The document summarizes a reproductive health summit organized by the American College of Rheumatology to discuss management of pregnant and lactating women with autoimmune diseases. It provides an overview of presentations given at the summit, including discussions on regulatory challenges presented by the FDA, research interests of the NIH and NICHD, and information on how pregnancy alters disease pathophysiology and drug metabolism. Experts discussed placental and lactation physiology as it relates to drug transport, and presented data on specific autoimmune diseases and their impacts on pregnancy. The overall message was that uncontrolled maternal inflammation can adversely impact the fetus.
Breastfeeding And The Risk Of Postneonatal Death In The United StatesBiblioteca Virtual
This study examined the association between breastfeeding and postneonatal mortality in the United States using data from the 1988 National Maternal and Infant Health Survey. The study found that children who were ever breastfed had a 21% lower risk of postneonatal death compared to children who were never breastfed. Longer durations of breastfeeding were associated with even lower risk. The protective effect of breastfeeding was seen across different causes of postneonatal death, including infections, injuries, and sudden infant death syndrome.
Isotretinoin is a novel treatment for severe, recalcitrant nodular acne sold under the brand names Accutane®, Amnesteem®, Claravis®, and Sotret®. It is the most widely used teratogenic drug in the United States. From a population based perspective, women and men use the drug in near equal proportions but the risks are exponentially greater for women of childbearing years. Serious developmental abnormalities have displayed a high tendency to occur in clusters in fetuses exposed to isotretinoin. This review of medical literature focuses on the public health implications of isotretinoin use and develops a case for continued risk management. Reduction of fetal isotretinoin exposure is contingent upon effective programming and continued adherence to strict standards.
Medical complications in pregnancy cmt april 2010NESSlideShare
This document discusses three cases related to medical complications in pregnancy. Case 1 describes a woman who died of an undiagnosed pulmonary embolism during pregnancy. Case 2 involves a woman admitted with renal problems during pregnancy. The document then discusses prescribing medications during pregnancy, including the risks of certain anti-epileptic drugs. Case 3 presents a woman with epilepsy who is now pregnant.
FIGO release Guidelines for Gestational diabetes as its a Global health problem a Pragmative Guide for Diagnsis,Managment and Care through its Journal,International Journal of Gynaecology and Obstetrics
The document summarizes the 25th International Conference of Organization of Teratology Information Specialists that was held in Baltimore in 2012. It discusses presentations on topics such as patient perception of teratogenic risks, how economic challenges are affecting teratology information services, epidemiological research on various exposures, and counseling approaches. The document also describes a visit by the director of the Korean Motherisk Program to learn about the program in Toronto to help shape the vision and future of the Korean Motherisk Program.
Breastfeeding And The Risk Of Postneonatal Death In The United StatesBiblioteca Virtual
This study examined the association between breastfeeding and postneonatal mortality in the United States using data from the 1988 National Maternal and Infant Health Survey. The study found that children who were ever breastfed had a 21% lower risk of postneonatal death compared to children who were never breastfed. Longer durations of breastfeeding were associated with even lower risk. The protective effect of breastfeeding was seen across different causes of postneonatal death, including infections, injuries, and sudden infant death syndrome.
Isotretinoin is a novel treatment for severe, recalcitrant nodular acne sold under the brand names Accutane®, Amnesteem®, Claravis®, and Sotret®. It is the most widely used teratogenic drug in the United States. From a population based perspective, women and men use the drug in near equal proportions but the risks are exponentially greater for women of childbearing years. Serious developmental abnormalities have displayed a high tendency to occur in clusters in fetuses exposed to isotretinoin. This review of medical literature focuses on the public health implications of isotretinoin use and develops a case for continued risk management. Reduction of fetal isotretinoin exposure is contingent upon effective programming and continued adherence to strict standards.
Medical complications in pregnancy cmt april 2010NESSlideShare
This document discusses three cases related to medical complications in pregnancy. Case 1 describes a woman who died of an undiagnosed pulmonary embolism during pregnancy. Case 2 involves a woman admitted with renal problems during pregnancy. The document then discusses prescribing medications during pregnancy, including the risks of certain anti-epileptic drugs. Case 3 presents a woman with epilepsy who is now pregnant.
FIGO release Guidelines for Gestational diabetes as its a Global health problem a Pragmative Guide for Diagnsis,Managment and Care through its Journal,International Journal of Gynaecology and Obstetrics
The document summarizes the 25th International Conference of Organization of Teratology Information Specialists that was held in Baltimore in 2012. It discusses presentations on topics such as patient perception of teratogenic risks, how economic challenges are affecting teratology information services, epidemiological research on various exposures, and counseling approaches. The document also describes a visit by the director of the Korean Motherisk Program to learn about the program in Toronto to help shape the vision and future of the Korean Motherisk Program.
This document discusses teratogenesis and environmental exposures that can increase risks during pregnancy. It defines a teratogen as an agent that can interfere with normal embryo or fetal development. While major birth defects are usually considered, teratogens can also increase risks of other adverse outcomes. About 10% of major birth defects are due to environmental exposures. The document reviews historical cases of recognized teratogens like thalidomide and discusses principles of teratology, mechanisms of pathogenesis, adverse case reports, and pregnancy registries for monitoring drug safety.
Treat the Patient: Not the Pregnancy April 2015PASaskatchewan
This document provides information on safely managing common medical conditions during pregnancy and lactation. It discusses medication classification systems and factors affecting drug transfer across the placenta and into breastmilk. Guidelines are presented for treating depression, diabetes, thyroid disorders, infections, pain, nausea, and other issues. Many prescription and over-the-counter drugs are deemed safe to use when necessary, such as most antibiotics, acetaminophen, ranitidine, and antidepressants. Untreated medical conditions pose greater risks than potential side effects of approved medications. Resources for further information and guidance are also referenced.
A prospective observational study was conducted in the Neonatal Unit of Indraprastha Apollo Hospital over a period of 10 months. A total of 86 high-risk newborns were included to study the mortality and morbidity patterns. Majority of these (68%) were outborn male babies: 65% were pre-term and 36% were low birth weight. Overall survival was 77.2% and was better in inborn babies. Survival was directly proportional to gestation and birth weight. Systemic infection was associated with higher mortality and morbidity. Klebsiella was the commonest organism cultured followed by Candida. Hyaline membrane disease was the commonest respiratory morbidity. Sixty-seven percent required ventilatory support, and mortality was directly proportional to the duration of ventilation. Only 6% of the survivors had neurodevelopmental delay at 6 months and one baby had hearing impairment requiring cochlear implant. They continue to be on long-term follow-up.
A prospective observational study was conducted in the Neonatal Unit of Indraprastha Apollo Hospital over a period of 10 months. A total of 86 high risk newborns were included to study the mortality and morbidity pattern. Majority of these (68%) were outborn male babies. Sixty five percent were preterm and 36% low birth weight. Overall survival was 77.2% and was better in inborn babies. Survival was directly proportional to gestation and birth weight. Systemic infection was associated with higher mortality and morbidity. Klebsiella was the commonest organism cultured followed by Candida. Hyaline membrane disease was the commonest Respiratory morbidity. Sixty Seven pecent required ventilatory support and mortality was directly proportional to the duration of ventilation. Only six percent of the survivors had Neurodevelopmental delay at 6 months and 1 baby had hearing impairment requiring Cochlear implant. They continue to be on long term follow up.
Prediccion y prevencion del parto preterminorubenhuaraz
This document discusses screening and prevention of preterm birth, which is the leading cause of neonatal mortality in the US. It describes various risk factors for preterm birth such as a prior preterm birth, short cervical length on ultrasound, vaginal bleeding, infections, and behavioral factors like smoking. Transvaginal ultrasound is an effective way to screen for short cervical length, which is a strong predictor of preterm birth risk. The document reviews evidence for different proposed screening and treatment methods, noting that while some risk factors are associated with preterm birth, treatments have not been shown to consistently and definitively reduce that risk.
This document summarizes the principles of teratology and developmental toxicology. It discusses key concepts like critical periods of development, dose-response relationships, mechanisms of action of teratogens, and manifestations of deviant development. Historical cases of thalidomide, Bendectin, and diethylstilbestrol are reviewed. The limitations of animal studies for assessing human teratogenic risk are covered. Methods for evaluating safety and risk of drugs in pregnancy are examined, including FDA classification systems and graphical representations. The roles of teratology information services like the Korean Motherisk Program in counseling on inadvertent exposures are described.
Teratology is the study of abnormalities in fetal development and birth defects. Some key causes of birth defects include certain medications (such as thalidomide, diethylstilbestrol, valproic acid), infections (rubella, toxoplasmosis), and environmental factors (alcohol). There are critical periods in development when the fetus is most susceptible to teratogens. Understanding how teratogens act can help prevent birth defects and develop new safe drugs for pregnant women.
This document provides guidelines from the American College of Obstetricians and Gynecologists (ACOG) on the clinical management of intrauterine growth restriction (IUGR). It defines key terms like IUGR and small for gestational age (SGA). IUGR refers to a fetus whose weight is less than expected, usually below the 10th percentile. SGA refers to infants with a birth weight below the 10th percentile. The document discusses the etiology of IUGR, which can be due to maternal, fetal or placental factors like hypertension, smoking, malnutrition, infections or genetic disorders. It provides background on terminology and outlines recommendations for diagnosis and management of IUGR.
The document discusses newborn screening for metabolic disorders using tandem mass spectrometry (MS/MS). It begins with the story of Tyler Wayne who died from undiagnosed galactosemia. It then explains that MS/MS allows for early detection of treatable metabolic disorders before symptoms appear, preventing complications. The document outlines the process and benefits of newborn screening as well as the status of screening programs in various countries including the UAE.
WHO's Medical Eligibility Criteria: Global Contraceptive Guidance Sharon Phillips
1) The document summarizes key information from a presentation on the WHO Medical Eligibility Criteria for Contraceptive Use. It discusses the unmet need for contraception, benefits of meeting this need, and contraceptive methods.
2) It provides an overview of the WHO Medical Eligibility Criteria, which recommends the safety of contraceptive methods for people with certain health conditions. The criteria use a numeric system and were recently updated for several populations.
3) The presentation reviews two case presentations and explains the WHO recommendations for contraceptive use in women with migraines and in breastfeeding women. The guidance has been updated for these groups.
This document provides an overview of Oncolytics Biotech and their lead product, REOLYSIN.
It discusses three clinical development pathways for REOLYSIN: 1) Combinations with chemotherapy to directly lyse tumor cells, 2) Combinations with immunotherapy to activate immune responses, and 3) Combinations with targeted therapies to modulate innate immunity.
For pathway 1, a phase 2 trial showed REOLYSIN in combination with paclitaxel significantly improved overall survival over paclitaxel alone in metastatic breast cancer patients. This provides the basis for a planned 400-patient phase 3 registration study in this indication.
This presentation provides an overview of Oncolytics Biotech and its lead product candidate REOLYSIN. Key points include:
- REOLYSIN is a first-in-class immuno-oncolytic virus being developed for solid tumors and blood cancers. It has a dual mechanism of action selectively killing cancer cells while activating the immune system.
- In a phase 2 trial in metastatic breast cancer, REOLYSIN combined with paclitaxel more than doubled overall survival compared to paclitaxel alone in ER+/PR+/HER2- patients.
- The clinical development plan is pursuing combinations with chemotherapy, immunotherapy agents like Keytruda, and targeted therapies. This includes an ongoing myel
Screening for and treatment of asymptomatic bacteriuria in high-risk pregnant women reduces the risk of preterm birth. However, routine screening of all pregnant women in the first trimester with urine culture is not currently recommended due to the low prevalence of asymptomatic bacteriuria in the general pregnant population and the costs of universal screening.
This document summarizes common neonatal morbidities that can result from complications during pregnancy and delivery. It discusses how conditions like diabetes, hypertension, infection, and nutritional imbalances in the mother can negatively impact the health of the newborn. The summary provides management considerations for treating infants born with various medical issues and outlines how close collaboration between obstetric and neonatal clinicians is important for counseling families and ensuring the best outcomes for both mother and baby.
This document summarizes guidelines for using hormonal contraception in women with common autoimmune diseases. It discusses that combined oral contraceptives are generally safe to use in women with rheumatoid arthritis and stable systemic lupus erythematosus outside of flares. Progesterone-only contraceptives like the mini pill do not seem to increase disease activity in lupus or rheumatoid arthritis and have less risk of thrombosis than combined methods. Hormonal contraception is generally not recommended for women with antiphospholipid syndrome due to increased thrombosis risk.
Common systemic dermatologoical medications and pregnancymohamed fotoh90
This document discusses the safety and risks of various medications that may be used to treat dermatological conditions during pregnancy. It categorizes medications such as corticosteroids, antihistamines, antibiotics, antivirals, antifungals and immunosuppressants based on FDA risk categories. While some medications like prednisone and cephalosporins are considered relatively safe, others like fluconazole and griseofulvin carry higher risks of fetal abnormalities and should generally be avoided during pregnancy. Hydroxychloroquine therapy appears to be safe for treating conditions like lupus in pregnant patients based on existing studies.
Sodium valproate is contraindicated in pregnancy due to significant risks of congenital malformations and developmental effects in infants exposed to it in utero. The risk of congenital malformations has been estimated between 6-12% for infants exposed to sodium valproate, compared to background rates of 2-3%. Children exposed to valproate in utero also face risks of reduced IQ, autism spectrum disorder (around 4% risk), and behavioral issues. While reducing valproate doses below 1000 mg/day and using high-dose folate around conception may lower some risks, sodium valproate should generally not be used in women who could become pregnant unless other treatments are ineffective or not tolerated due to its serious
Two new member firms have joined the global accountancy network UHY, strengthening its presence in Central America. ASCOFI, based in San José, Costa Rica, provides audit, accounting, tax, and consulting services with 3 partners and 12 staff. Castro Díaz y Asociados, based in San Pedro Sula, Honduras, provides similar services with 4 partners and 8 staff serving national and international clients. UHY's chairman commented that the addition of these firms extends their capabilities in Latin America through their regional expertise.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive function. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms.
This document discusses teratogenesis and environmental exposures that can increase risks during pregnancy. It defines a teratogen as an agent that can interfere with normal embryo or fetal development. While major birth defects are usually considered, teratogens can also increase risks of other adverse outcomes. About 10% of major birth defects are due to environmental exposures. The document reviews historical cases of recognized teratogens like thalidomide and discusses principles of teratology, mechanisms of pathogenesis, adverse case reports, and pregnancy registries for monitoring drug safety.
Treat the Patient: Not the Pregnancy April 2015PASaskatchewan
This document provides information on safely managing common medical conditions during pregnancy and lactation. It discusses medication classification systems and factors affecting drug transfer across the placenta and into breastmilk. Guidelines are presented for treating depression, diabetes, thyroid disorders, infections, pain, nausea, and other issues. Many prescription and over-the-counter drugs are deemed safe to use when necessary, such as most antibiotics, acetaminophen, ranitidine, and antidepressants. Untreated medical conditions pose greater risks than potential side effects of approved medications. Resources for further information and guidance are also referenced.
A prospective observational study was conducted in the Neonatal Unit of Indraprastha Apollo Hospital over a period of 10 months. A total of 86 high-risk newborns were included to study the mortality and morbidity patterns. Majority of these (68%) were outborn male babies: 65% were pre-term and 36% were low birth weight. Overall survival was 77.2% and was better in inborn babies. Survival was directly proportional to gestation and birth weight. Systemic infection was associated with higher mortality and morbidity. Klebsiella was the commonest organism cultured followed by Candida. Hyaline membrane disease was the commonest respiratory morbidity. Sixty-seven percent required ventilatory support, and mortality was directly proportional to the duration of ventilation. Only 6% of the survivors had neurodevelopmental delay at 6 months and one baby had hearing impairment requiring cochlear implant. They continue to be on long-term follow-up.
A prospective observational study was conducted in the Neonatal Unit of Indraprastha Apollo Hospital over a period of 10 months. A total of 86 high risk newborns were included to study the mortality and morbidity pattern. Majority of these (68%) were outborn male babies. Sixty five percent were preterm and 36% low birth weight. Overall survival was 77.2% and was better in inborn babies. Survival was directly proportional to gestation and birth weight. Systemic infection was associated with higher mortality and morbidity. Klebsiella was the commonest organism cultured followed by Candida. Hyaline membrane disease was the commonest Respiratory morbidity. Sixty Seven pecent required ventilatory support and mortality was directly proportional to the duration of ventilation. Only six percent of the survivors had Neurodevelopmental delay at 6 months and 1 baby had hearing impairment requiring Cochlear implant. They continue to be on long term follow up.
Prediccion y prevencion del parto preterminorubenhuaraz
This document discusses screening and prevention of preterm birth, which is the leading cause of neonatal mortality in the US. It describes various risk factors for preterm birth such as a prior preterm birth, short cervical length on ultrasound, vaginal bleeding, infections, and behavioral factors like smoking. Transvaginal ultrasound is an effective way to screen for short cervical length, which is a strong predictor of preterm birth risk. The document reviews evidence for different proposed screening and treatment methods, noting that while some risk factors are associated with preterm birth, treatments have not been shown to consistently and definitively reduce that risk.
This document summarizes the principles of teratology and developmental toxicology. It discusses key concepts like critical periods of development, dose-response relationships, mechanisms of action of teratogens, and manifestations of deviant development. Historical cases of thalidomide, Bendectin, and diethylstilbestrol are reviewed. The limitations of animal studies for assessing human teratogenic risk are covered. Methods for evaluating safety and risk of drugs in pregnancy are examined, including FDA classification systems and graphical representations. The roles of teratology information services like the Korean Motherisk Program in counseling on inadvertent exposures are described.
Teratology is the study of abnormalities in fetal development and birth defects. Some key causes of birth defects include certain medications (such as thalidomide, diethylstilbestrol, valproic acid), infections (rubella, toxoplasmosis), and environmental factors (alcohol). There are critical periods in development when the fetus is most susceptible to teratogens. Understanding how teratogens act can help prevent birth defects and develop new safe drugs for pregnant women.
This document provides guidelines from the American College of Obstetricians and Gynecologists (ACOG) on the clinical management of intrauterine growth restriction (IUGR). It defines key terms like IUGR and small for gestational age (SGA). IUGR refers to a fetus whose weight is less than expected, usually below the 10th percentile. SGA refers to infants with a birth weight below the 10th percentile. The document discusses the etiology of IUGR, which can be due to maternal, fetal or placental factors like hypertension, smoking, malnutrition, infections or genetic disorders. It provides background on terminology and outlines recommendations for diagnosis and management of IUGR.
The document discusses newborn screening for metabolic disorders using tandem mass spectrometry (MS/MS). It begins with the story of Tyler Wayne who died from undiagnosed galactosemia. It then explains that MS/MS allows for early detection of treatable metabolic disorders before symptoms appear, preventing complications. The document outlines the process and benefits of newborn screening as well as the status of screening programs in various countries including the UAE.
WHO's Medical Eligibility Criteria: Global Contraceptive Guidance Sharon Phillips
1) The document summarizes key information from a presentation on the WHO Medical Eligibility Criteria for Contraceptive Use. It discusses the unmet need for contraception, benefits of meeting this need, and contraceptive methods.
2) It provides an overview of the WHO Medical Eligibility Criteria, which recommends the safety of contraceptive methods for people with certain health conditions. The criteria use a numeric system and were recently updated for several populations.
3) The presentation reviews two case presentations and explains the WHO recommendations for contraceptive use in women with migraines and in breastfeeding women. The guidance has been updated for these groups.
This document provides an overview of Oncolytics Biotech and their lead product, REOLYSIN.
It discusses three clinical development pathways for REOLYSIN: 1) Combinations with chemotherapy to directly lyse tumor cells, 2) Combinations with immunotherapy to activate immune responses, and 3) Combinations with targeted therapies to modulate innate immunity.
For pathway 1, a phase 2 trial showed REOLYSIN in combination with paclitaxel significantly improved overall survival over paclitaxel alone in metastatic breast cancer patients. This provides the basis for a planned 400-patient phase 3 registration study in this indication.
This presentation provides an overview of Oncolytics Biotech and its lead product candidate REOLYSIN. Key points include:
- REOLYSIN is a first-in-class immuno-oncolytic virus being developed for solid tumors and blood cancers. It has a dual mechanism of action selectively killing cancer cells while activating the immune system.
- In a phase 2 trial in metastatic breast cancer, REOLYSIN combined with paclitaxel more than doubled overall survival compared to paclitaxel alone in ER+/PR+/HER2- patients.
- The clinical development plan is pursuing combinations with chemotherapy, immunotherapy agents like Keytruda, and targeted therapies. This includes an ongoing myel
Screening for and treatment of asymptomatic bacteriuria in high-risk pregnant women reduces the risk of preterm birth. However, routine screening of all pregnant women in the first trimester with urine culture is not currently recommended due to the low prevalence of asymptomatic bacteriuria in the general pregnant population and the costs of universal screening.
This document summarizes common neonatal morbidities that can result from complications during pregnancy and delivery. It discusses how conditions like diabetes, hypertension, infection, and nutritional imbalances in the mother can negatively impact the health of the newborn. The summary provides management considerations for treating infants born with various medical issues and outlines how close collaboration between obstetric and neonatal clinicians is important for counseling families and ensuring the best outcomes for both mother and baby.
This document summarizes guidelines for using hormonal contraception in women with common autoimmune diseases. It discusses that combined oral contraceptives are generally safe to use in women with rheumatoid arthritis and stable systemic lupus erythematosus outside of flares. Progesterone-only contraceptives like the mini pill do not seem to increase disease activity in lupus or rheumatoid arthritis and have less risk of thrombosis than combined methods. Hormonal contraception is generally not recommended for women with antiphospholipid syndrome due to increased thrombosis risk.
Common systemic dermatologoical medications and pregnancymohamed fotoh90
This document discusses the safety and risks of various medications that may be used to treat dermatological conditions during pregnancy. It categorizes medications such as corticosteroids, antihistamines, antibiotics, antivirals, antifungals and immunosuppressants based on FDA risk categories. While some medications like prednisone and cephalosporins are considered relatively safe, others like fluconazole and griseofulvin carry higher risks of fetal abnormalities and should generally be avoided during pregnancy. Hydroxychloroquine therapy appears to be safe for treating conditions like lupus in pregnant patients based on existing studies.
Sodium valproate is contraindicated in pregnancy due to significant risks of congenital malformations and developmental effects in infants exposed to it in utero. The risk of congenital malformations has been estimated between 6-12% for infants exposed to sodium valproate, compared to background rates of 2-3%. Children exposed to valproate in utero also face risks of reduced IQ, autism spectrum disorder (around 4% risk), and behavioral issues. While reducing valproate doses below 1000 mg/day and using high-dose folate around conception may lower some risks, sodium valproate should generally not be used in women who could become pregnant unless other treatments are ineffective or not tolerated due to its serious
Two new member firms have joined the global accountancy network UHY, strengthening its presence in Central America. ASCOFI, based in San José, Costa Rica, provides audit, accounting, tax, and consulting services with 3 partners and 12 staff. Castro Díaz y Asociados, based in San Pedro Sula, Honduras, provides similar services with 4 partners and 8 staff serving national and international clients. UHY's chairman commented that the addition of these firms extends their capabilities in Latin America through their regional expertise.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive function. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms.
UHY is an international network of independent accounting and consulting firms operating in over 89 countries. The document discusses UHY's services, including audit, tax, advisory, and corporate finance services. It highlights UHY's global network of over 7,660 professionals in 296 offices as providing clients with both local expertise and international capabilities. UHY works with clients to understand their needs and deliver customized solutions through its consistent values and culture across the global network.
The document outlines the topics that will be covered in a personality development phase, including the scope of contribution, embarking on becoming a contributor, design solutions, and focusing on value. It then provides brief examples and lists of individuals to illustrate some of the topics, such as characteristics of a contributor, leaders like Narendra Modi, and names and enrollment numbers of students.
1) Tinea incognito is a dermatophytic infection that presents with an atypical clinical appearance due to previous treatment with topical or systemic corticosteroids or immunomodulators like pimecrolimus and tacrolimus.
2) Tinea incognito often mimics conditions like neurodermatitis, atopic dermatitis, rosacea, and seborrheic dermatitis, making diagnosis difficult.
3) The use of topical corticosteroids is a common cause of tinea incognito by suppressing the immune response to dermatophytes and altering the clinical presentation of the infection.
The document discusses current concepts in systemic and topical therapy for superficial mycoses. It summarizes the main systemic agents used which include griseofulvin, imidazoles/triazoles like ketoconazole and itraconazole, and allylamines like terbinafine. It also discusses the main topical agents used which include imidazoles, allylamines/benzylamines, polyenes like nystatin, and ciclopirox olamine. The document provides indications, dosages, safety considerations and interactions for these various agents in treating superficial fungal infections.
Microsporum spp infections, particularly M. canis, have significantly changed in recent decades. While historically more common in boys and involving the scalp, infections now affect all ages and genders. Deep kerion lesions of the scalp, once typically caused by T. mentagrophytes, are now often due to M. canis. Onychomycosis and disseminated infections associated with immunosuppression are also increasingly linked to M. canis. The pathogen has taken on varied clinical presentations, sometimes mimicking other skin conditions. These shifts reflect changes in epidemiology and highlight the need for accurate diagnosis and treatment of Microsporum spp infections.
Tinea incognito is a dermatophytic fungal infection that presents with atypical clinical features due to previous treatment with corticosteroids or immunomodulators like pimecrolimus and tacrolimus. This modifies the infection's appearance, making diagnosis difficult. Tinea incognito lesions may resemble various inflammatory skin conditions and often affect the face and arms. Definitive diagnosis requires microscopic identification of fungal elements in skin scrapings or cultures. Treatment involves oral antifungals for 2-4 weeks to clear the infection.
This document discusses onychomycosis, a common nail fungus. It begins by defining onychomycosis and describing the most common causes as dermatophytes (fungi that infect skin, hair, and nails) such as Trichophyton rubrum, yeasts such as Candida species, and other molds. It then discusses the different clinical presentations of onychomycosis and outlines the primary diagnostic methods of direct microscopic examination, culture, and histopathology to confirm the presence of fungi in the nail. The document focuses on proper sampling techniques for these diagnostic tests and stresses the importance of culture to identify the infecting species and determine appropriate treatment.
16-0729 Material&Metalworktechniques FINAL2Cynthia Gale
Sterling silver, bronze, brass, base metals, semi-precious stones, fossil bamboo, Swarovski crystals, leather, abalone, mother of pearl, and various metalworking techniques such as repousse, filigree, hammering, granulation, casting, enameling, and carved mother of pearl are described as raw materials and processes used in metalwork. Specific tools are shown for repousse, filigree, hammering, and granulation techniques. Collectible concepts like birthstone charms, stackable jewelry, and spinning rings are also outlined.
Fisiopatologia cardiorespiratoria en pancreatitis agudacsanoja2020
This document summarizes the pathophysiological mechanisms involved in severe acute pancreatitis (SAP). It discusses how initial events localized in the pancreas, such as premature enzyme activation and impaired calcium homeostasis, lead to pancreatic inflammation. Neurotransmitters like substance P are also released, amplifying the inflammatory response through vasodilation and recruitment of immune cells. This localized damage then spreads systemically through systemic inflammatory response syndrome (SIRS), impairing cardiovascular and other organ functions. SIRS is characterized by pulmonary, cardiovascular and renal issues. Hypotension in particular is a risk factor for death in SAP patients. The document reviews the cascade of events from initial pancreatic damage through neurogenic inflammation and SIRS that ultimately results in multi
Motor disorders can involve the muscles of the pharyngoesophageal region or the esophageal body and lower esophageal sphincter. Proximal disorders cause oropharyngeal dysphagia while distal disorders produce vague symptoms. Diagnosis of proximal disorders involves endoscopy and videofluoroscopy while distal disorders are diagnosed using endoscopy, barium swallow, and manometry. Achalasia is caused by loss of inhibitory neurons and treated initially with pneumatic dilation or botulinum toxin injection. Minimally invasive techniques are becoming more common for treating proximal disorders like Zenker's diverticulum.
This textbook provides a comprehensive overview of hepatology. It was created by a team of international experts and is available free online. This second edition has been updated to reflect recent advances. It covers the epidemiology, virology and treatment of viral hepatitis types A, B, C, D and E. It also addresses diagnostic procedures, prophylaxis, vaccination strategies and complications of chronic liver disease. The editors aim to regularly update the content so it remains a valuable clinical reference.
This document discusses evidence for drug safety and efficacy in pregnancy. It notes that while prospective safety data from clinical trials is preferable, registries provide some reassurance in the absence of such data. Large prospective treatment trials in pregnancy are also absent. The document then examines infection risk and specific infections in pregnancy like urinary tract infections. It discusses how physiologic changes in pregnancy affect drug pharmacokinetics and considerations for drug selection and treatment of conditions like nausea/vomiting, hypertension, and migraines in pregnancy.
Oral surgery during pregnancy
Dr. Ahmed M. Adawy
Professor Emeritus, Dep. Oral & Maxillofacial Surg.
Former Dean, Faculty of Dental Medicine
Al-Azhar University
Pregnancy, also known as gestation, is the time during which a fetus develops inside a woman's uterus. Pregnancy is typically divided into three trimesters. The common belief has been that, if an oral surgery procedure is recommended, but it’s not an emergency, the second trimester is the ideal time. Pregnancy however, is not a disease and pregnant woman should not be treated differently than the general population. In short, it could be concluded that:
• Dental care is safe and essential during pregnancy
• Pregnancy is not a reason to defer routine dental care or treatment
• Diagnostic measures, including needed dental x-rays, can be undertaken safely
• Emergency care should be provided at any time during pregnancy
Vaccine safety requires careful monitoring both before and after vaccines are approved. Pre-approval clinical trials evaluate efficacy and safety but are too small to detect rare issues. The Vaccine Adverse Event Reporting System (VAERS) monitors safety after approval by collecting reports from healthcare providers and the public. While VAERS detects potential problems, it cannot determine if a vaccine caused a specific adverse event. Additional studies are needed to evaluate potential safety issues found through VAERS. Ongoing research is also important to improve understanding of vaccine safety and adverse events.
Thai chậm tăng trưởng trong tử cung ACOG SMFM 2019Võ Tá Sơn
This document provides an overview of fetal growth restriction (FGR), including terminology, prevalence, etiology, diagnostic tools, and guidance for management and delivery timing. It defines FGR as an estimated fetal weight below the 10th percentile and small for gestational age (SGA) as a birth weight below the 10th percentile. FGR can result from maternal medical conditions, substance use, malnutrition, infection, genetic/structural fetal issues, or placental dysfunction. Diagnosis relies on ultrasound to measure fetal size and check for signs of placental insufficiency. Management may include increased surveillance and determining optimal delivery timing to improve neonatal outcomes.
The document discusses the teratogenicity of psychotropic drugs. It notes that while mental illness in mothers poses risks, discontinuing medication during pregnancy may not be possible. The guiding principles are to minimize exposure to untreated illness and psychotropics, continue prior effective medications, and monitor infants for potential drug effects if exposed during lactation or late pregnancy. Risks include teratogenesis, perinatal effects, and potential long-term neurodevelopmental impacts, though studies have shown mixed results. Among SSRIs, paroxetine carries greater risks while sertraline and citalopram generally pose less risk and are considered first-line treatments.
Pharmacovigilance involves monitoring the safety of drugs at all stages, from development through post-marketing. It aims to detect, understand, and prevent adverse drug reactions through activities like adverse event reporting, drug monitoring, and studying medication errors and drug-related deaths. Pharmacovigilance is important for protecting public health as patterns of drug use change over time with globalization and advances in technology and medicine.
This document summarizes the 43rd Annual meeting of the European Teratology Society. It discusses new FDA labeling requirements for pregnancy and lactation information, including removing pregnancy categories and providing risk summaries. It outlines the specific content requirements for sections 8.1 on Pregnancy, 8.2 on Lactation, and 8.3 on Females and Males of Reproductive Potential. Timelines are provided for applications to conform to the new requirements. Presentations are described on inflammation in pregnancy and effects on fetal development, and using zebrafish embryos for chemical screening.
This document from the American Academy of Pediatrics outlines their policy statement on breastfeeding and the use of human milk. The key points are:
1) Extensive research has demonstrated significant health benefits for infants and mothers from breastfeeding, including reduced risk of infectious diseases, sudden infant death syndrome, diabetes, obesity, and improved cognitive development.
2) The policy statement provides recommendations for pediatricians and healthcare professionals to promote, protect, and support breastfeeding through individual practice, hospitals, medical schools, and communities.
3) Certain infectious diseases like HIV may preclude breastfeeding in some situations, but exclusive breastfeeding for the first 6 months does not increase HIV transmission risk according to some studies in developing countries.
This document summarizes key aspects of pharmacovigilance in pediatrics. It notes that drug safety profiles in children are often less well known than in adults due to limited clinical trials. Off-label use is also common in pediatrics due to a lack of approved formulations and dosing recommendations for children. Certain adverse drug reactions are specific to pediatric patients and can be related to developmental factors. Spontaneous reporting and epidemiological studies are important for monitoring drug safety in children but underreporting remains an issue. The incidence of adverse drug reactions in children varies depending on factors like treatment setting and country.
Safety of Mebendazole Use During Lactationmothersafe
This case series study evaluated the safety of mebendazole use in 45 lactating women and their infants. Mebendazole was administered using single or repeated doses and was well tolerated by both the mothers and infants, with no adverse effects observed in infants. Mild GI irritability occurred in two treated mothers. This study provides the first evidence that mebendazole is safe for use in breastfeeding.
This document reviews the risks and considerations for using 11 broad-spectrum antibiotics during pregnancy and lactation. The antibiotics range from having no known teratogenic risk (penicillin G, penicillin VK) to unlikely risk (amoxicillin, chloramphenicol, ciprofloxacin, doxycycline, levofloxacin, rifampin) to undetermined risk (clindamycin, gentamicin, vancomycin). Most antibiotics are compatible with breastfeeding except chloramphenicol. Pharmacokinetic changes during pregnancy may require dosage adjustments for some antibiotics like penicillins, fluoroquinolones, and gentamicin. Health care professionals should consider each antibiotic's risk profile when prescribing
This document discusses pharmacotherapy for pediatric HIV infection. It covers antiretroviral therapy (ART) used during pregnancy and delivery to prevent mother-to-child transmission of HIV. ART regimens aim to achieve high drug levels in the fetus to prevent transmission. Short-term neonatal ART prophylaxis is also used. While ART has significantly reduced pediatric HIV infections, challenges remain due to limited access in developing countries, where most new pediatric HIV cases occur. Ongoing research monitors potential long-term effects of in utero ART exposure on children.
Pharmacovigilance (PV) Companies: Ensuring Drug Safety in Personalized Treatm...ClinosolIndia
Pharmacovigilance, a critical component of the healthcare and pharmaceutical industry, plays a pivotal role in monitoring and ensuring the safety of drugs. As personalized treatment approaches gain prominence, the responsibilities of PV companies become even more significant. This article explores the key functions of pharmacovigilance companies in the context of personalized medicine, focusing on their role in ensuring drug safety and mitigating potential risks associated with tailored therapeutic interventions.
Antipsychotics and mood stabilizers in pregnancyMohamed Sedky
Objectives:
Background risk of spontaneous congenital anomalies
The impact of mental illness on pregnancy
The impact of pregnancy on mental illness
The impact Antipsychotics and mood stabilizers on pregnancy outcome
Recommendations for prescribing during pregnancy
What to include in discussions with a pregnant women
Journal club anticonvulsivantes 13-03-2012Ruber Arias
This document summarizes research on the risk of birth defects in infants born to women taking antiepileptic drugs (AEDs) during pregnancy. It describes a study that compared the risk of major malformations in infants exposed to lamotrigine or carbamazepine as monotherapy or polytherapy during the first trimester. The study found the risk was highest with polytherapy, including polytherapies containing valproate, and lowest with lamotrigine monotherapy. It discusses limitations but concludes the findings provide useful information for counseling women on AED fetal risks.
This document provides an overview of the effects of maternal medication on the fetus and newborn. It discusses the pharmacokinetics and physiological changes during pregnancy that impact drug therapy. It explains how drugs can cross the placenta and be excreted in breastmilk. The document outlines the FDA drug categories during pregnancy and provides examples of commonly used medications in pregnancy, their effects, and safety classifications. Key points covered include the window of susceptibility to teratogens, drug safety evaluation, and management of conditions like hypertension, diabetes, and thyroid disorders during pregnancy.
The document discusses guidelines for prepregnancy counseling. It recommends that prepregnancy counseling should begin by asking patients if they plan to become pregnant within the next year. The goals of counseling are to optimize a woman's health, address risks, and provide education to reduce risks to the woman, fetus, and neonate. Counseling should occur multiple times and manage medical conditions, review medications, screen for infections and violence, and encourage a healthy lifestyle.
Treatment of many dermatologic conditions is elective. Some drugs which used by the dermatologist for the patient who is pregnant or lactating may have potentially harmful effects on the mother and fetus or nursing infant. Likewise, not every pregnancy (in the absence of drug therapy) results
challenges in obstetric prescription
Beautiful Slide Show By Editor Dr. Ragini Agrawal And Dr. Tamkeen khan
Dr. Ragini Agrawal, Chairperson Food , Drug & medico surgical Equipment Committee 2009-2011
1. ACR Reproductive Health Summit on the Management of
Pregnant and Lactating Women with Autoimmune Diseases
Kathryn Dao, MD; John J. Cush, MD; Arthur Kavanaugh, MD and Michael Weisman MD
On January 10, 2014, a Reproductive Health Summit on
Autoimmune Diseases convened in Washington, D.C. The
two-day event, organized by the American College of
Rheumatology (ACR) Drug Safety Committee, included
presentations by representatives from the Food Drug
Administration (FDA), the National Institute of Health (NIH),
the National Institute of Child Health and Human Development
(NICHD), experts in obstetrics, maternal and fetal medicine,
pediatrics, rheumatology, gastroenterology, dermatology, as
well as patient support and advocacy groups. The idea for
the Reproductive Health Summit arose from discussions at
the 2012 ACR Drug Safety Summit (see DSQ Aug 2012). At
that meeting, drug safety during pregnancy and breastfeeding
were recognized as being among the top safety issues
concerning both patients and rheumatologists, and it was
considered important enough to dedicate another meeting
specifically to this topic. Over the ensuing year and a half,
plans for this summit were developed by ACR Drug Safety
subcommittee co-chairs Drs. Michael Weisman and Artie
Kavanaugh, DSC members and Dr. Jack Cush. Herein we
present a brief summary of the information presented during
the meeting.
The meeting opened with discussions led by Drs. Larissa
Lapteva and Sally Seymour from the FDA, who provided a
view of the regulatory challenges and forthcoming labeling
changes that will address pregnancy and lactation. The FDA
recognizes the immense knowledge deficits in drug safety
and reproductive health, particularly in autoimmune diseases
where the scope of changes in immunity is broad and clinical
trials on pregnant and breastfeeding women are lacking.
Most of what is known is limited and is based on observations
from incidental pregnancies while on drug. The coupling of
pregnancy with different autoimmune diseases poses a
challenge for physicians and researchers as pregnancy alters
disease pathophysiology and drug metabolism, and the
disease and drug have unpredictable effects on the unborn
child. In addition, pregnant and lactating women have typically
been excluded from drug trials due to ethical concerns; they
are considered a “vulnerable” population. Hence, current
FDA pregnancy drug categories “A”, “B”, “C”, “D”, and “X”
are based on animal data, limited registry information, and
case series/reports. These labels are often confusing and do
not fully disclose the risks and benefits of drug exposure
during pre-conceptual planning, pregnancy, and lactation.
The idea that drug safety in pregnancy is a continuum from
X to A is not correct; these categories generally relate to the
presence or absence of human or animal data. Notably, 90%
of pregnant women take 1 or more prescription medicines
and about half take at least 4 medications during pregnancy.
The FDA understands the urgency to provide consumers and
prescribers with usable information and is committed to work
on updating the labels and to improve communication of risk.
Furthermore, under the FDA Amendments Act of 2007, the
FDA now is requiring pharmaceutical companies to conduct
post-marketing trials on pregnant and lactating women and
formulate risk evaluation and management strategies (REMS).
The NIH and NICHD are interested in collaborating and
promoting research in pregnant women and children with
autoimmune diseases in basic, translational and clinical
research, focusing on drug pharmacokinetics (PK),
D r u g S a f e t y Q u a r t e r l y
1
D S Q
Drug Safety Quarterly
a n o n l i n e p u b l i c a t i o n o f t h e A C R D r u g S a f e t y C o m m i t t e e
Inside
ACR Reproductive Health Summit
on the Management of Pregnant
and Lactating Women with
Autoimmune Diseases..................1
Demyelinating Complications
Associated with Rituximab
and Other Non-Tumor Necrosis
Factor-α Inhibitor Biologics .........1
FDA MedWatch: Spring 2014 ......4
Safety Signals: March 2014.........5
This Issue
see ACR Reproductive Health Summit on the Management of Pregnant and Lactating Women with Autoimmune Diseases, page 2
Demyelinating Complications Associated with Rituximab and Other Non-Tumor Necrosis
Factor-α Inhibitor Biologics
Antonia Valenzuela, MD and Lorinda Chung, MD
Non-Tumor Necrosis Factor (TNF)-α-inhibitor biologics, including rituximab,
anakinra, abatacept, and tocilizumab are treatment options for patients with
rheumatoid arthritis (RA) when one or more TNF-inhibitors have failed.1
Although
less common than with TNF-inhibitors, demyelinating complications have
been associated with some of these medications. Herein we will focus on the
demyelinating complications reported with rituximab therapy, and provide a table
summarizing the available data for other non-TNF-α-inhibitor biologics (Table).
Rituximab, a chimeric anti-CD20 antibody that promotes cell-mediated
and complement-mediated cytotoxicity, inhibits early B cell activation and
differentiation, resulting in B cell depletion. The two demyelinating complications
reported with rituximab are progressive multifocal leukoencephalopathy (PML)
and Guillain-Barre syndrome (GBS).2
Interestingly, rituximab has been evaluated
as a therapeutic option in multiple sclerosis,3
neuromyelitis optica spectrum
disorders,4
and chronic inflammatory demyelinating polyneuropathy.5
PML is a serious opportunistic infection caused by reactivation of the JC
virus.6,7
PML is characterized by progressive inflammation and demyelination
of the white matter of the brain,8
and commonly presents with altered mental
status, motor deficits, gait ataxia, and visual symptoms.9
Rituximab has been
see Demyelinating Complications Associated with Rituximab and Other Non-Tumor Necrosis Factor-α Inhibitor Biologics, page 3
Vol. 5 (1)
Spring 2014
2. D r u g S a f e t y Q u a r t e r l y
D S Q
2
D S Q
2
ACR Reproductive Health Summit on the Management of Pregnant and Lactating Women
with Autoimmune Diseases continued from cover
pharmacodynamics (PD), and pharmacogenomics. Dr. Christina Chambers from
the OTIS Mother-to-Baby registry spoke of the OTIS experience in tracking
pregnant patients with autoimmune diseases with the hope of revealing the
effects of certain rheumatologic medications and vaccines on pregnancy loss,
malformations or early childhood functional deficits. Unfortunately, recruitment
numbers and diversity of samples pose a challenge for OTIS. Dr. Jeffrey Curtis
also offered his views on strengths and weaknesses of registry data in assessing
risks of drugs during pregnancy. He noted that in studying pregnancy, registries
are effective in that they are flexible in capturing data and have greater internal
validity than spontaneous FDA adverse event reporting. However, there are
threats to the validity of registry data owing to confounding factors (e.g.,
channeling bias, disease severity, sample sizes, comorbidities). Often, there
is no denominator for comparison. Most data collected are voluntary and based
on recall.
Next, Drs. Mahmoud Ahmed and Lisa
Sammaritano, basic science and
clinical research experts in placental
and lactation physiology and drug
transport, summarized their own and
existing data. The placenta is a
functional barrier that changes
during pregnancy. The permeability
of compounds is differentially regulated during each trimester; hence, it cannot
be assumed that only compounds of a certain molecular weight or structure
can cross the placenta. Each drug must be studied independently, and rodent
models are not adequate for safety labeling. Likewise, many variables exist
with lactation that would influence drug level in infant blood. These include:
transfer rate of drug to breast milk, age of infant, variability in absorption, and
genetic differences of infants. Highly protein bound drugs are unlikely to cross
into breast milk, and drugs that are found in breast milk may not be detectable
in infants’ blood. As most milk is produced prior to nursing, the timing of nursing
is important as to how much dose of drug is delivered to the infant. For example,
with prednisone, less than 10% of the dose is excreted in breast milk. Peak
levels of prednisone in milk occur 2 hours after the dose; it is recommended
that breastfeeding occurs 4 hours after any dose > 20 mg/day, and infants
whose mothers take more than 40 mg/day of prednisone should be monitored
for steroid effects. Drugs generally considered safe in breastfeeding include:
hydroxychloroquine, sulfasalazine, tacrolimus, warfarin, heparin, and IVIG.
Though insufficient data exist for azathioprine, the World Health Organization
and American Academy of Pediatrics recommend against breastfeeding while
taking azathioprine due to theoretical concerns for bone marrow suppression,
susceptibility for infection, and pancreatitis; however, one study published
results of 8 infants of women on azathioprine bid who were breastfeeding and
had undetectable drug metabolites in their blood (1)
. Medication use where
mothers should avoid breastfeeding include: methotrexate, mycophenolate
mofetil, leflunomide and cyclophosphamide (these too are based on theoretical
risks, rather than data). Although small amounts of IgG1 are secreted in breast
milk, tumor necrosis factor inhibitors (TNFi) are generally thought to be safe
in breastfeeding as the infant’s digestive tract will break down the protein.
Currently, no data is available regarding the safety of rituximab or tocilizumab
in lactation.
Drs. Uma Mahadevan, Megan Clowse, and Eliza Chakravarty presented data
on different disease states (inflammatory bowel disease [IBD], rheumatoid
arthritis [RA], and systemic lupus erythematosus [SLE], respectively) and their
effects on pregnancy. The one message that was consistent across all disease
states was: Uncontrolled inflammation adversely affecting the mother will
create a hostile environment for the fetus. Dr. Mahadevan noted that while
TNFi are generally considered safe in pregnancy, clinicians should consider
stopping infliximab and adalimumab in the 3rd trimester as 80% of
immunoglobulins (including IgG bound biologics) cross the placenta at this time.
The concern is that giving live vaccines such as BCG to these infants may cause
disseminated disease as has been reported in a case where the mother was
receiving infliximab 10 mg/kg every 8 weeks, and the baby died of disseminated
BCG (2)
. Dr. Clowse noted that while RA is expected to improve in pregnancy,
disease activity may persist and flares do occur. Patients who have higher
disease activity are at increased risk for preterm labor and deliver babies with
smaller birth weights. Treating flares with prednisone may not be the optimal
approach as the drug may increase risk for infection, preeclampsia, and preterm
labor. TNFi are frequently used in IBD patients prior to and during pregnancy
as patients are highly prone to flares and complications (especially ulcerative
colitis patients) when TNFi or thiopurines are withdrawn. Thus far, the IBD
experience has shown no increased risk for malformations with TNFi use, and
the same can be said for RA patients exposed to TNFi during pregnancy. In the
event that patients suspend TNFi therapy, Dr. Clowse suggested restarting
drug 1-2 weeks post-partum to reduce the risk for postpartum flares. In SLE,
pregnancy morbidity is a recognized complication as cited by Dr. Chakravarty.
Risks for pregnancy loss, preterm labor, and maternal adverse events are
significantly higher in patients who have active disease at the onset of pregnancy.
In addition, distinguishing preeclampsia from active lupus nephritis is often
difficult as there are no good biomarkers to differentiate the two. Studies have
shown that hydroxychloroquine improves pregnancy outcomes and that
azathioprine and cyclosporine can be safely administered during pregnancy(1)
.
Rituximab, cyclophosphamide, and IVIG have been used safely in life threatening
or organ threatening disease in established pregnancy. Despite improved
management of lupus pregnancies, there are still more questions than answers.
Methotrexate and mycophenolate mofetil (commonly used in SLE) are thus not
recommended during pregnancy.
The meeting concluded with final remarks from Dr. Gideon Koren, a leading
pediatrician, pharmacologist, toxicologist and founder of Toronto’s MOTHERISK
program (www.motherrisk.org). He emphasized that there are less than 30
drugs on the market that are known teratogens and only one (Accutane) that
carries the same magnitude of teratogenic risk as thalidomide. He stated the
only clear teratogens used in rheumatology are methotrexate and mycophenolate.
Leflunomide (a category X drug) is “probably not” a teratogen as there is a
small OTIS study of 45 leflunomide-exposed RA patients that showed no
untoward outcomes (3)
. Nevertheless, patients will often assign high teratogenic
risk to a drug even when the drug is non-teratogenic. He noted that it is
necessary to disseminate good information to avoid unnecessary pregnancy
termination.
Currently, an unfortunate communication chasm exists between those managing
pregnant and lactating women (e.g., obstetricians/gynecologists, maternal
fetal medicine, pediatricians, family practitioners) and those who manage
their complex and chronic autoimmune diseases (e.g., rheumatologists,
gastroenterologists, dermatologists). The goal of the Reproductive Health
Summit was to identify what is known and what is remaining unanswered
with regard to managing patients with autoimmune diseases antenatally and
postnatally. The full proceedings of the Reproductive Health Summit will be
published in the near future with the hope of improving communications and
pregnancy management across all specialties. D S Q
References
1. Christensen LA, Dahlerup JF, Nielsen MJ, Fallingborg JF, Schmiegelow K. Azathioprine treatment
during lactation. Aliment Pharmacol Ther. 2008 Nov 15;28(10):1209-13. doi: 10.1111/j.1365-
2036.2008.03843.x. Epub 2008 Aug 30. PubMed PMID: 18761704.
2. Cheent K, Nolan J, Shariq S, Kiho L, Pal A, Arnold J. Case Report: Fatal case of disseminated BCG
infection in an infant born to a mother taking infliximab for Crohn's disease. J Crohns Colitis. 2010
Nov;4(5):603-5. doi: 10.1016/j.crohns.2010.05.001. Epub 2010 Jun 9. PMID: 21122568.
3. Cassina M, Johnson DL, Robinson LK, Braddock SR, Xu R, Jimenez JL, Mirrasoul N, Salas E, Luo YJ,
Jones KL, Chambers CD; Organization of Teratology Information Specialists Collaborative Research
Group. Pregnancy outcome in women exposed to leflunomide before or during pregnancy. Arthritis
Rheum. 2012 Jul;64(7):2085-94. doi: 10.1002/art.34419. PMID: 22307734.
The FDA understands the
urgency to provide consumers
and prescribers with usable
information and is committed to
work on updating the labels to
improve communication of risk.
3. 3
drug safety quarterly
Vol. 5 (1)
Spring 2014
a n o n l i n e p u b l i c a t i o n o f t h e A C R D r u g S a f e t y C o m m i t t e e
associated with more than 60 cases of PML,10
including 14 in the setting of
rheumatic diseases, with an estimated cumulative risk of 5/100000 exposed
RA patients.6
Molloy et al6
reviewed all cases of PML and JC infection within
the Food and Drug Administration Adverse Event Reporting System database
from November 1997 to March 2010 and identified 34 cases of PML associated
with rheumatic diseases. Rituximab was the most recent biologic agent in 14
cases of PML confirmed by detection of JC virus DNA in the cerebrospinal
fluid or brain biopsy specimen. PML developed after a median of 2 courses
of rituximab and a median time interval of 12 months after the first infusion,
resulting in death of 5 patients. Of note, PML was not reported in association
with the use of tocilizumab or abatacept although belatacept, a biologic with
structural similarities to abatacept has been linked to PML. Determining the
risk of PML with rituximab is confounded by the concomitant use of other
immunosuppressive drugs and the unclear incidence of PML in rheumatic
diseases in the absence of therapy.2
Anecdotal observations of the development of GBS have been reported in
immunocompromised patients with hematologic diseases who have been
treated with rituximab.11-13
Jaso et al11
reported a case of GBS in an 86-years-old
patient with idiopathic thrombocytopenic purpura treated with rituximab 750 mg
once a week for 4 weeks. 39 days after receiving the last dose he developed
acutely ascending progressive quadriparesis and recovered completely after
discontinuation of the drug and treatment with intravenous immunoglobulin
(IVIG). Carmona et al12
reported the case of a 57 years old male with diffuse
large-B cell lymphoma in complete remission who developed GBS while receiving
maintenance treatment with rituximab 375 mg/m2
weekly for four weeks at
six-month intervals. He was treated with IVIG and recovered rapidly with very
little residual disability. Finally, Terenghi et al13
published the case of a 51-year-old
man with B-cell Non-Hodgkin lymphoma (NHL) treated with combined CHOP
(cyclophosphamide, doxorubicin, vincristine, and methylprednisolone) and
rituximab (375 mg/m2
) therapy every two weeks. After the third course, the
patient complained of mild paresthesia at the fingertips. He was subsequently
diagnosed with GBS and treated with IVIG with complete recovery over 2 months.
Although the causal relationship in the pathogenesis of demyelinating disorders
remains uncertain, and these are rare adverse events, the devastating nature of
PML mandates physicians who prescribe non-TNF-inhibitor biologics, especially
rituximab, to be aware of the potential for the development of PML.6 8
Other
demyelinating complications have rarely been reported, but physicians should
be vigilant for the development of new neurologic symptoms and signs when
patients are taking these agents. D S Q
References
1. Smolen JS, Landewe R, Breedveld FC, et al. EULAR recommendations for the management of
rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013
update. Annals of the Rheumatic Diseases. Oct 25 2013.
2. CliffordDB,AncesB,CostelloC,etal.Rituximab-associatedprogressivemultifocalleukoencephalopathy
in rheumatoid arthritis. Archives of Neurology. Sep 2011;68(9):1156-1164.
3. Rubbert-Roth A. Assessing the safety of biologic agents in patients with rheumatoid arthritis.
Rheumatology (Oxford, England). Jul 2012;51 Suppl 5:v38-47.
4. Kim SH, Huh SY, Lee SJ, Joung A, Kim HJ. A 5-year follow-up of rituximab treatment in patients
with neuromyelitis optica spectrum disorder. JAMA Neurology. Sep 1 2013;70(9):1110-1117.
5. Gorson KC, Natarajan N, Ropper AH, Weinstein R. Rituximab treatment in patients with IVIg-
dependent immune polyneuropathy: a prospective pilot trial. Muscle & Nerve. Jan 2007;35(1):66-69.
6. Molloy ES, Calabrese LH. Progressive multifocal leukoencephalopathy associated with
immunosuppressive therapy in rheumatic diseases: evolving role of biologic therapies. Arthritis
and Rheumatism. Sep 2012;64(9):3043-3051.
7. Arkema EV, van Vollenhoven RF, Askling J. Incidence of progressive multifocal leukoencephalopathy
in patients with rheumatoid arthritis: a national population-based study. Annals of the Rheumatic
Diseases. Nov 2012;71(11):1865-1867.
Continued on next page
Demyelinating Complications Associated with Rituximab and Other Non-Tumor Necrosis
Factor-α Inhibitor Biologics continued from page 1
Molecule Mechanism of action Source of data Patients N Potential side effects
Rituximab B-cell depletion Observational study6 Rheumatic diseases (RA,
SLE, SS, DM, vasculitis)
14 PML
Cases study2
RA/SS 4 PML
Systematic review and
meta-analysis of 3 RCT14-17 RA 938 No demyelinating complications
Case report11
ITP 1 GBS
Case report12 Diffuse large B-cell
lymphoma
1 GBS
Case report 13
NHL 1 GBS
Anakinra IL-1 inhibition RCT18
RA 1414 No demyelinating complications
Case–control19
RA 104958 MS and Optic neuritis
Abatacept
T-cell costimulation
blockade
RCT20
JIA 153 MS
Observational study21
RA 1138 No demyelinating complications
RCT22
RA 652 No demyelinating complications
RCT23
RA 317 No demyelinating complications
Tocilizumab IL-6 inhibition RCT24
RA 4211 No demyelinating complications
Table 1: Summary table
4. D r u g S a f e t y Q u a r t e r l y
D S Q
4
Demyelinating Complications Associated with Rituximab and Other Non-Tumor Necrosis
Factor-α Inhibitor Biologics continued from page 3
8. Bharat A, Xie F, Baddley JW, et al. Incidence and risk factors for progressive multifocal
leukoencephalopathy among patients with selected rheumatic diseases. Arthritis Care & Research.
Apr 2012;64(4):612-615.
9. Tavazzi E, Ferrante P, Khalili K. Progressive multifocal leukoencephalopathy: an unexpected
complication of modern therapeutic monoclonal antibody therapies. Clinical Microbiology and
Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious
Diseases. Dec 2011;17(12):1776-1780.
10. Tyler KL. Progressive multifocal leukoencephalopathy: can we reduce risk in patients receiving
biological immunomodulatory therapies? Annals of Neurology. Sep 2010;68(3):271-274.
11. Jaso R, Sierra M, Calleja J, Valero C, Pascual J. Guillain-Barre syndrome after rituximab in a
patient with idiopathic thombocytopenic purpura: a causal association? Journal of Neurology.
Mar 2010;257(3):488-489.
12. Carmona A, Alonso JD, de las Heras M, Navarrete A. Guillain-Barre syndrome in a patient with
diffuse large B-cell lymphoma, and rituximab maintenance therapy. An association beyond anecdotal
evidence? Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology
Societies and of the National Cancer Institute of Mexico. Oct 2006;8(10):764-766.
13. Terenghi F, Ardolino G, Nobile-Orazio E. Guillain-Barre syndrome after combined CHOP and
rituximab therapy in non-Hodgkin lymphoma. Journal of the Peripheral Nervous System: JPNS.
Jun 2007;12(2):142-143.
14. Lee YH, Bae SC, Song GG. The efficacy and safety of rituximab for the treatment of active rheumatoid
arthritis: a systematic review and meta-analysis of randomized controlled trials. Rheumatology
International. Nov 2011;31(11):1493-1499.
15. Emery P, Fleischmann R, Filipowicz-Sosnowska A, et al. The efficacy and safety of rituximab in
patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB
randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis and Rheumatism. May
2006;54(5):1390-1400.
16. Edwards JC, Szczepanski L, Szechinski J, et al. Efficacy of B-cell-targeted therapy with rituximab in
patients with rheumatoid arthritis. The New England Journal of Medicine. Jun 17 2004;350(25):2572-
2581.
17. Cohen SB, Emery P, Greenwald MW, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor
necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase
III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis and Rheumatism. Sep
2006;54(9):2793-2806.
18. Fleischmann RM, Schechtman J, Bennett R, et al. Anakinra, a recombinant human interleukin-1
receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: A large, international,
multicenter, placebo-controlled trial. Arthritis and Rheumatism. Apr 2003;48(4):927-934.
19. Bernatsky S, Renoux C, Suissa S. Demyelinating events in rheumatoid arthritis after drug exposures.
Annals of the Rheumatic Diseases. Sep 2010;69(9):1691-1693.
20. Ruperto N, Lovell DJ, Quartier P, et al. Long-term safety and efficacy of abatacept in children with
juvenile idiopathic arthritis. Arthritis and Rheumatism. Jun 2010;62(6):1792-1802.
21. Nusslein HG, Alten R, Galeazzi M, et al. Real-world effectiveness of abatacept for rheumatoid
arthritis treatment in European and Canadian populations: a 6-month interim analysis of the 2-year,
observational, prospective ACTION study. BMC Musculoskeletal Disorders. Jan 11 2014;15(1):14.
22. Kremer JM, Russell AS, Emery P, et al. Long-term safety, efficacy and inhibition of radiographic
progression with abatacept treatment in patients with rheumatoid arthritis and an inadequate
response to methotrexate: 3-year results from the AIM trial. Annals of the Rheumatic Diseases.
Oct 2011;70(10):1826-1830.
23. Genovese MC, Schiff M, Luggen M, et al. Longterm safety and efficacy of abatacept through 5 years
of treatment in patients with rheumatoid arthritis and an inadequate response to tumor necrosis
factor inhibitor therapy. The Journal of Rheumatology. Aug 2012;39(8):1546-1554.
24. Genovese MC, Rubbert-Roth A, Smolen JS, et al. Longterm safety and efficacy of tocilizumab in
patients with rheumatoid arthritis: a cumulative analysis of up to 4.6 years of exposure. The Journal
of Rheumatology. Jun 2013;40(6):768-780.
FDA MEDWATCH: Spring 2014
NSAIDS are indistinguishable from each other with respect to
cardiovascular risks. In its advisory meeting on February 10 and 11th, 2014,
the arthritis advisory committee and drug safety and risk management advisory
committees voted 16 to 9 to continue the cardiovascular risk warning label for
NSAIDS. This discussion was prompted by a recent systematic review performed
by Oxford University researchers who reviewed results from more than 700
NSAID studies involving roughly 350,000 patients. The committee carefully
reviewed the data on risk differences between various NSAIDS and ruled
that any potential benefit accrued by lifting the warning for one (Naproxen) or
more NSAIDS will be offset by the risks associated with NSAIDS. Since 2005
all NSAIDS (including over the counter products) include labels that warn the
users about the potential adverse cardiovascular outcomes. A second vote,
promoted by a Dutch study that indicated that the adverse risk of NSAIDS
become apparent as early as a few days and that chronic use is not necessary,
assessed the need for updating the package label warning. A majority 14 to
11 voted to recommend revising the package labels incorporating the short
term risk warnings.
Ibuprofen in dietary supplement. The FDA is advising consumers not to
purchase or use Arth-Q, a product promoted and sold as a dietary supplement
for joint, muscle and arthritic pain since FDA laboratory analysis revealed that
Arth-Q contains ibuprofen. This hidden drug ingredient may interact with other
medications and significantly increase the risk of adverse events, particularly
when consumers may already be using NSAID-containing products. Arth-Q is
labeled in English, but is also promoted to the Korean-speaking community.
Red particulates in lidocaine vials. The manufacturer Hospira is recalling
Lidocaine HCl Injection 2%, 5mL distributed between September 2013 and
October 2013. Smaller pieces of the particulate may pass through the catheter
into the patient, resulting in local inflammation or mechanical disruption of tissue.
In addition, local granuloma formulation is possible following sequestration.
There is also a concern that iron, if present in these reddish particulates will
pose a safety risk for those undergoing MR imaging.
Low dose diclofenac for osteoarthritis. The FDA has accepted for review the
supplemental New Drug Application (sNDA) for Zorvolex (diclofenac), a lower
dose nonsteroidal anti-inflammatory drug for the treatment of osteoarthritis pain
in adults. This sNDA application is based on data from a 12-week, multi-center,
randomized, double-blind, parallel-group, placebo-controlled trial that enrolled
305 patients, aged 41-90 years, with osteoarthritis of the hip or knee. Participants
were randomized to Zorvolex 35mg three times daily or 35mg twice daily, or
placebo. The sNDA also included data from a 12-month open-label study that
enrolled more than 600 patients. Zorvolex was developed to address the FDA's
public health advisory recommending that NSAIDs be used at the lowest effective
dose for the shortest duration consistent with individual patient treatment goals.
The manufacturer states that the advantages of this preparation of diclofenac
include about 23% less systemic exposure to diclofenac and avoidance and
sodium and potassium in the preparations. Zorvolex is already approved for
the treatment of mild to moderate acute pain in adults. The retail price of this
proprietary product is expected to be substantially high (>$150 per month)
compared to generic diclofenac of any strength.
Tightening the prescription guidelines for acetaminophen. Based on
emerging evidence suggesting that doses greater than 325 mg acetaminophen
per dosing unit do not have any additional benefit to the patient, and some
suggestion that it increases the risk for overdose, the FDA no longer wants higher
strength acetaminophen to be used. This is not a new move. Limiting the amount
of acetaminophen in combination products has been on the FDA's agenda since
its initial communication with manufacturers back in January 2011 when they
were asked to cease production of high-strength acetaminophen. While some
products with higher doses still remain on the market, pharmacists who receive
prescriptions for products containing more than 325 mg of acetaminophen per
dosage unit should contact the prescriber to discuss products that contain a
lower dose. Higher doses (such as 650 mg) are still permitted as long as multiple
capsules/tablets of the lower strength are dispensed..
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