A presentation on a new product Rose-Hip Vital, a powerful antioxidant made from 100% natural rosehip (Rosa Canina) which may help temporarily relieve the pain of arthritis, rheumatism and osteoarthritis.
Pain control with ultrasound-guided inguinal field block compared with spinal...Arjun Rajagopalan
In this study, ultrasound-guided IFB provided lesser dynamic pain scores during the first postoperative day and reduced use of analgesics for 1 week compared with spinal anesthesia after inguinal hernia repair. Our technique could become a substitute performed by anesthesiologists in settings in which IFB is not performed routinely by surgeons.
A presentation on a new product Rose-Hip Vital, a powerful antioxidant made from 100% natural rosehip (Rosa Canina) which may help temporarily relieve the pain of arthritis, rheumatism and osteoarthritis.
Pain control with ultrasound-guided inguinal field block compared with spinal...Arjun Rajagopalan
In this study, ultrasound-guided IFB provided lesser dynamic pain scores during the first postoperative day and reduced use of analgesics for 1 week compared with spinal anesthesia after inguinal hernia repair. Our technique could become a substitute performed by anesthesiologists in settings in which IFB is not performed routinely by surgeons.
NeuroMed7 is an OTC Topical Anesthetic with uses that include local anesthesia prior to:
Injections
Immunizations
Venipuncture
Minimally invasive procedures
Cosmetic/aesthetic procedures
Also post procedural analgesia
NeuroMed7 is a formula combination of the topical anesthetic, lidocaine HCl 4% and trans-dermal penetration enhancers created to promote a rapid onset of action and trans-dermal penetration
Benefits include:
Rapid onset of action
trans-dermal penetration
Affordable cost
Clinical size and multi-dose packaging
Manufacturer, Supplier and Exporter of Rubber Stoppers & Aluminum Seals such as Single Dose Injectable Rubber Stoppers, Single Dose Injectable Rubber Stoppers, Single Dose Injectable Rubber Stoppers, Antibiotic And Serum Rubber Stoppers, Infusion Rubber Stoppers, Lyo Rubber Stoppers, Rubber Stoppers. In addition to this, we are also offering Dental Plungers And Seals which are widely used in dental clinics for suction applications.
IRIS is a radiopharmaceutical injector that performs calibrated injections to patients, starting from a multi-dose solution of FDG or other radiopharmaceuticals.
Injection safety According to CDC guidelineDerar ALJarrah
Preventing Unsafe Injection Practices
Safe Injection Practices are a set of recommendations within Standard Precautions, which are the foundation for preventing transmission of infections during patient care in all healthcare settings including hospitals, long-term care facilities, ambulatory care, home care and hospice.
Every occupation has work hazards and same is true for doctors and nurses also. Doctors and nurses are prone to needle stick injury while working and there is always risk of getting blood borne infection like HIV, Hepatitis B and HIV
Initial evaluation of the patient with acute abnormal uterine bleeding should include a prompt assessment for signs of hypovolemia and potential hemodynamic instability. After initial assessment and stabilization, the etiologies of acute abnormal uterine bleeding should be classified using the PALM–COEIN system. Medical management should be the initial treatment for most patients, if clinically appropriate. Options include intravenous conjugated equine estrogen, multi-dose regimens of combined oral contraceptives or oral progestins, and tranexamic acid. Decisions should be based on the patient’s medical history and contraindications to therapies. Surgical management should be considered for patients who are not clinically stable, are not suitable for medical management, or have failed to respond appropriately to medical management. The choice of surgical management should be based on the patient’s underlying medical conditions, underlying pathology, and desire for future fertility. Once the acute bleeding episode has been controlled, transitioning the patient to long-term maintenance therapy is recommended.
Tablets are solid dosage forms usually obtained by single or multiple compression of powders or granules. In certain cases tablets may be obtained by molding or extrusion techniques. They are uncoated or coated. Tablets are normally right circular solid cylinders, the end surfaces of which are flat or convex and the edges of which may be bevelled. They may have lines or break-marks (scoring), symbols or other markings.Tablets contain one or more active ingredients. They may contain excipients such as diluents, binders, disintegrating agents, glidants, lubricants, substances capable of modifying the behaviour of the dosage forms and the active ingredient(s) in the gastrointestinal tract, colouring matter authorized by the appropriate national or regional authority and flavouring substances. When such excipients are used it is necessary to ensure that they do not adversely affect the stability, dissolution rate, bioavailability, safety or efficacy of the active ingredient(s); there must be no incompatibility between any of the components of the dosage form.
Tablets are single-dose preparations intended for oral administration. Some are intended to be swallowed whole, some after being chewed and some after being crushed, some are intended to be dissolved or dispersed in water before being taken and some are intended to be retained in the mouth where the active ingredient(s) is/are liberated.
This is a powerpoint presentation I gave to junior nursing students reviewing injections and injection technique in preparation for medical-surgical clinical.
NeuroMed7 is an OTC Topical Anesthetic with uses that include local anesthesia prior to:
Injections
Immunizations
Venipuncture
Minimally invasive procedures
Cosmetic/aesthetic procedures
Also post procedural analgesia
NeuroMed7 is a formula combination of the topical anesthetic, lidocaine HCl 4% and trans-dermal penetration enhancers created to promote a rapid onset of action and trans-dermal penetration
Benefits include:
Rapid onset of action
trans-dermal penetration
Affordable cost
Clinical size and multi-dose packaging
Manufacturer, Supplier and Exporter of Rubber Stoppers & Aluminum Seals such as Single Dose Injectable Rubber Stoppers, Single Dose Injectable Rubber Stoppers, Single Dose Injectable Rubber Stoppers, Antibiotic And Serum Rubber Stoppers, Infusion Rubber Stoppers, Lyo Rubber Stoppers, Rubber Stoppers. In addition to this, we are also offering Dental Plungers And Seals which are widely used in dental clinics for suction applications.
IRIS is a radiopharmaceutical injector that performs calibrated injections to patients, starting from a multi-dose solution of FDG or other radiopharmaceuticals.
Injection safety According to CDC guidelineDerar ALJarrah
Preventing Unsafe Injection Practices
Safe Injection Practices are a set of recommendations within Standard Precautions, which are the foundation for preventing transmission of infections during patient care in all healthcare settings including hospitals, long-term care facilities, ambulatory care, home care and hospice.
Every occupation has work hazards and same is true for doctors and nurses also. Doctors and nurses are prone to needle stick injury while working and there is always risk of getting blood borne infection like HIV, Hepatitis B and HIV
Initial evaluation of the patient with acute abnormal uterine bleeding should include a prompt assessment for signs of hypovolemia and potential hemodynamic instability. After initial assessment and stabilization, the etiologies of acute abnormal uterine bleeding should be classified using the PALM–COEIN system. Medical management should be the initial treatment for most patients, if clinically appropriate. Options include intravenous conjugated equine estrogen, multi-dose regimens of combined oral contraceptives or oral progestins, and tranexamic acid. Decisions should be based on the patient’s medical history and contraindications to therapies. Surgical management should be considered for patients who are not clinically stable, are not suitable for medical management, or have failed to respond appropriately to medical management. The choice of surgical management should be based on the patient’s underlying medical conditions, underlying pathology, and desire for future fertility. Once the acute bleeding episode has been controlled, transitioning the patient to long-term maintenance therapy is recommended.
Tablets are solid dosage forms usually obtained by single or multiple compression of powders or granules. In certain cases tablets may be obtained by molding or extrusion techniques. They are uncoated or coated. Tablets are normally right circular solid cylinders, the end surfaces of which are flat or convex and the edges of which may be bevelled. They may have lines or break-marks (scoring), symbols or other markings.Tablets contain one or more active ingredients. They may contain excipients such as diluents, binders, disintegrating agents, glidants, lubricants, substances capable of modifying the behaviour of the dosage forms and the active ingredient(s) in the gastrointestinal tract, colouring matter authorized by the appropriate national or regional authority and flavouring substances. When such excipients are used it is necessary to ensure that they do not adversely affect the stability, dissolution rate, bioavailability, safety or efficacy of the active ingredient(s); there must be no incompatibility between any of the components of the dosage form.
Tablets are single-dose preparations intended for oral administration. Some are intended to be swallowed whole, some after being chewed and some after being crushed, some are intended to be dissolved or dispersed in water before being taken and some are intended to be retained in the mouth where the active ingredient(s) is/are liberated.
This is a powerpoint presentation I gave to junior nursing students reviewing injections and injection technique in preparation for medical-surgical clinical.
Long-acting local anesthetics - present and futurescanFOAM
A presentation by Joseph Cravero at the 2017 meeting of the Scandinavian Society of Anaestesiology and Intensive Care Medicine.
All available content from SSAI2017: https://scanfoam.org/ssai2017/
Delivered in collaboration between scanFOAM, SSAI & SFAI.
A – Assess, Prevent and Manage Pain
B – Both SATs and SBTs
C – Choice of Sedation
D – Delirium: Assess, Prevent and Manage
E – Early Mobility and Exercise
F – Family Engagement and Empowerment
*www.iculiberation.org
Acute neuropathic pain - Stephan Schug - SSAI2017scanFOAM
A talk by Stephan Schug at the 2017 meeting of the Scandinavian Society of Anaestesiology and Intensive Care Medicine.
All of the conference content can be found here: https://scanfoam.org/ssai2017/
Developed in collaboration between scanFOAM, SSAI and SFAI.
This slide show reflects general considerations of Bio-availability & Bio-equivalence studies for orally administered drugs. The presentation also accommodates US - FDA's approach and specific recommendations for such studies.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- 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
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the 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 lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
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. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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
2. Najib Babul, PharmD
Conflict of Interest Statement
• Pharmaceutical sponsors with submissions
or pending submissions before Divisions
550 and 170
• Funding: No external funding
• Views expressed are solely those of
TheraQuest Biosciences
3. Najib Babul, PharmD
Single-Dose Evaluation
in
Acute Pain
• Screen patient
• Initiate acute insult
• Recovery
• Pain stimulus threshold
• Dose patient
• Evaluate response over one dose
• Terminate assessments after dosing interval or
first rescue
5. Najib Babul, PharmD
Multidose Analgesic Evaluation
• Growing request for data
• “Rhetoric” far outpaces the “science”
• Objectives:
Establish efficacy?
Demonstrate effectiveness?
Establish dosing frequency?
Test draft Package Insert?
Evaluate safety?
6. Najib Babul, PharmD
Challenges to Multidose Evaluation
in Acute Pain
• Natural trajectory
• Assay sensitivity
• Reduced hospitalization
• Reduced postsurgical pain
• Consent to multidose placebo control
• “Data contamination” with rescue use
• Shortage of trained analgesic observers/raters
• Approaches to data analysis
7. Najib Babul, PharmD
Proposed Solutions
• Use only active controls
• Use pseudo-placebos
• Rescue analgesic consumption as an endpoint
• Integrate rescue and pain assessment data
• Substitute serial assessments with pain recall
• Use take-home diaries
8. Najib Babul, PharmD
Integration of Pain and Rescue:
Rationale
• Traditional studies discard data after first rescue
• Rescue confounds analgesic response evaluation
• Rescue differentially confounds data within and
between treatment groups (single and multiple
dose phases)
• How to evaluate analgesic response in the face of
rescue?
• Integrate pain and rescue scores
9. Najib Babul, PharmD
Use of Pain Recall Instruments
• Pain recall is prominent in diagnosis and Rx
• Validity of pain recall viewed as “suspect”
• Recall frequently used in chronic pain RCT’s
• Frequent serial pain assessments the norm in acute
pain RCT’s
• Hourly assessments a challenge in multidose
studies
• Are less frequent assessments a substitute?
10. Najib Babul, PharmD
Study Design
• 88 patients - 77 evaluable
• Orthopedic surgery
• Hourly pain intensity VAS assessments (pain
now) for 48 hours
• 24 and 48 hour assessments of “Worst”
(maximum), “Least” (minimum) and “Usual”
(average) pain
Babul et al. Annals of Pharmacotherapy 1993;27:9-12 & Pain 1994;57:131-32
11. Najib Babul, PharmD
Experienced vs Recalled Pain Intensity
Actual and Recalled Pain Intensity
0-24h 0-48h
Pain Intensity on VAS (mean+ SE) (mean+SE)
Worst (recall) 65.4+SE) 60.2+3.4
Maximum (hourly VAS) 66.2+2.8 66.7+2.8
Differenceb
-0.8+1.7 -6.4+1.9c
Least (recall) 9.7+1.2 5.0+0.9
Minimum (hourly VAS) 9.4+1.2 4.3+0.8
Differenceb
0.3+0.7 0.6+0.5
Usual (recall) 31.4+2.1 25.2+2.1
Mean (hourly VAS) 32.1+1.9 25.8+1.8
Differenceb
-0.6+0.9 0.6+1.0
a
n=77. b
Mean recall variable minus corresponding mean hourly VAS variable.
c
p=0.001
Babul et al. Annals of Pharmacotherapy 1993;27:9-12 & Pain 1994;57:131-32Babul et al. Annals of Pharmacotherapy 1993;27:9-12 & Pain 1994;57:131-32
13. Rofecoxib Postorthopedic Surgical Pain (Days 2-5)
** PP=0.005 rofecoxib 50 mg compared with placebo.=0.005 rofecoxib 50 mg compared with placebo.
Data on file.Data on file.
Lortab 7.5 mg Use PostsurgeryLortab 7.5 mg Use Postsurgery
Mean%Mean%
2020
4040
6060
8080
PlaceboPlacebo
(n=53)(n=53)
RofecoxibRofecoxib
50 mg50 mg
(n=54)(n=54)
Patients With Good to ExcellentPatients With Good to Excellent
ResponseResponse
00
11
22
33
44
PlaceboPlacebo
(n=53)(n=53)
RofecoxibRofecoxib
50 mg50 mg
(n=54)(n=54)
MeanTablets/Day±SEMeanTablets/Day±SE
**
00
** PP=0.005 rofecoxib 50 mg compared with placebo.=0.005 rofecoxib 50 mg compared with placebo.
Data on file.Data on file.
Lortab 7.5 mg Use PostsurgeryLortab 7.5 mg Use Postsurgery
Mean%Mean%
2020
4040
6060
8080
PlaceboPlacebo
(n=53)(n=53)
RofecoxibRofecoxib
50 mg50 mg
(n=54)(n=54)
Patients With Good to ExcellentPatients With Good to Excellent
ResponseResponse
00
11
22
33
44
PlaceboPlacebo
(n=53)(n=53)
RofecoxibRofecoxib
50 mg50 mg
(n=54)(n=54)
MeanTablets/Day±SEMeanTablets/Day±SE
**
00
Najib Babul, PharmD
14. Najib Babul, PharmD
6
8
10
12
14
16
18
20
22
24
26
28 Placebo Celecoxib Rofecoxib
Placebo 22 19 20 19 18 18
Celecoxib 14 16 21 19 19 18
Rofecoxib 14 13 11 11 11 11
4 hr 8 hr 12 hr 16 hr 20 hr 24 hr
MeanMorphineUse
perTimeInterval(mg)
* *
**
†
Postoperative Time Interval
Anesth Analg. 2000;91: 1221-1225.
* Significantly less morphine used in the rofecoxib group vs. the placebo group (p<.0001)
** Significantly less morphine used in the celecoxib group vs. the placebo group (p<.03)
† Significantly less morphine used in the rofecoxib group vs. the celecoxib group (p<.01)
*
****
† *
†
*
†
*
†
MORPHINE CONSUMPTION
Pre-operative Analgesia with Rofecoxib and Celecoxib
15. Najib Babul, PharmD
71 mg ± 7Rofecoxib
107 mg ± 17Celecoxib
117 mg ± 13Placebo
Morphine UsedGroup
Total Morphine Used for 24 Hours
Anesth Analg. 2000;91: 1221-1225.
MORPHINE CONSUMPTION
Pre-operative Analgesia with Rofecoxib and Celecoxib
Editor's Notes
Good Morning. My name is Najib Babul. I would like to address the FDA Arthritis Advisory Committee and the Division on the issue of multi-dose analgesic development. This is one of the questions that the Division has asked the committee to consider in terms of evaluating analgesics in acute pain.
Najib Babul. Transcript of the FDA Arthritis Advisory Committee, Tuesday, July 30, 2002, Bethesda, MD.
I have previously provided a conflict of interest statement and that stays on record so I won&apos;t repeat it here.
Najib Babul. Transcript of the FDA Arthritis Advisory Committee, Tuesday, July 30, 2002, Bethesda, MD.
This slide shows the essential approach that we have been taking for the last two decades to evaluation and approval of analgesics in acute pain. Certainly, from an efficacy perspective, we do some of those studies by screening a patient, initiating some sort of an acute insult, having some sort of a period of recovery when the pain stimulus reaches a particular intensity, moderate or severe usually. We will then dose the patient. We evaluate the response over a single dose and then we terminate assessments either after the dosing interval is over, which is generally 8, 12 or 24 hours, or at the time that the patient requests their first rescue analgesic.
Najib Babul. Transcript of the FDA Arthritis Advisory Committee, Tuesday, July 30, 2002, Bethesda, MD.
There are compelling reasons why pharmaceutical sponsors have not gone down the path of efficacy evaluations in the multi-dose arena, and I would like to address these and propose some potential solutions.
Najib Babul. Transcript of the FDA Arthritis Advisory Committee, Tuesday, July 30, 2002, Bethesda, MD.
There is no doubt that there is no growing request for data. I recall that even at the Vioxx FDA advisory committee meeting there was discussion of the availability or relative lack of multi-dose data in the dossier. There have been increasing requests from both FDA Division 550 and 170 for such data. I think the challenge here is, if I can just be frank and I guess this is for the record, that our collective rhetoric perhaps outpaces the actual science of drug development. In other words, our methodologic ability, to echo what Dr. Laska was saying, to actually tease out some of those differences is not always there. In order to address this issue of multi-dose analgesic evaluation from an efficacy perspective, we need to ask ourselves precisely what our objectives are. Are they to establish efficacy? Are they to demonstrate effectiveness? Are we trying to establish dosing frequency? Are we trying to prospectively test a draft package insert? Or, are we merely trying to provide some sort of supportive safety data in a perioperative setting where perhaps patients might be critically ill and otherwise compromised?
Najib Babul. Transcript of the FDA Arthritis Advisory Committee, Tuesday, July 30, 2002, Bethesda, MD.
Here are some of the challenges to evaluating these drugs in acute pain. The first issue, and this has been alluded to earlier, is that the natural trajectory of acute pain is such that, whether treated or untreated, for the most part it diminishes. To be sure, and Dr. Katz referred earlier to thoracotomy patients or lumbar laminectomy patients who may have somewhat long-term pain. To be sure, some patients may have a longer trajectory, but a majority of these patients have a relatively short trajectory. So, this introduces an issue that most analgesiologists have called assay sensitivity. We are also faced with a reduced duration of hospitalization. A significant number of patients after major surgery are home within four days to a week&apos;s time. There is also a growing trend towards surgical techniques that reduce surgical pain. For instance, hip arthroplasty, as is currently being conducted, requires substantially less postoperative opioids than perhaps 10 or 15 years ago and this presents a bit of a challenge. Furthermore, patients will sometimes refuse to consent to multi-dose placebo controlled studies. It is one thing to convince patients to do a single-dose placebo controlled study, but to tell them you are going to repeatedly be give placebo over the next five or seven days presents a bit of a challenge. We also have this issue of data contamination when you give rescue analgesia, and we have a problem in terms of availability of trained analgesic observers or nurse raters. This is a very specific discipline requiring an exceptionally well-trained individual who truly understands analgesic methodology, and there is a real shortage of such folks. Your most senior study coordinator usually wants to work the day shift so you have 72 hours more to go beyond that to evaluate the patient.
Najib Babul. Transcript of the FDA Arthritis Advisory Committee, Tuesday, July 30, 2002, Bethesda, MD.
I would like to suggest some proposed approaches without getting too prescriptive. Some of these have really been spurred through discussions with Division 550 with Dr. Witter and Dr. Simon and others. One option clearly is to use active controls, with the Division&apos;s prior consent. That is certainly one possibility to consider. The other option is to use what I call pseudo placebos. So, these would not be placebos but would be perhaps ultra low dose of an approved agent, to allow us to get some assay sensitivity. Yet another option, and this was discussed previously by Dr. Laska, is to use rescue analgesia as an endpoint. This has been used successfully but only with a modest degree of success in the past. We can also integrate rescue and pain assessment data, and there are some techniques available for that. Of course, because of the shortage of trained study coordinators, we can perhaps consider doing serial assessments long term. We can use recall instruments to assess pain.
Najib Babul. Transcript of the FDA Arthritis Advisory Committee, Tuesday, July 30, 2002, Bethesda, MD.
The rationale for integrating rescue and pain scores to come up with some composite scores is given on this slide, and I am going to be brief here. Traditional studies have tended to discard rescue after the first dose. The issue is that rescue tends to confound our analgesic evaluation. Furthermore, rescue differentially confounds the analgesic response. Dr. David Silverman in the Department of Anesthesiology at Yale, for instance, has suggested a rather elegant but simple approach to integrating rescue and analgesia scores.
Najib Babul. Transcript of the FDA Arthritis Advisory Committee, Tuesday, July 30, 2002, Bethesda, MD.
Alternative approaches that are available involve the use of recall instruments. We know that recall, at least among analgesiologists, is viewed as somewhat suspect but we, and others, have shown and have published data demonstrating that recall is actually quite sensitive. We have done studies where we have looked at recall in orthopedic pain and other models, and we think that this allows you perhaps to conserve on the resources that are a problem in multi-dose studies.
Najib Babul. Transcript of the FDA Arthritis Advisory Committee, Tuesday, July 30, 2002, Bethesda, MD.
Alternative approaches that are available involve the use of recall instruments. We know that recall, at least among analgesiologists, is viewed as somewhat suspect but we, and others, have shown and have published data demonstrating that recall is actually quite sensitive. We have done studies where we have looked at recall in orthopedic pain and other models, and we think that this allows you perhaps to conserve on the resources that are a problem in multi-dose studies.
Najib Babul. Transcript of the FDA Arthritis Advisory Committee, Tuesday, July 30, 2002, Bethesda, MD.
Najib Babul. Transcript of the FDA Arthritis Advisory Committee, Tuesday, July 30, 2002, Bethesda, MD.
The last potential option that one ought to consider is rescue analgesia as an endpoint. I believe it is a potential endpoint. It does have some risks because the variability is not insignificant.
Najib Babul. Transcript of the FDA Arthritis Advisory Committee, Tuesday, July 30, 2002, Bethesda, MD.
These are data that were presented in 1998 at the Arthritis Advisory Committee in the review of the Rofecoxib submission. As you can see in this particular study, over day two to five there was a difference between placebo and rofecoxib in terms or rescue consumption. It was a one tablet per day difference. Now, whether this is clinically meaningful is a separate issue but it certainly provided some assay sensitivity in an attempt to look for differences. In summary, the methodology for multi-dose efficacy evaluation is not quite cooked; it is not established. I think there are some possible options that are available, but we need to understand that there are some compelling reasons why evidence from single-dose studies have formed the primary basis for efficacy evaluation. None of these techniques can meaningfully, in my opinion, answer questions related to the time course of effect and dose response. Those questions, and they are critical questions, need to be addressed in single-dose efficacy evaluations. Thank you
Najib Babul. Transcript of the FDA Arthritis Advisory Committee, Tuesday, July 30, 2002, Bethesda, MD.