Timing of therapy for latent tuberculosis infection among immigrants presenting to a U.S. public health clinic: a retrospective study

<p>Abstract</p> <p>Background</p> <p>In the U.S. more than half of incident tuberculosis (TB) cases occur in immigrants. Current guidelines recommend screening and treatment for latent TB infection (LTBI) within 5 years of arrival to the U.S. This study evaluates the timing of LTBI therapy among immigrants presenting for care to a public health TB clinic.</p> <p>Methods</p> <p>Retrospective chart review of patients prescribed LTBI treatment based on medical records from Prince Georges County Health Department.</p> <p>Results</p> <p>1882 immigrants received LTBI therapy at Prince Georges County Health Department between 1999 and 2004. 417 of these patients were diagnosed with LTBI through contact investigations and were excluded from the analysis. Among the remaining 1465 individuals, median time from arrival to the U.S. until initiation of LTBI therapy was 5 months (range 0–42.4 years). 16% of all immigrants initiated therapy more than 5 years after arrival to the U.S. A logistic regression model using risks identified on univariate analysis revealed that referral for therapy by non-immigration proceedings was the strongest predictor of initiation of therapy more than 5 years after arrival to the U.S. Other factors associated with > 5 year U.S. residence prior to initiation of LTBI therapy included female gender (adjusted odds ratio (AOR) 1.8, 95% CI 1.2–2.6), age ≥ 35 (AOR = 4.1, 95% 2.5–6.6), and originating from Latin American and the Caribbean (AOR = 1.9, 95% CI 1.3–3.0).</p> <p>Conclusion</p> <p>Foreign-born individuals who are not referred for LTBI therapy through immigration proceedings are less likely to receive LTBI therapy within 5 years of arrival to the U.S. These data highlight the need to explore other mechanisms for timely LTBI screening beyond services provided by immigration.</p

Biomechanical comparison of a new stand-alone anterior lumbar interbody fusion cage with established fixation techniques – a three-dimensional finite element analysis

<p>Abstract</p> <p>Background</p> <p>Initial promise of a stand-alone interbody fusion cage to treat chronic back pain and restore disc height has not been realized. In some instances, a posterior spinal fixation has been used to enhance stability and increase fusion rate. In this manuscript, a new stand-alone cage is compared with conventional fixation methods based on the finite element analysis, with a focus on investigating cage-bone interface mechanics and stress distribution on the adjacent tissues.</p> <p>Methods</p> <p>Three trapezoid 8° interbody fusion cage models (dual paralleled cages, a single large cage, or a two-part cage consisting of a trapezoid box and threaded cylinder) were created with or without pedicle screws fixation to investigate the relative importance of the screws on the spinal segmental response. The contact stress on the facet joint, slip displacement of the cage on the endplate, and rotational angle of the upper vertebra were measured under different loading conditions.</p> <p>Results</p> <p>Simulation results demonstrated less facet stress and slip displacement with the maximal contact on the cage-bone interface. A stand-alone two-part cage had good slip behavior under compression, flexion, extension, lateral bending and torsion, as compared with the other two interbody cages, even with the additional posterior fixation. However, the two-part cage had the lowest rotational angles under flexion and torsion, but had no differences under extension and lateral bending.</p> <p>Conclusion</p> <p>The biomechanical benefit of a stand-alone two-part fusion cage can be justified. This device provided the stability required for interbody fusion, which supports clinical trials of the cage as an alternative to circumferential fixations.</p

Factors associated with mortality in patients with drug-susceptible pulmonary tuberculosis

<p>Abstract</p> <p>Background</p> <p>Tuberculosis is a leading cause of death worldwide, yet the determinants of death are not well understood. We sought to determine risk factors for mortality during treatment of drug-susceptible pulmonary tuberculosis under program settings.</p> <p>Methods</p> <p>Retrospective chart review of patients with drug-susceptible tuberculosis reported to the San Francisco Tuberculosis Control Program from 1990-2001.</p> <p>Results</p> <p>Of 565 patients meeting eligibility criteria, 37 (6.6%) died during the study period. Of 37 deaths, 12 (32.4%) had tuberculosis listed as a contributing factor. In multivariate analysis controlling for follow-up time, four characteristics were independently associated with mortality: HIV co-infection (HR = 2.57, p = 0.02), older age at tuberculosis diagnosis (HR = 1.52 per 10 years, p = 0.001); initial sputum smear positive for acid fast bacilli (HR = 3.07, p = 0.004); and experiencing an interruption in tuberculosis therapy (HR = 3.15, p = 0.002). The association between treatment interruption and risk of death was due to non-adherence during the intensive phase of treatment (HR = 3.20, p = 0.001). The median duration of treatment interruption did not differ significantly in either intensive or continuation phases between those who died and survived (23 versus 18 days, and 37 versus 29 days, respectively). No deaths were directly attributed to adverse drug reactions.</p> <p>Conclusions</p> <p>In addition to advanced age, HIV and characteristics of advanced tuberculosis, experiencing an interruption in anti-tuberculosis therapy, primarily due to non-adherence, was also independently associated with increased risk of death. Improving adherence early during treatment for tuberculosis may both improve tuberculosis outcomes as well as decrease mortality.</p

Factors associated with mortality in HIV-infected and uninfected patients with pulmonary tuberculosis

<p>Abstract</p> <p>Background</p> <p>HIV has fuelled the TB epidemic in sub-Saharan Africa. Mortality in patients co-infected with TB and HIV is high. Managing factors influencing mortality in TB patients might help reducing it. This study investigates factors associated with mortality including patients' HIV sero-status, CD4 cell count, laboratory, nutritional and demographic characteristics in AFB smear positive pulmonary TB patients.</p> <p>Methods</p> <p>We studied 887 sputum smear positive PTB patients, between 18 and 65 years of age receiving standard 8 months anti-TB treatment. Demographic, anthropometric and laboratory data including HIV, CD4 and other tests were collected at baseline and at regular intervals. Patients were followed for a median period of 2.5 years.</p> <p>Results</p> <p>Of the 887 participants, 155 (17.5%) died, of whom 90.3% (140/155) were HIV-infected, a fatality of 29.7% (140/471) compared to 3.6% (15/416) among HIV-uninfected. HIV infection, age, low Karnofsky score, CD4 cell counts and hemoglobin, high viral load, and oral thrush were significantly associated with high mortality in all patients.</p> <p>Conclusion</p> <p>Mortality among HIV-infected TB patients is high despite the use of effective anti-TB therapy. Most deaths occur after successful completion of therapy, an indication that patients die from causes other than TB. HIV infection is the strongest independent predictor of mortality in this cohort.</p

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

A longitudinal investigation of psychological morbidity in patients with ovarian cancer

Ovarian cancer patients may experience psychological disorders due to the aggressive nature of the illness and treatment. We investigated the presence of psychological disorders longitudinally in women with a new diagnosis of ovarian cancer and the factors that predicted development and maintenance of these disorders. Patients were assessed in a prospective longitudinal study at the beginning of chemotherapy treatment, mid-treatment, end of treatment and 3 months follow-up for depression, anxiety, perceived social support, neuroticism and cognitive strategies to control unwanted thoughts. A total of 121 patients were recruited and 85 patients were assessed at all four time points. Three different longitudinal profiles of anxiety and depression caseness were found: non-cases (never cases), occasional cases (cases on at least one but not all four occasions) and stable cases (cases on all four occasions). Most of the women were occasional cases of anxiety (52%, 44), whereas for depression, the majority of women were non-cases (55%, 47). A subset of patients were stable cases of anxiety (22%, 19). Neuroticism and marital status were significant independent predictors of anxiety caseness profile. Neuroticism and use of anti-depressants were independent predictors of depression caseness profile. Social support was not related to psychological morbidity

Perceived Conflict of Interest in Health Science Partnerships

University scientists conducting research on topics of potential health concern often want to partner with a range of actors, including government entities, non-governmental organizations, and private enterprises. Such partnerships can provide access to needed resources, including funding. However, those who observe the results of such partnerships may judge those results based on who is involved. This set of studies seeks to assess how people perceive two hypothetical health science research collaborations. In doing so, it also tests the utility of using procedural justice concepts to assess perceptions of research legitimacy as a theoretical way to investigate conflict of interest perceptions. Findings show that including an industry collaborator has clear negative repercussions for how people see a research partnership and that these perceptions shape people’s willingness to see the research as a legitimate source of knowledge. Additional research aimed at further communicating procedures that might mitigate the impact of industry collaboration is suggested

p53 Amino-Terminus Region (1–125) Stabilizes and Restores Heat Denatured p53 Wild Phenotype

BACKGROUND:The intrinsically disordered N-ter domain (NTD) of p53 encompasses approximately hundred amino acids that contain a transactivation domain (1-73) and a proline-rich domain (64-92) and is responsible for transactivation function and apoptosis. It also possesses an auto-inhibitory function as its removal results in remarkable reduction in dissociation of p53 from DNA. PRINCIPAL FINDINGS/METHODOLOGY:In this report, we have discovered that p53-NTD spanning amino acid residues 1-125 (NTD125) interacted with WT p53 and stabilized its wild type conformation under physiological and elevated temperatures, both in vitro and in cellular systems. NTD125 prevented irreversible thermal aggregation of heat denatured p53, enhanced p21-5'-DBS binding and further restored DBS binding activity of heat-denatured p53, in vitro, in a dose-dependent manner. In vivo ELISA and immunoprecipitation analysis of NTD125-transfected cells revealed that NTD125 shifted equilibrium from p53 mutant to wild type under heat stress conditions. Further, NTD125 initiated nuclear translocation of cytoplasmic p53 in transcriptionally active state in order to activate p53 downstream genes such as p21, Bax, PUMA, Noxa and SUMO. CONCLUSION/SIGNIFICANCE:Here, we showed that a novel chaperone-like activity resides in p53-N-ter region. This study might have significance in understanding the role of p53-NTD in p53 stabilization, conformational activation and apoptosis under heat-stress conditions