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Salpe Malkon,1 Björn Wettermark,1 Thomas Kahan,2 Pia Bastholm-Rahmner,3 Jan Hasselström,4 Miriam Qvarnström1 1Department of Pharmacy, Uppsala University, Uppsala, Sweden; 2Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Stockholm, Sweden; 3Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; 4Department of Neurobiology and Care Sciences and Society, Karolinska Institutet, Stockholm, SwedenCorrespondence: Miriam Qvarnström, Department of Pharmacy, Faculty of Pharmacy, Uppsala University, Box 580, Uppsala, 751 23, Sweden, Email miriam.qvarnstrom@farmaci.uu.sePurpose: Few studies explored what patients initiated on blood pressure medication in primary care think about their disease and their medications. The aim of this study was to gain an understanding of hypertensive patients’ views on and experiences of hypertension and the use of antihypertensive medications.Methods: A qualitative study based on open-ended questions from a survey on medication adherence, which captured treated hypertensive patients’ perspective on their condition and treatment. Data were collected for 219 patients on antihypertensive medication, ≥ 30 years old, who consulted 25 primary health care centers in Stockholm, Sweden, during 2016. Thematic analysis with both inductive and deductive approach was applied.Results: We identified 21 codes from the data and grouped them under the World Health Organization’s five dimensions of adherence: condition-, therapy-, health care team and system-, patient-, and socioeconomic-related factors. The analyses revealed that many patients with hypertension have limited knowledge of their disease, are afraid of drug side effects and experience various issues in primary health care that may negatively impact adherence, including short doctor appointments, prescribing without communication and room for improvement in individualization of therapy and a person-centered approach.Conclusion: Many patients with hypertension have limited understanding of their hypertension and fear of adverse events from their antihypertensive medications. There is also room for improvement in how the patients are managed in primary health care. Interventions should focus on these issues to promote a better blood pressure target achievement.Plain Language Summary: Few studies have explored what patients initiated on blood pressure medication in primary care think about their disease and their medications.In this study, we analyzed free comments collected from 219 patients responding to a survey on medication adherence. Those who responded used antihypertensive medication, were ≥ 30 years old, and consulted primary health care centers in Stockholm, Sweden.The analyses revealed that many patients with hypertension have limited knowledge of their disease, are afraid of drug side effects and experience various issues in primary health care that may negatively impact adherence, including short doctor appointments, prescribing without communication and room for improvement in individualization of therapy and a person-centered approach.Interventions to promote a better blood pressure treatment would likely benefit from targeting these problems raised by patients.Keywords: hypertension, antihypertensive treatment, medication adherence, patient perspectives, primary health care, qualitative studies

Abstract Background Chronic obstructive pulmonary disease (COPD) is an underdiagnosed cause of morbidity and mortality worldwide. Prevalence of COPD has been shown to be highly associated with positive smoking history and increasing age. Spirometry is the method used for diagnosing COPD. However, identifying patients at risk of COPD to undergo spirometry tests has been challenging. Therefore, there is a need for new cost-effective and feasible diagnostic screening procedures for use in primary care centers. Our aim was to describe the prevalence and severity of undiagnosed COPD in a group of patients with respiratory infections attending urgent primary care, and to identify those variables in patients' history that could be used to detect the disease. Methods Patients of 40-75 years (n = 138) attending urgent primary care center with acute respiratory tract infection, positive smoking history and no previously known pulmonary disease underwent pre- and post bronchodilator spirometry testing four to five weeks after the acute infection. Prevalence and severity of COPD were estimated following the Global Initiative for COPD (GOLD) criteria. Variables such as sex, age, current smoking status, smoking intensity (pack years) and type of infection diagnosis were assessed for possible associations with COPD. Results The prevalence of previously undiagnosed COPD in our study group was 27%, of which 45% were in stage 1 (FEV1 ≥ 80% of predicted), 53% in stage 2 (50 ≤ FEV1 < 80% of predicted), 3% in stage 3 (30 ≤ FEV1 < 50% of predicted) and 0% in stage 4 (FEV1 < 30% of predicted). We found a significant association between COPD and age ≥ 55 (OR = 10.9 [95% CI 3.8-30.1]) and between COPD and smoking intensity (pack years > 20) (OR = 3.2 [95% CI 1.2-8.5]). Sex, current smoking status and type of infection diagnosis were not shown to be significantly associated with COPD. Conclusion A middle-aged or older patient with any type of common respiratory tract infection, positive smoking history and no previously known pulmonary disease has an increased likelihood of having underlying COPD. These patients should be offered spirometry testing for diagnosis of COPD.

The aim was to study if nurse-managed hypertension care was associated with differences in pharmacotherapy, lifestyle counseling, and prevalence of comorbid cardiometabolic diseases among patients receiving care at primary health care centers. To assess the extent of nurses' involvement in the hypertension care, a questionnaire was distributed to all primary health care centers in Region Stockholm. Age-adjusted logistic regression models were used to analyze the results, odds ratios with 99% confidence intervals. Data was acquired from VAL, the administrative databases of Region Stockholm in Sweden, encompassing all individuals 30 years or older with a registered hypertension diagnosis who attended to the primary health care center they were registered at. Our analysis comprised 119 267 patients diagnosed with hypertension registered in one of the 224 included primary health care centers. Of the 81 primary health care centers that responded to the questionnaire, 54 reported having nurse-managed hypertension care. Nurse-managed hypertension care was not significantly associated with differences in pharmacotherapy or patients' comorbidity, except for diabetes. Primary health care centers with nurse-managed hypertension care had a 10% greater adherence to national guidelines for lifestyle counseling (33.5%) compared to those without nurse-managed hypertension care (22.5%). Regardless of the organizational form of hypertension care management, more men received lifestyle counseling according to guidelines compared to women. In-house routines for hypertension care, with designated nurses, and booking systems were associated with more lifestyle counseling, which has been associated with signs of better hypertension care., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

The study aimed to investigate differences in hypertensive- and cardio-preventive pharmacotherapy depending on if patients with hypertension received lifestyle counseling or not, including the difference between men and women. Data from the Region Stockholm VAL database was used to identify all patients with a hypertension diagnosis and had visited a primary health care center within the past five years. Data included registered diagnoses, pharmacotherapy, and codes for lifestyle counseling. Logistic regression adjusted for age and comorbidity (diabetes, stroke, coronary heart disease, atrial fibrillation, gout, obesity, heart failure) was used, presenting results as odds ratios (OR) with 99% confidence interval (CI). The study included 130,030 patients with hypertension; 63,402 men and 66,628 women. Patients receiving recommended lifestyle counseling were more frequently treated with three or more hypertensive drugs: women OR 1.38 (1.31, 1.45) and men = 1.36 (1.30, 1.43); certain drug classes: calcium antagonists: women 1.09 (1.04, 1.14) and men 1.11 (1.06, 1.16); thiazide diuretics: women 1.26 (1.20, 1.34) and men 1.25 (1.19, 1.32); and aldosterone antagonists: women 1.25 (1.12, 1.41) and men 1.49 (1.34, 1.65). Patients receiving recommended level of lifestyle counseling with concomitant coronary heart disease, atrial fibrillation, diabetes, or stroke were more frequently treated with statins than those who did not. Further, recommended lifestyle counseling was significantly associated with anticoagulant treatment in patients with atrial fibrillation. Lifestyle counseling according to recommendations in national guidelines was significantly associated with a more thorough pharmacological treatment of hypertension, statins, and antithrombotic drugs as well as anticoagulants, in both men and women., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: Many individuals with hypertension remain undiagnosed. We aimed to develop a predictive model for hypertension using diagnostic codes from prevailing electronic medical records in Swedish primary care., Methods: This sex- and age-matched case-control (1:5) study included patients aged 30-65 years living in the Stockholm Region, Sweden, with a newly recorded diagnosis of hypertension during 2010-19 (cases) and individuals without a recorded hypertension diagnosis during 2010-19 (controls), in total 507,618 individuals. Patients with diagnoses of cardiovascular diseases or diabetes were excluded. A stochastic gradient boosting machine learning model was constructed using the 1,309 most registered ICD-10 codes from primary care for three years prior the hypertension diagnosis., Results: The model showed an area under the curve (95 % confidence interval) of 0.748 (0.742-0.753) for females and 0.745 (0.740-0.751) for males for predicting diagnosis of hypertension within three years. The sensitivity was 63 % and 68 %, and the specificity 76 % and 73 %, for females and males, respectively. The 25 diagnoses that contributed the most to the model for females and males all exhibited a normalized relative influence >1 %. The codes contributing most to the model, all with an odds ratio of marginal effects >1 for both sexes, were dyslipidaemia, obesity, and encountering health services in other circumstances., Conclusions: This machine learning model, using prevailing recorded diagnoses within primary health care, may contribute to the identification of patients at risk of unrecognized hypertension. The added value of this predictive model beyond information of blood pressure warrants further study., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Hazardous alcohol use increases the risk of hypertension but is underdetected in primary healthcare (PHC) patients. Use of the biomarker phosphatidylethanol (PEth), which reflects the last 2-3 weeks of alcohol consumption, is increasing in Swedish PHC, but studies exploring its use for hypertension are scarce or missing., Aim: To explore GPs' experiences of using PEth to identify hazardous alcohol use in the context of managing hypertension., Design & Setting: A qualitative study of GPs ( n = 12) experienced in using PEth in hypertension management who were recruited at Swedish primary healthcare centres (PHCC) in 2021., Method: The GPs participated in five focus group interviews. A questioning route was used. The interviews were audio-recorded, transcribed verbatim, and analysed with inductive qualitative content analysis., Results: 'I don't hesitate anymore' was the overall theme, which reflected both the disappearance of GPs' fear that the PEth result might upset the patient, as this rarely occurred, and that the positive effects of PEth predominated in the findings. The theme is underpinned by the following four sub-themes: serving as an eye-opener; improving the dialogue; using with care; and learning by doing., Conclusion: PEth is a useful tool that changed GPs' routines for addressing alcohol and identifying hazardous alcohol use in patients with hypertension managed in PHC. The GPs advocated adopting PEth as a routine test in the treatment of hypertension. However, PEth needs to be used with care to maximise benefit and minimise harm., (Copyright © 2023, The Authors.)

Objectives: The aim of this study was to describe the practice variation in dispensation of secondary stroke preventive drugs among patients at different primary care centres (PCCs) in Stockholm region and to identify factors that may explain the variation., Design: Cohort study using administrative data from the Stockholm region., Setting: Stockholm Health Care Region, Sweden, serving a population of 2.3 million inhabitants, hospital and PCC data., Participants: All patients (n=9761) with ischaemic stroke treated in hospital from 1 July 2009 to 30 June 2014 were included. Of these, 7562 patients registered with 187 PCCs were analysed. Exclusion criteria were; deceased patients, age <18, haemorrhagic stroke and/or switching PCC., Primary and Secondary Outcome Measures: As primary outcome the impact of PCC organisation variables and patient characteristics on the dispensation of statins, antiplatelets, antihypertensives and anticoagulants were analysed. Secondarily, the unadjusted practice variation of preventive drug dispensation of 187 PCCs is described., Results: There was up to fourfold practice variation in dispensation of all secondary preventive drugs. Factors associated with a lower level of dispensed statins were privately run PCCs (OR 0.91 (95% CI 0.82 to 1.00)) and the patient being woman. Increased statin use was associated with a higher number of specialists in family medicine (OR 1.03 (95% CI 1.01 to 1.05)) and a higher proportion of patients registered with a specific physician (OR 1.37 (95% CI 1.11 to 1.68)). Women had on average a lower number of dispensed antihypertensives., Conclusions: A high practice variation for dispensation of all secondary preventive drugs was observed. Patient and PCC level factors indicating good continuity of care and high level of general practitioner education were associated with higher use of statins. Findings are of importance to policymakers as well as individual providers of care, and more research and actions are needed to minimise inequality in healthcare., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The aim of the present study was to investigate the predictive ability for lung cancer of symptoms reported in an adaptive e-questionnaire, separately for never smokers, former smokers, and current smokers., Patients and Methods: Consecutive patients referred for suspected lung cancer were recruited between September 2014 and November 2015 from the lung clinic at the Karolinska University Hospital, Stockholm, Sweden. A total of 504 patients were later diagnosed with lung cancer (n = 310) or no cancer (n = 194). All participants answered an adaptive e-questionnaire with a maximum of 342 items, covering background variables and symptoms/sensations suspected to be associated with lung cancer. Stochastic gradient boosting, stratified on smoking status, was used to train and test a model for predicting the presence of lung cancer., Results: Among never smokers, 17 predictors contributed to predicting lung cancer with 82% of the patients being correctly classified, compared with 26 predictors with an accuracy of 77% among current smokers and 36 predictors with an accuracy of 63% among former smokers. Age, sex, and education level were the most important predictors in all models., Conclusion: Methods or tools to assess the likelihood of lung cancer based on smoking status and to prioritize investigative and treatment measures among all patients seeking care with diffuse symptoms are much needed. Our study presents risk assessment models for patients with different smoking status that may be developed into clinical risk assessment tools that can help clinicians in assessing a patient's risk of having lung cancer., Competing Interests: The authors have declared that no competing interests exist.

Background: Care transitions following stroke should be bridged with collaboration between hospital staff and home rehabilitation teams since well-coordinated transitions can reduce death and disability following a stroke. However, health services are delivered within organisational structures, rather than being based on patients' needs. The aim of this study protocol is to assess the feasibility, operationalised here as fidelity and acceptability, of a codesigned care transition support for people with stroke., Methods: This study protocol describes the evaluation of a feasibility study using a non-randomised controlled design. The codesigned care transition support includes patient information using videos, leaflets and teach back; what-matters-to me dialogue; a coordinated rehabilitation plan; bridged e-meeting; and a message system for cross-organisational collaboration. Patients with stroke, first time or recurrent, who are to be discharged home from hospital and referred to a rehabilitation team in primary healthcare for continued rehabilitation in the home will be included. One week after stroke, data will be collected on the primary outcome, namely satisfaction with the care transition support, and on the secondary outcome, namely health literacy and medication adherence. Data on use of healthcare will be obtained from a register of healthcare contacts. The outcomes of patients and significant others will be compared with matched controls from other geriatric stroke and acute stroke units, and with matched historic controls from a previous dataset at the intervention and control units. Data on acceptability and fidelity will be assessed through interviews and observations at the intervention units., Ethics and Dissemination: Ethical approvals have been obtained from the Swedish Ethical Review Authority. The results will be published open-access in peer-reviewed journals. Dissemination also includes presentation at national and international conferences., Discussion: The care transition support addresses a poorly functioning part of care trajectories in current healthcare. The development of this codesigned care transition support has involved people with stroke, significant other, and healthcare professionals. Such involvement has the potential to better identify and reconceptualise problems, and incorporate user experiences., Trial Registration Number: http://www.clinicaltrials.gov id: NCT02925871. Date of registration 6 October 2016., Protocol Version: 1., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Drug-disease interactions (DDSIs) are present when a drug prescribed for one disease worsens a concomitant disease. The prevalence of DDSIs in older patients in primary care is largely unknown, as well as to what extent physicians individualize drug prescribing in relation to concomitant diseases. We therefore analysed the prevalence of DDSIs in older patients in primary care and explored to what extent physicians take possible DDSIs into account when prescribing. Design and Setting: Cross-sectional population-based register study in primary care in Region Stockholm, Sweden. Thirty-one DDSIs derived from Irish STOPP-START-Criteria were assessed. We derived data from a regional administrative healthcare database including information on all healthcare consultations and dispensed prescription drugs in the region. Data on demography, diagnoses, drug dispensations and healthcare consumption were extracted. Drugs were assessed during 2016., Subjects: A total of 336,295 patients aged ≥65 registered with one of the 206 primary care practices in Region Stockholm., Main Outcome Measures: Prevalence and prevalence differences for DDSIs., Results: In 10.8% of older patients, at least one DDSI was observed. Non-steroidal anti-inflammatory drugs (NSAIDs) were implicated in more than 75% of cases. The most common DDSI was NSAID/hypertension (8.1%), followed by NSAID/cardiovascular disease and loop diuretics/urinary incontinence (both 0.7%). The use of NSAIDs among patients with heart failure or impaired renal function was 15% lower than among patients without these diseases., Conclusion: DDSIs were present in every tenth older patient in primary care. Patients with cardiovascular disease receive NSAIDs to a lower extent, possibly indicating physician awareness of DDSI. Key points Evidence on the prevalence of drug-disease interactions in older patients in primary care is sparse despite their potential to cause harm. In this study, we found that every 10th older patient attending primary care had at least one drug-disease interaction. Interactions with NSAIDs were far more common than interactions with other drugs. The use of NSAIDs among patients with heart failure or impaired renal function was 15% lower than among patients without these diseases.

Objective: In this study we aimed to estimate the effect of diabetes, educational level and income on the risk of mortality and cardiovascular events in primary care patients with hypertension., Methods: We followed 62,557 individuals with hypertension diagnosed 2001-2008, in the Swedish Primary Care Cardiovascular Database. Study outcomes were death, myocardial infarction, and ischemic stroke, assessed using national registers until 2012. Cox regression models were used to estimate adjusted hazard ratios of outcomes according to diabetes status, educational level, and income., Results: During follow-up, 13,231 individuals died, 9981 were diagnosed with diabetes, 4431 with myocardial infarction, and 4433 with ischemic stroke. Hazard ratios (95% confidence intervals) for diabetes versus no diabetes: mortality 1.57 (1.50-1.65), myocardial infarction 1.24 (1.14-1.34), and ischemic stroke 1.17 (1.07-1.27). Hazard ratios for diabetes and ≤9 years of school versus no diabetes and >12 years of school: mortality 1.56 (1.41-1.73), myocardial infarction 1.36 (1.17-1.59), and ischemic stroke 1.27 (1.08-1.50). Hazard ratios for diabetes and income in the lowest fifth group versus no diabetes and income in the highest fifth group: mortality 3.82 (3.36-4.34), myocardial infarction 2.00 (1.66-2.42), and ischemic stroke 1.91 (1.58-2.31)., Conclusions: Diabetes combined with low income was associated with substantial excess risk of mortality, myocardial infarction and ischemic stroke among primary care patients with hypertension., Competing Interests: The authors have declared that no competing interests exist.

Aims: Despite evidence-based therapeutic approaches, target blood pressure is obtained by less than half of patients with hypertension. Hypertension is associated with a significant risk for heart failure, in particular heart failure with preserved left ventricular (LV) ejection fraction (HFpEF). Although treatment is suggested to be given early after hypertension diagnosis, there is still no evidence-based medical treatment for HFpEF. We aim to study the underlying mechanisms behind the transition from uncomplicated hypertension to hypertensive heart disease (HHD) and HFpEF. To this end, we will combine cardiac imaging techniques and measurements of circulating fibrosis markers to longitudinally monitor fibrosis development in patients with hypertension., Methods and Results: In a prospective cohort study, 250 patients with primary hypertension and 60 healthy controls will be characterized at inclusion and after 1 and 6 years. Doppler echocardiography, cardiac magnetic resonance imaging, and electrocardiogram will be used for measures of cardiac structure and function over time. Blood biomarkers reflecting myocardial fibrosis, inflammation, and endothelial dysfunction will be analysed. As a proxy for HFpEF development, the primary endpoint is to measure echocardiographic changes in LV function and structure (E/e' and LAVI) and to relate these measures of LV filling to blood pressure, biomarkers, electrocardiogram, and cardiac magnetic resonance., Conclusions: We aim to study the timeline and transition from uncomplicated hypertension to HHD and HFpEF. In order to identify subjects prone to develop HHD and HFpEF, we want to find biomarkers and cardiac imaging variables to explain disease progression. Ultimately, we aim at finding new pathways to prevent HFpEF., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: The aim of this study was to explore whether recording in primary care of a previously recorded hospital diagnosis was associated with increased patient utilisation of recommended medications., Design: Registry-based prospective cohort study., Setting and Participants: 19 072 patients with a hospital discharge diagnosis of transient ischaemic attack (TIA), stroke or acute coronary syndrome from hospitals in Stockholm County 2010-2013 were included in the study., Main Outcome Measure: The outcome of the study was medication dispensation as a marker of adherence to recommended medications. Adherence was defined as having had at least two filled prescriptions in the third year following hospital discharge., Results: Recording a diagnosis was associated with higher utilisation of all recommended medications with the exception of antihypertensives in patients with TIA. The differences between the groups with and without a recorded diagnosis remained after adjusting for age, sex, index year and visits to private practitioners. Dispensation of antithrombotics was high overall, 80%-90% in patients without a recorded diagnosis and 90%-94% for those with a diagnosis. Women with recorded ischaemic stroke/TIA/acute coronary syndrome were dispensed more statins (56%-71%) than those with no recorded diagnosis (46%-59%). Similarly, 68%-83% of men with a recorded diagnosis were dispensed statins (57%-77% in men with no recorded diagnosis). The rate of diagnosis recording spanned from 15% to 47% and was especially low in TIA (men 15%, women 16%)., Conclusion: Recording a diagnosis of TIA/stroke or acute coronary syndrome in primary care was found to be associated with higher dispensation of recommended secondary preventive medications. Further study is necessary in order to determine the mechanisms underlying our results and to establish the utility of our findings., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The aim was to study persistence to, and switching between, antihypertensive drug classes and to determine factors associated with poor persistence.This was an observational cohort study. The Swedish Primary Care Cardiovascular Database includes data from medical records, socioeconomic data, filled prescriptions, and hospitalizations from national registries for 75,000 patients with hypertension. Patients included in the study were initiated on antihypertensive drug treatment in primary healthcare in 2006 to 2007. We defined class persistence as the proportion remaining on the initial drug class, including 30 days of gap. Patients with a filled prescription of another antihypertensive drug class after discontinuation of the initial drug, including 30 days of gap, were classified as switchers. Persistence to the various drug classes were compared with that for diuretics.We identified 4997 patients (mean age 60 ± 12 years in men and 63 ± 13 years in women). Out of these, 95 (2%) filled their first prescription for fixed combination therapy and 4902 (98%) for monotherapy, including angiotensin converting enzyme inhibitors (37%), angiotensin receptor blockers (4%), beta blockers (21%), calcium channel blockers (8%), and diuretics (28%). Persistence to the initial drug class was 57% after 1 year and 43% after 2 years. There were no differences in persistence between diuretics and any of the other antihypertensive drug classes, after adjustment for confounders. Discontinuation (all adjusted) was more common in men (P = 0.004), younger patients (P < 0.001), those with mild systolic blood pressure elevation (P < 0.001), and patients born outside the Nordic countries (P < 0.001). Among 1295 patients who switched drug class after their first prescription, only 21% had a blood pressure recorded before the switch occurred; and out them 69% still had high blood pressures.In conclusion, there appears to be no difference in drug class persistence between diuretics and other major antihypertensive drug classes, when factors known to be associated with poor persistence are taken into account., Competing Interests: The authors have no conflicts of interest to disclose.

We investigated and documented the most common presenting complaints of elderly patients ≥80 years of age in Västerbotten at the emergency department of Umeå University hospital. We found that the ten most common presenting complaints represented more than half of all emergency department visits. The three most common presenting complaints were abdominal pain, chest pain and dyspnoea. On average, around 80 % of all patients were admitted to a ward and for the three most common presenting complaints the number was even higher. The main conclusions from this study were that a surprisingly high proportion of elderly patients are admitted to a ward after the emergency department visit at Umeå University hospital and that patients seeking with one of the three most common presenting complaints often had complex discharge diagnoses involving typically chronic geriatric diseases which were hidden behind general presenting complaints.

Objective: To determine whether a pharmacist-led medications review in primary care reduces the number of drugs and the number of drug-related problems., Design: Prospective randomized controlled trial., Setting: Liljeholmen Primary Care Centre, Stockholm, Sweden., Subjects: 209 patients aged ≥ 65 years with five or more different medications. Intervention. Patients answered a questionnaire regarding medications. The pharmacist reviewed all medications (prescription, non-prescription, and herbal) regarding recommendations and renal impairment, giving advice to patients and GPs. Each patient met the pharmacist before seeing their GP. Control patients received their usual care., Main Outcome Measures: Drug-related problems and number of drugs. Secondary outcomes included health care utilization and self-rated health during 12 months of follow-up., Results: No significant difference was seen when comparing change in drug-related problems between the groups. However, a significant decrease in drug-related problems was observed in the intervention group (from 1.73 per patient at baseline to 1.31 at follow-up, p < 0.05). The change in number of drugs was more pronounced in the intervention group (p < 0.046). Intervention group patients were not admitted to hospital on fewer occasions or for fewer days, and there was no significant difference between the two groups regarding utilization of primary care during follow-up. Self-rated health remained unchanged in the intervention group, whereas a drop (p < 0.02) was reported in the control group. This resulted in a significant difference in change in self-rated health between the groups (p < 0.047)., Conclusions: The addition of a skilled pharmacist to the primary care team may contribute to reductions in numbers of drugs and maintenance of self-rated health in elderly patients with polypharmacy.

1. The kinetics of codeine and seven of its metabolites codeine-6-glucuronide (C6G), norcodeine (NC), NC-glucuronide (NCG), morphine (M), M-3 (M3G) and 6-glucuronides (M6G), and normorphine (NM) were investigated after a single oral dose of 50 mg codeine phosphate in 14 healthy Caucasian subjects including eight extensive (EM) and six poor (PM) hydroxylators of debrisoquine. The plasma and urine concentrations of codeine and the metabolites were measured by h.p.l.c. 2. The mean area under the curve (AUC), half-life and total plasma clearance of codeine were 1020 +/- 340 nmol l-1 h, 2.58 +/- 0.57 h and 2.02 +/- 0.73 l h-1 kg-1, respectively. There were no significant differences between EM and PM in these aspects. 3. PM had significantly lower AUC of M3G, the active metabolites M6G, NM and M (P less than 0.0001), and lower partial metabolic clearance by O-demethylation (P less than 0.0001). In contrast, the PM had higher AUC of NC (P less than 0.05) than the EM. There was no difference between PM and EM in the AUC of C6G and NCG, nor in the partial clearances by N-demethylation and glucuronidation. 4. Among EM, the AUC of C6G was 15 times higher than that of codeine, which in turn was 50 times higher than that of M. The AUCs of M6G and NM were about 6 and 10 times higher than that of M, respectively. The partial clearance by glucuronidation was about 8 and 12 times higher than those by N- and O-demethylations, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

1. The oral and intravenous kinetics of morphine were investigated in seven cirrhotic patients with a history of encephalopathy. The plasma concentrations of morphine and its metabolites morphine-3 (M3G) and morphine-6 (M6G) were measured by h.p.l.c. 2. The mean terminal elimination half-life of morphine was 4.2 h (95% CI 3.6-4.8) the mean volume of distribution was 4.1 l kg-1 (95% CI 2.9-5.4) and the mean plasma clearance was 11.4 ml min-1 kg-1 (95% CI 8.1-14.7). The mean oral bioavailability was 101% (95% CI 56-147). 3. The plasma clearance of morphine was significantly lower, its terminal elimination half-life longer and its oral bioavailability greater in the cirrhotic patients compared with patients with normal liver function. The metabolic ratio M3G/morphine was significantly lower in the cirrhotic patients than in control subjects after oral dosing, but did not differ after intravenous dosing. 4. The average urinary recoveries of morphine plus M3G and M6G were 49.9% after i.v. and 57.7% after oral administration. There were no statistically significant differences in the urinary recovery between the two routes of administration or between the cirrhotic patients and controls. 5. Specific changes in the EEG pattern could not be detected after intravenous dosage. 6. The metabolism of morphine is impaired significantly in patients with severe cirrhosis. Clinically important findings were a high oral bioavailability and a long elimination half-life. These findings call for cautious dosing of oral and intravenous morphine in patients with severe end stage liver disease.

We report a case of long lasting respiratory depression after intravenous administration of morphine to a 7 year old girl with haemolytic uraemic syndrome. The plasma concentrations of the active metabolite M6G were more than 10 times those normally seen and the half-lives of M6G and morphine were prolonged.