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1.
Diabetes Care ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38709662

ABSTRACT

OBJECTIVE: Type 2 diabetes often coexists with other conditions that are amenable to pharmacological treatment. We hypothesized that polypharmacy among individuals with type 2 diabetes has increased since 2000. RESEARCH DESIGN AND METHODS: Using Danish national registries, we established a cohort of all Danish individuals (aged ≥18 years) with type 2 diabetes between 2000 and 2020. We analyzed their medication use and prevalence of varying degrees of polypharmacy (≥5 or ≥10 medications), stratifying by age, sex, number of chronic diseases, and socioeconomic status. RESULTS: The cohort grew from 84,917 patients in 2000 to 307,011 in 2020, totaling 461,849 unique patients. The number of daily medications used per patient increased from (mean ± SD) 3.7 ± 2.8 (in 2000) to 5.3 ± 3.2 (in 2020). The lifetime risk of polypharmacy was substantial, with 89% (n = 409,062 of 461,849) being exposed to ≥5 medications at some point and 47% (n = 217,467of 461,849) to ≥10 medications. The increases were driven by an expanding group of medications, with analgesics, antihypertensives, proton pump inhibitors, and statins having the largest net increase. Advanced age, male sex, lower socioeconomic status, and Danish ethnicity positively correlated with polypharmacy but could not explain the overall increase in polypharmacy. CONCLUSIONS: Medication use and polypharmacy have increased among patients with type 2 diabetes. Although the implications and appropriateness of this increased medication use are uncertain, the results stress the increasing need for health care personnel to understand the potential risks associated with polypharmacy, including medication interactions, adverse effects, and over- and underprescribing.

2.
Genes Chromosomes Cancer ; 63(4): e23236, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38656617

ABSTRACT

OBJECTIVE: This study aims to evaluate the developments in the testing of Kirsten Rat Sarcoma viral oncogene homolog (KRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations across different cancer types and regions in Denmark from 2010 to 2022. STUDY DESIGN AND SETTING: Using comprehensive data from the Danish health registries, we linked molecular test results from the Danish Pathology Registry with cancer diagnoses from the Danish National Patient Registry between 2010 and 2022. We assessed the frequency and distribution of KRAS and BRAF mutations across all cancer types, years of testing, and the five Danish regions. RESULTS: The study included records of KRAS testing for 30 671 patients and BRAF testing for 30 860 patients. Most KRAS testing was performed in colorectal (78%) and lung cancer (18%), and BRAF testing in malignant melanoma (13%), colorectal cancer (67%), and lung cancer (12%). Testing rates and documentation mutational subtypes increased over time. Reporting of wildtype results varied between lung and colorectal cancer, with underreporting in lung cancer. Regional variations in testing and reporting were observed. CONCLUSION: Our study highlights substantial progress in KRAS and BRAF testing in Denmark from 2010 to 2022, evidenced by increased and more specific reporting of mutational test results, thereby improving the precision of cancer diagnosis and treatment. However, persistent regional variations and limited testing for cancer types beyond melanoma, colorectal, and lung cancer highlight the necessity for a nationwide assessment of the optimal testing approach.


Subject(s)
Genetic Testing , Proto-Oncogene Proteins B-raf , Proto-Oncogene Proteins p21(ras) , Female , Humans , Male , Colorectal Neoplasms/genetics , Colorectal Neoplasms/diagnosis , Denmark , Genetic Testing/methods , Genetic Testing/statistics & numerical data , Genetic Testing/standards , Mutation , Neoplasms/genetics , Neoplasms/diagnosis , Precision Medicine/methods , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Registries
3.
Clin Ther ; 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38493002

ABSTRACT

PURPOSE: Metronidazole, a widely used antimicrobial medication, has been linked to neurologic adverse drug reactions. This study investigates the association between metronidazole use and first-time neurologic events. METHODS: We conducted a case-time-control study using data from the Danish National Patient Register and the National Prescription Register in years 2013 to 2021. Patients with a first-time diagnosis of encephalopathy, cerebellar dysfunction, or peripheral neuropathy were included. Conditional logistic regression analyses were performed to estimate the risk of neurologic events associated with metronidazole use. FINDINGS: Out of 476,066 first-time metronidazole prescriptions, the 100-day cumulative incidence of peripheral neuropathy was 0.016%, and 0.002% for cerebellar dysfunction or encephalopathy. In the case-time control study, we identified 17,667 persons with a first-time neurologic event and were included for the analysis. The estimated odds ratio for the combined neurologic events was 0.98 (95% CI, 0.59-1.64, P = 0.95) with no statistically significant association across different subgroups and time windows. IMPLICATIONS: Our findings suggest that metronidazole-induced neurologic events may be rarer than previously described, and we did not find any consistent or statistically significant association between metronidazole exposure. Nonetheless, clinicians should remain vigilant to potential neurologic risks in patients receiving metronidazole, to ensure its safe and effective use.

4.
Br J Clin Pharmacol ; 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38450747

ABSTRACT

We report a poisoning with paliperidone palmitate, a once-monthly, long-acting injectable antipsychotic. The patient suffered from deep sedation and dystonia. She had been treated with extended release intramuscular paliperidone for several years and had received her last injection 8 days prior to admission. The plasma paliperidone was nearly five times higher than the upper reference range. Paliperidone is a substrate of p-glycoprotein and we therefore aimed to increase its elimination by inducing p-glycoprotein through treatment with St John's wort. This seemed to have a limited effect on paliperidone clearance. Plasma concentration levels decreased with time as did the dystonia. All antipsychotic treatment was discontinued after this unfortunate event, and the patient did specifically not receive any prescriptions of paliperidone or risperidone. However, the plasma paliperidone concentration was in the low end of the normal therapeutic range 2.5 years after the last dose of paliperidone was administered, and the patient still had some extrapyramidal symptoms.

5.
Lancet Healthy Longev ; 4(12): e685-e692, 2023 12.
Article in English | MEDLINE | ID: mdl-38042161

ABSTRACT

BACKGROUND: The pharmacotherapeutic guidelines for type 2 diabetes have changed considerably during the past decades. SGLT2 inhibitors and GLP-1 receptor agonists have emerged as first-line agents by preventing cardiovascular events within a few years of treatment. In contrast, sulphonylureas and insulin have been deprioritised due to less beneficial effects and the risk of hypoglycaemia-particularly in older people who are frail. We hypothesised that medications with a high risk of hypoglycaemia were used more often in older people compared with younger people. METHODS: In a nationwide cohort of people with type 2 diabetes in Denmark from 2019 to 2020, we described the use of specific glucose-lowering medications in relation to age and glycated haemoglobin A1C (HbA1c) by descriptive statistics and regression models adjusted for sex, socioeconomic factors, renal function, and several comorbidities. FINDINGS: Among 290 890 people with type 2 diabetes, glucose-lowering medication usage peaked at age 70 years. Increasing age was associated with relatively less use of metformin, GLP-1 receptor agonists, and SGLT2 inhibitors and more use of basal insulin, DDP-4 inhibitors, and sulphonylureas. When comparing 80-year-olds with 60-year-olds at similar HbA1c levels of 6·5% (48 mmol/mol), 80-year-olds used 8% (95% CI 7-10%) fewer glucose-lowering medications, were 55% less likely to receive GLP-1 receptor agonists or SGLT2 inhibitors (relative ratio 0·45, 95% CI 0·42-0·48), and 65% more likely to receive sulphonylureas (1·65, 1·54-1·76). Among 23 032 individuals aged 80 years or older with HbA1c levels of less than 6·5% (<48 mmol/mol), 2291 (10%) used sulphonylureas or insulin. INTERPRETATION: In Danish people with type 2 diabetes, the likelihood of using glucose-lowering medications with a high risk of hypoglycaemia (eg, sulphonylureas and basal insulin) increased with age, whereas the likelihood of using GLP-1 receptor agonists and SGLT2 inhibitors decreased. Some people aged 80 years or older with an HbA1c level of less than 6·5% (48 mmol/mol) were potentially overtreated with sulphonylureas or insulin. These findings emphasise the importance of frequently re-evaluating glucose-lowering treatments. FUNDING: None. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.


Subject(s)
Age Factors , Diabetes Mellitus, Type 2 , Healthcare Disparities , Hypoglycemia , Sodium-Glucose Transporter 2 Inhibitors , Aged , Humans , Cross-Sectional Studies , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Glucagon-Like Peptide-1 Receptor/agonists , Glycated Hemoglobin , Hypoglycemia/chemically induced , Hypoglycemia/epidemiology , Hypoglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sulfonylurea Compounds/therapeutic use , Aged, 80 and over
6.
Drugs Aging ; 40(11): 1009-1015, 2023 11.
Article in English | MEDLINE | ID: mdl-37658195

ABSTRACT

INTRODUCTION: Certain clinical events reduce life expectancy and necessitate a reassessment of patient treatment. OBJECTIVE: To describe medication changes in relation to a cancer diagnosis and the end of life and to highlight challenges and limitations with such descriptions. METHODS: From a cohort with all Danish patients with type 2 diabetes, we matched patients with incident cancer during 2000-2021 (n = 41,745) with patients without cancer (n = 166,994) using propensity scores. We described their medication usage from cancer diagnosis until death. RESULTS: The 1- and 5-year mortality were 51% and 86%, respectively, in the cancer group, and 13% and 59% in the non-cancer group. In relation to cancer diagnosis and death, the use of symptomatic medications (e.g., opioids, benzodiazepines) increased (10-60 incident medications per 100 patient-months), and the use of preventive medications (e.g., antihypertensives, statins) decreased (5-30% fewer users). The changes in relation to the diagnosis were driven by patients with short observed lengths of survival (< 2 years). In contrast, changes occurring within a year before death were less dependent on survival strata, and > 60% used preventive medications in their last months. CONCLUSIONS: Medication changes in relation to a cancer diagnosis were frequent and correlated to the length of survival. The results showcase the challenges and limited clinical utility of anchoring analyses on events or death. While the former diluted the results by averaging changes across patients with vastly different clinical courses, the latter leveraged information unavailable to the treating clinicians. While medication changes were common near death, preventive medications were often used until death.


Subject(s)
Diabetes Mellitus, Type 2 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Neoplasms , Humans , Diabetes Mellitus, Type 2/drug therapy , Neoplasms/drug therapy , Antihypertensive Agents/therapeutic use , Benzodiazepines/therapeutic use
7.
Br J Clin Pharmacol ; 89(11): 3291-3301, 2023 11.
Article in English | MEDLINE | ID: mdl-37254818

ABSTRACT

AIMS: To provide posthoc analyses of a clinical trial that reported beneficial effects of medication reviews on health-related quality of life. Specifically, to describe the medication changes with a focus on deprescribing and to explore patient- and medication-related factors that may identify patients most likely to benefit from medication reviews. METHODS: Posthoc analyses of data from a pragmatic, nonblinded, randomized clinical trial investigating a medication review intervention (NCT03911934) in 408 geriatric outpatients treated with ≥9 medicines. RESULTS: In the medication review group (n = 196), 26% of the medicines prescribed at baseline were discontinued with 82% still being discontinued after 13 months. The most common reason for discontinuation was lack of indication (72% of discontinuations). The medicines most often discontinued in the medication review group compared with usual care included: metoclopramide (11/15 = 73% discontinued vs. 1/12 = 8% in usual care), acetylsalicylic acid (20/48 = 42% vs. 2/47 = 4%), simvastatin (18/48 = 38% vs. 2/58 = 3%), zopiclone (23/59 = 39% vs. 4/54 = 7%), quinine (9/14 = 64% vs. 6/16 = 38%), citalopram (4/18 = 22% vs. 0/20 = 0%) and tramadol (18/37 = 49% vs. 8/30 = 27%). Factors associated with number of deprescribed medicines included: number of prescribed medicines, Drug Burden Index, patient motivation for medicine changes, and prescriptions of metoclopramide, iron preparations, antidepressants other than selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs, or drugs for urinary incontinence. CONCLUSION: Physician-led medication reviews resulted in persistent deprescribing of medicines in older polypharmacy patients treated with ≥9 medicines. Motivation for having their medicine changed, treatment with more medicines, and a higher burden of sedative and anticholinergic medicines characterized the patients most likely to benefit from physician-led medication reviews.


Subject(s)
Deprescriptions , Humans , Aged , Medication Review , Outpatients , Polypharmacy , Quality of Life , Metoclopramide
8.
Lung Cancer ; 178: 172-182, 2023 04.
Article in English | MEDLINE | ID: mdl-36868178

ABSTRACT

OBJECTIVES: We aimed to characterize the advanced NSCLC population in terms of KRAS G12C prevalence, patient characteristics, and survival outcomes after the introduction of immunotherapies. MATERIALS AND METHODS: We identified adult patients diagnosed with advanced NSCLC between January 1, 2018 and June 30, 2021 using the Danish health registries. Patients were grouped by mutational status (any KRAS mutation, KRAS G12C, and KRAS/EGFR/ALK wildtype [Triple WT]). We analyzed KRAS G12C prevalence, patient and tumor characteristics, treatment history, time-to-next-treatment (TTNT), and overall survival (OS). RESULTS: We identified 7,440 patients of whom 40% (n = 2,969) were KRAS tested prior to the first line of therapy (LOT1). Among the KRAS tested, 11% (n = 328) harbored KRAS G12C. More KRAS G12C patients were women (67%), smokers (86%), had a high (≥50%) level of PD-L1 expression (54%), and more frequently received anti-PD-L1 treatment than any other group. From the date of the mutational test result, OS (7.1-7.3 months) was similar between the groups. OS from LOT1 (14.0 months) and LOT2 (10.8 months), and TTNT from LOT1 (6.9 months) and LOT2 (6.3 months) was numerically longer for the KRAS G12C mutated group compared to any other group. However, from LOT1 and LOT2, the OS and TTNT were comparable when stratifying the groups by PD-L1 expression level. Regardless of the mutational group, OS was markedly longer for patients with high PD-L1 expression. CONCLUSION: In patients diagnosed with advanced NSCLC after the implementation of anti-PD-1/L1 therapies, the survival in KRAS G12C mutated patients is comparable to patients with any KRAS mutation, Triple WT, and all NSCLC patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Adult , Humans , Female , Male , Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/genetics , Lung Neoplasms/therapy , Lung Neoplasms/metabolism , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Mutation , Denmark/epidemiology , B7-H1 Antigen/metabolism
9.
Diabet Med ; 40(4): e15052, 2023 04.
Article in English | MEDLINE | ID: mdl-36681891

ABSTRACT

AIMS: Medication reviews can be used to promote appropriate pharmacotherapy and negate the harmful consequences of polypharmacy. This study aimed to evaluate the effect of physician-led medication reviews and increased cross-sectoral communication as a supplement to standard care in a type 2 diabetes outpatient clinic. METHODS: This pragmatic randomised clinical trial enrolled patients with type 2 diabetes treated with at least 12 medications. The subjects were randomised to either standard care (standard care consultation at the outpatient clinic) or standard care plus a medication review consultation and increased cross-sectoral communication. The primary outcome was the number of medications used after six months. Health-related quality of life was quantified using the EuroQoL 5-dimension 5-level (EQ5D-5 L) questionnaire. RESULTS: We recruited 50 participants with a median age of 72 (IQR 67-75) years. The mean number of medications per patient changed from 17.9 to 14.3 in the intervention group and 17.6 to 17.2 in the control group (rate ratio 0.81). The reasons for discontinuations were medication no longer indicated (60%), safety issues (20%), efficacy issues (15%) or patient preferences (5%). There was a significant difference in the change in health-related quality of life (EQ5D-5 L index score) in favour of the intervention (0.111, 95% CI 0.001 to 0.221). CONCLUSIONS: Physician-led medication reviews and increased cross-sectoral communication in patients with type 2 diabetes treated with at least 12 medications reduced the number of medications used and improved health-related quality of life. Implementing and further investigating similar interventions as standard care seems reasonable.


Subject(s)
Diabetes Mellitus, Type 2 , Physicians , Polypharmacy , Quality of Life , Medication Review
10.
Br J Clin Pharmacol ; 89(6): 1820-1833, 2023 06.
Article in English | MEDLINE | ID: mdl-36519217

ABSTRACT

AIMS: To evaluate the experience with use of sotrovimab following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in high-risk groups. METHODS: In a nationwide, population-based cohort study, we identified all individuals treated with sotrovimab (N = 2933) and stratified them by 4 high-risk groups: (A) malignant haematological disease, (B) solid organ transplantation, (C) anti-CD20 therapy ≤1 year and (D) other risks. Cox regression analysis was used to calculate hazard ratios for hospitalization, death and associated prognostic factors. RESULTS: Of 2933 sotrovimab-treated individuals, 83% belonged to high-risk groups (37.6% haematological malignancy, 27.4% solid organ transplantation and 17.5% treatment with anti-CD20 ≤1 year). Only 17.8% had other risks (11.8% were pregnant, 10.7% primary immunodeficiency, 21.2% other malignancy, 4.3% received anti-CD20 >1 year and 52.0% other/unknown causes). Within 90 days of infusion, 30.2% were hospitalized and 5.3% died. The main prognostic factors were the predefined high-risk groups, mainly malignant haematological disease and age ≥65 years. Number of COVID-19 vaccines (≥3) was associated with a decreased risk of hospitalization. The Delta but not the Omicron BA.2 variant was associated with a higher risk of death compared to the BA.1 variant. CONCLUSION: More than 90% of the patients treated with sotrovimab belonged to the very high-risk groups as described in the Danish guidelines. Sotrovimab-treated individuals remained at a high risk of hospitalization and death which was strongly associated with the underlying immunocompromised state and age. Having received >3 COVID-19 vaccines was association with decreased risk of death and hospitalization.


Subject(s)
COVID-19 , SARS-CoV-2 , Female , Pregnancy , Humans , Aged , COVID-19 Vaccines , Cohort Studies , Denmark/epidemiology
12.
Basic Clin Pharmacol Toxicol ; 131(1): 83-92, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35538919

ABSTRACT

Tramadol is a commonly used opioid with a potential of addiction and abuse. Using Danish nationwide registers, we aimed to (1) characterise opioid poisonings; (2) assess the 30-day mortality following morphine, oxycodone, and mixed poisonings compared to tramadol poisonings; and (3) assess the development in tramadol poisonings during a 12-year period. Poisonings were identified from 2006 to 2017. A Cox proportional hazards regression model was used to estimate adjusted hazard ratios (aHRs) along with 95% confidence intervals (CIs) for 30-day mortality following morphine, oxycodone or mixed poisonings compared to tramadol poisonings. We identified 7718 opioid poisonings among 6365 patients. The patients with a tramadol poisoning were younger and had less comorbidities than the patients with a morphine, oxycodone or mixed poisoning. Within 30 days, a total of 205 patients died. The 30-day mortality risk was higher following morphine (aHR 3.2, 95% CI 2.0-5.1), oxycodone (aHR 2.1, 95% CI 1.2-3.6) and mixed poisonings (aHR 1.6, 95% CI 1.0-2.7) compared to tramadol poisonings. The annual number of tramadol poisonings increased from 233 in 2006 to 501 in 2013 and declined to 348 in 2017. In conclusion, despite a lower mortality risk compared to other opioid poisonings, physicians should consider the poisoning and abuse risks when prescribing tramadol.


Subject(s)
Tramadol , Analgesics, Opioid , Anti-Inflammatory Agents, Non-Steroidal , Denmark/epidemiology , Humans , Morphine , Oxycodone , Tramadol/adverse effects
13.
Ther Adv Psychopharmacol ; 12: 20451253211072341, 2022.
Article in English | MEDLINE | ID: mdl-35273789

ABSTRACT

Introduction: The antipsychotic drug clozapine remains underutilized partly because of the risk of life-threatening adverse effects, such as neutropenia. Therefore, an extensive hematological monitoring program was set up to detect neutropenia. Methods: In this retrospective cohort study, we used registry-based data from the Capital Region of Denmark to investigate incidence rates of neutropenia among patients with a diagnosis of schizophrenia or other psychotic disorders and treated with clozapine for the first time. In a within-subject design, we compared rates of neutropenia in time periods where patients were exposed to clozapine versus time periods, where they were not exposed to clozapine. We also investigated whether the lengths of clozapine-associated neutropenia (CAN) were related to discontinuation of clozapine treatment. Results: Data from 520 clozapine users were included. The incidence rate of CAN was 3.2 cases per 100 person-years (95% confidence interval [CI]: 2.1-4.8) throughout the entire study. There was no significant difference in incidence rates of neutropenia during clozapine exposure and non-clozapine exposure, with an incidence rate ratio of 0.7 (95% CI: 0.4-1.3). One episode of severe neutropenia was detected. Episodes of CAN with only one sub-threshold neutrophil count were not associated with higher clozapine discontinuation (26%) than CAN episodes of more than one sub-threshold neutrophil count (28%). Conclusion: In the present study, we could not confirm that clozapine treatment was associated with neutropenia.

14.
Acta Psychiatr Scand ; 145(6): 557-567, 2022 06.
Article in English | MEDLINE | ID: mdl-35320582

ABSTRACT

OBJECTIVE: To investigate the association between mirtazapine exposure in pregnancy and risk of specific adverse pregnancy outcomes. METHODS: A register-based nationwide cohort study was conducted including all registered pregnancies in Denmark from 1997 to 2016. Mirtazapine-exposed pregnancies were compared with mirtazapine unexposed pregnancies in a 1:4 ratio matched according to propensity scores. Outcomes were major congenital malformations analyzed using log binomial models, and spontaneous abortion, stillbirth and neonatal death analyzed using Cox proportional hazard regression. RESULTS: From a source population of 1,650,649 pregnancies, the propensity score-matched cohort included 4475 pregnancies (895 mirtazapine exposed) in the analysis of major congenital malformations. The analyses of spontaneous abortion included 9 500 pregnancies (1900 mirtazapine exposed), and for the analyses of stillbirths and neonatal deaths 9725 (1 945 mirtazapine-exposed) and 4485 pregnancies (897 mirtazapine-exposed) were included, respectively. Thirty-one (3.5%) children were diagnosed with major congenital malformation among the mirtazapine exposed compared with 152 (4.3%) among the unexposed pregnancies (OR=0.81, 95% CI 0.55-1.20). Spontaneous abortion occurred in 237 (12.5%) of the mirtazapine exposed compared with 931 (12.3%) of the unexposed pregnancies (HR = 1.04%, 95% CI 0.91-1.20). The analyses revealed no increased risk of stillbirth (HR = 0.88%, 95% CI 0.34-2.29) or neonatal death (HR = 0.60%, 95% CI 0.18-2.02). CONCLUSIONS: In this nationwide Danish register study, mirtazapine exposure in pregnancy was not associated with major congenital malformations, spontaneous abortion, stillbirth, or neonatal death. Clinicians and patients can be reassured that mirtazapine is safe in pregnancy.


Subject(s)
Abortion, Spontaneous , Perinatal Death , Abortion, Spontaneous/chemically induced , Abortion, Spontaneous/epidemiology , Child , Cohort Studies , Female , Humans , Infant, Newborn , Mirtazapine/adverse effects , Pregnancy , Stillbirth/epidemiology
15.
Clin Microbiol Infect ; 28(9): 1291.e1-1291.e5, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35306190

ABSTRACT

OBJECTIVES: To evaluate safety and effectiveness of prophylactic anticoagulation with low molecular weight heparin (LMWH) in individuals hospitalised for COVID-19. METHODS: Using healthcare records from the Capital Region of Denmark (March 2020-February 2021) and Karolinska University Hospital in Sweden (February 2020-September 2021), we conducted an observational cohort study comparing clinical outcomes 30 days after admission among individuals hospitalised for COVID-19 starting prophylactic LMWH during the first 48 hours of hospitalisation with outcomes among those not receiving prophylactic anticoagulation. We used inverse probability weighting to adjust for confounders and bias due to missing information. Risk ratios, risk differences and robust 95% confidence intervals (CI) were estimated using binomial regression. Country-specific risk ratios were pooled using random-effects meta-analysis. RESULTS: We included 1692 and 1868 individuals in the Danish and Swedish cohorts. Of these, 771 (46%) and 1167 (62%) received prophylactic LMWH up to 48 hours after admission. The combined mortality in Denmark and Sweden was 12% (N = 432) and the pooled risk ratio was 0.91 (CI 0.60-1.38) comparing individuals who received LMWH to those who did not. The relative risk of ICU admission was 1.12 (0.76-1.66), while we observed no increased risk of bleeding 0.63 (0.13-2.94). The relative risk of venous thromboembolism was 0.80 (0.43-1.47). CONCLUSION: We found no benefit on mortality with prophylactic LMWH and no increased risk of bleeding among COVID-19 patients receiving prophylactic LMWH.


Subject(s)
COVID-19 Drug Treatment , Heparin, Low-Molecular-Weight , Anticoagulants/adverse effects , Cohort Studies , Denmark/epidemiology , Hemorrhage , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Observational Studies as Topic , Sweden/epidemiology
16.
Br J Clin Pharmacol ; 88(7): 3360-3369, 2022 07.
Article in English | MEDLINE | ID: mdl-35184324

ABSTRACT

AIM: To investigate the effects of a comprehensive medication review intervention on health-related quality of life (HRQoL) and clinical outcomes in geriatric outpatients exposed to polypharmacy. METHODS: Pragmatic, nonblinded, randomized clinical trial with follow-up after 4 and 13 months. Participants were geriatric outpatients taking ≥9 medicines. The intervention was an additional consultation with a physician focusing on reviewing medication, informing patients about their medicines and increasing cross-sectoral communication as supplement to and compared with usual care. The primary outcome was change in HRQoL after 4 months measured with the EuroQoL 5-dimension 5-level (EQ-5D-5L) questionnaire. Secondary outcomes were HRQoL after 13 months, mortality, admissions, falls and number of medicines after 4 and 13 months. RESULTS: Of 785 eligible patients, 408 were included (age: mean 80.6 [standard deviation 7.22] years; number of medicines: median 12 [interquartile range 10-14]; females 71%). After 4 months, the adjusted between-group difference in EQ-5D-5L index score was 0.066 in favour of the medication consultation (95% confidence interval 0.01 to 0.12, P = .02). After 4 months, two (1%) participants had died in the medication-consultation group and nine (4%) in the usual-care group (log-rank test, P = .045). The medication consultation reduced the number of medicines by 2.0 (15.8%) after 4 months and 1.3 (10.7%) after 13 months. There were no statistically significant differences in mortality or HRQoL after 13 months, and no differences in falls or admissions. CONCLUSIONS: An additional consultation with medication review and increased communication as supplement to usual geriatric outpatient care improved HRQoL and reduced mortality after 4 months.


Subject(s)
Polypharmacy , Quality of Life , Aged , Child , Female , Humans , Medication Review , Outpatients , Surveys and Questionnaires
17.
Sci Rep ; 11(1): 18959, 2021 09 23.
Article in English | MEDLINE | ID: mdl-34556789

ABSTRACT

The COVID-19 pandemic has put massive strains on hospitals, and tools to guide hospital planners in resource allocation during the ebbs and flows of the pandemic are urgently needed. We investigate whether machine learning (ML) can be used for predictions of intensive care requirements a fixed number of days into the future. Retrospective design where health Records from 42,526 SARS-CoV-2 positive patients in Denmark was extracted. Random Forest (RF) models were trained to predict risk of ICU admission and use of mechanical ventilation after n days (n = 1, 2, …, 15). An extended analysis was provided for n = 5 and n = 10. Models predicted n-day risk of ICU admission with an area under the receiver operator characteristic curve (ROC-AUC) between 0.981 and 0.995, and n-day risk of use of ventilation with an ROC-AUC between 0.982 and 0.997. The corresponding n-day forecasting models predicted the needed ICU capacity with a coefficient of determination (R2) between 0.334 and 0.989 and use of ventilation with an R2 between 0.446 and 0.973. The forecasting models performed worst, when forecasting many days into the future (for large n). For n = 5, ICU capacity was predicted with ROC-AUC 0.990 and R2 0.928, and use of ventilator was predicted with ROC-AUC 0.994 and R2 0.854. Random Forest-based modelling can be used for accurate n-day forecasting predictions of ICU resource requirements, when n is not too large.


Subject(s)
COVID-19/epidemiology , Forecasting/methods , Intensive Care Units/trends , Area Under Curve , Computational Biology/methods , Critical Care/statistics & numerical data , Critical Care/trends , Denmark/epidemiology , Hospitalization/trends , Hospitals/trends , Humans , Machine Learning , Pandemics , ROC Curve , Respiration, Artificial/statistics & numerical data , Respiration, Artificial/trends , Retrospective Studies , Risk Assessment/methods , Risk Factors , SARS-CoV-2/pathogenicity , Ventilators, Mechanical/trends
18.
Dan Med J ; 68(5)2021 Apr 28.
Article in English | MEDLINE | ID: mdl-33913417

ABSTRACT

INTRODUCTION: This study describes the types and health consequences of medication errors in residential facilities for which the Danish Poison Information Center (DPIC) was contacted. METHODS: This study is based on all inquiries made by residential facilities to the DPIC during a 13-month period. Information about inquirers and residents, data related to the medication error, symptoms, risk assessments and recommendations was collected, and a follow-up phone call was made to evaluate the clinical outcomes, preferably within one week. RESULTS: During the study period, the DPIC received 146 inquiries concerning medication errors in residential facilities. Nearly all inquiries concerned excess administration of medication (96%) and often involved medications targeting the nervous system (65%). In 9% of cases, the DPIC recommended hospitalisation. Most medication errors (92%) were considered of "no or minor risk". Administration of medication to the wrong resident is a frequent reason for consulting the DPIC (45%) in cases with medication errors. CONCLUSIONS: In this study, we inventoried the inquiries made to the DPIC about medication errors in residential facilities in Denmark. Most medication errors did not carry a risk of serious health consequences, but continued monitoring is warranted to minimise risk in this vulnerable population. FUNDING: Copenhagen Center for Health Technology (5001105002), Department of Clinical Pharmacology (Bispebjerg Hospital, The Capital Region) (1152871001). TRIAL REGISTRATION: not relevant.


Subject(s)
Poisons , Denmark/epidemiology , Humans , Information Centers , Medication Errors , Residential Facilities
20.
Basic Clin Pharmacol Toxicol ; 128(3): 542-549, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33150720

ABSTRACT

The Danish Poison Information Centre (DPIC) regularly receives inquiries about nursing home residents who have been exposed to a medication error. The aim of this prospective cohort study was to describe and discuss the types and consequences of these errors. Data were collected from 1 March 2018 to 31 March 2019. Registered data included characteristics of caller and resident, data related to the suspected medication error, risk assessment and recommendation. Consequences and clinical outcomes were assessed by follow-up telephone calls. Over the study period, the DPIC was consulted about 145 medication errors occurring at Danish nursing homes. The median number of substances administered by error was two (interquartile range 1-5). Hospitalization was recommended in 21% of cases. In one-third of the cases where consultation with the DPIC was done with the resident either on his/her way to or in hospital, hospitalization was found unnecessary, and the resident could have stayed in accustomed surroundings for observation. Follow-up demonstrated that very few medication errors had a severe outcome. This prospective study illustrates that consulting with a poison information centre can qualify risk assessment and potentially reduce hospital admissions following medication errors in a nursing home setting.


Subject(s)
Information Centers , Medication Errors , Nursing Homes , Risk Assessment , Aged , Aged, 80 and over , Female , Hospitalization , Humans , Male , Middle Aged , Poison Control Centers , Prospective Studies
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