ABSTRACT
AIMS: Patients with heart failure (HF) and iron deficiency experience poor health-related quality of life (HRQoL). We evaluated the impact of intravenous (IV) ferric carboxymaltose (FCM) vs. placebo on HRQoL for the AFFIRM-AHF population. METHODS AND RESULTS: The baseline 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which was completed for 1058 (535 and 523) patients in the FCM and placebo groups, respectively, was administered prior to randomization and at Weeks 2, 4, 6, 12, 24, 36, and 52. The baseline KCCQ-12 overall summary score (OSS) mean ± standard error was 38.7 ± 0.9 (FCM group) and 37.1 ± 0.8 (placebo group); corresponding values for the clinical summary score (CSS) were 40.9 ± 0.9 and 40.1 ± 0.9. At Week 2, changes in OSS and CSS were similar for FCM and placebo. From Week 4 to Week 24, patients assigned to FCM had significantly greater improvements in OSS and CSS scores vs. placebo [adjusted mean difference (95% confidence interval, CI) at Week 4: 2.9 (0.5-5.3, P = 0.018) for OSS and 2.8 (0.3-5.3, P = 0.029) for CSS; adjusted mean difference (95% CI) at Week 24: 3.0 (0.3-5.6, P = 0.028) for OSS and 2.9 (0.2-5.6, P = 0.035) for CSS]. At Week 52, the treatment effect had attenuated but remained in favour of FCM. CONCLUSION: In iron-deficient patients with HF and left ventricular ejection fraction <50% who had stabilized after an episode of acute HF, treatment with IV FCM, compared with placebo, results in clinically meaningful beneficial effects on HRQoL as early as 4 weeks after treatment initiation, lasting up to Week 24.
Subject(s)
Anemia, Iron-Deficiency , Heart Failure , Quality of Life , Humans , Anemia, Iron-Deficiency/drug therapy , Ferric Compounds/therapeutic use , Heart Failure/complications , Heart Failure/drug therapy , Iron/therapeutic use , Maltose/therapeutic use , Stroke Volume , Treatment Outcome , Ventricular Function, LeftABSTRACT
BACKGROUND: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. METHODS: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin <100 µg/L, or 100-299 µg/L with transferrin saturation <20%), and had a left ventricular ejection fraction of less than 50%. Before hospital discharge, participants were randomly assigned (1:1) to receive intravenous ferric carboxymaltose or placebo for up to 24 weeks, dosed according to the extent of iron deficiency. To maintain masking of patients and study personnel, treatments were administered in black syringes by personnel not involved in any study assessments. The primary outcome was a composite of total hospitalisations for heart failure and cardiovascular death up to 52 weeks after randomisation, analysed in all patients who received at least one dose of study treatment and had at least one post-randomisation data point. Secondary outcomes were the composite of total cardiovascular hospitalisations and cardiovascular death; cardiovascular death; total heart failure hospitalisations; time to first heart failure hospitalisation or cardiovascular death; and days lost due to heart failure hospitalisations or cardiovascular death, all evaluated up to 52 weeks after randomisation. Safety was assessed in all patients for whom study treatment was started. A pre-COVID-19 sensitivity analysis on the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT02937454, and has now been completed. FINDINGS: Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57·2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72·5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0·79, 95% CI 0·62-1·01, p=0·059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0·80, 95% CI 0·64-1·00, p=0·050). There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0·96, 95% CI 0·70-1·32, p=0·81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0·74; 95% CI 0·58-0·94, p=0·013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0·80, 95% CI 0·66-0·98, p=0·030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0·67, 95% CI 0·47-0·97, p=0·035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group. INTERPRETATION: In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death. FUNDING: Vifor Pharma.
Subject(s)
Anemia, Iron-Deficiency/drug therapy , Ferric Compounds/therapeutic use , Heart Failure/drug therapy , Maltose/analogs & derivatives , Administration, Intravenous , Aged , Aged, 80 and over , Double-Blind Method , Female , Ferric Compounds/administration & dosage , Heart Failure/complications , Heart Failure/mortality , Hospitalization/statistics & numerical data , Humans , Male , Maltose/administration & dosage , Maltose/therapeutic use , Middle Aged , Patient Discharge , Treatment Outcome , Ventricular Function, LeftABSTRACT
AIMS: Although diabetes mellitus (DM) is a common co-morbidity in chronic heart failure (HF) patients, European data on concurrent HF and DM treatment are lacking. Therefore, we have studied the HF treatment of patients with and without DM. Additionally, with the recent breakthrough of sodium-glucose cotransporter 2 (SGLT2) inhibitors in the field of HF, we studied the potential impact of this new drug in a large cohort of HF patients. METHODS AND RESULTS: A total of 7488 patients with chronic HF with a left ventricular ejection fraction <50% from 34 Dutch outpatient HF clinics between 2013 and 2016 were analysed on diabetic status and background HF therapy. Average age of the total population was 72.8 years (±11.7 years), and 64% of the patients were male. Diabetes was present in 29% of the patients (N = 2174). Diabetics had a worse renal function (mean estimated glomerular filtration rate 56 vs. 61 mL/min/1.73 m2 , P < 0.001). Renin-angiotensin system inhibitors were less often prescribed in diabetics compared with non-diabetics (79% vs. 82%, P = 0.001), while no significant differences regarding other guideline-recommended HF drugs were found. Target doses of beta-blockers (23% vs. 16%, P < 0.001), renin-angiotensin system inhibitors (47% vs. 43%, P = 0.009), and mineralocorticoid receptor antagonists (57% vs. 51%, P = 0.005) were more often prescribed in diabetics than non-diabetics. Based on the latest trials on SGLT2 inhibitors, 31-64% of all HF patients would fulfil the eligibility or enrichment criteria (with vs. without N-terminal prohormone BNP criterion). CONCLUSIONS: In this large real-world HF registry, a high prevalence of DM was observed and diabetics more often received guideline-recommended target doses. Based on current evidence, the majority of patients would fulfil the enrichment criteria of SGLT2 trials in HF and the impact of this new drug class will be large.
Subject(s)
Diabetes Mellitus , Heart Failure , Aged , Heart Failure/drug therapy , Heart Failure/epidemiology , Humans , Male , Mineralocorticoid Receptor Antagonists/pharmacology , Mineralocorticoid Receptor Antagonists/therapeutic use , Stroke Volume , Ventricular Function, LeftABSTRACT
Patients with a pectus excavatum frequently experience medical problems such as dyspnoea, fatigue and palpitations. After surgical intervention most patients are alleviated of their symptoms. Pectus excavatum can easily be diagnosed by a proper inspection of the chest. In the Atrium Medical Center photographic documentation of the deformation of the chest is part of the treatment protocol before and after surgical correction of a pectus excavatum. In addition to the normal photographic routine two special recording techniques are applied: measuring the depth of the excavation with a rule, and documenting the depth of the excavation in a 3-D grid-projection image. The applied 3-D technique (raster stereography) can also be an asset to other medical specialty areas in which changes in body shape and appearance play a major role.
Subject(s)
Funnel Chest/surgery , Photography/methods , Plastic Surgery Procedures/methods , Documentation/methods , Funnel Chest/diagnosis , Humans , Outcome and Process Assessment, Health Care/methods , Photography/instrumentationABSTRACT
OBJECTIVE: To compare the treatment effect on lifestyle-related risk factors (LRFs) in older (≥65 years) versus younger (<65 years) patients with coronary artery disease (CAD) in The Randomised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists 2 (RESPONSE-2) trial. METHODS: The RESPONSE-2 trial was a community-based lifestyle intervention trial (n=824) comparing nurse-coordinated referral with a comprehensive set of three lifestyle interventions (physical activity, weight reduction and/or smoking cessation) to usual care. In the current analysis, our primary outcome was the proportion of patients with improvement at 12 months follow-up (n=711) in ≥1 LRF stratified by age. RESULTS: At baseline, older patients (n=245, mean age 69.2±3.9 years) had more adverse cardiovascular risk profiles and comorbidities than younger patients (n=579, mean age 53.7±6.6 years). There was no significant variation on the treatment effect according to age (p value treatment by age=0.45, OR 1.67, 95% CI 1.22 to 2.31). However, older patients were more likely to achieve ≥5% weight loss (OR old 5.58, 95% CI 2.77 to 11.26 vs OR young 1.57, 95% CI 0.98 to 2.49, p=0.003) and younger patients were more likely to show non-improved LRFs (OR old 0.38, 95% CI 0.22 to 0.67 vs OR young 0.88, 95% CI 0.61 to 1.26, p=0.01). CONCLUSION: Despite more adverse cardiovascular risk profiles and comorbidities among older patients, nurse-coordinated referral to a community-based lifestyle intervention was at least as successful in improving LRFs in older as in younger patients. Higher age alone should not be a reason to withhold lifestyle interventions in patients with CAD.
Subject(s)
Ambulatory Care , Coronary Artery Disease/nursing , Healthy Lifestyle , Nurse Clinicians , Risk Reduction Behavior , Secondary Prevention , Adult , Age Factors , Aged , Aged, 80 and over , Comorbidity , Coronary Artery Disease/diagnosis , Coronary Artery Disease/physiopathology , Diet, Healthy , Exercise , Female , Heart Disease Risk Factors , Humans , Male , Middle Aged , Netherlands , Risk Assessment , Smoking Cessation , Time Factors , Treatment Outcome , Weight LossABSTRACT
AIMS: Iron deficiency (ID) is a common co-morbidity in heart failure (HF), associated with impaired functional capacity, poor quality of life and increased morbidity and mortality. Treatment with intravenous (i.v.) ferric carboxymaltose (FCM) has shown improvements in functional capacity, symptoms and quality of life in stable HF patients with reduced ejection fraction. The effect of i.v. iron supplementation on morbidity and mortality in patients hospitalised for acute HF (AHF) and who have ID has yet to be established. The objective of the present article is to present the rationale and design of the AFFIRM-AHF trial (ClinicalTrials.gov NCT02937454) which will investigate the effect of i.v. FCM (vs. placebo) on recurrent HF hospitalisations and cardiovascular (CV) mortality in iron-deficient patients hospitalised for AHF. METHODS: AFFIRM-AHF is a multicentre, randomised (1:1), double-blind, placebo-controlled trial which recruited 1100 patients hospitalised for AHF and who had iron deficiency ID defined as serum ferritin <100 ng/mL or 100-299 ng/mL if transferrin saturation <20%. Eligible patients were randomised (1:1) to either i.v. FCM or placebo and received the first dose of study treatment just prior to discharge for the index hospitalisation. Patients will be followed for 52 weeks. The primary outcome is the composite of recurrent HF hospitalisations and CV mortality. The main secondary outcomes include the composite of recurrent CV hospitalisations and CV mortality, recurrent HF hospitalisations and safety-related outcomes. CONCLUSION: The AFFIRM-AHF trial will evaluate, compared to placebo, the effect of i.v. FCM on morbidity and mortality in iron-deficient patients hospitalised for AHF.
Subject(s)
Anemia, Iron-Deficiency/drug therapy , Ferric Compounds/administration & dosage , Heart Failure/drug therapy , Hospitalization/trends , Inpatients , Maltose/analogs & derivatives , Aged , Anemia, Iron-Deficiency/etiology , Anemia, Iron-Deficiency/mortality , Dose-Response Relationship, Drug , Double-Blind Method , Female , Follow-Up Studies , Heart Failure/complications , Heart Failure/mortality , Humans , Injections, Intravenous , Male , Maltose/administration & dosage , Middle Aged , Quality of Life , Retrospective Studies , Survival Rate/trends , Switzerland/epidemiology , Treatment OutcomeABSTRACT
Objectives: A standard coronary artery calcium scan includes part of the aorta. This additional information is often not included in routine analyses. We aimed to determine the feasibility of assessing the Agatston score of the descending aorta calcification (DAC) on standard coronary calcium scans and the association of this score with coronary events in a low-risk study population. Methods: Between January 2008 and March 2011, 390 consecutive patients who were referred for cardiac CT as part of work-up for pulmonary vein isolation (n=115) or assessment of presence of coronary artery disease (n=275) were included. At baseline, all patients were free of a history of cardiovascular disease. Two independent observers determined the Agatston score of the ascending aorta and descending aorta. Results: A total of 16 patients (4.1%) developed coronary events (acute coronary syndrome (n=6) and symptomatic significant coronary artery disease requiring treatment (n=10)) during a follow-up of 67±12 months, with more events in patients with calcifications in the descending aorta than in those without (8.4% vs 3.7 %; p=0.08). Multivariable Cox regression, corrected for Framingham Risk Score (FRS) and coronary Agatston score (CAC), revealed that DAC was independently associated with coronary events (per 100 units; HR: 1.06, 95% CI 1.02 to 1.09; p=0.001). DAC furthermore increased the identification of patients that will experience a coronary event (area under the curve: 0.68 for FRS only, 0.75 for FRS+CAC and 0.78 for FRS+CAC+DAC). Conclusions: The Agatston score of the descending aorta could be included in the standard analysis of cardiac CT scans of low-risk patients since it holds valuable information for the prediction of coronary events.
ABSTRACT
During a routine physical examination, the degree of pectus excavatum (PE) is not always appreciated as the external appearance does not always reflect the severity of the deformity. In the patient in this case report, the severity had been underestimated for 33â years. The physicians, having requested standard two-view chest radiographs, had relied solely on the radiological reports, where the PE had been ambiguously described as 'moderate' or 'substantial'. In patients where PE has been observed, it is essential that an objective numeric measure of severity, using the Haller index, is included in radiological reports.
Subject(s)
Funnel Chest/diagnostic imaging , Radiography, Thoracic/methods , Adult , Delayed Diagnosis , Funnel Chest/physiopathology , Humans , Male , Severity of Illness Index , Tomography, X-Ray ComputedABSTRACT
AIMS: Internationally, research indicates that pharmacotherapy for chronic heart failure (CHF) is sub-optimal. Traditionally, assessment of drug use in heart failure has focused on the use of individual agents irrespective of CHF severity. This study investigates drug use for CHF patients in general practice with respect to the available evidence, incorporating both disease severity and the use of combination drug regimes. METHODS AND RESULTS: A cross-sectional survey of 769 Dutch CHF patients was performed as part of IMPROVEMENT of HF study. For each New York Heart Association severity classification the minimum treatment appropriate for the heart failure severity according to the scientific evidence available at the time of the study (1999) was defined. The proportion of patients treated with each drug increased with increasing severity, with the exception of the beta-blockers. Patients with less severe heart failure were approximately four to eight times more likely to receive evidence-based treatment than those with more severe heart failure. DISCUSSION: To assess pharmacological treatment of heart failure, in relation to the available evidence, it is important to take severity into account. While the number of drugs prescribed increased with increasing severity, the use of evidence-based regimes was lower in patients with more severe heart failure.
Subject(s)
Drug Therapy , Evidence-Based Medicine , Family Practice , Heart Failure/drug therapy , Adrenergic beta-Antagonists/therapeutic use , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Comorbidity , Cross-Sectional Studies , Digoxin/therapeutic use , Diuretics/therapeutic use , Drug Therapy, Combination , Female , Heart Failure/classification , Heart Failure/epidemiology , Humans , Hypertension/drug therapy , Hypertension/epidemiology , Male , Middle Aged , Myocardial Infarction/drug therapy , Myocardial Infarction/epidemiology , Severity of Illness Index , Treatment OutcomeABSTRACT
Objectives. Doctors all over the world consider a pectus excavatum usually as an incidental finding. There is some evidence suggesting that a pectus excavatum may cause symptoms in the elderly. It is not known how often a pectus excavatum occurs and how strong the relation is with symptoms. Methods. In hospitals and general practice data, we searched for evidence of a connection between cardiac symptoms and the presence of a pectus excavatum in a retrospective survey among patients in whom a pectus excavatum was found in a chest X-ray. In radiology reports, we searched for "pectus excavat(∗) " in almost 160000 chest X-rays. The identified X-rays were reviewed by 2 radiologists. Reported symptoms were combined to a severity sum score and the relation with pectus excavatum was assessed through logistic regression. Results. Pectus excavatum was found in 1 to 2 per 1000 chest X-rays. In 32% of patients (N = 117), we found symptoms that might reflect the presence of symptomatic pectus excavatum. We found a significant relation between the SPES sum score and the radiological level of pectus excavatum. Conclusions. A pectus excavatum found when examining the patient should not be neglected and should be considered as a possible explanation for symptoms like dyspnoea, fatigue, or palpitations.
ABSTRACT
OBJECTIVE: To quantify the impact of a practical, hospital-based nurse-coordinated prevention programme on cardiovascular risk, integrated into the routine clinical care of patients discharged after an acute coronary syndrome, as compared with usual care only. DESIGN: RESPONSE (Randomised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists) was a randomised clinical trial. SETTING: Multicentre trial in secondary and tertiary healthcare settings. PARTICIPANTS: 754 patients admitted for acute coronary syndrome. INTERVENTION: A nurse-coordinated prevention programme, consisting of four outpatient nurse clinic visits, focusing on healthy lifestyles, biometric risk factors and medication adherence, in addition to usual care. MAIN OUTCOME MEASURES: The main outcome was 10-year cardiovascular mortality risk as estimated by Systematic Coronary Risk Evaluation at 12 months follow-up. Secondary outcomes included Framingham Coronary Risk Score at 12 months, in addition to changes in individual risk factors. Risk factor control was classified as 'poor' if 0 to 3 factors were on target, 'fair' if 4 to 6 factors were on target, and 'good' if 7 to 9 were on target. RESULTS: The mean Systematic Coronary Risk Evaluation at 12 months was 4.4 per cent (SD 4.5) in the intervention group and 5.4 per cent (SD 6.2) in the control group (p=0.021), representing a 17.4% relative risk reduction. At 12 months, risk factor control classified as 'good' was achieved in 35% of patients in the intervention group compared with 25% in the control group (p=0.003). Attendance to the nurse-coordinated prevention programme was 92%. In the intervention group, 86 rehospitalisations were observed against 132 in the control group (relative risk reduction 34.8%, p=0.023). CONCLUSIONS: The nurse-coordinated hospital-based prevention programme in addition to usual care is a practical, yet effective method for reduction of cardiovascular risk in patients with coronary disease. Our data suggest that the counselling component of the programme may lead to a reduction in hospital readmissions. TRIAL REGISTRATION TRIALREGISTERNL IDENTIFIER: TC1290.
Subject(s)
Acute Coronary Syndrome/nursing , Ambulatory Care , Medication Adherence , Risk Reduction Behavior , Secondary Prevention/methods , Acute Coronary Syndrome/mortality , Aged , Chi-Square Distribution , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Netherlands , Patient Education as Topic , Risk Assessment , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
Pectus excavatum is usually considered meaningless and without clinical significance. The following case may put a different complexion on the matter. A healthy 59-year-old male patient complained of progressive heart palpitations, fatigue and postural dyspnoea; bending over caused a clear increase of dyspnoea. At repeated examinations no overt abnormality or explanation was found, except a supraventricular arrhythmia and a nodal tachycardia. In the years to follow the symptoms led to considerable physical impairments. Finally, the patient himself, after searching the web, came up with a possible cause: his pectus excavatum. A lateral chest x-ray with the patient bending over and a lateral computed tomography of the thorax revealed an impression of the heart by the sternum. Ten years after the patient's signs and symptoms first appeared, a modified Ravitch procedure was carried out, after which the physical condition of the patient improved rapidly.
ABSTRACT
BACKGROUND: The aim of the present study was to investigate the analytical and diagnostic utility of B-type natriuretic peptide (BNP) and the N-terminus of this prohormone, N-terminal pro-BNP (NT-pro-BNP) testing in the emergency department to identify acute congestive heart failure (CHF). METHODS: A blood sample taken from patients presenting to the emergency department with acute dyspnoea (n=80) was analyzed for natriuretic peptides using three different assays [Triage BNP (Biosite), Centaur BNP (Bayer) and Elecsys NT-pro-BNP (Roche)]. A cardiologist and a pulmonologist, blinded to the actual natriuretic peptide levels, reviewed all test results (including echocardiography, etc.) retrospectively and made a diagnosis of dyspnoea due to CHF or not. RESULTS: Analytical testing showed good correlation and coefficients of variation of less than 10% for all three assays. Cardiac-related dyspnoea was found in 40 patients (50%). NT-proBNP and BNP values were significantly elevated in these patients. For identifying patients with CHF, BNP and NT-proBNP scored equally well (area under the receiver operating characteristic curve of 0.78, 0.77 and 0.78 for the Biosite, Roche and Bayer assays, respectively). CONCLUSIONS: In general, the different assays tested for BNP and NT-pro-BNP correlate very well in patients with suspected CHF and may aid in the risk stratification process in emergency departments. However, the value must always be interpreted in conjunction with other clinical information. It should also be considered that renal impairment can affect the results.
Subject(s)
Emergency Medical Services/methods , Heart Failure/diagnosis , Natriuretic Peptides/blood , Area Under Curve , Clinical Laboratory Techniques/standards , Dyspnea/diagnosis , Dyspnea/etiology , Humans , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Reagent Kits, Diagnostic/standardsABSTRACT
Effects of a post-hospitolization group health education programme for patients with coronary heart disease. A health education programme was offered to groups of coronary heart patients and their partners after discharge from hospital. A randomized pre-test post-test control group design was used to evaluate the effects of this experimental intervention. The health education programme was offered to 109 coronary heart patients in groups of between five and eight patients together with their partners in addition to standard medical care and physical training. A control group of 108 patients received only standard medical care and physical training. The intervention consisted of eight weekly two-hour group health education sessions and one follow-up session. All sessions focused on the promotion of healthy habits and the reduction of adverse psychosocial consequences of the incident. In the short term (about four months after the incident) the health education programme showed statistically significant intervention effects on knowledge about coronary heart diseases, smoking cessation, healthy eating habits and the number of consultations with the family physician, but no effects on emotional distress. In the long term (one year after the incident) there was only a significant intervention effect on smoking cessation. These results suggest that the effects of the programme are modest, especially in terms of maintenance of behavioural change. As a consequence, it is suggested that the programme should not be offered to all coronary patients during cardiac rehabilitation, but only to those who can be expected to profit most from it.