International Journal of Environmental Research and Public Health
Real-life data that support effectiveness of secukinumab (SEC), an interleukin 17A inhibitor, in ... more Real-life data that support effectiveness of secukinumab (SEC), an interleukin 17A inhibitor, in Poland are few. We aimed to evaluate SEC effectiveness based on drug retention and safety measures reported in electronic medical records (EMRs) of patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS) from two tertiary-care centers in the region of Lesser Poland. A total one-hundred eighty seven (127 PsA and 60 AS) first (n = 112), second (n = 59) and third-line SEC users were enrolled. The mean (SD) age of the sample was 45.7 (12.9), and 48% were male. All patients were classified with active and severe disease prior to initiation. Administrative delays for SEC users last a median 2 weeks. Median delay from symptom onset to diagnosis was 4 years (IQR 8), and differed by predominant disease subtype. The inefficacy rate was 10.7% and 18.6% for first and second-line users with median (IQR) drug maintenance estimated at 1.22 years (1.46) and 1.51 (1.38), respectively. Fir...
Psoriatic arthritis (PsA) is characterized by delays in diagnosis and modest effect of treatment ... more Psoriatic arthritis (PsA) is characterized by delays in diagnosis and modest effect of treatment in terms of joint response. An understanding of molecular pathomechanisms may aid in developing diagnostic and prognostic models. Genetic susceptibility (e.g., HLA class I genes, IL-23-related genes) can be responsible for the pattern of psoriatic manifestations and affinity for tissue involvement. Gene expression analysis indicates an inflammatory profile that is distinct for PsA, but disparate across tissues. This has clinical implications, as for example, dual blockade of IL-17A and IL-17F can lead to superior clinical effects if there is differential expression of IL-17 receptors in tissues. Structural and functional impairment of barrier tissue, including host-microbiome interactions, may be the source of immune activation. Interplay between different cell populations of innate and adaptive immunity is emerging, potentially providing a link between the transition of skin-to-joint di...
Wspolcześnie pojecie „leki biologiczne”, czyli „biofarmaceutyki”, oznacza leki, ktorych substancj... more Wspolcześnie pojecie „leki biologiczne”, czyli „biofarmaceutyki”, oznacza leki, ktorych substancja czynna zostala wytworzona przez zywe komorki hodowane in vitro. W wiekszości leki biologiczne są duzymi cząsteczkami bialkowymi. Synteza bialek w zywych komorkach moze ulegac pewnym zmianom. Tym samym mozliwe są pewne roznice (najcześciej dotyczące modyfikacji posttranslacyjnych) w budowie lekow. Muszą one mieścic sie w precyzyjnie określonych granicach. Lek biopodobny to lek biologiczny wyprodukowany jako bardzo podobna kopia leku biologicznego innowacyjnego wcześniej zarejestrowanego. Lek biopodobny nie jest lekiem generycznym w ujeciu farmakologicznym. Dopuszczenie leku biopodobnego do stosowania wymaga badan określających jego podobienstwo strukturalne, badan za pomocą testow biologicznych, badan farmakokinetycznych i badan klinicznych oceniających skutecznośc i bezpieczenstwo terapii. Lek biopodobny musi cechowac sie określoną biorownowaznością i jego produkcja, podobnie jak produ...
Background The aim of our study was to investigate the risk factors for falls in the rheumatoid a... more Background The aim of our study was to investigate the risk factors for falls in the rheumatoid arthritis (RA) patient population in Poland. This would be a major step towards the development of new fall prevention programs. Material/Methods There were 450 RA patients who met the criteria of the American College of Rheumatology who participated in this study. The average age of patient participants was 54.2 years; the average RA duration was 15.1 years. All patients filled out the study questionnaire regarding falls, medications, and diseases, and they filled out the Polish version of the Health Assessment Questionnaire (HAQ). Results Of the 400 patients, 203 patients (51%) experienced falls. Out of the 268 falls experienced by study patients, 113 falls (42%) were due to an environmental cause, the remainder 155 falls were caused by health conditions. The number of falls positively correlated with HAQ scores (r=0.42, P<0.01) and the duration of RA (r=0.39, P<0.05). For individuals who had fallen 3 or more times, there was a stronger positive correlation between the number of falls and the total HAQ score (r=0.61, P<0.01). The main risk factors for falls in the study group were dizziness (odds ratio [OR]=3.42), the use of hypotensive medication (OR=2.82), foot deformities (OR=4.09), and a high HAQ score (OR=2.59). Other factors such as drug use (e.g., glucocorticoids), pain, and duration of RA were measured using a visual analogue scale, and were found not to have increased the risk for falls and fractures (P>0.05). Conclusions Knowledge about risk factors can help identify high-risk patients to help decrease their risk of falling, thus preventing fall-related injuries.
Introduction: Real-world data indicate disparities in biologic access across Europe. Objectives: ... more Introduction: Real-world data indicate disparities in biologic access across Europe. Objectives: To describe the national structure of PsA care in Poland, with a particular focus on the population of inadequate responders (IRs) and difficulties associated with biologic therapy access. Methods: A pool of rheumatologic and dermatologic care centers was created based on National Health Fund contract lists (n = 841), from which 29 rheumatologic and 10 dermatologic centers were sampled randomly and successfully met the inclusion criterium. Additionally, 33 tertiary care centers were recruited. For successful center recruitment, one provider had to recruit at least one patient that met the criteria for one of the four pre-defined clinical subgroups, in which all patients had to have active PsA and IR status to at least 2 conventional synthetic disease-modifying drugs (csDMARDs). Self-assessment questionnaires were distributed among physicians and their patients. Results: Barriers to biolo...
Psoriatic arthritis (PsA) is a seronegative spondyloarthropathy characterized by skin lesions, da... more Psoriatic arthritis (PsA) is a seronegative spondyloarthropathy characterized by skin lesions, dactylitis, and enthesitis. Patients with PsA suffer from a variety of psychosocial difficulties and nonspecific symptoms early on in the disease course and continue to experience progressive disease due to delays in diagnosis and treatment. Symptoms initially viewed as somatization could lead to undertreatment and promote psychological distress, poor coping, and negative patient–provider relationships. Pain and fatigue are important complaints that affect the patient’s perception and may need to be addressed with a multidisciplinary approach. Maladaptive cognitive responses can lead to a negative illness perception and impact patient beliefs and concerns over treatment, as well as nonadherence. An underlying inflammatory component in affective disorders has been examined, though whether and how it may interact mechanistically in PsA warrants interest. Cognitive behavioral therapy represen...
Tofacitinib is a newly approved small-molecule targeted synthetic disease-modifying antirheumatic... more Tofacitinib is a newly approved small-molecule targeted synthetic disease-modifying antirheumatic drug. The drug was designed as a selective and specific inhibitor of pro-inflammatory receptor signalling. Tofacitinib inhibits the process of intracellular signalling from the receptor to the cellular nucleus and inhibits the inflammation process via a new pathway (inhibition of the Janus kinases), which is unavailable to biological medicines. Tofacitinib has been approved for use in the treatment of patients with moderate to severe active RA. The drug may be used in combination with methotrexate or another conventional synthetic disease-modifying antirheumatic drug or in monotherapy. The efficacy of tofacitinib has been confirmed in several clinical trials. The drug inhibits radiographic progression of the disease. The innovative mechanism of action of tofacitinib is a noteworthy feature because it offers hope of effective treatment for patients who fail to respond to other drugs. The...
Ankylosing spondylitis (AS) is associated with high cardiovascular morbidity and mortality. Recen... more Ankylosing spondylitis (AS) is associated with high cardiovascular morbidity and mortality. Recent studies indicate that microvascular dysfunction may underlie cardiovascular risk in AS. We hypothesized, that microvascular morphology and dysfunction is linked to AS activity and is modifiable by TNF-α inhibitor (TNFi) treatment. Functional Laser Doppler Flowmetry with post-occlusive reactive hyperemia, and structural nailfold capillaroscopy were performed in 54 patients with AS and 28 matched controls. Active AS was diagnosed based on BASDAI ≥ 4 (n = 37). Effects of 3-month TNFi on microcirculation in active AS were studied. AS was associated with prolonged time to peak hyperemia compared to healthy controls. High disease activity was associated with increased time to peak hyperemia and decreased peak hyperemia when compared to patients with inactive AS. In capillaroscopy, AS was associated with morphological abnormalities indicating increased neoangiogenesis and pericapillary edema ...
Evidence from over 10 years of clinical experience demonstrates that biosimilar medicines approve... more Evidence from over 10 years of clinical experience demonstrates that biosimilar medicines approved in the European Union can be used for all their registered indications as safely as their originators and with no negative impact on therapeutic efficacy. The debate on the use of biosimilars in rheumatology focuses specifically on the safety of switching between biosimilars and reference products. Studies conducted to date, including randomised double-blind and open-label extension trials, have not demonstrated any significant differences in therapeutic efficacy or safety between patients switched from one medicine to another and those who were continued on a single medicine. According to the latest recommendations for the use of biosimilars in rheumatic diseases, developed by an international task force in 2017, there is no clinical evidence that a single switch from an originator to a biosimilar medicine is associated with any significant risk for patient safety or reduction in ther...
Younger age is a predictor of good clinical response to treatment with tumour necrosis factor (TN... more Younger age is a predictor of good clinical response to treatment with tumour necrosis factor (TNF) α inhibitors in ankylosing spondylitis (AS) patients; therefore, the aim of the study was to determine age-related differences in cellular functions, which can predict the response. High disease activity AS patients were treated with TNFα inhibitors for 12 weeks. Based on the percentage of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) improvement, patients were divided into responding or non-responding groups. Cytometric and clinical assessment were determined at baseline, 4, and 12 weeks after initiation of anti-TNFα treatment. Expression of activation markers on T cells and intracellular cytokine staining was performed. Baseline percentage of TNFα-producing CD8 cells was lower in responders than in non-responders (20.8 ± 2.9 vs 40.7 ± 8.2; P = 0.04 in T test) and increased in the responding group during the first month of treatment (20.8 ± 2.9 vs 30.3 ± 2.5; P = 0.02)....
The objective of this study was to determine the length of delay in diagnosis of inflammatory rhe... more The objective of this study was to determine the length of delay in diagnosis of inflammatory rheumatic diseases, and to indicate the main factors responsible for such delays. A retrospective multi-centre questionnaire survey carried out among 197 patients with diagnosed inflammatory rheumatic diseases or undergoing the diagnostic process. The most common early symptoms of inflammatory rheumatic disease included joint pain (94%), joint swelling (78%), morning joint stiffness (77%), fatigue (76%), and sleep disturbed by joint pain (74%). When asked about the reasons for seeking medical help, most patients indicated intensification of the symptoms (89%) and the fact that the symptoms made them unable to perform daily activities or work (86%). Limited access to specialists (70%) and the conviction that the symptoms will resolve spontaneously (57%) had the biggest impact on delaying a visit to a doctor. Before visiting a rheumatologist, the patients consulted their symptoms with their g...
Mycophenolate mofetil (MMF) is an inhibitor of inosine monophosphate dehydrogenase, which affects... more Mycophenolate mofetil (MMF) is an inhibitor of inosine monophosphate dehydrogenase, which affects de novo purine synthesis and T- and B-cell proliferation. So far its efficacy and safety as an immunosuppressive treatment have been proven in organ transplantations and also in various autoimmune diseases. A literature search was conducted by using PubMed and the Cochrane library. This review focuses primarily on current treatment with MMF for systemic lupus erythematosus, systemic sclerosis, vasculitis and idiopathic inflammatory myopathies.
Leflunomide (LMF) is an immunemodulatory drug used in the therapy of Rheumatoid Arthritis (RA). A... more Leflunomide (LMF) is an immunemodulatory drug used in the therapy of Rheumatoid Arthritis (RA). After oral administration in the mucosa of digestive tract LMF is quickly converted to an active metabolite A77126 which is a competitive inhibitor of dihydroorotate dehydrogenase--enzyme required in pirymidyne synthesis resulting in decreased proliferation of T and B lymphocytes. As animal studies showed A77126 embryo- and fetotoxity and no relevant epidemiological research in humans were available, LMF received category X pregnancy destination. This is a detailed presentation of two pregnancy cases during LMF therapy in Poland. The first patient was a multiparous woman suffering from RA for 17 years and treated with LM during the last 16 months. The second woman was a primigravida with RA diagnosed 4 years ago and treated with LMF for the last 20 months. LMF wash-out procedures were started immediately as the patients referred with diagnosed early pregnancies with oral administration of...
International Journal of Environmental Research and Public Health
Real-life data that support effectiveness of secukinumab (SEC), an interleukin 17A inhibitor, in ... more Real-life data that support effectiveness of secukinumab (SEC), an interleukin 17A inhibitor, in Poland are few. We aimed to evaluate SEC effectiveness based on drug retention and safety measures reported in electronic medical records (EMRs) of patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS) from two tertiary-care centers in the region of Lesser Poland. A total one-hundred eighty seven (127 PsA and 60 AS) first (n = 112), second (n = 59) and third-line SEC users were enrolled. The mean (SD) age of the sample was 45.7 (12.9), and 48% were male. All patients were classified with active and severe disease prior to initiation. Administrative delays for SEC users last a median 2 weeks. Median delay from symptom onset to diagnosis was 4 years (IQR 8), and differed by predominant disease subtype. The inefficacy rate was 10.7% and 18.6% for first and second-line users with median (IQR) drug maintenance estimated at 1.22 years (1.46) and 1.51 (1.38), respectively. Fir...
Psoriatic arthritis (PsA) is characterized by delays in diagnosis and modest effect of treatment ... more Psoriatic arthritis (PsA) is characterized by delays in diagnosis and modest effect of treatment in terms of joint response. An understanding of molecular pathomechanisms may aid in developing diagnostic and prognostic models. Genetic susceptibility (e.g., HLA class I genes, IL-23-related genes) can be responsible for the pattern of psoriatic manifestations and affinity for tissue involvement. Gene expression analysis indicates an inflammatory profile that is distinct for PsA, but disparate across tissues. This has clinical implications, as for example, dual blockade of IL-17A and IL-17F can lead to superior clinical effects if there is differential expression of IL-17 receptors in tissues. Structural and functional impairment of barrier tissue, including host-microbiome interactions, may be the source of immune activation. Interplay between different cell populations of innate and adaptive immunity is emerging, potentially providing a link between the transition of skin-to-joint di...
Wspolcześnie pojecie „leki biologiczne”, czyli „biofarmaceutyki”, oznacza leki, ktorych substancj... more Wspolcześnie pojecie „leki biologiczne”, czyli „biofarmaceutyki”, oznacza leki, ktorych substancja czynna zostala wytworzona przez zywe komorki hodowane in vitro. W wiekszości leki biologiczne są duzymi cząsteczkami bialkowymi. Synteza bialek w zywych komorkach moze ulegac pewnym zmianom. Tym samym mozliwe są pewne roznice (najcześciej dotyczące modyfikacji posttranslacyjnych) w budowie lekow. Muszą one mieścic sie w precyzyjnie określonych granicach. Lek biopodobny to lek biologiczny wyprodukowany jako bardzo podobna kopia leku biologicznego innowacyjnego wcześniej zarejestrowanego. Lek biopodobny nie jest lekiem generycznym w ujeciu farmakologicznym. Dopuszczenie leku biopodobnego do stosowania wymaga badan określających jego podobienstwo strukturalne, badan za pomocą testow biologicznych, badan farmakokinetycznych i badan klinicznych oceniających skutecznośc i bezpieczenstwo terapii. Lek biopodobny musi cechowac sie określoną biorownowaznością i jego produkcja, podobnie jak produ...
Background The aim of our study was to investigate the risk factors for falls in the rheumatoid a... more Background The aim of our study was to investigate the risk factors for falls in the rheumatoid arthritis (RA) patient population in Poland. This would be a major step towards the development of new fall prevention programs. Material/Methods There were 450 RA patients who met the criteria of the American College of Rheumatology who participated in this study. The average age of patient participants was 54.2 years; the average RA duration was 15.1 years. All patients filled out the study questionnaire regarding falls, medications, and diseases, and they filled out the Polish version of the Health Assessment Questionnaire (HAQ). Results Of the 400 patients, 203 patients (51%) experienced falls. Out of the 268 falls experienced by study patients, 113 falls (42%) were due to an environmental cause, the remainder 155 falls were caused by health conditions. The number of falls positively correlated with HAQ scores (r=0.42, P<0.01) and the duration of RA (r=0.39, P<0.05). For individuals who had fallen 3 or more times, there was a stronger positive correlation between the number of falls and the total HAQ score (r=0.61, P<0.01). The main risk factors for falls in the study group were dizziness (odds ratio [OR]=3.42), the use of hypotensive medication (OR=2.82), foot deformities (OR=4.09), and a high HAQ score (OR=2.59). Other factors such as drug use (e.g., glucocorticoids), pain, and duration of RA were measured using a visual analogue scale, and were found not to have increased the risk for falls and fractures (P>0.05). Conclusions Knowledge about risk factors can help identify high-risk patients to help decrease their risk of falling, thus preventing fall-related injuries.
Introduction: Real-world data indicate disparities in biologic access across Europe. Objectives: ... more Introduction: Real-world data indicate disparities in biologic access across Europe. Objectives: To describe the national structure of PsA care in Poland, with a particular focus on the population of inadequate responders (IRs) and difficulties associated with biologic therapy access. Methods: A pool of rheumatologic and dermatologic care centers was created based on National Health Fund contract lists (n = 841), from which 29 rheumatologic and 10 dermatologic centers were sampled randomly and successfully met the inclusion criterium. Additionally, 33 tertiary care centers were recruited. For successful center recruitment, one provider had to recruit at least one patient that met the criteria for one of the four pre-defined clinical subgroups, in which all patients had to have active PsA and IR status to at least 2 conventional synthetic disease-modifying drugs (csDMARDs). Self-assessment questionnaires were distributed among physicians and their patients. Results: Barriers to biolo...
Psoriatic arthritis (PsA) is a seronegative spondyloarthropathy characterized by skin lesions, da... more Psoriatic arthritis (PsA) is a seronegative spondyloarthropathy characterized by skin lesions, dactylitis, and enthesitis. Patients with PsA suffer from a variety of psychosocial difficulties and nonspecific symptoms early on in the disease course and continue to experience progressive disease due to delays in diagnosis and treatment. Symptoms initially viewed as somatization could lead to undertreatment and promote psychological distress, poor coping, and negative patient–provider relationships. Pain and fatigue are important complaints that affect the patient’s perception and may need to be addressed with a multidisciplinary approach. Maladaptive cognitive responses can lead to a negative illness perception and impact patient beliefs and concerns over treatment, as well as nonadherence. An underlying inflammatory component in affective disorders has been examined, though whether and how it may interact mechanistically in PsA warrants interest. Cognitive behavioral therapy represen...
Tofacitinib is a newly approved small-molecule targeted synthetic disease-modifying antirheumatic... more Tofacitinib is a newly approved small-molecule targeted synthetic disease-modifying antirheumatic drug. The drug was designed as a selective and specific inhibitor of pro-inflammatory receptor signalling. Tofacitinib inhibits the process of intracellular signalling from the receptor to the cellular nucleus and inhibits the inflammation process via a new pathway (inhibition of the Janus kinases), which is unavailable to biological medicines. Tofacitinib has been approved for use in the treatment of patients with moderate to severe active RA. The drug may be used in combination with methotrexate or another conventional synthetic disease-modifying antirheumatic drug or in monotherapy. The efficacy of tofacitinib has been confirmed in several clinical trials. The drug inhibits radiographic progression of the disease. The innovative mechanism of action of tofacitinib is a noteworthy feature because it offers hope of effective treatment for patients who fail to respond to other drugs. The...
Ankylosing spondylitis (AS) is associated with high cardiovascular morbidity and mortality. Recen... more Ankylosing spondylitis (AS) is associated with high cardiovascular morbidity and mortality. Recent studies indicate that microvascular dysfunction may underlie cardiovascular risk in AS. We hypothesized, that microvascular morphology and dysfunction is linked to AS activity and is modifiable by TNF-α inhibitor (TNFi) treatment. Functional Laser Doppler Flowmetry with post-occlusive reactive hyperemia, and structural nailfold capillaroscopy were performed in 54 patients with AS and 28 matched controls. Active AS was diagnosed based on BASDAI ≥ 4 (n = 37). Effects of 3-month TNFi on microcirculation in active AS were studied. AS was associated with prolonged time to peak hyperemia compared to healthy controls. High disease activity was associated with increased time to peak hyperemia and decreased peak hyperemia when compared to patients with inactive AS. In capillaroscopy, AS was associated with morphological abnormalities indicating increased neoangiogenesis and pericapillary edema ...
Evidence from over 10 years of clinical experience demonstrates that biosimilar medicines approve... more Evidence from over 10 years of clinical experience demonstrates that biosimilar medicines approved in the European Union can be used for all their registered indications as safely as their originators and with no negative impact on therapeutic efficacy. The debate on the use of biosimilars in rheumatology focuses specifically on the safety of switching between biosimilars and reference products. Studies conducted to date, including randomised double-blind and open-label extension trials, have not demonstrated any significant differences in therapeutic efficacy or safety between patients switched from one medicine to another and those who were continued on a single medicine. According to the latest recommendations for the use of biosimilars in rheumatic diseases, developed by an international task force in 2017, there is no clinical evidence that a single switch from an originator to a biosimilar medicine is associated with any significant risk for patient safety or reduction in ther...
Younger age is a predictor of good clinical response to treatment with tumour necrosis factor (TN... more Younger age is a predictor of good clinical response to treatment with tumour necrosis factor (TNF) α inhibitors in ankylosing spondylitis (AS) patients; therefore, the aim of the study was to determine age-related differences in cellular functions, which can predict the response. High disease activity AS patients were treated with TNFα inhibitors for 12 weeks. Based on the percentage of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) improvement, patients were divided into responding or non-responding groups. Cytometric and clinical assessment were determined at baseline, 4, and 12 weeks after initiation of anti-TNFα treatment. Expression of activation markers on T cells and intracellular cytokine staining was performed. Baseline percentage of TNFα-producing CD8 cells was lower in responders than in non-responders (20.8 ± 2.9 vs 40.7 ± 8.2; P = 0.04 in T test) and increased in the responding group during the first month of treatment (20.8 ± 2.9 vs 30.3 ± 2.5; P = 0.02)....
The objective of this study was to determine the length of delay in diagnosis of inflammatory rhe... more The objective of this study was to determine the length of delay in diagnosis of inflammatory rheumatic diseases, and to indicate the main factors responsible for such delays. A retrospective multi-centre questionnaire survey carried out among 197 patients with diagnosed inflammatory rheumatic diseases or undergoing the diagnostic process. The most common early symptoms of inflammatory rheumatic disease included joint pain (94%), joint swelling (78%), morning joint stiffness (77%), fatigue (76%), and sleep disturbed by joint pain (74%). When asked about the reasons for seeking medical help, most patients indicated intensification of the symptoms (89%) and the fact that the symptoms made them unable to perform daily activities or work (86%). Limited access to specialists (70%) and the conviction that the symptoms will resolve spontaneously (57%) had the biggest impact on delaying a visit to a doctor. Before visiting a rheumatologist, the patients consulted their symptoms with their g...
Mycophenolate mofetil (MMF) is an inhibitor of inosine monophosphate dehydrogenase, which affects... more Mycophenolate mofetil (MMF) is an inhibitor of inosine monophosphate dehydrogenase, which affects de novo purine synthesis and T- and B-cell proliferation. So far its efficacy and safety as an immunosuppressive treatment have been proven in organ transplantations and also in various autoimmune diseases. A literature search was conducted by using PubMed and the Cochrane library. This review focuses primarily on current treatment with MMF for systemic lupus erythematosus, systemic sclerosis, vasculitis and idiopathic inflammatory myopathies.
Leflunomide (LMF) is an immunemodulatory drug used in the therapy of Rheumatoid Arthritis (RA). A... more Leflunomide (LMF) is an immunemodulatory drug used in the therapy of Rheumatoid Arthritis (RA). After oral administration in the mucosa of digestive tract LMF is quickly converted to an active metabolite A77126 which is a competitive inhibitor of dihydroorotate dehydrogenase--enzyme required in pirymidyne synthesis resulting in decreased proliferation of T and B lymphocytes. As animal studies showed A77126 embryo- and fetotoxity and no relevant epidemiological research in humans were available, LMF received category X pregnancy destination. This is a detailed presentation of two pregnancy cases during LMF therapy in Poland. The first patient was a multiparous woman suffering from RA for 17 years and treated with LM during the last 16 months. The second woman was a primigravida with RA diagnosed 4 years ago and treated with LMF for the last 20 months. LMF wash-out procedures were started immediately as the patients referred with diagnosed early pregnancies with oral administration of...
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Papers by Bogdan Batko