Both acuity and long term prognosis are important Emergency Department metrics: comparison of mobility assessment with the Emergency Severity Index.

OBJECTIVE: To compare the SUHB mobility scale (i.e., stable(S), unstable gait(U), needing help to walk(H), or bedridden(B)) and the Emergency Severity Index (ESI) associations with admission and mortality outcomes. DESIGN: Post-hoc analysis of a prospective observational study including all consenting presenting to the ED over a period of 3 weeks. Odd ratios and AUCs were calculated to assess predictive performance of SUHB and compared with ESI. RESULTS: Out of 2422 patients, 65% presented with a stable gait, 45% with an ESI level 3. With increasing mobility impairment on the SUHB scale, the probability for admission and mortality increased. SUHB had a higher AUC than ESI for 1-year mortality. CONCLUSION: SUHB was a better predictor than ESI of long-term mortality. The scale, which is rapid, requires little additional training, and no extra costs, could be used as a useful supplement to the triage process.

Emergency presentations of older patients living with frailty: Presenting symptoms compared with non-frail patients.

BACKGROUND AND OBJECTIVE: Symptoms may differ between frail and non-frail patients presenting to Emergency Departments (ED). However, the association between frailty status and type of presenting symptoms has not been investigated. We aimed to systematically analyse presenting symptoms in frail and non-frail older emergency patients and hypothesized that frailty may be associated with nonspecific complaints (NSC), such as generalised weakness. METHODS: Secondary analysis of a prospective, single centre, observational all-comer cohort study conducted in the ED of a Swiss tertiary care hospital. All presentations of patients aged 65 years and older were analysed. At triage, presenting symptoms and frailty were systematically assessed using a questionnaire. Patients with a Clinical Frailty Scale (CFS) > 4 were considered frail. Presenting symptoms, stratified by frailty status, were analysed. The association between frailty and generalised weakness was tested by logistic regression. RESULTS: Overall, 2'416 presentations of patients 65 years and older were analysed. Mean age was 78.9 (SD 8.4) years, 1'228 (50.8%) patients were female, and 885 (36.6%) patients were frail (CFS > 4). Generalised weakness, dyspnea, localised weakness, speech disorder, loss of consciousness and gait disturbance were recorded more often in frail patients, whereas chest pain was reported more often by non-frail patients. Generalised weakness was reported as presenting symptom in 166 (18.8%) frail patients and in 153 (10.0%) non-frail patients. Frailty was associated with generalised weakness after adjusting for age, gender and elevated National Early Warning Score 2 (NEWS) ≥ 3 (OR 1.19, CI 1.10-1.29, p < 0.001). CONCLUSION: Presenting symptoms differ in frail and non-frail patients. Frailty is associated with generalised weakness at ED presentation.

D-dimer levels for Risk Stratification in Patients with Suspected COVID-19 - A Prospective Observational Study.

BACKGROUND: Elevated D-dimer levels have been observed in COVID-19 and are of prognostic value, but have not been compared to an appropriate control group. METHODS: Observational cohort study including emergency patients with suspected or confirmed COVID-19. Logistic regression defined the association of D-dimer levels, COVID-19 positivity, age, and gender with 30-day-mortality. RESULTS: 953 consecutive patients (median age 58, 43% women) presented with suspected COVID-19: 12 (7.4%) patients with confirmed SARS-CoV-2-infection died, compared with 28 (3.5%) patients without SARS-CoV-2-infection. Overall, most (56%) patients had elevated D-dimer levels (≥0.5mg/l). Age (OR 1.07, CI 1.05-1.10), D-dimer levels ≥0.5mg/l (OR 2.44, CI 0.98-7.39), and COVID-19 (OR 2.79, CI 1.28-5.80) were associated with 30-day-mortality. CONCLUSION: D-dimer levels are effective prognosticators in both patient groups.

Usability of a Web-based Software Tool for History Taking in the Emergency Department.

Medical history taking is an important step within the diagnostic process. This study aims to assess the quality and usability (effectiveness, satisfaction, efficiency) of a web-based medical history taking app in the emergency department. During three weeks, patients and junior physicians filled out study questionnaires about the app. Senior physicians rated the quality of medical histories taken by junior physicians and app. In 241 patients, the studied app showed excellent usability with patients not in need of immediate medical attention. Senior physicians rated medical histories as more complete when app was used by patients in comparison to conventional history taking alone (p<0.01). Current app could not substitute medical history taking by physicians, but could definitely rather be used to gather ancillary information.

Mid-regional pro-atrial natriuretic peptide and the assessment of volaemic status and differential diagnosis of profound hyponatraemia.

BACKGROUND: Hyponatraemia is common and its differential diagnosis and consequent therapy management is challenging. The differential diagnosis is mainly based on the routine clinical assessment of volume status, which is often misleading. Mid-regional pro-atrial natriuretic peptide (MR-proANP) is associated with extracellular and cardiac fluid volume. METHODS: A total of 227 consecutive patients admitted to the emergency department with profound hypo-osmolar hyponatraemia (Na < 125 mmol L(-1) ) were included in this prospective multicentre observational study conducted in two tertiary centres in Switzerland. A standardized diagnostic evaluation of the underlying cause of hyponatraemia was performed, and an expert panel carefully evaluated volaemic status using clinical criteria. MR-proANP levels were compared between patients with hyponatraemia of different aetiologies and for assessment of volume status. RESULTS: MR-proANP levels were higher in patients with hypervolaemic hyponatraemia compared to patients with hypovolaemic or euvolaemic hyponatraemia (P = 0.0002). The area under the curve (AUC) to predict an excess of extracellular fluid volume, compared to euvolaemia, was 0.73 [95% confidence interval (CI) 0.62-0.84]. Additionally, in multivariate analysis, MR-proANP remained an independent predictor of excess extracellular fluid volume after adjustment for congestive heart failure (P = 0.012). MR-proANP predicted the syndrome of inappropriate antidiuresis (SIAD) versus hypovolaemic and hypervolaemic hyponatraemia with an AUC of 0.77 (95% CI 0.69-0.84). CONCLUSION: MR-proANP is associated with extracellular fluid volume in patients with hyponatraemia and remains an independent predictor of hypervolaemia after adjustment for congestive heart failure. MR-proANP may be a marker for discrimination between the SIAD and hypovolaemic or hypervolaemic hyponatraemia.

Clinical intuition ratings are associated with morbidity and hospitalisation.

OBJECTIVE: To evaluate how the rating of the severity of sickness - as performed by the physician, nurse and patient - is associated with hospitalisation and acute morbidity. METHODS: Prospective observational study, performed in the emergency department of a tertiary hospital. Patients, physicians and nurses were interviewed separately after the first contact from 21 October through to 11 November 2013. RESULTS: Of 2426 presenting patients, 1861 were screened, and 1196 were included. A total of 299 (25%) were hospitalised, 504 (42%) suffered acute morbidity. In the univariate analysis, the physician's, nurse's and patient's rating of severity of sickness, expressed on a scale from 0 to 10, was significantly associated with hospitalisation (physicians: OR 1.61, 95% CI 1.50-1.73; nurses: OR 1.52, 1.41-1.64; patients: OR 1.16, 1.10-1.22), and with acute morbidity (OR 1.49, 1.40-1.59; OR 1.39, 1.30-1.48 and OR 1.05, 1.003-1.09 respectively). The area under the curve of the receiver operating characteristic curves was 0.77, 0.72 and 0.61 for hospitalisation, and 0.72, 0.68 and 0.54 for acute morbidity. The interrater reliability was estimated by the intraclass correlation, which was 0.49 for physician/nurse, 0.17 for nurse/patient and 0.07 for physician/patient. In a multivariable analysis model consisting of age, male sex, ethnic origin, ratings of severity of sickness, symptoms, ability to go home and hospitalisation during the preceding 12 months, only age, and the physician's and nurses' rating of severity of sickness remained significantly associated with both outcomes. CONCLUSION: The first impression of severity of sickness was associated with hospitalisation and morbidity.

Biphasic anaphylactic reactions: occurrence and mortality.

BACKGROUND: Monitoring after complete resolution of anaphylactic reactions is recommended. The aim of this study was to define the occurrence of biphasic - and clinically important biphasic - anaphylactic reactions, the number of transfers to intensive care units (ICU) because of anaphylaxis, and the number of deaths within 10 days of presentation to the emergency department (ED). METHODS: Clinical records of patients visiting the ED of a tertiary care hospital were analysed retrospectively. Hospital databases, direct contact with patients and caregivers, and the Internet were used to obtain mortality rates. RESULTS: Of 259 557 ED presentations from February 2001 through to August 2013, 1334 (0.51%) episodes of allergic reactions were detected, and 532 (0.20%) episodes in 495 patients fulfilled the definition of anaphylaxis. In 227 (44.8%) episodes, the length of hospital stay was ≥8 h (median 22 h, IQR 16-24). There were 507 uniphasic and 25 (4.5%) biphasic anaphylactic reactions. Twelve (2.3%) were clinically important, including 2 (0.36%) that occurred during hospital stay, one of whom (0.19%) was transferred to ICU for shock. No risk factors for biphasic reactions could be found. Eight patients were lost to follow-up. There were no deaths during the 10-day follow-up. CONCLUSION: Biphasic anaphylactic reactions, especially clinically important ones, occurred rarely, and no mortality was found, whether the monitoring was for ≥8 h or for <8 h. Our study could motivate physicians to consider discharging patients after complete resolution of an anaphylactic reaction and to dispense with prolonged monitoring.

[Initial patient assessment of infectious diseases and diagnostic steps with fever]. / Infektiologische Erstbeurteilung und erste Abklärungsschritte bei Fieber.

The initial assessment of patients with infectious diseases is challenging because of the extremely broad differential diagnosis as well as different host pathogen interactions influenced by a different immune status. The formal initial assessment, including the present and past medical history, thorough physical examination, clinical first impressions as well as routine laboratory analyses, is the basis of every preliminary diagnosis. Specific chief complaints have to be recognized in order to narrow down the differential diagnosis. In cases of life-threatening illnesses, such as septicemia, endocarditis, bacterial meningitis and severe pneumonia, the first diagnostic and therapeutic steps should be performed in a rapid sequence: bacterial blood samples, sputum and/or liquor samples are required and the initial antibiotic therapy has to be chosen empirically as the relevant bacterial spectrum related to the suspected illness must be covered. In less urgent cases it is recommended that a multi-step diagnostic approach be carried out which takes the differential diagnosis into account and prioritizes the probabilities. In the latter situation antibiotic treatment should be delayed to diagnose the infection correctly. Importantly, atypical courses must necessitate careful and critical reassessment of the diagnosis.

A fast emergency department triage score based on mobility, mental status and oxygen saturation compared with the emergency severity index: a prospective cohort study.

BACKGROUND: Waiting for triage in overburdened emergency departments (ED) has become an increasing problem, which endangers patients. A fast triage system to rapidly identify low-acuity patients should divert care and resources to more urgent cases. AIM: The objective of this study was to compare the performance of the Kitovu Hospital fast triage (KFT) score with the Emergency Severity Index (ESI), using mortality and hospital admission as proxies for the patients' acuity. DESIGN: This is a prospective observational study of consecutive patients presenting to a Swiss academic ED. METHODS: Patients were prospectively triaged into one of five ESI strata and retrospectively assessed by the KFT score, which awards one point each for altered mental status, impaired mobility and oxygen saturation <94%. RESULTS: The KFT score had a lower discrimination than the ESI for hospital admission, but a higher discrimination for mortality from 24 h to 1 year after ED presentation. A total of 5544 (67%) patients were assigned to the lowest acuity by the KFT score compared with 2374 (28.7%) by the ESI; there was no significant difference in the 24-h mortality of patients who were deemed low acuity by either score. CONCLUSION: Compared to the ESI, the KFT score identifies more than twice as many patients at low risk of early death. Therefore, this score might help to identify patients who could be managed through alternative pathways. This may be particularly helpful in situations of ED crowding and access block.

Anterior pituitary axis hormones and outcome in acute ischaemic stroke.

BACKGROUND: Early and accurate prediction of outcome in acute stroke is important and influences risk-optimized therapeutic strategies. Endocrine alterations of the hypothalamic-pituitary axis are amongst the first measurable alterations after cerebral ischaemia. We therefore evaluated the prognostic value of cortisol, triiodothyronine (T3), free thyroxine (fT4), thyroid-stimulating hormone (TSH) and growth hormone (GH) in patients with an acute ischaemic stroke. METHODS: In an observational study including 281 patients with ischaemic stroke, anterior pituitary axis hormones (i.e. cortisol, T3, fT4, TSH and GH) were simultaneously assessed to determine their value to predict functional outcome and mortality within 90 days and 1 year. RESULTS: In receiver operating characteristic curve analysis, the prognostic accuracy of cortisol was higher compared to all measured hormones and was in the range of the National Institutes of Health Stroke Scale (NIHSS). Cortisol was an independent prognostic marker of functional outcome and death [odds ratio (OR) 1.0 (1.0-1.01) and 1.62 (1.37-1.92), respectively, P<0.0002 for both, adjusted for age and the NIHSS] in patients with ischaemic stroke, but added no significant additional predictive value to the clinical NIHSS score. CONCLUSION: Cortisol is an independent prognostic marker for death and functional outcome within 90 days and 1 year in patients with ischaemic stroke. By contrast, other anterior pituitary axis hormones such as peripheral thyroid hormones and GH are only of minor value to predict outcome in stroke.

Comparison of midregional pro-atrial natriuretic peptide with N-terminal pro-B-type natriuretic peptide in the diagnosis of heart failure.

OBJECTIVES: The concentration of atrial natriuretic peptide (ANP) in the circulation is approximately 10- to 50- fold higher than B-type natriuretic peptide (BNP). We sought to compare the accuracy of midregional pro-atrial natriuretic peptide (MRproANP) measured with a novel sandwich immunoassay with N-terminal pro-B-type natriuretic peptide (NTproBNP) in the diagnosis of heart failure. DESIGN: The diagnosis of heart failure was adjudicated by two independent cardiologists using all available clinical data (including BNP levels) in 287 consecutive patients presenting with dyspnoea to the emergency department (ED). MRproANP and NTproBNP levels were determined at presentation in a blinded fashion. RESULTS: Heart failure was the adjudicated final diagnosis in 154 patients (54%). Median MRproANP was significantly higher in patients with heart failure as compared to patients with other causes of dyspnoea (400 vs. 92 pmol L(-1), P < 0.001). The diagnostic accuracy of MRproANP was very high with an area under the receiver operating characteristic curve of 0.92 and was comparable with that of NTproBNP (0.92, P = 0.791). Moreover, MRproANP provided incremental diagnostic information to BNP and NTproBNP in patients presenting with BNP levels in the grey zone between 100 and 500 pg mL(-1). CONCLUSION: Midregional pro-atrial natriuretic peptide is as accurate in the diagnosis of heart failure as NTproBNP. MRproANP seems to provide incremental information on top of BNP or NT-proBNP in some subgroups and should be further investigated in other studies.

Use of B-type natriuretic peptide in the risk stratification of community-acquired pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is the leading infectious cause of death in developed countries. Risk stratification has previously been difficult. METHODS: Markers of cardiac stress (B-type natriuretic peptide, BNP) and inflammation (C-reactive protein, white blood cell count, procalcitonin) as well as the pneumonia severity index (PSI) were determined in 302 consecutive patients presenting to the emergency department (ED) with CAP. The accuracy of these parameters to predict death was evaluated as the primary endpoint. Prediction of treatment failure was considered as the secondary endpoint. RESULTS: B-type natriuretic peptide levels increased with rising disease severity as classified by the PSI (P = 0.015). BNP levels were significantly higher in nonsurvivors compared to survivors [median 439.2 (IQR 137.1-1384.6) vs. 114.3 (51.3-359.6) pg mL(-1), P < 0.001]. In a receiver operating characteristic analysis for the prediction of survival the area under the curve (AUC) for BNP was comparable to the AUC of the PSI (0.75 vs. 0.71, P = 0.52). Importantly, the combination of BNP and the PSI significantly improved the prognostic accuracy of the PSI alone (AUC 0.78 vs. 0.71; P = 0.02). The optimal cut-off for BNP was 279 pg mL(-1). The accuracy of BNP to predict treatment failure was identical to the accuracy to predict death (AUC 0.75). CONCLUSIONS: In patients with CAP, BNP levels are powerful and independent predictors of death and treatment failure. When used in conjunction with the PSI, BNP levels significantly improve the risk prediction when compared with the PSI alone.

End-of-life decisions in emergency patients: prevalence, outcome and physician effect.

BACKGROUND: End-of-life decisions (EOLD) represent potentially highly consequential decisions often made in acute situations, such as 'do not attempt resuscitation' (DNAR) choices at emergency presentation. AIM: We investigated DNAR decisions in an emergency department (ED) to assess prevalence, associated patient characteristics, potential medical and economic consequences and estimate contributions of patients and physicians to DNAR decisions. DESIGN: Single-centre retrospective observation, including ED patients with subsequent hospitalization between 2012 and 2016. Primary outcome was a DNAR decision and associated patient characteristics. Secondary outcomes were mortality, admission to intensive care unit and use of resources. METHODS: Associations between DNAR and patient characteristics were analysed using logistic mixed effects models, results were reported as odds ratios (OR). Median odds ratios (MOR) were used to estimate patient and physician contributions to variability in DNAR. RESULTS: Patients of 10 458 were attended by 315 physicians. DNAR was the choice in 23.3% of patients. Patients' characteristics highly associated with DNAR were age (OR = 4.0, 95% CI = 3.6-4.3) and non-trauma presentation (OR = 2.3, 95% CI = 1.9-2.9). In-hospital mortality was significantly higher (OR = 5.4, CI = 4.0-7.3), and use of resources was significantly lower (OR = 0.7, CI = 0.6-0.8) in patients choosing DNAR. There was a significant effect on DNAR by both patient (MOR = 1.8) and physician (MOR = 2.0). CONCLUSIONS: DNAR choices are common in emergency patients and closely associated with age and non-trauma presentation. Mortality was significantly higher, and use of resources significantly lower in DNAR patients. Evidence of a physician effect raises questions about the choice autonomy of emergency patients in the process of EOLD.

Systematically assessed symptoms as outcome predictors in emergency patients.

INTRODUCTION: It is known that symptoms are predictive of mortality in "nonsurgical" emergency patients. It is unknown whether a prospective, systematic, and "unscreened" assessment of all symptoms is of any prognostic value. Therefore, we aimed to examine the association between symptoms and outcomes in an all-comer population. METHODS: Data were acquired during 6weeks at the ED of the University Hospital Basel, a tertiary hospital. Consecutive patients presenting to the ED were included. Symptoms at presentation were systematically assessed using a comprehensive questionnaire. RESULTS: A consecutive sample of 3960 emergency patients with a median age of 51years (51.7% male) was studied. The median number of symptoms was two. In the group of patients with the most prevalent symptoms, the median number of symptoms ranged between two and five. Overall, hospitalisation rate was 31.2%, referral to intensive care was 5.5%, in-hospital-mortality was 1.4%, and one-year mortality was 5.8%. In-hospital mortality ranged from 0% to 4.3%, and one-year mortality from 0% to 14.4% depending on the presenting symptoms. Dyspnoea and weakness were significant predictors of one-year mortality (14.4% and 9.2%, respectively). DISCUSSION: Most emergency patients indicated two or more symptoms. Systematically assessed symptoms at presentation can be used for prediction of outcomes. While dyspnoea is a known predictor, weakness has not been identified as predictor of mortality before. This knowledge could be used to improve risk stratification- thereby reducing the risk of adverse outcomes.

Risk stratification using D-dimers in patients presenting to the emergency department with nonspecific complaints.

BACKGROUND: Patients with nonspecific complaints (NSC) such as generalized weakness present frequently to acute care settings. These patients are at risk of adverse health outcomes. The aim of our study was to test the hypothesis whether D-dimers are predictive for 30-day mortality in patients with NSCs. METHODS: Delayed type cross-sectional diagnostic study with a 30-day follow-up period, registered with ClinicalTrials.gov (NCT00920491). This study took place in 2 EDs in Northwestern Switzerland. Patients were enrolled in the study if they were over 18years of age, gave informed consent, and if they presented with NSCs such as generalized weakness. D-dimer levels were determined at ED presentation. RESULTS: The final study population consisted of 524 patients. Median age was 82years (IQR=75 to 87years); 40.5% were men. There were 489 survivors and 35 non-survivors at 30-day follow-up. Twenty-one (60%) of the non-survivors were males. D-dimer levels were significantly higher in non-survivors than in survivors (p<0.001). Univariate Cox regression models for D-dimer resulted in a C-index of 0.77 for prediction of mortality. A model including sex, age, Katz ADL and D-dimer in a multivariate Cox regression lead to a C-Index of 0.80. CONCLUSION: D-dimer testing might be an effective risk stratification tool in patients with NSC by helping to identify patients at low risk of short-term mortality with a sensitivity of 0.97 and a negative likelihood ratio of 0.121. The use of D-dimers for risk stratification in patients with NSC should be confirmed with prospective studies.

Lethal autoimmune myocarditis in interferon-gamma receptor-deficient mice: enhanced disease severity by impaired inducible nitric oxide synthase induction.

BACKGROUND: Interferon-gamma (IFN-gamma) is an essential cytokine in the regulation of inflammatory responses in autoimmune diseases. Little is known about its role in inflammatory heart disease. METHODS AND RESULTS: We showed that IFN-gamma receptor-deficient mice (IFN-gammaR(-/-)) on a BALB/c background immunized with a peptide derived from cardiac alpha-myosin heavy chain develop severe myocarditis with high mortality. Although myocarditis subsided in wild-type mice after 3 weeks, IFN-gammaR(-/-) mice showed persistent disease. The persistent inflammation was accompanied by vigorous in vitro CD4 T-cell responses and impaired inducible nitric oxide synthase expression, together with evidence of impaired nitric oxide production in IFN-gammaR(-/-) hearts. Treatment of wild-type mice with the nitric oxide synthetase inhibitor N:-nitro-l-arginine-methyl-ester enhanced in vitro CD4 T-cell proliferation and prevented healing of myocarditis. CONCLUSIONS: Our data provide evidence that IFN-gamma protects mice from lethal autoimmune myocarditis by inducing the expression of inducible nitric oxide synthase followed by the downregulation of T-cell responses.

Impact of physical activity on cardiovascular risk factors in IDDM.

OBJECTIVE: To study the impact of physical activity on glycemic control and plasma lipids [HDL cholesterol (HDL-C), HDL-C subfractions, triglycerides, lipoprotein(a)], blood pressure, weight, and abdominal fat and to determine the necessary short-term adaptations in diabetes management during intensive endurance training in patients with IDDM. RESEARCH DESIGN AND METHODS: Well-controlled subjects with IDDM (n = 20; HbA1c = 7.6%) engaged in a regular exercise program over a period of 3 months involving endurance sports such as biking, long-distance running, or hiking. Subjects were instructed to exercise at least 135 min per week. If baseline activity exceeded this level, subjects were to increase further their physical activity as much as possible and record the type and time of such activity. RESULTS: During the 3-month intervention, physical activity increased from 195 +/- 176 to 356 +/- 164 min (mean +/- SD) per week (P < 0.001). Physical fitness as assessed by VO2max increased from 2,914 +/- 924 to 3,092 +/- 905 ml/min (P < 0.001), and insulin sensitivity increased significantly (steady-state plasma glucose [SSPG] decreased from 10.5 +/- 4.8 to 7.0 +/- 3.3 mmol/l; P < 0.01). Subsequently, LDL cholesterol decreased by 14% (P < 0.05), and HDL and HDL3-C subfraction increased by 10 (P < 0.05) and 16% (P < 0.05), respectively. Systolic and diastolic blood pressure decreased significantly from 127 +/- 9 to 124 +/- 8 (P < 0.05) and from 80 +/- 5 to 77 +/- 5 mmHg (P < 0.01), respectively. Resting heart rate decreased from 63 +/- 6 to 59 +/- 7 bpm (P < 0.01). Waist-to-hip circumference ratio decreased from 0.882 +/- 0.055 to 0.858 +/- 0.053 (P < 0.001), body weight decreased from 70.7 +/- 10.4 to 68.7 +/- 10.2 kg (P = 0.003), with a consequent decrease in body fat from 21.9 +/- 8.2 to 18.0 +/- 6.3% (P < 0.001) and an increase in lean body mass from 54.9 +/- 12.2 to 56.8 +/- 11.0 kg. These effects occurred independently of glycemic control. The overall frequency of severe hypoglycemic episodes was reduced from 0.14 to 0.10 per patient-year during the study period. CONCLUSIONS: This study shows that increasing physical activity is safe and does not result in more hypoglycemic episodes and that there is a linear dose-response between increased physical activity and loss of abdominal fat and a decrease in blood pressure and lipid-related cardiovascular risk factors, with a preferential increase in the HDL3-C subfraction.