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Issues. The last two or three decades have seen some valuable investment in workforce development. However, significant challenges remain in developing effective practice across various systems. Despite the relevance alcohol, tobacco and other drug use have for a range of staff across diverse organisations, adoption of cross-sector and collaborative effective practice is not widespread. The most common response involves a rather singular focus on strategies that develop practitioner knowledge and skills, with much less consideration given to the complex nature of the work environment and the belief systems of people who work in these environments. Approach. This paper explores the barriers to and facilitators of effective practice, extending beyond the common focus on education and training initiatives. A model of capacity building is explored as a template to inform workforce and organisational development strategies. Key Findings. Numerous barriers, outside education and training, must be considered in order to develop and maintain effective practice across various systems of prevention and treatment. The paper culminates with recommendations on how to overcome such challenges. Implications. Workforce and organisational development must extend beyond education and training initiatives. Along with a focus on organisational and system factors, we must also attend to the marginalisation of people affected by drug use and associated pejorative attitudes. Conclusion. Developing effective practice in the drug field involves changing the structures, and expected outcomes of these structures, in which people work, not just encouraging a few to use new ways of working in spite of the system.[Allsop SJ, Stevens CF. Evidence-based practice or imperfect seduction? Developing capacity to respond effectively to drug-related problems. Drug Alcohol Rev 2009;28:541–549] [ABSTRACT FROM AUTHOR]

This paper builds on a suite of research studies examining the metamorphosis in industry organisation, as Penrose calls it, regarding the centrality of firm capabilities in biosciences. Whereas knowledge leadership capabilities used to be inside global corporations now they have given way to university laboratories and dedicated biotechnology firm networks to access innovative research. The basic argument is that research centre and small firm knowledge capabilities have generally outstripped those of the multinationals in knowledge-intensive industry, a consequence of which is a re-alignment in cause-and-effect outcomes shaping economic geography. This is particularly pronounced in biosciences and pharmaceuticals. The paper mobilises a new theoretical framework and new data that support the thesis that a realignment of industry organisation around knowledge capabilities was pioneered in biosciences, is active in other industries, and biosciences is now entering a new phase. This mirrors a rise in systems biology that re-asserts the dominance of key nodes in global bioeconomy hierarchies. [ABSTRACT FROM AUTHOR]

This paper analyzes the negotiation process, which leads to basic research funding and price setting for new drugs in regulated health insurance markets. Its results bring answers to the following questions: Should basic research be privately funded, publicly funded, or produced by an independent lab? Under which conditions is public integration of basic research efficient? How do pharmaceutical prices respond to different organizations of basic research? We show that efficiency and prices are higher when basic research is integrated in the firm that commercializes the drug as compared with independent basic research. In both organizations, the higher the negotiation power of the research labs relative to the one of the public health authority is, the higher the prices and the efficiency are. We thereby confirm the traditional trade-off between price containment and dynamic efficiency. We identify one important exception to this trade-off. Indeed, public integration of basic research can result in lowest prices and highest efficiency, as compared with the other possible organizations, in particular when basic and applied research are highly complementary. [ABSTRACT FROM AUTHOR]

Background: This paper provides a critical review of the decision‐making process of the Ontario Ministry of Health and Long‐Term Care (MOHLTC) regarding which migraine treatment drugs will be covered under the Ontario Drug Benefit Formulary (ODB). Main Text: Under MOHLTC policy, triptans and OnabotulinumtoxinA are available to patients only through the Exceptional Access Program (EAP). This policy, and justifications for it, are examined with reference to clinical guidelines, patient experiences, and health policy literature. The contexts and consequences of compromised access are outlined. Improvements in access to these treatments are suggested by highlighting how a country with similar healthcare infrastructure – Australia – employs policies that more adequately meet the needs of migraine patients as they secure treatments. Conclusions: Despite clinically significant gains in the discovery of safe and effective migraine‐specific treatments the ODB thus far has failed to align its practice with current clinical recommendations. This forces patients to rely heavily on medication that, while still effective for some, is potentially suboptimal. This review concludes it is prudent, at minimum, to follow clinical recommendations that advocate for the removal of triptans from EAP and recategorize them as Limited Use drugs. Ideally, moving them to a general benefit would further remove the barriers experienced by patients attempting to access this treatment. [ABSTRACT FROM AUTHOR]

Background: Opioid prescribing by dentists for older patients receiving medications with potential contraindications and the subsequent impact on acute care outcomes is not well described. Objectives: Our objective of this paper was to evaluate the use of potentially inappropriate medication combinations (PIMCs) involving opioids prescribed by dentists according to the Beers Criteria and risks of 30‐day emergency department (ED) visits and all‐cause hospitalization among commercially insured dental patients ages 65 years and older. Methods: We conducted a retrospective cohort study of 40,800 older dental patient visits in which opioids were prescribed between 2011 and 2015 using the IBM MarketScan databases. Data collection from dental, medical, and pharmacy claims included information on the concurrent use of PIMCs and outcomes of all‐cause acute care utilization over the 30‐day period after dental encounters. Results: For the overall cohort, the median age was 69 years, and 45% were women. The prevalence of PIMCs per Beers Criteria was 10.4%. A total of 947 all‐cause acute care events were observed in the 30 days post‐dental visit. Patients with PIMCs involving opioids prescribed by dentists according to the Beers Criteria had higher rates of acute care use (3.3% vs 2.2%, p<0.001), which were associated with an increased risk of all‐cause acute care utilization (adjusted risk ratio [RR] 1.23, 95% confidence interval [CI] 1.02–1.48). A dose‐response relationship was seen with increasing oral morphine equivalents prescribed and increased acute care utilization (p<0.001). Conclusion: A significant proportion of older patients receiving opioids at dental visits use psychotropic medications that in combination should be avoided according to the American Geriatric Society Beers Criteria. [ABSTRACT FROM AUTHOR]

Developing highly efficient and nontoxic drug carriers, which can work well for both chemotherapy drugs and photosensitizers, is an urgent demand to improve the efficacy of chemo‐photodynamic therapy and to promote its clinical applications. In this paper, a facile way is proposed to construct a DNA‐based nanocarrier, to achieve the synergetic loading and delivery of doxorubicine (Dox) and porphyrin/G‐quadruplex composited photosensitizer. The nanocarrier contains a gold nanoparticle (AuNP) core and a DNA layer. It is prepared via a nontemplated extension of short DNA primers on AuNP core through terminal deoxynucleotidyl transferase catalysis and subsequent DNA hybridization. Through the intercalation of Dox in duplex DNA and the forming of porphyrin/G‐quadruplex complex, the drugs responsible for chemotherapy and photodynamic therapy are efficiently loaded in the nanocarrier, and then delivered to and accumulated at tumor sites. Inside tumor cells, i‐motif may form under acidic conditions, thus triggering pH‐responsive payload release, and making the drug concentration achieving the therapeutic limitation in a short time. Highly efficient drug delivery and antitumor performance of the nanocarrier system are well demonstrated by both in vitro and in vivo experiments. The proposed nanocarrier may be developed as a promising tool for clinical drug delivery and disease therapy. [ABSTRACT FROM AUTHOR]

The United States spends nearly 1/5th of its GDP on healthcare. Yet, to achieve value‐based care, the Economist describes the US healthcare system as handicapped by multiple, disparate silos that prevent the organization and sharing of data. This paper explores the current state of clinical oncology drug research and its relationship to value‐based cancer care. Clinical Chemotherapy Pathways are proposed as a unifying structure to bring together disparate sources of data to increase value. [ABSTRACT FROM AUTHOR]

Hair analysis is capable of determining both an individual's long‐term drug history and a single exposure to a drug, which can be particularly important for corroborating incidents of drug‐facilitated crimes. As a source of forensic evidence that may be used in a court of law, it must be credible, impartial and reliable, yet the pathways of drug and metabolite entry into hair are still uncertain. Many variables may influence drug analysis results, most of which are outside of the control of an analyst. An individual's pharmacokinetic and metabolic responses, hair growth rates, drug incorporation routes, axial migration, ethnicity, age and gender, for example, all display interpersonal variability. At present there is little standardization of the analytical processes involved with hair analysis. Both false positives and negative results for drugs are frequently encountered, regardless of whether a person has consumed a drug or not. In this regard, we have categorized these variables and proposed a three‐stage analytical approach to facilitate forensic toxicologists, hair analysis experts, judiciaries and service users in the analytical and interpretation process. The analysis of drugs in hair has the potential to be used as a powerful source of forensic evidence. However, the biological processes involved are still not fully understood. This paper discusses the factors that can influence the outcome of hair analysis results and suggests a three‐stage interpretation of the many variables that an analyst should consider when presenting analytical data. [ABSTRACT FROM AUTHOR]

Cellular evolution develops several conserved mechanisms by which cells can tolerate various difficult conditions and overall maintain homeostasis. Autophagy is a well‐developed and evolutionarily conserved mechanism of catabolism, which endorses the degradation of foreign and endogenous materials via autolysosome. To decrease the burden of the ubiquitin‐proteasome system (UPS), autophagy also promotes the selective degradation of proteins in a tightly regulated way to improve the physiological balance of cellular proteostasis that may get perturbed due to the accumulation of misfolded proteins. However, the diverse as well as selective clearance of unwanted materials and regulations of several cellular mechanisms via autophagy is still a critical mystery. Also, the failure of autophagy causes an increase in the accumulation of harmful protein aggregates that may lead to neurodegeneration. Therefore, it is necessary to address this multifactorial threat for in‐depth research and develop more effective therapeutic strategies against lethal autophagy alterations. In this paper, we discuss the most relevant and recent reports on autophagy modulations and their impact on neurodegeneration and other complex disorders. We have summarized various pharmacological findings linked with the induction and suppression of autophagy mechanism and their promising preclinical and clinical applications to provide therapeutic solutions against neurodegeneration. The conclusion, key questions, and future prospectives sections summarize fundamental challenges and their possible feasible solutions linked with autophagy mechanism to potentially design an impactful therapeutic niche to treat neurodegenerative diseases and imperfect aging. [ABSTRACT FROM AUTHOR]

Clinical guidance is often sought when prescribing drugs for patients with primary mitochondrial disease. Theoretical considerations concerning drug safety in patients with mitochondrial disease may lead to unnecessary withholding of a drug in a situation of clinical need. The aim of this study was to develop consensus on safe medication use in patients with a primary mitochondrial disease. A panel of 16 experts in mitochondrial medicine, pharmacology, and basic science from six different countries was established. A modified Delphi technique was used to allow the panellists to consider draft recommendations anonymously in two Delphi rounds with predetermined levels of agreement. This process was supported by a review of the available literature and a consensus conference that included the panellists and representatives of patient advocacy groups. A high level of consensus was reached regarding the safety of all 46 reviewed drugs, with the knowledge that the risk of adverse events is influenced both by individual patient risk factors and choice of drug or drug class. This paper details the consensus guidelines of an expert panel and provides an important update of previously established guidelines in safe medication use in patients with primary mitochondrial disease. Specific drugs, drug groups, and clinical or genetic conditions are described separately as they require special attention. It is important to emphasise that consensus‐based information is useful to provide guidance, but that decisions related to drug prescribing should always be tailored to the specific needs and risks of each individual patient. We aim to present what is current knowledge and plan to update this regularly both to include new drugs and to review those currently included. [ABSTRACT FROM AUTHOR]

Background: Patient and public involvement and co‐production are widely used, but nevertheless contested concepts in applied health research. There is much confusion about what they are, how they might be undertaken and how they relate to each other. There are distinct challenges and particular gaps in public involvement in alcohol research, especially when the study focus is on health matters other than alcohol dependence. Objective: To explore how patient and public involvement and co‐production have been interpreted and applied within a multi‐disciplinary research programme in the development of a complex intervention on alcohol and medicine use in community pharmacies. Design: The paper presents the authors' critical reflection on a grounded example of how public involvement concepts have been translated into practice in the intervention development phase of a publicly funded research programme, noting its impact on the programme to date. Discussion: Co‐production adds another layer of complexity in the development of a complex intervention. The research planning requirements for publicly funded research circumscribe the possibilities for co‐production, including impacting on the possibility of stability and continuity over time. [ABSTRACT FROM AUTHOR]

The risk of postoperative bleeding is a daily concern for many general dental practitioners. A thorough medical and medication history must be taken to consider all risk factors, particularly drugs, that contribute to bleeding risk. While the risk from drugs such as aspirin, warfarin and clopidogrel are well known, the extent to which new antiplatelet agents and direct oral anticoagulants affect bleeding risk is less well understood. In addition, there are drugs other than antithrombotics, such as antidepressants and complementary medicines that also impair haemostasis. The aim of this paper is to provide dentists with an updated overview of the drugs commonly encountered in general dental practice that can contribute to a patient's postoperative bleeding risk. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is the most common genetic disease that causes infant mortality. Its treatment and prevention represent the paradigmatic example of the ethical dilemmas of 21st‐century medicine. New therapies (nusinersen and AVXS‐101) hold the promise of being able to treat, but not cure, the condition. Alternatively, genomic analysis could identify carriers, and carriers could be offered in vitro fertilization and preimplantation genetic diagnosis. In the future, gene editing could prevent the condition at the embryonic stage. How should these different options be evaluated and compared within a health system? In this paper, we discuss the ethical considerations that bear on the question of how to prioritize the different treatments and preventive options for SMA, at a policy level. We argue that despite the tremendous value of what we call 'ex‐post' approaches to treating SMA (such as using pharmacological agents or gene therapy), there is a moral imperative to pursue 'ex‐ante' interventions (such as carrier screening in combination with prenatal testing and preimplantation genetic diagnosis, or gene editing) to reduce the incidence of SMA. There are moral reasons relating to autonomy, beneficence and justice to prioritize ex‐ante methods over ex‐post methods. [ABSTRACT FROM AUTHOR]

Quantitative systems pharmacology (QSP) approaches have been increasingly applied in the pharmaceutical since the landmark white paper published in 2011 by a National Institutes of Health working group brought attention to the discipline. In this perspective, we discuss QSP in the context of other modeling approaches and highlight the impact of QSP across various stages of drug development and therapeutic areas. We discuss challenges to the field as well as future opportunities. [ABSTRACT FROM AUTHOR]

Introduction: Intra‐articular injections of various drugs are commonly used in patients with degenerative osteoarthritis and also in haemophilic patients. Haemophilic arthropathy is a particular type of secondary osteoarthritis (OA), but the degeneration of strong synovial, cartilaginous and subchondral constituents is provoked by the direct action of iron and blood in the joint. Aim of the study: The aim of this study is to review the literature regarding the use of various intra‐articular drugs in joints affected by haemophilic arthropathy. Methods: We reviewed the data from the literature; the search was performed on three medical electronic databases (PubMed, Cochrane Library and Scopus Web of Science) by three authors (B. E., A. M. and V. N.) from 3 December 2018 till 15 December 2018. The search string was as follows: (hyaluronic acid OR viscosupplementation OR platelet‐rich plasma OR corticosteroid OR mesenchymal stem cells) AND (haemophilia OR haemophilic arthropathy OR haemophilic arthritis). Results: Once the research was performed, a total of 300 articles were identified. 47 selected articles were analysed by the reviewers, and the eligibility of the study inclusion was assessed independently. Twelve papers were included based on clear fulfilment of the inclusion criteria. Thirty‐five articles were excluded for the following reasons: no full text or accessible data for 14 of them, 15 involved surgery or rehabilitation therapy as the primary topic and 6 were systematic reviews (the main topics were beyond the haemophilic arthropathy). Conclusion: Although the degree of scientific evidence of the publications on intra‐articular injections of various drugs (hyaluronic acid, corticosteriods, PRP and MSCs) in haemophilia is very low, it seems that intra‐articular injections of hyaluronic acid can relieve joint pain for months and can be repeated every 6‐12 months, which is why they can be recommended. Corticosteroid injections seem to relieve joint pain for a few weeks, but their routine use is not recommended in haemophilia. The efficacy of PRP and MSCs in haemophilic arthropathy is pending confirmation, which is why they are not currently recommended. [ABSTRACT FROM AUTHOR]

Diversion strategies aim to redirect drug-involved offenders away from the criminal justice system and into treatment. Despite the interest in diversionary practices, the emergence of an empirical evaluation literature has been slow. A methodological review of published outcome studies was conducted to investigate the current strength of evidence for the efficacy of diversion and aftercare practices for criminal offenders. Twenty outcome studies were identified for review: 19 on diversion and one on aftercare. The vast majority of studies were non-randomised evaluations, reflecting the paucity of rigorous evaluation work in this area. Although most studies were prospective, very few reported on long-term outcomes following treatment. Detail was lacking with regard to basic study characteristics, such as eligibility criteria and outcomes. Despite these methodological shortcomings, results provide some tentative evidence that diversion and aftercare programmes could be effective. Best practice elements of diversion and aftercare programmes are identified and feasible strategies to improve the methodological quality of future evaluations are considered. [Harvey E, Shakeshaft A, Hetherington K, Sannibale C, Mattick RP. The efficacy of diversion and aftercare strategies for adult drug-involved offenders: a summary and methodological review of the outcome literature. Drug Alcohol Rev 2007;26:379 - 387] [ABSTRACT FROM AUTHOR]

This paper presents a review of the recent economics literature in the area of illicit drug use. Particular attention is paid to the economics of addiction and the rational addiction model, the welfare economics framework for analysing the social costs of drug use, and the attempts that have been made by economists to evaluate recent or proposed policy interventions. A dominant theme in this review is the problem of poor data availability. This is particularly true when it comes to implementing the Rational Addiction model, but it is also apparent in the literature on estimating the costs of illicit drug use to society as a whole. One of the main conclusions of this review is that until recently public policy has not been particularly influenced by research carried out by economists. It is not clear whether this is because economists have had to grapple with inadequate data, and hence their conclusions are couched in uncertainty, or whether it is because drugs researchers have assumed a very limited role for economists in their analysis. [ABSTRACT FROM AUTHOR]

This paper reviews the principal family therapy journals for the year 1999. In a series of articles about the value of integrating systemic theory and practice into the delivery of Head Start programmers some authors described how family therapy trainees were attached to programmes as part of their training in an excellently articulated analysis of family therapy within client families' homes, focus on how involvement in Head Start changed trainees' practice. The paper discusses the challenges to contemporary families: drug misuse, sexual freedom, urban stress, family fragmentation, work demands and social violence, to name but a few. In the face of these challenges, the authors believe that family therapy which is built upon the concept of the "privatized family" merely compounds the blame that society wishes to apportion to families themselves. Rather, they encourage therapists to borrow from other models including those from feminism, psychoeducational and public health approaches in order to construct a therapy that helps families collaborate in changing the whole system in which children grow up.

Population pharmacokinetic (PK) models are widely used to inform drug development by pharmaceutical companies and facilitate drug evaluation by regulatory agencies. Developing a population PK model is a multi‐step, challenging, and time‐consuming process involving iterative manual model fitting and evaluation. A tool for fully automatic model development (AMD) of common population PK models is presented here. The AMD tool is implemented in Pharmpy, a versatile open‐source library for pharmacometrics. It consists of different modules responsible for developing the different components of population PK models, including the structural model, the inter‐individual variability (IIV) model, the inter‐occasional variability (IOV) model, the residual unexplained variability (RUV) model, the covariate model, and the allometry model. The AMD tool was evaluated using 10 real PK datasets involving the structural, IIV, and RUV modules in three sequences. The different sequences yielded generally consistent structural models; however, there were variations in the results of the IIV and RUV models. The final models of the AMD tool showed lower Bayesian Information Criterion (BIC) values and similar visual predictive check plots compared with the available published models, indicating reasonable quality, in addition to reasonable run time. A similar conclusion was also drawn in a simulation study. The developed AMD tool serves as a promising tool for fast and fully automatic population PK model building with the potential to facilitate the use of modeling and simulation in drug development. [ABSTRACT FROM AUTHOR]

The motor impairments experienced by people with Parkinson's disease (PD) are exacerbated during memory‐guided movements. Despite this, the effect of antiparkinson medication on memory‐guided movements has not been elucidated. We evaluated the effect of antiparkinson medication on motor control during a memory‐guided reaching task with short and long retention delays in participants with PD and compared performance to age‐matched healthy control (HC) participants. Thirty‐two participants with PD completed the motor section of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS III) and performed a memory‐guided reaching task with two retention delays (0.5 s and 5 s) while on and off medication. Thirteen HC participants completed the MDS‐UPDRS III and performed the memory‐guided reaching task. In the task, medication increased movement velocity, decreased movement time, and decreased reaction time toward what was seen in the HC. However, movement amplitude and reaching error were unaffected by medication. Shorter retention delays increased movement velocity and amplitude, decreased movement time, and decreased error, but increased reaction times in the participants with PD and HC. Together, these results imply that antiparkinson medication is more effective at altering the neurophysiological mechanisms controlling movement velocity and reaction time compared with other aspects of movement control. [ABSTRACT FROM AUTHOR]

Camera‐based Driver Monitoring Systems (DMS) have the potential to exploit eye tracking correlates of alcohol intoxication to detect drunk driving. This study investigates how glance, blink, saccade, and fixation metrics are affected by alcohol, and whether possible effects remain stable across three different camera setups, as well as when the driver is out‐of‐the‐loop during level 4 automated driving (Wizard‐of‐Oz setup). Thirty‐five participants drove on a test track first sober and then with increasing intoxication levels reaching a breath alcohol concentration (BrAC) of 1‰. Linear Mixed‐Effects Regression analyses showed that with increasing intoxication levels, eye blinks became longer and slower, glances and fixations became fewer and longer, and more attention was directed to the road area, at the expense of more peripheral areas. Fixation and blink metrics were more robust to changes in automation mode, whereas glance‐based metrics were highly context dependent. Not all effects of alcohol intoxication could be measured with all eye tracking setups, where one‐camera systems showed lower data availability and higher noise levels compared to a five‐camera system. This means that lab findings based on higher quality eye tracking data might not be directly applied to production settings because of hardware limitations. [ABSTRACT FROM AUTHOR]

We present a novel case of an urticaria multiforme‐type drug reaction to the new cystic fibrosis medication Trikafta (elexacaftor + tezacaftor + ivacaftor). Equipped with this information, clinicians may be more prepared to counsel and treat patients if they experience similar symptoms after beginning Trikafta. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Jølving et al paper. To view this article, visit https://doi.org/10.1111/apt.16578 [ABSTRACT FROM AUTHOR]

This paper analyses the relationship of history to two current and inter-related policy issues, AIDS and drugs. AIDS, in particular in its early years, was a disease surrounded by history; and historians and others actively brought the 'lesson of history' into the public debates. Cholera and the Black Death provided historical examples of reactions to past epidemic disease; and the record of voluntarism in Britain in the area of sexually transmitted diseases was used to justify a non-punitive response to AIDS. As the perception of AIDS has changed from epidemic to chronic disease, as reactions to the disease have become 'normalized; so the type of historical input has also altered. The 'lesson of history' approach has appeared less relevant, or has changed focus to encompass chronic--TB, multiple sclerosis--rather than epidemic disease. The concept of AIDS itself as an historic event, of the 'contemporary history' of AIDS has also come to the fore. The paper contrasts the relationship of AIDS and history with the ahistorical reaction to the particular impact of AIDS on drug policy. The policy reaction to illicit drugs has been historically conscious, in particular in the 1960's. But little of this historical perspective filtered into the reaction to AIDS on drug policy. Drugs, unlike AIDS, was not an open policy arena. The paper argues that overall drug policy objectives were already clear and it suited no policy interest to call on the historical record. The achievement of established policy objectives was better achieved by an emphasis on the newness of development, a response to potentially epidemic and unusual circumstances. [ABSTRACT FROM AUTHOR]

Introduction and Aims: Nigeria is composed of six geopolitical zones plus one Federal Capital Territory. Differences between zones can differentially influence the adoption of risk behaviours by adolescents. This paper aims to describe the knowledge, attitudes, beliefs, risk perception, skills and substance use among Nigerian secondary school students highlighting the differences by geopolitical zone.Design and Methods: The population size of each zone was taken into account in extracting the 32 schools for the survey. The characteristics of the social environment, tobacco, alcohol and substance use, knowledge, beliefs, risk perception, attitudes, personal skills and school climate were investigated through an anonymous questionnaire.Results: A total of 4078 adolescents participated in the survey: 5.1% reported they had smoked cigarettes at least once in their life, 33.6% drank alcohol, 13.1% experienced drunkenness, 7.5% used cannabis and 11.6% other drugs. The highest rates of alcohol use were observed in the South, whilst the use of tobacco, cannabis and other drugs was higher in the North. Knowledge about tobacco, alcohol and marijuana was quite low across all zones. Scores for self-esteem, decision-making and refusal skills, risk perception and beliefs were lower in the North.Discussion and Conclusions: This study shows a high prevalence of adolescent alcohol and substance use in Nigeria. There is a need for planning and implementing evidence-based drug education and prevention programs across the country. Prevention activities targeting adolescents could help to reduce the later life burden of disease related to use of tobacco, alcohol and other drugs. [ABSTRACT FROM AUTHOR]

Drug metabolism is a critical stage in the development of new chemical entities to understand how the drug will behave in the body and to reveal potential toxic metabolites. In this Review, we discuss how a renaissance in the applications of synthetic electrochemistry can be employed both to identify drug metabolites (and mechanisms) and enable electrosynthetic preparation of drug metabolites for further analysis. Recent advances in electro‐oxidative drug reactions are reviewed together with a perspective on the future use of electrosynthesis to diversify lead stage drug molecules to enable rapid testing of advanced analogues. A focus on the remarkable advances in the last decade with the inclusion of seminal papers for contextual analysis are reviewed. [ABSTRACT FROM AUTHOR]

N‐heterocycles are ubiquitous structural units in a variety of biologically active compounds, pharmaceutical preparations, and natural complex molecules. Thousands of original scientific papers are published annually on various aspects of the formation of nitrogenous heterocycles and the study of their chemical and biological properties. Among them, the synthesis of pyridines and their dihydrogenated derivatives attracts the attention of chemists, which develop synthetic techniques, including those ones based on α,β‐unsaturated aldehydes. The minireview summarizes and highlights the recent advancements in the construction of pyridines, 1,2‐dihydropyridines, and 1,4‐dihydropyridines from transformations of 2‐alkenals, covering the publications of the last five years. [ABSTRACT FROM AUTHOR]

This study explores the social organisation of risk within online drug‐related communities. Drawing on in‐depth interviews with participants from two Norwegian Internet drug forums, the paper illustrates how participation in such forums influenced notions of risk, and how it supported notions of participants as being informed, responsible and empowered. First, the forums facilitated an easy exchange of user‐generated drug information, which helped members present themselves as informed and competent. Second, members used the communal resources on the forums to negotiate their drug‐using identities, in which they resisted stigma and argued for a responsible drug‐using identity. Third, the social inclusion and sense of community within the forums formed the basis for collective support, which helped empower those involved. Conceptualised as community‐consumerism, these findings highlight the social mechanisms involved in the information self‐sufficiency and decentralisation of authority on the Internet, in which members created an alternative frame of reference for drug use and associated health. The concept of community‐consumerism offers a perspective on the social organisation of risk within online communities and ought to be of relevance for future studies on online health‐related discourses, not only those related to drugs. [ABSTRACT FROM AUTHOR]

Background: Illicitly manufactured fentanyl and its analogues are appearing in countries throughout the world, often disguised as heroin or counterfeit prescription pills, with resulting high overdose mortality. Possible explanations for this phenomenon include reduced costs and risks to heroin suppliers, heroin shortages, user preferences for a strong, fast‐acting opioid and the emergence of Dark Web cryptomarkets. This paper addresses these potential causes and asks three questions: (1) can users identify fentanyl; (2) do users desire fentanyl; and (3) if users want fentanyl, can they express this demand in a way that influences the supply? Argument/analysis: Existing evidence, while limited, suggests that some users can identify fentanyl, although not reliably, and some desire it, but because fentanyl is frequently marketed deceptively as other drugs, users lack information and choice to express demand effectively. Even when aware of fentanyl's presence, drug users may lack fentanyl‐free alternatives. Cryptomarkets, while difficult to quantify, appear to offer buyers greater information and competition than offline markets. However, access barriers and patterns of fentanyl‐related health consequences make cryptomarkets unlikely sources of user influence on the fentanyl supply. Market condition data indicate heroin supply shocks and shortages prior to the introduction of fentanyl in the United States and parts of Europe, but the much lower production cost of fentanyl compared with heroin may be a more significant factor Conclusion: Current evidence points to a supply‐led addition of fentanyl to the drug market in response to heroin supply shocks and shortages, changing prescription opioid availability and/or reduced costs and risks to suppliers. Current drug users in affected regions of the United States, Canada and Europe appear largely to lack both concrete knowledge of fentanyl's presence in the drugs they buy and access to fentanyl‐free alternatives. [ABSTRACT FROM AUTHOR]

Summary: In this paper, we present the results from novel microscopy‐based approaches aimed at providing further insight into the mechanism of film formation and associated mechanical response in polymer lattices. Firstly, a 'simple' methodology, combining the use of variable pressure scanning electron microscopy and a recently introduced enhanced coolstage (–50 to +50°C), was successfully developed and not only used to study dynamic processes, e.g. different stages of latex film formation, but also for high‐resolution imaging of 'freeze‐dried' structures. By using the enhanced freeze‐drying capability of the system, it was also possible to preserve the structure and features of the studied system with minimum shrinkage and distortion and in the case of polymer lattices at a desired stage of film formation. Moreover, specimens can then be readily imaged, without the need of conductive coatings and at much lower chamber gas pressures, thus minimizing the beam skirting effects and allowing higher resolutions to be achieved. The second and final part of our study consider the mechanical response of the studied latex dried under different conditions, with the particular emphasis on the effects of drying rate [% relative humidity (RH)]. Atomic force microscopy force distance curve measurements revealed that while the %RH did not have an effect on the structures formed, it did have an effect on the adhesive properties of the studied system. It is strongly believed that the methodologies developed and used here can be applied to other material systems, including biologicals and pharmaceuticals. [ABSTRACT FROM AUTHOR]

The fast development of laboratory methods has revealed increased amounts of trace concentrations of pharmaceuticals and personal care products (PPCP) in waste waters in the Czech Republic. This paper focuses on the expected costs to solve this problem by quaternary treatment of waste water based on activated carbon filtration. The one‐time investment costs in 155 wastewater treatment plants (WWTPs) with a capacity of over 10 000 population equivalent (PE) would represent an amount of around 300 million EUR. The increase in end‐user operating costs would be 0.4 EUR/m3, which would mean a 15% increase in water and sewage costs. A sociological survey showed that most respondents (65%) would agree with an increase in price but only by 10%. Currently the cost of the quaternary treatment of wastewater is based primarily on estimates. Therefore changes in legislation leading to stricter limits and an increase in the efficiency of wastewater treatment should be preceded by additional applied research. [ABSTRACT FROM AUTHOR]

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This paper traces the modern history of alcohol and drug policy research through a series of four monographs that were written collaboratively by international groups of career scientists. The books promoted the view, supported by a considerable amount of evidence, that alcohol and drug problems can be reduced, if not prevented, through organized policy action by governments and public health organizations. The books used a problem-focused integrative approach to align research more effectively with public policy. A common thread that runs throughout the monographs is the influence of Professor Griffith Edwards. [ABSTRACT FROM AUTHOR]

This white paper examines recent progress, applications, and challenges in predicting unbound and total tissue and intra/subcellular drug concentrations using in vitro and preclinical models, imaging techniques, and physiologically based pharmacokinetic (PBPK) modeling. Published examples, regulatory submissions, and case studies illustrate the application of different types of data in drug development to support modeling and decision making for compounds with transporter‐mediated disposition, and likely disconnects between tissue and systemic drug exposure. The goals of this article are to illustrate current best practices and outline practical strategies for selecting appropriate in vitro and in vivo experimental methods to estimate or predict tissue and plasma concentrations, and to use these data in the application of PBPK modeling for human pharmacokinetic (PK), efficacy, and safety assessment in drug development. [ABSTRACT FROM AUTHOR]

Membrane transporters play diverse roles in the pharmacokinetics and pharmacodynamics of small‐molecule drugs. Understanding the mechanisms of drug‐transporter interactions at the molecular level is, therefore, essential for the design of drugs with optimal therapeutic effects. This white paper examines recent progress, applications, and challenges of molecular modeling of membrane transporters, including modeling techniques that are centered on the structures of transporter ligands, and those focusing on the structures of the transporters. The goals of this article are to illustrate current best practices and future opportunities in using molecular modeling techniques to understand and predict transporter‐mediated effects on drug disposition and efficacy.Membrane transporters from the solute carrier (SLC) and ATP‐binding cassette (ABC) superfamilies regulate the cellular uptake, efflux, and homeostasis of many essential nutrients and significantly impact the pharmacokinetics of drugs; further, they may provide targets for novel therapeutics as well as facilitate prodrug approaches. Because of their often broad substrate selectivity they are also implicated in many undesirable and sometimes life‐threatening drug–drug interactions (DDIs).5,6 [ABSTRACT FROM AUTHOR]

This white paper provides updated International Transporter Consortium (ITC) recommendations on transporters that are important in drug development following the 3rd ITC workshop. New additions include prospective evaluation of organic cation transporter 1 (OCT1) and retrospective evaluation of organic anion transporting polypeptide (OATP)2B1 because of their important roles in drug absorption, disposition, and effects. For the first time, the ITC underscores the importance of transporters involved in drug‐induced vitamin deficiency (THTR2) and those involved in the disposition of biomarkers of organ function (OAT2 and bile acid transporters). [ABSTRACT FROM AUTHOR]

Objectives: The maintenance phase of bipolar disorder is arguably the most important. The aim of management during this time is to maintain wellness and prevent future episodes of illness. Medication is often the mainstay of treatment during this phase, but adherence to treatment is a significant problem. In recent years, long‐acting injectable (LAI) solutions have been proposed, but these too have limitations. This paper discusses the options that are currently available and critically appraises the effectiveness of this strategy. Method: The authors reviewed the small number of open‐label and randomised studies on LAI medications in bipolar disorder and evaluated the efficacy and safety of these medications. Results: The studies reviewed show benefit of LAIs for the management of bipolar disorder but have several key limitations to the generalisability of findings to routine practice. Conclusions: LAIs have an emerging role in the management of bipolar disorder and, although it is not without limitations, this strategy addresses some issues of long‐term treatment and medication. Patients with bipolar disorder that are non‐adherent or have an unstable illness with a predilection towards mania are possibly better suited to the use of LAIs, though more research is required to fully assess the effectiveness of this approach. [ABSTRACT FROM AUTHOR]

Non-adherence to medication is highly prevalent in patients with schizophrenia. Adherence therapy aims to improve medication adherence of these patients by applying techniques of cognitive behavioural therapy, psycho-education, and motivational interviewing. Even though adherence therapy is frequently discussed and researched, its effectiveness is still uncertain. This paper aims to review the effectiveness of adherence therapy on the medication adherence of patients with schizophrenia. To this end, six electronic databases were systematically searched for randomized, controlled trials on adherence therapy from January 2002 to March 2013. Four trials met the inclusion criteria and were incorporated into the review. The findings suggest that adherence therapy does not improve patients' medication adherence in comparison to treatment as usual or a control intervention. However, all the studies reviewed showed high-adherence ratings at baseline. Thus, further well-designed studies that target adherence therapy to patients who are non-adherent to their medication are needed for a more profound understanding of its effectiveness. In addition, if adherence therapy is aimed not only at improving medication adherence, but also to reach an agreement whereby the patient's decision not to take his medication is accepted, the shared decision-making process needs to be assessed as well. [ABSTRACT FROM AUTHOR]

This is a highlight on the paper by Bonnet et al.: A Lock‐and‐Kill Anticancer Photoactivated Chemotherapy Agent. which constitutes an important step toward establishing photoactivated chemotherapy (PACT) as a widespread tool to treat different health issues, specially tumors. PACT can be a useful technique to deliver already tested drugs, where the effect of the desired molecule is directed only to its target after light irradiation, even in the cases in which it is difficult to achieve a precise delivery in the desired organ or tissue. Ruthenium‐polipyridyl caged‐compounds are near ideal devices to deliver a drug in that precise fashion, albeit they usually fail in revealing their actual location due to their weak light emission properties. The mentioned work introduces a simple and clever idea: the use of a covalently linked fluorophore to map the caged‐compounds in‐vivo distribution prior to the eventual irradiation to activate the chemotherapy. [ABSTRACT FROM AUTHOR]

The concept of health consciousness (HC), previously studied as a dispositional construct, holds promise for brief prevention training in work settings. The current study developed a more process‐oriented model of HC. Employer’s increasing concerns about worker prescription drug (Rx) misuse represents an opportunity to study and improve HC. Two pilot studies delivered a brief training program and assessed short‐term, pre‐ to post–self‐reports of factors related to HC. The first pilot (n = 162) attempted to evaluate a stress/resilience program (“Raw Coping Power”) that sought to improve worker ability to recognize and correct unhealthy coping behaviors. A second pilot (n = 114) attempted to evaluate an Rx misuse prevention program that sought to enhance awareness of HC as a protective factor. Both pilots used a driver analysis to examine correlates of improved HC. These correlates included increased confidence in one’s ability to evaluate risks, and awareness of healthy alternatives. Many employees also found the concept of HC useful. Previous writings about HC, in combination with current results, informed the design of a new, process‐oriented model of HC. The current paper offers this model and a driver analysis methodology that future researchers can use to further explore and more fully evaluate brief HC interventions in work settings. [ABSTRACT FROM AUTHOR]

Although the world has experienced remarkable progress in health care since the last half of the 20th century, global health inequalities still persist. In some poor countries life expectancy is between 37-40 years lower than in rich countries; furthermore, maternal and infant mortality is high and there is lack of access to basic preventive and life-saving medicines, as well a high prevalence of neglected diseases, HIV/AIDS, tuberculosis, and malaria. Moreover, globalization has made the world more connected than before such that health challenges today are no longer limited within national or regional boundaries, making all persons equally vulnerable. Because of this, diseases in the most affluent countries are closely connected with diseases in the poorest countries. In this paper, we argue that, because of global health inequalities, in a situation of equal vulnerability, there is need for global solidarity not only as a means of reducing health inequalities, but also as a way of putting up a united force against global health challenges. We argue for an African approach to solidarity in which the humanity of a person is not determined by his/her being human or rational capacity, but by his/her capacity to live a virtuous life. According to this view of solidarity, because no one is self-sufficient, no individual can survive alone. If we are to collectively flourish in a world where no individual, nation or region has all the health resources or protection needed for survival, we must engage in solidarity where we remain compassionate and available to one another at all times. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To review systematically the published literature on extended‐release naltrexone (XR‐NTX, Vivitrol®), marketed as a once‐per‐month injection product to treat opioid use disorder. We addressed the following questions: (1) how successful is induction on XR‐NTX; (2) what are adherence rates to XR‐NTX; and (3) does XR‐NTX decrease opioid use? Factors associated with these outcomes as well as overdose rates were examined. Methods: We searched PubMed and used Google Scholar for forward citation searches of peer‐reviewed papers from January 2006 to June 2017. Studies that included individuals seeking treatment for opioid use disorder who were offered XR‐NTX were included. Results: We identified and included 34 studies. Pooled estimates showed that XR‐NTX induction success was lower in studies that included individuals that required opioid detoxification [62.6%, 95% confidence interval (CI) = 54.5–70.0%] compared with studies that included individuals already detoxified from opioids (85.0%, 95% CI = 78.0–90.1%); 44.2% (95% CI = 33.1–55.9%) of individuals took all scheduled injections of XR‐NTX, which were usually six or fewer. Adherence was higher in prospective investigational studies (i.e. studies conducted in a research context according to a study protocol) compared to retrospective studies of medical records taken from routine care (6‐month rates: 46.7%, 95% CI = 34.5–59.2% versus 10.5%, 95% CI = 4.6–22.4%, respectively). Compared with referral to treatment, XR‐NTX reduced opioid use in adults under criminal justice supervision and when administered to inmates before release. XR‐NTX reduced opioid use compared with placebo in Russian adults, but this effect was confounded by differential retention between study groups. XR‐NTX showed similar efficacy to buprenorphine when randomization occurred after detoxification, but was inferior to buprenorphine when randomization occurred prior to detoxification. Conclusions: Many individuals intending to start extended‐release naltrexone (XR‐NTX) do not and most who do start XR‐NTX discontinue treatment prematurely, two factors that limit its clinical utility significantly. XR‐NTX appears to decrease opioid use but there are few experimental demonstrations of this effect. [ABSTRACT FROM AUTHOR]

ABSTRACT: When individuals become ill, they want to understand and give meaning to their illness. The interpretation of this illness experience, or illness perception, is influenced by a range of individual, contextual, and cultural factors. Some of these factors may be modifiable by nursing interventions. The purpose of this systematic review was to investigate which modifiable factors were correlated with illness perceptions across studies of adults with different chronic somatic diseases. Using search terms tailored to each of four electronic databases, studies retrieved were reviewed by two independent evaluators, and each relevant article was assessed for methodological quality. Results were standardized by calculating correlation coefficients. Fifteen papers on illness perceptions in a variety of chronic diseases met the inclusion criteria. All used standardized measures of illness perceptions. We identified five groups of modifiable correlates of illness perceptions: illness‐related factors, psychosocial factors, medication beliefs, information provision and satisfaction with information received, and quality of care. Our findings add to the knowledge of modifiable factors correlated with illness perceptions, including the importance of illness‐related factors and psychosocial factors such as anxiety and depression. Knowledge of these correlates can facilitate understanding of patients' illness perceptions and might be useful in tailoring patient education programs. [ABSTRACT FROM AUTHOR]

Background: There is considerable public and political interest in the use of cannabis products for medical purposes.Methods: The task force of the European Pain Federation (EFIC) conducted a survey with its national chapters representatives on the status of approval of all types of cannabis-based medicines, the covering of costs and the availability of a position paper of a national medical association on the use of medical cannabis for chronic pain and for symptom control in palliative/supportive care.Results: Thirty-one out of 37 contacted councillors responded. Plant-derived tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray is approved for spasticity in multiple sclerosis refractory to conventional treatment in 21 EFIC chapters. Plant-derived THC (dronabinol) is approved for some palliative care conditions in four EFIC chapters. Synthetic THC analogue (nabilone) is approved for chemotherapy-associated nausea and vomiting refractory to conventional treatment in four EFIC chapters'. Eight EFIC chapters' countries have an exceptional and six chapters an expanded access programme for medical cannabis. German and Israeli pain societies recommend the use of cannabis-based medicines as third-line drug therapies for chronic pain within a multicomponent approach. Conversely, the German medical association and a team of finish experts and officials do not recommend the prescription of medical cannabis due to the lack of high-quality evidence of efficacy and the potential harms.Conclusions: There are marked differences between the countries represented in EFIC in the approval and availability of cannabis-based products for medical use. EFIC countries are encouraged to collaborate with the European Medicines Agency to publish a common document on cannabis-based medicines.Significance: There are striking differences between European countries in the availability of plant-derived and synthetic cannabinoids and of medical cannabis for pain management and for symptom control in palliative care and in the covering of costs by health insurance companies or state social security systems. [ABSTRACT FROM AUTHOR]

Context The National Institute for Health and Care Excellence ( NICE) has an explicit mandate to include patient and public involvement in the appraisal of medicines to be available for funding on the NHS. NICE involves an appraisal committee who are required to take on board experiential evidence from patient experts alongside population-based evidence on clinical and cost-effectiveness when making a decision whether to fund a drug. Objective This paper considers how NICE Single Technological Appraisal ( STA) committees attempt to incorporate the views of patients in making decisions about funding medicines on the NHS. Methods A prospective design was employed to follow three pharmaceutical products involving three different appraisal committees. Three data collection methods were used: analysis of documentary evidence sent by NICE, non-participant unstructured observations of the open and closed sessions of meetings and qualitative interviews. Settings and participants Unstructured non-participant observations were carried out at nine STA meetings, and 41 semi-structured interviews were undertaken with committee members from NICE's STA committees, patient experts, analysts from NICE's project team and drug manufacturers. Results Our analysis showed how the committees displayed a preference for an ideal-type of patient representative, disagreement among the committee when weighing-up patient statements in the STA process and more pre-preparation support for patient involvement. Conclusions Although NICE has attempted to adopt an approach flexible to patients and carers through formal decision-making arrangements that incorporate patient views, nonetheless, the processes of the STAs can in fact undermine the very evidence collected from patient representatives. [ABSTRACT FROM AUTHOR]

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Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow-on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow-on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow-up were identified: (1) assessment of critical attributes to establish equivalence for follow-on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified. [ABSTRACT FROM AUTHOR]

Nowadays, the focus of diabetes treatment has switched from lowering the glucose level to preserving glycemic homeostasis and slowing the disease progression. The main pathophysiology of both type 1 diabetes and long‐standing type 2 diabetes is pancreatic β‐cell mass loss and dysfunction. According to recent research, human pancreatic β‐cells possess the ability to proliferate in response to elevated insulin demands. It has been demonstrated that in insulin‐resistant conditions in humans, such as obesity or pregnancy, the β‐cell mass increases. This ability could be helpful in developing novel treatment approaches to restore a functional β‐cell mass. Treatment strategies aimed at boosting β‐cell function and mass may be a useful tool for managing diabetes mellitus and stopping its progression. This review outlines the processes of β‐cell failure and detail the many β‐cell abnormalities that manifest in people with diabetes mellitus. We also go over standard techniques for determining the mass and function of β‐cells. Lastly, we provide the therapeutic implications of utilizing antidiabetic drugs in controlling the mass and function of pancreatic β‐cells. [ABSTRACT FROM AUTHOR]

Aim: To investigate changes in the clinical characteristics of patients who abused benzodiazepine receptor agonists (BZRA) or over‐the‐counter (OTC) drugs before and after COVID‐19 based on the 2018 and 2022 data of the "Nationwide Psychiatric Hospital (NPH) Survey on Drug‐related Psychiatric Disorders." Method: A total of 446 and 155 cases, and 435 and 273 cases, who mainly abused BZRAs or OTC drugs, respectively, were extracted from the database of the two NPH Surveys. Demographic variables, education, employment, criminal record, drug use during the previous year, psychiatric diagnosis, and types of abused drugs were compared between 2018 and 2022. Result: A comparison of BZRA abusers revealed a decreased number of users during the previous year and an increase in the comorbidity rate of other disorders (F3 and F4 in ICD‐10) in 2022. Etizolam, flunitrazepam, triazolam, and zolpidem were used most in both years, with an increase in zolpidem and a decrease in triazolam in 2022. A comparison of OTC drug abusers revealed a higher proportion of women and young patients in 2022. An increase in the comorbidity rate of F3 and F9 and a significant increase in the use of dextromethorphan products were observed in 2022, although codeine products were in the majority in both years. Conclusion: By comparing NPH Surveys before and after the COVID‐19 pandemic, both BZRA abusers and OTC drug abusers present complex pathologies, requiring tailor‐made treatment. The younger OTC drug abusers were particularly evident among women, and the abuse of dextromethorphan‐containing OTC drugs has increased alarmingly. [ABSTRACT FROM AUTHOR]

New advancements in nanocarrier technologies are revolutionizing the delivery of drugs through the skin, allowing for precise treatment with better absorption, stability, and bioavailability. This review investigates lipid and inorganic nanocarriers like liposomes, ethosomes, and inorganic nanoparticles and assesses their potential for delivering drugs through the skin. It emphasizes the mechanisms that enable controlled release and deeper skin penetration, which are crucial for ensuring effectiveness in clinical applications. The review synthesizes existing research, acknowledging that only few nanocarriers are successfully deployed in clinical settings. By offering a comprehensive overview, it sheds light on the progress and future obstacles to using nanocarriers for drug delivery through the skin. [ABSTRACT FROM AUTHOR]