Epidemiology and Outcomes Associated with New Persistent Opioid Use After Transabdominal Operation.

BACKGROUND: Overall, 3-12% of opioid-naïve patients develop persistent opioid use after surgery. It's still unclear whether persistent opioid use after transabdominal surgery is associated with adverse surgical outcomes. We aimed to assess if new persistent opioid use after transabdominal surgery is associated with increased long-term mortality and readmission rates. METHODS: Opioid-naïve patients >18 years undergoing transabdominal surgery at Landspitali University Hospital, the only tertiary hospital in Iceland, from 2006-2018 were included. Persistent opioid use was defined as opioid use more than 3 months postoperatively. Inverse probability weighting (IPW) was used to yield balanced study groups accounting for baseline characteristics. Long-term mortality (during median follow-up of 5.2 years) was compared using propensity-weighted Cox regression and readmission within 3-6 months using propensity-weighted logistic regression. RESULTS: Overall, 3923 patients were included (laparoscopy-2680, laparotomy-1243). Rates of new persistent opioid use were 13.0%. Rates were higher after laparotomy than laparoscopy in the crude analysis but not in the propensity-weighted analysis. New persistent opioid use was associated with higher long-term mortality (hazard ratio 1.84, 95% CI 1.41-2.40) and readmission rates (odds ratio 3.24, 95% CI 2.25-4.76). This was consistent for both patients undergoing laparoscopy and laparotomy. Moreover, there were signs of a dose-response relationship, with patients in higher quartiles of postoperative opioid consumption having higher mortality and readmission rates. CONCLUSIONS: New persistent opioid use following transabdominal surgery was associated with higher rates of mortality and readmission rates. This calls for increased postoperative support for at-risk patients and increased support during transitions of care for these patients.

Potentially Inappropriate Medication Use and Polypharmacy Before and After Admission to Internal Medicine for Older Patients.

BACKGROUND: With the aging of the population and the increase in chronic diseases, there is an inherent risk of polypharmacy and inappropriate medication use. This study aimed to determine the prevalence and incidence of potentially inappropriate medication use and its correlation with polypharmacy. METHODS: This was a retrospective, population-based cohort study among patients ≥ 65 years hospitalized at The National University Hospital of Iceland from 2010-2020. Data on medication usage were retrieved from the National Prescription Medicine Registry. Based on the number of medications filled in the year prior to admission and post-discharge, participants were categorized as non-polypharmacy (<5), polypharmacy (5-9), and hyper-polypharmacy (≥10). The prevalence and incidence of potentially inappropriate medication use was assessed based on the 2019 Beers criteria. Regression models were used to correlate sociodemographic, clinical, and pharmacoepidemiologic variables and the odds of new potentially inappropriate medication use. RESULTS: The cohort comprised 55,859 patients (48.5% male) with a median [interquartile range] age of 80 [73-86] years. The prevalence of inappropriate medication use in the year preceding admission was 34.0%, 77.7%, and 96.4% for patients with non-polypharmacy, polypharmacy, and hyper-polypharmacy, respectively. The incidence of new potentially inappropriate medication use was 46.7% (95% confidence interval 45.6%-47.6%) among those with no potentially inappropriate medication use pre-admission. Factors associated with higher odds of new potentially inappropriate medication use after discharge were the use of multi-dose dispensing services, dementia, polypharmacy, and hyper-polypharmacy. CONCLUSIONS: An increased emphasis is needed to review and reevaluate the appropriateness of medication use among the older population in internal medicine.

The association of degree of polypharmacy before and after among hospitalised internal medicine patients and clinical outcomes: a retrospective, population-based cohort study.

OBJECTIVES: To determine the prevalence and incidence of polypharmacy/hyperpolypharmacy and which medications are most prescribed to patients with varying burden of polypharmacy. DESIGN: Retrospective, population-based cohort study. SETTING: Iceland. PARTICIPANTS: Including patients (≥18 years) admitted to internal medicine services at Landspitali - The National University Hospital of Iceland, between 1 January 2010 with a follow-up of clinical outcomes through 17 March 2022. MAIN OUTCOMES MEASURES: Participants were categorised into medication use categories of non-polypharmacy (<5), polypharmacy (5-10) and hyperpolypharmacy (>10) based on the number of medications filled in the year predischarge and postdischarge. The primary outcome was prevalence and incidence of new polypharmacy. Secondary outcomes were mortality, length of hospital stay and re-admission. RESULTS: Among 85 942 admissions (51% male), the median (IQR) age was 73 (60-83) years. The prevalence of preadmission non-polypharmacy was 15.1% (95% CI 14.9 to 15.3), polypharmacy was 22.9% (95% CI 22.6 to 23.2) and hyperpolypharmacy was 62.5% (95% CI 62.2 to 62.9). The incidence of new postdischarge polypharmacy was 33.4% (95% CI 32.9 to 33.9), and for hyperpolypharmacy was 28.9% (95% CI 28.3 to 29.5) for patients with preadmission polypharmacy. Patients with a higher level of medication use were more likely to use multidose drug dispensing and have a diagnosis of adverse drug reaction. Other comorbidities, including responsible subspeciality and estimates of comorbidity and frailty burden, were identical between groups of varying polypharmacy. There was no difference in length of stay, re-admission rate and mortality. CONCLUSIONS: Preadmission polypharmacy/hyperpolypharmacy and postdischarge new polypharmacy/hyperpolypharmacy is common amongst patients admitted to internal medicine. A higher level of medication use category was not found to be associated with demographic, comorbidity and clinical outcomes. Medications that are frequently inappropriately prescribed were among the most prescribed medications in the group. An increased focus on optimising medication usage is needed after hospital admission. TRIAL REGISTRATION NUMBER: NCT05756400.

The incidence and prevalence of proton pump inhibitor usage among internal medicine patients after hospital admission: A retrospective cohort study.

BACKGROUND: The use of proton pump inhibitors (PPIs) has increased over the past decades. One potential gateway into new PPI use is following a hospital admission. The study aimed to examine the incidence of new PPI usage following admission to internal medicine services and the ratio of new persistent users. METHODS: A retrospective descriptive study was conducted among all adults who had been admitted to internal medicine wards at the National University Hospital of Iceland from 2010-2020. Data was obtained from the Icelandic Internal Medicine Database. The proportion of patients who started treatment with PPI within 3 months of discharge (new users) and the proportion of patients who continued to use it after 3 months (persistent users) were examined. RESULTS: Among 85.942 admissions during the study period, 7238 (15.6%) became new users, and of those 4942 (68%) were new persistent users. The incidence of new PPI use was highest for patients discharged from gastroenterology (32.2%), hematology (31.8%), and oncology (29.2%). Patients with new PPI use more commonly had a history of malignancy (19.5%) and liver disease (22.7%) and more commonly were admitted to the ICU during their hospitalization. The highest ratio of persistent usage was among patients discharged from geriatric medicine (84%). CONCLUSION: One in every six patients admitted to internal medicine wards filled out a prescription for PPI within 3 months from discharge, and a large proportion of them became persistent users. The high rate of new PPI users from oncology and hematology is noteworthy and requires further research.

Epidemiology and association with outcomes of polypharmacy in patients undergoing surgery: retrospective, population-based cohort study.

BACKGROUND: The aim of this study was to determine the prevalence of preoperative polypharmacy and the incidence of postoperative polypharmacy/hyper-polypharmacy in surgical patients and their association with adverse outcomes. METHODS: This was a retrospective, population-based cohort study among patients older than or equal to 18 years undergoing surgery at a university hospital between 2005 and 2018. Patients were categorized based on the number of medications: non-polypharmacy (fewer than 5); polypharmacy (5-9); and hyper-polypharmacy (greater than or equal to 10). The 30-day mortality, prolonged hospitalization (greater than or equal to 10 days), and incidence of readmission were compared between medication-use categories. RESULTS: Among 55 997 patients, the prevalence of preoperative polypharmacy was 32.3 per cent (95 per cent c.i. 33.5 to 34.3) and the prevalence of hyper-polypharmacy was 25.5 per cent (95 per cent c.i. 25.2 to 25.9). Thirty-day mortality was higher for patients exposed to preoperative hyper-polypharmacy (2.3 per cent) and preoperative polypharmacy (0.8 per cent) compared with those exposed to non-polypharmacy (0.6 per cent) (P < 0.001). The hazards ratio (HR) of long-term mortality was higher for patients exposed to hyper-polypharmacy (HR 1.32 (95 per cent c.i. 1.25 to 1.40)) and polypharmacy (HR 1.07 (95 per cent c.i. 1.01 to 1.14)) after adjustment for patient and procedural variables. The incidence of longer hospitalization (greater than or equal to 10 days) was higher for hyper-polypharmacy (11.3 per cent) and polypharmacy (6.3 per cent) compared with non-polypharmacy (4.1 per cent) (P < 0.001). The 30-day incidence of readmission was higher for patients exposed to hyper-polypharmacy (10.2 per cent) compared with polypharmacy (6.1 per cent) and non-polypharmacy (4.8 per cent) (P < 0.001). Among patients not exposed to polypharmacy, the incidence of new postoperative polypharmacy/hyper-polypharmacy was 33.4 per cent (95 per cent c.i. 32.8 to 34.1), and, for patients exposed to preoperative polypharmacy, the incidence of postoperative hyper-polypharmacy was 16.3 per cent (95 per cent c.i. 16.0 to 16.7). CONCLUSION: Preoperative polypharmacy and new postoperative polypharmacy/hyper-polypharmacy are common and associated with adverse outcomes. This highlights the need for increased emphasis on optimizing medication usage throughout the perioperative interval. REGISTRATION NUMBER: NCT04805151 (http://clinicaltrials.gov).

[The incidence of postoperative and persistent usage of proton pump inhibitors following surgery].

INTRODUCTION: The use of proton pump inhibitors (PPI) has increased over the past decades. Some patients use the medication without an indication. It is possible that new use will start following surgery. The study aimed to examine the incidence of postoperative use of PPI following surgeries and the ratio of new persistent users over three months postoperatively as well as patient- and procedural variables associated with new use and new persistent use. METHODS: Data of surgeries among adults that had undergone surgeries at the National University Hospital of Iceland from 2006 to 2018. The data were from the Icelandic perioperative database, containing information regarding medication usage preceding and following surgeries. The ratio of those who started using PPI within three months of surgery was assessed, and the ratio of persistent users. RESULTS: Altogether, 2886 out of 42.530 patients filled PPI prescription within three months after their first surgery. Annual incidence was 67 per 1.000 surgeries, and the ratio of persistent users was 54%, although both the varied between years. The use was more common among women, highest in age group 56-65 years old, patients with polypharmacy (5-9 medicines) and who underwent abdominal surgeries. CONCLUSIONS: New postoperative PPI use is common following surgery and half of the patients with new use develop new persistent use. The usage increased similar to the increased number of prescriptions and sales of PPI in other patient groups during the period. The results indicate the need for further monitoring of patients with PPI prescriptions following surgeries in Iceland.

The incidence of new and persistent benzodiazepine use after surgery.

BACKGROUND: It is possible that a portion of new and new persistent use of benzodiazepines is among individuals who start using the medications before or after surgery. We studied the incidence of new and new persistent benzodiazepine use among patients undergoing surgery. METHODS: Retrospective, single-center, population-based cohort of all individuals ≥18 years undergoing first surgery between January 2, 2006 and December 31, 2018 with a year of follow-up for filled medications. Benzodiazepine-naïve patients were defined as not filling a prescription from a year to 31 days before surgery. Patients with new use were naïve patients who filled a prescription between 30 days before and 14 days after surgery, and patients with new persistent use were patients with new use who filled a prescription between 15 days and a year after surgery. Patient and procedural characteristics and prescription filling patterns between the groups were compared. RESULTS: A total of 55,997 patients (32,136 women [57.4%]; median [interquartile range] age, 55 [39, 69] years) were included. The incidence of new use among naïve patients was 2.7% (95% confidence interval, 2.6%-2.8%; n = 1,311), and, of those, 43.7% (95% confidence interval, 41.0%-46.5%; n = 571) had new persistent benzodiazepine use. Approximately 10% of patients with new use filled a prescription for benzodiazepine in every 30-day window during the follow-up period. CONCLUSION: A small portion of surgical patients begin benzodiazepine use perioperatively, but subsequently half fill criteria for persistent use. This highlights the importance of identifying strategies to minimize both new use and the progression of new use into persistent use in surgical patients.

A retrospective study on adherence to secondary prevention medications after coronary bypass surgery.

OBJECTIVES: We assessed adherence to statins, beta-blockers and renin-angiotensin system (RAS) inhibitors after coronary artery bypass graft surgery and factors associated with non-adherence. METHODS: This nationwide retrospective cohort study included all individuals undergoing coronary artery bypass surgery from 22 May 2007 to 20 December 2018, at Landspitali-the National University Hospital (n = 1536). Data on dispensed prescriptions were retrieved from the National Prescription Medicine Registry. Adherence was estimated by the proportion of days covered up to 2 years after hospital discharge, with cut-offs for strict adherence and non-adherence at over 80% and under 50%, respectively. Multivariable logistic regression was used to assess variables associated with non-adherence. RESULTS: Criteria for strict adherence were met by 39.2%, 36.9% and 30.1% of patients for statins, beta-blockers and RAS inhibitors, respectively. Non-adherence criteria were met for 14.4%, 25.9% and 43.6% of patients for statins, beta-blockers and RAS inhibitors, respectively. High Hospital Frailty Risk Score Class (statins: odds ratio (OR) 2.29, confidence interval (CI) 1.02-4.86; RAS inhibitors: OR 2.06, CI 1.04-4.04), concomitant aortic valve replacement (statins: OR 1.64, CI 1.11-2.38; RAS inhibitors: OR 1.78, CI 1.26-2.52) and a new prescription for a medication class following surgery (statins: OR 2.87, CI 2.06-4.01; beta-blockers: OR 1.70, CI 1.32-2.18; RAS inhibitors: OR 6.95, CI 5.27-9.25) were associated with non-adherence. CONCLUSIONS: Non-adherence to medical therapy after coronary artery bypass surgery is common. Patients with a higher burden of frailty and patients naive to the medical treatment of coronary artery disease should be a target group for efforts to increase medication adherence.

Paracetamol poisoning: a population-based study from Iceland.

OBJECTIVE: To examine the incidence and severity of paracetamol poisoning in a population-based cohort in Iceland. A previous study showed a decrease in the incidence during a financial crisis in Iceland, by approximately half (16/100,000 annually). The aims of the study were to assess the incidence and nature of paracetamol poisoning after economic recovery in Iceland and to compare intentional and accidental poisoning. METHODS: Paracetamol serum concentrations were used to identify patients in this retrospective study from 2010-2017. A search was undertaken in laboratory databases for patients with serum paracetamol concentrations, which were grouped by <66 µmol/L (below detection limit) and ≥66 µmol/L. Medical records were reviewed and relevant laboratory and clinical information obtained to determine whether paracetamol poisoning had occurred. RESULTS: Altogether 542 cases of paracetamol poisoning were identified. The mean annual incidence was 27/100,000 (range 22-33). Intentional poisoning was observed in 437/542 (81%) cases, most frequently among females 16-25 years of age. Males ≥65 years were more likely to overdose by accident, which was associated with worse outcomes. Twenty-five (4.6%) patients developed severe paracetamol-induced liver injury and coagulopathy. Overall, six (1.1%) cases were fatal in which paracetamol contributed to the cause of death, with accidental poisoning found in 67% (4/6). CONCLUSIONS: The incidence of paracetamol poisoning has increased in recent years associated with economic recovery in Iceland. Most patients had favourable outcomes. Intentional overdose was most common in young females, whereas accidental overdose was more common in older males and more frequently associated with a fatal outcome.

[Use of medication, supplements and natural products during pregnancy].

INTRODUCTION: Evidence-based information regarding the use of medication during pregnancy is lacking, even though the use of medication during pregnancy is considered common and often neccesary. The aim of this study was to obtain reliable information on the use of medications during the first 20 weeks of pregnancy and the use of vitamins, minerals, fatty acids, herbs and other natural products. Women´s attitude and beliefs towards the use of medications was also examined. MATERIAL AND METHODS: The study was conducted at the Prenatal Diagnosis Unit at Landspitali from January to April 2017. Women who attended routine ultrasound examination at 20 weeks were offered to participate. A questionnaire was submitted to partici-pants in an interview with the researcher following the doctor's appointment. RESULTS: Of the 213 participants, 90% used medication at least once during the first 20 weeks of pregnancy. Approximately 80% of these medications belong to FASS safety classes A and B and are considered safe during pregnancy. The proportion of women who did not use folic acid was 14% which was associated with residence in rural areas (p=0.03) and younger age (p=0.019). Natural products were used by 14% but information about their safety is lacking. The majority (81%) was satisfied with the information they received when a drug was prescribed and 94% said they had sufficient access to information about medication use during pregnancy. The most commonly used sources of information were the internet (51%) and the local midwive (44%). CONCLUSION: The use of medications and supplements during pregnancy is common. Most medications being used are considered safe during pregnancy. The majority of pregnant women take folic acid. Pregnant women have a logical and generally a positive attitude towards medication use during pregnancy.

The development and appraisal of a tool designed to find patients harmed by falsely labelled, falsified (counterfeit) medicines.

BACKGROUND: Falsely labelled, falsified (counterfeit) medicines (FFCm's) are produced or distributed illegally and can harm patients. Although the occurrence of FFCm's is increasing in Europe, harm is rarely reported. The European Directorate for the Quality of Medicines & Health-Care (EDQM) has therefore coordinated the development and validation of a screening tool. METHODS: The tool consists of a questionnaire referring to a watch-list of FFCm's identified in Europe, including symptoms of their use and individual risk factors, and a scoring form. To refine the questionnaire and reference method, a pilot-study was performed in 105 self-reported users of watch-list medicines. Subsequently, the tool was validated under "real-life conditions" in 371 patients in 5 ambulatory and in-patient care sites ("sub-studies"). The physicians participating in the study scored the patients and classified their risk of harm as "unlikely" or "probable" (cut-off level: presence of ≥2 of 5 risk factors). They assessed all medical records retrospectively (independent reference method) to validate the risk classification and documented their perception of the tool's value. RESULTS: In 3 ambulatory care sites (180 patients), the tool correctly classified 5 patients as harmed by FFCm's. The positive and negative likelihood ratios (LR+/LR-) and the discrimination power were calculated for two cut-off levels: a) 1 site (50 patients): presence of two risk factors (at 10% estimated health care system contamination with FFCm's): LR + 4.9/LR-0, post-test probability: 35%; b) 2 sites (130 patients): presence of three risk factors (at 5% estimated prevalence of use of non-prescribed medicines (FFCm's) by certain risk groups): LR + 9.7/LR-0, post-test probability: 33%. In 2 in-patient care sites (191 patients), no patient was confirmed as harmed by FFCm's. The physicians perceived the tool as valuable for finding harm, and as an information source regarding risk factors. CONCLUSIONS: This "decision aid" is a systematic tool which helps find in medical practice patients harmed by FFCm's. This study supports its value in ambulatory care in regions with health care system contamination and in certain risk groups. The establishment of systematic communication between authorities and the medical community concerning FFCm's, current patterns of use and case reports may sustain positive public health impacts.