Q2: ANSWER: D

Critique

This is a patient with severe alcoholic hepatitis complicated by sepsis with a Maddrey’s discriminant function greater than 32. Pentoxifylline 400 mg t.i.d. would be the most appropriate choice for treatment. Pentoxifylline is a nonselective phosphodiesterase inhibitor that decreases tumor necrosis factor gene transcription. In one study of severe alcoholic hepatitis, it appeared to reduce both mortality and renal failure. It may have a beneficial effect in preventing HRS. Prednisone would not be optimal in the setting of active infection and sepsis. Anti-TNF treatment has been associated with increased risk of severe infections and this and propylthiouracil have not shown benefit in the treatment of alcoholic hepatitis. For this patient with severe alcoholic hepatitis, treatment will improve survival and observation would not be adequate.

References

1. O’Shea R.S., Dasarathy S., McCullough A.J.. Alcoholic liver disease. Hepatology 2010;51:307-28.
2. Mathurin P., Mendenhall C.L., et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis (AH): individual data analysis of the last three randomized placebo controlled double blind trials of corticosteroids in severe AH. J Hepatol. 2002;36:480-7.

Q2: ANSWER: D

Critique

This is a patient with severe alcoholic hepatitis complicated by sepsis with a Maddrey’s discriminant function greater than 32. Pentoxifylline 400 mg t.i.d. would be the most appropriate choice for treatment. Pentoxifylline is a nonselective phosphodiesterase inhibitor that decreases tumor necrosis factor gene transcription. In one study of severe alcoholic hepatitis, it appeared to reduce both mortality and renal failure. It may have a beneficial effect in preventing HRS. Prednisone would not be optimal in the setting of active infection and sepsis. Anti-TNF treatment has been associated with increased risk of severe infections and this and propylthiouracil have not shown benefit in the treatment of alcoholic hepatitis. For this patient with severe alcoholic hepatitis, treatment will improve survival and observation would not be adequate.

References

1. O’Shea R.S., Dasarathy S., McCullough A.J.. Alcoholic liver disease. Hepatology 2010;51:307-28.
2. Mathurin P., Mendenhall C.L., et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis (AH): individual data analysis of the last three randomized placebo controlled double blind trials of corticosteroids in severe AH. J Hepatol. 2002;36:480-7.

Q2: ANSWER: D

Critique

This is a patient with severe alcoholic hepatitis complicated by sepsis with a Maddrey’s discriminant function greater than 32. Pentoxifylline 400 mg t.i.d. would be the most appropriate choice for treatment. Pentoxifylline is a nonselective phosphodiesterase inhibitor that decreases tumor necrosis factor gene transcription. In one study of severe alcoholic hepatitis, it appeared to reduce both mortality and renal failure. It may have a beneficial effect in preventing HRS. Prednisone would not be optimal in the setting of active infection and sepsis. Anti-TNF treatment has been associated with increased risk of severe infections and this and propylthiouracil have not shown benefit in the treatment of alcoholic hepatitis. For this patient with severe alcoholic hepatitis, treatment will improve survival and observation would not be adequate.

References

1. O’Shea R.S., Dasarathy S., McCullough A.J.. Alcoholic liver disease. Hepatology 2010;51:307-28.
2. Mathurin P., Mendenhall C.L., et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis (AH): individual data analysis of the last three randomized placebo controlled double blind trials of corticosteroids in severe AH. J Hepatol. 2002;36:480-7.

Pain is one of the most common symptoms for which patients seek medical care, with an associated estimated annual cost of $600 billion.¹ Using a multimodal approach to care—thorough evaluation, cognitive-behavioral and psychophysiological therapy, physical therapy, medications, and other interventions—can help patients effectively manage their condition and achieve healthier outcomes.

Evaluating a patient with pain
When developing a safe, comprehensive, and effective treatment plan for patients with chronic pain, first perform a thorough history and physical exam using the following elements:

Pain history. The PQRST mnemonic (Table 1) can help you obtain critical information and assist in determining the appropriate diagnosis and cause of the patient’s pain complaints.

Psychiatric history. Document the mental health history of the patient and first-degree relatives.

Medical history. Knowing the medical history could reveal comorbidities contributing to a patient’s pain complaint.

Treatment history. Listing past and current treatments for pain, including effectiveness, helps the clinician understand if an existing treatment plan should be modified.

Functional status. Document current level of daily activity, how life activities are affected by pain; strategies used to help cope with pain; level of physical and emotional support provided in home, work, and school environments; and active stressors (eg, financial, interpersonal).

Psychosocial history. Document historical information related to coping skills, trauma history, family of origin, abuse, interpersonal relationships, social support, and academic and vocational functioning.

Substance use or abuse. Assess for use of controlled substances (ie, early refills; lost medications; obtaining medications from multiple prescribers, friends, families, or strangers; use of prescribed and non-prescribed medications for non-medical and medical purposes), nicotine, alcohol, illicit substances, and caffeine. A thorough inventory can help to identify substances a patient is using that could affect daily functioning and pain level.

Behavioral observations. Assessing mental status (eg, insight, pain behavior, co­operation) can be useful. Paying attention to pain behaviors, such as complaints of pain, decreased activity, increased medication intake, or altered facial expressions or body posture, can help the clinician gain insight to the extent that pain affects the patient’s quality of life.

The information gathered in the patient evaluation can be used to design a multimodal treatment plan to achieve maximum effectiveness.

Assessing psychiatric illness
Current approaches to pain evaluation and treatment recommend use of a biopsychosocial orientation because psychological, behavioral, and social factors can influence the experience and impact of pain, regardless of the primary cause.² A comprehensive psychiatric evaluation, diagnosis, and treatment plan should consider the broader context in which a patient’s pain occurs.

Regarding psychiatric illness, past and current symptoms, treatment history, and risk assessment should all be included. Using the “AMPS approach” (Figure)³—assessing Anxiety, Mood (depression and mania), Psychotic symptoms (paranoid ideation and hallucinations), and Substance use—helps screen for comorbid psychiatric conditions in patients with chronic pain.

Sleep assessment
Chronic pain patients often experience significant sleep disturbance that could be caused by physiological aspects of the pain condition, environmental factors (eg, uncomfortable bedding), a comorbid sleep disorder (eg, sleep apnea), a psychiatric disorder, or a combination of the above.

Obstructive and central sleep apnea are characterized by nighttime hypoxia, which leads to frequent disruption of the sleep-wake cycle and often manifests as daytime fatigue, irritability, depression, drowsiness, headaches, and increased pain sensitivity. Changes in sleep arousal can lead to neuro­psychological changes during the day, such as decreased attention, memory problems, impaired executive functioning, and reduced impulse control.

Screen patients for central and obstructive sleep apnea before prescribing opioids or benzodiazepines for pain because these medications can cause or exacerbate underlying sleep apnea. Although many screening tools, such as the Epworth Sleepiness Scale, assess daytime somnolence,⁴ the STOP-BANG questionnaire is a quick, validated, and efficient screening tool that often is used to assess sleep apnea risk^5,6 (Table 2). The presence of ≥3 risk factors identifies patients at increased risk and warrants consideration for further workup by a sleep specialist.^7,8

Pharmacotherapy for chronic pain
Non-opioid medications. Pain can be broadly categorized as neuropathic or nociceptive. Neuropathic pain can be described by patients as numbness, burning, electric-like, and tingling, and is associated with nerve damage. Nociceptive pain commonly is described as similar to a toothache with descriptors such as stabbing, sharp, or a dull aching sensation; it is often, but not always, associated with acute injury or ongoing trauma to tissue. Drug treatment is most successful when the appropriate class of medication is matched to the specific type of pain.

Nociceptive pain often is successfully treated with non-steroidal anti-inflammatory drugs and acetaminophen. Non-selective COX inhibitors (eg, ibuprofen, indomethacin, ketorolac) and COX-2 selective inhibitors (eg, celecoxib) have been associated with cardiovascular, gastrointestinal, and renal disease; acetaminophen is associated with liver dysfunction.^9-11 However, the absolute risk for complications in healthy patients is low.¹² To minimize risk, use these agents for the shortest duration and at the lowest effective dosage possible.

Neuropathic pain can be addressed with certain antidepressants¹³—specifically, those that increase serotonin and norepinephrine (eg, tricyclic antidepressants [TCAs] and serotonin-norepinephrine reuptake inhibitors [SNRIs]), or medications that block ion channels (eg, anticonvulsants). TCAs (eg, desipramine, nortriptyline, amitriptyline) are among the best studied and most cost effective medications for treating neuropathic pain,^14,15 but they can have sedating and anticholinergic effects, as well as cardiac adverse effects (ie, prolongation of the QTc interval). SNRIs (eg, venlafaxine, desvenlafaxine, duloxetine, and milnacipran) can be effective and often are better tolerated than TCAs.¹⁴

Some newer anticonvulsants (eg, gabapentin and pregabalin) have been found to be more effective than placebo for a variety of neuropathic pain conditions.^16,17 Although they have few drug-drug interactions, anticonvulsants can cause dizziness, forgetfulness, and sedation. These adverse effects can be minimized by starting at a low dosage and titrating carefully. Because hepatic or renal impairment can affect metabolism or excretion of these drugs, review the prescribing information to determine safe dosing.

Targeted injection of medications to major pain generators (eg, an epidural steroid for radicular neck and back pain; facet injections for facet-related neck and back pain; trigger point injections for myofascial pain; occipital nerve blocks for occipital neuralgia; and botulinum toxin A injections for chronic migraine headache) can be effective in reducing discomfort and increasing function in patients with chronic pain. A detailed discussion of such therapies is beyond the scope of this article, but have been reviewed extensively elsewhere.^18,19

Opioids. Although there is little evidence of long-term efficacy with chronic opioid therapy for most patients, a trial of opioids might be warranted for select patients who do not respond to other medications. Because the risk–benefit ratio for chronic opioid therapy is high,^20-22 a decision to initiate a trial of a low-dosage opioid should be made only after careful consideration of those risks. It is generally agreed that treatment of chronic pain with low-dosage opioid therapy is more likely to be successful when it is used as an adjuvant to non-opioid modalities (eg, physical reconditioning, injection therapies, spinal cord stimulation, neurobehavioral interventions, non-opioid medications).

The Federation of State Medical Boards has stated that excessive reliance on opioid medications for treating chronic pain is a deviation from best practices.²³ To maximize benefit and minimize risk, clinicians should carefully select appropriate patients, establish functional goals, and regularly monitor for efficacy and compliance. Thoroughly document these steps in the patient’s record for later reference.²³

After establishing a clinical diagnosis for the cause of the pain, you should determine the risk of opioid abuse or misuse by using any one of the available risk assessment tools (Box). Understand, however, that no single tool has been shown to be more effective than others.

Although patients and some clinicians tend to overvalue the benefits of chronic opioid therapy, many do not fully appreciate the risks (eg, respiratory depression and death), which can be exacerbated if the patient is using other substance that suppress respiration (eg, benzodiazepines, alcohol, and illicit substances). Written informed consent and treatment agreement is highly recommended; components of such a document are listed in Table 3.²³

Develop a treatment plan that emphasizes functional goals based on the patient’s physical limitations and that incorporates some type of daily, atraumatic physical activity. This plan should be documented and reviewed regularly to help monitor treatment effectiveness.

After an initial trial of a few weeks, the patient and clinician should meet to review the 5 “A”s (Table 4)²⁴ to determine the success of the opioid regimen. Consulting your state’s prescription drug monitoring program (if one is available), obtaining a random urine drug test, and doing a pill count can provide useful, objective data. If the patient has not made progress but has experienced no adverse effects, then a small dosage increase might be warranted. If any of the 5 “A”s indicates lack of improvement or increased risk, consider stopping opioid therapy and exploring non-opioid options to manage chronic pain.

Referrals to a pain specialist or an addiction specialist, or both, might be needed, depending on the patient’s condition at any given follow-up visit. Such referral decisions, as well as all treatment plans, should be documented clearly in the medical record to prevent any misunderstanding, false accusations, or medicolegal repercussions regarding the rationale for continuing or terminating opioid-based treatment.

Non-pharmaceutical therapy for treating pain
The pain management field has successfully integrated the biopsychosocial model into regular practice. This model advocates the use of multimodal non-drug interventions in conjunction with opioid and non-opioid medications. Such interventions address behavioral, cognitive, sociocultural (psychosocial), lifestyle, and physiological dimensions of pain. A partial list of non-drug interventions is provided in Table 5.

Integration of these interventions within a biopsychosocial framework can assist you in making a comprehensive treatment plan. For example, patients with focal myofascial shoulder and back pain might derive only transient benefit from trigger point injection. However, concurrent referral to a pain psychologist and physical therapist could substantially improve functional outcomes by addressing factors that directly and indirectly influence myofascial pain. Inclusion of cognitive-behavioral therapy (addressing psychosocial and lifestyle dimensions), surface electromyography, psychophysiological interventions/biofeedback (addressing psychosocial, lifestyle, and physiological dimensions), and physical therapy (addressing lifestyle and physiological dimensions) allows the patient to learn coping skills, decrease physiological arousal that can lead to unnecessary tensing of muscles, and strengthen core muscle groups.

Pain is one of the most common symptoms for which patients seek medical care, with an associated estimated annual cost of $600 billion.¹ Using a multimodal approach to care—thorough evaluation, cognitive-behavioral and psychophysiological therapy, physical therapy, medications, and other interventions—can help patients effectively manage their condition and achieve healthier outcomes.

Evaluating a patient with pain
When developing a safe, comprehensive, and effective treatment plan for patients with chronic pain, first perform a thorough history and physical exam using the following elements:

Pain history. The PQRST mnemonic (Table 1) can help you obtain critical information and assist in determining the appropriate diagnosis and cause of the patient’s pain complaints.

Psychiatric history. Document the mental health history of the patient and first-degree relatives.

Medical history. Knowing the medical history could reveal comorbidities contributing to a patient’s pain complaint.

Treatment history. Listing past and current treatments for pain, including effectiveness, helps the clinician understand if an existing treatment plan should be modified.

Functional status. Document current level of daily activity, how life activities are affected by pain; strategies used to help cope with pain; level of physical and emotional support provided in home, work, and school environments; and active stressors (eg, financial, interpersonal).

Psychosocial history. Document historical information related to coping skills, trauma history, family of origin, abuse, interpersonal relationships, social support, and academic and vocational functioning.

Substance use or abuse. Assess for use of controlled substances (ie, early refills; lost medications; obtaining medications from multiple prescribers, friends, families, or strangers; use of prescribed and non-prescribed medications for non-medical and medical purposes), nicotine, alcohol, illicit substances, and caffeine. A thorough inventory can help to identify substances a patient is using that could affect daily functioning and pain level.

Behavioral observations. Assessing mental status (eg, insight, pain behavior, co­operation) can be useful. Paying attention to pain behaviors, such as complaints of pain, decreased activity, increased medication intake, or altered facial expressions or body posture, can help the clinician gain insight to the extent that pain affects the patient’s quality of life.

The information gathered in the patient evaluation can be used to design a multimodal treatment plan to achieve maximum effectiveness.

Assessing psychiatric illness
Current approaches to pain evaluation and treatment recommend use of a biopsychosocial orientation because psychological, behavioral, and social factors can influence the experience and impact of pain, regardless of the primary cause.² A comprehensive psychiatric evaluation, diagnosis, and treatment plan should consider the broader context in which a patient’s pain occurs.

Regarding psychiatric illness, past and current symptoms, treatment history, and risk assessment should all be included. Using the “AMPS approach” (Figure)³—assessing Anxiety, Mood (depression and mania), Psychotic symptoms (paranoid ideation and hallucinations), and Substance use—helps screen for comorbid psychiatric conditions in patients with chronic pain.

Sleep assessment
Chronic pain patients often experience significant sleep disturbance that could be caused by physiological aspects of the pain condition, environmental factors (eg, uncomfortable bedding), a comorbid sleep disorder (eg, sleep apnea), a psychiatric disorder, or a combination of the above.

Obstructive and central sleep apnea are characterized by nighttime hypoxia, which leads to frequent disruption of the sleep-wake cycle and often manifests as daytime fatigue, irritability, depression, drowsiness, headaches, and increased pain sensitivity. Changes in sleep arousal can lead to neuro­psychological changes during the day, such as decreased attention, memory problems, impaired executive functioning, and reduced impulse control.

Screen patients for central and obstructive sleep apnea before prescribing opioids or benzodiazepines for pain because these medications can cause or exacerbate underlying sleep apnea. Although many screening tools, such as the Epworth Sleepiness Scale, assess daytime somnolence,⁴ the STOP-BANG questionnaire is a quick, validated, and efficient screening tool that often is used to assess sleep apnea risk^5,6 (Table 2). The presence of ≥3 risk factors identifies patients at increased risk and warrants consideration for further workup by a sleep specialist.^7,8

Pharmacotherapy for chronic pain
Non-opioid medications. Pain can be broadly categorized as neuropathic or nociceptive. Neuropathic pain can be described by patients as numbness, burning, electric-like, and tingling, and is associated with nerve damage. Nociceptive pain commonly is described as similar to a toothache with descriptors such as stabbing, sharp, or a dull aching sensation; it is often, but not always, associated with acute injury or ongoing trauma to tissue. Drug treatment is most successful when the appropriate class of medication is matched to the specific type of pain.

Nociceptive pain often is successfully treated with non-steroidal anti-inflammatory drugs and acetaminophen. Non-selective COX inhibitors (eg, ibuprofen, indomethacin, ketorolac) and COX-2 selective inhibitors (eg, celecoxib) have been associated with cardiovascular, gastrointestinal, and renal disease; acetaminophen is associated with liver dysfunction.^9-11 However, the absolute risk for complications in healthy patients is low.¹² To minimize risk, use these agents for the shortest duration and at the lowest effective dosage possible.

Neuropathic pain can be addressed with certain antidepressants¹³—specifically, those that increase serotonin and norepinephrine (eg, tricyclic antidepressants [TCAs] and serotonin-norepinephrine reuptake inhibitors [SNRIs]), or medications that block ion channels (eg, anticonvulsants). TCAs (eg, desipramine, nortriptyline, amitriptyline) are among the best studied and most cost effective medications for treating neuropathic pain,^14,15 but they can have sedating and anticholinergic effects, as well as cardiac adverse effects (ie, prolongation of the QTc interval). SNRIs (eg, venlafaxine, desvenlafaxine, duloxetine, and milnacipran) can be effective and often are better tolerated than TCAs.¹⁴

Some newer anticonvulsants (eg, gabapentin and pregabalin) have been found to be more effective than placebo for a variety of neuropathic pain conditions.^16,17 Although they have few drug-drug interactions, anticonvulsants can cause dizziness, forgetfulness, and sedation. These adverse effects can be minimized by starting at a low dosage and titrating carefully. Because hepatic or renal impairment can affect metabolism or excretion of these drugs, review the prescribing information to determine safe dosing.

Targeted injection of medications to major pain generators (eg, an epidural steroid for radicular neck and back pain; facet injections for facet-related neck and back pain; trigger point injections for myofascial pain; occipital nerve blocks for occipital neuralgia; and botulinum toxin A injections for chronic migraine headache) can be effective in reducing discomfort and increasing function in patients with chronic pain. A detailed discussion of such therapies is beyond the scope of this article, but have been reviewed extensively elsewhere.^18,19

Opioids. Although there is little evidence of long-term efficacy with chronic opioid therapy for most patients, a trial of opioids might be warranted for select patients who do not respond to other medications. Because the risk–benefit ratio for chronic opioid therapy is high,^20-22 a decision to initiate a trial of a low-dosage opioid should be made only after careful consideration of those risks. It is generally agreed that treatment of chronic pain with low-dosage opioid therapy is more likely to be successful when it is used as an adjuvant to non-opioid modalities (eg, physical reconditioning, injection therapies, spinal cord stimulation, neurobehavioral interventions, non-opioid medications).

The Federation of State Medical Boards has stated that excessive reliance on opioid medications for treating chronic pain is a deviation from best practices.²³ To maximize benefit and minimize risk, clinicians should carefully select appropriate patients, establish functional goals, and regularly monitor for efficacy and compliance. Thoroughly document these steps in the patient’s record for later reference.²³

After establishing a clinical diagnosis for the cause of the pain, you should determine the risk of opioid abuse or misuse by using any one of the available risk assessment tools (Box). Understand, however, that no single tool has been shown to be more effective than others.

Although patients and some clinicians tend to overvalue the benefits of chronic opioid therapy, many do not fully appreciate the risks (eg, respiratory depression and death), which can be exacerbated if the patient is using other substance that suppress respiration (eg, benzodiazepines, alcohol, and illicit substances). Written informed consent and treatment agreement is highly recommended; components of such a document are listed in Table 3.²³

Develop a treatment plan that emphasizes functional goals based on the patient’s physical limitations and that incorporates some type of daily, atraumatic physical activity. This plan should be documented and reviewed regularly to help monitor treatment effectiveness.

After an initial trial of a few weeks, the patient and clinician should meet to review the 5 “A”s (Table 4)²⁴ to determine the success of the opioid regimen. Consulting your state’s prescription drug monitoring program (if one is available), obtaining a random urine drug test, and doing a pill count can provide useful, objective data. If the patient has not made progress but has experienced no adverse effects, then a small dosage increase might be warranted. If any of the 5 “A”s indicates lack of improvement or increased risk, consider stopping opioid therapy and exploring non-opioid options to manage chronic pain.

Referrals to a pain specialist or an addiction specialist, or both, might be needed, depending on the patient’s condition at any given follow-up visit. Such referral decisions, as well as all treatment plans, should be documented clearly in the medical record to prevent any misunderstanding, false accusations, or medicolegal repercussions regarding the rationale for continuing or terminating opioid-based treatment.

Non-pharmaceutical therapy for treating pain
The pain management field has successfully integrated the biopsychosocial model into regular practice. This model advocates the use of multimodal non-drug interventions in conjunction with opioid and non-opioid medications. Such interventions address behavioral, cognitive, sociocultural (psychosocial), lifestyle, and physiological dimensions of pain. A partial list of non-drug interventions is provided in Table 5.

Integration of these interventions within a biopsychosocial framework can assist you in making a comprehensive treatment plan. For example, patients with focal myofascial shoulder and back pain might derive only transient benefit from trigger point injection. However, concurrent referral to a pain psychologist and physical therapist could substantially improve functional outcomes by addressing factors that directly and indirectly influence myofascial pain. Inclusion of cognitive-behavioral therapy (addressing psychosocial and lifestyle dimensions), surface electromyography, psychophysiological interventions/biofeedback (addressing psychosocial, lifestyle, and physiological dimensions), and physical therapy (addressing lifestyle and physiological dimensions) allows the patient to learn coping skills, decrease physiological arousal that can lead to unnecessary tensing of muscles, and strengthen core muscle groups.

Pain is one of the most common symptoms for which patients seek medical care, with an associated estimated annual cost of $600 billion.¹ Using a multimodal approach to care—thorough evaluation, cognitive-behavioral and psychophysiological therapy, physical therapy, medications, and other interventions—can help patients effectively manage their condition and achieve healthier outcomes.

Evaluating a patient with pain
When developing a safe, comprehensive, and effective treatment plan for patients with chronic pain, first perform a thorough history and physical exam using the following elements:

Pain history. The PQRST mnemonic (Table 1) can help you obtain critical information and assist in determining the appropriate diagnosis and cause of the patient’s pain complaints.

Psychiatric history. Document the mental health history of the patient and first-degree relatives.

Medical history. Knowing the medical history could reveal comorbidities contributing to a patient’s pain complaint.

Treatment history. Listing past and current treatments for pain, including effectiveness, helps the clinician understand if an existing treatment plan should be modified.

Functional status. Document current level of daily activity, how life activities are affected by pain; strategies used to help cope with pain; level of physical and emotional support provided in home, work, and school environments; and active stressors (eg, financial, interpersonal).

Psychosocial history. Document historical information related to coping skills, trauma history, family of origin, abuse, interpersonal relationships, social support, and academic and vocational functioning.

Substance use or abuse. Assess for use of controlled substances (ie, early refills; lost medications; obtaining medications from multiple prescribers, friends, families, or strangers; use of prescribed and non-prescribed medications for non-medical and medical purposes), nicotine, alcohol, illicit substances, and caffeine. A thorough inventory can help to identify substances a patient is using that could affect daily functioning and pain level.

Behavioral observations. Assessing mental status (eg, insight, pain behavior, co­operation) can be useful. Paying attention to pain behaviors, such as complaints of pain, decreased activity, increased medication intake, or altered facial expressions or body posture, can help the clinician gain insight to the extent that pain affects the patient’s quality of life.

The information gathered in the patient evaluation can be used to design a multimodal treatment plan to achieve maximum effectiveness.

Assessing psychiatric illness
Current approaches to pain evaluation and treatment recommend use of a biopsychosocial orientation because psychological, behavioral, and social factors can influence the experience and impact of pain, regardless of the primary cause.² A comprehensive psychiatric evaluation, diagnosis, and treatment plan should consider the broader context in which a patient’s pain occurs.

Regarding psychiatric illness, past and current symptoms, treatment history, and risk assessment should all be included. Using the “AMPS approach” (Figure)³—assessing Anxiety, Mood (depression and mania), Psychotic symptoms (paranoid ideation and hallucinations), and Substance use—helps screen for comorbid psychiatric conditions in patients with chronic pain.

Sleep assessment
Chronic pain patients often experience significant sleep disturbance that could be caused by physiological aspects of the pain condition, environmental factors (eg, uncomfortable bedding), a comorbid sleep disorder (eg, sleep apnea), a psychiatric disorder, or a combination of the above.

Obstructive and central sleep apnea are characterized by nighttime hypoxia, which leads to frequent disruption of the sleep-wake cycle and often manifests as daytime fatigue, irritability, depression, drowsiness, headaches, and increased pain sensitivity. Changes in sleep arousal can lead to neuro­psychological changes during the day, such as decreased attention, memory problems, impaired executive functioning, and reduced impulse control.

Screen patients for central and obstructive sleep apnea before prescribing opioids or benzodiazepines for pain because these medications can cause or exacerbate underlying sleep apnea. Although many screening tools, such as the Epworth Sleepiness Scale, assess daytime somnolence,⁴ the STOP-BANG questionnaire is a quick, validated, and efficient screening tool that often is used to assess sleep apnea risk^5,6 (Table 2). The presence of ≥3 risk factors identifies patients at increased risk and warrants consideration for further workup by a sleep specialist.^7,8

Pharmacotherapy for chronic pain
Non-opioid medications. Pain can be broadly categorized as neuropathic or nociceptive. Neuropathic pain can be described by patients as numbness, burning, electric-like, and tingling, and is associated with nerve damage. Nociceptive pain commonly is described as similar to a toothache with descriptors such as stabbing, sharp, or a dull aching sensation; it is often, but not always, associated with acute injury or ongoing trauma to tissue. Drug treatment is most successful when the appropriate class of medication is matched to the specific type of pain.

Nociceptive pain often is successfully treated with non-steroidal anti-inflammatory drugs and acetaminophen. Non-selective COX inhibitors (eg, ibuprofen, indomethacin, ketorolac) and COX-2 selective inhibitors (eg, celecoxib) have been associated with cardiovascular, gastrointestinal, and renal disease; acetaminophen is associated with liver dysfunction.^9-11 However, the absolute risk for complications in healthy patients is low.¹² To minimize risk, use these agents for the shortest duration and at the lowest effective dosage possible.

Neuropathic pain can be addressed with certain antidepressants¹³—specifically, those that increase serotonin and norepinephrine (eg, tricyclic antidepressants [TCAs] and serotonin-norepinephrine reuptake inhibitors [SNRIs]), or medications that block ion channels (eg, anticonvulsants). TCAs (eg, desipramine, nortriptyline, amitriptyline) are among the best studied and most cost effective medications for treating neuropathic pain,^14,15 but they can have sedating and anticholinergic effects, as well as cardiac adverse effects (ie, prolongation of the QTc interval). SNRIs (eg, venlafaxine, desvenlafaxine, duloxetine, and milnacipran) can be effective and often are better tolerated than TCAs.¹⁴

Some newer anticonvulsants (eg, gabapentin and pregabalin) have been found to be more effective than placebo for a variety of neuropathic pain conditions.^16,17 Although they have few drug-drug interactions, anticonvulsants can cause dizziness, forgetfulness, and sedation. These adverse effects can be minimized by starting at a low dosage and titrating carefully. Because hepatic or renal impairment can affect metabolism or excretion of these drugs, review the prescribing information to determine safe dosing.

Targeted injection of medications to major pain generators (eg, an epidural steroid for radicular neck and back pain; facet injections for facet-related neck and back pain; trigger point injections for myofascial pain; occipital nerve blocks for occipital neuralgia; and botulinum toxin A injections for chronic migraine headache) can be effective in reducing discomfort and increasing function in patients with chronic pain. A detailed discussion of such therapies is beyond the scope of this article, but have been reviewed extensively elsewhere.^18,19

Opioids. Although there is little evidence of long-term efficacy with chronic opioid therapy for most patients, a trial of opioids might be warranted for select patients who do not respond to other medications. Because the risk–benefit ratio for chronic opioid therapy is high,^20-22 a decision to initiate a trial of a low-dosage opioid should be made only after careful consideration of those risks. It is generally agreed that treatment of chronic pain with low-dosage opioid therapy is more likely to be successful when it is used as an adjuvant to non-opioid modalities (eg, physical reconditioning, injection therapies, spinal cord stimulation, neurobehavioral interventions, non-opioid medications).

The Federation of State Medical Boards has stated that excessive reliance on opioid medications for treating chronic pain is a deviation from best practices.²³ To maximize benefit and minimize risk, clinicians should carefully select appropriate patients, establish functional goals, and regularly monitor for efficacy and compliance. Thoroughly document these steps in the patient’s record for later reference.²³

After establishing a clinical diagnosis for the cause of the pain, you should determine the risk of opioid abuse or misuse by using any one of the available risk assessment tools (Box). Understand, however, that no single tool has been shown to be more effective than others.

Although patients and some clinicians tend to overvalue the benefits of chronic opioid therapy, many do not fully appreciate the risks (eg, respiratory depression and death), which can be exacerbated if the patient is using other substance that suppress respiration (eg, benzodiazepines, alcohol, and illicit substances). Written informed consent and treatment agreement is highly recommended; components of such a document are listed in Table 3.²³

Develop a treatment plan that emphasizes functional goals based on the patient’s physical limitations and that incorporates some type of daily, atraumatic physical activity. This plan should be documented and reviewed regularly to help monitor treatment effectiveness.

After an initial trial of a few weeks, the patient and clinician should meet to review the 5 “A”s (Table 4)²⁴ to determine the success of the opioid regimen. Consulting your state’s prescription drug monitoring program (if one is available), obtaining a random urine drug test, and doing a pill count can provide useful, objective data. If the patient has not made progress but has experienced no adverse effects, then a small dosage increase might be warranted. If any of the 5 “A”s indicates lack of improvement or increased risk, consider stopping opioid therapy and exploring non-opioid options to manage chronic pain.

Referrals to a pain specialist or an addiction specialist, or both, might be needed, depending on the patient’s condition at any given follow-up visit. Such referral decisions, as well as all treatment plans, should be documented clearly in the medical record to prevent any misunderstanding, false accusations, or medicolegal repercussions regarding the rationale for continuing or terminating opioid-based treatment.

Non-pharmaceutical therapy for treating pain
The pain management field has successfully integrated the biopsychosocial model into regular practice. This model advocates the use of multimodal non-drug interventions in conjunction with opioid and non-opioid medications. Such interventions address behavioral, cognitive, sociocultural (psychosocial), lifestyle, and physiological dimensions of pain. A partial list of non-drug interventions is provided in Table 5.

Integration of these interventions within a biopsychosocial framework can assist you in making a comprehensive treatment plan. For example, patients with focal myofascial shoulder and back pain might derive only transient benefit from trigger point injection. However, concurrent referral to a pain psychologist and physical therapist could substantially improve functional outcomes by addressing factors that directly and indirectly influence myofascial pain. Inclusion of cognitive-behavioral therapy (addressing psychosocial and lifestyle dimensions), surface electromyography, psychophysiological interventions/biofeedback (addressing psychosocial, lifestyle, and physiological dimensions), and physical therapy (addressing lifestyle and physiological dimensions) allows the patient to learn coping skills, decrease physiological arousal that can lead to unnecessary tensing of muscles, and strengthen core muscle groups.

Q1: ANSWER: C

Critique

The diagnosis of H. pylori may be made using either invasive or noninvasive methods. Invasive diagnostic methods either detect organisms directly (i.e., histological identification with appropriate stains or bacterial culture) or indirectly (i.e., rapid urease testing of biopsy specimens). Noninvasive methods include serum antibody, stool antigen, and detecting the metabolites of the bacterial enzyme urease (i.e., urea breath testing). It should be noted that serology should not be used to test for eradication as the antibodies may remain elevated for years after successful eradication therapy.

Treatment of H. pylori infection has become problematic recently primarily due to increasing antibiotic resistance. The eradication rate of standard triple therapy consisting of a proton pump inhibitor combined with clarithromycin (500 mg) and amoxicillin (1 g) (or metronidazole (500 mg), all given b.i.d. for 7-14 days has now declined to unacceptable levels, averaging 70%-80% but reported as low as 55%. It is currently recommended that a noninvasive method be used (other than serology) to confirm eradication in patients in whom eradication is deemed necessary.

References

1. Malfertheiner P., Megraud F., O’Morain C.A., et al. European Helicobacter Study Group. Management of Helicobacter pylori infection – the Maastricht IV/ Florence Consensus Report. Gut 2012;61:646-64.
2. De F., Giorgio F., Hassan C., et al. Worldwide H. pylori antibiotic resistance: a systematic review. J Gastrointestin Liver Dis. 2010;19:409-14.
3. Kearney D.J., Brousal A.. Treatment of Helicobacter pylori infection in clinical practice in the United States – Results from 224 patients. Dig Dis Sci. 2000;45:265-71.

Q1: ANSWER: C

Critique

The diagnosis of H. pylori may be made using either invasive or noninvasive methods. Invasive diagnostic methods either detect organisms directly (i.e., histological identification with appropriate stains or bacterial culture) or indirectly (i.e., rapid urease testing of biopsy specimens). Noninvasive methods include serum antibody, stool antigen, and detecting the metabolites of the bacterial enzyme urease (i.e., urea breath testing). It should be noted that serology should not be used to test for eradication as the antibodies may remain elevated for years after successful eradication therapy.

Treatment of H. pylori infection has become problematic recently primarily due to increasing antibiotic resistance. The eradication rate of standard triple therapy consisting of a proton pump inhibitor combined with clarithromycin (500 mg) and amoxicillin (1 g) (or metronidazole (500 mg), all given b.i.d. for 7-14 days has now declined to unacceptable levels, averaging 70%-80% but reported as low as 55%. It is currently recommended that a noninvasive method be used (other than serology) to confirm eradication in patients in whom eradication is deemed necessary.

References

1. Malfertheiner P., Megraud F., O’Morain C.A., et al. European Helicobacter Study Group. Management of Helicobacter pylori infection – the Maastricht IV/ Florence Consensus Report. Gut 2012;61:646-64.
2. De F., Giorgio F., Hassan C., et al. Worldwide H. pylori antibiotic resistance: a systematic review. J Gastrointestin Liver Dis. 2010;19:409-14.
3. Kearney D.J., Brousal A.. Treatment of Helicobacter pylori infection in clinical practice in the United States – Results from 224 patients. Dig Dis Sci. 2000;45:265-71.

Q1: ANSWER: C

Critique

The diagnosis of H. pylori may be made using either invasive or noninvasive methods. Invasive diagnostic methods either detect organisms directly (i.e., histological identification with appropriate stains or bacterial culture) or indirectly (i.e., rapid urease testing of biopsy specimens). Noninvasive methods include serum antibody, stool antigen, and detecting the metabolites of the bacterial enzyme urease (i.e., urea breath testing). It should be noted that serology should not be used to test for eradication as the antibodies may remain elevated for years after successful eradication therapy.

Treatment of H. pylori infection has become problematic recently primarily due to increasing antibiotic resistance. The eradication rate of standard triple therapy consisting of a proton pump inhibitor combined with clarithromycin (500 mg) and amoxicillin (1 g) (or metronidazole (500 mg), all given b.i.d. for 7-14 days has now declined to unacceptable levels, averaging 70%-80% but reported as low as 55%. It is currently recommended that a noninvasive method be used (other than serology) to confirm eradication in patients in whom eradication is deemed necessary.

References

1. Malfertheiner P., Megraud F., O’Morain C.A., et al. European Helicobacter Study Group. Management of Helicobacter pylori infection – the Maastricht IV/ Florence Consensus Report. Gut 2012;61:646-64.
2. De F., Giorgio F., Hassan C., et al. Worldwide H. pylori antibiotic resistance: a systematic review. J Gastrointestin Liver Dis. 2010;19:409-14.
3. Kearney D.J., Brousal A.. Treatment of Helicobacter pylori infection in clinical practice in the United States – Results from 224 patients. Dig Dis Sci. 2000;45:265-71.

The diversity of hospitalist practice—from the variety of settings (such as inpatient acute, observation, post-discharge clinics, and post-acute-care facilities) to the differences in relationships with their facilities—is a strength of the specialty. It reflects the ability of the specialty to adapt to the unique needs of its local patients and institutions.

At the same time, it presents some unique challenges to developing strategies for identifying and assessing hospitalists. As the Medicare physician payment system moves toward value-based payment, hospitalists must report quality measures in the Physician Quality Reporting System (PQRS) or face ever-increasing penalties.

Many hospitalists are part of multispecialty groups aligned with a range of physicians employed by the same facility, including many academic hospitalists and those in integrated healthcare systems. Frequently for hospitalists in these groups, the group reports via a group-practice reporting option that uses measures for outpatient providers, capitalizing on the performances of those outpatient primary care providers in the group and making it generally unnecessary for these hospitalists to independently worry about PQRS reporting. Due to their employment model, they might also be somewhat insulated from seeing firsthand any value-based reimbursement adjustments from Medicare.

Hospitalists commonly are employed by single-specialty groups, medium or large in number of HM-focused providers, or increasingly a mix of hospitalists, emergency physicians, and hospitalists focused on skilled nursing facility (SNF) care. Still others are in small hospitalist groups or independent practitioners of hospital medicine. For these hospitalists, successful reporting of PQRS is important; they cannot rely on broad-based primary care group reporting options, and penalties can have an immediate impact on revenue streams.

PQRS, just like its hospital counterpart, the Inpatient Quality Reporting (IQR) system, was designed for use in an isolated healthcare delivery silo: PQRS was meant for physicians; IQR, for hospitals. This explicit design makes the measuring of hospitalists difficult within the current value-based payment programs because while the patient-care goals of hospitalists and their hospitals overlap, hospitalists are forced to report on physician-level metrics. Following this silo logic, the Centers for Medicare & Medicaid Services (CMS) has been removing physician-level PQRS measures that it views as redundant with facility-level IQR metrics, which has contributed to the detrimental reduction of relevant PQRS metrics for hospitalists over the years.

However, in large part due to the significant advocacy efforts of SHM around last year’s Medicare Access and CHIP Reauthorization Act (MACRA), CMS now has the ability to reverse this trend and include metrics from other programs, such as IQR metrics, as part of the quality or cost component of physician value-based payment. This would help to eliminate the artificial misalignment of quality goals and metrics for hospitalists and their facilities. Including hospital IQR metrics in the mandatory Medicare physician reporting programs would help to ensure hospitalists receive credit for the care they are providing for hospitalized patients and for the measures they are commonly held accountable for as part of their jobs.

As SHM advocates for hospitalists as the new Merit-Based Incentive Payment System (MIPS) reporting program unrolls as part of MACRA, we will keep these principles in mind: reduce administrative and reporting burdens, make metrics and their resulting data as actionable and useful as possible, and account for the important work hospitalists are doing in their facilities. As we are looking ahead at the future, we encourage you to make sure you are reporting in PQRS for 2016.

For more information about 2016 PQRS reporting, visit www.hospitalmedicine.org/pqrs. TH

Joshua Lapps is SHM’s government relations manager.

The diversity of hospitalist practice—from the variety of settings (such as inpatient acute, observation, post-discharge clinics, and post-acute-care facilities) to the differences in relationships with their facilities—is a strength of the specialty. It reflects the ability of the specialty to adapt to the unique needs of its local patients and institutions.

At the same time, it presents some unique challenges to developing strategies for identifying and assessing hospitalists. As the Medicare physician payment system moves toward value-based payment, hospitalists must report quality measures in the Physician Quality Reporting System (PQRS) or face ever-increasing penalties.

Many hospitalists are part of multispecialty groups aligned with a range of physicians employed by the same facility, including many academic hospitalists and those in integrated healthcare systems. Frequently for hospitalists in these groups, the group reports via a group-practice reporting option that uses measures for outpatient providers, capitalizing on the performances of those outpatient primary care providers in the group and making it generally unnecessary for these hospitalists to independently worry about PQRS reporting. Due to their employment model, they might also be somewhat insulated from seeing firsthand any value-based reimbursement adjustments from Medicare.

Hospitalists commonly are employed by single-specialty groups, medium or large in number of HM-focused providers, or increasingly a mix of hospitalists, emergency physicians, and hospitalists focused on skilled nursing facility (SNF) care. Still others are in small hospitalist groups or independent practitioners of hospital medicine. For these hospitalists, successful reporting of PQRS is important; they cannot rely on broad-based primary care group reporting options, and penalties can have an immediate impact on revenue streams.

PQRS, just like its hospital counterpart, the Inpatient Quality Reporting (IQR) system, was designed for use in an isolated healthcare delivery silo: PQRS was meant for physicians; IQR, for hospitals. This explicit design makes the measuring of hospitalists difficult within the current value-based payment programs because while the patient-care goals of hospitalists and their hospitals overlap, hospitalists are forced to report on physician-level metrics. Following this silo logic, the Centers for Medicare & Medicaid Services (CMS) has been removing physician-level PQRS measures that it views as redundant with facility-level IQR metrics, which has contributed to the detrimental reduction of relevant PQRS metrics for hospitalists over the years.

However, in large part due to the significant advocacy efforts of SHM around last year’s Medicare Access and CHIP Reauthorization Act (MACRA), CMS now has the ability to reverse this trend and include metrics from other programs, such as IQR metrics, as part of the quality or cost component of physician value-based payment. This would help to eliminate the artificial misalignment of quality goals and metrics for hospitalists and their facilities. Including hospital IQR metrics in the mandatory Medicare physician reporting programs would help to ensure hospitalists receive credit for the care they are providing for hospitalized patients and for the measures they are commonly held accountable for as part of their jobs.

As SHM advocates for hospitalists as the new Merit-Based Incentive Payment System (MIPS) reporting program unrolls as part of MACRA, we will keep these principles in mind: reduce administrative and reporting burdens, make metrics and their resulting data as actionable and useful as possible, and account for the important work hospitalists are doing in their facilities. As we are looking ahead at the future, we encourage you to make sure you are reporting in PQRS for 2016.

For more information about 2016 PQRS reporting, visit www.hospitalmedicine.org/pqrs. TH

Joshua Lapps is SHM’s government relations manager.

The diversity of hospitalist practice—from the variety of settings (such as inpatient acute, observation, post-discharge clinics, and post-acute-care facilities) to the differences in relationships with their facilities—is a strength of the specialty. It reflects the ability of the specialty to adapt to the unique needs of its local patients and institutions.

At the same time, it presents some unique challenges to developing strategies for identifying and assessing hospitalists. As the Medicare physician payment system moves toward value-based payment, hospitalists must report quality measures in the Physician Quality Reporting System (PQRS) or face ever-increasing penalties.

Many hospitalists are part of multispecialty groups aligned with a range of physicians employed by the same facility, including many academic hospitalists and those in integrated healthcare systems. Frequently for hospitalists in these groups, the group reports via a group-practice reporting option that uses measures for outpatient providers, capitalizing on the performances of those outpatient primary care providers in the group and making it generally unnecessary for these hospitalists to independently worry about PQRS reporting. Due to their employment model, they might also be somewhat insulated from seeing firsthand any value-based reimbursement adjustments from Medicare.

Hospitalists commonly are employed by single-specialty groups, medium or large in number of HM-focused providers, or increasingly a mix of hospitalists, emergency physicians, and hospitalists focused on skilled nursing facility (SNF) care. Still others are in small hospitalist groups or independent practitioners of hospital medicine. For these hospitalists, successful reporting of PQRS is important; they cannot rely on broad-based primary care group reporting options, and penalties can have an immediate impact on revenue streams.

PQRS, just like its hospital counterpart, the Inpatient Quality Reporting (IQR) system, was designed for use in an isolated healthcare delivery silo: PQRS was meant for physicians; IQR, for hospitals. This explicit design makes the measuring of hospitalists difficult within the current value-based payment programs because while the patient-care goals of hospitalists and their hospitals overlap, hospitalists are forced to report on physician-level metrics. Following this silo logic, the Centers for Medicare & Medicaid Services (CMS) has been removing physician-level PQRS measures that it views as redundant with facility-level IQR metrics, which has contributed to the detrimental reduction of relevant PQRS metrics for hospitalists over the years.

However, in large part due to the significant advocacy efforts of SHM around last year’s Medicare Access and CHIP Reauthorization Act (MACRA), CMS now has the ability to reverse this trend and include metrics from other programs, such as IQR metrics, as part of the quality or cost component of physician value-based payment. This would help to eliminate the artificial misalignment of quality goals and metrics for hospitalists and their facilities. Including hospital IQR metrics in the mandatory Medicare physician reporting programs would help to ensure hospitalists receive credit for the care they are providing for hospitalized patients and for the measures they are commonly held accountable for as part of their jobs.

As SHM advocates for hospitalists as the new Merit-Based Incentive Payment System (MIPS) reporting program unrolls as part of MACRA, we will keep these principles in mind: reduce administrative and reporting burdens, make metrics and their resulting data as actionable and useful as possible, and account for the important work hospitalists are doing in their facilities. As we are looking ahead at the future, we encourage you to make sure you are reporting in PQRS for 2016.

For more information about 2016 PQRS reporting, visit www.hospitalmedicine.org/pqrs. TH

Joshua Lapps is SHM’s government relations manager.

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

New research suggests that people living in the Appalachian region of the US are more likely to develop cancer than people in the rest of the country.

The study showed that Appalachians had a significantly higher incidence of cancer overall and higher rates of many solid tumor malignancies.

However, lymphoma rates were similar between Appalachians and non-Appalachians, and Appalachians had a significantly lower rate of myeloma.

This research was published in Cancer Epidemiology, Biomarkers & Prevention.

“The Appalachian region, which extends from parts of New York to Mississippi, spans 420 counties in 13 US states, and about 25 million people reside in this area,” said study author Reda Wilson, MPH, of the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.

“This region is primarily made up of rural areas, with persistent poverty levels that are at least 20%, which is higher than the national average.”

In 2007, the CDC’s National Program of Cancer Registries (NPCR) published a comprehensive evaluation of cancer incidence rates in Appalachia between 2001 and 2003.

The data showed higher cancer rates in Appalachia than in the rest of the US. However, this publication had some shortcomings, including data that were not available for analysis.

“The current analyses reported here were performed to update the earlier evaluation by expanding the diagnosis years from 2004 to 2011 and including data on 100% of the Appalachian and non-Appalachian populations,” Wilson said.

For this study, Wilson and her colleagues used data from the NPCR and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. Together, NPCR and SEER cover 100% of the US population.

The researchers analyzed the Appalachian population by region (north, central, and south Appalachia), gender, race (black and white only), and Appalachian Regional Commission-designated economic status (distressed, at-risk, transitional, competitive, and attainment). And the team compared these data with data on the non-Appalachian population.

The results showed that cancer incidence rates (IRs) were elevated among Appalachians regardless of how they were categorized. The IRs were per 100,000 people, age-adjusted to the 2000 US standard population.

The IR for all cancers was 565.8 for males in Appalachia and 543.0 for non-Appalachian males (P<0.05). And the cancer IRs for females were 428.7 in Appalachia and 418.2 outside the region (P<0.05).

There was no significant difference between the regions in IRs for lymphomas. The Hodgkin lymphoma IRs were 3.1 in Appalachian males, 3.2 in non-Appalachian males, and 2.5 for females in both regions.

The non-Hodgkin lymphoma IRs were 23.3 in Appalachian males, 23.4 in non-Appalachian males, 16.4 in Appalachian females, and 16.3 in non-Appalachian females.

Myeloma IRs were significantly lower in Appalachia (P<0.05). The myeloma IRs were 7.3 in Appalachian males, 7.5 in non-Appalachian males, 4.7 in Appalachian females, and 4.9 in non-Appalachian females.

There was no significant difference in leukemia IRs among males, but females in Appalachia had a significantly higher leukemia IR (P<0.05). The leukemia IRs were 16.9 in Appalachian males, 16.7 in non-Appalachian males, 10.4 in Appalachian females, and 10.2 in non-Appalachian females.

“Appalachia continues to have higher cancer incidence rates than the rest of the country,” Wilson said. “But a promising finding is that we’re seeing the gap narrow in the incidence rates between Appalachia and non-Appalachia since the 2007 analysis, with the exception of cancers of the oral cavity and pharynx, larynx, lung and bronchus, and thyroid.”

“This study helps identify types of cancer in the Appalachian region that could be reduced through more evidence-based screening and detection. Our study also emphasizes the importance of lifestyle changes needed to prevent and reduce cancer burden.”

The researchers noted that this study did not differentiate urban versus rural areas within each county, and data on screening and risk factors were based on self-reported responses.

Furthermore, cancer IRs were calculated for all ages combined and were not evaluated by age groups. Future analyses will be targeted toward capturing these finer details, Wilson said.

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

New research suggests that people living in the Appalachian region of the US are more likely to develop cancer than people in the rest of the country.

The study showed that Appalachians had a significantly higher incidence of cancer overall and higher rates of many solid tumor malignancies.

However, lymphoma rates were similar between Appalachians and non-Appalachians, and Appalachians had a significantly lower rate of myeloma.

This research was published in Cancer Epidemiology, Biomarkers & Prevention.

“The Appalachian region, which extends from parts of New York to Mississippi, spans 420 counties in 13 US states, and about 25 million people reside in this area,” said study author Reda Wilson, MPH, of the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.

“This region is primarily made up of rural areas, with persistent poverty levels that are at least 20%, which is higher than the national average.”

In 2007, the CDC’s National Program of Cancer Registries (NPCR) published a comprehensive evaluation of cancer incidence rates in Appalachia between 2001 and 2003.

The data showed higher cancer rates in Appalachia than in the rest of the US. However, this publication had some shortcomings, including data that were not available for analysis.

“The current analyses reported here were performed to update the earlier evaluation by expanding the diagnosis years from 2004 to 2011 and including data on 100% of the Appalachian and non-Appalachian populations,” Wilson said.

For this study, Wilson and her colleagues used data from the NPCR and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. Together, NPCR and SEER cover 100% of the US population.

The researchers analyzed the Appalachian population by region (north, central, and south Appalachia), gender, race (black and white only), and Appalachian Regional Commission-designated economic status (distressed, at-risk, transitional, competitive, and attainment). And the team compared these data with data on the non-Appalachian population.

The results showed that cancer incidence rates (IRs) were elevated among Appalachians regardless of how they were categorized. The IRs were per 100,000 people, age-adjusted to the 2000 US standard population.

The IR for all cancers was 565.8 for males in Appalachia and 543.0 for non-Appalachian males (P<0.05). And the cancer IRs for females were 428.7 in Appalachia and 418.2 outside the region (P<0.05).

There was no significant difference between the regions in IRs for lymphomas. The Hodgkin lymphoma IRs were 3.1 in Appalachian males, 3.2 in non-Appalachian males, and 2.5 for females in both regions.

The non-Hodgkin lymphoma IRs were 23.3 in Appalachian males, 23.4 in non-Appalachian males, 16.4 in Appalachian females, and 16.3 in non-Appalachian females.

Myeloma IRs were significantly lower in Appalachia (P<0.05). The myeloma IRs were 7.3 in Appalachian males, 7.5 in non-Appalachian males, 4.7 in Appalachian females, and 4.9 in non-Appalachian females.

There was no significant difference in leukemia IRs among males, but females in Appalachia had a significantly higher leukemia IR (P<0.05). The leukemia IRs were 16.9 in Appalachian males, 16.7 in non-Appalachian males, 10.4 in Appalachian females, and 10.2 in non-Appalachian females.

“Appalachia continues to have higher cancer incidence rates than the rest of the country,” Wilson said. “But a promising finding is that we’re seeing the gap narrow in the incidence rates between Appalachia and non-Appalachia since the 2007 analysis, with the exception of cancers of the oral cavity and pharynx, larynx, lung and bronchus, and thyroid.”

“This study helps identify types of cancer in the Appalachian region that could be reduced through more evidence-based screening and detection. Our study also emphasizes the importance of lifestyle changes needed to prevent and reduce cancer burden.”

The researchers noted that this study did not differentiate urban versus rural areas within each county, and data on screening and risk factors were based on self-reported responses.

Furthermore, cancer IRs were calculated for all ages combined and were not evaluated by age groups. Future analyses will be targeted toward capturing these finer details, Wilson said.

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

New research suggests that people living in the Appalachian region of the US are more likely to develop cancer than people in the rest of the country.

The study showed that Appalachians had a significantly higher incidence of cancer overall and higher rates of many solid tumor malignancies.

However, lymphoma rates were similar between Appalachians and non-Appalachians, and Appalachians had a significantly lower rate of myeloma.

This research was published in Cancer Epidemiology, Biomarkers & Prevention.

“The Appalachian region, which extends from parts of New York to Mississippi, spans 420 counties in 13 US states, and about 25 million people reside in this area,” said study author Reda Wilson, MPH, of the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.

“This region is primarily made up of rural areas, with persistent poverty levels that are at least 20%, which is higher than the national average.”

In 2007, the CDC’s National Program of Cancer Registries (NPCR) published a comprehensive evaluation of cancer incidence rates in Appalachia between 2001 and 2003.

The data showed higher cancer rates in Appalachia than in the rest of the US. However, this publication had some shortcomings, including data that were not available for analysis.

“The current analyses reported here were performed to update the earlier evaluation by expanding the diagnosis years from 2004 to 2011 and including data on 100% of the Appalachian and non-Appalachian populations,” Wilson said.

For this study, Wilson and her colleagues used data from the NPCR and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. Together, NPCR and SEER cover 100% of the US population.

The researchers analyzed the Appalachian population by region (north, central, and south Appalachia), gender, race (black and white only), and Appalachian Regional Commission-designated economic status (distressed, at-risk, transitional, competitive, and attainment). And the team compared these data with data on the non-Appalachian population.

The results showed that cancer incidence rates (IRs) were elevated among Appalachians regardless of how they were categorized. The IRs were per 100,000 people, age-adjusted to the 2000 US standard population.

The IR for all cancers was 565.8 for males in Appalachia and 543.0 for non-Appalachian males (P<0.05). And the cancer IRs for females were 428.7 in Appalachia and 418.2 outside the region (P<0.05).

There was no significant difference between the regions in IRs for lymphomas. The Hodgkin lymphoma IRs were 3.1 in Appalachian males, 3.2 in non-Appalachian males, and 2.5 for females in both regions.

The non-Hodgkin lymphoma IRs were 23.3 in Appalachian males, 23.4 in non-Appalachian males, 16.4 in Appalachian females, and 16.3 in non-Appalachian females.

Myeloma IRs were significantly lower in Appalachia (P<0.05). The myeloma IRs were 7.3 in Appalachian males, 7.5 in non-Appalachian males, 4.7 in Appalachian females, and 4.9 in non-Appalachian females.

There was no significant difference in leukemia IRs among males, but females in Appalachia had a significantly higher leukemia IR (P<0.05). The leukemia IRs were 16.9 in Appalachian males, 16.7 in non-Appalachian males, 10.4 in Appalachian females, and 10.2 in non-Appalachian females.

“Appalachia continues to have higher cancer incidence rates than the rest of the country,” Wilson said. “But a promising finding is that we’re seeing the gap narrow in the incidence rates between Appalachia and non-Appalachia since the 2007 analysis, with the exception of cancers of the oral cavity and pharynx, larynx, lung and bronchus, and thyroid.”

“This study helps identify types of cancer in the Appalachian region that could be reduced through more evidence-based screening and detection. Our study also emphasizes the importance of lifestyle changes needed to prevent and reduce cancer burden.”

The researchers noted that this study did not differentiate urban versus rural areas within each county, and data on screening and risk factors were based on self-reported responses.

Furthermore, cancer IRs were calculated for all ages combined and were not evaluated by age groups. Future analyses will be targeted toward capturing these finer details, Wilson said.

Panobinostat (Farydak)

Photo courtesy of Novartis

The National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending panobinostat (Farydak) be made available on the National Health Service.

In the European Union, panobinostat is approved for use in combination with bortezomib and dexamethasone to treat adults with relapsed and/or refractory multiple myeloma who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent.

NICE’s recommendation of panobinostat is contingent upon the drug being provided with the discount agreed upon in the patient access scheme.

NICE previously issued a guidance in which it did not recommend panobinostat, but the drug’s manufacturer, Novartis, submitted a revised economic analysis that allowed NICE to recommend the drug.

Novartis has agreed to a patient access scheme with the Department of Health. This scheme provides a discount to the list price of panobinostat, with the discount applied at the point of purchase or invoice.

The level of the discount is commercial in confidence, but the Department of Health said this patient access scheme does not constitute an excessive administrative burden on the National Health Service.

Panobinostat costs £776 per 20 mg tablet. The recommended starting dose is 20 mg, taken orally once a day, on days 1, 3, 5, 8, 10, and 12 of a 21-day cycle. Patients should receive panobinostat for 8 cycles. If they show clinical benefit, they should continue the treatment for 4 additional cycles of 6 weeks each. 

Panobinostat (Farydak)

Photo courtesy of Novartis

The National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending panobinostat (Farydak) be made available on the National Health Service.

In the European Union, panobinostat is approved for use in combination with bortezomib and dexamethasone to treat adults with relapsed and/or refractory multiple myeloma who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent.

NICE’s recommendation of panobinostat is contingent upon the drug being provided with the discount agreed upon in the patient access scheme.

NICE previously issued a guidance in which it did not recommend panobinostat, but the drug’s manufacturer, Novartis, submitted a revised economic analysis that allowed NICE to recommend the drug.

Novartis has agreed to a patient access scheme with the Department of Health. This scheme provides a discount to the list price of panobinostat, with the discount applied at the point of purchase or invoice.

The level of the discount is commercial in confidence, but the Department of Health said this patient access scheme does not constitute an excessive administrative burden on the National Health Service.

Panobinostat costs £776 per 20 mg tablet. The recommended starting dose is 20 mg, taken orally once a day, on days 1, 3, 5, 8, 10, and 12 of a 21-day cycle. Patients should receive panobinostat for 8 cycles. If they show clinical benefit, they should continue the treatment for 4 additional cycles of 6 weeks each. 

Panobinostat (Farydak)

Photo courtesy of Novartis

The National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending panobinostat (Farydak) be made available on the National Health Service.

In the European Union, panobinostat is approved for use in combination with bortezomib and dexamethasone to treat adults with relapsed and/or refractory multiple myeloma who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent.

NICE’s recommendation of panobinostat is contingent upon the drug being provided with the discount agreed upon in the patient access scheme.

NICE previously issued a guidance in which it did not recommend panobinostat, but the drug’s manufacturer, Novartis, submitted a revised economic analysis that allowed NICE to recommend the drug.

Novartis has agreed to a patient access scheme with the Department of Health. This scheme provides a discount to the list price of panobinostat, with the discount applied at the point of purchase or invoice.

The level of the discount is commercial in confidence, but the Department of Health said this patient access scheme does not constitute an excessive administrative burden on the National Health Service.

Panobinostat costs £776 per 20 mg tablet. The recommended starting dose is 20 mg, taken orally once a day, on days 1, 3, 5, 8, 10, and 12 of a 21-day cycle. Patients should receive panobinostat for 8 cycles. If they show clinical benefit, they should continue the treatment for 4 additional cycles of 6 weeks each. 

DNA helix

Image by Spencer Phillips

Researchers say they have made an improvement in CRISPR-Cas9 technology that enables a success rate of 60% when replacing a short stretch of DNA

with another.

They say this technique could be especially useful when trying to repair genetic mutations that cause hereditary diseases, such as sickle cell disease.

The technique allows researchers to patch an abnormal section of DNA with the normal sequence and potentially correct the defect.

“The exciting thing about CRISPR-Cas9 is the promise of fixing genes in place in our genome, but the efficiency for that can be very low,” said Jacob Corn, PhD, of the University of California, Berkeley.

“If you think of gene editing as a word processor, we know how to cut, but we need a more efficient way to paste and glue a new piece of DNA where we make the cut.”

Dr Corn and his colleagues described their more efficient technique in Nature Biotechnology.

“In cases where you want to change very small regions of DNA, up to 30 base pairs, this technique would be extremely effective,” said study author Christopher Richardson, PhD, of the University of California, Berkeley.

Dr Richardson invented the new approach after finding that the Cas9 protein, which does the actual DNA cutting, remains attached to the chromosome for up to 6 hours, long after it has sliced through the double-stranded DNA.

Dr Richardson looked closely at the Cas9 protein bound to the 2 strands of DNA and discovered that while the protein hangs onto 3 of the cut ends, 1 of the ends remains free.

When Cas9 cuts DNA, repair systems in the cell can grab a piece of complementary DNA, called a template, to repair the cut. Researchers can add templates containing changes that alter existing sequences in the genome.

Dr Richardson reasoned that bringing the substitute template directly to the site of the cut would improve the patching efficiency. So he constructed a piece of DNA that matches the free DNA end and carries the genetic sequence to be inserted at the other end.

The technique allowed successful repair of a mutation with up to 60% efficiency.

“Our data indicate that Cas9 breaks could be different, at a molecular level, from breaks generated by other targeted nucleases, such as TALENS and zinc-finger nucleases, which suggests that strategies like the ones we are using can give you more efficient repair of Cas9 breaks,” Dr Richardson said.

The researchers also showed that variants of the Cas9 protein that bind DNA but do not cut can also paste a new DNA sequence at the binding site, possibly by forming a “bubble” structure on the target DNA that also acts to attract the repair template.

Gene editing using Cas9 without genome cutting could be safer than typical gene editing by removing the danger of off-target cutting in the genome, Dr Corn said.

DNA helix

Image by Spencer Phillips

Researchers say they have made an improvement in CRISPR-Cas9 technology that enables a success rate of 60% when replacing a short stretch of DNA

with another.

They say this technique could be especially useful when trying to repair genetic mutations that cause hereditary diseases, such as sickle cell disease.

The technique allows researchers to patch an abnormal section of DNA with the normal sequence and potentially correct the defect.

“The exciting thing about CRISPR-Cas9 is the promise of fixing genes in place in our genome, but the efficiency for that can be very low,” said Jacob Corn, PhD, of the University of California, Berkeley.

“If you think of gene editing as a word processor, we know how to cut, but we need a more efficient way to paste and glue a new piece of DNA where we make the cut.”

Dr Corn and his colleagues described their more efficient technique in Nature Biotechnology.

“In cases where you want to change very small regions of DNA, up to 30 base pairs, this technique would be extremely effective,” said study author Christopher Richardson, PhD, of the University of California, Berkeley.

Dr Richardson invented the new approach after finding that the Cas9 protein, which does the actual DNA cutting, remains attached to the chromosome for up to 6 hours, long after it has sliced through the double-stranded DNA.

Dr Richardson looked closely at the Cas9 protein bound to the 2 strands of DNA and discovered that while the protein hangs onto 3 of the cut ends, 1 of the ends remains free.

When Cas9 cuts DNA, repair systems in the cell can grab a piece of complementary DNA, called a template, to repair the cut. Researchers can add templates containing changes that alter existing sequences in the genome.

Dr Richardson reasoned that bringing the substitute template directly to the site of the cut would improve the patching efficiency. So he constructed a piece of DNA that matches the free DNA end and carries the genetic sequence to be inserted at the other end.

The technique allowed successful repair of a mutation with up to 60% efficiency.

“Our data indicate that Cas9 breaks could be different, at a molecular level, from breaks generated by other targeted nucleases, such as TALENS and zinc-finger nucleases, which suggests that strategies like the ones we are using can give you more efficient repair of Cas9 breaks,” Dr Richardson said.

The researchers also showed that variants of the Cas9 protein that bind DNA but do not cut can also paste a new DNA sequence at the binding site, possibly by forming a “bubble” structure on the target DNA that also acts to attract the repair template.

Gene editing using Cas9 without genome cutting could be safer than typical gene editing by removing the danger of off-target cutting in the genome, Dr Corn said.

DNA helix

Image by Spencer Phillips

Researchers say they have made an improvement in CRISPR-Cas9 technology that enables a success rate of 60% when replacing a short stretch of DNA

with another.

They say this technique could be especially useful when trying to repair genetic mutations that cause hereditary diseases, such as sickle cell disease.

The technique allows researchers to patch an abnormal section of DNA with the normal sequence and potentially correct the defect.

“The exciting thing about CRISPR-Cas9 is the promise of fixing genes in place in our genome, but the efficiency for that can be very low,” said Jacob Corn, PhD, of the University of California, Berkeley.

“If you think of gene editing as a word processor, we know how to cut, but we need a more efficient way to paste and glue a new piece of DNA where we make the cut.”

Dr Corn and his colleagues described their more efficient technique in Nature Biotechnology.

“In cases where you want to change very small regions of DNA, up to 30 base pairs, this technique would be extremely effective,” said study author Christopher Richardson, PhD, of the University of California, Berkeley.

Dr Richardson invented the new approach after finding that the Cas9 protein, which does the actual DNA cutting, remains attached to the chromosome for up to 6 hours, long after it has sliced through the double-stranded DNA.

Dr Richardson looked closely at the Cas9 protein bound to the 2 strands of DNA and discovered that while the protein hangs onto 3 of the cut ends, 1 of the ends remains free.

When Cas9 cuts DNA, repair systems in the cell can grab a piece of complementary DNA, called a template, to repair the cut. Researchers can add templates containing changes that alter existing sequences in the genome.

Dr Richardson reasoned that bringing the substitute template directly to the site of the cut would improve the patching efficiency. So he constructed a piece of DNA that matches the free DNA end and carries the genetic sequence to be inserted at the other end.

The technique allowed successful repair of a mutation with up to 60% efficiency.

“Our data indicate that Cas9 breaks could be different, at a molecular level, from breaks generated by other targeted nucleases, such as TALENS and zinc-finger nucleases, which suggests that strategies like the ones we are using can give you more efficient repair of Cas9 breaks,” Dr Richardson said.

The researchers also showed that variants of the Cas9 protein that bind DNA but do not cut can also paste a new DNA sequence at the binding site, possibly by forming a “bubble” structure on the target DNA that also acts to attract the repair template.

Gene editing using Cas9 without genome cutting could be safer than typical gene editing by removing the danger of off-target cutting in the genome, Dr Corn said.

Prescription medications

Photo courtesy of the CDC

An article published in Blood suggests pharmaceutical companies use several strategies to keep affordable generic drugs from the US market.

“The timely availability of affordable generic drugs is the difference between life or death for patients with cancer and other diseases who cannot afford brand-name pharmaceuticals, the majority of which are priced at monopoly levels and protected by 20-year patents,” said lead author Hagop Kantarjian, MD, of The University of Texas MD Anderson Cancer Center in Houston.

“Unfortunately, these sorely needed generics are increasingly out of reach. As we sought to understand what keeps these affordable drugs from the market, we identified several specific strategies that pharmaceutical companies use to extend their patents and eliminate competition.”

Dr Kantarjian and his colleagues assert that pharmaceutical companies use a variety of strategies to delay, prevent, and suppress the timely availability of affordable generic drugs.

Among them, the authors detail “pay-for-delay,” in which the company that owns the patent pays a generic company to delay entry into the market. The Federal Trade Commission estimates that the pay-for-delay settlements cost taxpayers, insurance companies, and consumers approximately $3.5 billion per year.

In other cases detailed in the article, the patent-holder deters competition by creating its own version of drugs at generic prices.

While this practice may reduce costs for consumers by 4% to 8% in the short-term, the authors suggest that companies often use the authorized generics as a bargaining chip in “pay-for-delay” deals, pledging not to release their own drugs in return for the true generic company promising to delay market entry.

Other strategies the authors discuss include investing heavily in advertising the brand-name drug (often spending more on marketing than on research and development) and lobbying for laws that prevent patients from importing cheaper generics from other countries, which the authors write can cost as little as 20% to 50% of US prices.

The authors also say some drug companies buy out competitors and then increase the price of a newly acquired generic drug by several fold overnight.

In addition, the authors describe a strategy they call “product hopping,” which involves switching the market for a drug to a reformulated “new and improved” version with a slightly different tablet or capsule dose that offers no therapeutic advantage over the original but has a later-expiring patent.

The company then heavily advertises the new brand-name drug in an effort to convince patients and physicians to switch.

As a result, when the generic version of the original becomes available, pharmacists cannot substitute it for the new branded version because state laws allow substitution only if certain characteristics, such as dosing, remain the same.

In recognition of the harm and expense the authors suggest these strategies impart on both patients and the economy, they propose several solutions that would support timely access to affordable generic drugs.

These include allowing Medicare to negotiate drug prices, monitoring and penalizing pay-for-delay deals, allowing transportation of pharmaceuticals across borders for individual use, and challenging weak patents.

“Each day, in my clinic, I see leukemia patients who are harmed because they cannot afford their treatment, some risking death because they cannot pay for the medicine keeping them alive,” Dr Kantarjian said.

“Overall, these strategies demonstrate that the trend of high brand-name drug prices has recently infected generic drugs, as companies value profit at the expense of long-term utility to society. We must be vigilant in recognizing these strategies and advocating for solutions that will allow companies to accomplish their dual mission: make reasonable profits and help save and/or improve patients’ lives.”

Prescription medications

Photo courtesy of the CDC

An article published in Blood suggests pharmaceutical companies use several strategies to keep affordable generic drugs from the US market.

“The timely availability of affordable generic drugs is the difference between life or death for patients with cancer and other diseases who cannot afford brand-name pharmaceuticals, the majority of which are priced at monopoly levels and protected by 20-year patents,” said lead author Hagop Kantarjian, MD, of The University of Texas MD Anderson Cancer Center in Houston.

“Unfortunately, these sorely needed generics are increasingly out of reach. As we sought to understand what keeps these affordable drugs from the market, we identified several specific strategies that pharmaceutical companies use to extend their patents and eliminate competition.”

Dr Kantarjian and his colleagues assert that pharmaceutical companies use a variety of strategies to delay, prevent, and suppress the timely availability of affordable generic drugs.

Among them, the authors detail “pay-for-delay,” in which the company that owns the patent pays a generic company to delay entry into the market. The Federal Trade Commission estimates that the pay-for-delay settlements cost taxpayers, insurance companies, and consumers approximately $3.5 billion per year.

In other cases detailed in the article, the patent-holder deters competition by creating its own version of drugs at generic prices.

While this practice may reduce costs for consumers by 4% to 8% in the short-term, the authors suggest that companies often use the authorized generics as a bargaining chip in “pay-for-delay” deals, pledging not to release their own drugs in return for the true generic company promising to delay market entry.

Other strategies the authors discuss include investing heavily in advertising the brand-name drug (often spending more on marketing than on research and development) and lobbying for laws that prevent patients from importing cheaper generics from other countries, which the authors write can cost as little as 20% to 50% of US prices.

The authors also say some drug companies buy out competitors and then increase the price of a newly acquired generic drug by several fold overnight.

In addition, the authors describe a strategy they call “product hopping,” which involves switching the market for a drug to a reformulated “new and improved” version with a slightly different tablet or capsule dose that offers no therapeutic advantage over the original but has a later-expiring patent.

The company then heavily advertises the new brand-name drug in an effort to convince patients and physicians to switch.

As a result, when the generic version of the original becomes available, pharmacists cannot substitute it for the new branded version because state laws allow substitution only if certain characteristics, such as dosing, remain the same.

In recognition of the harm and expense the authors suggest these strategies impart on both patients and the economy, they propose several solutions that would support timely access to affordable generic drugs.

These include allowing Medicare to negotiate drug prices, monitoring and penalizing pay-for-delay deals, allowing transportation of pharmaceuticals across borders for individual use, and challenging weak patents.

“Each day, in my clinic, I see leukemia patients who are harmed because they cannot afford their treatment, some risking death because they cannot pay for the medicine keeping them alive,” Dr Kantarjian said.

“Overall, these strategies demonstrate that the trend of high brand-name drug prices has recently infected generic drugs, as companies value profit at the expense of long-term utility to society. We must be vigilant in recognizing these strategies and advocating for solutions that will allow companies to accomplish their dual mission: make reasonable profits and help save and/or improve patients’ lives.”

Prescription medications

Photo courtesy of the CDC

An article published in Blood suggests pharmaceutical companies use several strategies to keep affordable generic drugs from the US market.

“The timely availability of affordable generic drugs is the difference between life or death for patients with cancer and other diseases who cannot afford brand-name pharmaceuticals, the majority of which are priced at monopoly levels and protected by 20-year patents,” said lead author Hagop Kantarjian, MD, of The University of Texas MD Anderson Cancer Center in Houston.

“Unfortunately, these sorely needed generics are increasingly out of reach. As we sought to understand what keeps these affordable drugs from the market, we identified several specific strategies that pharmaceutical companies use to extend their patents and eliminate competition.”

Dr Kantarjian and his colleagues assert that pharmaceutical companies use a variety of strategies to delay, prevent, and suppress the timely availability of affordable generic drugs.

Among them, the authors detail “pay-for-delay,” in which the company that owns the patent pays a generic company to delay entry into the market. The Federal Trade Commission estimates that the pay-for-delay settlements cost taxpayers, insurance companies, and consumers approximately $3.5 billion per year.

In other cases detailed in the article, the patent-holder deters competition by creating its own version of drugs at generic prices.

While this practice may reduce costs for consumers by 4% to 8% in the short-term, the authors suggest that companies often use the authorized generics as a bargaining chip in “pay-for-delay” deals, pledging not to release their own drugs in return for the true generic company promising to delay market entry.

Other strategies the authors discuss include investing heavily in advertising the brand-name drug (often spending more on marketing than on research and development) and lobbying for laws that prevent patients from importing cheaper generics from other countries, which the authors write can cost as little as 20% to 50% of US prices.

The authors also say some drug companies buy out competitors and then increase the price of a newly acquired generic drug by several fold overnight.

In addition, the authors describe a strategy they call “product hopping,” which involves switching the market for a drug to a reformulated “new and improved” version with a slightly different tablet or capsule dose that offers no therapeutic advantage over the original but has a later-expiring patent.

The company then heavily advertises the new brand-name drug in an effort to convince patients and physicians to switch.

As a result, when the generic version of the original becomes available, pharmacists cannot substitute it for the new branded version because state laws allow substitution only if certain characteristics, such as dosing, remain the same.

In recognition of the harm and expense the authors suggest these strategies impart on both patients and the economy, they propose several solutions that would support timely access to affordable generic drugs.

These include allowing Medicare to negotiate drug prices, monitoring and penalizing pay-for-delay deals, allowing transportation of pharmaceuticals across borders for individual use, and challenging weak patents.

“Each day, in my clinic, I see leukemia patients who are harmed because they cannot afford their treatment, some risking death because they cannot pay for the medicine keeping them alive,” Dr Kantarjian said.

“Overall, these strategies demonstrate that the trend of high brand-name drug prices has recently infected generic drugs, as companies value profit at the expense of long-term utility to society. We must be vigilant in recognizing these strategies and advocating for solutions that will allow companies to accomplish their dual mission: make reasonable profits and help save and/or improve patients’ lives.”