Drug Utilization Research Articles

Trends in Proton Pump Inhibitor Use in Sweden by Sex and Age: A Drug Utilisation Study.

Proton pump inhibitors (PPIs) are among the most popular drugs worldwide. Yet, there are concerns on long-term safety and poor adherence to prescription guidelines. Off-label use in children and increasing maintenance use in older adults may be particularly worrisome. To assess differences in PPI use by age, sex calendar year and PPI type, and to explore potential underlying indications (ulcerogenic drugs, and indications) in Sweden. Proton pump inhibitor drug utilisation study based on the Swedish nationwide prescribed drug (2006-2023) and patient registries (2006-2022). Proton pump inhibitors were used by 14.4% (women) and 10.5% (men) of adults; and 1.0-1.5% of children and adolescents (aged < 20 years). Proton pump inhibitor use was higher in women in all age-groups except small children (aged < 5 years). Proton pump inhibitor use has increased in all age groups, especially in young children (aged < 10 years) and the oldest groups (aged > 65 years). Proton pump inhibitor users aged > 85 years filled most prescriptions with an annual average of 9.5 (men), 11.6 (women) prescriptions. Most prescriptions were for omeprazole and esomeprazole: 63.7% and 23.5% in adults; 23.5% and 44.7% in children (2023). Prescriptions for other drugs for peptic ulcers/reflux became rare, with 99% of prescriptions in this category being PPIs by 2023. Gastro-intestinal diagnoses were predominantly recorded in men, became less prevalent and only explained part of PPI use, while ulcerogenic drugs were common (particularly in women), suggesting PPIs are regularly used for gastroprotection. Proton pump inhibitor use has doubled in children and increased 50% in adults over the study period, in both sexes, while recorded gastrointestinal indications decreased. Alternative therapies were rarely prescribed in Sweden.

Diverse phenotypes, consistent treatment: a study of 30,997 South Asian and White IBD patients using the UK IBD BioResource.

To evaluate South Asian (SA) and White (WH) inflammatory bowel disease (IBD) phenotypes, and to explore treatment approach variations between these cohorts in the UK using the IBD BioResource database. Differences between WH and SA IBD patients were analysed using demographic, phenotypic and outcome data. Drug utilisation patterns and surgical outcomes were assessed in propensity score-matched (PSM) cohorts with multivariable logistic regression, Cox regression and Kaplan-Meier analysis. 30,997 eligible patients were included. UC was the predominant disease subtype in SA (p<0.001). SA were younger at diagnosis (p<0.001), had a male preponderance (p<0.001), and were less likely to have a smoking history at diagnosis. The SA CD phenotype differed from WH, with less ileal (SA 30.3%, WH 38.4%, p=0.008) and stricturing (SA 16.9%, WH 25.6%, p<0.001) disease, but more perianal disease (SA 38.5%, WH 32.2%, p=0.009). More SA UC patients had extensive disease (SA 41.7%, WH 34.1%, p<0.001). In PSM cohorts, comparing treatments, there were no differences in 5-aminosalicylate, corticosteroid, thiopurine, anti-TNF or vedolizumab use. Survival analysis in matched cohorts showed no difference in time to surgery (CD) or colectomy (UC), and SA ethnicity was not associated with a difference in risk of surgery/colectomy. Demographic and phenotypic differences exist between UK SA and WH IBD patients, highlighting distinct ethnicity-related variance, and the need for a research focus on under-represented populations. In comparing matched SA and WH patients, no disparity in medical and surgical IBD therapy in UK healthcare has been demonstrated: treatment is consistent regardless of ethnicity.

Drug utilisation study in hospitalised chronic kidney disease patients, using World Health Organisation prescribing indicators: an observational study.

Chronic kidney disease (CKD) is associated with comorbidities and altered pharmacokinetics, making appropriate prescribing, and monitoring necessary to minimise drug-related problems (DRPs). Therefore, this study aimed to describe the drug-utilisation pattern in hospitalised CKD patients. An observational study was conducted in hospitalised adult (≥18 years old) CKD patients in the UK using WHO prescribing indicators, from November 2021 to April 2022 in a large teaching hospital in England from admission until discharge. This study used STATA version 16 for analysis. The mean number of drugs per prescription was 11.1(±5), the percentage of encounters resulting in the prescription of an antibiotic was 62%, the percentage of drugs prescribed by generic name was 90%, the percentage of encounters resulting in the prescription of an injection was 94%, and the percentage of drugs prescribed from essential drugs list or formulary was 89%. The most frequent drug group prescribed Alimentary Tract and Metabolism was 22%. Longer hospital stays, admission to a renal ward, and the number of comorbidities were independently associated with polypharmacy. Not all prescribing indicators evaluated in this study were in full compliance with WHO recommendations. Polypharmacy was found in most participants which might require interventions to avoid DRPs. Further research is needed to evaluate factors associated with prescribing in the CKD population and prescriber perspectives on decision-making in the context of available guidelines and patient factors.

Targeted Bacterial Keratitis Treatment with Polyethylene Glycol-Dithiothreitol- Boric Acid Hydrogel and Gatifloxacin.

To prolong the ocular residence time of gatifloxacin and enhance its efficacy against bacterial keratitis, this study developed a velocity-controlled polyethylene glycol-dithiothreitol- boric acid (PDB) hydrogel loaded with gatifloxacin. First, the basic properties of the synthesized PDB hydrogel and the gatifloxacin- loaded PDB hydrogel were assessed. Secondly, the in vitro degradation rate of the drugloaded PDB was measured in a simulated body fluid environment with pH 7.4/5.5. The release behavior of the drug-loaded PDB was studied using a dialysis method with PBS solution of pH 7.4/5.5 as the release medium. Finally, a mouse model of bacterial keratitis was established, and tissue morphology was observed using hematoxylin-eosin staining. Additionally, mouse tear fluid was extracted to observe the antibacterial effect of the gatifloxacin-loaded PDB hydrogel. The results showed that the PDB hydrogel had a particle size of 124.9 nm and a zeta potential of -23.3 mV, with good porosity, thermosensitivity, viscosity distribution, rheological properties, and high cell compatibility. The encapsulation of gatifloxacin did not alter the physical properties of the PDB hydrogel and maintained appropriate swelling and stability, with a high drug release rate in acidic conditions. Furthermore, animal experiments demonstrated that the gatifloxacin- loaded PDB hydrogel exhibited superior therapeutic effects compared to gatifloxacin eye drops and displayed strong antibacterial capabilities against bacterial keratitis. This study successfully synthesized PDB hydrogel and developed a gatifloxacin drug release system. The hydrogel exhibited good thermosensitivity, pH responsiveness, stability, and excellent biocompatibility, which can enhance drug retention, utilization, and therapeutic effects on the ocular surface.

Cost-effectiveness analysis of immune checkpoint inhibitors combined with targeted therapy and chemotherapy for HPV/HIV-related cervical cancer.

To systematically assess the cost-effectiveness of immune checkpoint inhibitors compared to the current standard therapy for human papillomavirus (HPV) and human immunodeficiency virus (HIV)-related cervical cancer. A partitioned survival model spanning a 20-year period was created to evaluate the cost and effectiveness of atezolizumab combined with bevacizumab and chemotherapy (ABC), and pembrolizumab combined with bevacizumab and chemotherapy (PBC) vs bevacizumab combined with chemotherapy (BC), based on clinical data from the BEATcc and KEYNOTE-826 trials. Royston-Parmar models were used for survival estimation. Costs and health state utilities were sourced from existing literature and publicly accessible databases. Cumulative costs (in US dollars), life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured and compared. The evaluation was from the US healthcare payer perspective, with the willingness-to-pay threshold set at $100,000 to $150,000. Deterministic sensitivity analysis (DSA), probabilistic sensitivity analysis (PSA), and scenario analyses were conducted. The base-case analysis showed QALYs of 2.05 for BC, 3.18 for PBC, and 2.85 for ABC. PBC increased life-years by 1.76 and ABC by 1.18, with PBC showing the highest effectiveness. Total costs were $272,377 for BC, $715,472 for ABC, and $694,239 for PBC; severe adverse event (SAE) costs were $6189 for BC, $7603.31 for ABC, and $13,640 for PBC, indicating BC had the lowest SAE costs. The ICERs compared to BC were $372,151/QALY for PBC and $553,995/QALY for ABC. Given that the willingness-to-pay threshold was $100,000 to $150,000/QALY, both PBC and ABC exceed this threshold and were not considered cost-effective. BC had the lowest QALYs and the lowest costs, making it the least expensive option and the most cost-effective choice. DSA results indicated that drug prices and utility values were the main factors affecting cost-effectiveness. PSA confirmed BC as the most cost-effective option within a willingness-to-pay threshold of $0 to $300,000, primarily because it was the least costly. Immune checkpoint inhibitors significantly improve survival benefits for patients. However, their addition is costly and unlikely to be cost-effective for HPV/HIV-related metastatic cervical cancer.

Prospective Drug Utilization Evaluation Analysis in Outpatient Departments with Ear, Nose, and Throat Outpatients: Incorporating Benchmarks and World Health Organization Indicators.

Drug utilization studies are tools for determining the effectiveness of drug use. The aim of the study was to evaluate drug usage patterns in ear, nose, and throat (ENT) outpatient settings by incorporating established benchmarks and World Health Organization (WHO) indicators. A cross-sectional study on drug utilization evaluation (DUE) was conducted on 800 patients from the ENT outpatient department. We gathered data on currently prescribed medications and identified any discrepancies with a thorough analysis. Continuing educational activities such as "dear doctor" letters and personal consultations were used to rectify any irrational prescribing patterns among physicians. The WHO/International Network for Rational Use of Drugs core drug use indicators, specifically prescribing and patient care indicators, and established benchmarks were applied to encourage rational prescribing. The three most common diagnoses were pharyngitis (51.49%), allergic rhinitis (25.11%), and acute suppurative otitis media (21.17%). Montelukast, in combination with levocetirizine (13.77%) and amoxicillin in combination with clavulanic acid (8.81%), was the most frequently prescribed medication. The average number of drugs per prescription was 4.2% (±1.1), with low usage of generic names (33.0%) and suboptimal reliance on the essential drugs list (76.7%). Furthermore, patient care indicators demonstrated room for improvement, particularly concerning consultation times (6 minutes), dispensing times (30 seconds), and drug labeling practices (0% labeled). The DUE improved the prescribing rate of first-line drugs for five diseases and few aspects of prescribing and patient care indicators. There is an overuse of prescribed drugs, a need for more utilization of generic names, and less than optimal use of the essential drugs list. Additionally, shortcomings in patient care were observed, including issues in consultation, drug dispensing times, and labeling. However, DUE effectively improved WHO patient care metrics and the prescription of first-line drugs warranting its implementation.

Protein kinase A and local signaling in cancer.

Protein kinase A (PKA) is a basophilic kinase implicated in the modulation of many cell-signaling and physiological processes. PKA also contributes to cancer-relevant events such as growth factor action, cell cycle control, cell migration and tumor metabolism. Germline and somatic mutations in PKA, gene amplifications, and chromosome rearrangements that encode kinase fusions, are linked to a growing number of malignant neoplasms. Mislocalization of PKA by exclusion from A-Kinase Anchoring Protein (AKAP) signaling islands further underlies cancer progression. This article highlights the influence of AKAP signaling and local kinase action in selected hallmarks of cancer. We also feature the utility of kinase inhibitor drugs as frontline and future anti-cancer therapies.

Respiratory Syncytial Virus Vaccine (mRNA).

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy and Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433.

A PROSPECTIVE, OBSERVATIONAL DRUG UTILIZATION STUDY IN THE DERMATOLOGY OUT-PATIENT DEPARTMENT OF A GOVERNMENT HOSPITAL, NANDYAL, ANDHRA PRADESH

Objective: The data regarding drug utilization in dermatology departments of southern parts of India is limited. Recent studies on drug utilization in dermatology across India, reported high prescription of branded drugs, low adoption of essential drugs and polypharmacy. Hence, this study was conducted to analyze the drug utilization pattern for common skin diseases as per WHO prescribing indicators. Methods: This study was done in the Out-patient department (OPD) of dermatology at Government General Hospital (GGH), Nandyal, in collaboration with department of Pharmacology for a period of 4 mo and Institutional ethical committee (IEC) permission was taken before conducting the study. Results: A total number of 344 prescriptions were analyzed. Average number of drugs per prescription was 2.5 (including Fixed drug combination (FDC) drugs). Total number of drugs accounted to 860. Majority of prescriptions have 3 drugs per prescription (57.1%) and only 8.7% of prescriptions have more than 3 drugs per prescription. Analyzed data as per World Health Organization (WHO) prescribing indicators indicate 74% of prescribed drugs were from National List of Essential Medicines (NLEM), 2.5% were FDC drugs and 13.14% of the drugs prescribed were antibiotics. Polypharmacy was noted to be only 0.7% in the study. Conclusion: A periodic audit of prescriptions will reduce errors and motivate the health care professionals for rational drug use. Special consideration is to be given to extended public health initiatives to prevent skin infections because they account for about 70% of diseases in daily life.

Assessment of postoperative medication utilization in a surgical ward of a Tertiary Care Teaching Hospital

: The primary aim of this study was to evaluate the drug utilization pattern of post-operative medications using World Health Organization (WHO) drug use indicators in post-operative patients in the surgical ward. The goal was to promote the rational use of medicines and reduce adverse effects in surgical patients in a tertiary teaching hospital.: A prospective observational study was conducted at D Y Patil Medical College, Navi Mumbai, India, involving post-operative surgical patients. A total of 493 prescriptions and case records were reviewed. Data were analyzed using WHO drug use indicators.: Of the 493 cases analyzed, 60% were male and 40% female. Appendicitis (37.93%) and various types of hernias were the most common reasons for admission. The average number of drugs per patient encounter was 7.69. The most commonly prescribed drugs were antiulcer agents, analgesics, antibiotics, and intravenous fluids. Antibiotics were prescribed in 99.59% of encounters, and injections in 100%. Drugs were prescribed by their generic name in 87.16% of cases, and 99.1% of prescriptions were from the National List of Essential Medicines 2022.: This study highlights the drug use patterns in post-operative patients at a tertiary care hospital. Widespread use of injectable medications and polypharmacy were noted, which suggests room for improvement in prescribing practices. Rational use of antibiotics is recommended to minimize the risk of antibiotic resistance.

INCREASED COST BURDEN ON PATIENTS OF MENTAL DISORDERS CORRELATED WITH POOR MEDICATION ADHERENCE: A CROSS-SECTIONAL STUDY AT A TERTIARY CARE HOSPITAL IN NORTH INDIA DURING COVID-19 PANDEMIC

Objective: This study was planned to evaluate the correlation between cost borne by the patient and medication adherence in common mental disorder patients during COVID-19 pandemic. Methods: A descriptive cross-sectional drug utilization study was undertaken in 200 patients. Pattern of psychotropic drugs usage was analyzed as per WHO/INRUD guidelines and average monthly cost borne by the patient/hospital per prescription was correlated with medication adherence of the patients. Results: The average monthly costs borne by patients and hospital were observed to be more during the pandemic as compared to pre-pandemic time. It was observed that patients bearing some cost on their own had significantly lower medication adherence compared to those patients whose cost of treatment was borne by the government-funded hospital (p-value of 0.017). The medication adherence in patients of mental disorders was found to be negatively correlated to the cost was borne by the patients. Conclusion: The COVID-19 pandemic has escalated the total cost borne by the patients as well as the financial burden on government-funded hospitals.

Microneedle patches incorporating zinc-doped mesoporous silica nanoparticles loaded with betamethasone dipropionate for psoriasis treatment

Treating psoriasis presents a major clinical challenge because of the limitations associated with traditional topical glucocorticoid therapy. This study introduced a drug delivery system utilizing zinc-doped mesoporous silica nanoparticle (Zn-MSN) and microneedle (MN), designed to enhance drug utilization for prolonged anti-inflammatory and anti-itch effects. The MN system facilitated the transdermal delivery of betamethasone dipropionate (BD), allowing its slow release. The BD@Zn-MSN-MN system promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype, achieving superior anti-inflammatory effects compared to the clinically used BD cream. Additionally, this study demonstrated that BD@Zn-MSN-MN could further alleviate itching in psoriasis-afflicted mice by decreasing the excitability of the transient receptor potential vanilloid V1 (TRPV1) ion channel positive neurons and reducing the release of calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG). These findings offer new insights and effective therapeutic options for the future design of transdermal drug delivery for psoriasis.

Adverse events associated with oseltamivir and baloxavir marboxil in against influenza virus therapy: A pharmacovigilance study using the FAERS database.

Influenza virus is a widespread pathogen that poses significant health risks to humans. Oseltamivir and Baloxavir Marboxil are commonly utilized medications for both treating and preventing influenza infections. Despite their widespread use, there remains a need to thoroughly investigate their safety profiles and potential adverse reactions. This study aims to comprehensively analyze the adverse events associated with oseltamivir and baloxavir marboxil in real-world clinical settings, with the goal of assessing their safety and potential risks in the management of influenza virus infections. We conducted a retrospective analysis utilizing data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database, spanning from the first quarter of 2004 to the third quarter of 2023. The analysis encompassed examination of drug utilization patterns, types of adverse events reported, patient demographics, and other pertinent factors. From the first quarter of 2004 to the third quarter of 2023, FAERS collected over 17,035,521 adverse event reports (AE reports). Among these reports, there were 38,384 reports associated with oseltamivir, and 3,364 reports associated with baloxavir marboxil. Oseltamivir and Baloxavir Marboxil were primarily used for the treatment of influenza virus infections, accounting for 62.43% and 67.49% of their total usage, respectively. The main adverse reactions reported for oseltamivir were vomiting (case reports = 1402) followed by confusional state (case reports = 353), while for baloxavir marboxil, adverse reactions mainly centered around off-label use (case reports = 378) and intentional product use issues (case reports = 278). In terms of systemic adverse reactions, oseltamivir primarily affected psychiatric disorders (n = 45), whereas baloxavir marboxil mainly impacted the gastrointestinal system (n = 7). Additionally, regarding adverse reactions in pregnant women, the occurrence of normal newborns was a significant signal for oseltamivir, suggesting a certain level of safety during maternal use. Conversely, reports of adverse reactions such as respiratory arrest were documented for baloxavir marboxil, while no such reports were associated with oseltamivir. This study provides a comprehensive analysis of the adverse reactions observed with the clinical use of oseltamivir and baloxavir marboxil, revealing the safety and risks associated with these two drugs in the treatment and prevention of influenza virus infections. Firstly, although both drugs are used for influenza treatment, they exhibit different types of adverse reactions. Oseltamivir predominantly affects the psychiatric system, while baloxavir marboxil primarily impacts the gastrointestinal system. Additionally, oseltamivir demonstrates a certain level of safety for use in pregnant women, while reports of adverse reactions such as respiratory arrest are associated with baloxavir marboxil. Despite the clinical significance of this study, limitations exist due to the voluntary nature of data reporting, which may lead to reporting biases and incomplete information. Future research could employ more rigorous prospective study designs, integrating clinical trials and epidemiological studies, to more accurately assess the safety risks of oseltamivir and baloxavir marboxil.

Impact of hospital-physician vertical integration on physician-administered drug spending and utilization.

We estimate the effects of hospital-physician vertical integration on spending and utilization of physician-administered drugs for hematology-oncology, ophthalmology, and rheumatology. Using a 100% sample of Medicare fee-for-service medical claims from 2013 to 2017, we find that vertical integration shifts treatments away from physician offices and toward hospital outpatient departments. These shifts are accompanied by increases in physician-administered drug administration spending per procedure for all three specialties. Spending on Part B drugs also increasesfor hematologist-oncologists. At the same time, physician treatment intensity, as measured by the number of beneficiaries who receive drug infusions/injections and the number of drug infusions, decreases across all three specialties. These results suggest that the incentives of the Medicare reimbursement system, particularly site-of-care payment differentials and outpatient drugreimbursement rates, interact with vertical integration to lead to higher overall spending. Policies and merger guidelines should attempt to restrain spending increases attributed to vertical integration.

Metabolically inducing defects in DNA repair sensitizes BRCA-wild-type cancer cells to replication stress.

Metabolic reprogramming from oxidative respiration to glycolysis is generally considered to be advantageous for tumor initiation and progression. However, we found that breast cancer cells forced to perform glycolysis acquired a vulnerability to PARP inhibitors. Small-molecule inhibition of mitochondrial respiration-using glyceollin I, metformin, or phenformin-induced overproduction of the oncometabolite lactate, which acidified the extracellular milieu and repressed the expression of homologous recombination (HR)-associated DNA repair genes. These serial events created so-called "BRCAness," in which cells exhibit an HR deficiency phenotype despite lacking germline mutations in HR genes such as BRCA1 and BRCA2, and, thus, sensitized the cancer cells to clinically available poly(ADP-ribose) polymerase inhibitors. The increase in lactate repressed HR-associated gene expression by decreasing histone acetylation. These effects were selective to breast cancer cells; normal epithelial cells retained HR proficiency and cell viability. These mechanistic insights into the BRCAness-prone properties of breast cancer cells support the therapeutic utility and cancer cell-specific potential of mitochondria-targeting drugs.

Effects of antipsychotic drugs during radiotherapy in breast cancer in South Korea: a retrospective cohort study

In this study, we aimed to investigate the nationwide utilization of antipsychotic drugs (APDs) during radiotherapy and evaluate their association with survival in patients with breast cancer. This retrospective cohort study used the National Health Insurance Service database in Korea and included patients diagnosed with breast cancer from 2010 to 2020 who received radiotherapy. The APDs included in the analysis were aripiprazole, quetiapine, olanzapine, risperidone, haloperidol, and chlorpromazine, and the APD prescription details included prescription time, dosage, and duration. Among 170,226 patients with breast cancer treated with radiotherapy, 3361 (1.97%) received APD during radiotherapy. Use of APDs was significantly associated with higher mortality in all patients and in a subgroup of patients excluding those with metastasis or other cancers. Among patients taking APD during radiotherapy, those with accompanied psychiatric history and long-term APD use for ≥ 3 months were associated with lower mortality, whereas patients who started APD during radiotherapy had higher mortality than those who started APD before radiotherapy. The high mortality observed in breast cancer patients using APDs during radiotherapy could be influenced by the underlying conditions that necessitated APD use. Further studies are needed to determine the effects of APDs during radiotherapy in patients with breast cancer.

The addition of cannabis to prescription drug monitoring programs and medication fills in Medicaid.

To date, there is considerable evidence of the medical applications of cannabis, however concerns regarding the safety of cannabis are also mounting. To improve the safety of cannabis, nine states have added medical cannabis to their state PDMPs, helping providers to take patient cannabis use into consideration when making prescribing decisions. Across a variety of models using Medicaid State Drug Utilization claims data, I find statistically significant reductions in severely and moderately contraindicated medication fills across two outcomes. In my main specification, adding cannabis to a state PDMP is associated with a 14.4% (p<0.01) and 7.74% (p<0.001) decrease in the units per prescription, for severely and moderately contraindicated medications, respectively, as compared to states with legal medical cannabis dispensaries open. An interesting spillover effect of adding cannabis to PDMPs is an apparent decrease in the prescribing of scheduled narcotics, with Schedule II medications seeing a moderately significant decrease and Schedule IV medications seeing a 11.4% decrease (p<0.01) in the prescribing rate and a 16.2% decrease (p<0.001) in the units per prescription. The main analysis was conducted using the Borusyak etal. (2023) Imputation Estimator with a robustness check using the Callaway and Sant'Anna (2021) difference-in-difference. This work presents evidence that adding cannabis to a state PDMP impacts provider prescribing decisions involving medications that are contraindicated for use with cannabis as well as controlled substances. This paper demonstrates that adding cannabis to PDMPs influences prescribing and thus has the potential to make medical cannabis use safer. Conversely, this work indicates providers may have bias against patients who use cannabis and deny them life-improving medications (like controlled ADHD medication or opioids) on the basis of medical cannabis use. This paper also contributes to the literature comparing DD outcomes estimated using Borusyak, Jaravel, and Spiess' (2023) Imputation Estimator and Callaway and Sant'Anna's (2021) DD Estimator.

A Cross-Sectional Study Identifying Medication Adherence Technologies (MATech) in Sweden Using Behavior Change Techniques.

Poor medication adherence is a well-recognized problem, and behavior change techniques (BCTs) have shown promise in improving patient adherence to prescribed drug treatment. Through the utilization of medication adherence technologies (MATech), these BCT interventions could be delivered effectively in a person-centered way. MATech can be defined as systems, services or physical devices (hardware), with a digital component, used to support patients in their drug utilization. However, there is a lack of knowledge regarding their availability and to what extent they apply evidence-based BCTs. This study aimed to identify and describe MATech with BCT interventions available in the Swedish language. A cross-sectional survey study was conducted in 2023. After identifying potential MATech developers by contacting umbrella organizations in the private sector, public agencies and regions, and conducting an app search, a survey was distributed to 381 potential MATech developers. Included MATech were in Swedish, used by patients, incorporated a BCT intervention, and had survey response from the developer. The survey was based on the BCT taxonomy and the framework of attributes from the COST ENABLE project, and included questions regarding BCT features. Following correspondence with 189 potential developers, 32 with products of interest responded to the survey, and 21 MATech were identified (12 standalone software and nine hardware solutions). Among the 21 MATech identified, nine were hardware and ten were specifically designed for a particular disease or medication. The majority of technologies incorporated BCTs of reminding the patient to take the medication (81%), information about the treatment (71%) and providing feedback on the monitoring of medication adherence or clinical outcomes (76%). Swedish-language MATech employing BCTs are available, encompassing both hardware and software solutions. There is a need to enhance the visibility of these technologies, enabling patients to discover and utilize the support they provide.

FXR activation remodels hepatic and intestinal transcriptional landscapes in metabolic dysfunction-associated steatohepatitis.

The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes.

Biologics Used for Psoriasis: A Drug Utilization Study Based on Two Nationwide Danish Data Sources.

Biological treatment has been a game changer in the management of moderate-to-severe psoriasis. In Denmark, biological treatment for psoriasis is registered in two data sources. We aimed to describe the utilization of biologics for psoriasis in Denmark using data from both data sources separately. We used data from two different nationwide Danish data sources: The healthcare registries and the clinical quality database, Dermbio. Utilization patterns were described by three different parameters: (1) distribution of drugs used in the first treatment episodes, (2) treatment cascade on a population level, and (3) drug survival using Kaplan Meier (KM) analysis and the proportion of patients covered (PPC) method. From January 1, 2011, to December 31, 2018, we found 1878 users of biologics in the healthcare registries and 2264 in Dermbio. Adalimumab, ustekinumab, and secukinumab were the most common first-choice treatments throughout the study period. According to the healthcare registries, it was most common to have more than one treatment episode with the same drug. In Dermbio, most were registered to have only one observable treatment episode overall in the study period. Ustekinumab showed the longest drug survival in both databases. Drug survival was longer for all biologics in Dermbio than in the healthcare registries. Adalimumab, ustekinumab, and secukinumab were the most common first-choice treatments in Denmark. Overall, ustekinumab showed the longest drug survival. We observed important differences in treatment cascades and drug survival between Dermbio and the healthcare registries, which should be considered when using these data sources to perform drug utilization studies on biologics.