Introduction: Respiratory Sinus Arrhythmia (RSA) is the differential change of Heart Rate (HR) in response to inspiration and expiration. This is a noninvasive sensitive index of parasympathetic cardiac control.
Aim: To evaluate changes in RSA by utilizing a simple and cost-effective analysis of electrocardiographic (ECG) tracings obtained during performance of four pranayama techniques.
Materials and Methods: Fifty two trained volunteers performed the following pranayamas with different ratios for inspiration and expiration: sukha (1:1), traditional (1:2), pranava (1:3) and savitri (2:1:2:1) and ECG was recorded while performing the techniques with rest period of 5 minutes in-between. HR was calculated and maximum HR during inspiration (Imax), minimum HR during expiration (Emin), differences between Imax and Emin (?), percentage differences between Imax and Emin (?%) and expiration: inspiration ratio (E:I) calculated by respective formulae. Statistical analysis was carried out using repeated measures of ANOVA with Tukey-Kramer multiple comparisons test.
Results: There were significant differences between groups in all five aspects namely: p= 0.0093 for mean Imax, p = 0.0009 for mean Emin, and p < 0.0001 for ? HR (I-E), ?% HR (I-E) and E:I ratio. Pranava pranayama produced the greatest changes in all five comparisons.
Conclusion: We suggest that further short and long term studies be undertaken with pranava pranayama in patients to further qualitatively and quantitatively evaluate inherent mechanisms of this simple technique. Addition of these cost-effective techniques to the medical armory will help patients of rhythm disorders and other cardiovascular conditions.
A Mathematical model for Impact of citalopram on the HPA system and combined ...IJERA Editor
In this paper we introduce bivariate sinh-normal distribution, which has seven parameters. Due to presence of seven parameters it is a very flexible distribution .Different properties of this new distribution has been established. We consider a bivariate model which can be obtained by transforming the sinh-normal distribution and it is a generalization of the bivariate Birnbaum-Saunders distribution. Several properties of the bivariate Birnbaum-Saunders distribution can be obtained as special cases of the proposed generalized bivariate Birnbaum-Saunders distribution. Twenty three patients responded (≥50% reduction in the score), and 17 of them also reached criteria of remission (HDRS≤ 7). Baseline (dexamethasone suppressed) and CRH stimulated ACTH concentrations significantly decreased from day 0 to day 28. CRH stimulated cortisol concentrations also fell, although not significantly, but baseline cortisol concentrations exhibited a significant increase from day 0 to day 28.Finally we conclude that the medical curve and Mathematical curve for disease control is higher than the probability density functions which are monotonic functions.
IMMEDIATE EFFECT OF CHANDRANADI PRANAYAM ON HEART RATE VARIABILITY AND CARDIO...Yogacharya AB Bhavanani
Diabetes mellitus (DM) and hypertension (HT) are widely prevalent psychosomatic lifestyle disorders that often coexist. Chandranadi pranayama (CNP), an exclusive left nostril breathing technique, has been reported to be useful in reducing heart rate (HR) and blood pressure (BP) in normal subjects as well as hypertensives and is part of yoga therapy schedules for patients of HT and DM. This study investigated the immediate effects of 5 minutes of CNP on HR, BP and heart rate variability (HRV) in patients of HT, DM and in those having both (DMHT). Thirty nine participants receiving standard medical care from the department of medicine, JIPMER were recruited. HR, BP and short- term supine HRV were recorded before and after 5 minutes of CNP. Analysis showed significant (p < 0.05) fall of HR and BP indices in all three groups with no difference between groups. However in short term HRV analysis, there were differences between the responses of DM and HT patients with regard to mean RR and mean HR. Preexisting intergroup differences with regard to SDNN, RMSSD, HF power and total power were negated after the performance of CNP. Pre-post intra group comparisons showed significant increases in Mean RR and Mean HR in both HT and HTDM groups while there were significant increases in LFnu and LF/HF ratio with significant decrease in HFnu in DM group. The post CNP responses of DM group in Mean RR, SDNN, Mean HR, RMSSD, LF power and total power were contrary to responses in the other groups. This is the first report comparing immediate effects of CNP in patients of HT and DM. The reduction in HR and BP indices in all three groups may be attributed to an overall normalization of autonomic cardiovascular rhythms along with improvement in baroreflex sensitivity irrespective of the disorder. The HRV findings are more complicated but show a trend towards a normalization of the pre existing autonomic differences between groups that is typical of Yoga techniques. HRV changes in DM patients were contrary to HT and DMHT patients in many parameters and this may be due to a greater degree of cardiac autonomic neuropathy in them. Further studies are required to enable better understanding of mechanisms involved as well as to determine how long such effects persist. We recommend the addition of this simple and cost effective technique to regular management protocols of HT and DM.
This paper appeared in Yoga Mimamsa 2013; 45 (1&2): 1-13.
Introduction: Respiratory Sinus Arrhythmia (RSA) is the differential change of Heart Rate (HR) in response to inspiration and expiration. This is a noninvasive sensitive index of parasympathetic cardiac control.
Aim: To evaluate changes in RSA by utilizing a simple and cost-effective analysis of electrocardiographic (ECG) tracings obtained during performance of four pranayama techniques.
Materials and Methods: Fifty two trained volunteers performed the following pranayamas with different ratios for inspiration and expiration: sukha (1:1), traditional (1:2), pranava (1:3) and savitri (2:1:2:1) and ECG was recorded while performing the techniques with rest period of 5 minutes in-between. HR was calculated and maximum HR during inspiration (Imax), minimum HR during expiration (Emin), differences between Imax and Emin (?), percentage differences between Imax and Emin (?%) and expiration: inspiration ratio (E:I) calculated by respective formulae. Statistical analysis was carried out using repeated measures of ANOVA with Tukey-Kramer multiple comparisons test.
Results: There were significant differences between groups in all five aspects namely: p= 0.0093 for mean Imax, p = 0.0009 for mean Emin, and p < 0.0001 for ? HR (I-E), ?% HR (I-E) and E:I ratio. Pranava pranayama produced the greatest changes in all five comparisons.
Conclusion: We suggest that further short and long term studies be undertaken with pranava pranayama in patients to further qualitatively and quantitatively evaluate inherent mechanisms of this simple technique. Addition of these cost-effective techniques to the medical armory will help patients of rhythm disorders and other cardiovascular conditions.
A Mathematical model for Impact of citalopram on the HPA system and combined ...IJERA Editor
In this paper we introduce bivariate sinh-normal distribution, which has seven parameters. Due to presence of seven parameters it is a very flexible distribution .Different properties of this new distribution has been established. We consider a bivariate model which can be obtained by transforming the sinh-normal distribution and it is a generalization of the bivariate Birnbaum-Saunders distribution. Several properties of the bivariate Birnbaum-Saunders distribution can be obtained as special cases of the proposed generalized bivariate Birnbaum-Saunders distribution. Twenty three patients responded (≥50% reduction in the score), and 17 of them also reached criteria of remission (HDRS≤ 7). Baseline (dexamethasone suppressed) and CRH stimulated ACTH concentrations significantly decreased from day 0 to day 28. CRH stimulated cortisol concentrations also fell, although not significantly, but baseline cortisol concentrations exhibited a significant increase from day 0 to day 28.Finally we conclude that the medical curve and Mathematical curve for disease control is higher than the probability density functions which are monotonic functions.
IMMEDIATE EFFECT OF CHANDRANADI PRANAYAM ON HEART RATE VARIABILITY AND CARDIO...Yogacharya AB Bhavanani
Diabetes mellitus (DM) and hypertension (HT) are widely prevalent psychosomatic lifestyle disorders that often coexist. Chandranadi pranayama (CNP), an exclusive left nostril breathing technique, has been reported to be useful in reducing heart rate (HR) and blood pressure (BP) in normal subjects as well as hypertensives and is part of yoga therapy schedules for patients of HT and DM. This study investigated the immediate effects of 5 minutes of CNP on HR, BP and heart rate variability (HRV) in patients of HT, DM and in those having both (DMHT). Thirty nine participants receiving standard medical care from the department of medicine, JIPMER were recruited. HR, BP and short- term supine HRV were recorded before and after 5 minutes of CNP. Analysis showed significant (p < 0.05) fall of HR and BP indices in all three groups with no difference between groups. However in short term HRV analysis, there were differences between the responses of DM and HT patients with regard to mean RR and mean HR. Preexisting intergroup differences with regard to SDNN, RMSSD, HF power and total power were negated after the performance of CNP. Pre-post intra group comparisons showed significant increases in Mean RR and Mean HR in both HT and HTDM groups while there were significant increases in LFnu and LF/HF ratio with significant decrease in HFnu in DM group. The post CNP responses of DM group in Mean RR, SDNN, Mean HR, RMSSD, LF power and total power were contrary to responses in the other groups. This is the first report comparing immediate effects of CNP in patients of HT and DM. The reduction in HR and BP indices in all three groups may be attributed to an overall normalization of autonomic cardiovascular rhythms along with improvement in baroreflex sensitivity irrespective of the disorder. The HRV findings are more complicated but show a trend towards a normalization of the pre existing autonomic differences between groups that is typical of Yoga techniques. HRV changes in DM patients were contrary to HT and DMHT patients in many parameters and this may be due to a greater degree of cardiac autonomic neuropathy in them. Further studies are required to enable better understanding of mechanisms involved as well as to determine how long such effects persist. We recommend the addition of this simple and cost effective technique to regular management protocols of HT and DM.
This paper appeared in Yoga Mimamsa 2013; 45 (1&2): 1-13.
Russian Stimulation, Burst Mode Alternating Current (BMAC) and Aussie Stimula...ACN
Neurodyn Aussie Sport is electric current application equipment for applying electrical current via electrodes in direct contact with the patient. It is a transcutaneous neuromuscular stimulator which uses microcomputer technology, that is, it is controlled by a computer, and is operated by touch screen. All the information related to the parameters selected by the physiotherapist will be shown in the alphanumeric liquid crystal display.
Neurodyn Aussie Sport stimulator produces AUSSIE CURRENT (also called Australian Current), a “new generation” of electrical current for stimulation with some advantages on the traditional methods of stimulation (Russian, Interferential, TENS e FES). This technique is non-invasive, non-addictive, and without undesirable side effects.
http://ibramedusa.com/physical-rehabilitation/neurodyn-aussie-sport/
Interferential Current or therapy for Physiotherapy studentsSaurab Sharma
This lecture intends to provide general outline about the uses, parameters, precautions and contraindications of interferential current for undergraduate physiotherapy students at Kathmandu University School of Medical Sciences, Nepal. After the lecture, students will explore the evidences about current practices on the uses of IFT in various musculoskeletal pain conditions, critically appraise them and present the evidences to the class.
Transcranial Magnetic Stimulation ( TMS) for Chronic PainDr. Rafael Higashi
Aula sobre avanço no tratamento da dor crônica com o uso de Estimulação Magnética Transcraniana (EMT) ministrada por Dr. Rafael Higashi, médico neurologista, no departamento de tratamento da dor do Centro Médico da Universidade de Nova York, NYU, EUA.
www.estimulacaoneurologica.com.br
Neurodyn Aussie Sport is muscle stimulator device for applying electrical current via electrodes in direct contact with the patient. All the information related to the parameters selected by the physiotherapist will be shown in the alphanumeric liquid crystal display.
Sonopulse III is microcontrolled therapeutic ultrasound equipment at frequenc...ACN
Sonopulse III is microcontrolled therapeutic ultrasound equipment at frequencies of 1 MHz and 3 MHz developed to be used in physiotherapy and aesthetics. It presents the ERA (Effective Radiation Area) of 7 cm², allowing the selection of frequency of 1 MHz or 3 MHz. The ultrasound maximum output power is of 21 Watts..
The ultrasound emission mode can be adjusted for continuous or pulsed, being the pulsed mode with pulse repetition frequency of 100 Hz, 48 Hz or 16 Hz and with pulse ratio of 1/2 (50%) and 1/5 (20%). It also has a key called PROG which allows the choice of pre-programmed treatment programs (recorded in the device memory).
The therapeutic ultrasound is commonly indicated for pain relief, reduction of muscle spasms, increase of local blood flow, and increase in movement amplitude of joint contractures using heat associated with stretching techniques, cellulite and localized fat.
The equipment should only be used under prescription and supervision of a licensed professional.
Ibramed convention program workshop sessions 2015 ACN
This two-day Conference will provide the clinician with evidence
based utilization of electrophysical agents (EPAs) including
neuromuscular electrical stimulation (NMES), electro-pain
modulation (TENS), functional electrical stimulation (FES), and
ultrasound. This will be accomplished through a combination of
lecture and hands-on workshop sessions aimed at identifying the
indications for and evidence-based use of these electrophysical
agents. Day 1 will consist of lectures addressing the physiologic
basis and biophysical properties of EPAs including current best
evidence for use, administration, parameter selection, and integration
of EPAs into the complete patient care plan. Techniques to be
demonstrated and practiced during Day 2 workshops will include
NMES for muscle training and strengthening including functional
clinical applications to a variety of musculoskeletal diagnoses,
identification of proper dosing with NMES, use and progression of
FES in various populations, selection and rationale for use of electropain
modulation and ultrasound. All speakers are internationally
recognized for their clinical utilization, research, and
peer-reviewed publications in the respective EPAs.
Neurodyn Aussie Sport is electric current application equipment for applying electrical current via electrodes in direct contact with the patient. It is a transcutaneous neuromuscular stimulator which uses microcomputer technology, that is, it is controlled by a computer, and is operated by touch screen. All the information related to the parameters selected by the physiotherapist will be shown in the alphanumeric liquid crystal display.
Neurodyn Aussie Sport stimulator produces AUSSIE CURRENT (also called Australian Current), a “new generation” of electrical current for stimulation with some advantages on the traditional methods of stimulation (Russian, Interferential, TENS e FES). This technique is non-invasive, non-addictive, and without undesirable side effects.
Neurodyn Aussie Sport is electric current application equipment for applying electrical current via electrodes in direct contact with the patient. It is a transcutaneous neuromuscular stimulator which uses microcomputer technology, that is, it is controlled by a computer, and is operated by touch screen. All the information related to the parameters selected by the physiotherapist will be shown in the alphanumeric liquid crystal display.
Neurodyn Aussie Sport stimulator produces AUSSIE CURRENT (also called Australian Current), a “new generation” of electrical current for stimulation with some advantages on the traditional methods of stimulation (Russian, Interferential, TENS e FES). This technique is non-invasive, non-addictive, and without undesirable side effects.
QS Health started as a family business dedicated to providing blood pressure monitors and orthopedic devices to customers in need. They quickly realized their competitors were imposing massive mark-ups on certain industry products and then passing the costs on to their customers. QS Health decided to change all that and make it possible for everyone to acquire their needed devices without being overcharged. That mindset, the idea behind QS Health, that no one should be paying too much for their healthcare products, has propelled a small family–run company into a successful world-renowned business that now enjoys sales all over the world.
They’ve come a long way in a short time! QS Health has been designing and delivering products for over 10 years now. They are backed by a team of professional, experienced health-care directors who are always looking for ways to provide the latest technology at the best prices.
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
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.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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
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
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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.
2. A.R. Ward et al. / Physiotherapy 95 (2009) 280–288 281
Fig. 1. (a) Biphasic pulsed current, (b) rectangular burst-modulated alternating current (BMAC), and (c) BMAC with sinusoidal modulation (interferential
current).
one statistically significant outcome measure supporting an
actual TENS effect rather than a placebo response. Thus, it
appears probable that TENS is an effective electrotherapeutic
treatment for pain management.
The analgesic effects of BMAC were examined in six of
the 18 studies identified. These studies only examined one
particular form of IFC/BMAC, namely IFC. Five of these
studies compared IFC with sham, control and/or pre–post
treatment baseline [10–14]. The remaining study compared
different IFC burst (‘beat’) frequencies with one another [15].
Significant results (P≤0.05) confirming positive analgesic
effects with the use of IFC were identified in three of the
five studies [10,12,16]. Of the other two studies, Tabasam
and Johnson reported that the comparative effect of BMAC
versus sham during treatment cycles was not significant [11].
However, small subject numbers were used, raising the possi-bility
of a type II statistical error as opposed to no true effect.
Stephenson and Walker [14] found no significant differ-ences
when comparing BMAC with control and sham groups
(P = 0.49). However, the study design and small number of
subjects reduces confidence in these results. The balance of
evidence suggests that IFC is also an effective electrother-apeutic
treatment for pain management, but the evidence is
less strong than that for TENS.
Only six of the 18 studies identified directly compared
the effectiveness of TENS and BMAC [16–21]. Four of
the studies compared TENS and IFC with either sham
or control groups [16–19]. Three of these four studies
found significant analgesic effects of both TENS and IFC
[16,18,19], but none found any significant difference between
the TENS and IFC interventions. Johnson and Tabasam
[19] used 100-Hz stimulation and measured a greater effect
with TENS than premodulated IFC. The measured dif-ference
was not statistically significant (P = 0.09), but the
study only had seven participants in each group so the
lack of significance could have been due to low statistical
power. Shanahan et al. [21] reported a similar experimental
study using a crossover design with larger participant num-bers.
They found that TENS at a frequency of 100 Hz
had a greater analgesic effect than premodulated IFC at a
beat frequency of 100 Hz (P = 0.015). The balance of evi-dence
thus indicates that IFC is less effective than TENS.
Ward and Oliver [20] surmised that the lesser analgesic
effect of premodulated IFC might be due to the relatively
long and unpredictable effective burst duration with IFC
(Fig. 1c). They compared the analgesic effectiveness of 4-
millisecond bursts of 1-kHz AC applied at a burst frequency
of 50 Hz with 50-Hz pulsed current (TENS) of the same
phase duration. The study found no significant difference
between TENS and this particular form of BMAC, and
little chance of a type II error (P = 0.39). The authors con-cluded
that the lack of difference between the stimulus types
was due to the short burst duration of the BMAC stimu-lus.
The published evidence thus suggests that both TENS and
BMAC have a significant analgesic effect; however, there has
been very little research into the comparative effectiveness of
TENS and BMAC treatments and optimum analgesic param-eters
for both modalities. Of the fewcomparative studies, only
one [21] reported a statistically significant result, with 100-
Hz TENS being more effective than premodulated 100-Hz
IFC. The lack of significant results in previous comparative
3. 282 A.R. Ward et al. / Physiotherapy 95 (2009) 280–288
studies is possibly due to more stringent demands on sta-tistical
power and study design. If both TENS and IFC are
effective in inducing hypoalgesia, it is much more demand-ing
to evaluate whether one is better than the other than it is
to evaluate whether each one alone is effective.
Stimulation parameters
The stimulation parameters for TENS and BMAC/IFC
are different, but they have two important parameters in
common: frequency and phase duration. Frequency is the
number of pulses per second (TENS) or bursts per second
(BMAC). Phase duration is the timed length of individual
pulses for TENS or the duration of pulses within a burst for
BMAC. Conventional TENS is low-frequency (usually less
than 200 Hz) pulsed current with a duration in the range of
20–600 microseconds [4].BMACused for pain control isAC,
usually with a frequency of 4–5 kHz, a lowburst frequency of
50–200 Hz, and a phase duration of 100–125 microseconds
[4].
With a frequency of 4–5 kHz, each phase ofBMACcannot
elicit a nerve impulse due to the absolute refractory period
(period of time following a nerve impulse whereby no stim-ulus
can cause a subsequent action potential) [3,22]. Rather,
successive subthreshold pulses in a burst can summate at
kHz frequencies. Summation refers to successive subthresh-old
pulses ofACpushing a nerve fibre closer to threshold with
each pulse in a burst. Membrane threshold is reached when
successive pulses cause sufficient depolarisation to produce
an action potential. Depolarisation due to summation occurs
more readily at higher kHz frequencies because the mem-brane
has less time to recover between successive pulses.
Summation is responsible for the Gildemeister effect, which
is a decrease in threshold intensity as the burst duration is
increased [3,22].
TENS applied clinically is normally a low-frequency
pulsed current applied for pain relief [3]. Sensory-level stimu-lation
is referred to as ‘conventional TENS’, in which sensory
fibres (A fibres) are stimulated. As TENS involves single
pulses applied repetitively, frequency and pulse duration can
be altered without having an effect on one another (Fig. 1a).
BMAC applied clinically consists of bursts of AC with a typ-ical
frequency of 1–10 kHz. The AC bursts are applied at
low frequencies (less than 200 Hz), corresponding to the fre-quencies
used for TENS stimulation. BMAC current can be
delivered in rectangular bursts (Russian and Aussie current
[23], Fig. 1b) or sinusoidally modulated (premodulated IFC,
Fig. 1c).
The two types of BMAC that are in common clinical use
are Russian current and premodulated IFC. Russian current
is 2500-Hz AC delivered in a series of bursts (10-millisecond
burst and a 10-millisecond interval, or 50% duty cycle).
This is similar to Fig. 1b but with equal burst and interburst
intervals [3]. Premodulated IFC is a series of sinusoidally
modulated bursts (Fig. 1c).
A less commonly used form of BMAC is Aussie current
[20]. Aussie current is similar to Russian current in being
burst modulated; however, the bursts are of shorter duration.
Aussie current has a lower burst duration than Russian current
(2–4 milliseconds vs 10 milliseconds) (Fig. 1b). In contrast to
premodulated IFC and Russian current, there is less possibil-ity
of multiple nerve firing during a burst with Aussie current
[20,22].
The present study
A limitation of Ward and Oliver’s study [20] was that
1-kHz AC was used and compared with pulsed current of
the same phase duration (500 microseconds). The parameters
chosen were based on conclusions made earlier [24] regard-ing
torque rather than pain relief. Ward et al. [24] compared
different duty cycles and frequencies of BMAC, and found
that a short burst duration (a low duty cycle of 20–25%) was
most effective for torque production and comfort, and that
1 kHz was the optimum AC frequency for torque production
[24]. However, for pain control, higher AC frequencies (typi-cally
4 kHz in the form of premodulated IFC) andTENSpulse
durations of less than 500 microseconds are normally used
clinically [3]. Furthermore, the earlier study [24] identified
that 4 kHz, while not optimal for torque production, was best
in terms of producing minimal discomfort. Accordingly, it
was decided to compare the analgesic effectiveness of 50-Hz,
4-millisecond bursts of 4-kHz AC with 50-Hz pulsed current
of the same phase duration (125 microseconds). 50 Hz was
selected based on research by Johnson et al. [6] that com-pared
the analgesic effects of TENS on cold-induced pain
at different frequencies. Frequencies of 10, 20, 40, 80 and
160 Hz were compared. The study found that 40-Hz stimula-tion
was more effective than the other frequencies. A plot of
change in pain threshold versus stimulus frequency [6, Fig.
3] illustrated that maximum pain tolerancewas achieved with
frequencies in the range of 40–60 Hz, substantially lower than
the common clinically used frequency of 100 Hz.
The present study utilised a single-blinded, within-group
crossover design. Each subject experienced both TENS and
BMAC on separate days in a randomly allocated predeter-mined
order. A sham group was not included since the aim of
the study was to compare the analgesic difference between
the two modalities, rather than their individual effectiveness
compared with sham stimulation. Pain threshold was the
selected outcome measure since it obtained the most con-sistent
results in previous research, most probably because
the outcome is objective and quantifiable (time).
Method
Participants
Twenty subjects volunteered to participate in the research,
11 females and nine males aged between 19 and 25 years
4. A.R. Ward et al. / Physiotherapy 95 (2009) 280–288 283
(mean age 21 years, standard deviation ±1.7 years). Poten-tial
participants were excluded if their non-dominant arm
was affected by any orthopaedic, neurological or circulatory
pathology, or if the skin in the area under the elec-trodes
was broken or irritated. Participants were instructed
not to take any analgesic or anti-inflammatory medication
(or apply them as creams or gels to their non-dominant
forearm) in the 12 hours prior to each testing session.
No volunteers were excluded when these criteria were
applied.
Research design
The research design used in this study was based on that
used by Shanahan et al. [21] and Ward and Oliver [20]. This
design increased statistical power by allowing more sub-jects
per group, since subjects participated in both TENS
and BMAC trials. More importantly, the design eliminated
any effect of between-subject variation on the outcome mea-sures.
Individual participant comparisons of the effectiveness
of TENS and BMAC allowed for separation of between-subject
effects and intervention effects. This would not have
been possible had a traditional, independent-groups design
been used. Power calculations were not used to establish the
required number of participants; instead, the numbers used
were the same as in previous studies which demonstrated ade-quate
statistical power using the same experimental design
[20,21].
Subjects received TENS andBMAC on two separate days,
in a randomly allocated order to prevent an order bias effect.
Random allocation was performed prior to testing via sealed
gender-specific envelopes selected by the participant. The
dependent variable was the time to pain threshold (seconds).
This variable allowed comparison with previous research
since it has been used commonly in similar studies. Previous
studies [6,19–21,25] found that the subjective pain intensity
and unpleasantness measures were poor indicators of hypoal-gesic
efficacy. These measures required that participants hold
their hands in ice-cold water for a further 30 seconds after
reaching their pain threshold, after which pain intensity and
unpleasantness were rated by subjects on two, 10-cm visual
analogue scales. Since these measures were such poor indi-cators
of hypoalgesic efficacy, they were not included in the
present study.
Electrical stimulation
Subjects received both TENS and BMAC from the same
purpose-built electrical stimulator; thus, a potential source
of bias was eliminated as participants had no indication
of which intervention they were receiving. A BMAC fre-quency
of 4 kHz was chosen for this study as this is the
frequency commonly used for IFC stimulation [3,4]. At
4 kHz, one sinewave is 250 microseconds, so each phase
(one positive, one negative) of a single cycle has a dura-tion
of 125 microseconds. Therefore, to keep parameters as
constant as possible, the pulse width for the monophasic
TENS current was set at 125 microseconds. Finally, a 4-
millisecond burst duration (20% duty cycle) for BMAC was
selected, since a previous study [24] found that a 20–25%
duty cycle was most comfortable, and the study by Ward
and Oliver [20], which used 1-kHz BMAC, found that a
4-millisecond burst duration was as effective as TENS for
hypoalgesia.
Two rectangular 44×40mmconductive rubber electrodes
were applied to each subject’s forearm using conduc-tive,
adhesive skin mounts (American Imex type 00200)
and connected to the electrical stimulator via leads. The
middle of the anterior electrode was positioned on the
midpoint between the medial epicondyle and the radial
styloid. The middle of the posterior electrode was posi-tioned
on the midpoint between the lateral epicondyle
and the ulnar styloid. This procedure ensured accurate
and standardised electrode placement between sessions and
participants.
Procedure
On arrival, participants were invited to read and sign
the informed consent form approved by the Faculty Human
Ethics Committee. Subjects were then screened for exclu-sion
criteria. Once eligibility had been confirmed and the
informed consent form completed, participants were seated
with their non-dominant arm closest to the water baths. The
non-dominant arm was cleaned with an alcohol swab in order
to remove any oil, dead skin cells or other barriers that may
impede current flow through the skin. Electrodes were then
positioned as described above.
Cold pain induction
Cold-induced pain was administered using two water
baths of uniform size and shape, one maintained at 37 ◦C
and the other at 0 ◦C (±0.2 ◦C). A Heidolph heater stirrer
unit (Accurex Equipment, Brunswick, Victoria, Australia)
was used in each bath to ensure that temperatures were kept
constant. The temperature of each bath was checked rou-tinely
at 5-minute intervals with a thermometer. A digital
stopwatch was used during the procedure to measure 5-
minute increments and the time to pain threshold (seconds).
The cold pain method was based on that used in previous
research [6,10,19–21]. On the ‘Start’ command, the par-ticipant
placed their hand into the 37 ◦C water bath down
to the distal wrist crease. The participant’s hand remained
in the bath for 5 minutes in order to standardise the hand
temperature between sessions and across participants. The
subject was then instructed to move their hand into the 0 ◦C
water bath, again down to the distal wrist crease. The par-ticipant
was asked to concentrate on the sensations of the
hand until they felt the onset of a deep, dull aching pain,
at which time the subject was to state ‘Pain’ and withdraw
their hand from the water. The time from hand immer-
5. 284 A.R. Ward et al. / Physiotherapy 95 (2009) 280–288
sion to pain was recorded as the pain threshold (seconds).
After removing their hand from the bath, it was placed on
a table to rest at room temperature for the remainder of the
5 minutes since the beginning of the hand immersion in the
0 ◦C bath. At this point (completion of the 10-minute cycle),
the next cycle was commenced, with hand immersion back
into the 37 ◦C bath. In total, six cycles were performed per
session.
Electrical stimulation
Electrical stimulation was applied via the electrodes
attached to the participant’s forearm. The electrical stimula-tion,
either TENS orBMACdepending on random allocation,
commenced at the beginning of Cycle 3 and continued unin-terruptedly
until the conclusion of Cycle 4, i.e. 20 minutes in
total. The stimulation intensity was increased by the instruc-tor
until the participant felt the sensation was strong but
comfortable, but never above the motor threshold. If a motor
response was detected, the intensity was reduced to eliminate
any muscle contraction. The subject was asked at 1-minute
intervals whether the stimulation remained strong but com-fortable,
or whether it needed to be adjusted in order to fit this
description. The stimulation was not adjusted at all during
cold water immersion.
At the conclusion of the first session, the participants
were advised against taking analgesics or anti-inflammatory
medication, or applying anti-inflammatory cream to the non-dominant
(tested) arm in the 12 hours prior to the following
session.
The second sessionwas conducted no earlier than 12 hours
following the initial testing procedure in order to minimise the
risk of a carry-over effect. The second session was identical
to the first; however, the alternate modality was utilised. At
the end of the second testing session, participants were asked
two questions: ‘Which of the two modalities, if either, seemed
more effective?’ and ‘Which of the two modalities, if either,
felt more comfortable?’ The subjects were also given the
opportunity to make any other comments.
Analysis
Pain threshold
Statistical analyses were performed using Statistical Pack-age
for the Social Sciences Version 14 (SPSS Inc., Chicago,
IL, USA). Prior to analysis, participants were excluded if
the pain threshold during one or more of the six cycles was
300 seconds or more. These results were excludable outliers,
since 300 seconds was 4.2 standard deviations from the mean
(69 seconds in the present study). Furthermore, immersion in
coldwater for a minimum of 300 seconds eliminated recovery
time before the start of the following cycle, and thus unless
eliminated may have confounded the results by producing a
carry-over effect.
Pain threshold data for TENS and BMAC were first
analysed separately. Since individual pain thresholds vary
largely, as demonstrated previously [20,21], pain threshold
changes in this study were analysed for each of TENS and
BMAC using a two factor without replication analysis of
variance (ANOVA) in order to separate between-subject and
intervention effects. Post-hoc t-tests were then carried out
and confidence intervals (CI) were calculated to establish
whether the observed intervention effects were statistically
significant. The pain threshold during each type of electri-cal
stimulation (T3 and T4 averaged) was compared with
the baseline pain threshold (T1 and T2 averaged) using a
two-tailed paired t-test. Averaging of intervention data (T3
and T4) was performed since the aim of this study was to
compare the intervention effect of two modalities, rather
than the effect of time on the intervention. This method
was also used to increase statistical power and avoid a large
Bonferroni correction as a result of multiple comparisons.
The same method was applied to the post-intervention data
(T5 and T6 averaged) compared with the baseline threshold.
Since two comparisons were made with baseline (T3 and T4
average, T5 and T6 average), a Bonferroni-corrected accept-able
P-value of 0.05/2 = 0.025 was used and 97.5%CI were
calculated.
In order to establish whether there was a significant dif-ference
between the interventions and whether the effects
of each modality were greater at T4 than T3, a two-way
repeated-measures ANOVA (cycle×intervention type) was
calculated. The pre-intervention data (T1 and T2 averaged)
were subtracted from each of the with-intervention mea-sures
(T3 and T4) and the differences were used for the
analysis.
Results
The outcome measures analysed were pain threshold (time
to pain tolerance limit, measured in seconds) and subjec-tive
comments regarding effectiveness and comfort of each
type of stimulation. These measures were used to test three
hypotheses: (a) that both forms of electrical stimulation ele-vate
pain threshold; (b) that TENS and BMAC are equally
effective; and (c) thatBMACis more comfortable than TENS.
When the exclusion criteria were applied, three of the 20 sub-jects
were excluded from the study since they failed to reach
their pain thresholds within 5 minutes of ice-cold immersion
during one or more of the allocated measurement cycles. It
is worth noting that two of the three excluded subjects only
exceeded the 5-minute pain threshold whilst electrical stim-ulation
was applied (one with TENS, one with BMAC). The
data set therefore included 17 subjects for analysis.
Pain threshold
Pain threshold data were analysed in terms of change
from baseline to the time of pain tolerance limit for each
6. A.R. Ward et al. / Physiotherapy 95 (2009) 280–288 285
Table 1
Group-averaged pain threshold changes from baseline for Cycles 3–6.Values
shown are mean±standard deviation.
Cycle Threshold change
TENS (seconds)
Threshold change
BMAC (seconds)
T3 14.1 ± 23.8 14.7 ± 21.4
T4 16.8 ± 27.4 15.6 ± 24.8
T5 −6.0 ± 20.8 −3.5 ± 13.0
T6 −5.2 ± 25.6 5.3 ± 23.7
TENS, transcutaneous electrical nerve stimulation;BMAC, burst-modulated
medium-frequency alternating current.
modality. Baseline was calculated as the average time (sec-onds)
to pain threshold during Cycles 1 and 2 (T1 and T2).
Change in pain threshold during Cycles 3–6 was calculated
by subtracting the baseline value from the Cycle 3–6 pain
threshold values (T3–T6). Table 1 shows the average change
from baseline (mean±standard deviation) for Cycles 3–6 for
both interventions.
In Cycle 3, BMAC thresholds were increased, on aver-age,
by 14.7 seconds and TENS thresholds were increased
by 14.1 seconds. Both the TENS and BMAC pain thresh-olds
were greater during Cycle 4 than Cycle 3; TENS by
a further 2.7 seconds and BMAC by 0.9 seconds. Although
the Cycle 4 rise in pain threshold was not as great as that
between baseline and Cycle 3, it does suggest that the
longer the stimulation is applied, the greater the elevation
in pain threshold. The pain threshold during stimulation
(T3 and T4 averaged) was elevated by 15.2 seconds (22%
increase) with TENS and 15.5 seconds (25% increase) with
BMAC.
Once the electrical stimulation was switched off at the
end of Cycle 4, thresholds returned close to baseline. Both
TENS and BMAC pain threshold values fell below base-line
at T5, suggesting no carry-over effect of TENS and
BMAC immediately following stimulation. Pain threshold
changes from baseline continued to remain low during the
final cycle, with T6 for TENS averaging below baseline
and T6 for BMAC averaging above baseline. The variation
observed most likely represents the inherent experimental
error.
Statistical analysis
Intervention effects
The hypotheses of this study were tested using a two
factor (subject×intervention) without replication ANOVA
for each modality to first determine whether an interven-tion
effect was present by separating between-subject and
between-intervention effects. The data were not normally
distributed, and a Huynh-Feldt correction of 0.67 for TENS
and 0.60 for BMAC was required. Both modalities pro-duced
statistically significant intervention effects (TENS:
F(5,16) = 4.75, P = 0.004; BMAC: F(5,16) = 4.28, P = 0.009).
Between-subject effects for both modalities were also found
to be highly significant, presumably because pain thresh-olds
vary greatly between individuals (TENS: F(16,5) = 22.52,
P 0.001; BMAC: F(16,5) = 24.46, P 0.001). The lower P-values
indicate that the large standard deviations of each
mean (Table 1) were mainly due to between-subject effects.
Post-hoc tests (paired t-tests) were conducted to answer
two questions: is there a significant intervention effect and
is there a significant carry-over (post-intervention) effect?
To minimise the number of post hoc tests and thus avoid
the need for a large Bonferroni correction, pre-intervention
data (T1 and T2) were averaged, as were the during-intervention
measures (T3 and T4) and post-intervention
measures (T5 and T6). Two paired t-tests were then con-ducted
using a Bonferroni-corrected acceptable P-value of
0.05/2 = 0.025 and 97.5%CI were calculated. Comparing the
pre- and during-intervention averages, a significant interven-tion
effect was found (TENS: 15.4 seconds, 97.5%CI 2.5
to 28.4, P = 0.017; BMAC: 15.2 seconds, 97.5%CI 3.1 to
27.2,P = 0.012).Nosignificant differencewas found between
pre- and post-intervention measures (TENS: −5.6 seconds,
97.5%CI −18.0 to 6.8, P = 0.324; BMAC: 0.9 seconds,
97.5%CI −7.7 to 9.6, P = 0.816).
Data were analysed to establish whether either form
of stimulation produced a greater intervention effect and
whether the effects were greater at T4 than T3. Each
participant’s increase in pain threshold was calculated by
averaging the pre-intervention baseline measures (T1 and
T2) and subtracting this from each of the with-intervention
measures (T3 and T4). The increases were used in a
two-way repeated-measures ANOVA (cycle×intervention).
Data for post-intervention measures (T5 and T6) were not
used at this stage of the analysis, as there was no carry-over
(pre- vs post-intervention) effect with either form of
stimulation so any further comparison would be meaning-less.
The ANOVA established that the between-cycle dif-ferences
(T3 vs T4) were not statistically significant
(F(1,16) = 0.094, P = 0.76), and that between-intervention
effects were not only not significantly different, but TENS
and BMAC were ‘significantly the same’ (F(1,16) = 0.002,
P = 0.97, mean difference = 0.3 seconds, CI −15.3 to 15.9).
When P-values are in the range 0.05–0.95, an acceptable con-clusion
is that there is no significant difference. It cannot,
however, be concluded that the intervention effects are the
same without risking making a type II error. When a P-value
greater than 0.95 is obtained (1− 0.05), the equivalence
of the interventions is considered to be statistically significant
as the risk of a type II statistical error is acceptably minimised
[26].
Comfort of stimulation
At the end of the second session, participants were asked
which of the two types of intervention felt most comfortable.
A majority preferring BMAC was evident. Twelve subjects
7. 286 A.R. Ward et al. / Physiotherapy 95 (2009) 280–288
(71%) reported BMAC to be the most comfortable, and the
remaining five (29%) felt that TENS was the most comfort-able.
Effectiveness of stimulation
At the end of the second session, participants were also
asked which modality felt more effective for pain relief.
Ten subjects (58%) reported that BMAC was most effec-tive,
three (18%) felt that TENS was the most effective,
and four (24%) reported that both interventions were equally
effective.
Discussion
Hypoalgesic efficacy
The results clearly demonstrate a significant interven-tion
effect for both TENS and BMAC with P-values of
0.017 and 0.012, respectively. These findings confirm the
first hypothesis that both modalities elevate the cold pain
threshold.
The main aim of this study, however, was to compare the
analgesic effectiveness of one particular form of BMAC (4-
kHz AC with a 4-millisecond burst duration) with TENS of
the same phase duration (125 microseconds) and frequency
(50 Hz). TENS and BMAC were found to be statistically
equivalent in elevating the cold-induced pain threshold in
healthy subjects. The P-value obtained (P = 0.97) allows the
conclusion that TENS and BMAC are equally effective in
pain modulation.With these results, one can be confident that
a type II error has not occurred, i.e. a false-negative result,
since the P-value falls outside the conventionally accepted
questionable range (0.05–0.95).
These results provide an important contribution to the
existing literature, since no previous research has compared
the analgesic effectiveness of pulsed current (TENS) with that
of 4-kHz AC with a 4-millisecond burst duration (BMAC) at
the same frequency and using the same phase duration. The
present results support the findings of Ward and Oliver [20]
who used a different AC frequency (1 kHz) but the same 4-
millisecond burst duration and 50-Hz burst/pulse frequency,
and found that with short burst durations for BMAC, the
modalities were equally effective in elevating pain threshold.
In contrast, Shanahan et al. [21] found that TENS (100-Hz
pulsed current) was significantly more effective than pre-modulated
interferential current (5-kHz AC, modulated at
100 Hz) in elevating pain threshold. ‘Premodulated interfer-ential
current’ as used in the study by Shanahan et al. [21]
was sinusoidally modulated (Fig. 1c) so, strictly speaking,
the duty cycle is effectively 100%, as the intensity only drops
to zero instantaneously between each burst. The burst dura-tion
is maximum (20 milliseconds) and the effective burst
duration (i.e. the time that the stimulus is above any effec-tive
threshold) is difficult to predict but, for most nerve
fibres, it would be much larger than the 4-millisecond burst
duration used in the present study and that of Ward and
Oliver [20].
The difference between the present findings and those of
Shanahan et al. [21] can be explained in terms of different
nerve fibre firing rates produced by the two forms of electrical
stimulation. The authors hypothesise that with long bursts of
AC, as used with premodulated interferential currents, sen-sory
nerve fibres fire multiple times during each burst, i.e.
during a burst, sensory fibres undergo repeated cycles of fir-ing,
recovering and firing again. Hence the sensory nerve
firing rate will be some multiple of the burst frequency. While
stimulation at 50 or 100 Hz is beneficial for hypoalgesia, stim-ulation
at higher multiples (150, 200, 250. . . Hz) might not be
as effective. This seems to be a reasonable, physiologically
based assumption, but only one study has actually tested this
hypothesis and examined a wide range of TENS stimula-tion
frequencies (10–160 Hz). Johnson et al. [6] found that
higher frequencies of pulsed current (above 50 Hz) resulted in
a lesser hypoalgesic effect. The between-frequencies differ-ences
in the study by Johnson et al. [6] were not statistically
significant, possibly due to the small sample size, but a down-ward
trend is clearly evident above 40 Hz. Since the present
study and a previous study [20] have found that short-duration
burst-modulated AC is as effective as pulsed current (TENS)
in elevating pain threshold, the authors speculate that a short
burst duration prevents or severely restricts multiple firing of
sensory nerve fibres, and instead produces one action poten-tial
per burst. The hypoalgesic effects are thus equivalent to
TENS.
Subjective comments
The majority of participants subjectively reported that
BMAC was more effective and comfortable than TENS,
thus supporting the original hypothesis. The results are in
accordance with previous studies [20,21,23], which reported
BMAC to be significantly more comfortable than TENS. The
current results and previous TENS and BMAC comparative
studies strengthen the conclusion drawn by Ward et al. [24]
that low-duty-cycle, burst-modulated AC is more comfort-able
than conventional low-frequency pulsed current.
Clinical implications
The present research demonstrates that the particular
forms of TENS andBMACwhich were compared are equally
effective, in fact ‘statistically the same’, at elevating the pain
threshold in healthy subjects. Furthermore, since previous
research by Shanahan et al. [21] found that TENS was signif-icantly
more effective than premodulated IFC, one can infer,
with a degree of confidence, that this form of BMAC also has
greater hypoalgesic effects than premodulated IFC.
However, whilst the objective effectiveness of a modal-ity
is an important component of the patient experience,
8. A.R. Ward et al. / Physiotherapy 95 (2009) 280–288 287
there are other factors that influence the efficacy of the treat-ment.
Patient-perceived comfort and effectiveness are two
other factors. There was a definite preference for BMAC
in terms of both perceived comfort and effectiveness. This
result combined with previous research [20,21,23] suggests
the likelihood of greater patient acceptance and compliance
withBMAC, since it is perceived to be more comfortable and
effective. Therefore, it is concluded that BMAC utilising a 4-
millisecond burst duration should be used clinically for the
treatment of acute pain because it is as effective as TENS in
hypoalgesic effects but is reportedly more comfortable, and
thus provides an overall improved patient experience. A third
factor is the expense of treating a patient with IFC in a clinic
using a mains-powered, high-output machine compared with
the home use of a portable TENS machine and the inconve-nience
of the patient travelling to a clinic for every treatment.
In the case of low back or neck pain, the travelling runs the
risk of undoing any gains made by the treatment. TENS-like,
portable BMAC machines could provide the convenience of
safe, home treatment between clinical consultations.
Conclusion
The major conclusion of the present study is that 50-Hz
TENS with a 125-microsecond pulse duration and 4-kHz
BMAC with a 4-millisecond burst duration (20% duty cycle)
are equally effective in elevating cold-induced pain in healthy
subjects. However,BMACis subjectively reported to be more
comfortable and effective. It is therefore recommended that
BMAC in the form of 4-millisecond bursts should be trialled
clinically since greater patient compliance and acceptance of
the treatment is a likely consequence of the lesser discomfort.
TENS machines have long been established as a useful
treatment tool since they are effective in elevating pain
threshold and are a cheap and portable option for home use.
The present findings suggest that ‘take home’ TENS units
would be more successful if they delivered 4-kHz BMAC
with a 4-millisecond burst duration rather than pulsed current.
Ethical approval: Human Research Ethics Committee
of the Faculty of Health Sciences, La Trobe University.
Approval number FHEC06/160.
Funding: Research grants from the Faculty of Health
Sciences, La Trobe University and the School of Human
Biosciences, La Trobe University.
Conflict of interest: None declared.
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