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Regulatory approvals for cardiovascular polypills are increasing rapidly across more than 30 countries. The evidence clearly shows polypills improve adherence and cardiovascular disease risk factors for patients with indications for use of polypill components—ie, those with established cardiovascular disease or at high risk. However, the implementation of polypills into clinical practice has many challenges. The clinical trials literature provides insights into the clinical impact of a polypill strategy, including cost-effectiveness, safety of use, substantial improvement in adherence, and better risk factor control than usual care. Despite the clear need for such a strategy and the available clinical data backing up the use of the polypill in different patient populations, challenges to widespread implementation, such as an absence of government reimbursement and poor physician uptake (identified from on the ground experience in countries following commercial rollout), have greatly obstructed real-world implementation. Obtaining the full public health benefit of polypills will require education, advocacy, endorsement, and implementation by key global agencies such as WHO and national clinical bodies, as well as endorsement from governments.

BackgroundHigh blood pressure (BP) is a significant global health issue, with many treated patients failing to achieve BP control. The Triple Pill vs Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial evaluated the effectiveness, cost-effectiveness and acceptability of early use of low-dose triple fixed-dose combination of BP-lowering drugs (‘triple pill’) compared with usual care in the management of hypertension. The TRIUMPH trial showed superior BP control with the triple pill strategy compared with usual care. This process evaluation of the TRIUMPH trial aimed to explore the contextual factors that influenced the trial outcomes, implementation of the triple pill strategy, mechanisms of its effects and potential barriers and facilitators for implementing the triple pill strategy in routine practice.MethodsGuided by the UK Medical Research Council’s framework, semistructured interviews were conducted with 23 patients and 13 healthcare providers involved in the TRIUMPH trial. Data were analysed using the framework analysis method in NVivo.ResultsHypertension care in Sri Lanka was hindered by the absence of systematic screening and overcrowded public clinics. Despite free medication provision at public clinics, long waiting times and occasional stock-outs posed challenges. In the TRIUMPH trial, both intervention and usual care were delivered in the context of ‘better than usual’ care, including team-based management, reduced waiting times, monetary assistance for travel, routine adherence monitoring and intensive follow-up. The triple pill strategy provided a simplified regimen, better access to BP-lowering medications and better BP-lowering efficacy. Key barriers to implementation in routine practice included the triple pill’s large size, therapeutic inertia and restrictive regulatory policies regarding fixed-dose combinations.ConclusionsImplementation of the triple pill strategy into routine practice requires health system strengthening, provider training and supportive policy measures to replicate its effectiveness seen in the trial.Trial registration numberACTRN12612001120864, SLCTR/2015/020.

ObjectiveThis study investigates consumer views of pharmacist-led professional services in Australia, emphasising factors influencing their uptake and attributes valued by users.DesignSemi-structured online focus groups explored the awareness, experiences and expectations of pharmacists and pharmacy professional services. Audio recordings were transcribed verbatim and de-identified. Data were analysed using the thematic analysis technique to identify common themes.SettingThree online focus groups were conducted, inviting participants from AustraliaParticipants15 adults aged 18 years and above, English-speaking and self-identified as a consumer of health services or a health carer.ResultsParticipants recognised pharmacists primarily as medication experts but also valued additional services like health screening, vaccination and chronic disease management. Consumer perceptions and experiences of professional pharmacy services focused on three themes: (1) convenience, (2) credibility and trust, and (3) communication and awareness. More specifically, attributes that influence service uptake include pharmacist competency, general practitioner (GP) endorsement, service availability, convenience, awareness and cost. Competency was associated with visible qualifications and specialised training, fostering consumer trust. Limited awareness of available services and privacy concerns posed barriers. Collaborative relationships between pharmacists and GPs, flexible hours and minimal waiting times, provision of services within pharmacists’ scope of practice and recognition from the government were particularly appealing factors.ConclusionsThe findings highlight opportunities to expand pharmacists’ roles in primary care, emphasising the need for tailored attributes, robust competency frameworks, GP endorsement and government support for sustainable service models. This work contributes to the growing evidence base on enhancing consumer-centred pharmacy services, guiding policy and practice improvements to meet evolving healthcare demands. Future research quantifying how much consumers value each attribute can help providers with limited resources prioritise better.

The catalytic activity of nickel complexes in hydrophosphination involving secondary phosphines is not a commonly studied transformation. Beyond a small number of stand-out examples, many reports in the literature focus on the use of simple nickel salts. β-Diketiminates have been proven to be incredibly effective ligands for catalysis using a range of metal centers. This synthetic study investigates the catalytic ability of a Ni(II) β-diketiminate complex in the hydrophosphination of alkenes and alkynes, with a serendipitous discovery of its ability to effect alkyne cyclotrimerization and phosphine dehydrocoupling.

Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on average. There is a pressing need for blood pressure-control strategies with improved efficacy and tolerability. We aimed to assess whether ultra-low-dose combination therapy could meet these needs. We did a randomised, placebo-controlled, double-blind, crossover trial of a quadpill—a single capsule containing four blood pressure-lowering drugs each at quarter-dose (irbesartan 37·5 mg, amlodipine 1·25 mg, hydrochlorothiazide 6·25 mg, and atenolol 12·5 mg). Participants with untreated hypertension were enrolled from four centres in the community of western Sydney, NSW, Australia, mainly by general practitioners. Participants were randomly allocated by computer to either the quadpill or matching placebo for 4 weeks; this treatment was followed by a 2-week washout, then the other study treatment was administered for 4 weeks. Study staff and participants were unaware of treatment allocations, and masking was achieved by use of identical opaque capsules. The primary outcome was placebo-corrected 24-h systolic ambulatory blood pressure reduction after 4 weeks and analysis was by intention to treat. We also did a systematic review of trials evaluating the efficacy and safety of quarter-standard-dose blood pressure-lowering therapy against placebo. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614001057673. The trial ended after 1 year and this report presents the final analysis. Between November, 2014, and December, 2015, 55 patients were screened for our randomised trial, of whom 21 underwent randomisation. Mean age of participants was 58 years (SD 11) and mean baseline office and 24-h systolic and diastolic blood pressure levels were 154 (14)/90 (11) mm Hg and 140 (9)/87 (8) mm Hg, respectively. One individual declined participation after randomisation and two patients dropped out for administrative reasons. The placebo-corrected reduction in systolic 24-h blood pressure with the quadpill was 19 mm Hg (95% CI 14–23), and office blood pressure was reduced by 22/13 mm Hg (p<0·0001). During quadpill treatment, 18 (100%) of 18 participants achieved office blood pressure less than 140/90 mm Hg, compared with six (33%) of 18 during placebo treatment (p=0·0013). There were no serious adverse events and all patients reported that the quadpill was easy to swallow. Our systematic review identified 36 trials (n=4721 participants) of one drug at quarter-dose and six trials (n=312) of two drugs at quarter-dose, against placebo. The pooled placebo-corrected blood pressure-lowering effects were 5/2 mm Hg and 7/5 mm Hg, respectively (both p<0·0001), and there were no side-effects from either regimen. The findings of our small trial in the context of previous randomised evidence suggest that the benefits of quarter-dose therapy could be additive across classes and might confer a clinically important reduction in blood pressure. Further examination of the quadpill concept is needed to investigate effectiveness against usual treatment options and longer term tolerability. National Heart Foundation, Australia; University of Sydney; and National Health and Medical Research Council of Australia.

Background Hip fracture creates a major burden on society due to high mortality, loss of independence and excess medical costs for older people. A multidisciplinary co-managed model of care is widely considered as the best practice for the management of older patients with hip fracture. The study aims to develop a conceptual framework to inform the future scale-up of this model of care through the identification of barriers and enablers that may influence successful uptake. Methods This qualitative study was conducted within an interventional study, which aimed to test the effectiveness of co-managed model of care for older patients with hip fracture. Health providers and health administrators from three hospitals were purposively selected and interviewed in-depth. The Consolidated Framework for Implementation Research (CFIR) was used to develop interview guides, collect and analyse data. Inductive and deductive approaches were used to generate enablers or barriers, aligned with the CFIR constructs. All barriers or enablers were inductively summarised to a conceptual framework with essential components to guide the implementation of co-managed model of care in other hospitals. Results A total of 13 health providers and 3 health administrators were recruited. The main barriers to co-managed care implementation included perceived complexity of implementation, insufficient international collaboration and incentives, the absence of national guideline support and lack of digital health applications for communication between health providers, insufficient number of health providers and beds, and poor understanding about the effectiveness of this care model. A conceptual framework for future scale-up was then developed, consisting of the following essential components: hospital authority support, enabling environment, adequate number of beds, sufficient and skilled health providers, use of digital health technology, regular quality supervision, evaluation and feedback, and external collaborations. Conclusions Despite the complexity of the intervention, the co-managed model of care has the potential to be implemented and promoted in China and in similar settings, although there is a need to demonstrate feasibility in different settings.

In this month's editorial, PLOS Medicine Editorial Board member Anushka Patel and Ruth Webster discuss how applying rules for drug efficacy trials can impede pragmatic trials of interventions for noncommunicable diseases.

ObjectiveTo describe the pharmacists’ workflow, including tasks and time spent, to better understand their work capacity.DesignCross-sectional, observational, time and motion study.SettingCommunity pharmacies in Western Australia and New South Wales, Australia.ParticipantsCurrently registered and practising pharmacists were approached using snowball sampling and selected using purposive techniques to obtain balance representation of metropolitan and rural pharmacies, as well as high and low script volumes where possible.ResultsTwenty-four pharmacists across 15 pharmacies participated during the 135 sessions totalling over 274 hours of observation. Dispensing (30%), indirect patient services (17%), counselling (15%) and professional management activities (15%) were the top four duties pharmacists performed, while only 2% of time was spent on professional services such as pain clinics and influenza vaccinations. Tasks were frequently interrupted and often performed simultaneously. Breaks and consumer-contact times were limited. More time was spent on professional service activities in non-metropolitan pharmacies, in pharmacies with greater daily prescription volumes and those with one or more support pharmacists.ConclusionsThis is the first study to quantify the pharmacists’ tasks in Australian community pharmacies. Much time is being spent on dispensing, supply and management activities with little time for providing additional professional services. An extra supporting pharmacist is likely necessary to increase professional services. These findings could support future research around barriers and enablers of conducive workflows and of extended professional services.

Background Process evaluation is increasingly recognized as an important component of effective implementation research and yet, there has been surprisingly little work to understand what constitutes best practice. Researchers use different methodologies describing causal pathways and understanding barriers and facilitators to implementation of interventions in diverse contexts and settings. We report on challenges and lessons learned from undertaking process evaluation of seven hypertension intervention trials funded through the Global Alliance of Chronic Diseases (GACD). Methods Preliminary data collected from the GACD hypertension teams in 2015 were used to inform a template for data collection. Case study themes included: (1) description of the intervention, (2) objectives of the process evaluation, (3) methods including theoretical basis, (4) main findings of the study and the process evaluation, (5) implications for the project, policy and research practice and (6) lessons for future process evaluations. The information was summarized and reported descriptively and narratively and key lessons were identified. Results The case studies were from low- and middle-income countries and Indigenous communities in Canada. They were implementation research projects with intervention arm. Six theoretical approaches were used but most comprised of mixed-methods approaches. Each of the process evaluations generated findings on whether interventions were implemented with fidelity, the extent of capacity building, contextual factors and the extent to which relationships between researchers and community impacted on intervention implementation. The most important learning was that although process evaluation is time consuming, it enhances understanding of factors affecting implementation of complex interventions. The research highlighted the need to initiate process evaluations early on in the project, to help guide design of the intervention; and the importance of effective communication between researchers responsible for trial implementation, process evaluation and outcome evaluation. Conclusion This research demonstrates the important role of process evaluation in understanding implementation process of complex interventions. This can help to highlight a broad range of system requirements such as new policies and capacity building to support implementation. Process evaluation is crucial in understanding contextual factors that may impact intervention implementation which is important in considering whether or not the intervention can be translated to other contexts.

Cardiovascular disease (CVD) is still the leading cause of death and disability worldwide despite the availability of well-established and effective preventive options. Accurate perception of a patient's risk by both the patient and the doctors is important as this is one of the components that determine health-related behavior. Doctors tend to not use cardiovascular (CV) risk calculators and underestimate the absolute CV risk of their patients. Patients show optimistic bias when considering their own risk and consistently underestimate it. Poor patient health literacy and numeracy must be considered when thinking about this problem. Patients must possess a reasonably high level of understanding of numerical processes when doctors discuss risk, a level that is not possessed by large numbers of the population. In order to overcome this barrier, doctors need to utilize various tools including the appropriate use of visual aids to accurately communicate risk with their patients. Any intervention has been shown to be better than nothing in improving health understanding. The simple process of repeatedly conveying risk information to a patient has been shown to improve accuracy of risk perception. Doctors need to take responsibility for the accurate assessment and effective communication of CV risk in their patients in order to improve patient uptake of cardioprotective lifestyle choices and preventive medications.