Bengal Junior doctors refuse to end cease-work
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New research has shown that, contrary to some previous studies, low levels of lipoprotein (a)-a parcel of fats and protein in the blood-do not cause type 2 diabetes.
The findings may alleviate concerns that drugs aimed at reducing lipoprotein (a) (known as Lp(a)) might be increasing patients’ risk of diabetes. High levels of Lp(a) are known to increase the risk of a range of cardiovascular diseases, such as clogged arteries, heart attack and stroke, and so doctors usually try to reduce Lp(a) but may be worried about a possible link with diabetes.
In a study presented by Professor Tadeusz Osadnik from Medical University of Silesia in Katowice, Poland, at the ESC Congress today and published simultaneously in Cardiovascular Diabetology, researchers have used a genetic method called Mendelian randomisation (MR) to show that, in fact, it is high levels of fasting insulin (hyperinsulinaemia) that cause the reduction in Lp(a). Hyperinsulinaemia leads to the development of pre-diabetes and type 2 diabetes.
Prof. Osadnik told the Congress: “Our findings suggest that hyperinsulinaemia, triggered by insulin resistance, can partially explain the inverse relationship between low Lp(a) concentrations and an increased risk of type 2 diabetes. They show that insulin produced by the body has a slight tendency to reduce levels of Lp(a).”
Prof. Osadnik and Maciej Banach, Professor of Cardiology at the Medial University of Lodz, Poland, and Johns Hopkins University School of Medicine, Baltimore, USA, published a study earlier this year [3] that used MR to show there was no correlation between genetically predicted Lp(a) concentrations on the incidence of type 2 diabetes. However, they wanted to investigate further as there was some evidence that other factors might be involved. MR is a method that uses measured variations in inherited genes to see if a particular risk factor (such as low Lp(a)) causes an effect on health (in this case, hyperinsulinaemia), rather than just being associated with it, and reduces the likelihood of reverse causation.
The researchers used information from UK Biobank to identify genetic variants, called single-nucleotide polymorphisms or SNPs, that were strongly associated with fasting insulin levels. They conducted several statistical analyses to understand the relationship between the SNPs and fasting insulin.
Prof. Banach, who was also at the ESC Congress, said: “Our analyses show that higher genetically predicted fasting insulin levels cause a decrease in Lp(a) concentration, and there is no evidence of reverse causality, in which it would be the other way round.
“The question now is whether these observations may have any important clinical relevance? First, we can confirm that the relationship between Lp(a) and diabetes exists, but Lp(a) is unlikely to be a risk factor for the development of diabetes, independent of pre-existing hyperinsulinaemia and insulin resistance. Second, the observational relationship between low Lp(a) and diabetes risk may not translate to possible adverse effects of therapies that reduce Lp(a) levels. More research is needed to investigate this further.”
Prof. Osadnik said: “Although therapies aimed at reducing insulin resistance, high levels of insulin in the blood and high blood sugar levels may increase Lp(a), it is almost certain that their cardiometabolic benefits outweigh the increased cardiovascular risk caused by an increase in Lp(a). This is demonstrated by the fact that good control of blood sugar levels improves patient survival. As elevated Lp(a) is an independent and incremental risk factor for outcomes for patients with coronary artery disease, with and without diabetes, we should do our best to reduce elevated Lp(a).”
Prof. Banach concluded: “This study also clearly shows that our patients can be complicated, and often have other concurrent risk factors and medical conditions. We should always take a holistic approach to their health, looking at all these other factors as well. We should not be focused just on Lp(a), or cholesterol levels or diabetes, but try to identify all other residual cardiovascular risk factors. We need to look at the whole patient; this is the only way to reduce cardiovascular disease effectively in our patients.”
Limitations of the study include: it relied on summary data from UK Biobank and so it was not possible to analyse the influence of non-genetic factors that might affect Lp(a), such as sex, hormones or diet; bias may have been introduced because it included patients with diabetes; the data came from people of European descent, so it might not be possible to generalise the findings to people of different ethnicities; and insulin and blood sugar levels are complex and interconnected, so further research is required to understand if indirect effects of insulin on Lp(a) levels exist.
Reference:
Lejawa, M., Goławski, M., Fronczek, M. et al. Causal associations between insulin and Lp(a) levels in Caucasian population: a Mendelian randomization study. Cardiovasc Diabetol 23, 316 (2024). https://doi.org/10.1186/s12933-024-02389-7.
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A next-generation COVID-19 mucosal vaccine is set to be a gamechanger not only when delivering the vaccine itself, but also for people who are needle-phobic.
New Griffith University research, published in Nature Communications, has been testing the efficacy of delivering a COVID-19 vaccine via the nasal passages.
Professor Suresh Mahalingam from Griffith’s Institute for Biomedicine and Glycomics has been working on this research for the past four years.
“This is a live attenuated intranasal vaccine, called CDO-7N-1, designed to be administered intranasally, thereby inducing potential mucosal immunity as well as systemic immunity with just a single dose,” Professor Mahalingam said.
“The vaccine induces strong memory responses in the nasal mucosa offering long-term protection for up to a year or more.
“It’s been designed to be administered as single dose, ideally as a booster vaccine, as a safe alternative to needles with no adverse reactions in the short or long term.”
Live-attenuated vaccines offer several significant advantages over other vaccine approaches.
They induce potent and long-lived humoral and cellular immunity, often with just a single dose.
Live-attenuated vaccines comprise the entire virus thereby providing broad immunity, in contrast to a single antigen which is used in many other vaccine platforms.
Lead author Dr Xiang Liu said the vaccine provides cross-protection against all variants of concern, and has neutralising capacity against SARS-CoV-1.
“The vaccine offers potent protection against transmission, prevents reinfection and the spread of the virus, while also reducing the generation of new variants,” Dr Liu said.
“Unlike the mRNA vaccine which targets only the spike protein, CDO-7N-1 induces immunity to all major SARS-CoV-2 proteins and is highly effective against all major variants to date.
“Importantly, the vaccine remains stable at 4°C for seven months, making it ideal for low- and middle-income countries.”
The vaccine has been licensed to Indian Immunologicals Ltd, a major vaccine manufacturer.
Dr. K. Anand Kumar, co-author of the publication and Managing Director of Indian Immunologicals Ltd. Said: “We are a leading ‘One Health’ company that has developed and launched several vaccines for human and animal use in India and are currently exporting to 62 countries.”
“We have completed all the necessary studies of this novel COVID-19 vaccine which offers tremendous advantages over other vaccines.
“We now look forward to taking the vaccine candidate to clinical trials.”
Professor Lee Smith, Acting Director of the Institute for Biomedicine and Glycomics, said he was delighted with the research findings.
“These results towards developing a next-generation COVID-19 vaccine are truly exciting,” Professor Smith said.
“Our researchers are dedicated to providing innovative and, crucially, more accessible solutions to combat this high-impact disease.”
Reference:
Liu, X., Ng, W.H., Zusinaite, E. et al. A single-dose intranasal live-attenuated codon deoptimized vaccine provides broad protection against SARS-CoV-2 and its variants. Nat Commun 15, 7225 (2024). https://doi.org/10.1038/s41467-024-51535-y
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A recent subgroup analysis published in the American Journal of Ophthalmology revealed promising results for a novel topical treatment to improve visual function in patients with early-stage age-related cataracts. The study explored the efficacy of a 2.6% EDTA ophthalmic solution (C-KAD) by specifically focusing on its ability to improve the contrast sensitivity (CS) that deteriorates in the early stages of cataract development.
This multicenter phase 1/2 clinical trial included a total of 41 eyes from subjects who had mesopic contrast sensitivity scores between 1 and 7 grating patches at baseline which indicates mild to moderate loss of CS. These subjects were part of the intent-to-treat population in the original trial. The primary objective of this study was to determine the proportion of eyes showing clinically significant improvements in mesopic CS, defined as an improvement of 0.30 logCS or greater, equivalent to a 100% improvement in CS, at two or more spatial frequencies.
The results of this analysis found 66.7% of the eyes treated with C-KAD to demonstrate significant mesopic CS improvements by Day 120, when compared to only 35.0% in the placebo group (P = .043). This finding not only met the primary endpoint but also highlighted the potential of C-KAD as a noninvasive pharmacological treatment for early-stage cataract patients.
Further analysis showed that the proportion of eyes achieving significant improvements in the area under the log contrast sensitivity function (AULCSF) was also significantly higher in the C-KAD group (42.9%) when compared to the placebo group (15.0%, P = .050). The mean change in AULCSF was markedly larger in the C-KAD group, with an average improvement of 0.25 logCS versus just 0.06 logCS in the placebo group (P = .020). Also, C-KAD showed significant improvements in mesopic CS at specific spatial frequencies, particularly at 3 cycles per degree (cpd) and 6 cpd. The mean CS improvements at these frequencies were 0.28 logCS (P = .004) and 0.31 logCS (P = .047), respectively by further highlighting the efficacy of the treatment.
Exploratory outcomes, such as best-corrected visual acuity (BCVA) and lens density changes, were also examined in a smaller subset of eyes. Positive trends in BCVA and statistically significant reductions in lens density were observed in the C-KAD group which suggests additional benefits beyond CS improvement. Overall, the study unveiled that C-KAD offers a significant improvement in visual function and quality of vision for patients with early-stage cataracts.
Source:
KUBOI, T., CHUCK, R. S., PINEDA, R., II, BHUSHAN, R., GOSWAMY, A., & OLSON, R. J. (2024). Subgroup Analysis from a Phase 1/2 Randomized Clinical Trial of 2.6% EDTA Ophthalmic Solution in Patients with Age-Related Cataract. In American Journal of Ophthalmology (Vol. 268, pp. 155–164). Elsevier BV. https://doi.org/10.1016/j.ajo.2024.07.038
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Research evidence has established that the consumption of dried fruit may significantly lower the risk of type-2 diabetes (T2D). Jianbin G. and colleagues published a recent article in the journal Nutrition and Metabolism using a two-sample Mendelian randomization design to provide some evidence that dietary intake of dried fruit might be protective against T2D. In this study, summary statistics for the exposure and outcome variables were derived, based on genome-wide association studies, in an effort to elucidate this possible causal relationship.
Previous studies into the relationship between dried fruit consumption and the risk of type 2 diabetes have been inconclusive, and the causal effects remain unclear. To this end, the current study estimates the causal impact of dietary factors on health outcomes using Mendelian randomization with genetic variants. The approach limits most of the bias associated with conventional observational trans-sectional studies in terms of confounding variables and reverse causality.
Summary statistics from the genome-wide association study (GWAS) analyses were used as input for performing a two-sample bidirectional MR to investigate the potential causal association between T2D and dried fruit consumption. The primary method for analysis was by the inverse-variance weighted approach. As a validation method, MR-Egger and weighted median methods were employed. Cochrane’s Q test, MR-Egger intercept test, and leave-one-out analysis were conducted for sensitivity analyses to check its robustness against bias and confounding. Funnel plots were plotted to assess publication bias.
Key Findings
• The IVW analysis indicated that dried fruit intake is associated with a significant reduction in T2D risk, with an odds ratio (OR) of 0.392 (95% confidence interval [CI]: 0.241–0.636, p-value = 0.0001).
• This suggests that higher consumption of dried fruit could lower the likelihood of developing T2D by approximately 60%.
• The weighted median method confirmed the results obtained from the IVW analysis, supporting the robustness of the findings.
• Both methods demonstrated a consistent protective effect of dried fruit intake against T2D.
• The sensitivity analyses, including Cochrane’s Q test and MR-Egger intercept test, showed that the results were not influenced by heterogeneity or horizontal pleiotropy. The leave-one-out analysis further validated the reliability of the MR results.
• The funnel plot illustrated a symmetrical distribution, indicating no significant publication bias affecting the study’s findings.
This study provides very strong evidence that dried fruit consumption is related to a reduced risk of T2D and thus can be a preventive measure by which dried fruits can be introduced to the diet. Since these results are strong, reasonable dried fruit consumption would already be applicable as a pragmatic means of primary diabetes prevention.
Reference:
Guan, J., Liu, T., Yang, K., & Chen, H. (2024). Dried fruit intake and lower risk of type 2 diabetes: a two-sample mendelian randomization study. Nutrition & Metabolism, 21(1). https://doi.org/10.1186/s12986-024-00813-z
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New research presented at the ESC Congress 2024 in London, UK (30 August-2 September) shows that women in the menopause transition period show changes in their blood cholesterol profiles which could have an adverse impact on their cardiovascular health.
“There is an increase in ‘bad’ low-density type lipoprotein (LDL) particles and a decrease in ‘good’ high-density lipoprotein particles (HDL) that takes place during and after the menopause transition,” says study author Dr Stephanie Moreno, University of Texas Southwestern Medical Center, Dallas, TX, USA. “Taken together, these changes suggest that menopause is associated with a transition to a higher-risk lipoprotein profile that could be more likely to cause cardiovascular disease, such as coronary artery disease.”
Cardiovascular disease (CVD) is the biggest killer of women, despite the misconceptionthat CVD is a ‘man’s disease’ – 40% of all deaths in women are from CVD. While women develop cardiovascular disease (CVD) approximately ten years later than men, risk of CVD in women rises after menopause. The mechanisms underlying this acceleration in CVD risk are not well understood, but adverse changes in blood fat (lipid) measures are known to occur during the perimenopause period. Previous investigations have been largely restricted to traditional lipid measures (LDL [bad] cholesterol, HDL [good] cholesterol, and triglycerides) and have not examined changes in advanced lipids, including lipid subfractions and particle number which have been shown to be more predictive of cardiovascular disease in various studies.
In this study, the authors examined the changes over time in lipoprotein particles that occur during the menopause transition. A total of 1246 participants in the Dallas Heart Study (DHS) with known menopause status underwent measurement of common lipoproteins associated with CVD, including atherogenic LDL-P and small dense-LDL. Using nuclear magnetic resonance (NMR) technology, at two time points (DHS1 and DHS2) they compared longitudinal changes in lipoprotein measures between pre-, peri-, post-menopausal women and men using statistical modelling. For their analysis peri- is the group that was pre-menopause at DHS I and post-menopause at DHS 2.
There were also 1346 men (reference group) included in the study with a mean age of 43 years. There was a total of 1246 women with a mean age of 42 years for the peri-group, 54 years for the post-group, and 34 years for the pre-group. Of the women 440 (35%) were pre-menopausal, 298 (24%) were peri-menopausal, and 508 (41%) were post-menopausal.
Over a median follow-up time of 7 years. All three female groups had an increase in LDL-P but the greatest percent change was found to be between peri and post groups at 8.3%. When compared to men the post-group has the greatest percent change of HDL-P with a negative change of 4.8%.
Small-dense LDL had a greater percent change in the peri- group when compared to men with a change of 213%. This percent change is ~15% higher than both pre- and post-menopause groups.
“We found that menopause is associated with adverse changes in lipoprotein profiles, with the most pronounced changes found to be in increases in ‘bad’ LDL-particles and subfractions observed for peri-menopausal women,” said Dr Moreno. “When looked at together, these changes could help explain the increase of cardiovascular disease in post-menopausal women and help determine if earlier interventions are warranted.”
She concludes: “More research is needed to investigate whether these adverse changes in lipoproteins translate to greater cardiovascular risk.”
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Eat sleep console care useful for improving breastfeeding outcomes among infants with neonatal opioid withdrawal syndrome suggests a new study published in the JAMA.
Infants with neonatal opioid withdrawal syndrome (NOWS) cared for with the Eat, Sleep, Console (ESC) care approach receive less pharmacologic treatment and have shorter hospital stays compared to usual care with the Finnegan Neonatal Abstinence Scoring Tool, but the effects of these approaches on feeding and weight are unknown. A study was done to evaluate feeding practices and weight trajectories in infants cared for with ESC vs usual care. ESC-NOW is a cluster randomized trial of infants with NOWS born at 36 weeks’ gestation or later at 26 US hospitals from September 2020 to March 2022. Each site transitioned from usual care to ESC (the study intervention) at a randomized time.
Feeding was per site practice and not specified by the intervention. Feeding and weight outcomes were assessed at hospital discharge. Outcomes include prospectively identified secondary end points related to feeding and weight. z Scores were used for growth to account for corrected gestational age at the time of measurement. All analyses were intention to treat and adjusted for study design. Maternal/infant characteristics were included in adjusted models. Results: The analyses included 1305 infants (702 in usual care and 603 in ESC; mean [SD] gestational age, 38.6 [1.3] weeks; 655 [50.2%] male and 650 [49.8%] female). Baseline demographic characteristics were similar between groups.
The proportion of breastfed infants was higher in the ESC group (52.7% vs 41.7%; absolute difference, 11%; 95% CI, 1.0-20.9). A higher proportion of infants cared for with ESC received exclusive breast milk (15.1% vs 6.7%; absolute difference, 8.4%; 95% CI, 0.9-5.8) or any breast milk (38.8% vs 27.4%; absolute difference, 11.4%; 95% CI, 0.2-23.1) and were directly breastfeeding at discharge (35.2% vs 19.5%; absolute difference, 15.7%; 95% CI, 4.1-27.3). There was no difference in proportion of infants with weight loss greater than 10% or maximum percentage weight loss, although infants cared for with ESC had a lower weight z score on day of life 3 (−1.08 vs −1.01; absolute difference, 0.07; 95% CI, 0.02-0.12). When pharmacologic treatment was added into the model, no breastfeeding outcomes were statistically significant. In this study, infants cared for with ESC were more likely to initiate and continue breastfeeding and had no difference in percentage weight loss. The improvement in breastfeeding with ESC may be driven by reduction in pharmacologic treatment and provision of effective nonpharmacologic care.
Reference:
Merhar SL, Hu Z, Devlin LA, et al. Infant Feeding and Weight Trajectories in the Eat, Sleep, Console Trial: A Secondary Analysis of a Randomized Clinical Trial. JAMA Pediatr. Published online August 12, 2024. doi:10.1001/jamapediatrics.2024.2578
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Liver resection is a challenging surgical procedure with inherent risks for both the anesthesiologist and the surgeon. Prof. Henrik Kehlet’s concept of Enhanced Recovery After Surgery (ERAS) focuses on evidence-based strategies to minimize the physiological stress of surgery, resulting in quicker recovery, shorter hospital stays, and better postoperative results. Recent retrospective cohort study focuses on the compliance to Enhanced Recovery After Surgery (ERAS) in liver resection and its correlation with patient outcomes. The study evaluates the compliance with 21 out of 25 ERAS recommendations for liver surgery and its association with the length of hospital stay (LOS) and the development of complications. The study included 44 hepatectomy patients and showed an overall compliance of 77%. Individual component compliance varied, with lower compliance rates in aspects such as fasting, carbohydrate loading, minimally invasive surgical techniques, and avoidance or early removal of the drain. The study divided the cohort into two groups based on their compliance with ERAS components. Group 1 had compliance to ≥75% of the elements, while group 2 had compliance to <75%. The results indicated that higher ERAS compliance was associated with reduced complications, although LOS differences were not statistically significant. Severe complications such as re‑exploration and death were noted in patients with compliance to fewer than 75% of the components. The paper stresses the potential clinical and financial benefits of increased ERAS compliance for patients undergoing liver resection surgery.
ERAS Principles and Global Application
The paper highlights the stress response associated with major abdominal surgery and the relevance of implementing evidence-based ERAS practices to reduce surgical stress, promote faster recovery times, and improve surgical outcomes. It emphasizes the global adoption of ERAS principles and the application of the concept to surgical specialties beyond colorectal surgeries. The study also discusses the variability in individual compliance rates with various ERAS components, with some components showing good compliance rates and others showing lower compliance rates.
The paper acknowledges the limitations of its retrospective design and relatively small sample size. It suggests the need for larger, preferably prospective, and randomized studies to further investigate the observations. Despite the limitations, the study demonstrates the potential for implementing ERAS protocols in liver surgery through institutional protocols and a multidisciplinary approach. It underscores the overall effectiveness of the ERAS protocol and encourages healthcare practitioners to closely follow it to benefit patients undergoing liver resection surgery.
Key Points
1. The research paper is a retrospective cohort study that evaluates the compliance to Enhanced Recovery After Surgery (ERAS) in liver resection and its correlation with patient outcomes. It includes 44 hepatectomy patients and shows an overall compliance of 77% with 21 out of 25 ERAS recommendations for liver surgery.
2. The study divides the cohort into two groups based on their compliance with ERAS components, with Group 1 having compliance to ≥75% of the elements, and Group 2 having compliance to <75%. Higher ERAS compliance is associated with reduced complications, although length of hospital stay (LOS) differences were not statistically significant. Patients with compliance to fewer than 75% of the components experienced severe complications such as re‑exploration and death.
3. The paper emphasizes the global adoption of ERAS principles and their relevance in reducing surgical stress, promoting faster recovery, and improving surgical outcomes. It highlights the variability in individual compliance rates with various ERAS components, with some components showing good compliance rates and others showing lower compliance rates.
4. It stresses the potential clinical and financial benefits of increased ERAS compliance for patients undergoing liver resection surgery, advocating for the implementation of evidence-based ERAS practices to improve patient outcomes. The study underscores the overall effectiveness of the ERAS protocol and encourages healthcare practitioners to closely follow it.
5. The paper acknowledges the limitations of its retrospective design and relatively small sample size, suggesting the need for larger, preferably prospective, and randomized studies to further investigate the observations. It emphasizes the potential for implementing ERAS protocols in liver surgery through institutional protocols and a multidisciplinary approach.
6. The study promotes the importance of complying with ERAS recommendations for liver surgery, particularly in aspects such as fasting, carbohydrate loading, minimally invasive surgical techniques, and avoidance or early removal of the drain, to benefit patients undergoing liver resection surgery.
Reference –
Pradhan A, Sarkar A, Haldar S, Chakraborty A, Pal AR. Compliance to enhanced recovery program in liver resection surgery: A retrospective cohort study. J Anaesthesiol Clin Pharmacol 2024.
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