Predictors and treatment response with cardiac resynchronization therapy in patients with heart failure characterized by dyssynchrony: a pre-defined analysis from the CARE-HF trial.

AIMS: The cardiac resynchronization therapy in heart failure trial (CARE-HF) demonstrated that cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with heart failure and cardiac dyssynchrony. The aim of this study was to develop a prognostic model to evaluate the relationship between prospectively defined patient characteristics and treatment on the trial primary outcome of death from any cause or unplanned hospitalization for a major cardiovascular event. METHODS AND RESULTS: A total of 813 patients were enrolled in the CARE-HF study and were followed for a mean of 29.4 months. A Cox Proportional Hazards Model was fitted to identify predictors of the primary outcome and any predictors that modified the effect of CRT. Ischaemic aetiology, more severe mitral regurgitation and increased N-terminal pro-brain natriuretic peptide, were associated with an increased risk of death or unplanned cardiovascular hospitalization irrespective of cardiac resynchronization [Hazard ratio (HR) 1.89, 95% CI 1.45-2.46, HR 1.71, 95% CI 1.38-2.12 and HR 1.31, 95% CI 1.17-1.47, respectively] and increasing systolic blood pressure with a decreasing risk of an event (HR 0.99, 95% CI 0.98-1.00). The benefits of cardiac resynchronization were modified by systolic blood pressure and interventricular mechanical delay (IVMD). Patients with increasing systolic blood pressure appear to receive reduced benefit from CRT (HR 1.02, 95% CI 1.00-1.03), whereas those patients with more severe IVMD appear to benefit more from treatment (HR 0.99, 95% CI 0.98-1.00). CONCLUSION: Patients with echocardiographic evidence of more severe cardiac dyssynchrony and low systolic blood pressure obtain greater benefit from CRT, although benefits were substantial across the range of subjects included in the trial.     

Physical activity,mental health and well-being of adults during initial COVID-19 containment strategies: A multi-country cross-sectional analysis

ObjectivesTo assess physical activity (PA), mental health and well-being of adults in the United Kingdom (UK), Ireland, New Zealand and Australia during the initial stages of National governments’ Coronavirus disease (COVID-19) containment responses.DesignObservational, cross-sectional.MethodsAn online survey was disseminated to adults (n = 8,425; 44.5 ± 14.8y) residing in the UK, Ireland, New Zealand and Australia within the first 2-6 weeks of government-mandated COVID-19 restrictions. Main outcome measures included: Stages of Change scale for exercise behaviour change; International Physical Activity Questionnaire (short-form); World Health Organisation-5 Well-being Index; and the Depression Anxiety and Stress Scale-9.ResultsParticipants who reported a negative change in exercise behaviour from before initial COVID-19 restrictions to during the initial COVID-19 restrictions demonstrated poorer mental health and well-being compared to those demonstrating either a positive-or no change in their exercise behaviour (p < 0.001). Whilst women reported more positive changes in exercise behaviour, young people (18-29y) reported more negative changes (both p < 0.001). Individuals who had more positive exercise behaviours reported better mental health and well-being (p < 0.001). Although there were no differences in PA between countries, individuals in New Zealand reported better mental health and well-being (p < 0.001).ConclusionThe initial COVID-19 restrictions have differentially impacted upon PA habits of individuals based upon their age and sex, and therefore have important implications for international policy and guideline recommendations. Public health interventions that encourage PA should target specific groups (e.g., men, young adults) who are most vulnerable to the negative effects of physical distancing and/or self-isolation.     

Feasibility and indicative results from a 12-month low-energy liquid diet treatment and maintenance programme for severe obesity

Background

There is no established primary care solution for the rapidly increasing numbers of severely obese people with body mass index (BMI) > 40 kg/m².

Aim

This programme aimed to generate weight losses of ≥15 kg at 12 months, within routine primary care.

Design and setting

Feasibility study in primary care.

Method

Patients with a BMI ≥40 kg/m² commenced a micronutrient-replete 810–833 kcal/day low-energy liquid diet (LELD), delivered in primary care, for a planned 12 weeks or 20 kg weight loss (whichever was the sooner), with structured food reintroduction and then weight-loss maintenance, with optional orlistat to 12 months.

Result

Of 91 patients (74 females) entering the programme (baseline: weight 131 kg, BMI 48 kg/m², age 46 years), 58/91(64%) completed the LELD stage, with a mean duration of 14.4 weeks (standard deviation [SD] = 6.0 weeks), and a mean weight loss of 16.9 kg (SD = 6.0 kg). Four patients commenced weight-loss maintenance omitting the food-reintroduction stage. Of the remaining 54, 37(68%) started and completed food reintroduction over a mean duration of 9.3 weeks (SD = 5.7 weeks), with a further mean weight loss of 2.1 kg (SD = 3.7 kg), before starting a long-term low-fat-diet weight-loss maintenance plan. A total of 44/91 (48%) received orlistat at some stage. At 12 months, weight was recorded for 68/91 (75%) patients, with a mean loss of 12.4 kg (SD = 11.4 kg). Of these, 30 (33% of all 91 patients starting the programme) had a documented maintained weight loss of ≥15 kg at 12 months, six (7%) had a 10–15 kg loss, and 11 (12%) had a 5–10 kg loss. The indicative cost of providing this entire programme for wider implementation would be £861 per patient entered, or £2611 per documented 15 kg loss achieved.

Conclusion

A care package within routine primary care for severe obesity, including LELD, food reintroduction, and weight-loss maintenance, was well accepted and achieved a 12-month-maintained weight loss of ≥15 kg for one-third of all patients entering the programme.     

In vitro activity of daptomycin in combination with low-dose colistin against a diverse collection of Gram-negative bacterial pathogens

The activity of colistin in combination with daptomycin was assessed using 30 Gram-negative type strains and multidrug-resistant isolates with defined mechanisms of resistance. Daptomycin minimum inhibitory concentrations (MICs) were determined with and without sub-inhibitory concentrations of colistin. The activity of daptomycin was not affected with respect to Escherichia coli, Klebsiella pneumoniae or Pseudomonas aeruginosa. For colistin-susceptible Acinetobacter baumannii, sensitisation factors ranged from 8 to 128 (median 32), with the daptomycin MIC being reduced to the Clinical and Laboratory Standards Institute (CLSI) enterococci susceptibility breakpoint of 4 μg/ml for the ATCC 19606 type strain. A combination of daptomycin and colistin may be useful for the treatment of A. baumannii but not infections due to other Gram-negative species.     

The effect of different storage media on the monomer elution and hardness of CAD/CAM composite blocks

ObjectiveThis study aimed to assess the effect of different storage media on the hardness and monomer elution of CAD/CAM composite blocks.MethodsFive resin-composite blocks (RCB), one polymer-infiltrated ceramic network (PICN) block (Enamic (EN)), one ceramic-filled poly ether ether ketone (PEEK) block (Dentokeep (DK)), and one feldspathic ceramic block. Microhardness was measured using a Vickers indenter tester (FM-700, Future Tech Corp., Japan). In addition 4 conventional resin-composites were investigated for monomer elution using high performance liquid chromatography (HPLC) after storage in different media for 3 months. The data were analysed by three-way ANOVA, two-way ANOVA, one-way ANOVA, Tukey’s post hoc test and the independent t-test (α = 0.05 for all tests).ResultsThe specimens stored in the water had a hardness reduction ranging from 0.9% to 24.4%. In artificial saliva, the specimens had a hardness reduction ranging from 2.8% to 23.2%. The hardness reduction percentage in 75% Ethanol/Water (E/W) ranged between 3.8% and 35.3%. All materials, except GR (resin-composite block) and DK (Polyetheretherketone (PEEK)), showed a variable extent of monomer elution into 75% E/W with significantly higher amounts eluted from conventional composites. GRA and GND (conventional resin-composites) eluted TEGDMA in artificial saliva and GRA eluted TEGDMA in water.SignificanceThe hardness of CAD/CAM composite blocks was affected by different storage media, and they were not as stable as ceramic, with PICN exhibited superior hardness stability to all of the resin-composite blocks in all the storage media and was comparable to ceramic block. The hardness reduction percentage of the CAD/CAM composite blocks was influenced by the filler loading and resin-matrix composition.Minimal or no monomer elution from CAD/CAM blocks was detected.