BACKGROUND: The contribution of random and regular factors in the process of epidemic hemorrhagic fever is unknown, which necessitates the search for the reasons for the formation of severe and fatal cases. AIM: Based on the incidence of epidemic hemorrhagic fever in Primorsky Krai over a long period, we aimed to establish the role of the main determinants of the epidemic process and to demonstrate the causality of local manifestations in epidemic foci in patients with epidemic hemorrhagic fever. MATERIALS AND METHODS: In this comprehensive descriptive epidemiological and clinical study, we undertook the epidemiological analysis of the incidence of epidemic hemorrhagic fever and data from examinations of the foci of infection. We performed a clinical observation (case study) of a case of epidemic hemorrhagic fever with a fatal outcome at the Regional Clinical Infectious Diseases Hospital in March 2022. The object of the study is statistical data on officially registered cases of epidemic hemorrhagic fever in Primorsky Krai from 1995 to 2021. RESULTS: The proportion of random factors in the epidemic process of epidemic hemorrhagic fever in the period under review was 28.7% of the incidence, which formed deviations from the typical curve, but did not participate in the formation of cyclicity in the long-term dynamics. Variable factors that formed cyclicity and random deviations together determined 53.4% of the incidence. They were fully related to seasonal morbidity (67.8%). Moreover, the remaining 14.4% of seasonality was formed by constant factors for each month. Factors constant for all months of the year form a year-round form, that is, 32.2% of the incidence. In the clinical and epidemiological observation of a lethal case of epidemic hemorrhagic fever, infection was noted under conditions of dust formation, such as when restoring order in a closed room at a negative temperature (sweeping) and high titers of specific antibodies resulting from repeated encounters with the pathogen in residential and occupational types of morbidity and the accompanying illnesses. CONCLUSIONS: The study of the incidence of epidemic hemorrhagic fever demonstrated a high resolution of epidemiological analysis by using a binary method in zoonoses. The patterns and features of human morbidity were controlled by natural and social factors more strictly than by biological ones. The determinants of the socio-ecological system in epidemic hemorrhagic fever in Primorsky Krai make it possible to specify the tactics and strategy for the implementation of epidemiological surveillance.

The paper presents an analysis of parasitological situation with paragonimiasis in Primorsky Krai over the past 30 years. In the early 1990s regular medical checkups detected paragonimiasis in 1–6% of the inhabitants of the region. Since 1996, the situation in the south of the Russian Far East has changed dramatically. Within 1–2 years, the crayfish population decreased significantly in watercourses from southern Primorye up to the Amur basin. Therefore, the incidence of the disease in population of the region has decreased to zero level since 2000. From 2014 the number of crayfish in watercourses of Primorsky Krai started growing. In 2019 the first patient with larval paragonimiasis was reported. The paper reviews the experience of the Regional Clinical Hospital of Vladivostok in treatment of 368 patients with larval paragonimiasis for the period from 1967 to 1996. On average, the disease manifested itself in 1–4 weeks from the moment of infection. The diagnosis was confirmed in 97.9% of cases via serological method. The praziquantel treatment of patients with larval paragonimiasis resulted in a cure rate of 89%. The disease duration ranged from 1–2 to 10 or more years.

BACKGROUND An important area of effective control of the coronavirus disease 19 (COVID-19) pandemic is the study of the pathogenic features of severe acute respiratory syndrome coronavirus 2 infection, including those based on assessing the state of the intestinal microbiota and permeability.AIM To study the clinical features of the new COVID-19 in patients with mild and moderate severity at the stage of hospitalization, to determine the role of hepatobiliary injury, intestinal permeability disorders, and changes in the qualitative and quantitative composition of the microbiota in the development of systemic inflammation in patients with COVID-19.METHODS The study was performed in 80 patients with COVID-19, with an average age of 45 years, 19 of whom had mild disease, and 61 had moderate disease severity. The scope of the examination included traditional clinical, laboratory, biochemical, instrumental, and radiation studies, as well as original methods for studying microbiota and intestinal permeability.RESULTS The clinical course of COVID-19 was studied, and the clinical and biochemical features, manifestations of systemic inflammation, and intestinal microbiome changes in patients with mild and moderate severity were identified. Intestinal permeability characteristics against the background of COVID-19 were evaluated by measuring levels of proinflammatory cytokines, insulin, faecal calprotectin, and zonulin.CONCLUSION This study highlights the role of intestinal permeability and microbiota as the main drivers of gastroenterological manifestations and increased COVID-19 severity.

Primorsky Region is an epidemic focus of hemorrhagic fever with renal syndrome , where the morbidity is caused by two orthohunts of the Hantaan virus (including its variant Amur) and Seoul. The average long-term morbidity rate in Primorsky Region for 10 years (2011-2020) accounted for 2.7 per 100 thousand people, (in some years up to 4.4 per 100 thousand people). The mortality rate made 3.2% (in 2018 – 9.1%). Distribution of the clinical forms of the disease for the last 10 years showed that moderate form of the disease is prevalent (66%), severe forms accounted for about 30% of all regional cases. A clinical case of severe hemorrhagic fever with renal syndrome, complicated by subarachnoid hemorrhage, gastric bleeding, acute renal failure, rupture of the kidney capsule and encephalopathy with hallucinosis of intoxication genesis is presented. The treatment resulted in the patient's recovery.

An effect of the antiviral drug Kagocel on the levels of metalloproteinases MMP-8 and MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 in induced sputum during treatment of community-acquired viral-bacterial pneumonia was analyzed. 60 adult patients with verified community-acquired pneumonia of viral-bacterial etiology were included in the follow-up monitoring. Materials and methods. All patients were randomly stratified into 2 groups: group 1 (comparison group) consisted of 30 patients receiving Ceftriaxone monotherapy; group 2 (main group) - 30 subjects who were prescribed Ceftriaxone and the antiviral drug Kagocel as etiotropic treatment. Both groups were comparable in gender, age and time of admission to the hospital. Results. During hospitalization, patients in both groups had elevated levels of MMP-8, MMP-9, TIMP-1 and TIMP-2 in induced sputum compared to the reference values. By 7 days of inpatient treatment, the level of MMP-8 was still significantly higher than the reference values in both groups, being in patients from group 2 it decreased compared to baseline values, whereas in patients from group 1, on the contrary, it was markedly elevated. The activity of MMP-9 during hospitalization was also high in patients from both groups compared with its level in healthy subjects. By day 7 of therapy, changes in various parameters were recorded. The level of MMP-9 in patients from group 1 increased, whereas in group 2 - on the contrary - decreased. The level of TIMP-1 decreased in patients of the 1st group below the control value, and in patients of the 2nd group - reached the reference values. The level of TIMP-2 decreased in both groups and reached that of in control group. Conclusion. Antiviral drug Kagocel being included in the standard antibacterial regimen of community-acquired viral-bacterial pneumonia reduces the level of MMR-9 and intensity in imbalance between MMP and TIMP parameters by 7 days of therapy, which leads to accelerated clinical recovery.

Background . The relationship between pathogens of new diseases and tick-borne infections is an underinvestigated direction in the problem of infectious diseases. The aim . To show the features of identifying the markers of Borrelia burgdorferi, tickborne encephalitis and SARS-CoV-2 pathogens on the example of a case of a triple mixed infection (Lyme disease, tick-borne encephalitis and COVID-19) and using comprehensive studies. Methods . In 2019–2021, a comprehensive study of 7 blood samples from a patient with mixed infection was carried out. We used real-time polymerase chain reaction (PCR), enzyme immunoassay (ELISA) and determined antigen, IgM, IgG antibodies, and avidity index (AI) of IgG antibodies. Results . Ixodid tick-borne borreliosis was diagnosed in a patient 5 months after contagion. Only high-avid Lyme-IgG antibodies were detected. Low-avid Lyme- IgG antibodies appeared against the background of a reduced general condition. At the same time, high-avid IgG (cut-off index (COI) – 7.8) and IgM (COI = 1.2) antibodies to the TBE virus were detected. In July 2020, the patient was infected with SARSCoV-2. TBE virus which passed into the body simultaneously with Borrelia in the fall of 2019 was activated. Although the patient did not have specific symptoms of TBE, in subsequent blood samples (No. 4, 5, 6) we found TBEV antigen (optical density (OD) – 4.3; 1.9 and 2.0 respectively) and IgM (COI = 1.3; 0,9 and 0 respectively). These results were recognized as TBEV activation, which contributed to an increase in the avidity of IgG antibodies (AI = 65 %; 100 % and 63 % respectively). IgM antibodies to SARSCoV-2 virus were not detected, as opposed to the high levels of IgG (COI = 8.2; 8.1; 8.4 and 14.7 respectively). Conclusions . Therefore, using not only the common methods of diagnosing (PCR and ELISA), but also the determination of the antibody avidity degree, we have shown that when analyzing a case of a triple mixed infection, B. burgdorferi dominates in the human body and causes a long-term chronic course of the disease.

The coexistence of various pathogens inside the patient’s body is one of the poorly studied and current issues. The aim of the study is to identify the relationship between the indicators of complex laboratory diagnostics and the clinical manifestations of a mixed disease during subsequent infection with the SARS-CoV-2 virus using the example of a case of chronic encephalitis-borreliosis infection. Seven blood serum samples were collected from the patient over the course of a year. For the etiological verification of the causative agents of TBE, Lyme disease and COVID-19, the methods of ELISA and PCR diagnostics were used. The patient was diagnosed with Lyme disease on the basis of the detection of IgG antibodies to Borrelia 5 months after the onset of the disease, since she denied the tick bite. In the clinical picture, there was an articular syndrome and erythema migrans. Later, IgG antibodies to the TBEV were found in the blood. Throughout the study, IgM antibodies to Borrelia were not detected. The exacerbation of Lyme disease could be judged by the clinical manifestations of this disease and by the growth of specific IgG antibodies. A feature of this case was that during an exacerbation of the Lyme disease, an infection with the SARS-CoV-2 virus occurred. Treatment (umifenovir, hydroxychloroquine, azithromycin, ceftriaxone) was prescribed, which improved the condition of the underlying disease, decreased joint pain, decreased IgG levels to borrelia. However, during this period, serological markers of TBEV appear: antigen, IgM antibodies, and the titer of IgG antibodies increases. Most likely, this was facilitated by the switching of the immune system to the SARS-CoV-2 virus, with the simultaneous suppression of borrelia with antibiotics and the appointment of hydroxychloroquine, which has an immunosuppressive effect. Despite the activation of the virus, clinical manifestations of TBE were not observed in the patient, which is most likely associated with infection with a weakly virulent TBEV strain. The further course of tick-borne infections revealed the dominant influence of B. burgdorferi in relation to TBEV. Laboratory studies have shown that suppression of the activity of the borreliosis process by etiotropic treatment subsequently led to the activation of the persistent TBEV.

Natural foci of clonorchiasis are localized on the territory of Primorsky Territory. The incidence of clonorchiasis ranged from 0.57 per 100 thousand population in 2014 (10 cases) to 1.5 per 100 thousand in 2012 (28 cases), and in 2010 (35 cases) to 1.9 per 100 thousand population is the maximum level. Analyzed 100 case histories of patients with clonorchiasis. Women predominated (63%). The age of the patients ranged from 3 to 77 years, the average age was 37 years. 82% of cases fell on the age of 18-70 years, 15% - on children from 3 to 18 years old, 3% - people over 70 years old. In 26% of patients, clonorchiasis proceeded in an acute form, in 74% - in a subclinical form. 89% had C. sinensis cleansing after taking praziquantel. Key words: clonorchiasis, acute, chronic, C. sinensis, Primorsky Krai.

An effect of the antiviral drug Kagocel on the levels of metalloproteinases MMP-8 and MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 in induced sputum during treatment of community-acquired viral-bacterial pneumonia was analyzed. 60 adult patients with verified community-acquired pneumonia of viral-bacterial etiology were included in the follow-up monitoring. Materials and methods. All patients were randomly stratified into 2 groups: group 1 (comparison group) consisted of 30 patients receiving Ceftriaxone monotherapy; group 2 (main group) 30 subjects who were prescribed Ceftriaxone and the antiviral drug Kagocel as etiotropic treatment. Both groups were comparable in gender, age and time of admission to the hospital. Results. During hospitalization, patients in both groups had elevated levels of MMP-8, MMP-9, TIMP-1 and TIMP-2 in induced sputum compared to the reference values. By 7 days of inpatient treatment, the level of MMP-8 was still significantly higher than the reference values in both groups, being in patients from group 2 it decreased compared to baseline values, whereas in patients from group 1, on the contrary, it was markedly elevated. The activity of MMP-9 during hospitalization was also high in patients from both groups compared with its level in healthy subjects. By day 7 of therapy, changes in various parameters were recorded. The level of MMP-9 in patients from group 1 increased, whereas in group 2 on the contrary decreased. The level of TIMP-1 decreased in patients of the 1st group below the control value, and in patients of the 2nd group reached the reference values. The level of TIMP-2 decreased in both groups and reached that of in control group. Conclusion. Antiviral drug Kagocel being included in the standard antibacterial regimen of community-acquired viral-bacterial pneumonia reduces the level of MMR-9 and intensity in imbalance between MMP and TIMP parameters by 7 days of therapy, which leads to accelerated clinical recovery.

The present study focuses on the comparative assessment of the therapeutic efficacy of the antiviral drugs riamilovir and umifenovir in the treatment of patients diagnosed with influenza. The aim of the study was to compare the clinical efficacy and safety, as well as the incidence of complications, of the use of antiviral drugs riamilovir and umifenovir and the use of only symptomatic therapy in patients with a confirmed diagnosis of influenza. All patients were hospitalized at the Regional Clinical Hospital No. 2 in Vladivostok. The study included 150 patients, who were divided into 3 groups (50 patients in each group), comparable in gender, age, and admission to the hospital. Patients of the first group received riamilovir, the second group received uminofenovir, patients of the third group received only symptomatic therapy (control group). The duration of clinical manifestations of the disease, hematological disorders, as well as the content of cytokines TNF-α and IL-10 in blood serum were assessed. The incidence of complications in each group was taken into account. As a result of the study, it was found that the inclusion of the antiviral drugs riamilovir and umifenovir in the therapy of influenza decreases the amount of the pro-inflammatory cytokine TNF-α after 5 days of treatment; and in case of symptomatic therapy its level significantly exceeded the reference values. The level of anti-inflammatory cytokine IL-10 on the 5th day of treatment in the main group was three times lower than in the control group. Thus, riamilovir and umifenovir effectively relieve the main symptoms of the disease, reduce the incidence of complications, and reduce the severity of the inflammatory response by the 5th day of treatment.

For the period 1967-1996 he was observed 368 patients in the age 16-65 years with levelnum paragonimiasis with disease duration from 1-2 to more than 10 years. 248 patients had acute paragonimiasis with disease duration up to 1 year, 20 – subacute (duration of illness over 1 year), and 100 – chronic disease (proceeded more than 2 years). The disease is characterized by fever, cough, chest pain, focal and infiltrative darkening in the lungs, cystic formations, exudative pleurisy, spontaneous pneumothorax, leukocytosis and eosinophilia in peripheral blood. The diagnosis was confirmed in 97.9% of cases by serological method. Recovery was achieved in 89% of patient’s levelnum paragonimiasis (PL) when using praziquantel.

Introduction. Cytokines regulate intercellular and intersystem interactions and are involved in the development and prevention of various pathologies. Purposes of work were a comparative assessment of the dynamics of the levels of pro- and anti-inflammatory blood cytokines (TNF-α and IL‑10) in patients with community-acquired viral-bacterial pneumonia (CAVBP) with ceftriaxone monotherapy with antibiotic and combined use this antibiotic with the antiviral drug Kagocel, and comparison of getting data with native (reference) indicators of healthy patients.Materials and methods.The study included 60 patients, aged 18–65 years, with a confirmed diagnosis of community-acquired pneumonia of moderate severity, divided into two groups equal in number, comparable by gender, age and timing of admission to the hospital. The first group received intravenous monotherapy only with the antibacterial drug Ceftriaxone, and the second group received a combination of Ceftriaxone with the oral antiviral drug Kagocel.Results. A pronounced imbalance of the levels of proand anti-inflammatory cytokines in patients with CAVBP of both groups was demonstrated both during the onset of the disease and on the 7th day hospitalization. When analyzing the concentration ratio of TNF-α / IL‑10, it was found that monotherapy with an antibacterial drug did not lead to a decrease in this indicator, while when using a combination of an antibiotic with an antiviral drug, a significant decrease in its values to normal was observed on the 7th day treatment. Good tolerance of the combination therapy and the absence of adverse reactions were noted.Conclusion.The addition of Kagocel to the treatment regimen for CAVBP with ceftriaxone contributed to the decrease the concentration of TNF-α and increases the level of IL‑10, which is clinically reflected in a reduction in the duration of fever, symptoms of general intoxication, catarrhal phenomena and the duration of hospitalization (by 1 day) compared with ceftriaxone monotherapy.

An open prospective comparative study of the efficacy of influenza monotherapy with antiviral drug versus combination therapy of two antiviral drugs with different mechanisms of action (within the limits of registered medical use for the drug) was performed in 200 patients with influenza A (H1N1) pdm09. In all patients, the clinical diagnosis was confirmed by the indication of the virus in nasopharyngeal washings by polymerase chain reaction with pre-reverse transcription (RT-PCR) in real time. All patients were randomly divided into 4 groups of 50 people, they were equivalent in terms of admission to hospital, age, sex, and the length of treatment from the onset of the disease. Group 1 received monotherapy with Umifenovir 800 mg/day in 4 divided doses for 5 days; Group 2 - monotherapy with Oseltamivir 150 mg/day in two doses for 5 days; Group 3 - Umifenovir according to the described scheme in combination with Kagocel 72 mg/day in 3 doses for the first 2 days and 36 mg/day in 3 doses in the following 2 days; Group 4 - Oseltamivir according to the described scheme in combination with Kagocel 72 mg/day in 3 doses for the first 2 days and 36 mg/day in 3 doses in the following 2 days. Criteria for the clinical efficacy of antiviral therapy were the time of temperature normalization, decrease of intoxication, catarrhal symptoms, frequency of the main clinical manifestations, and the frequency of complications development after the end of treatment in comparison with the state before it began. In assessing the duration of the symptomatology, the end point was the absence of symptoms of the disease within 24 hours. The study showed that the combination of etiotropic drugs Oseltamivir (Tamiflu®) and Umifenovir (Arbidol®) with the antiviral agent Kagocel® makes it possible to significantly improve the therapeutic efficacy compared with the corresponding monotherapy, which is expressed by a decrease in the frequency of manifestation of the main clinical indicators, a reduction in the duration of clinical symptoms, and a decrease in the frequency of complications. Good tolerability of treatment by patients was noted.

СОСТОЯНИЕ СЛИЗИСТОЙ ОБОЛОЧКИ НОСА И ГЛОТКИ У БЕРЕМЕННЫХ С ХРОНИЧЕСКИМ ПРОСТЫМ БРОНХИТОМ В СТАДИИ РЕМИССИИ И.Н.Гориков1, В.П.Колосов1, Л.Г.Нахамчен1, А.Н.Одиреев1, И.А.Андриевская1, А.Ф.Попов4, А.А.Сергиевич3, Т.А.Баталова2, Е.А.Бородин2, Е.С.Лобанова2 1Федеральное государственное бюджетное научное учреждение «Дальневосточный научный центр физиологии и патологии дыхания», 675000, г. Благовещенск, ул. Калинина, 22 2Федеральное государственное бюджетное образовательное учреждение высшего образования «Амурская государственная медицинская академия» Министерства здравоохранения Российской Федерации, 675000, г. Благовещенск, ул. Горького, 95 3Федеральное государственное автономное образовательное учреждение высшего образования «Дальневосточный федеральный университет», 690990, г. Владивосток, ул. Суханова, 8 4Федеральное государственное бюджетное образовательное учреждение высшего образования «Тихоокеанский государственный медицинский университет» Министерства здравоохранения Российской Федерации, 690002, г. Владивосток, пр-т Острякова, 2

Objective: to establish clinical and epidemiological patterns of chickenpox in adults in the Primorsky Territory to improve treatment and prevention work. Materials and methods: The study used statistics on the incidence of chicken pox in the Primorsky Territory from 2009 to 2017 and demographic data on the population for the specified period. A clinical characteristic of 102 cases of varicella in patients hospitalized in the infectious disease ward of Primorsky Regional Clinical Hospital No. 2 (Vladivostok) in 2015-2017 is given. Results: From 2009 to 2017, the incidence of chickenpox in the Primorsky Territory was consistently high, with an average of 636.2 per 100,000 population. Analysis of the structure of patients showed that the maximum proportion of cases of chicken pox occur in organized children 3-6 years old (55.9%), schoolchildren (19.1%) and children 1–2 years old (11.6%). The proportion of 15–17 year olds was 3.0%. Adults, from 18 years old – 4.9%. The proportion of unorganized children 3–6 years old (2.9%) and children in the first year of life (2.6%) is not high. High risk of infection was detected in Vladivostok (57.8 per 100.000), Yakovlevsky (52.1% ooo), Olginsky (45.9% ooo), Lazovsky (42.8% ooo) and Shkotovsky (40, 2% ooo) areas. In the annual dynamics, a pronounced spring-summer seasonal rise was formed. The clinical course of varicella in the group of adults was characterized by an average duration of the initial period of the disease of 1.4 ± 0.7 days. For clinical diagnosis, an important time was the appearance of the rash, which varied within four days. The phenomenon of “spillage” was noted in 97% of patients. The rash was polymorphic, with the formation of crusts. The period of height was characterized by the presence of catarrhal manifestations. The granularity of the posterior pharyngeal wall was observed in all patients without exception. In 84.3% of patients there was a bright hyperemia of the pharynx. In 14.7% of cases, enantema was detected on the soft palate, palatine arches, and posterior pharyngeal wall. Dry cough was detected in 28 of 103 patients, which probably increased their epidemiological significance. Findings: The clinical picture of varicella was typical and was represented by a combination of intoxication, exanthema, and catarrhal syndrome. The epidemic process of varicella in adults in Primorsky Krai was characterized by relative autonomy of manifestations in adults, children up to one year old, and unorganized children. When implementing chickenpox epidemiological surveillance, priority should be given to interventions in epidemic foci.

Viruses that cause acute respiratory infections are currently widespread and are reported worldwide. Among the most dangerous among them are influenza viruses, with a difficult to predict course and the possibility of rapidly developing life-threatening complications that can lead to death.The purpose of the research work: to analyze the effectiveness and safety of the treatment of community-acquired viral-bacterial pneumonia in hospital patients using only antibacterial therapy as an etiotropic treatment in comparison with the combined use of antibacterial therapy and the antiviral drug Kagocel®.Materials and methods. An open, prospective comparative study was conducted (from January 1 to December 31, 2018) to study the effectiveness of monotherapy compared with combination therapy with the antiviral drug Kagocel® for 60 patients diagnosed with community-acquired pneumonia who were admitted during the period of an epidemic rise in the incidence of acute respiratory viral infections and influenza. All patients were treated in the infectious ward of the Regional Clinical Hospital No. 2, (Vladivostok, Russia). Patients were divided into 2 groups, 30 people each, comparable in age, gender and timing of admission to the hospital. The age of patients ranged from 18 to 65 years. The first group consisted of patients who received an antibacterial drug (control group) as an etiotropic therapy, the second group — those who received a combination of antibacterial and antiviral (Kagocel®) drugs (experimental group).Results. In the group of patients receiving both antibacterial and antiviral therapy with Kagocel®, there was a significant reduction in the duration of the febrile period and catarrhal manifestations compared with patients taking only antibiotics as part of etiotropic therapy. An analysis of the data showed that the use of Kagocel® in the treatment of viral-bacterial pneumonia significantly facilitates the patient’s condition during the illness, shortens the duration of the disease, reduces the duration of the main clinical symptoms of pneumonia, namely the duration of intoxication, catarrhal syndromes, and physical changes in the lungs.Conclusions. The use of the antiviral drug Kagocel® in the treatment of community-acquired viral-bacterial pneumonia leads to a more rapid relief of the main symptoms of the disease and reduces the duration of the disease. Good tolerance of the therapy, the absence of adverse reactions was noted.

Pregnant women are at the high risk for the development of severe both pandemic and seasonal influenza. There were analyzed medical histories of 277 influenza pregnant women observed in 2009-2016. Patients were divided into two groups: I (113 cases, 40.8%) - influenza A women (H1N1) pdm09, II (164 patients, 59.2%) - seasonal influenza pregnant women: A (H3N2) (109 females, 66.5%) or B (55 cases, 33.5%). Most women developed influenza in the second and third trimester of the gestation (114 cases, 41.2%, and 94 cases, 33.9%, respectively). The duration of inpatient treatment of pregnant women in the first group was significantly longer than in cases from the second group (p