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By Vijay Kumar Malesu Nov 23 2023 Reviewed by Lily Ramsey, LLM

In a recent study published in Journal of Clinical Medicine, researchers systematically reviewed and analyzed the therapeutic efficacy of low-dose local anesthetics (LAs) in various clinical conditions, highlighting gaps in current research for future exploration.

Study:  Therapeutic Use of Low-Dose Local Anesthetics in Pain, Inflammation, and Other Clinical Conditions: A Systematic Scoping Review . Image Credit: daniiD/Shutterstock.com Background 

Since the first use of cocaine as an LA by Carl Koller in 1894, LAs have evolved significantly in therapeutic applications. Initially utilized for their immediate pain-relieving properties, their scope expanded with the discovery of procaine in 1905 and its inflammation-reducing effects.

This evolution gave rise to neural therapy (NT), predominantly in Europe, employing LAs for more than just pain management. Modern applications extend to targeting the autonomic nervous system (ANS) to provide sustained relief from pain and other dysfunctions.

Further research is needed to comprehensively understand the scope, efficacy, and safety of low-dose local anesthetics in various conditions, as current studies vary in design, and a unified understanding is yet to be established. About the study 

In the present study, the researchers conducted a systematic scoping review using the Arksey and O’Malley framework, comprising five stages: defining the research question, identifying relevant studies, selecting studies, charting data, and summarizing and reporting results.

The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews (PRISMA-ScR) guidelines, and the research question sought to understand the therapeutic applications of low-dose LAs in various medical conditions.

The team selected studies focusing solely on LAs, emphasizing measuring efficacy or safety. The review included a wide array of study designs, from experimental setups like randomized controlled trials (RCTs) to observational analyses including cohort and case-control studies. Systematic reviews, qualitative studies, and meta-analyses that met the inclusion criteria were also considered, excluding narrative reviews, expert opinions, and studies involving LAs combined with other treatments.

The literature search was comprehensive, covering major databases like MEDLINE, Cochrane Library, and LILACS, with no language or publication date restrictions. They supplemented this with searches on Google Scholar and references from included studies.

Two reviewers independently screened titles and abstracts, with full-text reviews for those meeting the inclusion criteria. Conflicts were resolved through discussion or a third reviewer's input. The study used Rayyan Qatar Computing Re­search Institute (QCRI) for data management during the screening phases. Related StoriesDay-to-day painkiller use doesn't lower empathy levels, but misuse might, according to recent surveyStudy finds pleasurable music and 'chills' predict music-induced hypoalgesiaNew insights into migraine etiology: the role of hepatocyte growth factor

Data extraction was thorough, capturing key information such as authorship, publication year, study objectives, population characteristics, study type, intervention details, outcomes, and main findings. Special attention was given to data on the safety of the interventions. A third reviewer resolved any discrepancies in data extraction.

Finally, the team performed a narrative synthesis of the results, using text and tables from the studies for a descriptive summary.

This synthesis not only outlined the characteristics and findings of the studies but also highlighted gaps in the evidence and offered potential interpretations and implications of the results. Study results 

The initial search across Medline, LILACS, and the Cochrane Library yielded 9614 publications, supplemented by 52 articles from citation searches and grey literature.

After duplicate removal, 7,670 publications were manually screened based on titles and abstracts, excluding 7,250 publications. This process left 420 articles for full-text assessment, with ten being inaccessible, and after thorough evaluation, 315 studies were further excluded. 

The researchers also considered 52 publications identified through citation searching, of which six could not be retrieved. Out of the 46 assessed for eligibility, 12 were excluded for being opinion articles, and 129 studies were included in the review. 

These included studies comprising 49 clinical trials (both non-randomized and randomized), 71 observational studies, and nine systematic reviews. The observational studies varied, including case reports or series, cohort studies, qualitative studies, and before-and-after studies.

The median patient number across these studies was 44. The studies primarily reported on procaine, lidocaine, and bupivacaine, focusing on their therapeutic applications and potential adverse effects.

Geographically, the studies spanned multiple countries, with the most contributions from Türkiye, Germany, the United States, and Cuba, among others. The median publication year was 2016, with a concentration of studies published between 2011 and March 2022.

These studies were predominantly published in general medical journals, although some appeared in specialized journals focused on pain management, neurology, psychiatry, and anesthesiology.

Regarding indications, the primary use of low-dose, short-acting LAs was in managing chronic pain, followed by acute pain. The most common conditions treated were musculoskeletal and/or myofascial pain and migraines. Additionally, 14% of the studies focused on non-pain-related indications.

In the studies, LAs were applied in various ways, including segmental application, local application, ganglion injections, and mixed approaches. The study’s Figure 5 highlights the evidence gaps in the literature regarding the types of indications and study designs.

The review found that 96.12% of the studies primarily assessed the efficacy of LAs, with a smaller portion focusing on safety. The key outcomes included pain relief, improvements in quality of life, reduced analgesic intake, and better scores on anxiety and depression scales.

While 53.48% of these studies also considered safety, reporting mild and transient adverse reactions, no severe adverse allergic responses or reactions were documented.

The study revealed that lidocaine and procaine were the most researched LAs, with lidocaine showing a slightly higher frequency of adverse events, though neither exhibited major adverse effects.

The interventions predominantly showed positive or potentially positive effects, with a minority reporting no effect or providing unclear evidence. A specific focus on acute stress revealed positive impacts, with studies on anxiety and depression as secondary outcomes showing varying degrees of improvement. Journal reference:

Vinyes D, Muñoz-Sellart M, Fischer L. (2023) Therapeutic Use of Low-Dose Local Anesthetics in Pain, Inflammation, and other Clinical Conditions: A Systematic Scoping Review. Journal of Clinical Medicine. doi:https://doi.org/10.3390/jcm12237221. https://www.mdpi.com/2077-0383/12/23/7221 

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Under siege in Ukraine, schools go underground to keep life as normal as possible for children

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Under siege in Ukraine, schools go underground to keep life as normal as possible for children

If you know a teacher, or you are a teacher, you’ll understand that many in the profession consider their jobs one of the best in the world, while also acknowledging it can be one of the most stressful.

Teaching in a war zone takes it to another level on both fronts.

But imagine teaching in a war zone in say the London Underground or the Paris or New York metros?

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Students learning in lessons

Well, that’s exactly what is happening in Kharkiv, Ukraine’s second largest city – a city attacked by Russia on a constant basis.

In 2023, the authorities banned children from being taught in regular school buildings here because of the threat they were under from missile strikes.

So Kharkiv city and its education department started working on a plan.

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That plan has concluded with the construction of six schools in six metro stations, teaching 4,800 children daily whose families haven’t fled the war.

Intrigued by this new educational experiment, as it’s still considered, we were told to meet at the University metro station in the centre of the city and wait to be taken to the school.

Soviet-era metro stations, and particularly the platforms, are universally grand and ornate, although Ukraine’s are slightly more modest.

A young child at school in Kharkiv's underground system
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A young child at his desk in the underground school

The school (left) and the metro system (right)
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The school (left) and the metro system (right)

Pedestrian walkways though are always crammed with florists, newspaper stands, mobile phone shops and cafes, and Kharkiv’s are no different.

What is different though is that next to the main platform entrance, an adjacent passageway has been sealed off by a white wall with three doors built into it.

We were ushered inside, past a guard and into a concourse with two desks.

Inside the classrooms in a city under siege
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Inside the classrooms in a city under siege

The classrooms are brightly decorated to try and maintain morale for the children
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The classrooms are brightly decorated to try and maintain morale for the children

In front of us, we could see a wide staircase leading to a long corridor. Above us, large, shiny silver metal tubes stretched into the distance, pumping in air from above ground.

Lining the corridor, we could see a series of white interconnecting cabins, all brightly lit, and from them, we could hear the sounds of children laughing, music, and teachers conducting class in this strange subterranean school.

Perhaps the only school in the world with one corridor.

A door to one of the classes opened, and in pairs, a class of six and seven-year-olds emerged – their teacher at the front and an assistant at the rear.

They’re heading to the bathroom for a toilet break, the staff must keep an eye on them.

If any of the children were to make it out of the school, they could easily get lost in the underground system.

The pupils are spread across seven classrooms with a mix of yellow and green desks and chairs, and walls decorated with bright pictures like rainbows, sunshine and sunflowers, to try to create a cheery atmosphere.

“At first, the children were bewildered by studying here, it felt unfamiliar to them, but interacting with each other and with their teachers helped them to adapt,” Iryna Tarasenko from Kharkiv’s education department told me.

Iryna Tarasenko from Kharkiv's education department
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Iryna Tarasenko from Kharkiv’s education department

Sky News chief correspondent Stuart Ramsay and Kharkiv education official Iryna Tarasenko
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Sky News’ Stuart Ramsay and Kharkiv education official Iryna Tarasenko

Iryna is showing me around the school. They feel it’s their way of contributing to the war effort.

She said: “In the summer of 2023, the Defence Council didn’t permit children to study in regular school buildings, so, we had to find a solution. This is our frontline – our educational frontline.”

There are of course health concerns for both the teachers and the pupils spending so much time underground, so medical examinations are done on a regular basis.

It is an opportunity for doctors and behavioural specialists to monitor the effects of this war on them.

Dmytro Mitelyov is the neurologist on duty monitoring the children’s behaviour, checking for any signs of stress – physical and mental.

He gently asks each child how they’re feeling, and asks if they have any aches and pains.

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Dmytro Mitelyov (centre), the neurologist on duty monitoring the children as they spend large parts of their days underground, speaks to a child
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Neurologist Dmytro Mitelyov (centre) monitors children as they spend large parts of their days underground

“These are children who haven’t left Kharkiv since the war began, they live in a constant state of stress, multifaceted stress caused by a range of factors. They are exposed to things they see and hear, like alarms, explosions, and they feel it all,” Dmytro told me.

“When these children grow older, all the trauma they’ve endured during their formative years can, unfortunately, leave a lasting and serious imprint on their mental health. They haven’t had a healthy, carefree childhood – the kind where they can learn, play, and feel safe as children normally would.”

As the first group’s school day ends, children from one of Kharkiv’s most bombed districts, wrap up warm before being led to the surface to catch a school bus to their old school – which was hit by a missile.

It’s still where they meet their parents for normal pick-up.

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Students eating in their classrooms in Kharkiv's metro system
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Students eating in their classrooms in Kharkiv’s metro system

We jump on the bus with them for the journey past destroyed government buildings, shopping centres and restaurants.

When the air raid suddenly sounds, I look around to see how the children and teachers on this bus will react.

They barely flinch it’s so common.

“People have, to some extent, adapted,” one of the headmistresses, Olena Nikolienko, said.

“If we see missiles coming, heaven forbid, we’ll stop near a designated shelter, following our evacuation plan, and that’s where the children will go for cover.”

Headmistresses Olena Nikolienko
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Headmistress Olena Nikolienko

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Remember, these children are safe underground at school, up here they are not.

During the bus ride, 10-year-old Alisa began quietly sobbing. Her teacher told me her grandfather was killed four months ago on the frontline, and since then she has been prone to tears.

Alisa’s teacher comforted her and told her everything would be ok.

It feels like everyone here has to carry their own sadness.

Everyone.

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‘Ukraine war will end sooner under Trump’

Parents, standing in the first snowfall of the season, greet the children as they get off the bus.

The kids run off the bus, and start throwing snowballs at each other, enjoying this precious moment.

It will be the last time they’re outside today.

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Xi Jinping says China is ‘ready to work’ with Donald Trump during last meeting with Joe Biden

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Xi Jinping says China is 'ready to work' with Donald Trump during last meeting with Joe Biden

Joe Biden has met with Xi Jinping for the last time as US president, where the Chinese leader said he is “ready to work” with Donald Trump.

Speaking at the Asia-Pacific Economic Cooperation forum in Lima, Peru, Mr Biden said the US and China’s relationship should be about “competition, not conflict”.

“We haven’t always agreed, but our conversations have always been candid and always been frank,” he said.

“We’ve never kidded one another. These conversations prevent miscalculations, and they ensure the competition between our two countries will not veer into conflict.

“We’ve been level with one another. I think that’s vital.”

Their last-ever meeting comes as president-elect Donald Trump vows to introduce blanket 60% tariffs on US imports of Chinese goods as part of a series of “America First” trade measures.

Pic: Reuters
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Pic: Reuters

But despite Mr Trump’s proposed measures, Mr Xi said his country’s goal “of a stable, healthy and sustainable China-US relationship remains unchanged”.

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“Our commitment to mutual respect, peaceful coexistence and… cooperation as principles for handling China-US relations remains unchanged,” he added.

The Chinese president then said the country is “ready to work with the new US administration to maintain communication, expand cooperation and manage differences, so as to strive for a steady transition”.

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Neither Mr Xi nor Mr Biden responded to a question about whether there were concerns about Mr Trump’s proposed tariffs.

The president-elect has also named several China hawks to his transition team, such as Senator Marco Rubio as secretary of state and Representative Mike Waltz as national security adviser.

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Under Mr Biden, Washington has introduced restrictions on US investment in Chinese artificial intelligence, quantum computing and semiconductors.

Former house speaker Nancy Pelosi also visited the island of Taiwan – which China views as a breakaway province – in April 2022.

In their meeting at this time last year – which followed a surge in tensions when an alleged Chinese spy balloon was shot down over the US – both leaders said direct communication between American and Chinese military forces would be restored.

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Mike Tyson reveals he ‘almost died’ ahead of fight with YouTuber-turned-boxer Jake Paul

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Mike Tyson reveals he 'almost died' ahead of fight with YouTuber-turned-boxer Jake Paul

Former heavyweight champion Mike Tyson says the health scare in June, which forced the postponement of his boxing match with Jake Paul, almost cost him his life.

“I almost died in June,” Tyson wrote on X, adding that he “had 8 blood transfusions. Lost half my blood and 25lbs in hospital”.

The 58-year-old, who lost to the YouTuber-turned-boxer in a unanimous points decision in Texas, tweeted that the situation was far worse than people had realised.

Following Tyson’s recovery, after reportedly suffering an ulcer flareup, he reflected on the result of the fight.

“This is one of those situations when you lost but still won… no regrets to get in the ring one last time,” he said.

That contrasts with Tyson’s comments after the match in which he refused to confirm whether it would be his last fight.

“It depends on the situation,” Tyson said before suggesting a fight with Paul’s older brother, Logan Paul, who was standing near him in the ring.

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Critics argued that the revised match – which involved fewer and shortened rounds, as well as heavier gloves – fell short of entertaining.

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Paul beats Tyson by unanimous decision

Some claimed it appeared more like a glorified sparring session.

It was Tyson’s first sanctioned pro bout since 2005, when he lost to Kevin McBride and then went into retirement – only briefly reappearing for an exhibition match in 2020 against Roy Jones Jr.

Jake Paul is driven to the ring before a heavyweight boxing match against Mike Tyson, Friday, Nov. 15, 2024, in Arlington, Texas. (AP Photo/Julio Cortez)
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Jake Paul believes he can fight for a championship belt within two years. Pic: AP

Paul has plenty to prove

Paul, 27, still has plenty to prove. The social media influencer wants to be a championship fighter and compete for a championship belt within two years. “I think it could happen in the next 24 months,” Paul said.

“I truly, truly believe in my skills and my ability and my power. And the cruiserweight division is seemingly open for the taking on that timeline,” he added.

The only professional match he has lost so far has been to Tommy Fury, the less-accomplished brother of former heavyweight champion Tyson Fury.

But there are questions about when Paul will fight a contender in his prime, as opposed to former champions or mixed martial artists.

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Could Paul really take on Alvarez?

Intriguingly, in the days before his fight with Tyson, Paul mentioned super middleweight champion Canelo Alvarez, considered one of the best boxers in the world.

According to reports, the Texas bout earned Paul $40m (£31.7m) versus $20m (£15.8m) for Tyson.

Netflix said 60 million households worldwide viewed the contest on its streaming platform, and nearly 50 million tuned in to watch the undercard which saw Ireland’s Katie Taylor beat Puerto Rico’s Amanda Serrano.

Even so there were some technical glitches. More than 90,000 users reported problems on Netflix at its peak, according to the website Downdetector, which tracks outages.

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