Arsenic speciation in Chinese Herbal Medicines and human health implications for inorganic arsenic

Rice and drinking water are recognized as the dominant sources of arsenic (As) for human intake, while little is known about As accumulation and speciation in Chinese Herbal Medicines (CHMs), which have been available for many hundreds of years for the treatment of diseases in both eastern and western cultures. Inorganic arsenic was the predominant species in all of CHMs samples. The levels of inorganic arsenic in CHMs from fields and markets or pharmacies ranged from 63 to 550 ng/g with a mean of 208 ng/g and 94 to 8683 ng/g with a mean of 1092 ng/g, respectively. The highest concentration was found in the Chrysanthemum from pharmacies. It indicates that the risk of inorganic As in CHMs to human health is higher in medicines from markets or pharmacies than that collected directly from fields. Some CHMs may make a considerable contribution to the human intake of inorganic arsenic.

Ginkgolide B and bilobalide block the pore of the 5-HT3 receptor at a location that overlaps the picrotoxin binding site

Extracts from the Ginkgo biloba tree are widely used as herbal medicines, and include bilobalide (BB) and ginkgolides A and B (GA and GB). Here we examine their effects on human 5-HT(3)A and 5-HT(3)AB receptors, and compare these to the effects of the structurally related compounds picrotin (PTN) and picrotoxinin (PXN), the two components of picrotoxin (PTX), a known channel blocker of 5-HT3, nACh and GABA(A) receptors. The compounds inhibited 5-HT-induced responses of 5-HT3 receptors expressed in Xenopus oocytes, with IC50 values of 470 mu M (BB), 730 mu M (GB), 470 mu M (PTN), 11 mu M (PXN) and > 1 mM (GA) in 5-HT(3)A receptors, and 3.1 mM (BB), 3.9 mM (GB), 2.7 mM (PTN), 62 mu M (PXN) and > 1 mM (GA) in 5-HT(3)AB receptors. Radioligand binding on receptors expressed in HEK 293 cells showed none of the compounds displaced the specific 5-HT3 receptor antagonist [H-3]granisetron, confirming that they do not act at the agonist binding site. Inhibition by GB at 5-HT(3)A receptors is weakly use-dependent, and recovery is activity dependent, indicating channel block. To further probe their site of action at 5-HT(3)A receptors, BB and GB were applied alone or in combination with PXN, and the results fitted to a mathematical model; the data revealed partially overlapping sites of action. We conclude that BB and GB block the channel of the 5-HT(3)A receptor. Thus these compounds have comparable, although less potent, behaviour than at some other Cys-loop receptors, demonstrating their actions are conserved across the family. (C) 2010 Published by Elsevier Ltd.

The effect of lutein- and zeaxanthin-rich foods v. supplements on macular pigment level and serological markers of endothelial activation inflammation and oxidation pilot studies in healthy volunteers:pilot studies in healthy volunteers

The aim of the present study was to compare the effect of lutein- and zeaxanthin-rich foods and supplements on macular pigment level (MPL) and serological markers of endothelial activation, inflammation and oxidation in healthy volunteers. We conducted two 8-week intervention studies. Study 1 (n 52) subjects were randomised to receive either carrot juice (a carotene-rich food) or spinach powder (a lutein- and zeaxanthin-rich food) for 8 weeks. Study 2 subjects (n 75) received supplements containing lutein and zeaxanthin, ß-carotene, or placebo for 8 weeks in a randomised, double-blind, placebo-controlled trial. MPL, serum concentrations of lipid-soluble antioxidants, inter-cellular adhesion molecule 1, vascular cell adhesion molecule 1, C-reactive protein and F2-isoprostane levels were assessed at baseline and post-intervention in both studies. In these intervention studies, no effects on MPL or markers of endothelial activation, inflammation or oxidation were observed. However, the change in serum lutein and zeaxanthin was associated or tended to be associated with the change in MPL in those receiving lutein- and zeaxanthin-rich foods (lutein r 0.40, P = 0.05; zeaxanthin r 0.30, P = 0.14) or the lutein and zeaxanthin supplement (lutein r 0.43, P = 0.03; zeaxanthin r 0.22, P = 0.28). In both studies, the change in MPL was associated with baseline MPL (food study r - 0.54, P <0.001; supplement study r - 0.40, P <0.001). We conclude that this 8-week supplementation with lutein and zeaxanthin, whether as foods or as supplements, had no significant effect on MPL or serological markers of endothelial activation, inflammation and oxidation in healthy volunteers, but may improve MPL in the highest serum responders and in those with initially low MPL.

The Global Financial Crisis and UK PPPs

Purpose – This paper seeks to examine how Public Private Partnerships (PPPs) have been affected by the global financial crisis (GFC). After briefly discussing PPPs and the GFC, the paper considers whether the latter has been a contributing factor in the declining number of projects reaching financial close.

Design/methodology/approach – The paper employs document content analysis to compare the time between notification of a project in the Official Journal of the European Union and its financial close in order to assess whether this period has increased since the beginning of the GFC. Two case studies are also presented.

Findings – Apart from a very small number of projects, the time between official project notification and financial close is lengthening, with the case studies providing some possible explanations for this.

Originality/value – Whilst Burger et al. provide some general statistics on the impact of the GFC on PPPs in a number of countries, this paper examines over 600 PPPs in the UK and supplements this analysis with two case studies, in order to assess whether the GFC has led to delays in projects reaching financial close.

Children’s views on unlicensed/off-label paediatric prescribing and paediatric clinical trials.

Objectives: To explore the views and perspectives of children on the unlicensed/off-label use of medicines in children and on the participation of children in clinical trials. Methods: Focus-group discussions, involving school children, were carried out in a range of primary and secondary schools in Northern Ireland. A purposeful sample was chosen to facilitate representation of various socioeconomic groupings. Results: A total of 123 pupils, aged from 10 to 16 years, from six schools, participated in 16 focus groups. In general, pupils viewed the unlicensed/off-label use of medicines in children as unsafe and unethical and felt it is necessary to test medicines in children to improve the availability of licensed products. The majority felt that older children should be told, and that parents should be told, about the unlicensed/off-label use of medicines in children, yet they recognised some implications of this, such as potential medication non-adherence. Conclusions: This is the first study to explore the views of healthy children on unlicensed medicine use in children. Children were able to recognise potential risks associated with the unlicensed use of medicines and felt it is necessary to test and license more medicines in children. Practice implications Health care professionals should consider the views of children in decisions that affect their health.

The influence of evidence-based medicine training on decision-making in relation to over-the-counter medicines: a qualitative study

Objectives
To explore the role of evidence of effectiveness when making decisions about over-the-counter (OTC) medication and to ascertain whether evidence-based medicine training raised awareness in decision-making. Additionally, this work aimed to complement the findings of a previous study because all participants in this current study had received training in evidence-based medicine (unlike the previous participants).

Methods
Following ethical approval and an e-mailed invitation, face-to-face, semi-structured interviews were conducted with newly registered pharmacists (who had received training in evidence-based medicine as part of their MPharm degree) to discuss the role of evidence of effectiveness with OTC medicines. Interviews were recorded and transcribed verbatim. Following transcription, all data were entered into the NVivo software package (version 8). Data were coded and analysed using a constant comparison approach.

Key findings
Twenty-five pharmacists (7 males and 18 females; registered for less than 4 months) were recruited and all participated in the study. Their primary focus with OTC medicines was safety; sales of products (including those that lack evidence of effectiveness) were justified provided they did no harm. Meeting patient expectation was also an important consideration and often superseded evidence. Despite knowledge of the concept, and an awareness of ethical requirements, an evidence-based approach was not routinely implemented by these pharmacists. Pharmacists did not routinely utilize evidence-based resources when making decisions about OTC medicines and some felt uncomfortable discussing the evidence-base for OTC products with patients.

Conclusions
The evidence-based medicine training that these pharmacists received appeared to have limited influence on OTC decision-making. More work could be conducted to ensure that an evidence-based approach is routinely implemented in practice

Self-reported use of natural health products:A cross-sectional telephone survey in older Ontarians

Background: The self-reported use of natural health products (NHPs) (herbal products and vitamin and mineral supplements) has increased over the past decade in Canada. Because the elderly population might have comorbidities and concurrently administered medications, there is a need to explore the perceptions and behaviors associated with NHPs in this age group. Objective: The goal of this study was to assess the use of NHPs in a cohort of older Canadian residents and the characteristics, perceptions, and behaviors associated with NHP use. Methods: Survey participants aged =60 years were randomly selected from telephone listings in the area of greater Hamilton, Ontario, Canada. Data were collected using a standardized computer-assisted telephone interview system. Self-reported data covering 7 domains were collected: (1) demographics; (2) self-reported 12-month NHP use; (3) reasons for NHP use; (4) self-reported 12-month prescription medication use; (5) expenditures on NHPs; (6) patient-reported adverse events and drug-NHP interactions; and (7) perceptions of physicians' attitudes regarding NHPs. Descriptive statistics were used to compare the characteristics of NHP users with those of nonusers and to assess the characteristics of NHP users across these 7 domains. Multivariate regression analysis was conducted to determine the demographic variables that might be associated with NHP user status. Results: Of 2528 persons identified as age =60 years, 1206 (48%) completed the telephone interview. Six hundred sixteen of these respondents (51%) reported the use of =1 NHP during the previous 12 months. On the initial univariate analysis, younger age and higher income were significantly associated with reporting NHP use (mean age, users vs nonusers, 71.1 vs 72.7 years, respectively; 95% CI, 1.02-1.06; P <0.001; income more than Can $26,000 was 28% and 22% in users and nonusers, respectively; P = 0.028). One hundred seventy of 616 users (28%) used an NHP to treat the same condition for which they were concurrently receiving a prescription medication, and 43 (25%) had not informed their physicians about their NHP use. Patients' characteristics such as sex, education, smoking status, and self-reported health status did not differ significantly between users and nonusers. In individuals who regularly spent money to purchase NHPs (n = 394), the mean cost was $20.38/mo. NHP expenditure was not significantly associated with age, sex, or income. Conclusion: Based on these findings, a substantial proportion of those Ontarians aged =60 years reported NHP use, and there is a need for greater communication with physicians to avoid potential drug-NHP interactions. © 2009 Excerpta Medica Inc. All rights reserved.

Views of pharmacy graduates and pharmacist tutors on evidence-based practice in relation to over-the-counter consultations: a qualitative study

RATIONALE, AIMS AND OBJECTIVES: Health care services offered to the public should be based on the best available evidence. We aimed to explore pharmacy tutors' and trainees' views on the importance of evidence when making decisions about over-the-counter (OTC) medicines and also to investigate whether the tutor influenced the trainee in practice.

METHODS: Following ethical approval and piloting, semi-structured interviews were conducted with pharmacy graduates (trainees) and pharmacist tutors. Transcribed interview data were entered into the NVivo software package (version 10), coded and analysed via thematic analysis.

RESULTS: Twelve trainees (five males, seven females) and 11 tutors (five males, six females) participated. Main themes that emerged were (in)consistency and contradiction, confidence, acculturation, and continuation and perpetuation. Despite having an awareness of the importance and potential benefits, an evidence-based approach did not seem to be routinely or consistently implemented in practice. Confidence in products was largely derived from personal use and patient feedback. A lack of discussion about evidence was justified on the basis of not wanting to lessen patient confidence in requested product(s) or possibly negating the placebo effect. Trainees became acculturated to 'real-life' practice; university teaching and evidence was deemed less relevant than meeting customer expectations. The tutor's actions were mirrored by their trainee resulting in continuation and perpetuation of the same professional attitudes and behaviours.

CONCLUSIONS: Evidence appeared to have limited influence on OTC decision making. The tutor played a key role in the trainee's professional development. More work could be performed to investigate how evidence can be regarded as relevant and something that is consistently implemented in practice.

Treatment adherence and health outcomes in patients with bronchiectasis

Background: We aimed to determine adherence to inhaled antibiotics, other respiratory medicines and airway clearance and to determine the association between adherence to these treatments and health outcomes (pulmonary exacerbations, lung function and Quality of Life Questionnaire-Bronchiectasis [QOL-B]) in bronchiectasis after 12 months.

Methods: Patients with bronchiectasis prescribed inhaled antibiotics for Pseudomonas aeruginosa infection were recruited into a one-year study. Participants were categorised as " adherent" to medication (medication possession ratio ≥80% using prescription data) or airway clearance (score ≥80% in the Modified Self-Reported Medication-Taking Scale). Pulmonary exacerbations were defined as treatment with a new course of oral or intravenous antibiotics over the one-year study. Spirometry and QOL-B were completed at baseline and 12 months. Associations between adherence to treatment and pulmonary exacerbations, lung function and QOL-B were determined by regression analyses.

Results: Seventy-five participants were recruited. Thirty-five (53%), 39 (53%) and 31 (41%) participants were adherent to inhaled antibiotics, other respiratory medicines, and airway clearance, respectively. Twelve (16%) participants were adherent to all treatments. Participants who were adherent to inhaled antibiotics had significantly fewer exacerbations compared to non-adherent participants (2.6 vs 4, p = 0.00) and adherence to inhaled antibiotics was independently associated with having fewer pulmonary exacerbations (regression co-efficient = -0.51, 95% CI [-0.81,-0.21], p < 0.001). Adherence to airway clearance was associated with lower QOL-B Treatment Burden (regression co-efficient = -15.46, 95% CI [-26.54, -4.37], p < 0.01) and Respiratory Symptoms domain scores (regression co-efficient = -10.77, 95% CI [-21.45; -0.09], p < 0.05). There were no associations between adherence to other respiratory medicines and any of the outcomes tested. Adherence to treatment was not associated with FEV₁ % predicted.

Conclusions: Treatment adherence is low in bronchiectasis and affects important health outcomes including pulmonary exacerbations. Adherence should be measured as part of bronchiectasis management and future research should evaluate bronchiectasis-specific adherence strategies. 

Bronchiolitis

INTRODUCTION: Bronchiolitis is the most common lower respiratory tract infection in infants, occurring in a seasonal pattern, with highest incidence in the winter in temperate climates and in the rainy season in warmer countries. Bronchiolitis is a common reason for attendance at and admission to hospital.

METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of prophylactic interventions for bronchiolitis in high-risk children? What are the effects of measures to prevent transmission of bronchiolitis in hospital? What are the effects of treatments for children with bronchiolitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

RESULTS: We found 59 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, bronchodilators (oral, inhaled salbutamol, inhaled adrenaline [epinephrine], hypertonic saline), chest physiotherapy, continuous positive airway pressure, corticosteroids, fluid management, heliox, montelukast, nasal decongestants, nursing interventions (cohort segregation, hand washing, gowns, masks, gloves, and goggles), oxygen, respiratory syncytial virus immunoglobulins, pooled immunoglobulins, or palivizumab (monoclonal antibody), ribavirin, or surfactants.

Patterns of use of natural health products by Ontario seniors

A random dialing telephone survey of 1,071 60+ year-olds in 4 Ontario communities identified 553 (52%) users of natural health products. Mean age was 72 yrs (min-max:60-95); 76% were female. The most frequently reported natural health products were: echinacea (27%), glucosamine (26%), garlic (20%), ginkgo biloba (10%), St. John's wort (5%), ginseng (5%), flax seed oil (3%), evening primrose oil (2%), devil's claw (2%), saw palmetto (2%). Natural source vitamin use was reported by 24% of users, and 6% reporting using herbal teas. 51% of users used 2 or more herbal products and 8% used 5 or more products. 19% of herbal users also used a conventional prescription drug to manage the same health problem as the herbal product. The reported range of monthly expenditures for these products varied from a few cents (grew their own) to $288 (CAN). Thirty-five percent of users did not know the price of at least one of their natural products. Of the 75% of respondents willing to disclose their annual household income ($CAN), 20 had an income of $46,000. The widespread use and potential for significant expenditure of limited resources would suggest that more study is required into the efficacy, safety and value of these products.