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Veronica Milos Nymberg,1,2 Cecilia Lenander,1,2 Beata Borgström Bolmsjö1,2 1Department of Clinical Sciences, Lund University, Malmö, Sweden; 2CPF, Center for Primary Healthcare Research, Malmö, SwedenCorrespondence: Beata Borgström BolmsjöCPF, Center for Primary Health Care Research, Clinical Research Centre (CRC), Building 28, Floor 11, Jan Waldenström Street 35, Malmö SE-205 02, SwedenEmail beata.borgstrom_bolmsjo@med.lu.seBackground: Drug-related problems among the elderly population are common and increasing. Multi-professional medication reviews (MR) have arisen as a method to optimize drug therapy for frail elderly patients. Research has not yet been able to show conclusive evidence of the effect of MRs on mortality or hospital admissions.Aim: The aim of this study was to assess the impact of MRs’ on hospital admissions and mortality after six and 12 months in a frail population of 369 patients in primary care in a cohort from a randomized controlled study.Methods: Patients were blindly randomized to an intervention group (receiving MRs) and a control group (receiving usual care). Descriptive data on mortality and hospital admissions at six and 12 months were collected. Survival analysis was performed for time to death and time to the first hospital admission within 12 months.Results: An observational follow-up was performed in a cohort of 369 patients, previously randomized to an intervention group (182) and a control group (187). Most of the patients (75%) were females and lived in nursing homes. At six months, 50 patients of the baseline population (27%) in the control group had been admitted to hospital at least once, compared to 40 patients (21%) in the intervention group. At 12 months, the percentage had increased to 70 (37%) in the control group compared to 53 (29%) in the intervention group. Compared to usual care, we found that MRs reduced the risk of hospital admissions within 12 months by 42% (HR = 0.58, 95% CI 0.37– 0.92, p=0.021), but found no difference in mortality (HR = 1.12, 95% CI 0.78– 1.61, p=0.551) between the groups.Conclusion: We suggest that MRs should be recommended in the care of frail elderly patients with expected benefits on delayed hospital admissions. The study is registered at ClinicalTrials.gov, registration number NCT04040855, Unique Protocol ID 2018/8.Keywords: medication reviews, primary care, elderly, randomized controlled study, hospital admissions, mortality

Aim: Polyps of the colon and rectum are considered to be premalignant lesions in the development of colorectal cancer. However, knowledge of how normal epithelial cells gain invasive properties is limited. Laminin 5 γ2 chain expression was investigated to determine the role of laminin 5 as a marker of potential invasiveness in colorectal polyps. Material/methods: Sixty seven polyps of different types (15 hyperplastic polyps, 12 serrated adenomas, 16 tubular adenomas, and 24 adenomas with a villous component) were assessed for γ2 chain expression of laminin 5 by immunohistochemistry on archival, paraffin wax embedded sections. Results: Ten polyps stained positive and the number of polyps expressing the laminin 5 γ2 chain increased significantly as the phenotype of the adenomas became more atypical: none of the 15 hyperplastic polyps, two of the 16 tubular adenomas (12.5%), and six of the 24 adenomas with a villous component (25%) were positive. Two of 12 (17%) serrated adenomas, regarded as a distinct form of colorectal neoplasia, showed γ2 chain expression. Furthermore, laminin 5 γ2 chain expression correlated with lesion size. Polyps smaller than 10 mm expressed the γ2 chain less frequently than did those equal to or larger than 10mm. Conclusion: Laminin 5 γ2 chain expression was found to increase progressively towards a more atypical phenotype of adenoma. The results suggest that, in the future, laminin 5 γ2 chain expression may be used as an indicator of incipient malignant transformation of a benign colorectol adenoma. [ABSTRACT FROM AUTHOR]

Expression of the γ2 chain at the invasive front of different tumors has indicated an important role for laminin-5 in cell migration during tumor invasion and tissue remodeling. As there is considerable need for reliable invasion and prognostic markers we evaluated the correlation of laminin-5 γ2 chain expression with clinicopathologic parameters and patient survival in 93 primary colon carcinomas. Epithelial cells of normal mucosa were consistently negative for staining. In contrast, positive cytoplasmic staining was observed in 89 tumors (96%). Twenty-four (26%) cases were scored as sparse, 34 (37%) as moderate, and 31 (33%) as frequent γ2 chain expression. There was a significant association of laminin-5 γ2 chain expression and local invasiveness of colon carcinomas according to Dukes stage (A-C) (p=0.001) and tumor budding (p<0.001). A statistical significance could also be noted in decreasing tumor differentiation (p<0.001) and correlation to tumor size (p=0.032). No correlation was observed to tumor site. Univariate analysis identified laminin-5 (p=0.010), tumor differentiation (p=0.006) and Dukes grade (p<0.001) as significant variables in predicting prognosis. However, by multivariate analyses, this study could not demonstrate that laminin-5 γ2 chain expression is an independent predictive factor for survival.The results indicate that laminin-5 γ2 chain expression is up-regulated during the progression of human colon cancer and that it plays a role in the aggressiveness of these tumors. Demonstration of laminin-5 γ2 chain positivity also facilitates detection of individual cells or minor cell clusters invading the surrounding stroma.Figures on http://www.esacp.org/acp/2001/22-4/lenander.htm. [ABSTRACT FROM AUTHOR]

The genetic susceptibility to colorectal cancer (CRC) has been estimated to be around 35% and yet high-penetrance germline mutations found so far explain less than 5% of all cases. Much of the remaining variations could be due to the co-inheritance of multiple low penetrant variants. The identification of all the susceptibility alleles could have public health relevance in the near future. To test the hypothesis that what are considered polymorphisms in human CRC genes could constitute low-risk alleles, we selected eight common SNPs for a pilot association study in 1785 cases and 1722 controls. One SNP, rs3219489:G>C (MUTYH Q324H) seemed to confer an increased risk of rectal cancer in homozygous status (OR=1.52; CI=1.06-2.17). When the analysis was restricted to our 'super-controls', healthy individuals with no family history for cancer, also rs1799977:A>G (MLH1 I219V) was associated with an increased risk in both colon and rectum patients with an odds ratio of 1.28 (CI=1.02-1.60) and 1.34 (CI=1.05-1.72), respectively (under the dominant model); while 2 SNPs, rs1800932:A>G (MSH6 P92P) and rs459552:T>A (APC D1822V) seemed to confer a protective effect. The latter, in particular showed an odds ratio of 0.76 (CI=0.60-0.97) among colon patients and 0.73 (CI=0.56-0.95) among rectal patients. In conclusion, our study suggests that common variants in human CRC genes could constitute low-risk alleles. [ABSTRACT FROM AUTHOR]

Objective: To examine associations between body mass index (BMI) in early pregnancy and gestational weight gain (GWG) with cardiovascular health in middle age using the 'Life's Essential 8' (LE8) concept of the American Heart Association (AHA)., Design: Population-based cohort study., Setting: Swedish CardioPulmonary bioImage Study (SCAPIS)., Population: A total of 8871 women from SCAPIS were included., Methods: Information on cardiovascular health in middle age was collected from SCAPIS and linked to pregnancy weight data obtained from the Swedish Medical Birth Register, with an average follow-up time of 24.5 years. An LE8 score between 0 and 100 was determined, where a score under 60 points was defined as poor cardiovascular health. Binary logistic regression and restricted cubic splines were used., Main Outcome Measures: Cardiovascular health according to LE8 in middle age., Results: The odds of having poor cardiovascular health in middle age were significantly higher in women who had overweight (adjusted odds ratio, aOR 3.30, 95% CI 2.82-3.88) or obesity (aOR 7.63, 95% CI 5.86-9.94), compared with women classified as being of normal weight in pregnancy. Higher odds were also found for excessive GWG (aOR 1.31, 95% CI 1.09-1.57), compared with women who gained weight within the recommendations., Conclusions: A high BMI in early pregnancy and excessive GWG were associated with greater odds of poor cardiovascular health in middle age. Although further studies are needed, our results highlight pregnancy as an important period to support long-term cardiovascular health., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Life's Essential 8 (LE8) is a score that includes modifiable risk factors for cardiovascular disease. Four health behaviors (diet, physical activity, nicotine exposure and sleep health) and four health factors (non-HDL cholesterol, blood glucose, blood pressure and body mass index) are included. These modifiable risk factors promote inflammation, and inflammation is one of the biological mechanisms of cardiovascular disease development. Thus, we examined the relationship between cardiovascular health measured by LE8 and low-grade inflammation measured by high-sensitivity C-reactive protein (hs-CRP) in the cross-sectional population-based Swedish CArdioPulmonary bioImage Study (SCAPIS). The study consisted of 28,010 participants between 50 and 64 years (51.5% women, mean age 57.5 years). All individual LE8 components were assigned a score between 0 (unhealthy) and 100 (healthy) points, and a global score was calculated. The association between LE8 scores and high-risk hs-CRP (defined as > 3.0 mg/L) was analyzed using adjusted logistic regression with spline analyses. There was a strong, dose response and inverse association between LE8 scores and levels of hs-CRP. Thus, those with a low LE8 score (= 50.0 points) had 5.8 higher (95% confidence interval [CI] 5.2-6.4) odds ratio (OR) of having high hs-CRP as compared to those with a high LE8 score (= 80.0 points). In conclusion, our findings show strong inverse associations between LE8 scores and levels of hs-CRP., (© 2024. The Author(s).)

Background: Cardiovascular disease (CVD) is a major global health issue, primarily caused by atherosclerosis. Psychological factors may play a role in the development and progression of CVD. However, the relationship between psychological factors and atherosclerosis is complex and poorly understood. This study, therefore, aimed to examine the association of psychological factors with (i) coronary and carotid atherosclerosis and (ii) cardiovascular health according to Life's Essential 8, in a large Swedish cohort., Methods: This study utilized data from the Swedish CArdioPulmonary bioImage Study (SCAPIS), a large population-based project including individuals aged 50 to 65 years. Several psychological factors were analysed: general stress, stress at work, financial stress, major adverse life events, locus of control, feeling depressed, and depression. Coronary atherosclerosis was assessed as the degree of stenosis by coronary computed tomography angiography (CCTA) and coronary artery calcification (CAC) scores. Carotid atherosclerosis was examined using ultrasound. In addition, cardiovascular health was examined using the Life's Essential 8 concept created by the American Heart Association, which includes four health behaviors and four health factors. Associations were examined through binomial logistic regression (atherosclerosis variables) and linear regression (Life's Essential 8)., Results: A total of 25,658 participants were included in the study. The presence of financial stress, higher locus of control, and depression was weakly associated with increased odds of CCTA stenosis, CAC ≥ 1 and the presence of carotid plaques (all odds ratios: 1.10-1.21, 95% CI: 1.02-1.32) after adjusting for sex, age, and study site. However, these associations were attenuated and not statistically significant after additional adjustments for socioeconomic factors and health behaviors. Conversely, we observed inverse associations between the worst category for all psychological factors and cardiovascular health according to Life's Essential 8 score (all standardized β-Coefficient ≤-0.033, p < 0.001)., Conclusion: While there were no strong and consistent associations between psychological factors and atherosclerosis, the consistent associations of psychological factors with cardiovascular health by Life's Essential 8 may have relevance for future CVD risk. However, further studies are needed to elucidate the long-term effects of psychological factors on atherosclerosis development and cardiovascular health., (© 2024. The Author(s).)

Purpose: To monitor cardiovascular health, in 2022, the American Heart Association (AHA) updated the construct "Life's Simple 7" (LS7) to "Life's Essential 8" (LE8). This study aims to analyze the associations and capacity of discrimination of LE8 and LS7 in relation to self-rated health (SRH) and health-related quality of life (HRQoL)., Methods: This study from the Swedish CArdioPulmonary bioImage Study (SCAPIS) included 28 731 Swedish participants, aged 50-64 years. Three different scores were derived from the SF-12 questionnaire: 1-item question SRH ("In general, would you say your health is …?"), mental-HRQoL and physical-HRQoL. Logistic regression, restricted cubic splines, and ROC analysis were used to study the associations between the AHA scores in relation to SRH and HRQoL., Results: Compared to those with a LE8 score of 80, participants with a LE8 score of 40 were 14.8 times more likely to report poor SRH (OR: 14.8, 95% CI: 13.0-17.0), after adjustments. Moreover, they were more likely to report a poor mental-HRQoL (OR: 4.9, 95% CI: 4.2-5.6) and a poor physical-HRQoL (OR: 8.0, 95% CI: 7.0-9.3). Area under curves for discriminating poor SRH were 0.696 (95% CI: 0.687-0.704), 0.666 (95% CI: 0.657-0.674), and 0.643 (95% CI: 0.634-0.651) for LE8, LS7 (0-14), and LS7 (0-7), respectively, all p values < 0.001 in the DeLong's tests., Conclusion: LE8 and LS7 had strong and inverse associations with SRH, mental-HRQoL, and physical-HRQoL, though LE8 had a somewhat higher capacity of discrimination than LS7. The novel LE8, a construct initially conceived to monitor cardiovascular health, also conveys SRH and HRQoL., (© 2024. The Author(s).)

Objectives: To examine the associations between physical fitness in male adolescents and coronary and carotid atherosclerosis in middle age., Methods: This population-based cohort study linked physical fitness data from the Swedish Military Conscription Register during adolescence to atherosclerosis data from the Swedish CArdioPulmonary bioImage Study in middle age. Cardiorespiratory fitness was assessed using a maximal cycle-ergometer test, and knee extension muscular strength was evaluated through an isometric dynamometer. Coronary atherosclerosis was evaluated via Coronary Computed Tomography Angiography (CCTA) stenosis and Coronary Artery Calcium (CAC) scores, while carotid plaques were evaluated by ultrasound. The associations were analysed using multinomial logistic regression, adjusted (marginal) prevalences and restricted cubic splines., Results: The analysis included 8986 male adolescents (mean age 18.3 years) with a mean follow-up of 38.2 years. Physical fitness showed a reversed J-shaped association with CCTA stenosis and CAC, but no consistent association was observed for carotid plaques. After adjustments, compared with adolescents in the lowest tertile of cardiorespiratory fitness and muscular strength, those in the highest tertile had 22% (OR 0.78; 95% CI 0.61 to 0.99) and 26% (OR 0.74; 95% CI 0.58 to 0.93) lower ORs for severe (≥50%) coronary stenosis, respectively. The highest physical fitness group (high cardiorespiratory fitness and muscular strength) had 33% (OR 0.67; 95% CI 0.52 to 0.87) lower OR for severe coronary stenosis compared with those with the lowest physical fitness., Conclusion: This study supports that a combination of high cardiorespiratory fitness and high muscular strength in adolescence is associated with lower coronary atherosclerosis, particularly severe coronary stenosis, almost 40 years later., Competing Interests: Competing interests: EH reports payments to institution from Pfizer and Amgen, small personal fees from Amgen, NovoNordisk, Bayer and AstraZeneca, small personal fee from Amarin AB for participation on advisory board. He is the co-chair of the Swedish secondary prevention registry and the national coordinator for the trials DalCore DAL301 DalGne, Regeneron R1500-CL-1643 and Aegis II/Perfuse. The remaining authors report no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To examine the associations between the American Heart Association scores ("Life's Essential 8" [LE8] and "Life's Simple 7" [LS7]) and 2 subclinical coronary atherosclerosis indicators: coronary computed tomographic angiography (CCTA)-stenosis and coronary artery calcium (CAC)., Patients and Methods: We included a population-based sample, aged 50 to 64 years, recruited between 2013 and 2018 from the Swedish Cardiopulmonary Bioimage Study (n=24,819, 50.3% women). CCTA-stenosis was graded as no stenosis, stenosis (1%-49%) or severe stenosis (≥50%), whereas CAC was graded as 0, 1 to 99, 100 to 399, or ≥400 Agatston units. Multinomial logistic regression and receiver operating characteristic (ROC) curves were used to study the associations between cardiovascular health scores and subclinical coronary atherosclerosis., Results: Odds ratios (ORs) for CCTA-stenosis and severe CCTA-stenosis between the lowest (<50 points) vs the highest (≥80 points) LE8 group were 4.18 (95% CI, 3.56 to 4.91) and 11.17 (95% CI, 8.36 to 14.93), respectively. For corresponding CAC results, ORs were 3.36 (95% CI, 2.84 to 3.98), 7.72 (95% CI, 6.03 to 9.89), and 14.94 (95% CI, 10.47 to 21.31) for CAC scores of 1 to 99, 100 to 399, and ≥400, respectively. Area under ROC curves for predicting any stenosis were 0.642 (95% CI, 0.635 to 0.649) and 0.631 (95% CI, 0.624 to 0.638, P<.001) for LE8 and LS7, respectively., Conclusion: Our data indicate that LE8 showed a strong, graded, and inverse association with CCTA-stenosis and CAC score. The capacity to predict CCTA-stenosis was comparable between LE8 and LS7, although LE8 had slightly higher prediction capacity of any stenosis. This study provides novel evidence that the LE8 score may be a useful tool for monitoring cardiovascular health., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A high number of drug-related problems has previously been shown among community-dwelling patients in primary healthcare in Skåne County, Sweden. Medication reviews are one way to solve these problems, but their impact is largely dependent on the process. We aimed to evaluate medication reviews for community-dwelling patients regarding the clinical relevance of the pharmacists' recommendations, and their implementation by general practitioners. We also wanted to investigate if the general practitioners' tendency to act on drug-related problems was correlated to different factors of the process., Methods: This was a cohort study, where patients in primary healthcare considered in need of a medication review were selected. Pharmacists identified drug-related problems and gave written recommendations on how to solve the problems to the general practitioner, via the medical record, and in addition in some cases via verbal communication. The clinical relevance of the recommendations was graded according to the Hatoum scale, ranging from one (adverse significance) to six (extremely significant). Descriptive statistics were used regarding the clinical relevance and the general practitioners´ tendency to act on drug-related problems. Multiple logistic regression analysis was used to examine the association between the tendency to act and different factors of the process., Results: A total of 96.1% of the 384 assessed recommendations from the pharmacists were graded as significant or more for the patient (Hatoum grade 3 or higher). The general practitioners acted on 63.8% of the drug-related problems. Fewer recommendations per patient, as well as verbal communication in addition to written contact, significantly increased the general practitioners' tendency to act on a drug-related problem. No significant association was seen between the tendency to act and the clinical relevance of the recommendation., Conclusions: The high proportion of clinically relevant recommendations from the pharmacists in this study strengthens medication reviews as an important tool for reducing drug-related problems. Verbal communication between the pharmacist and the general practitioner is important for measures to be taken. Multiple recommendations for the same patient reduced their likelihood to of being addressed by the general practitioner., (© 2023. The Author(s).)

Background: To quantify cardiovascular health (CVH), the American Heart Association (AHA) recently launched an updated construct of the "Life's Simple 7" (LS7) score, the "Life's Essential 8" (LE8) score. This study aims to analyse the association between both CVH scores and carotid artery plaques and to compare the predictive capacity of such scores for carotid plaques., Methods: Randomly recruited participants aged 50-64 years from the Swedish CArdioPulmonary bioImage Study (SCAPIS) were analysed. According to the AHA definitions, two CVH scores were calculated: i) the LE8 score (0, worst CVH; 100, best CVH) and two different versions of the LS7 score [(0-7) and (0-14), 0 indicating the worst CVH]. Ultrasound-diagnosed carotid plaques were classified as no plaque, unilateral, and bilateral plaques. Associations were studied by adjusted multinomial logistic regression models and adjusted (marginal) prevalences, while comparison between LE8 and LS7 scores was performed through receiver operating characteristic (ROC) curves., Results: After exclusions, 28,870 participants remained for analysis (50.3% women). The odds for bilateral carotid plaques were almost five times higher in the lowest LE8 (<50 points) group [OR: 4.93, (95% CI: 4.19-5.79); adjusted prevalence 40.5%, (95% CI: 37.9-43.2)] compared to the highest LE8 (≥80 points) group [adjusted prevalence 17.2%, (95% CI: 16.2-18.1)]. Also, the odds for unilateral carotid plaques were more than two times higher in the lowest LE8 group [OR: 2.14, (95% CI: 1.82-2.51); adjusted prevalence 31.5%, (95% CI: 28.9-34.2)] compared to the highest LE8 group [adjusted prevalence 29.4%, (95% CI: 28.3-30.5)]. The areas under ROC curves were similar between LE8 and LS7 (0-14) scores: for bilateral carotid plaques, 0.622 (95% CI: 0.614-0.630) vs. 0.621 (95% CI: 0.613-0.628), P  = 0.578, respectively; and for any carotid plaque, 0.602 (95% CI: 0.596-0.609) vs. 0.600 (95% CI: 0.593-0.607), P  = 0.194, respectively., Conclusion: The new LE8 score showed inverse and dose-response associations with carotid plaques, particularly bilateral plaques. The LE8 did not outperform the conventional LS7 score, which showed similar ability to predict carotid plaques, especially when scored as 0-14 points. We conclude that both the LE8 and LS7 may be useful in clinical practice for monitoring CVH status in the adult population., Competing Interests: JS reports stock ownership in Anagram kommunikation AB and Symptoms Europe AB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Herraiz-Adillo, Ahlqvist, Higueras-Fresnillo, Berglind, Wennberg, Lenander, Daka, Ekstedt, Sundström, Ortega, Östgren, Rådholm and Henriksson.)

The aim of the current study was to examine the prevalence of ideal cardiovascular health (iCVH) in the general Swedish middle-aged population. To address this aim, we utilised data from the Swedish CArdioPulmonary bioImage Study (SCAPIS) which is a large Swedish population-based study ( N =30,154) that combined comprehensive state-of-the-art imaging technology with clinical examinations and included all iCVH components. A total iCVH score was calculated as the number of iCVH metrics at an ideal level for the seven components and classified as: ideal (⩾5 ideal components), intermediate (3-4 ideal components) and poor (⩽2 ideal components). Our results showed that only 18.2% of the population reached ideal status (i.e. ⩾5 components at the ideal level), whereas 51.9% were classified as intermediate status and 29.9% as poor status of iCVH. Women had a higher prevalence of iCVH status (23.9% vs. 12.0%) and a lower prevalence of poor iCVH status (23.5% vs. 36.8%). Our data may serve as benchmarks for future national and international comparisons and motivate efforts to promote cardiovascular health in the general population, given the strong link between iCVH with all-cause and cardiovascular disease mortality and morbidity.

Background: Medication treatment can reduce morbidity but can also cause drug-related problems (DRPs). One method to identify and solve DRPs is medication reviews (MRs) that are aimed at increased patient safety and quality in drug treatment. In Skåne county, Sweden, a well-established multi-professional model for MRs in nursing homes is practiced. However, a demand for MRs regarding community-dwelling patients has emerged. These patients may be extra vulnerable since they have less supervision from healthcare personnel., Aim: To describe the community-dwelling patients in primary healthcare considered in need of an MR, as well as the outcomes of these pharmacist-led MRs., Methods: Personnel from 14 primary healthcare centers selected patients for the MRs. Based on electronic medical records, the symptom assessment tool PHASE-20 (PHArmacotherapeutical Symptom Evaluation 20 questions) and medication lists, pharmacists conducted MRs and communicated adjustment suggestions via the medical record to the general practitioners (GPs)., Results: A total of 109 patients were included in the study and 90.8% (n = 99) of the patients were exposed to at least one DRP, with an average of 3.9 DRPs per patient. Patients with impaired renal function (glomerular filtration rate, GFR < 45 ml/min) or ≥ 10 medications were exposed to a significantly higher number of DRPs per patient, 5.1 DRP and 5.3 respectively. The most frequent DRP-categories were Unnecessary drug therapy and Adverse drug reaction, which represented 23.0% respectively 22.9% of the total amount of DRPs., Conclusions: Our results indicate a prioritized need for MRs for community-dwelling patients, specifically with impaired renal function or polypharmacy., (© 2022. The Author(s).)

Since the start of the Swedish National Research School in General Practice, 120 Swedish PhD candidates in general practice have been admitted to the school, out of whom 89 during the first 10-year period. We have evaluated the academic achievements of the 53 (60%) PhD candidates that finished their thesis 2011-2020 by a questionnaire and bibliometric data collected from the Web of Science Core Collection. The questionnaire was answered by 52 (98%) and showed that 45 (87%) had continued with research work after their dissertation. Ten (19%) had done a post doc and four (8%) had become associate professors, out of whom one (2%) was a full professor. We found 519 peer-reviewed scientific publications authored by the alumni. The co-authors of these publications were affiliated all around the world, mainly in Sweden, followed by Australia and Germany. The National Research School will continue to strive towards increased quality of primary care research.

Aims: Antimicrobial resistance presents an increasingly serious threat to global public health, which is directly related to how antibiotic medication is used in society. Actions aimed towards the optimised use of antibiotics should be implemented on equal terms and according to the needs of the population. Previous research results on differences in antibiotic use between socio-economic and demographic groups in Sweden are not entirely coherent, and have typically focused on the effects of singular socio-economic variables. Using an intersectional approach, this study provides a more precise analysis of how the dispensation of antibiotic medication was distributed across socio-economic and demographic groups in Sweden in 2016-2017. Methods: Using register data from a nationwide cohort and adopting an intersectional analysis of individual heterogeneity and discriminatory accuracy, we map the dispensation of antibiotics according to age, sex, country of birth and income. Results: While women and high-income earners had the highest antibiotic dispensation prevalence, no large differences in the dispensation of antibiotics were identified between socio-economic groups. Conclusions: Public-health interventions aiming to support the reduced and optimised use of antibiotics should be directed towards the whole Swedish population rather than towards specific groups. Correspondingly, an increased focus on socio-economic or demographic factors is not warranted in interventions aimed at improving antibiotic prescription patterns among medical practitioners.

Rationale, Aims, and Objectives: Drug-related morbidity is common, which results in suffering for the patients and a high cost to society. SÄKLÄK2 is a multi-professional intervention model aiming at improving drug safety in primary health care. The objective of this study was to elucidate the perceptions of the participants' regarding the efficiency of the intervention and the feasibility to introduce this model widely., Method: SÄKLÄK2 is a multi-professional intervention model in primary health care in Sweden that consisted of self-assessment, peer-review, written feedback, and agreements for change. Web-based surveys were sent to both the management of participating primary health care centres (PHC) and to reviewers. The participating PHCs were fairly well-staffed and had a high interest in improvement work. Descriptive analysis and content analysis was used., Results: For the PHC management, the following categories were formed: Comprehensive project, Time-consuming, Multi-professional character, Relevant action agreements, and Feasible to implement. For the reviewers, the following categories were formed: Multi-professional character, Relevant action agreements, Feasible to implement, Useful self-assessment questionnaire, and Valuable visit at the PHC. There was a high degree of consistency between the PHC management and the reviewers' answers, especially regarding the efficiency of the model to improve drug safety and the feasibility to implement it on a broad front., Conclusion: SÄKLÄK2, a model with self-assessment, peer review, written feedback, and the formation of action agreements was considered by both the participating heads of the PHC centres and the reviewers to be effective to improve drug safety in primary health care. Though time-consuming, this multi-professional model was considered to be feasible to implement on a broad front and might thereby be one way of working with quality improvement regarding drug safety., (© 2019 John Wiley & Sons, Ltd.)

Background: Drug use among the elderly population is generally extensive and the use of potentially inappropriate medications (PIMs) is common, which increases the risk for drug-related problems (DRP). Medication reviews are one method to improve drug therapy by identifying, preventing and solving DRPs. The aim of this study was to evaluate the effect of medication reviews on total drug use and potentially inappropriate drug use in elderly patients, as well as describe the occurrence and types of drug-related problems., Method: This was a cross-sectional analysis to study medication reviews conducted by trained clinical pharmacists followed by team-based discussions with general practitioners (GPs) and nurses, for elderly primary care patients in Skåne, Sweden. Included in the analysis were patients ≥75 years living in nursing homes or in their own homes with home care, who received a medication review during 2011-2012. Documented DRPs were described as both the type of DRPs and as pharmacists' recommendations to the GP. The usage of ≥3 psychotropics and PIMs (antipsychotics, anticholinergics, long-acting benzodiazepines, tramadol and propiomazine) at baseline and after medication review were also studied., Results: The analysis included a total of 1720 patients. They were on average aged 87.5 years, used typically 11.3 drugs (range 1-35) and 61% of them used 10 drugs or more. Of the patients, 84% had at least one DRP with a mean of 2.2 DRPs/patient. Of the DRPs, 12% were attributable to PIMs. The proportion of patients with ≥ one PIM was reduced significantly (p < 0.001) as was the use of ≥3 psychotropics (p < 0.001). The most common DRP was unnecessary drug therapy (39%), followed by dose too high (21%) and wrong drug (20%). Drug withdrawal was the most common result., Conclusion: This study shows that medication reviews performed in everyday care are one way of improving drug use among elderly patients. The use of potentially inappropriate medications and use of three or more psychotropic drugs decreased after the medication review. Our study also shows that drug use is extensive in nursing home residents and elderly patients with homecare, and that unnecessary drug therapy is a common problem.

Background: Tumor budding and a proficient mismatch repair (pMMR) status are considered adverse prognostic factors in colorectal cancer (CRC). The aim of this pilot study was to assess tumor budding in primary CRC with pMMR versus that with deficient mismatch repair (dMMR)., Materials and Methods: Tumor budding was retrospectively examined in the tumor from 134 patients with stage II and stage III CRC with known MMR status. The 29 available dMMR cases who developed recurrence or distant metastases (met+) were matched with a dMMR group with no recurrence or metastases (met-), and the pMMR/met+ group with pMMR/met- cases., Results: Using tumor budding cut-offs of 5 and 10, a significantly higher percentage of high-grade tumor budding (≥5 and ≥10) was only found in the dMMR/met+ compared to pMMR/met+ subgroup (p=0.01 and p=0.02, respectively)., Conclusion: A significantly higher grade of tumor budding was observed in the dMMR/met+ group, suggesting that tumor budding can provide prognostic information for patients with a dMMR status., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Antipsychotics form a class of drugs that should be used with caution among elderly people because of a high risk of adverse events. Despite the risks and modest effects, their use is estimated to be high, especially in nursing homes., Objective: The aim was to explore the effects of medication reviews on antipsychotic drug use for elderly primary care patients and describe the extent of, and reasons for, the prescription of antipsychotics., Methods: In this cross-sectional study in primary care in Skåne, Sweden, patients aged ≥75 years living in nursing homes or in their own homes with home care were included. The effects of medication reviews were documented, as were the use of antipsychotics and the differences in characteristics between patients receiving or not receiving antipsychotics., Results: A total of 1683 patients aged 87.6 (±5.7) years were included in the analysis. Medication reviews reduced the use of antipsychotics by 23% (p < 0.001) in this study. Of the 206 patients using antipsychotics, 43% (n = 93) had an approved indication, while for 15% (n = 32) the indication was not given. Antipsychotic drug use was more common with increasing number of drugs (p = 0.001), and in nursing home residents (p < 0.01). It was also more frequent in patients with cognitive impairment, depressive symptoms or sleeping problems., Conclusion: The use of antipsychotic drugs is high in elderly patients in nursing homes. They are often given for indications that are not officially approved or are poorly documented. Medication reviews appear to offer one useful strategy for reducing excessive use of these drugs.

Background: Polypharmacy is known to increase the risk for drug-related problems, and some drugs, potentially inappropriate medications (PIMs), are especially troublesome., Objective: To analyse the effects on prescription of PIMs of the SÄKLÄK project, an intervention model created to improve medication safety for elderly patients in primary care., Method: The SÄKLÄK project was a multiprofessional intervention in primary care consisting of self-assessment, peer review, feedback and written agreements for change. Five Swedish primary care centres participated in the intervention and five served as comparison group. Data were collected from the Swedish Prescribed Drug Register on PIMs (long-acting benzodiazepines, anticholinergics, tramadol, propiomazine, antipsychotics and non-steroidal anti-inflammatory drugs) prescribed to patients aged 65 years and older. Total number of patients and change in patients using PIMs before and after intervention with-in groups was analysed as well as differences between intervention and comparison group., Results: A total of 32566 prescriptions of PIMs were dispensed before the intervention, 19796 in the intervention group and 12770 in the comparison group. After intervention a decrease was seen in both groups, intervention-22.2% and comparison-8.8%. All groups of PIMs decreased, except for antipsychotics in the comparison group. For the intervention group, a significant decrease in mean dose/patient was seen after the intervention but not in the comparison group., Conclusion: Our study shows this method has some effects on prescription of PIMs. The evaluation indicates this is a feasible method for improvement of medication use in primary care and the method should be tested on a larger scale., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There is an urgent need to improve patient safety in the area of medication treatment among the elderly. The aim of this study was to explore which improvement needs and strengths, relating to medication safety, arise from a multi-professional intervention in primary care and further to describe and follow up on the agreements for change that were established within the intervention., Methods: The SÄKLÄK project was a multi-professional intervention in primary care consisting of self-assessment, peer-review, feedback and written agreements for change. Data were obtained from five primary care units randomised to the intervention group. Reviewer feedback reports and agreements for change were analysed using content analysis., Results: Strengths that were identified included a committed leadership, work methods to enhance medication safety and access to consultants. Methods for securing an accurate medication list, knowledge and methods of working of the prescriber and patient's ability to contribute to medication safety were areas that gave rise to three predesigned categories for improvement needs on a local level. Another category became apparent during the analysis; namely learning from mistakes and from results. In all categories, apparent shortcomings were identified. These included inaccurate medication lists, lack of medication reconciliation, lack of time for follow-up of elderly patients, need for further education in geriatrics and pharmacotherapy and lack of information on indication and maximum dosage. An increased number of medication reviews were among the most common agreements for change seen., Conclusions: This study identified substantial shortcomings, like poorly updated medication lists, which affected medication safety in the participating Swedish primary care units. Similar shortcomings are most likely present in other primary care units in the country. Working together multi-professionally, including performing medication reviews, could be one way of improving medication safety. On the other hand, the individual physician must possess enough pharmaceutical knowledge and the working conditions must allow time for follow-up of prescriptions. Strengths of the primary care unit, such as successful methods of working, must be taken advantage of. The culture in primary care may affect the ability to successfully implement routines that improve patient safety and reduce risk of medication errors.

Background: The elderly population is increasing and with advanced age comes a higher risk for contracting diseases and excessive medicine use. Polypharmacy can lead to drug-related problems and an increased need of health care. More needs to be done to help overcome these problems. In order for new models to be successful and possible to implement in health care they have to be accepted by caregivers. The aim of this study was to evaluate participants' perceptions of the SÄKLÄK project, which aims to enhance medication safety, especially for elderly patients, in primary care., Methods: This is a qualitative study within the SÄKLÄK project. The SÄKLÄK project is a multi-professional intervention in primary care consisting of self-assessment, peer review, feedback and written agreements for change. A total of 17 participants from the intervention's primary care units were interviewed. Most of the interviews were done on a one-to-one basis. The interviews were recorded and transcribed verbatim. A survey was also sent to the primary care unit heads. Qualitative content analysis was used to explore the participants' perceptions., Results: The analysis of the interviews yielded six categories: multi-professional co-operation, a focus on areas of improvement, the joy of sharing knowledge, disappointment with the focus of the feedback, spend time to save time and impact on work. From these categories a theme developed: "Medication safety is a large area. In order to make improvements time needs to be invested and different professions must contribute.", Conclusions: This study shows that our studied intervention method is feasible to use in primary care and that the multi-professional approach was perceived as being very positive by the participants. Multi-professional co-operation was time consuming, but was also deemed as an investment and an opportunity to share knowledge. Some points of improvement of the method were identified such as simplification of the self-assessment form and clearer instructions for reviewers. In addition, to have an impact on work the focus must lie in areas within the primary care units' scope.

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.

The establishment and maintenance of apical-basal cell polarity is essential for the functionality of glandular epithelia. Cell polarity is often lost in advanced tumours correlating with acquisition of invasive and malignant properties. Despite extensive knowledge regarding the formation and maintenance of polarity, the mechanisms that deregulate polarity in metastasizing cells remain to be fully characterized. Here we show that AmotL2 expression correlates with loss of tissue architecture in tumours from human breast and colon cancer patients. We further show that hypoxic stress results in activation of c-Fos-dependent expression of AmotL2 leading to loss of polarity. c-Fos/hypoxia-induced p60 AmotL2 interacts with the Crb3 and Par3 polarity complexes retaining them in large vesicles and preventing them from reaching the apical membrane. The resulting loss of polarity potentiates the response to invasive cues in vitro and in vivo in mice. These data provide a molecular mechanism how hypoxic stress deregulates cell polarity during tumour progression.

Background: Studying the invading edge of colorectal carcinomas it was previously noticed that the neoplastic glands with pores could contain mucin, inflammatory cells and/or necrotic material., Aims: To systematically record the type of intraglandular materials found in the neoplastic glands with pores at the invading edge of sporadic colonic carcinomas., Materials and Methods: Histological sections from 12 adenocarcinomas were selected when the following materials were predominantly found in the neoplastic glands with pores at the invading tumor edge: mucin (3 cases, group I), neutrophilic granulocyes (3 cases, group II), necrotic material (3 cases, group III) and invaginated stroma (3 cases, group IV). Surgical histological sections were stained with hematoxylin and eosin (H&E) and analyzed at 20 magnifications. The length of the invading edge was measured with a translucent millimetre ruler and the number of glands with pores per mm was calculated in each case., Results: Two hundred and ninety-five glands with pores were analyzed in the 12 cases. Mucus was found in 68% (n=55) of the 81 glands with pores in group I, granulocytes in 95% (n=41) of the 43 glands with pores in group II, necrotic material in 72% (n=84) of the 117 glands with pores in group III and stromal invaginations in 61% (n=33) of the 54 glands with pores in group IV. The mean number of glands with pores per mm was 1.02 (55 glands/54 mm) in group I, 0.93 (41 glands/44 mm) in group II, 1.22 (84 glands /69 mm) in group III and 0.62 (33 glands /53 mm) in group IV., Discussion and Conclusion: Neoplastic glands with pores at the invading front of colonic adenocarcinomas may predominantly contain various biological materials. These materials may differ in different individuals. While tumor mucins harbour proteolytic enzymes able to digest the juxtaposed stroma of the host, the possible significance of the other intraglandular materials contributed by the host, such as neutrophils, necrotic material and/or stromal invaginations on tumor growth, is still poorly understood. Further studies are necessary to assess whether each one of these intraglandular materials has any bearing on the progression of colonic carcinomas.

Previous studies have shown the presence of dilated neoplastic glands with cellular gaps called glandular pores (GPs) and laminin 5gamma2 expression at the invading edge of colonic carcinomas. We now extended our studies to explore a possible association between GP formation and laminin 5gamma2 expression at the invading edge of colonic carcinomas. Immunostain was performed on sections of five consecutive neoplastic glands with and without GPs from 86 colonic adenocarcinomas to assess the expression of laminin 5gamma2. Neoplastic glands with GPs were observed in 85% (73/86) of the tumors. Laminin 5gamma2 was expressed in 92% (335/365) of the neoplastic glands with GPs but only in 17% (63/365) of the neoplastic glands without GPs (p<0.05). Laminin 5gamma2 was overexpressed in the cells at the free ends of the pores in 88% of the neoplastic glands with GPs, but only in 14% of those without pores (p<0.05). Hence, at the growing edge of colonic carcinomas, laminin 5gamma2 was frequently expressed in neoplastic glands having GPs. Remarkably, the tumor cells at the free ends of the GPs overexpressed laminin 5gamma2, indicating increased production of this adhesion-migration macromolecule. The results suggest a close interaction between this adhesion-migration macromolecule, PG formation and the local progression of colonic carcinomas.

Purpose: Recently a common variant of the TGFBR1 gene, TGFBR1*6A, has been proposed to act as a low-penetrance tumor susceptibility allele for colorectal cancer, but data from published studies with individually low statistical power are conflicting. To further evaluate the relationship between TGFBR1*6A and colorectal cancer risk, we have conducted a large case-control study and a meta-analysis of previously published studies., Experimental Design: A total of 1,042 colorectal cancer cases and 856 population controls were genotyped for the TGFBR1*6A polymorphism. Previously published case-control studies of the relationship between TGFBR1*6A and colorectal cancer were identified, and a meta-analysis was conducted., Results: We found no evidence that homozygosity, heterozygosity or carrier status for the TGFBR1*6A allele confers an increased risk of colorectal cancer; respective odds ratios (OR) were 1.05 [95% confidence interval (95% CI), 0.83-1.32], 0.82 (95% CI, 0.34-1.99), and 0.92 (95% CI, 0.74-1.15), respectively. A meta-analysis of our case-control study and seven other studies that provided data on 2,627 colorectal cancer cases and 3,387 controls also yielded no evidence that possession of the TGFBR1*6A allele is associated with an elevated risk of colorectal cancer; pooled estimate of the OR were 1.20 (95% CI, 0.64-2.24) for homozygosity, 1.11 (95% CI, 0.96-1.29) for heterozygosity, and 1.13 (95% CI, 0.98-1.30) for carriers of TGFBR1*6A., Conclusion: Current data provide limited support for the hypothesis that sequence variation in TGFBR1 defined by the TGFBR1*6A allele confers an elevated risk of colorectal cancer.