Personal and Societal Health Quality Lost to Tuberculosis

BACKGROUND: In developed countries, tuberculosis is considered a disease with little loss of Quality-Adjusted Life Years (QALYs). Tuberculosis treatment is predominantly ambulatory and death from tuberculosis is rare. Research has shown that there are chronic pulmonary sequelae in a majority of patients who have completed treatment for pulmonary tuberculosis (PTB). This and other health effects of tuberculosis have not been considered in QALY calculations. Consequently both the burden of tuberculosis on the individual and the value of tuberculosis prevention to society are underestimated. We estimated QALYs lost to pulmonary TB patients from all known sources, and estimated health loss to prevalent TB disease. METHODOLOGY/PRINCIPAL FINDINGS: We calculated values for health during illness and treatment, pulmonary impairment after tuberculosis (PIAT), death rates, years-of-life-lost to death, and normal population health. We then compared the lifetime expected QALYs for a cohort of tuberculosis patients with that expected for comparison populations with latent tuberculosis infection and without tuberculosis infection. Persons with culture-confirmed tuberculosis accrued fewer lifetime QALYs than those without tuberculosis. Acute tuberculosis morbidity cost 0.046 QALYs (4% of total) per individual. Chronic morbidity accounted for an average of 0.96 QALYs (78% of total). Mortality accounted for 0.22 QALYs lost (18% of total). The net benefit to society of averting one case of PTB was about 1.4 QALYs. CONCLUSIONS/SIGNIFICANCE: Tuberculosis, a preventable disease, results in QALYs lost owing to illness, impairment, and death. The majority of QALYs lost from tuberculosis resulted from impairment after microbiologic cure. Successful TB prevention efforts yield more health quality than previously thought and should be given high priority by health policy makers. (Refer to Abstracto S1 for Spanish language abstract)

Effect of Dysglycemia on Urinary Lipid Mediator Profiles in Persons With Pulmonary Tuberculosis

Background: Oxidized lipid mediators such as eicosanoids play a central role in the inflammatory response associated with tuberculosis (TB) pathogenesis. Diabetes mellitus (DM) leads to marked changes in lipid mediators in persons with TB. However, the associations between diabetes-related changes in lipid mediators and clearance of M. tuberculosis (Mtb) among persons on anti-TB treatment (ATT) are unknown. Quantification of urinary eicosanoid metabolites can provide insights into the circulating lipid mediators involved in Mtb immune responses. // Methods: We conducted a multi-site prospective observational study among adults with drug-sensitive pulmonary TB and controls without active TB; both groups had sub-groups with or without dysglycemia at baseline. Participants were enrolled from RePORT-Brazil (Salvador site) and RePORT-South Africa (Durban site) and stratified according to TB status and baseline glycated hemoglobin levels: a) TB-dysglycemia (n=69); b) TB-normoglycemia (n=64); c) non-TB/dysglycemia (n=31); d) non-TB/non-dysglycemia (n=29). We evaluated the following urinary eicosanoid metabolites: 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (major urinary metabolite of prostaglandin E2, PGE-M), tetranor-PGE1 (metabolite of PGE2, TN-E), 9α-hydroxy-11,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (metabolite of PGD2, PGD-M), 11-dehydro-thromboxane B2 (11dTxB2), 2,3-dinor-6-keto-PGF1α (prostaglandin I metabolite, PGI-M), and leukotriene E4 (LTE4). Comparisons between the study groups were performed at three time points: before ATT and 2 and 6 months after initiating therapy. // Results: PGE-M and LTE4 values were consistently higher at all three time-points in the TB-dysglycemia group compared to the other groups (p<0.001). In addition, there was a significant decrease in PGI-M and LTE4 levels from baseline to month 6 in the TB-dysglycemia and TB-normoglycemia groups. Finally, TB-dysglycemia was independently associated with increased concentrations of PGD-M, PGI-M, and LTE4 at baseline in a multivariable model adjusting for age, sex, BMI, and study site. These associations were not affected by HIV status. // Conclusion: The urinary eicosanoid metabolite profile was associated with TB-dysglycemia before and during ATT. These observations can help identify the mechanisms involved in the pathogenesis of TB-dysglycemia, and potential biomarkers of TB treatment outcomes, including among persons with dysglycemia

"...because I am something special" or "I think I will be something like a guinea pig": information and assent of legal minors in clinical trials – assessment of understanding, appreciation and reasoning

<p>Abstract</p> <p>Background</p> <p>The aim of this study is to assess and evaluate the capacities for understanding, appreciation and reasoning of legal minors with psychiatric disorders and their parents and their competence to consent or assent to participation in clinical trials. The beliefs, fears, motivation and influencing factors for decision-making of legal minors and parents were also examined.</p> <p>Methods</p> <p>Using the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), an instrument developed for adults whose capacities to consent are unclear, we provided information about clinical trials and assessed understanding, appreciation and reasoning. We adapted this tool for legal minors and examined 19 children and adolescents between the ages of 7 and 15 with attention deficit/hyperactivity disorder (ADHD) or ADHD combined with oppositional defiant disorder (DSM-IV 314.00/314.01/312.8) enrolled in clinical trials. Parents were also examined using the MacCAT-CR.</p> <p>Results</p> <p>Facts such as the procedures involved in trials or their duration were well understood by legal minors, but more abstract issues like the primary purpose of the trial were not understood by children and adolescents or by many parents. Legal minors also had difficulties understanding the nature of placebo and the probability of receiving placebo. Children's and adolescents' decisions were influenced by fears about their disorder worsening and by problems in their relationship with their parents. Parents wanted the best therapy for their children in order to minimize problems in school.</p> <p>Conclusion</p> <p>Legal minors and parents need to be informed more precisely about specific issues like placebo and the primary purpose of trials. In general, the reasoning of children and adolescents was influenced by their experience with their disorder and decision making was based on reasonable arguments. Their fears were based on everyday experiences such as school performance or family relationships.</p

Pain relief is associated with decreasing postural sway in patients with non-specific low back pain

Background Increased postural sway is well documented in patients suffering from non-specific low back pain, whereby a linear relationship between higher pain intensities and increasing postural sway has been described. No investigation has been conducted to evaluate whether this relationship is maintained if pain levels change in adults with non-specific low back pain. Methods Thirty-eight patients with non-specific low back pain and a matching number of healthy controls were enrolled. Postural sway was measured by three identical static bipedal standing tasks of 90 sec duration with eyes closed in narrow stance on a firm surface. The perceived pain intensity was assessed by a numeric rating scale (NRS-11). The patients received three manual interventions (e.g. manipulation, mobilization or soft tissue techniques) at 3-4 day intervals, postural sway measures were obtained at each occasion. Results A clinically relevant decrease of four NRS scores in associated with manual interventions correlated with a significant decrease in postural sway. In contrast, if no clinically relevant change in intensity occurred ([less than or equal to]1 level), postural sway remained similar compared to baseline. The postural sway measures obtained at follow-up sessions 2 and 3 associated with specific NRS level showed no significant differences compared to reference values for the same pain score. Conclusions Alterations in self-reported pain intensities are closely related to changes in postural sway. The previously reported linear relationship between the two variables is maintained as pain levels change. Pain interference appears responsible for the altered sway in pain sufferers. This underlines the clinical use of sway measures as an objective monitoring tool during treatment or rehabilitation

The effect of body mass index on global brain volume in middle-aged adults: a cross sectional study

BACKGROUND: Obesity causes or exacerbates a host of medical conditions, including cardiovascular, pulmonary, and endocrine diseases. Recently obesity in elderly women was associated with greater risk of dementia, white matter ischemic changes, and greater brain atrophy. The purpose of this study was to determine whether body type affects global brain volume, a marker of atrophy, in middle-aged men and women. METHODS: T1-weighted 3D volumetric magnetic resonance imaging was used to assess global brain volume for 114 individuals 40 to 66 years of age (average = 54.2 years; standard deviation = 6.6 years; 43 men and 71 women). Total cerebrospinal fluid and brain volumes were obtained with an automated tissue segmentation algorithm. A regression model was used to determine the effect of age, body mass index (BMI), and other cardiovascular risk factors on brain volume and cognition. RESULTS: Age and BMI were each associated with decreased brain volume. BMI did not predict cognition in this sample; however elevated diastolic blood pressure was associated with poorer episodic learning performance. CONCLUSION: These findings suggest that middle-aged obese adults may already be experiencing differentially greater brain atrophy, and may potentially be at greater risk for future cognitive decline

Differences in HIV Natural History among African and Non-African Seroconverters in Europe and Seroconverters in Sub-Saharan Africa

Introduction It is unknown whether HIV treatment guidelines, based on resource-rich country cohorts, are applicable to African populations. Methods We estimated CD4 cell loss in ART-naïve, AIDS-free individuals using mixed models allowing for random intercept and slope, and time from seroconversion to clinical AIDS, death and antiretroviral therapy (ART) initiation by survival methods. Using CASCADE data from 20 European and 3 sub-Saharan African (SSA) cohorts of heterosexually-infected individuals, aged ≥15 years, infected ≥2000, we compared estimates between non-African Europeans, Africans in Europe, and Africans in SSA. Results Of 1,959 (913 non-Africans, 302 Europeans - African origin, 744 SSA), two-thirds were female; median age at seroconversion was 31 years. Individuals in SSA progressed faster to clinical AIDS but not to death or non-TB AIDS. They also initiated ART later than Europeans and at lower CD4 cell counts. In adjusted models, Africans (especially from Europe) had lower CD4 counts at seroconversion and slower CD4 decline than non-African Europeans. Median (95% CI) CD4 count at seroconversion for a 15–29 year old woman was 607 (588–627) (non-African European), 469 (442–497) (European - African origin) and 570 (551–589) (SSA) cells/µL with respective CD4 decline during the first 4 years of 259 (228–289), 155 (110–200), and 199 (174–224) cells/µL (p<0.01). Discussion Despite differences in CD4 cell count evolution, death and non-TB AIDS rates were similar across study groups. It is therefore prudent to apply current ART guidelines from resource-rich countries to African populations

The impact of psychological factors on recovery from injury: a multicentre cohort study

Purpose Unintentional injuries have a significant long-term health impact in working age adults. Depression, anxiety and post-traumatic stress disorder are common post-injury, but their impact on self-reported recovery has not been investigated in general injury populations. This study investigated the role of psychological predictors 1 month post-injury in subsequent self-reported recovery from injury in working-aged adults. Methods A multicentre cohort study was conducted of 668 unintentionally injured adults admitted to five UK hospitals followed up at 1, 2, 4 and 12 months post-injury. Logistic regression explored relationships between psychological morbidity 1 month post-injury and self-reported recovery 12 months post-injury, adjusting for health, demographic, injury and socio-legal factors. Multiple imputations were used to impute missing values. Results A total of 668 adults participated at baseline, 77% followed up at 1 month and 63% at 12 months, of whom 383 (57%) were included in the main analysis. Multiple imputation analysis included all 668 participants. Increasing levels of depression scores and increasing levels of pain at 1 month and an increasing number of nights in hospital were associated with significantly reduced odds of recovery at 12 months, adjusting for age, sex, centre, employment and deprivation. The findings were similar in the multiple imputation analysis, except that pain had borderline statistical significance. Conclusions Depression 1 month post-injury is an important predictor of recovery, but other factors, especially pain and nights spent in hospital, also predict recovery. Identifying and managing depression and providing adequate pain control are essential in clinical care post-injury

Systematic review of the epidemiological evidence comparing lung cancer risk in smokers of mentholated and unmentholated cigarettes

<p>Abstract</p> <p>Background</p> <p>US mentholated cigarette sales have increased considerably over 50 years. Preference for mentholated cigarettes is markedly higher in Black people. While menthol itself is not genotoxic or carcinogenic, its acute respiratory effects might affect inhalation of cigarette smoke. This possibility seems consistent with the higher lung cancer risk in Black men, despite Black people smoking less and starting smoking later than White people. Despite experimental data suggesting similar carcinogenicity of mentholated and non-mentholated cigarettes, the lack of convincing evidence that mentholation increases puffing, inhalation or smoke uptake, and the similarity of lung cancer rates in Black and White females, a review of cigarette mentholation and lung cancer is timely given current regulatory interest in the topic.</p> <p>Methods</p> <p>Epidemiological studies comparing lung cancer risk in mentholated and non-mentholated cigarette smokers were identified from MedLine and other sources. Study details were extracted and strengths and weaknesses assessed. Relative risk estimates were extracted, or derived, for ever mentholated use and for long-term use, overall and by gender, race, and current/ever smoking, and meta-analyses conducted.</p> <p>Results</p> <p>Eight generally good quality studies were identified, with valid cases and controls, and appropriate adjustment for age, gender, race and smoking. The studies afforded good power to detect possible effects. However, only one study presented results by histological type, none adjusted for occupation or diet, and some provided no results by length of mentholated cigarette use.</p> <p>The data do not suggest any effect of mentholation on lung cancer risk. Adjusted relative risk estimates for ever use vary from 0.81 to 1.12, giving a combined estimate of 0.93 (95% confidence interval 0.84-1.02, n = 8), with no increase in males (1.01, 0.84-1.22, n = 5), females (0.80, 0.67-0.95, n = 5), White people (0.87, 0.75-1.03, n = 4) or Black people (0.90, 0.73-1.10, n = 4). Estimates for current and ever smokers are similar. The combined estimate for long-term use (0.95, 0.80-1.13, n = 4) again suggests no effect of mentholation.</p> <p>Conclusion</p> <p>Higher lung cancer rates in Black males cannot be due to their greater preference for mentholated cigarettes. While some study weaknesses exist, the epidemiological evidence is consistent with mentholation having no effect on the lung carcinogenicity of cigarettes.</p

Definitions and pathophysiology of vasoplegic shock.

Vasoplegia is the syndrome of pathological low systemic vascular resistance, the dominant clinical feature of which is reduced blood pressure in the presence of a normal or raised cardiac output. The vasoplegic syndrome is encountered in many clinical scenarios, including septic shock, post-cardiac bypass and after surgery, burns and trauma, but despite this, uniform clinical definitions are lacking, which renders translational research in this area challenging. We discuss the role of vasoplegia in these contexts and the criteria that are used to describe it are discussed. Intrinsic processes which may drive vasoplegia, such as nitric oxide, prostanoids, endothelin-1, hydrogen sulphide and reactive oxygen species production, are reviewed and potential for therapeutic intervention explored. Extrinsic drivers, including those mediated by glucocorticoid, catecholamine and vasopressin responsiveness of the blood vessels, are also discussed. The optimum balance between maintaining adequate systemic vascular resistance against the potentially deleterious effects of treatment with catecholamines is as yet unclear, but development of novel vasoactive agents may facilitate greater understanding of the role of the differing pathways in the development of vasoplegia. In turn, this may provide insights into the best way to care for patients with this common, multifactorial condition

Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk of Alzheimer's Disease: a cross-sectional study

BACKGROUND: The presence of the apolipoprotein E (APOE) ε4 allele is a major risk factor for the development of Alzheimer's disease (AD), and has been associated with metabolic brain changes several years before the onset of typical AD symptoms. Functional MRI (fMRI) is a brain imaging technique that has been used to demonstrate hippocampal activation during measurement of episodic encoding, but the effect of the ε4 allele on hippocampal activation has not been firmly established. METHODS: The present study examined the effects of APOE genotype on brain activation patterns in the medial temporal lobe (MTL) during an episodic encoding task using a well-characterized novel item versus familiar item contrast in cognitively normal, middle-aged (mean = 54 years) individuals who had at least one parent with AD. RESULTS: We found that ε3/4 heterozygotes displayed reduced activation in the hippocampus and MTL compared to ε3/3 homozygotes. There were no significant differences between the groups in age, education or neuropsychological functioning, suggesting that the altered brain activation seen in ε3/4 heterozygotes was not associated with impaired cognitive function. We also found that participants' ability to encode information on a neuropsychological measure of learning was associated with greater activation in the anterior MTL in the ε3/3 homozygotes, but not in the ε3/4 heterozygotes. CONCLUSION: Together with previous studies reporting reduced glucose metabolism and AD-related neuropathology, this study provides convergent validity for the idea that the MTL exhibits functional decline associated with the APOE ε4 allele. Importantly, these changes were detected in the absence of meaningful neuropsychological differences between the groups. A focus of ongoing work in this laboratory is to determine if these findings are predictive of subsequent cognitive decline