Hypertension is a global health issue that is responsible for many deaths worldwide each year. Combination therapy using two or more antihypertensive drugs from different classes is often necessary to control blood pressure, especially for patients with co-morbid conditions like diabetes or heart disease. Guidelines recommend starting with a combination of first-line drugs like a diuretic, calcium channel blocker, angiotensin converting enzyme inhibitor, or angiotensin receptor blocker based on the individual's condition. Single pill combinations have advantages over free drug combinations in terms of adherence, efficacy, and tolerability. The appropriate combination of antihypertensives depends on any associated diseases and should target relevant organ systems and pathways.
newer drug combinations in management of hypertension,esp in presence of CAD, making them more potent anti-hypertensives, with lesser side effects especially pedal edema
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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
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
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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
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
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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
2. Hypertension global burden
Globally prevalence in adults aged > 25 years : 40%.
It is estimated to cause 7.5 million deaths;12.8% of the total deaths.
Hypertension accounts for 57 million disability adjusted life years (DALYS)
or 3.7% of total DALYS
62% of cerebrovascular diseases and 49% of ischemic heart diseases are
attributable to suboptimal BP.
One in three adults worldwide has high blood pressure.
Tanu Midha etal, World J Meta-Anal 2013 August 26; 1(2): 83-8
3. BP Control Rates are Suboptimal
Despite the clear benefits of reducing BP to target levels,
rates of BP control are suboptimal in most countries
BP control rates are particularly poor in low-income
countries
BP control rates are <30% in several Asia-Pacific countries
1. http://www.who.int/healthinfo/global_burden_disease/GlobalHealthRisks_r
eport_part2.pdf
2. Peter L, Int. J. Epidemiol. (2014), 1- 13
3. C-E Chiang,,Journal of Human Hypertension (2008) 22, 441–443
4. Get The Pressure Down!!
Awareness, Diagnosis & Best
antihypertensive which
prevent complications will
save lives !
Of Deaths
from Stroke
51%
Of Deaths
from Coronary
Heart Disease
45%
Deaths due to
HT
7.5 million
Total global
deaths
13%
http://www.who.int/gho/ncd/risk_factors/blood_pressure_prevalence_text/en/
7. Reasons for Not Achieving BP Control
Poor adherence and persistence with therapy.
Physicians’ reluctance to switch to an alternative treatment
and/or increase doses if BP remains uncontrolled.
Selected antihypertensive drug does not target the
mechanism causing the patient’s hypertension.
http://www.mayoclinic.org/diseases-conditions/high-blood-
pressure/basics/treatment/con-20019580 accessed on 9-oct-2015
9. Combination Therapy: A Practical Necessity
Required in ~ 75% of hypertensives to achieve target BP
Greater efficacy
Faster achievement of target BP
Higher response rates
May make therapy effective in broader population
Additive antihypertensive effects through complimentary pharmacologic
mechanisms
In some cases, improved side effect profile
•Gradman AH, Basile JN, Carter BL, et al. J Clin Hypertens (Greenwich).
2011;13:146–154.
10. Combination Therapy is More Effective Than
High Dose Monotherapy
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
Thiazide Beta-blocker ACEI CCB All classes
Combination Double dose
Incremental
SBP
reduction
ratio
of
observed
to
expected
additive
effects
Wald DS, et al. Am J Med 2009;122:290-300
11. Higher BP Control Rates Are Achieved With
Single Pill Combinations
26
55
0
10
20
30
40
50
60
Freecombination Singlepill
11
Change
in
proportion
of
patients
achieving
BP
goals
relative
to
monotherapy
(%)
Patients receiving a single pill combination are more likely to
achieve BP goals than those receiving free combinations or
monotherapy
Gu Q, et al. Circulation 2012;126:2105-14
*p<0.05 vs monotherapy
**p<0.01 vs. monotherapy
Regional guidelines on combination therapy| March 2013
12. Single Pill Combinations are
Recommended by Guidelines
Single pill combinations (SPCs) or fixed-dose combinations have
numerous advantages over multiple drug combination therapy
Current hypertension guidelines generally recommend SPCs over
multiple drug treatment with their individual components
1. Gupta AK, et al. Hypertension 2010;55:399-407
2. Bangalore S, et al. Am J Med 2007;120:713-9
3. Dusig R. VHRM 2010;6:321-5
4. Mancia G, et al. J Hypertens 2009;27:2121-58
13. Comparison of Monotherapy and Free
and Single Pill Combinations
Monotherapy Free
combination
Single pill
combination
Convenience ✔ ✗ ✔✔a
Adherence − − ✔
Efficacy ✗ ✔ ✔
Tolerability ✗ ✔ ✔b
Flexibility ✔✔ ✔✔ ✔c
a Switching and dose titration less likely to be required than for monotherapy
b Single pill may be better tolerated as doses tend to be lower than in free combinations
c Flexibility with single pill combinations is increasing as the range of doses increases
Xinhuan Wana et al., Asian Journal of Pharmaceutical Sciences Volume 9, Issue 1, February
2014, 1–7
25. Treatment of Hypertension in Patients with Ischemic
Heart Disease
• Caution should be exercised when combining a non DHP-CCB and a beta-blocker
• If abnormal systolic left ventricular function: avoid non DHP-CCB (Verapamil or
Diltiazem)
• Dual therapy with an ACEI and an ARB are not recommended in the absence of
refractory heart failure
• The combination of an ACEi and CCB is preferred
1. Beta-blocker
2. Long-acting CCB
Stable angina
ACEI are recommended for most
patients with established CAD*
ARBs are not inferior to ACEI in IHD
Short-acting
nifedipine
*Those at low risk with well controlled risk factors may not benefit from ACEI therapy
CHEP guidelines 2014
26. Treatment of Hypertension in Patients with Recent ST Segment
Elevation-MI or non-ST Segment Elevation-MI
Long-acting
Dihydropyridine
CCB*
Beta-blocker
and ACEI or
ARB
Recent
myocardial
infarction
Heart
Failure
?
NO
YES
Long-acting CCB
If beta-blocker
contraindicated
or not effective
*Avoid non dihydropyridine CCBs (diltiazem, verapamil)
CHEP guidelines 2014
27. Treatment of Hypertension with Left Ventricular
Systolic Dysfunction
Beta-blockers used in clinical trials were bisoprolol, carvedilol and metoprolol.
If additional therapy is needed:
• Diuretic (Thiazide for hypertension; Loop for volume control)
• for CHF class II-IV or post MI and selected patients with LV
dysfunction (see notes): Aldosterone Antagonist
Systolic
cardiac
dysfunction
• ACEI and Beta blocker
• if ACEI intolerant: ARB
Titrate doses of ACEI or ARB to those used in clinical trials
If ACEI and ARB are contraindicated: Hydralazine and Isosorbide
dinitrate in combination
If additional antihypertensive therapy is needed:
• ACEI / ARB Combination
• Long-acting DHP-CCB (Amlodipine)
Non
dihydropyridine
CCB
CHEP guidelines 2014
28. Treatment of Hypertension in Patients with Non
Diabetic Chronic Kidney Disease
Chronic kidney
disease and
proteinuria *
ACEI/ARB:
Bilateral renal
artery stenosis
ACEI or ARB (if ACEI intolerant)
Combination with other agents
Additive therapy: Thiazide diuretic.
Alternate: If volume overload: loop diuretic
Target BP: < 140/90 mmHg
* albumin:creatinine ratio [ACR] > 30 mg/mmol
or urinary protein > 500 mg/24hr
Monitor serum potassium and creatinine carefully in patients with CKD prescribed an ACEI or ARB
Combinations of a ACEI and a ARB are specifically not recommended in the absence of proteinuria
CHEP guidelines 2014
29. Treatment of Hypertension in association
with Diabetes Mellitus
Threshold equal or over 130/80 mmHg and Target below 130/80 mmHg
with
Nephropathy*
*Urinary albumin to creatinine
ratio > 2.0 mg/mmol in men or
> 2.8mg/mmol in women*
Diabetes
without
Nephropathy**
Isolated
Systolic
Hypertension
Systolic-
diastolic
Hypertension
* based on at least 2 of 3 measurements
A combination of 2 first line drugs may
be considered as initial therapy if the
blood pressure is >20 mmHg systolic
or >10 mmHg diastolic above target
Combinations of an ACEI with an ARB are specifically
not recommended in the absence of proteinuria
CHEP guidelines 2014
30. Treatment of Hypertension in association
with Diabetic Nephropathy
If Creatinine over 150 µmol/L or creatinine clearance below 30 ml/min ( 0.5
ml/sec), a loop diuretic should be substituted for a thiazide diuretic if control
of volume is desired
THRESHOLD equal or over 130/80 mmHg and TARGET below 130/80 mmHg
DIABETES
with
Nephropathy
ACE Inhibitor
or ARB
IF ACEI and ARB are
contraindicated or not
tolerated,
SUBSTITUTE
• Long-acting CCB or
• Thiazide diuretic
Addition of one or more of
Long-acting CCB or Thiazide
diuretic
3 - 4 drugs combination may
be needed
Monitor serum potassium and creatinine carefully in patients with CKD prescribed an ACEI or ARB
CHEP guidelines 2014
31. Treatment of Systolic-Diastolic
Hypertension without Diabetic Nephropathy
1. ACE Inhibitor or ARB or
2. Dihydropyridine CCB or
Thiazide diuretic
IF ACE Inhibitor and ARB and
DHP-CCB and Thiazide are
contraindicated or not
tolerated,
SUBSTITUTE
• Cardioselective BB* or
• Long-acting NON DHP-CCB
More than 3 drugs may be needed to reach target values for diabetic patients
* Cardioselective BB: Acebutolol, Atenolol, Bisoprolol , Metoprolol
Threshold equal or over 130/80 mmHg and TARGET below 130/80 mmHg
Combination of first line
agents
Addition of one or more of:
Cardioselective BB or
Long-acting CCB
Diabetes
without
Nephropathy
DHP: dihydropyridine
Combinations of an ACE Inhibitor with an ARB are specifically not recommended in the
absence of proteinuria
CHEP guidelines 2014
33. Summary 1
Controlling hypertension reduces CV outcomes
Doubling of CV risk with BP increases of 20/10mmHg
Majority of patients require >2 drugs to achieve BP goal
The use of single pill combinations can further improve BP
control and reduce cardiovascular morbidity and mortality
Combination therapy is recommended in treatment
guidelines