Clinical study on human subjects according to all guidelines to form a ideal protocol and requirement to conduct clinical trial with very efficient way mainly considering to India and ICH associated countries
Clinical study on human subjects according to all guidelines to form a ideal protocol and requirement to conduct clinical trial with very efficient way mainly considering to India and ICH associated countries
ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
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
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.
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
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.
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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
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
2. “clinical trial” means
an investigation in a human subject which is
intended to discover or verify the clinical,
pharmacological or other pharmacodynamics
effects of an investigational drug product or to
identify any adverse reactions to an
investigational drug product;
3. Types of Clinical Trials:
(as defined by the National Institutes of Health)
Treatment Trials - test new treatments, new
combination of drugs or new approaches to
surgery or radiation.
Prevention Trials - look for better ways to prevent
diseases.
4. Types of Clinical Trials:
Diagnostic Trials - determine better tests or
procedures for diagnosing a particular disease or
condition.
Screening Trials - test the best way to detect or
treat diseases.
Quality of Life Trials - explore and measure ways to
improve the comfort and quality of life of people with
a chronic illness.
5.
6. Clinical Trials are Done in
Phases:
First, a Pre-Clinical Trial must
be done before the Clinical
Trial starts.
Preclinical trial – research
on a new drug or a new
medical device or procedure,
usually done on animals, to
learn about mechanisms of
action, determine how well the
treatment works, and see if it
is safe to test on humans.
7. Scientific Aspects of
Clinical Trial
Phases of Clinical Trial
Phase I : First in man safety
Phase II : First in patient dose, dosage form
Phase III : Efficacy, ADRs
Post marketing surveillance or Phase IV : Evaluation
in the real clinical setting
8.
9. Phase I
• Objectives
1. To assess a safe & tolerated dose
2. To see if pharmacokinetics differ much from animal to
man
3. To see if kinetics show proper absorption, bioavailability
4. To detect effects unrelated to the expected action
5. To detect any predictable toxicity
– Inclusion criteria
– Healthy volunteers : Uniformity of subjects: age, sex,
nutritional status [Informed consent a must]
– Exception: Patients only for toxic drugs Eg AntiHIV,
Anticancer
– Exclusion criteria
– Women of child bearing age, children,
10. Phase I contd
• Methods:
– First in Man : Small number of healthy volunteers
– First in a small group of 20 to 25
– Start with a dose of about 1/10 to 1/5 tolerated animal
dose
– Slowly increase the dose to find a safe tolerated dose
– If safe in a larger group of up to about 50 –75
– No blinding
– Performed by clinical pharmacologists
– Centre has emergency care & facility for kinetics
study
– Performed in a single centre
– Takes 3 – 6 months [ 70% success rate]
11. Phase II
• First in patient [ different from healthy volunteer]
• Early phase [20 – 200 patients with relevant disease]
– Therapeutic benefits & ADRs evaluated
– Establish a dose range to be used in late phase
– Single blind [Only patient knows] comparison with standard
drug
• Late phase [ 50 – 500]
– Double blind
– Compared with a placebo or standard drug
• Outcomes
– Assesses efficacy against a defined therapeutic endpoint
– Detailed P.kinetic & P.dynamic data
– Establishes a dose & a dosage form for future trials
• Takes 6 months to 2 years [ 35% success rate]
12. Phase III
• Large scale, Randomised, Controlled trials
• Target population: 250 – 1000 patients
• Performed by Clinicians in the hospital
• Minimises errors of phases I and II
• Methods
– Multicentric Ensures geographic & ethnic variations
– Diff patient subgroups Eg pediatric, geriatric, renal impaired
– Randomised allocation of test drug /placebo / standard drug
– Double blinded:
– Cross over design
– Vigilant recording of all adverse drug reactions
– Rigorous statistical evaluation of all clinical data
• Takes a long time: up to 5 years [25% success]
13. Cross over design
Group Week 1 Week2 Week3
I Standard Placebo Test
II Placebo Test Standard
III Test Standard Placebo
* A wash out period of a week between two weeks
of therapy
14. Phase IV or Post marketing
Surveillance
• No fixed duration / patient population
• Starts immediately after marketing
• Report all ADRs
• Helps to detect
– rare ADRs
– Drug interactions
– Also new uses for drugs [Sometimes called Phase V]
15. Clinical Trial: Legal & Procedural
aspects
Elements of a Clinical Trial
• Aim or objective
• Protocol : study design
• Ethics committee clearance
• Regulatory approval whenever required
• Informed consent
• Implementation of protocol
• Collection of data
• Compilation of data, analysis and interpretation
• Report writing
16. Participating Parties in Clinical Trial
1. Patient / Healthy volunteer
2. Clinical Pharmacologist, Clinical Investigator
& team: [Qualified and competent]
3. Institution where trials are held : [Approval
required]
4. Ethical Review Board or Institutional Ethical
Committee:
5. Sponsor
6. Regulatory Authorities:
17. Functions of participating parties
– [1] Patient / Healthy volunteer : Subject of
the trial
– [2] Clinical Pharmacologist, Clinical
Investigator & team:
– Conducts the clinical trial; reports all adverse
events
– [3] Institution where trials are held :
– Provides all facilities [Approval required]
18. Functions of parties contd.
– [4] Ethical Review Board or Institutional Ethical
Committee:
– Supervises and monitors every step;
– Safeguard the welfare and the rights of the
participants
– [5] Sponsor :
– Pays for all expenses;
– Appoints competent investigators,
– Ships all drugs for the trial,
– Files all papers to legal / regulatory authorities,
– [6] Regulatory Authorities:
– Legal authority on the outcomes of the trial
19. Clinical Trial Protocol
• Title & Abstract
• Introduction
– General statement of purpose
– Complete Preclinical results on animal study
– Clinical data if available
– Time frame
• Goals: Primary & secondary objectives
• Study Design:
– Type of study
– Recruitment criteria : Exclusion & Inclusion criteria
– Randomisation criteria and Sample size
– Duration of study
• Data Analysis:
– Case report forms, Statistical Analysis, Bibliography
20. Informed Consent
• Informed consent form:
– Voluntary
– Explained in simple nontechnical language
– Translated in the native language of the subject
– Comprehensive information regarding the trials
• Benefit of new therapy over existing ones
• Alternative treatments available
– All possible adverse reactions
– Freedom to withdraw from the trial
• at any time,
• without giving any reason
21. Institutional Ethical Committee
– Independent
– Competent
– 5 – 7 members; 5 required for quorum.
– Member Sec from same Institution
– Others: A mix of medical non-medical,
scientific & non-scientific including lay public
– Multidisciplinary & Multisectorial
22. Responsibilities of IEC
1. To protect the dignity, rights & well being of
patients / volunteers
2. Ensure a competent review of the protocol
3. Advise on all aspects of welfare & safety
4. Ensure scientific soundness of the proposal
23. The composition of IEC
1. Chairperson
2. 1-2 basic medical scientists.
3. 1-2 clinicians from various Institutes
4. One legal expert or retired judge
5. One social scientist / representative of NGO
6. One philosopher / ethicist / theologian
7. One lay person from the community
8. Member Secretary
– Individuals from other institutions if required
– Adequate representation of age, gender, community,
24. Problem areas
• Compensation in drug related injuries
– Mild and Severe
• Patient Rights
– Confidentiality of data
– Right to withdraw
• Collection procedures & amount of biological material
taken
• Compensation & Insurance claims
• Sending bio-material abroad
• Selection of Patients
25. Research Concepts
In many studies, the new drug is
compared to a placebo. A placebo is a
product that looks like the new drug, but it
does not have the active ingredient in it.
People do not know that they are getting
the placebo.
Sometimes the test compares the new
treatment against an existing treatment to
see if better results can be obtained.
26. Research Concepts
Blind and Double Blind Trials are frequently
done.
A Blind Trial is a trial in which the patients do not
know if they are receiving the treatment or a
placebo.
A Double Blind Trial is a trial in which the
patients and the researchers do not know who is
receiving the treatment.
Why would the above be good ideas?
27. Research Concepts
Randomization is the process by which patients
are assigned a group for the Clinical Trial.
Groups are assigned randomly, not purposefully.
Some people will receive the new treatment, some
may receive an already approved treatment, and
some may receive a placebo.
If one treatment is found superior, the trial is
stopped so that the fewest patients possible
receive the less beneficial treatment.
28. Use of Placebo Control
The “placebo effect” is well documented
Could be
No treatment + placebo
Standard care + placebo
Matched placebos necessary so patients & investigators
cannot decode the treatment assignment
eg. Vitamin C trial for common cold
Placebo was used, but was distinguishable
Many on placebo dropped out of study – not blinded
Those who knew they were on vitamin C reported fewer
cold symptoms and duration than those on vitamin who
didn't know
29. NDA UG
An application for authorisation to conduct a clinical trial shall be made by a sponsor
who shall be
(a) the holder of the patent of the drug;
(b) a licensed person;
(c) the manufacturer of the drug; or
(d) an agent of the holder of the patent or the manufacturer, of the
drug.
Where an application for authorisation to conduct a clinical trial is made by an agent,
the agent shall submit a power of attorney attesting to the appointment as an agent
or a letter of authorisation
30. The application shall be accompanied by the following —
(a) the clinical trial protocol;
(b) evidence of approval of the clinical trial by the Uganda National Council of Science
and Technology or an institution approved by the Uganda National Council for
Science and Technology;
(c) the investigator’s brochure or prescribing information data sheet
(d) a declaration by the principal investigator made using
(e) a declaration by the monitor made
(f) the financial declaration by the sponsor and the principal investigator
(g) the information to be provided to the subjects and the written consent forms of the
subjects;
(h) valid evidence of the insurance of the subjects;
(i) pharmaceutical data on the dosage form of the investigational medicinal
(j) capacity building plans for the training of the staff to be involved in the clinical trial;
(k) the prescribed fees; and
(l) any other requirement as may be determined by the Authority.
Editor's Notes
Clinical trial: a prospectively planned experiment for the purpose of evaluating potentially beneficial therapies or treatments
In general, these studies are conducted under as many controlled conditions as possible so that they provide definitive answers to pre-determined, well-defined questions
New medicines originate in the laboratory where researchers identify, isolate and study thousands of molecules for their potential as future anticancer therapies.
Once a candidate molecule (compound) has been identified in the laboratory, it is subjected to rigorous pre-clinical testing (in the laboratory and/or in animals) to assess its chemical, biological and toxicological properties (how harmful it is).
These pre-clinical tests allow researchers a snapshot of whether a compound may have anticancer activity.
If results of pre-clinical studies are positive, the compound may be entered into a clinical trial program: this involves several ‘phases’ of study, starting with small studies usually in healthy volunteers and progressing in steps through to evaluation of the drug in people with the disease. At each phase, only those compounds that meet strict criteria for safety and effectiveness (efficacy) advance to the next phase.
When results of clinical trials indicate the compound being studied is safe and effective the company applies to regulatory authorities for marketing authorization (permission to sell, and use the drug in daily medical practice). This usually occurs following a successful Phase III study, but may occur earlier in diseases where there are very few treatment options, sometimes described as a ‘high medical need’.
Finally, if the marketing authorization is granted, the new treatment is made available as prescribed by doctors. There are strict rules regarding the license given to the treatment – the pharmaceutical company may only promote the product for the treatment of patients with the diseases (indications) described in the license or label.
The medicine’s use continues to be carefully monitored in accordance with approved current medical practices
See Powerpoint in this module on Pre-Clinical Trials for more information.
Having a blind or double blind trial helps prevent any bias the patients and researchers might have. For example, patients think they feel better just because they are getting a medicine! Physicians might want the drug to work, so they might be biased when it comes to looking at results.
True randomness is not always a good idea. For example, you might want each treatment group to have an equal number of people with certain characteristics, such as half male, half female in each group, or equal numbers in each category of physical characteristics. With proper statistical significance, the results could show that the new treatment works only on certain people (age group, sex, etc.)