Cluster-Randomized Controlled Trial of An Athletic Trainer-Directed Spit (Smokeless) Tobacco Intervention for Collegiate Baseball Athletes: Results After 1 Year

Context: Athletes in the United States are at high risk for using spit (smokeless) tobacco (ST) and incurring its associated adverse health effects.Objective: To examine whether an athletic trainer-directed ST intervention could decrease initiation and promote cessation of ST use among male collegiate baseball athletes.Design: Stratified, cluster-randomized controlled trial.Setting: Fifty-two California colleges.Patients or Other Participant(s): A total of 883 subjects in 27 intervention colleges and 702 subjects in 25 control colleges participated, as did 48 certified athletic trainers.Intervention(s): For college athletic trainers and associated dental professionals, a 3-hour video conference, and for collegiate athletes, an oral cancer screening with feedback and brief counseling during the preseason health screenings, athletic trainer support for cessation, and a peer-led educational baseball team meeting.Main Outcome Measure(s): The subjects' ST use over 1 year was assessed by self-report. At the end of the study, the certified athletic trainers were mailed a survey assessing their tobacco use and perceptions and behavior related to tobacco control in the athletic environment. We used multivariable logistic regression models for clustered responses (generalized estimating equations) to test the difference between groups in ST-use initiation and cessation and to identify significant overall predictors of noninitiation and cessation of ST use.Results: Of the 1585 athletes recruited, 1248 (78.7%) were followed up at 12 months. In addition, 48 of the 52 athletic trainers (92%) responded to the 1-year follow-up survey. The ST-use initiation (incidence) was 5.1% in intervention colleges and 8.4% in control colleges (generalized estimating equation odds ratio = 0.58, 95% confidence interval = 0.35-0.99). Predictors of ST noninitiation were low lifetime tobacco and monthly alcohol use (odds ratio = 1.98, 95% confidence interval = 1.40- 2.82) and athletic trainers' report that the baseball coach supported ST-use prevention activities (odds ratio = 1.43, 95% confidence interval = 1.11-1.83). Although at 1 year, cessation of ST use was relatively high in both groups (36%), we noted no significant difference between the groups (odd ratio = 0.94, 95% confidence interval = 0.70-1.27).Conclusions: The intervention was significantly effective in preventing incident ST use but did not significantly increase cessation beyond that seen in the control group. The latter finding is inconsistent with previous studies and may be explained by spillover of the intervention to control colleges, other anti-tobacco activity in control colleges, and/or the small sample of dependent ST users enrolled in the study.     

Phase I and pharmacologic study of infusional topotecan and Carboplatin in relapsed and refractory acute leukemia.

PURPOSE: To assess the maximum tolerated dose, toxicities, pharmacokinetics, and antileukemic activity of topotecan and carboplatin in adults with recurrent or refractory acute leukemias. EXPERIMENTAL DESIGN: Patients received topotecan and carboplatin by 5-day continuous infusion at nine dose levels. Patients achieving a complete remission received up to two additional courses for consolidation. Plasma topotecan and ultrafilterable platinum were assayed on days 1 to 5. In addition, pretreatment levels of various polypeptides in leukemic cells were examined by immunoblotting to assess possible correlations with response. RESULTS: Fifty-one patients received a total of 69 courses of therapy. Dose-limiting toxicity consisted of grade 4/5 typhlitis and grade 3/4 mucositis after one course of therapy or grade 4 neutropenia and thrombocytopenia lasting >50 days when a second course was administered on day 21. Among 45 evaluable patients, there were 7 complete remissions, 2 partial remissions, 1 incomplete complete remission, and 1 reversion to chronic-phase chronic myelogenous leukemia. Topotecan steady-state plasma concentrations increased with dose. No accumulation of topotecan or ultrafilterable platinum occurred between days 1 and 5 of therapy. Leukemic cell levels of topoisomerase I, checkpoint kinase 1, checkpoint kinase 2, and Mcl-1 correlated with proliferating cell nuclear antigen but not with response. In contrast, low Bcl-2 expression correlated with response (P = 0.014, Mann-Whitney U test). CONCLUSIONS: The maximum tolerated dose was 1.6 mg/m(2)/d topotecan plus 150 mg/m(2)/d carboplatin. The complete remission rate in a heavily pretreated population was 16% (33% at the highest three dose levels). Responses seem to correlate with low pretreatment blast cell Bcl-2 expression.     

A Concise Panel of Biomarkers Identifies Neurocognitive Functioning Changes in HIV-Infected Individuals

Neurocognitive (NC) impairment (NCI) occurs commonly in people living with HIV. Despite substantial effort, no biomarkers have been sufficiently validated for diagnosis and prognosis of NCI in the clinic. The goal of this project was to identify diagnostic or prognostic biomarkers for NCI in a comprehensively characterized HIV cohort. Multidisciplinary case review selected 98 HIV-infected individuals and categorized them into four NC groups using normative data: stably normal (SN), stably impaired (SI), worsening (Wo), or improving (Im). All subjects underwent comprehensive NC testing, phlebotomy, and lumbar puncture at two timepoints separated by a median of 6.2 months. Eight biomarkers were measured in CSF and blood by immunoassay. Results were analyzed using mixed model linear regression and staged recursive partitioning. At the first visit, subjects were mostly middle-aged (median 45) white (58 %) men (84 %) who had AIDS (70 %). Of the 73 % who took antiretroviral therapy (ART), 54 % had HIV RNA levels below 50 c/mL in plasma. Mixed model linear regression identified that only MCP-1 in CSF was associated with neurocognitive change group. Recursive partitioning models aimed at diagnosis (i.e., correctly classifying neurocognitive status at the first visit) were complex and required most biomarkers to achieve misclassification limits. In contrast, prognostic models were more efficient. A combination of three biomarkers (sCD14, MCP-1, SDF-1α) correctly classified 82 % of Wo and SN subjects, including 88 % of SN subjects. A combination of two biomarkers (MCP-1, TNF-α) correctly classified 81 % of Im and SI subjects, including 100 % of SI subjects. This analysis of well-characterized individuals identified concise panels of biomarkers associated with NC change. Across all analyses, the two most frequently identified biomarkers were sCD14 and MCP-1, indicators of monocyte/macrophage activation. While the panels differed depending on the outcome and on the degree of misclassification, nearly all stable patients were correctly classified.     

Unbalanced 1;7 translocation and therapy-induced hematologic disorders: a possible relationship

An identical chromosome abnormality, which appears to be derived from a 1;7 translocation [+der(1),t(1;7)(p11;p11)], was observed in the bone marrow of 12 patients with various hematologic disorders at the Mayo Clinic from 1980 to 1984. At the time of cytogenetic evaluation, nine of the patients had either a myeloproliferative disorder or a myelodysplastic syndrome, one had an acute leukemia, and two had treated multiple myeloma with no morphologic evidence of evolving myeloproliferative disease. Of the 11 patients for whom information about previous therapy was available, seven had a history of exposure to chemotherapy for a previous malignant disorder; we were unable to establish whether the remaining patient had had prior treatment. This study suggests a possible relationship between +der(1),t(1;7)(p11;p11) and some treatment-induced hematologic disorders. Such chromosome abnormalities may be the result of a reciprocal chromatid translocation and adjacent I segregation of a quadriradial configuration in metaphase.     

Methamphetamine Exposure Combined with HIV-1 Disease or gp120 Expression: Comparison of Learning and Executive Functions in Humans and Mice

Methamphetamine dependence is a common comorbid condition among people living with HIV, and may exacerbate HIV-associated neurocognitive disorders. Animal models of neuroAIDS suggest that the gp120 protein may also cause cognitive impairment. The present work evaluated the separate and combined effects of HIV/gp120 and methamphetamine on learning and executive functions in both humans and transgenic mice. Human participants were grouped by HIV serostatus (HIV+ or HIV−) and lifetime methamphetamine dependence (METH+ or METH−). A neurocognitive test battery included domain-specific assessments of learning and executive functions. Mice (gp120+ and gp120−) were exposed to either a methamphetamine binge (METH+) or saline (METH−), then tested in the attentional-set-shifting task to assess learning and executive functions. In humans, HIV status was associated with significant impairments in learning, but less so for executive functions. The frequency of learning impairments varied between groups, with the greatest impairment observed in the HIV+/METH+ group. In mice, gp120 expression was associated with impairments in learning but not reversal learning (executive component). The greatest proportion of mice that failed to complete the task was observed in the gp120+/METH+ group, suggesting greater learning impairments. Our cross-species study demonstrated that HIV in humans and gp120 in mice impaired learning, and that a history of methamphetamine exposure increased the susceptibility to HIV-associated neurocognitive deficits in both species. Finally, the similar pattern of results in both species suggest that the gp120 protein may contribute to HIV-associated learning deficits in humans.     

Chronically elevated depressive symptoms interact with acute increases in inflammation to predict worse neurocognition among people with HIV

Journal of NeuroVirology - We examined the joint effects of depressive symptoms (Beck Depression Inventory-II (BDI-II)) and systemic inflammation (plasma C-reactive protein (CRP)) on longitudinal...     

Extracorporeal lithotripsy endoscopically controlled by ureterorenoscopy (LECURS): a new concept for the treatment of kidney stones—first clinical experience using digital ureterorenoscopes

Purpose

To evaluate the feasibility and usefulness of extracorporeal lithotripsy endoscopically controlled by simultaneous flexible ureterorenoscopy (LECURS) and combined with Holmium laser lithotripsy for kidney stones surgery.

Methods

Retrograde flexible ureteroscopy allowed stone visualization and intrarenal relocation when possible. Extracorporeal schock wave lithotripsy (ESWL) was performed under direct vision allowing constant focal zone adjustment for optimal stone fragmentation. Holmium laser lithotripsy was used simultaneously when necessary. Post-operative assessment included ultrasound at day one and abdominal CT scan 3 weeks later to evaluate for residual fragments.

Results

Six patients with kidney stones were recruited including 3 with relative contraindication to ESWL. One patient had a stone beyond an infundibular stenosis and 2 had multiple stones in a horseshoe kidney with an uretero-pelvic junction (UPJ) stricture. A 100 % stone fragmentation rate was obtained. Post-operative ultrasound was normal in 5 patients and showed slight peri-renal infiltration in the other. One patient developed an obstructive pyelonephritis requiring antibiotics and changing a double J to a ureteral catheter. No other complications were noted. Three patients (50 %) were stone free after LECURS. Three patients underwent a second-look procedure for small (<3 mm) retained residual fragments. No damage was seen with the digital ureteroscopes, laser fibers or stone baskets.

Conclusions

This initial experience with LECURS has shown to be feasible and safe. This opens the opportunity for further evaluation of this approach in order to improve outcomes of both approaches.     

A history of alcohol dependence augments HIV-associated neurocognitive deficits in persons aged 60 and older

Excessive alcohol use is common among people living with HIV. Given the growing prevalence of older HIV+ adults and observations indicating higher risk for neurocognitive impairment in older adults with either HIV infection or alcoholism, an increased understanding of their combined impact in the context of this increasingly aged population is crucial. We conducted comprehensive neurocognitive assessment in 112 older HIV+ individuals aged 50 to 69 years. Regression analyses were conducted to examine the interaction between age and the presence of lifetime alcohol dependence on neurocognitive measures, controlling for years of education, hepatitis C serostatus, and lifetime non-alcohol substance use disorder. Significant interactions of age and alcohol dependence history were found for global neurocognitive function, which was driven by the domains of executive function, processing speed, and semantic memory. Follow-up analyses indicated adverse effects of alcohol use history on neurocognitive measures that were evident only in HIV+ individuals 60 years and older. While mounting evidence in younger cohorts indicates adverse synergistic HIV/alcohol effects on neurocognitive function, our novel preliminary findings in this elderly HIV+ cohort demonstrated the importance of even a relatively distant alcohol use history on the expression of HIV-associated neurocognitive disorders that may not become apparent until much later in life.