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Health Canada approved pembrolizumab in the first-line setting for advanced non-small-cell lung cancer with PD-L1 ≥ 50% and no EGFR/ALK aberration. The keynote 024 trial showed 55% of such patients progress with pembrolizumab monotherapy. We propose that the combination of baseline CT and clinical factors can help identify those patients who may progress. In 138 eligible patients from our institution, we retrospectively collected their baseline variables, including baseline CT findings (primary lung tumor size and metastatic site), smoking pack years, performance status, tumor pathology, and demographics. The treatment response was assessed via RECIST 1.1 using the baseline and first follow-up CT. Associations between the baseline variables and progressive disease (PD) were tested by logistic regression analyses. The results showed 46/138 patients had PD. The baseline CT “number of involved organs” by metastasis and smoking pack years were independently associated with PD (p < 0.05), and the ROC analysis showed a good performance of the model that integrated these variables in predicting PD (AUC: 0.79). This pilot study suggests that the combination of baseline CT disease and smoking PY can identify who may progress on pembrolizumab monotherapy and can potentially facilitate decision-making for the optimal first-line treatment in the high PD-L1 cohort.

AIM: This study tested three dopaminergic medications against a common unmatched placebo condition: hydergine 1 mg three times daily (n = 15); levodopa/carbidopa 25/100 mg three times daily (n = 15); cabergoline 0.5 mg per week (n = 15); and placebo three times daily (n = 15) as potential pharmacotherapies for cocaine dependence. DESIGN: The four-parallel group, Cocaine Rapid Efficacy Screening Trial (CREST) design featured a 2-week baseline period followed by randomization to an 8-week medication condition that included 1 hour per week of cognitive behavioral drug counseling. A safety evaluation was conducted 4 weeks after termination. MEASURES: Outcomes included cocaine metabolites measured in urine, retention and self-reports for drug use, cocaine craving, clinical improvement, mood and HIV risk behaviors. RESULTS: Participants assigned to receive cabergoline provided more urine samples negative for cocaine metabolites (42.4%) than those assigned to receive placebo (25.0%), a statistically significant difference after controlling for baseline differences in self-reported cocaine use (F = 2.95, df = 3; P = 0.05). Cabergoline-treated participants demonstrated a significant improvement over placebo from baseline to week 8 when measured using the Addiction Severity Index (ASI) employment subscale (overall change = - 0.09, SD = 0.10, t = 2.36, P < 0.05). Safety and adverse event measures showed similar rates and types of complaints by treatment condition. CONCLUSIONS: These results, combined with the apparent safety of cabergoline when used with this population, provide empirical support for conducting a larger study of the medication. [ABSTRACT FROM AUTHOR]

A multi-site, open-label study of methylphenidate for treating patients with comorbid diagnoses of attention deficit/hyperactivity disorder and cocaine dependence was performed. Forty-one participants, who met DSM-IV criteria for adult attention deficit/hyperactivity disorder and cocaine dependence, were enrolled into this ten week outpatient study. The targeted total daily dose of methylphenidate was 60 mg (20 mg TID). Participants received individual substance abuse therapy throughout the trial. Safety measures included adverse events, vital signs, and electrocardiograms. Methylphenidate's efficacy was assessed by both objective and subjective measures. Seventy percent of the participants completed final study measures. Safety measures indicated that methylphenidate was well tolerated by the participants. Subjective efficacy measures suggested that participants evidenced improvement in both cocaine dependence and adult attention deficit/hyperactivity disorder symptoms. Quantitative benzoylecgonine indicated that only those participants categorized as being compliant showed improvement. A double-blind, placebo-controlled study of methylphenidate for this population may be warranted. [ABSTRACT FROM AUTHOR]

Abstract The use of Global Positioning Systems (GPS) and Geographical Information Systems (GIS) in disease surveys and reporting is becoming increasingly routine, enabling a better understanding of spatial epidemiology and the improvement of surveillance and control strategies. In turn, the greater availability of spatially referenced epidemiological data is driving the rapid expansion of disease mapping and spatial modeling methods, which are becoming increasingly detailed and sophisticated, with rigorous handling of uncertainties. This expansion has, however, not been matched by advancements in the development of spatial datasets of human population distribution that accompany disease maps or spatial models. Where risks are heterogeneous across population groups or space or dependent on transmission between individuals, spatial data on human population distributions and demographic structures are required to estimate infectious disease risks, burdens, and dynamics. The disease impact in terms of morbidity, mortality, and speed of spread varies substantially with demographic profiles, so that identifying the most exposed or affected populations becomes a key aspect of planning and targeting interventions. Subnational breakdowns of population counts by age and sex are routinely collected during national censuses and maintained in finer detail within microcensus data. Moreover, demographic and health surveys continue to collect representative and contemporary samples from clusters of communities in low-income countries where census data may be less detailed and not collected regularly. Together, these freely available datasets form a rich resource for quantifying and understanding the spatial variations in the sizes and distributions of those most at risk of disease in low income regions, yet at present, they remain unconnected data scattered across national statistical offices and websites. In this paper we discuss the deficiencies of existing spatial population datasets and their limitations on epidemiological analyses. We review sources of detailed, contemporary, freely available and relevant spatial demographic data focusing on low income regions where such data are often sparse and highlight the value of incorporating these through a set of examples of their application in disease studies. Moreover, the importance of acknowledging, measuring, and accounting for uncertainty in spatial demographic datasets is outlined. Finally, a strategy for building an open-access database of spatial demographic data that is tailored to epidemiological applications is put forward.

Divergent thinking is an essential aspect of creativity and has been shown to be affected both by music and physical exercise. While it has been shown that making music and physical exercise can be beneficial for Divergent Thinking in isolation, it is unclear whether the effects can be combined. The present experiment investigated the relation of physical exertion and being in control of music on Divergent Thinking and the possibility of an interaction effect. Seventy-seven predominantly young, German participants were tested with measurements of Divergent Thinking collected after either (1) physical exercise with music listening, (2) making music with a knob setup without physical effort (music control only), or (3) making physical exercise with musical feedback (Jymmin™). Results showed greater increases in Divergent Thinking scores following music-feedback exercise compared to conditions of physical exercise with music listening and music control only. The data thus demonstrate that making music part of a physical exercise routine more strongly leads to the benefit of increased creative capacities, which we argue will be beneficial for athletes to prepare for certain types of competition/performance and as part of regeneration training., (Copyright © 2020 Fritz, Montgomery, Busch, Schneider and Villringer.)

The endogenous presence of gamma-hydroxybutyric acid (GHB) complicates the interpretation of results in cases where an exogenous dosing is suspected. Due to GHB's rapid metabolism and clearance following exogenous doses, hair has become a preferential matrix for confirmation of GHB exposure in drug-facilitated crimes. However, unlike blood and urine where an agreed-upon cut-off concentration for differentiation between endogenous and exogenous GHB has been made, there has been no consensus on a cut-off concentration for hair. This is due in part to the wide inter- and intra-individual variation that has been observed in endogenous GHB hair studies. A large (>50) population study of 214 donors was conducted to better understand these variations and to evaluate whether a cut-off concentration could be established for endogenous GHB in human hair. As seen in our previous study, the inter-individual variation was large, with concentrations ranging from <0.40 to 5.47 ng/mg. This range made an absolute cut-off concentration recommendation inappropriate, so an alternative approach for GHB discrimination was investigated utilizing the intra-individual variation. Male donors appeared to have greater intra-individual variation than female donors, yet it was noted that segment-to-segment variation along the length of hair had minimal change between individual donor's adjacent segments. Overall, 97.1% of the adjacent segment differences were within ±0.5 ng/mg. Therefore, instead of a recommended cut-off concentration, it appears that using adjacent segment concentration differences could be a strategy to assist in differentiating endogenous from single exogenous GHB exposure. In the absence of controlled dosing data, previously published segmented results from controlled and suspected dosing donors are examined using the adjacent segmental difference approach and the results compared to currently used ratio-based calculations., (Published by Oxford University Press 2020.)

While earlier studies have attempted to resolve the challenges encountered when interpreting gamma-hydroxybutyric acid (GHB) concentrations in hair (primarily due to its endogenous presence), few have had large sample sizes. The first objective of this study was to evaluate the inter-individual variation of endogenous GHB concentrations. The second objective, to be detailed in another report, was to assess intra-individual variation and the impact on exogenous GHB discrimination. Over 2,000 hair segments from 141 women and 73 men (all processed hair 3-12 cm long) were analyzed in this study. The raw calculated range of endogenous GHB concentrations was <0.40-5.47 ng/mg with 97.5% of the segmental results calculated less than 2.00 ng/mg. Imputation, assuming a lognormal distribution, was applied to the data to include non-detect (ND) data (

The variation in drug concentrations in human head hair from 22 donors was measured using a synthetic hair matrix (SMx™ hair). This matrix is being reported for the first time as a calibrator for an endogenous substance. In comparison to authentic hair or melanin, the synthetic hair provided a reliable batch-to-batch source of liquid matrix similar in composition to authentic hair, but without detectable concentrations of endogenous gamma-hydroxybutyric acid (GHB). Using the synthetic matrix for calibrator samples, validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantitative method for GHB in human head hair was completed. Validation included the evaluation of the following parameters: accuracy, precision, calibration model, carryover, interferences, limit of detection (LOD), limit of quantitation (LOQ) and processed sample stability. The method was valid over a range of 0.4-12 ng/mg, and its LOD and LOQ were both experimentally estimated to be 0.4 ng/mg. After validation, the variation in endogenous GHB concentrations across multiple donors and locations in the vertex posterior region of the human head were evaluated. Results for 11 non-GHB users showed minimal variability (average 3.0% RSD) across the vertex posterior for hair samples taken from three different areas. There was also low variability (average 1.8% RSD) in repeat samples taken from the same location for 11 other non-users. Endogenous GHB concentrations from the LOD/LOQ to 5.60 ng/mg were determined for the 22 donors using the synthetic hair as a calibrator. These results demonstrate the successful application of a synthetic hair matrix in the analysis of GHB in human hair., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: In neurocysticercosis, the larval form of the pork tapeworm Taenia solium appears to evolve through three phases-active, degenerative and sometimes calcification-before disappearance. The antihelmintic drug, albendazole, has been shown to hasten the resolution of active cysts in neurocysticercosis. Little is known about the time cysts take to progress through each phase, with or without treatment., Methods: We reconfigured brain imaging data from patient level to cyst level for 117 patients in a randomized clinical trial of albendazole in which images were taken at baseline, 1, 6, 12 and 24 mo. Applying a multistate model, we modelled the hazard of a cyst evolving to subsequent cyst phases before the next imaging (vs no change). We examined the impact of albendazole treatment overall and by patient and cyst characteristics on the hazard., Results: Albendazole accelerated the evolution from the active to degenerative phase (HR=2.7, 95% CI 1.3 to 6.5) and from the degenerative phase to disappearance (HR=1.9, 95% CI 1.1 to 3.9). Albendazole's impact was stronger for patients who were male, did not have calcified cysts at baseline and who had multiple cysts in different locations., Conclusions: This research provides a better understanding of where in the cyst trajectory albendazole has the greatest impact., (© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The abuse of gamma-hydroxybutyric acid (GHB) and its suspicion in cases of suspected drug-facilitated sexual assault is of keen interest to forensic toxicology laboratories. This paper reports an extraction, separation and detection procedure for GHB in hair utilizing a combination of liquid-liquid extraction and solid-phase extraction using ethyl acetate and Oasis Max(®) cartridge, respectively, after the hair sample was digested. Analysis was by LC-MS-MS using a gradient separation on an Acclaim(®) Trinity(TM) P1 column performing three multiple-reaction monitoring (MRM) transitions each for GHB and its internal standard. The procedure was validated over a range from 0.4 to 50 ng/mg with estimated limit of detection (LOD) of 0.33 and an administratively set limit of quantitation (LOQ) of 1.2 ng/mg. Twenty hair specimens collected from individuals with no known exposure to GHB were analyzed for matrix interferences and to establish initial background levels of GHB. A wide range of endogenous GHB levels were observed in these samples (from less than the LOQ to 4.4 ng/mg). The results suggest the need for additional studies to better establish the full range of endogenous GHB levels in hair and that extreme caution is required in interpreting GHB findings in hair samples., (Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Samples from a self-proclaimed cocaine (COC) user, from 19 drug users (postmortem) and from 27 drug chemists were extensively washed and analyzed for COC, benzoylecgonine, norcocaine (NC), cocaethylene (CE) and aryl hydroxycocaines by liquid chromatography-tandem mass spectrometry. Published wash criteria and cutoffs were applied to the results. Additionally, the data were used to formulate new reporting criteria and interpretation guidelines for forensic casework. Applying the wash and reporting criteria, hair that was externally contaminated with COC was distinguished from hair collected from individuals known to have consumed COC. In addition, CE, NC and hydroxycocaine metabolites were only present in COC users' hair and not in drug chemists' hair. When properly applied, the use of an extended wash, along with the reporting criteria defined here, will exclude false-positive results from environmental contact with COC., (Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Studies examining refugees from conflict areas have found that persecution in the place of origin is a risk factor for depression. No studies have looked at this association between mental health and the experience of premigration harm due to race, gender or religion in the general population of United States immigrants. The New Immigrant Survey baseline questionnaire was administered to a random sample of adults receiving legal permanent residency in the U.S. in 2003 (n = 8,573), including refugees, asylees and other immigrants. In multivariate analysis controlling for visa type, premigration harm was a predictor of general depression of borderline statistical significance [odds ratio (OR), 1.33; 95 % CI 0.98-1.80, p = 0.068] and a significant predictor of major depression with dysphoria (OR, 2.24; 95 % CI 1.48-3.38, p = 0.0001). These findings suggest that premigration harm is a risk factor for depression in the general immigrant population and not just among refugees.

Existing and proposed metrics for household drinking-water services are intended to measure the availability, safety and accessibility of water sources. However, these attributes can be highly variable over time and space and this variation complicates the task of creating and implementing simple and scalable metrics. In this paper, we highlight those factors - especially those that relate to so-called improved water sources - that contribute to variability in water safety but may not be generally recognized as important by non-experts. Problems in the provision of water in adequate quantities and of adequate quality - interrelated problems that are often influenced by human behaviour - may contribute to an increased risk of poor health. Such risk may be masked by global water metrics that indicate that we are on the way to meeting the world's drinking-water needs. Given the complexity of the topic and current knowledge gaps, international metrics for access to drinking water should be interpreted with great caution. We need further targeted research on the health impacts associated with improvements in drinking-water supplies.

Objectives: The objective of this study was to investigate the quality of on-plot piped water and rainwater at the point of consumption in an area with rapidly expanding coverage of 'improved' water sources., Methods: Cross-sectional study of 914 peri-urban households in Kandal Province, Cambodia, between July-August 2011. We collected data from all households on water management, drinking water quality and factors potentially related to post-collection water contamination. Drinking water samples were taken directly from a subsample of household taps (n = 143), stored tap water (n = 124), other stored water (n = 92) and treated stored water (n = 79) for basic water quality analysis for Escherichia coli and other parameters., Results: Household drinking water management was complex, with different sources used at any given time and across seasons. Rainwater was the most commonly used drinking water source. Households mixed different water sources in storage containers, including 'improved' with 'unimproved' sources. Piped water from taps deteriorated during storage (P < 0.0005), from 520 cfu/100 ml (coefficient of variation, CV: 5.7) E. coli to 1100 cfu/100 ml (CV: 3.4). Stored non-piped water (primarily rainwater) had a mean E. coli count of 1500 cfu/100 ml (CV: 4.1), not significantly different from stored piped water (P = 0.20). Microbial contamination of stored water was significantly associated with observed storage and handling practices, including dipping hands or receptacles in water (P < 0.005), and having an uncovered storage container (P = 0.052)., Conclusions: The microbial quality of 'improved' water sources in our study area was not maintained at the point of consumption, possibly due to a combination of mixing water sources at the household level, unsafe storage and handling practices, and inadequately treated piped-to-plot water. These results have implications for refining international targets for safe drinking water access as well as the assumptions underlying global burden of disease estimates, which posit that 'improved' sources pose minimal risks of diarrhoeal diseases., (© 2013 John Wiley & Sons Ltd.)

This paper presents a fully validated method for the qualitative identification of bromadiolone, brodifacoum, coumachlor, coumatetralyl, difenacoum and warfarin in whole blood specimens. Samples are protein precipitated with acetonitrile, processed via solid-phase extraction and analyzed by high-performance liquid chromatography with high resolution tandem mass spectrometric detection. Limits of detection were 10 ng/mL or better for all analytes.

Oligomerization of the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) is important for optimal ligand binding and internalization. M6P/IGF2R is a tumor suppressor gene that exhibits loss of heterozygosity and is mutated in several cancers. We tested the potential dominant-negative effects of two cancer-associated mutations that truncate M6P/IGF2R in ectodomain repeats 9 and 14. Our hypothesis was that co-expression of the truncated receptors with the wild-type/endogenous full-length M6P/IGF2R would interfere with M6P/IGF2R function by heterodimer interference. Immunoprecipitation confirmed formation of heterodimeric complexes between full-length M6P/IGF2Rs and the truncated receptors, termed Rep9F and Rep14F. Remarkably, increasing expression of either Rep9F or Rep14F provoked decreased levels of full-length M6P/IGF2Rs in both cell lysates and plasma membranes, indicating a dominant-negative effect on receptor availability. Loss of full-length M6P/IGF2R was not due to increased proteasomal or lysosomal degradation, but instead arose from increased proteolytic cleavage of cell-surface M6P/IGF2Rs, resulting in ectodomain release, by a mechanism that was inhibited by metal ion chelators. These data suggest that M6P/IGF2R truncation mutants may contribute to the cancer phenotype by decreasing the availability of full-length M6P/IGF2Rs to perform tumor-suppressive functions such as binding/internalization of receptor ligands such as insulin-like growth factor II., (© 2012 The Authors Journal compilation © 2012 FEBS.)

Background: Inappropriate prescribing of certain medications known as Beers drugs may be harmful to the elderly, because the potential risk for an adverse outcome outweighs the potential benefit., Objectives: (1) To assess Beers drug use in dual enrollees compared to non-duals; (2) to explore the association between dual enrollment status and Beers use, controlling for the effects of age, gender, race/ethnicity, census region, and health status; (3) to assess which medication therapeutic category had the highest Beers use., Design: Cross sectional retrospective review of 2007 Centers for Medicare & Medicaid Service Part D data. Potentially inappropriate medication use was assessed, independent of diagnosis, using the 2003 update by Fick et al., Findings: The likelihood of Beers drug use among duals approximates that of non-duals (OR 1.023, 95% CI 1.020-1.026). Characteristics associated with the receipt of a Beers medication include Hispanic origin, younger age, female gender, poor health status, and residence outside of the U.S.' Northeast region. Genitourinary products had the highest Beers use within medication therapeutic categories among both dual and non-dual enrollees (21.1% and 19.9%, respectively)., Conclusions: Part D data can be successfully used to monitor Beers drug use. With adjustments for several important and easily measured demographic, health, and prescription drug use covariates, Beers drug use appears to be as common among non-dual enrollees as it is among dual enrollees in the Part D program. New Part D drug utilization policies that apply to all beneficiaries may need to be enacted to reduce Beers drug use.

Objectives: (1) to assess non-compliance among Medicare Part D recipients for the cardiovascular medication classes; (2) to identify the probability of noncompliance for each medication class when controlling for the potential risk factors of age, gender, race/ethnic origin, census region, disease burden, dual eligibility enrollment status, Part D plan status, relative out-of-pocket (OOP) non-class costs, and relative OOP daily class costs., Design: Cross sectional retrospective review of 2007 Centers for Medicare & Medicaid Services (CMS) Part D data. All drugs within a drug class were used to conduct the assessment., Findings: Non-compliance was found to be lower than previously reported. Patients who are male, age 65 to 74, Black, or residing in the South are associated with higher noncompliance for cardiovascular medications among the therapeutic classes we studied. Dual eligibility enrollment is typically associated with improved compliance; enrollment in a Medicare Advantage Prescription Drug (MAPD) plan may or may not improve compliance dependent on the therapeutic class under study. Increased disease burden is associated with lower compliance. OOP non-class costs had an opposing effect on compliance as compared to OOP daily costs; higher OOP non-class costs were associated with better compliance., Conclusion: Identifying patient characteristics that may contribute positively or negatively to medication compliance is an essential step to improved therapy. As a strategy to improve compliance, the proper selection of therapy that fits a particular patient is paramount., (Public Domain.)

Segmental analysis of hair for drugs, metabolites, and poisons has been widely reported in the scientific literature over the past two decades. Two fundamental assumptions in interpreting results of such analyses are (1) an average linear growth rate of head hair of 1cm/month and (2) that sample collections occur with the hair being cut directly next to the scalp. The purpose of this study was to evaluate the variability associated with growth rate of human head hair, as well as the ability to uniformly collect hair next to the scalp. The results were used to determine how these factors affect the interpretation of results generated in segmental analysis of hair. A thorough literature review was conducted to assess the range of linear growth of human head hair from the vertex posterior and occipital regions. The results were compiled to establish the average (1.06cm/month), as well as the range of possible growth rates of head hair. The range was remarkable and suggests that conclusions based on the 1-cm/month growth rate could be significantly skewed. A separate study was undertaken to evaluate collection of hair next to the scalp. Fourteen individuals were provided oral instructions, as well as a written standard collection procedure for head hair. The experience levels among the collectors varied from novice to expert. Each individual collected hair from dolls with short- and long-hair. Immediately following each collection, the sampling area was evaluated to determine how close to the scalp the cuts were made, as well as the variability in the lengths of hair remaining at the sampled area. From our collection study, we determined that 0.8±0.1cm of hair was left on the scalp after cutting. When taking into account the amount of hair left on the scalp after collecting, the use of a growth rate of 1.06cm/month, and the assumption that it takes two weeks for newly formed hair in the follicle to reach the scalp, we find that the first 1-cm segment of hair typically corresponds to hair formed 1.3±0.2 to 2.2±0.4 months (95% confidence) earlier. The impact of these findings as it relates to the corresponding time for each additional segment is demonstrated. As a result, we recommend that hair collection be delayed 8 weeks after a suspected ingestion to ensure that the sample fully represents the exposure period. The results of this study suggest that the variability in the growth rate of human head hair, as well as the inconsistent collection of hair, significantly affect the interpretation of results from segmental analysis of hair., (Published by Elsevier Ireland Ltd.)

The purpose of this study is to assess prescription medication poisoning among psychoactive and nonpsychoactive medications used by elderly (65 years or older) Medicare & Medicaid dual enrollees as well as examine contextual components associated with poisoning. Our primary research goal was to compare medication poisonings among psychoactive medications to nonpsychoactive medications. Our second research goal was to identify components influencing medication poisonings and how they interrelate. The approach used a cross-sectional retrospective review of calendar year 2003 Centers for Medicare & Medicaid Service's Medicaid Pharmacy claims data for elderly dual enrollees. Poisonings were identified based on ICD-9-CM categorizations. Poisonings associated with the psychoactive medications were proportionally over twice as high as compared to nonpsychoactive medications (14.3 per 100,000 enrollees and 6.6 per 100,000 enrollees, respectively). Additionally, the two contextual components of (a) use of many drugs and (b) familiarity with the medication have a direct, but competing impact on poisoning. The reasons behind unintentional poisoning in the elderly have been somewhat a mystery. This study is among the first to attempt to distinguish between poisoning events associated with psychoactive medications versus nonpsychoactive medications as well as assess the impact of differing contextual components on medication poisoning.

Few studies have examined the physical isolation of households with trachoma cases. Thus, in this study, we sought to examine the association between household isolation, as measured by distance to social gathering facilities, and risk of trachoma. We hypothesized that households located closer to such facilities would have a decreased risk of trachoma, due to a variety of social, economic, and cultural reasons. To test this hypothesis we conducted a case-control study of 668 households (93 cases, 575 controls) in eight villages in Kongwa District, Tanzania, in 2007. Case households were defined as having a child aged 1-5 years with clinical signs of trachoma. Distance of household's place of residence to three main social gathering facilities - bars/cafés, religious establishments, and commercial/government center - was measured with a portable geographic positioning system. Multiple logistic regression analyses, which controlled for potential confounders and accounted for clustering, demonstrated increased risk of trachoma with increasing distance to social gathering facilities. Compared with distances of ≤700 m, odds of trachoma were approximately two-fold higher for households living >1400 m from bars/cafés and from religious establishments, suggesting increased risk of trachoma for households at the fringes of communities. Targeting these isolated households with special programming along with dissemination through trusted social gathering facilities may improve effectiveness of current prevention efforts., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Marijuana is one of the most commonly used illicit substances. The high usage of this substance results in it being commonly encountered in clinical samples throughout the USA and Europe. Due to its wide availability and use, marijuana is also commonly encountered in forensic toxicology laboratories. The proposed method utilized an automated solid phase extraction (SPE) coupled to liquid chromatography/mass spectrometry (LC/MS). The automated SPE procedure was developed using Hysphere C8-EC sorbent, and the high performance liquid chromatography (HPLC) separation was performed using an Xterra MS C(18) column with a total runtime of 10 min. The standard curves linearity generally fell between 6 and 500 ng/mL. The limits of detection ranged from 2 to 4 ng/mL, and the limits of quantitation ranged from 8 to 12 ng/mL. The bias and imprecision were determined using a simple analysis of variance (single factor). The results demonstrate bias as <11% and percent imprecision as <12% for all components at four quality control levels. This method has been in use for over 2 years and has been applied to numerous forensic samples. When compared to other published methods, it exceeds others in its simplicity and speed of analysis. This method takes advantage of robotics and automation for a total analysis time of 10 min, including sample preparation, separation, and detection.

Objective: To describe current practice during stabilisation of children presenting with critical illness to the district general hospital (DGH), preceding retrieval to intensive care., Design: Observational study using prospectively collected transport data., Setting: A centralised intensive care retrieval service in England and referring DGHs., Patients: Emergency transports to intensive care during 2-month epochs from 4 consecutive years (2005-2008)., Interventions: None., Main Outcome Measures: Proportion of key airway, breathing, and circulatory and neurological stabilisation procedures, such as endotracheal intubation, mechanical ventilation, vascular access, and initiation of inotropic agents, performed by referring hospital staff prior to the arrival of the retrieval team., Results: 706 emergency retrievals were examined over a 4-year period. The median age of transported children was 10 months (IQR, 18 days to 43 months). DGH staff performed the majority of endotracheal intubations (93.7%, CI 91.3% to 95.5%), initiated mechanical ventilation in 76.9% of cases (CI 73.0% to 80.4%), inserted central venous catheters frequently (67.4%, CI 61.7% to 72.6%), and initiated inotropic agents in 43.7% (CI 36.6% to 51.1%). The retrieval team was more likely to perform interventions such as reintubation for air leak, repositioning of misplaced tracheal tubes, and administration of osmotic agents for raised intracranial pressure. The performance of one or more interventions by the retrieval team was associated with severity of illness, rather than patient age, diagnostic group, or team response time (OR 3.62, 95% CI 1.47 to 8.92)., Conclusions: DGH staff appropriately performs the majority of initial stabilisation procedures in critically ill children prior to retrieval. This practice has not changed significantly for the past 4 years, attesting to the crucial role played by district hospital staff in a centralised model of paediatric intensive care.

This study seeks to understand how much beneficiaries knew about the Medicare prescription drug benefit (Part D) and low-income subsidy (LIS) programs and what their experiences were with the programs. Part D enrollees who automatically qualified for the LIS were less likely to report awareness that they could switch among different plans, had lower knowledge scores, and were more likely to have medications not covered by the plan compared to beneficiaries who applied for the LIS and others who enrolled in Part D but did not receive the LIS. Communication efforts to the LIS population, particularly for beneficiaries deemed automatically eligible for the LIS, need to continually make them aware of their benefits and protections in Part D.

The existing evidence regarding latrines and trachoma is inconclusive. Using more precise sanitation measures we examine the association between use and quality of latrines and risk of trachoma. We conducted a case-control study of 678 households (95 cases, 583 controls) in eight villages in Kongwa District, Tanzania. Case households were defined as having a sentinel child with clinical signs of trachoma. A latrine quality score was calculated based on seven indicators and case and control households were compared with respect to use and quality of latrines. Logistic regression analyses controlled for potential confounders. Latrine use was significantly greater in control households than in case households (90.4 vs. 76.8%, P=0.03). The protective effect of latrine use persisted even after controlling for household characteristics significant at P <0.20 (adjusted OR=0.56 [95% CI: 0.32-0.98]). Contrary to expectation, we did not find an inverse association between increasing latrine quality and decreasing odds of trachoma. Although latrine use in the communities was high, latrines, regardless of quality, were significantly associated with decreased risk of trachoma. These findings underscore the importance of achieving 100% latrine use in communities., (Copyright 2009 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.)

Sharing latrines is common in sub-Saharan Africa with anecdotal accounts suggesting a link between water-, sanitation-, and hygiene-related disease and poorly maintained communal latrines. This study examines this link by assessing the association between shared latrines compared with private latrines and risk of trachoma. In 2007, as part of a larger case-control study, we conducted a sub-study on latrine sharing in 594 households (92 cases, 502 controls) in seven rural Tanzanian communities. Case households were defined by having a child with clinical signs of trachoma. Latrine use was associated with a decreased risk of trachoma and there was no difference in risk between households using shared compared with private latrines (adjusted odds ratio = 0.95 [95% confidence interval = 0.55-1.67]). This study emphasizes the need to promote latrine use, which can be facilitated through latrine sharing in resource scarce areas, for prevention of trachoma.

γ-Hydroxybutyric acid (GHB) and its metabolic precursors, γ-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), may be among the most favored drugs used to commit drug-facilitated sexual assault (DFSA). In fact, federal legislation was enacted in the form of the Hillory J. Farias and Samantha Reid Date-Rape Drug Prohibition Act of 2000 to control and penalize use and distribution of GHB, GBL, and 1,4-BD. Unfortunately, solid proof of their use in many cases is difficult to obtain because GHB, GBL, and 1,4-BD have strong sedative and memory-impairing effects and are rapidly eliminated after ingestion. To further complicate the matter, GHB is a metabolite of γ-aminobutyric acid (GABA), a naturally occurring neurotransmitter in humans. This review focuses on the chemistry and pharmacology of these drugs and their use in DFSA. An overview of analytical techniques used to identify their presence is provided, as well as guidance on the toxicological interpretation of findings of GHB in biological specimens., (Copyright © 2010 Central Police University.)

While there is a general belief throughout parts of the world that drug-facilitated sexual assault (DFSA) cases have dramatically increased in recent times, the true prevalence of DFSA will never be fully realized. This is due to the general underreporting of sexual assaults, the pharmacodynamics of the drugs used to commit these crimes, the challenges that delayed reporting can impose on the charges associated with these cases, and the lack of a uniform system of defining and statistically capturing data on sexual assaults that are facilitated by drugs. Over the years, a number of studies have attempted to quantitate the frequency of DFSA in various countries throughout the world. Unfortunately, no two studies have taken the same approach in their assessment of DFSA; therefore, it is difficult to combine their results to allow for a realistic evaluation of how prevalent DFSA really is. This manuscript reviews the studies that have attempted such an assessment of DFSA prevalence to compare and contrast their results., (Copyright © 2010 Central Police University.)

This article provides the reader with an understanding of the numerous challenges of drug-facilitated sexual assaults (DFSA). The challenges are categorized as follows: the drugs, reporting the crime, evidence collection, and laboratory analysis of specimens. The challenges associated with the drugs used to commit DFSA emphasizes the pharmacological effects of strong central nervous system depressants and how the pharmacokinetics and pharmacodynamics of these drugs create difficulties in an investigation. For example, while sexual assaults are generally considered to be a significantly underreported crime, the drug effects further complicate victims' reporting to law enforcement. Any delay in reporting decreases the ability of a laboratory to detect the presence of drugs or metabolites in useful evidentiary specimens such as blood and urine. Finally, differences in instrumentation and mission from one laboratory to the next will impact the ability to provide consistent identification of DFSA drugs or metabolites in these cases. Although the true prevalence of DFSAs will never be fully known, acknowledgment of the many challenges that come with these cases provides insight as to how to improve chances of successfully investigating DFSA allegations., (Copyright © 2010 Central Police University.)

Benzodiazepines are one of the classes of drugs most commonly associated with drug-facilitated sexual assault. As a widely prescribed class of medications and abused drugs, benzodiazepines are extensively available. Their sedating and amnesic effects make them effective candidates for use in drug-facilitated assaults. Detection methods for benzodiazepines and their metabolites in biological fluids are plentiful, but methods must be tailored to the low concentrations of drugs and metabolites expected to be encountered in these cases., (Copyright © 2010 Central Police University.)

Objectives: To address the association between inappropriate prescribing for the elderly and adverse outcomes and to identify the magnitude of the cost of medication-associated injury in this population., Design: Cross sectional., Setting: United States, 2003., Patients: 5,412,678 dually eligible Medicare/Medicaid enrollees aged 65 years or older., Intervention: Beers and non-Beers medications with potential central nervous system adverse effects of dizziness/vertigo, drowsiness, and/or fainting were assessed. Emergency department (ED) visits with admitting diagnoses pertaining to injuries for elderly enrollees dually eligible for Medicare and Medicaid during the calendar year were linked to prescriptions filled during the 90 days preceding the visit., Main Outcome Measure: For each drug, the proportion of ED-related fills and the Medicare average revenue charge per injury-related ED visit were calculated., Results: Several drugs not currently on the Beers list were found to be associated with high proportions of ED-related fills: methadone had the highest proportion of any of the drugs studied (12.3 per 1,000 fills), and bethanechol (7.8 per 1,000 fills) had the highest proportion among genitourinary products. Regarding narcotic analgesics, propoxyphene (7.7 per 1,000 fills) had a higher association with injury than morphine (6.6 per 1,000 fills) or tramadol (6.5 per 1,000 fills). For cardiovascular agents, clonidine (4.7 per 1,000 fills) and doxazosin (3.6 per 1,000 fills) had higher associations with injury than nifedipine (3.3 per 1,000 fills). Fentanyl, a non-Beers medication, was associated with the most expensive injury-related ED visits ($1,263 average revenue charge)., Conclusion: Beers medications are associated with high injury-related ED visit rates for the elderly, and a number of drugs not currently on the Beers list also pose an apparent risk for injury-related visits.

The Medicare Part D drug benefit created choices for beneficiaries among many prescription drug plans with varying levels of coverage. As a result, Medicare enrollees with high prescription drug costs have strong incentives to enroll in Part D, especially in plans with more comprehensive coverage. To measure this potential problem of "adverse selection," which could threaten plans' finances, we compared baseline characteristics among groups of beneficiaries with various drug coverage arrangements in 2006. We found some significant differences. For example, enrollees in stand-alone prescription drug plans, especially in plans offering benefits in the coverage gap, or "doughnut hole," had higher baseline drug costs and worse health than enrollees in Medicare Advantage prescription drug plans. Although risk-adjusted payments and other measures have been put in place to account for selection, these patterns could adversely affect future Medicare costs and should be watched carefully.

Marijuana is one of the most commonly abused illicit substances in the USA, making cannabinoids important to detect in clinical and forensic toxicology laboratories. Historically, cannabinoids in biological fluids have been derivatized and analyzed by gas chromatography/mass spectrometry (GC/MS). There has been a gradual shift in many laboratories towards liquid chromatography/mass spectrometry (LC/MS) for this analysis due to its improved sensitivity and reduced sample preparation compared with GC/MS procedures. This paper reports a validated method for the analysis of Delta(9)-tetrahydrocannabinol (THC) and its two main metabolites, 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH) and 11-hydroxy-Delta(9)-tetrahydrocannabinol (THC-OH), in whole blood samples. The method has also been validated for cannabinol (CBD) and cannabidiol (CDN), two cannabinoids that were shown not to interfere with the method. This method has been successfully applied to samples both from living people and from deceased individuals obtained during autopsy. This method utilizes online solid-phase extraction (SPE) with LC/MS. Pretreatment of samples involves protein precipitation, sample concentration, ultracentrifugation, and reconstitution. The online SPE procedure was developed using Hysphere C8-EC sorbent. A chromatographic gradient with an Xterra MS C(18) column was used for the separation. Four multiple-reaction monitoring (MRM) transitions were monitored for each analyte and internal standard. Linearity generally fell between 2 and 200 ng/mL. The limits of detection (LODs) ranged from 0.5 to 3 ng/mL and the limits of quantitation (LOQs) ranged from 2 to 8 ng/mL. The bias and imprecision were determined using a simple analysis of variance (ANOVA: single factor). The results demonstrate bias as <7%, and imprecision as <9%, for all components at each quantity control level., (Published in 2009 by John Wiley & Sons, Ltd.)

The presence of norovirus (NoV) genogroup I (GI) and II (GII) was evaluated using real-time reverse transcription polymerase chain reaction (rRT-PCR) in the influent, two midtreatment locations, and final effluent of a three-pond serial waste stabilization pond system from December 2005 through June 2006. Additionally, influent and effluent samples were filtered through a cascade of three membrane filters with sequentially smaller pores to determine the size range of particles with which GI and GII were associated. NoV GI and GII removal occurs primarily in the third pond. Viruses were found on large settleable particles (retained on a 180 microm filter), on smaller suspended particles (retained on a 0.45 microm filter), on colloidal particles (retained on a positively charged 0.45 microm filter), and in the final filtrate. Both GI and GII in influent samples were found to be dominantly associated with particles smaller than 180 microm, thereby suggesting that particle settling is not the main virus removal mechanism in the waste stabilization pond system. On average, NoV detected in filtered effluent samples were associated with particles between 0.45 and 180 microm in diameter (47 and 67% of detected GI and GII, respectively). The presence of NoV GI and GII in the final filtrate of influent and effluent samples shows that positively charged membrane filters often used for viral concentration methods are not capable of trapping all viruses present in wastewater samples.

As laboratories are called upon to develop novel, fast, and sensitive methods, here we present a completely automated method for the analysis of cocaine and its metabolites (benzoylecgonine, ecgonine methyl ester, ecgonine and cocaethylene) from whole blood. This method utilizes an online solid-phase extraction (SPE) with high performance liquid chromatographic separation and tandem mass spectrometric detection. Pretreatment of samples involve only protein precipitation and ultracentrifugation. An efficient online solid-phase extraction (SPE) procedure was developed using Hysphere MM anion sorbent. A gradient chromatography method with a Gemini C6-Phenyl (50mmx3.00mm i.d., 5microm) column was used for the complete separation of all components. Analysis was by positive ion mode electrospray ionization tandem mass spectrometry, using multiple reaction monitoring (MRM) to enhance the selectivity and sensitivity of the method. For the analysis, two MRM transitions are monitored for each analyte and one transition is monitored for each internal standard. With a 30-microL sample injection, linearity was analyte dependent but generally fell between 8 and 500ng/mL. The limits of detection (LODs) for the method ranged from 3 to 16ng/mL and the limits of quantitation (LOQs) ranged from 8 to 47ng/mL. The bias and precision were determined using a simple analysis of variance (ANOVA: single factor). The results demonstrate bias as <7%, and %precision as <9% for all components at each QC level.

A rapid, simple, and completely automated method for the analysis of cocaine and its metabolites in urine has been developed. The method utilizes online solid-phase extraction (SPE) with liquid chromatographic separation and tandem mass spectrometric detection (MS-MS). An efficient online SPE procedure was developed using Hyspheretrade mark MM anion sorbent. A gradient chromatography method with a Gemini C6-Phenyl (50 x 3.00-mm i.d., 5 microm) column was used for the separation of all compounds. Detection was by positive ion mode electrospray ionization MS-MS. Multiple reaction monitoring (MRM) was used to enhance the selectivity and sensitivity of the method. Two MRM transitions were monitored for each analyte and one transition for each internal standard. Linearity was analyte-dependent but generally ranged from 7 to 1000 ng/mL. The limits of detection for the method ranged from 3 to 23 ng/mL and the limits of quantitation ranged from 7 to 69 ng/mL. Quality control (QC) samples were analyzed for each analyte in triplicate at 50, 200, and 800 ng/mL. The bias and precision were determined using a simple analysis of variance (ANOVA: single factor). The results demonstrated bias as < 5% and % precision as < 9% for all components at each QC level.

This letter reports a straightforward means of collecting two-dimensional electronic (2D-E) spectra using optical tools common to many research groups involved in ultrafast spectroscopy and quantum control. In our method a femtosecond pulse shaper is used to generate a pair of phase stable collinear laser pulses which are then incident on a gas or liquid sample. The pulse pair is followed by an ultrashort probe pulse that is spectrally resolved. The delay between the collinear pulses is incremented using phase and amplitude shaping and a 2D-E spectrum is generated following Fourier transformation. The partially collinear beam geometry results in perfectly phased absorptive spectra without phase twist. Our approach is much simpler to implement than standard non-collinear beam geometries, which are challenging to phase stabilize and require complicated calibrations. Using pulse shaping, many new experiments are now also possible in both 2D-E spectroscopy and coherent control.

Background: The potential efficacy of tiagabine for treating cocaine dependence is suggested by both pre-clinical research and two small clinical trials., Method: One hundred and forty one participants who met DSM-IV criteria for cocaine dependence were enrolled into this 12-week, double blind, placebo controlled outpatient trial. Participants received either tiagabine (20 mg/day) or matching placebo. All participants received 1h of manualized individual cognitive behavioral therapy on a weekly basis. Outcome measures included cocaine use as determined by self-report confirmed with urine benzoylecgonine (BE) results, and qualitative and quantitative urine toxicology measures. Safety measures included adverse events, EKGs, vital signs, and laboratory tests., Results: Seventy-nine participants (i.e., 56%) completed the 12-week trial. The safety results suggest that tiagabine was safe and generally well tolerated by the participants. Participants in both groups improved significantly on cocaine craving and global functioning, with no significant differences between the groups. There were no significant changes in cocaine use as measured by self-report confirmed by urine BE or by quantitative urine toxicology results. Qualitative urine toxicology results suggest a possible weak effect for tiagabine in reducing cocaine use., Conclusion: These results suggest that tiagabine, at a dose of 20 mg/day, did not have a robust effect in decreasing cocaine use.