OBJECTIVE: To construct a clinical prediction rule for coronary artery disease (CAD) presenting with chest pain in primary care.

STUDY DESIGN AND SETTING: Meta-Analysis using 3,099 patients from five studies. To identify candidate predictors, we used random forest trees, multiple imputation of missing values, and logistic regression within individual studies. To generate a prediction rule on the pooled data, we applied a regression model that took account of the differing standard data sets collected by the five studies.

RESULTS: The most parsimonious rule included six equally weighted predictors: age ≥55 (males) or ≥65 (females) (+1); attending physician suspected a serious diagnosis (+1); history of CAD (+1); pain brought on by exertion (+1); pain feels like "pressure" (+1); pain reproducible by palpation (-1). CAD was considered absent if the prediction score is <2. The area under the ROC curve was 0.84. We applied this rule to a study setting with a CAD prevalence of 13.2% using a prediction score cutoff of <2 (i.e., -1, 0, or +1). When the score was <2, the probability of CAD was 2.1% (95% CI: 1.1-3.9%); when the score was ≥ 2, it was 43.0% (95% CI: 35.8-50.4%).

CONCLUSIONS: Clinical prediction rules are a key strategy for individualizing care. Large data sets based on electronic health records from diverse sites create opportunities for improving their internal and external validity. Our patient-level meta-analysis from five primary care sites should improve external validity. Our strategy for addressing site-to-site systematic variation in missing data should improve internal validity. Using principles derived from decision theory, we also discuss the problem of setting the cutoff prediction score for taking action.

Little is known about postprandial release of serum ghrelin, glucagon, and glucagon-like peptide-1 (GLP-1) in relation with differing fasting insulin levels. We hypothesized that these hormones are affected by insulin resistance, and hence, we compared different postprandial responses of GLP-1, glucagon, and ghrelin in subjects with relatively high (RHI) or relatively low (RLI) fasting insulin levels. The trial was a randomized crossover study with 4 different meal conditions. Fourteen nonobese or obese, healthy, men and 14 women were randomly assigned to the order of supervised intake of a 750 kcal drink with the same protein contents but with 20 energy-percent (E%) or 55 E% from carbohydrates, and the remaining energy from fat. Participants were also randomized to consume the drinks as 1 large beverage or as five 150-kcal portions every 30 minutes. The 28 subjects were divided into 2 equally sized groups based on fasting insulin levels. Statistics were done with general linear mixed model. Fasting insulin levels were 3-fold higher in the group with RHI compared with the RLI group (RHI: 1004 +/- 510 pg/mL, RLI: 324 +/- 123 pg/mL, P amp;lt; .0005). Serum GLP-1 was highest in the RHI group after both single meals and after 5 drinks and following high- and low-carbohydrate meals (both P amp;lt;= .002), and this was the case also for glucagon levels (both P amp;lt;= .018), whereas ghrelin levels did not differ between groups. Thus, subjects with RHI displayed both higher postprandial serum GLP-1 and glucagon than the participants with RLI, suggesting that glucagon could play a role in the advent of dysglycemia by insulin resistance. (C) 2019 Elsevier Inc. All rights reserved.

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Background: The characteristics of patients with on-going myocardial infarction (MI) contacting the primary healthcare (PHC) centre before hospitalisation are not well known. Prompt diagnosis is crucial in patients with MI, but many patients delay seeking medical care. The aims of this study was to 1) describe background characteristics, symptoms, actions and delay times in patients contacting the PHC before hospitalisation when falling ill with an acute MI, 2) compare those patients with acute MI patients not contacting the PHC, and 3) explore factors associated with a PHC contact in acute MI patients. Methods: This was a cross-sectional multicentre study, enrolling consecutive patients with MI within 24 hours of admission to hospital from Nov 2012 until Feb 2014. Results: A total of 688 patients with MI, 519 men and 169 women, were included; the mean age was 66 +/- 11 years. One in five people contacted PHC instead of the recommended emergency medical services (EMS), and 94% of these patients experienced cardinal symptoms of an acute MI; i.e., chest pain, and/or radiating pain in the arms, and/or cold sweat. Median delay time from symptom-onset-to-decision-to-seek-care was 2:15 hours in PHC patients and 0:40 hours in non-PHC patients (pamp;lt;0.01). The probability of utilising the PHC before hospitalisation was associated with fluctuating symptoms (OR 1.74), pain intensity (OR 0.90) symptoms during off-hours (OR 0.42), study hospital (OR 3.49 and 2.52, respectively, for two of the county hospitals) and a final STEMI diagnosis (OR 0.58). Conclusions: Ambulance services are still underutilized in acute MI patients. A substantial part of the patients contacts their primary healthcare centre before they are diagnosed with MI, although experiencing cardinal symptoms such as chest pain. There is need for better knowledge in the population about symptoms of MI and adequate pathways to qualified care. Knowledge and awareness amongst primary healthcare professionals on the occurrence of MI patients is imperative.

Objective: Primary care staff faces a complex work environment including a heavy administrative work load and perceive some work tasks as illegitimate. This study aimed to elucidate associations between the perceived legitimacy of work tasks, the psychosocial work environment, and the utilization of work time among Swedish primary care staff.

Design and setting: The study was designed as a multicenter study involving all staff categories, i.e. registered nurses, primary care physicians, care administrators, nurse assistants and allied professionals, at eleven primary care centers in Sweden.

Subjects: Participants completed the Bern Illegitimate Tasks Scale and the Copenhagen Psychosocial Questionnaire. They also recorded time spent on all work tasks, day by day during two separate weeks.

Main outcome measures and results: More than a quarter (27%) of primary care physicians perceived a high proportion of unnecessary work tasks. After adjusting for profession, age and gender, the perception of having to perform unreasonable work tasks was positively associated with experiencing role conflicts and with the proportion of organization-related administration and service work tasks.

Conclusion: Across all staff groups, the perception of unreasonable work tasks was more pronounced among staff with a high proportion of non-patient related administration. Also, the perception of having to perform a large amount of illegitimate work tasks affected the psychosocial work environment negatively, which might influence staffs perception of their professional roles. These results illuminate the importance of decision makers to thoroughly consider the distribution and allocation of non-patient related work tasks among staff in primary care.Key pointsWe observed an interaction between perception of having a large proportion of illegitimate work tasks and impaired psychosocial work environment. • More than a quarter of the primary care physicians perceived a high proportion of unnecessary work tasks.• Across all staff groups, performing unreasonable work tasks was associated with an experience of having role conflicts.• Across all staff groups, a perception of performing unreasonable work tasks was associated with the proportion of non-patient related administrative work tasks.

Background: Over the past decades, reorganizations and structural changes in Swedish primary care have affected time utilization among health care professionals. Consequently, increases in administrative tasks have substantially reduced the time available for face-to-face consultations. This study examined how work-time was utilized and the association between work time utilization and the perceived psychosocial work environment in Swedish primary care settings. Methods: This descriptive, multicentre, cross-sectional study was performed in 2014-2015. Data collection began with questionnaire. In the first section, respondents were asked to estimate how their workload was distributed between patients (direct and indirect patient work) and other work tasks. The questionnaire also comprised the Copenhagen Psychosocial Questionnaire, which assessed the psychosocial work environment. Next a time study was conducted where the participants reported their work-time based on three main categories: direct patient-related work, indirect patient-related work, and other work tasks. Each main category had a number of subcategories. The participants recorded the time spent (minutes) on each work task per hour, every day, for two separate weeks. Eleven primary care centres located in southeast Sweden participated. All professionals were asked to participate (n = 441), including registered nurses, primary care physicians, care administrators, nurse assistants, and allied professionals. Response rates were 75% and 79% for the questionnaires and the time study, respectively. Results: All health professionals allocated between 30.9% - 37.2% of their work-time to each main category: direct patient work, indirect patient work, and other work. All professionals estimated a higher proportion of time spent in direct patient work than they reported in the time study. Physicians scored highest on the psychosocial scales of quantitative demands, stress, and role conflicts. Among allied professionals, the proportion of work-time spent on administrative tasks was associated with more role conflicts. Younger staff perceived more adverse working conditions than older staff. Conclusions: This study indicated that Swedish primary care staff spent a limited proportion of their work time directly with patients. PCPs seemed to perceive their work environment in negative terms to a greater extent than other staff members. This study showed that work task allocations influenced the perceived psychosocial work environment.

Objective Blood pressure variability (BPV) has been associated with risk of cardiovascular events in observational studies, independently of mean BP levels. In states with higher autonomic imbalance, such as in diabetes, the importance of BP variability may theoretically be even greater. We aimed to investigate the incremental value of BPV for prediction of cardiovascular and all-cause mortality in patients with type 2 diabetes. Methods We identified 9,855 patients without pre-existing cardiovascular disease who did not change BP-lowering treatment during the observation period from a Swedish primary health care cohort of patients with type 2 diabetes. BPV was summarized as the standard deviation (SD), coefficient of variation (CV), or variation independent of mean (VIM). Patients were followed for a median of 4 years and associations with cardiovascular and all-cause mortality were investigated using Cox proportional hazards models. Results BPV was not associated with cardiovascular specific or all-cause mortality in the total sample. In patients who were not on BP-lowering drugs during the observation period (n = 2,949), variability measures were associated with all-cause mortality: hazard ratios were 1.05, 1.04 and 1.05 for 50% increases in SD, CV and VIM, respectively, adjusted for Framingham risk score risk factors, including mean BP. However, the addition of the variability measures in this subgroup only led to very minimal improvement in discrimination, indicating they may have limited clinical usefulness (change in C-statistic ranged from 0.000-0.003 in all models). Conclusions Although BPV was independently associated with all-cause mortality in diabetes patients in primary care who did not have pre-existing cardiovascular disease or BP-lowering drugs, it may be of minimal clinical usefulness above and beyond that of other routinely measured predictors, including mean BP.

Objectives: To investigate the effect of 15 weeks of resistance training on the frequency of moderate to severe hot flushes in postmenopausal women. Study design: Postmenopausal women with at least 4 moderate or severe hot flushes or night sweats per day day were randomized to a 15-week resistance training intervention or unchanged physical activity. Participants did not exercise regularly at baseline and had not used any therapy for hot flushes two months prior to study entry. The resistance training was performed three times per week and the program contained 8 exercises performed with 8-12 repetitions in 2 sets. Loads were set individually from eight-repetition maximum-strength tests and increased progressively. Main outcome measures: The primary outcome was change in mean moderate or severe hot flushes per day from baseline to week 15, assessed with symptom diaries. Secondary outcomes included change in hot flush score and time spent on physical activity. Results: Between November 19, 2013, and October 26, 2016, 65 women were enrolled; 58 completed the trial and were included in the analyses. The mean age was 55 and the mean number of moderate or severe hot flushes per day at baseline was 7.1; there were no baseline differences between groups. The frequency of hot flushes decreased more in the intervention group than in the control group (mean difference -2.7, 95% CI -4.2 to -1.3). The mean percentage change was -43.6% (-56.0 to -31.3) in the intervention group and -2.0% (16.4-12.4) in the control group. Conclusion: A 15-week resistance-training program decreased the frequency of moderate and severe hot flushes among postmenopausal women and could be an effective and safe treatment option to alleviate vasomotor symptoms.

Aims: Obesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons. Methods: We prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight amp;lt; 25 kg/m(2), overweight 25-29 kg/m(2), and obesity amp;gt;= 30 kg/m(2) ). Echocardiography was performed at the beginning of the study and after 4-years in the patient group. Results: Univariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/e (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. - 18.6% (2.3%) for normal weight patients, 53% (8%) vs. - 17.5% (2.3%) for overweight, and 49% (9%) vs. - 16.2% (3.0%) for obese (p amp;lt; 0.05 vs. p amp;lt;0.05). Corresponding results in the control group were 58% (6%) vs. -22.3% (3.0%), 55% (7%) vs. - 20.8% (3.1%) and 54% (8%) - 19.6% (4.0%) (p amp;lt;0.05 vs. p amp;lt;0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by - 1.0 (9.0) % (n =187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n =179) (p amp;lt;0.05). Conclusion: Overweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons.

Aim: The aim of the present study was to study the renal function and the relationship of deterioration in renal function with major outcomes in elderly nursing home residents. A second aim was to compare the internationally recommended formulae for estimated glomerular filtration rate (eGFR) consisting of both creatinine and cystatin C in a nursing home population. Methods: A total of 429 patients from 11 nursing homes were included during 2008-2011. GFR was estimated, from formulae based on both creatinine and cystatin C, at baseline and after 1 and 2 years. The patients were divided into groups based on chronic kidney disease level, and comparisons were made for mortality, morbidity, the use of medications and between the different formulae for eGFR. Results: Survival was lower in the groups with lower renal function. Over 60% of the residents had impaired renal function. Those with impaired renal function were older, had a higher number of medications and a higher prevalence of heart failure. Higher number of medications was associated with a greater risk of rapid decline in renal function with an odds ratio of 1.2 (95% confidence interval 1.06-1.36, P = 0.003). The compared eGFR formulae based on both cystatin C and creatinine were in excellent concordance with each other. Conclusions: Decreased renal function was associated with increased mortality. A majority of nursing home residents had declining renal function, which should be considered when prescribing medications. The more medications, the higher the risk for rapidly declining renal function.

Background: Diabetic kidney disease (DKD) is a leading risk factor for end-stage renal disease and is one of the most important risk factors for cardiovascular disease in patients with diabetes. It is possible that novel markers portraying the pathophysiological underpinning processes may be useful. Aim: To investigate the associations between 80 circulating proteins, measured by a proximity extension assay, and prevalent DKD and major adverse cardiovascular events (MACE) in type 2 diabetes. Methods: We randomly divided individuals with type 2 diabetes from three cohorts into a two-thirds discovery and one-third replication set (total n = 813, of whom 231 had DKD defined by estimated glomerular filtration rate amp;lt;60 mg/mL/1.73 m(2) and/or urinary albumin-creatinine ratio amp;gt;= 3 g/mol). Proteins associated with DKD were also assessed as predictors for incident major adverse cardiovascular events (MACE) in persons with DKD at baseline. Results: Four proteins were positively associated with DKD in models adjusted for age, sex, cardiovascular risk factors, glucose control, and diabetes medication: kidney injury molecule-1 (KIM-1, odds ratio [OR] per standard deviation increment, 1.65, 95% confidence interval [CI] 1.27-2.14); growth differentiation factor 15 (GDF-15, OR 1.40, 95% CI 1.16-1.69); myoglobin (OR 1.57, 95% CI 1.30-1.91), and matrix metalloproteinase 10 (MMP-10, OR 1.43, 95% CI 1.17-1.74). In patients with DKD, GDF-15 was significantly associated with increased risk of MACE after adjustments for baseline age, sex, microalbuminuria, and kidney function and (59 MACE events during 7 years follow-up, hazard ratio per standard deviation increase 1.43 [95% CI 1.03-1.98]) but not after further adjustments for cardiovascular risk factors. Conclusion: Our proteomics approach confirms and extends previous associations of higher circulating levels of GDF-15 with both micro- and macrovascular disease in patients with type 2 diabetes. Our data encourage additional studies evaluating the clinical utility of our findings.

Background Identifying simple, low-cost and scalable means of supporting lifestyle change and medication adherence for patients following a cardiovascular (CV) event is important. Objective The TEXTMEDS (TEXT messages to improve MEDiGation adherence and Secondary prevention) study aims to investigate whether a cardiac education and support programme sent via mobile phone text message improves medication adherence and risk factor levels in patients following an acute coronary syndrome (ACS). Study design A single-blind, multicentre, randomised clinical trial of 1400 patients after an ACS with 12 months follow-up. The intervention group will receive multiple weekly text messages that provide information, motivation, support to adhere to medications, quit smoking (if relevant) and recommendations for healthy diet and exercise. The primary endpoint is the percentage of patients who are adherent to cardioprotective medications and the key secondary outcomes are mean systolic blood pressure (BP) and low density lipoprotein cholesterol. Secondary outcomes will also include total cholesterol, mean diastolic BP, the percentage of participants who are adherent to each cardioprotective medication class, the percentage of participants who achieve target levels of CV risk factors, major vascular events, hospital readmissions and all-cause mortality. The study will be augmented by formal economic and proGess evaluations to assess acceptability, utility and Gost-effectiveness. Summary The study will provide multicentre randomised trial evidence of the effects of a text message-based programme on cardioprotective medication adherence and levels of CV risk factors. Ethics and dissemination Primary ethics approval was received from Western Sydney Local Health District Human Research EthiGs Committee (HREC2012/12/4.1 (3648) AU RED HREC/13ANMEAD/15). Results will be disseminated via peer-reviewed publications and presentations at international conferences.

In 2008, Ecuador underwent a major health reform with the aim of universal coverage. Little is known about the implementation of the reform and its perceived effects in rural parts of the country. The aim of this study was to explore the perceived effects of the 2008 health reform implementation, on rural primary health care services and financial access of the rural poor. A qualitative study using focus group discussions was conducted in a rural region in Ecuador, involving health staff, local health committee members, village leaders, and community health workers. Qualitative content analysis focusing on the manifest content was applied. Three categories emerged from the texts: (1) the prereform situation, which was described as difficult in terms of financial access and quality of care; (2) the reform process, which was perceived as top-down and lacking in communication by the involved actors; lack of interest among the population was reported; (3) the effects of the reform, which were mainly perceived as positive. However, testimonies about understaffing, drug shortages, and access problems for those living furthest away from the health units show that the reform has not fully achieved its intended effects. New problems are a challenging health information system and people without genuine care needs overusing the health services. The results indicate that the Ecuadorean reform has improved rural primary health care services. Still, the reform faces challenges that need continued attention to secure its current achievements and advance the health system further.

Introduction: In many low- and middle-income countries emergency care is provided anywhere in the health system; however, no studies to date have looked at which providers are chosen by patients with perceived emergencies. Ecuador has universal health coverage that includes emergency care. However, earlier research indicates that patients with emergencies tend to seek private care. Our primary research questions were these: What is the scope of perceived emergencies?; What is their nature?; and What is the related healthcare-seeking behavior? Secondary objectives were to study determinants of healthcare-seeking behavior, compare health expenditure with expenditure from the past ordinary illness, and measure the prevalence of catastrophic health expenditure related to perceived emergencies. 

Methods: We conducted a cross-sectional survey of 210 households in a rural region of northwestern Ecuador. The households were sampled with two-stage cluster sampling and represent an estimated 20% of the households in the region. We used two structured, pretested questionnaires. The first questionnaire collected demographic and economic household data, expenditure data on the past ordinary illness, and presented our definition of perceived emergency. The second recorded the number of emergency events, symptoms, further case description, healthcare-seeking behavior, and health expenditure, which was defined as being catastrophic when it exceeded 40% of a household´s ability to pay.

Results: The response rate was 85% with a total of 74 reported emergency events during the past year (90/1,000 inhabitants). We further analyzed the most recent event in each household (n=54). Private, for-profit providers, including traditional healers, were chosen by 57.4% (95% confidence interval [CI] [44-71%]). Public providers treated one third of the cases. The mean health expenditure per event was $305.30 United States dollars (USD), compared to $135.80 USD for the past ordinary illnesses. Catastrophic health expenditure was found in 24.4% of households. 

Conclusion: Our findings suggest that the provision of free health services may not be sufficient to reach universal health coverage for patients with perceived emergencies. Changes in the organization of public emergency departments and improved financial protection for emergency patients may improve the situation.

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Context: GH is a strong regulator of metabolism. In obesity, both GH secretion and adipose tissue GHR gene expression are decreased. More detailed information on the regulation of GHR, STAT3/5, and downstream-regulated genes in human adipose tissue during diet-induced weight loss and weight gain is lacking. Objective: The aim of the present study was to investigate the gene expression patterns of GHR and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway (JAK2, STAT3, STAT5A, and STAT5B) in human subcutaneous adipose tissue in relation to energy restriction and overfeeding. Design, Patients, and Interventions: Tissue distribution was analyzed in a data set generated by RNA sequencing containing information on global expression in human tissues. Subcutaneous adipose tissue or adipocyte gene expression (measured by DNA microarrays) was investigated in the following settings: (i) individuals with obesity vs individuals with normal weight; (ii) energy restriction; and (iii) overfeeding. Results: GHR expression was decreased in subjects with obesity compared with subjects with normal weight (P amp;lt; 0.001). It was increased in response to energy restriction and decreased in response to overfeeding (P = 0.015 and P = 0.030, respectively). STAT3 expression was increased in subjects with obesity (P amp;lt; 0.001). It was decreased during energy restriction and increased during overfeeding (P = 0.004 and P = 0.006, respectively). STAT3-regulated genes showed an overall view of overexpression in obesity. Conclusions: The results of the present study have shown that GHR, STAT3, and STAT3-regulated genes are dynamically, and reciprocally, regulated at the tissue level in response to energy restriction and overfeeding, suggesting that GH signaling is perturbed in obesity.

Objective: The aim of the study was to describe and explore patient agency through resistance in decision-making about cardiovascular preventive drugs in primary care. Design: Six general practitioners from the southeast of Sweden audiorecorded 80 consultations. From these, 28 consultations with proposals from GPs for cardiovascular preventive drug treatments were chosen for theme-oriented discourse analysis. Results: The study shows how patients participate in decision-making about cardiovascular preventive drug treatments through resistance in response to treatment proposals. Passive modes of resistance were withheld responses and minimal unmarked acknowledgements. Active modes were to ask questions, contest the address of an inclusive we, present an identity as a non-drugtaker, disclose non-adherence to drug treatments, and to present counterproposals. The active forms were also found in anticipation to treatment proposals from the GPs. Patients and GPs sometimes displayed mutual renouncement of responsibility for decision-making. The decision-making process appeared to expand both beyond a particular phase in the consultations and beyond the single consultation. Conclusions: The recognition of active and passive resistance from patients as one way of exerting agency may prove valuable when working for patient participation in clinical practice, education and research about patient-doctor communication about cardiovascular preventive medication. We propose particular attentiveness to patient agency through anticipatory resistance, patients disclosures of non-adherence and presentations of themselves as non-drugtakers. The expansion of the decision-making process beyond single encounters points to the importance of continuity of care.

Objective The aim of this study was to investigate whether the effects on local blood flow and metabolic changes observed in the skin after an endogenous systemic increase in insulin are mediated by the endothelial nitric oxide pathway, by administering the nitric oxide synthase inhibitor N-G-monomethyl l-arginine using microdialysis. Methods Microdialysis catheters, perfused with N-G-monomethyl l-arginine and with a control solution, were inserted intracutaneously in 12 human subjects, who received an oral glucose load to induce a systemic hyperinsulinemia. During microdialysis, the local blood flow was measured by urea clearance and by laser speckle contrast imaging, and glucose metabolites were measured. Results After oral glucose intake, microvascular blood flow and glucose metabolism were both significantly suppressed in the N-G-monomethyl l-arginine catheter compared to the control catheter (urea clearance: P amp;lt; .006, glucose dialysate concentration: P amp;lt; .035). No significant effect of N-G-monomethyl l-arginine on microvascular blood flow was observed with laser speckle contrast imaging (P = .81). Conclusion Local delivery of N-G-monomethyl l-arginine to the skin by microdialysis reduces microvascular blood flow and glucose delivery in the skin after oral glucose intake, presumably by decreasing local insulin-mediated vasodilation.

Objective We aimed to evaluate the effects on depression scores of a lifestyle-focused cardiac support programme delivered via mobile phone text messaging among patients with coronary heart disease (CHD). Design Substudy and secondary analysis of a parallel-group, single-blind randomised controlled trial of patients with CHD. Setting A tertiary hospital in Sydney, Australia. Intervention The Tobacco, Exercise and dieT MEssages programme comprised four text messages per week for 6 months that provided education, motivation and support on diet, physical activity, general cardiac education and smoking, if relevant. The programme did not have any specific mental health component. Outcomes Depression scores at 6 months measured using the Patient Health Questionnaire-9 (PHQ-9). Treatment effect across subgroups was measured using log-binomial regression model for the binary outcome (depressed/not depressed, where depressed is any score of PHQ-9 amp;gt;= 5) with treatment, subgroup and treatment by subgroup interaction as fixed effects. Results Depression scores at 6 months were lower in the intervention group compared with the control group, mean difference 1.9 (95% CI 1.5 to 2.4, pamp;lt;0.0001). The frequency of mild or greater depressive symptoms (PHQ-9 scores amp;gt;= 5) at 6 months was 21/333 (6.3%) in the intervention group and 86/350 (24.6%) in the control group (relative risk (RR) 0.26, 95% CI 0.16 to 0.40, pamp;lt;0.001). This proportional reduction in depressive symptoms was similar across groups defined by age, sex, education, body mass index, physical activity, current smoking, current drinking and history of depression, diabetes and hypertension. In particular, the rates of PHQ-9 amp;gt;= 5 among people with a history of depression were 4/44 (9.1%) vs 29/62 (46.8%) in intervention vs control (RR 0.19, 95% CI 0.07 to 0.51, pamp;lt;0.001), and were 17/289 (5.9%) vs 57/288 (19.8%) among others (RR 0.30, 95% CI 0.18 to 0.50, pamp;lt;0.001). Conclusions Among people with CHD, a cardiac support programme delivered via mobile phone text messaging was associated with fewer symptoms of mild-to-moderate depression at 6 months in the treatment group compared with controls.

Skin and kidney microvascular functions may be affected independently in diabetes mellitus. We investigated skin microcirculatory function in 79 subjects with diabetes type 2, where 41 had microalbuminuria and 38 not, and in 41 age-matched controls. The oxygen saturation, fraction of red blood cells and speed-resolved microcirculatory perfusion (% red blood cells x mm/s) divided into three speed regions: 0-1, 1-10 and above 10 mm/s, were assessed during baseline and after local heating of the foot with a new device integrating diffuse reflectance spectroscopy and laser Doppler flowmetry. Arterial stiffness was assessed as carotid-femoral pulse wave velocity. Subjects with diabetes and microalbuminuria had significantly higher carotid-femoral pulse wave velocity compared to subjects without microalbuminuria and to controls. The perfusion for speeds 0-1 mm/s and red blood cell tissue fraction were reduced in subjects with diabetes at baseline and after heating, independent of microalbuminuria. These parameters were correlated to HbA1c. In conclusion, the reduced nutritive perfusion and red blood cell tissue fraction in type 2 diabetes were related to long-term glucose control but independent of microvascular changes in the kidneys and large-vessel stiffness. This may be due to different pathogenic pathways in the development of nephropathy, large-vessel stiffness and cutaneous microvascular impairment.

We have determined in vivo optical scattering properties of normal human skin in 1734 subjects, mostly with fair skin type, within the Swedish CArdioPulmonary bioImage Study. The measurements were performed with a noninvasive system, integrating spatially resolved diffuse reflectance spectroscopy and laser Doppler flowmetry. Data were analyzed with an inverse Monte Carlo algorithm, accounting for both scattering, geometrical, and absorbing properties of the tissue. The reduced scattering coefficient was found to decrease from 3.16 ± 0.72 to 1.13 ± 0.27 mm-1 (mean ± SD) in the 475- to 850-nm wavelength range. There was a negative correlation between the reduced scattering coefficient and age, and a significant difference between men and women in the reduced scattering coefficient as well as in the fraction of small scattering particles. This large study on tissue scattering with mean values and normal variation can serve as a reference when designing diagnostic techniques or when evaluating the effect of therapeutic optical systems.

The Australian Dietary Guidelines (ADGs) and Health Star Rating (HSR) front-of-pack labelling system are two national interventions to promote healthier diets. Our aim was to assess the degree of alignment between the two policies. Methods: Nutrition information was extracted for 65,660 packaged foods available in The George Institutes Australian FoodSwitch database. Products were classified core or discretionary based on the ADGs, and a HSR generated irrespective of whether currently displayed on pack. Apparent outliers were identified as those products classified core that received HSR amp;lt;= 2.0; and those classified discretionary that received HSR amp;gt;= 3.5. Nutrient cut-offs were applied to determine whether apparent outliers were high in salt, total sugar or saturated fat, and outlier status thereby attributed to a failure of the ADGs or HSR algorithm. Results: 47,116 products (23,460 core; 23,656 discretionary) were included. Median (Q1, Q3) HSRs were 4.0 (3.0 to 4.5) for core and 2.0 (1.0 to 3.0) for discretionary products. Overall alignment was good: 86.6% of products received a HSR aligned with their ADG classification. Among 6324 products identified as apparent outliers, 5246 (83.0%) were ultimately determined to be ADG failures, largely caused by challenges in defining foods as core or discretionary. In total, 1078 (17.0%) were determined to be true failures of the HSR algorithm. Conclusion: The scope of genuine misalignment between the ADGs and HSR algorithm is very small. We provide evidence-informed recommendations for strengthening both policies to more effectively guide Australians towards healthier choices.

Aims: To compare long-term changes in healthcare utilization and costs for type 2 diabetes patients before and after insulin initiation, as well as healthcare costs after insulin versus non-insulin anti-diabetic (NIAD) initiation. Methods: Patients newly initiated on insulin (n = 2823) were identified in primary health care records from 84 Swedish primary care centers, between 1999 to 2009. First, healthcare costs per patient were evaluated for primary care, hospitalizations and secondary outpatient care, before and up to seven years after insulin initiation. Second, patients prescribed insulin in second line were matched to patients prescribed NIAD in second line, and the healthcare costs of the matched groups were compared. Results: The total mean annual healthcare cost increased from 1656 per patient 2 years before insulin initiation to 3814 seven years after insulin initiation. The total cumulative mean healthcare cost per patient at year 5 after second-line treatment was 13,823 in the insulin group compared to 9989 in the NIAD group. Conclusions: Initiation of insulin in type 2 diabetes patients was followed by increased healthcare costs. The increases in costs were larger than those seen in a matched patient population initiated on NIAD treatment in second-line. (C) 2016 The Author(s). Published by Elsevier Ltd on behalf of Primary Care Diabetes Europe. This is an open access article under the CC BY-NC-ND license.

Background

Atrial fibrillation (AF) is associated with substantial morbidity, in particular stroke. Despite good evidence for the reduction of stroke risk with anticoagulant therapy, there remains significant undertreatment. The main aim of the current study was to investigate whether a clinical decision support tool (CDS) for stroke prevention integrated in the electronic health record could improve adherence to guidelines for stroke prevention in patients with AF.

Methods and findings

We conducted a cluster-randomized trial where all 43 primary care clinics in the county of Östergötland, Sweden (population 444,347), were randomized to be part of the CDS intervention or to serve as controls. The CDS produced an alert for physicians responsible for patients with AF and at increased risk for thromboembolism (according to the CHA2DS2-VASc algorithm) without anticoagulant therapy. The primary endpoint was adherence to guidelines after 1 year. After randomization, there were 22 and 21 primary care clinics in the CDS and control groups, respectively. There were no significant differences in baseline adherence to guidelines regarding anticoagulant therapy between the 2 groups (CDS group 70.3% [5,186/7,370; 95% CI 62.9%–77.7%], control group 70.0% [4,187/6,009; 95% CI 60.4%–79.6%], p = 0.83). After 12 months, analysis with linear regression with adjustment for primary care clinic size and adherence to guidelines at baseline revealed a significant increase in guideline adherence in the CDS (73.0%, 95% CI 64.6%–81.4%) versus the control group (71.2%, 95% CI 60.8%–81.6%, p = 0.013, with a treatment effect estimate of 0.016 [95% CI 0.003–0.028]; number of patients with AF included in the final analysis 8,292 and 6,508 in the CDS and control group, respectively). Over the study period, there was no difference in the incidence of stroke, transient ischemic attack, or systemic thromboembolism in the CDS group versus the control group (49 [95% CI 43–55] per 1,000 patients with AF in the CDS group compared to 47 [95% CI 39–55] per 1,000 patients with AF in the control group, p = 0.64). Regarding safety, the CDS group had a lower incidence of significant bleeding, with events in 12 (95% CI 9–15) per 1,000 patients with AF compared to 16 (95% CI 12–20) per 1,000 patients with AF in the control group (p = 0.04). Limitations of the study design include that the analysis was carried out in a catchment area with a high baseline adherence rate, and issues regarding reproducibility to other regions.

Conclusions

The present study demonstrates that a CDS can increase guideline adherence for anticoagulant therapy in patients with AF. Even though the observed difference was small, this is the first randomized study to our knowledge indicating beneficial effects with a CDS in patients with AF.

Background Atrial fibrillation (AF) is associated with substantial morbidity, in particular stroke. Despite good evidence for the reduction of stroke risk with anticoagulant therapy, there remains a significant undertreatment. The main aim of the current study is to investigate whethera clinical decision support tool for stroke prevention (CDS) integrated in the electronic health record can improve adherence to guidelines for stroke prevention in patients with AF. Methods We will conduct a cluster randomized trial where 43 primary care clinics in the county of Ostergotland, Sweden (population 444,347), will be randomized to be part of the CDS intervention or serve as controls. The CDS will alert responsible physicians of patients with AF and increased risk for thromboembolism according to the CHA(2)DS(2)VASc (Congestive heart failure, Hypertension, Age 74 years, Diabetes mellitus, previous Stroke/TIA/thromboembolism, Vascular disease, Age 65-74 years, Sex category (i.e. female sex)) algorithm without anticoagulant therapy. The primary end point will be adherence to guidelines after 1 year. Conclusion The present study will investigate whether a clinical decision support system integrated in an electronic health record can increase adherence to guidelines regarding anticoagulant therapy in patients with AF.

Although previous research has indicated some recurrent themes and similarities between what patients from different cultures regard as a good death, the concept is complex and there is lack of studies from the Nordic countries. The aim of this study was to explore the perception of a good death in dying cancer patients in Sweden. Interviews were conducted with 66 adult patients with cancer in the palliative phase who were recruited from home care and hospital care. Interviews were analysed using qualitative content analysis. Participants viewed death as a process. A good death was associated with living with the prospect of imminent death, preparing for death and dying comfortably, e.g., dying quickly, with independence, with minimised suffering and with social relations intact. Some were comforted by their belief that death is predetermined. Others felt uneasy as they considered death an end to existence. Past experiences of the death of others influenced participants views of a good death. Healthcare staff caring for palliative patients should consider asking them to describe what they consider a good death in order to identify goals for care. Exploring patients personal experience of death and dying can help address their fears as death approaches.

Objective: To investigate clinicians perspectives on the factors that shape the process of advance care planning in a nursing home context. Design: Interviews. Latent qualitative content analysis. Setting: Nine nursing homes in Sweden. Subjects: 14 physicians and 11 nurses working at nursing homes. Main outcome measures: Participants views on advance care planning (ACP) at nursing homes. Results: The analysis of the interviews resulted in four manifest categories: Exploration of preferences and views, e.g. exploring patient wishes regarding end-of-life issues and restrictions in care at an early stage, and sensitivity to patients readiness to discuss end-of-life issues; Integration of preferences and views, e.g. integration of patients preferences and staffs and family members views; Decision amp; documentation of the ACP, e.g. clear documentation in patients medical records that are up-to-date and available for staff caring for the patient, and Implementation amp; re-evaluation of the ACP, e.g. nurse following up after ACP-appointment to confirm the content of the documented ACP. The latent theme, Establishing beneficence - defending oneself against tacit accusations of maleficence, emerged as a deeper meaning of all the four (manifest) parts of the ACP-process Conclusion: This study stresses the importance of involving patients, family members, and the team in the work with advance care planning in nursing homes. In addition, clear medical record documentation and proficiency in end-of-life communication related to advance care planning for physicians as well as nurses may also be factors that significantly shape advance care planning in a nursing home context.

BACKGROUND:

Spousal concordance on risk factors and lifestyle habits exists and can partly be explained by patients' and spouses' health beliefs and underuse of cardiac rehabilitation. However, there have been very few qualitative comparisons of health beliefs between patients and spouses after a cardiac event.

AIM:

To examine and qualitatively compare the health beliefs of patients with coronary heart disease and their spouses about lifestyle habits, 1 year after the cardiac event.

DESIGN:

Explorative and descriptive.

METHOD:

Semi-structured focus group interviews were conducted with patients (n = 14) 1 year after a cardiac event, as well as individual interviews with spouses (n = 8). The transcriptions underwent a deductive qualitative content analysis, within the framework of the Health Belief Model.

FINDINGS:

Patients' and spouses' health beliefs about lifestyle habits qualitatively differed in most predetermined main analytical categories of the Health Belief Model. The patients relied more on their own capacity and the healthcare system than on collaboration with their spouses who instead emphasised the importance of mutual activities to establish lifestyle habits. The spouses therefore experienced problems with different family preferences compared to the patients' wishes. Moreover, only patients believed supervised exercise was beneficial for risk reduction of coronary heart disease and they related barriers for medication to a self-healing body and a meaningless life without relatives and old habits. Patients and spouses agreed that despite the severity of illness, life was captured and that normalisation to a life as usual was possible.

CONCLUSION:

The patients' and spouses' qualitatively different health beliefs regarding health-related behaviours imply a new approach. Nurses and associated professionals need to follow-up patients' and spouses' in primary health care to support them in a tailored way, for example in problem-based sessions. Recognition and understanding of their different views and otherness could lead to compromises and goals to work with.

Background

In managing a life with coronary heart disease and the possibility of planning and following a rehabilitation plan, patients’ empowerment and self-efficacy are considered important. However, currently there is limited data on levels of empowerment among patients with coronary heart disease, and demographic and clinical characteristics associated with patient empowerment are not known.

The purpose of this study was to assess the level of patient empowerment and general self-efficacy in patients six to 12 months after the cardiac event. We also aimed to explore the relationship between patient empowerment, general self-efficacy and other related factors such as quality of life and demographic variables.

Methods

A sample of 157 cardiac patients (78% male; age 68 ± 8.5 years) was recruited from a Swedish hospital. Patient empowerment was assessed using the SWE-CES-10. Additional data was collected on general self-efficacy and well-being (EQ5D and Ladder of Life). Demographic and clinical variables were collected from medical records and interviews.

Results

The mean levels of patient empowerment and general self-efficacy on a 0–4 scale were 3.69 (±0.54) and 3.13 (±0.52) respectively, and the relationship between patient empowerment and general self-efficacy was weak (r = 0.38). In a simple linear regression, patient empowerment and general self-efficacy were significantly correlated with marital status, current self-rated health and future well-being. Multiple linear regressions on patient empowerment (Model 1) and general self-efficacy (Model 2) showed an independent significant association between patient empowerment and current self-rated health. General self-efficacy was not independently associated with any of the variables.

Conclusions

Patients with a diagnosis of coronary heart disease reported high levels of empowerment and general self-efficacy at six to 12 months after the event. Clinical and demographic variables were not independently associated with empowerment or low general self-efficacy. Patient empowerment and general self-efficacy were not mutually interchangeable, and therefore both need to be measured when planning for secondary prevention in primary health care.

Background Prognostic factors in patients with localized primary cutaneous malignant melanoma (CMM) are well described. However, prognostic factors for recurrence are less documented. Objectives The aim of this study was to identify prognostic risk factors for first recurrence in patients with localized stages I-II CMM using population-based data. Methods This study included 1437 CMM patients registered in one region of Sweden during 1999-2012 follow-up through 31 December 2012. To identify first recurrence of CMM disease, data from a care data warehouse, the pathology and radiology department registries were used. Patients were also followed through a census register and the national Cause of Death Register. Results The 5- and 10-year recurrence-free survival (RFS) were 85.7% and 81.2%, respectively. The most common site of first recurrence was regional lymph node metastasis closely followed by distant metastasis. After adjusting for all prognostic factors, women had 50% lower risk of recurrence than men (HR = 0.5, 95% CI 0.4-0.7) and patients = 70 had higher risk compared to patients 55-69 years (HR = 1.7, 95% CI 1.2-2.5). Other significant prognostic factors for risk of recurrence were tumour thickness, presence of ulceration, Clarks level of invasion and histogenetic type. Conclusion Tumour thickness was found to be the predominant risk factor for recurrence. The prognostic factors for recurrence coincided with prognostic factors for CMM death. The most common site of first recurrence in stages I-II CMM is regional lymph node (42.8%) closely followed by distant metastases (37.6%), a fact which has to be taken into consideration when choosing follow-up strategies.

BACKGROUND: In the light of increasing skin cancer incidences worldwide, preventive measures to promote sun protection in individuals with risky sun habits have continued relevance and importance.

AIM: To report the long-term effect of individualised sun protection advice given in primary health care (PHC), on sun habits and sun protection behaviour.

DESIGN & SETTING: In 2005, 309 PHC patients were enrolled in a randomised controlled study performed in a Swedish PHC setting.

METHOD: At baseline, the study participants completed a Likert scale-based questionnaire, mapping sun habits, propensity to increase sun protection, and attitudes towards sun exposure, followed by randomisation into three intervention groups, all receiving individualised sun protection advice: in Group 1 (n = 116) by means of a letter, and in Group 2 (n = 97) and 3 (n = 96) communicated personally by a GP. In Group 3, participants also underwent a skin ultraviolet-sensitivity phototest, with adjusted sun protection advice based on the result. A repeated questionnaire was administered after 3 and 10 years.

RESULTS: Statistically significant declines were observed in all groups for sun exposure mean scores over time. When using a cumulative score, according to the Sun Exposure and Protection Index (SEPI), significantly greater decrease in SEPI mean score was observed in Groups 2 and 3 (GP), compared to Group 1 (letter); P<0.01. The addition of a phototest did not enhance the effect of the intervention.

CONCLUSION: Individualised sun protection advice mediated verbally by the GP can lead to sustained improvement of sun protective behaviour.

Previous work indicates that erythrocytes (RBCs) accumulate β-amyloid X-40 (Aβ40) in individuals with Alzheimer disease (AD) and to a lesser extent in healthy elderly. The toxin damages RBCs and increases their mean corpuscular volume (MCV). Furthermore, AD platelets demonstrate lower reactivity. This study investigated interactions between RBCs and platelets. Older individuals with moderate hypertension (n = 57) were classified into two groups, depending on MCV in whole blood: The MCV(high) group comprised individuals with higher MCV (n = 27; 97 ± 3(SD) fl) and MCV(low) group had relatively lower MCV (n = 30; 90 ± 3(SD) fl). Flow cytometry was used to determine platelet reactivity, i.e., the surface binding of fibrinogen after provocation. Adenosine diphosphate (ADP) and a thrombin receptor-activating protein (TRAP-6) were used as agonists. Subsequently, blood cells were divided according to density into 17 subfractions. Intra-RBC Aβ40 content was analyzed and in all platelet populations surface-bound fibrinogen was determined to estimate platelet in vivo activity. We found Aβ40 inside RBCs of approximately 50% of participants, but the toxin did not affect MCV and platelet reactivity. In contrast, MCV associated inversely with platelet reactivity as judged from surface-attached fibrinogen after ADP (1.7 μmol/L) (p < 0.05) and TRAP-6 provocation (57 μmol/L (p = 0.01) and 74 μmol/L (p < 0.05)). In several density fractions (nos. 3, 4, 8, 11-13 (p < 0.05) and nos. 5-7 (p < 0.01)) MCV linked inversely with platelet-attached fibrinogen. In our community-dwelling sample, enhanced MCV associated with decreased platelet reactivity and lower in vivo platelet activity. It resembles RBCs and platelet behavior in AD-type dementia.

Aims/hypothesis Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. Methods We combined data from six prospective epidemiological studies of 30-77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularised Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample. Results Of 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (+/- SD) of 6.4 +/- 2.3 years. We replicated associations (amp;lt; 5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)-12, IL-27 subunit alpha (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF)-23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis-inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample. Conclusions/interpretation We identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardiovascular event.

BackgroundIrritable Bowel Syndrome (IBS) is a chronic gastrointestinal disorder characterised by recurrent abdominal pain and disturbed bowel habits and unclear aetiology. IBS is also associated with psychosocial factors, impaired quality of life and lost work productivity. This study sought to determine whether the association between IBS and lost work productivity might be accounted for by poor coping strategies and loss of confidence in the healthcare system.MethodsCase-control design was employed sampling IBS and non-gastrointestinal (non-GI) primary healthcare seekers in a defined region in Sweden. Non-GI patients were of similar age and sex distribution to the IBS patients. Questionnaires applied in this study included instruments designed to measure confidence in the social security system and in the community, as well as questions about whether gastrointestinal problems might affect working life and Sense of coherence (SOC) questionnaire. The studys primary hypothesis was evaluated via an a priori path model.ResultsStatistically significant differences were found between IBS cases (n=305) and controls (n=369) concerning abdominal pain or discomfort affecting everyday performance at work (pamp;lt;0.0001). IBS cases also showed significantly lower (p=0.001) confidence in public healthcare. The studys hypothesis was supported with the finding of a statistically significant indirect association via poor coping strategies, although the indirect associations were lesser in magnitude than the direct association.ConclusionsThis study found a clear association between clinically diagnosed IBS status and interference in work by gastrointestinal symptoms in which sense of coherence might be of importance.

Aims

To study the association between baseline level of C-peptide and all-cause death, cardiovascular death and cardiovascular complications among persons with newly diagnosed type 2 diabetes.

Methods

The Skaraborg Diabetes Register contains data on baseline C-peptide concentrations among 398 persons <65 years with newly diagnosed type 2 diabetes 1996–1998. National registries were used to determine all-cause death, cardiovascular death and incidence of myocardial infarction and ischemic stroke until 31 December 2014. The association between baseline C-peptide and outcomes were evaluated with adjustment for multiple confounders by Cox regression analysis. Missing data were handled by multiple imputation.

Results

In the imputed and fully adjusted model there was a significant association between 1 nmol/l increase in C-peptide concentration and all-cause death (HR 2.20, 95% CI 1.49–3.25, p < 0.001, number of events = 104), underlying cardiovascular death (HR 2.69, 1.49–4.85, p = 0.001, n = 35) and the composite outcome of underlying cardiovascular death, myocardial infarction or ischemic stroke (HR 1.61, 1.06–2.45, p = 0.027, n = 90).

Conclusions

Elevated C-peptide levels at baseline in persons with newly diagnosed type 2 diabetes are associated with increased risk of all-cause and cardiovascular mortality. C-peptide might be used to identify persons at high risk of cardiovascular complications and premature death.

Aims Patients with type 2 diabetes have a high risk of cardiovascular disease (CVD). Central obesity has been particularly associated with this risk relationship. We aimed to evaluate waist to height ratio (WHtR) as a predictor of risk in such patients. Methods WHtR was evaluated as a predictor of the risk of CVD and mortality amongst 11125 participants with type 2 diabetes in the ADVANCE and ADVANCE-ON studies, and was compared with body mass index (BMI), waist circumference and waist hip ratio (WHR). Primary outcome was a composite of death from CVD, non-fatal myocardial infarction or non-fatal stroke. Secondary outcomes were myocardial infarction, stroke, cardiovascular death and death from any cause. Cox models were used, with bootstrapping to compare associations between anthropometric measures for the primary outcome. Results Median follow-up time was 9.0 years. There was a positive association between WHtR and adverse outcomes. The hazard ratio (HR) (confidence interval), per SD higher WHtR, was 1.16 (1.11-1.22) for the primary endpoint, with no heterogeneity by sex or region, but a stronger effect in individuals aged 66 years or older. The other 3 anthropometric measurements showed similar associations, although there was evidence that WHtR marginally outperformed BMI and WHR. Based on commonly used BMI cut-points, the equivalent WHtR cut-points were estimated to be 0.55 and 0.6, with no evidence of a difference across subgroups. Conclusions In patients with diabetes, WHtR is a useful indicator of future adverse risk, with similar effects in different population subgroups.

Background: Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events. We report the effects on heart failure (HF) and cardiovascular death overall, in those with and without a baseline history of HF, and in other participant subgroups. Methods: The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) enrolled 10142 participants with type 2 diabetes mellitus and high cardiovascular risk. Participants were randomly assigned to canagliflozin or placebo and followed for a mean of 188 weeks. The primary end point for these analyses was adjudicated cardiovascular death or hospitalized HF. Results: Participants with a history of HF at baseline (14.4%) were more frequently women, white, and hypertensive and had a history of prior cardiovascular disease (all Pamp;lt;0.001). Greater proportions of these patients were using therapies such as blockers of the renin angiotensin aldosterone system, diuretics, and -blockers at baseline (all Pamp;lt;0.001). Overall, cardiovascular death or hospitalized HF was reduced in those treated with canagliflozin compared with placebo (16.3 versus 20.8 per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67-0.91), as was fatal or hospitalized HF (HR, 0.70; 95% CI, 0.55-0.89) and hospitalized HF alone (HR, 0.67; 95% CI, 0.52-0.87). The benefit on cardiovascular death or hospitalized HF may be greater in patients with a prior history of HF (HR, 0.61; 95% CI, 0.46-0.80) compared with those without HF at baseline (HR, 0.87; 95% CI, 0.72-1.06; P interaction =0.021). The effects of canagliflozin compared with placebo on other cardiovascular outcomes and key safety outcomes were similar in participants with and without HF at baseline (all interaction P values amp;gt;0.130), except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of HF (P=0.03). Conclusions: In patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease, canagliflozin reduced the risk of cardiovascular death or hospitalized HF across a broad range of different patient subgroups. Benefits may be greater in those with a history of HF at baseline. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01032629 and NCT01989754.

Background and aims: Obesity is associated with diabetes type 2 and one of the most important risk factors for cardiovascular disease. We explored if sagittal abdominal diameter (SAD) is a better predictor of major cardiovascular events than waist circumference (WC) and body mass index (BMI) in type 2 diabetes. Methods and results: The CARDIPP study consists of a cohort of patients with type 2 diabetes. In this study we used data from 635 participants with no previous myocardial infarction or stroke, with a mean follow-up time of 7.1 years. SAD, WC and BMI were measured at baseline and the end-point was first cardiovascular event, measured as a composite of ICD-10 codes for acute myocardial infarction, stroke or cardiovascular mortality. SAD was significantly higher in the major cardiovascular event group compared to participants that did not suffer a major cardiovascular event during follow-up (p amp;lt; 0.001). SAD amp;gt; 25 cm was the only anthropometric measurement that remained associated with major cardiovascular events when adjusted for modifiable and non-modifiable factors (hazard ratio 2.81, 95% confidence interval 1.37-5.76, p = 0.005). Conclusion: SAD with the cut off level of amp;gt; 25 cm, if confirmed in larger studies, may be used as a more independent risk-assessment tool compared with WC in clinical practice, to identify persons with type 2 diabetes at high cardiovascular risk. (C) 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Aim: Sodium glucose co-transporter 2 (SGLT2) inhibitors appear to protect against increased risks of cardiovascular and kidney disease in patients with type 2 diabetes but also cause some harms. Whether effects are comparable across drug class or specific to individual compounds is unclear. This meta-analysis assessed the class and individual compound effects of SGLT2 inhibition versus control on cardiovascular events, death, kidney disease and safety outcomes in patients with type 2 diabetes. Methods: MEDLINE, EMBASE, the Cochrane Library and regulatory databases were systematically searched for data from randomized clinical trials that included reporting of cardiovascular events, deaths or safety outcomes. We used fixed effects models and inverse variance weighting to calculate relative risks with the 95% confidence intervals. Results: The analyses included data from 82 trials, four overviews and six regulatory reports and there were 1,968 major cardiovascular events identified for analysis. Patients randomly assigned to SGLT2 had lower risks of major cardiovascular events (RR 0.85, 95% CI 0.77-0.93), heart failure (RR 0.67, 95% CI 0.55-0.80), all-cause death (RR 0.79, 95% CI 0.70-0.88) and serious decline in kidney function (RR 0.59, 0.49-0.71). Significant adverse effects were observed for genital infections (RR 3.06, 95% CI 2.73-4.43), volume depletion events (RR 1.24, 95% CI 1.07-1.43) and amputation (RR 1.44 95% CI 1.13-1.83). There was a high likelihood of differences in the associations of the individual compounds with cardiovascular death, hypoglycaemia and amputation (all I-2 amp;gt; 80%) and a moderate likelihood of differences in the associations with non-fatal stroke, all-cause death, urinary tract infection and fracture (all I-2 amp;gt; 30%). Conclusion: There are strong overall associations of SGLT2 inhibition with protection against major cardiovascular events, heart failure, serious decline in kidney function and all-cause death. SGLT2 inhibitors were also associated with infections, volume depletion effects and amputation. Some associations appear to differ between compounds. (C) 2018 Elsevier B.V. All rights reserved.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors prevent cardiovascular complications in type 2 diabetes. We aimed to study whether they have similar effects in women and men by summarizing the effects of SGLT2 inhibitors compared to placebo on vascular and safety outcomes stratified by sex. We included patients with type 2 diabetes enrolled in the EMPA-REG OUTCOME, CANVAS Program, DECLARE TIMI-58 and CREDENCE trials. There were no differences in the risk ratios between men and women, SGLT2 versus control (placebo), for vascular efficacy outcomes or death (all P for interaction amp;gt;=.12), with clear protection shown against major adverse cardiovascular events, heart failure, vascular death and total mortality. SGLT2 inhibitor treatment was also associated with similar relative risks in women and men for the safety outcomes of amputation, fracture, genital infection and urinary tract infection (all P for interaction amp;gt;=.17). SGLT2 inhibition provided similar protection against vascular risks and death, and similar risks of serious adverse events, for women and men.

Aims: To describe weight-change pathways in patients with type 2 diabetes (T2D) and associated healthcare costs using repeated BMI measurements and healthcare utilization data. Methods: Patients with newly-diagnosed T2D with body mass index (BMI, kg/m(2)) at diagnosis and subsequent measures at year 1-3 were identified. Based on three-year BMI change, patients were assigned to one of 27 BMI change pathways defined by annual BMI change: BMI NE arrow (amp;gt;= 1 BMI unit increase), BMI -amp;gt; (amp;lt;1 BMI unit change), and BMI SE arrow (amp;gt;= 1 BMI unit decrease). Mean annual and three-year cumulative healthcare costs were estimated for each pathway by combining Swedish unit costs with resource use from primary care and national patient registers. Results: Cohort consisted of 15,819 patients; 44% women, mean age of 61 years, HbA1c of 6.7% (50 mmol/mol), BMI of 30.6 kg/m(2). Most common BMI pathways (mean costs): BMI -amp;gt;-amp;gt;-amp;gt; ((sic)5,311), BMI SE arrow -amp;gt;-amp;gt;((sic)5,461), and BMI -amp;gt;-amp;gt;SE arrow((sic)6,281). General trends: BMI)-amp;gt;-amp;gt;-amp;gt; linked to lowest, BMI NE arrow -amp;gt;NE arrow linked to highest costs. Conclusion: In patients with newly -diagnosed T2D, weight stability was the most common BMI change pattern over 3 years and associated with lowest healthcare costs. Relationship between weight change and healthcare costs appears complex warranting further investigation. (C) 2017 The Authors. Published by Elsevier Ltd on behalf of Primary Care Diabetes Europe.

Aim We aimed to explore the association between vitamin D and cardiovascular morbidity and mortality in people with Type 2 diabetes recruited from a community-based study because there is limited and inconsistent research of this group. Methods A prospective community-based cohort study among people aged 55-66 years with Type 2 diabetes as part of The Cardiovascular Risk in Type 2 Diabetes -A Prospective Study in Primary Care (CARDIPP). We analysed serum 25-hydroxyvitamin D-3 [25(OH)D-3] at baseline. Cox regression analyses were used to calculate hazard ratios (HR) for the first myocardial infarction, stroke or cardiovascular mortality according to 25(OH)D-3. Results We examined 698 people with a mean follow-up of 7.3 years. Serum 25(OH)D-3 was inversely associated with the risk of cardiovascular morbidity and mortality: HR 0.98 [95% confidence interval (CI) 0.96 to 0.99, P = 0.001]. Compared with the fourth quartile (Q4) [25(OH)D-3 amp;gt; 61.8 nmol/l], HR (with 95% CI) was 3.46 (1.60 to 7.47) in Q1 [25(OH)D-3 amp;lt; 35.5 nmol/l] (P = 0.002); 2.26 (1.01 to 5.06) in Q2 [25(OH)D-3 35.5-47.5 nmol/l] (P = 0.047); and 1.62 (0.70 to 3.76) in Q3 [25(OH)D-3 47.5-61.8 nmol/l] (P = 0.26) when adjusting for age, sex and season. The results remained significant after adjusting also for cardiovascular risk factors, physiological variables including parathyroid hormone and previous cardiovascular disease (P = 0.027). Conclusions Low 25(OH)D-3 is associated with an increased risk of cardiovascular morbidity and mortality in people with Type 2 diabetes independent of parathyroid hormone. Vitamin D could be considered as a prognostic factor. Future studies are needed to explore whether vitamin D deficiency is a modifiable risk factor in Type 2 diabetes.

Background: There are several cognitive assessment tools used in primary care, e.g., the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment. The Cognitive Assessment Battery (CAB) was introduced as a sensitive tool to detect cognitive decline in primary care. However, primary care validation is lacking. Therefore, we investigated the accuracy of the CAB in a primary care population. 

Objective: To investigate the accuracy of the CAB in a primary care population. 

Methods: Data from 46 individuals with cognitive impairment and 33 individuals who visited the primary care with somatic noncognitive symptoms were analyzed. They were investigated with the MMSE, the CAB, and a battery of neuropsychological tests; they also underwent consultation with a geriatric specialist. The accuracy of the CAB was assessed using c-statistics and the area under the receiver operating characteristic curve (AUC) was used to quantify the binary outcomes (“no cognitive impairment” or “cognitive impairment”).

Results: The “cognitive impairment” group was significantly different from the unimpaired group for all the subtests of the CAB. When accuracy was based on binary significant reduction or not in one or several domains of the CAB, the AUC varied between 0.685 and 0.772. However, when a summation or logistic regression of several subcategories was performed, using the numerical values for each subcategory, the AUC was >0.9. For comparison, the AUC for the MMSE was 0.849.

Conclusions: The accuracy of the CAB in a primary care population is poor to good when using binary cutoffs. Accuracy can be improved to high when using a summation or logistic regression of the numerical data of the subcategories. Considering CAB time, lack of adequate age norms, and a good accuracy for the MMSE, implementation of the CAB in primary care is not recommended at present based on the results of this study.

In the present study we describe an outbreak where PVL positive MRSA belonging to spa-type t002 and multi-locus sequence type ST2659 persisted in a Swedish dairy herd for at least two years, despite efforts to hinder transmission between animals and between the farmer and his animals. This is the first description of persistence and spread of MRSA in a dairy herd in Sweden. Sampling of animals in the herd was initiated by the finding of MRSA in the farmer and was performed at eight occasions from November 2012 to September 2014. In total, MRSA was detected in 25 animals and in 16 of these MRSA was detected in milk samples. In addition, MRSA was also detected in bulk milk samples. Whole genome sequencing (WGS) of twelve isolates from farmer (n?=?1), animals (n?=?9) and bulk milk (n?=?2) revealed high relatedness, implying a common source. MRSA may initially have been transmitted from humans to cows with further spread within the herd. WGS showed minor differences in one isolate (loss of phage FN315) which could indicate adaption of the strain to an animal host.

Aim: The objective of this study was to examine young adults healthcare utilisation and its possible association with health literacy. Background: Many countries struggle with insufficient accessibility at emergency departments (EDs) and primary healthcare centres (PHCs). Young adults, aged 20-29 years old, account for a substantial number of unnecessary doctor visits where health literacy could be an explanatory factor. Method: This study incorporated a combined retrospective and cross-sectional study design with analysis of registry data, including all registered outpatient doctor visits between 2004 and 2014 (n = 1 086 432), and strategic sample questionnaire data (n = 207), focusing on socio-demographics, symptoms and information-seeking behaviour. Mean differences between first-year and last-year doctor visits for each age group were calculated using registry data. Fischers exact test was applied to questionnaire data to analyse group differences between ED and PHC visitors as well as between patients with sufficient health literacy and insufficient health literacy. Binary logistic regression was used to investigate covariation. Findings: Healthcare utilisation has increased among young adults during the past decade, however, not comparatively more than for other age groups. ED patients (n = 49) compared to PHC patients (n = 158) were more likely to seek treatment for gastrointestinal symptoms (P = 0.001), had shorter duration of symptoms (P = 0.001) and sought care more often on the recommendation of a healthcare professional (P = 0.001). Insufficient/problematic health literacy among young adults was associated with having lower reliance on the healthcare system (P = 0.03) and with a greater likelihood of seeking treatment for psychiatric symptoms (P = 0.002). Conclusion: Young adults do not account for the increase in healthcare utilisation during the last decade to a greater extent than other age groups. Young adults reliance on the healthcare system is associated with health literacy, an indicator potentially important for consideration when studying health literacy and its relationship to more effective use of healthcare services.

Background amp; objectives: To improve the interpretation of fatal intoxications by establishing fatal and non-fatal reference concentrations of metformin in postmortem femoral blood and to further evaluate risk factors associated with fatal metformin intoxication. Methods: All forensic autopsies in Sweden where metformin was detected in femoral blood 2011-2016 were identified in the National Board of Forensic Medicine databases (NFMD). The cases were classified as single substance intoxications, A (n = 22), multiple substance intoxications, B (N = 7) and postmortem controls, C (N = 13). The control group consisted of cases where metformin was detected, but the cause of death excluded the incapacitation by metformin or other substances. Strict inclusion criteria were used, and all postmortem cases were assessed by two independent reviewers. All other cases where the inclusion criteria of groups A-C where not met formed group O (N = 78). The forensic findings logged in the NFMD where linked to national registers whereby information on comorbidities, dispensed drugs and clinical data could be obtained. Results: The mean age was 66 +/- 10 years in the total study population and did not differ between the groups. The proportion of men was 64% in group A, 71% in B, 77% in C and 74% in group O. The median values of metformin in group A (48.5 mu g/g; range 13.0-210 mu g/g) and B (21.0 mu g/g; range 4.40-95.0 mu g/g) were significantly (p amp;lt; 0.001 and p = 0.015 respectively) higher than those of the control group C (2.30 mu g/g; range 0.70-21.0 mu g/g). The median concentration of metformin in group A and B was also significantly higher than in group O (4.60 mg/g; range 0.64-54.0 mu g/g) (p amp;lt; 0.001 and p = 0.040 respectively). The results suggest that intoxication with metformin as a cause of death should be considered when the postmortem femoral blood level exceeds about 10 mg/g, although higher levels may be seen in postmortem in cases without incapacitation. The metformin intoxication was confirmed to be intentional in 23% (n = 5) of the single intoxications. Underlying factors identified as important for the remaining fatal metformin intoxications included living alone, any contraindication for the use of metformin, known alcohol abuse and a history of stroke or cardiovascular disease. Conclusions: The reported post mortem femoral blood concentrations of metformin can hopefully contribute to a better interpretation of results in suspected poisonings and obscure cases. Living in a single household, history of cardiovascular disease and contraindications, predominantly alcohol abuse, were associated with fatal metformin intoxication. (C) 2019 Elsevier B.V. All rights reserved.

OBJECTIVES: To compare cardiovascular risk factors as well as rates of cardiovascular diseases in middle-aged women from urban areas in Scotland and Sweden.

DESIGN: Comparative cross-sectional study.

SETTING: Data from the general population in urban areas of Scotland and the general population in two major Swedish cities in southeast Sweden, south of Stockholm.

PARTICIPANTS: Comparable data of middle-aged women (40-65 years) from the Scottish Health Survey (n=6250) and the Swedish QWIN study (n=741) were merged together into a new dataset (n=6991 participants).

MAIN OUTCOME MEASURE: We compared middle-aged women in urban areas in Sweden and Scotland regarding risk factors for cardiovascular disease (CVD), CVD diagnosis, anthropometrics, psychological distress and lifestyle.

RESULTS: In almost all measurements, there were significant differences between the countries, favouring the Swedish women. Scottish women demonstrated a higher frequency of alcohol consumption, smoking, obesity, low vegetable consumption, a sedentary lifestyle and also more psychological distress. For doctor-diagnosed coronary heart disease, there were also significant differences, with a higher prevalence among the Scottish women.

CONCLUSIONS: This is one of the first studies that clearly shows that Scottish middle-aged women are particularly affected by a worse profile of CVD risks. The profound differences in CVD risk and outcome frequency in the two populations are likely to have arisen from differences in the two groups of women's social, cultural, political and economic environments.

Background/Objectives: Dementia and cognitive impairment are common in nursing homes. Few studies have studied the impact of unnoted cognitive impairment on medical care. This study aimed to estimate the prevalence of diagnostic failure of cognitive impairment in a sample of Swedish nursing home residents and to analyze whether diagnostic failure was associated with impaired medical care. 

Method: A total of 428 nursing home residents were investigated during 2008–2011. Subjects without dementia diagnosis were grouped by result of the Mini Mental State Examination (MMSE), where subjects with <24 points formed a possible dementia group and the remaining subjects a control group. A third group consisted of subjects with diagnosed dementia. These three groups were compared according to baseline data, laboratory findings, drug use, and mortality. 

Results: Dementia was previously diagnosed in 181 subjects (42%). Among subjects without a dementia diagnosis, 72% were cognitively impaired with possible dementia (MMSE <24). These subjects were significantly older, did not get anti-dementia treatment, and had higher levels of brain natriuretic peptide compared to the diagnosed dementia group, but the risks of malnutrition and pressure ulcers were similar to the dementia group. 

Conclusions: Unnoted cognitive impairment is common in nursing home residents and may conceal other potentially treatable conditions such as heart failure. The results highlight a need to pay increased attention to cognitive impairment among nursing home residents.