Mediterranean diet tied to one-fifth lower risk of death in women: JAMA

Investigators from Brigham and Women’s Hospital identified and assessed underlying mechanisms that may explain the Mediterranean diet’s 23 percent reduction in all-cause mortality risk for American women

The health benefits of the Mediterranean diet have been reported in multiple studies, but there is limited long-term data of its effects in U.S. women and little understanding about why the diet may reduce risk of death. In a new study that followed more than 25,000 initially healthy U.S. women for up to 25 years, researchers from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, found that participants who had greater Mediterranean diet intake had up to 23% lower risk of all-cause mortality, with benefits for both cancer mortality and cardiovascular mortality. The researchers found evidence of biological changes that may help explain why: they detected changes in biomarkers of metabolism, inflammation, insulin resistance and more. Results are published in JAMA.

“For women who want to live longer, our study says watch your diet! The good news is that following a Mediterranean dietary pattern could result in about one quarter reduction in risk of death over more than 25 years with benefit for both cancer and cardiovascular mortality, the top causes of death in women (and men) in the US and globally,” said senior author Samia Mora, MD, a cardiologist and the director of the Center for Lipid Metabolomics at the Brigham.

The Mediterranean diet is a plant-based diverse diet that is rich in plants (nuts, seeds, fruits, vegetables, whole grains, legumes). The main fat is olive oil (usually extra virgin), and the diet additionally includes moderate intake of fish, poultry, dairy, eggs, and alcohol, and rare consumption of meats, sweets, and processed foods.

The current study investigated the long-term benefit of adherence to a Mediterranean diet in a U.S. population recruited as part of the Women’s Health Study, and explored the biological mechanisms that may explain the diet’s health benefits. The study investigators evaluated a panel of approximately 40 biomarkers representing various biological pathways and clinical risk factors.

Biomarkers of metabolism and inflammation made the largest contribution, followed by triglyceride-rich lipoproteins, adiposity, insulin resistance. Other biological pathways relate to branched-chain amino acids, high-density lipoproteins, low-density lipoproteins, glycemic measures, and hypertension have smaller contribution.

“Our research provides significant public health insight: even modest changes in established risk factors for metabolic diseases—particularly those linked to small molecule metabolites, inflammation, triglyceride-rich lipoproteins, obesity, and insulin resistance—can yield substantial long-term benefits from following a Mediterranean diet. This finding underscores the potential of encouraging healthier dietary habits to reduce the overall risk of mortality,” said lead author Shafqat Ahmad, PhD, an associate professor of Epidemiology at Uppsala University Sweden and a researcher in the Center for Lipid Metabolomics and the Division of Preventive Medicine at the Brigham.

The current study identifies important biological pathways that may help explain all-cause mortality risk. However, the authors note some key limitations, including that the study was limited to middle aged and older well-educated female health professionals who were predominantly non-Hispanic and white. The study relied on food-frequency questionnaires and other self-reported measures, such as height, weight and blood pressure. But the study’s strengths include its large scale and long follow up period.

The authors also note that as the concept of the Mediterranean diet has gained popularity, the diet has been adapted in different countries and cultures.

“The health benefits of the Mediterranean diet are recognized by medical professionals, and our study offers insights into why the diet may be so beneficial. Public health policies should promote the healthful dietary attributes of the Mediterranean diet and should discourage unhealthy adaptations,” said Mora.

Reference:

Ahmad S, Moorthy MV, Lee I, et al. Mediterranean Diet Adherence and Risk of All-Cause Mortality in Women. JAMA Netw Open. 2024;7(5):e2414322. doi:10.1001/jamanetworkopen.2024.14322.

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Case study links omega-3 supplementation to lower aggression

People who regularly eat fish or take fish oil supplements are getting omega-3 fatty acids, which play a critical role in brain function. Research has long shown a basis in the brain for aggressive and violent behavior, and that poor nutrition is a risk factor for behavior problems.

Penn neurocriminologist Adrian Raine has for years been studying whether omega-3 supplementation could therefore reduce aggressive behavior, publishing five randomized controlled trials from different countries. He found significant effects but wanted to know whether these findings extended beyond his laboratory.

Now, Raine has found further evidence for the efficacy of omega-3 supplementation by conducting a meta-analysis of 29 randomized controlled trials. It shows modest short-term effects-he estimates this intervention translates to a 30% reduction in aggression-across age, gender, diagnosis, treatment duration, and dosage. Raine is the lead author of a new paper published in the journal Aggressive and Violent Behavior, with Lia Brodrick of the Perelman School of Medicine.

“I think the time has come to implement omega-3 supplementation to reduce aggression, irrespective of whether the setting is the community, the clinic, or the criminal justice system,” Raine says. “Omega-3 is not a magic bullet that is going to completely solve the problem of violence in society. But can it help? Based on these findings, we firmly believe it can, and we should start to act on the new knowledge we have.”

He notes that omega-3 also has benefits for treating heart disease and hypertension, and it is inexpensive and safe to use. “At the very least, parents seeking treatment for an aggressive child should know that in addition to any other treatment that their child receives, an extra portion or two of fish each week could also help,” Raine says.

This meta-analysis shows that omega-3 reduced both reactive aggression, which is behavior in response to a provocation, and proactive aggression, which is planned.

The study included 35 independent samples from 29 studies conducted in 19 independent laboratories from 1996 to 2024 with 3,918 participants. It found statistically significant effects whether averaging effect sizes by study, independent sample, or by laboratory.

Only one of the 19 labs followed up with participations after supplementation ended, so the analysis focused on changes in aggression from beginning to end of treatment for experimental and control groups, a period averaging 16 weeks. “While there is value in knowing whether omega-3 reduces aggression in the short-term,” the paper states, “the next step will be to evaluate whether omega-3 can reduce aggression in the long-term.”

The paper notes several other possible avenues for future research, such as determining whether brain imaging shows that omega-3 supplementation enhances prefrontal functioning, whether genetic variation impacts the outcome of omega-3 treatment, and whether self-reported measures of aggression provide stronger evidence for efficacy than observer reports.

“At the very least, we would argue that omega-3 supplementation should be considered as an adjunct to other interventions, whether they be psychological (e.g. CBT) or pharmacological (e.g. risperidone) in nature, and that caregivers are informed of the potential benefits of omega-3 supplementation,” the authors write. They conclude, “We believe the time has come both to execute omega-3 supplementation in practice and also to continue scientifically investigating its longer-term efficacy.”

Reference:

Adrian Raine, Lia Brodrick, Omega-3 supplementation reduces aggressive behavior: A meta-analytic review of randomized controlled trials, Aggression and Violent Behavior, https://doi.org/10.1016/j.avb.2024.101956.

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Study Finds Substantial Follow-Up Procedures Needed for Xen 45 Gel Stent Implant in Open-Angle Glaucoma

Researchers have found that while the Xen 45 gel stent implant shows beneficial long-term outcomes for treating open-angle glaucoma, a significant proportion of patients required follow-up operations or bleb needling. These findings were based on a real-world retrospective analysis of data from an observational registry, shedding light on the practical challenges associated with this treatment. The study was published in The British Journal of Ophthalmology by Arnould and colleagues.

Open-angle glaucoma is a chronic eye condition characterized by elevated intraocular pressure (IOP), leading to progressive vision loss. Traditional treatments include laser therapy and eye drops, with more severe cases often requiring surgical intervention. The Xen 45 gel stent, a 6-mm-long microtube made of gelatin, is designed to lower IOP by allowing fluid to pass from inside the eye to the external subconjunctival space. Despite initial non-randomized trials showing promise, real-world data has become crucial to understanding the true efficacy and complications associated with this device.

The study utilized data from the international Fight Glaucoma Blindness registry, focusing on 638 eyes among adult patients diagnosed with ocular hypertension or open-angle glaucoma between January 1, 2012, and December 31, 2020. Patients who had previously undergone glaucoma filtration surgery were excluded. The analysis included a baseline cohort with 69% having primary open-angle glaucoma, 51% being men, and a mean age of 72.4 years. The mean preoperative IOP was 21.4 mm Hg, with patients on an average of 2.7 IOP-lowering medications.

  • At 24 months, the rate of complete success — defined as an IOP reduction of at least 20% from preoperative levels and an IOP between 6 and 18 mm Hg without secondary procedures or IOP-lowering medications — was 26%.

  • The rate of qualified success, which allowed the use of IOP-lowering medications, was 48%.

  • However, 18% of patients required secondary procedures, and bleb needling was performed in 28.4% of cases.

  • Worse outcomes with combined cataract surgery: Complete success 16%, qualified success 42%

  • Better outcomes with Xen 45-alone: Complete success 33%, qualified success 52%

  • Mean IOP at 24 months: 16.8 mm Hg (mean reduction of 21.7%)

  • Mean IOP-lowering medications at 24 months: 1.2

The study highlighted that the success rates for the Xen 45 gel stent were lower than anticipated. Notably, outcomes were worse when the stent implantation was combined with cataract surgery, suggesting that clinicians should consider performing these procedures separately when possible. Despite the lower success rates, the Xen 45 stent still offers a viable alternative to traditional filtration surgeries, such as trabeculectomy or tube shunt surgery, which carry higher risks of complications like hypotony.

Dr. Mitchell Lawlor from Sydney Eye Hospital emphasized the variability in glaucoma surgery outcomes based on success definitions, following the World Glaucoma Association’s recommendations. Dr. Leo Seibold from the University of Colorado noted the study’s valuable real-world insights but was surprised by the relatively low overall success rates. He suggested that patients with IOP goals in the mid-teens or higher might be more suitable candidates for the Xen 45 stent.

The study concludes that while the Xen 45 gel stent provides beneficial long-term outcomes for open-angle glaucoma, the need for follow-up procedures remains significant. This highlights the importance of careful patient selection and the potential benefits of avoiding combined surgeries to maximize the probability of success.

Reference:

Arnould, L., Balsat, E., Hashimoto, Y., White, A., Kong, G., Dunn, H., Fan, L., Gabrielle, P.-H., Bron, A. M., Creuzot-Garcher, C. P., & Lawlor, M. (2024). Two-year outcomes of Xen 45 gel stent implantation in patients with open-angle glaucoma: real-world data from the Fight Glaucoma Blindness registry. The British Journal of Ophthalmology, bjo-2023-325077. https://doi.org/10.1136/bjo-2023-325077

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Tactical training to revolutionize access to acute stroke treatment in regional Australia: results fromTACTICS Trial

TACTICS, a non-randomised intervention trial that aimed to optimsze workflow and implement specialized imaging, has shown promise in improving access to endovascular thrombectomy (EVT) for patients in regional and rural areas of Australia. EVT is a minimally invasive procedure that removes blood clots from blocked arteries in the brain, significantly improving outcomes for stroke patients.

“While EVT has revolutionized stroke treatment, access remains a challenge for patients outside major urban centers,” explains Dr. Delcourt, the investigator who presented the results of TACTICS today at the European Stroke Organisation Conference (ESOC) 2024. “The TACTICS trial investigated a multi-faceted intervention designed to address this disparity.”

The TACTICS trial involved six regional clusters in Australia, each with a central hub that is able to provide EVT and associated spoke hospitals. Each cluster underwent a three-month pre-intervention period followed by a three-month intervention, and a three-month post- intervention period. During the intervention, hospitals were exposed to a combination of face-to-face, video and virtual reality-based education. Additionally, the hospitals were fitted and trained to use multimodal brain imaging to optimise workflow and pathways, improve diagnosis and aid earlier detection of candidates for EVT.

The study enrolled 1,011 patients across the six clusters and a total of 34 hospitals. Compared to the pre-intervention period, the odds of receiving EVT in the pooled intervention and post-intervention period increased by 44%. Notably, these improvements were consistent across all participating clusters.

Dr Christopher Levi, lead investigator of TACTICS concludes: “These findings suggest that this intervention has the potential to be a valuable tool for healthcare systems worldwide, particularly those grappling with geographic barriers to stroke care.”

Further research is needed to confirm the long-term sustainability and generalizability of the TACTICS approach.

Reference:

TRIAL OF ADVANCED CT IMAGING AND COMBINED EDUCATION SUPPORT FOR DRIP AND SHIP(TACTICS): PRIMARY RESULTS. Presented at the European Stroke Organisation Conference; 15 May 2024; Basel, Switzerland.

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A silent killer- Periodontal disease linked to startling mortality risks in new study

Researchers have found that severe periodontal disease (PD) significantly increases the risk of all-cause and cause-specific mortality. This conclusion comes from a comprehensive prospective cohort study using data from the National Health and Nutrition Examination Survey (NHANES) and the National Death Index, underscoring the critical impact of oral health on overall mortality risk. The recent study was published in the Journal Of Clinical Periodontology by Harriet Larvin and colleagues.

Periodontal disease, a common inflammatory condition affecting the tissues surrounding the teeth, has been linked to various systemic diseases. Previous studies have suggested associations between PD and increased mortality, but robust evidence has been lacking. This study aimed to investigate the relationship between PD and mortality more thoroughly, considering demographic, lifestyle, clinical measurements, and comorbidities.

The study included 15,030 adult participants recruited from six NHANES cycles (1999-2014). Baseline clinical periodontal examinations were conducted by trained and calibrated examiners. Participants were followed up until December 2019, resulting in a median follow-up period of 9 years. All-cause and cause-specific mortality were modeled using multivariable Cox proportional hazards and Fine-Gray models to account for competing risks. Adjustments were made for demographic variables, lifestyle factors, clinical measurements, and comorbidities.

  • The study revealed that individuals with periodontal disease had a 22% higher risk of all-cause mortality compared to those without PD (adjusted hazard ratio [HR]: 1.22, 95% confidence interval [CI]: 1.12-1.31).

  • The risks were even more pronounced for specific causes of death among participants with severe PD.

  • For cardiovascular diseases (CVD), the sub-distribution hazard ratio (SHR) was 1.38 (95% CI: 1.16-1.64).

  • For respiratory diseases, the SHR was 1.62 (95% CI: 1.07-2.45), and for diabetes-related mortality, the SHR was 1.68 (95% CI: 1.12-2.53).

These findings highlight the significant impact of severe periodontal disease on mortality risk. The elevated risks for all-cause mortality, as well as specific causes like CVD, respiratory diseases, and diabetes, suggest that PD may exacerbate underlying conditions or contribute to systemic inflammation, leading to worse health outcomes. The results emphasize the importance of oral health care and periodontal disease management in reducing overall mortality risk.

This large-scale, prospective study provides strong evidence that severe periodontal disease is associated with increased risks of all-cause and cause-specific mortality among US adults. These findings underscore the critical need for integrating oral health into general health care practices to mitigate the adverse outcomes associated with periodontal disease.

Reference:

Larvin, H., Baptiste, P. J., Gao, C., Muirhead, V., Donos, N., Pavitt, S., Kang, J., & Wu, J. (2024). All‐cause and cause‐specific mortality in US adults with periodontal diseases: A prospective cohort study. Journal of Clinical Periodontology. https://doi.org/10.1111/jcpe.14002

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Kidney transplants from deceased donors previously on dialysis increase risk of delayed graft function: JAMA

In a recent study published in the Journal of American Medical Association illuminated the outcomes for kidney transplant recipients whose donors had undergone dialysis before donating. This comprehensive analysis compared the results of transplant recipients who received kidneys from deceased donors who had dialysis with those donors who did not undergo dialysis. 

Kidneys from deceased donors previously on dialysis may be tied delayed graft function

This retrospective cohort analysis drew data from 58 U.S. organ procurement organizations. This spanned from 2010 to 2018 and included a total of 805 deceased kidney donors who had received dialysis prior to their donation. These donors were meticulously matched with an equal number of deceased donors who had not undergone dialysis using a sophisticated rank-based distance matrix algorithm. The study ultimately evaluated close to 1,944 kidney transplant recipients.

The research focused on four main outcomes which were the delayed graft function, all-cause graft failure, death-censored graft failure and recipient death. The key findings highlighted marked differences between the two groups.

The most significant finding was the higher incidence of delayed graft function among the recipients of kidneys from donors who had undergone dialysis. Also, 59.2% of these recipients underwent delayed graft function when compared to just 24.6% of recipients from donors who had not received dialysis. The adjusted odds ratio for this outcome was 4.17 which indicated a substantially increased risk.

When it came to longer-term outcomes such as graft failure and recipient death, the differences were not statistically significant. The incidence rates for all-cause graft failure were similar between the two groups with 43.1 events per 1,000 person-years for recipients of kidneys from dialysis-experienced donors and 46.9 events per 1,000 person-years for the control group. The adjusted hazard ratio was 0.90 by suggesting no significant difference.

Death-censored graft failure rates were also comparable with 22.5 events per 1,000 person-years in the dialysis group and 20.6 in the non-dialysis group. The adjusted hazard ratio was 1.18 which again indicated no significant difference. For recipient death, the rates were 24.6 per 1,000 person-years in the dialysis group against 30.8 in the non-dialysis group with an adjusted hazard ratio of 0.76 by showing no significant difference in mortality.

The outcomes found that while receiving a kidney from a deceased donor who underwent dialysis before donation is associated with a higher risk of delayed graft function, it does not significantly impact longer-term outcomes such as graft failure or recipient death. This finding is pivotal as it highlights the importance of considering the dialysis history of donors while also reassuring them about the long-term viability of these kidneys.

Reference:

Wen, Y., Mansour, S. G., Srialluri, N., Hu, D., Thiessen Philbrook, H., Hall, I. E., Doshi, M. D., Mohan, S., Reese, P. P., & Parikh, C. R. (2024). Kidney Transplant Outcomes From Deceased Donors Who Received Dialysis. In JAMA. American Medical Association (AMA). https://doi.org/10.1001/jama.2024.8469

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HPV vaccine prevents most cervical cancer cases in more deprived groups, major study shows

The human papillomavirus, or HPV, vaccine is cutting cases of cervical cancer right across the socio-economic spectrum, with most cases being prevented in more deprived groups, according to a major study funded by Cancer Research UK.

Until now, there had been concerns that the HPV vaccine could have an unequal impact across society. After carrying out the longest follow-up on the effectiveness of the HPV vaccine, researchers at Queen Mary University of London concluded the HPV vaccination programme in England is helping to close some inequalities in cervical cancer. 

Due to a typically higher incidence of cervical cancer in more deprived groups, researchers found that more cases were prevented in the most deprived group (around 190), compared to the least deprived group (around 60). BMJ

Published in the BMJ medical journal, the data reflected the huge success of the school-based vaccination programme, showing that well-executed public health interventions can help to reduce health inequalities.

Today’s news adds even more weight to evidence that HPV vaccination works. Researchers found that over a 12-year period, the vaccine reduced cervical cancer incidence rates by nearly 90% and pre-cancerous conditions by around 95% in women who were offered routine vaccination at 12-13 years old in England. The study shows that the vaccine is much more effective when taken up by people in year 8 (aged 12-13) than later in life.

Although the life-saving HPV vaccine currently reaches people from all backgrounds, Cancer Research UK warns that some inequalities remain in cervical cancer incidence, and more work is needed to improve the health of the most deprived groups. Uptake of the HPV vaccine in the UK has also fallen in recent years.

Overall, cervical cancer rates are higher in people from deprived backgrounds across the UK. Researchers said this is partly due to people being at greater risk from HPV and barriers that can drive lower screening attendance.

Professor Peter Sasieni, lead author from Queen Mary University of London, said:

“Our research highlights the power of HPV vaccination to benefit people across all social groups.

“Historically, cervical cancer has had greater health inequalities than almost any other cancer and there was concern that HPV vaccination may not reach those at greatest risk. Instead, this study captures the huge success of the school-based vaccination programme in helping to close these gaps and reach people from even the most deprived communities.

“In the UK, the elimination of cervical cancer as a public health problem in our lifetime is possible with continued action to improve access to vaccination and screening for all.”

The HPV vaccine, combined with cervical screening, can dramatically reduce cervical cancer incidence to the point where almost no one develops it. Improving people’s access to both programmes is at the heart of NHS England’s recent pledge to eliminate cervical cancer as a public health problem by 2040. 

This research, however, lands when uptake of the HPV vaccine and screening attendance has fallen in recent years across the UK and coverage rates are yet to recover from the disruption of the COVID pandemic.

With huge progress in tackling cervical cancer at risk of stalling, Cancer Research UK is encouraging all eligible people to take up the offer of vaccination and screening. The charity is also calling on the UK Government to ensure both programmes in England are backed by sufficient resources and modern IT infrastructure.

Cancer Research UK’s senior health information manager, Sophia Lowes, said:

“Every year, around 3,300 people receive a cervical cancer diagnosis in the UK. This research shows us that HPV vaccination works, and increased coverage can help to bring about a future virtually free from this disease.

“But we can’t lose momentum. We’re calling for targeted action to ensure that as many young people as possible get the lifesaving HPV vaccine. Better reporting on uptake by deprivation and ethnicity, along with more research, will help us understand how to reach those most at risk.

“We encourage people to take up the HPV vaccine if they are eligible. If you are concerned that you or your child has missed out on the HPV vaccine, you can contact your child’s school nurse, school immunisation service or GP surgery to find out more.”

Cancer Research UK scientists helped to prove the link between HPV and cervical cancer 25 years ago. This discovery put the gears in motion for the HPV vaccination programme and improved cervical cancer screening. Thanks to these scientific developments, cervical cancer rates in the UK have fallen by almost a third since the early 1990s. 

The HPV vaccination programme was first introduced to England in 2008. Since then, girls aged 11-13 in the UK have been offered the vaccine and since September 2019, boys of the same age can also get it. Anyone who missed their vaccine can request it through the NHS up to the age of 25.

It’s also available to men who have sex with men and some transgender people up to the age of 45 through sexual health and HIV clinics.

Cancer Research UK chief executive, Michelle Mitchell OBE, said:

“Today’s news is promising – the HPV vaccination programme is paving the way to make cervical cancer a rare disease for all.

“The UK Government and the NHS must continue to work with communities and services, so the HPV vaccine is taken up by as many eligible people as possible, and accurate information reaches those who most need it.

“We want to see a world where everyone shares in this scientific and research progress equally.” 

Reference:

Falcaro M, Soldan K, Ndlela B, Sasieni P. Effect of the HPV vaccination programme on incidence of cervical cancer and grade 3 cervical intraepithelial neoplasia by socioeconomic deprivation in England: population based observational study BMJ 2024; 385 :e077341 doi:10.1136/bmj-2023-077341.

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Clofazimine effective alternative of rifampicin for treating Mycobacterium avium complex pulmonary disease: Study

Clofazimine is an effective alternative to rifampicin for treating Mycobacterium avium complex pulmonary disease suggests a study published in the CHEST.

Results of retrospective studies have suggested clofazimine as an alternative for rifampicin in the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). In this single-center, nonanonymized clinical trial, adult patients with MAC-PD were randomly assigned in a 1:1 ratio to receive rifampicin or clofazimine as adjuncts to an ethambutol-macrolide regimen. The primary outcome was sputum culture conversion following 6 months of treatment. Results: Forty patients were assigned to receive either rifampicin (n = 19) or clofazimine (n = 21) in addition to ethambutol and a macrolide. Following 6 months of treatment, both arms showed similar percentages of sputum culture conversion based on an intention-to-treat analysis: 58% (11 of 19) for rifampicin and 62% (13 of 21) for clofazimine. Study discontinuation, mainly due to adverse events, was equal in both arms (26% vs 33%). Based on an on-treatment analysis, sputum culture conversion following 6 months of treatment was 79% in both groups. In the clofazimine arm, diarrhea was more prevalent (76% vs 37%; P = .012), while arthralgia was more frequent in the rifampicin arm (37% vs 5%; P = .011). No difference in the frequency of corrected QT interval prolongation was seen between groups.A clofazimine-ethambutol-macrolide regimen showed similar results to the standard rifampicin-ethambutol-macrolide regimen and should be considered in the treatment of MAC-PD. The frequency of adverse events was similar in both arms, but their nature was different. Individual patient characteristics and possible drug-drug interactions should be taken into consideration when choosing an antibiotic regimen for MAC-PD.

Reference:

Zweijpfenning SMH, Aarnoutse R, Boeree MJ, Magis-Escurra C, Stemkens R, Geurts B, van Ingen J, Hoefsloot W. Safety and Efficacy of Clofazimine as an Alternative for Rifampicin in Mycobacterium avium Complex Pulmonary Disease Treatment: Outcomes of a Randomized Trial. Chest. 2024 May;165(5):1082-1092. doi: 10.1016/j.chest.2023.11.038. Epub 2023 Nov 29. PMID: 38040054.

Keywords:

Clofazimine, effective, alternative, rifampicin, treating, Mycobacterium, avium, complex, pulmonary disease, study, chest, Zweijpfenning SMH, Aarnoutse R, Boeree MJ, Magis-Escurra C, Stemkens R, Geurts B, van Ingen J, Hoefsloot W

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Study Explores Unreported Allergic Contact Dermatitis due to Salicylic Acid

A recent study from a dermatology clinic, published in the recent issue of Contact Dermatitis journal highlighted the underreported issue of allergic contact dermatitis (ACD) which is caused by salicylic acid (SA). Despite the well-documented cross-reactivity among salicylates, the reports of such reactivity that specifically involved SA have been scarce.

The objective of the study was to describe the clinic’s experience with patch testing for SA by highlighting seven notable cases of allergic reactions. The study analyzed results from patch tests conducted between January 1, 2020 and February 9, 2024 using a 5% SA in petrolatum solution.

Out of 489 patients who underwent patch testing for SA, 27.5% (approximately 135 patients) were tested. Among these, 21 participants showed positive reactions. The breakdown of reactions included seven doubtful (+/−) cases and 14 weak positive (+) cases. Also, there were no strong or extreme positive reactions observed. Four more irritant reactions were documented which indicated some level of irritation but not necessarily an allergic response.

Of the 14 weak positive reactions, 7 cases were deemed to have definite or probable clinical relevance which means the allergic reaction was likely connected to their clinical symptoms. Also, five of these seven relevant cases also expressed reactivity to other salicylates that suggests a probable cross-reactivity.

The study concludes that ACD to SA is likely underreported due to insufficient testing. The findings indicate that patch testing with 5% SA in petrolatum is generally tolerable for patients which showed minimal significant irritation. The probable cross-reactivity between SA and other salicylates underlines the need for more comprehensive testing and awareness among clinicians.

The outcomes of this research emphasize that while SA appears to be a primary sensitizer in some cases, further studies are imperative to determine its role as a potential marker for the salicylate allergy. This discovery could lead to better diagnostic practices and management strategies for the patients with suspected salicylate allergies.

The results of this study highlight the necessity for increased vigilance and reporting of ACD cases related to SA. Given the widespread use of SA in various skincare and medicinal products, understanding its allergenic potential is highly crucial for both patients and healthcare providers. Improved awareness and more rigorous testing protocols could lead to more accurate diagnoses and enhanced patient outcomes in the participants with salicylate sensitivities.

Source:

Brumley, C., Arora, P., Neeley, A., & Hylwa, S. (2024). Allergic contact dermatitis to salicylic acid: A case series of relevant sensitization. In Contact Dermatitis. Wiley. https://doi.org/10.1111/cod.14573

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Flavonoid supplement Diosmin reduces lower-extremity swelling and pain after total knee arthroplasty: Study

China: Diosmin use after total knee arthroplasty (TKA) reduces lower-extremity swelling and pain during motion and is not tied to an increased risk of short-term complications, a recent study published in The Journal of Bone & Joint Surgery has shown. Diosmin is a flavonoid supplement derived from citrus fruits. 

“For patients undergoing total knee arthroplasty, treatment with diosmin reduced swelling of the knee and leg and some measures of associated pain can be achieved, reports the clinical trial by Pengde Kang, PhD, MD, of Sichuan University, Chengdu, China, and colleagues.

Possible new approach to alleviate painful swelling after TKA

Swelling is a common problem in patients undergoing TKA, and one that contributes to pain and patient dissatisfaction. “Postoperative lower-extremity swelling is a major hindrance to the enhanced recovery of patients undergoing TKA,” the researchers write. Various measures have been proposed to decrease swelling, including rest, cold packs, and compressive bandages, with mixed success. Currently, there are no effective medication choices to reduce swelling after TKA.

Diosmin – often in combination with a related flavonoid called hesperidin – has been used to reduce swelling of the limbs in patients with venous disorders. Although diosmin is not approved as a prescription medication in the United States or Europe, experience suggests that it is well tolerated with low toxicity. Based on these characteristics, the researchers designed a clinical trial to evaluate the effectiveness and safety of diosmin in patients undergoing TKA.

The exploratory study included 330 patients undergoing TKA at 13 university-affiliated hospitals. Patients were randomly assigned to either a treatment group, receiving a 14-day course of diosmin starting postoperative day 1; or to a control group, receiving no study treatment. Both groups received standard pain medications.

Swelling at specific locations was measured at 1, 2, 3, and 14 days postoperatively and compared between the diosmin and control groups. Pain scores, knee function, complication rates, and blood levels of certain inflammatory markers (C-reactive protein and interleukin-6) were also assessed.

Diosmin reduces swelling and pain scores with movement

The results showed reduced swelling at the knee, calf, and thigh up to 14 days after TKA in patients assigned to diosmin. The reduction in swelling was associated with lower pain scores on knee movement. In contrast, pain scores at rest were not significantly different for the diosmin versus control groups. Assessments of knee function recovery and levels of inflammatory biomarkers were similar as well.

Short-term complication rates were also similar between groups, supporting the safety of diosmin. Thsere was a trend toward decreased rates of postoperative nausea and vomiting with diosmin, although the difference was not significant.

The study provides preliminary evidence that diosmin is a safe and effective treatment to reduce swelling and pain with movement after TKA. However, questions remain as to how diosmin exerts these effects – particularly since the study finds no change in inflammatory biomarker levels between groups.

“This negative result may reflect the efficacy of the other anti-inflammatory drugs that were administered to both groups,” Dr. Kang and colleagues write. They emphasize the need for further studies to assess the mechanism by which diosmin reduces swelling, and whether some alternative dosing regimen might be more effective. 

Reference:

Wang, Qiuru ,Jin, Qunhua ; Cai, Lijun , Zhao, Chengcheng Feng, Pengfei  Efficacy of Diosmin in Reducing Lower-Extremity Swelling and Pain After Total Knee Arthroplasty: A Randomized, Controlled Multicenter Trial. The Journal of Bone and Joint Surgery ():10.2106/JBJS.23.00854, December 18, 2023. | DOI: 10.2106/JBJS.23.00854.

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