Cryotherapy: Very Few Proven Benefits but Very Real Side Effects

©Photo by Scott Rodgerson on Unsplash

In 2010, Inserm and the French Directorate-General of Health signed a partnership agreement to evaluate the health benefits of various forms of alternative medicine practiced in France. In a new report published today, researchers from Inserm focused on cryotherapy, a technique in which the body is exposed for 2 to 3 minutes to intense cold ranging from -110 to -170 °C.

Originally intended for high-level athletes in order to prevent or treat muscle pain after exercise, this practice is now proposed in inflammatory and neurological diseases, and even when there is no disease.

Following analysis of the scientific literature and accounts by experts and patients, the Inserm report concludes that the findings supportive of a positive effect of cryotherapy are modest and had only been measured on a very short term basis.

Furthermore, given the shortcomings in the methodology of the existing studies, the researchers feel that “the positive effects reported must be kept in perspective,” warning that “in any case, cryotherapy can in no way claim to effectively treat cancer or other severe somatic diseases“.

According to the researchers, whole-body cryotherapy also poses genuine safety concerns. Very real side effects have been reported, including burns, headache and chronic cold urticaria. Finally, the report concludes that better quality studies and evaluations of this technique are essential, and that the conditions required to perform these will need to be made possible.

Orthoptic Training and Reduced Screen Exposure: A Winning Combination for Treating Vergence Disorder-Induced Dizziness in Children

boy and girl standing in front of laptop

© stem.T4L on Unsplash

In order to see objects clearly, our eyes need to be able to work together by superimposing the images perceived by each eye: by rotating inwards (convergence) when the object is close, and by releasing this convergence when switching to object farther away. This ability of our eyes to perform symmetrical and coordinated movements (at the same speed and amplitude) is called binocular vergence. Vergence disorders or orthoptic disorders are therefore characterized by poor coordination of the two eyes. In children, these can generate incapacitating symptoms (dizziness, instability, difficulty reading, etc.) which can be responsible for school absenteeism and learning difficulties.

A team of researchers led by Sylvette R. Wiener-Vacher (AP-HP practitioner) and Maria Pia Bucci (CNRS researcher) in Unit 1141 NeuroDiderot: Neurodevelopmental and neurovascular diseases (Inserm/Université de Paris), had previously shown that children presenting with dizziness and normal neurological and vestibular[1] examinations should be screened for vergence disorders. Their latest research, published in Frontiers in Integrative Neuroscience, shows that dizziness linked to vergence disorders in children could be treated by a combination of orthoptic training and reduced screen time.

Over a 3-year period, the research team evaluated the efficacy of orthoptic training in children referred to the ENT Department of Robert-Debré hospital – AP-HP for dizziness. Forty-nine children presenting with vergence insufficiency as sole cause of their symptoms were enrolled in this study, along with 109 healthy control children. Each child was followed up for 9 months and underwent orthoptic evaluation (vergence capacity tests) as well as recordings of the eye movements at various stages of the study: before and 3 months after the start of orthoptic training, and 6 months after the end of the training. The researchers also advised all children to reduce their use of video screens which was intensive (~ 3.6 h per day) and which appeared as a potential aggravating factor. 

In all patients, the dizziness disappeared after the end of the orthoptic training and all eye movement parameters improved significantly.  Six months after the end of the training, this improvement remained stable or continued.

These findings indicate that orthoptic treatment, when combined with instructions to reduce screen time, shows a significant long-term effect on the symptoms of dizziness and on the oculomotor performance of the children being monitored.

“These new findings could have a positive effect on the recognition of the efficacy of orthoptic training, which remains controversial”, specify the authors.

The results of this study also suggest that intensive screen use can aggravate pre-existing latent orthoptic problems, with the researchers specifying that “Today many children are exposed to small video screens for long periods of time. The increasing prevalence of symptomatic vergence insufficiency that we observed could be explained by this lifestyle. ” The authors recommend the inclusion of orthoptic training in clinical tests for children suffering from dizziness as well as reduced exposure to video screens, particularly for children presenting vergence disorders.

[1] The vestibule is part of the inner ear which is involved in maintaining balance.

Apparent age of the elderly : a diagnostic tool for primary care physicians?

To estimate the health of their elderly patients, healthcare professionals have various clinical tools at their disposal: geriatric assessment scales, health questionnaires and frailty scores. However, although these tests are appropriate to a medical context, they are more difficult for primary care physicians (PCPs) to implement because they require time and equipment that they do not necessarily possess. When evaluating the general health of an elderly patient, the PCP will first go on their detailed knowledge of him or her as well as the various signs observed during the consultation (physical appearance, gait, etc.).

The objective of the S.AGES cohort[1] was to describe between 2009 and 2014 the medical and paramedical management of patients over the age of 65 using a database generated by PCPs. Practitioners throughout France were enrolled to participate in this study involving the 3-year follow-up of some of their non-institutionalized patients presenting with a satisfactory state of health. In addition to collecting social, demographic and medical data, each PCP was asked to categorize their patients by their apparent age in response to the following question: “In your opinion, does your patient look younger or older than their age or do they look their age? “.

It was on the statistical analysis of the responses to this question that Inserm researchers from the Center for Research in Epidemiology and Population Health focused their attention. The objectives of this study were to analyze the characteristics associated with the PCPs’ estimations and to determine whether these made it possible to predict death within the 3-year follow-up period

The researchers observed that heart problems, depression, obesity, and low levels of autonomy in activities of daily living were primarily linked to patients whose estimated age was higher than their actual age, whereas high levels of education, normal levels of autonomy, lack of depression, lack of vascular problems and chronic hypertension, and low levels of medication were associated with patients who looked younger than their age. Only two variables impacted apparent age in either direction: quality of autonomy and the presence/absence of depression.

Of the patients who died during the 3 years of follow-up: 7.5% belonged to those who looked younger, 8.7% to those who looked their age and 13.8% to those who looked older. It can therefore be taken away from this study that patients who look older present an increased risk of mortality: the age estimation performed by the PCPs is therefore significantly linked to mortality risk.

These results suggest that such age evaluation could be represent a relatively reliable tool in the daily practice of PCPs when estimating the general health of patients. This does not mean replacing the frailty scores but using the practitioner’s clinical sense to support the diagnosis.

[1] The S.AGES cohort was funded by Sanofi and approved by the Ile de France XI ethics committee and the French medicines and health products safety agency

Repurposing Drugs to Fight the Flu: a Phase 2 Clinical Trial for FLUNEXT


The VirPath team from the International Center for Infectiology Research (CIRI, Inserm Unit 1111 – CNRS Joint Research Unit 5308  – ENS Lyon – UCBL1), in collaboration with the laboratory of Dr. Guy Boivin (Canada Research Chair in Emerging Viruses, Infectious Diseases Research Center of the University Hospital of Quebec – Université Laval), has developed and validated an innovative strategy which involves the identification and direct exploitation of clinical samples from infected patients in order to select and use drugs marketed for the treatment of other viruses. A strategy known as “drug repurposing”. This program has been funded by Inserm, the French Directorate of Health Care Supply (DGOS), the French National Research Agency, the Auvergne Rhône-Alpes region, Université Claude Bernard and Université Laval.

This novel and accelerated bedside-to-bench and bench-to-bedside approach is particularly well-suited to acute respiratory infections because it enables the identification and rapid validation of new generations of antivirals which are more effective and treat a broader spectrum of diseases. In addition, the regulatory and financial benefits of this drug repurposing strategy are evident when compared with the long and very costly traditional new-drug development process. The team’s Drug Discovery platform has already demonstrated its potential (three international patents protecting eight repurposed drugs) with the identification of diltiazem (Tildiem®) – usually used in heart pathologies – as an anti-infectious agent in flu viruses.

On the basis of these findings, a phase 2 clinical trial, called FLUNEXT, led by Manuel Rosa-Calatrava, Inserm researcher and Julien Poissy (Inserm Unit 995, Lille Inflammation Research International Center) of Lille University Hospital, began in January 2018. The objective of this national trial is to evaluate the effects of diltiazem in combination with an antiviral, oseltamivir (Tamiflu®), for the treatment of severe flu infections. It intends to enroll 300 patients in ten intensive care units, over two periods of flu epidemic, with final results expected in 2019.

The validation of this strategy and the results already obtained have led to the creation of a startup called Signia Therapeutics. The laboratory’s research program will now be extended to include other respiratory diseases, such as human respiratory syncytial virus and human metapneumovirus, responsible for severe respiratory infections in young children and the elderly.

For more information on the VirPath team and CIRI:

The VirPath website

The CIRI website

Drug overconsumption in pregnant women in France


Pregnancy is a sensitive time, particularly in the first months. Pregnant women are therefore strongly advised to limit their use of medicines, as some of their effects are yet poorly known. Nevertheless, a recent study conducted by Inserm researchers from Unit 1181 “Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases”, reveals that pregnant French women are among the largest consumers of drugs worldwide with around ten medicines prescribed during pregnancy. A rate which remained stable throughout the period analyzed (2011-2014).

In the 28,500 women studied, this research reveals that out of the recommended medications, the consumption of antianemia products greatly exceeded the actual prevalence of anemia (72.5% for around 25%). Between 2011 and 2014, the consumption of recommended vitamins (B9 and D) increased by 10% whereas the percentage of women receiving the influenza vaccine increased by only 1%. More worryingly, the exposure to medicines with fetotoxic effects (impairing fetal organ growth and function) and teratogenic effects (causing malformations), while being low, was still too high.

Finally, according to the researchers: “the situation of low-income pregnant women is of additional concern because of their higher average consumption of drug except for recommended vitamins. “

This research was published in Pharmacoepidemiology and Drug Safety.

Benefits of Unit-Dose Antibiotic Sale

Between November 2014 and November 2015, a study conducted by Inserm (Unit 912 SESSTIM – Economic and Social Sciences, Health Systems and Medical Informatics), Université Aix-Marseille, IRD, CNRS and the PACA Regional Health Observatory, trialed the unit-dose dispensing of certain antibiotics across four regions in France. Out of 100 volunteer pharmacies, 75 pharmacies were randomly selected to offer unit-dose dispensing of treatment to patients with a prescription stating one or more of the 14 antibiotics concerned. The results of this trial, published in PLos ONE on September 19, 2017, are as follows:

  • Acceptability of unit-dose dispensing of antibiotics (UDD): 80% of patients with a prescription for an antibiotic treatment concerned by the trial agreed to unit-dose dispensing.
  • Impact on the volumes of medicinal products dispensed: deconditioning was necessary for 60% of patients exposed to unit-dose dispensing. The unit-dose dispensing method reduces the volume of tablets dispensed by approximately 10%, compared to traditional sale.
  • Proper use of treatments: The unit-dose dispensing method prevents the problem of improperly recycled tablets (this is the case for 13% of prescribed antibiotics observed in the study). Lastly, unit-dose dispensing of antibiotics is associated with improved patient adherence to the prescription, according to the measurement of ‘compliance’ based on the number of unused tablets remaining at the end of treatment.

13/11 attacks: young people deeply marked

One year after the 13 November attacks, the survey “Conditions de vie et Aspirations” (Living Conditions and Aspirations) by CRÉDOC (Research Centre for the Study and Monitoring of Living Standards), part of the 13 Novembre programme initiated by Inserm, CNRS and héSam Université, reports on the strong impact of the attacks on the French population, particularly the young.

A sample of 2,000 people representative of the French population responded to a series of questions such as “Can you say which terrorist acts, committed in the world or in France, have affected you most since the year 2000? What are the main consequences of the attacks that occurred on 13 November 2015?”

From this survey, we particularly learn that:

80% of French people say they have been marked by the attacks of 13 November 2015, even though three quarters of them have no personal link to the victims or places involved.
65% of 18-24 year olds and 63% of 25-39 year olds show strong feelings of fear, compared with 54% of people above that age range
The existence of cultural and religious tensions within society is the reason most often invoked to explain the attacks, and for nearly 40% of the population, they are inexplicable acts.
26% of French people have a personal link to the events (victim, witness, familiarity with the places), and 25% consider that there is too much talk about the 13 November.

Note: the interviews took place before the attacks in Nice on 14 July, and before those in Saint-Étienne de Rouvray on 26 July 2016.

Centenarian athletes: flawless performances?

When the upcoming 2016 Summer Olympics are held, some centenarian athletes will be able to witness this competition, 80 years after their own participation for some of them. An Inserm study conducted by researchers from Unit 1093, “Cognition, Motor Activity and Sensorimotor Plasticity,” at the University of Burgundy, analysed the records of centenarian athletes in various disciplines compared with world records, for all age categories combined. The record of centenarian cyclist Robert Marchand, who cycled nearly 27 kilometres in an hour, appears to be the most impressive, since the reduction in his performance is quite limited given his age.


(c) Fotolia

Previous studies have essentially demonstrated that, from the age of 40, and depending on the sport, performances decline steadily by 7–14% every 10 years. Using data from websites of sports associations and federations, Romuald Lepers and his colleagues identified 60 performances by 19 centenarians, in 3 disciplines: athletics, swimming and cycling. Generally, and although they show genuine prowess, their results are obviously very far from being world records: – 78% on average for centenarians compared with the world record. The performance of centenarian Robert Marchand in cycling is exceptional, since he shows only 50.6% of a reduction in his performance, compared with the current world record in this discipline, obtained by Bradley Wiggins in 2015, with over 54 kilometres.


By way of comparison, Robert Marchand cycles half as fast as the record holder in his discipline, whereas other centenarian athletes run or swim at an average of a quarter of the speed. Although these differences seem large, they correspond to genuine exploits.

“Can you imagine achieving these performances at over 100 years of age?” emphasises Romuald Lepers, the main author of this publication.

In addition to Robert Marchand’s remarkable physiological characteristics for his age, the researchers also demonstrated a smaller age-related decline in performances for cycling compared with athletics or swimming.


This work, published in the journal Age and Ageing on Monday 4 July 2016, offers new perspectives for improving our understanding of how the human body can resist the deleterious effects of ageing.

Academic Doping: Psychostimulant Use Among Medical Students

Under severe pressure owing to an intense workload, medical students are attempting to boost their performance by any means. An Inserm study has revealed possible psychostimulant use among a third of these students.

A population of 1,718 French medical students (average age 27 years, 37% male) was interviewed on the subject of psychostimulant use. Inserm researchers recorded the participants’ motives, together with their sociodemographic and academic characteristics.

Among those interviewed, 33% use psychostimulants (29.7% take over-the-counter medicines, 6.7% prescription medicines, and 5.2% illegal drugs). For the majority of students using over-the-counter substances (energy drinks and caffeine-based products), the aim is to enhance memory and concentration in preparation for exams. This type of use is, however, predictive of subsequent medically prescribed psychostimulant use. Out of these products, corticosteroids take the lead (4.5%), followed by methylphenidate and modafinil.

According to the study results, there is a high probability that public health recommendations aiming to restrict the prescribing of methylphenidate and modafinil are indeed effective.  These substances are therefore used to a lesser extent by students who fall back on corticosteroids, which are easier to access.  According to the researchers, this constitutes a new public health problem given the potential severe side effects of these substances.

Final results of JIKI trial

The final conclusions of the JIKI clinical trial, testing the efficacy of favipiravir in reducing mortality in individuals infected by Ebola virus in Guinea, are published in PLoS Medicine this week. This work was carried out under the leadership of Prof. Denis Malvy, Inserm, with the help of a large team of international researchers. Although the conclusions are qualified, they have nonetheless made it possible to collect data and benchmarks that will enable researchers to base their future trials on robust hypotheses and criteria.


Ebola fever is an extremely lethal disease, for which there is no proven effective treatment. In September 2014, at the height of the epidemic, the World Health Organisation released a shortlist of drugs suitable for studies on Ebola virus (EBOV) disease, including favipiravir, an antiviral drug developed for the treatment of severe forms of influenza. An international team under the auspices of Inserm carried out a study called JIKI (meaning “hope” in the Malinke language) in Guinea. The goal of the study was to test the feasibility and acceptability of an emergency trial carried out during a large epidemic of Ebola virus disease, and to collect preliminary data on the safety and efficacy of favipiravir in reducing mortality and viral load in patients with Ebola virus disease. Because of the exceptional circumstances of the recent epidemic of Ebola fever, the study was a pilot, proof-of-concept, non-randomised, multicentre trial, with a so-called historical comparator group, in which 126 participants received favipiravir in addition to standard basic care.


According to the results of the study, it is unlikely that favipiravir monotherapy is effective in patients presenting with very high viraemia, but the drug deserves continued evaluation in patients presenting with intermediate to high viraemia. This conclusion is based on two results—the mortality rates observed, and the dynamics of the EBOV RNA load during treatment.

In patients presenting with very high viraemia, mortality was 7% higher than the pre-trial value, and the viral load did not decrease. This suggests that a future trial is unlikely to demonstrate any benefit of favipiravir in these patients

In patients with lower viraemia, mortality was 33% lower than the pre-trial value, and the viral load decreased rapidly with treatment. The trial was non-randomised, and the 95% confidence interval included the pre-trial value. As a result, the present findings do not prove that favipiravir was effective in these patients, but they do suggest that the question remains open, and provide an indication on how to better address it.

The authors conclude, “In the middle of a health crisis such as an epidemic of Ebola fever, researchers can be faced with a situation in which random assignment of patients to groups receiving standard care or standard care plus an experimental treatment is not acceptable from an ethical point of view. In these rare circumstances, it may be decided not to conduct a trial, but to wait for more favourable circumstances, or to conduct a non-randomised trial. In this pilot experiment, we chose this second option. Our conclusions are qualified. On the one hand, we cannot draw conclusions on the efficacy of the drug, and our conclusions regarding tolerance, although encouraging, cannot be as definite as they would have been with randomisation. On the other hand, we have learned a great deal on how to define and conduct a trial under such unusual circumstances, working closely with the community and non-government organisations. We incorporated research work on care, so that care can be improved; we rapidly generated interim data useful in designing studies on Ebola fever, and shared them with the scientific community; and we collected evidence enabling researchers to base their future trials on solid preliminary hypotheses and criteria.