15-minute power-point to present the research of a two-phase informative study that collected survey and qualitative data through a series of focus groups regarding the current description and future implications of PCOS multidisciplinary clinics while emphasizing the role, importance, and challenges for dietitians.
Do Women With Polycystic Morphology Without Any Other Features of PCOS Benefi...Alex Swanton
Women with ovaries of polycystic morphology (PCO), without any other features of polycystic ovary syndrome(PCOS), respond similarly to women with PCOS when stimulated with exogenous gonadotrophins, and both groups share various endocrinological disturbances underlying their pathology.
A group of physiological abnormalities such as an increase in blood pressure, diabetes, increase in cholesterol levels and obesity is known as Metabolic Syndrome. Women in their pregnancy period are highly prone to this problem. Doctors are taking the issue of metabolic syndrome in obstetric practice seriously as it may risk the pregnancy.
15-minute power-point to present the research of a two-phase informative study that collected survey and qualitative data through a series of focus groups regarding the current description and future implications of PCOS multidisciplinary clinics while emphasizing the role, importance, and challenges for dietitians.
Do Women With Polycystic Morphology Without Any Other Features of PCOS Benefi...Alex Swanton
Women with ovaries of polycystic morphology (PCO), without any other features of polycystic ovary syndrome(PCOS), respond similarly to women with PCOS when stimulated with exogenous gonadotrophins, and both groups share various endocrinological disturbances underlying their pathology.
A group of physiological abnormalities such as an increase in blood pressure, diabetes, increase in cholesterol levels and obesity is known as Metabolic Syndrome. Women in their pregnancy period are highly prone to this problem. Doctors are taking the issue of metabolic syndrome in obstetric practice seriously as it may risk the pregnancy.
2019 02-21 Oxford Global 14th Biomarker Congress, Manchester, Alain van GoolAlain van Gool
Outline of innovations in clinical X-omics approaches towards personalized diagnostics in our clinical laboratory, presented for an audience of experienced diagnostic and pharmaceutical biomarker scientists.
This seminar explores the potential connection between two inositol stereoisomers supplements and improvements in insulin sensitivity and various metabolic parameters.
Audio and slides for this presentation are available on YouTube: http://youtu.be/UVRYzgFqVGM
Dana-Farber Nutritionist Hillary Wright presents on how to fight cancer with your fork. She discusses the importance of healthy eating, and dispels some of the common myths about certain foods and cancer.
2019 02-21 Oxford Global 14th Biomarker Congress, Manchester, Alain van GoolAlain van Gool
Outline of innovations in clinical X-omics approaches towards personalized diagnostics in our clinical laboratory, presented for an audience of experienced diagnostic and pharmaceutical biomarker scientists.
This seminar explores the potential connection between two inositol stereoisomers supplements and improvements in insulin sensitivity and various metabolic parameters.
Audio and slides for this presentation are available on YouTube: http://youtu.be/UVRYzgFqVGM
Dana-Farber Nutritionist Hillary Wright presents on how to fight cancer with your fork. She discusses the importance of healthy eating, and dispels some of the common myths about certain foods and cancer.
*I hope its help you all for preparation part 1 exam for MRCOG & MOG and your daily job.Good Luck May ALLAH bless our work and study,Good luck to all.dont forget to pray to ALLAH.if i wrong please correct me..process of learning..
COUNSELLING IN HIV/AIDS
Qurrot Ulain Taher
P.G Diploma in Nutrition & Dietetics
Dietetic Techniques & Patient Counseling
HIV/AIDS
HIV stands for Human Immunodeficiency Virus. AIDS stands for Acquired Immune Deficiency Syndrome. AIDS is a result of the development of the HIV virus into a more serious condition. AIDS was first recognised by the U.S. Centers for Disease Control and Prevention in 1981 and its cause, HIV, identified in the early 1980s.
Understanding HIV
HIV is a contagious infection which attacks the immune system, reducing its effectiveness and leaving the body susceptible to infections. The HIV infection damages the cells the body needs to fight illnesses. AIDS can be diagnosed when the number of immune system cells (CD4 cells) in the blood of a person with HIV drops below a certain level.
There is no cure for HIV or AIDS, but there are treatments that can slow down the disease, and help prevent the onset of AIDS. It takes around ten years for someone with HIV to develop AIDS, but it can be prevented with early detection and treatment of the HIV
PREVENTION OF Mother to child transmission
Treatment for HIV and AIDS
HAART
TYPES OF HIV TESTS
Why Is Counseling Necessary
Objectives
Whom to counsel
Characteristics of a Counselor
Skills Required in Counseling
Stages of Counseling
Risk assessment counseling
Pre test counseling
Post test counseling
Follow up counseling
Role of Counselor
Advocacy role
Health education
Referral
Clinical and therapeutic role
Special Situations in HIV Counseling
Pregnant women
Childless couples
Breast feeding positive mothers
Spouse and family members of HIV infected persons
Ovarian reserve refers to the reproductive potential left within a woman's two ovaries based on number and quality of eggs. Diminished ovarian reserve is the loss of normal reproductive potential in the ovaries due to a lower count or quality of the remaining eggs
IOSR Journal of Pharmacy and Biological Sciences(IOSR-JPBS) is an open access international journal that provides rapid publication (within a month) of articles in all areas of Pharmacy and Biological Science. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Pharmacy and Biological Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Explore the intricacies of ovulation induction in intrauterine insemination (IUI) with Dr Laxmi Shrikhande's informative slide share presentation. From understanding the hormonal mechanisms to the latest techniques, this presentation offers insights into optimizing fertility through IUI. Whether you're a clinician seeking to enhance patient outcomes or an individual navigating fertility treatments, this resource provides valuable knowledge for your journey towards conception.
Healthy Choices are the key!
Healthy diet including raw foods & avoiding processed food or high fat diet is the best way to eliminate toxins from your body. Toxins damage your egg follicles.
Katherine Promer Flores, MD (she/her)
Staff Physician
Division of Infectious Diseases and Global Public Health
Department of Medicine
University of California San Diego
Daniel Lee, MD
Clinical Professor of Medicine
Division of Infectious Diseases & Global Public Health
Department of Medicine
University of California, San Diego
Leandro Mena, MD, MPH
Chair and Professor of Population Health Science
Department of Population Health Science
University of Mississippi Medical Center
Maile Young Karris, MD
Associate Professor
Co-Director San Diego Center for AIDS Research Clinical Investigations Core
Divisions of Infectious Diseases & Global Public Health and Geriatrics & Gerontology
Department of Medicine
University of California San Diego
Edward Cachay, MD, MAS
Professor of Medicine
Division of Infectious Diseases & Global Public Health
Department of Medicine
University of California, San Diego
Gabriel Wagner, MD
Associate Clinical Professor
Division of Infectious Diseases & Global Public Health
Department of Medicine
University of California, San Diego
Jocelyn Keehner, MD
Infectious Disease Fellow
Division of Infectious Diseases & Global Public Health
Department of Medicine
University of California, San Diego
Richard Garfein, PhD, MPH
Professor
Herbert Wertheim School of Public Health and Human Longevity Science
Adjunct Professor
Division of Infectious Disease and Global Public Health
Department of Medicine
University of California, San Diego
Laura Bamford, MD, MSCE
Associate Professor of Medicine
Medical Director, Owen Clinic
Division of Infectious Diseases and Global Public Health
Department of Medicine
University of California, San Diego
Davey Smith, MD, MAS
Professor of Medicine
Chief, Division of Infectious Diseases and Global Public Health
Co-Director, San Diego Center for AIDS Research (CFAR)
Department of Medicine
University of California, San Diego
Elliot Welford, MD
Infectious Diseases Fellow
Division of Infectious Diseases & Global Public Health
Department of Medicine
University of California, San Diego
Darcy Wooten, MD
Assistant Professor of Medicine
Associate Program Director, Infectious Diseases Fellowship
Division of Infectious Diseases & Global Public Health
Department of Medicine
University of California, San Diego
Amutha Rajagopal, MD
Associate Physician Diplomate
Division of Infectious Diseases & Global Public Health
Department of Medicine
University of California, San Diego
More from UC San Diego AntiViral Research Center (20)
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
Follow us on: Pinterest
Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...
Updates in Antiretroviral Pharmacology & Dosing during Pregnancy
1. AIDS CLINICAL ROUNDS
The UC San Diego AntiViral Research Center sponsors weekly
presentations by infectious disease clinicians, physicians and
researchers. The goal of these presentations is to provide the most
current research, clinical practices and trends in HIV, HBV, HCV, TB
and other infectious diseases of global significance.
The slides from the AIDS Clinical Rounds presentation that you are
about to view are intended for the educational purposes of our
audience. They may not be used for other purposes without the
presenter’s express permission.
2. Updates in Antiretroviral Pharmacology &
Dosing during Pregnancy
Brookie M. Best, PharmD, MAS
Associate Professor of Clinical Pharmacy & Pediatrics
3. Roadmap
• Gender Effects
• Pregnancy Effects
• IMPAACT P1026s Methods
• Findings from Past Several Years
• Analyses Underway
• Future Plans
• Conclusion
4. When did I get started studying pregnant women?
Pediatric Clinical Pharmacology Research Fellowship:
2000 – 2004
November, 2001
September, 2004
5. HIV Global Epidemic
• As of 2011:
– 34.2 million people worldwide
living with HIV infection
– About half are women
– Most infected women are of childbearing age
• Women particularly vulnerable
– Insufficient knowledge about AIDS, lack of access to
prevention services, inability to negotiate safer sex,
lack of female-controlled HIV prevention methods
6. Indications for Treatment during Pregnancy
• For maternal health, according to same criteria
used for non-pregnant adults
• PLUS, to prevent vertical transmission of HIV
in basically all other women
• Regimens proven to reduce transmission:
– 3 part zidovudine (PACTG 076)
– Single maternal/infant nevirapine (HIVNET 012)
– Zidovudine/lamivudine oral from 36 weeks through
labor + 1 week in infant (PETRA)
– Others
7. Indications for Treatment during Pregnancy
• Observational cohort in U.S. transmission rates
– No therapy = 20%
– Zidovudine = 10.4%
– Combination therapy without protease inhibitors = 3.8%
– Combination therapy with protease inhibitors = 1.2%
“Regardless of plasma HIV RNA copy number or CD4-T
lymphocyte count, all pregnant HIV-infected women should
receive a combination ARV drug regimen antepartum to
prevent perinatal transmission. A combination regimen is
recommended both for women who require therapy for their
own health and for prevention of perinatal transmission, in
those who do not yet require therapy.”
Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission.
Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1 Infected Women for Maternal Health and
Interventions to Reduce Perinatal HIV Transmission in the United States. Accessed November 1, 2012.
8. Considerations for Therapy during Pregnancy
• Does the dose need to be altered?
• What is the potential for short or long-term toxic
effects on the fetus (if known)?
• How effective are the drugs at reducing perinatal
transmission?
• When is elective cesarean section
recommended?
9. Pharmacokinetics Pharmacodynamics
ACTIVATION
Dose of drug Drug Drug Pharmacologic
administered concentration concentration Effect
in systemic at site of
circulation action
ABSORPTION
DISTRIBUTION
ELIMINATION
Drug in
tissues of Drug
distribution metabolized or
excreted
10. Gender Differences in Drug Exposure
• Body size and composition differences
• Large differences in rodents, less pronounced in
humans
• Women have modestly increased concentrations of
efavirenz, enfuvirtide, lopinavir, nevirapine, ritonavir
and saquinavir
• Higher ritonavir and saquinavir associated with
increased side effects and improved virologic response
• Women have similar NRTI plasma concentrations, but
increased intracellular zidovudine and lamivudine
triphosphate concentrations
Fletcher CV, Jiang H, Brundage RC, et al. Sex-based differences in saquinavir pharmacology and virologic response in AIDS Clinical Trials
Group Study 359. J Infect Dis 2004;189(7):1176-84.
Gatti G, Di Biagio A, Casazza R, et al. The relationship between ritonavir plasma levels and side-effects: implications for therapeutic drug
monitoring. Aids 1999;13(15):2083-9.
Anderson PL, Kakuda TN, Kawle S, Fletcher CV. Antiviral dynamics and sex differences of zidovudine and lamivudine triphosphate
concentrations in HIV-infected individuals. Aids 2003;17(15):2159-68.
12. Drug Absorption in Pregnancy
• Increased progesterone → decreased GI motility,
prolonged gastric emptying and transit times
– Effect = Delayed drug absorption and lower peak
concentrations
• Nausea and vomiting may limit tolerability
• Food intake altered – high fat meals frequently
necessary for optimal protease inhibitor
absorption
13. Changes Affecting Drug Distribution
• Body composition • Increased volume
– Total body water of distribution
increased by 8 liters
– Plasma volume • Decreased peak
increased by 50% plasma
– Increased body fat concentrations
stores
• Protein Binding • Increased free or
– Decreased albumin unbound drug
(dilution)
– Increased Increased effect
competitors in blood
– Free fatty acids
& steroids
14. Physiologic Changes in Pregnancy that
Affect Drug Elimination
• Increased Cardiac • Increased elimination
Output of renally cleared
– Renal plasma flow drugs
increase 25-50%
– GFR increases up to • Lower trough
50% concentrations
• Cholestasis may reflect changes in transport
activity
• Changes in drug metabolizing enzyme activity –
dependent on isoform
15. Cytochrome P450 Enzyme Changes
% Change in Activity Compared to PostPartum
90
60
30
0
-30
-60
-90
14-18 24-28 36-40
CYP 1A CYP 2D6 CYP 3A
Tracy TS, Venkataramanan R, Glover DD, Caritis SN. Temporal changes in drug metabolism (CYP1A2,
CYP2D6, and CYP3A activity) during pregnancy. Am J Ob Gyn 2005;192:633-9.
16. Phase II Enzyme (UGT) Changes
300
Lamotrigine Clearance (L/hr)
250
200
150
100
50
0
Pre-conception 1st Tri 2nd Tri 3rd Tri Post Partum
WT adjusted
Pennell PB, Newport DJ, Stowe ZN, Helmers SL, Montgomery JQ, Henry TR. The impact of
pregnancy and childbirth on the metabolism of lamotrigine. Neurology 2004;62:292-5.
17. Challenges to pregnancy research
• Women of reproductive age used to be routinely
excluded from clinical trials
• Ethical and liability concerns with fetal exposure
• Difficult to recruit to rigorous pharmacokinetic studies
Need for pregnancy research
• Appropriate dosing is critical:
• Under-dosing
• poor viral control, resistance, MTCT
• Over-dosing
• maternal and fetal toxicity
18. IMPAACT P1026s
• “Pharmacokinetic properties of antiretroviral drugs during
pregnancy”
• Intensive 12 or 24 PK profiles in 3rd trimester and
postpartum (2nd trimester for some drugs)
• Opportunistic design, pregnant women already taking
drugs of interest for clinical care
• Real-time reporting to clinicians, with comparison to
expected values in non-pregnant adults
• Clinical monitoring of off-label doses
• Adjustment of dose and repeat PK evaluation available
• Opened in 2003, Enrollment as of Sept. 2012:
– 513 pregnant women, 197 infants
19. Protease Inhibitors (PIs):
P1026s: Atazanavir/Ritonavir in Pregnancy
3rd trimester and postpartum: 300mg/100mg
Mirochnick M, Best BM, Stek A, et al. Atazanavir pharmacokinetics with and without tenofovir during pregnancy. JAIDS 2011;56(5):412-9.
20. PIs: Atazanavir/Ritonavir in Pregnancy
2nd trimester and postpartum: 300mg/100mg
3rd trimester: 400mg/100mg
Mirochnick M, Stek A, Capparelli E, et al. Pharmacokinetics of increased dose atazanavir with and without tenofovir during
pregnancy. 12th International Workshop on Clinical Pharmacology of HIV Therapy, 2011 Apr 13-15, Coral Gables, FL.
21. PIs: Atazanavir/Ritonavir + Tenofovir
3rd trimester and postpartum: 300mg/100mg
Mirochnick M, Best BM, Stek A, et al. Atazanavir pharmacokinetics with and without tenofovir during pregnancy. JAIDS 2011;56(5):412-9.
22. PIs: Atazanavir/Ritonavir + Tenofovir
2nd trimester and postpartum: 300mg/100mg
3rd trimester: 400mg/100mg
Mirochnick M, Stek A, Capparelli E, et al. Pharmacokinetics of increased dose atazanavir with and without tenofovir during
pregnancy. 12th International Workshop on Clinical Pharmacology of HIV Therapy, 2011 Apr 13-15, Coral Gables, FL.
23. PIs: Darunavir/Ritonavir
600/100 mg BID
Capparelli E, Best B, Stek A, et al. Pharmacokinetics of darunavir once or twice daily during pregnancy and postpartum. 3rd
International Workshop on HIV Pediatrics, 2011 Jul15-16, Rome, Italy.
24. PIs: Darunavir/Ritonavir
800/100 mg QD
Capparelli E, Best B, Stek A, et al. Pharmacokinetics of darunavir once or twice daily during pregnancy and postpartum. 3rd
International Workshop on HIV Pediatrics, 2011 Jul15-16, Rome, Italy.
25. PIs: Fosamprenavir/Ritonavir
Capparelli E, Stek A, Best B, et al. Boosted fosamprenavir pharmacokinetics in pregnancy. CROI 2010. 17th
Conference on Retroviruses and Opportunistic Infections, 2010 Feb 16 – 19; San Francisco, CA. [abstract 908].
26. PIs: Indinavir/Ritonavir in Thai women
Cressey T, Best B, Achalapong J, et al. Effect of pregnancy on pharmacokinetics of indinavir boosted ritonavir. 13th
International Workshop on Clinical Pharmacology of HIV Therapy; 2012 Apr 16-18. Barcelona, Spain.
27. Efavirenz in Pregnancy
Cressey TR, Stek A, Capparelli E, et al. Efavirenz pharmacokinetics during the third trimester of
pregnancy and postpartum. J Acquir Immune Defic Syndr. 2012 Mar 1;59(3):245-252.
28. Integrase Inhibitors:
P1026s: Raltegravir in Pregnancy
Best B, Capparelli E, Stek A, et al. Raltegravir pharmacokinetics in pregnancy. 50th ICAAC. 2010 Interscience Conference
on Antimicrobial Agents and Chemotherapy, 2010 Sep 12-15; Boston, MA. Abstract H-1668a.
29. Maternal Fetal Transfer of Study ARVs
Ratio Cord/Maternal Blood
• NNRTIs
• Efavirenz 0.49
• PIs
• Amprenavir/r 0.23
• Atazanavir/r 0.15
• Darunavir/r 0.25
• Indinavir/r 0.12
• IIs
• Raltegravir 1.31
32. P1026s Coming Attractions:
• DRV/RTV, 800 or 900/100 mg BID during 3rd trimester
• Rilpivirine
• Still evaluating: ddI, ETV, MVC, NFV 1875 mg BID, TPVr
• ARVs with TB treatment
– EFV, LPVr, or NVP with rifampicin-containing TB regimen
• Uninfected women (Control) with TB treatment
• ARVs with postpartum contraception
– LPVr or ATVr with EE-containing COC
– LPVr or ATVr with etonogestrel (Implanon)
33. Conclusions
• Many factors alter drug disposition in pregnant
patients and may require alteration in dosing.
• Detailed knowledge of drug characteristics can
help predict these differences.
• Maintaining consistent and optimal ARV
exposure is critical for long-term treatment
success.
• Understanding PK of maternal-infant drug
transfer can lead to effective and economical
therapies for the prevention of HIV transmission.
34. Acknowledgements
• UCSD Team: Steve Rossi, Rowena Espina, Nina Ilog,
Diane Holland, Edmund Capparelli, Steve Spector,
Andrew Hull, Linda Proctor, James Connor, Victor
Nizet
• NIAID, NICHD
• PACTG/IMPAACT
• Pediatric Pharmacology Research Unit
• P1026s Study Team, Clinical Sites and Participants
• Many Team & Lab Members, including: Mark Mirochnick, Alice
Stek, Sandy Burchett, Jennifer Read, Betsy Smith, Courtney
Fletcher, Jiajia Wang, David Shapiro, Chengcheng Hu,
Heather Watts, Fran Aweeka, Patty Lizak, Tim Cressey, Regis
Kreitchmann & others