Antipsychotics for dementia linked to more harms than previously acknowledged: BMJ

Antipsychotic use in people with dementia is associated with elevated risks of a wide range of serious adverse outcomes including stroke, blood clots, heart attack, heart failure, fracture, pneumonia, and acute kidney injury, compared with non-use, finds a study published by The BMJ today.

These findings show a considerably wider range of harms associated with antipsychotic use in people with dementia than previously acknowledged in regulatory alerts, with risks highest soon after starting the drugs, underscoring the need for increased caution in the early stages of treatment.

Despite safety concerns, antipsychotics continue to be widely prescribed for behavioural and psychological symptoms of dementia such as apathy, depression, aggression, anxiety, irritability, delirium, and psychosis.

Previous regulatory warnings when prescribing antipsychotics for these symptoms are based on evidence of increased risks for stroke and death, but evidence of other adverse outcomes is less conclusive amongst people with dementia.

To address this uncertainty, researchers set out to investigate the risks of several adverse outcomes potentially associated with antipsychotic use in people with dementia.

The outcomes of interest were stroke, major blood clots (venous thromboembolism), heart attack (myocardial infarction), heart failure, irregular heart rhythm (ventricular arrhythmia), fractures, pneumonia, and acute kidney injury.

Using linked primary care, hospital, and mortality data in England, they identified 173,910 people (63% women) diagnosed with dementia at an average age of 82 between January 1998 and May 2018 who had not been prescribed an antipsychotic in the year before their diagnosis.

Each of the 35,339 patients prescribed an antipsychotic on or after the date of their dementia diagnosis was then matched with up to 15 randomly selected patients who had not used antipsychotics.

Patients with a history of the specific outcome under investigation before their diagnosis were excluded from the analysis of that outcome.

The most commonly prescribed antipsychotics were risperidone, quetiapine, haloperidol, and olanzapine, which together accounted for almost 80% of all prescriptions.

Potentially influential factors including personal patient characteristics, lifestyle, pre-existing medical conditions, and prescribed drugs were also taken into account.

Compared with non-use, antipsychotic use was associated with increased risks for all outcomes, except ventricular arrhythmia. For example, in the first three months of treatment, rates of pneumonia among antipsychotic users were 4.48% vs 1.49% for non-users. At one year, this rose to 10.41% for antipsychotic users vs 5.63% for non-users.

Risks were also high among antipsychotic users for acute kidney injury (1.7-fold increased risk), as well as stroke and venous thromboembolism (1.6-fold increased risk) compared with non-users.

For almost all outcomes, risks were highest during the first week of antipsychotic treatment, particularly for pneumonia.

The researchers estimate that over the first six months of treatment, antipsychotic use might be associated with one additional case of pneumonia for every 9 patients treated, and one additional heart attack for every 167 patients treated. At two years, there might be one additional case of pneumonia for every 15 patients treated, and one additional heart attack for every 254 patients treated.

This is an observational study so no firm conclusions can be drawn about cause and effect, and the researchers cautioned that some misclassification of antipsychotic use may have occurred. And although they adjusted for a range of factors, they can’t rule out the possibility that other unmeasured variables may have affected their results.

However, this was a large analysis based on reliable health data that investigated a wide range of adverse events and reported both relative and absolute risks over several periods.

As such, the researchers say antipsychotics are associated with a considerably wider range of serious adverse outcomes than previously highlighted in regulatory alerts, with the highest risks soon after starting treatment, and are therefore of direct relevance to guideline developers, regulators, clinicians, patients and their carers.

Any potential benefits of antipsychotic treatment need to be weighed against risk of serious harm and treatment plans should be reviewed regularly, they add.

The findings of this study will equip healthcare professionals with more nuanced data to help guide personalised treatment decisions, say US researchers in a linked editorial.

They explain that international guidelines advise restricting use to adults with severe behavioural and psychological symptoms of dementia, but the rate of prescribing has risen in recent years, partly due to the relative scarcity of effective non-drug alternatives and the substantial resources needed to implement them.

“Increased priority on more patient centric care, tailored care plans, regular reassessment of management options, and a move away from the overprescription of antipsychotics is overdue,” they conclude.

Reference:

https://www.bmj.com/content/385/bmj-2023-076268

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FAPI-PET imaging may enhance detection of lepidic subtype lung cancer, reveals study

A recent study introduced a new diagnostic imaging technique that could significantly improve the detection of certain lung cancer subtypes traditionally elusive to standard PET scans. This resaerch focused on the diagnostic capabilities of a novel PET imaging method using 68Ga-labeled fibroblast activation protein inhibitors (FAPIs) that could revolutionize how oncologists identify and treat lung cancers, particularly the lepidic subtype that often does not show up on conventional 18F-FDG PET scans. The key findings of the study were published in the Journal of Nuclear Medicine.

Lung cancer remains one of the most challenging malignancies to diagnose and treat, primarily because of its varied subtypes and the limitations of current imaging technologies. 18F-FDG PET often fails to detect lepidic lung cancer and to address this, Manuel Röhrich and team evaluated the effectiveness of 68Ga-FAPI-46 PET in detecting 18F-FDG–negative pulmonary lesions.

The study included 19 patients with suspected lung cancer and who underwent surgery or biopsy for a definitive histologic diagnosis after their PET scans. The research utilized FAP immunohistochemistry on tissue samples to corroborate the PET findings and to confirm the presence of FAP-positive cancer-associated fibroblasts predominantly in lepidic lung cancer.

During the clinical trials, both static and dynamic 68Ga-FAPI-46 PET scans were performed along with the standard 18F-FDG PET. The results showed that lung cancer lesions expressed significantly higher uptake of 68Ga-FAPI-46 which reflected in increased maximum and mean standardized uptake values (SUVmax and SUVmean) and tumor-to-background ratios (TBR) when compared to benign lesions. The dynamic imaging results differentiated lung cancer from non-cancerous lesions through distinct time-activity curve patterns. These patterns included an initial increase in activity typical of lung cancer that contrasted with the decreasing curves which were indicative of benign conditions.

The findings underline the superior sensitivity and specificity of 68Ga-FAPI-46 PET in distinguishing between malignant and benign pulmonary lesions in cases where 18F-FDG PET falls short. The introduction of 68Ga-FAPI-46 PET could thus lead to better patient stratification and more patient-specific treatment approaches by improving outcomes for the individuals with hard-to-diagnose subtypes of lung cancer.

Reference:

Röhrich, M., Daum, J., Gutjahr, E., Spektor, A.-M., Glatting, F. M., Sahin, Y. A., Buchholz, H. G., Hoppner, J., Schroeter, C., Mavriopoulou, E., Schlamp, K., Grott, M., Eichhorn, F., Heußel, C. P., Kauczor, H. U., Kreuter, M., Giesel, F., Schreckenberger, M., Winter, H., & Haberkorn, U. (2024). Diagnostic Potential of Supplemental Static and Dynamic68Ga-FAPI-46 PET for Primary18F-FDG–Negative Pulmonary Lesions. In Journal of Nuclear Medicine (p. jnumed.123.267103). Society of Nuclear Medicine. https://doi.org/10.2967/jnumed.123.267103

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Remdesivir may lower risk of in hospital death among COVID-19 patients not requiring oxygen: Study

Remdesivir may lower the risk of in-hospital death among COVID-19 patients not requiring oxygen suggests a new study published in the Open Forum Infectious Diseases.

Use of Remdesivir was linked to a significant decline in in-hospital death at both 14 and 28 days, regardless of variant of concern. Remdesivir has demonstrated benefit in some hospitalized patients with COVID-19 on supplemental oxygen and in non-hospitalized patients at room air. The durability of this benefit across time periods with different circulating SARS-CoV-2 variants of concern (VOC) is unknown. This comparative effectiveness study compares inpatient mortality among patients hospitalized for COVID-19 not receiving supplemental oxygen at admission initiating remdesivir treatment in the first two days of admission vs. no remdesivir during the hospitalization across different VOC periods. Using a large, multicenter US hospital database, in-hospital mortality was compared among patients hospitalized for COVID-19 not requiring supplemental oxygen at admission between December 2020 and April 2022. Patients receiving remdesivir upon hospital admission were matched 1:1 to those not receiving remdesivir during hospitalization using propensity score matching. Cox proportional hazards models were used to assess 14- and 28-day in-hospital mortality or discharge to hospice. Results: Among the 121,336 eligible patients, 58,188 remdesivir-treated patients were matched to 17,574 unique non-remdesivir patients. Overall, 5.4% of remdesivir-treated and 7.3% of non-remdesivir patients died within 14 days, while 8.0% of remdesivir-treated and 9.8% of non-remdesivir patients died within 28 days. Remdesivir treatment was associated with a statistically significant reduction in in-hospital mortality compared to non-remdesivir treatment (14-day adjusted hazard ratio (aHR): 0.75, 95% confidence interval (CI): 0.68-0.83; 28-day aHR: 0.83, 0.76-0.90). This significant mortality benefit endured across the different VOC periods. Remdesivir initiation in patients hospitalized for COVID-19, not requiring supplemental oxygen at admission, was associated with a statistically significant reduction in in-hospital mortality. These findings highlight a potential survival benefit when clinicians initiated remdesivir upon admission across the dominant variant eras of the evolving pandemic.

Reference:

Essy Mozaffari, Aastha Chandak, Chidinma Chima-Melton, Andre C Kalil, Heng Jiang, EunYoung Lee, Celine Der-Torossian, Mark Thrun, Mark Berry, Richard Haubrich, Robert L Gottlieb, Remdesivir is associated with reduced mortality in patients hospitalized for COVID-19 not requiring supplemental oxygen, Open Forum Infectious Diseases, 2024;, ofae202, https://doi.org/10.1093/ofid/ofae202

Keywords:

Remdesivir, lower risk, hospital, death, among, COVID-19 patients, oxygen, study, Open Forum Infectious Diseases, Essy Mozaffari, Aastha Chandak, Chidinma Chima-Melton, Andre C Kalil, Heng Jiang, EunYoung Lee, Celine Der-Torossian, Mark Thrun, Mark Berry, Richard Haubrich, Robert L Gottlieb, COVID-19, comparative effectiveness research, hospitalization, mortality, remdesivir

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Non-thermal atmospheric-pressure plasma novel approach to treatment of bone fractures: Study

“Break a leg!” is a welcome blessing of good luck, but who wants to hear that they have actually broken a bone? What’s worse, fractures that are displaced or complex require surgery and possibly lengthy recovery times while the patient remains partly or wholly immobilized.

Aiming to shorten recovery times, an Osaka Metropolitan University-led research group is focusing on plasma irradiation as a treatment method to speed up bone healing.

The Department of Orthopedic Surgery’s Kosuke Saito, a graduate student in the Graduate School of Medicine, Associate Professor Hiromitsu Toyoda, and Professor Hiroaki Nakamura, and Graduate School of Engineering Professor Jun-Seok Oh were among the researchers who used laboratory rats for their experiment.

The researchers broke the legs of the rats in two ways. One group of 24 rats had normal fractures that are generally easy to heal. The other group of 20 rats had fractures known as non-union ones where healing is usually prolonged or does not happen. Some were then irradiated with non-thermal atmospheric-pressure plasma, which didn’t offer the normal fracture group any significant advantages but boosted the healing and recovery time of the rats with non-union fractures. The strength of the healed areas of the irradiated non-union rats was also about 3.5 times stronger than that of the nonirradiated ones.

Furthermore, in vitro study of pre-osteoblastic cells irradiated with the plasma for 5 to 15 seconds showed that the activity of a protein that is an indicator of osteoblast differentiation increased, indicating that maturation of these bone-forming cells was progressing.

“Collaboration between the medical and engineering fields creates new medical technologies that have never before existed,” Professor Toyoda declared. “In the future, combining this treatment method with current fracture treatments is expected to contribute to more reliable bone fusion and shorter recovery times.”

Reference:

Kosuke Saito,Hiromitsu Toyoda ,Mitsuhiro Okada,Jun-Seok Oh,Katsumasa Nakazawa,Yoshitaka Ban,Kumi Orita,Akiyoshi Shimatani,Hana Yao,Tatsuru Shirafuji,Hiroaki Nakamura, Fracture healing on non-union fracture model promoted by non-thermal atmospheric-pressure plasma, PLoS ONE, https://doi.org/10.1371/journal.pone.0298086

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Childhood Adiposity Linked to Polycystic Ovary Syndrome Risk later on, suggests study

Researchers have found in a new study that excess adiposity and dysfunction in adipose tissue during childhood may signal a higher risk of developing Polycystic Ovary Syndrome (PCOS) later in life. The new study has been published in the journal of Pediatrics. This study offers insights into early indicators of PCOS risk, emphasizing the importance of early detection and intervention in pediatric populations. The study was conducted by Rachel C. and colleagues.

PCOS is a common endocrine disorder among females, characterized by a range of metabolic and reproductive issues. Early detection of risk factors such as adiposity and hormonal imbalances can lead to more effective interventions and preventive measures. This study investigates the development of PCOS in a pediatric cohort and identifies potential early signs of the condition.

The prospective Project Viva cohort study included 417 females and assessed cardiometabolic biomarkers and adiposity at three visits: mid childhood (mean age 7.9 years), early teen (mean age 13.1 years), and midteen (mean age 17.8 years). PCOS was defined either through self-reported diagnosis or the presence of ovulatory dysfunction with hyperandrogenism in adolescence. Researchers used multivariable logistic regression to explore associations between metabolic and adiposity markers at each visit and the risk of developing PCOS.

The key findings of the study were:

  • Adolescents with PCOS (n = 56, 13%) had higher mean BMI z-scores and truncal fat mass compared to those without PCOS at all three visits.

  • At the early teen visit, PCOS patients had lower adiponectin-to-leptin ratios (0.65 [0.69]) compared to those without PCOS (1.04 [0.97]).

  • Logistic regression analyses revealed that higher truncal fat mass at mid childhood and early teen visits was associated with increased odds of developing PCOS.

  • A lower adiponectin-to-leptin ratio at the midteen visit was associated with decreased odds of PCOS.

  • The study found that at the mid childhood visit, patients with PCOS had a mean BMI z-score of 0.66 compared to 0.30 in those without PCOS.

  • By the early teen visit, the mean BMI z-score of PCOS patients was 0.88 compared to 0.25 in those without PCOS.

  • Truncal fat mass was higher in PCOS patients at all visits, with an average of 3.5 kg at mid childhood, 9.4 kg at the early teen visit, and 11.6 kg at the midteen visit.

  • These values were notably higher than those in the non-PCOS group. Adiponectin-to-leptin ratio was found to be lower in PCOS patients compared to those without PCOS, especially at the midteen visit (0.33 vs. 0.75).

  • The adjusted models indicated an odds ratio of 1.42 for mid childhood truncal fat mass and 1.61 for early teen truncal fat mass, suggesting a significant association with PCOS risk.

  • The lower adiponectin-to-leptin ratio at the midteen visit was linked to a significantly lower odds ratio of 0.14 for developing PCOS.

Excess adiposity and adipose tissue dysfunction during childhood could serve as early indicators of future PCOS risk. By identifying these factors early, healthcare providers may be able to implement preventative measures and interventions to reduce the risk of developing PCOS in later life.

Reference:

Whooten, R. C., Rifas-Shiman, S. L., Perng, W., Chavarro, J. E., Taveras, E., Oken, E., & Hivert, M.-F. (2024). Associations of childhood adiposity and cardiometabolic biomarkers with adolescent PCOS. Pediatrics, e2023064894. https://doi.org/10.1542/peds.2023-064894

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Non-invasive light-based techniques may improve detection of skin cancer, reveals study

A study conducted by Aston University researchers has demonstrated that the appearance of ageing skin looks noticeably different compared to younger skin, when examined under polarised laser light.

The scientists believe that their new finding could pave the way for new, non-invasive light-based techniques to detect diseases, including cancer, in older individuals.

This could significantly enhance early-stage treatment options for various skin conditions.

It has already been established that two classes of polarised, linearly and circularly, can detect changes in skin that aren’t visible to the human eye.

The new study indicates that the altered light scattering properties of ageing skin are largely due to changes in the skin’s texture, which are associated with the depletion of collagen fibres in the dermal layer.

The research was led by Igor Meglinski, professor in quantum biophotonics & biomedical engineering and conducted under his guidance with Dr Viktor Dremin from Aston University’s Institute of Photonic Technologies.

The paper “Incremental residual polarization caused by aging in human skin” will be published in the May 2024 edition of the Journal of Biomedical Optics.

The researchers analysed images of the middle fingers of 32 volunteers aged 22 to 76 to study skin aging.

They also used the Monte Carlo method, a mathematical technique, to represent the effects of light circulation within the human skin.

This technique was developed by Professor Meglinski in 2001.

Combined with the visual data from the images, this enabled the researchers to draw conclusions about the optical properties of ageing skin.

Professor Meglinski said: “Our research offers a comprehensive analysis of how aging affects human skin polarisation properties. This could be a stepping stone to developing non-invasive, light-based techniques for early detection of skin conditions, including cancer, in the elderly.”

The findings of the research could support the development of a method of skin analysis which doesn’t rely on the patient undergoing biopsies or surgery.

It could provide instant assessments of age-related skin changes that can be extended to monitor changes associated with the development of diabetes and other conditions.

Reference:

Viktor Dremin, Elena Zharkikh, Ivan Lopushenko, Zbignevs Marcinkevics, Alexander Bykov, Igor Meglinski. Incremental residual polarization caused by aging in human skin. Journal of Biomedical Optics, 2023; 29 (05) DOI: 10.1117/1.JBO.29.5.052912.

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Infusion of human apolipoprotein A1 fails to reduce cardiovascular events in acute MI patients: NEJM

A recent international clinical trial by C. Michael Gibson and colleagues investigated the efficacy of CSL112 (human Apolipoprotein A1) which helps in reducing the risk of recurrent cardiovascular events in patients who have experienced acute myocardial infarction. The findings were published in The New England Journal of Medicine  and highlight the potential of CSL112 to improve the patient outcomes following such critical cardiac events.

This double-blind, placebo-controlled trial enrolled a substantial group with a total of 18,219 patients who underwent acute myocardial infarction, multivessel coronary artery disease and additional cardiovascular risk factors. The participants were randomly assigned to receive either four weekly infusions of 6 grams of CSL112 or a matching placebo where the first infusion was administered within five days after the initial medical contact for the heart attack.

Despite the promising premise of CSL112, the results of the trial found that over the 90-day follow-up period, there was no significant difference observed between the CSL112 group and the placebo group in terms of the primary endpoint, which is a composite of myocardial infarction, stroke or death from cardiovascular causes. This lack of divergence persisted throughout the 180-day and 365-day follow-up periods as well.

Also, the data revealed that 4.8% of patients in the CSL112 group experienced primary endpoint events at 90 days when compared to the 5.2% in the placebo group. At 180 days, the rates were 6.9% against 7.6%, and at 365 days, 9.8% against 10.5%, respectively. It is important to note that the percentages of adverse events were comparable between the two groups, although an increased number of hypersensitivity events were reported in the CSL112 group.

This comprehensive investigation suggests that among patients with acute myocardial infarction, multivessel coronary artery disease and additional cardiovascular risk factors, the administration of four weekly infusions of CSL112 did not lower the risk of myocardial infarction, stroke or death from cardiovascular causes when compared to placebo over a 90-day period.

While these results may come as a setback for post-myocardial infarction care, it helps in understanding the complexities involved in addressing recurrent cardiovascular events. Further research and development efforts are warranted to explore alternative strategies or refine existing approaches to improve patient outcomes and reduce the burden of cardiovascular disease.

Reference:

Gibson, C. M., Duffy, D., Korjian, S., Bahit, M. C., Chi, G., Alexander, J. H., Lincoff, A. M., Heise, M., Tricoci, P., Deckelbaum, L. I., Mears, S. J., Nicolau, J. C., Lopes, R. D., Merkely, B., Lewis, B. S., Cornel, J. H., Trebacz, J., Parkhomenko, A., Libby, P., … Harrington, R. A. (2024). Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction. In New England Journal of Medicine. Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2400969

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Hearing Loss Linked to Faster Brain Atrophy and Cognitive Decline in Older Adults: Study

Recent research has suggested a potential link between hearing loss and an increased risk of dementia. However, the underlying mechanisms and how they relate to neurodegeneration and cognitive decline remain unclear. A new study sheds light on these relationships and their impact on dementia risk. The study was published in the Journal Of Neurology Neurosurgery and Psychiatry. The study was conducted by Thomas D. and colleagues.

Hearing loss has been proposed as a modifiable risk factor for dementia, but the specific pathways involved are not well understood. This study aimed to investigate how hearing impairment relates to brain atrophy and cognitive decline, and whether pathological processes such as Alzheimer’s disease and cerebrovascular disease influence these relationships.

The study analyzed data from 287 adults born in the same week of 1946 who underwent baseline pure tone audiometry at an average age of 70.6 years. Participants also underwent two time point cognitive assessment and multimodal brain imaging with a mean interval of 2.4 years. Hearing impairment was defined as a pure tone average of greater than 25 decibels in the best hearing ear. Rates of change for whole brain, hippocampal, and ventricle volume were estimated from structural MRI. Cognitive function was assessed using the Pre-clinical Alzheimer’s Cognitive Composite. Regression models were used to evaluate the associations between baseline hearing impairment, brain atrophy, and cognitive decline, adjusting for confounding factors including β-amyloid deposition and white matter hyperintensity volume.

The key findings of the study were as follows:

  • Out of the 287 participants, 111 had hearing impairment.

  • Hearing impaired individuals had faster rates of whole brain atrophy compared to those with preserved hearing.

  • Worse hearing (higher pure tone average) predicted faster rates of hippocampal atrophy.

  • In participants with hearing impairment, faster rates of whole brain atrophy were associated with greater cognitive decline.

  • These relationships were independent of β-amyloid deposition and white matter hyperintensity volume, suggesting that hearing loss may influence dementia risk via distinct pathways.

The study suggests that hearing loss may contribute to dementia risk through pathways separate from those typically associated with Alzheimer’s and cerebrovascular disease. Understanding these pathways could lead to new strategies for dementia prevention and intervention in older adults with hearing impairment.

Reference:

Parker, T. D., Hardy, C., Keuss, S., Coath, W., Cash, D. M., Lu, K., Nicholas, J. M., James, S.-N., Sudre, C., Crutch, S., Bamiou, D.-E., Warren, J. D., Fox, N. C., Richards, M., & Schott, J. M. (2024). Peripheral hearing loss at age 70 predicts brain atrophy and associated cognitive change. Journal of Neurology, Neurosurgery, and Psychiatry, jnnp-2023-333101. https://doi.org/10.1136/jnnp-2023-333101

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Use of Low-Dose Colchicine Safe for Prevention of Coronary artery Disease, new Study Reveals

In a recent review, researchers have shed light on the safety profile of low-dose colchicine, offering reassuring evidence for its use in secondary prevention among patients with coronary artery disease. The study, drawing from a comprehensive analysis of contemporary systemic reviews, case reports, drug registries, and placebo-controlled trials, aims to inform healthcare professionals and patients about the absolute risks associated with continuous use of this medication.

Also Read: Low-dose colchicine may help prevent CV events in patients with type 2 diabetes and MI: COLCOT trial

The study results were published in the European Heart Journal. The FDA has recently granted approval for the use of low-dose colchicine (0.5 mg daily) in the secondary prevention of coronary disease, marking a significant milestone in clinical practice. A comprehensive State-of-the-Art Review was conducted to gather data from contemporary systemic reviews, case reports, drug registries, and placebo-controlled trials. This analysis aimed to assess the safety implications associated with the continuous administration of colchicine across various clinical contexts. The goal was to provide crucial insights to physicians, pharmacists, and patients regarding the absolute risks linked with the sustained use of low-dose colchicine, including its impact on individuals concurrently prescribed statin therapy.

Findings:


  • One of the key findings highlighted in the review is the overwhelmingly positive safety profile of low-dose colchicine.
  • According to the data collated, the most commonly reported side effect is mild diarrhea, typically occurring during the initiation phase of treatment and subsiding within a week for the vast majority of patients.
  • Crucially, the review found no significant adverse effects of low-dose colchicine on renal, liver, or cognitive function.
  • Furthermore, the medication does not appear to impact bleeding, wound healing, fertility, or pregnancy outcomes.
  • No evidence was found to suggest an increased risk of cancer, serious infection, or cause-specific mortality associated with its use.
  • Of particular interest is the investigation into potential interactions between low-dose colchicine and statin therapy, a commonly prescribed treatment for cardiovascular disease.
  • Contrary to concerns, the data indicate that patients concurrently taking statins do not face heightened risks of myelosuppression, myotoxicity, or serious drug interactions when prescribed low-dose colchicine.
Also Read: Colchicine Flops in Reducing AF or Myocardial Injury Following Non-Cardiac Surgery

The implications of these findings are profound for clinical practice. Physicians, pharmacists, and patients can now approach the use of low-dose colchicine with greater confidence, especially in the context of reducing cardiovascular risk among individuals with atherosclerosis. Importantly, the review suggests that when appropriately prescribed to patients without significant renal or hepatic impairment, the risks associated with continuous use of low-dose colchicine are minimal. This study marks a significant milestone in our understanding of low-dose colchicine, paving the way for its wider adoption in clinical practice as a safe and effective therapy for cardiovascular disease.

Further research: Nidorf, Stefan Mark et al. “Low-dose colchicine for atherosclerosis: long-term safety.” European heart journal, ehae208. 10 Apr. 2024, doi:10.1093/eurheartj/ehae208. 

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Evidence of lasting lung damage, impaired lung function found in TB patients even after successful treatment: Study

New research being presented at this year’s ESCMID Global Congress (formerly ECCMID) in Barcelona, Spain (27-30 April) has found compelling evidence that tuberculosis (TB) can have a lasting impact on the lungs of individuals who have been successfully treated for the disease.

TB survivors have smaller lungs with narrower airways and slower air flow, the analysis of data on tens of thousands of individuals from around the world found.

“This damage could have a profound effect on long-term health, reduce quality of life and affect ability to work and carry out day-to-day tasks,” says lead researcher Dr Sharenja Ratnakumar, of St George’s, University of London, London, UK. “And, with growing numbers of people being successfully treated for TB, the finding strongly indicates that post-TB lung disease is an under-recognised global challenge.”

TB can be cured with antibiotics and, worldwide, an estimated 155 million people are alive today as a result of successful diagnosis and treatment of the bacterial infection.

However, although significant progress has been made in combating TB in recent decades, the number of new diagnoses has increased since the COVID-19 pandemic. Some 7.5 million were diagnosed globally in 2022 – the highest number since monitoring began in 1995 and above the pre-Covid baseline of 7.1 million in 2019, according to WHO’s 2023 Global Tuberculosis Report.1

The burden is highest in sub-Saharan Africa and south east Asia but even low incidence countries such as the UK are seeing diagnoses increase. According to provisional data from the UK Health Security Agency, there were 4,850 new diagnoses in England in 2023. This is above pre-Covid levels and represents a rise of more than 10% on 2022, when there were 4,380 diagnoses.2

Previous research has found that between 18% and >80% of survivors will be left with lung damage3 that reduces their quality of life and life expectancy4 but data on the size and type of respiratory impairment is scarce. To find out more, Dr Ratnakumar and colleagues carried out a systematic review and meta-analysis of existing research on the topic.

The Medline, Embase and CINAHL databases were searched from 1/01/00 to 31/01/23 for studies that compared the lung function of individuals with a history of TB with that of healthy controls.

The meta-analysis included data on 75,631 individuals from 15 studies conducted in 17 countries with varying TB incidence and income levels.

The 7,377 TB survivors had an average age range of 11-65 years. Many of the studies were skewed towards a younger population (<50years) from mainly low- and middle-income countries.

Four measures of lung function were included in the analysis: forced expiratory volume in 1 second (FEV1, the volume of air can be forcefully exhaled in one second); forced vital capacity (FVC, the volume of air that can be forcefully exhaled in a single breath); FEV1/FVC ratio; FVC as a percentage of the predicted value (compares the volume to the average of a healthy person of the same age, sex and height).

The study, which was supported by the charity Breathing Matters, found that, compared to the healthy controls, the participants with prior TB had significantly lower results on all four measures of lung function, with FEV1 more affected than FVC.

Dr Ratnakumar says: “FEV1 was 230 millilitres lower compared to healthy controls and FVC was 140 millilitres lower. A decrease in FEV1 of 100 millilitres is considered clinically significant and is associated with an increased risk of cardiovascular and respiratory disease.”5

The results as a whole point to the TB survivors having smaller lungs (restrictive disease) and narrower airways with slower air flow (obstructive disease). This means that the breaths they take are smaller and take longer; breathing is less efficient and less able to respond to increased ventilatory demands such as during exercise.

Analysis of data from five of the studies showed the TB survivors to have 65% higher odds of airflow obstruction (AFO) than the healthy controls.

The results suggest TB can leave a lasting and widespread impact on the lungs, especially in terms of how the airways are structured. This valuable insight can help guide rehabilitation strategies and, in the longer term, aid in the development of new therapies, say the researchers.

Dr Ratnakumar explains: “Our results strongly indicate that post-tuberculosis lung disease is an under-recognised global challenge – and one that has significant implications for clinical practice and policy.

“The focus, until now, has been on the treatment of acute TB, but even when treatment is successful, individuals can be left with significant lung damage.

“This can cause breathlessness that can affect their ability to work and go about their day-to-day lives and reduces their quality of life.

“This legacy of TB has been overlooked for too long and it is vital it is recognised.

“With an estimated 74 million lives saved through tuberculosis treatment between 2000 and 2020 and a rising life expectancy, there is an urgent need for evidence-based recommendations on the diagnosis, treatment and management of post-tuberculosis lung disease.

“Our study also provides compelling evidence that the long-term care of individuals with post-tuberculosis lung disease should be an explicit component of the WHO’s End TB strategy.”

Tuberculosis can have a lasting impact on the lung health of individuals who have been successfully treated for the disease ESCMID Global (ECCMID 2024)

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