Inhibition of P-glycoprotein - Mediated Efflux of Digoxinand Its Metabolites by Macrolide Antibiotics

This study was conducted to determine the rate of P-glycoprotein (P-gp) mediated efflux of digoxin analogues and metabolites, and to assess the effects of macrolide antibiotics on this efflux. Bidirectional transport studies were conducted using our Caco-2 sub clone with high P-gp expression (CLEFF9). HPLC methods were employed to measure drug transport. All digoxin metabolites were P-gp substrates, although digoxin had the greatest efflux ratio. Erythromycin had no effect on the transport of digoxin, maintaining a Basolateral to apical efflux ratio of 14.8, although it did reduce the efflux ratio of dihydrodigoxin and digoxigenin by 34% and 43%, respectively. Azithromycin also had little effect on the transport of digoxin or any of its metabolites. In contrast, clarithromycin and roxithromycin almost eliminated basolateral targeted efflux. Using paclitaxel as a known P-gp substrate, erythromycin demonstrated only partial P-gp inhibitory capacity maintaining an efflux ratio over 100. In contrast, clarithromycin and roxithromycin were 10 fold greater P-gp inhibitors. Clarithromycin and roxithromycin are likely to exhibit drug interactions with digoxin via inhibition of efflux mechanisms. Azithromycin appears to have little influence on P-gp mediated digoxin absorption or excretion and would be the safest macrolide to use concurrently with oral digoxin

Evaluating an interprofessional disease state and medication management review model

There is lack of literature data reporting an incorporation of medication management reviews in students’ interprofessional education (IPE) and practice programs in aged care settings. This pilot study reports how an interprofessional disease state and medication management review program (DSMMR) was established in a residential aged care facility in Perth, Western Australia. Students from the professions of nursing, pharmacy and physiotherapy focused on a wellness check in the areas of cognition, falls and continence while integrating a medication management review. Students’ attitudes were explored using a pre- and post-placement questionnaire. Students indicated positive experience with the IPE DSMMR program which also resulted in their positive attitudinal shift towards IPE and practice. These findings indicated that aged care can be a suitable setting for student interprofessional programs focusing on DSMMR

The clinical suitability of an artificial intelligence-enabled pain assessment tool for use in infants: Feasibility and usability evaluation study

Background: Infants are unable to self-report their pain, which, therefore, often goes underrecognized and undertreated. Adequate assessment of pain, including procedural pain, which has short- and long-term consequences, is critical for its management. The introduction of mobile health–based (mHealth) pain assessment tools could address current challenges and is an area requiring further research. Objective: The purpose of this study is to evaluate the accuracy and feasibility aspects of PainChek Infant and, therefore, assess its applicability in the intended setting. Methods: By observing infants just before, during, and after immunization, we evaluated the accuracy and precision at different cutoff scores of PainChek Infant, which is a point-of-care mHealth–based solution that uses artificial intelligence to detect pain and intensity based solely on facial expression. We used receiver operator characteristic analysis to assess interpretability and establish a cutoff score. Clinician comprehensibility was evaluated using a standardized questionnaire. Other feasibility aspects were evaluated based on comparison with currently available observational pain assessment tools for use in infants with procedural pain. Results: Both PainChek Infant Standard and Adaptive modes demonstrated high accuracy (area under the curve 0.964 and 0.966, respectively). At a cutoff score of ≥ 2, accuracy and precision were 0.908 and 0.912 for Standard and 0.912 and 0.897 for Adaptive modes, respectively. Currently available data allowed evaluation of 16 of the 17 feasibility aspects, with only the cost of the outcome measurement instrument unable to be evaluated since it is yet to be determined. PainChek Infant performed well across feasibility aspects, including interpretability (cutoff score defined), ease of administration, completion time (3 seconds), and clinician comprehensibility. Conclusions: This work provides information on the feasibility of using PainChek Infant in clinical practice for procedural pain assessment and monitoring, and demonstrates the accuracy and precision of the tool at the defined cutoff score

Field testing a protocol to facilitate the involvement of pharmacists in community based palliative care

Most palliative care patients and their carers will interact with a pharmacist, particularly when obtaining medication during their illness. Pharmacists working in the community do not have a formal role in the care of patients who are receiving palliative care. Objective: The aim of this study was to field test a protocol to coordinate a formal medication management review of palliative care patients by an accredited pharmacist. Methods: Eligible patients resident in the community were recruited by a palliative care nurse. Patients consented to a formal review of their medication by an accredited pharmacist. The request for the review was endorsed by the patient’s doctor. One accredited pharmacist, from a list of 18 accredited pharmacists who had attended a short course on palliative care and who had access to an experienced palliative care pharmacist, reviewed the medication at the patient’s residence. The pharmacist then reported their recommendations to a project manager who passed them back to the doctor. Patients and relatives were able to consult the pharmacist if they required further help for a number of weeks post-review.Results: Forty patients and 13 pharmacists participated over a four month period. Between two and 30 days elapsed from patient consent to the pharmacist’s report to the referring doctor (M = 10.6 days, SD = 6.0). Thirteen pharmacists conducted 0–9 reviews each and made 145 recommendations. Only three pharmacists recorded post-review patient interactions in diaries. Out of all interactions that took place between these three pharmacists and corresponding patients, almost half were initiated by the pharmacist. These were used mainly to share or request information, although two resulted in medication changes. Experts in palliative care and the patients were generally very positive about the results of the medication review. Conclusions: An innovation that builds on the existing system for Medication Management Review to engage with patients in palliative care is valuable. This project was an important first step in developing a suitable protocol. In this case the protocol was only partially successful although the project contributes to existing knowledge and understanding in this area

The prevalence of co-administration of clopidogrel and proton pump inhibitors

Background: Recent studies have suggested that proton pump inhibitors (PPIs) may inhibit the antiplatelet activity of clopidogrel, increasing the risk of major cardiovascular events in patients taking clopidogrel and PPIs together. Aim The primary aim of this study was to determine the prevalence of co-prescription of clopidogrel and PPIs amongst residents of aged-care facilities in New South Wales, Australia. Methods: One-year prescription records of 791 aged-care residents were analysed for prevalence of co-prescribing of clopidogrel and PPIs, and aspirin with clopidogrel and PPIs. Prevalence of co-prescribing of clopidogrel, aspirin and PPI in diabetic patients and clopidogrel with various CYP2C19 inhibitors was also examined. Results: Of the 791 residents studied, 60 were prescribed clopidogrel, 248 were on aspirin and 326 were prescribed a PPI.Among residents who were prescribed PPIs, 155 were prescribed omeprazole, 72 pantoprazole, 15 lansoprazole, 44 esomeprazole and 51 rabeprazole. Eleven of these residents had taken more than one PPI during the study period. Thirty-nine residents took a combination of clopidogrel and a PPI (any PPI) for a mean 203 days (SD 12). Thirteen residents were on the combination of aspirin and clopidogrel for a mean of 202 days (SD 111). Nine residents took the combination of clopidogrel, aspirin and a PPI (any PPI) for a mean of 173 days (SD 81). Only one patient on clopidogrel was receiving a CYP2C19 inhibitor in addition to a PPI. Conclusions: A significant number of residents in this cohort were taking a combination of clopidogrel and a PPI, mainly omeprazole. Residents who were on the combination of clopidogrel and a PPI, with or without aspirin,were on these combinations for a significantly long duration, which could increase their risk of adverse cardiovascular events

AXAF VETA-I mirror encircled energy measurements and data reduction

The AXAF VETA-I mirror encircled energy was measured with a series of apertures and two flow gas proportional counters at five X-ray energies ranging from 0.28 to 2.3 keV. The proportional counter has a thin plastic window with an opaque wire mesh supporting grid. Depending on the counter position, this mesh can cause the X-ray transmission to vary as much as +/-9 percent, which directly translates into an error in the encircled energy. In order to correct this wire mesh effect, window scan measurements were made, in which the counter was scanned in both horizontal (Y) and vertical (Z) directions with the aperture fixed. Post VETA measurement of the VXDS setup were made to determine the exact geometry and position of the mesh grid. Computer models of the window mesh were developed to simulate the X-ray transmission based on this measurement. The window scan data were fitted to such mesh models and corrections were made. After this study, the mesh effect was well understood and the final results of the encircled energy were obtained with an uncertainty of less than 0.8 percent

Exploring the community pharmacist's role in palliative care: Focusing on the person not just the prescription

Objective: Changes in health care provision have led to an emphasis on providing end of life care within the home. Community pharmacists are well positioned to provide services to community-based palliative care patients and carers. Methods: A multiple qualitative case study design was adopted. A total of 16 focus groups and 19 interviews with pharmacists, nurses, general practitioners and carers were undertaken across metropolitan and regional settings in Western Australia, New South Wales, Queensland and Victoria. Data were analysed thematically using a framework that allowed similarities and differences across stakeholder groups and locations to be examined and compared. Results: Three main themes emerged: effective communication; challenges to effective communication; and: towards best practice, which comprised two themes: community pharmacists’ skills and community pharmacists’ needs. Discussion: A key component of the provision of palliative care was having effective communication skills. Although community pharmacists saw an opportunity to provide interpersonal support, they suggested that they would need to develop more effective communication skills to fulfil this role. Conclusion: There is clear need for continuing professional development in this area – particularly in communicating effectively and managing strong emotions. Practice implications: Community pharmacists are willing to support palliative care patients and carers but need education, support and resources

Calcium channel blockers and breast cancer incidence: An updated systematic review and meta-analysis of the evidence

Controversy exists regarding the potential association between taking calcium channel blockers (CCBs) and the development of breast cancer. As a positive association would have important public health implications due to the widespread use of CCBs, this study aimed to incorporate new evidence to determine whether an association is likely to exist. We searched MEDLINE, EMBASE and the Cochrane Library to 28 June 2016 for relevant literature. References and citing articles were checked and authors contacted as necessary. Two authors independently selected articles and extracted data. Twenty-nine studies were reviewed; 26 were non-randomised studies (NRS). Meta-analysis of study data where adjustment for ‘confounding by indication’ was judged to be present suggests that an association, if any, is likely to be modest in magnitude (pooled odds/risk ratio 1.09 (95% confidence interval (CI) 1.03–1.15, I 2 = 0%, 8 sub-studies; pooled hazard ratio 0.99 (95% CI 0.94–1.03, I 2 = 35%, 9 sub-studies)). There are credible study data showing an increased relative risk with long-term use of CCBs, but the results of our meta-analysis and of meta-regression of log relative risk against minimum follow-up time are mixed. The current summative evidence does not support a clear association between taking CCBs and developing breast cancer. However, uncertainty remains, especially for long-term use and any association might not be uniform between different populations and/or breast cancer sub-types. We t hus recommend further NRS in settings where CCB use is highly prevalent and population-based cancer, prescription and health-registries exist, to resolve this continuing uncertainty. PROSPERO, CRD42015026712

Pharmacist and physician perspectives on diabetes service delivery within community pharmacies in Indonesia: a qualitative study

Objective: To explore perspectives of physicians and pharmacists on diabetes service delivery within community pharmacies in Indonesia. Methods: In depth interviews were conducted with 10 physicians and 10 community pharmacists in Surabaya, Indonesia, using a semi-structured interview guide. Nvivo version 9 was used to facilitate thematic content analysis to identify barriers/facilitators for community pharmacists to provide diabetes services. Key findings: The identified themes indicating barriers/facilitators for diabetes service delivery within Indonesian community pharmacies included: (1) pharmacist factors − i.e. positive views (facilitator) and perceived lack of competence (barrier);(2) pharmacist–physician relationships – i.e. physicians’ lack of support and accessibility (barriers); (3) pharmacist–patient relationships – i.e. perceived patients’ lack of support and accessibility (barriers); (4) pharmacy environment − i.e. business orientation (barrier), lack of staff and poor pharmacist availability (barriers), and availability of supporting resources, such as counselling areas/rooms, procedures/protocols and IT systems for labelling and patient records (facilitators); and (5)external environment − i.e. a health system to support pharmacist roles, remuneration, marketing and professional assistance (facilitators). Conclusion: Issues related to the pharmacist–physician–patient relationships, pharmacy environment and external environment need to be addressed before Indonesian community pharmacists can provide additional pharmacy services for type 2 diabetes patients. Collaboration between the Government, Ikatan Apoteker Indonesia (Indonesian Pharmacists Association) and Ikatan Dokter Indonesia (Indonesian Medical Association) is required to improve the pharmacy professional environment and facilities