Alcohol, Tobacco, and Marijuana use Among Individuals Receiving Prescription Opioids for Pain Management.

OBJECTIVE: Substance use among individuals receiving prescription opioids for pain may be associated with poorer functioning. The purpose was to examine whether use of substances (i.e., alcohol, marijuana, or tobacco) among individuals prescribed opioids for pain management was associated with pain, psychiatric disorders, and opioid misuse. METHODS: Patients with non-cancer pain and a new opioid prescription were recruited from two health systems. Participants (N= 827) completed measures regarding pain severity, pain interference, psychiatric symptoms, and substance use. RESULTS: Substance use was common with 58.0%, 26.2%, and 28.9% reporting alcohol, tobacco, and marijuana use, respectively. Use of tobacco or marijuana was associated with poorer functioning. Those with tobacco use had greater pain severity, interference, number of pain sites, and concern for opioid misuse, and were more likely to have probable depression, anxiety, and PTSD. Participants reporting marijuana use were more likely to have higher concern for opioid misuse scores and probable depression, anxiety, and PTSD. Use of alcohol was associated with lower pain severity and interference and fewer number of pain sites. DISCUSSION: Substance use is common among individuals receiving prescription opioids. Some types of substance use may be related to poorer opioid, pain, and psychiatric functioning. Clinicians prescribing opioids for pain management should assess for substance use, including tobacco, and be aware of the association with poorer functioning. Interventions could target pain, psychiatric symptoms, and substance use simultaneously to optimize outcomes for individuals with pain and substance use.

Enzyme Activity Inhibition of α-Amylase Using Molecularly Imprinted Polymer (MIP) Hydrogel Microparticles.

Molecularly imprinted polymers (MIPs) are a class of synthetic recognition materials that offer a cost-effective and robust alternative to antibodies. While MIPs have found predominant use in biosensing and diagnostic applications, their potential for alternative uses, such as enzyme inhibition, remains unexplored. In this work, we synthesized a range of acrylamide-based hydrogel MIP microparticles (35 µm) specific for the recognition of α-amylase. These MIPs also showed good selectivity toward the target protein with over 96% binding of the target protein, compared with the control nonimprinted polymer (NIP) counterparts. Specificity of the MIPs was determined with the binding of nontarget proteins, trypsin, human serum albumin (HSA), and bovine serum albumin (BSA). The MIPs were further evaluated for their ability to inhibit α-amylase enzymatic activity, showing a significant decrease in activity. These findings highlight the potential of MIPs as enzyme inhibitors, suggesting an innovative application beyond their conventional use.

Efflux pumps and membrane permeability contribute to intrinsic antibiotic resistance in Mycobacterium abscessus.

Mycobacterium abscessus is a pulmonary pathogen that exhibits intrinsic resistance to antibiotics, but the factors driving this resistance are incompletely understood. Insufficient intracellular drug accumulation could explain broad-spectrum resistance, but whether antibiotics fail to accumulate in M. abscessus and the mechanisms required for drug exclusion remain poorly understood. We measured antibiotic accumulation in M. abscessus using mass spectrometry and found a wide range of drug accumulation across clinically relevant antibiotics. Of these compounds, linezolid accumulates the least, suggesting that inadequate uptake impacts its efficacy. We utilized transposon mutagenesis screening to identify genes that cause linezolid resistance and found multiple transporters that promote membrane permeability or efflux, including an uncharacterized, M. abscessus-specific protein that effluxes linezolid and several chemically related antibiotics. This demonstrates that membrane permeability and drug efflux are critical mechanisms of antibiotic resistance in M. abscessus and suggests that targeting membrane transporters could potentiate the efficacy of certain antibiotics.

Sensitive Electrochemical and Thermal Detection of Human Noroviruses Using Molecularly Imprinted Polymer Nanoparticles Generated against a Viral Target.

Norovirus (NoV) is the predominant cause of foodborne illness globally; current detection methods are typically expensive, have inadequate sensitivities, and utilize biological receptors with poor stability. Therefore, accurate, cost-effective, and highly stable detection methods are needed to screen for NoV in foods. We developed molecularly imprinted polymer nanoparticles (nanoMIPs) to detect NoV using a small target epitope (12 amino acids) with a solid-phase synthesis approach. The performance of three batches of nanoMIPs with varying monomer compositions (nanoMIP-1, -2, and -3) were compared both experimentally and computationally. Surface plasmon resonance examined nanoMIP binding affinity to norovirus virus-like particles (NoV-LPs), whereby nanoMIP-1 had the lowest KD value of 0.512 µM. This is significant, as traditional targets for generation of norovirus ligands previously reported were generated against drastically larger norovirus capsid segments that have limitations in ease of production. Further, an electrochemical sensor was developed by covalently attaching the nanoMIPs to glassy carbon electrodes. In agreement with our predictions from density functional theory simulations, electrochemical impedance spectroscopy showed a sensitive response toward NoV-LPs for nanoMIP batches tested; however, nanoMIP-1 was optimal, with an excellent detection limit of 3.4 pg/mL (1.9 × 105 particles/mL). Due to its exceptional performance, nanoMIP-1 was immobilized to screen-printed electrodes and utilized within a thermal sensor, where it exhibited a low detection limit of 6.5 pg/mL (3.7 × 105 particles/mL). Crucially, we demonstrated that nanoMIP-1 could detect NoV in real food samples (romaine lettuce) by using electrochemical and thermal sensors. Consequently, the study highlights the exceptional potential of nanoMIPs to replace traditional biological materials (e.g., antibodies) as sensitive, versatile, and highly stable receptors within NoV sensors.

The use of quantitative clinical pharmacology approaches to support moxidectin dosing recommendations in lactation.

Moxidectin is approved by the US Food and Drug Administration (US FDA) for the treatment of onchocerciasis (river-blindness) due to Onchocerca volvulus in patients aged 12 years and older. In onchocerciasis-endemic areas, mass drug administration (MDA) programs with ivermectin, with or without vector control, aim to control the disease, reduce morbidity, interrupt transmission, and more recently, achieve elimination. Moxidectin has the potential to be used in MDA programs. In countries where onchocerciasis is endemic, infants are often breastfed up to the age of 2 years, suggesting that some women are likely to be lactating during such periodic MDA programs. Quantitative analyses of non-clinical and clinical data using non-compartmental analysis and population based pharmacokinetic (popPK) modeling as well as physiologically based pharmacokinetic modeling (PBPK) were performed to determine the amount of moxidectin excreted in breast milk and subsequent exposures in the infant. The results of the analyses were similar. Concentrations of moxidectin in breast milk followed a similar pattern to those in plasma, with maximum concentrations occurring approximately 4 hours after dosing followed by a rapid decline in both breast milk and plasma. As early as two days after dosing, concentrations of moxidectin in breast milk were below the threshold for acceptable daily intake levels established by the European Medicines Agency (EMA) and FDA for secondary exposures from veterinary use, and below the WHO recommended relative infant dose (RID) safety threshold. The analyses were conducted to support prescribers and policy makers on dosing recommendations for moxidectin in lactation.

Double Imprinted Nanoparticles for Sequential Membrane-to-Nuclear Drug Delivery.

Efficient and site-specific delivery of therapeutics drugs remains a critical challenge in cancer treatment. Traditional drug nanocarriers such as antibody-drug conjugates are not generally accessible due to their high cost and can lead to serious side effects including life-threatening allergic reactions. Here, these problems are overcome via the engineering of supramolecular agents that are manufactured with an innovative double imprinting approach. The developed molecularly imprinted nanoparticles (nanoMIPs) are targeted toward a linear epitope of estrogen receptor alfa (ERα) and loaded with the chemotherapeutic drug doxorubicin. These nanoMIPs are cost-effective and rival the affinity of commercial antibodies for ERα. Upon specific binding of the materials to ERα, which is overexpressed in most breast cancers (BCs), nuclear drug delivery is achieved via receptor-mediated endocytosis. Consequentially, significantly enhanced cytotoxicity is elicited in BC cell lines overexpressing ERα, paving the way for precision treatment of BC. Proof-of-concept for the clinical use of the nanoMIPs is provided by evaluating their drug efficacy in sophisticated three-dimensional (3D) cancer models, which capture the complexity of the tumor microenvironment in vivo without requiring animal models. Thus, these findings highlight the potential of nanoMIPs as a promising class of novel drug compounds for use in cancer treatment.

Molecularly imprinted nanogels as synthetic recognition materials for the ultrasensitive detection of periodontal disease biomarkers.

Periodontal disease affects supporting dental structures and ranks among one of the top most expensive conditions to treat in the world. Moreover, in recent years, the disease has also been linked to cardiovascular and Alzheimer's diseases. At present, there is a serious lack of accurate diagnostic tools to identify people at severe risk of periodontal disease progression. Porphyromonas gingivalis is often considered one of the most contributing factors towards disease progression. It produces the Arg- and Lys-specific proteases Rgp and Kgp, respectively. Within this work, a short epitope sequence of these proteases is immobilised onto a magnetic nanoparticle platform. These are then used as a template to produce high-affinity, selective molecularly imprinted nanogels, using the common monomers N-tert-butylacrylamide (TBAM), N-isopropyl acrylamide (NIPAM), and N-(3-aminopropyl) methacrylamide hydrochloride (APMA). N,N-Methylene bis(acrylamide) (BIS) was used as a crosslinking monomer to form the interconnected polymeric network. The produced nanogels were immobilised onto a planar gold surface and characterised using the optical technique of surface plasmon resonance. They showed high selectivity and affinity towards their template, with affinity constants of 79.4 and 89.7 nM for the Rgp and Kgp epitope nanogels, respectively. From their calibration curves, the theoretical limit of detection was determined to be 1.27 nM for the Rgp nanogels and 2.00 nM for the Kgp nanogels. Furthermore, they also showed excellent selectivity against bacterial culture supernatants E8 (Rgp knockout), K1A (Kgp knockout), and W50-d (wild-type) strains in complex medium of brain heart infusion (BHI).

Social support and the association between post-traumatic stress disorder and risk for long-term prescription opioid use.

ABSTRACT: Post-traumatic stress disorder (PTSD) is common in patients with chronic pain, adversely affects chronic pain outcomes, and is associated with opioid use and adverse opioid outcomes. Social support is a robust predictor of PTSD incidence and course as well as chronic pain outcome. We determined whether the association between PTSD and persistent opioid use was modified by emotional support in a cohort of patients receiving opioids for noncancer pain. Eligible participants were ≥18 years and had completed a new period of prescription opioid use lasting 30 to 90 days. Bivariate associations between cohort characteristics and each key variable was assessed using χ 2 tests for categorical variables and t -tests for continuous variables. Interaction between PTSD and emotional support was assessed by a priori stratification on low vs high emotional support. Participants (n = 808) were 53.6 (SD ± 11.6) years of age, 69.8% female, 69.6% White, and 26.4% African American. Overall, 17.2% had probable PTSD. High emotional support was significantly ( P < 0.0001) more common among those without probable PTSD. Prescription opioid use at 6-month follow-up was significantly ( P = 0.0368) more common among patients with vs without probable PTSD. In fully adjusted models, PTSD was no longer associated with opioid use at 6-month follow-up among participants with high emotional support. Among those with lower emotional support, PTSD was significantly associated with opioid use at 6-month follow-up in unadjusted (odds ratio = 2.40; 95% confidence interval: 1.24-4.64) and adjusted models (odds ratio = 2.39; 95% confidence interval: 1.14-4.99). Results point to the hypothesis that improvement of emotional support in vulnerable patients with chronic pain and PTSD may help reduce sustained opioid use.

A randomized trial of collaborative support for opioid taper after trauma hospitalization.

The COTAT (Collaborative Opioid Taper After Trauma) Study was a randomized trial of an opioid taper support program using a physician assistant (PA) to provide pain and opioid treatment guidance to primary care providers assuming care for adult patients with moderate to severe trauma discharged from a Level I trauma center on opioid therapy. Patients were recruited, assessed, and randomized individually by a surgery research recruitment team one to two days prior to discharge to home. Participants randomized to the opioid taper support program were contacted by phone within a few days of discharge by the PA interventionist to confirm enrollment and their primary care provider (PCP). The intervention consisted of PA support as needed to the PCP concerning pain and opioid care at weeks 1, 2, 4, 8, 12, 16, and 20 after discharge or until the PCP office indicated they no longer needed support or the patient had tapered off opioids. The PA was supervised by a pain physician-psychiatrist, a family physician, and a trauma surgeon. Patients randomized to usual care received standard hospital discharge instructions and written information on managing opioid medications after discharge. Trial results were analyzed using repeated measures analysis. 37 participants were randomized to the intervention and 36 were randomized to usual care. The primary outcomes of the trial were pain, enjoyment, general activity (PEG score) and mean daily opioid dose at 3 and 6 months after hospital discharge. Treatment was unblinded but assessment was blinded. No significant differences in PEG or opioid outcomes were noted at either time point. Physical function at 3 and 6 months and pain interference at 6 months were significantly better in the usual care group. No significant harms of the intervention were noted. COVID-19 (corona virus 2019) limited recruitment of high-risk opioid tolerant subjects, and limited contact between the PA interventionist and the participants and the PCPs. Our opioid taper support program failed to improve opioid and pain outcomes, since both control and intervention groups tapered opioids and improved PEG scores after discharge. Future trials of post-trauma opioid taper support with populations at higher risk of persistent opioid use are needed. This trial is registered at clinicaltrials.gov under NCT04275258 19/02/2020. This trial was funded by a grant from the Centers for Disease Control and Prevention to the University of Washington Harborview Injury Prevention & Research Center (R49 CE003087, PI: Monica S. Vavilala, MD). The funder had no role in the analysis or interpretation of the data.

Characteristics of patients with non-cancer pain and long-term prescription opioid use who have used medical versus recreational marijuana.

OBJECTIVE: Marijuana use is increasingly common among patients with chronic non-cancer pain (CNCP) and long-term opioid therapy (LTOT). We determined if lifetime recreational and medical marijuana use were associated with more frequent and higher dose prescription opioid use. DESIGN: Cross-sectional SUBJECTS: Eligible patients (n=1,037), who had a new period of prescription opioid use lasting 30-90 days, were recruited from two midwestern health care systems to a study of long-term prescription opioid use and mental health outcomes. The present cross-sectional analyses uses baseline data from this on-going cohort study. METHODS: Primary exposures were participant reported lifetime recreational and medical marijuana use versus no lifetime marijuana use. Prescription opioid characteristics included daily versus non-daily opioid use and ≥50 morphine milligram equivalent (MME) dose per day vs. <50 MME. Multivariate, logistic regression models estimated the association between lifetime recreational and medical marijuana use vs. no use and odds of daily and higher dose prescription opioid use, before and after adjusting for confounding. RESULTS: The sample was an average of 54.9 (SD±11.3) years of age, 57.3% identified as female gender, 75.2% identified as White, and 22.5% identified as Black race. Among all participants, 44.4% were never marijuana users, 21.3% were recreational only, 7.7% medical only and 26.6% were both recreational and medical marijuana users. After controlling for all confounders, lifetime recreational marijuana use, as compared to no use, was significantly associated with increased odds of daily prescription opioid use (OR=1.61; 95%CI:1.02-2.54). There was no association between lifetime recreational or medical marijuana use and daily opioid dose. CONCLUSION: Lifetime medical marijuana use is not linked to current opioid dose, but lifetime recreational use is associated with more than a 60% odds of being a daily prescription opioid user. Screening for lifetime recreational marijuana use may identify patients with chronic pain who are vulnerable to daily opioid use which increases risk for adverse opioid outcomes. Prospective data is needed to determine how marijuana use influences the course of LTOT and vice versa.

An ecological approach for skill development and performance in soccer goalkeeper training: Empirical evidence and coaching applications.

Ecological approaches in sport consider that athletes adapt to properties of the task and the surrounding environment. Thus, task and environment are key constraints of performance. Yet, the influence of task and environmental constraints on athletes' performance needs empirical examination, especially in sport-specific contexts such as soccer goalkeeping. This study aimed to examine if and how task and environmental constraints influenced goalkeepers (GKs') performances. We monitored performance coefficients of two professional female GKs across 13 training tasks that varied based on 9 constraints, referring to both interactions among athletes and properties of the surrounding landscape. Results showed that constraints explain ~ 47% of the observed variability in GKs' performances. Numerical complexity (i.e., the potential interactions between athletes) showed a major influence on performance, which indicates that number of interactions among athletes may constrain GKs' perceived opportunities for action. Field dimensions and landscape representativity (including elements such as penalty area(s), target goal(s) and constraints for shooting) showed positive relationships with performance, supporting that training designs retaining closer proximity to the game may benefit GKs' performances. Overall, results supported that athlete-environment couplings could be understood as a multifactorial model and hence, a combination of task constraints are necessary for designing effective learning environments.

Factors Associated With Interest in Engaging in Psychological Interventions for Pain Management.

OBJECTIVE: Engagement in evidence-based psychological interventions for pain management is low. Identifying characteristics associated with interest in interventions can inform approaches to increase uptake and engagement. The purpose of this study was to examine factors associated with interest in psychological interventions among persons with chronic noncancer pain receiving prescription opioids. METHODS: Participants with chronic noncancer pain and a new 30 to 90 day opioid prescription were recruited from 2 health systems. Participants (N=845) completed measures regarding pain, opioid use, psychiatric symptoms, emotional support, and interest in psychological interventions for pain management. RESULTS: There were 245 (29.0%) participants who reported a high interest in psychological interventions for pain management. In bivariate analyses, variables associated with interest included younger age, female sex, greater pain severity, greater pain interference, greater number of pain sites, lower emotional support, depression, anxiety, and post-traumatic stress disorder ( P <0.05). In a multivariate model, greater pain severity (odds ratio [OR]=1.17; CI: 1.04-1.32), depression (OR=2.10; CI: 1.39-3.16), post-traumatic stress disorder (OR=1.85; CI: 1.19-2.95), and lower emotional support (OR=0.69; CI: 0.5-0.97) remained statistically significant. DISCUSSION: The rate of interest in psychological interventions for pain management was low, which may indicate that patients initiating opioid treatment of chronic noncancer pain have low interest in psychological interventions. Greater pain severity and psychiatric distress were related to interest, and patients with these characteristics may especially benefit from psychological interventions. Providers may want to refer to psychological interventions before or when opioids are initiated. Additional work is needed to determine whether this would reduce long-term opioid use.

Design of a Multicenter Randomized Controlled Trial comparing the effectiveness of shared decision making versus motivational interviewing plus cognitive behavioral therapy for voluntary opioid tapering: The INSPIRE study protocol.

BACKGROUND: This paper describes the design and protocol of a pragmatic, randomized trial to evaluate the comparative effectiveness of shared decision making versus motivational interviewing plus cognitive behavioral therapy for chronic pain for the voluntary tapering of opioid dose in adults with chronic noncancer pain. Integrated Services for Pain: Interventions to Reduce Pain Effectively (INSPIRE) is a multicenter, randomized trial conducted at three academic health centers in the southeastern United States. Participants are adults receiving long-term opioid therapy of at least 20 morphine milligram equivalents daily for chronic noncancer pain. METHODS: Participants were randomized to either the shared decision-making intervention or the motivational interviewing session and cognitive behavioral therapy for chronic pain intervention. All participants also received guideline-concordant care supporting opioid pharmacotherapy. The primary outcome was change from baseline in average daily prescribed opioid dose at 12 months, using prescribing data from electronic health records. Secondary outcomes were Patient-Reported Outcomes Measurement Information System Pain Interference and Physical Function at 12 months. CONCLUSION: This trial evaluates the comparative effectiveness of shared decision making versus motivational interviewing plus cognitive behavioral therapy for chronic pain for the voluntary tapering of opioid dose in adults with chronic noncancer pain. Results from this study can guide clinicians, researchers, and policymakers as they seek to reduce opioid prescribing and improve management of chronic pain. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT03454555 (https://clinicaltrials.gov/ct2/show/record/NCT03454555). Participant enrollment began on June 26, 2019.

Baseline Characteristics From a New Longitudinal Cohort of Patients With Noncancer Pain and Chronic Opioid Use in the United States.

Retrospective cohort studies have consistently observed that long-term prescription opioid use is a risk factor for new major depressive episodes. However, prospective studies are needed to confirm these findings and establish evidence for causation. The Prescription Opioids and Depression Pathways cohort study is designed for this purpose. The present report describes the baseline sample and associations between participant characteristics and odds of daily versus nondaily opioid use. Second, we report associations between participant characteristics and odds of depression, dysthymia, anhedonia, and vital exhaustion. Patients with noncancer pain were eligible if they started a new period of prescription opioid use lasting 30 to 90 days. Participants were 54.8 (standard deviation ± 11.3) years of age, 57.3% female and 73% White race. Less than college education was more common among daily versus nondaily opioid users (32.4% vs 27.3%; P = .0008), as was back pain (64.2% vs 51.3%; P < .0001), any nonopioid substance use disorder (12.8% vs 4.8%; P < .0001), and current smoking (30.7% vs 18.4% P < .0001). High pain interference (50.9% vs 28.4%; P < .0001) was significantly associated with depression, as was having more pain sites (6.9 ± 3.6 vs 5.7 ± 3.6; P < .0001), and benzodiazepine comedication (38.2% vs 23.4%; P < .0001). High pain interference was significantly more common among those with anhedonia (46.8% vs 27.4%; P < .0001), and more pain sites (7.0 ± 3.7 vs 5.6 ± 3.6; P < .0001) were associated with anhedonia. Having more pain sites (7.9 ± 3.6 vs 5.5 ± 3.50; P < .0001) was associated with vital exhaustion, as was back pain (71.9% vs 56.8%; P = .0001) and benzodiazepine comedication (42.8% vs 22.8%; P < .0001). Patients using prescription opioids for noncancer pain have complex pain, psychiatric, and substance use disorder comorbidities. Longitudinal data will reveal whether long-term opioid therapy leads to depression or other mood disturbances such as anhedonia and vital exhaustion. PERSPECTIVE: This study reports baseline characteristics of a new prospective, noncancer pain cohort study. Risk factors for adverse opioid outcomes were most common in those with depression and vital exhaustion and less common in dysthymia and anhedonia. Baseline data highlight the complexity of patients receiving long-term opioid therapy for noncancer pain.

Utilisation of molecularly imprinting technology for the detection of glucocorticoids for a point of care surface plasmon resonance (SPR) device.

Herein, we describe the synthesis and characterisation of four synthetic recognition materials (nanoMIPs) selective for the glucocorticoid steroids - prednisolone, prednisone, dexamethasone, and cortisone. Using a solid-phase synthesis approach, these materials were then applied in the development of a surface plasmon resonance (SPR) sensor for the detection of these four targets in doped urine, to mimic the routine testing of agricultural waste for possible environmental exposure. The synthesised particles displayed a range of sizes between 104 and 160 nm. Affinity studies were performed, and these synthetic materials were shown to display nanomolar affinities (15.9-62.8 nM) towards their desired targets. Furthermore, we conducted cross-reactivity studies to assess the materials selectivity towards their desired target and the materials showed excellent selectivity when compared to the non-desired target, with selectivity factors calculated. Furthermore, through the use of 3D visualisation it can be seen that small changes between structures (such as a hydroxyl to ketone transformation) there is excellent selectivity between the compounds in the ranges of 100 fold plus. Using Surine™ doped samples the materials offered comparable nanomolar affinities (10.7-75.7 nM) towards their targets when compared to the standardised buffer preparation. Detection levels in urine for all compounds was in the nanomolar range. The developed sensor offers potential for these devices to be used in the prevention of these pharmaceutical compounds to enter the surrounding environment through agricultural waste through monitoring at source. Likewise, they can be used to monitor use in clinical samples.

A facility-level self-assessment of Autonomous Pharmacy Framework levels.

PURPOSE: The objective of this study was to understand at what level of the Autonomous Pharmacy Framework facilities are operating, in terms of the current state of data collection and analysis in the medication-use process, and to gather insights about systems integration and automation use. METHODS: The Autonomous Pharmacy Advisory Board, a group of chief pharmacy officers and operational leaders, developed a self-assessment instrument based on the previously published Autonomous Pharmacy Framework, made the self-assessment instrument available via the internet, and reviewed respondents' self-reported results. The data collection period for the survey started in March of 2021 and ended in January of 2023. RESULTS: A total of 119 facility-level self-assessments were completed and analyzed. On a scale of 1 to 5, where 1 represented little or no data-driven automation with lots of manual tasks and 5 represented the utmost data-driven automation with few manual tasks, the average overall facility-level score was 2.77 (range, 1.38-4.41). Results revealed slight variance by facility bed capacity. Much more variation was found in the degrees to which individual facilities have automated core processes like inventory management, intravenous medication preparation, and financial reporting. CONCLUSION: As a baseline, this automation-focused facility self-assessment suggests that for essentially all health-system pharmacy facilities and their larger organizations, a substantial body of work needs to be done to further develop and upgrade technology and practice in tandem, greatly expand data collection and analysis, and thereby achieve better operational, financial, and clinical outcomes. Significant advancements are needed to arrive at the highly reliable, highly automated, data-driven medication-use process involving few repetitive manual tasks envisioned in the Autonomous Pharmacy Framework.

There is no copy and paste, but there is resonation and inhabitation: Integrating a contemporary player development framework in football from a complexity sciences perspective.

Socio-cultural constraints shape behaviour in complexifying ways. In sport, for example, interconnected constraints play an important role in shaping the way a game is played, coached, and spectated. Here, we contend that player development frameworks in sport cannot be operationalised without careful consideration of the complex ecosystem in which they reside. Concurrently, we highlight issues associated with frameworks designed in isolation from the contexts in which they are introduced for integration, guised as trying to "copy and paste" templates from country to country. As such, there is a need to understand the oft-shrouded socio-cultural dynamics that continuously influence practice in order to maximize the utility of player development frameworks in sport. Ecological dynamics offers a complexity-oriented theoretical lens that supports the evolution of context-dependent player development frameworks. Further, tenets of the Learning in Development Research Framework can show how affordances are not just material invitations but constitute a vital component of a broader socio-cultural form of life. These ideas have the potential to: (1) push against a desire to "copy and paste" what is perceived to be "successful" elsewhere, and (2), guide the integration of player development frameworks by learning to resonate with the nuanced complexities of the broader environment inhabited.