Document d'orientation sur la distribution et l'utilisation de trousses de naloxone à emporter par les intervenants et intervenantes communautaires en cas de surdose au Canada.

CONTEXTE: La toxicité croissante des opioïdes dans le marché illicite des drogues a fait exploser le nombre de surdoses au Canada et ailleurs dans le monde; le programme de naloxone à emporter (NàE) est une intervention fondée sur des données probantes qui consiste à distribuer des trousses contenant de la naloxone aux membres de la communauté susceptibles d'être témoins d'une surdose. L'objectif du présent document d'orientation est de formuler des recommandations stratégiques à l'intention des programmes fédéraux, provinciaux et territoriaux de NàE, en s'appuyant sur des données probantes issues de la documentation scientifique, de la littérature grise et des communautés, à la lumière de 11 années de distribution de NàE au Canada. MÉTHODES : Le groupe d'élaboration des documents d'orientation sur la naloxone, une équipe multidisciplinaire composée de personnes ayant une expertise et une expérience vécue en matière de toxicomanie, a appliqué l'outil AGREE II (Appraisal of Guidelines for Research & Evaluation) afin d'éclairer l'élaboration du présent document d'orientation. En vue de l'élaboration de nos recommandations, nous avons procédé entre décembre 2021 et septembre 2022 à une revue systématique de tous les types d'ouvrages dans le but de recueillir les données probantes publiées, ainsi que les données probantes et l'expertise issues de la communauté. Nous avons sollicité des commentaires sur nos recommandations préliminaires par le biais d'un comité de révision externe et d'un processus de participation du public. Le projet a été financé par les Instituts de recherche en santé du Canada dans le cadre de l'Initiative canadienne de recherche sur l'abus de substances (ICRAS). Nous avons appliqué les principes du Réseau international en matière de lignes directrices (Guidelines International Network) pour gérer les intérêts concurrents. RECOMMANDATIONS: Les données probantes existantes issues de la documentation sur la NàE étaient de faible qualité. Pour élaborer nos recommandations, nous avons incorporé des données probantes tirées de la documentation scientifique et de la littérature grise, ainsi que l'expertise de la communauté. Nos recommandations portent sur 3 volets : les voies d'administration de la naloxone, le contenu des trousses de NàE et les interventions en cas de situations de surdose. Les trousses distribuées par les programmes de naloxone à emporter doivent offrir le choix entre les préparations intramusculaire et intranasale. Le contenu recommandé de la trousse comprend la naloxone, un dispositif d'administration de la naloxone, un équipement de protection individuelle, des instructions et un étui de transport. Les intervenants et intervenantes communautaires formés à la réponse aux surdoses doivent prioriser la respiration artificielle en cas de dépression respiratoire, et la réanimation cardiorespiratoire (RCR) conventionnelle en cas d'arrêt cardiaque, entre autres interventions. INTERPRÉTATION : Ce projet d'élaboration d'un document d'orientation vise à guider les programmes de NàE au Canada dans un contexte où les données probantes publiées sont rares; les recommandations ont été élaborées en collaboration avec diverses parties prenantes.

Qmatey: an automated pipeline for fast exact matching-based alignment and strain-level taxonomic binning and profiling of metagenomes.

Metagenomics is a powerful tool for understanding organismal interactions; however, classification, profiling and detection of interactions at the strain level remain challenging. We present an automated pipeline, quantitative metagenomic alignment and taxonomic exact matching (Qmatey), that performs a fast exact matching-based alignment and integration of taxonomic binning and profiling. It interrogates large databases without using metagenome-assembled genomes, curated pan-genes or k-mer spectra that limit resolution. Qmatey minimizes misclassification and maintains strain level resolution by using only diagnostic reads as shown in the analysis of amplicon, quantitative reduced representation and shotgun sequencing datasets. Using Qmatey to analyze shotgun data from a synthetic community with 35% of the 26 strains at low abundance (0.01-0.06%), we revealed a remarkable 85-96% strain recall and 92-100% species recall while maintaining 100% precision. Benchmarking revealed that the highly ranked Kraken2 and KrakenUniq tools identified 2-4 more taxa (92-100% recall) than Qmatey but produced 315-1752 false positive taxa and high penalty on precision (1-8%). The speed, accuracy and precision of the Qmatey pipeline positions it as a valuable tool for broad-spectrum profiling and for uncovering biologically relevant interactions.

The impact of relaxing restrictions on take-home doses during the COVID-19 pandemic on program effectiveness and client experiences in opioid agonist treatment: a mixed methods systematic review.

BACKGROUND: The COVID-19 pandemic led to an unprecedented relaxation of restrictions on take-home doses in opioid agonist treatment (OAT). We conducted a mixed methods systematic review to explore the impact of these changes on program effectiveness and client experiences in OAT. METHODS: The protocol for this review was registered in PROSPERO (CRD42022352310). From Aug.-Nov. 2022, we searched Medline, Embase, CINAHL, PsycInfo, Web of Science, Cochrane Register of Controlled Trials, and the grey literature. We included studies reporting quantitative measures of retention in treatment, illicit substance use, overdose, client health, quality of life, or treatment satisfaction or using qualitative methods to examine client experiences with take-home doses during the pandemic. We critically appraised studies using the Mixed Methods Appraisal Tool. We synthesized quantitative data using vote-counting by direction of effect and presented the results in harvest plots. Qualitative data were analyzed using thematic synthesis. We used a convergent segregated approach to integrate quantitative and qualitative findings. RESULTS: Forty studies were included. Most were from North America (23/40) or the United Kingdom (9/40). The quantitative synthesis was limited by potential for confounding, but suggested an association between take-home doses and increased retention in treatment. There was no evidence of an association between take-home doses and illicit substance use or overdose. Qualitative findings indicated that take-home doses reduced clients' exposure to unregulated substances and stigma and minimized work/treatment conflicts. Though some clients reported challenges with managing their medication, the dominant narrative was one of appreciation, reduced anxiety, and a renewed sense of agency and identity. The integrated analysis suggested reduced treatment burden as an explanation for improved retention and revealed variation in individual relationships between take-home doses and illicit substance use. We identified a critical gap in quantitative measures of patient-important outcomes. CONCLUSION: The relaxation of restrictions on take-home doses was associated with improved client experience and retention in OAT. We found no evidence of an association with illicit substance use or overdose, despite the expansion of take-home doses to previously ineligible groups. Including patient-important outcome measures in policy, program development, and treatment planning is essential to ensuring that decisions around take-home doses accurately reflect their value to clients.

Guidance on take-home naloxone distribution and use by community overdose responders in Canada.

BACKGROUND: The increasing toxicity of opioids in the unregulated drug market has led to escalating numbers of overdoses in Canada and worldwide; takehome naloxone (THN) is an evidence-based intervention that distributes kits containing naloxone to people in the community who may witness an overdose. The purpose of this guidance is to provide policy recommendations for territorial, provincial and federal THN programs, using evidence from scientific and grey literature and community evidence that reflects 11 years of THN distribution in Canada. METHODS: The Naloxone Guidance Development Group - a multidisciplinary team including people with lived and living experience and expertise of drug use - used the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument to inform development of this guidance. We considered published evidence identified through systematic reviews of all literature types, along with community evidence and expertise, to generate recommendations between December 2021 and September 2022. We solicited feedback on preliminary recommendations through an External Review Committee and a public input process. The project was funded by the Canadian Institutes of Health Research through the Canadian Research Initiative in Substance Misuse. We used the Guideline International Network principles for managing competing interests. RECOMMENDATIONS: Existing evidence from the literature on THN was of low quality. We incorporated evidence from scientific and grey literature, and community expertise to develop our recommendations. These were in 3 areas: routes of naloxone administration, THN kit contents and overdose response. Take-home naloxone programs should offer the choice of both intramuscular and intranasal formulations of naloxone in THN kits. Recommended kit contents include naloxone, a naloxone delivery device, personal protective equipment, instructions and a carrying case. Trained community overdose responders should prioritize rescue breathing in the case of respiratory depression, and conventional cardiopulmonary resuscitation in the case of cardiac arrest, among other interventions. INTERPRETATION: This guidance development project provides direction for THN programs in Canada in the context of limited published evidence, with recommendations developed in collaboration with diverse stakeholders.

Provider experiences with relaxing restrictions on take-home medications for opioid use disorder during the COVID-19 pandemic: A qualitative systematic review.

BACKGROUND: Historical restrictions on take-home medications for opioid use disorder have generated considerable debate. The COVID-19 pandemic shifted the perceived risks and benefits of daily clinic attendance and led to widespread policy reform, creating an unprecedented opportunity to explore the impact of more flexible prescribing. We conducted a qualitative systematic review to synthesize the evidence on providers' experiences with relaxing restrictions on take-home doses of medications prescribed for opioid use disorder during the COVID-19 pandemic. METHODS: The protocol for this systematic review was registered in PROSPERO (CRD42022360589; https://www.crd.york.ac.uk/prospero/). From Sept.-Nov. 2022, we searched Medline, Embase, CINAHL, PsycInfo, Web of Science, the Cochrane Register of Controlled Trials, and the grey literature from 2020 onward. Studies were eligible for inclusion if they used qualitative methods to investigate providers' experiences with relaxed restrictions on take-home medications for opioid use disorder during the COVID-19 pandemic. We appraised study quality using the CASP qualitative checklist and used thematic synthesis and GRADE-CERQual to synthesize the results. RESULTS: We retrieved 13 articles representing 11 studies. Six were conducted in the United States and most focused on changes to methadone treatment. Providers' experiences with increased flexibilities around take-homes were broadly positive, despite widespread initial concern over client safety and the potential for medication misuse. For a small number of providers, concerns about diversion were a specific manifestation of more general unease with loss of control over clients and the treatment process. Most providers appreciated increased flexibilities and described them as enabling more individualized, person-centered care. CONCLUSION: Our findings support the continuation of flexibilities around take-homes and demonstrate that regulations and policies that reduce flexibility around take-homes conflict with person-centered approaches to care. Stronger guidance and support from professional regulatory agencies may help increase uptake of flexibilities around take-homes.

Race, Toxic Exposures, and Environmental Health: The Contestation of Lupus among Farmworkers.

Extant research has established that low-wage workers of color are at higher risk for occupational exposures. While the medical sociology literature regarding contested illness provides insights into the dynamics surrounding workplace exposures, some environmental illnesses such as lupus have gotten scant analytical attention. This is a significant gap because women of color, who are more likely to hold these high-risk jobs, are disproportionately affected by the disease. We examine a case of pesticide exposure among Black women farmworkers in Florida. We investigate how race and occupation intersect to shape lived experiences with toxics and what role race plays in the process of contesting exposures and illness. Our data include in-depth interviews (N = 36), media coverage, and archival materials. Our findings indicate that race-related factors played an important part in shaping the farmworkers' experiences with exposures, illness, and interaction with elite actors.

Identification of Thresholds on Population Density for Understanding Transmission of COVID-19.

Pathways of transmission of coronavirus (COVID-19) disease in the human population are still emerging. However, empirical observations suggest that dense human settlements are the most adversely impacted, corroborating a broad consensus that human-to-human transmission is a key mechanism for the rapid spread of this disease. Here, using logistic regression techniques, estimates of threshold levels of population density were computed corresponding to the incidence (case counts) in the human population. Regions with population densities greater than 3,000 person per square mile in the United States have about 95% likelihood to report 43,380 number of average cumulative cases of COVID-19. Since case numbers of COVID-19 dynamically changed each day until 30 November 2020, ca. 4% of US counties were at 50% or higher probability to 38,232 number of COVID-19 cases. While threshold on population density is not the sole indicator for predictability of coronavirus in human population, yet it is one of the key variables on understanding and rethinking human settlement in urban landscapes.

Data-driven models for replication kinetics of Orthohantavirus infections.

The Hantaviridae constitute a family of viruses harbored by mice, rats, shrews, voles, moles and bats. Intriguingly, only viruses harbored by mice and rats may cause disease in humans with up to 40% case fatality rate in the Americas. Transmission of virus from rodents to humans occurs via the respiratory route and results in replication of the virus in the microvascular endothelial cells of the lung or kidney. Understanding the replication kinetics of these viruses in various cell types and how replication is abrogated by the host is critical to the development of effective therapeutics for treatment for which there are none. We formulate several new ordinary differential equation (ODE) models to examine the replication kinetics of Prospect Hill orthohantavirus (PHV). The models are distinguished by the distribution of the viral replication delay. A new threshold, RGE, the genome equivalent replication number, is defined in terms of the model parameters. New final density relations are derived that associate RGE to the asymptotic number of virions in each model. All models are fit to real time (qRT)-PCR data of genomic RNA from PHV released from Vero E6 cells over 192 h. A sensitivity analysis of the parameters is performed and models are tested for best fit. Our findings provide a basis for future research into formulating more complex mathematical models for evaluation of the replication of hantaviruses in various cell types and sources.

Guideline development in harm reduction: Considerations around the meaningful involvement of people who access services.

Background: Harm reduction seeks to minimizes the negative effects of drug use while respecting the rights of people with lived and living experience of substance use (PWLLE). Guideline standards ("guidelines for guidelines") provide direction on developing healthcare guidelines. To identify essential considerations for guideline development within harm reduction, we examined whether guideline standards are consistent with a harm reduction approach in their recommendations on involving people who access services. Methods: We searched the literature from 2011-2021 to identify guideline standards used in harm reduction and publications on involving PWLLE in developing harm reduction services. We used thematic analysis to compare their guidance on involving people who access services. Findings were validated with two organizations of PWLLE. Results: Six guideline standards and 18 publications met inclusion criteria. We identified three themes related to involving people who access services: Reasons for Involvement, Methods of Involvement, and Factors in Success. Subthemes varied across the literature. We identified five essential considerations for guideline development in harm reduction: establishing a shared understanding of reasons for involving PWLLE; respecting their expertise; partnering with PWLLE to ensure appropriate engagement; incorporating perspectives of populations disproportionately affected by substance use; and securing resources. Conclusion: Guideline standards and the harm reduction literature approach the involvement of people who access services from different perspectives. Thoughtful integration of the two paradigms can improve guidelines while empowering PWLLE. Our findings can support the development of high-quality guidelines that align with the fundamental principles of harm reduction in their involvement of PWLLE.

Protocol and Preliminary Results of the Nutritarian Women's Health Study: A Longitudinal Effectiveness-Implementation Hybrid Study Assessing Dietary Intake and Health Outcomes.

Whole-food plant-rich dietary patterns have been shown to be associated with significant health benefits and disease-risk reduction. One such program, which has been gaining popularity, is the micronutrient-dense plant-rich (mNDPR) "Nutritarian" diet. The goal of this study is to determine the feasibility of implementing an online mNDPR "Nutritarian" intervention program and to determine the effectiveness of this program in reducing risk of chronic disease in women. The Nutritarian Women's Health Study is a long-term online longitudinal hybrid effectiveness-implementation study. Participants are recruited through social media, medical professionals/offices, and nutrition-related events and conferences. Participants receive online nutrition education and complete regular self-reported questionnaires regarding lifestyle, nutrition practices, and health. The online intervention program appears to be feasible and effective. Some decline in dietary adherence, particularly for certain food types, was observed during the study. For groups at risk, based on body mass index or waist-to-height ratio, there were initial decreases in body mass index and waist-to-height that leveled off over time, in some cases returning to baseline measures. The study suggests the implementation of the Nutritarian dietary pattern, through an online intervention component, may be effective in reducing the risk of chronic disease, with implications for clinical and public health practice.

Defining Success for A Declining Resource: Mental Models of Oyster Management in Apalachicola, Florida.

Wild oyster populations are in decline globally, affecting communities of generational fishers and changing the cultural dynamics of coastal communities. Managers have employed a range of approaches to conserve and restore oyster populations and sustainable fisheries; yet there is little agreement among managers, scientists, and resource users regarding what constitutes success. This study uses a qualitative, mental models approach to compare understandings of management, perceptions of management success, and barriers to achieving successful management outcomes among three critical stakeholder groups: natural resource managers, oyster harvesters, and aquaculture farmers. We found similarities among the mental models of all three groups in the causes and consequences of the oyster fishery decline, but major differences in definitions of management, factors needed for successful management, and barriers to success. This study takes a more comprehensive look at the understandings of stakeholders than previous research by mapping the causes and effects, from the decline of the oyster fishery to expectations of future success. Managers can improve stakeholder investment in management projects by gaining a better understanding of the differing definitions of project success, stakeholder participation, and stakeholder understanding of the role of management.

Cholesterotic fibrous histiocytoma: Case report and literature review.

Cholesterotic fibrous histiocytoma is a particularly rare variant of dermatofibroma that is distinguished histopathologically by the presence of prominent cholesterol deposits within the lesion. We report the case of a 54-year-old male with poorly controlled hyperlipidemia who presented with a firm violaceous papule on the right shin, diagnosed as a cholesterotic fibrous histiocytoma. We also review and summarize the existing literature on this uncommon entity.

Impact of a 6-Month Micronutrient-Dense Plant-Rich Nutrition Intervention on Health and Well-Being at the Worksite.

This nonrandomized pilot study utilized the health belief model and the theory of planned behavior to assess the effectiveness of perceived behavioral control to determine the impact of a micronutrient-dense plant-rich (mNDPR) dietary intervention on employee health and wellness at the worksite. Seventy-one employees and/or spouses (≥18 years) who met the inclusion criteria were recruited from a regional medical center and a local university. Participants were provided more than 14 hours of in-person lecture combined with take-home materials, and electronic resources to support participants in their transition and adherence to the dietary plan. The study consisted of a 6-hour introductory session followed by weekly 1-hour meetings for 7 consecutive weeks and then monthly 1-hour meetings, for 4 consecutive months over the span of 6 months. Retention of participants was approximately 55 percent. Participants were assessed for measures of weight, waist circumference, and blood pressure; physiological measures of blood cholesterol, triglycerides, blood glucose, and hemoglobin A1c; and well-being measures of gastroesophageal reflux disease, depression, sleep, pain, and worksite productivity, pre-, mid-, and post-intervention. A significant reduction was seen in weight (F(2, 78) = 19.81, p < 0.001) with a mean reduction of 6.65 lb., waist circumference (F(2, 72) = 40.914, p < 0.001) with a mean reduction of 2.8 inches, total cholesterol (F(2, 70) = 19.09, p < 0.001) with a mean reduction of 17.81 mg/dL, HDL (F(2, 70) = 4.005, p=0.023) with a mean reduction of 3.61 mg/dL, LDL (F(2, 56) = 10.087, p < 0.001) with a mean reduction of 13.1 mg/dL, blood glucose (F(2, 70) = 6.995, p=0.002) with a mean reduction of 3.7 mg/dL, hemoglobin A1c (paired samples t (39) = 2.689, p=0.01) with a mean reduction of 0.118%, GERD (F(2, 72) = 7.940, p=0.001, MSE = 4.225) with a mean reduction of 1.4, depressive symptoms as measured by the PHQ 9 (F(2, 72) = 10.062, p < 0.001, MSE = 5.174) with a mean reduction of 2.0, and an improvement in sleep quality was seen as measured by the PSQI (F(2, 74) = 11.047, p < 0.001, MSE = 2.269) with a mean improvement of 1.3. In most cases, improvement occurred across the first two time periods and then leveled off. Blood pressure, triglycerides, pain measurements, and WPAI did not change over time. Effect sizes for significant pairwise comparisons indicated medium to large effects of practical significance. This intervention was therefore effective at improving employee health and well-being. Widespread worksite implementation should be considered to improve the overall wellness of employees.

Reversibility of the effects of natalizumab on peripheral immune cell dynamics in MS patients.

OBJECTIVE: To characterize the reversibility of natalizumab-mediated changes in pharmacokinetics/pharmacodynamics in patients with multiple sclerosis (MS) following therapy interruption. METHODS: Pharmacokinetic/pharmacodynamic data were collected in the Safety and Efficacy of Natalizumab in the Treatment of Multiple Sclerosis (AFFIRM) (every 12 weeks for 116 weeks) and Randomized Treatment Interruption of Natalizumab (RESTORE) (every 4 weeks for 28 weeks) studies. Serum natalizumab and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured using immunoassays. Lymphocyte subsets, α4-integrin expression/saturation, and vascular cell adhesion molecule-1 (VCAM-1) binding were assessed using flow cytometry. RESULTS: Blood lymphocyte counts (cells/L) in natalizumab-treated patients increased from 2.1 × 109 to 3.5 × 109. Starting 8 weeks post last natalizumab dose, lymphocyte counts became significantly lower in patients interrupting treatment than in those continuing treatment (3.1 × 109 vs 3.5 × 109; p = 0.031), plateauing at prenatalizumab levels from week 16 onward. All measured cell subpopulation, α4-integrin expression/saturation, and sVCAM changes demonstrated similar reversibility. Lymphocyte counts remained within the normal range. Ex vivo VCAM-1 binding to lymphocytes increased until ≈16 weeks after the last natalizumab dose, then plateaued, suggesting reversibility of immune cell functionality. The temporal appearance of gadolinium-enhancing lesions was consistent with pharmacodynamic marker reversal. CONCLUSIONS: Natalizumab's effects on peripheral immune cells and pharmacodynamic markers were reversible, with changes starting 8 weeks post last natalizumab dose; levels returned to those observed/expected in untreated patients ≈16 weeks post last dose. This reversibility differentiates natalizumab from MS treatments that require longer reconstitution times. Characterization of the time course of natalizumab's biological effects may help clinicians make treatment sequencing decisions. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the pharmacodynamic markers of natalizumab are reversed ≈16 weeks after stopping natalizumab.

A Quasi Experiment to Determine the Effectiveness of a "Partially Flipped" versus "Fully Flipped" Undergraduate Class in Genetics and Evolution.

Two sections of Genetics and Evolution were taught by one instructor. One group (the fully flipped section) had the entire class period devoted to active learning (with background material that had to be watched before class), and the other group (the partially flipped section) had just a portion of class time spent on active learning (with the background material presented during class time). The same materials and assessments were used for both sections. Analysis of objective measures revealed that there was no significant difference between the learning outcomes of students in the two sections. There was no main effect of gender, major, or ethnicity on success in the whole cohort or in either section. There appeared to be a significant main effect of class standing, with freshmen performing significantly less well than sophomores, juniors, or seniors (who all performed equally well) in both sections (p < 0.01); however, this was a very preliminary observation, as there were very few freshmen in either section. The only predictor of success in the two sections was prior grade point average. An anonymous end-of-semester survey showed no significant difference between the two sections in interest in the subject matter.

A tale of two sections: an experiment to compare the effectiveness of a hybrid versus a traditional lecture format in introductory microbiology.

Two sections of an introductory microbiology course were taught by one instructor. One was taught through a hybrid format and the other through a traditional format. Students were randomly assigned to the two sections. Both sections were provided with identical lecture materials, in-class worksheets, in-class assessments, and extra credit opportunities; the main difference was in the way the lecture material was delivered-online for the hybrid section and in person for the traditional section. Analysis of final grades revealed that students in the traditional section did significantly better than those in the hybrid section (p<0.001). There was a significant main effect of class standing (p<0.01). When performance in the two sections was compared for each class year separately, the differences were only significant for sophomores (p<0.001); freshmen, juniors, and seniors did not perform differently in the hybrid versus the traditional section. An anonymous midterm survey suggested factors likely contributing to the overall lower success of students in the hybrid section: some students in the hybrid section did not take lecture notes and/or use the audio component of the online lectures, suggesting minimal interaction with the lecture material for these students.

Targeted protein destabilization reveals an estrogen-mediated ER stress response.

Accumulation of unfolded proteins within the endoplasmic reticulum (ER) of eukaryotic cells leads to an unfolded protein response (UPR) that either restores homeostasis or commits the cells to apoptosis. Tools traditionally used to study the UPR are proapoptotic and thus confound analysis of long-term cellular responses to ER stress. Here, we describe an ER-localized HaloTag (ERHT) protein that can be conditionally destabilized using a small-molecule hydrophobic tag (HyT36). Treatment of ERHT-expressing cells with HyT36 induces acute, resolvable ER stress that results in transient UPR activation without induction of apoptosis. Transcriptome analysis of late-stage responses to this UPR stimulus reveals a link between UPR activity and estrogen signaling.

When and why placebo-prescribing is acceptable and unacceptable: a focus group study of patients' views.

BACKGROUND: Surveys of doctors suggest that they use placebos and placebo effects clinically to help patients. However, patients' views are not well-understood. We aimed to identify when and why placebo-prescribing in primary care might be acceptable and unacceptable to patients. METHODS: A purposive diverse sample of 58 English-speaking adults (18 men; aged 19-80 years) participated in 11 focus groups. Vignettes describing doctors prescribing placebos in primary care were used to initiate discussions. Data were analyzed inductively. RESULTS: Participants discussed diverse harms and benefits of placebo-prescribing for individual patients, carers, healthcare providers, and society. Two perspectives on placebo-prescribing were identified. First, the "consequentialist" perspective focused on the potential for beneficial outcomes of placebo-prescribing. Here, some participants thought placebos are beneficial and should be used clinically; they often invoked the power of the mind or mind-body interactions. Others saw placebos as ineffective and therefore a waste of time and money. Second, the "respecting autonomy" perspective emphasized the harms caused by the deceptive processes thought necessary for placebo-prescribing. Here, participants judged placebo-prescribing unacceptable because placebo-prescribers deceive patients, thus a doctor who prescribes placebos cannot be trusted and patients' autonomy is compromised. They also saw placebo-responders as gullible, which deterred them from trying placebos themselves. Overall, the word "placebo" was often thought to imply "ineffective"; some participants suggested alternative carefully chosen language that could enable doctors to prescribe placebos without directly lying to patients. CONCLUSIONS: Negative views of placebos derive from beliefs that placebos do not work and/or that they require deception by the doctor. Positive views are pragmatic in that if placebos work then any associated processes (e.g. mechanisms, deception) are deemed unimportant. Public education about placebos and their effects is warranted and research to identify optimal ways of harnessing placebo effects in clinical practice is needed.

Distribution of nucleosides in populations of Cordyceps cicadae.

A rapid HPLC method had been developed and used for the simultaneous determination of 10 nucleosides (uracil, uridine, 2'-deoxyuridine, inosine, guanosine, thymidine, adenine, adenosine, 2'-deoxyadenosine and cordycepin) in 10 populations of Cordyceps cicadae, in order to compare four populations of Ophicordyceps sinensis and one population of Cordyceps militaris. Statistical analysis system (SAS) 8.1 was used to analyze the nucleoside data. The pattern of nucleoside distribution was analyzed in the sampled populations of C. cicadae, O. sinensis and C. militaris, using descriptive statistical analysis, nested analysis and Q cluster analysis. The total amount of the 10 nucleosides in coremium was 1,463.89-5,678.21 µg/g in 10 populations of C. cicadae, 1,369.80-3,941.64 µg/g in sclerotium. The average contents of the 10 analytes were 4,392.37 µg/g and 3,016.06 µg/g in coremium and sclerotium, respectively. The coefficient of variation (CV) of nucleosides ranged from 8.36% to 112.36% in coremium of C. cicadae, and from 10.77% to 155.87% in sclerotium of C. cicadae. The CV of the nucleosides was wide within C. cicadae populations. The nested variation analysis by the nine nucleosides' distribution indicated that about 42.29% of the nucleoside variability in coremium was attributable to the differentiation among populations, and the remaining 57.71% resided in the populations. It was also shown that about 28.94% of the variation in sclerotium was expressed between populations, while most of the variation (71.06%) corresponded to the populations.