Acute Pulpitis: Dental Practice Perspective and Application of Aceclofenac Paracetamol Combination

Tooth pulp, a complex connective tissue within teeth, comprises nerves, blood vessels, and various cell types. Pulpitis is referred to as inflammation of tooth pulp, resulting from different irritant stimuli. Pulpitis can be categorized into focal reversible pulpitis, acute pulpitis, and chronic pulpitis.[1,2,3] Acute pulpitis is a painful dental condition characterized by inflammation in the tooth’s innermost pulp due to bacterial infections, often stemming

from tooth decay or trauma. It presents with a severe toothache, heightened sensitivity to temperature changes, localized swelling, and sometimes a bad taste in the mouth. [4]

Among Indian females, the lowest incidence of reversible pulpitis is in the 46-75 age group, while the highest is in the 18-30 age group. In contrast, the highest incidence of irreversible pulpitis is reported among males aged 18-30 years, with the lowest cases found in females aged 46-75 years. This brings out a unique pattern of acute pulpitis distribution in the Indian population.[5]

Effective pain management in acute pulpitis is essential for patient well-being and successful treatment outcomes. It alleviates discomfort during dental procedures, enhancing the overall treatment experience and ensuring patient comfort.[6]

Acute Pulpitis: Practice Perspective Overview

Etiology of Acute Pulpitis: Acute pulpitis results from bacterial invasion into the tooth’s pulp due to dental problems like cavities, trauma, or fractures, exacerbated by inadequate oral hygiene. Risk factors include environmental factors (lack of fluoridated water), medical conditions (diabetes), and habits (high-sugar diets, teeth grinding). Exposure to extreme temperatures, sugary foods, and chewing on hard objects can worsen inflammation and discomfort.[1]

Pathophysiology, Clinical Presentation & Evaluation of Acute Pulpitis: Dental pulp has A-delta and C-fiber nerve pathways that respond to rapid and slow pain stimuli. Pain thresholds differ by tooth region; factors like temperature changes or chemicals activate these nerves. Symptomatic reversible pulpitis causes short, sharp pain, usually triggered by cold, and it subsides when the cause is removed.[1,8]

Diagnosing acute pulpitis entails examining symptoms, signs of inflammation, and diagnostic tests. Pulp vitality, thermal sensitivity, and percussion evaluation help to assess the pulp’s condition. [9]

Differential diagnosis is crucial, considering conditions with similar symptoms such as apical periodontitis, marginal periodontitis, and non-dental conditions like herpes zoster infection, requiring careful evaluation for accurate diagnosis of acute pulpitis.[10,11,12]

Assessing pain in cases of acute pulpitis entails a comprehensive examination of pain intensity and its distinctive attributes as reported by the patient. The Visual Analogue Scale (VAS) is a widely employed method to gauge pain intensity, with patients rating their pain on a scale ranging from 0 to 10. In addition to VAS, alternative scales like verbal rating scales and behavioral rating scales can also be utilized to effectively evaluate and document the patient’s pain experience.[13]

Management Approaches in Acute Pulpitis

Managing acute pulpitis conservatively involves precise diagnosis through clinical assessment and diagnostic tests. Pain relief is a priority, optimally utilizing analgesics and anti-inflammatory medications and considering antibiotics for treating infections, as indicated. Local anesthesia provides immediate relief during pulp capping with materials like calcium hydroxide or Mineral Trioxide Aggregate (MTA). A pulpotomy retains tooth vitality for reversible pulpitis by partially removing the inflamed pulp. Patient education on oral hygiene and dietary modifications is crucial, along with regular follow-up & monitoring to preserve tooth function and health.[14,15]

Dentists are pivotal in acute pulpitis management, focusing on pain control, patient education, and informed consent. Their expertise in understanding pain mechanisms and diagnostics is essential for effective treatment. Dentists need a deep knowledge of applying drug mechanisms to address endodontic pain, ensuring patient comfort and well-being.[16] Nonsteroidal anti-inflammatory drugs (NSAIDs) find frequent application in the prevention and management of postoperative endodontic pain. In dentistry, a principle often referred to as the ‘3-D’s’ (comprising diagnosis, dental treatment, and drug therapy) serves as a guiding framework for pain management, where pharmacological interventions are considered supplementary to dental procedures.[17,18]

Pharmacological Management in Acute Pulpitis

Effective and safe pain management is a paramount objective in dental practice, particularly in the context of pulpitis and pulpitis-related pain. Dental procedures, especially those addressing acute pulpitis, can induce discomfort and postoperative pain. Hence, dentists must employ suitable analgesics to ensure both the treatment’s success and the alleviation of pain linked to inflammation and surgical interventions in pulpitis cases.[19] The pharmacological therapies can be broadly grouped as follows:

  • Pain Relief Medications: Non-steroidal anti-inflammatory drugs (NSAIDs) for pain and inflammation. Paracetamol for pain and associated pyrexia relief. [20]
  • Opioids: Opioids may be considered for severe pain management in acute pulpitis.[20]
  • Steroids: Steroids such as dexamethasone may be considered in cases of acute pulpitis with significant inflammation to help reduce swelling and discomfort.[20]
  • Multimodal drug therapy: It involves using a combination of medications with different mechanisms of action to manage pain and inflammation effectively. [21]

Clinical Applicability of Aceclofenac and Paracetamol Combination in Acute Pulpitis

Aceclofenac, an oral NSAID, effectively manages painful inflammatory conditions like pulpitis. It’s known for tolerability and fewer gastrointestinal side effects, leading to better patient compliance. NSAIDs, including Aceclofenac, play a crucial role in managing pulpal pain before and after dental procedures. [22]

Paracetamol is widely used as an analgesic and antipyretic. It works uniquely by targeting COX peroxidase activity, especially at low peroxide levels, focusing on the central nervous system without peripheral anti-inflammatory effects. Due to its effectiveness in managing pain, paracetamol is often combined with other NSAIDs and/or opioids to enhance overall pain relief.[19]

The synergistic combination of Aceclofenac and Paracetamol offers a well-rounded approach to dental pain management. While Aceclofenac tackles inflammation at the tissue site, Paracetamol provides effective pain relief, making this combination a valuable consideration option for addressing pulpitis and pulpitis-related dental pain.[19,22,23]

Aceclofenac & Paracetamol: Clinical Evidence

Beneficial Effects of Aceclofenac and Paracetamol in Acute Pulpitis- An Indian Experience:

In a prospective clinical trial conducted by Solete and Ramesh, 120 patients with symptomatic irreversible pulpitis were enrolled. After root canal shaping and cleaning, participants were randomly divided into four groups: placebo, piroxicam 20mg, and two groups involving paracetamol and aceclofenac sodium, one with 325 mg of paracetamol and the other with 650 mg of paracetamol. Pain scores were assessed at 6, 12, and 24 hours. Results demonstrated that the combination of aceclofenac and paracetamol, when compared to a placebo, significantly reduced pain severity (p < 0.01) at 6 hours and exhibited superior pain reduction (p < 0.05) at 12 and 24 hours after root canal procedures. This study highlights the effectiveness of aceclofenac and paracetamol in alleviating dental pain in cases of acute pulpitis.[24]

Effectiveness of Aceclofenac in Acute Irreversible Pulpitis:

In a randomized double-blind trial study conducted by Pavithra P. et al. involving 85 patients with acute irreversible pulpitis, the analgesic effectiveness of Aceclofenac and Ibuprofen was compared. Among the 50 eligible patients, Group A received 400mg of Ibuprofen, while Group B received 100mg of Aceclofenac. Pain intensity, assessed using the Visual Analog Scale (0-100), significantly decreased after drug administration. At 45 minutes, Group B (Aceclofenac) demonstrated a notably lower pain intensity of 9.16+1.57 (P<0.001) compared to Group A (Ibuprofen) with 40.36+4.241. The study concluded that Aceclofenac 100mg exhibited a superior analgesic effect in patients with irreversible pulpitis, highlighting its potential for effective postoperative pain management. [22]

NSAID plus Paracetamol for Postoperative Endodontic Pain related to Pulpitis:

In a systematic review and meta-analysis encompassing 27 studies involving 2,188 patients, Shirvani et al. discovered that non-narcotic analgesics, including NSAIDs and paracetamol, exhibited remarkable effectiveness in mitigating postoperative endodontic pain. The meta-regression analysis revealed that non-narcotic analgesics, including NSAIDs and paracetamol were significantly more effective than placebo in managing post-operative pain, resulting in standardized mean differences of -0.50 (95% CI= -0.70, -0.30), -0.76 (95% CI= -0.95, -0.56), -1.15 (95% CI= -1.52, -0.78), and -0.65 (95% CI= -1.05, -0.26) immediately after the procedure and at 6, 12, and 24 hours post-operative follow-ups, respectively (P < 0.001). These findings underscore the efficacy of NSAIDs and paracetamol in managing post-endodontic dental pain, directly pertinent to relieving pain and inflammation related to pulpitis. [25]

Clinical Benefits of Aceclofenac and Paracetamol

  • Effective Pain Management: Aceclofenac and Paracetamol effectively relieve pain, making them suitable for painful dental conditions. [19,22,23]
  • Reduced Inflammation: Aceclofenac has anti-inflammatory properties that can help reduce inflammation associated with acute pulpitis. [22,23]
  • Comprehensive Relief: When Aceclofenac and Paracetamol are combined, they provide comprehensive relief by simultaneously addressing pain and fever, offering a comprehensive approach to symptom management. [19,22,23]
  • Synergetic Efficacy: This combination offers synergistic efficacy, effectively managing pain and fever and improving overall symptom control. [19,22,23]
  • Rapid Onset of Action: These medications are known for their quick onset of action, ensuring patients experience pain relief in a relatively short time. [19,22,23]

Take Home Messages

  • Acute pulpitis is a distressing dental condition characterized by inflammation in the innermost part of the tooth’s pulp, resulting in excruciating toothache and heightened sensitivity to temperature variations. [1,2,3]
  • Acute pulpitis primarily arises from bacterial invasion into the dental pulp, often stemming from dental issues like cavities, trauma, or poor oral hygiene. Environmental factors, systemic conditions, and lifestyle choices can further contribute to the risk of pulpitis. [1]
  • A rational approach to managing acute pulpitis includes precise diagnosis, appropriate pain relief through analgesics and anti-inflammatory medications, and, antibiotics, when necessary. The choice of pharmacological pain relief agents is important for prompt and effective pain relief. [14,15,16,17,18]
  • The combination of Aceclofenac and Paracetamol has shown remarkable efficacy in reducing dental pain in multiple clinical trials, making it a valuable consideration in acute pulpitis management.[19,22,23,24,25]
  • Aceclofenac and Paracetamol offer effective pain management, reduce inflammation, and provide dual-action pain relief. The combination exhibits a rapid onset of action, ensuring prompt relief for patients suffering from acute pulpitis.[19,22,23,24,25]

The combination of Aceclofenac and Paracetamol offers a promising approach to manage acute pulpitis effectively, providing comprehensive pain relief and improving patient well-being. [19,20,21,22,23,24,25]

References:

1. Dr Syed Gufaran Ali1, Dr Sanjyot Mulay. Pulpitis: A review. IOSR Journal of Dental and Medical Sciences,2015;14(8):92-97 https://www.researchgate.net/publication/281228037_Pulpitis_A_review

2. Mahsa Dastpak 1, Jamileh Ghoddusi 2, Amir Hossein Jafarian 3, Majid Sarmad Association between Clinical Symptoms and Histological Features of Molars with Acute Pulpitis. Iranian Endodontic Journal 2023;18(2): 91-95 https://pubmed.ncbi.nlm.nih.gov/37152857/

3. Bahadur F.Alieva , Latafat A. Gardashovab. Selection of an optimal treatment method for acute pulpitis disease. Procedia Computer Science,2017;120:539–546 https://doi.org/10.1016/j.procs.2017.11.276

4. Valentina NICOLAICIUC. Dental Pulpitis and Elements Of Endodontic Therapy. The State University Of Medicine and Pharmacy, Medicina,2013;107:181-186 https://propedeutica.usmf.md/wp-content/blogs.dir/130/files/sites/130/2018/03/Dental-pulpitis.pdf

5. Govula Kiranmayi, Lavanya Anumala, Richard Kirubakaran. Estimation of the Prevalence of Pulpitis in the Tertiary Care Hospital in Nellore district- A cross-sectional study. IOSR Journal of Dental and Medical Sciences,2018;18(8):63-66 https://www.researchgate.net/publication/338229885_Estimation_of_the_Prevalence_of_Pulpitis_in_the_Tertiary_Care_Hospital_in_Nellore_district-A_cross_sectional_study#:~:text=Results%3A%20The%20total%20prevalence%20rate,age%20group%2018%2D30%20years.

6. Thompson, W., Howe, S., Pitkeathley, C., Coull, C., & Teoh, L. Outcomes to evaluate care for adults with acute dental pain and infection: a systematic narrative review. BMJ Open,2022;12(2):e057934. https://doi.org/10.1136/bmjopen-2021-057934

7. Yu, C., & Abbott, P. V. An overview of the dental pulp: its functions and responses to injury. Australian Dental Journal,2007;52(s1):s4-16. https://doi.org/10.1111/j.1834-7819.2007.tb00525.x

8. Bender, I. Pulpal pain diagnosis—A review. Journal of Endodontics,2000;26(3):175–179. https://doi.org/10.1097/00004770-200003000-00012

9. Adriano Piattelli, MD, DDS* Tonino Traini, DDS, PhD*. DIAGNOSIS AND MANAGING PULPITIS: REVERSIBLE OR IRREVERSIBLE? Practical procedures & aesthetic dentistry,2007;19(2). https://www.researchgate.net/publication/6236907_Diagnosis_and_managing_pulpitis_reversible_or_irreversible

10. Klausen, B., Helbo, M., & Dabelsteen, E. A differential diagnostic approach to the symptomatology of acute dental pain. Oral Surgery, Oral Medicine, and Oral Pathology,1985;59(3):297–301. https://doi.org/10.1016/0030-4220(85)90170-7

11. Lopes, M. A., de Souza Filho, F. J., Jorge Júnior, J., & de Almeida, O. P. Herpes zoster infection as a differential diagnosis of acute pulpitis. Journal of Endodontics,1998;24(2):143–144. https://doi.org/10.1016/s0099-2399(98)80095-2

12. Tonetto, M. R., de Andrade, M. F., Bandéca, M. C., Kuga, M. C., Keine, K. C., Pereira, K. F., Magro, M. G., Diniz, A. C. S., Galoza, M. O. G., & de Barros, Y. B. A. M. Differential Diagnosis and Treatment Proposal for Acute Endodontic Infection. The Journal of Contemporary Dental Practice,2015;16(12):977–983. https://doi.org/10.5005/jp-journals-10024-1791

13. Korsantiia, N. B., Davarashvili, X. T., Gogiashvili, L. E., Mamaladze, M. T., Tsagareli, Z. G., & Melikadze, E. B. Correlation between dental pulp demyelination degree and pain visual analogue scale scores data under acute and chronic pulpitis. Georgian Medical News,2013;218:62-7.https://pubmed.ncbi.nlm.nih.gov/23787510/

14. Akhmedov Muzaffarbek Ulugbek ugli1. CONSERVATIVE TREATMENT OF PULPITIS. EURASIAN JOURNAL OF ACADEMIC RESEARCH,2021;1(3);635-342. https://zenodo.org/record/5055700

15. Yong, D., & Cathro, P. Conservative pulp therapy in the management of reversible and irreversible pulpitis. Australian Dental Journal,2021;66(S1)S4-S14. https://doi.org/10.1111/adj.12841

16. Khan, A. A., & Diogenes, A. Pharmacological management of acute endodontic pain. Drugs,2021;81(14):1627–1643. https://doi.org/10.1007/s40265-021-01564-4

17. Manuela Favarin SANTINI, Ricardo Abreu da ROSA, Maria Beatriz Cardoso FERREIRA, Fernando Branco BARLETTA, Angela Longo do NASCIMENTO, Theodoro WEISSHEIMER, Carlos ESTRELA, Marcus Vincius Reis SÓ. Medications used for prevention and treatment of postoperative endodontic pain: a systematic review. European Endodontic Journal,2020;6(1):15-24. https://doi.org/10.14744/eej.2020.85856

18. Hargreaves, K., & Abbott, P. V. Drugs for pain management in dentistry. Australian Dental Journal,2005;50(s2):S14-22. https://doi.org/10.1111/j.1834-7819.2005.tb00378.x

19. Kim, S.-J., & Seo, J. T. Selection of analgesics for the management of acute and postoperative dental pain: a mini-review. Journal of Periodontal & Implant Science,2020;50(2):68-73 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192823/

20. Akhil Rajput1 , Umesh Kumar2 , Nikhil Sinha3 , Gulshan Kumar4 , Ruchi Vashisht5 , Krishan Gauba6 , Anup Kanase. Emergency Pain Management of Untreated Pulpitis during COVID-19 Lockdown by Telephonic Communication. World Journal of Dentistry, 2022;13(4):358–361. https://doi.org/10.5005/jp-journals-10015-2067

21. Christina M. A. P. Schuh1†, Bruna Benso2,3† and Sebastian Aguayo2*. Potential Novel Strategies for the Treatment of Dental Pulp-Derived Pain: Pharmacological Approaches and Beyond. Frontiers in Pharmacology,2019;10. https://doi.org/10.3389/fphar.2019.01068

22. P.Pavithra, 2M. Dhanraj, 3 Prathap Sekhar. Analgesic Effectiveness of Ibuprofen and Aceclofenac in the Management of Acute Pulpitis – A Randomized Double-Blind Trial. International Journal of Pharmaceutical Sciences Review and Research,2015;35(2):70-74. https://globalresearchonline.net/journalcontents/v35-2/14.pdf

23. Joseph V. Pergolizzia , Peter Magnussonb,c, Jo Ann LeQuanga , Christopher Gharibod and Giustino Varrassie,f. The pharmacological management of dental pain. Expert Opinion on Pharmacotherapy,2020. The pharmacological management of dental pain: Expert Opinion on Pharmacotherapy: Vol 21, No 5 (tandfonline.com)

24. Solete, P., Sindhu Ramesh & department of Conservative Dentistry and Endodontics, Saveetha Dental College, Saveetha University, Saveetha Institute of Medical and Technical Sciences, Chennai 600077, India. (2021). Comparative evaluation of various analgesics in irreversible pulpitis to reduce pain. Bioinformation,2021;17(2):313–319. https://doi.org/10.6026/97320630017313

25. A Shirvani 1, S Shamszadeh 2, M J Eghbal 2, S Asgary. The efficacy of non‐narcotic analgesics on post‐operative endodontic pain: A systematic review and meta‐analysis: The efficacy of non-steroidal anti-inflammatory drugs and/or paracetamol on post-operative endodontic pain. Journal of Oral Rehabilitation,2017;44(9):709–721. https://doi.org/10.1111/joor.12519

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Japan accepts GSK Arexvy regulatory application to prevent RSV disease in adults aged 50-59 at increased risk

London: GSK plc has announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) has accepted for review a regulatory application to extend the indication of GSK’s respiratory syncytial virus (RSV) vaccine (recombinant adjuvanted) for the prevention of RSV disease in adults aged 50-59 at increased risk.

This regulatory submission follows Japan’s approval of GSK’s vaccine for the prevention of RSV disease in adults from the age of 60 years, and the recent announcement of the positive results of a phase III trial [NCT05590403] evaluating the immune response and safety of GSK’s RSV vaccine in adults aged 50-59, including those at increased risk for RSV lower respiratory tract disease (LRTD) due to certain underlying medical conditions.

The burden of RSV disease in adults is likely to be underestimated due to lack of awareness and standardised testing, as well as under-detection within surveillance studies, but people with underlying medical conditions – such as chronic obstructive pulmonary disease (COPD), asthma, chronic heart failure and diabetes– are at increased risk for RSV disease. RSV can exacerbate these conditions and lead to pneumonia, hospitalisation, or death. An international systematic review of the prevalence of respiratory viruses in patients with acute exacerbations of COPD, for example, showed that RSV was detected 1 in 10 cases.

Further announcements on regulatory progress in the US and EU are expected in early 2024.

Read also: GSK RSV shot Arexvy approved in Britain for adults aged 60 years and older

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Gene polymorphisms linked to development of recurrent urolithiasis

Researchers have found in a new study that Gene polymorphisms is linked to development of recurrent urolithiasis. 

The findings of the study have been published in the Journal BMC Nephrology. 

Urolithiasis is one of the most prevalent diseases worldwide. Its prevalence is rising, both in developing and developed countries. Currently, the incidence and prevalence of urolithiasis is on the rise worldwide. Approximately 12% population of the world was affected by urolithiasis regardless of age, race, or sex.

It is known that genetic factors play big roles in the development of urolithiasis. One of the suspected factors is gene polymorphism. This study aims to find an accurate estimate of the association between genetic polymorphism and the risk of recurrent urolithiasis.

A systematic review and meta-analysis were performed on 12 studies from 3 databases that investigated gene polymorphism as an risk factor of urolithiasis. The review was done using Review Manager® version 5.3.The study was conducted through a comprehensive search from Medline/PubMed, Scopus, and Cochrane electronic databases for studies published between January 2000 and June 2023.

Results

Insignificant heterogenicity was found in this study. Populations from Asia and the Middle East are more likely to experience recurrent urolithiasis. Additionally, variation in the VDR and urokinase genes, particularly in the Asian population, increases the risk of developing recurrent urolithiasis.

The researchers found that Gene polymorphisms have significant roles in the development of urolithiasis, especially in the Middle Eastern region.Additionally, both VDR and urokinase gene polymorphism contributes to the susceptibility of recurrent urolithiasis particularly for the Asian population in the latter. Studies with a variety of population characteristics are recommended to be performed to further support our results.

Reference:

Rasyid, N., Soedarman, S. Genes polymorphism as risk factor of recurrent urolithiasis: a systematic review and meta-analysis. BMC Nephrol 24, 363 (2023). https://doi.org/10.1186/s12882-023-03368-y

Keywords:

Gene, polymorphisms, linked, development, urolithiasis, BMC Nephrology, Rasyid, N., Soedarman, S

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Middle ear pressure therapy using special device effectively controls vertigo symptoms

A recent study has shed light on the promising long-term benefits of Middle Ear Pressure Therapy (MEPT) utilizing the EFET01 device in patients diagnosed with Ménière’s disease (MD) and delayed endolymphatic hydrops (DEH) in Japan. The investigation aimed to evaluate the effects of MEPT over two years in reducing vertigo attacks and improving hearing in individuals with MD and DEH. This study was published in Acta Oto-Laryngologica journal by Do Tram Anh and colleagues.

Conducted retrospectively from December 2018 to April 2021, the study included 32 MD patients and 2 DEH patients who underwent MEPT with the EFET01 device. Patients were assessed based on the Japan Society for Equilibrium Research (JSER) guidelines, tracking the frequency of vertigo attacks and changes in hearing levels for 6 months before treatment initiation up to 18–24 months post-treatment.

The results revealed significant reductions in the frequency of vertigo attacks in both MD and DEH patients following MEPT. Furthermore, the study noted a sustained stability in hearing levels for the majority of patients post-treatment.

The findings underscore the efficacy of MEPT utilizing the EFET01 device in effectively managing vertigo symptoms associated with MD and DEH. The therapy showcased its potential as a safe and beneficial option, especially for patients who had not responded well to conventional medical treatments.

These promising outcomes pave the way for MEPT to be considered as a valuable alternative in the management of MD and DEH, offering hope for individuals who have experienced limited success with traditional therapies. The sustained reduction in vertigo attacks and stability in hearing levels post-treatment emphasize the potential of MEPT to significantly impact the quality of life for these patients over an extended period.

Reference:

Tram Anh, D., Takakura, H., Nakazato, A., Morita, Y., & Shojaku, H. Long-term effects of middle ear pressure therapy with the EFET01 device in patients with Ménière’s disease and delayed endolymphatic hydrops in Japan. Acta Oto-Laryngologica,2023;1–5. https://doi.org/10.1080/00016489.2023.2284336

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CAMH develops potential new drug treatment for multiple sclerosis

CAMH-led pre-clinical studies using a small molecule drug have shown promise as a potential new treatment for multiple sclerosis (MS). The results have been published today in the journal Science Advances.

Expanding on Dr. Fang Liu’s earlier work that identified a novel drug target for the treatment of MS, she and her team have now created a small molecule compound that is effective in two different animal models of MS. This represents a key advancement that brings this MS research closer to the clinic to impact patient care.

MS is a progressive neurological disease that currently has no cure. It is associated with a wide-range of debilitating symptoms, including problems with coordination, cognition, muscle weakness and depression. For unknown reasons, it is more common in northern latitudes and more than twice as common in women.

It is known that MS damages myelin, a protective sheath that forms around nerves in the brain and spinal cord. As the myelin damage is triggered by inflammation in the immune system, up until now all current drug treatments for MS target the immune system.

In this study, CAMH Senior Scientist Dr. Fang Liu and her team treated MS in a completely different way-targeting the glutamate system. Study results showed that the newly synthesized lead compound not only reduced MS-like symptoms, it also may repair the damaged myelin in two different pre-clinical models of MS.

“Our compound had a stunning effect on rescuing myelin and motor function in the lab models, and I hope these effects will translate to the clinic to add to current treatments and bring new hope to patients with MS,” said Dr. Liu. “As with cancer chemotherapy drug cocktails, simultaneous targeting of the MS disease pathway at multiple points can have synergistic effects and result in better outcomes.”

Dr. Iain Greig, Reader in Medicinal Chemistry at the University of Aberdeen, alongside his team, are working to turn the molecules identified by Dr. Liu into advanced “drug-like” molecules suitable for continued development towards clinical use in patients. He added: “In all my years as a medicinal chemist, I have never seen a more promising starting point for a drug development project. It has been a huge pleasure to be involved in this program and I am looking forward to continuing to drive it towards to the clinic.”

Much of the funding for this novel treatment for MS, which Dr. Fang and her team have been investigating for over a decade, has come from the Multiple Sclerosis Society of Canada and the National Multiple Sclerosis Society USA’s Fast Forward commercial research program.

“We are pleased to have helped enable the early development of a novel neuroprotective strategy for MS, and look forward to seeing it progress through the critical next stages needed to determine its potential benefits for people living with MS,” said Walt Kostich, PhD, head of the National MS Society (USA)’s Fast Forward commercial research program.

Dr. Liu believes that the evidence of efficacy and tolerability generated in this study for the small molecule drug makes it a good candidate to be developed for human trials. The next steps in drug development will involve some further pre-clinical research, including investigating safety and stability of the compound. CAMH and the University of Aberdeen have already filed patent applications to protect this research and are actively seeking industry partners to further advance this work towards clinical trials over the next few years.

Reference:

Dongxu Zhai et al. ,Small-molecule targeting AMPA-mediated excitotoxicity has therapeutic effects in mouse models for multiple sclerosis.Sci. Adv.9,eadj6187(2023).DOI:10.1126/sciadv.adj6187.

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Routine Premolar extraction as part of orthodontic treatment may impact mandibular kinematics

Austria: Findings from a recent study published in the European Journal of Dentistry support the notion of discouraging the routine practice of premolar extraction as part of orthodontic treatment.

The researchers showed that premolar extraction altered mandibular kinematics in at least 25% of the cases within the study sample, and the transversal discrepancy between retrusive and protrusive tracings was even predictive of group affiliation.

The practice of premolar extraction in orthodontics remains controversial owing to its potentially detrimental effects on the stomatognathic system. However, there is no proper understanding of how premolar extraction affects mandibular function. Alejandra Londoño, Department of Research in Occlusion Medicine, Vienna School of Interdisciplinary Dentistry — VieSID, Klosterneuburg, Austria, and colleagues, therefore, aimed to assess the impact of premolar extraction on mandibular kinematics by evaluating axiographic tracings.

For this purpose, the researchers compared forty-five orthodontically treated patients with premolar teeth extraction with 45 paired untreated controls, selected for the absence of malocclusions. Mandibular movements were recorded by systematic three-dimensional axiography for protrusive–retrusive movements and speech. The transversal deviations, length of the movements, and rotation angle were recorded for both sides during the speech.

The permutation test and Wilcoxon rank-sum test were used to analyze the differences between the axiographic variables. Linear regression was performed to test whether axiographic parameters predicted group affiliation. Dot plots were used to explore the distribution of each of the axiographic outcomes. Isometric principal component analysis was used to assess the differences between the cumulative effects of premolar extraction on jaw motion.

The study led to the following findings:

  • The mandibular lateral translation in protrusion–retrusion and speech, the amount of rotation as well and the length of mandibular movements during speech were significantly higher in the treated subjects than in the controls, while retral stability did not differ.
  • The linear regression yielded significant results for the mandibular lateral translation in protrusion–retrusion.
  • The isometric principal component analysis showed higher values of the axiographic variables for 11 out of 45 individuals in the study sample compared with the control group.

“These results support the notion that the routine practice of premolar extraction as part of the orthodontic treatment should be discouraged,” the researchers wrote.

Additionally, the team suggests recommending the evaluation of mandibular movements as an integral part of diagnostic and follow-up assessment of treatment outcomes.

“To assess whether a disrupted kinematics of the mandible is associated with temporomandibular disorders, it is compelling to perform further studies,” they concluded.

Reference:

Londoño A, Assis M, Fornai C, Greven M. Premolar Extraction Affects Mandibular Kinematics. Eur J Dent. 2023 Jul;17(3):756-764. doi: 10.1055/s-0042-1755629. Epub 2022 Sep 27. PMID: 36167318; PMCID: PMC10569881.

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Use of calcium channel blockers tied to more severe actinic keratosis on face and scalp: Study

Brazil: New research published in the International Journal of Dermatology has confirmed lower skin phototype classifications, older age, and a personal history of skin cancer as severity risk factors for actinic keratosis (AK). The use of calcium channel blockers (CCBs) was associated with more severe AK.

Actinic keratosis is a skin condition associated with sun exposure, age, and immunosuppression. Certain drugs, such as calcium channel blockers and photosensitizing medications have been linked to AK. Ingrid S. Gioppo, Hospital Geral de Curitiba, Curitiba, Brazil, and colleagues explored the impact of behavioural, individual, and exposure factors on the severity of AKs on the scalp and face in a multicenter cross-sectional study.

The study involved immunocompetent individuals with at least one actinic keratosis on their scalp or face and assessed sun exposure and protection, demographic factors, history of skin cancer, and use of medications within the last six months. The primary outcome of the study was determined as the Actinic Keratosis Area and Severity Index (AKASI) score, and the variation in AKASI scores was evaluated using a hierarchical generalized linear model, adjusting for age, gender, and skin prototype. A total of two hundred seventy subjects between 39 and 92 years were evaluated.

The study revealed the following findings:

· The majority had phototype I or II (77%), male gender (51%), low adherence to sunscreen use (29%), and personal history of skin cancer (55%).

· The use of photosensitizing medications was reported by 61%.

· Through multivariate analysis, older age (βSE = 0.14), lighter skin phototype (βSE = 0.15), sunburning (βSE = 0.12), history of skin cancer (βSE = 0.12), and use of CCBs (βSE = 0.11) were identified as independent risk factors for AK severity.

· Photosensitizing drugs were not identified as risk factors.

“We confirmed lower skin phototype classifications, older age, and a personal history of skin cancer as severity risk factors for actinic keratosis, while CCB use was associated with more severe AK,” the researchers concluded.

Reference:

Gioppo, I. S., Martins, C., Santos, S. S., R. Preto, J. F., Miola, A. C., & Miot, H. A. (2023). Association between calcium channel blockers and the severity of actinic keratosis on face and scalp: A cross-sectional study. International Journal of Dermatology, 62(12), 1511-1519. https://doi.org/10.1111/ijd.16871

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Young age at menarche tied to elevated risk of diabetes in mid-life: BMJ

USA: A recent study published in BMJ Nutrition Prevention & Health reveals an association between earlier age at menarche and type 2 diabetes among young and middle-aged women and with stroke complications among these women with diabetes.

“Starting menstrual cycles at a young age before the age of 13 is linked to a heightened risk of developing type 2 diabetes in mid-life,” the US study stated. 

It also seems to be associated with an increased risk of having a stroke before the age of 65 in those with the disease, particularly those who started having periods before the age of 10 or younger, the findings indicate.

Diabetes and its complications are on the rise among young and middle-aged US adults, while the age at which women start having periods is falling worldwide, note the researchers.

They therefore wanted to find out if there might be a link between these two phenomena in younger women, and drew on responses to the nationally representative National Health and Nutrition Examination Survey (NHANES) 1999–2018.

Some 17,377 women aged between 20 and 65 were included in the study, all of whom specified the age at which they had had their first menstrual cycle. This was categorised as 10 or younger, 11, 12, 13, 14 and 15 and older.

Of the total, 1773 (10%) reported a diagnosis of type 2 diabetes. And of these, 205 (11.5%) reported some type of cardiovascular disease.

Starting periods before the average age of 13 was associated with a heightened risk of type 2 diabetes, after accounting for a range of potentially influential factors, including age, race/ethnicity, education, motherhood, menopausal status and family history of diabetes, smoking, physical activity, alcohol consumption and weight (BMI).

This ranged from 32% greater (10 or younger) through 14% greater (age 11) to 29% greater (age 12).

Among women with diabetes, earlier age at first menstrual cycle was associated with a heightened risk of stroke, although not cardiovascular disease in general, after accounting for the same set of potentially influential factors.

Very early age at first menstrual cycle-10 or younger-was associated with a more than doubling in stroke risk among women below the age of 65 with diabetes, after similar adjustments for influential factors.

This risk fell in tandem with increasing age: 81% among those with their first menstrual bleed at the age of 11, to 32% at the age of 12, and to 15% at the age of 14.

This is an observational study, and as such, can’t establish causal factors. But, suggest the researchers: “Earlier age at [first menstrual cycle] may be one of early life indicators of the cardiometabolic disease trajectory in women.”

They explain: “One potential pathway explanation may be that [such] women are exposed to oestrogen for longer periods of time, and early [menstruation] has been associated with higher oestrogen levels.”

They point out that while the observed associations between age at first menstrual cycle and stroke complications weakened slightly after accounting for weight, these still remained statistically significant.

“Therefore, adiposity may also play a role in the observed association between early age at [first menstrual cycle] and stroke complications, as higher childhood adiposity is associated with earlier age at [menstruation] and with cardiometabolic diseases later in life,” they suggest.

“These findings add another dimension to the potentially less well understood determinants of cardiometabolic risk, particularly in women who have been relatively underrepresented in this area of research,” comments Professor Sumantra Ray, Executive Director of the NNEdPro Global Centre for Nutrition & Health, which co-owns BMJ Nutrition Prevention & Health.

“And they provide a clear steer on the need to design interventional studies looking at the prevention of cardiometabolic disease in ethnically diverse groups of women who start menstruating at a young age,” he adds.

Reference:

Santos MP, Li Y, Bazzano LA, et alAge at menarche, type 2 diabetes and cardiovascular disease complications in US women aged under 65 years: NHANES 1999–2018BMJ Nutrition, Prevention & Health 2023;e000632. doi: 10.1136/bmjnph-2023-000632.

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Novel X-ray shield cuts radiation exposure to the operator by greater than 80 per cent: Study

Norway: Radiation shielding is necessary during cardiac catheterization, but there is a need to improve ease of use and efficacy. A recent study published in Circulation: Cardiovascular Interventions sought to evaluate the shielding effect and user feedback for a novel flexible multiconfiguration x-ray shield (FMX).

The researchers found that the reusable and flexible radiation shield that lays across the patient like a blanket can reduce tradition to operators in that cath lab by as much as 84% compared with routine protection strategies.

“The reductions in radiation dose to the operators were similar for diagnostic angiography and PCI and similar in female and male operators,” reported Cedric Davidsen, Haukeland University Hospital, Bergen, Norway, and colleagues. According to them, the novel device they developed and tested offered protection against scatter that may be missed by table- and ceiling-mounted shields.

“The FMX was designed to maintain ease of use and protection across a variety of patients, procedure types, and access sites,” the study stated. “The system can be fully and immediately removed or repositioned in seconds according to clinical need.”

The 0.5-mm Pb equivalent FMX can be configured selectively to accommodate for variations in access site, patient morphology, and type of procedure with maintained visualization, shielding, and vascular access. Relative operator dose (operator dose indexed for given dose) was measured during 103 consecutive procedures randomized in the proportion of 1:1 to the current routine setup or FMX+routine, to evaluate the efficacy. User feedback was collected on relevance, function, and likelihood of adoption into clinical practice.

The study revealed the following findings:

  • The median relative operator dose was 3.63 μSv/µGy·m2×10-3 with routine setup and 0.57 μSv/µGy·m2×10-3 with FMX+routine, which amounts to an 84.4% reduction.
  • For 500 procedures/year, this corresponds to an estimated yearly dose reduction from 3.6 to 0.7 mSv.
  • User feedback regarding size, ease of use, functionality, likelihood to use, critical issues, draping, shielding, vascular access, procedure time, patient discomfort, and risk was 99% positive.
  • No critical issues were identified. There was no significant difference in patient radiation exposure.

“The FMX considerably reduced radiation exposure and represents an attractive and effective solution for radiation protection that can easily be implemented in existing workflow,” the researchers wrote.

“FMX has the potential for general use with maintained visualization, shielding, and vascular access in routine cardiac catheterization,” they concluded.

Reference:

Davidsen C, Ytre-Hauge K, Samnøy AT, Vikenes K, Lancellotti P, Tuseth V. Efficacy and User Experience of a Novel X-Ray Shield on Operator Radiation Exposure During Cardiac Catheterization: A Randomized Controlled Trial. Circ Cardiovasc Interv. 2023 Nov 13:e013199. doi: 10.1161/CIRCINTERVENTIONS.123.013199. Epub ahead of print. PMID: 37955163.

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Smartwatches to detect abnormal heart rhythms in kids

Smart watch is a fashion in recent times, it keeps you notified on your daily routine and your fitness schedule. Smart watches can help physicians detect and diagnose irregular heart rhythms in children, according to a new study from the Stanford School of Medicine.

The finding comes from a survey of electronic medical records for pediatric cardiology patients receiving care at Stanford Medicine Children’s Health. The study published online Dec. 13 in Communications Medicine.

Over a four-year period, patients’ medical records mentioned “Apple Watch” 145 times. Among patients whose medical records mentioned the smartwatch, 41 had abnormal heart rhythms confirmed by traditional diagnostic methods; of these, 29 children had their arrythmias diagnosed for the first time.

The Stanford Medicine research team plans to conduct a study to further assess the utility of the Apple Watch for detecting children’s heart problems. The study will measure whether, in kids, heart rate and heart rhythm measurements from the watches match measurements from standard diagnostic devices.

The study is open only to children who are already cardiology patients at Stanford Medicine Children’s Health. Apple’s Irregular Rhythm Notification and ECG app are cleared by the Food and Drug Administration for use by people 22 years of age or older. The high heart rate notification is available only to users 13 years of age or older

 “I was surprised by how often our standard monitoring didn’t pick up arrythmias and the watch did,” said senior study author Scott Ceresnak, MD, professor of pediatrics. Ceresnak is a pediatric cardiologist who treats patients at Stanford Medicine. “It’s awesome to see that newer technology can really make a difference in how we’re able to care for patients.”

The study’s lead author is Aydin Zahedivash, MD, a clinical instructor in pediatrics.

Most of the abnormal rhythms detected were not life-threatening, Ceresnak said. However, he added that the arrythmias detected can cause distressing symptoms such as a racing heartbeat, dizziness and fainting. Skipping a beat, sometimes doctors face two challenges in diagnosing children’s cardiac arrythmias, or heart rhythm abnormalities.

The first is that cardiac diagnostic devices, though they have improved in recent years, still aren’t ideal for kids. Ten to 20 years ago, a child had to wear, for 24 to 48 hours, a Holter monitor consisting of a device about the size of a smartphone attached by wires to five electrodes that were adhered to the child’s chest. Patients can now wear event monitors-in the form of a single sticker placed on the chest-for a few weeks. Although the event monitors are more comfortable and can be worn longer than a Holter monitor, they sometimes fall off early or cause problems such as skin irritation from adhesives.

The second challenge is that even a few weeks of continuous monitoring may not capture the heart’s erratic behavior, as children experience arrythmias unpredictably. Kids may go months between episodes, making it tricky for their doctors to determine what’s going on.

From 145 mentions of the smartwatch in patient records, 41 patients had arrythmias confirmed. Of these, 18 patients had collected an ECG with their watches, and 23 patients had received a notification from the watch about a high heart rate.

The information from the smartwatches prompted the children’s physicians to conduct medical workups, from which 29 children received new arrythmia diagnoses. In 10 patients, the smartwatch diagnosed arrythmias that traditional monitoring methods never picked up.

 “The wearable market is exploding, and our kids are going to use them,” Ceresnak said. “We want to make sure the data we get from these devices is reliable and accurate for children. Down the road, we’d love to help develop pediatric-specific algorithms for monitoring heart rhythm.”

“These irregular heartbeats are not life-threatening, but they make kids feel terrible,” Ceresnak said. “They can be a problem and they’re scary, and if wearable devices can help us get to the bottom of what this arrythmia is, that’s super helpful.”

Reference: Smartwatches can pick up abnormal heart rhythms in kids, Stanford Medicine study finds; STANFORD MEDICINE, Communications Medicine

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