The impact of global falsified medicines regulation on healthcare stakeholders in the legitimate pharmaceutical supply chain: a systematic review.

Background: Falsified medicines and their international regulation impacts all healthcare sectors and their actors. These regulations aim to strengthen and protect the global pharmaceutical supply chain against falsified medicines. However, an evaluation of the impacts of these regulations on key stakeholders within the legitimate supply chain have not been explored. Objective: This research aimed to evaluate both the positive and negative impacts of falsified medicines regulation on key stakeholders within the global pharmacy sector including including manufacturers, wholesalers, hospital pharmacies, community pharmacy and patients. Design: This research consists of a systematic review and thematic analysis concerning falsified medicines regulation and the subsequent impacts of existing global regulations on healthcare. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and checklist were utilized for reporting in this systematic review. Data sources and methods: A search of three databases, Embase, ProQuest and PubMed, was undertaken to determine studies applicable to the research question. The Mixed Methods Appraisal Tool (MMAT) was used to assess methodological quality and risk of bias for all included studies. Results: From the initial 657 studies, a final set of 13 relevant studies were identified. The most frequently reported falsified medicines regulation was the Falsified Medicines Directive (FMD) [n = 11]. The impact of falsified medicines regulation in the literature related to four areas: (1) Financial, (2) Social, (3) Organizational, and (4) Pharmacy Practice. These common themes across the included studies frequently relate to challenges and/or concerns associated with falsified medicines regulation implementation as well as both the logistics and practicality of incorporating falsified medicines regulations into daily operations. Conclusion: Implementation and enforcement of falsified medicines regulation does not yet appear to categorically fulfill the primary aim of the regulations, to strengthen the drug supply chain. However, in recent years, such regulations have challenged the legitimate pharmaceutical supply change actors as they attempt to successfully implement these regulations. Studies mainly detail the negative impacts of regulation during the implementation phase but with the overall benefit pertaining to the prioritization and enhancement of patient care and safety within the healthcare sector.

The response of the Irish pharmaceutical manufacturing sector to the COVID-19 pandemic with a focus on Lean and JIT.

Background: Just in Time (JIT) and Lean manufacturing are concepts that originated in the automotive industry and were then adopted by pharmaceutical and biopharmaceutical companies during the 1990s. However, the Covid-19 pandemic and the urgent demand for pharmaceutical treatment challenged JIT and Lean manufacturing processes. Production of Covid-19-related medicines increased, putting pressure on global supply chains and operations. This also hindered the production of medicines using the same or similar materials. Thus, questions are raised concerning JIT and Lean supply chains in the pharmaceutical industry. Objectives: The present study aimed to explore (1) if material and supply constraints occurred due to the Covid-19 pandemic, (2) how companies were impacted and managed and (3) if changes are required to future proof the JIT supply chain approach for future global events. Design: A mixed-method cross-sectional survey design was used and focused on material supply, qualification and validation in Irish pharmaceutical manufacturing sites. Methods: Employees working in the Irish pharmaceutical manufacturing industry were recruited using convenience sampling through online advertisement using the social media platform 'LinkedIn'. Quantitative data was analysed using percentages and qualitative data from free-text responses were used to add context to the quantitative survey questions. Results: A total of 41 participants were recruited. The results suggested that the pandemic had a negative effect on material availability according to 81% of participants. This translated to delays or stoppage of production activity and was mainly handled by sourcing new materials (70%). To cope with future global crises, 60% of participants recommended more flexibility in future validation processes while 78% of participants acknowledged the importance of validating additional suppliers. A hybrid model of manufacturing and supply chain management was also a preferred approach to exclusive Lean and JIT (42%). Conclusions: The production of non-Covid-19 medicines was adversely affected by the Covid-19 pandemic, but the pharmaceutical industry in Ireland demonstrated resilience and collaboration in response to these challenges. This study suggests that the JIT and Lean manufacturing model should be adjusted to ensure medicine supply chains are not disrupted during future global events.

The Impact of Climate Change on Health Services in Low- and Middle-Income Countries: A Systematised Review and Thematic Analysis.

Aim: The aim of this study was to assess the impact of climate change on health services as categorized by the WHO's Building Blocks for creating Climate-Resilient Health Systems. Objective: The objective was to conduct a systematized review of the published literature concerning the impact of climate change, using a thematic analysis approach to address our aim and identify areas for further research. Design: A search was conducted on 8 February 2022 using the Embase and PubMed research databases. Peer-reviewed scientific studies that were published in English from 2012 to 2022, which described at least one report concerning the impact of climate change on health services in LMICs, were included. Studies were organized based on their key characteristics, which included the date of publication, objective, method, limitations, participants, and geographical focus. The Mixed-Methods Appraisal Tool (MMAT) was used to assess the risk of bias in the included studies. Results: Twenty-three studies were included in this review. Five areas of health services which align with the WHO building blocks framework were impacted by climate change. These health service areas included: (1) Service Delivery, (2) Human Resources, (3) Health Finance, (4) Healthcare Products and Technology, and (5) Leadership and Governance. However, research concerning the impact of climate change on health information systems, which is part of the WHO building blocks framework, did not feature in our study. The climatic effects were divided into three themes: meteorological effects, extreme weather events, and general. The research in this study found that climate change had a detrimental impact on a variety of health services, with service delivery being the most frequently reported. The risk of bias varied greatly between studies. Conclusions: Climate change has negatively impacted health services in a variety of different ways, and without further actions, this problem is likely to worsen. The WHO building blocks have provided a useful lens through which to review health services. We built an aligned framework to describe our findings and to support future climate change impact assessments in this area. We propose that further research concerning the impact of climate change on health information systems would be valuable, as well as further education and responsible policy changes to help build resilience in health services affected by climate change.

What is the impact of antidepressant side effects on medication adherence among adult patients diagnosed with depressive disorder: A systematic review.

BACKGROUND: Medication adherence is a prerequisite to achieving beneficial treatment outcomes. In major depressive disorder, many patients fail to complete medication regimens, raising concern for poor treatment outcomes. It is usual to experience adverse drug reactions (ADRs) while taking antidepressants, and relative discomfort is reported by patients. AIMS: The present review focuses on the presence of antidepressant-related side effects and the subsequent relationship with medication non-adherence. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Following the preliminary research, the research question and eligibility criteria were created based on the PICO framework. All articles retrieved from the selected databases were exported to Covidence, a Systematic Review managing software tool. Two reviewers assessed the papers to identify the risk of bias using the Joanna Briggs Institute critical appraisal tool for cross-sectional studies. Seven studies with a low-moderate risk of bias fulfilled the eligibility criteria and were conducted from 2013 to 2020 in Europe, Africa and Asia. RESULTS: The results demonstrated high levels of suboptimal adherence ranging from 46% to 83% amongst the studied population. A variety of side effects were reported by a significant number of participants predominantly with moderate severity. A correlation between the presence of ADRs and suboptimal rates of adherence to antidepressants was found. Somnolence and headaches among other unspecified ADRs were found to increase the dropout rates for selective serotonin reuptake inhibitors. CONCLUSIONS: The present study elucidates the need for effective interventions to facilitate antidepressant adherence and enhance doctor-patient communication, benefiting both the individuals and the healthcare system and leading to better clinical outcomes and reduction of relapse-related costs.

Access and use of immunoglobulins in secondary supportive cancer care: A systematic literature review.

Background: Immunoglobulin replacement therapy (IgRT) benefits patients with primary immuno deficiency (PID) originating from the innate or polygenic defects in the immune system. However, evidence supporting their therapeutic role is not as explicit in secondary immuno deficiency (SID) resulting from the treatment of haematological malignancies. Objectives: This study aimed to (1) create a dataset of relevant research papers, which explore the use of IgRT in SID for analysis, (2) assess the risk of bias within this dataset and (3) study the characteristics of these papers. Design: This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. In addition to the risk of bias, the study characteristics explored in this article included study design, study geographical location and year of publication. Data Sources and Methods: To identify studies relevant to the research question, EMBASE and PubMed databases were searched. The Population, Intervention, Comparison and Outcome (PICO) framework was used to assess study quality. Risk of bias and quality of studies were assessed in accordance with the study design. As one model was not appropriate to assess bias in all articles, several tools were used. Results: A total of 43 studies were identified from the literature search as relevant to the research objective. The most common study design was a retrospective case-control cohort study (n = 16/43), and randomised trials were among the least commonly used approaches (n = 1). Research in this area is occurring around the globe including the United States (n = 7), Italy (n = 7), China, India, Japan and throughout Europe. The annual number of papers in this area has varied from 2012 (n = 1) to 2021 (n = 7). The studies in this article demonstrated a varied risk of bias, with 9 of the 20 cohort studies scoring less than 5 out of 9 stars. Conclusions: Randomised controlled trials are less frequently used to assess access and use of immunoglobulins. More commonly, a retrospective case-control cohort study was used which correlates with the higher risk of bias seen in the studies in this article. Most of the research concerning immunoglobulin use and access occurs in higher-income countries.

Medicine authentication technology: a quantitative study of incorrect quarantine, average response times and offline issues in a hospital setting.

OBJECTIVES: To introduce serialised medicines into an operational hospital dispensary and assess the technical effectiveness of digital medicine authentication (MA) technology under European Union Falsified Medicines Directive (EU FMD) conditions. DESIGN: Thirty medicine lines were serialised using 2D data matrix labels and introduced into an operational UK National Health Service (NHS) hospital dispensary. Staff were asked to check medicines for two-dimensional (2D) data matrices and scan those products, in addition to their usual medicine preparation and checking processes. Four per cent of the study medicines were labelled with a 2D barcode which generated a pop-up, identifying the medicine as either authenticated elsewhere (falsified), authenticated here, expired or recalled. SETTING: An NHS teaching hospital based in the UK, the same site as the Naughton et al 2016 study. PARTICIPANTS: General Pharmaceutical Council registered, accredited accuracy checking technicians and pharmacists. PRIMARY OUTCOME MEASURES: Average response times, offline issues, instances of incorrect quarantine and workarounds. The EU FMD maximum response time is 300 milliseconds (ms). RESULTS: During the checking stage of medicine preparation, the average response time for MA in this study was 131 ms. However, 4.67% of attempted authentications experienced offline issues, an increase of 4.23% from the previous study. An increase in offline instances existed alongside an increase in incorrect quarantine. CONCLUSIONS: Digital drug screening has the capability of operating with average response times which are below the maximum EU FMD limit of 300 ms. However, there was an increased incidence of offline errors and cases of incorrect quarantine. The practical and legal implications of supplying a substandard or falsified medicine during offline periods without prior authentication or withholding supply until online status resumes are not yet fully understood.

The European Falsified Medicines Directive in Poland: background, implementation and potential recommendations for pharmacists.

By February 2019, the Polish pharmaceutical industry, community and hospital pharmacies, wholesalers and parallel traders must all comply with the EU-wide Falsified Medicines Directive (FMD) legislation (2011/62/EU), to ensure that no medicinal product is dispensed to a patient without proper tracking and authentication. Here we describe how Poland is complying with the new EU regulations, the actions that have been taken to incorporate the FMD into Polish Pharmaceutical Law and whether or not these actions are sufficient. We found that Poland is only partially compliant with the FMD and further actions need to be undertaken to fully meet the Delegated Act (DA) requirements. Moreover, there is lack of awareness in Poland about the prevalence of falsified medication and the time scale required for implementation of the DA. Based on our findings, we suggest that a public awareness campaign should be started to raise awareness of the increased number of falsified medicines in the legal supply chain and that drug authorisation systems are implemented by Polish pharmacies to support the FMD.