Beyond diagnosis: investigating hospital referral impact on biological treatment initiation, hospital admission, and surgery patterns in inflammatory bowel disease - a Danish population based study.

OBJECTIVES: Early biological treatment in patients with inflammatory bowel disease (IBD) is important in disease control. Previous studies have suggested that patients with IBD from Non-Academic Hospitals were less likely to receive biologics. The aims of this study were (1) to use the granular data in the clinical database, GASTROBIO, to study detailed differences in time from IBD diagnosis to first administration of biologics, hospital admission, and surgery in patients referred to Academic Hospitals versus to Non-Academic Hospitals, and (2) to explore differences in disease extent, behavior, and indication for biological treatment. MATERIAL AND METHODS: This was a retrospective cross-sectional descriptive population-based quality study of patients with IBD initiating biologics in the North Denmark Region between 2016 and 2018. Data from GASTROBIO were extracted, namely demographic data, time of diagnosis, biological treatments with indications, hospital admission, and surgery. RESULTS: Of the 146 patients included, 84 were from the Academic and 62 from the Non-Academic Hospitals. No significant differences in median time from diagnosis to (1) treatment, (2) hospital admission or (3) IBD surgery between the groups were observed. A higher percentage of patients with luminal Crohn's disease were treated with biologics at the Academic Hospital (78% and 66%). CONCLUSIONS: Based on the findings of this population-based study, we found no evidence that the referral area had a significant impact on the duration from diagnosis to the initiation of biological treatment, hospital admissions, or surgery. However, the data suggested that fewer patients with luminal Crohn's disease were referred to biologics from Non-Academic Hospitals.

Less prevalent use of biologics for inflammatory bowel disease in patients from Non-Academic hospitals - a Danish register-based study of a region with 580,000 citizens.

INTRODUCTION: Biologic therapy is widely used for inflammatory bowel disease (IBD) and may decrease surgery rates. However, it remains uncertain if there is unwarranted geographic variation in access to biologic therapy. The aim of the study was to explore if all patients had equal access to biologic therapy in the North Denmark Region. METHODS: A cross-sectional register-based study of use of biologics, hospital contacts and surgery among all IBD patients having a hospital contact in the geographically well-defined North Denmark Region during 2016-2018. ICD-10 diagnosis codes, hospital contacts and procedure codes were retrieved from the region's hospital registry. The population is served by an Academic Hospital and two Non-Academic Hospitals constituting three referral areas (according to postal codes). RESULTS: In total, 2371 patients with ulcerative colitis (UC) and 1383 patients with Crohn's disease (CD) had a hospital contact in the region during 2016-2018. Compared to patients from the Academic Hospital, patients from the Non-Academic Hospitals experienced a lower incidence of biologic therapy for UC IRR 0.786 (0.621: 0.994), as well as for CD IRR 0.912 (0.781: 1.065). The incidence of bowel related hospital contacts were higher in patients from Non-Academic hospitals for both UC IRR 1.318 (1.207: 1.438) and CD IRR 1.165 (0.915: 1.483). CONCLUSIONS: Patients with IBD living in a referral area to a Non-Academic Hospital in the North Denmark Region are less likely to receive biologics. This was associated with an increased prevalence of IBD related surgical procedures.

Oral absorption of oxycodone in patients with short bowel syndrome.

BACKGROUND: Short bowel syndrome is a disorder with several complications such as malnutrition and failure of drug therapy. Treatment with opioids is needed in many patients, and oral medication is preferred. However, optimal dosing is a difficult task as current guidelines are based on an intact gastrointestinal tract. Hence, the aim of this explorative case study was to assess the pharmacokinetics of orally administered oxycodone in patients with short bowel syndrome. METHODS: Six patients with short bowel syndrome were administered 10 mg oral solution oxycodone after an overnight fast. Oxycodone plasma concentrations were determined over a 6-hour period. Pharmacokinetic profiles were visually inspected. Pharmacokinetic parameters: maximum plasma concentration, time of maximum concentration and area under the curve were calculated. Data were also compared to mean values obtained in healthy participants. RESULTS: A clinically relevant concentration of oxycodone was found in all patients, although with large inter-individual variation. The absorption fraction tended to correlate positively with total intestinal length. Additionally, preservation of some or the entire colon seemed further to increase the absorption fraction. Time of maximum concentration varied from 30 min to approximately 90 min. CONCLUSIONS: Oxycodone is absorbed in a clinically relevant extent in patients with short bowel syndrome, but bioavailability varies greatly between patients, which shall be taken into consideration. Absorption is related to functional small intestinal length, but preservation of colon is also beneficial. Still, optimal therapeutic dosing must be individualized, and other factors such as those related to malnutrition and motility shall also be taken into consideration.

Quantifying the Adequacy of Opioid Analgesic Consumption Globally: An Updated Method and Early Findings.

Opioid analgesics are the mainstay for treatment of moderate and severe pain but, in many countries, the consumption of these medicines is inadequate. Over time, various groups have published opioid analgesic metrics, including authors from the World Health Organization. They linked consumption to a level considered adequate based on the actual consumption in developed countries. In this study, we present our current results on the adequacy of opioid analgesic consumption. We included statistics for 18 controlled opioid medicines that are primarily used as analgesics, and we developed the Adequacy of Opioid Consumption (AOC) Index. The average of the 20 most developed countries for 2015 is set as equal to an AOC Index of 100. An AOC Index of 100 or higher is considered adequate consumption. The average opioid analgesic consumption of the top-20 countries of the Human Development Index increased from 84 morphine milligram equivalents per capita (2000) to 256 morphine milligram equivalents per capita (2015). The extremes we found for 2015 were Germany (AOC Index: 304) and Nigeria (AOC Index: 0.0069). These extremes differ by 44 000 times. Adequacy of opioid analgesic consumption continues to be problematic around the world.

Multivariate analysis of single-sweep evoked brain potentials for pharmaco-electroencephalography.

BACKGROUND AND AIMS: Current findings on altered evoked potentials (EPs) caused by morphine are based on common alterations for a group of subjects after drug administration. However, this ignores the analysis of individual responses, which may explain the clinical differences in efficacy. Therefore, we explored the individual responses to morphine in terms of the altered single-sweep characteristics in a placebo-controlled crossover study. To account for multifactorial mechanisms, several characteristics were assessed simultaneously by multivariate pattern analysis (MVPA). METHODS: EPs were recorded from 62 channels and obtained before and after morphine and placebo administration during repeated electrical stimulations of the oesophagus in 12 healthy males. Additionally, the pain detection threshold was recorded to reflect the subjective analgesic effect in each subject. The characteristics of the sweeps were extracted by a multivariate matching pursuit algorithm with Gabor atoms implemented with a variable amplitude and constant phase across the sweeps. The single-sweep amplitudes were used as input to an MVPA algorithm to discriminate individual responses. The accuracy of the MVPA for each individual subject was used for correlation analysis of the analgesic effect. RESULTS: The mean classification accuracy when discriminating pre- and posttreatment morphine responses was 72% (p = 0.01). The individual classification accuracy was positively correlated to the analgesic effect of morphine (p = 0.03). Furthermore, the 2 posttreatment responses were classified and validated by the classification of the 2 pretreatment responses (p = 0.001). CONCLUSIONS: The alterations in the single-sweep EPs after morphine reflect the analgesic effect. The MVPA approach is a novel methodology for monitoring the individual efficacy of analgesics.

Randomized clinical trial: efficacy and safety of PPC-5650 on experimental esophageal pain and hyperalgesia in healthy volunteers.

OBJECTIVE: Gastroesophageal reflux disease (GERD) is a common condition associated with symptoms as heart burn, regurgitation, chest pain, and gastrointestinal discomfort. PPC-5650 is a new pharmacological agent that can modulate acid-sensing ion channel activity, potentially leading to reduction in the pain signal. In healthy volunteers the esophagus was sensitized with acid to mimic GERD with the aims: 1) to assess the efficacy of a single bolus of PPC-5650 locally applied to the esophagus using multimodal pain stimulations, and 2) to assess the safety profile of PPC-5650. MATERIALS AND METHODS: The study was a randomized, double-blinded, placebo-controlled, crossover trial in healthy males. Esophageal electrical, thermal, mechanical, and chemical stimulations were performed, pain perception was rated, and referred pain areas were drawn. Sensitization was induced by intraluminal esophageal acid perfusions. Adverse events were registered. RESULTS: Twenty-five healthy males completed the study (mean age 23.4 ± 2.0 years). About 90 min after drug administration, PPC-5650 increased the volume tolerated at moderate pain during mechanical stimulation compared to placebo (difference 13.5, 95% CI: 0.58-26.47, p = 0.04), but there was no effects on thermal-, electrical-, and chemical-induced pain (all p > 0.05). PPC-5650 did not affect referred pain areas to any stimulation (all p > 0.05). Ten participants reported adverse events during the placebo treatment period, and nine participants reported adverse events during the PPC-5650 treatment period (p = 0.8). CONCLUSION: Sensitization to mechanical stimulation of the esophagus was reduced by PPC-5650 compared to placebo. The overall safety and tolerability of PPC-5650 was acceptable. Thus, PPC-5650 may play a role in the future treatment of patients with GERD.

Stochastic Pharmacokinetic-Pharmacodynamic Analysis of the Effect of Transdermal Buprenorphine on Electroencephalogram and Analgesia.

BACKGROUND: The analgesic effect of opioids is often based on subjective one dimensional measurements. Electroencephalography (EEG) offers a possibility to objectively quantify the brain's activity before and after the administration of opioids. The aim of this study was to investigate the pharmacokinetic-pharmacodynamic (PKPD) properties of the buprenorphine transdermal patch on resting EEG and pain tolerance. METHOD: Twenty-two healthy male subjects (mean age 23.1 ± 3.8 years) were studied. They received a 144-hour buprenorphine (20 µg/h) or placebo transdermal patch in this experimental, randomized, crossover, double-blind study. Skin heat pain tolerance was measured on the arm before the recordings of resting EEG. From the EEG, the ratio of slow and fast oscillations was calculated for further analysis. A population PKPD model with a stochastic differential equation for drug absorption from the patch was used to analyze the PK and PD data simultaneously by use of the statistical analysis package NONMEM. RESULTS: Buprenorphine increased EEG ratio (P = 0.0006) and skin pain tolerance (P = 0.0008) compared with placebo. The stochastic model adequately characterized the concentration-time and effect-time courses for both the skin heat stimulation and the resting EEG outcomes with variations in the drug's absorption rate during the 144-hour treatment period. As measured by the potency parameter, the EEG effect was 10 ± 3 (median ± SE) times more sensitive to buprenorphine than the skin pain test. CONCLUSIONS: Using a stochastic PKPD analysis, the effect of a 144-hour buprenorphine patch application on resting EEG and skin pain tolerance was quantified successfully. Both end points were affected by buprenorphine, although the resting EEG was more sensitive to buprenorphine. The stochastic PKPD analysis allowed the computation of a time-dependent variability in drug absorption from patch to blood. The data suggest that the resting EEG is an attractive and objective alternative for assessing opioid effect.

Human experimental pain models for assessing the therapeutic efficacy of analgesic drugs.

Pain models in animals have shown low predictivity for analgesic efficacy in humans, and clinical studies are often very confounded, blurring the evaluation. Human experimental pain models may therefore help to evaluate mechanisms and effect of analgesics and bridge findings from basic studies to the clinic. The present review outlines the concept and limitations of human experimental pain models and addresses analgesic efficacy in healthy volunteers and patients. Experimental models to evoke pain and hyperalgesia are available for most tissues. In healthy volunteers, the effect of acetaminophen is difficult to detect unless neurophysiological methods are used, whereas the effect of nonsteroidal anti-inflammatory drugs could be detected in most models. Anticonvulsants and antidepressants are sensitive in several models, particularly in models inducing hyperalgesia. For opioids, tonic pain with high intensity is attenuated more than short-lasting pain and nonpainful sensations. Fewer studies were performed in patients. In general, the sensitivity to analgesics is better in patients than in healthy volunteers, but the lower number of studies may bias the results. Experimental models have variable reliability, and validity shall be interpreted with caution. Models including deep, tonic pain and hyperalgesia are better to predict the effects of analgesics. Assessment with neurophysiologic methods and imaging is valuable as a supplement to psychophysical methods and can increase sensitivity. The models need to be designed with careful consideration of pharmacological mechanisms and pharmacokinetics of analgesics. Knowledge obtained from this review can help design experimental pain studies for new compounds entering phase I and II clinical trials.

Unravelling the mystery of capsaicin: a tool to understand and treat pain.

A large number of pharmacological studies have used capsaicin as a tool to activate many physiological systems, with an emphasis on pain research but also including functions such as the cardiovascular system, the respiratory system, and the urinary tract. Understanding the actions of capsaicin led to the discovery its receptor, transient receptor potential (TRP) vanilloid subfamily member 1 (TRPV1), part of the superfamily of TRP receptors, sensing external events. This receptor is found on key fine sensory afferents, and so the use of capsaicin to selectively activate pain afferents has been exploited in animal studies, human psychophysics, and imaging studies. Its effects depend on the dose and route of administration and may include sensitization, desensitization, withdrawal of afferent nerve terminals, or even overt death of afferent fibers. The ability of capsaicin to generate central hypersensitivity has been valuable in understanding the consequences and mechanisms behind enhanced central processing of pain. In addition, capsaicin has been used as a therapeutic agent when applied topically, and antagonists of the TRPV1 receptor have been developed. Overall, the numerous uses for capsaicin are clear; hence, the rationale of this review is to bring together and discuss the different types of studies that exploit these actions to shed light upon capsaicin working both as a tool to understand pain but also as a treatment for chronic pain. This review will discuss the various actions of capsaicin and how it lends itself to these different purposes.

Review: application of the Safety Attitudes Questionnaire (SAQ) in primary care - a systematic synthesis on validity, descriptive and comparative results, and variance across organisational units.

Patient safety research has focused mostly on the hospital and acute care setting whereas assessments of patient safety climate in primary health care settings are warranted. Valid questionnaires as e.g., the Safety Attitudes Questionnaire (SAQ) may capture staff perceptions of patient safety climate but until now, an overview of the use of SAQ in primary care has not been systematically presented. Thus, the aim of this systematic review is to present an overview of SAQ used in primary care.Methods The electronic databases: PubMed, Embase, Cinahl, PsycInfo and Web of Science were used to find studies that used any version of SAQ in primary care. Studies were excluded if only abstract or poster was available, as the information in abstract and posters was deemed insufficient. Commentaries and nonempirical studies (e.g., study protocols) were excluded. Only English manuscripts were included.Results A total of 43 studies were included and 40 of them fell into four categories: 1) validation analysis, 2) descriptive analysis, 3) variance assessment and 4) intervention evaluation and were included in further analyses. Some studies fell into more than one of the four categories. Seventeen studies aimed to validate different versions of SAQ in a variety of settings and providers. Twenty-five studies from fourteen different countries reported descriptive findings of different versions of SAQ in a variety of settings. Most studies were conducted in primary health care centres, out-of-hours clinics, nursing homes and general practice focusing on greatly varying populations. One study was conducted in home care. Three studies investigated variance of SAQ scores. Only five studies used SAQ to assess the effects of interventions/events. These studies evaluated the effect of electronic medical record implementation, a comprehensive Unit-based Safety Program or COVID-19.Conclusion The synthesis demonstrated that SAQ is valid for use in primary care, but it is important to adapt and validate the questionnaire to the specific setting and participants under investigation. Moreover, differences in SAQ factor scores were related to a variety of descriptive factors, that should be considered in future studies More studies, especially variance and intervention studies, are warranted in primary care.Trial registration This systematic review was not registered in any register.

Deprescribing in primary care without deterioration of health-related outcomes: A real-life, quality improvement project.

Medication reviews focusing on deprescribing can reduce potentially inappropriate medication; however, evidence regarding effects on health-related outcomes is sparse. In a real-life quality improvement project using a newly developed chronic care model, we investigated how a general practitioner-led medication review intervention focusing on deprescribing affected health-related outcomes. We performed a before-after intervention study including care home residents and community-dwelling patients affiliated with a large Danish general practice. The primary outcomes were changes in self-reported health status, general condition and functional level from baseline to 3-4 months follow-up. Of the 105 included patients, 87 completed the follow-up. From baseline to follow-up, 255 medication changes were made, of which 83% were deprescribing. Mean self-reported health status increased (0.55 [95% CI: 0.22 to 0.87]); the proportion with general condition rated as 'average or above' was stable (0.06 [95% CI: -0.02 to 0.14]); and the proportion with functional level 'without any disability' was stable (-0.05 [95% CI: -0.09 to 0.001]). In conclusion, this general practitioner-led medication review intervention was associated with deprescribing and increased self-reported health status without the deterioration of general condition or functional level in real-life primary care patients. The results should be interpreted carefully given the small sample size and lack of control group.

Use of drugs with pharmacogenomics (PGx)-based dosing guidelines in a Danish cohort of persons with chronic kidney disease, both on dialysis and not on dialysis: Perspectives for prescribing optimization.

AIM: The objective of this registry study is to assess the utilization of pharmacogenomic (PGx) drugs among patients with chronic kidney disease (CKD). METHODS: This study was a retrospective study of patients affiliated with the Department of Nephrology, Aalborg University Hospital, Denmark in 2021. Patients diagnosed with CKD were divided into CKD without dialysis and CKD with dialysis. PGx prescription drugs were retrieved from the Patient Administration System. Actionable dosing guidelines (AG) for specific drug-gene pairs for CYP2D6, CYP2C9, CYP2C19 and SLCO1B1 were retrieved from the PharmGKB homepage. RESULTS: Out of 1241 individuals, 25.5% were on dialysis. The median number of medications for each patient was 9 within the non-dialysis group and 16 within the dialysis group. Thirty-one distinct PGx drugs were prescribed. Altogether, 76.0% (943 individuals) were prescribed at least one PGx drug and the prevalence of prescriptions of PGx drugs was higher in the dialysis group compared to the non-dialysis group. The most frequently prescribed drugs with AG were metoprolol, pantoprazole, atorvastatin, simvastatin and warfarin. CONCLUSION: This study demonstrated that a substantial proportion of patients with CKD are exposed to drugs or drug combinations for which there exists AG related to PGx of CYP2D6, CYP2C19, CYP2C9 and SLCO1B1.

Quantitative sensory testing, psychological factors, and quality of life as predictors of current and future pain in patients with knee osteoarthritis.

ABSTRACT: Substantial interindividual variability characterizes osteoarthritis (OA) pain. Previous findings identify quantitative sensory testing (QST), psychological factors, and health-related quality of life as contributors to OA pain and predictors of treatment outcomes. This exploratory study aimed to explain baseline OA pain intensity and predict OA pain after administration of a nonsteroidal anti-inflammatory drug in combination with paracetamol for 3 weeks. The Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score was used to estimate OA pain presentation. One hundred one patients were assessed at baseline and follow-up using QST (pressure pain thresholds and temporal summation of pain [TSP]), symptoms of depression and anxiety, pain catastrophizing scales (PCSs), and health-related quality of life. Linear regression with backward selection identified that PCS significantly explained 34.2% of the variability in baseline KOOS pain, with nonsignificant contributions from TSP. Pain catastrophizing score and TSP predicted 29.3% of follow-up KOOS pain, with nonsignificant contributions from symptoms of anxiety. When assessed separately, PCS was the strongest predictor (32.2% of baseline and 24.1% of follow-up pain), but QST, symptoms of anxiety and depression, PCS, and quality of life also explained some variability in baseline and follow-up knee OA pain. Further analyses revealed that only TSP and PCS were not mediated by any other included variables, highlighting their role as unique contributors to OA pain presentation. This study emphasizes the importance of embracing a multimodal approach to OA pain and highlights PCS and TSP as major contributors to the baseline OA pain experience and the OA pain experience after OA treatment.

Deprescribing as a Way to Reduce Inappropriate Use of Drugs for Overactive Bladder in Primary Care (DROP): Protocol for a Cluster Randomized Controlled Trial With an Embedded Explanatory Sequential Mixed Methods Study.

BACKGROUND: Potentially inappropriate medication remains a significant concern in general practices, particularly in the context of overactive bladder (OAB) treatment for individuals aged 65 years and older. This study focuses on the exploration of alternative options for treating OAB and the deprescribing of anticholinergic drugs commonly used in OAB. The research aims to comprehensively evaluate the efficiency of deprescribing through a mixed methods approach, combining quantitative assessment and qualitative exploration of perceptions, experiences, and potential barriers among patients and health care personnel. OBJECTIVE: This study aims to evaluate the efficiency and safety of the intervention in which health care staff in primary care encourage patients to participate in deprescribing their drugs for OAB. In addition, we aim to identify factors contributing to or obstructing the deprescribing process that will drive more informed decisions in the field of deprescribing and support effective and safe treatment of patients. METHODS: The drugs for overactive bladder in primary care (DROP) study uses a rigorous research design, using a randomized controlled trial (RCT) with an embedded sequential explanatory mixed methods approach. All general practices within the North Denmark Region will be paired based on the number of general practitioners (GPs) and urban or rural locations. The matched pairs will be randomized into intervention and control groups. The intervention group will receive an algorithm designed to guide the deprescribing of drugs for OAB, promoting appropriate medication use. Quantitative data will be collected from the RCT including data from Danish registries for prescription analysis. Qualitative data will be obtained through interviews and focus groups with GPs, staff members, and patients. Finally, the quantitative and qualitative findings are merged to understand deprescribing for OAB comprehensively. This integrated approach enhances insights and supports future intervention improvement. RESULTS: The DROP study is currently in progress, with randomization of general practices underway. While they have not been invited to participate yet, they will be. The inclusion of GP practices is scheduled from December 2023 to April 2024. The follow-up period for each patient is 6 months. Results will be analyzed through an intention-to-treat analysis for the RCT and a thematic analysis for the qualitative component. Quantitative outcomes will focus on changes in prescriptions and symptoms, while the qualitative analysis will explore experiences and perceptions. CONCLUSIONS: The DROP study aims to provide an evidence-based intervention in primary care that ensures the deprescription of drugs for OAB when there is an unfavorable risk-benefit profile. The DROP study's contribution lies in generating evidence for deprescribing practices and influencing best practices in health care. TRIAL REGISTRATION: ClinicalTrials.gov NCT06110975; https://clinicaltrials.gov/study/NCT06110975. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56277.

Person-centred medicine in the care home setting: development of a complex intervention.

BACKGROUND: Person-centred medicine is recommended in the care of older patients. Yet, involvement of care home residents and relatives in medication processes remains limited in routine care. Therefore, we aimed to develop a complex intervention focusing on resident and relative involvement and interprofessional communication to support person-centred medicine in the care home setting. METHODS: The development took place from October 2021 to March 2022 in the Municipality of Aarhus, Denmark. The study followed the Medical Research Council guidance on complex intervention development using a combination of theoretical, evidence-based, and partnership approaches. The patient involvement tool, the PREparation of Patients for Active Involvement in medication Review (PREPAIR), was included in a preliminary intervention model. Study activities included developing programme theory, engaging stakeholders, and exploring key uncertainties through interviews, co-producing workshops, and testing with end-users to develop the intervention and an implementation strategy. The Consolidated Framework for Implementation Research and the Interprofessional Shared Decision Making Model were used. Data were analysed using a rapid analysis approach. RESULTS: Before the workshops, six residents and four relatives were interviewed. Based on their feedback, PREPAIR was modified to the PREPAIR care home to fit the care home population. In total, ten persons participated in the co-producing workshops, including health care professionals and municipal managerial and quality improvement staff. The developed intervention prototype was tested for three residents and subsequently refined to the final intervention, including two fixed components (PREPAIR care home and an interprofessional medication communication template) delivered in a flexible three-stage workflow. Additionally, a multi-component implementation strategy was formed. In line with the developed programme theory, the intervention supported health care professionals´ awareness about resident and relative involvement. It provided a structure for involvement, empowered the residents to speak, and brought new insights through dialogue, thereby supporting involvement in medication-related decisions. The final intervention was perceived to be relevant, acceptable, and feasible in the care home setting. CONCLUSION: Our results indicate that the final intervention may be a viable approach to facilitate person-centred medicine through resident and relative involvement. This will be further explored in a planned feasibility study.

Potential medicine waste in the process of outpatients receiving cost-free medicines from medicine pick-up lockers in the North Denmark region.

OBJECTIVES: In the Danish healthcare system, restructuring is an ongoing process to accommodate the rising number of patients and to optimise resource allocation. To ease departmental burdens at hospitals in the North Denmark Region, outpatients are empowered to collect their cost-free medicines from medication pick-up lockers. The lockers function similarly to a package box, thereby enhancing patient freedom. Due to lack of evidence within the published literature regarding cost-free medicines and medicine waste, the aim of our study was to identify the common medications delivered to medicine pick-up lockers and secondly, to evaluate potential medicine waste. METHODS: Data from ApoVision provided insights into medications delivered to medicine pick-up lockers from March to October 2023 in the North Denmark Region. To estimate unused medicines we obtained data on the number of medications returned from medicine pick-up lockers. RESULTS: From 2020 to 2023, the number of patients receiving cost-free medicines at medication pick-up lockers increased. In total, approximately 30 000 packages of medicine were delivered to medicine pick-up lockers from March to October 2023 in the North Denmark Region; 1.7% were returned. Methotrexate, adalimumab, and omalizumab were among the most common deliveries and were also the three most returned from the medicine pick-up lockers. CONCLUSIONS: This study is an initial attempt to investigate potential medicine waste in cost-free medicines dispensed to outpatients via pick-up lockers. Antineoplastic and immunomodulating agents were the most common medicines delivered to medication pick-up lockers in the North Denmark Region from March to October 2023. In this period, approximately 2% of all delivered medicine packages were returned to the hospital pharmacy. Our analysis solely focuses on waste associated with medications left uncollected from medicine pick-up lockers. Addressing the impact of medicine waste in a hospital setting requires a comprehensive approach, thus future studies should also focus on other sites relevant for medication waste as, for example, the patient's household.

Patient Safety Climate in Danish Primary Care: Adaption and Validation of the Danish Safety Attitudes Questionnaire (SAQ-DK-PRIM).

Background: A lack of instruments to assess patient safety climate within primary care exists. The objectives of this study were as follows: 1) To adapt the Danish hospital version of the Safety Attitudes Questionnaire (SAQ-DK) for use in primary care; 2) Test the internal consistency and the construct validity of this version; 3) Present benchmark data; and 4) Analyze variance. Methods: The SAQ-DK was adapted for use in Danish primary care settings (SAQ-DK-PRIM) and distributed to healthcare staff members from nursing homes (N = 11), homecare units (N = 4) and healthcare units (N = 2), within the municipality of Aarhus, Central Denmark Region, Denmark. Face- and content validity were assessed. The construct validity was evaluated by a set of goodness-of-fit indices. The internal reliability was evaluated using the item-rest correlations, the inter-item correlations, and Cronbach's alpha (α). Results: The adaptation process resulted in a questionnaire of 10 items. Eight hundred and thirty healthcare staffs participated (78% of the eligible respondents). In total 586 (70.6%) responses were complete and were included in the analysis. Goodness-of-fit indices from the confirmatory factor analysis showed: Chi2=46.90CFI=0.97, RMSEA = 0.063 (90% CI: 0.044-0.084), Probability RMSEA (p close)=0.12. Internal reliability was high (Cronbach's α=0.76). Proportions of participants with a positive attitude was 41.1% and did not differ between the healthcare services. Scale mean score was 70.19 (SD: 18.05) and differed between healthcare services. The safety climate scale scores did not vary according to healthcare service type. ICC was 0.68% indicating no clustering of scores by healthcare service type. Conclusion: Considering the questionnaire's applicability, short length, strengthened focus on one area of interest and validity, the SAQ-DK-PRIM can serve as a valuable tool for measuring patient safety climate within primary care settings in Denmark.

Gender, variation in opioid receptor genes and sensitivity to experimental pain.

BACKGROUND: Pain tolerance is subject to considerable inter-individual variation, which may be influenced by a number of genetic and non-genetic factors. The mu, delta and kappa opioid receptors play a role in pain perception and are thought to mediate different pain modalities. The aim of this study was to explore associations between pain thresholds and gender and genetic variants in the three opioid receptor genes (OPRM, OPRD and OPRK). Experimental multi-modal pain data from previously published studies carried out in healthy Caucasian volunteers were used in order to limit the number of confounders to the study outcome. Data on thermal skin pain (n=36), muscle pressure pain (n=31) and mechanical visceral pain (n=50)) tolerance thresholds were included. RESULTS: Nineteen genetic polymorphisms were included in linear regression modeling. Males were found to tolerate higher thermal and muscle pressure pain than females (p=0.003 and 0.02). Thirty four percent of variability in thermal skin pain was accounted for by a model consisting of OPRK rs6473799 and gender. This finding was just outside significance when correction for multiple testing was applied. Variability in muscle pressure pain tolerance was associated with OPRK rs7016778 and rs7824175. These SNPs accounted for 43% of variability in muscle pressure pain sensitivity and these findings remained significant after adjustment for multiple testing. No association was found with mechanical visceral pain. CONCLUSION: This is a preliminary and hypothesis generating study due to the relatively small study size. However, significant association between the opioid receptor genes and experimental pain sensitivity supports the influence of genetic variability in pain perception. These findings may be used to generate hypotheses for testing in larger clinical trials of patients with painful conditions.

Drug absorption from oral formulations in patients with short bowel syndrome: a comprehensive update of the literature.

INTRODUCTION: Drug absorption is often altered and typically diminished in patients with short bowel syndrome (SBS). It is important to understand the patient's gastrointestinal anatomy, the absorptive capacity of the remaining bowel, and the physicochemical and pharmacokinetic properties of the drug to optimize oral pharmacotherapy. AREAS COVERED: The primary focus was to provide an updated understanding of the absorption of various drugs in patients with short bowel syndrome. Forty-seven studies covering 13 different drug classes were included in the review and study details, patient characteristics, drug characteristics and pharmacokinetic findings were summarized for each drug class. EXPERT OPINION: Improving and simplifying drug treatment in patients with SBS have high priority, but the patients are multi diseased so knowledge regarding absorption of drugs as e.g. antithrombotic agents, immunosuppressants is urgently needed. Therefore, it is crucial to advance our understanding of the fundamental factors involved in drug absorption, spanning from drug design to pathophysiology. With the growing knowledge in drug design and gastrointestinal pathophysiology, we anticipate the development of computer models that can accurately predict optimal absorption in the future.

Safe Medication in Nursing Home Residents Through the Development and Evaluation of an Intervention (SAME): Protocol for a Fully Integrated Mixed Methods Study With a Cocreative Approach.

BACKGROUND: Medication safety is increasingly challenging patient safety in growing aging populations. Developing positive patient safety cultures is acknowledged as a primary goal to improve patient safety, but evidence on the interventions to do so is inconclusive. Nursing home residents are often cognitively and physically impaired and are therefore highly reliant on frontline health care providers. Thus, interventions to improve medication safety of nursing home residents through patient safety culture among providers are needed. Using cocreative partnerships, integrating knowledge of residents and their relatives, and ensuring managerial support could be beneficial. OBJECTIVE: The primary aim of the Safe Medication of Nursing Home Residents Through Development and Evaluation of an Intervention (SAME) study is to improve medication safety for nursing home residents through developing an intervention by gaining experiential knowledge of patient safety culture in cocreative partnerships, integrating knowledge of residents and their relatives, and ensuring managerial support. METHODS: The fully integrated mixed method study will be conducted using an integrated knowledge translation approach. Patient safety culture within nursing homes will first be explored through qualitative focus groups (stage 1) including nursing home residents, their relatives, and frontline health care providers. This will inform the development of an intervention in a multidisciplinary panel (stage 2) including cocreators representing the medication management process across the health care system. Evaluation of the intervention will be done in a randomized controlled trial set at nursing homes (stage 3). The primary outcome will be changes in the mean scale score of an adapted version of the Danish "Safety Attitudes Questionnaire" (SAQ-DK) for use in nursing homes. Patient safety-related outcomes will be collected through Danish health registers to assess safety issues and effects, including medication, contacts to health care, diagnoses, and mortality. Finally, a mixed methods analysis on patient safety culture in nursing homes will be done (stage 4), integrating qualitative data (stage 1) and quantitative data (stage 3) to comprehensively understand patient safety culture as a key to medication safety. RESULTS: The SAME study is ongoing. Focus groups were carried out from April 2021 to September 2021 and the workshop in September 2021. Baseline SAQ-DK data were collected in January 2022 with expected follow-up in January 2023. Final data analysis is expected in spring 2024. CONCLUSIONS: The SAME study will help not only to generate evidence on interventions to improve medication safety of nursing home residents through patient safety culture but also to give insight into possible impacts of using cocreativity to guide the development. Thus, findings will address multiple gaps in evidence to guide future patient safety improvement efforts within primary care settings of political and scientific scope. TRIAL REGISTRATION: ClinicalTrials.gov NCT04990986; https://clinicaltrials.gov/ct2/show/NCT04990986. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43538.