Background
The Seven Countries study in the 1960s showed that populations in the Mediterranean region experienced lower coronary heart disease (CHD) mortality probably as a result of different ...dietary patterns. Later observational studies have confirmed the benefits of adherence to a Mediterranean dietary pattern on cardiovascular disease (CVD) risk factors but clinical trial evidence is more limited.
Objectives
To determine the effectiveness of a Mediterranean‐style diet for the primary and secondary prevention of CVD.
Search methods
We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 9); MEDLINE (Ovid, 1946 to 25 September 2018); Embase (Ovid, 1980 to 2018 week 39); Web of Science Core Collection (Thomson Reuters, 1900 to 26 September 2018); DARE Issue 2 of 4, 2015 (Cochrane Library); HTA Issue 4 of 4, 2016 (Cochrane Library); NHS EED Issue 2 of 4, 2015 (Cochrane Library). We searched trial registers and applied no language restrictions.
Selection criteria
We selected randomised controlled trials (RCTs) in healthy adults and adults at high risk of CVD (primary prevention) and those with established CVD (secondary prevention). Both of the following key components were required to reach our definition of a Mediterranean‐style diet: high monounsaturated/saturated fat ratio (use of olive oil as main cooking ingredient and/or consumption of other traditional foods high in monounsaturated fats such as tree nuts) and a high intake of plant‐based foods, including fruits, vegetables and legumes. Additional components included: low to moderate red wine consumption; high consumption of whole grains and cereals; low consumption of meat and meat products and increased consumption of fish; moderate consumption of milk and dairy products. The intervention could be dietary advice, provision of relevant foods, or both. The comparison group received either no intervention, minimal intervention, usual care or another dietary intervention. Outcomes included clinical events and CVD risk factors. We included only studies with follow‐up periods of three months or more defined as the intervention period plus post intervention follow‐up.
Data collection and analysis
Two review authors independently assessed studies for inclusion, extracted data and assessed risk of bias. We conducted four main comparisons:
1. Mediterranean dietary intervention versus no intervention or minimal intervention for primary prevention;
2. Mediterranean dietary intervention versus another dietary intervention for primary prevention;
3. Mediterranean dietary intervention versus usual care for secondary prevention;
4. Mediterranean dietary intervention versus another dietary intervention for secondary prevention.
Main results
In this substantive review update, 30 RCTs (49 papers) (12,461 participants randomised) and seven ongoing trials met our inclusion criteria. The majority of trials contributed to primary prevention: comparisons 1 (nine trials) and 2 (13 trials). Secondary prevention trials were included for comparison 3 (two trials) and comparison 4 (four trials plus an additional two trials that were excluded from the main analyses due to published concerns regarding the reliability of the data).
Two trials reported on adverse events where these were absent or minor (low‐ to moderate‐quality evidence). No trials reported on costs or health‐related quality of life.
Primary prevention
The included studies for comparison 1 did not report on clinical endpoints (CVD mortality, total mortality or non‐fatal endpoints such as myocardial infarction or stroke). The PREDIMED trial (included in comparison 2) was retracted and re‐analysed following concerns regarding randomisation at two of 11 sites. Low‐quality evidence shows little or no effect of the PREDIMED (7747 randomised) intervention (advice to follow a Mediterranean diet plus supplemental extra‐virgin olive oil or tree nuts) compared to a low‐fat diet on CVD mortality (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.50 to 1.32) or total mortality (HR 1.0, 95% CI 0.81 to 1.24) over 4.8 years. There was, however, a reduction in the number of strokes with the PREDIMED intervention (HR 0.60, 95% CI 0.45 to 0.80), a decrease from 24/1000 to 14/1000 (95% CI 11 to 19), moderate‐quality evidence). For CVD risk factors for comparison 1 there was low‐quality evidence for a possible small reduction in total cholesterol (‐0.16 mmol/L, 95% CI ‐0.32 to 0.00) and moderate‐quality evidence for a reduction in systolic (‐2.99 mmHg (95% CI ‐3.45 to ‐2.53) and diastolic blood pressure (‐2.0 mmHg, 95% CI ‐2.29 to ‐1.71), with low or very low‐quality evidence of little or no effect on LDL or HDL cholesterol or triglycerides. For comparison 2 there was moderate‐quality evidence of a possible small reduction in LDL cholesterol (‐0.15 mmol/L, 95% CI ‐0.27 to ‐0.02) and triglycerides (‐0.09 mmol/L, 95% CI ‐0.16 to ‐0.01) with moderate or low‐quality evidence of little or no effect on total or HDL cholesterol or blood pressure.
Secondary prevention
For secondary prevention, the Lyon Diet Heart Study (comparison 3) examined the effect of advice to follow a Mediterranean diet and supplemental canola margarine compared to usual care in 605 CHD patients over 46 months and there was low‐quality evidence of a reduction in adjusted estimates for CVD mortality (HR 0.35, 95% CI 0.15 to 0.82) and total mortality (HR 0.44, 95% CI 0.21 to 0.92) with the intervention. Only one small trial (101 participants) provided unadjusted estimates for composite clinical endpoints for comparison 4 (very low‐quality evidence of uncertain effect). For comparison 3 there was low‐quality evidence of little or no effect of a Mediterranean‐style diet on lipid levels and very low‐quality evidence for blood pressure. Similarly, for comparison 4 where only two trials contributed to the analyses there was low or very low‐quality evidence of little or no effect of the intervention on lipid levels or blood pressure.
Authors' conclusions
Despite the relatively large number of studies included in this review, there is still some uncertainty regarding the effects of a Mediterranean‐style diet on clinical endpoints and CVD risk factors for both primary and secondary prevention. The quality of evidence for the modest benefits on CVD risk factors in primary prevention is low or moderate, with a small number of studies reporting minimal harms. There is a paucity of evidence for secondary prevention. The ongoing studies may provide more certainty in the future.
There have been recent mounting concerns regarding multiple reports stating a significantly elevated relative-risk of COVID-19 mortality amongst the Black and Minority Ethnic (BAME) population. An ...urgent national enquiry investigating the possible reasons for this phenomenon has been issued in the UK. Inflammation is at the forefront of COVID-19 research as disease severity appears to correlate with pro-inflammatory cytokine dysregulation. This narrative review aims to shed light on the novel, pathophysiological role of inflammation in contributing towards the increased COVID-19 mortality risk amongst the BAME population.
Searches in PubMed, Medline, Scopus, medRxiv and Google Scholar were performed to identify articles published in English from inception to 18th June 2020. These databases were searched using keywords including: ‘COVID-19’ or ‘Black and Minority Ethnic’ or ‘Inflammation’. A narrative review was synthesized using these included articles.
We suggest a novel pathophysiological mechanism by which acute inflammation from COVID-19 may augment existing chronic inflammation, in order to potentiate a ‘cytokine storm’ and thus the more severe disease phenotype observed in the BAME population. Obesity, insulin resistance, cardiovascular disease, psychological stress, chronic infections and genetic predispositions are all relevant factors which may be contributing to elevated chronic systemic inflammation amongst the BAME population.
Overall, this review provides early insights and directions for ongoing research regarding the pathophysiological mechanisms that may explain the severe COVID-19 disease phenotype observed amongst the BAME population. We suggest ‘personalization’ of chronic disease management, which can be used with other interventions, in order to tackle this.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Consideration of pelvic mobility when positioning implants for total hip arthroplasty (THA) has been shown to reduce the risk of complications such as dislocation, squeaking and excessive wear. We ...aim to test the repeatability of pelvic tilt measurements taken between three positions (standing, flexed-seated and step-up) by an inertial measurement unit (IMU) and hence, evaluate their reliability in screening for high pelvic mobility in patients undergoing THA. The repeated IMU measurements of pelvic tilt were analysed for consistency and compared with measures taken by x-ray analysis. Our study showed greater variation in measures taken by the IMU particularly in the flexed-seated position. The patient's pelvic tilt in this position negatively correlated with their mid-back angle, suggesting the posture of the patient is a source of variation in the flexed-seated position if not kept consistent during assessments. IMUs were overall able to produce accurate and reliable measurements of pelvic tilt; however, protocols will need to be adjusted to factor in a patient's mid-back angle when taking future readings.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
ABSTRACT
Transient receptor potential vanilloid 1 (TRPV1) is involved in sensory nerve nociceptive signaling. Recently, it has been discovered that TRPV1 receptors also regulate basal body ...temperature in multiple species from mice to humans. In the present study, we investigated whether TRPV1 modulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild‐type (WT) mice and TRPV1 knockout (KO) mice were implanted with radiotelemetry probes for measurement of core body temperature. AMG 9810∗∗∗ (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected intraperitoneally. Adrenoceptor antagonists or vehicle (5 ml/kg saline) was injected subcutaneously. In WT mice, the TRPV1 antagonist, AMG9810, caused significant hyperthermia, associated with increased noradrenaline concentrations in brown adipose tissue. The hyperthermia was significantly attenuated by the β‐adrenoceptor antagonist propranolol, the mixed α‐/β‐adrenoceptor antagonist labetalol, and the α1‐adrenoceptor antagonist prazosin. TRPV1 KO mice have a normal basal body temperature, indicative of developmental compensation. D‐Amphetamine (potent sympathomimetic) caused hyperthermia in WT mice, which was reduced in TRPV1 KO mice, suggesting a decreased sympathetic drive in KOs. This study provides new evidence that TRPV1 controls thermoregulation upstream of the SNS, providing a potential therapeutic target for sympathetic hyperactivity thermoregulatory disorders.—Alawi, K. M., Aubdool, A. A., Liang, L., Wilde, E., Vepa, A., Psefteli, M.‐P., Brain, S. D., Keeble, J. E. The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature. FASEB J. 29, 4285‐4298 (2015). www.fasebj.org
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Diet plays a major role in cardiovascular disease (CVD) risk.
To determine the effectiveness of a Mediterranean-style diet for the primary and secondary prevention of CVD.
We searched for randomised ...controlled trials (RCTs) of Mediterranean-style diets in healthy adults and those at increased risk of CVD (primary prevention) and with established CVD (secondary prevention).
Thirty RCTs were included, 22 in primary prevention and eight in secondary prevention. Clinical endpoints were reported in two trials where there was moderate quality evidence for a reduction in strokes for primary prevention, and low quality evidence for a reduction in total and CVD mortality in secondary prevention. We found moderate quality evidence of improvement in CVD risk factors for primary prevention and low quality evidence of little or no effect in secondary prevention.
There is still some uncertainty regarding the effects of a Mediterranean-style diet in CVD prevention.
There is increasing evidence that pelvic mobility is a critical factor to consider in implant alignment during total hip arthroplasty (THA). Here, we test the feasibility of using an inertial sensor ...fitted across the sacrum to measure change in pelvic tilt, and hence screen for patients with high pelvic mobility. Patients (
= 32, mean age: 57.4 years) due to receive THA surgery participated in the study. Measures of pelvic tilt were captured simultaneously using the device and radiograph in three functional positions: Standing, flexed-seated, and step-up. We found a strong correlation between the device and radiograph measures for the change in pelvic tilt measure from standing to flexed-seated position (R
= 0.911); 75% of absolute errors were under 5 degrees. We demonstrated that the device can be used as a screening tool to rapidly identify patients who would benefit from more detailed surgical planning of implant positioning to reduce future risks of impingement and dislocation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background: Within the UK, COVID-19 has contributed towards over 103,000 deaths. Although multiple risk factors for COVID-19 have been identified, using this data to improve clinical care has proven ...challenging. The main aim of this study is to develop a reliable, multivariable predictive model for COVID-19 in-patient outcomes, thus enabling risk-stratification and earlier clinical decision-making. Methods: Anonymised data consisting of 44 independent predictor variables from 355 adults diagnosed with COVID-19, at a UK hospital, was manually extracted from electronic patient records for retrospective, case–control analysis. Primary outcomes included inpatient mortality, required ventilatory support, and duration of inpatient treatment. Pulmonary embolism sequala was the only secondary outcome. After balancing data, key variables were feature selected for each outcome using random forests. Predictive models were then learned and constructed using Bayesian networks. Results: The proposed probabilistic models were able to predict, using feature selected risk factors, the probability of the mentioned outcomes. Overall, our findings demonstrate reliable, multivariable, quantitative predictive models for four outcomes, which utilise readily available clinical information for COVID-19 adult inpatients. Further research is required to externally validate our models and demonstrate their utility as risk stratification and clinical decision-making tools.
Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or COVID-19, has emerged as an epidemic contributing to more than 247,000 deaths worldwide as of 4th May 2020. It commonly ...presents with respiratory and occasionally gastrointestinal symptoms. Here we describe a rare case of COVID-19 presenting with acute psychosis which was also complicated by a false negative RT-PCR nasopharyngeal swab upon hospital admission. Case Report: A 40 year old, previously fit and healthy male, presented to accident and emergency with respiratory tract symptoms and fever during the COVID-19 outbreak. His first RT-PCR nasopharyngeal swab tested negative for COVID-19, but due to a strong clinical suspicion of COVID-19, CT imaging was conducted which justified the sending of a repeat swab. In the meantime, he started to exhibit symptoms of acute psychosis such as hallucinations, paranoid delusions, an attempted suicide, derealisation and depersonalization. Due to failed conservative measures and haloperidol in managing acute psychosis, the patient was intubated for 24 hours. After extubating the patient recovered to baseline within 2 days. Discussion: There are two clinically relevant learning points to be noted from this case report. Firstly, RT-PCR nasopharyngeal COVID-19 swabs are estimated to be only 70-75% sensitive, whereas CT scan changes are estimated to be as high as 97%-98% sensitive. CT imaging can thus be useful when there is a strong suspicion of COVID-19 despite negative nasopharyngeal swabs. Secondly, in order to reduce the work of breathing secondary to agitation, the cross-infection risks to others, and the risk of repeated suicide attempts, this patient was successfully managed with intubation and ventilation, despite the absence of respiratory failure. Conclusion: False negative rate with RT-PCR COVID-19 nasopharyngeal swabs is high and this identifies a crucial diagnostic role for CT Thorax in swab-negative, symptomatic patients with suspected COVID-19. Secondly, acute psychosis is an emerging indication for intubation to consider when managing patients with highly virulent respiratory infections, such as COVID-19. Keywords: COVID-19; Case Report; nasopharyngeal swab; acute psychosis; intubation; diagnosis; cross-infection Keywords: COVID-19; Abbreviations: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, or, COVID-19), World Health Organisation (WHO), Real Time-Polymerase Chain Reaction (RT-PCR), Respiratory Syncytial Virus (RSV), Antero-Posterior (AP), Computerized Tomography (CT), Ground-Glass Opacification (GGO)
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Transient receptor potential vanilloid 1 (TRPV1) is involved in pain and neurogenic inflammation. It has recently been found that TRPV1 anatgonism causes hyperthermia in multiple species from mice to ...humans. In the present study, we investigated whether TRPV1 regulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild-type (WT) mice and TRPV1 knockout (KO) mice were implanted with radio-telemetry probes for measurement of core body temperature. AMG9810 (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected via the peritoneal route. Adrenoceptor antagonists or vehicle (5 ml/kg saline) was injected s.c. In WT mice, theTRPVl antagonist, AMG9810, caused a significantincrease in body temperature, along with increased noradrenaline concentrations in brown adipose tissue. The hyperthermia was significantly attenuated by the (^-adrenoceptor antagonist propranolol, the mixed a-/p-adrenoceptor antagonist labetalol, and the al-adrenoceptor antagonist prazosin. TRPV1 KO mice have a normal basal body temperature, indicative of developmental compensatory events. Amphetamine (potent sympathomimetic) caused hyperthermia in WT mice, which was reduced in TRPV1 KO mice, suggesting a decreased sympathetic drive in KOs. This study provides new evidence thatTRPVl regulates thermoregulatory pathways, upstream of the SNS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
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