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Recent Research Articles from UNTHSC

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Updated: 13 min 15 sec ago

Clinical utility of sequential minimal residual disease measurements in the context of risk-based therapy in childhood acute lymphoblastic leukaemia: a prospective study.

13 min 15 sec ago
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Clinical utility of sequential minimal residual disease measurements in the context of risk-based therapy in childhood acute lymphoblastic leukaemia: a prospective study.

Lancet Oncol. 2015 Apr;16(4):465-74

Authors: Pui CH, Pei D, Coustan-Smith E, Jeha S, Cheng C, Bowman WP, Sandlund JT, Ribeiro RC, Rubnitz JE, Inaba H, Bhojwani D, Gruber TA, Leung WH, Downing JR, Evans WE, Relling MV, Campana D

Abstract
BACKGROUND: The level of minimal residual disease during remission induction is the most important prognostic indicator in patients with acute lymphoblastic leukaemia (ALL). We aimed to establish the clinical significance of minimal residual disease in a prospective trial that used sequential minimal residual disease measurements to guide treatment decisions.
METHODS: Between June 7, 2000, and Oct 24, 2007, 498 assessable patients with newly diagnosed ALL were enrolled in a clinical trial at St Jude Children's Research Hospital. We provisionally classified the risk of relapse as low, standard, or high according to patients' baseline clinical and laboratory features. Final risk assignment to establish treatment intensity was based mainly on minimal residual disease levels measured on days 19 and 46 of remission induction, and on week 7 of maintenance treatment. Additional measurements of minimal residual disease were made on weeks 17, 48, and 120 (end of treatment). The primary aim was to establish the association between event-free survival and patients' minimal residual disease levels during remission induction and sequentially post-remission. This trial was registered at ClinicalTrials.gov, number NCT00137111.
FINDINGS: Irrespective of the provisional risk classification, 10-year event-free survival was significantly worse for patients with 1% or greater minimal residual disease levels on day 19 compared with patients with lower minimal residual disease levels (69·2%, 95% CI 49·6-82·4, n=36 vs 95·5%, 91·7-97·5, n=244; p<0·001 for the provisional low-risk group and 65·1%, 50·7-76·2, n=56 vs 82·9%, 75·6-88·2, n=142; p=0·01 for the provisional standard-risk group). 12 patients with provisional low-risk ALL and 1% or higher minimal residual disease levels on day 19 but negative minimal residual disease (<0·01%) on day 46 were treated for standard-risk ALL and had a 10-year event-free survival of 88·9% (43·3-98·4). For the 280 provisional low-risk patients, a minimal residual disease level of less than 1% on day 19 predicted a better outcome, irrespective of the minimal residual disease level on day 46. Of provisional standard-risk patients with minimal residual disease of less than 1% on day 19, the 15 with persistent minimal residual disease on day 46 seemed to have an inferior 10-year event-free survival compared with the 126 with negative minimal residual disease (72·7%, 42·5-88·8 vs 84·0%, 76·3-89·4; p=0·06) after receiving the same post-remission treatment for standard-risk ALL. Of patients attaining negative minimal residual disease status after remission induction, minimal residual disease re-emerged in four of 382 studied on week 7, one of 448 at week 17, and one of 437 at week 48; all but one of these six patients died despite additional treatment. By contrast, relapse occurred in only two of the 11 patients who had decreasing minimal residual disease levels between the end of induction and week 7 of maintenance therapy and were treated with chemotherapy alone.
INTERPRETATION: Minimal residual disease levels during remission induction treatment have important prognostic and therapeutic implications even in the context of minimal residual disease-guided treatment. Sequential minimal residual disease monitoring after remission induction is warranted for patients with detectable minimal residual disease.
FUNDING: National Institutes of Health and American Lebanese Syrian Associated Charities.

PMID: 25800893 [PubMed - indexed for MEDLINE]

Ionic derivatives of betulinic acid exhibit antiviral activity against herpes simplex virus type-2 (HSV-2), but not HIV-1 reverse transcriptase.

4 hours 14 min ago
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Ionic derivatives of betulinic acid exhibit antiviral activity against herpes simplex virus type-2 (HSV-2), but not HIV-1 reverse transcriptase.

Bioorg Med Chem Lett. 2015 Jun 6;

Authors: Visalli RJ, Ziobrowski H, Badri KR, He JJ, Zhang X, Arumugam SR, Zhao H

Abstract
Betulinic acid (1) has been modified to ionic derivatives (2-5) to improve its water solubility and biological activities. The binding properties of these derivatives with respect to human serum albumin (HSA) was examined and found to be similar to current anti-HIV drugs. These compounds did not inhibit HIV reverse transcriptase, however, 1, 2 and 5 inhibited herpes simplex type 2 (HSV-2) replication at concentrations similar to those reported for acyclovir (IC50 ∼0.1-10μM) and with minimal cellular cytotoxicity. IC50 values for antiviral activity against HSV-2 186 were 1.6, 0.6, 0.9, 7.2, and 0.9μM for compounds 1-5, respectively.

PMID: 26112446 [PubMed - as supplied by publisher]

CXCL8 as a Potential Therapeutic Target for HIV-Associated Neurocognitive Disorders.

4 hours 14 min ago
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CXCL8 as a Potential Therapeutic Target for HIV-Associated Neurocognitive Disorders.

Curr Drug Targets. 2015 Jun 26;

Authors: Mamika MK, Ghorpadeb A

Abstract
Chemokine CXCL8 is a low molecular weight neutrophil chemoattractant implicated in various neurodegenerative disorders including Alzheimer's disease and stroke. Increased expression of CXCL8 has been reported in serum, plasma and brain of human immunodeficiency virus (HIV)-1 infected individuals with neurocognitive impairment, indicating its role in neuroinflammation associated with HIV-1 infection of the brain. Since chemokines are critical in eliciting immune responses in the central nervous system (CNS), CXCL8 is of particular importance for being one of the first chemokines described in the brain. Activation of astrocytes and microglia by HIV-1 and virus associated proteins results in production of this chemokine in the brain microenvironment. Consequently, CXCL8 exerts its effect on target cells via G-protein coupled receptors CXCR1 and CXCR2. Neutrophils are the main target cells for CXCL8; however, microglia and neurons also express CXCR1/CXCR2 and therefore are important targets for CXCL8-mediated crosstalk. The objective of this review is to focus on CXCL8 production, signaling and regulation in neuronal and glial cells in response to HIV-1 infection. We highlight the role of HIV-1 secreted proteins such as trans-activator of transcription, envelope glycoprotein, negative regulatory factor and viral protein r in the regulation of CXCL8. We discuss dual role of CXCL8 in neurodegeneration as well as neuroprotection in the CNS. Thus, targeting CXCL8 through the development of CXCR1/CXCR2-based therapeutic strategies to either selectively agonize or antagonize receptors may be able to selectively promote neuroprotective and anti-inflammatory outcomes, leading to significant clinical applications in many neuroinflammatory CNS diseases, including HIV-associated neurocognitive disorders.

PMID: 26112047 [PubMed - as supplied by publisher]

Efficacy of a Telehealth Intervention on Colonoscopy Uptake when Cost is a Barrier: The Family CARE Cluster Randomized Controlled Trial.

Sat, 06/27/2015 - 3:31am
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Efficacy of a Telehealth Intervention on Colonoscopy Uptake when Cost is a Barrier: The Family CARE Cluster Randomized Controlled Trial.

Cancer Epidemiol Biomarkers Prev. 2015 Jun 22;

Authors: Steffen LE, Boucher KM, Damron BH, Pappas LM, Walters ST, Flores KG, Boonyasiriwat W, Vernon SW, Stroup AM, Schwartz MD, Edwards SL, Kohlmann WK, Lowery JT, Wiggins CL, Hill DA, Higginbotham JC, Burt R, Simmons RG, Kinney AY

Abstract
BACKGROUND: We tested the efficacy of a remote tailored intervention (TeleCARE) compared to a mailed educational brochure for improving colonoscopy uptake among at-risk relatives of colorectal cancer patients and examined subgroup differences based on participant reported cost barriers.
METHODS: Family members of colorectal cancer patients who were not up-to-date with colonoscopy were randomly assigned as family units to TeleCARE (N=232) or an educational brochure (N=249). At the 9-month follow-up, a cost resource letter listing resources for free or reduced-cost colonoscopy was mailed to participants who had reported cost barriers and remained non-adherent. Rates of medically-verified colonoscopy at the 15-month follow-up were compared based on group assignment and within group stratification by cost barriers.
RESULTS: In intent-to-treat analysis, 42.7% of participants in TeleCARE and 24.1% of participants in the educational brochure group had a medically-verified colonoscopy [OR = 2.37; 95% confidence interval (CI) 1.59 to 3.52]. Cost was identified as a barrier in both groups (TeleCARE = 62.5%; educational brochure = 57.0%). When cost was not a barrier, the TeleCARE group was almost four times as likely as the comparison to have a colonoscopy (OR = 3.66; 95% CI= 1.85 to 7.24). The intervention was efficacious among those who reported cost barriers; the TeleCARE group was nearly twice as likely to have a colonoscopy (OR = 1.99; 95% CI = 1.12 to 3.52).
CONCLUSIONS: TeleCARE increased colonoscopy regardless of cost barriers.
IMPACT: Remote interventions may bolster screening colonoscopy regardless of cost barriers and be more efficacious when cost barriers are absent.

PMID: 26101306 [PubMed - as supplied by publisher]

Δ9-Tetrahydrocannabinol-like discriminative stimulus effects of compounds commonly found in K2/Spice.

Sat, 06/27/2015 - 3:31am
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Δ9-Tetrahydrocannabinol-like discriminative stimulus effects of compounds commonly found in K2/Spice.

Behav Pharmacol. 2014 Dec;25(8):750-7

Authors: Gatch MB, Forster MJ

Abstract
A number of cannabinoid compounds are being sold in the form of incense as 'legal' alternatives to marijuana. The purpose of these experiments was to determine whether the most common of these compounds have discriminative stimulus effects similar to Δ-tetrahydrocannabinol (Δ-THC), the main active component in marijuana. Locomotor depressant effects of JWH-018, JWH-073, JWH-200, JWH-203, JWH-250, AM-2201, and CP 47,497-C8-homolog were tested in mice. The compounds were then tested for substitution in rats trained to discriminate Δ-THC (3 mg/kg, intraperitoneally). The time course of the peak dose of each compound was also tested. Each of the synthetic cannabinoids dose-dependently decreased locomotor activity for 1-2 h. Each of the compounds fully substituted for the discriminative stimulus effects of Δ-THC, mostly at doses that produced only marginal amounts of rate suppression. JWH-250 and CP 47,497-C8-homolog suppressed response rates at doses that fully substituted for Δ-THC. The time courses varied markedly between compounds. Most of the compounds had a shorter onset than Δ-THC, and the effects of three of the compounds lasted substantially longer (JWH-073, JWH-250, and CP 47,497-C8-homolog). Several of the most commonly used synthetic cannabinoids produce behavioral effects comparable with those of Δ-THC, which suggests that these compounds may share the psychoactive effects of marijuana responsible for abuse liability. The extremely long time course of the discriminative stimulus effects and adverse effects of CP 47,497-C8-homolog suggest that CP 47,497-C8-homolog may be associated with increased hazards among humans.

PMID: 25325289 [PubMed - indexed for MEDLINE]

Orthopedic emergencies: a practical emergency department classification (US-VAGON) in pelvic fractures.

Sat, 06/27/2015 - 3:31am
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Orthopedic emergencies: a practical emergency department classification (US-VAGON) in pelvic fractures.

Emerg Med Clin North Am. 2015 May;33(2):451-73

Authors: Wang H, Coppola PT, Coppola M

Abstract
Trauma is one of the leading causes of death before the age of 40 years and approximately 5% of patients with trauma who require hospital admission have pelvic fractures. This article updates the emergency department classification of pelvic fractures first described in 2000. This information is of practical value to emergency physicians in identifying the potential vascular, genitourinary, gastrointestinal, orthopedic, and neurologic complications and further assists them in the initial evaluation and treatment of patients with pelvic fractures.

PMID: 25892731 [PubMed - indexed for MEDLINE]

Pyruvate stabilizes electrocardiographic and hemodynamic function in pigs recovering from cardiac arrest.

Wed, 06/24/2015 - 3:28am
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Pyruvate stabilizes electrocardiographic and hemodynamic function in pigs recovering from cardiac arrest.

Exp Biol Med (Maywood). 2015 Jun 18;

Authors: Cherry BH, Nguyen AQ, Hollrah RA, Williams AG, Hoxha B, Olivencia-Yurvati AH, Mallet RT

Abstract
Cardiac electromechanical dysfunction may compromise recovery of patients who are initially resuscitated from cardiac arrest, and effective treatments remain elusive. Pyruvate, a natural intermediary metabolite, energy substrate, and antioxidant, has been found to protect the heart from ischemia-reperfusion injury. This study tested the hypothesis that pyruvate-enriched resuscitation restores hemodynamic, metabolic, and electrolyte homeostasis following cardiac arrest. Forty-two Yorkshire swine underwent pacing-induced ventricular fibrillation and, after 6 min pre-intervention arrest, 4 min precordial compressions followed by transthoracic countershocks. After defibrillation and recovery of spontaneous circulation, the pigs were monitored for another 4 h. Sodium pyruvate or NaCl were infused i.v. (0.1 mmol·kg(-1)·min(-1)) throughout precordial compressions and the first 60 min recovery. In 8 of the 24 NaCl-infused swine, the first countershock converted ventricular fibrillation to pulseless electrical activity unresponsive to subsequent countershocks, but only 1 of 18 pyruvate-treated swine developed pulseless electrical activity (relative risk 0.17; 95% confidence interval 0.13-0.22). Pyruvate treatment also lowered the dosage of vasoconstrictor phenylephrine required to maintain systemic arterial pressure at 15-60 min recovery, hastened clearance of excess glucose, elevated arterial bicarbonate, and raised arterial pH; these statistically significant effects persisted up to 3 h after sodium pyruvate infusion, while infusion-induced hypernatremia subsided. These results demonstrate that pyruvate-enriched resuscitation achieves electrocardiographic and hemodynamic stability in swine during the initial recovery from cardiac arrest. Such metabolically based treatment may offer an effective strategy to support cardiac electromechanical recovery immediately after cardiac arrest.

PMID: 26088865 [PubMed - as supplied by publisher]

BSA Au clusters as a probe for enhanced fluorescence detection using multipulse excitation scheme.

Wed, 06/24/2015 - 3:28am
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BSA Au clusters as a probe for enhanced fluorescence detection using multipulse excitation scheme.

Curr Pharm Biotechnol. 2014;14(13):1139-44

Authors: Raut SL, Rich R, Fudala R, Kokate R, Kimball JD, Borejdo J, Vishwanatha JK, Gryczynski Z, Gryczynski I

Abstract
Although BSA Au clusters fluoresce in red region (λmax: 650 nm), they are of limited use due to low fluorescence quantum yield (~6%). Here we report an enhanced fluorescence imaging application of fluorescent bio-nano probe BSA Au clusters using multipulse excitation scheme. Multipulse excitation takes advantage of long fluorescence lifetime (> 1 µs) of BSA Au clusters and enhances its fluorescence intensity 15 times over short lived cellular auto-fluorescence. Moreover we have also shown that by using time gated detection strategy signal (fluorescence of BSA Au clusters) to noise (auto-fluorescence) ratio can be increased by 30 fold. Thereby with multipulse excitation long lifetime probes can be used to develop biochemical assays and perform optical imaging with zero background.

PMID: 24853092 [PubMed - indexed for MEDLINE]

An Impaired Neuroimmune Pathway Promotes the Development of Hypertension in Systemic Lupus Erythematosus.

Sat, 06/20/2015 - 3:30am
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An Impaired Neuroimmune Pathway Promotes the Development of Hypertension in Systemic Lupus Erythematosus.

Am J Physiol Regul Integr Comp Physiol. 2015 Jun 17;:ajpregu.00143.2015

Authors: Mathis KW

Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that affects nearly 2 million people in the United States. The majority of SLE cases occur in women at an age in which the prevalence of hypertension and cardiovascular disease is typically low. However, women with SLE have a high prevalence of hypertension for reasons that remain unclear. Because immune cells and chronic inflammation have been implicated in the pathogenesis of both hypertension and SLE and because inflammation has been shown to be regulated by the autonomic nervous system, studies investigating neuroimmune mechanisms of hypertension could have direct and significant clinical implications. The purpose of this review is to introduce a recently described neuroimmune pathway and discuss its potential importance in the development of hypertension and renal injury during SLE.

PMID: 26084696 [PubMed - as supplied by publisher]

An evaluation of the RapidHIT(®) system for reliably genotyping reference samples.

Fri, 06/19/2015 - 3:29am
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An evaluation of the RapidHIT(®) system for reliably genotyping reference samples.

Forensic Sci Int Genet. 2014 Nov;13:104-11

Authors: LaRue BL, Moore A, King JL, Marshall PL, Budowle B

Abstract
Short tandem repeat (STR) typing is used routinely for associating or excluding individuals with biological evidence left at a crime scene. Improvements have been made to reduce the turnaround time and labor involved with profile generation, but there is still some lag time between sample collection and interpretation of results. The RapidHIT(®) (IntegenX; Pleasanton, CA, USA) system is an automated instrument that is configured to perform DNA extraction, bead-based DNA normalization, amplification, electrophoresis of PCR amplicons, and data analysis of five reference swabs simultaneously. The RapidHIT system provided reliable STR profiles from reference buccal swabs in approximately 90min with nominal "hands-on" sample loading time with no evidence of contamination between samples. The overall success rate of typing buccal swabs was comparable to standard typing systems. In the event of a failed run due to instrument failure, the swab can be removed from the cartridge and reanalyzed in the RapidHIT system or with standard STR genotyping workflows.

PMID: 25086874 [PubMed - indexed for MEDLINE]

Nomenclature update and allele repeat structure for the markers DYS518 and DYS449.

Fri, 06/19/2015 - 3:29am
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Nomenclature update and allele repeat structure for the markers DYS518 and DYS449.

Forensic Sci Int Genet. 2014 Nov;13:e3

Authors: Mulero J, Ballantyne J, Ballantyne K, Budowle B, Coble M, Gusmão L, Roewer L, Kayser M

PMID: 24854343 [PubMed - indexed for MEDLINE]

Mitochondrial Dihydrolipoamide Dehydrogenase Is Upregulated in Response to Intermittent Hypoxic Preconditioning.

Thu, 06/18/2015 - 3:28am

Mitochondrial Dihydrolipoamide Dehydrogenase Is Upregulated in Response to Intermittent Hypoxic Preconditioning.

Int J Med Sci. 2015;12(5):432-40

Authors: Li R, Luo X, Wu J, Thangthaeng N, Jung ME, Jing S, Li L, Ellis DZ, Liu L, Ding Z, Forster MJ, Yan LJ

Abstract
Intermittent hypoxia preconditioning (IHP) has been shown to protect neurons against ischemic stroke injury. Studying how proteins respond to IHP may identify targets that can help fight stroke. The objective of the present study was to investigate whether mitochondrial dihydrolipoamide dehydrogenase (DLDH) would respond to IHP and if so, whether such a response could be linked to neuroprotection in ischemic stroke injury. To do this, we subjected male rats to IHP for 20 days and measured the content and activity of DLDH as well as the three α-keto acid dehydrogenase complexes that contain DLDH. We also measured mitochondrial electron transport chain enzyme activities. Results show that DLDH content was indeed upregulated by IHP and this upregulation did not alter the activities of the three α-keto acid dehydrogenase complexes. Results also show that the activities of the five mitochondrial complexes (I-V) were not altered either by IHP. To investigate whether IHP-induced DLDH upregulation is linked to neuroprotection against ischemic stroke injury, we subjected both DLDH deficient mouse and DLDH transgenic mouse to stroke surgery followed by measurement of brain infarction volume. Results indicate that while mouse deficient in DLDH had exacerbated brain injury after stroke, mouse overexpressing human DLDH also showed increased brain injury after stroke. Therefore, the physiological significance of IHP-induced DLDH upregulation remains to be further investigated.

PMID: 26078703 [PubMed - in process]

Capsule commentary on Albrecht et al., Hospital discharge instructions: comprehension and compliance among older adults.

Thu, 06/18/2015 - 3:28am
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Capsule commentary on Albrecht et al., Hospital discharge instructions: comprehension and compliance among older adults.

J Gen Intern Med. 2014 Nov;29(11):1529

Authors: Tak HJ

PMID: 25103123 [PubMed - indexed for MEDLINE]

Over-the-counter fish oil use in a county hospital: Medication use evaluation and efficacy analysis.

Wed, 06/17/2015 - 3:29am

Over-the-counter fish oil use in a county hospital: Medication use evaluation and efficacy analysis.

J Clin Lipidol. 2015 May-Jun;9(3):326-33

Authors: Tatachar A, Pio M, Yeung D, Moss E, Chow D, Boatright S, Quinones M, Mathew A, Hulstein J, Adams-Huet B, Ahmad Z

Abstract
BACKGROUND: Little is known about the use and effectiveness of over-the-counter (OTC) fish oil supplements for triglyceride (TG) lowering.
OBJECTIVES: To (1) perform a medication-use evaluation (MUE) and (2) assess the efficacy of OTC fish oil.
METHODS: Retrospective, observational cohort study using electronic medical records and the pharmacy database from Parkland Health and Hospital System in Dallas, Texas. Parkland is a tax-supported county institution that provides patients with single-brand OTC fish oil. Two separate analyses were conducted. Six hundred seventeen patients (prescribed fish oil between July 1, 2012, and August 31, 2012) were included in the MUE analysis and 235 patients (109 fish oil, 72 fenofibrate, and 54 gemfibrozil, prescribed between January 1, 2012, and July 31, 2013) were included in the efficacy analysis. The main outcome measure for the MUE was fish oil prescribing habits including dosages and patient adherence, as defined by medication possession ratio. The main outcome measure for the efficacy analysis was change in lipids measured using the last value before fish oil treatment and the first value after fish oil treatment.
RESULTS: MUE: 617 patients received prescriptions for OTC fish oil. Sixty-four percent were prescribed a total daily dose of 2000 mg. Only 25% of patients were adherent. Efficacy analysis: despite being prescribed suboptimal doses, fish oil reduced TGs by 29% (95% confidence interval, 34.3-22.7). Compared with fish oil therapy, fibrate therapy resulted in a greater TG reduction: 48.5% (55.1-41.0) with fenofibrate and 49.8% (57.6-40.5) with gemfibrozil (P < .0001, both medications compared with fish oil).
CONCLUSIONS: Health care providers prescribe suboptimal doses of fish oil, and adherence is poor. Even at low doses (2 g/d), though, fish oil lowers TGs by 29%.

PMID: 26073390 [PubMed - in process]

A news media analysis of the economic and reputational penalties of the hospital readmissions reduction program.

Wed, 06/17/2015 - 3:29am
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A news media analysis of the economic and reputational penalties of the hospital readmissions reduction program.

Inquiry. 2014;51

Authors: Winborn MS, Alencherril J, Pagán JA

Abstract
Section 3025 of the Affordable Care Act (ACA) of 2010 established the Hospital Readmissions Reduction Program (HRRP), an initiative designed to penalize hospitals with excess 30-day readmissions. This study investigates whether readmission penalties under HRRP impose significant reputational effects on hospitals. Data extracted from 2012 to 2013 news stories suggest that the higher the actual penalty, the higher the perceived cost of the penalty, the more likely it is that hospitals will state they have no control over the low-income patients they serve or that they will describe themselves as safety net providers. The downside of being singled out as a low-quality hospital deserving a relatively high penalty seems to be larger than the upside of being singled out as a high-quality hospital facing a relatively low penalty. Although the financial burden of the penalties seems to be low, hospitals may be reacting to the fact that information about excess readmissions and readmission penalties is being released widely and is scrutinized by the news media and the general public.

PMID: 25500753 [PubMed - indexed for MEDLINE]

Mortality hazard and survival after tuberculosis treatment.

Wed, 06/17/2015 - 3:29am
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Mortality hazard and survival after tuberculosis treatment.

Am J Public Health. 2015 May;105(5):930-7

Authors: Miller TL, Wilson FA, Pang JW, Beavers S, Hoger S, Sharnprapai S, Pagaoa M, Katz DJ, Weis SE

Abstract
OBJECTIVES: We compared mortality among tuberculosis (TB) survivors and a similar population.
METHODS: We used local health authority records from 3 US sites to identify 3853 persons who completed adequate treatment of TB and 7282 individuals diagnosed with latent TB infection 1993 to 2002. We then retrospectively observed mortality after 6 to 16 years of observation. We ascertained vital status as of December 31, 2008, using the Centers for Disease Control and Prevention's National Death Index. We analyzed mortality rates, hazards, and associations using Cox regression.
RESULTS: We traced 11 135 individuals over 119 772 person-years of observation. We found more all-cause deaths (20.7% vs 3.1%) among posttreatment TB patients than among the comparison group, an adjusted average excess of 7.6 deaths per 1000 person-years (8.8 vs 1.2; P < .001). Mortality among posttreatment TB patients varied with observable factors such as race, site of disease, HIV status, and birth country.
CONCLUSIONS: Fully treated TB is still associated with substantial mortality risk. Cure as currently understood may be insufficient protection against TB-associated mortality in the years after treatment, and TB prevention may be a valuable opportunity to modify this risk.

PMID: 25790407 [PubMed - indexed for MEDLINE]

Association of hypothyroidism with low-level arsenic exposure in rural West Texas.

Wed, 06/17/2015 - 3:29am
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Association of hypothyroidism with low-level arsenic exposure in rural West Texas.

Environ Res. 2015 Apr;138:154-60

Authors: Gong G, Basom J, Mattevada S, Onger F

Abstract
It has been reported recently that a higher airborne arsenic level was correlated with higher urinary arsenic concentration and lower serum thyroxin level among urban policemen and rural highway workmen in Italy. The current study was to determine whether exposure to low-level arsenic groundwater (2-22µg/L) is associated with hypothyroidism among 723 participants (118 male and 267 female Hispanics; 108 male and 230 female non-Hispanic whites, NHW) living in rural West Texas counties. Arsenic and iodine levels in their groundwater used for drinking and or cooking were estimated by the inverse distance weighted (IDW) interpolation technique. Groundwater arsenic was ≥8µg/L in 36% of the subjects' wells while iodine concentration was <1µg/L in 91% of their wells. Logistic regression analysis showed that arsenic in groundwater ≥8µg/L and cumulative arsenic exposure (groundwater arsenic concentration multiplied by the number of years living in the current address) but not groundwater iodine concentration were significant predictors for hypothyroidism among Hispanics (p<0.05) but not NHW after adjusting for covariates such as age, gender, annual household income and health insurance coverage. The ethnic difference may be due to a marginally higher percentage of Hispanics (p=0.0622) who lived in areas with groundwater arsenic ≥8µg/L compared with NHW. The prevalence of hypothyroidism was significantly higher in Hispanics or NHW of this rural cohort than the national prevalence. Measures should be taken to reduce arsenic in drinking water in order to prevent hypothyroidism in rural areas.

PMID: 25721242 [PubMed - indexed for MEDLINE]

HIV virological failure and drug resistance among injecting drug users receiving first-line ART in China.

Tue, 06/16/2015 - 3:28am
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HIV virological failure and drug resistance among injecting drug users receiving first-line ART in China.

BMJ Open. 2014;4(10):e005886

Authors: Leng X, Liang S, Ma Y, Dong Y, Kan W, Goan D, Hsi JH, Liao L, Wang J, He C, Zhang H, Xing H, Ruan Y, Shao Y

Abstract
OBJECTIVE: To explore HIV virological failure and drug resistance among injecting drug users (IDUs) receiving first-line antiretroviral treatment (ART) in China.
DESIGN: A series of cross-sectional surveys from 2003 to 2012 from the Chinese National HIV Drug Resistance (HIVDR) Surveillance and Monitoring Network.
SETTING: China.
PARTICIPANTS: Data were analysed by the Chinese National (HIVDR) Surveillance and Monitoring Network from 2003 to 2012. Demographic, ART and laboratory data (CD4+ cell count, viral load and drug resistance) were included. Factors associated with virological failure were identified by logistic regression analysis.
RESULTS: 929 of the 8556 individuals in the Chinese HIVDR database were IDUs receiving first-line ART. For these 929 IDUs, the median duration of treatment was 14 months (IQR 6.0-17.8). 193 of the 929 IDUs (20.8%) experienced virological failure (HIV viral load ≥1000 copies/mL). The prevalence of HIVDR among patients with virological failure was 38.9% (68/175). The proportion of patients with drug resistance to non-nucleoside reverse transcriptase inhibitor (NNRTIs), nucleoside reverse transcriptase inhibitor (NRTIs) and protease inhibitors (PIs) was 52.9%, 76.5% and 4.4%, respectively. Factors independently associated with virological failure include: ethnic minorities, junior high school education or less, farmers, self-reported missing doses in the past month, CD4 cell count at survey from 200 to 349 cells/mm(3) or from 0 to 199 cells/mm(3), and residence of Guangxi and Yunnan provinces.
CONCLUSIONS: The proportion of virological failure was high among IDUs receiving first-line ART in China. However, better treatment outcomes were observed in Guangxi and Yunnan, which indicates the importance of ART education and adherence to intervention, especially for patients who are farmers, minorities or have a poor educational background.

PMID: 25319999 [PubMed - indexed for MEDLINE]

Longevity loss among cured tuberculosis patients and the potential value of prevention.

Tue, 06/16/2015 - 3:28am
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Longevity loss among cured tuberculosis patients and the potential value of prevention.

Int J Tuberc Lung Dis. 2014 Nov;18(11):1347-52

Authors: Hoger S, Lykens K, Beavers SF, Katz D, Miller TL

Abstract
BACKGROUND: Evidence of substantial, quantifiable and preventable burdens of mortality hazard even after anti-tuberculosis treatment and cure would be a compelling, concrete, and useful measure of the value of prevention.
METHODS: We compared years of potential life lost between a cohort of 3 933 cured tuberculosis (TB) patients and 9 166 persons with latent tuberculous infection. We constructed a regression model to predict the expected years of potential life lost in each cohort and for demographic subgroups.
RESULTS: Among decedents, a history of fully treated TB is associated with a predicted average 3.6 more years of potential life loss than a comparable population without active TB. Greater longevity losses were predicted among those identified as White and Hispanic than among Black and Asian counterparts.
CONCLUSION: We found significant differences in predicted longevity of treated TB survivors relative to a similar group without active TB. These excess losses are substantial: a total of 14 158 life-years or the equivalent of more than 188 75-year lifespans. These findings illustrate an important opportunity cost associated with each preventable TB case - an average of 3.6 potential years of life. We conclude that substantial preventable mortality burdens remain despite adequate anti-tuberculosis treatment, a compelling rationale for more widespread and systematic use of prevention.

PMID: 25299869 [PubMed - indexed for MEDLINE]

Δ9-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids found on the gray market.

Sat, 06/13/2015 - 3:30am

Δ9-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids found on the gray market.

Behav Pharmacol. 2015 Jun 6;

Authors: Gatch MB, Forster MJ

Abstract
When synthetic cannabinoid compounds became controlled by state and federal governments, different, noncontrolled compounds began to appear as marijuana substitutes. Unlike the scheduled cannabinoids, the newer compounds have not been characterized for potency and efficacy in preclinical studies. The purpose of these experiments was to determine whether some of the more recent synthetic compounds sold as marijuana substitutes have behavioral effects similar to those of Δ-tetrahydrocannabinol (Δ-THC), the pharmacologically active compound in marijuana. The compounds UR-144, XLR-11, AKB-48 (APINACA), PB-22 (QUPIC), 5F-PB-22, and AB-FUBINACA were tested for locomotor depressant effects in male Swiss-Webster mice and subsequently for their ability to substitute for Δ-THC (3 mg/kg, intraperitoneally) in drug discrimination experiments with male Sprague-Dawley rats. UR-144, XLR-11, AKB-48, and AB-FUBINACA each decreased locomotor activity for up to 90 min, whereas PB-22 and 5F-PB-22 produced depressant effects lasting 120-150 min. Each of the compounds fully substituted for the discriminative stimulus effects of Δ-THC. These findings confirm the suggestion that these compounds have marijuana-like psychoactive effects and abuse liability.

PMID: 26061356 [PubMed - as supplied by publisher]

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