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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.

Maja Thaarup,1 Peter Brønnum Nielsen,1,2 Anne Estrup Olesen,3,4 Maria Bitsch Poulsen,4,5 Torben Bjerregaard Larsen,1,2 Felix Wittström,3,6 Thure Filskov Overvad2,3 1Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; 2Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 3Department of Clinical Pharmacology, Aalborg University Hospital, Aalborg, Denmark; 4Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 5Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark; 6Department of Medicine Solna, Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, SwedenCorrespondence: Thure Filskov Overvad, Aalborg University Hospital, Hobrovej 18-22, Aalborg, 9100, Denmark, Tel +45 51 55 53 55, Email t.overvad@rn.dkPurpose: The majority of bleeding diagnoses in the Danish National Patient Registry have not been validated despite extensive use in epidemiological research. Therefore, we examined the positive predictive value (PPV) of non-traumatic bleeding diagnoses in the Danish National Patient Registry.Study Design: Population-based validation study.Patients and Methods: Based on a manual review of electronic medical records, we estimated the PPV of diagnostic coding (International Classification of Diseases, Tenth Revision (ICD‐10)) for non-traumatic bleeding for all patients ≥ 65 years of age with any hospital contact in the North Denmark Region during March–December 2019 as registered in the Danish National Patient Registry. We calculated PPVs and associated 95% confidence intervals (CI) for non-traumatic bleeding diagnoses overall and stratified according to primary or secondary diagnosis, and according to major anatomical sites.Results: A total of 907 electronic medical records were available for review. The population mean age was 79.33 years (standard deviation (SD)=7.73) and 57.6% were males. Primary bleeding dia

Introduction Paracetamol poisoning is a frequent cause of hospitalization in Denmark. On 30 September 2013, the Danish authorities restricted packages available without a prescription in pharmacy outlets to contain a maximum of 10 g of paracetamol. We aimed to investigate the effects of this regulation. Methods This was a cross-sectional study of two groups of patients admitted consecutively to a Danish University Hospital due to poisoning with paracetamol in 365 days in 2012–13 before 30 September 2013, and a corresponding 365-day period in 2017–18. Data were extracted from patient records. Results In 2012–2013 and 2017–18, 156 and 92 admissions in 127 and 78 unique patients, respectively, were identified. Ingestion of more than 20 g paracetamol occurred in a significantly higher proportion of cases in 2012–13 compared to 2017–18 (29% vs 13%, P < 0.01). In accordance, there were no cases of international normalized ratio >1.5 or alanine aminotransferase activity >1000 U/L in the post-legislation period, and seven and five cases in the pre-legislation period, respectively. Females accounted for 80% and 78% of patients in the two periods, respectively, and were considerably younger than males (median [interquartile range]: 22 [17–40] vs. 47 [30–56], P < 0.01 in 2012–13, and 23 [18–46] vs. 43 [27–49] years, P = 0.02 in 2017–18). Furthermore, in 2012-13, intentional poisonings occurred in a higher proportion of females than males 2012–13 (97% vs 85%, P < 0.01). Conclusions The present study demonstrated a lower number of paracetamol poisonings, a decreased proportion of poisonings involving ingestion of more than 20 g of paracetamol, and a lower occurrence of hepatotoxicity after the regulation. However, circumstances other than pack size restrictions, such as increased public awareness of the danger of paracetamol poisonings, may affect these associations. Furthermore, the study showed that females and males co, Introduction: Paracetamol poisoning is a frequent cause of hospitalization in Denmark. On 30 September 2013, the Danish authorities restricted packages available without a prescription in pharmacy outlets to contain a maximum of 10 g of paracetamol. We aimed to investigate the effects of this regulation. Methods: This was a cross-sectional study of two groups of patients admitted consecutively to a Danish University Hospital due to poisoning with paracetamol in 365 days in 2012–13 before 30 September 2013, and a corresponding 365-day period in 2017–18. Data were extracted from patient records. Results: In 2012–2013 and 2017–18, 156 and 92 admissions in 127 and 78 unique patients, respectively, were identified. Ingestion of more than 20 g paracetamol occurred in a significantly higher proportion of cases in 2012–13 compared to 2017–18 (29% vs 13%, P < 0.01). In accordance, there were no cases of international normalized ratio >1.5 or alanine aminotransferase activity >1000 U/L in the post-legislation period, and seven and five cases in the pre-legislation period, respectively. Females accounted for 80% and 78% of patients in the two periods, respectively, and were considerably younger than males (median [interquartile range]: 22 [17–40] vs. 47 [30–56], P < 0.01 in 2012–13, and 23 [18–46] vs. 43 [27–49] years, P = 0.02 in 2017–18). Furthermore, in 2012-13, intentional poisonings occurred in a higher proportion of females than males 2012–13 (97% vs 85%, P < 0.01). Conclusions: The present study demonstrated a lower number of paracetamol poisonings, a decreased proportion of poisonings involving ingestion of more than 20 g of paracetamol, and a lower occurrence of hepatotoxicity after the regulation. However, circumstances other than pack size restrictions, such as increased public awareness of the danger of paracetamol poisonings, may affect these associations. Furthermore, the study showed that females and males constitute two distinct groups in term

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.

Moderate to severe pain is often treated with opioids, but central mechanisms underlying opioid analgesia are poorly understood. Findings thus far have been contradictory and none could infer opioid specific effects. This placebo-controlled, randomized, 2-way cross-over, double-blinded study aimed to explore opioid specific effects on central processing of external stimuli. Twenty healthy male volunteers were included and 3 sets of assessments were done at each of the 2 visits: 1) baseline, 2) during continuous morphine or placebo intravenous infusion and 3) during simultaneous morphine + naloxone or placebo infusion. Opioid antagonist naloxone was introduced in order to investigate opioid specific effects by observing which morphine effects are reversed by this intervention. Quantitative sensory testing, spinal nociceptive withdrawal reflexes (NWR), spinal electroencephalography (EEG), cortical EEG responses to external stimuli and resting EEG were measured and analyzed. Longer lasting pain (cold-pressor test – hand in 2° water for 2 minutes, tetanic electrical), deeper structure pain (bone pressure) and strong nociceptive (NWR) stimulations were the most sensitive quantitative sensory testing measures of opioid analgesia. In line with this, the principal opioid specific central changes were seen in NWRs, EEG responses to NWRs and cold-pressor EEG. The magnitude of NWRs together with amplitudes and insular source strengths of the corresponding EEG responses were attenuated. The decreases in EEG activity were correlated to subjective unpleasantness scores. Brain activity underlying slow cold-pressor EEG (1-4Hz) was decreased, whereas the brain activity underlying faster EEG (8-12Hz) was increased. These changes were strongly correlated to subjective pain relief. This study points to evidence of opioid specific effects on perception of external stimuli and the underlying central responses. The analgesic response to opioids is likely a synergy of opioids acting at