data at different levels; reducing system operations costs; and improving communications to reporting sources. These recommendations are generalizable to other FSU republics. Summary The AIDSS was complex and sensitive, yet costly and inefficient. The flexibility, representativeness, and timeliness were good because of a comprehensive health-care system and compulsory reporting. Some data were questionable and some had no utility.</p

Influence of inhaled nitric oxide on gas exchange during normoxic and hypoxic exercice in highly trained cyclists

Une étude sur les effets de l'inhalation d'oxyde nitrique (20 ppm) sur les échanges gazeux au cours d'un exercice normoxique et hypoxique chez 7 cyclistes entrainés. Evaluation et comparaison de la consommation d'oxygène et du taux de saturation artérielle d'oxyhémoglobine en condition hypoxique et normoxique

Population Pharmacokinetics of Pyrazinamide in Patients with Tuberculosis

The current treatment used for tuberculosis (TB) is lengthy and needs to be shortened and improved. Pyrazinamide (PZA) has potent sterilizing activity and has the potential to shorten the TB treatment duration, if treatment is optimized. The goals of this study were (i) to develop a population pharmacokinetic (PK) model for PZA among patients enrolled in PK substudies of Tuberculosis Trial Consortium (TBTC) trials 27 and 28 and (ii) to determine covariates that affect PZA PK. (iii) We also performed simulations and target attainment analysis using the proposed targets of a maximum plasma concentration (Cmax) of &gt;35 μg/ml or an area under the concentration-versus-time curve (AUC) of &gt;363 μg · h/ml to see if higher weight-based dosing could improve PZA efficacy. Seventy-two patients participated in the substudies. The mean (standard deviation [SD]) Cmax was 30.8 (7.4) μg/ml, and the mean (SD) AUC from time zero to 24 h (AUC0-24) was 307 (83) μg · h/ml. A one-compartment open model best described PZA PK. Only body weight was a significant covariate for PZA clearance. Women had a lower volume of distribution (V/F) than men, and both clearance (CL/F) and V/F increased with body weight. Our simulations show that higher doses of PZA (&gt;50 mg/kg of body weight) are needed to achieve the therapeutic target of an AUC/MIC of &gt;11.3 in &gt;80% of patients, while doses of &gt;80 mg/kg are needed for target attainment in 90% of patients, given specific assumptions about MIC determinations. For the therapeutic targets of a Cmax of &gt;35 μg/ml and/or an AUC of &gt;363 μg · h/ml, doses in the range of 30 to 40 mg/kg are needed to achieve the therapeutic target in &gt;90% of the patients. Further clinical trials are needed to evaluate the safety and efficacy of higher doses of PZA

Tuberculin skin test result and risk of death among persons with active TB.

BACKGROUND: Although the tuberculin skin test (TST) is frequently used to aid in the diagnosis of tuberculosis (TB) disease and to identify persons with latent TB infection, it is an imperfect test and approximately 10-25% of persons with microbiologically confirmed TB disease have a negative TST. Previous studies have suggested that persons with a negative TST are more likely to present with severe TB disease and have an increased rate of TB-related death. METHODS: We analyzed culture-confirmed TB cases captured in US TB surveillance data from 1993 to 2008 and performed multivariate logistic regression analysis to determine the association between TST result and death. RESULTS: Of 284,866 cases of TB reported in the US, 58,180 persons were eligible for inclusion in the analysis and 3,270 of those persons died after initiating TB treatment. Persons with a negative TST accounted for only 14% of the eligible cases but accounted for 42% of the deaths. Persons with a TST≥15 mm had 67% lower odds of death than persons with a negative TST (adjusted odds ratio 0.33, 95% confidence interval 0.30-0.36). CONCLUSIONS: A negative TST is associated with an increased risk of death among persons with culture-confirmed TB disease, even after adjustment for HIV status, site of TB disease, sputum smear AFB status, drug susceptibility, age, sex, and origin of birth. In addition to indicating risk of developing disease, the TST may also be a marker for increased risk of death

Effects of Tuberculosis, Race, and Human Gene SLCO1B1 Polymorphisms on Rifampin Concentrations▿ ‖

Rifampin has concentration-dependent activity against Mycobacterium tuberculosis. However, marked intersubject variation of rifampin concentrations occurs. In this study, we evaluated rifampin pharmacokinetics in relation to tuberculosis, geographic region, race, and single nucleotide polymorphisms of the human transporter genes SLCO1B1, SLCO1B3, and MDR1. Seventy-two adults with pulmonary tuberculosis from Africa, North America, and Spain were evaluated during multidrug intensive-phase therapy, and their results were compared to those from 16 healthy controls from North America. Rifampin pharmacokinetic values were similar between tuberculosis patients and controls (geometric mean [GM] area under the concentration-time curve from 0 to 24 h [AUC0-24] of 40.2 versus 40.9 μg·h/ml; P = 0.9). However, in multivariable analyses, the rifampin AUC0-24 was significantly affected by rifampin dosage (in mg/kg of body weight), polymorphisms in the SLCO1B1 gene, and the presence of tuberculosis by geographic region. The adjusted rifampin AUC0-24 was lowest in patients with tuberculosis from Africa compared to that in non-African patients or control subjects. The adjusted rifampin AUC0-24 was also 36% lower among participants with SLCO1B1 genotype c.463CA than that among participants with SLCO1B1 genotype c.463CC (adjusted GM, 29.8 versus 46.7 μg·h/ml; P = 0.001). Polymorphisms in the SLCO1B1 gene associated with lower rifampin exposure were more frequent among black subjects. In conclusion, marked intersubject variation of the rifampin AUC0-24 values was observed, but the mean values of the AUC0-24 did not significantly vary between patients with tuberculosis and healthy controls. Lower rifampin exposure was associated with the polymorphism of the SLCO1B1 c.463C>A gene. When adjusted for the patient mg/kg dosage and transporter gene polymorphisms, rifampin exposure was lower in patients with tuberculosis, which suggests that additional absorption or metabolic processes affect rifampin exposure with tuberculosis disease