Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction

BACKGROUND: Beta-blockers and inhibitors of the renin-angiotensin-aldosterone system improve survival and reduce morbidity in people with heart failure with reduced left ventricular ejection fraction (LVEF); a review of the evidence is required to determine whether these treatments are beneficial for people with heart failure with preserved ejection fraction (HFpEF). OBJECTIVES: To assess the effects of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and mineralocorticoid receptor antagonists in people with HFpEF. SEARCH METHODS: We updated searches of CENTRAL, MEDLINE, Embase, and one clinical trial register on 14 May 2020 to identify eligible studies, with no language or date restrictions. We checked references from trial reports and review articles for additional studies.  SELECTION CRITERIA: We included randomised controlled trials with a parallel group design, enrolling adults with HFpEF, defined by LVEF greater than 40%. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 41 randomised controlled trials (231 reports), totalling 23,492 participants across all comparisons. The risk of bias was frequently unclear and only five studies had a low risk of bias in all domains. Beta-blockers (BBs) We included 10 studies (3087 participants) investigating BBs. Five studies used a placebo comparator and in five the comparator was usual care. The mean age of participants ranged from 30 years to 81 years. A possible reduction in cardiovascular mortality was observed (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.62 to 0.99; number needed to treat for an additional benefit (NNTB) 25; 1046 participants; three studies), however, the certainty of evidence was low. There may be little to no effect on all-cause mortality (RR 0.82, 95% CI 0.67 to 1.00; 1105 participants; four studies; low-certainty evidence). The effects on heart failure hospitalisation, hyperkalaemia, and quality of life remain uncertain. Mineralocorticoid receptor antagonists (MRAs) We included 13 studies (4459 participants) investigating MRA. Eight studies used a placebo comparator and in five the comparator was usual care. The mean age of participants ranged from 54.5 to 80 years. Pooled analysis indicated that MRA treatment probably reduces heart failure hospitalisation (RR 0.82, 95% CI 0.69 to 0.98; NNTB = 41; 3714 participants; three studies; moderate-certainty evidence). However, MRA treatment probably has little or no effect on all-cause mortality (RR 0.91, 95% CI 0.78 to 1.06; 4207 participants; five studies; moderate-certainty evidence) and cardiovascular mortality (RR 0.90, 95% CI 0.74 to 1.11; 4070 participants; three studies; moderate-certainty evidence). MRA treatment may have little or no effect on quality of life measures (mean difference (MD) 0.84, 95% CI -2.30 to 3.98; 511 participants; three studies; low-certainty evidence). MRA treatment was associated with a higher risk of hyperkalaemia (RR 2.11, 95% CI 1.77 to 2.51; number needed to treat for an additional harmful outcome (NNTH) = 11; 4291 participants; six studies; high-certainty evidence). Angiotensin-converting enzyme inhibitors (ACEIs) We included eight studies (2061 participants) investigating ACEIs. Three studies used a placebo comparator and in five the comparator was usual care. The mean age of participants ranged from 70 to 82 years. Pooled analyses with moderate-certainty evidence suggest that ACEI treatment likely has little or no effect on cardiovascular mortality (RR 0.93, 95% CI 0.61 to 1.42; 945 participants; two studies), all-cause mortality (RR 1.04, 95% CI 0.75 to 1.45; 1187 participants; five studies) and heart failure hospitalisation (RR 0.86, 95% CI 0.64 to 1.15; 1019 participants; three studies), and may result in little or no effect on the quality of life (MD -0.09, 95% CI -3.66 to 3.48; 154 participants; two studies; low-certainty evidence). The effects on hyperkalaemia remain uncertain. Angiotensin receptor blockers (ARBs) Eight studies (8755 participants) investigating ARBs were included. Five studies used a placebo comparator and in three the comparator was usual care. The mean age of participants ranged from 61 to 75 years. Pooled analyses with high certainty of evidence suggest that ARB treatment has little or no effect on cardiovascular mortality (RR 1.02, 95% 0.90 to 1.14; 7254 participants; three studies), all-cause mortality (RR 1.01, 95% CI 0.92 to 1.11; 7964 participants; four studies), heart failure hospitalisation (RR 0.92, 95% CI 0.83 to 1.02; 7254 participants; three studies), and quality of life (MD 0.41, 95% CI -0.86 to 1.67; 3117 participants; three studies). ARB was associated with a higher risk of hyperkalaemia (RR 1.88, 95% CI 1.07 to 3.33; 7148 participants; two studies; high-certainty evidence). Angiotensin receptor neprilysin inhibitors (ARNIs) Three studies (7702 participants) investigating ARNIs were included. Two studies used ARBs as the comparator and one used standardised medical therapy, based on participants' established treatments at enrolment. The mean age of participants ranged from 71 to 73 years. Results suggest that ARNIs may have little or no effect on cardiovascular mortality (RR 0.96, 95% CI 0.79 to 1.15; 4796 participants; one study; moderate-certainty evidence), all-cause mortality (RR 0.97, 95% CI 0.84 to 1.11; 7663 participants; three studies; high-certainty evidence), or quality of life (high-certainty evidence). However, ARNI treatment may result in a slight reduction in heart failure hospitalisation, compared to usual care (RR 0.89, 95% CI 0.80 to 1.00; 7362 participants; two studies; moderate-certainty evidence). ARNI treatment was associated with a reduced risk of hyperkalaemia compared with valsartan (RR 0.88, 95% CI 0.77 to 1.01; 5054 participants; two studies; moderate-certainty evidence). AUTHORS' CONCLUSIONS: There is evidence that MRA and ARNI treatment in HFpEF probably reduces heart failure hospitalisation but probably has little or no effect on cardiovascular mortality and quality of life. BB treatment may reduce the risk of cardiovascular mortality, however, further trials are needed. The current evidence for BBs, ACEIs, and ARBs is limited and does not support their use in HFpEF in the absence of an alternative indication. Although MRAs and ARNIs are probably effective at reducing the risk of heart failure hospitalisation, the treatment effect sizes are modest. There is a need for improved approaches to patient stratification to identify the subgroup of patients who are most likely to benefit from MRAs and ARNIs, as well as for an improved understanding of disease biology, and for new therapeutic approaches

Chromium-induced accumulation of peroxide content, stimulation of antioxidative enzymes and lipid peroxidation in green gram (Vigna radiata L. cv. Wilczek) leaves

Chromium (Cr)-induced oxidative damage and changes in contents of chlorophyll, protein, peroxide and malondialdehyde (MDA) and activities of enzymatic antioxidants were investigated in 4-day-old green gram (Vigna radiata L. cv. Wilczek) seedlings. Cr increased the contents of peroxide and MDA but decreased the contents of chlorophyll and proteins. Cr reduced the activities of catalase (CAT) and glutathione reductase (GR), but increased the activity of superoxide dismutase (SOD) in green gramleaves. Lipid peroxidation is considered to be an important mechanism of Cr-induced oxidative damage in green gram leaves. The peroxidation of lipids can be initiated by free radicals. The effects of Crinducedoxidative damage and increase in the contents of peroxide and MDA in green gram leaves can be minimized by pretreatment with ascorbic acid (AA) and reduced glutathione (GSH) or both

Nonlinear Behaviour of Perforated Plate with Lining

Perforated plate with lining has a construction of plate with perforation and a lining plate welded together to form a single plate. This type of plate is used as an acoustic sonar dome. Perforated plate with lining (PPL) is prone to stress concentration and subsequently such structural system falls into the large strain category. Experimental investigation on PPL is carried out in the present study to determine the static deflection of the plate. Numerical method is also followed for geometric nonlinear analysis using finite element method as an iterative interactive procedure. The deflection obtained from the numerical method is 8 per cent less than that obtained from experimental method. From numerical analysis, von Mises stress and maximum principal stress is also estimated to understanda bout the failure mode characteristics of PPL.Defence Science Journal, 2012, 62(4), pp.248-251, DOI:http://dx.doi.org/10.14429/dsj.62.92

A questionnaire-based study to assess the knowledge, attitude and behaviour about leprosy among paramedical staff in a tertiary care hospital in Chennai

Background: The paramedical staff has an important part in the management of leprosy patients. They have a role in counselling, wound management, performing investigations etc. This study aimed at assessing the knowledge, attitude and behaviour of paramedical workers in a tertiary care hospital in Chennai.Methods: This cross-sectional study comprised of 100 paramedical workers of which 41 were males and 59 were females. Following classes of workers were included: nursing staff, auxiliary nursing midwives, ASHA workers, laboratory technicians, pharmacists and allied medical workers. Of these, the nursing staff comprised of the highest proportion (44%). The paramedical workers were given a questionnaire consisting of their demographic profile and further 32 questions to assess knowledge, attitude and behaviour towards leprosy. The data hence obtained over a period of 1 month was later systematically analysed.Results: The knowledge of paramedical workers was considered sufficient in the nursing staff, ANM and ASHA workers. It was consistently found that those workers who had some experience in the field of leprosy (39%) showed good level of knowledge, while others had a scope for improvement. The paramedical workers’ attitudes and behaviour were deemed to be overall appropriate, while there is a clear need to improve outreach initiatives in order to properly train them.Conclusions: The training of paramedical workers in leprosy should be prioritised. They are the initial point of contact for patients. There should be a greater emphasis on raising awareness and providing accurate information about the disease

Genetic diversity in green gram [Vigna radiata (L.)] landraces analyzed by using random amplified polymorphic DNA (RAPD)

Green gram [Vigna radiata (L.)] landraces were collected from various localities of Southern Tamil Nadu, India, to determine the extent of genetic diversity at DNA level by random amplified polymorphic DNA (RAPD) analysis using 20 decamer primers. All the primers produced polymorphic amplificationproducts with some extent of variation. A total of 200 bands were generated with an average of 10 per primer and exhibited 83.0% polymorphism. Jaccard’s similarity coefficient ranged from 0.64 to 0.93 and concentrated mostly between 0.76 to 0.93. This indicated a rather narrow genetic base of tested green gram landraces. Clustering of green gram landraces into two groups showed reasonable variability that may be exploited for selecting parents for breeding purposes. Generally distinct phenotypes identifiedusing RAPD markers could be potential sources of germplasm for green gram improvemen

Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction

Background: Beta‐blockers and inhibitors of the renin‐angiotensin aldosterone system improve survival and reduce morbidity in people with heart failure with reduced left ventricular ejection fraction. There is uncertainty whether these treatments are beneficial for people with heart failure with preserved ejection fraction and a comprehensive review of the evidence is required. Objectives: To assess the effects of beta‐blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and mineralocorticoid receptor antagonists in people with heart failure with preserved ejection fraction. Search methods: We searched CENTRAL, MEDLINE, Embase and two clinical trial registries on 25 July 2017 to identify eligible studies. Reference lists from primary studies and review articles were checked for additional studies. There were no language or date restrictions. Selection criteria: We included randomised controlled trials with a parallel group design enrolling adult participants with heart failure with preserved ejection fraction, defined by a left ventricular ejection fraction of greater than 40 percent. Data collection and analysis: Two review authors independently selected studies for inclusion and extracted data. The outcomes assessed included cardiovascular mortality, heart failure hospitalisation, hyperkalaemia, all‐cause mortality and quality of life. Risk ratios (RR) and, where possible, hazard ratios (HR) were calculated for dichotomous outcomes. For continuous data, mean difference (MD) or standardised mean difference (SMD) were calculated. We contacted trialists where neccessary to obtain missing data. Main results: 37 randomised controlled trials (207 reports) were included across all comparisons with a total of 18,311 participants. Ten studies (3087 participants) investigating beta‐blockers (BB) were included. A pooled analysis indicated a reduction in cardiovascular mortality (15% of participants in the intervention arm versus 19% in the control arm; RR 0.78; 95% confidence interval (CI) 0.62 to 0.99; number needed to treat to benefit (NNTB) 25; 1046 participants; 3 studies). However, the quality of evidence was low and no effect on cardiovascular mortality was observed when the analysis was limited to studies with a low risk of bias (RR 0.81; 95% CI 0.50 to 1.29; 643 participants; 1 study). There was no effect on all‐cause mortality, heart failure hospitalisation or quality of life measures, however there is uncertainty about these effects given the limited evidence available. 12 studies (4408 participants) investigating mineralocorticoid receptor antagonists (MRA) were included with the quality of evidence assessed as moderate. MRA treatment reduced heart failure hospitalisation (11% of participants in the intervention arm versus 14% in the control arm; RR 0.82; 95% CI 0.69 to 0.98; NNTB 41; 3714 participants; 3 studies; moderate‐quality evidence) however, little or no effect on all‐cause and cardiovascular mortality and quality of life measures was observed. MRA treatment was associated with a greater risk of hyperkalaemia (16% of participants in the intervention group versus 8% in the control group; RR 2.11; 95% CI 1.77 to 2.51; 4291 participants; 6 studies; high‐quality evidence). Eight studies (2061 participants) investigating angiotensin converting enzyme inhibitors (ACEI) were included with the overall quality of evidence assessed as moderate. The evidence suggested that ACEI treatment likely has little or no effect on cardiovascular mortality, all‐cause mortality, heart failure hospitalisation, or quality of life. Data for the effect of ACEI on hyperkalaemia were only available from one of the included studies. Eight studies (8755 participants) investigating angiotensin receptor blockers (ARB) were included with the overall quality of evidence assessed as high. The evidence suggested that treatment with ARB has little or no effect on cardiovascular mortality, all‐cause mortality, heart failure hospitalisation, or quality of life. ARB was associated with an increased risk of hyperkalaemia (0.9% of participants in the intervention group versus 0.5% in the control group; RR 1.88; 95% CI 1.07 to 3.33; 7148 participants; 2 studies; high‐quality evidence). We identified a single ongoing placebo‐controlled study investigating the effect of angiotensin receptor neprilysin inhibitors (ARNI) in people with heart failure with preserved ejection fraction. Authors' conclusions: There is evidence that MRA treatment reduces heart failure hospitalisation in heart failure with preserverd ejection fraction, however the effects on mortality related outcomes and quality of life remain unclear. The available evidence for beta‐blockers, ACEI, ARB and ARNI is limited and it remains uncertain whether these treatments have a role in the treatment of HFpEF in the absence of an alternative indication for their use. This comprehensive review highlights a persistent gap in the evidence that is currently being addressed through several large ongoing clinical trials

Organisational Elements Controlling the Labour Efficiency in Sri Lankan Road Construction Projects: Engineers’ Perspective

Labour efficiency is crucial for a construction firm’s long-term viability. According to recent studies, modernising organisational and administrative procedures is essential to improving labour efficiency in many developing countries, including Sri Lanka. The perspectives of construction engineers play a key role in strengthening organisational policies and management practices in the construction industry. As a result, based on the viewpoint of construction engineers, this study aims to identify the critical organisational elements that highly influence labour efficiency in Sri Lankan road construction projects. The elements/factors were qualitatively discovered after a thorough literature review. Then, a questionnaire survey was conducted among construction engineers employed by 31 Sri Lankan road construction contractors. The Relative Importance Index (RII) method was used to quantify each element’s level of influence on labour efficiency. Based on RII values, 33 organisational elements were determined as critical, where lack of communication and cooperation between the parties, delay in salary payment and lack of labour training facilities were determined as the top three ranking elements in the list. The validity and reliability of the results were confirmed by additional statistical tests. Using problem-based communication strategies, industry consultations were conducted among construction experts to determine the necessary future measures from relevant authorities based on the identified critical elements. These consultation outcomes suggest that the organisational policies of construction enterprises currently in place addressing financial procedures, communication strategies, resource management, performance management and training development practices must be improved in light of the new normal conditions facing the industry. The study findings might help to close the gap between management/organisational policies and workforce practices. Despite the fact that the study findings are limited to the Sri Lankan road construction industry, some of them could be used to address comparable issues in other developing nations

Water Requirements on the Journey Through Mordor

This paper considers the water requirements of the two hobbits, Frodo and Sam, on their journey through Mordor to Mount Doom. The number of kcal expended per day are calculated and from this the water requirement in litres is found. The ability of the hobbits to carry their water is investigated and the conclusion is reached that they would not have had the strength to carry all the water necessary for their needs