استكشف المجموعة الواسعة من العناوين المتاحة.

Although a majority of patients with hypertension require a multidrug therapy, this is rarely considered when measuring adherence from refill data. Moreover, investigating the association between refill non-adherence to antihypertensive therapy (AHT) and elevated blood pressure (BP) has been advocated. Identify factors associated with non-adherence to AHT, considering the multidrug therapy, and investigate the association between non-adherence to AHT and elevated BP. A retrospective cohort study including patients with hypertension, identified from a random sample of 5025 Swedish adults. Two measures of adherence were estimated by the proportion of days covered method (PDC≥80%): (1) Adherence to any antihypertensive medication and, (2) adherence to the full AHT regimen. Multiple logistic regressions were performed to investigate the association between sociodemographic factors (age, sex, education, income), clinical factors (user profile, number of antihypertensive medications, healthcare use, cardiovascular comorbidities) and non-adherence. Moreover, the association between non-adherence (long-term and a month prior to BP measurement) and elevated BP was investigated. Non-adherence to any antihypertensive medication was higher among persons < 65 years (Odds Ratio, OR 2.75 [95% CI, 1.18-6.43]) and with the lowest income (OR 2.05 [95% CI, 1.01-4.16]). Non-adherence to the full AHT regimen was higher among new users (OR 2.04 [95% CI, 1.32-3.15]), persons using specialized healthcare (OR 1.63, [95% CI, 1.14-2.32]), and having multiple antihypertensive medications (OR 1.85 [95% CI, 1.25-2.75] and OR 5.22 [95% CI, 3.48-7.83], for 2 and ≥3 antihypertensive medications, respectively). Non-adherence to any antihypertensive medication a month prior to healthcare visit was associated with elevated BP. Sociodemographic factors were associated with non-adherence to any antihypertensive medication while clinical factors with non-adherence to the full AHT regimen. These differing findings support considering the use of multiple antihypertensive medications when measuring refill adherence. Monitoring patients' refill adherence prior to healthcare visit may facilitate interpreting elevated BP.

Aims Impaired renal function is a major contributor to the low proportion of mineralocorticoid receptor antagonist (MRA) treatment in patients with heart failure with reduced ejection fraction (HFrEF). Our aims were to investigate the impact of MRA treatment on all-cause mortality and worsening renal function (WRF) in patients with HFrEF and moderately impaired renal function. Methods Retrospective data between 2010-2018 on HFrEF patients from a single-centre hospital with estimated glomerular renal function (eGFR) < 60 ml/min/1.73 m.sup.2 were analysed. WRF was defined as a decline of by eGFR [greater than or equal to] 20%. Results 416 patients were included, 131 patients on MRA and 285 without MRA, mean age was 77 years (SD ± 9) and 82 years (SD ± 9), respectively. Median follow-up was 2 years. 128 patients (32%) experienced WRF, 25% in the MRA group and 30% in patients without MRA (p = 0.293). In multivariable analysis, hospitalization for heart failure and systolic blood pressure were associated with WRF (p = 0.015 and p = <0.001), but not use of MRA (p = 0.421). MRA treatment had no impact on the risk of adjusted all-cause mortality (HR 0.93; 95% CI, 0.66-1.32 p = 0.685). WRF was associated with increased adjusted risk of all-cause mortality (HR 1.43; 95% CI, 1.07-1.89 p = 0.014). Use of MRA did not increase the adjusted overall risk of mortality even when experiencing WRF (HR 1.15; 95% CI, 0.81-1.63 p = 0.422). Conclusion In this cohort of elderly HFrEF patients with moderately impaired renal function, MRA did not increase risk for WRF or all-cause mortality.

Business organizations may expand internationally by replicating a part of their value chain, such as a sales and marketing format, in other countries. However, little is known regarding how such \"international replicators\" build a format for replication, or how they can adjust it in order to adapt to local environments and under the impact of new learning. To illuminate these issues, we draw on a longitudinal in-depth study of Swedish home furnishing giant IKEA, involving more than 70 interviews. We find that IKEA has developed organizational mechanisms that support an ongoing learning process aimed at frequent modification of the format for replication. Another finding is that IKEA treats replication as hierarchical: lower-level features (marketing efforts, pricing, etc.) are allowed to vary across IKEA stores in response to market-based learning, while higher-level features (fundamental values, vision, etc.) are replicated in a uniform manner across stores, and change only very slowly (if at all) in response to learning (\"flexible replication\"). We conclude by discussing the factors that influence the approach to replication adopted by an international replicator.

The Water Poverty Index (WPI), a tool designed for integrated analysis of water issues, was set-up in a community in Madhya Pradesh, India through a transparent and participatory process. Though the aim of the WPI is to primarily use existing statistical data, quantitative information from census and local records was combined with qualitative data from community interviews and participatory exercises. The inclusion of community chosen indicators and the adjustment of values so that higher numbers represent water prosperity rather than water poverty, led to the Water Prosperity Index (WPI + ). The WPI  +  score was contrasted with the WPI at community level. It was also calculated for two community areas with different caste and socio-economic characteristics and weighted separately according to water issues prioritized by men and women. The WPI  +  revealed a great difference in water access between the two areas and in prioritized issues between men and women illustrating the importance of appropriate spatial representation and gender sensitive assessments for revealing important disparities. Results also showed that highly aggregated data hide these differences making it more difficult to target the most vulnerable groups when planning measures to increase equitable water allocation. While quantitative data reveal an important perspective of the water situation, qualitative data about adequacy of resources, services or institutions, improve understanding of which issues to prioritize. A valid and useful community water index must be based on representative participation, transparency and local influence on the methodology and subsequent results.

Aims/hypothesis The secretion of glucagon is controlled by blood glucose and inappropriate secretion of glucagon contributes to hyperglycaemia in diabetes. Besides its role in glucose regulation, glucagon regulates amino acid metabolism in hepatocytes by increasing ureagenesis. Disruption of this mechanism causes hyperaminoacidaemia, which in turn increases glucagon secretion. We hypothesised that hepatic insulin resistance (secondary to hepatic steatosis) via defective glucagon signalling/glucagon resistance would lead to impaired ureagenesis and, hence, increased plasma concentrations of glucagonotropic amino acids and, subsequently, glucagon. Methods To examine the association between glucagon and amino acids, and to explore whether this relationship was modified by hepatic insulin resistance, we studied a well-characterised cohort of 1408 individuals with normal and impaired glucose regulation. In this cohort, we have previously reported insulin resistance to be accompanied by increased plasma concentrations of glucagon. We now measure plasma levels of amino acids in the same cohort. HOMA-IR was calculated as a marker of hepatic insulin resistance. Results Fasting levels of glucagonotropic amino acids and glucagon were significantly and inversely associated in linear regression models (persisting after adjustment for age, sex and BMI). Increasing levels of hepatic, but not peripheral insulin resistance ( p  > 0.166) attenuated the association between glucagon and circulating levels of alanine, glutamine and tyrosine, and was significantly associated with hyperaminoacidaemia and hyperglucagonaemia. A doubling of the calculated glucagon–alanine index was significantly associated with a 30% increase in hepatic insulin resistance, a 7% increase in plasma alanine aminotransferase levels, and a 14% increase in plasma γ-glutamyltransferase levels. Conclusions/interpretation This cross-sectional study supports the existence of a liver–alpha cell axis in humans: glucagon regulates plasma levels of amino acids, which in turn feedback to regulate the secretion of glucagon. With hepatic insulin resistance, reflecting hepatic steatosis, the feedback cycle is disrupted, leading to hyperaminoacidaemia and hyperglucagonaemia. The glucagon–alanine index is suggested as a relevant marker for hepatic glucagon signalling.

Sixteen SNPs were determined and clinical factors examined in two Scandinavian cohorts that were followed for a median of 23.5 years. Type 2 diabetes developed in 11.7% of the subjects. The inclusion of common genetic risk factors, many of which impair the capacity of beta cells to increase insulin secretion, in risk models modestly improved the prediction of future type 2 diabetes. Sixteen SNPs were determined and clinical factors examined in two Scandinavian cohorts that were followed for a median of 23.5 years. Type 2 diabetes developed in 11.7 percent of the subjects. Type 2 diabetes mellitus is a complex polygenic disorder in which common genetic variants interact with environmental factors to unmask the disease. The identification of persons at high risk for the disease may aid in disease prevention. A family history of diabetes, an increase in body-mass index (BMI, the weight in kilograms divided by the square of the height in meters), and impaired insulin secretion and action are risk factors for type 2 diabetes. 1 – 4 A challenge has been to identify genetic variants that explain the excess risk associated with a family history of diabetes. From a long list of . . .

Aims/hypothesis Fasting plasma levels of branched-chain amino acids (BCAAs) are associated with insulin resistance, but it remains unclear whether there is a causal relation between the two. We aimed to disentangle the causal relations by performing a Mendelian randomisation study using genetic variants associated with circulating BCAA levels and insulin resistance as instrumental variables. Methods We measured circulating BCAA levels in blood plasma by NMR spectroscopy in 1,321 individuals from the ADDITION-PRO cohort. We complemented our analyses by using previously published genome-wide association study (GWAS) results from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) ( n  = 46,186) and from a GWAS of serum BCAA levels ( n  = 24,925). We used a genetic risk score (GRS), calculated using ten established fasting serum insulin associated variants, as an instrumental variable for insulin resistance. A GRS of three variants increasing circulating BCAA levels was used as an instrumental variable for circulating BCAA levels. Results Fasting plasma BCAA levels were associated with higher HOMA-IR in ADDITION-PRO (β 0.137 [95% CI 0.08, 0.19] p  = 6 × 10 −7 ). However, the GRS for circulating BCAA levels was not associated with fasting insulin levels or HOMA-IR in ADDITION-PRO (β −0.011 [95% CI −0.053, 0.032] p  = 0.6 and β −0.011 [95% CI −0.054, 0.031] p  = 0.6, respectively) or in GWAS results for HOMA-IR from MAGIC (β for valine-increasing GRS −0.012 [95% CI −0.069, 0.045] p  = 0.7). By contrast, the insulin-resistance-increasing GRS was significantly associated with increased BCAA levels in ADDITION-PRO (β 0.027 [95% CI 0.005, 0.048] p  = 0.01) and in GWAS results for serum BCAA levels (β 1.22 [95% CI 0.71, 1.73] p  = 4 × 10 −6 , β 0.96 [95% CI 0.45, 1.47] p  = 3 × 10 −4 , and β 0.67 [95% CI 0.16, 1.18] p  = 0.01 for isoleucine, leucine and valine levels, respectively) and instrumental variable analyses in ADDITION-PRO indicated that HOMA-IR is causally related to higher circulating fasting BCAA levels (β 0.73 [95% CI 0.26, 1.19] p  = 0.002). Conclusions/interpretation Our results suggest that higher BCAA levels do not have a causal effect on insulin resistance while increased insulin resistance drives higher circulating fasting BCAA levels.

The European Water Framework Directive puts strong emphasis on stakeholder and public participation in water management. Several practical questions regarding who should be involved, why, when, and how still remain unanswered. This paper investigates stakeholders' own experiences and views of increased public participation in water management. The article also explores the potential for increasing levels of participation by forming catchment committees with representation from stakeholder groups and through the use of various practical methods for participation. For both these aspects of participation, the views, expectations, and apprehensions of different stakeholder groups involved in nutrient loss management are investigated. Stakeholder opinions were collected by inviting representatives from five stakeholder groups within the Rönneå catchment in southern Sweden to a catchment dialog process.

IntroductionMineralocorticoid receptor antagonists (MRAs) reduce mortality and morbidity in patients with heart failure and reduced ejection fraction (HFrEF), but are largely underused. We evaluated the frequency, motives, predictors and outcomes of MRA discontinuation in a real-world heart failure population.Methods and resultsThis was a single-centre, retrospective cohort study where medical record-based data were collected on patients with HFrEF between 2010 and 2018. In the final analysis, 572 patients were included that comprised the continued MRA group (n=275) and the discontinued MRA group (n=297). Patients that discontinued MRA were older, had a higher comorbidity index and a lower index estimated glomerular filtration rate (eGFR). Predictors of MRA discontinuations were increased S-potassium, lower eGFR, lower systolic blood pressure, higher frequency of comorbidities and a higher left ventricular ejection fraction. The most common reason for MRA discontinuation was renal dysfunction (n=97, 33%) with 59% of these having an eGFR <30 mL/min/1.73m2, and elevated S-potassium (n=71, 24%) with 32% of these having an S-potassium >5.5 mmol/L. Discontinuation of MRA increased the adjusted risk of all-cause mortality (HR 1.48; 95% CI 1.07 to 2.05; p=0.019).ConclusionsHalf of all patients with HFrEF initiated on MRA discontinued the treatment. A substantial number of patients discontinued MRA without meeting the guideline-recommended levels of eGFR and S-potassium where mild to moderate hyperkalaemia seems to be the most decisive predictor. Further, MRA discontinuation was associated with increased adjusted risk of all-cause mortality.

Two models for predicting the hydration status of lichens were developed as a first step towards a mechanistic lichen productivity model. A biophysical model included the water potential of the air, derived from measurements of air temperature, relative humidity and species-specific rate constants for desiccation and rehydration. A reduced physical model, included only environmental parameters, assuming instantaneous equilibration between the lichen and the air. These models were developed using field and laboratory data for three green algal lichens: the foliose epiphytic Platismatia glauca (L.) W. Culb., the fruticose epiphytic Alectoria sarmentosa (Ach.) Ach. and the fruticose, terricolous and mat-forming Cladina rangiferina (L.) Weber ex Wigg. The models were compared and validated for the same three species using data from a habitat with a different microclimate. Both models predicted the length and timing of lichen hydration periods, with those for A. sarmentosa and P. glauca being highly accurate--nearly 100% of the total wet time was predicted by both the biophysical and physical models. These models also predicted an accurate timing of the total realized wet time for A. sarmentosa and P. glauca when the lichens were wet. The model accuracy was lower for C. rangiferina compared to the epiphytes, both for the total realized wet time and for the accuracy of the timing for the hydration period. These results demonstrate that the stochastic and continually varying hydration status of lichens can be simulated from biophysical data. Further development of these models to also include water-related activity, light and temperature conditions during the hydration events will then be a potent tool to assess potential lichen productivity in landscapes and habitats of various microclimatic conditions.