Isothermal microcalorimetry: an analytical technique for assessing the dynamic chemical stability of UHMWPE

In this work, isothermal microcalorimetry (IMC) was utilized to measure the exothermic heat flow from specimens of ultra-high-molecular-weight polyethylene (UHMWPE), that had been sterilized by various standard methods, under simulated shelf storage (air at 25 degrees C, 30% r.h.) and simulated implantation (phosphate buffered saline, PBS, at 37 degrees C) conditions. Gamma-radiation sterilized UHMWPE yielded initial heat flow rates approximately 7-10 times higher in simulated shelf storage and 2-3 times higher in simulated implantation (even after 1 month in PBS) than specimens which were unsterilized or sterilized using either ethylene oxide gas (ETO) or gas plasma (GP). These results show that gamma sterilization of UHMWPE produces many more unstable bonds in the polymer than is the case when ETO or GP is used, and that the net exothermic physico-chemical change proceeds steadily in a diffusion-limited manner in air or saline. In addition, gamma sterilization in nitrogen rather than in air did not prevent the creation of unstable bonds, but did defer physico-chemical change until the UHMWPE was exposed to oxygen. These results demonstrate the usefulness of IMC as a viable method for studying the stability of polymeric implant materials.     

Refractory venous leg ulcers: observational evaluation of innovative new technology

This observational case series reports the evaluation of a novel neuromuscular electrical stimulation device (geko™) that stimulates the common peroneal nerve at the fibular head as an adjunctive therapy in patients with non‐healing venous leg ulcers. The aim was to evaluate and determine if the geko™ device was effective in this population and should be added to the medical supply formulary. Patients whose wounds had failed to heal within 24 weeks of standard therapy were identified in two community settings in Ontario. A total of 11 patients consented to the evaluation with a combined 107‐year history of recalcitrant leg ulcers. Although the pre‐geko™ healing rate was unknown, all ulcers were considered non‐healing. With geko™, the average weekly percentage reduction in surface area for all patients was 4·5% and for the six adherent to geko™ and best practices 7·0%. By comparison, the average weekly percentage reduction for measurable wounds in the five non‐adherent patients was 1·8%. Requirements for success appear to include an arterial status adequate for healing, effective and prompt management of wound infections and adherence to the treatment schedule. The geko™ device has been added to the medical supply formulary in one centre and is pending in the other.     

Risk factors for early hospital readmission in patients with AIDS and pneumonia

OBJECTIVE: To determine risk factors for early readmission to the hospital in patients with AIDS and pneumonia. DESIGN: Case-control analysis. SETTING: A municipal teaching hospital serving an indigent population. PATIENTS: Case patients were all AIDS patients hospitalized with Pneumocystis carinii pneumonia or bacterial pneumonia between January 1992 and March 1995 who were readmitted for any nonelective reason within 2 weeks of discharge (n = 90). Control patients were randomly selected AIDS patients admitted during the study period who were not early readmissions (n = 87), matched by proportion of Pneumocystis carinii to bacterial pneumonia. MEASUREMENTS AND MAIN RESULTS: Demographics, social support, health-related behaviors, clinical aspects of the acute hospitalization, and general medical status were the main predictors measured. RESULTS: Patients were at significantly increased risk of early readmission if they left the hospital unaccompanied by family or friend (odds ratio [OR] 4.76; 95% confidence interval [CI] 2.06, 11.0; p =.0003), used crack cocaine (OR 3.40; 95% CI 1.02, 11.3; p =. 046), had one or more coincident AIDS diagnoses (OR 3.65; 95% CI 1. 44, 9.26; p =.0065), or had been admitted in the preceding 6 months (OR 2.82; 95% CI 1.21, 6.57; p =.016). Demographic characteristics, alcoholism, intravenous drug use, illness severity on admission, and length of hospitalization did not predict early readmission. CONCLUSIONS: Absence of companion at discharge and crack use were important risk factors for early readmission in patients with AIDS and pneumonia. Additional AIDS comorbidity and recent antecedent hospitalization were also risk factors; however, demographics and measures of acute illness during index hospitalization did not predict early readmission.     

An Algorithm for the Stochastic Simulation of Gene Expression and Heterogeneous Population Dynamics

We present an algorithm for the stochastic simulation of gene expression and heterogeneous population dynamics. The algorithm combines an exact method to simulate molecular-level fluctuations in single cells and a constant-number Monte Carlo method to simulate time-dependent statistical characteristics of growing cell populations. To benchmark performance, we compare simulation results with steady-state and time-dependent analytical solutions for several scenarios, including steady-state and time-dependent gene expression, and the effects on population heterogeneity of cell growth, division, and DNA replication. This comparison demonstrates that the algorithm provides an efficient and accurate approach to simulate how complex biological features influence gene expression. We also use the algorithm to model gene expression dynamics within "bet-hedging" cell populations during their adaption to environmental stress. These simulations indicate that the algorithm provides a framework suitable for simulating and analyzing realistic models of heterogeneous population dynamics combining molecular-level stochastic reaction kinetics, relevant physiological details and phenotypic variability.     

Directly Observed Antidepressant Medication Treatment and HIV Outcomes Among Homeless and Marginally Housed HIV-Positive Adults: A Randomized Controlled Trial

Objectives. We assessed whether directly observed fluoxetine treatment reduced depression symptom severity and improved HIV outcomes among homeless and marginally housed HIV-positive adults in San Francisco, California, from 2002 to 2008.Methods. We conducted a nonblinded, randomized controlled trial of once-weekly fluoxetine, directly observed for 24 weeks, then self-administered for 12 weeks (n = 137 persons with major or minor depressive disorder or dysthymia). Hamilton Depression Rating Scale score was the primary outcome. Response was a 50% reduction from baseline and remission a score below 8. Secondary measures were Beck Depression Inventory-II (BDI-II) score, antiretroviral uptake, antiretroviral adherence (measured by unannounced pill count), and HIV-1 RNA viral suppression (< 50 copies/mL).Results. The intervention reduced depression symptom severity (b = −1.97; 95% confidence interval [CI] = −0.85, −3.08; P < .001) and increased response (adjusted odds ratio [AOR] = 2.40; 95% CI = 1.86, 3.10; P < .001) and remission (AOR = 2.97; 95% CI = 1.29, 3.87; P < .001). BDI-II results were similar. We observed no statistically significant differences in secondary HIV outcomes.Conclusions. Directly observed fluoxetine may be an effective depression treatment strategy for HIV-positive homeless and marginally housed adults, a vulnerable population with multiple barriers to adherence.Depressive, pain, and substance use disorders are highly prevalent among persons living with HIV/AIDS1,2 and among the homeless and marginally housed.3–5 The triple diagnosis of depression, HIV, and substance use poses unique treatment challenges for clinicians: successful management of one condition is often dependent on successful management of the others, and the optimal sequencing of depression treatment, substance use treatment, and stabilization of psychosocial comorbidities remains unclear. Adherence to the entire continuum of HIV care is often hampered by depression6–8 and substance use.9,10 For homeless persons, the need to address subsistence concerns such as obtaining food and shelter may not only adversely affect mental well-being11 but may also divert attention away from medication adherence and regular clinic attendance.12 Timely and effective depression treatment is critical for HIV-positive persons, because depression has been associated with CD4⁺ T-lymphocyte cell count decline,13 progression to AIDS,14 and AIDS-related mortality.15 Yet depression remains pervasively underdiagnosed and undertreated among the homeless16–18 and among HIV-positive persons.19,20Depression treatment might be expected to improve virological or immunologic outcomes through improved adherence, but this has not been conclusively demonstrated.21–23 We therefore sought to determine whether treatment with once-weekly fluoxetine reduced depression symptom severity among homeless and marginally housed persons with comorbid depression and HIV. Because this population faces many psychosocial barriers to successful medication adherence,12,24 in addition to depression,25 we employed a directly observed treatment strategy similar to that used for treatment and management of patients with tuberculosis and HIV.26 This strategy reduced the potential for incomplete adherence to reduce the effectiveness of antidepressant treatment. A secondary aim was to determine whether depression treatment improved antiretroviral therapy (ART) uptake among persons eligible for treatment and ART adherence and viral suppression among treated persons.     

Periodontal disease as a risk factor for sporadic colorectal cancer: results from COLDENT study

Cancer Causes & Control - Colorectal cancer remains the top leading cancer worldwide. Accumulating evidence suggests periodontal pathogens are involved in colorectal carcinogenesis, indicating...