Bleeding in patients on concurrent treatment with a selective serotonin reuptake inhibitor (SSRI) and low-dose acetylsalicylic acid (ASA) compared with SSRI or low-dose ASA alone-A systematic review and meta-analysis.

AIMS: The aim of this study was to systematically review whether concurrent treatment with an SSRI and low-dose ASA increases the risk of bleeding compared with treatment with an SSRI alone or ASA alone. METHODS: Medline, Embase, the Cochrane Library, PsycINFO and Web of Science (from database inception to January 2023) were searched according to PICO: P = patients on treatment with an SSRI and/or low-dose ASA; I = intervention: SSRI + ASA; C = comparison: ASA or SSRI alone; O = outcomes: bleeding/major bleeding. The included articles were assessed using checklists. Studies without major risk of bias formed the basis for the conclusions. Extracted data were pooled using random-effects meta-analyses. Certainty of evidence was assessed according to GRADE. RESULTS: Twenty-four studies met the PICO and were included. One randomized and six nonrandomized studies were assessed not to have major risk of bias. Regarding SSRI + ASA vs. ASA only, the pooled hazard ratio of three nonrandomized studies (n = 38 467) was 1.37 (95% confidence interval: 1.10; 1.70; I2 = 0%), and the pooled odds ratio of two nonrandomized studies (n = 28 296) was 0.95 (0.77; 1.19; I2 = 0%). Regarding SSRI + ASA vs. SSRI only, the randomized controlled trial (n = 1048) reported a hazard ratio of 1.82 (0.66; 5.02), the hazard ratio being 1.60 (1.24; 2.06) for ASA vs. placebo in patients without SSRI treatment; and one nonrandomized controlled study (n = 18 920) reported an incidence rate ratio of 1.03 (0.96; 1.12). CONCLUSIONS: The compiled evidence was too uncertain to support an interaction when an SSRI is added to low-dose ASA. Low-dose ASA added to an SSRI may imply an increased risk of bleeding primarily attributable to the initiation of ASA.

Reliability and validity of the Swedish indicator 'Drugs that should be avoided in older people'-an appraisal of a set of potentially inappropriate medications.

PURPOSE: To analyse the reliability and validity of the Swedish indicator 'Drugs that should be avoided in older people'. METHODS: From a previous study that included consecutive primary care patients ≥ 65 years of age, all patients ≥ 75 years of age were analysed. Two physicians independently screened their medication lists and medical records, applying the Swedish indicator which includes potentially inappropriate medications (PIMs): long-acting benzodiazepines, drugs with anticholinergic action, tramadol, propiomazine, codeine, and glibenclamide. The clinical relevance of identified PIMs was independently assessed. Thereafter, the physicians determined in consensus whether some medical action related to the drug treatment was medically justified and prioritised before the next regular visit. If so, the drug treatment was considered inadequate, and if not, adequate. RESULTS: A total of 1,146 drugs were assessed in 149 patients (75‒99 years, 62% female, 0‒20 drugs per patient). In 29 (19%) patients, at least one physician identified ≥ 1 PIM according to the indicator at issue; 24 (16%) patients were concordantly identified with ≥ 1 such PIM (kappa: 0.89). Of 26 PIMs concordantly identified, the physicians concordantly assessed four as clinically relevant and 12 as not clinically relevant (kappa: 0.17). After the consensus discussion, six (4%) patients had ≥ 1 PIM according to the studied indicator that merited action. Using the area under the receiver operating characteristic (ROC) curve, the indicator did not outperform chance in identifying inadequate drug treatment: 0.56 (95% confidence interval: 0.46 to 0.66). CONCLUSION: The Swedish indicator has strong reliability regarding PIM detection but does not validly reflect the adequacy of drug treatment.

Age of onset for increased dose-adjusted serum concentrations of antidepressants and association with sex and genotype: An observational study of 34,777 individuals.

PURPOSE: The aim of this study was to examine the age of onset for increased dose-adjusted serum concentrations (C/D ratio) of common antidepressant drugs and to explore the potential association with sex and CYP2C19/CYP2D6 genotype. METHODS: Serum concentrations and prescribed daily doses for citalopram, escitalopram, sertraline, venlafaxine and mirtazapine, and CYP genotypes, were obtained from a therapeutic drug monitoring (TDM) service. Segmented linear regression analysis was used to examine the relationship between age and antidepressant log C/D ratio in (i) all individuals, (ii) men and women, and (iii) CYP2D6/CYP2C19 normal metabolizers (NMs) and CYP2D6/CYP2C19 intermediate or poor metabolizers (IMs/PMs). RESULTS: A total of 34,777 individuals were included in the study; CYP genotype was available for 21.3%. An increase in C/D ratio started at 44‒55 years of age. Thereafter, the increase progressed more rapidly for citalopram and escitalopram than for venlafaxine and mirtazapine. A doubled C/D ratio was estimated to occur at 79 (citalopram), 81 (escitalopram), 86 (venlafaxine), and 90 years (mirtazapine). For sertraline, only modest changes in C/D ratio were observed. For escitalopram and venlafaxine, the observed increase in C/D ratio started earlier in women than in men. The results regarding CYP genotype were inconclusive. CONCLUSION: The age-related increase in C/D ratio starts in middle-aged adults and progresses up to more than twofold higher C/D ratio in the oldest old. Sertraline seems to be less prone to age-related changes in C/D ratio than the other antidepressants.

Validation of the Swedish Patient-Reported Outcomes in Parkinson's Disease Scale in Outpatients.

BACKGROUND: Successful treatment of Parkinson's disease (PD) requires symptom monitoring. Patient-Reported Outcomes in Parkinson's Disease (PRO-PD) is a broad scale that covers 35 motor and nonmotor symptoms, but its validation is limited. OBJECTIVE: The aim was to validate PRO-PD in a random sample of outpatients with PD. METHODS: Of 2123 PD patients who visited outpatient clinics in West Sweden over a 12-month period, 25% were randomly selected and invited to participate in a longitudinal observational study. Included patients were assessed at baseline, 1 year, and 3 years, with a subset also assessed at 3 to 6 months. The assessments included PRO-PD, other patient-reported scales, and Clinical Impression of Severity Index for Parkinson's Disease (CISI-PD). RESULTS: The study included 286 PD patients. PRO-PD ratings were available from 716 (96%) of 747 study visits. All PRO-PD items exhibited positive skewness without ceiling effects. Internal consistency at baseline was excellent (Cronbach's α: 0.93). Six-month test-retest reliability was good (intraclass correlation coefficient: 0.87). Convergent validity was good, with correlation coefficients between total PRO-PD and the 8-Item Parkinson's Disease Questionnaire of 0.70, the Non-Motor Symptoms Questionnaire of 0.70, EuroQoL Five-Dimension Five-Level Scale of 0.71, and CISI-PD of 0.69. Median PRO-PD score at baseline was 995 (interquartile range: 613-1399), with a median yearly increase of 71 (interquartile range: -21 to 111). Items representing axial motor symptoms increased most over time. The minimal clinically important change in total score was 119. CONCLUSIONS: PRO-PD was found reliable and valid for monitoring symptoms in a representative sample of outpatients with PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Revisiting the inter-rater reliability of drug treatment assessments according to the STOPP/START criteria.

AIMS: The aim of this study is to revisit the inter-rater reliability of drug treatment assessments according to the Screening Tool of Older Persons' Prescriptions (STOPP)/Screening Tool to Alert to Right Treatment (START) criteria. METHODS: Potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) were independently identified by two physicians in two cohorts of older people (I: 200 hip fracture patients, median age 85 years, STOPP/START version 1; II: 302 primary care patients, median age 74 years, STOPP/START version 2). Kappa statistics were used to evaluate inter-rater agreement. RESULTS: In cohort I, a total of 782 PIMs/PPOs, related to 68 (78%) out of 87 criteria, were identified by at least one assessor, 500 (64%) of which were discordantly identified by the assessors, that is, by one assessor but not the other. For four STOPP criteria, all PIMs (n = 9) were concordantly identified. In cohort II, 955 PIMs/PPOs, related to 80 (70%) out of 114 criteria, were identified, 614 (64%) of which were discordantly identified. For three STOPP criteria, all PIMs (n = 3) were concordantly identified. For no START criterion, with ≥1 PPO identified, were all assessments concordant. The kappa value for PIM/PPO identification was 0.52 in both cohorts. In cohort II, the kappa was 0.37 when criteria regarding influenza and pneumococcal vaccines were excluded. Further analysis of discordantly identified PIMs/PPOs revealed methodological aspects of importance, including the data source used and criteria wording. CONCLUSIONS: When the STOPP/START criteria are applied in PIM/PPO research, reliability seems to be an issue not encountered in previous reliability studies.

Drug information sources in professional work-a questionnaire study on physicians' usage and preferences (the drug information study).

PURPOSE: This study aimed to explore physicians' use of drug information in professional work, with special focus on those working in primary care, and also in relation to personal characteristics of physicians. METHODS: A web-based questionnaire was distributed by e-mail to physicians in five regions in Sweden. The questions concerned drug-related queries at issue when searching for information, sources used, and factors of importance for the choice of source, as well as responder characteristics. RESULTS: A total of 3254 (85%) out of 3814 responding physicians stated that they searched for drug information every week. For physicians working in primary health care, the corresponding number was 585 (96%). The most common drug-related issues searched for by 76% of physicians every week concerned pharmacotherapeutic aspects (e.g., dosing), followed by adverse drug reactions (63%). For 3349 (88%) physicians, credibility was the most important factor for the choice of sources of drug information, followed by easy access online (n = 3127, 82%). Further analyses among physicians in primary care showed that some personal characteristics, like seniority, sex, and country of education, as well as research experience, were associated with usage and preferences of drug information sources. CONCLUSIONS: This study confirms that physicians often use drug information sources in professional work, in particular those who work in primary health care. Credibility and easy access are key factors for usage. Among physicians in primary care, personal factors influenced the choice of drug information sources.

Child and maternal benefits and risks of caseload midwifery - a systematic review and meta-analysis.

BACKGROUND: It has been reported that caseload midwifery, which implies continuity of midwifery care during pregnancy, childbirth, and the postnatal period, improves the outcomes for the mother and child. The aim of this study was to review benefits and risks of caseload midwifery, compared with standard care comparable to the Swedish setting where the same midwife usually provides antenatal care and the checkup postnatally, but does not assist during birth and the first week postpartum. METHODS: Medline, Embase, Cinahl, and the Cochrane Library were searched (Nov 4th, 2021) for randomized controlled trials (RCTs). Retrieved articles were assessed and pooled risk ratios calculated when possible, using random-effects meta-analyses. Certainty of evidence was assessed according to GRADE. RESULTS: In all, 7,594 patients in eight RCTs were included, whereof five RCTs without major risk of bias, including 5,583 patients, formed the basis for the conclusions. There was moderate certainty of evidence for little or no difference regarding the risk of Apgar ≤ 7 at 5 min, instrumental birth, and preterm birth. There was low certainty of evidence for little or no difference regarding the risk of perinatal mortality, neonatal intensive care, perineal tear, bleeding, and acute caesarean section. Caseload midwifery may reduce the overall risk of caesarean section. Regarding breastfeeding after hospital discharge, maternal mortality, maternal morbidity, health-related quality of life, postpartum depression, health care experience/satisfaction and confidence, available studies did not allow conclusions (very low certainty of evidence). For severe child morbidity and Apgar ≤ 4 at 5 min, there was no literature available. CONCLUSIONS: When caseload midwifery was compared with models of care that resembles the Swedish one, little or no difference was found for several critical and important child and maternal outcomes with low-moderate certainty of evidence, but the risk of caesarean section may be reduced. For several outcomes, including critical and important ones, studies were lacking, or the certainty of evidence was very low. RCTs in relevant settings are therefore required.

Methodological issues in research on drug-related admissions: A meta-epidemiological review with focus on causality assessments.

AIM: To investigate methodological aspects potentially related to the diverging scientific literature on the prevalence of drug-related hospitalisations, focusing on causality assessments. METHODS: Original studies contributing data to a recent meta-analysis were reviewed. Methodological aspects, in particular those related to causality assessments, were extracted and compiled. RESULTS: Thirteen studies provided data on the prevalence of drug-related admissions. Seven studies focused on adverse drug reactions (prevalences 1.3-10%), and six studies used the broader concept of drug-related problems (prevalences 4.5-41%). In 10 out of 13 studies, causality between the drug and the specified problem was assessed. One study required a probable causal relationship; the remaining studies merely required a possible causal relationship. Five studies assessed the association between the problem assumed to be related to drug therapy and the admission, at one end requiring the former to be demonstrated as the underlying cause and, at the other, merely requiring a temporal relationship between drug intake and admission. Three out of eight studies involving multiple assessors for all/some cases reported the inter-rater agreement, ranging from none to almost perfect. Physicians were involved in the assessments in five studies, reporting prevalences of 3.2% to 4.5%, while studies without such medical input reported prevalences of 8.8% to 41%. CONCLUSIONS: This review illustrates that methodological issues contribute to the diverse literature on drug-related admissions. We provide suggestions for harmonisation of research, including explicitly assessing the drug-problem-admission relationships from a medical perspective, focusing on problems where the drug treatment is the probable culprit.

Efficacy and Safety of Clopidogrel Versus Ticagrelor as Part of Dual Antiplatelet Therapy in Acute Coronary Syndrome-A Systematic Review and Meta-analysis.

ABSTRACT: The efficacy and safety of clopidogrel compared with ticagrelor as part of dual antiplatelet therapy in patients, and in older patients, with acute coronary syndrome is reviewed. PubMed, Embase, the Cochrane Library, MEDLINE, and HTA databases were searched (September 2, 2020) for randomized controlled trials (RCTs). Pooled risk differences (clopidogrel minus ticagrelor) were estimated using random-effects meta-analyses, and certainty of evidence was assessed according to Grading of Recommendations Assessment, Development, and Evaluation. In all, 29 RCTs were identified. The risk difference for all-cause mortality was 0.6% (-0.03% to 1.3%), cardiovascular (CV) mortality: 0.6% (95% confidence interval: 0.01% to 1.1%), myocardial infarction (MI): 0.9% (0.4% to 1.3%), stent thrombosis: 0.7% (0.4 to 1.1%), clinically significant bleeding: -1.9% (-3.7% to -0.2%), major bleeding: -0.9% (-1.6% to -0.1%), and dyspnea: -5.8% (-7.7% to -3.8%). In older patients, there were no differences between the comparison groups regarding all-cause mortality, CV mortality, and MI, whereas the risk of clinically significant bleeding and major bleeding was lower in the clopidogrel group, -5.9% (-11 to -0.9%, 1 RCT) and -2.4% (-4.4% to -0.3%), respectively. Compared with ticagrelor, clopidogrel may result in little or no difference regarding all-cause mortality. Although not evident in older patients, it cannot be excluded that clopidogrel may be slightly less efficient in reducing the risk of CV mortality and MI, whereas ticagrelor is probably more efficacious in reducing the risk of stent thrombosis. Clopidogrel results in a reduced risk of dyspnea and clinically significant bleeding and in older people probably in a reduced risk of major bleeding.

Clinical relevance of potentially inappropriate medications and potential prescribing omissions according to explicit criteria-a validation study.

PURPOSE: To investigate the clinical relevance of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs), and to evaluate the association between PIMs/PPOs and inadequate drug treatment. METHODS: PIMs/PPOs, concordantly identified by two physicians applying the STOPP/START criteria, the EU(7)-PIM list, and a Swedish set in 302 consecutive older primary care patients, were assessed regarding clinical relevance for the specific patient. The physicians determined, in consensus, whether an action related to the medication was medically justified prior to the next regular consultation. If so, the drug treatment was categorised as inadequate, and if not, the treatment was considered adequate. RESULTS: In all, 259 (86%) patients had 1010 PIMs/PPOs, 150 (15%) of which, in 81 (27%) patients, were assessed as clinically relevant (kappa: 0.26). A total of 75 (50%) clinically relevant PIMs and PPOs were prioritised for medical action before the next regular consultation. Action-requiring clinically relevant PIMs most often concerned acetylsalicylic acid (ASA) for primary prevention (four out of 68 patients on ASA). The corresponding PPOs concerned beta-blockers in ischaemic heart disease (four out of 61 patients with this condition). When an overall medical perspective was applied, 164 (63%) out of 259 patients with PIMs/PPOs were assessed as having adequate treatment. In adjusted logistic regression, number of PIMs and/or PPOs and number of drugs were associated with inadequate drug treatment. CONCLUSION: One in seven PIMs/PPOs may be clinically relevant, half of these not of priority for medical action. Cautious interpretation is warranted when PIMs/PPOs are used as outcome measures.

Prevalence and initiation of statin therapy in the oldest old-a longitudinal population-based study.

PURPOSE: To investigate the prevalence and initiation of statins as well as treatment intensity in the oldest old, with younger olds as a reference. METHODS: A population-based cohort was used, including record-linked data from the Total Population Register, the Swedish Prescribed Drug Register, and the Swedish Patient Register. In each year over the study period (2009-2015), statin use was described in individuals 85 years or older and 65-84 years of age, and initiation rates were calculated among individuals with no statin treatment during a preceding 3-year period. RESULTS: A total of 1,764,836 individuals ≥ 65 years in 2009, increasing to 2,022,764 in 2015, were included in the analyses. In individuals 85 years or older, the prevalence of statin therapy increased from 11% in 2009 to 16% in 2015, the corresponding initiation rates being 1.3% and 1.7%, respectively. Corresponding prevalence and incidence figures in 65-84-year-olds were 23 to 25% and 3.0 to 3.3%, respectively. Overall, the proportion of individuals initiating statin with high-intensity treatment (atorvastatin ≥ 40 mg or rosuvastatin ≥ 20 mg) in the oldest old increased from 1 to 36% during the study period, and a similar increase was seen in the younger age group. Over the study years, the presence of an established indication for statin treatment varied between 70 and 76% in the oldest old and between 30 and 39% in the younger olds. CONCLUSION: Prevalence and initiation of statin therapy are increasing among the oldest old, despite the fact that randomized controlled trials focusing on this age group are lacking and safety signals are difficult to detect.

Drug interaction alerts in older primary care patients, and related medically justified actions.

PURPOSE: To describe presented interaction alerts in older patients, and the extent to which these require further medical action for the specific patient or are already being addressed. METHODS: Interaction alerts presented at a physician consultation, for 274 consecutive primary care patients treated with two or more drugs (median age: 75 years; 59% female), were extracted. These alerts are based on Janusmed, a decision support integrated in the medical records that provides recommendations for managing the interactions. One general practitioner (GP) and one GP/clinical pharmacologist determined in retrospect, first independently and then in consensus, whether the alerts justified further medical action, considering each patient's health condition. RESULTS: In all, 405 drug interaction alerts in 151 (55%) patients were triggered. Medical action in response was deemed medically justified for 35 (9%) alerts in 26 (17%) patients. These actions most often involved a switch to a less interacting drug from the same drug class (n = 10), a separate intake (n = 9), or the ordering of a laboratory test (n = 8). Out of 531 actions suggested by the alert system, only 38 (7%) were applicable to the specific patient, as, for instance, laboratory parameters were already being satisfactorily monitored or a separate intake implemented. CONCLUSIONS: More than every other older patient receives drug treatment that triggers drug interaction alerts. Nine in ten alerts were already being addressed or were not relevant in the clinical setting, whereas, for the remaining tenth, some medical action, that for unknown reasons had not been taken, was reasonable. These findings show that interaction alerts are questionable as indicators of problematic prescribing.

Sports nutrition supplements and adverse events - a meta-epidemiological study of case reports specifically addressing causality assessment.

PURPOSE: This meta-epidemiological study aimed to systematically review case reports regarding sports nutrition supplements and adverse events (AEs), specifically addressing the issue of causality assessments. METHODS: Through a systematic literature search we identified all published case reports of AEs associated with sports nutrition supplements between 1 January 2008 and 1 March 2019. Data regarding AEs, suspected supplements, relevant causality assessment factors and the reporting of clinical reasoning and/or systematic causality assessment methods were extracted. RESULTS: In all, 72 publications were included, reporting 134 supplements and 37 different AEs in 97 patients (85% males; median age: 30 years [range: 14-60]). Information regarding previous health and regular prescription drugs was not presented in 30% (29/97) and 46% (45/97) of cases, respectively. In 23% (22/97) of the cases, no alternative cause was mentioned. Clinical reasoning was identified in 63% (61/97), and in 13% (8/61) of these, a systematic causality assessment method was applied. In cases with clinical reasoning, a theoretic rationale (92% vs 78%, P = 0.05), a description of previous cases (90% vs 72%, P = 0.021) and body fluid analysis (18% vs 3%, P = 0.027) were reported to a greater extent. Among cases with clinical reasoning, the application of a systematic causality assessment method captured additional important aspects: use of medication (100% vs 55%, P = 0.015), alcohol use (88% vs 43%, P = 0.020) and illicit drug use (88% vs 40%, P = 0.011). CONCLUSIONS: In published case reports where sports nutrition supplements were suspected to have caused AEs, essential factors for causality assessment were left out in a non-negligible proportion. Clinical reasoning was identified in most cases whereas a systematic causality assessment method was applied in a minority. Factors of importance for causality assessment were reported to a greater extent in cases including clinical reasoning, and the application of a systematic causality assessment method captured additional aspects of importance.

Inter-rater reliability of assessments regarding the quality of drug treatment, and drug-related hospital admissions.

AIMS: To investigate inter-rater agreement on the quality of drug treatment, and the relationship between the drug treatment and hospital admission. METHODS: Three specialist physicians and two resident physicians determined, independently and in consensus, the quality of drug treatment from an overall medical perspective, and its association with admission, in 30 randomly selected patients (50% female, median age 72 years) admitted to Sahlgrenska University Hospital, Sweden, in April 2018. The inter-rater agreement was evaluated with Gwet's agreement coefficient (AC1 ). RESULTS: In all, 200 (95%) out of 210 drugs at admission and 238 (97%) out of 245 drugs at discharge were assessed as reasonable drug treatment by all assessors. Conversely, none of the drugs at admission, and two at discharge, were assessed as unreasonable drug treatment by all assessors (AC1 : 0.88 and 0.94 [all], 0.86 and 0.95 [specialists], 0.92 and 0.92 [residents], respectively). The assessments regarding the association between the drug treatment and the hospital admission (not related or main/contributory reason) were consistent between the assessors for 16 out of 30 patients (AC1 : 0.67 [all], 0.74 [specialists], 0.54 [residents]). In none of the three cases where the hospital admission was considered possibly attributable to a prescribing error did the assessors make consistent assessments. CONCLUSIONS: As the inter-rater agreement ranged between weak and almost perfect, the reliability of assessments of drug treatment quality, as well as adverse consequences, appears to be a methodological concern. To yield acceptably reliable results regarding both drug treatment aspects at issue, specialist physicians should be involved.

Low SSRI dosing in clinical practice-a register-based longitudinal study.

OBJECTIVE: Since several recent meta-analyses report a dose-response relationship for the antidepressant effect of the selective serotonin reuptake inhibitors (SSRIs), we investigated how these drugs are dosed in clinical practice. METHODS: Through linkage of nation- or region-wide registers, we describe SSRI doses in 50,365 individuals residing in Region Västra Götaland, Sweden, with an incident diagnosis of depression and initiating SSRI treatment between 2007 and 2016. The primary question was to elucidate to what extent these individuals had been prescribed a daily dose that according to recent meta-analyses is required to elicit the maximum antidepressant effect, that is >20 mg citalopram, >10 mg escitalopram, >10 mg fluoxetine, >10 mg paroxetine or >50 mg sertraline. RESULTS: In all, 21,049 (54%) out of 38,868 individuals <65 years of age, and 9,131 (79%) out of 11,497 individuals ≥65 years of age, never received an SSRI dose reported to exert maximum antidepressant effect. These prescribing practices were seen for citalopram, escitalopram and sertraline, but not for fluoxetine and paroxetine, and were frequent in both primary and secondary/tertiary care. Suggesting that doses here defined as maximum efficacy doses, when prescribed, are usually not intolerable, between 59% and 68% of individuals <65 years of age received such a dose also for the subsequent prescription, that is as frequently as in those prescribed a sub-maximum efficacy dose (52-69%). CONCLUSION: Most patients being prescribed an SSRI to treat their depression never receive the dose that according to recent meta-analyses is most likely to effectively combat their condition. The lack of consensus regarding effective dosing of SSRIs may have contributed to this state of affairs.

Serum concentrations of antidepressants, antipsychotics, and antiepileptics over the bariatric surgery procedure.

PURPOSE: As a substantial proportion of bariatric surgery patients use psychotropic/antiepileptic drugs, we investigated the impact of this procedure on serum concentrations. METHODS: In a naturalistic, longitudinal, prospective case series, we compared dose-adjusted trough concentrations of antidepressants, antipsychotics, or antiepileptics in consecutive patients before and after bariatric surgery. Adherence to treatment over 2 weeks preceding each sampling was considered. RESULTS: In all, 85 participants were included (86% female, median age 45 years, median body mass index 42 kg/m2). They were being treated with 18 different psychotropic/antiepileptic drugs (7 substances: 6-17 individuals, 11 substances: 1-4 individuals) and contributed 237 samples over a median of 379 days after surgery. For four out of seven substances with pre-/post-surgery samples available from six or more individuals, the dose-adjusted concentration was reduced (sertraline: 51%, mirtazapine: 41%, duloxetine: 35%, citalopram: 19%). For sertraline and mirtazapine, the low-calorie-diet before surgery entirely explained this reduction. A consistent finding, irrespective of drug, was the association between the mean ratio of the post-/pre-diet dose-adjusted concentration and the lipophilicity of the drug (logD; correlation coefficient: -0.69, P = 0.0005), the low-calorie diet often affecting serum concentration more than the surgery itself. CONCLUSIONS: Serum concentrations of psychotropic/antiepileptic drugs vary after bariatric surgery and can be hard to predict in individual patients, suggesting that therapeutic drug monitoring is of value. Conversely, effects of the pre-surgery, low-calorie diet appear generalizable, with decreased concentrations of highly lipophilic drugs and increased concentrations of highly hydrophilic drugs. Interaction effects (surgery/dose/concentration) were not evident but cannot be excluded.

Association between recorded medication reviews in primary care and adequate drug treatment management - a cross-sectional study.

OBJECTIVE: To investigate the association between a recorded procedure code for a medication review and adequate drug treatment management, and to explore factors associated with this code. DESIGN AND SETTING: Cross-sectional study; two primary health care centres, in Region Västra Götaland, Sweden. SUBJECTS: A total of 302 consecutive patients (≥65 years old, 59% female; median number of drugs: six) requiring a non-urgent consultation with a physician in October-November 2017. MAIN OUTCOME MEASURE: Adequate drug treatment management (treatment that did not require any further action), determined in consensus by two specialists in family medicine blinded to the medication review code. RESULTS: Adequate drug treatment management was, overall, less common in those with a recorded medication review over the last year: 63% versus 73% (p = 0.047). This negative association was evident among patients aged 65-74 years: 49% versus 74% (p = 0.003), but absent in those ≥75 years old: 67% versus 70% (p = 0.77). Recommendations from consensus included the search for additional information to be able to make a decision regarding initiation or withdrawal of a drug (n = 53), withdrawal of a drug (n = 41), or ordering a laboratory test (n = 25). Factors associated with a recorded procedure code included age above the remuneration limit of 75 years (odds ratio: 9.8; 95% confidence interval 5.0-19), type 2 diabetes (3.0 (1.5-6.2)), hypertension (2.4 (1.2-4.8)), and depression (2.5 (1.02-6.0)). CONCLUSIONS: The presence of a recorded medication review was not positively associated with adequate drug treatment management but was associated with the age limit for remuneration, and some chronic diseases.Key pointsTo improve drug treatment in older people in primary care, a remuneration system linked to recorded medication reviews has been introduced.In this study, fewer patients with than without a recorded medication review (63% versus 73%) had adequate drug treatment management.A recorded medication review was ten times more common in those ≥75 years, that is, the age limit for remuneration.Recorded codes for medication reviews were also common in those with type 2 diabetes, hypertension, and depression.

"It's helpful to get the time and opportunity to discuss drug treatment; that's what I think is the most important thing."-A qualitative study on prescribing education in junior physicians.

BACKGROUND: As prescribing skills are a prerequisite for rational use of medicines, and education and training are important in acquiring these skills, we aimed to explore what aspects junior physicians find important when being taught the art of prescribing. METHODS: Written feedback from 34 interns after participating in an educational session as part of a randomized controlled study at a university hospital formed the qualitative data in this study. Manifest content analysis was performed, guided by the research question "Educating junior physicians in the art of prescribing: what aspects do they find important?" Meaning units were extracted and categorized, and emergent themes were identified. RESULTS: Five themes emerged. The first, clinical relevance, was exemplified by the categories valuable for health care; perceived relevance for one's own work; and translating theory into practice while the second, applicable content, included categories such as clinical advice; practical tips on using the electronic medical record system; and tools that facilitate. The third and fourth themes, reality-based teaching and creative discussions, were exemplified by the categories patient cases and feedback; and discussion-based teaching; wide-ranging discussions and a permissive and open atmosphere, respectively. In the last theme, effective structure, we identified the categories clear structure; small group teaching; allocated time for discussion; well-organized administration; and home assignment for practice. CONCLUSION: Creative discussions, effectively structured in small group sessions, with clinically relevant, reality-based content built on case studies and feedback, are aspects which junior physicians find important when educated in the art of prescribing.

Personalised medicine and the decision to withhold chemotherapy in early breast cancer with intermediate risk of recurrence - a systematic review and meta-analysis.

PURPOSE: To assess the evidence for decision making, at the health care and the patient levels, regarding the use of gene expression assays to inform chemotherapy decisions in breast cancer patients with intermediate clinical risk of recurrence. METHODS: Systematic literature searches were performed (January 2002-April 2020) in Medline, Embase, PubMed, Cochrane Library, PsycINFO and HTA databases. INCLUSION CRITERIA: patients (P) were individuals with post-surgical breast cancer at intermediate clinical risk of recurrence; intervention (I)/comparison (C) was (i) use of, versus no use of, a gene expression assay and (ii) withholding versus providing chemotherapy; outcomes (O) were overall survival (OS), health-related quality of life (HRQL), and recurrence. Randomised controlled trials (RCTs) and non-RCTs were included. Random-effects meta-analyses were performed where possible. RESULTS: Three inconclusive non-RCTs, respectively, compared OS and recurrence with and without a gene expression assay. No studies investigated HRQL. Regarding the comparison withholding versus providing chemotherapy based on a gene expression assay, one RCT and four non-RCTs evaluated OS. In the RCT, 93.9% (I) versus 93.8% (C) were alive at 9 years. Three RCTs and seven non-RCTs evaluated recurrence. Three RCTs could be pooled regarding distant recurrence; 4.29% versus 3.88% had such an event (risk ratio: 1.12 (95% confidence interval: 0.90 to 1.39). CONCLUSION: Regarding the use of gene expression assays in breast cancer, evidence on patient effects, informing patient-level chemotherapy decision making, is available. However, evidence for prioritisation at the overall health care level, i.e. use of, versus no use of, such assays, is largely lacking.

Evidence synthesis based on non-randomised studies-a critical review of studies leading to conclusions on fall risk properties of loop diuretics/beta-blockers.

PURPOSE: To describe methodological and reporting issues in non-randomised comparative drug safety studies pooled in meta-analyses, with focus on confounding by indication. METHODS: All studies included in statistically significant meta-analyses in a recent publication investigating fall risk properties of cardiovascular drugs were reviewed. Study characteristics were extracted and assessed. RESULTS: Nine studies, including between 498 and 321,995 individuals, contributed data to the significant meta-analyses in which loop diuretics and beta-blockers were associated with falls, five published in 2015. Five individual studies reported a statistically significant association. In the five cohort studies, characteristics of exposed vs unexposed individuals were either not reported (n = 3) or differed substantially regarding morbidity (n = 2). Drug treatment was determined at baseline, and data on falls were collected for up to 2 years thereafter. Out of the four case-control studies, the cases and controls in only one study were matched for morbidity. Morbidity characteristics of fallers compared with non-fallers were either not reported (n = 2) or they differed (n = 1) or were reported according to the matched-for diseases (n = 1). Confounding by indication was explicitly discussed in two studies. None of the abstract conclusions considered causality issues or the possibility of confounding by indication. CONCLUSIONS: Confounding by indication is a major issue in non-randomised comparative drug safety studies, a problem which may be concealed in meta-analyses. To enhance such research, compared groups need to be balanced regarding relevant factors including morbidities and characteristics adequately reported. Confounding by indication needs to be explicitly discussed and highlighted in the abstract conclusion.