Differences in onset and abuse/dependence episodes between prescription opioids and heroin: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

OBJECTIVES: To examine patterns of onset and abuse/dependence episodes of prescription opioid (PO) and heroin use disorders in a national sample of adults, and to explore differences by gender and substance abuse treatment status. METHODS: Analyses of data from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). RESULTS: Of all respondents, 5% (n = 1815) reported a history of nonmedical PO use (NMPOU) and 0.3% (n = 150) a history of heroin use. Abuse was more prevalent than dependence among NMPOUs (PO abuse, 29%; dependence, 7%) and heroin users (heroin abuse, 63%; dependence, 28%). Heroin users reported a short mean interval from first use to onset of abuse (1.5 years) or dependence (2.0 years), and a lengthy mean duration for the longest episode of abuse (66 months) or dependence (59 months); the corresponding mean estimates for PO abuse and dependence among NMPOUs were 2.6 and 2.9 years, respectively, and 31 and 49 months, respectively. The mean number of years from first use to remission from the most recent episode was 6.9 years for PO abuse and 8.1 years for dependence; the mean number of years from first heroin use to remission from the most recent episode was 8.5 years for heroin abuse and 9.7 years for dependence. Most individuals with PO or heroin use disorders were remitted from the most recent episode. Treated individuals, whether their problem was heroin or POs, tended to have a longer mean duration of an episode than untreated individuals. CONCLUSION: Periodic remissions from opioid or heroin abuse or dependence episodes occur commonly but take a long time. Timely and effective use of treatment services are needed to mitigate the many adverse consequences from opioid/heroin abuse and dependence.

A Prescription for the Future of Religious Studies: Second-Order Tradition and the Spirit of Modern Science

An examination of the efficacy of religious studies scholarship through a Kuhnian lens.

Patterns in blood pressure medication use in US incident dialysis patients over the first 6 months.

BACKGROUND: Several observational studies have evaluated the effect of a single exposure window with blood pressure (BP) medications on outcomes in incident dialysis patients, but whether BP medication prescription patterns remain stable or a single exposure window design is adequate to evaluate effect on outcomes is unclear. METHODS: We described patterns of BP medication prescription over 6 months after dialysis initiation in hemodialysis and peritoneal dialysis patients, stratified by cardiovascular comorbidity, diabetes, and other patient characteristics. The cohort included 13,072 adult patients (12,159 hemodialysis, 913 peritoneal dialysis) who initiated dialysis in Dialysis Clinic, Inc., facilities January 1, 2003-June 30, 2008, and remained on the original modality for at least 6 months. We evaluated monthly patterns in BP medication prescription over 6 months and at 12 and 24 months after initiation. RESULTS: Prescription patterns varied by dialysis modality over the first 6 months; substantial proportions of patients with prescriptions for beta-blockers, renin angiotensin system agents, and dihydropyridine calcium channel blockers in month 6 no longer had prescriptions for these medications by month 24. Prescription of specific medication classes varied by comorbidity, race/ethnicity, and age, but little by sex. The mean number of medications was 2.5 at month 6 in hemodialysis and peritoneal dialysis cohorts. CONCLUSIONS: This study evaluates BP medication patterns in both hemodialysis and peritoneal dialysis patients over the first 6 months of dialysis. Our findings highlight the challenges of assessing comparative effectiveness of a single BP medication class in dialysis patients. Longitudinal designs should be used to account for changes in BP medication management over time, and designs that incorporate common combinations should be considered.

Impact of a Point-of-Care Rapid Influenza Test on Antibiotic Prescribing Patterns in Southern Sri Lanka

Background: Acute febrile respiratory illnesses, including influenza, account for a large proportion of ambulatory care visits worldwide. In the developed world, these encounters commonly result in unwarranted antibiotic prescriptions; data from more resource-limited settings are lacking. The purpose of this study was to describe the epidemiology of influenza among outpatients in southern Sri Lanka and to determine if access to rapid influenza test results was associated with decreased antibiotic prescriptions.

Methods: In this pretest- posttest study, consecutive patients presenting from March 2013- April 2014 to the Outpatient Department of the largest tertiary care hospital in southern Sri Lanka were surveyed for influenza-like illness (ILI). Patients meeting World Health Organization criteria for ILI-- acute onset of fever ≥38.0°C and cough in the prior 7 days--were enrolled. Consenting patients were administered a structured questionnaire, physical examination, and nasal/nasopharyngeal sampling. Rapid influenza A/B testing (Veritor System, Becton Dickinson) was performed on all patients, but test results were only released to patients and clinicians during the second phase of the study (December 2013- April 2014).

Results: We enrolled 397 patients with ILI, with 217 (54.7%) adults ≥12 years and 188 (47.4%) females. A total of 179 (45.8%) tested positive for influenza by rapid testing, with April- July 2013 and September- November 2013 being the periods with the highest proportion of ILI due to influenza. A total of 310 (78.1%) patients with ILI received a prescription for an antibiotic from their outpatient provider. The proportion of patients prescribed antibiotics decreased from 81.4% in the first phase to 66.3% in the second phase (p=.005); among rapid influenza-positive patients, antibiotic prescriptions decreased from 83.7% in the first phase to 56.3% in the second phase (p=.001). On multivariable analysis, having a positive rapid influenza test available to clinicians was associated with decreased antibiotic use (OR 0.20, 95% CI 0.05- 0.82).

Conclusions: Influenza virus accounted for almost 50% of acute febrile respiratory illness in this study, but most patients were prescribed antibiotics. Providing rapid influenza test results to clinicians was associated with fewer antibiotic prescriptions, but overall prescription of antibiotics remained high. In this developing country setting, a multi-faceted approach that includes improved access to rapid diagnostic tests may help decrease antibiotic use and combat antimicrobial resistance.

Local kinetic interpretation of entropy production through reversed diffusion.

The time reversal of stochastic diffusion processes is revisited with emphasis on the physical meaning of the time-reversed drift and the noise prescription in the case of multiplicative noise. The local kinematics and mechanics of free diffusion are linked to the hydrodynamic description. These properties also provide an interpretation of the Pope-Ching formula for the steady-state probability density function along with a geometric interpretation of the fluctuation-dissipation relation. Finally, the statistics of the local entropy production rate of diffusion are discussed in the light of local diffusion properties, and a stochastic differential equation for entropy production is obtained using the Girsanov theorem for reversed diffusion. The results are illustrated for the Ornstein-Uhlenbeck process.

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.