Fourth-generation folic acid active metabolite Quatrefolic® and micronized, microencapsulated iron Lipofer®: innovative approaches for iron and folic acid deficiencies in women (a review)

I.N. Kononova1, E.N. Kareva1,2&nbsp; 1Pirogov Russian National Research Medical University, Moscow, Russian Federation 2I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation To review up-to-date management algorithms for iron and folic acid deficiency in women of reproductive age, we selected relevant publications in the PubMed and Google Scholar databases (2012–2022). Current limitations of using peroral iron salts (malabsorption, poor adherence to treatment due to gastrointestinal adverse reactions, risks of oxidative stress, and ferroptosis resulting from iron overload) were prerequisites for developing innovative technology, Lipofer®. Lipofer® is a micronized and microencapsulated iron in a phospholipid coat which provides better absorption independent of hepcidin status and targeted iron delivery in tissues with minimization of adverse reaction risks. Limitations of using folic acid include low bioavailability in polymorphisms of folate cycle enzymes (dihydrofolate reductase/DHFR and methylenetetrahydrofolate reductase/MTHFR) which results in potential toxic effects of unmetabolized folic acid and abnormal homocysteine clearance (risk factors for vascular disorders and B12-deficiency anemia masking). These entities were prerequisites for the development of Quatrefolic®. Quatrefolic® is the glucosamine salt of (6S)-5-methyltetrahydrofolate, an active metabolite of folic acid with high solubility and bioavailability ready to enter the folate cycle without involving reductases. Quatrefolic® is safe and has no risks of overdosing or effects on B12-deficiency anemia diagnosis. A combination of two high-tech molecules is an innovative therapeutic tool for essential microelement requirements in women with high risks of iron and folic acid deficiencies. Keywords: iron-deficiency anemia, ferric pyrophosphate, microencapsulated iron, liposomal form, Lipofer, neural tube defect, folic acid, polymorphism, Quatrefolic, glucosamine salt. For citation: Kononova I.N., Kareva E.N.&nbsp;Fourth-generation folic acid active metabolite Quatrefolic® and micronized, microencapsulated iron Lipofer®: innovative approaches for iron and folic acid deficiencies in women (a review). Russian Journal of Woman and Child Health. 2022;5(1):18–27 (in Russ.). DOI: 10.32364/2618-8430-2022-5-1-18-27. </p

Evaluation of the sucrosomial iron efficacy in the patient treatment with stage 1–2 iron deficiency anemia during heavy menstrual bleeding

I.N. Kononova1,2, Yu.E. Dobrokhotova1, E.N. Kareva1,3, N.A. Shmakova4, I.V. Graban5, T.A. Ogurtsova6 1Pirogov Russian National Research Medical University, Moscow, Russian Federation 2Transregional Center for Continuing Professional Education LLC, Moscow, Russian Federation 3I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation 4Medical Center "Angio Line plus" LLC, Yekaterinburg, Russian Federation 5Medical Center "Edelweiss", Yekaterinburg, Russian Federation 6Yekaterinburg Clinical Perinatal Center, Yekaterinburg, Russian Federation Aim: to evaluate the clinical efficacy of Sucrosomial® iron (SiderAL® Forte) in the treatment of stage 1–2 iron deficiency anemia (IDA) in patients with menorrhagia in the setting of ovulation disorders. Patients and Methods: a prospective randomized multicenter clinical case study of 110 patients with stage 1–2 IDA developed in the setting of menorrhagia as a result of ovulation disorders was conducted. Female patients of the main group (n=74) received Sucrosomial® iron 30 mg 2 times a day for 60 days. In the control group (n=36), a liposomal iron preparation of 30 mg 2 times a day was also prescribed for 60 days. Results: during Sucrosomial® iron ferrotherapy, an increase in Hb levels by more than 20 g/L was observed after 30 days of administration in 65 (87%) female patients, after 60 days in 73 (98.6%) female patients, which demonstrated higher therapeutic efficacy versus liposomal iron preparation (69.4 and 88.8%, respectively, p=0.0001). There was also a greater adherence to therapy (98.6%) during Sucrosomial® iron intake versus liposomal iron intake (86.1%, p=0.0001), due to fewer (1.4%) adverse events compared with the control group (5.5%, p=0.0002). Conclusion: oral ferrotherapy with Sucrosomial® iron is a reasonable option for the IDA treatment in patients with menorrhagia due to its higher efficacy versus the liposomal iron. The effect occurs after 30 days of drug intake with a minimum number of adverse events, due to the unique structural, physico-chemical and pharmacokinetic characteristics of the sucrosomial iron, thanks to which it is protected from the gastric juice action, does not contact with the gastrointestinal mucosa and is absorbed through special intestinal M-cells with further iron release in liver cells. Keywords: iron deficiency anemia, menorrhagia, ovulation disorders, Sucrosomial® iron, women, therapy. For citation: Kononova I.N., Dobrokhotova Yu.E., Kareva E.N., Shmakova N.A., Graban I.V., Ogurtsova T.A. Evaluation of the sucrosomial iron efficacy in the patient treatment with stage 1–2 iron deficiency anemia during heavy menstrual bleeding. Russian Journal of Woman and Child Health. 2023;6(4):332–339 (in Russ.). DOI: 10.32364/2618-8430-2023-6-4-2. <br

Minocycline (Minolexin®) clinical efficacy and tolerability evaluation in women with bacterial-associated chronic cervicitis

Yu.E. Dobrokhotova1, I.N. Kononova1,2, E.N. Kareva1,3, N.A. Shmakova4, I.V. Graban5, T.A. Ogurtsova6 1Pirogov Russian National Research Medical University, Moscow, Russian Federation 2LLC "Interregional Center for Continuing Professional Education", Moscow, Russian Federation 3I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation 4LLC Medical Center "ANGIO LINE PLUS", Yekaterinburg, Russian Federation 5LLC Medical Center "Edelweiss", Aramil, Russian Federation 6Yekaterinburg Clinical Perinatal Center, Yekaterinburg, Russian Federation Background: bacterial-associated chronic cervicitis (CC) occupies a leading place in the cervical pathology structure. At the same time, the disease recurrence rate reaches 59–68% in the setting of resistance to antibacterial therapy, which determines the need to find new effective drugs. Aim: to evaluate the clinical efficacy, safety and compliance of therapy with minocycline in patients with bacterial-associated CC. Patients and Methods: a multicenter prospective observational clinical study was conducted in women's health clinics and medical centers in Yekaterinburg. The study included 60 female patients with a confirmed diagnosis of bacterial-associated CC. Group 1 (n=31) received the antibacterial drug minocycline (Minolexin®) 100 mg twice a day in the morning and evening, 10 days + antimycotic prebiotic 1 suppository once a day intravaginally for 6 days, starting from the 3rd day of antibiotic therapy. Group 2 (n=29) received doxycycline 100 mg twice a day for 10 days + antimycotic prebiotic 1 suppository once a day intravaginally for 6 days, starting from the 3rd day of antibiotic therapy. Clinical and laboratory efficacy (cervicitis signs, results of laboratory microbiome research methods) and drug tolerability were evaluated 10 and 30 days after the treatment initiation. Results: as a result of CC antibacterial therapy with minocycline, pathogen eradication was observed in 83.9% of female patients (group 2 — in 69.9%, p=0.0001), the original squamous epithelium 30 days after the minocycline was detected in 27 (87.1%) female patients (group 2 — in 19 (65.5±5.8%) female patients, p=0.0001), which indicates a higher efficacy of minocycline versus doxycycline. Patients of the minocycline group had more therapy adherence — 96.8% vs. 82.9% in the doxycycline group (p=0.0001) due to the minimal number of side effects (3.2% vs. 17.2%, respectively; p=0.0001). Conclusion: minocycline is a systemic antibiotic of the tetracycline group, which can be considered as the front-line drug for antibacterial therapy of patients with CC due to its high clinical efficacy, minimal risk of side effects and high compliance. Keywords: chronic cervicitis, antibacterial therapy, tetracyclines, minocycline, efficacy. For citation: Dobrokhotova Yu.E., Kononova I.N., Kareva E.N., Shmakova N.A., Graban I.V., Ogurtsova T.A. Minocycline (Minolexin®) clinical efficacy and tolerability evaluation in women with bacterial-associated chronic cervicitis. Russian Journal of Woman and Child Health. 2023;6(4):340–346 (in Russ.). DOI: 10.32364/2618-8430-2023-6-4-3. <br

Assessment of the efficacy and compliance with Vojea® in women during the pregravid preparation and the early stages of pregnancy

I.N. Kononova1,2, E.N. Kareva1,3, E.V. Stebenyaeva4, N.A. Shmakova5, I.V. Graban6, T.A. Ogurtsova7, Yu.E. Dobrokhotova1, S.V. Orlova8 1Pirogov Russian National Research Medical University, Moscow, Russian Federation 2LLC "Interregional Center for Continuing Professional Education", Moscow, Russian Federation 3I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation 4LLC "SMARTLAB", Yekaterinburg, Russian Federation 5LLC Medical Center "ANGIO LINE PLUS", Yekaterinburg, Russian Federation 6LLC Medical Center "Edelweiss", Aramil, Russian Federation 7Yekaterinburg Clinical Perinatal Center, Yekaterinburg, Russian Federation 8Russian University of Peoples' Friendshiр, Moscow, Russian Federation Aim: to assess the clinical efficacy, safety and tolerability of Vojea® in the prevention of iron-deficiency anemia and folic acid deficiency in women during the preconception (pregravid) period and early stages of pregnancy, as well as to evaluate patient compliance with this product. Patients and Methods: this prospective multi-center observational study was performed in 2022 in four medical centers and women's health clinics of Ekaterinburg. The study included 87 women with latent iron deficiency (mean ferritin level below 15 ng/ml). The first group consisted of 37 women during the pregravid preparation period, and the second group consisted of 50 pregnant patients with up to 12 weeks of pregnancy. Patients received the Vojea® once daily for three months. Clinical and laboratory efficacy (the absence of objective anemia signs and the changes in hemoglobin level, folate and ferritin blood tests over time), as well as tolerability (the rate of adverse events, tolerability of the taken product evaluated using the visual analog scale) was assessed at days 30, 60 and 90 after the beginning of treatment. Results: beginning from the first month of treatment with the studied complex, some positive changes in clinical symptoms and laboratory findings were reported in both groups. By the third month of therapy, the increment of hemoglobin level in the pregravid preparation group was 17 (13.9%) units, the level of ferritin increased by 6.3 times (clinically significant after two months of the product intake), and the level of blood serum folates increased by 4.6 times. In group 2, the increment of hemoglobin level, as pregnancy was progressing, in three months of the product intake reached 19 units (17%), the level of ferritin increased by 5.9 times (clinically significant after two months of treatment), and the level of blood serum folates increased by 3.9 times. In group 1, adverse events were reported only in 2/37 (5.4%) patients who had dark stool color on the 2nd month of follow-up. In group 2, such adverse events as nausea were reported in 3/50 (6%) patients during the 1st month of product intake. All patients informed that the product was well tolerated which ensured high patient compliance. Conclusion: maintaining iron and folic acid homeostasis by oral intake of the Vojea® complex during three months in the preconception period and early stages of pregnancy is a feasible option based on its high efficacy and good tolerability with the minimal risk of side effects, encouraging high patient compliance. Keywords: ferric pyrophosphate, folic acid, pregravid preparation, pregnancy, active metabolite of folic acid, methyltetrahydrofolate, glucosamine salt, Quatrefolic, micronized microencapsulated ferric iron, Vojea, compliance. For citation: Kononova I.N., Kareva E.N., Stebenyaeva E.V. et al. Assessment of the efficacy and compliance with Vojea® in women during the pregravid preparation and the early stages of pregnancy. Russian Journal of Woman and Child Health. 2023;6(2):95–104 (in Russ.). DOI: 10.32364/2618-8430-2023-6-2-95-104. </p

РЕКОМЕНДАЦИИ ПО ВЕДЕНИЮ ПЕРВИЧНЫХ ПАЦИЕНТОВ С СИМПТОМАМИ ДИСПЕПСИИ

Aim: To develop evidence-based recommendations for primary care physicians and general practitioners (GP) on choosing the proper management tactics and making valuable & quick diagnostic decisions at outpatient phase for patients with symptoms of dyspepsia, and also reveal possible oncology on time. Summary of recommendations: Approximately 40% of the patients in Russia presenting to primary care with symptoms of dyspepsia. A doctor has to focus on the warning signs, which may require an urgent additional examination & the consultation with a surgeon/onco-surgeon or other specialists if required. With regard to a risk of cancer, a doctor should be more cautious in patients over 45 years of age. Early diagnosis of oncology depends mainly on cautiousness of GP, primary care physicians and their knowledge, future tactics with regard to the patients. From the mandatory diagnostic tests during the first visit, esophagogastroduodenoscopy and H. pylori diagnostics helps to exclude any organic esophagus and stomach pathology, possible oncology. While waiting for endoscopy results, a physician should use the preliminary diagnoses “Uninvestigated Dyspepsia” (ICD-10 К 31.9) (disease of stomach and duodenum, unspecified). After exclusion of all warning signs, therapy of dyspepsia should be in accordance to the order of the Ministry of Health No 248 which gives an option to use proton pump inhibitors (omeprazole or rabeprazole 20 mg daily) in combination with prokinetic (domperidone 30 mg daily). Fixed drug combination of omeprazole 20 mg and modified-release domperidone 30 mg/daily (Omez® DSR) is medically reasonable. Conclusion: The introduction of this recommendation into clinical practice will help clinicians to prevent diagnostic mistakes, unreasonable use of expensive diagnostic examinations and inappropriate treatment leads to improvement in the overall prognosis and quality of life for the patients.Цель. Представить рекомендации диагностики и лечения пациентов с симптомами диспепсии на этапе амбулаторно-поликлинической помощи, обобщающие зарубежный и отечественный опыт ведения данной категории больных. Основная цель рекомендаций - помочь терапевту и врачу общей практики (ВОП) на амбулаторном этапе принять правильное решение о тактике ведения больного, и в максимально короткий срок поставить правильный диагноз, а также вовремя выявить у пациента наличие онкологической патологии. Основные положения. Около 40% обращений пациентов на амбулаторно-поликлиническом приеме в России связано с симптомами диспепсии. Врач, в первую очередь, должен исключить наличие «тревожных признаков», которые требуют незамедлительного дополнительного обследования пациента, привлечения хирурга и/или других специалистов и госпитализации больного. Доктор должен иметь онкологическую настороженность, особенно, при обращении пациентов в возрасте 45 лет и старше, так как ранняя диагностика злокачественных новообразований (ЗНО) зависит главным образом от онкологической настороженности терапевтов, врачей общей практики и их знаний, дальнейшей тактики в отношении больного. Эзофагогастродуоденоскопия и тесты на H. pylori являются обязательными методами исследования на этапе диагностического поиска и позволяют исключить органические заболевания пищевода и желудка, наличие онкологии. До получения результатов эндоскопического исследования следует выставлять предварительный диагноз «Диспепсия Неуточненная» и шифровать под рубрикой МКБ-10 К 31.9 (болезнь желудка и двенадцатиперстной кишки неуточненная). После исключения «тревожных признаков» терапия диспепсии проводится согласно Приказу МЗ РФ № 248 и включает назначение ингибиторов протонной помпы (омепразол или рабепразол 20 мг/сут) в комбинации с прокинетиком (домперидон 30 мг/сут). Оправдано применение фиксированной комбинации омепразола 20 мг с домперидоном модифицированного высвобождения 30 мг/сут (Омез® ДСР). Заключение. Внедрение рекомендаций в клиническую практику поможет врачу избежать ошибок при постановке диагноза, применения необоснованных и нередко дорогостоящих методов обследования, нерационального лечения, что позволит улучшить прогноз и качество жизни пациентов

РЕКОМЕНДАЦИИ ПО ВЕДЕНИЮ ПЕРВИЧНЫХ ПАЦИЕНТОВ С СИМПТОМАМИ ДИСПЕПСИИ

Aim: To develop evidence-based recommendations for primary care physicians and general practitioners (GP) on choosing the proper management tactics and making valuable & quick diagnostic decisions at outpatient phase for patients with symptoms of dyspepsia, and also reveal possible oncology on time. Summary of recommendations: Approximately 40% of the patients in Russia presenting to primary care with symptoms of dyspepsia. A doctor has to focus on the warning signs, which may require an urgent additional examination & the consultation with a surgeon/onco-surgeon or other specialists if required. With regard to a risk of cancer, a doctor should be more cautious in patients over 45 years of age. Early diagnosis of oncology depends mainly on cautiousness of GP, primary care physicians and their knowledge, future tactics with regard to the patients. From the mandatory diagnostic tests during the first visit, esophagogastroduodenoscopy and H. pylori diagnostics helps to exclude any organic esophagus and stomach pathology, possible oncology. While waiting for endoscopy results, a physician should use the preliminary diagnoses “Uninvestigated Dyspepsia” (ICD-10 К 31.9) (disease of stomach and duodenum, unspecified). After exclusion of all warning signs, therapy of dyspepsia should be in accordance to the order of the Ministry of Health No 248 which gives an option to use proton pump inhibitors (omeprazole or rabeprazole 20 mg daily) in combination with prokinetic (domperidone 30 mg daily). Fixed drug combination of omeprazole 20 mg and modified-release domperidone 30 mg/daily (Omez® DSR) is medically reasonable. Conclusion: The introduction of this recommendation into clinical practice will help clinicians to prevent diagnostic mistakes, unreasonable use of expensive diagnostic examinations and inappropriate treatment leads to improvement in the overall prognosis and quality of life for the patients.Цель. Представить рекомендации диагностики и лечения пациентов с симптомами диспепсии на этапе амбулаторно-поликлинической помощи, обобщающие зарубежный и отечественный опыт ведения данной категории больных. Основная цель рекомендаций - помочь терапевту и врачу общей практики (ВОП) на амбулаторном этапе принять правильное решение о тактике ведения больного, и в максимально короткий срок поставить правильный диагноз, а также вовремя выявить у пациента наличие онкологической патологии. Основные положения. Около 40% обращений пациентов на амбулаторно-поликлиническом приеме в России связано с симптомами диспепсии. Врач, в первую очередь, должен исключить наличие «тревожных признаков», которые требуют незамедлительного дополнительного обследования пациента, привлечения хирурга и/или других специалистов и госпитализации больного. Доктор должен иметь онкологическую настороженность, особенно, при обращении пациентов в возрасте 45 лет и старше, так как ранняя диагностика злокачественных новообразований (ЗНО) зависит главным образом от онкологической настороженности терапевтов, врачей общей практики и их знаний, дальнейшей тактики в отношении больного. Эзофагогастродуоденоскопия и тесты на H. pylori являются обязательными методами исследования на этапе диагностического поиска и позволяют исключить органические заболевания пищевода и желудка, наличие онкологии. До получения результатов эндоскопического исследования следует выставлять предварительный диагноз «Диспепсия Неуточненная» и шифровать под рубрикой МКБ-10 К 31.9 (болезнь желудка и двенадцатиперстной кишки неуточненная). После исключения «тревожных признаков» терапия диспепсии проводится согласно Приказу МЗ РФ № 248 и включает назначение ингибиторов протонной помпы (омепразол или рабепразол 20 мг/сут) в комбинации с прокинетиком (домперидон 30 мг/сут). Оправдано применение фиксированной комбинации омепразола 20 мг с домперидоном модифицированного высвобождения 30 мг/сут (Омез® ДСР). Заключение. Внедрение рекомендаций в клиническую практику поможет врачу избежать ошибок при постановке диагноза, применения необоснованных и нередко дорогостоящих методов обследования, нерационального лечения, что позволит улучшить прогноз и качество жизни пациентов