An integrated alcohol abuse and medical treatment model for patients with hepatitis C.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) infection have high rates of alcohol consumption, which is associated with progression of fibrosis and lower response rates to HCV treatment. AIMS: This prospective cohort study examined the feasibility of a 24-week integrated alcohol and medical treatment to HCV-infected patients. METHODS: Patients were recruited from a hepatology clinic if they had an Alcohol Use Disorders Identification Test score >4 for women and >8 for men, suggesting hazardous alcohol consumption. The integrated model included patients receiving medical care and alcohol treatment within the same clinic. Alcohol treatment consisted of 6 months of group and individual therapy from an addictions specialist and consultation from a study team psychiatrist as needed. RESULTS: Sixty patients were initially enrolled, and 53 patients participated in treatment. The primary endpoint was the Addiction Severity Index (ASI) alcohol composite scores, which significantly decreased by 0.105 (41.7% reduction) between 0 and 3 months (P < 0.01) and by 0.128 (50.6% reduction) between 0 and 6 months (P < 0.01) after adjusting for covariates. Alcohol abstinence was reported by 40% of patients at 3 months and 44% at 6 months. Patients who did not become alcohol abstinent had reductions in their ASI alcohol composite scores from 0.298 at baseline to 0.219 (26.8% reduction) at 6 months (P = 0.08). CONCLUSION: This study demonstrated that an integrated model of alcohol treatment and medical care could be successfully implemented in a hepatology clinic with significant favorable impact on alcohol use and abstinence among patients with chronic HCV.

Medical education as moral formation: an Aristotelian account of medical professionalsim.

The medical professionalism movement, bolstered by many influential medical organizations and institutions, has in the last decade produced a number of conceptual definitions of professionalism and a number of concrete proposals for its measurement and teaching. These projects, however laudable, are misguided when they treat professionalism as a unitary descriptive concept rather than as a contested and therefore primarily evaluative one; when they conceive professionalism as a domain of medical practice separable in principle from other domains; and when they treat professionalism as, in principle, a specifiable goal or product of sufficiently well designed educational curricula. The logic of professionalism-as-product corresponds to the logic of techne (art or practical skill) in Aristotle's Nicomachean Ethics. Aristotle provides a cogent argument, however, that the moral excellences denoted by "professionalism" cannot be "produced" or even prespecified in the concrete; rather, they must be acquired through long practice under the careful concrete guidance of teachers who themselves embody these moral excellences. Phronesis (practical wisdom) rather than techne must therefore be the guiding logic of educational initiatives in medical professional formation, with particular emphasis on close mentorship and on the moral character both of students and of those who teach them.

Pharmacological enhancement of naltrexone treatment for opioid dependence: a review.

PURPOSE: Opioid dependence (OD) is a serious and growing clinical condition with increasing social costs that requires expanding treatment beyond opioid agonist substitution. The opioid antagonist naltrexone has displayed a remarkable association of theoretical effectiveness and poor clinical utility in treating OD due to noncompliant behavior and low acceptability among patients, only partly modified by psychosocial interventions. We reviewed pharmacological studies, including naltrexone depot formulations and combination treatments. METHOD: We searched PubMed for clinical studies on the use of naltrexone implants and slow-release injections in OD, and investigations using adjunct medications to improve naltrexone maintenance therapy of OD. We discussed the results in view of their application to the clinical practice. RESULTS: Significant reduction in opioid use and improved retention in treatment have been found in several studies using depot naltrexone formulations, some of which are controlled clinical trials. Pilot investigations have gathered initial positive results on the use of naltrexone in combination with serotonin reuptake inhibitors, α-2 adrenergic, opioid, and γ-aminobutyric acid agonist medications. CONCLUSION: Current evidence suggests that more research on effectiveness and safety is needed in support of depot naltrexone treatment for OD. Further research comparing slow-release with oral naltrexone and opioid agonist medications will help characterize the role of opioid antagonist-mediated treatment of OD. Preliminary investigations on naltrexone combination treatments suggest the opportunity to continue study of new mixed receptor activities for the treatment of OD and other drug addictions.

Practices and outcomes of self-treatment with helminths based on physicians' observations.

The successful use of helminths as therapeutic agents to resolve inflammatory disease was first recorded 40 years ago. Subsequent work in animal models and in humans has demonstrated that the organisms might effectively treat a wide range of inflammatory diseases, including allergies, autoimmune disorders and inflammation-associated neuropsychiatric disorders. However, available information regarding the therapeutic uses and effects of helminths in humans is limited. This study probes the practices and experiences of individuals 'self-treating' with helminths through the eyes of their physicians. Five physicians monitoring more than 700 self-treating patients were interviewed. The results strongly support previous indications that helminth therapy can effectively treat a wide range of allergies, autoimmune conditions and neuropsychiatric disorders, such as major depression and anxiety disorders. Approximately 57% of the self-treating patients observed by physicians in the study had autism. Physicians reported that the majority of patients with autism and inflammation-associated co-morbidities responded favourably to therapy with either of the two most popular organisms currently used by self-treaters, Hymenolepis diminuta and Trichuris suis. However, approximately 1% of paediatric patients experienced severe gastrointestinal pains with the use of H. diminuta, although the symptoms were resolved with an anti-helminthic drug. Further, exposure to helminths apparently did not affect the impaired comprehension of social situations that is the hallmark of autism. These observations point toward potential starting points for clinical trials, and provide further support for the importance of such trials and for concerted efforts aimed at probing the potential of helminths, and perhaps other biologicals, for therapeutic use.

Systematic review and metasummary of attitudes toward research in emergency medical conditions

Emergency departments are challenging research settings, where truly informed consent can be difficult to obtain. A deeper understanding of emergency medical patients' opinions about research is needed. We conducted a systematic review and meta-summary of quantitative and qualitative studies on which values, attitudes, or beliefs of emergent medical research participants influence research participation. We included studies of adults that investigated opinions toward emergency medicine research participation. We excluded studies focused on the association between demographics or consent document features and participation and those focused on non-emergency research. In August 2011, we searched the following databases: MEDLINE, EMBASE, Google Scholar, Scirus, PsycINFO, AgeLine and Global Health. Titles, abstracts and then full manuscripts were independently evaluated by two reviewers. Disagreements were resolved by consensus and adjudicated by a third author. Studies were evaluated for bias using standardised scores. We report themes associated with participation or refusal. Our initial search produced over 1800 articles. A total of 44 articles were extracted for full-manuscript analysis, and 14 were retained based on our eligibility criteria. Among factors favouring participation, altruism and personal health benefit had the highest frequency. Mistrust of researchers, feeling like a 'guinea pig' and risk were leading factors favouring refusal. Many studies noted limitations of informed consent processes in emergent conditions. We conclude that highlighting the benefits to the participant and society, mitigating risk and increasing public trust may increase research participation in emergency medical research. New methods for conducting informed consent in such studies are needed.

Monte Carlo Analysis and Physics Characterization of a Novel Nanoparticle Detector for Medical and Micro-dosimetry Applications

The outcomes for both (i) radiation therapy and (ii) preclinical small animal radio- biology studies are dependent on the delivery of a known quantity of radiation to a specific and intentional location. Adverse effects can result from these procedures if the dose to the target is too high or low, and can also result from an incorrect spatial distribution in which nearby normal healthy tissue can be undesirably damaged by poor radiation delivery techniques. Thus, in mice and humans alike, the spatial dose distributions from radiation sources should be well characterized in terms of the absolute dose quantity, and with pin-point accuracy. When dealing with the steep spatial dose gradients consequential to either (i) high dose rate (HDR) brachytherapy or (ii) within the small organs and tissue inhomogeneities of mice, obtaining accurate and highly precise dose results can be very challenging, considering commercially available radiation detection tools, such as ion chambers, are often too large for in-vivo use.

In this dissertation two tools are developed and applied for both clinical and preclinical radiation measurement. The first tool is a novel radiation detector for acquiring physical measurements, fabricated from an inorganic nano-crystalline scintillator that has been fixed on an optical fiber terminus. This dosimeter allows for the measurement of point doses to sub-millimeter resolution, and has the ability to be placed in-vivo in humans and small animals. Real-time data is displayed to the user to provide instant quality assurance and dose-rate information. The second tool utilizes an open source Monte Carlo particle transport code, and was applied for small animal dosimetry studies to calculate organ doses and recommend new techniques of dose prescription in mice, as well as to characterize dose to the murine bone marrow compartment with micron-scale resolution.

Hardware design changes were implemented to reduce the overall fiber diameter to <0.9 mm for the nano-crystalline scintillator based fiber optic detector (NanoFOD) system. Lower limits of device sensitivity were found to be approximately 0.05 cGy/s. Herein, this detector was demonstrated to perform quality assurance of clinical 192Ir HDR brachytherapy procedures, providing comparable dose measurements as thermo-luminescent dosimeters and accuracy within 20% of the treatment planning software (TPS) for 27 treatments conducted, with an inter-quartile range ratio to the TPS dose value of (1.02-0.94=0.08). After removing contaminant signals (Cerenkov and diode background), calibration of the detector enabled accurate dose measurements for vaginal applicator brachytherapy procedures. For 192Ir use, energy response changed by a factor of 2.25 over the SDD values of 3 to 9 cm; however a cap made of 0.2 mm thickness silver reduced energy dependence to a factor of 1.25 over the same SDD range, but had the consequence of reducing overall sensitivity by 33%.

For preclinical measurements, dose accuracy of the NanoFOD was within 1.3% of MOSFET measured dose values in a cylindrical mouse phantom at 225 kV for x-ray irradiation at angles of 0, 90, 180, and 270˝. The NanoFOD exhibited small changes in angular sensitivity, with a coefficient of variation (COV) of 3.6% at 120 kV and 1% at 225 kV. When the NanoFOD was placed alongside a MOSFET in the liver of a sacrificed mouse and treatment was delivered at 225 kV with 0.3 mm Cu filter, the dose difference was only 1.09% with use of the 4x4 cm collimator, and -0.03% with no collimation. Additionally, the NanoFOD utilized a scintillator of 11 µm thickness to measure small x-ray fields for microbeam radiation therapy (MRT) applications, and achieved 2.7% dose accuracy of the microbeam peak in comparison to radiochromic film. Modest differences between the full-width at half maximum measured lateral dimension of the MRT system were observed between the NanoFOD (420 µm) and radiochromic film (320 µm), but these differences have been explained mostly as an artifact due to the geometry used and volumetric effects in the scintillator material. Characterization of the energy dependence for the yttrium-oxide based scintillator material was performed in the range of 40-320 kV (2 mm Al filtration), and the maximum device sensitivity was achieved at 100 kV. Tissue maximum ratio data measurements were carried out on a small animal x-ray irradiator system at 320 kV and demonstrated an average difference of 0.9% as compared to a MOSFET dosimeter in the range of 2.5 to 33 cm depth in tissue equivalent plastic blocks. Irradiation of the NanoFOD fiber and scintillator material on a 137Cs gamma irradiator to 1600 Gy did not produce any measurable change in light output, suggesting that the NanoFOD system may be re-used without the need for replacement or recalibration over its lifetime.

For small animal irradiator systems, researchers can deliver a given dose to a target organ by controlling exposure time. Currently, researchers calculate this exposure time by dividing the total dose that they wish to deliver by a single provided dose rate value. This method is independent of the target organ. Studies conducted here used Monte Carlo particle transport codes to justify a new method of dose prescription in mice, that considers organ specific doses. Monte Carlo simulations were performed in the Geant4 Application for Tomographic Emission (GATE) toolkit using a MOBY mouse whole-body phantom. The non-homogeneous phantom was comprised of 256x256x800 voxels of size 0.145x0.145x0.145 mm3. Differences of up to 20-30% in dose to soft-tissue target organs was demonstrated, and methods for alleviating these errors were suggested during whole body radiation of mice by utilizing organ specific and x-ray tube filter specific dose rates for all irradiations.

Monte Carlo analysis was used on 1 µm resolution CT images of a mouse femur and a mouse vertebra to calculate the dose gradients within the bone marrow (BM) compartment of mice based on different radiation beam qualities relevant to x-ray and isotope type irradiators. Results and findings indicated that soft x-ray beams (160 kV at 0.62 mm Cu HVL and 320 kV at 1 mm Cu HVL) lead to substantially higher dose to BM within close proximity to mineral bone (within about 60 µm) as compared to hard x-ray beams (320 kV at 4 mm Cu HVL) and isotope based gamma irradiators (137Cs). The average dose increases to the BM in the vertebra for these four aforementioned radiation beam qualities were found to be 31%, 17%, 8%, and 1%, respectively. Both in-vitro and in-vivo experimental studies confirmed these simulation results, demonstrating that the 320 kV, 1 mm Cu HVL beam caused statistically significant increased killing to the BM cells at 6 Gy dose levels in comparison to both the 320 kV, 4 mm Cu HVL and the 662 keV, 137Cs beams.