According to the state report, the distribution of industrial enterprises among sanitary and epidemiological safety groups in 2018 compared to 2015 changed. There is a slight increase in the share of enterprises of group I (satisfactory) with a simultaneous reduction of enterprises of group III (extremely unsatisfactory) and group II with its industrial enterprises of unsatisfactory sanitary and epidemiological well-being [1, 2].
The share of industrial enterprises of the 1st group of sanitary and epidemiological well-being consistently increased from 25.03% in 2012 to 27.48% in 2021, while the share of industrial enterprises of the 3rd group of sanitary and epidemiological well-being decreased accordingly from 10.23% in 2012 to 7.13% in 2021
The share of enterprises of groups II and III of sanitary and epidemiological safety, the workplaces of which for the most part do not meet the requirements of sanitary and epidemiological rules and regulations, continues to remain significant - 72.53%.
At the same time, the share of newly diagnosed occupational diseases during periodic medical examinations is steadily decreasing - from 69.7% in 2013 to 58.13% in 2021, while with active treatment there is an increase in the proportion of newly diagnosed diseases - from 30.3% in 2013 to 41.87% in 2021
The frequency of occupational injuries from exposure to physical factors and functional overstrain remains quite high. A significant place among these lesions is occupied by diseases of the musculoskeletal system of occupational origin, the development of which may be associated with the effects of physical overload, general vibration, and functional overstrain [3].
The leading place in this nosology is occupied by vertebrogenic syndromes caused by degenerative-dystrophic changes in the cervical and lumbosacral localization, in particular spondyloarthrosis, such as muscular-tonic, compression-radicular. Vertebrogenic pathology is also included in the structure of vibration disease from exposure to general vibration (radiculopathy of the lumbosacral level) [4, 5].
According to the modern list of occupational diseases, the syndrome of vertebrogenic diseases from physical overload and functional overstrain is as follows [6]:
4.4.1. Muscular-tonic (myofascial) syndrome of the cervical level M53.1.
4.4.2. Radiculopathy (compression-ischemic syndrome) of the cervical level M 54.1.
4.4.3. Myeloradiculopathy of the cervical level M 53.8.
4.4.4. Muscular-tonic (myofascial) syndrome of the lumbosacral level M 54.5.
4.4.5. Radiculopathy (compression-ischemic syndrome) of the lumbosacral level M 54.3.
4.4.6. Myeloradiculopathy of the lumbosacral level M 53.8.
Vertebrogenic syndrome in the structure of vibration disease:
2.6.2. Vibration disease (T75.2) associated with exposure to general vibration:
- manifestations: peripheral angiodystonic syndrome (including Raynaud's syndrome), polyneuropathy of the upper and lower extremities, including with sensory and autonomic-trophic disorders, polyneuropathy of the extremities in combination with radiculopathy of the lumbosacral level, cerebral angiodystonic syndrome.
Taking into account the age of patients with vibration disease and occupational diseases of the musculoskeletal system, obligate morphological changes in the spine are arthrosis of the facet joints (spondyloarthrosis, facet syndrome), mainly in the cervical and lumbosacral regions. Therefore, an obligatory component of pathogenetic treatment is the use of chondroprotectors along with the prescription of non-steroidal anti-inflammatory drugs and muscle relaxants.
The purpose of the study is to study the effectiveness of the drug Alflutop in the treatment of patients with occupational vertebrogenic pathology in the structure of vibration disease and from physical overload and functional overstrain (as a chondroprotector) in accordance with the instructions for use (registration certificate No. 012210/01 dated 05.10.17) with analysis severity of pain syndrome, motor activity of patients.
One of the most famous, widespread, used in practical medicine for many years and has repeatedly proven its effectiveness in the treatment of joint diseases is the drug Alflutop. The drug is an injection solution. The active component is a bioactive concentrate from small sea fish. The concentrate contains mucopolysaccharides (chondroitin-4 and 6-sulfate), amino acids, peptides, sodium, potassium, calcium, magnesium, iron, copper and zinc ions, glucuronic acid. The results of clinical studies prove the main effects of Alflutop: chondroprotective; anti-inflammatory; improved joint function and mobility; increase in the thickness of the cartilage of the articular surface; reducing the dose of non-steroidal anti-inflammatory drugs (NSAIDs) taken; restoration of the level of prostaglandins in the gastric mucosa, reduced while taking NSAIDs. The effectiveness and safety of Alflutop in the treatment of patients with vertebrogenic pathology has been demonstrated in a number of clinical studies by domestic and foreign authors [7, 8].
Material and methods
The case histories of 87 patients with spondyloarthrosis in the structure of occupational pathology of the musculoskeletal system from physical overload and functional overstrain were retrospectively assessed. All patients underwent clinical and physiological examination. Duration of observation: 5 years (2013–2017).
Inclusion criteria: age 18 years and older, presence of facet syndrome at the lumbosacral and/or cervical level, confirmed by neuroimaging, and signed informed consent.
Exclusion criteria: contraindications in accordance with the instructions for use of the drug Alflutop, taking chondroprotectors for 1 month before inclusion in the study. During hospital observation, patients did not take NSAIDs or analgesics. Additionally, B vitamins, muscle relaxants (tizanidine or tolperisone), metabolites were prescribed, physiotherapy was carried out according to indications (sinusoidal modulated current therapy, diadynamic therapy, electrophoresis of drugs, for example halidor), massage.
All observation cases were divided into two groups: group 1 consisted of 31 patients (20 women, 11 men), group 2 - 56 patients (25 women, 31 men). In group 1, Alflutop was injected 10 times paravertebrally into four points at the lumbosacral level (2 ml) or into two points at the lumbosacral level (1 ml) and two points at the cervical level (1 ml). In group 2, Alflutop was administered 10 times intramuscularly, 1-2 ml deep.
Demographic information is shown in the table.
Group Demographics
Of the peculiarities in the groups, it is worth noting that among the patients of group 1, 3 women and 5 men suffered from vibration disease, the remaining 23 patients suffered from muscular-tonic and radicular compression syndromes of the cervical and/or lumbosacral level. In all patients, neuroimaging reveals spinal spondyloarthrosis.
In group 2, 8 patients were diagnosed with vibration disease with radiculopathy of the lumbosacral level, the remaining 48 patients had diagnosed muscular-tonic and radicular compression syndromes of the cervical and/or lumbosacral level. Neuroimaging revealed spinal spondyloarthrosis in all patients.
All patients underwent a standard neurological examination. The main tool for pain assessment was the visual analogue scale (VAS). The number of exacerbations of back pain over 1 year was also assessed.
For statistical analysis, the R software package was used (The R Project for Statistical Computing, https://www.r-project.org). All statistical tests were two-sided, with a significance level of 5%; all confidence intervals (CIs) were two-sided 95%; Continuous data are represented by the number of observations, mean with standard deviation (SD), median (Me) and range; discrete quantities are described by absolute and relative frequencies.
International application experience
For control, we will use the well-known non-steroidal anti-inflammatory drug meloxicam, a selective COX-2 inhibitor, which has been successfully used for a long time, including as a drug for the treatment of intervertebral hernias. The US National Library of Medicine website contains 2,065 links to articles, clinical trials, reviews, protocols and other resources related to research on meloxicam, the original drug of which is Berlin-Chemie's Movalis.
What is known on this authoritative international medical website about Alflutop? Only 9 articles were found on PubMed (https://www.ncbi.nlm.nih.gov/pubmed/?term=Alflutop) All these articles were published in domestic Russian journals, and these journals were published in Russian. The first publication about Alflutop is dated 2001, the latest - 2021. It is very important that all these articles are devoted to the use of this remedy for any pathology. For example, “Alflutop in local therapy of brachial periarthritis.” Accordingly, all this cannot claim to be a solid study with a high level of evidence: A, B, or at least C. Alflutop does not have a single serious study according to international standards. It is unknown in other countries.
A simple conclusion can be drawn from this. International medical science is not interested in this drug, does not consider it worthy of using it, or studying its effects. Why is this drug used in the Russian Federation, and why is it quite expensive, and unreasonably expensive?
Results and discussion
When analyzing the clinical picture of the disease, syndromes of cervicalgia, lumbodynia, and radiculopathy at the lumbosacral level were identified in most patients.
When assessing pain, a significant decrease in the severity of pain was noted over 5 years in all study groups, but especially in the 1st group. Thus, in group 1 pain was assessed:
— by 8 points in 2013, 11 people, in 2014, 1 patient, in the next 3 years, not a single patient had 8 points on the VAS scale;
— by 7 points in 2013 13 patients, in 2014 6, in 2015 3, in 2021 2; in 2021, this level of pain was not noted in any patient;
— pain was rated 6 points in 2013 by 7 patients, in 2014 by 18, in 2015 by 13, in 2021 by 12, in 2021 by 3.
It is worth noting that in 2021, 20 patients already rated pain on the VAS as less than 5 points (Fig. 1)
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Rice.
1. Dynamics of pain severity according to VAS in group 1. Thus, during the observation period, there was a redistribution of patients from groups with severe pain syndrome (6-8 points) in favor of groups with less severe pain syndrome (less than 5 points).
In group 2 (intramuscular administration of Alflutop) there was also a decrease in the severity of pain during observation:
— 6 patients assessed pain as 8 points in 2013, 2 in 2014; in subsequent years, no one had 8 points on the VAS scale;
— pain syndrome was reported as 7 points in 2013 by 36 patients, in 2014 7 points were recorded in 34 people; in 2015 - 30, in 2016 - 18; in 2021, a pain level of 7 points was not noted in any patient;
— pain was rated 6 points in 2013 by 14 people, in 2014 by 20, in 2015 by 20, in 2021 by 26, in 2021 by 26;
— pain was rated below 5 points in 2015 by 6 patients.
It is noted that in 2021, already 13 people rated their pain as less than 5 points (Fig. 2)
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Rice.
2. Dynamics of pain severity according to VAS in group 2. Thus, in group 2 there was also a redistribution of patients from groups with severe pain syndrome (6-8 points) in favor of groups with less severe pain syndrome (less than 5 points).
It is also worth noting that in the group of patients in whom Alflutop was administered paravertebrally (group 1), the average pain score in 2013 was 7.1 points, in 2014 - 6.1 points, in 2015 - 5. 9 points, in 2021 - 5.3 points, in 2021 - 5.1 points, i.e. there was a decrease in the average severity of pain within 3 points.
In the group of patients who received Alflutop intramuscularly, the average pain score in 2013 was 6.9 points, in 2014 - 6.7 points, in 2015 - 6.4 points, in 2021 - 6.1 points , in 2021 - 5.2 points, i.e. there was a decrease in the average severity of pain within 1 point (Fig. 3)
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Rice.
3. Dynamics of the average pain value according to VAS by group. When assessing the number of exacerbations of back pain in patients of both groups, a tendency to decrease was revealed throughout all years of observation.
Thus, in group 1, the largest number of exacerbations (6) per year in 1 patient was registered in 2013 in 3 patients. In subsequent years, such a frequency of exacerbations was not recorded in anyone. In the same year, 4 exacerbations were registered in 17 patients, 3 in 11. In 2014, the largest number of exacerbations (5) were in 4 patients, 4 in 15, 3 in 10, 1 in 2. In 2015 d. 5 exacerbations were registered in 1 patient, 4 in 10, 3 in 14, 2 in 5; 1 patient had no exacerbations within a year. In 2021, the largest number of exacerbations (4) was recorded in 2 people, 3 in 19, 2 in 10. In 2017, the largest number of exacerbations (3) was registered in 7 patients, 2 in 16, 1 at 8 ( Fig. 4)
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Rice.
4. Dynamics of the frequency of exacerbations per year in group 1. Thus, the average number of exacerbations per year in the group of patients in whom Alflutop was administered paravertebrally was 3.8 cases in 2013, 3.6 in 2014, 3.1 in 2015, 2.7 in 2021 , in 2017 1.9; i.e., it has decreased by almost 2 times over 5 years.
In the 2nd group of patients, the largest number of exacerbations per year (6 exacerbations) was registered in 2013 in 26 patients. In the same year, 11 patients had 5 exacerbations, 8 had 4, 11 had 3. In 2014, 12 patients had 6 exacerbations, 23 had 5, 15 had 4, 3 had 3, 2 had 3. In 2015, 6 exacerbations were registered in 10 patients, 5 in 24, 4 in 11, 3 in 8, 2 in 3. In 2021, 6 exacerbations were in 7 people, 5 in 18, 4 — in 21, 3 — in 7, 2 — in 3. In 2021, 6 exacerbations were in 4 patients, 5 — in 9, 4 — in 27, 3 — in 12, 2 — in 4 ( Fig. 5
).
Rice.
5. Dynamics of the frequency of exacerbations per year in group 2. Thus, the average number of exacerbations per year in the group of patients who received Alflutop intramuscularly was 4.9 cases in 2013, 4.7 in 2014, 4.5 in 2015, 4.3 in 2021 , in 2017 3.9; i.e., it decreased by 20% over 5 years (Fig. 6)
.
Rice. 6. Dynamics of the average number of exacerbations per year.
Contraindications, side effects, overdose
Alflutop has a standard set of contraindications attached to it, which do not say anything about the effect of the drug, but simply repeat the most common categories of patients for all drugs. It is contraindicated:
- with increased sensitivity to components (this, in principle, can be written about ordinary water, since even water can cause itching);
- in pregnant and lactating women (this is a classic);
- in children under 18 years of age (the instructions indicate: due to lack of clinical data).
Before talking about clinical data at the third stage of drug research, it is advisable to conduct more fundamental studies: pharmacodynamics and pharmacokinetics. They are in the instructions for every normal, “self-respecting”, well-studied remedy. This is data about how the drug behaves in the body, what its half-life is, and how it is metabolized. In the case of Alflutop, not a word is said about this.
And how can we talk about pharmacodynamics and kinetics in general when we are not dealing with any one chemical substance, as in the case of meloxicam or ketoprofen. We are dealing with hundreds of types of organic molecules that add up to the extraction products of marine organisms.
Naturally, such drugs have been used for a very long time, and we will not find fault with Alflutop alone. Thus, mud therapy has been known for many tens and even hundreds of years. Therapeutic mud is used not only externally, but it is also administered in rectal and even vaginal tampons. But still, it’s one thing to use peloid therapy as a component of physiotherapy already at the stage of clinical remission, in a sanatorium. And it’s a completely different matter to prescribe a biological drug intramuscularly in the acute stage.
As for side effects, the official instructions indicate redness of the skin and burning at the injection site. This is natural, because in fact, large, including immunogenic, residues of protein molecules can be introduced; an allergy can also be to a preservative, namely phenol. Nothing is said here about any specific active ingredient of the medicine, because it simply does not exist.
No interactions with medications were detected, again due to the lack of active substance in Alflutop. About overdose it is said that “dose-dependent adverse drug reactions increase.” What this means is unclear. In the case of Movalis, there is a maximum single and daily dose, and an overdose leads to specific symptoms due to the mechanism of action. Everything here is extremely foggy.
In the “special instructions” there is a note that if the patient has an individual intolerance to seafood, there will be a risk of allergic reactions. Thus, the manufacturer does not even deny that the ampoules contain not even a deproteinized hemoderivative (as in Actovegin), but an incomprehensible mixture of various residues. Although the instructions say that the technological process includes “deproteinization,” that is, the elimination of proteins. Then why, if there are no proteins, is an allergic reaction possible?
Cost and analogues
Alflutop does not have analogues or generics, like serious imported drugs, for example, Movalis and Voltaren, which successfully eliminate pain from hernias. Alflutop is available as an injection solution:
- in ampoules of 1 ml, in a package - 10 ampoules;
- in ampoules of 2 ml, in a package - 5 ampoules.
The total volume of packaging in both cases is 10 milliliters. The dosage is 0.01 dry matter per ml. Alflutop is produced by a foreign, Romanian manufacturer, Rompharm Company Biotechnos. There are some variations, for example, Alflutop also produces Zentiva, but also in Romania. In general, all Alflutop entering the domestic market is produced exclusively in Romania. And this is clear, because Romania produces a lot of Black Sea fish.
One package of ampoules of one milliliter costs from 1266 rubles to 1600 rubles, and a package of 2 ml will cost from 1530 to 1782 rubles. Prices are valid for July 2021 for pharmacies of all forms of ownership in the Russian Federation.
Hernia on MRI.