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This research proposes a simple, new technique to obtain truthful answers to sensitive, categorical questions. The paired response technique (PRT) asks participants to merely report the sum of the answers to two paired questions, one baseline and one sensitive, with the answers to each question known only to the participants. The technique then statistically infers the prevalence of the sensitive characteristic and its potential drivers from the association of the baseline question with other questions in the survey. Monte Carlo simulations demonstrate the performance of the PRT under varying conditions. A representative survey (n = 4,649) in the Netherlands about legal and illegal purchases of prescription drugs to enhance sexual performance reveals that 17.4% of the target population has purchased medication to enhance sexual performance at least once. In contrast, in a control group surveyed with direct questioning, only 5.1% admit having done so. The great majority of these individuals opt to purchase illegally. Two further empirical applications, respectively, in the United States and the United Kingdom, show that the PRT reduces cognitive and affective costs of survey participation compared with a state-of-the-art randomized response technique for categorical questions. [ABSTRACT FROM AUTHOR]

Building on Schumpeter Mark I and Mark II, I propose an additional pattern of innovation and technological regime called the intellectual monopoly (IM) to explain the co-habitation of large incumbent firms with high entry and exit rates and provide evidence for pharmaceuticals and information technologies. I associate the IM pattern and technological regime with corporate innovation systems and illustrate that patterns not only evolve after changes in technological regimes but also due to economic, political, and institutional transformations. [ABSTRACT FROM AUTHOR]

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts. [ABSTRACT FROM AUTHOR]

Optimal omega-3 status, influenced by increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is vital for physiological health. This study investigated the impact of ad libitum fish oil supplementation on the omega-3 status of female athletes in a professional rugby league team during a competitive season. Twenty-four (n = 24) athletes participated, and their omega-3 status was assessed using the Omega-3 Index (O3I) and arachidonic acid (AA) to EPA ratio through finger-prick blood samples taken at the start and end of the season. They were given access to a fish oil supplement (PILLAR Performance, Australia) with a recommended daily dose of four capsules per day (2,160 mg EPA and 1,440 mg docosahexaenoic acid). At the beginning of the season, the group mean O3I was 4.77% (95% confidence interval [CI: 4.50, 5.04]) and the AA to EPA ratio was 14.89 (95% CI [13.22, 16.55]). None of the athletes had an O3I exceeding 8%. By the season's end, the O3I was a significantly increased to 7.28% (95% CI [6.64, 7.93], p <.0001) and AA to EPA ratio significantly decreased to a mean of 6.67 (95% CI [5.02, 8.31], p <.0001), driven primarily by the significant increase in EPA of +1.14% (95% CI [0.77, 1.51], p <.0001). However, these changes were varied between the athletes and most likely due to compliance. This study has demonstrated that using the objective O3I feedback scale is possible with elite female rugby athletes, but individual strategies will be required to achieve daily intake targets of EPA + DHA. [ABSTRACT FROM AUTHOR]

Product consumption is an important yet understudied aspect of marketing. Over-the-counter medicines present a unique consumption context because consumers are expected to follow product label instructions. For acetaminophen, a widely consumed over-the-counter drug, the authors study which consumers tend to deviate from the label instructions, why they do so, and the interventions that are most promising to mitigate such deviations. They develop a dynamic structural model of consumption that enables them to investigate the probability of different types of label deviations (e.g., >4 g per day) and drivers of such behaviors. Label deviations are infrequent "tail area" behaviors, and the model uncovers them well. The analysis is based on a unique online consumption diary in which consumers select from two classes of acetaminophen products (single ingredient or a combination of ingredients) to treat their pain or non-pain-related symptoms. Consumers have a higher probability of taking >4 g of acetaminophen when they have multiple symptoms, and a variety of observable factors explain the individual propensity to deviate from the label. The authors propose two interventions—a new label instruction and consumer education—to mitigate the observed label deviations and assess the expected impact of each. [ABSTRACT FROM AUTHOR]

Objectives: White spot lesions are more susceptible to staining agents due to their porous structure. This study examines the impact of white spot lesion treatments on discoloration caused by pediatric supplements. Method and materials: Three treatments (fluoride, casein phosphopeptide-amorphous calcium phosphate [CPP-ACP], resin infiltration), a control, and their respective syrup-based subgroups (iron and black elderberry syrups) were established, each with eight teeth. Artificial white spot lesions were induced, and weekly applications of fluoride varnish, daily applications of CPP-ACP paste, or a single resin infiltration procedure were performed on the white spot lesions within the treatment groups over 4 weeks. Simultaneously, samples were exposed daily to iron or black elderberry syrups. Spectrophotometer measurements were taken at baseline, after demineralization (T0), and after 1 (T1), 2 (T2), and 4 weeks (T4). ΔE00 values were calculated. Statistical analysis was conducted using a three-way mixed-design ANOVA, with the significance level set at P = .05. Results: At T4, ΔE00 values from all groups exceeded the clinical acceptability limit of 1.8. At T2 and T4, the ΔE00 values obtained from the black elderberry syrup subgroups were significantly higher (P < .001). At T4, the highest ΔE00 values were seen in the CPP-ACP groups (P < .001). The lowest ΔE00 values at T2 and T4 were observed in the resin infiltration groups (P < .05). Conclusions: Supplements containing ferrous sulfate and black elderberry extract caused color changes in white spot lesions that exceeded the clinical acceptability limit. Resin infiltration of white spot lesions provides advantages over remineralization treatments, particularly in minimizing discoloration induced by pediatric supplements. [ABSTRACT FROM AUTHOR]

In our paper, we encompass the topic of socioeconomic disparities intrinsic to drug pricing and look at ways to ensure that every individual in the United States can access antibiotics equally and equitably. In the United States, a multitude of individuals find themselves struggling with high, out-of-pocket costs for necessary antibiotics or medications.  These issues are generally caused by factors surrounding monopolistic drug markets, high costs for development, and the severity of disease that an individual is facing. We explore these challenges from a plethora of perspectives, such as; the role of specialty pharmacies, limited distribution networks, and the usage of psychotropic medications among youth with Autism Spectrum Disorders (ASD). High prices and restricted access of certain antibiotics for conditions like Hepatitis C highlight the systemic and intrinsic issues within the pharmaceutical industry and how it affects individuals who suffer from this disease or diseases similar to it. On a similar topic to that, ongoing shortages of ADHD medications continue to show the consistent and heavy impact of supply constraints amongst the pharmaceutical industry in the United States. We discuss potential solutions, including but not limited to, accelerating the approval of basic drugs, implementing ceiling prices to prevent high costs, and better integrating health-system specialty pharmacies. By concentrating on the need for policy reforms within the United States and collaboration amongst the various stakeholders that remain involved with drug pricing disparities, this study aims to offer a varied approach in reducing drug pricing disparities and making necessary medications accessible to every individual in the United States, regardless of socioeconomic or health status.

Specialty drugs treat complex, severe diseases and offer significant therapeutic advances. Despite their potential to transform patient care, little is known about the drivers of their diffusion. In this study, the authors develop a framework for the diffusion of specialty drugs that is motivated by the drugs' novelty, complexity, and importance, with a focus on the role of scientific evidence production. They propose that the effects of scientific evidence on specialty drug diffusion are multifaceted and generated through the three stages of the scientific evidence production process: unpublished clinical studies, publications in medical journals not cited in clinical guidelines, and clinical guidelines. The findings from the empirical analysis of two specialty drugs validate the framework, supporting the idea of multistage scientific evidence effects. In contrast, marketing activities do not have a significant effect. Although this could be attributed to specialty drug prescribers discounting information from commercial sources, it may also be due to limited marketing support. An additional analysis on a nonspecialty drug further validates the proposed framework. Calculations of scientific evidence contributions to trial prescriptions indicate that scientific evidence production can generate returns beyond the publication stage, which should provide specialty drug manufacturers with strong incentives to commit to quality and innovation. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to investigate whether psoriasis disease constitutes a risk factor for OLP, by assessing the prevalance of psoriasis in a test group with OLP and the control group without. Method and materials: A cohort of consecutive patients diagnosed clinically and histologically with OLP between 2014 and 2022 was analyzed. The results were contrasted with those obtained in control series matched for age and sex. The correlations between OLP and sex, age, tobacco, alcohol consumption, and psoriasis were assessed using Pearson chi-square test. Multivariate regression analysis was performed to evaluate the association between psoriasis and OLP. For the assessment of the quality of the statistical models, the Akaike information criterion was used. Results: The study involved 1,016 patients; 738 women (72.6%) and 278 men (27.4%). The average age was 59.38 ± 12.55 years. Of 508 patients with OLP, 16 (3.15%) had comorbid psoriasis, and this was 5 (0.98%) in the control group. Age, sex, smoking, and alcohol habits were not predictive variables in the relationship between psoriasis and OLP in these patients. There were statistically significant differences in relation to the number of locations, with greater extension in patients with OLP and psoriasis (P = .002). According to the multivariate analysis, the odds ratio of OLP for psoriasis was 3.13 (95% CI 1.20-9.68). Conclusions: This is the first study showing the potential association between psoriasis and OLP, and the results should be considered to improve knowledge of comorbidity of OLP. Based on the results, it is recommended that clinicians collect data regarding history of psoriasis in patients with OLP, and consider possible multiple intraoral locations. [ABSTRACT FROM AUTHOR]

Existing medical treatments for endometriosis-related pain are often ineffective, underscoring the need for new therapeutic strategies. In this study, we applied a computational drug repurposing pipeline to stratified and unstratified disease signatures based on endometrial gene expression data to identify potential therapeutics from existing drugs, based on expression reversal. Of 3,131 unique genes differentially expressed by at least one of six endometriosis signatures, only 308 (9.8%) were in common; however, 221 out of 299 drugs identified, (73.9%) were shared. We selected fenoprofen, an uncommonly prescribed NSAID that was the top therapeutic candidate for further investigation. When testing fenoprofen in an established rat model of endometriosis, fenoprofen successfully alleviated endometriosis-associated vaginal hyperalgesia, a surrogate marker for endometriosis-related pain. These findings validate fenoprofen as a therapeutic that could be utilized more frequently for endometriosis and suggest the utility of the aforementioned computational drug repurposing approach for endometriosis.

This study demonstrates that changes in mindfulness predict subsequent changes in well-being in a data set including individuals who recently engaged in psychedelic use.

ObjectiveTo perform a cost analysis of generic and brand-name Phosphodiesterase Type 5 (PDE5) inhibitors at different dosages and pharmacies across the US.MethodsUsing an all-payer retail pharmacy-claims database, we analyzed prescription drug data for three generic and six brand-name oral PDE5 inhibitors at different dosages across US chain and independent pharmacies in 2019.ResultsWe obtained cash price data from 60,186 pharmacies (35,976 chain and 24,210 independent). The nationwide mean cash price per unit (PPU) ranged from $8.6 ± 5.2 (sildenafil 20 mg at chain pharmacies) to $107.1 ± 71 (Adcirca 20 mg at independent pharmacies) equal to 1145.3% difference. Chain pharmacies provided significantly lower average prices for one brand-name and six generic PDE5 inhibitors. Tadalafil PPU was cheaper at higher quantities, however, PPU increased with quantity prescribed for sildenafil. Looking at the top 10 metropolitan statistical areas, the highest PPUs were observed for tadalafil (Cialis) 10 mg and sildenafil (Viagra) 50 mg in Atlanta ($67.4 ± 8.7) and Los Angeles ($50.3 ± 24.0), while New York ($9.7 ± 2.6) and Miami ($27.9 ± 16.4) had the lowest PPUs for tadalafil (Cialis) 5 mg and sildenafil (Viagra) 100 mg, respectively.ConclusionA substantial variability in PDE5 inhibitor cash prices exists across manufacturer, dosage, quantity, pharmacy type, and location. In addition, the pricing does not necessarily correlate with the regional socioeconomic factors. This highlights the importance of provider awareness and patient counseling on drug price including potentially assisting patients in identifying opportunities for cost savings.

BackgroundHIV or sexually transmitted infections remain a significant public health concern in the United States, with adolescents affected disproportionately. Adolescents engage in HIV/STI risk behaviors, including drug use and condomless sex, which increase the risk for HIV/STIs. At-risk adolescents, many of whom are racial minorities, experience HIV/STI disparities. Although at-risk adolescents are disproportionately affected by HIV/STI risk behaviors and infections and although the Centers for Disease Control and Prevention recommends routine HIV/STI testing for adolescents, relatively few adolescents report having ever been tested for HIV/STI. With expected increases in health clinic visits as a result of the Affordable Care Act combined with technological advances, health clinics and mobile health (mHealth), including apps, provide innovative contexts and tools to engage at-risk adolescents in HIV/STI prevention programs. Yet, there is a dearth of efficacious mHealth interventions in health clinics to prevent and reduce both condomless sex and drug use and increase HIV/STI testing for at-risk adolescents.ObjectiveTo address this gap in knowledge, we developed a theory-driven, culturally congruent mHealth intervention (hereon referred to as S4E [Storytelling 4 Empowerment]) that has demonstrated feasibility and acceptability in a clinical setting. The next step is to examine the preliminary efficacy of S4E on adolescent HIV/STI testing and risk behaviors. This goal will be accomplished by 2 aims: the first aim is to develop a cross-platform and universal version of S4E. The cross-platform and universal version of S4E will be compatible with both iOS and Android operating systems and multiple mobile devices, aimed at providing adolescents with ongoing access to the intervention once they leave the clinic, and the second aim is to evaluate the preliminary efficacy of S4E, relative to usual care control condition, in preventing or reducing drug use and condomless sex and increasing HIV/STI testing in a clinical sample of at-risk adolescents aged 14-21 years living in Southeast Michigan.MethodsIn this study, 100 adolescents recruited from a youth-centered community health clinic will be randomized via blocked randomization with random sequences of block sizes to one of the 2 conditions: S4E mHealth intervention or usual care. Theory-driven and culturally congruent, S4E is an mHealth adaptation of face-to-face storytelling for empowerment, which is registered with the Substance Abuse and Mental Health Services Administration's National Registry of Evidence-Based Programs and Practices.ResultsThis paper describes the protocol of our study. The recruitment began on May 1, 2018. This study was registered on December 11, 2017, in ClinicalTrials.gov. All participants have been recruited. Data analysis will be complete by the end of March 2024, with study findings available by December 2024.ConclusionsThis study has the potential to improve public health by preventing HIV/STI and substance use disorders.Trial registrationClinicalTrials.gov NCT03368456; https://clinicaltrials.gov/study/NCT03368456.International registered report identifier (irrid)DERR1-10.2196/47216.

Summary Background Methods Results Conclusions Different sedation regimens have been used to facilitate awake tracheal intubation, but the evidence has not been synthesised robustly, particularly with respect to clinically important outcomes. We conducted a systematic review and network meta‐analysis to determine the sedation techniques most likely to be associated with successful tracheal intubation, a shorter time to successful intubation and a lower risk of arterial oxygen desaturation.We searched for randomised controlled trials of patients undergoing awake tracheal intubation for any indication and reporting: overall tracheal intubation success rate; tracheal intubation time; incidence of arterial oxygen desaturation; and other related outcomes. We performed a frequentist network meta‐analysis for these outcomes if two or more sedation regimens were compared between included trials. We also performed a sensitivity analysis excluding trials with a high risk of bias.In total, 48 studies with 2837 patients comparing 33 different regimens were included. Comparing overall awake tracheal intubation success rates (38 studies, 2139 patients), there was no evidence suggesting that any individual sedation regimen was superior. Comparing times to successful tracheal intubation (1745 patients, 24 studies), any sedation strategy was superior to placebo. When we excluded trials with a high risk of bias, we found no evidence of a difference between any interventions for time to successful tracheal intubation. Thirty‐one studies (1753 patients) suggested that dexmedetomidine and magnesium sulphate were associated with a reduced risk of arterial oxygen desaturation compared with other interventions, but excluding trials with a high risk of bias suggested no relevant differences between interventions. The quality of evidence for each of our outcomes was low.To maximise effective and safe awake tracheal intubation, optimising oxygenation, topical airway anaesthesia and procedural performance may have more impact than any given sedation regimen. [ABSTRACT FROM AUTHOR]

Going beyond the conventional approach of pairwise conjugation between two molecules, the integration of multiple components onto a central scaffold molecule is essential for the development of high-performance molecular materials with multifunctionality. This approach also facilitates the creation of functionalized molecular probes applicable in diverse fields ranging from pharmaceuticals to polymeric materials. Among the various click functional groups, the azido group stands out as a representative click functional group due to its steric compactness, high reactivity, handling stability, and easy accessibility in the context of multi-azide scaffolds. However, the azido groups in multi-azide scaffolds have not been well exploited for site-specific use in molecular conjugation. In fact, multi-azide compounds have been well used to conjugate to the same multiple fragments. To circumvent problems of promiscuous and random coupling of multiple different fragments to multiple azido positions, it is imperative to distinguish specific azido positions and use them orthogonally for molecular conjugation. This review outlines methods and strategies to exploit specific azide positions for molecular conjugation in the presence of multiple azido groups. Illustrative examples covering di-, tri- and tetraazide click scaffolds are included. [ABSTRACT FROM AUTHOR]

This study aimed to ascertain how the current two ART regimens used in Ghana affected HIV patients' coagulation profiles. A case-control study was conducted on 102 HIV positive patients at the Mampong Municipal Hospital. Coagulation parameters measured showed APTT was normal in majority of ART-experienced participants but prolonged in majority of ART-naïve participants. The mean platelet count was significantly higher in ART-experienced participants. No significant differences were found between the coagulation profiles of ART-experienced patients on two different drug regimens. In conclusion, current ART can enhance the coagulation profiles in HIV-infected patients, by improving platelet count and APTT. [ABSTRACT FROM AUTHOR]

Introduction: In recent decades, an increase in the incidence of type 2 diabetes mellitus (T2DM) in children and adolescents has been observed. Pediatric‐onset T2DM differs from the adult‐onset form, particularly regarding the durability of glycemic control and earlier appearance of complications. However, the scarcity of approved treatments and comprehensive studies on T2DM management in youth persists. Ongoing clinical trials seek to ascertain the efficacy and safety of sodium‐glucose cotransporter 2 inhibitors (SGLT2i) in patients aged between 10 and 24 years with T2DM. Therefore, we aimed to perform a meta‐analysis exploring the efficacy and safety of SGLT2i in pediatric patients and young adults with T2DM. Methods: We searched PubMed, Embase, Cochrane, and Web of Science for randomized controlled clinical trials on the efficacy and safety of SGLT2i in children, adolescents, and young adults with T2DM compared with placebo. Statistical analysis was performed using RevMan 5.4 and R statistical software 4.2.1. Heterogeneity was assessed with I2 statistics. Results: We included three studies totaling 334 patients followed for 37.79 weeks. Reduction in HbA1C (MD = −0.93; 95% CI = −1.36 to −0.49; p < 0.0001; I2 = 0%) was significantly higher in SGLT2i group compared with placebo. The proportion of patients requiring rescue or discontinuation of study medication due to lack of efficacy was statistically lower in SGLT2i group compared with placebo (RR = 0.64; 95% CI = 0.43–0.94; p = 0.02; I2 = 0%). SGLT2i and placebo were similar in terms of any adverse event (RR = 1.10; 95% CI = 0.96–1.27; p = 0.17; I2 = 0%), serious side effects (RR = 1.06; 95% CI = 0.44–2.57; p = 0.90; I2 = 0%), and individual adverse effects. Conclusion: In children, adolescents, and young adults with T2DM, SGLT2i appears to be effective and safe for glycemic control. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Methods Results Conclusions Judicious antimicrobial use is essential for the continued treatment of infections in small and mixed animal veterinary medicine. To better support Washington (WA) State veterinarians in antimicrobial stewardship, we surveyed licensed small and mixed animal veterinarians and led group conversations regarding antimicrobial prescription practices.Survey questions included demographic information, factors influencing prescription practices and clinical cases. Responses were summarised and logistic regressions were performed to identify factors associated with antibiotic treatment choices. Group conversations, led by a licensed veterinarian, focused on resource gaps for veterinarians, management of clinical scenarios and interpretation of minimum inhibitory concentrations (MICs) and breakpoints. A systematic qualitative analysis of conversation transcripts identified key themes such as common barriers to stewardship.Among 53 responses to clinical scenarios, veterinarians selected the most appropriate treatment choice, according to a veterinary microbiologist, 62% of the time. Variability was observed in culture and susceptibility practices and antibiotic choices. Survey respondents reported an influence of the client ability to medicate (92%), considerations of resistance (91%), client finances (75%) and availability of antimicrobials (75%) on their prescription decisions. There were no significant associations between opinions about contributing factors to antimicrobial resistance (AMR) or guidelines used and treatment choices in clinical scenarios. Among 15 veterinarians interviewed in group conversations, a systematic qualitative analysis of conversation transcripts revealed key themes, including reliance on human medicine as a resource and a lack of support for veterinarians in interpreting MICs and breakpoints.The variability in veterinary antibiotic treatment decisions in this study suggests a need for further dissemination of standardised antimicrobial stewardship resources for veterinarians. Client‐related challenges and the cost of culture and susceptibility are major barriers to stewardship. To address these barriers, it is necessary to provide standardised, easy‐to‐access guidance for veterinarians in interpreting MICs and breakpoints, as well as develop antimicrobial use resources for clients. [ABSTRACT FROM AUTHOR]

Long-term alteration of dopaminergic neurotransmission is known to modulate the D2/D3 receptor expression in the brain. The modulation can occur as a response to pathological processes or pharmacological intervention. The receptor density can be monitored by in vivo positron emission tomography (PET) of [11C] raclopride. To obtain accurate measurements of receptor-ligand interaction, it is essential to estimate binding parameters at true (if transient) equilibrium of bound and unbound ligand quantities. We designed this study as a comparison of two quantitative approaches to transient equilibrium, the TRansient EquilibriuM BoLus Estimation (TREMBLE) method and the Transient Equilibrium Model (TEM) method, to determine binding parameters at transient equilibrium with bolus injection of the radioligand. The data demonstrates that TREMBLE unlike TEM identified the time at which equilibrium existed. TREMBLE revealed that equilibrium prevailed at one or more times after bolus injection and identified differences of receptor density among regions such as putamen and caudate nucleus. We demonstrated that TREMBLE is a quantitative approach suitable for the study of pathophysiological conditions of certain types of neurotransmission the brain. [ABSTRACT FROM AUTHOR]

Here we critique recent arguments proposing to distinguish ictal from non‐ictal generalized periodic discharges (GPDs) based on etiology and stimulation response, arguing that these are unreliable. We advocate for an empirical approach to GPDs: describe objectively, interpret through medication trials, and base further treatment on response. We call for evidence‐based approaches considering meaningful clinical outcomes. [ABSTRACT FROM AUTHOR]

Key points Heavy alcohol intake is one of the most common causes of acute pancreatitis (AP). We have previously shown that ethanol (EtOH) decreases the expression and activity of the cystic fibrosis transmembrane conductance regulator (CFTR), which plays a key role in alcohol‐induced AP development. The prescription drug, Orkambi (a combination of ivacaftor and lumacaftor) can correct impaired CFTR function and expression in cystic fibrosis (CF) patients. Thus, the present study aimed to investigate whether Orkambi can mitigate alcohol‐induced AP. Intact guinea‐pig pancreatic ducts were pre‐treated with different concentrations of ethanol (EtOH; 30, 50 and 100 mm) for 12 h alone or in combination with ivacaftor (VX770) and/or lumacaftor (VX‐809), and CFTR expression and activity were evaluated by immunostaining and by the patch clamp technique, respectively. Alcoholic AP was induced in Orkambi‐treated guinea‐pigs, and standard laboratory and histological parameters were measured. Ivacaftor and lumacaftor alone or in combination dose‐dependently restored the apical expression and activity of CFTR after EtOH treatment in vitro. Oral administration of Orkambi reduced the severity of alcohol‐induced AP and restored impaired CFTR activity and expression. Orkambi is able to restore the CFTR defect caused by EtOH and decreases the severity of alcohol‐induced pancreatitis. This is the first in vivo pre‐clinical evidence of Orkambi efficacy in the treatment of alcohol‐induced AP. Acute pancreatitis is one of the leading causes of hospital admission among gastrointestinal diseases in which the lack of a specific drug therapy plays a crucial role. The cystic fibrosis transmembrane conductance regulator (CFTR) plays an essential role in pancreatic ductal HCO3– secretion; inappropriate CFTR function, as seen in heavy alcohol consumption, increases the risk of pancreatitis development. CFTR modulators are able to prevent the inhibitory effect of ethanol and reduce pancreatic ductal injury and the severity of alcohol‐induced pancreatitis. CFTR modulators present a novel option in the pharmacotherapy of alcohol‐induced pancreatitis by enhancing pancreatic functions or preventing recurrence. [ABSTRACT FROM AUTHOR]

The presented review systematizes and summarizes the data on the synthesis of pyrrolidine derivatives, which are precursors for obtaining drugs. Based on the analysis of published data, the most promising directions in the synthesis of biologically active compounds containing a pyrrolidine ring are identified. Stereoselective synthesis methods are classified based on the source of the pyrrolidine ring. The first group includes methods that use a pyrrolidine ring as the starting compound. The second group combines stereoselective methods of cyclization of acyclic starting compounds, which lead to optically pure pyrrolidine derivatives. [ABSTRACT FROM AUTHOR]

Treatment planning for chronic diseases is a critical task in medical artificial intelligence, particularly in traditional Chinese medicine (TCM). However, generating optimized sequential treatment strategies for patients with chronic diseases in different clinical encounters remains a challenging issue that requires further exploration. In this study, we proposed a TCM herbal prescription planning framework based on deep reinforcement learning for chronic disease treatment (PrescDRL). PrescDRL is a sequential herbal prescription optimization model that focuses on long-term effectiveness rather than achieving maximum reward at every step, thereby ensuring better patient outcomes. We constructed a high-quality benchmark dataset for sequential diagnosis and treatment of diabetes and evaluated PrescDRL against this benchmark. Our results showed that PrescDRL achieved a higher curative effect, with the single-step reward improving by 117% and 153% compared to doctors. Furthermore, PrescDRL outperformed the benchmark in prescription prediction, with precision improving by 40.5% and recall improving by 63%. Overall, our study demonstrates the potential of using artificial intelligence to improve clinical intelligent diagnosis and treatment in TCM. [ABSTRACT FROM AUTHOR]

The availability of well-established analytical methods is crucial to cope with the fast-ongoing research for the development of new drug delivery formulations. In this work, a rapid highly green chromatographic method was developed for the simultaneous determination of nicotine (NIC) and caffeine (CAF) to be applied for an in-vitro release study from a newly prepared quick mist mouth spray co-formula (QMS), as a complementary synergistic fast-onset relief of cravings during smoking cessation. The chromatographic resolution was accomplished on a cyano column using isocratically delivered (1.0 mL/ min) glycerol: orthophosphoric acid (OPA) (0.2 M) adjusted to pH 3.0 using 0.05 M triethylamine (5:95, v/v) and UV detection at 260 nm. Well resolved peaks of NIC and CAF were eluted at 2.1 and 3.9 min (Rs = 5.64), with linear responses between 0.1 and 20.0 µg/mL and 0.2–40.0 µg/mL, and detection limits of 0.03 and 0.07 µg/mL for NIC and CAF, respectively. The developed method showed good analytical performance (accuracy, precision, robustness, and selectivity) as well as superiority in practicality and ecological profile compared to reported methods applying GAPI, analytical eco-scale, AGREE, BAGI, and whiteness metric tool. The developed method was successfully applied for NIC and CAF determination in their pharmaceutical preparations, and artificial saliva with no significant differences from reported method results (F-test and t-test). Moreover, an in-vitro release study of NIC and CAF from QMS was performed employing the developed method that revealed diffusion-controlled release, compared to mixed diffusion/ polymer chain relaxation for marketed single component formulation, showing the superiority of QMS in reducing drug level fluctuations of NIC and CAF and improving their bioavailability. [ABSTRACT FROM AUTHOR]

Bipolar disorder is the fourth most debilitating psychiatric illness in the world regarding Disability Adjusted Life Years and manic episodes frequently lead to lengthy hospitalizations which restricts the freedom of patients. Therefore, decreasing the length of hospitalization with safer agents is of utmost importance in the treatment of manic episodes. Aripiprazole is a medication known for its efficacy in managing mania associated with bipolar disorder. Aripiprazole long‐acting injection is approved for the treatment of mania associated with bipolar disorder in adults and found efficacious as a maintenance treatment. In the treatment of schizophrenia, European Medicines Agency has approved a simplified starting strategy of aripiprazole once a month, with two 400 mg injections and a single oral 20 mg dose of aripiprazole. To the best of our knowledge, no previous study has reported the safety, tolerability, and efficacy of this regimen in adult bipolar disorder patients. We present a case series of eight patients who were admitted to the hospital in a manic episode with psychotic features. We observed that the double injection start regimen was effective in treating manic symptoms with no specific severe adverse events. We conclude from a small sample of manic patients that a double injection start regimen has good efficacy and tolerability. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is the leading cause of dementia, and currently, no effective treatments are available to reverse or halt its progression in clinical practice. Although a plethora of studies have highlighted the benefits of physical exercise in combating AD, elder individuals often have limited exercise capacity. Therefore, mild physical exercise and nutritional interventions represent potential strategies for preventing and mitigating neurodegenerative diseases. Our research, along with other studies, have demonstrated that platycodin D (PD) or its metabolite, platycodigenin, derived from the medicinal plant Platycodon grandiflorus, exerts neuroprotective effects against amyloid b (Ab)-induced neuroinflammation. However, the combined effects of PD and physical exercise on alleviating AD have yet to be explored. The current study aimed to investigate whether combined therapy could synergistically ameliorate memory deficits and AD pathology in 5 x FAD mice. Methods: Five-month-old 5 x FAD mice were randomly assigned to four groups, and received either PD (5 mg/kg/day, p.o.), voluntary running, or a combination of both for 47 days. Nest building test, locomotion test, and Morris water maze test were used to evaluate the cognitive function. Immunohistochemical and ELISA analysis was performed to determine Ab build-up, microglia and astrocytes hyperactivation, and survival neurons in the hippocampus and perirhinal cortex. Real-time quantitative PCR analysis was used to assess the polarization of microglia and astrocytes. HPLC analysis was performed to measure monoamine neurotransmitters in the hippocampus. Results and discussion: The combination of PD and voluntary running synergistically restored nest-building behavior, alleviated recognition and spatial memory deficits, and showed superior effects compared to monotherapy. In addition, the PD and voluntary running combination reduced Ab build-up, decreased hyperactivation of microglia and astrocytes in the hippocampus and perirhinal cortex, promoted the polarization of inflammatory M1 microglia and reactive astrocytes toward beneficial phenotypes, and lowered systemic circulating pro-inflammatory cytokines while increasing anti-inflammatory cytokines in 5 x FAD mice. Furthermore, combined therapy effectively protected neurons and increased levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) in the hippocampus of 5 x FAD mice. In conclusion, the combination of PD and voluntary running holds great potential as a treatment for AD, offering promise for delaying onset or progression of AD. [ABSTRACT FROM AUTHOR]

Background: Medication non-adherence is a common issue in chronic illness. The World Health Organization has recognized a need for a valid and reliable method of measuring adherence to understand and mitigate non-adherence. This study aimed to psychometrically evaluate the English version of the Adelphi Adherence Questionnaire (ADAQ©), a questionnaire designed to assess patient-reported medication adherence across multiple therapy areas, in patients with Osteoarthritis (OA). Methodology: Data from the Adelphi OA Disease Specific Programme™, a survey of physicians and their consulting adult patients with OA conducted in the United States, November 2020 to March 2021, was used to assess the psychometric properties of the ADAQ. Patients completed the ADAQ, Adherence to Refills and Medication Scale (ARMS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and EQ-5D-3L. The measurement model of the 13-item ADAQ was assessed and refined using latent variable modelling (Multiple Indicator Multiple Cause, confirmatory and exploratory factor analyses, item response theory, Mokken scaling, and bifactor analyses). Correlational analyses (Spearman's rank and polyserial as appropriate) with ARMS, WOMAC, and EQ-5D-3L scores assessed construct validity. Anchor- and distribution-based analyses were performed to estimate between-group clinically important differences (CID). Results: Overall, 723 patients were included in this analysis (54.5% female, 69.0% aged ≥ 60). Latent variable modelling indicated a unidimensional reflective model was appropriate, with a bifactor model confirming an 11-item essentially unidimensional score. Items 12 and 13 were excluded from scoring as they measured a different concept. The ADAQ had high internal reliability with omega hierarchical and Cronbach's alpha coefficients of 0.89 and 0.97, respectively. Convergent validity was supported by moderate correlations with items of the ARMS, and physician-reported adherence and compliance. Mean differences in ADAQ score between high and low adherence groups yielded CID estimates between 0.49 and 1.05 points, with a correlation-weighted average of 0.81 points. Conclusion: This scoring model showed strong construct validity and internal consistency reliability when assessing medication adherence in OA. Future work should focus on confirming validity across a range of disease areas. [ABSTRACT FROM AUTHOR]

Patient experience is a key aspect of care quality. Since the 2007 release of the Consumer Assessment of Healthcare Providers and Systems Clinician and Group (CG-CAHPS) survey, no systematic review of factors associated with CG-CAHPS scores has been reported. We reviewed 52 peer-reviewed English language articles published in the United States using CG-CAHPS data. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and used the Checklist for Analytical Cross-Sectional Studies. We identified several interventions (eg, adding a care coordinator focused on chronic care management) associated with improved overall provider rating and 2 interventions (eg, peer shadow coaching) that improved provider communication scores. Studies evaluating the implementation of patient-centered medical homes or patient-reported outcomes found mixed results. We identified site-level factors (eg, better team communication) and provider-level factors (eg, physician empathy) associated with better patient experience. In contrast, patient-level factors (eg, medication adherence) found mixed associations with patient experience. Policymakers, clinicians, and healthcare leaders can leverage this evidence for quality improvement efforts and interventions supporting patient-centered care. [ABSTRACT FROM AUTHOR]

In recent years Scotland has been experiencing a disproportionally high number of drug related deaths compared to other European countries, causing significant individual, societal and economic burden. A possible cause of this is the increase in average number of substances involved in Scottish drug related deaths, as well as the changing pattern of substances involved. Opioids, cocaine, and alcohol have been consistently involved in the culture of drug use in Scotland, however recently National Records Scotland have identified that designer benzodiazepines such as etizolam, and prescription drugs such as gabapentinoids are increasingly being detected in Scottish toxicology reports. A systematic literature review following PRISMA guidelines was conducted through searching PubMed and Google Scholar to identify peer-reviewed articles published in English between 2013 and 2023 that investigated Scottish population data on gabapentinoids and etizolam to establish their contribution to the rise in Scottish drug related deaths. 18 studies were included in the review. A high use prevalence of etizolam and gabapentinoids in Scotland has been identified, with both substance-related deaths showing recent increase, marked since 2015. This pattern is replicated in the Scottish prison system. There has also been a significant increase of gabapentinoids prescriptions in Scotland. Polydrug use was identified as the most common determinant of both etizolam and gabapentinoids related adverse effects and fatality in Scotland, especially concurrent opioid use. The results indicate the literature on individual characteristics of Scottish at-risk users of gabapentinoids and etizolam is limited, however the data shows both substances are being used by older cohort, with adverse effects seen more in older women. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions To evaluate and compare the long‐term efficacy of medical treatments for normal tension glaucoma (NTG) in controlling intraocular pressure (IOP), and establish a hierarchical ranking based on their effectiveness. ‘Long‐term’ is defined as a treatment duration of over 12 weeks in randomised controlled trials (RCTs).This systematic review and model‐based network meta‐analysis (MBNMA) collected data of 795 patients with 997 eyes from RCTs. Patients with NTG were selected based on strict inclusion/exclusion criteria, with randomsation procedures and masking as reported in the individual trials. Eight different medications were compared, including prostaglandin analogues, beta‐blockers, brimonidine, unoprostone isopropyl, brovincamine, and palmitoylethanolamide (PEA). Notably, PEA is an oral medication, while other drugs are topical agents.Primary outcome is the long‐term efficacy of IOP control across medications with different follow‐up durations. Among the eight medications, PEA demonstrates the highest efficacy (Surface under the cumulative ranking, SUCRA = 7.46%), followed by two prostaglandin analogues: travoprost (SUCRA = 6.86%) and latanoprost (SUCRA = 6.76%), then two beta‐blockers: nipradilol (SUCRA = 4.90%) and timolol (SUCRA = 4.89%). Both brimonidine and unoprostone isopropyl have SUCRA scores below 4.0%, indicating modest but limited efficacy. Brovincamine has the lowest SUCRA score (1.32%), reflecting minimal effectiveness.This study revealed PEA as a promising agent for long‐term IOP control in NTG patients, suggesting potential use as primary or adjunctive therapy. The outcomes call for PEA's consideration in clinical practice and highlight the need for further research into its long‐term efficacy and safety for NTG. [ABSTRACT FROM AUTHOR]

Quantifying small molecule uptake across a biological membrane of a target cell is crucial for the development of efficacious and selective drugs. However, current methods to obtaining such data are not trivial. Herein, we present an accessible, higher-throughput (20 minutes), 1H NMR spectroscopy assay, which enables the quantification of small molecule phospholipid passive membrane permeation and membrane adhesion parameters. [ABSTRACT FROM AUTHOR]

Background: Abnormalities in biochemical parameters and changes in eating habits are considered complications of obesity. Oleoylethanolamide (OEA), an endocannabinoid-like compound, has been shown to have protective effects on many metabolic disorders. Given this evidence, the present study aimed to assess the effects of OEA on lipid profile parameters, fasting blood sugar (FBS), and dietary habits in healthy obese people. Methods: In this randomized, double-blind, placebo-controlled clinical trial, which was carried out in 2016 in Tabriz, Iran, 60 obese people were enrolled in the study based on inclusion criteria. The intervention group consumed 125 mg of OEA capsules, and the placebo group received the same amount of starch twice for 8 weeks. Blood samples (5 mL) were taken at baseline and the end of the study in a fasting state. Serum concentrations of FBS, triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC) were measured by enzymatic methods using commercial kits. The low-density lipoprotein cholesterol (LDL-C) concentration was obtained using the Friede-Wald formula. To assess dietary habits, a food frequency questionnaire (147 items) was used at baseline and the end of the study. A value less than < 0.05 was considered to indicate statistical significance. Results: The TG concentration decreased significantly in the intervention group (mean (SD): 166.29 (70.01) mg/dL to 142.22 (48.05) mg/dL, p = 0.047). Changes in the placebo group were not significant (p > 0.05). After adjusting for baseline values and demographic characteristics, the difference in TG between groups remained significant (p = 0.044). Changes in other biochemical parameters were not significant. There was no significant difference between or within groups in terms of food groups. Conclusion: OEA, as a complementary agent, plays a protective role in TG regulation. However, future studies with longer durations are needed to explore the impact of OEA on regulating dietary habits and to identify the mechanisms related to metabolic abnormalities in obese people. Trial Registration: The study was registered in the Iranian Registry of Clinical Trials (IRCT) center as IRCT201607132017N30 with URL. www.IRCT.IR in date 03/10/2016. [ABSTRACT FROM AUTHOR]

Adherence to antiretroviral therapy (ART) is essential for the effective management of HIV, which includes keeping the HIV viral load undetectable. This study aimed to determine whether certain ART medications are more "forgiving" of poor adherence in achieving viral suppression. We identified subgroups of ART medication usage and determined the extent to which ART adherence is associated with viral suppression across those subgroups. Data came from claims and clinical records (2017–2019) of 3,552 HIV-positive adult members of a Medicaid managed care plan. Pharmacy fill data were examined to characterize ART medications using latent class analysis (LCA), which captures the complexity of real-world ART usage (i.e., multiple medications, ART switching). LCA yielded five ART medication patterns over three years, mostly characterized by recent medications and formulations of ART, though they varied in number of tablets and in medication class. Mixed effects logistic regression models were estimated to determine whether odds of viral suppression differed by ART adherence level. After adjusting for covariates, those with at least 90% adherence (i.e., 90 to < 95%) did not significantly differ from those with 95% adherence or greater in terms of viral suppression, which corroborates existing clinical recommendations. These findings can inform provider-patient communication for people with HIV, especially those who have difficulty maintaining adherence. This includes those experiencing unstable housing, mental health conditions, or substance use. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Antipsychotics increase the risk of developing diabetes, but clinical trials are not generalizable with short follow‐up, while observational studies often lack important information, particularly hemoglobin A1c (HbA1c).We followed two Danish cohorts with schizophrenia. First, using Danish nationwide registers, we identified all individuals diagnosed with first‐episode schizophrenia (FES) between 1999 and 2019 (n = 31,856). Exposure was a redeemed prescription for an antipsychotic, and the outcome was diabetes, defined via hospital‐based diagnosis and redeemed prescriptions for glucose‐lowering drugs. Adjusted Cox regression calculated hazard rate ratios (HRR). Second, using data from the Central Denmark Region, we identified all individuals diagnosed with FES from October 2016 to September 2022 (n = 2671). Using a within‐subject design, we analyzed the change in HbA1c during the 2 years after initiation of specific antipsychotics compared to the 2 years before.In the nationwide cohort, 2543 (8.0%) individuals developed diabetes (incidence rate = 9.39 [95% CI = 9.03–9.76] per 1000 person‐years). Antipsychotics, compared to periods without, were associated with an increased risk of developing diabetes (HRR = 2.04, 95% CI = 1.75–2.38). We found a dose–response association, particularly for second‐generation antipsychotics, and different risk rates for specific antipsychotics. In the Central Denmark Region cohort, a total of 9.2% developed diabetes but mean HbA1c levels remained stable at 37 mmol/mol during the 2 years after initiation of antipsychotic medication.This comprehensive real‐world two‐cohort study emphasizes that diabetes affects almost 10% of patients with FES. Antipsychotics increase this risk, while HbA1c deterioration requires longer treatment. These findings are important for clinicians and young patients with FES. [ABSTRACT FROM AUTHOR]

A ternary mixture incorporating Hydroxyzine hydrochloride (HYX), Ephedrine hydrochloride (EPH) and Theophylline (THP) frequently prescribed for the treatment of respiratory diseases. Herein, two spectrophotometric methods are designated and applied to resolve these three components in their mixture. Method A is ratio-subtraction combined with derivative spectrophotometry, where THP can be determined directly at its λmax 271 nm (neither HYX or EPH interfere), then for determination of HYX and EPH, the ternary mixture was divided by 22 μg/mL of THP and after subtraction of the plateau region, HYX can be determined directly at its λmax 234.2 nm (absence of EPH intervention). Finally, the third derivative (3D) spectrophotometric approach was utilized to estimate EPH by detecting the peak amplitude at 222 nm with Δλ = 4 and a scaling factor 100. Principal Component Regression (PCR) and Partial Least Squares (PLS), two multivariate calibration approaches, were applied effectively in Method B. This method effectively quantified the mixture under investigation by using the absorption spectra obtained from suitable solutions of the three components in the 210–230 nm region. The calibration models were evaluated using cross-validation with PCR and PLS, producing statistical characteristics that demonstrate the effectiveness of the calibration models. Synthetic and pharmaceutical preparations were also used to conduct external validation. In pharmaceutical formulation, these methods were successfully applied to analyze HYX, EPH, and THP without overlap from formulation's excipients. Moreover, the study's findings were statistically contrasted with those of earlier reported HPLC method. Appraisal approaches were used to determine whether the new spectrophotometric methods had an adverse environmental impact involving the Green Analytical Procedure Index (GAPI) and the AGREE (Analytical Greenness). These evaluations delivered information about the methods' eco-friendliness and sustainability, proving that they are in line with ecologically attributed practices. Furthermore, the Blue Applicability Grade Index (BAGI) was utilized to identify and verify the feasibility and practicality of the suggested approaches. [ABSTRACT FROM AUTHOR]

Although most drugs currently approved are meant to treat specific diseases or symptoms, it has been hypothesized that some might bear a beneficial effect on lifespan in healthy older individuals, outside of their specific disease indication. Such drugs include, among others, metformin, SGLT2 inhibitors and rapamycin. Since 2006, the UK biobank has recorded prescription medication and mortality data for over 500′000 participants, aged between 40 and 70 years old. In this work, we examined the impact of the top 406 prescribed medications on overall mortality rates within the general population of the UK. As expected, most drugs were linked to a shorter lifespan, likely due to the life‐limiting nature of the diseases they are prescribed to treat. Importantly, a few drugs were associated with increased lifespans, including notably Sildenafil, Atorvastatin, Naproxen and Estradiol. These retrospective results warrant further investigation in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the short-term effects and safety of adjunct Suxiao Jiuxin Pills (SJPs) on conventional therapy in chronic coronary syndrome (CCS) patients who are intolerant to the adverse effects of long-acting nitrates. Methods: This was a multicenter, randomized, double-blind, placebo-controlled trial. A total of 174 CCS participants from eight clinical study centers in China were included in the modified intention-to-treat analyses. Participants with CCS and intolerance to the adverse effects of long-acting nitrates were recruited and randomized to either the SJPs or the placebo group for a duration of 4 weeks. Results: Compared to the placebo group, the SJPs group showed a significant improvement in the efficacy rate after 4 weeks (OR = 2.43, 95% CI = 1.32 to 4.47, P = 0.004). Besides, individuals without a history of alcohol consumption showed a greater improvement in the SAQ summary score compared to those with a history of alcohol consumption. Conclusion: Adjunctive SJPs enhance the effectiveness of short-term conventional anti-angina treatment for patients with CCS who experience intolerance to long-acting nitrates, without significant adverse effects during application. Trial registration: Chinese Clinical Trials Registry Platform, ChiCTR2100050066. Registered 16 August 2021, https://www.chictr.org.cn/showproj.html?proj=131470. [ABSTRACT FROM AUTHOR]

The role of P2X ionotropic receptors in the behavior of purinergic signaling on pathophysiological processes has been widely studied. In recent years, the important participation of P2X receptors in physiological and pathological processes, such as energy metabolism, characteristic inflammatory responses of the immune system, and nociceptive activity in response to pain stimuli, has been noted. Here, we explore the molecular characteristics of the P2X receptors and the use of the different agonist and antagonist agents recently described, focusing on their potential as new therapeutic targets in the treatment of diseases with emphasis on obesity, diabetes, and some of the complications derived from these pathologies. [ABSTRACT FROM AUTHOR]

In the past few decades, considerable attention has been focused on the development of novel drug delivery system (NDDS). The NDDS should ideally fulfil two prerequisites. Firstly, it should deliver the drug at a rate directed by the needs of the body, over the period of treatment. Secondly, it should channel the active entity to the site of action. Conventional dosage forms including prolonged release dosage forms are unable to meet none of these. At present, no available drug delivery system behaves ideally, but sincere attempts have been made to achieve them through various novel approaches in drug delivery. In the present review attempt was made to highlight the formulation consideration, characterization and applications of Niosomes. [ABSTRACT FROM AUTHOR]

Salbutamol sulphate is an antiasthamatic and bronchodilator agent, with half life of 1.6 hours and requires multiple daily doses to maintain adequate plasma concentrations. The objective of this present study is to develop a sustained release tablet of salbutamol sulphate which releases the drug in a sustained manner over a period, by using different polymers. The drug was formulated and evaluated as per standard procedure and it was found that F6 formulation gives optimum results. [ABSTRACT FROM AUTHOR]

Global drug policy is currently dominated by great enthusiasm about human rights, including the idea that rights can generate less punitive approaches to drugs. But if human rights were an effective framework for the prevention of punitive approaches towards drugs, why haven't they prevented them previously? One possibility is that rights are less reliable for those society considers 'less than human'. In Western liberal contexts that valorise voluntarity, rationality, authenticity, and order, people who use drugs figure as compulsive, irrational, duplicitous and chaotic. Rights can reproduce these logics of abjection, including through the repetition of ideas about drugs and proper ways of being. A body of critical drug scholarship seeks to intervene in these constructions. This work mobilises 'habit' as an otherwise to 'addiction' and argues that habit is the foundation of realities. Habits, and thus realities, can be changed. This paper draws on these approaches to explore whether insights from critical drug scholarship can help to generate something after rights, made possible by new habits and modes of connection. To make this argument, we consider habits as a site of both repetition and rupture. We ask whether habits can help us rethink or disrupt rights, and the 'human' therein. [ABSTRACT FROM AUTHOR]

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 akinetic crisis is defined as an acute, potentially life-threatening, levodopa-resistant, severe aggravation of rigidity, severe akinesia, associated with high fever, disturbance of consciousness, dysphagia and autonomic symptoms often due to disruption of dopaminergic medication or infections. The akinetic crisis is a relatively rare event, however subacute mild-moderate motor symptom deterioration in Parkinson´s disease (PD) patients is a frequent cause of hospitalization. In this review, we propose that the akinetic crisis is the upper end of a continuous spectrum of acute akinetic states depending on the degree of the progressive levodopa-resistance. Clinical symptomatology, risk factors, and instrumental diagnostics as the DAT-SPECT reflecting a biomarker of levodopa-resistance will be discussed to evaluate the spectrum of akinetic states. Pathophysiological considerations about the potential role of proinflammatory cytokines on the progressive levodopa-resistance will be discussed and therapeutical, consensus-based guidelines will be presented. [ABSTRACT FROM AUTHOR]

Advanced Parkinson´s disease (PD) is often complicated by fluctuations of disability depending on plasma levels of levodopa. For most patients OFF phases with worsening of tremor and immobility, but also pain, depression, autonomic symptoms are troublesome. While adjustments of levodopa administrations can relief such fluctuations for some time, "on demand" therapies become more and more important. These "on demand" therapies should provide fast and efficacious relief. During the past years, new options for on demand therapies in PD-associated OFF episodes have been developed, including new formulations of levodopa and apomorphine to provide fast and readily accessible on demand treatment. In this narrative review, the challenges of the treatment of PD-associated fluctuations and OFF states are addressed, with a special focus on sublingual apomorphine (SL-APO) including the results from recent clinical trials. [ABSTRACT FROM AUTHOR]

Over the past decade, increasing off‐label use of quetiapine has been reported worldwide from various sources. We wanted to investigate how this is reflected in therapeutic drug monitoring (TDM) data. Requisitions for serum concentration measurements of quetiapine from a TDM service in Central Norway during 2001–2019 were obtained and analysed for age, gender, trends in quetiapine doses, serum concentrations and indicators of diagnoses. There were 19 759 requisitions from 7459 individuals. Daily doses of quetiapine decreased by 24 mg per year (95% CI: −25.61 to −21.48, p < 0.001, N = 4505). A corresponding decrease in quetiapine serum concentrations was not seen. The proportion of requisitions with diagnoses indicating reimbursable use was 13% for the whole study period. Mean daily doses were slightly higher in the reimbursable group, but declined over time in these samples, as well. To our understanding, these results signal a trend towards lower prescribed doses of quetiapine, possibly reflecting drug repurposing and/or off‐label use. The discrepancy in the decrease of doses versus serum concentrations may reflect the intake of higher doses than prescribed and/or inappropriate TDM sampling. Our findings show that TDM data have limitations when it comes to making inferences about the use of quetiapine based on serum concentrations and clinical information on the requisitions. [ABSTRACT FROM AUTHOR]

Aims: To summarize the results of clinical studies of insulin icodec, an investigational insulin analog designed for once‐weekly administration, in adults with type 1 and type 2 diabetes. Methods: Thirteen published articles describing clinical studies of insulin icodec were identified in PubMed, and data pertinent to key study outcomes were selected for inclusion in this review. Results: In insulin‐naïve and insulin‐treated individuals, icodec demonstrated efficacy in glycaemic control superior or noninferior to that of insulins glargine U100, glargine U300 and degludec. Icodec exhibited a safety profile comparable to marketed insulins, with the exception of hypoglycaemic event rates. Conclusions: As a once‐weekly alternative to daily basal insulin, icodec is expected to improve patient adherence and satisfaction, reducing the required number of injections per year from 365 to 52 and providing a dosing option potentially attractive to a wide range of insulin users. However, clinical data suggest a notable risk of hypoglycaemia with weekly icodec administration, especially in individuals with type 1 diabetes. [ABSTRACT FROM AUTHOR]

The article focuses on the environmental impact of insulin delivery methods within the UK's National Health Service (NHS) amid efforts to address the climate crisis. Topics include the carbon footprint and plastic waste associated with disposable versus reusable insulin pens, the lack of national guidelines for sustainable prescribing practices, and the need for data on the environmental effects of different insulin delivery systems to inform clinicians and patients.

Despite recent therapeutic advances, diabetes remains the seventh leading cause of death in the United States. Clinicians caring for people with diabetes often find that low health literacy interferes with diabetes care. The aim of this cross-sectional study was to determine which diabetes-related misunderstandings or potentially maladaptive health beliefs were present among people at a low-income community clinic in Harris County, TX, and to determine the effect of such misconceptions on A1C values. [ABSTRACT FROM AUTHOR]