Strong selection on parasites, as well as on hosts, is crucial for fueling coevolutionary dynamics. Selection will be especially strong if parasites that encounter resistant hosts are destroyed and diluted from the local environment. We tested whether spores of the bacterial parasite Pasteuria ramosa were passed through the gut (the route of infection) of their host, Daphnia magna, and whether passaged spores remained viable for a “second chance” at infecting a new host. In particular, we tested if this viability (estimated via infectivity) depended on host genotype, whether or not the genotype was susceptible, and on initial parasite dose. Our results show that Pasteuria spores generally remain viable after passage through both susceptible and resistant Daphnia. Furthermore, these spores remained infectious even after being frozen for several weeks. If parasites can get a second chance at infecting hosts in the wild, selection for infection success in the first instance will be reduced. This could also weaken reciprocal selection on hosts and slow the coevolutionary process.
Daphnia; dilution effect; host–parasite coevolution; Pasteuria
Access to Cognitive behavioural therapy (CBT) for depression is limited. One solution is CBT self-help books.
Trial Objectives: To assess the impact of a guided self-help CBT book (GSH-CBT) on mood, compared to treatment as usual (TAU).
Hypotheses:GSH-CBT will have improved mood and knowledge of the causes and treatment of depression compared to the control receiving TAUGuided self-help will be acceptable to patients and staff.
Methods and Findings
Participants: Adults attending seven general practices in Glasgow, UK with a BDI-II score of ≥14. 141 randomised to GSH-CBT and 140 to TAU.
Interventions: RCT comparing ‘Overcoming Depression: A Five Areas Approach’ book plus 3–4 short face to face support appointments totalling up to 2 hours of guided support, compared with general practitioner TAU.
Primary outcome: The BDI (II) score at 4 months.
Numbers analysed: 281 at baseline, 203 at 4 months (primary outcome), 117 at 12 months.
Outcome: Mean BDI-II scores were lower in the GSH-CBT group at 4 months by 5.3 points (2.6 to 7.9, p<0.001). At 4 and 12 months there were also significantly higher proportions of participants achieving a 50% reduction in BDI-II in the GSH-CBT arm. The mean support was 2 sessions with 42.7 minutes for session 1, 41.4 minutes for session 2 and 40.2 minutes of support for session 3.
Adverse effects/Harms: Significantly less deterioration in mood in GSH-CBT (2.0% compared to 9.8% in the TAU group for BDI—II category change).
Weaknesses: Our follow-up rate of 72.2% at 4 months is better than predicted but is poorer at 12 months (41.6%). In the GSH-CBT arm, around 50% of people attended 2 or fewer sessions. 22% failed to take up treatment.
GSH-CBT is substantially more effective than TAU.
Interventions to promote positive parenting are often reported to offer good outcomes for children but they can consume substantial resources and they require rigorous appraisal.
Evaluations of the Triple P parenting program were subjected to systematic review and meta-analysis with analysis of biases. PsychInfo, Embase and Ovid Medline were used as data sources. We selected published articles reporting any child-based outcome in which any variant of Triple P was evaluated in relation to a comparison condition. Unpublished data, papers in languages other than English and some book chapters were not examined. Studies reporting Eyberg Child Behavior Inventory or Child Behavior Checklist scores as outcomes were used in the meta-analysis.
A total of 33 eligible studies was identified, most involving media-recruited families. Thirty-one of these 33 studies compared Triple P interventions with waiting list or no-treatment comparison groups. Most papers only reported maternal assessments of child behavior. Twenty-three papers were incorporated in the meta-analysis. No studies involved children younger than two-years old and comparisons of intervention and control groups beyond the duration of the intervention were only possible in five studies. For maternally-reported outcomes the summary effect size was 0.61 (95%CI 0.42, 0.79). Paternally-reported outcomes following Triple P intervention were smaller and did not differ significantly from the control condition (effect size 0.42 (95%CI -0.02, 0.87)). The two studies involving an active control group showed no between-group differences. There was limited evidence of publication bias, but there was substantial selective reporting bias, and preferential reporting of positive results in article abstracts. Thirty-two of the 33 eligible studies were authored by Triple-P affiliated personnel. No trials were registered and only two papers contained conflict of interest statements.
In volunteer populations over the short term, mothers generally report that Triple P group interventions are better than no intervention, but there is concern about these results given the high risk of bias, poor reporting and potential conflicts of interest. We found no convincing evidence that Triple P interventions work across the whole population or that any benefits are long-term. Given the substantial cost implications, commissioners should apply to parenting programs the standards used in assessing pharmaceutical interventions.
See related commentary: http://www.biomedcentral.com/1741-7015/10/145
parenting; public health; child psychology; behavioral family intervention; systematic review; meta-analysis
We describe the health of "revolving door" patients in general practice in Scotland, estimate changes in their number over the timescale of the study, and explore reasons for changes, particularly related to NHS and government policy.
A mixed methods predominantly qualitative study, using a grounded theory approach, set in Scottish general practice. Semi-structured interviews were conducted with professional key informants, 6 Practitioner Services staff who administer the GP registration system and 6 GPs with managerial or clinical experience of working with “revolving door” patients. Descriptive statistical analysis and qualitative analysis of patient removal episodes linked with routine hospital admissions, outpatient appointments, drug misuse treatment episodes and deaths were carried out with cohorts of “revolving door” patients identified from 1999 to 2005 in Scotland.
A “revolving door” patient is removed 4 or more times from GP lists in 7 years. Patients had complex health issues including substance misuse, psychiatric and physical health problems and were at high risk of dying. There was a dramatic reduction in the number of “revolving door” patients during the course of the study.
“Revolving door” patients in general practice had significant health problems. Their numbers have reduced dramatically since 2004 and this probably resulted from improved drug treatment services, pressure from professional bodies to reduce patient removals and the positive ethical regulatory and financial climate of the 2004 GMS GP contract. This is a positive development for the NHS.
Depression is frequently cited as the reason for sickness absence, and it is estimated that sickness certificates are issued in one third of consultations for depression. Previous research has considered GP views of sickness certification but not specifically in relation to depression.
This study aimed to explore GPs views of sickness certification in relation to depression.
A purposive sample of GP practices across Scotland was selected to reflect variations in levels of incapacity claimants and antidepressant prescribing. Qualitative interviews were carried out between 2008 and 2009.
A total of 30 GPs were interviewed. A number of common themes emerged including the perceived importance of GP advocacy on behalf of their patients, the tensions between stakeholders involved in the sickness certification system, the need to respond flexibly to patients who present with depression and the therapeutic nature of time away from work as well as the benefits of work. GPs reported that most patients with depression returned to work after a short period of absence and that it was often difficult to predict which patients would struggle to return to work.
GPs reported that dealing with sickness certification and depression presents distinct challenges. Sickness certificates are often viewed as powerful interventions, the effectiveness of time away from work for those with depression should be subject to robust enquiry.
Depression; Mood disorder; Primary care; Occupational; Environmental medicine; Doctor-patient relationship; Mental health
Previous pathogen exposure is an important predictor of the probability of becoming infected. This is deeply understood for vertebrate hosts, and increasingly so for invertebrate hosts. Here, we test if an initial pathogen exposure changes the infection outcome to a secondary pathogen exposure in the natural host–pathogen system Daphnia magna and Pasteuria ramosa. Hosts were initially exposed to an infective pathogen strain, a non-infective pathogen strain or a control. The same hosts underwent a second exposure, this time to an infective pathogen strain, either immediately after the initial encounter or 48 h later. We observed that an initial encounter with a pathogen always conferred protection against infection compared with controls.
within-generation immune priming; Daphnia; immunological loitering
GPs contribute to preventive child health care in various ways, including provision of child health surveillance (CHS) reviews, opportunistic preventive care, and more intensive support to vulnerable children. The number of CHS reviews offered in Scotland was reduced from 2005. This study aimed to quantify GPs’ provision of different types of preventive care to pre-school children before and after the changes to the CHS system.
GP consultation rates with children aged 0–4 years were examined for the 2½ years before and after the changes to the CHS system using routinely available data from 30 practices in Scotland. Consultations for CHS reviews; other aspects of preventive care; and all reasons were considered.
Prior to the changes to the CHS system, GPs often contributed to CHS reviews at 6–8 weeks and 8–9 and 39–42 months. Following the changes, GP provision of the 6–8 week review continued but other reviews essentially ceased. Few additional consultations with pre-school children are recorded as involving other aspects of preventive care, and the changes to CHS have had no impact on this. In the 2½ years before and after the changes, consultations recorded as involving any form of preventive care accounted for 11% and 7.5% respectively of all consultations with children aged 0–4 years, with the decline due to reductions in CHS reviews.
Effective preventive care through the early years can help children secure good health and developmental outcomes. GPs are well placed to contribute to the provision of such care. Consultations focused on preventive care form a small minority of GPs’ contacts with pre-school children, however, particularly since the reduction in the number of CHS reviews.
Child health; General practice; Preventive health services; Health promotion; General practitioners; Health visitors
Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) gene therapy improves mechanical function in heart failure, and is under evaluation in a clinical trial. A critical question is whether SERCA2a gene therapy predisposes to increased sarcoplasmic reticulum calcium (SR Ca2+) leak, cellular triggered activity and ventricular arrhythmias in the failing heart.
Methods and Results
We studied the influence of SERCA2a gene therapy upon ventricular arrhythmogenesis in a rat chronic heart failure model. ECG telemetry studies revealed a significant antiarrhythmic effect of SERCA2a gene therapy with reduction of both spontaneous and catecholamine-induced arrhythmias in vivo. SERCA2a gene therapy also reduced susceptibility to reentry arrhythmias in ex vivo programmed electrical stimulation studies. Subcellular Ca2+ homeostasis and spontaneous SR Ca2+ leak characteristics were measured in failing cardiomyocytes transfected in vivo with a novel AAV9.SERCA2a vector. SR Ca2+ leak was reduced following SERCA2a gene therapy, with reversal of the greater spark mass observed in the failing myocytes, despite normalisation of SR Ca2+ load. SERCA2a reduced ryanodine receptor phosphorylation, thereby resetting SR Ca2+ leak threshold, leading to reduced triggered activity in vitro. Both indirect effects of reverse remodelling and direct SERCA2a effects appear to underlie the antiarrhythmic action.
SERCA2a gene therapy stabilizes SR Ca2+ load, reduces ryanodine receptor phosphorylation and decreases SR Ca2+ leak, reduces cellular triggered activity in vitro and spontaneous and catecholamine-induced ventricular arrhythmias in vivo in failing hearts. SERCA2a gene therapy did not therefore predispose to arrhythmias, and may even represent a novel antiarrhythmic strategy in heart failure.
Arrhythmia; Gene Therapy; Calcium; Heart Failure; SERCA2a
Levels of antidepressant prescribing have dramatically increased in Western countries in the last two decades.
To explore GPs' views about, and explanations for, the increase in antidepressant prescribing in Scotland between 1995 and 2004.
Qualitative, interview study.
General practices, Scotland.
GPs in 30 practices (n = 63) purposively selected to reflect a range of practice characteristics and levels of antidepressant prescribing.
Interviews with GPs were taped and transcribed. Analysis followed a Framework Approach.
GPs offered a range of explanations for the rise in antidepressant prescribing in Scotland. Few doctors thought that the incidence of depression had increased, and many questioned the appropriateness of current levels of prescribing. A number of related factors were considered to have contributed to the increase. These included: the success of campaigns to raise awareness of depression; a willingness among patients to seek help; and the perceived safety of selective serotonin reuptake inhibitors, making it easier for GPs to manage depression in primary care. Many GPs believed that unhappiness, exacerbated by social deprivation and the breakdown of traditional social structures, was being ‘medicalised’ inappropriately.
Most antidepressant prescriptions in Scotland are issued by GPs, and current policy aims to reduce levels of prescribing. To meet this aim, GPs' prescribing behaviour needs to change. The findings suggest that GPs see themselves as responders to, rather than facilitators of, change and this has obvious implications for initiatives to reduce prescribing.
depression; drugs; mental health; qualitative research; primary care
Objectives To examine whether there was significant variation in levels of claiming incapacity benefit across general practices. To establish whether it is possible to identify people with mental health problems who are more at risk of becoming dependent on state benefits for long term health problems based on their general practice consulting behaviour.
Design Interrogation of routinely available data in the Scottish Health Surveys and the British Household Panel Survey.
Setting Scotland and the United Kingdom.
Participants Respondents to the Scottish Health Surveys in 1995, 1998, and 2003 (7932, 12 939 and 11 472 respondents, respectively). Respondents to the British Household Panel Survey, 1991-2007 (more than 5000 households).
Main outcome measures Intracluster correlation coefficient for probability of work incapacity by general practice. Caseness according to the general health questionnaire (GHQ-12) and frequency of consultation with general practitioner in years before and after starting to claim incapacity benefit.
Results There was a small and non-significant amount of variation across general practices in Scotland in rate of claims for incapacity benefit after adjustment for other explanatory variables (intracluster correlation coefficient 0.01, P=0.135). There was a significant increase in rates of GHQ-12 caseness from two years before the start of claiming incapacity benefit (odds ratio 1.6, 95% confidence interval 1.3 to 1.9) and an increase in frequent consultation with a general practitioner from three years before the start of claiming incapacity benefit (1.8, 1.3 to 2.4). People with GHQ-12 caseness showed a significant increase in frequent consultations with a general practitioner from two years before the start of claiming incapacity benefit (2.1, 1.4 to 3.2).
Conclusions There was no variation in levels of claiming incapacity benefit across general practices in Scotland after adjustment for differences in population characteristics and so initiatives targeted at practices with high levels are unlikely to be effective. People with mental health problems who are likely to have problems remaining in work can be identified up to three years before they transit on to long term benefits related to ill health.
β Blocker treatment may worsen glucose metabolism.
To study the development of new onset diabetes in a large cohort of patients with heart failure treated with either metoprolol or carvedilol.
Prospective and retrospective analysis of a controlled clinical trial.
Multinational multicentre study.
3029 patients with chronic heart failure.
Randomly assigned treatment with carvedilol (n = 1511, target dose 50 mg daily) or metoprolol tartrate (n = 1518, target dose 100 mg daily).
Diabetic events (diabetic coma, peripheral gangrene, diabetic foot, decreased glucose tolerance or hyperglycaemia) and new onset diabetes (clinical diagnosis, repeated high random glucose level or glucose lowering drugs) were assessed in 2298 patients without diabetes at baseline. Diabetic events occurred in 122/1151 (10.6%) patients in the carvedilol group and 149/1147 (13.0%) patients in the metoprolol group (hazard ratio (HR) = 0.78; 95% confidence interval (CI) 0.61 to 0.99; p = 0.039). New onset diabetes was diagnosed in 119/1151 (10.3%) v 145/1147 (12.6%) cases in the carvedilol and metoprolol treatment groups (HR = 0.78, CI 0.61 to 0.997; p = 0.048), respectively. Patients with diabetes at baseline had an increased mortality compared with non‐diabetic subjects (45.3% v 33.9%; HR = 1.45, CI 1.28 to 1.65). Both diabetic and non‐diabetic subjects at baseline had a similar reduction in mortality with carvedilol compared with metoprolol (RR = 0.85; CI 0.69 to 1.06 and RR = 0.82; CI 0.71 to 0.94, respectively).
A high prevalence and incidence of diabetes is found in patients with heart failure over a course of 5 years. New onset diabetes is more likely to occur during treatment with metoprolol than during treatment with carvedilol.
β adrenergic receptor antagonists; carvedilol; diabetes mellitus; heart failure; metoprolol
A standard metric to estimate absolute treatment effects is numbers-needed-to-treat (NNT), which implicitly assumes that all benefits reverse at trial-end. However, in-trial survival benefits typically do not reverse until long after trial-end, so that NNT will substantially underestimate lifetime benefits.
Methods and results
We developed a new concept, years-needed-to-treat (YNT) to add 1 year of life, that quantifies the expected average life expectancy for two treatments including the estimated years of life remaining post-trial. Numbers-needed-to-treat and YNT were calculated in the COMET trial, in which carvedilol vs. metoprolol tartrate resulted in 17% lower mortality over 4.8 years. A multivariate Cox model was used to predict survival. Remaining years of life were estimated using the mortality-life-table method. At trial-end, survival was 9% higher in the carvedilol arm. Assuming that patients remained on the same therapy post-trial, the average total years of life for carvedilol vs. metoprolol were 10.63 ± 0.19 vs. 9.48 ± 0.18 (P < 0.0001) or 1.15 (95% confidence interval 0.64–1.66) additional years of life. The YNT was 9.2, indicating that 9.2 person-years of treatment added 1 person-year of life, compared with NNT of 59.
Compared with NNT, the YNT method more accurately accounts for potential long-term benefits of interventions in randomized trials.
Heart failure; Prognostication; Outcomes; Epidemiology; Gompertz; Beta-blocker; Number-needed-to-treat; Years-needed-to-treat
The prescribing of antidepressants has been rising dramatically in developed countries.
As part of an investigation into the reasons for the rise and variation in the prescribing of antidepressants, this study aimed to describe, and account for, the variation in an age–sex standardised rate of antidepressant prescribing between general practices.
Design of study
Cross-sectional study involving analyses of routinely available data.
A total of 983 Scottish general practices.
Age–sex standardised prescribing rates were calculated for each practice. Univariate and multivariate regression analyses were undertaken to examine how the variation in prescribing was related to population, GP, and practice characteristics at individual practice level.
There was a 4.6-fold difference between the first and ninth deciles of antidepressant prescribing, standardised for registered patients' age and sex composition. The multivariate model explained 49.4% of the variation. Significantly higher prescribing than expected was associated with more limiting long-term illness (highly correlated with deprivation and the single most influential factor), urban location, and a greater proportion of female GPs in the practices. Significantly lower prescribing than expected was associated with single-handed practices, a higher than average list size, a greater proportion of GP partners born outside the UK, remote rural areas, a higher proportion of patients from minority ethnic groups, a higher mean GP age, and availability of psychology services. None of the quality-of-care indicators investigated was associated with prescribing levels.
Almost half of the variation in the prescription of antidepressants can be explained using population, GP, and practice characteristics. Initiatives to reduce the prescribing of antidepressants should consider these factors to avoid denying appropriate treatment to patients in some practices.
antidepressants; clinical practice variation; family practice; Scotland
It is time to do a trial of left ventricular assist devices for lifetime use
It is important to engage in regular physical activity in order to maintain a healthy lifestyle however a large portion of the population is insufficiently active. Understanding how different types of motivation contribute to exercise behavior is an important first step in identifying ways to increase exercise among individuals. The current study employs self-determination theory as a framework from which to examine how motivation contributes to various characteristics of exercise behavior.
Regular exercisers (N = 1079; n = 468 males; n = 612 females) completed inventories which assessed the frequency, intensity, and duration with which they exercise, as well as the Behavioral Regulation in Exercise Questionnaire including four additional items assessing integrated regulation.
Bivariate correlations revealed that all three behavioral indices (frequency, intensity, and duration of exercise) were more highly correlated with more autonomous than controlling regulations. Regression analyses revealed that integrated and identified regulations predicted exercise frequency for males and females. Integrated regulation was found to be the only predictor of exercise duration across both genders. Finally, introjected regulation predicted exercise intensity for females only.
These findings suggest that exercise regulations that vary in their degree of internalization can differentially predict characteristics of exercise behavior. Furthermore, in the motivational profile of a regular exerciser, integrated regulation appears to be an important determinant of exercise behavior. These results highlight the importance of assessing integrated regulation in exercise settings where the goal of understanding motivated behavior has important health implications.
Iron deficiency (ID) and anaemia are common in patients with chronic heart failure (CHF). The presence of anaemia is associated with increased morbidity and mortality in CHF, and ID is a major reason for the development of anaemia. Preliminary studies using intravenous (i.v.) iron supplementation alone in patients with CHF and ID have shown improvements in symptom status. FAIR-HF (Clinical Trials.gov NCT00520780) was designed to determine the effect of i.v. iron repletion therapy using ferric carboxymaltose on self-reported patient global assessment (PGA) and New York Heart Association (NYHA) in patients with CHF and ID.
Methods and results
This is a multi-centre, randomized, double-blind, placebo-controlled study recruiting ambulatory patients with symptomatic CHF with LVEF ≤ 40% (NYHA II) or ≤45% (NYHA III), ID [ferritin <100 ng/mL or ferritin 100–300 ng/mL when transferrin saturation (TSAT) < 20%], and haemoglobin 9.5–13.5 g/dL. Patients were randomized in a 2:1 ratio to receive ferric carboxymaltose (Ferinject®) 200 mg iron i.v. or saline i.v. weekly until iron repletion (correction phase), then monthly until Week 24 (maintenance phase). Primary endpoints are (i) self-reported PGA at Week 24 and (ii) NYHA class at Week 24, adjusted for baseline NYHA class.
This study will provide evidence on the efficacy and safety of iron repletion with ferric carboxymaltose in CHF patients with ID with and without anaemia.
Chronic heart failure; Iron deficiency; Anaemia; Treatment; Ferric carboxymaltose
Use of inotropic agents in patients with heart failure (HF) has been limited by adverse effects on outcomes. However, administration of positive inotropes at lower doses and concomitant treatment with beta-blockers might increase benefit–risk ratio. We investigated the effects of low doses of the positive inotrope enoximone on symptoms, exercise capacity, and major clinical outcomes in patients with advanced HF who were also treated with beta-blockers and other guideline-recommended background therapy.
Methods and results
The Studies of Oral Enoximone Therapy in Advanced HF (ESSENTIAL) programme consisted of two identical, randomized, double-blind, placebo-controlled trials that differed only by geographic location (North and South America: ESSENTIAL-I; Europe: ESSENTIAL-II). Patients with New York Heart Association class III–IV HF symptoms, left ventricular ejection fraction ≤30%, and one hospitalization or two ambulatory visits for worsening HF in the previous year were eligible for participation in the trials. The trials had three co-primary endpoints: (i) the composite of time to all-cause mortality or cardiovascular hospitalization, analysed in the two ESSENTIAL trials combined; (ii) the 6 month change from baseline in the 6 min walk test distance (6MWTD); and (iii) the Patient Global Assessment (PGA) at 6 months, both analysed in each trial separately. ESSENTIAL-I and -II randomized 1854 subjects at 211 sites in 16 countries. In the combined trials, all-cause mortality and the composite, first co-primary endpoint did not differ between the two treatment groups [hazard ratio (HR) 0.97; 95% confidence interval (CI) 0.80–1.17; and HR 0.98; 95% CI 0.86–1.12, respectively, for enoximone vs. placebo]. The two other co-primary endpoints were analysed separately in the two ESSENTIAL trials, as prospectively designed in the protocol. The 6MWTD increased with enoximone, compared with placebo, in ESSENTIAL-I (P = 0.025, not reaching, however, the pre-specified criterion for statistical significance of P < 0.020), but not in ESSENTIAL-II. No difference in PGA was observed in either trial.
Although low-dose enoximone appears to be safe in patients with advanced HF, major clinical outcomes are not improved.
Advanced heart failure; Inotropic agents; Enoximone
To determine the safety and efficacy of nebivolol in elderly heart failure (HF) patients with renal dysfunction.
Methods and results
SENIORS recruited patients aged 70 years or older with symptomatic HF, irrespective of ejection fraction, and randomized them to nebivolol or placebo. Patients (n = 2112) were divided by tertile of estimated glomerular filtration rate (eGFR). Mean age of patients was 76.1 years, 35% of patients had an ejection fraction of >35%, and 37% were women resulting in a unique cohort, far more representative of clinical practice than previous trials. eGFR was strongly associated with outcomes and nebivolol was similarly efficacious across eGFR tertiles. The primary outcome rate (all-cause mortality or cardiovascular hospital admission) and adjusted hazard ratio for nebivolol use in those with low eGFR was 40% and 0.84 (95% CI 0.67–1.07), 31% and 0.79 (0.60–1.04) in the middle tertile, and 29% and 0.86 (0.65–1.14) in the highest eGFR tertile. There was no interaction noted between renal function and the treatment effect (P = 0.442). Nebivolol use in patients with moderate renal impairment (eGFR <60) was not associated with major safety concerns, apart from higher rates of drug-discontinuation due to bradycardia.
Nebivolol is safe and has a similar effect in elderly HF patients with mild or moderate renal impairment.
Heart failure; Renal impairment; Beta-blocker; Nebivolol
Overproduction of pro-inflammatory cytokines is a well established factor in the progression of chronic heart failure (CHF). Changes in cellular immunity have not been widely studied, and the impact of standard medication is uncertain. Here we investigate whether a leukocyte redistribution occurs in CHF and whether this effect is influenced by beta-blocker therapy.
We prospectively studied 75 patients with systolic CHF (age: 68±11 years, left ventricular ejection fraction 32±11%, New York Heart Association class 2.5±0.7) and 20 age-matched healthy control subjects (age: 63±10 years). We measured the response of cells to endotoxin exposure in vitro, analysed subsets of lymphocytes using flow cytometry, and assessed plasma levels of the pro-inflammatory markers interleukin 1, 6, tumor necrosis factor-α, and soluble tumor necrosis factor receptors 1 and 2.
While no differences in the number of leukocytes were noted between patients with CHF and healthy controls, we detected relative lymphopenia in patients with CHF (p<0.001 vs. control), mostly driven by reductions in T helper cells and B cells (both p<0.05). The number of neutrophils was increased (p<0.01). These effects were pronounced in patients who were beta-blocker naïve (32% of all patients with CHF). Increased plasma levels of soluble tumor necrosis receptor-1 correlated with the relative number of lymphocyte subsets.
In patients with CHF, we detected a redistribution of leukocyte subsets, i.e. an increase in neutrophils with relative lymphopenia. These effects were pronounced in patients who were beta-blocker naïve. The underlying mechanism remains to be elucidated.
Objective To derive a risk score for the combination of death from all causes, myocardial infarction, and disabling stroke in patients with stable symptomatic angina who require treatment for angina and have preserved left ventricular function.
Design Multivariate Cox regression analysis of data from a large multicentre trial.
Setting Outpatient cardiology clinics in western Europe, Israel, Canada, Australia, and New Zealand.
Participants 7311 patients with all required data available.
Main outcome measure Death from any cause or myocardial infarction or disabling stroke during a mean follow-up of 4.9 years.
Results 1063 patients either died from any cause or sustained myocardial infarction or disabling stroke. The five year risk of this composite ranged from 4% for patients in the lowest tenth of risk to 35% for patients in the highest tenth. The risk score combines 16 routinely available clinical variables (in order of decreasing contribution): age, left ventricular ejection fraction, smoking, white blood cell count, diabetes, casual blood glucose concentration, creatinine concentration, previous stroke, at least one angina attack a week, coronary angiographic findings (if available), lipid lowering treatment, QT interval, systolic blood pressure ≥ 155 mm Hg, number of drugs used for angina, previous myocardial infarction, and sex. Fitting the same model separately to all cause death, myocardial infarction, and stroke gave similar results. The risk score did not seem to predict the nature of the event (death in 39%, myocardial infarction in 46%, and disabling stroke in 15%) or the incidence of angiography or revascularisation, which occurred in 29% of patients.
Conclusion This risk score is an objective aid in deciding on further management of patients with stable angina with the aim of reducing serious outcome events. The score can also be used in planning future trials.