The Whole Health Blog

andrewethan 29 March 2021 0 Comments

Everything You Need to Know About the Endocannabinoid System (Blog 7)

First identified in the early 1990s, the endocannabinoid system (ECS) has emerged as an important neuromodulatory system over recent years. The complex cell-signaling system regulates and controls many bodily functions, active in the body without the use of cannabis. A growing understanding of the ECS and the role it plays in a wide-range of biological pathways has placed it at the center of increasing international research and drug development efforts. As a result, the burgeoning field of ECS-targeted therapeutics and their approved applications in clinical practice are likely to expand exponentially in the near future.

What is the Endocannabinoid System?

The endocannabinoid system relies on three components: endocannabinoids, endocannabinoid receptors, and enzymes. Endocannabinoids, also known as endogenous cannabinoids, are produced naturally by the body to facilitate a variety of biological processes.

Endocannabinoid receptors can be found throughout the body; the main receptors are CB1 found in the central nervous system and CB2 receptors, located in the peripheral nervous system. The demonstrated effects of endocannabinoids are reliant upon the receptor location and type that they bind to.

For example, endocannabinoids targeting CB1 receptors in the spinal nerve can relieve local pain. Others might bind to a CB2 receptor in your immune cells to signal that your body’s experiencing inflammation, a common sign of autoimmune disorders.

Research reveals that CB1 receptors outnumber many of the other receptor types in the brain, controlling the levels and activity of other neurotransmitters. Meanwhile, CB2 receptors primarily exist in immune cells and are critical to modulating immunocompetence and inflammatory levels.

Finally, the third component of the system, enzymes, are responsible for the synthesis and degradation of endocannabinoids once they have fulfilled their function. These include fatty acid amide hydrolase and monoacylglycerol acid lipase.

The Role of the Endocannabinoid System

Still a topic of research, the endocannabinoid system has been shown to regulate and control many vital functions, playing an important role in central nervous system development, synaptic plasticity, as well as responses to endogenous and environmental triggers. It has also been found to impact sleep patterns, emotional processing, appetite, learning and memory, reproductive health, and immunocompetence. Although the ECS performs a variety of different tasks, it does with the same goal of homeostasis, or the maintenance of a stable internal environment.

Interactions with THC and CBD

Tetrohydrocannabinol (THC), and cannabidiol (CBD) are both compounds found in cannabis that directly interact with the endocannabinoid system. Similarly to endocannabinoids, both THC and CBD bind to ECS receptors. THC binds to both CB1 and CB2 receptors allowing it to produce a range of physiological and psychological effects.

Experts are still working to understand the precise mechanisms of how CBD interacts with the ECS system, with current evidence pointing to its role in preventing endocannabinoid degradation allowing endocannabinoids to have a more potent effect. Current literature suggests CBD can ease pain, nausea, and other symptoms associated with a large range of health conditions.

In order to best utilize the effects of these compounds on the ECS, research efforts aim to produce synthetic THC cannabinoids and CBD-based therapeutics that modulate the endocannabinoid system to produce optimal health benefits.

Therapeutic Targets

As emerging research has shown, cannabinoids are a promising potential therapeutic intervention for a range of chronic diseases, Alzheimer’s disease, cardiovascular and autoimmune conditions, as well as neurological health. Therapeutics targeting the endocannabinoid system can also influence numerous physiological conditions namely, energy balance, blood pressure management, memory and learning support, embryonic development, nausea control, and appetite stimulation. CBD-based therapies have already been introduced in the treatment of pediatric epilepsy, pain, inflammation, acne, and other conditions with a continuously growing list of approved indications.

Key Takeaways

The endocannabinoid system is comprised of endocannabinoids, receptors, and enzymes that work to sustain and stabilize critical biological processes. While research in this field continues, current knowledge indicates the vital function of the endocannabinoid system in maintaining homeostasis and supports further study of potential therapeutic interventions for the treatment of a variety of health conditions.

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Brain Health Benefits of Yoga Practice (Blog 6)

Despite being an exercise performed for many centuries in Eastern cultures, yoga has become increasingly popular over the past few decades among the Western population and alongside it, an exponential increase in research. People are drawn to the practice due to its multitude of mental and physical benefits, which include relaxation, muscle stretching, and an increased feeling of mindfulness. The health benefits of the physical exercise have been well established, yet there is a lack of research concerning the impact of yoga practice on the brain.

Today, yoga is the most popular form of complementary therapy practiced by over 13 million adults, with 58% of adults citing maintenance of health and well-being as their reason for practice per data reported by the National Center for Complementary and Integrative Health (NCCIH).

Recently, yoga has gained increased attention in the scientific community as well, as a research area of interest among exercise neuroscientists due to its promising potential therapeutic benefits with potential to combat widespread increases in the prevalence of age-related neurodegenerative diseases. Few studies have investigated the benefits of yoga on brain health yet recent research from the University of Illinois at Urbana-Champaign aims to analyze current literature related to yoga practice and its documented positive effects on brain structure and function.

Yoga and the Brain

The team of researchers analyzed 11 studies of the relationships between yoga and brain health including the impact of yoga practice on brain structures, function, and cerebral blood flow. Of those, 5 trials engaged participants with no prior yoga experience in one or more yoga sessions per week over a period of 10 to 24 weeks to compare brain health before and after the intervention. Meanwhile, the remaining studies measured differences in brain health between participants who regularly practiced yoga and those who did not.

To determine variations in brain structure and health, each study utilized brain-imaging technologies including MRI, functional MRI, or single-photon emission computerized tomography to analyze the impact of Hatha yoga practice – which incorporates body movements, meditation, and breathing exercises.

Positive Neuroprotective Effects

Overall, researchers found that the studies reported a beneficial effect of yoga practice on both the structure and functioning of the hippocampus, amygdala, prefrontal cortex, cingulate cortex, and brain networks. As many of these regions are known to be related to age-related atrophy, the early evidence is promising and implicates that regular yoga practice could work to mitigate age-related and neurodegenerative diseases.

“For example, we see increases in the volume of the hippocampus with yoga practice,” lead author Neha Gothe from the University of Illinois said. “Many studies looking at the brain effects of aerobic exercise have shown a similar increase in hippocampus size over time.”

In addition, the review of the studies found that brain changes related to yoga practice were linked to improved cognitive performance and measures of emotional regulation.

Changes in Brain Structure

According to Gothe and her colleague Jessica Damoiseaux psychology professor at Wayne State University, many of the studies were exploratory and not conclusive. Despite this, the researchers suggest their findings underline important brain changes associated with regular yoga practice, including amygdala growth which may be directly related to improved emotional regulation in yoga practitioners.

“The prefrontal cortex, cingulate cortex and brain networks such as the default mode network also tend to be larger or more efficient in those who regularly practice yoga,” Damoiseaux explains. “Like the amygdala, the cingulate cortex is part of the limbic system, a circuit of structures that plays a key role in emotional regulation, learning, and memory.”

Regular yoga practice may help improve the cortisol stress response; researchers found that participants who practiced yoga for eight weeks had an attenuated cortisol response which also contributed to improved testing performance in cases of decision-making, task-switching, and attention span. Overall, researchers believe that the positive implications of yoga on brain structures and emotional regulation improve total brain functioning and thus, may have neuroprotective effects.

Not only does a regular yoga practice have well-documented physical health benefits, but it appears to also promote healthy brain function. However, researchers caution that more research is needed in this field to uncover the mechanisms underlying the evident brain changes, recommending large intervention studies that engage participants in yoga practice for long periods of time and allow for comparisons with other forms of exercise.

“The science is pointing to yoga being beneficial for healthy brain function, but we need more rigorous and well-controlled intervention studies to confirm these initial findings,” Damoiseaux concludes.

Natural Ways to Address Muscle Soreness and Cramping (Blog 5)

By Michael Stanclift, ND

You’re feeling that rush as you catch your stride on your morning run. The air is perfect. Suddenly a cramp or muscle ache stops you dead in your tracks. You try to shake it off, but it just grabs more. Ah!

We still don’t completely understand why muscles tighten up involuntarily. Exercise, pregnancy, electrolyte imbalances, nerve compression, and diminished blood supply to the muscle all may contribute.^1,2So what can we do to combat these harmless but pesky discomforts? In this article we’ll look at what the research says. Surprisingly, some popular natural remedies don’t shine through in the current medical evidence.

What might not help with cramping

Magnesium and Epsom salts:

A Cochrane Review found that oral magnesium wasn’t likely to help with muscle cramps in older people, and the findings were inconsistent in pregnant women.³ A recent randomized, placebo-controlled trial in pregnant women found no difference in leg cramps with magnesium compared to placebo.⁴

Epsom salt (magnesium sulfate) baths have long been a go-to for muscle relaxation, and “float” centers with sensory deprivation tanks full of the magnesium-rich water have popped up as an urban refuge from the constant stimulation of modern life. A study in nonathletic healthy men found a one-hour float (in magnesium sulfate) after exercise reduced pain perception compared to one hour of passive recovery.⁵ However, these findings are tough to attribute to magnesium, as the study’s control didn’t match other potentially therapeutic factors, such as body positioning and sensory deprivation.⁵ So a relaxing bath may help with cramping and muscles, but it’s unclear if adding Epsom salt makes a significant difference.

Active cool-down and static stretching:

Many believe after exercising intensely a period of low-to-moderate intensity will prevent muscle soreness and injuries, but this doesn’t appear to be true.⁶ A 2018 review found evidence on active cool-downs shows it doesn’t significantly reduce soreness, stiffness, or range of motion and may inhibit muscular glycogen resynthesis (energy storage).⁶ This same review found that static stretching before or after exercise didn’t reduce muscle soreness.⁶

What might help with muscle cramping:

Foam rolling:

This surprisingly simple tool can be valuable if you suffer from muscle soreness and cramps. Using a foam roller after exercise can reduce muscle soreness and improve athletic performance the following day.⁶ Physical therapists from Harvard agree that 30-120 seconds per area can be helpful in relieving sore muscles and preventing cramps.⁷

Muscle soreness:

Tart cherry or pomegranate juice:

A small randomized, double-blind, placebo-controlled trial found 355 ml (~12 oz.) of tart cherry juice drunk twice a day for a week before a 26 km (16-mile) run reduced the amount of pain reported from participants.⁸ A research review found similar effects from drinking tart cherry juice twice a day, and one study found pomegranate juice reduced soreness.⁹ But the research on these two drinks in relation to muscle soreness has shown mixed results.⁹ A recent study compared tart cherry, pomegranate, and placebo drinks to analyze the impact on muscle soreness in nonresistance trained men.¹⁰ In this study, the researchers were surprised to find that neither of the fruit drinks appeared to help with muscle soreness when compared to placebo.¹⁰

Ginger:

In a small double-blind, randomized, placebo-controlled trial in experienced runners, 5 days of powdered ginger supplementation (1.4 g/day) moderately reduced muscle soreness from a run (on day 3) during the supplement period.¹¹ A review of randomized clinical trials found that consuming up to 4 g of ginger postintense exercise can reduce muscle soreness and improve muscle recovery.¹² Lower single dosages of 2 g ginger did not help with muscle soreness when compared to placebo.¹² This suggests it may take multiple days or higher doses to get the effect.

Curcumin:

It’s no surprise that curcumin, a bright orange compound from the spice turmeric is making news again. A research review found curcumin in a wide range of doses (150 mg-5,000 mg) can reduce muscle soreness after exercise.¹³ Curcumin can work when used on an “as needed” basis, with even a single dose (150-200 mg) showing effectiveness for muscle soreness following exercise.¹³ Interestingly, in this review they found small doses (90 mg twice a day) of curcumin taken for 7 days before exercise had no effect on postexercise soreness, while the same dosage taken after exercise for 4 days was effective.¹³ Other studies in the review at similar doses did not find curcumin improved muscle soreness compared to placebo, so differences in the trial participants and types of exercise may influence the effects.¹³

Conclusion:

Cramping and muscle soreness can ruin a good exercise session, but they don’t have to. When it comes to combatting these annoying aches, you have numerous options—but beware that some popular natural treatments might be more hype than help.

References:

1. Young G. Leg cramps. BMJ Clin Evid. 2015;2015:1113.
2. Mayo Clinic Staff. Muscle cramps. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/muscle-cramp/symptoms-causes/syc-20350820#:~:text=Overuse%20of%20a%20muscle%2C%20dehydration,Inadequate%20blood%20supply. Accessed February 11, 2021.
3. Garrison SR et al. Magnesium for skeletal muscle cramps. Cochrane Database Syst Rev. 2012;2012(9):CD009402.
4. Araújo CAL et al. Oral magnesium supplementation for leg cramps in pregnancy-An observational controlled trial. PLoS One. 2020;15(1):e0227497.
5. Morgan PM et al. The acute effects of flotation restricted environmental stimulation technique on recovery from maximal eccentric exercise. J Strength Cond Res. 2013;27(12):3467-3474.
6. Van Hooren B et al. Do we need a cool-down after exercise? A narrative review of the psychophysiological effects and the effects on performance, injuries and the long-term adaptive response. Sports Med. 2018;48(7):1575-1595.
7. Harvard Health Staff. Roll away muscle pain. Harvard Health Publishing. https://www.health.harvard.edu/staying-healthy/roll-away-muscle-pain#:~:text=Foam%20rollers%20are%20easy%2Dto,from%20exercise%2C%20and%20reduce%20injury.&text=As%20you%20age%2C%20occasional%20muscle,lightweight%20cylinder%20of%20compressed%20foam. Accessed February 11, 2021.
8. Kuehl KS et al. Efficacy of tart cherry juice in reducing muscle pain during running: a randomized controlled trial. J Int Soc Sports Nutr. 2010;7:17.
9. Bowtell J et al. Fruit-derived polyphenol supplementation for athlete recovery and performance. Sports Med. 2019;49(Suppl 1):3-23.
10. Lamb KL et al. No effect of tart cherry juice or pomegranate juice on recovery from exercise-induced muscle damage in non-resistance trained men. Nutrients. 2019;11(7):1593.
11. Wilson PB. A randomized double-blind trial of ginger root for reducing muscle soreness and improving physical performance recovery among experienced recreational distance runners. J Diet Suppl. 2020;17(2):121-132.
12. Rondanelli M et al. Clinical trials on pain lowering effect of ginger: A narrative review. Phytother Res. 2020;34(11):2843-2856.
13. Yoon WY et al. Curcumin supplementation and delayed onset muscle soreness (DOMS): effects, mechanisms, and practical considerations. Phys Act Nutr. 2020;24(3):39-43.

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The Connection between Hormones and Eating Habits (Blog 4)

While there are over 200 hormones in the body – estrogen, testosterone, cortisol, insulin, leptin, and thyroid hormones are the most commonly known and closely linked to metabolism, fertility, mood, and other vital functions. Changes in hormone production, such as under- or over-production, or interferences in signaling pathways contribute to the development of hormonal imbalances, which can lead to diabetes, weight gain, infertility, and other health concerns if not managed appropriately. Sudden weight fluctuations or changes in energy levels can signal hormonal abnormalities, as can muscle aches and weakness, joint inflammation, and increased temperature sensitivity. There are many possible causes of hormonal imbalances, such as medications, tumors, and underlying health conditions; diet-related hormonal fluctuations, including those spurred by eating disorders, are also prevalent and underscore the connection between the endocrine system and eating patterns.

Hormones and Dietary Habits

Dietary patterns have a significant effect on the production of hormones as well as the proper functioning of their signaling pathways. Energy management is conducted through neural pathways while the hypothalamus and brain stem send neural and endocrine signals to regulate short-term appetite. Food regulation communication relies on mechanoreceptors and chemoreceptors in the gut which are aided by several gut hormones and satiety peptides. These include ghrelin, known as the “hunger hormone” responsible for initiating food consumption and leptin, which is responsible for adiposity signaling to stop eating. Insulin plays an important role in regulating food consumption via adiposity signals while the hormone obestatin, which is still under scientific investigation, assists with long-term food intake regulation. Finally, satiety peptides such as peptide YY, cholecystokinin, pancreatic polypeptide, amylin, and others play a role in appetite regulation in addition to hormonal signaling.

Dietary Triggers and Beneficial Habits

A healthy diet can help keep hormones in sync while poor dietary habits may wreak havoc within the endocrine system, contributing to hormonal imbalances and long-term health consequences. Overall, the consumption of healthy fats, nuts and seeds, whole fruits and vegetables, as well as quality proteins is beneficial to hormonal health while pesticides, alcohol, and artificial sweeteners in the diet can negatively impact hormone levels. Furthermore, the frequent use of stimulants – such as caffeine – and depressants, excess sodium consumption, and eating processed sugars or genetically modified ingredients can interfere with metabolic processes, harm cardiovascular health, and increase the risk of hormonal repercussions.

Caloric needs are relevant factors to consider as well with female patients being particularly prone to sensitivities to calorie scarcity, which often result in the downregulation of sex hormone production.

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Exposure to Dogs Linked to Decreased Schizophrenia Risk (Blog 3)

Early-Life Exposure to Dogs Linked to Decreased Schizophrenia Risk

Owning a pet has been associated with many health benefits, ranging from decreased blood pressure and cholesterol levels to increased life expectancy. Pet dogs specifically provide opportunities for increased physical activity, socialization, and time spent outdoors while also improving emotional well-being by providing their owners with companionship. As a result, pet ownership is on the rise, according to data from the American Pet Products Association’s National Pet Owners Survey. Per current estimates, 67% of households in the United States own at least one pet – which equals approximately 85 million homes across the country.

The full extent of the health benefits – and risks – of pet ownership is yet unknown, however, the latest research reveals that there may be positive neurologic implications of owning a dog. Published online in the journal PLOS One, a recent study from Johns Hopkins Medicine implicates that exposure to dogs at an early age may have psychiatric health benefits, including the lessening of the likelihood of schizophrenia development in adulthood.

Early-Life Exposure to Household Pets and the Risk of Psychiatric Disorders

Bipolar disorder, schizophrenia, and other serious psychiatric disorders have been linked to early-life environmental exposures – which could also include contact with household pets. A team of researchers from John Hopkins Medicine investigated the relationship between exposure to household pets – cats or dogs – during the first 12 years of life and the subsequent diagnosis of either schizophrenia or bipolar disorder.

Led by chair of the Stanley Division of Pediatric Neurovirology and professor of neurovirology in pediatrics at the Johns Hopkins Children’s Center, Robert Yolken, MD, the team evaluated a cohort of 396 individuals with schizophrenia, 381 with bipolar disorder, and 594 control subjects. Participants were between the ages of 18 and 65 and had a household pet cat, dog, or both during the first 12 years of life. Control group members had no current or prior history of psychiatric disorders.

Researchers calculated hazard ratios using Cox Proportional and multivariate logistic regression models – which included socio-demographic covariates. Their analysis was conducted for four distinct age ranges: birth to age 3, 4 to 5, 6 to 8, and 9 to 12.

Dog Ownership and Schizophrenia

Dr. Yolken and his colleagues’ findings reveal that exposure to a household pet dog in childhood was associated with a significantly reduced likelihood of subsequent schizophrenia diagnosis (HR 0.75, p <.002). As much as a 24% decreased relative risk of schizophrenia was observed following exposure at birth and during the first years of life – or before the age of 3. However, there was no significant relationship between exposure to either household cats or dogs and the subsequent development of bipolar disorder. There was also no association between cat ownership in early life and schizophrenia diagnosis.

Although, Dr. Yolken notes that there was a slightly increased risk for both disorders in participants who were in contact with cats between the ages of 9 and 12. “This indicates that the time of exposure may be critical to whether or not it alters the risk,” he told ScienceDaily.

Early-Life Exposures and Environmental Risk Factors

Neuropsychiatric disorders contribute to extensive morbidity and mortality across the globe. While current knowledge identifies genetic and environmental factors as risks for the development of schizophrenia and bipolar disorder, little research has been conducted to evaluate the significance of early life exposures within the household, which may contribute to the known familial associations of disease risk.

“Serious psychiatric disorders have been associated with alterations in the immune system linked to environmental exposures in early life, and since household pets are often among the first things with which children have close contact, it was logical for us to explore the possibilities of a connection between the two,” Dr. Yolken explains. Prior research has identified cats and dogs as immunomodulatory factors, which can result in allergic responses, contact with animal bacteria and viruses, changes in household microbiome, and pet-induced stress reduction. This immune modulation is suspected to alter the risk of psychiatric disorder development in cases of genetic predisposition; however, the extent of the underlying mechanisms remains unknown.

The “protective effect” of dog exposure observed in the latest study may be due to compounds in the canine microbiome that either alter the immune system or mitigate genetic predisposition to schizophrenia, Yolken notes. If the hazard ratio found in the latest study accurately reflects relative risk, approximately 840,000 cases of schizophrenia – or 24% of 3.5 million Americans diagnosed with the disorder – could be prevented with early-life dog exposure.

Previous studies have investigated the link between cat exposure and psychiatric disorder development; however, this study is among the first to include household pet dogs in its analysis. As the trial’s findings reveal, the development of schizophrenia and other serious psychiatric disorders may be influenced by exposure to household pet dogs in childhood. Additional research is needed to confirm the recent findings, as well as to identify the factors contributing to the connection and define the risks of developing psychiatric disorders from household pet exposure during child, or lack thereof. Understanding the underlying mechanisms of the relationship between pet exposure and psychiatric disorders would allow for the development of improved prevention protocols and treatment strategies, bringing tremendous potential for enhanced patient care.

“Source: Early-Life Exposure to Dogs Linked to Decreased Schizophrenia Risk • A4M Blog “

WHAT IS COMPOUNDING (Blog 2)

Compounding combines an ageless art with the latest medical knowledge and state-of-the-art technology, allowing specially trained professionals to prepare customized medications to meet each patient’s specific needs. Compounding is fundamental to the profession of pharmacy and was a standard means of providing prescription medications before drugs began to be produced in mass quantities by pharmaceutical manufacturers. The demand for professional compounding has increased as healthcare professionals and patients realize that the limited number of strengths and dosage forms that are commercially available are unable to meet the unique needs of many patients. These patients may have a better response to a customized dosage form that is “just what the doctor ordered”.

Our compounding professionals can prepare

unique dosage forms containing the ideal dose of medication for each individual.
medications in dosage forms that are not commercially available, such as transdermal gels, troches, “chewies”, and lollipops.
medications free of problem-causing excipients such as dyes, sugar, lactose, or alcohol.
combinations of various compatible medications into a single dosage form for easier administration and improved compliance.
medications that are not commercially available.

Quality Compounding Maximizes Therapeutic Outcomes

The efficacy of any formulation is directly related to its preparation, which is why THE SELECTION OF YOUR COMPOUNDING PHARMACY IS CRITICAL. Ongoing training for compounding pharmacists and technicians, state-of-the-art equipment, and high-quality chemicals are essential. Experience and ingenuity are important factors as well. When modifying a formula or developing a unique preparation, the compounding pharmacist must consider physical and chemical properties of both the active ingredient and excipients, solubility, tonicity, viscosity, and the most appropriate dosage form or device for administering the needed medication. Standard Operating Procedures should be in place and appropriate potency testing should be performed.

Our compounding professionals can formulate suitable medications as sublingual drops, oral and nasal sprays, lollipops, and suppositories, and other customized dosage forms.

Compounding for Neuropathic Pain

Pain management is essential because even when the underlying disease process is stable, uncontrolled pain prevents patients from working productively, enjoying recreation, or taking pleasure in their usual roles in the family and society. Chronic pain may have a myriad of causes and perpetuating factors, and therefore can be much more difficult to manage than acute pain, requiring a multidisciplinary approach and customized treatment protocols to meet the specific needs of each patient.

Optimal treatment may involve the use of medications that possess pain-relieving properties, including some antidepressants, anticonvulsants, antiarrhythmics, anesthetics, antiviral agents, and NMDA (N-methyl-D-aspartate) antagonists. NMDA-receptor antagonists, such as dextromethorphan and ketamine, can block pain transmission in dorsal horn spinal neurons, reduce nociception, and decrease tolerance to and the need for opioid analgesics. [Anesth Analg 2001 Mar;92(3):739-44] By combining various agents which utilize different mechanisms to alter the sensation of pain, physicians have found that smaller concentrations of each medication can be used.

Topical and transdermal creams and gels can be formulated to provide high local concentrations at the site of application (e.g., NSAIDs for joint pain), for trigger point application (e.g., combinations of medications for neuropathic pain), or in a base that will allow systemic absorption. Side effects associated with oral administration can often be avoided when medications are used topically. Studies suggest that there are no great restrictions on the type of drug that can be incorporated into a properly compounded transdermal gel. When medications are administered transdermally, they are not absorbed through the gastrointestinal system and do not undergo first-pass hepatic metabolism.

We work together with patient and practitioner to solve problems by customizing medications that meet the specific needs of each individual. Please contact our compounding pharmacist to discuss the dosage form, strength, and medication or combination that is most appropriate for your patient.