Evaluation of a community pharmacy-based intervention for improving patient adherence to antihypertensives: a randomised controlled trial

BackgroundThe majority of patients using antihypertensive medications fail to achieve their recommended target blood pressure. Poor daily adherence with medication regimens and a lack of persistence with medication use are two of the major reasons for failure to reach target blood pressure. There is no single intervention to improve adherence with antihypertensives that is consistently effective. Community pharmacists are in an ideal position to promote adherence to chronic medications. This study aims to test a specific intervention package that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications - Hypertension Adherence Program in Pharmacy (HAPPY).Methods/DesignThe HAPPY trial is a multi-centre prospective randomised controlled trial. Fifty-six pharmacies have been recruited from three Australian states. To identify potential patients, a software application (MedeMine CVD) extracted data from a community pharmacy dispensing software system (FRED Dispense&reg;). The pharmacies have been randomised to either \u27Pharmacist Care Group\u27 (PCG) or \u27Usual Care Group\u27 (UCG). To check for \u27Hawthorne effect\u27 in the UCG, a third group of patients \u27Hidden Control Group\u27 (HCG) will be identified in the UCG pharmacies, which will be made known to the pharmacists at the end of six months. Each study group requires 182 patients. Data will be collected at baseline, three and six months in the PCG and at baseline and six months in the UCG. Changes in patient adherence and persistence at the end of six months will be measured using the self-reported Morisky score, the Tool for Adherence Behaviour Screening and medication refill data.DiscussionTo our knowledge, this is the first research testing a comprehensive package of evidence-based interventions that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications. The unique features of the HAPPY trial include the use of MedeMine CVD to identify patients who could potentially benefit from the service, control for the \u27Hawthorne effect\u27 in the UCG and the offer of the intervention package at the end of six months to patients in the UCG, a strategy that is expected to improve retention.Trial RegistrationAustralian New Zealand Clinical Trial Registry ACTRN12609000705280<br /

Revealing the Anti-Tumor Effect of Artificial miRNA p-27-5p on Human Breast Carcinoma Cell Line T-47D

microRNAs (miRNAs) cause mRNA degradation or translation suppression of their target genes. Previous studies have found direct involvement of miRNAs in cancer initiation and progression. Artificial miRNAs, designed to target single or multiple genes of interest, provide a new therapeutic strategy for cancer. This study investigates the anti-tumor effect of a novel artificial miRNA, miR P-27-5p, on breast cancer. In this study, we reveal that miR P-27-5p downregulates the differential gene expressions associated with the protein modification process and regulation of cell cycle in T-47D cells. Introduction of this novel artificial miRNA, miR P-27-5p, into breast cell lines inhibits cell proliferation and induces the first “gap” phase (G1) cell cycle arrest in cancer cell lines but does not affect normal breast cells. We further show that miR P-27-5p targets the 3′-untranslated mRNA region (3′-UTR) of cyclin-dependent kinase 4 (CDK4) and reduces both the mRNA and protein level of CDK4, which in turn, interferes with phosphorylation of the retinoblastoma protein (RB1). Overall, our data suggest that the effects of miR p-27-5p on cell proliferation and G1 cell cycle arrest are through the downregulation of CDK4 and the suppression of RB1 phosphorylation. This study opens avenues for future therapies targeting breast cancer

Evaluation of a community pharmacy-based intervention for improving patient adherence to antihypertensives: a randomised controlled trial

BackgroundThe majority of patients using antihypertensive medications fail to achieve their recommended target blood pressure. Poor daily adherence with medication regimens and a lack of persistence with medication use are two of the major reasons for failure to reach target blood pressure. There is no single intervention to improve adherence with antihypertensives that is consistently effective. Community pharmacists are in an ideal position to promote adherence to chronic medications. This study aims to test a specific intervention package that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications - Hypertension Adherence Program in Pharmacy (HAPPY).Methods/DesignThe HAPPY trial is a multi-centre prospective randomised controlled trial. Fifty-six pharmacies have been recruited from three Australian states. To identify potential patients, a software application (MedeMine CVD) extracted data from a community pharmacy dispensing software system (FRED Dispense&reg;). The pharmacies have been randomised to either \u27Pharmacist Care Group\u27 (PCG) or \u27Usual Care Group\u27 (UCG). To check for \u27Hawthorne effect\u27 in the UCG, a third group of patients \u27Hidden Control Group\u27 (HCG) will be identified in the UCG pharmacies, which will be made known to the pharmacists at the end of six months. Each study group requires 182 patients. Data will be collected at baseline, three and six months in the PCG and at baseline and six months in the UCG. Changes in patient adherence and persistence at the end of six months will be measured using the self-reported Morisky score, the Tool for Adherence Behaviour Screening and medication refill data.DiscussionTo our knowledge, this is the first research testing a comprehensive package of evidence-based interventions that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications. The unique features of the HAPPY trial include the use of MedeMine CVD to identify patients who could potentially benefit from the service, control for the \u27Hawthorne effect\u27 in the UCG and the offer of the intervention package at the end of six months to patients in the UCG, a strategy that is expected to improve retention.Trial RegistrationAustralian New Zealand Clinical Trial Registry ACTRN12609000705280<br /

Early intensive hand rehabilitation after spinal cord injury ("Hands On"): a protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Loss of hand function is one of the most devastating consequences of spinal cord injury. Intensive hand training provided on an instrumented exercise workstation in conjunction with functional electrical stimulation may enhance neural recovery and hand function. The aim of this trial is to compare usual care with an 8-week program of intensive hand training and functional electrical stimulation.</p> <p>Methods/design</p> <p>A multicentre randomised controlled trial will be undertaken. Seventy-eight participants with recent tetraplegia (C2 to T1 motor complete or incomplete) undergoing inpatient rehabilitation will be recruited from seven spinal cord injury units in Australia and New Zealand and will be randomised to a control or experimental group. Control participants will receive usual care. Experimental participants will receive usual care and an 8-week program of intensive unilateral hand training using an instrumented exercise workstation and functional electrical stimulation. Participants will drive the functional electrical stimulation of their target hands via a behind-the-ear bluetooth device, which is sensitive to tooth clicks. The bluetooth device will enable the use of various manipulanda to practice functional activities embedded within computer-based games and activities. Training will be provided for one hour, 5 days per week, during the 8-week intervention period. The primary outcome is the Action Research Arm Test. Secondary outcomes include measurements of strength, sensation, function, quality of life and cost effectiveness. All outcomes will be taken at baseline, 8 weeks, 6 months and 12 months by assessors blinded to group allocation. Recruitment commenced in December 2009.</p> <p>Discussion</p> <p>The results of this trial will determine the effectiveness of an 8-week program of intensive hand training with functional electrical stimulation.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01086930">NCT01086930</a> (12^thMarch 2010)</p> <p><a href="http://www.anzctr.org.au/ACTRN12609000695202.aspx">ACTRN12609000695202</a> (12^thAugust 2009)</p

SARM1 detection in myelinating glia: sarm1/Sarm1 is dispensable for PNS and CNS myelination in zebrafish and mice

Since SARM1 mutations have been identified in human neurological disease, SARM1 inhibition has become an attractive therapeutic strategy to preserve axons in a variety of disorders of the peripheral (PNS) and central nervous system (CNS). While SARM1 has been extensively studied in neurons, it remains unknown whether SARM1 is present and functional in myelinating glia? This is an important question to address. Firstly, to identify whether SARM1 dysfunction in other cell types in the nervous system may contribute to neuropathology in SARM1 dependent diseases? Secondly, to ascertain whether therapies altering SARM1 function may have unintended deleterious impacts on PNS or CNS myelination? Surprisingly, we find that oligodendrocytes express sarm1 mRNA in the zebrafish spinal cord and that SARM1 protein is readily detectable in rodent oligodendrocytes in vitro and in vivo. Furthermore, activation of endogenous SARM1 in cultured oligodendrocytes induces rapid cell death. In contrast, in peripheral glia, SARM1 protein is not detectable in Schwann cells and satellite glia in vivo and sarm1/Sarm1 mRNA is detected at very low levels in Schwann cells, in vivo, in zebrafish and mouse. Application of specific SARM1 activators to cultured mouse Schwann cells does not induce cell death and nicotinamide adenine dinucleotide (NAD) levels remain unaltered suggesting Schwann cells likely contain no functionally relevant levels of SARM1. Finally, we address the question of whether SARM1 is required for myelination or myelin maintenance. In the zebrafish and mouse PNS and CNS, we show that SARM1 is not required for initiation of myelination and myelin sheath maintenance is unaffected in the adult mouse nervous system. Thus, strategies to inhibit SARM1 function to treat neurological disease are unlikely to perturb myelination in humans.CM was funded by a Medical Research Council (UK) studentship (2251399). PA-F (206634/Z/17/Z), AL (210904/Z/18/Z), CC (220027/Z/19/Z), RB (203151/Z/16/Z) and MC (220906/Z/20/Z) were funded by the Wellcome Trust (UK). BS was supported by a Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (109408/Z/15/Z). KM was funded by the National Institute of Neurological Disorders and Stroke Awards (R01NS079445). JG-S was funded by a Miguel Servet Fellowship (CP22/00078) from the Instituto de Salud Carlos III and the Millennium Nucleus for the Study of Pain (MiNuSPain), Santiago, Chile. HC was funded by the Spanish “Ministerio de Economía y Competitividad” (BFU2016-75864R and PID2019-109762RB-I00), ISABIAL (UGP18-257 and UGP-2019-128), and Generalitat Valenciana (PROMETEO 2018/114). Y-PH and C-YC were funded by Academia Sinica, AS-IA-106-L04 to Y-PH.Peer reviewe

Business continuity planning for a U.S. supply chain

Thesis: M. Eng. in Logistics, Massachusetts Institute of Technology, Engineering Systems Division, 2014.Cataloged from PDF version of thesis.Includes bibliographical references (pages 79-80).The research objective was to provide a directional sense of some key considerations for business continuity planning (BCP) specific to a company's downstream distribution operations in the U.S. This was achieved via a two-pronged strategy comprised of quantitative and qualitative elements to complement insights gained from the literature review. By quantitatively assessing the financial impacts arising from four hypothetical scenarios, the business impact analysis (BIA) showcased the merits of short time-to-recovery (TTR) in the event of a disruption. However, available information also appears to suggest that the estimated financial impact from carrying high-value inventory is not necessarily insignificant. Hence, a company may want to mitigate the likelihood of a scenario whereby large amounts of inventory become damaged. Qualitative information from industry participants in the study highlighted the importance of tailoring continuity plans to the unique supply chain needs of an organization.by Arthur K. L. Chee and Tzu-Hsueh Lee.M. Eng. in Logistic

Understanding cultures and building capacity to bridge the cultural chasm : what are the perspectives of Chinese migrant about Australian general practice?

Context: There is anecdotal evidence suggesting that Chinese people lack confidence and trust in the primary health care system as they perceive general practitioners (GPs) to be ‘unsafe’ and ‘lowly’; preferring to consult more ‘esteemed’ specialists for even the most minute ailments. There is however a dearth of research exploring Chinese migrants’ perspectives on general practice in Australia and the factors which may pose as barriers to their uptake of primary care services. Objective: To explore the experience of Chinese migrants with general practice and GPs in Australia and the influence of cultural differences and their past experience in China on their current perspectives. Design: Qualitative research using a phenomenological approach. Semi-structured interviews will be conducted with 10–12 Chinese migrants purposively recruited and selected to achieve maximum variation. Interview questions have been developed based on components of the General Practice Assessment Questionnaire (GPAQ) and General Practice Patient Survey (GPPS) to explore patients’ perspectives on the quality of care provided by their general practice and GPs. The interviews will be audiotaped and transcribed, then thematically analysed. Setting: Melbourne, Australia. Participants: Chinese migrants from China. Findings: Recruitment and data collection are underway. Results will be available for presentation by July 2019. Implication(s) for practice: Findings are expected to help the general practice discipline in Australia understand the cultural factors influencing Chinese migrant patients’ perspectives and inform the development, implementation and evaluation of engagement strategies. This will contribute to GP development in Australia, potentially raising the standard and quality of general practice

Cost-utility analysis of telephone-based cognitive behavior therapy in chronic obstructive pulmonary disease (COPD) patients with anxiety and depression comorbidities: an application for willingness to accept concept

Background: This study evaluated the cost-utility of telephone-based cognitive behavioral therapy (TB-CBT) (experimental arm) in comparison with a placebo-befriending (control arm) program in COPD participants with mild to severe depression and/or anxiety. Methods: The decision rule was based on willingness-to-pay if there is an increased unit of effectiveness (a quality-adjusted life year [QALY] gain) and an increase in cost, and willingness-to-accept (WTA) if there is a reduced unit of effectiveness (a QALY loss) and decrease in cost (a cost-saving). Results: TB-CBT group was associated with a reduction in the incremental cost of AUS−$407.3 (p < 0.001, SE:34.1) plus a negative, nonsignificant incremental QALY gain of −0.008 (SE:0.011) per patient compared to control group. The point estimate of the mean incremental cost-utility ratio was AUS$50,284.0 cost saving per QALY sacrificed (the high value associated with small QALY value in the denominator). Ninety-five percent CI was AUS$13,426 cost sacrificed to AUS$32,018 cost gain (lower values associated with larger QALY values in the denominator). If the societal’s minimum (flooring threshold) WTA is AUS$64,000 per QALY forgone, the probability of TB-CBT being cost-effective was 42% Conclusions: This study showed that TB-CBT can be recommended as a cost-saving and preventive approach over usual care plus befriending program

Design and protocol for the Dialysis Optimal Health Program (DOHP) randomised controlled trial

BACKGROUND: Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are serious and growing health problems with enormous impact on psychological and social functioning. Despite high rates of comorbid depression and anxiety in these patient populations, and the adverse impact these have upon treatment adherence, quality of life, social connectedness and healthcare costs there has been little attention focused on the prevention or management of these problems. Thus, our aim was to evaluate the Dialysis Optimal Health Program (DOHP) that adopts a person-centred approach and engages collaborative therapy to educate and support those diagnosed with ESKD who are commencing dialysis. METHODS: The study design is a randomised controlled trial. Ninety-six adult patients initiating haemodialysis or peritoneal dialysis will be randomly allocated to either the intervention (DOHP) or usual care group. Participants receiving the intervention will receive nine (8 + 1 booster session) sequential sessions based on a structured information/workbook, psychosocial and educational supports and skills building. The primary outcome measures are depression and anxiety (assessed by the Hospital Anxiety and Depression Scale; HADS). Secondary outcomes include health-related quality of life (assessed by the Kidney Disease Quality of Life instrument; KDQOL), self-efficacy (assessed by General Self-Efficacy Scale) and clinical indices (e.g. albumin and haemoglobin levels). Cost-effectiveness analysis and process evaluation will also be performed to assess the economic value and efficacy of the DOHP. Primary and secondary measures will be collected at baseline and at 3-, 6-, and 12-month follow-up time points. DISCUSSION: We believe that this innovative trial will enhance knowledge of interventions aimed at supporting patients in the process of starting dialysis, and will broaden the focus from physical symptoms to include psychosocial factors such as depression, anxiety, self-efficacy, wellbeing and community support. The outcomes associated with this study are significant in terms of enhancing an at-risk population's psychosocial health and reducing treatment-related costs and associated pressures on the healthcare system. TRIAL REGISTRATION: ANZCTR no. 12615000810516 . Registered on 5 August 2015