A multi-component intervention increased access to smoking cessation treatment after hospitalization for atherosclerotic cardiovascular disease: a randomized trial.

Aims: To evaluate the effects of a multi-component intervention for smokers hospitalized for atherosclerotic cardiovascular disease (ASCVD) on the participation rate in community-based cessation programmes and the use of cessation drugs. Additionally, to explore the impact on the cessation rates at 6 months. Methods and results: A randomized parallel-group study was conducted at a Norwegian secondary care hospital in 2021. The intervention group was: (i) counselled using motivational interviewing techniques during hospitalization; (ii) given an information leaflet, detailing the cessation programme; and (iii) referred to the community-based smoking cessation treatment including a post-discharge pro-active telephone invitation. The control group received usual care and the same information leaflet containing clear contact details for initiating participation. Data were collected at baseline, 1, 3, and 6 months. Among 99 smokers hospitalized with ASCVD, 40 were excluded. Of 59 randomized patients, 4 were lost to follow-up and 55 completed the study. The mean age was 65.1 (standard deviation 9.3) years, 35% were female, and 88% had smoked >20 years. Co-morbidity was prevalent (mean Charlson score 4.8). The intervention group was more likely to participate in the smoking cessation treatment {48 vs. 7%, difference: 41% [95% confidence interval (CI): 14%, 63%]} and used cessation drugs more frequently [59 vs. 21%, difference: 38% (95% CI: 17%, 59%)]. At the 6 months point prevalence, we observed notable between-group differences in self-reported cessation rate (48 vs. 25%). Conclusion: The intervention significantly increased the participation rate at community-based smoking cessation programmes and the use of cessation drugs among multi-morbid smokers hospitalized for ASCVD.

Treatment patterns and adherence to lipid-lowering drugs during eight-year follow-up after a coronary heart disease event.

BACKGROUND AND AIMS: Proper prescription and high adherence to intensive lipid lowering drugs (LLD) in patients with coronary heart disease (CHD) are crucial and strongly recommended. The aim of this study is to investigate long-term treatment patterns and adherence to LLD following hospitalization for a CHD event. METHODS: Patients admitted to two Norwegian hospitals with a CHD event from 2011 to 2014 (N = 1094) attended clinical examination and completed a questionnaire, median 16 months later. Clinical data were linked to pharmacy dispensing data from 2010 to 2020. The proportions using high-intensity statin therapy (atorvastatin 40/80 mg or rosuvastatin 20/40 mg) and non-statin LLD after the CHD event were assessed. Adherence was evaluated by proportion of days covered (PDC) and gaps in treatment. RESULTS: Median age at hospitalization was 63 (IQR 12) years, 21 % were female. Altogether, 1054 patients (96 %) were discharged with a statin prescription, while treatment was dispensed in 85 % within the following 90 days. During median 8 (SD 2.5) years follow-up, the proportion using high-intensity statin therapy ranged 62-68 %, whereas the use of ezetimibe increased from 4 to 26 %. PDC <0.8 was found in 22 % of statin users and 26 % of ezetimibe users. The proportions with a treatment gap exceeding 180 days were 22 % for statins and 28 % for ezetimibe. Smoking at hospitalization and negative affectivity were significantly associated with reduced statin adherence, regardless of adherence measure. CONCLUSIONS: In this long-term follow-up of patients with CHD, less than 70 % used high-intensity statin therapy with only small changes over time, and only 25 % used additional treatment with ezetimibe. We identified factors associated with reduced statin adherence that may be target for interventions.

Validation of a novel direct method to determine reduced adherence to atorvastatin therapy.

AIMS: Objective methods to determine statin adherence are requested to improve lipid management. We have recently established a method to detect reduced adherence to atorvastatin therapy with cut-off values based on the sum of atorvastatin and its major metabolites in blood. We aimed to validate this method in patients with and without cardiovascular disease, and optimize previous cut-off values. METHODS AND RESULTS: The pharmacokinetic study included 60 participants treated with atorvastatin 20 mg (N=20), 40 mg (N=20), and 80 mg (N=20). Atorvastatin was then stopped and blood samples collected from day zero to day four. Quantification of the parent drug and its metabolites in blood plasma was performed with a liquid chromatography-tandem mass spectrometry assay. The cut-off values for reduced adherence were validated and optimized by calculating diagnostic sensitivity and specificity. Our candidate cut-off value of dose-normalized six-component sum of atorvastatin plus metabolites <0.10 nM/mg provided a sensitivity of 97% and a specificity of 93% for detecting ≥2 omitted doses. An optimized cut-off <0.062 nM/mg provided a sensitivity of 90% and a specificity of 100%. An alternative simplified two-component metabolite sum with cut-off value <0.05 nM/mg provided a sensitivity of 98% and a specificity of 76%. An optimized cut-off <0.02 nM/mg provided a sensitivity of 97% and a specificity of 98%. CONCLUSION: This validation study confirms that our direct method discriminates reduced adherence from adherence to atorvastatin therapy with high diagnostic accuracy. The method may improve lipid management in clinical practice and serve as a useful tool in future studies.

The atorvastatin metabolite pattern in muscle tissue and blood plasma is associated with statin muscle side effects in patients with coronary heart disease; An exploratory case-control study.

Background and aims: Statin-associated muscle symptoms (SAMS) is a prevalent cause of statin discontinuation. It is challenging and time-consuming for clinicians to assess whether symptoms are caused by the statin or not, and diagnostic biomarkers are requested. Atorvastatin metabolites have been associated with SAMS. We aimed to compare atorvastatin pharmacokinetics between coronary heart disease (CHD) patients with and without clinically statin intolerance and statin-dependent histopathological alterations in muscle tissue. Secondarily we aimed to assess genetic variants relevant for the observed pharmacokinetic variables. Methods: Twenty-eight patients with CHD and subjective SAMS were included in the exploratory MUSE biomarker study in 2020. Participants received atorvastatin 40 mg/day for seven weeks followed by no statins for eight weeks. Muscle biopsies and blood were collected at the end of each period. Four patients were categorized as clinically intolerant to ≥3 statins prior to study start whereas four patients had signs of muscle cell damage during treatment. Results: We found significantly lower levels of atorvastatin acids, and higher lactone/acid ratios in the statin intolerant, both in muscle and plasma. With optimal cut-off, the combination of 2-OH-atorvastatin acid and the 2-OH-atorvastatin lactone/acid ratio provided sensitivity, specificity, and predictive values of 100 %. Patients with variants in UGT1A1 and UGT1A3 had higher lactone metabolite levels than those with wild type, both in muscle and plasma. Conclusion: Atorvastatin metabolites appear promising as biomarkers for the identification of clinical statin intolerance in patients with self-perceived SAMS, but the findings have to be confirmed in larger studies.

Frailty, health literacy and self-care in patients admitted with acute heart failure. / Skrøpelighet, helsekompetanse og egenomsorg hos pasienter som innlegges med akutt hjertesvikt.

BACKGROUND: There is limited knowledge from Norway on clinical characteristics, self-care and health literacy in patients admitted to hospital with acute heart failure. Our aim was to identify these factors in this group. MATERIAL AND METHOD: We included patients admitted with acute heart failure over a period of six months (2022/2023) at Drammen Hospital and Vestfold Hospital Trust. Cardiac nurses collected information from the patients, including self-assessed knowledge on an ordinal scale from 0 (little knowledge) to 10 (good knowledge). Clinical frailty scores were calculated and data from the hospital records were recorded. RESULTS: Of 136 patients with acute heart failure, 81 were included. Median age was 79 (range 35-95) years, 35 (43 %) were women. A total of 35 (43 %) had been admitted with heart failure exacerbation in the past year. The patients had a median of 5 (1-10) diagnoses, and the median score on the clinical frailty scale was 4 (1-7), corresponding to 'vulnerable'. A total of 63 (78 %) had been diagnosed with heart failure before admission to hospital. Of these, 13 (21 %) were unaware of the diagnosis, and their self-assessed knowledge was median 3 (25th and 75th percentile, 0-5) for management of heart failure, 2 (25th and 75th percentile, 0-5) for lifestyle interventions and 0 (25th and 75th percentile, 0-2) for heart medications. Altogether 42 out of 63 (67 %) weighed themselves weekly, 13 (21 %) measured their blood pressure, while 3 (5 %) had a self-care plan. Of 50 patients with left ventricle ejection fraction ≤ 40 %, 32 (64 %) were discharged with betablockers and angiotensin II receptor blockers or a combination drug with a neprilysin inhibitor, whereas 11 (22 %) were also prescribed SGLT2 inhibitors and mineralocorticoid receptor antagonists. INTERPRETATION: The included patients were multimorbid and had a low level of self-care and health literacy. There is potential to optimise well-documented medicinal treatment.

Nausea Predicts Bacteremia in Immunocompetent Patients with Pneumococcal Community-Acquired Pneumonia: Secondary Data Analysis from a Prospective Cohort.

BACKGROUND: In pneumococcal community-acquired pneumonia (CAP), bacteremia is associated with increased mortality, but initial clinical severity scores frequently fail to identify bacteremic patients at risk. We have previously shown that gastrointestinal symptoms are common among patients admitted to the hospital with pneumococcal bacteremia. The aim of this study was to examine gastrointestinal symptoms and inflammatory responses in bacteremic and non-bacteremic pneumococcal CAP in a prospective cohort of immunocompromised and immunocompetent patients hospitalized with CAP. METHODS: Logistic regression analysis was used to estimate the predictive value of gastrointestinal symptoms for pneumococcal bacteremia in patients with CAP. The Mann-Whitney test was used to compare inflammatory responses in patients with bacteremic vs. non-bacteremic pneumococcal CAP. RESULTS: Eighty-one patients with pneumococcal CAP were included, of whom 21 (26%) had bacteremia. Immunocompetent patients with pneumococcal CAP had an odds ratio of 16.5 (95% CI 3.0-90.9, p = 0.001) for bacteremia if nausea was present, whereas no such association was found in the immunocompromised patients (OR 0.22, 95% CI 0.02-2.05, p = 0.18). The serum levels of C-reactive protein, procalcitonin and interleukin 6 were significantly higher in the patients with bacteremic pneumococcal CAP compared to non-bacteremic pneumococcal CAP patients (p < 0.001, p = 0.005, and p = 0.019, respectively). CONCLUSIONS: In immunocompetent patients hospitalized with pneumococcal CAP, nausea may be a predictor of bacteremia. Bacteremic pneumococcal CAP patients display an increased inflammatory response compared to non-bacteremic pneumococcal CAP patients.

Atorvastatin Metabolite Pattern in Skeletal Muscle and Blood from Patients with Coronary Heart Disease and Statin-Associated Muscle Symptoms.

Self-perceived statin-associated muscle symptoms (SAMS) are prevalent, but only a minority is drug-dependent. Diagnostic biomarkers are not yet identified. The local statin exposure in skeletal muscle tissue may correlate to the adverse effects. We aimed to determine whether atorvastatin metabolites in blood reflect the corresponding metabolite levels in skeletal muscle, and whether genetic variants of statin transporters modulate this relationship. We also addressed atorvastatin metabolites as potential objective biomarkers of SAMS. Muscle symptoms were examined in patients with coronary disease and self-perceived SAMS during 7 weeks of double-blinded treatment with atorvastatin 40 mg/day and placebo in randomized order. A subset of 12 patients individually identified with more muscle symptoms on atorvastatin than placebo (confirmed SAMS) and 15 patients with no difference in muscle symptom intensity (non-SAMS) attended the present follow-up study. All received 7 weeks of treatment with atorvastatin 40 mg/day followed by 8 weeks without statins. Biopsies from the quadriceps muscle and blood plasma were collected after each treatment period. Strong correlations (rho > 0.7) between muscle and blood plasma concentrations were found for most atorvastatin metabolites. The impact of the SLCO1B1 c.521T>C (rs4149056) gene variant on atorvastatin's systemic pharmacokinetics was translated into muscle tissue. The SLCO2B1 c.395G>A (rs12422149) variant did not modulate the accumulation of atorvastatin metabolites in muscle tissue. Atorvastatin pharmacokinetics in patients with confirmed SAMS were not different from patients with non-SAMS. In conclusion, atorvastatin metabolite levels in skeletal muscle and plasma are strongly correlated, implying that plasma measurements are suitable proxies of atorvastatin exposure in muscle tissue. The relationship between atorvastatin metabolites in plasma and SAMS deserves further investigation.

Monitoring Simvastatin Adherence in Patients With Coronary Heart Disease: A Proof-of-Concept Study Based on Pharmacokinetic Measurements in Blood Plasma.

BACKGROUND: Poor statin adherence remains a public health concern associated with adverse outcomes. We evaluated the use of pharmacokinetic measurements to monitor adherence to simvastatin in patients with coronary heart disease (CHD). METHODS: Eighteen patients with CHD taking an evening dose of simvastatin 20 mg (n = 7), 40 mg (n = 5), or 80 mg (n = 6) were examined at steady-state pharmacokinetics. Ten patients were instructed to interrupt simvastatin dosing and return for blood sampling for the subsequent 3 days. Dose-normalized plasma concentrations of simvastatin lactone and simvastatin acid and the sum of the 2 were evaluated to discriminate between adherent dosing and dose omission. Bioanalytical quantification was performed using liquid chromatography-tandem mass spectrometry. RESULTS: A simvastatin acid cutoff of 1.0 × 10 -2 nmol -1 ·L -1 ·mg -1 identified 100% of those omitting 2 doses and 60% of those omitting a single dose. Simvastatin acid showed superior ability to discriminate dose omission, as well as the best agreement between samples handled at ambient and cool temperatures (median deviation 3.5%; interquartile range -2.5% to 13%). The cutoff for a morning dose schedule, with a similar ability to discriminate, was estimated at 2.0 × 10 -3 nmol -1 ·L -1 ·mg -1 . CONCLUSIONS: The present method discriminated between adherence and reduced adherence to simvastatin therapy in patients with CHD. Sample handling is feasible for routine practice, and the assessment of adherence can be performed by direct measurement of simvastatin acid in a blood sample, according to defined cutoff values. Further studies validating the cutoff value and utility for clinical application are encouraged.

Hepcidin predicts 5-year mortality after community-acquired pneumonia.

BACKGROUND: Virtually all living organisms, including microbes and humans, depend on iron to survive and grow. During an infection, the plasma level of iron and several iron-related proteins change substantially. We hypothesized that iron and iron-related proteins could predict short- and long-term outcomes in community-acquired pneumonia. METHODS: Blood samples from a prospective cohort of 267 in-patients with community-acquired pneumonia were analysed for hepcidin, ferritin, iron, transferrin, transferrin saturation, and soluble transferrin receptor at admission and 6-weeks post-discharge. Adverse short-term outcome was defined as admission to intensive care unit or death within 30 days, and long-term outcome was assessed as 5-year overall mortality. Logistic regression, Kaplan Meier survival curves, and Cox regression models with cut-offs at median for the potential biomarkers were used for statistical evaluation. RESULTS: Low admission levels of hepcidin predicted 5-year overall mortality, independently of age, sex, comorbid conditions, and anaemia. Low levels of ferritin at admission as well as low levels of iron and transferrin saturation and high levels of soluble transferrin receptor at the 6-week follow-up were predictors of 5-year overall mortality in univariable, but not in multivariable analyses. Neither of these potential biomarkers predicted adverse short-term outcomes. CONCLUSIONS: In hospitalized patients with community-acquired pneumonia, low levels of hepcidin at admission predicted 5-year overall mortality, but not short-term adverse outcome.

Clinical and psychological factors in coronary heart disease patients with statin associated muscle side-effects.

BACKGROUND: To compare clinical and psychological factors among patients with self-perceived statin-associated muscle symptoms (SAMS), confirmed SAMS, and refuted SAMS in coronary heart disease patients (CHD). METHODS: Data were obtained from a cross-sectional study of 1100 CHD outpatients and a study of 71 CHD outpatients attending a randomized, double-blinded, placebo-controlled, crossover study to test effects of atorvastatin 40 mg/day on muscle symptom intensity. Clinical and psychosocial factors were compared between patients with and without SAMS in the cross-sectional study, and between patients with confirmed SAMS and refuted SAMS in the randomized study. RESULTS: Bilateral, symmetric muscle symptoms in the lower extremities during statin treatment were more prevalent in patients with confirmed SAMS compared to patients with refuted SAMS (75% vs. 41%, p = 0.01) in the randomized study. No significant differences in psychological factors (anxiety, depression, worry, insomnia, type D personality characteristics) were detected between patients with and without self-perceived SAMS in the cross-sectional study, or between patients with confirmed SAMS and refuted SAMS, in the randomized study. CONCLUSIONS: Patients with confirmed SAMS more often present with bilateral lower muscle symptoms compared to those with refuted SAMS. Psychological factors were not associated with self-perceived SAMS or confirmed SAMS. A careful pain history and a search for alternative causes of muscle symptoms are likely to promote communication in patients with SAMS, and may reduce the risk for statin discontinuation.

The relationship between directly measured statin adherence, self-reported adherence measures and cholesterol levels in patients with coronary heart disease.

BACKGROUND AND AIMS: We aimed to determine the relationship between statin adherence measured directly, and by self-report measures and serum cholesterol levels. METHODS: Patients prescribed atorvastatin (N = 373) participated in a cross-sectional study 2-36 months after a coronary event. Self-reported adherence included statin adherence the past week, the 8-item Morisky medication adherence scale (MMAS-8), and the Gehi et al. adherence question. Atorvastatin was measured directly in spot blood plasma by a novel liquid chromatography tandem mass-spectrometry method discriminating adherence (0-1 doses omitted) and reduced adherence (≥2 doses omitted). Participants were unaware of the atorvastatin analyses at study participation. RESULTS: Mean age was 63 (SD 9) years and 8% had reduced atorvastatin adherence according to the direct method. In patients classified with reduced adherence by the direct method, 40% reported reduced statin adherence, 32% reported reduced adherence with the MMAS-8 and 22% with the Gehi question. In those adherent by the direct method, 96% also reported high statin adherence, 95% reported high adherence on the MMAS-8 whereas 94% reported high adherence on the Gehi question. Cohen's kappa agreement score with the direct method was 0.4 for self-reported statin adherence, 0.3 for the Gehi question and 0.2 for the MMAS-8. Adherence determined by the direct method, self-reported statin adherence last week, and the Gehi question was inversely related to LDL-cholesterol levels with a p-value of <0.001, 0.001 and 0.004, respectively. CONCLUSIONS: Plasma-statin measurements reveal reduced adherence with higher sensitivity than self-report measures, relate to cholesterol levels, and may prove to be a useful tool to improve lipid management.

Hepcidin and Ferritin Predict Microbial Etiology in Community-Acquired Pneumonia.

BACKGROUND: Iron is crucial for survival and growth of microbes. Consequently, limiting iron availability is a human antimicrobial defense mechanism. We explored iron and iron-related proteins as potential biomarkers in community-acquired pneumonia and hypothesized that infection-induced changes in these potential biomarkers differ between groups of pathogens and could predict microbial etiology. METHODS: Blood samples from a prospective cohort of 267 patients with community-acquired pneumonia were analyzed for hepcidin, ferritin, iron, transferrin, and soluble transferrin receptor at admission, clinical stabilization, and a 6-week follow-up. A total of 111 patients with an established microbiological diagnosis confined to 1 microbial group (atypical bacterial, typical bacterial, or viral) were included in predictive analyses. RESULTS: High admission levels of ferritin predicted atypical bacterial versus typical bacterial etiology (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.18-4.32; P = .014). Furthermore, hepcidin and ferritin predicted atypical bacterial versus viral etiology (hepcidin: OR = 3.12, 95% CI = 1.34-7.28, P = .008; ferritin: OR = 2.38, 95% CI = 1.28-4.45, P = .006). The findings were independent of C-reactive protein and procalcitonin. CONCLUSIONS: Hepcidin and ferritin are potential biomarkers of microbial etiology in community-acquired pneumonia.

Effect of atorvastatin on muscle symptoms in coronary heart disease patients with self-perceived statin muscle side effects: a randomized, double-blinded crossover trial.

AIMS: To estimate the effect of atorvastatin on muscle symptom intensity in coronary heart disease (CHD) patients with self-perceived statin-associated muscle symptoms (SAMS) and to determine the relationship to blood levels of atorvastatin and/or metabolites. METHODS AND RESULTS: A randomized multi-centre trial consecutively identified 982 patients with previous or ongoing atorvastatin treatment after a CHD event. Of these, 97 (9.9%) reported SAMS and 77 were randomized to 7-week double-blinded treatment with atorvastatin 40 mg/day and placebo in a crossover design. The primary outcome was the individual mean difference in muscle symptom intensity between the treatment periods, measured by visual-analogue scale (VAS) scores. Atorvastatin did not affect the intensity of muscle symptoms among 71 patients who completed the trial. Mean VAS difference (statin-placebo) was 0.31 (95% CI: -0.24 to 0.86). The proportion with more muscle symptoms during placebo than atorvastatin was 17% (n = 12), 55% (n = 39) had the same muscle symptom intensity during both treatment periods whereas 28% (n = 20) had more symptoms during atorvastatin than placebo (confirmed SAMS). There were no differences in clinical or pharmacogenetic characteristics between these groups. The levels of atorvastatin and/or metabolites did not correlate to muscle symptom intensity among patients with confirmed SAMS (Spearman's rho ≤0.40, for all variables). CONCLUSION: Re-challenge with high-intensity atorvastatin did not affect the intensity of muscle symptoms in CHD patients with self-perceived SAMS during previous atorvastatin therapy. There was no relationship between muscle symptoms and the systemic exposure to atorvastatin and/or its metabolites. The findings encourage an informed discussion to elucidate other causes of muscle complaints and continued statin use.

A novel direct method to determine adherence to atorvastatin therapy in patients with coronary heart disease.

AIMS: Objective methods to monitor statin adherence are needed. We have established a liquid chromatography-tandem mass spectrometry assay for quantification of atorvastatin and its metabolites in blood. This study aimed to develop an objective drug exposure variable with cut-off values to discriminate among adherence, partial adherence and nonadherence to atorvastatin therapy in patients with coronary heart disease. METHODS: Twenty-five patients treated with atorvastatin 10 mg (n = 5), 20 mg (n = 6), 40 mg (n = 7) and 80 mg (n = 7) participated in a directly observed atorvastatin therapy study to confirm baseline adherence. After the directly observed therapy, half of the patients (test group) were instructed to stop taking atorvastatin and return for blood sample collection the subsequent 3 days. Levels of atorvastatin and metabolites were compared between the test group and the adherent control group. RESULTS: The sum of parent drug and all measured primary metabolites correlated well with the atorvastatin dose administered (Spearman's rho = 0.71, 95% CI 0.44-0.87). The dose-normalized atorvastatin plus metabolites concentrations completely separated the partially adherent test group from the controls at 0.18 nM/mg after 3 days without atorvastatin. To reduce the risk of misinterpreting adherent patients as partially adherent, a corresponding cut-off at 0.10 nM/mg is proposed. A metabolite level of 2-OH atorvastatin acid <0.014 nmol/L provided the optimal cut-off for nonadherence. CONCLUSION: A direct method to discriminate among adherence, partial adherence and nonadherence to atorvastatin therapy in patients with coronary heart disease has been developed. This tool may be important for novel studies on adherence and potentially useful in clinical practice.

Statin-associated muscle symptoms in coronary patients: design of a randomized study.

Objectives. Estimate the effect of atorvastatin on muscular symptom intensity in coronary patients with subjective statin-associated muscle symptoms (SAMS) and to determine the association with blood levels of atorvastatin and its metabolites, to obtain an objective marker for true SAMS. Design. A randomized, double-blinded, cross-over study will include 80 coronary patients with subjectively reported SAMS during ongoing atorvastatin therapy or previous muscle symptoms that led to discontinuation of atorvastatin. Patients will be randomized to 7-weeks treatment with atorvastatin 40 mg/day in the first period and matched placebo in the second 7-weeks period, or placebo in the first period and atorvastatin in the second period. Each period is preceded by 1-week wash-out. A control group (n = 40) without muscle symptoms will have 7 weeks open treatment with atorvastatin 40 mg/day. Blood samples will be collected at baseline and at the end of each treatment period, and muscular symptoms will be rated by the patients weekly using a Visual Analogue Scale (VAS). The primary outcome is the difference in aggregated mean VAS scores between the last three weeks of atorvastatin treatment and of placebo treatment. The main purpose is to develop an objective marker for true SAMS, by comparing SAMS associated with blinded atorvastatin treatment with blood concentrations of atorvastatin and its metabolites. Diagnostic and discrimination performance will be determined. Conclusions. The study provides new knowledge on SAMS in coronary patients and may contribute to more personalized statin treatment and monitoring, fewer side-effects and consequently improved adherence and lipid management in future practice.

Inflammatory biomarkers are associated with aetiology and predict outcomes in community-acquired pneumonia: results of a 5-year follow-up cohort study.

BACKGROUND: Biomarkers may facilitate clinical decisions in order to guide antimicrobial treatment and prediction of prognosis in community-acquired pneumonia (CAP). We measured serum C-reactive protein, procalcitonin (PCT) and calprotectin levels, and plasma pentraxin 3 (PTX3) and presepsin levels, along with whole-blood white cell counts, at three time-points, and examined their association with microbial aetiology and adverse clinical outcomes in CAP. METHODS: Blood samples were obtained at hospital admission, clinical stabilisation and 6-week follow-up from 267 hospitalised adults with CAP. Adverse short-term outcome was defined as intensive care unit admission and 30-day mortality. Long-term outcome was evaluated as 5-year all-cause mortality. RESULTS: Peak levels of all biomarkers were seen at hospital admission. Increased admission levels of C-reactive protein, PCT and calprotectin were associated with bacterial aetiology of CAP, while increased admission levels of PCT, PTX3 and presepsin were associated with adverse short-term outcome. In univariate and multivariate regression models, white blood cells and calprotectin at 6-week follow-up were predictors of 5-year all-cause mortality. CONCLUSIONS: Calprotectin emerges as both a potential early marker of bacterial aetiology and a predictor for 5-year all-cause mortality in CAP, whereas PCT, PTX3 and presepsin may predict short-term outcome.

A Method for Direct Monitoring of Atorvastatin Adherence in Cardiovascular Disease Prevention: Quantification of the Total Exposure to Parent Drug and Major Metabolites Using 2-Channel Chromatography and Tandem Mass Spectrometry.

BACKGROUND: Low adherence to statin therapy remains a public health concern associated with poor prognosis in cardiovascular disease patients. A feasible method for statin adherence monitoring in clinical practice has yet to be developed. In this article, we describe a novel method designed for the direct monitoring of atorvastatin adherence based on the sum of parent drug and major metabolites in blood samples. METHODS: Acid and lactone forms of atorvastatin, 2-OH-atorvastatin, and 4-OH-atorvastatin were assayed. Plasma proteins were precipitated with an acidified mixture of methanol, acetonitrile, and aqueous zinc sulfate, and the supernatant was analyzed with 2-channel reversed-phase chromatography coupled to tandem mass spectrometry. Assay validation was performed according to the guidelines provided by the European Medicines Agency and the US Food and Drug Administration. RESULTS: The effective run time was 1 minute and 45 seconds per sample. Mean accuracy ranged from 92% to 110%, and coefficients of variation were ≤8.1% over the measurement ranges for individual compounds. The sum of acids and corresponding lactones was stable in clinical plasma samples kept at ambient temperature for up to 6 days after blood sampling (mean sum within 96.6%-101% of baseline). CONCLUSIONS: A fast and reliable assay for the quantification of atorvastatin and its 5 major metabolites in clinical blood samples is reported. Limitations of preanalytical stability were solved using the sum of the acid and lactone forms. The assay is feasible for implementation in clinical practice, and the sum of parent drug and metabolites may be used for direct monitoring of atorvastatin adherence.

Managing patients with prediabetes and type 2 diabetes after coronary events: individual tailoring needed - a cross-sectional study.

BACKGROUND: Understanding the determinants associated with prediabetes and type 2 diabetes in coronary patients may help to individualize treatment and modelling interventions. We sought to identify sociodemographic, medical and psychosocial factors associated with normal blood glucose (HbA1c < 5.7%), prediabetes (HbA1c 5.7-6.4%), and type 2 diabetes. METHODS: A cross-sectional explorative study applied regression analyses to investigate the factors associated with glycaemic status and control (HbA1c level) in 1083 patients with myocardial infarction and/or a coronary revascularization procedure. Data were collected from hospital records at the index event and from a self-report questionnaire and clinical examination with blood samples at 2-36 months follow-up. RESULTS: In all, 23% had type 2 diabetes, 44% had prediabetes, and 33% had normal blood glucose at follow-up. In adjusted analyses, type 2 diabetes was associated with larger waist circumference (Odds Ratio 1.03 per 1.0 cm, p = 0.001), hypertension (Odds Ratio 2.7, p < 0.001), lower high-density lipoprotein cholesterol (Odds Ratio 0.3 per1.0 mmol/L, p = 0.002) and insomnia (Odds Ratio 2.0, p = 0.002). In adjusted analyses, prediabetes was associated with smoking (Odds Ratio 3.3, p = 0.001), hypertension (Odds Ratio 1.5, p = 0.03), and non-participation in cardiac rehabilitation (Odds Ratio 1.7, p = 0.003). In patients with type 2 diabetes, a higher HbA1c level was associated with ethnic minority background (standardized beta [ß] 0.19, p = 0.005) and low drug adherence (ß 0.17, p = 0.01). In patients with prediabetes or normal blood glucose, a higher HbA1c was associated with larger waist circumference (ß 0.13, p < 0.001), smoking (ß 0.18, p < 0.001), hypertension (ß 0.08, p = 0.04), older age (ß 0.16, p < 0.001), and non-participation in cardiac rehabilitation (ß 0.11, p = 0.005). CONCLUSIONS: Along with obesity and hypertension, insomnia and low drug adherence were the major modifiable factors associated with type 2 diabetes, whereas smoking and non-participation in cardiac rehabilitation were the factors associated with prediabetes. Further research on the effect of individual tailoring, addressing the reported significant predictors of failure, is needed to improve glycaemic control. TRIAL REGISTRATION: Retrospectively registered at ClinicalTrials.gov: NCT02309255 , December 5th 2014.

Admissions to the medical department - who admits and why. / Innleggelser i medisinsk avdeling ­ hvem legger inn og hvorfor.

BAKGRUNN: Hensikten med denne studien var å kartlegge grunnlaget for innleggelser ved en stor medisinsk avdeling i Norge. Vi har vurdert mulige alternativer til innleggelse og hvorvidt triagering kan bidra til å identifisere aktuelle pasienter. MATERIALE OG METODE: Alle innleggelser ved Medisinsk avdeling ved Drammen sykehus i en full uke høsten 2014 ble registrert med pasientens alder, kjønn, liggetid, innleggende lege/instans, hvor vedkommende ble innlagt fra og diagnose ved innleggelse og utskrivning. Alternativer til innleggelse vurdert ut fra tilstanden ved avreise fra primærhelsetjenesten ble systematisk evaluert av to fastleger og en erfaren lege ved medisinsk avdeling ved gjennomgang av innleggelsesskrivene. Pasientene ble triagert i akuttmottaket umiddelbart etter ankomst, og tilstandens alvorlighetsgrad ble sammenholdt med mulige alternativer til innleggelse. RESULTATER: Studien omfattet 255 innleggelser (52 % kvinner, gjennomsnittsalder 62 år). Innleggende lege var i 57 % av tilfellene fra primærhelsetjenesten (fastlege 26 %, legevakt 31 %) og i 24 %fra spesialisthelsetjenesten. Innleggelsen var uten direkte legehenvisning i 18 % av tilfellene. De hyppigste innleggelsesdiagnosene var hjertesykdommer (38 %), lungesykdommer (11 %) og infeksjoner (9 %). Hos 7 % av de pasientene som var innlagt av primærlege (fastlege/legevaktlege), fant vi mulige alternativer til innleggelse, oftest innleggelse i kommunal akutt døgnplass (KAD). Det var ingen sammenheng mellom triagering og alternativ til innleggelse. FORTOLKNING: Andelen innleggelser fra fastlege var høyere enn i tilsvarende studier. Én av 15 innleggelser (7 %) ble vurdert som aktuell for alternativ. Triagering skiller ikke ut pasientforløp som er egnet for alternativ til innleggelse.