What Matters

Nephrolithiasis occurs in 5%-12% of the population and frequently on Friday afternoons. Eighty percent of them are calcium oxalate, 20% are in the ureter on presentation, and all of the ones we see hurt ... a lot. We may have more of these with the launch of a new weight-loss medication containing topiramate ER. Topiramate is a carbonic anhydrase inhibitor associated with an increased risk for serum metabolic acidosis and kidney stones.

We have become more comfortable conservatively managing uninfected stones even if there is a degree of hydronephrosis. Stones that are less than 5 mm in size have an 85% chance of passing spontaneously, those that are 5-10 mm have a 50% chance, and those larger than 8 mm have a 20% chance. A systematic review demonstrated the efficacy of tamsulosin for facilitating expulsion of distal ureteral stones less than 10 mm in size (19% improvement) (Urol. Int. 2012;89:107-15). Tamsulosin antagonizes the alpha-1 adrenergic receptors that are present throughout the ureter but have a high concentration in the ureter’s distal third.

But sometimes the stones are stubborn. Is there anything else we can do?

Building on the theory that kidney stones in the ureter cause inflammation, investigators in India conducted a clinical trial investigating the safety and efficacy of alpha-1 adrenergic receptor antagonists combined with prednisolone for the expulsion of distal ureter stones (Korean J. Urol. 2013;54:311-5).

A total of 120 adults presenting with distal ureteral stones (below common iliac vessels as assessed by CT) between 5 mm and 10 mm in size were randomized to one of three groups: A) 0.4 mg tamsulosin plus 5 mg prednisolone; B) naftopidil (a selective alpha-1 adrenergic receptor antagonist not available in the United States) plus 5 mg prednisolone; and C) watchful waiting. Prednisolone was continued for a maximum of 1 week, and the alpha-1 adrenergic receptor antagonist was continued for a maximum of 4 weeks. Patients received intramuscular diclofenac as needed for pain.

The stone expulsion rate was 70%, 87.5%, and 32.5% in groups A, B, and C, respectively. Expulsion rates for groups A and B were significantly greater than group C but not significantly different from one another. In group A, the expulsion rate in the first week was 12.5% and 65% in the second week. No patients expelled stones in the third or fourth week. Use of analgesics was significantly lower in groups A and B. No serious adverse events were noted.

This study does not actually inform us if tamsulosin alone is better than tamsulosin plus steroids, but a previous study from 2006 suggests that this is the case (Eur. Urol. 2006;50:339-44). However, that 2006 study used a steroid equivalent dose five times the dose used in the current study. Recall that prednisolone is equivalent to prednisone, and 5 mg is not huge.

So, for patients with no contraindications for steroids, this might be a reasonable option.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

Nephrolithiasis occurs in 5%-12% of the population and frequently on Friday afternoons. Eighty percent of them are calcium oxalate, 20% are in the ureter on presentation, and all of the ones we see hurt ... a lot. We may have more of these with the launch of a new weight-loss medication containing topiramate ER. Topiramate is a carbonic anhydrase inhibitor associated with an increased risk for serum metabolic acidosis and kidney stones.

We have become more comfortable conservatively managing uninfected stones even if there is a degree of hydronephrosis. Stones that are less than 5 mm in size have an 85% chance of passing spontaneously, those that are 5-10 mm have a 50% chance, and those larger than 8 mm have a 20% chance. A systematic review demonstrated the efficacy of tamsulosin for facilitating expulsion of distal ureteral stones less than 10 mm in size (19% improvement) (Urol. Int. 2012;89:107-15). Tamsulosin antagonizes the alpha-1 adrenergic receptors that are present throughout the ureter but have a high concentration in the ureter’s distal third.

But sometimes the stones are stubborn. Is there anything else we can do?

Building on the theory that kidney stones in the ureter cause inflammation, investigators in India conducted a clinical trial investigating the safety and efficacy of alpha-1 adrenergic receptor antagonists combined with prednisolone for the expulsion of distal ureter stones (Korean J. Urol. 2013;54:311-5).

A total of 120 adults presenting with distal ureteral stones (below common iliac vessels as assessed by CT) between 5 mm and 10 mm in size were randomized to one of three groups: A) 0.4 mg tamsulosin plus 5 mg prednisolone; B) naftopidil (a selective alpha-1 adrenergic receptor antagonist not available in the United States) plus 5 mg prednisolone; and C) watchful waiting. Prednisolone was continued for a maximum of 1 week, and the alpha-1 adrenergic receptor antagonist was continued for a maximum of 4 weeks. Patients received intramuscular diclofenac as needed for pain.

The stone expulsion rate was 70%, 87.5%, and 32.5% in groups A, B, and C, respectively. Expulsion rates for groups A and B were significantly greater than group C but not significantly different from one another. In group A, the expulsion rate in the first week was 12.5% and 65% in the second week. No patients expelled stones in the third or fourth week. Use of analgesics was significantly lower in groups A and B. No serious adverse events were noted.

This study does not actually inform us if tamsulosin alone is better than tamsulosin plus steroids, but a previous study from 2006 suggests that this is the case (Eur. Urol. 2006;50:339-44). However, that 2006 study used a steroid equivalent dose five times the dose used in the current study. Recall that prednisolone is equivalent to prednisone, and 5 mg is not huge.

So, for patients with no contraindications for steroids, this might be a reasonable option.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

Nephrolithiasis occurs in 5%-12% of the population and frequently on Friday afternoons. Eighty percent of them are calcium oxalate, 20% are in the ureter on presentation, and all of the ones we see hurt ... a lot. We may have more of these with the launch of a new weight-loss medication containing topiramate ER. Topiramate is a carbonic anhydrase inhibitor associated with an increased risk for serum metabolic acidosis and kidney stones.

We have become more comfortable conservatively managing uninfected stones even if there is a degree of hydronephrosis. Stones that are less than 5 mm in size have an 85% chance of passing spontaneously, those that are 5-10 mm have a 50% chance, and those larger than 8 mm have a 20% chance. A systematic review demonstrated the efficacy of tamsulosin for facilitating expulsion of distal ureteral stones less than 10 mm in size (19% improvement) (Urol. Int. 2012;89:107-15). Tamsulosin antagonizes the alpha-1 adrenergic receptors that are present throughout the ureter but have a high concentration in the ureter’s distal third.

But sometimes the stones are stubborn. Is there anything else we can do?

Building on the theory that kidney stones in the ureter cause inflammation, investigators in India conducted a clinical trial investigating the safety and efficacy of alpha-1 adrenergic receptor antagonists combined with prednisolone for the expulsion of distal ureter stones (Korean J. Urol. 2013;54:311-5).

A total of 120 adults presenting with distal ureteral stones (below common iliac vessels as assessed by CT) between 5 mm and 10 mm in size were randomized to one of three groups: A) 0.4 mg tamsulosin plus 5 mg prednisolone; B) naftopidil (a selective alpha-1 adrenergic receptor antagonist not available in the United States) plus 5 mg prednisolone; and C) watchful waiting. Prednisolone was continued for a maximum of 1 week, and the alpha-1 adrenergic receptor antagonist was continued for a maximum of 4 weeks. Patients received intramuscular diclofenac as needed for pain.

The stone expulsion rate was 70%, 87.5%, and 32.5% in groups A, B, and C, respectively. Expulsion rates for groups A and B were significantly greater than group C but not significantly different from one another. In group A, the expulsion rate in the first week was 12.5% and 65% in the second week. No patients expelled stones in the third or fourth week. Use of analgesics was significantly lower in groups A and B. No serious adverse events were noted.

This study does not actually inform us if tamsulosin alone is better than tamsulosin plus steroids, but a previous study from 2006 suggests that this is the case (Eur. Urol. 2006;50:339-44). However, that 2006 study used a steroid equivalent dose five times the dose used in the current study. Recall that prednisolone is equivalent to prednisone, and 5 mg is not huge.

So, for patients with no contraindications for steroids, this might be a reasonable option.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

Herpes simplex virus type 1 is one of the most common human infections, with more than 90% of the population exposed. One-quarter of the population with HSV infection experiences periodic viral reactivation, which is commonly associated with herpes labialis lesions. Environmental factors are common triggers, such as sunlight, fever, or stress. Herpes labialis lesions result in significant psychosocial impairment and pain for some sufferers.

Clinical strategies for recurrent herpes labialis (RHL) range from observation to chronic suppressive therapy with nucleoside derivatives (acyclovir, valacyclovir, and famciclovir).

But given that chronic suppressive therapy can be expensive, how effective is it for preventing RHL?

Hanieh Rahimi, a former epidemiology and biostatistics student and current dental student at the University of Western Ontario, London, Canada, and her colleagues attempted to answer this question by conducting a review of the literature, including randomized controlled clinical trials including two arms evaluating both topical and systemic agents (Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2012;113:618-27). In these studies, a diagnosis of RHL was confirmed by history and/or laboratory testing. Studies were excluded if they included patients who were immunocompromised, had kidney or liver disease, or were receiving chemotherapy. Outcomes included episodes of recurrent, adverse events, and patient satisfaction.

Investigators included 10 studies with usable outcome data. When all studies were pooled, antiviral agents were associated with a significant reduction in RHL recurrences (relative risk, 0.70; 95% CI, 0.55-0.89). Acyclovir was more effective than placebo (RR, 0.68; 95% CI, 0.48-0.97). Valacyclovir was also superior to placebo (RR, 0.65; 95% CI, 0.43-0.98). Systemic therapy was superior to topical therapy (RR, 0.51; 95% CI, 0.29-0.88). Medication was well tolerated overall.

Prophylactic therapy appears to be effective for RHL. Patients without a prodrome (that is, pain, tingling, burning) to trigger dosing and who have painful or disfiguring lesions may be the ideal candidates for suppressive therapy. Cost considerations need to be made when choosing prophylactic therapy.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

Herpes simplex virus type 1 is one of the most common human infections, with more than 90% of the population exposed. One-quarter of the population with HSV infection experiences periodic viral reactivation, which is commonly associated with herpes labialis lesions. Environmental factors are common triggers, such as sunlight, fever, or stress. Herpes labialis lesions result in significant psychosocial impairment and pain for some sufferers.

Clinical strategies for recurrent herpes labialis (RHL) range from observation to chronic suppressive therapy with nucleoside derivatives (acyclovir, valacyclovir, and famciclovir).

But given that chronic suppressive therapy can be expensive, how effective is it for preventing RHL?

Hanieh Rahimi, a former epidemiology and biostatistics student and current dental student at the University of Western Ontario, London, Canada, and her colleagues attempted to answer this question by conducting a review of the literature, including randomized controlled clinical trials including two arms evaluating both topical and systemic agents (Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2012;113:618-27). In these studies, a diagnosis of RHL was confirmed by history and/or laboratory testing. Studies were excluded if they included patients who were immunocompromised, had kidney or liver disease, or were receiving chemotherapy. Outcomes included episodes of recurrent, adverse events, and patient satisfaction.

Investigators included 10 studies with usable outcome data. When all studies were pooled, antiviral agents were associated with a significant reduction in RHL recurrences (relative risk, 0.70; 95% CI, 0.55-0.89). Acyclovir was more effective than placebo (RR, 0.68; 95% CI, 0.48-0.97). Valacyclovir was also superior to placebo (RR, 0.65; 95% CI, 0.43-0.98). Systemic therapy was superior to topical therapy (RR, 0.51; 95% CI, 0.29-0.88). Medication was well tolerated overall.

Prophylactic therapy appears to be effective for RHL. Patients without a prodrome (that is, pain, tingling, burning) to trigger dosing and who have painful or disfiguring lesions may be the ideal candidates for suppressive therapy. Cost considerations need to be made when choosing prophylactic therapy.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

Herpes simplex virus type 1 is one of the most common human infections, with more than 90% of the population exposed. One-quarter of the population with HSV infection experiences periodic viral reactivation, which is commonly associated with herpes labialis lesions. Environmental factors are common triggers, such as sunlight, fever, or stress. Herpes labialis lesions result in significant psychosocial impairment and pain for some sufferers.

Clinical strategies for recurrent herpes labialis (RHL) range from observation to chronic suppressive therapy with nucleoside derivatives (acyclovir, valacyclovir, and famciclovir).

But given that chronic suppressive therapy can be expensive, how effective is it for preventing RHL?

Hanieh Rahimi, a former epidemiology and biostatistics student and current dental student at the University of Western Ontario, London, Canada, and her colleagues attempted to answer this question by conducting a review of the literature, including randomized controlled clinical trials including two arms evaluating both topical and systemic agents (Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2012;113:618-27). In these studies, a diagnosis of RHL was confirmed by history and/or laboratory testing. Studies were excluded if they included patients who were immunocompromised, had kidney or liver disease, or were receiving chemotherapy. Outcomes included episodes of recurrent, adverse events, and patient satisfaction.

Investigators included 10 studies with usable outcome data. When all studies were pooled, antiviral agents were associated with a significant reduction in RHL recurrences (relative risk, 0.70; 95% CI, 0.55-0.89). Acyclovir was more effective than placebo (RR, 0.68; 95% CI, 0.48-0.97). Valacyclovir was also superior to placebo (RR, 0.65; 95% CI, 0.43-0.98). Systemic therapy was superior to topical therapy (RR, 0.51; 95% CI, 0.29-0.88). Medication was well tolerated overall.

Prophylactic therapy appears to be effective for RHL. Patients without a prodrome (that is, pain, tingling, burning) to trigger dosing and who have painful or disfiguring lesions may be the ideal candidates for suppressive therapy. Cost considerations need to be made when choosing prophylactic therapy.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

Management of the ongoing prescription-opioid health crisis in the United States will require a multifaceted approach. Federal authorities must find ways to reduce opioid use within a regulatory framework. Pharmaceutical companies should continue to seek ways to reduce inappropriate use through drug formulation, such as modifying drug delivery when oxycodone is crushed and snorted. Serious patient education on drug abuse liability before prescribing, by the way, remains uncharted water.

But our challenge as prescribing clinicians may be to overcome old drug stereotypes and established practice patterns. If an opioid is deemed to be clinically necessary for pain control, maybe we need to be less willing to prescribe some opioids in favor of others.

Drug dependence – defined clinically by tolerance and withdrawal – with long-term opioid use is a predictable but acceptable and manageable risk in the face of chronic pain. Drug abuse – defined clinically by aberrant behaviors and adverse psychosocial consequences – is what we should be striving to avoid. The national prescription drug–abuse problem makes life more difficult for patients who have legitimate needs for opioid pain control.

The opioids we use in clinical medicine are all euphorigenic, but select opioids are preferred among the drug-abusing population. In this regard, not all opioids are created equal. Drug abuse is more likely with drugs that give the user a sensation of euphoria or a "high."

Dr. Rachel Wightman of New York University and her colleagues recently published a review of the literature on "opioid likeability" and "opioid abuse liability" (J. Med. Toxicol. 2012;8:335-40).

The studies included in the review showed no clinical difference between abuse liability of morphine and hydrocodone, with similar subjective positive and negative effects. In contrast, oxycodone demonstrated high subjective attractiveness.

Although morphine may be associated with more side effects than oxycodone, it is an effective opioid analgesic that is half the strength of oxycodone. Would it be unreasonable for us to tell our patients that they will receive morphine or hydrocodone for pain control?

Some emergency departments have become "oxy-free." This will be more challenging in a continuity practice in which patients come prepackaged with oxycodone on board, but at least we could consider establishing "no new oxy" clinical zones.

Dr. Ebbert is a professor of medicine and primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no conflicts of interest. The opinions expressed are those of the author. Reply via e-mail at [email protected].

Management of the ongoing prescription-opioid health crisis in the United States will require a multifaceted approach. Federal authorities must find ways to reduce opioid use within a regulatory framework. Pharmaceutical companies should continue to seek ways to reduce inappropriate use through drug formulation, such as modifying drug delivery when oxycodone is crushed and snorted. Serious patient education on drug abuse liability before prescribing, by the way, remains uncharted water.

But our challenge as prescribing clinicians may be to overcome old drug stereotypes and established practice patterns. If an opioid is deemed to be clinically necessary for pain control, maybe we need to be less willing to prescribe some opioids in favor of others.

Drug dependence – defined clinically by tolerance and withdrawal – with long-term opioid use is a predictable but acceptable and manageable risk in the face of chronic pain. Drug abuse – defined clinically by aberrant behaviors and adverse psychosocial consequences – is what we should be striving to avoid. The national prescription drug–abuse problem makes life more difficult for patients who have legitimate needs for opioid pain control.

The opioids we use in clinical medicine are all euphorigenic, but select opioids are preferred among the drug-abusing population. In this regard, not all opioids are created equal. Drug abuse is more likely with drugs that give the user a sensation of euphoria or a "high."

Dr. Rachel Wightman of New York University and her colleagues recently published a review of the literature on "opioid likeability" and "opioid abuse liability" (J. Med. Toxicol. 2012;8:335-40).

The studies included in the review showed no clinical difference between abuse liability of morphine and hydrocodone, with similar subjective positive and negative effects. In contrast, oxycodone demonstrated high subjective attractiveness.

Although morphine may be associated with more side effects than oxycodone, it is an effective opioid analgesic that is half the strength of oxycodone. Would it be unreasonable for us to tell our patients that they will receive morphine or hydrocodone for pain control?

Some emergency departments have become "oxy-free." This will be more challenging in a continuity practice in which patients come prepackaged with oxycodone on board, but at least we could consider establishing "no new oxy" clinical zones.

Dr. Ebbert is a professor of medicine and primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no conflicts of interest. The opinions expressed are those of the author. Reply via e-mail at [email protected].

Management of the ongoing prescription-opioid health crisis in the United States will require a multifaceted approach. Federal authorities must find ways to reduce opioid use within a regulatory framework. Pharmaceutical companies should continue to seek ways to reduce inappropriate use through drug formulation, such as modifying drug delivery when oxycodone is crushed and snorted. Serious patient education on drug abuse liability before prescribing, by the way, remains uncharted water.

But our challenge as prescribing clinicians may be to overcome old drug stereotypes and established practice patterns. If an opioid is deemed to be clinically necessary for pain control, maybe we need to be less willing to prescribe some opioids in favor of others.

Drug dependence – defined clinically by tolerance and withdrawal – with long-term opioid use is a predictable but acceptable and manageable risk in the face of chronic pain. Drug abuse – defined clinically by aberrant behaviors and adverse psychosocial consequences – is what we should be striving to avoid. The national prescription drug–abuse problem makes life more difficult for patients who have legitimate needs for opioid pain control.

The opioids we use in clinical medicine are all euphorigenic, but select opioids are preferred among the drug-abusing population. In this regard, not all opioids are created equal. Drug abuse is more likely with drugs that give the user a sensation of euphoria or a "high."

Dr. Rachel Wightman of New York University and her colleagues recently published a review of the literature on "opioid likeability" and "opioid abuse liability" (J. Med. Toxicol. 2012;8:335-40).

The studies included in the review showed no clinical difference between abuse liability of morphine and hydrocodone, with similar subjective positive and negative effects. In contrast, oxycodone demonstrated high subjective attractiveness.

Although morphine may be associated with more side effects than oxycodone, it is an effective opioid analgesic that is half the strength of oxycodone. Would it be unreasonable for us to tell our patients that they will receive morphine or hydrocodone for pain control?

Some emergency departments have become "oxy-free." This will be more challenging in a continuity practice in which patients come prepackaged with oxycodone on board, but at least we could consider establishing "no new oxy" clinical zones.

Dr. Ebbert is a professor of medicine and primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no conflicts of interest. The opinions expressed are those of the author. Reply via e-mail at [email protected].

A significant dissatisfier for both clinician and patient is that inhaled corticosteroids, commonly underutilized and potentially lifesaving medications, are almost never (if ever) covered at the lowest tier by insurance companies. We would select a first-tier medication if there were one that we could substitute for an ICS; but frequently there isn’t, so we can’t.

Because of this, patients may be financially motivated to simply stop the medication – especially if they perceive that they are on the lowest doses and believe the medication perhaps is not needed at all. Clinicians, meanwhile, are doing the balancing act of moving patients to the lowest doses in order to avoid side effects while maintaining optimal disease control.

So, what are the risks when patients stop using inhaled corticosteroids?

Dr. Matthew A. Rank of the Mayo Clinic, Rochester, Minn., and his colleagues recently published a systematic review of the literature to answer this question (J. Allergy Clin. Immunol. 2013;131:724-9). In this review, randomized, controlled clinical trials in which the study intervention was continuing or stopping low-dose ICSs were included. Studies had to have 4 or more weeks of a run-in with stable doses of ICSs to ensure a minimum period of asthma stability. Seven studies met inclusion criteria. Two studies were exclusively in children, and one was exclusively in adults.

Asthma exacerbations were more likely among patients who stopped ICSs, compared with those who did not (relative risk, 2.35; 95% CI: 1.88-2.92). The risk for an asthma exacerbation in the next 6 months on low-dose ICSs was 16% if patients continued taking the medications, and 38% if they stopped. For every five patients who stopped ICSs, one patient would be expected to have an asthma exacerbation in the next 6 months – which could have been prevented if steroids had been continued. The mean decrease in forced expiratory volume in 1 second associated with discontinued ICSs use was 130 mL.

Most patients can step down with ICSs if they are on long-acting beta-agonists. Expert panels have suggested that patients should be controlled for 3 months before stepping down therapy. Findings from this study further suggest that patients who discontinue low-dose ICSs are at an increased risk of asthma exacerbation.

We need to help our patients understand the risk of stopping low-dose ICSs and encourage them, as much as they are able, to stay on them.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

This column, "What Matters," appears regularly in Internal Medicine News.

A significant dissatisfier for both clinician and patient is that inhaled corticosteroids, commonly underutilized and potentially lifesaving medications, are almost never (if ever) covered at the lowest tier by insurance companies. We would select a first-tier medication if there were one that we could substitute for an ICS; but frequently there isn’t, so we can’t.

Because of this, patients may be financially motivated to simply stop the medication – especially if they perceive that they are on the lowest doses and believe the medication perhaps is not needed at all. Clinicians, meanwhile, are doing the balancing act of moving patients to the lowest doses in order to avoid side effects while maintaining optimal disease control.

So, what are the risks when patients stop using inhaled corticosteroids?

Dr. Matthew A. Rank of the Mayo Clinic, Rochester, Minn., and his colleagues recently published a systematic review of the literature to answer this question (J. Allergy Clin. Immunol. 2013;131:724-9). In this review, randomized, controlled clinical trials in which the study intervention was continuing or stopping low-dose ICSs were included. Studies had to have 4 or more weeks of a run-in with stable doses of ICSs to ensure a minimum period of asthma stability. Seven studies met inclusion criteria. Two studies were exclusively in children, and one was exclusively in adults.

Asthma exacerbations were more likely among patients who stopped ICSs, compared with those who did not (relative risk, 2.35; 95% CI: 1.88-2.92). The risk for an asthma exacerbation in the next 6 months on low-dose ICSs was 16% if patients continued taking the medications, and 38% if they stopped. For every five patients who stopped ICSs, one patient would be expected to have an asthma exacerbation in the next 6 months – which could have been prevented if steroids had been continued. The mean decrease in forced expiratory volume in 1 second associated with discontinued ICSs use was 130 mL.

Most patients can step down with ICSs if they are on long-acting beta-agonists. Expert panels have suggested that patients should be controlled for 3 months before stepping down therapy. Findings from this study further suggest that patients who discontinue low-dose ICSs are at an increased risk of asthma exacerbation.

We need to help our patients understand the risk of stopping low-dose ICSs and encourage them, as much as they are able, to stay on them.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

This column, "What Matters," appears regularly in Internal Medicine News.

A significant dissatisfier for both clinician and patient is that inhaled corticosteroids, commonly underutilized and potentially lifesaving medications, are almost never (if ever) covered at the lowest tier by insurance companies. We would select a first-tier medication if there were one that we could substitute for an ICS; but frequently there isn’t, so we can’t.

Because of this, patients may be financially motivated to simply stop the medication – especially if they perceive that they are on the lowest doses and believe the medication perhaps is not needed at all. Clinicians, meanwhile, are doing the balancing act of moving patients to the lowest doses in order to avoid side effects while maintaining optimal disease control.

So, what are the risks when patients stop using inhaled corticosteroids?

Dr. Matthew A. Rank of the Mayo Clinic, Rochester, Minn., and his colleagues recently published a systematic review of the literature to answer this question (J. Allergy Clin. Immunol. 2013;131:724-9). In this review, randomized, controlled clinical trials in which the study intervention was continuing or stopping low-dose ICSs were included. Studies had to have 4 or more weeks of a run-in with stable doses of ICSs to ensure a minimum period of asthma stability. Seven studies met inclusion criteria. Two studies were exclusively in children, and one was exclusively in adults.

Asthma exacerbations were more likely among patients who stopped ICSs, compared with those who did not (relative risk, 2.35; 95% CI: 1.88-2.92). The risk for an asthma exacerbation in the next 6 months on low-dose ICSs was 16% if patients continued taking the medications, and 38% if they stopped. For every five patients who stopped ICSs, one patient would be expected to have an asthma exacerbation in the next 6 months – which could have been prevented if steroids had been continued. The mean decrease in forced expiratory volume in 1 second associated with discontinued ICSs use was 130 mL.

Most patients can step down with ICSs if they are on long-acting beta-agonists. Expert panels have suggested that patients should be controlled for 3 months before stepping down therapy. Findings from this study further suggest that patients who discontinue low-dose ICSs are at an increased risk of asthma exacerbation.

We need to help our patients understand the risk of stopping low-dose ICSs and encourage them, as much as they are able, to stay on them.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

This column, "What Matters," appears regularly in Internal Medicine News.

If you see adolescents and young adults in your practice, you are managing complaints about acne. Acne pathogenesis is related to sebum production, occlusion of skin follicles, bacteria (Propionibacterium acnes), and inflammation. The social impact of this condition can be profound.

I would be fascinated to hear how my clinical practice colleagues address the issue of diet. One would envision that it ranges from avoiding the topic altogether to a "diet is everything" counseling session.

So who is right?

Registered dietitian Jennifer Burris and her colleagues recently published a brilliant systematic review on this topic (J. Acad. Nutr. Diet. 2013;113:416-30), providing luminescence to a debate plagued with more heat than light.

They remind us that the earliest research in the field pointed to an association between acne and chocolate, sugar, and fat. Causality was hypothesized to be related to the effect of these foods on skin oil production. Food restriction was, therefore, part of treatment approaches.

This was subsequently challenged in the 1960s by two studies that suffered from significant methodologic limitations. Shockingly, these studies became highly cited and profoundly influenced our medical culture. The relationship between acne and diet was not studied for another 40 years!

But now we have new and stronger data on the topic. Recent studies have observed an association between milk consumption and acne. Other studies have suggested a link between acne and food with a high glycemic index (GI) or glycemic load (GL).

Recall that the GI is a measure of how quickly blood sugar level rises after eating a particular type of food. The GL takes into account the actual amount of carbohydrate consumed by multiplying the GI by the carbohydrate content of the actual serving. Low-GL diets reduce hyperinsulinemia and have been associated with decreased total and inflammatory acne lesions. Online tools are available to determine the GI/GL of foods.

The authors conclude that epidemiologic, observational, and experimental evidence suggests an association between diet and acne. The link between dairy and acne remains unclear and may be due to milk, milk protein, or the effect of milk on insulin levels. The link between GI/GL appears to be stronger. Importantly, diet appears to affect the severity of acne rather than cause it.

So, if we are not doing so already, it now seems reasonable and evidence-based to counsel our patients on medical nutrition therapy to reduce the severity of acne. Many of our patients might be highly motivated to do so to treat this condition.

This column, "What Matters," appears regularly in Internal Medicine News. Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

If you see adolescents and young adults in your practice, you are managing complaints about acne. Acne pathogenesis is related to sebum production, occlusion of skin follicles, bacteria (Propionibacterium acnes), and inflammation. The social impact of this condition can be profound.

I would be fascinated to hear how my clinical practice colleagues address the issue of diet. One would envision that it ranges from avoiding the topic altogether to a "diet is everything" counseling session.

So who is right?

Registered dietitian Jennifer Burris and her colleagues recently published a brilliant systematic review on this topic (J. Acad. Nutr. Diet. 2013;113:416-30), providing luminescence to a debate plagued with more heat than light.

They remind us that the earliest research in the field pointed to an association between acne and chocolate, sugar, and fat. Causality was hypothesized to be related to the effect of these foods on skin oil production. Food restriction was, therefore, part of treatment approaches.

This was subsequently challenged in the 1960s by two studies that suffered from significant methodologic limitations. Shockingly, these studies became highly cited and profoundly influenced our medical culture. The relationship between acne and diet was not studied for another 40 years!

But now we have new and stronger data on the topic. Recent studies have observed an association between milk consumption and acne. Other studies have suggested a link between acne and food with a high glycemic index (GI) or glycemic load (GL).

Recall that the GI is a measure of how quickly blood sugar level rises after eating a particular type of food. The GL takes into account the actual amount of carbohydrate consumed by multiplying the GI by the carbohydrate content of the actual serving. Low-GL diets reduce hyperinsulinemia and have been associated with decreased total and inflammatory acne lesions. Online tools are available to determine the GI/GL of foods.

The authors conclude that epidemiologic, observational, and experimental evidence suggests an association between diet and acne. The link between dairy and acne remains unclear and may be due to milk, milk protein, or the effect of milk on insulin levels. The link between GI/GL appears to be stronger. Importantly, diet appears to affect the severity of acne rather than cause it.

So, if we are not doing so already, it now seems reasonable and evidence-based to counsel our patients on medical nutrition therapy to reduce the severity of acne. Many of our patients might be highly motivated to do so to treat this condition.

This column, "What Matters," appears regularly in Internal Medicine News. Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

If you see adolescents and young adults in your practice, you are managing complaints about acne. Acne pathogenesis is related to sebum production, occlusion of skin follicles, bacteria (Propionibacterium acnes), and inflammation. The social impact of this condition can be profound.

I would be fascinated to hear how my clinical practice colleagues address the issue of diet. One would envision that it ranges from avoiding the topic altogether to a "diet is everything" counseling session.

So who is right?

Registered dietitian Jennifer Burris and her colleagues recently published a brilliant systematic review on this topic (J. Acad. Nutr. Diet. 2013;113:416-30), providing luminescence to a debate plagued with more heat than light.

They remind us that the earliest research in the field pointed to an association between acne and chocolate, sugar, and fat. Causality was hypothesized to be related to the effect of these foods on skin oil production. Food restriction was, therefore, part of treatment approaches.

This was subsequently challenged in the 1960s by two studies that suffered from significant methodologic limitations. Shockingly, these studies became highly cited and profoundly influenced our medical culture. The relationship between acne and diet was not studied for another 40 years!

But now we have new and stronger data on the topic. Recent studies have observed an association between milk consumption and acne. Other studies have suggested a link between acne and food with a high glycemic index (GI) or glycemic load (GL).

Recall that the GI is a measure of how quickly blood sugar level rises after eating a particular type of food. The GL takes into account the actual amount of carbohydrate consumed by multiplying the GI by the carbohydrate content of the actual serving. Low-GL diets reduce hyperinsulinemia and have been associated with decreased total and inflammatory acne lesions. Online tools are available to determine the GI/GL of foods.

The authors conclude that epidemiologic, observational, and experimental evidence suggests an association between diet and acne. The link between dairy and acne remains unclear and may be due to milk, milk protein, or the effect of milk on insulin levels. The link between GI/GL appears to be stronger. Importantly, diet appears to affect the severity of acne rather than cause it.

So, if we are not doing so already, it now seems reasonable and evidence-based to counsel our patients on medical nutrition therapy to reduce the severity of acne. Many of our patients might be highly motivated to do so to treat this condition.

This column, "What Matters," appears regularly in Internal Medicine News. Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

The treatment of hypertension is the most common reason in the United States for the use of prescription medications and for office visits by nonpregnant adults. Effective treatments get us the numbers that we need and assure us that we are reducing patient risk for future adverse cardiovascular and cerebrovascular events.

Interestingly, epidemiologic studies have shown that lean patients with hypertension have a higher incidence of adverse cardiovascular outcomes, compared with obese individuals. This has been associated with a so-called "obesity paradox."

Most of us are aware of the decreased clinical efficacy of particular drug agents in certain racial groups. But how many of us are making decisions about antihypertensives based upon body weight?

To explore this question, investigators conducted a subgroup analysis with data from the ACCOMPLISH (Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension) trial (Lancet 2013;381:537-45).

ACCOMPLISH was a transnational, multicenter trial designed to compare combination angiotensin-converting enzyme (ACE) inhibitor (benazepril) and calcium channel blocker (CCB) (amlodipine) therapy with the effects of benazepril plus hydrochlorothiazide (HCTZ). The primary endpoint was reduction of a composite endpoint of cardiac death, nonfatal myocardial infarction, or nonfatal stroke among patients at risk for cardiovascular disease.

In the current analysis, patients were divided into obese (body mass index at least 30 kg/m²), overweight (from 25 to less than 30), or normal weight (less than 25).

Among obese subjects, no differences in risk for any outcome were observed between benazepril plus amlodipine or benazepril plus HCTZ. Within the overweight group, benazepril plus amlodipine was associated with a lower risk for the composite endpoint (hazard ratio, 0.76; 95% confidence interval, 0.59-0.94).

Within the normal-weight category, benazepril plus amlodipine was associated with significantly decreased risk for the composite endpoint (HR 0.57; CI, 0.39-0.84) and for MI (HR, 0.50; CI, 0.26-0.96), compared with benazepril plus HCTZ.

So, how do we put these findings into practice?

The evidence here supports the hypothesis that hypertension may be mediated by different mechanisms in obese patients (i.e., increased plasma volume) and nonobese patients (i.e., vasoconstriction). Drug selection, therefore, has a different impact on outcome based upon body weight.

Thus, CCB-based antihypertensive therapy may be the best first-line treatment for patients who are nonobese.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author. Reply via e-mail at [email protected].

The treatment of hypertension is the most common reason in the United States for the use of prescription medications and for office visits by nonpregnant adults. Effective treatments get us the numbers that we need and assure us that we are reducing patient risk for future adverse cardiovascular and cerebrovascular events.

Interestingly, epidemiologic studies have shown that lean patients with hypertension have a higher incidence of adverse cardiovascular outcomes, compared with obese individuals. This has been associated with a so-called "obesity paradox."

Most of us are aware of the decreased clinical efficacy of particular drug agents in certain racial groups. But how many of us are making decisions about antihypertensives based upon body weight?

To explore this question, investigators conducted a subgroup analysis with data from the ACCOMPLISH (Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension) trial (Lancet 2013;381:537-45).

ACCOMPLISH was a transnational, multicenter trial designed to compare combination angiotensin-converting enzyme (ACE) inhibitor (benazepril) and calcium channel blocker (CCB) (amlodipine) therapy with the effects of benazepril plus hydrochlorothiazide (HCTZ). The primary endpoint was reduction of a composite endpoint of cardiac death, nonfatal myocardial infarction, or nonfatal stroke among patients at risk for cardiovascular disease.

In the current analysis, patients were divided into obese (body mass index at least 30 kg/m²), overweight (from 25 to less than 30), or normal weight (less than 25).

Among obese subjects, no differences in risk for any outcome were observed between benazepril plus amlodipine or benazepril plus HCTZ. Within the overweight group, benazepril plus amlodipine was associated with a lower risk for the composite endpoint (hazard ratio, 0.76; 95% confidence interval, 0.59-0.94).

Within the normal-weight category, benazepril plus amlodipine was associated with significantly decreased risk for the composite endpoint (HR 0.57; CI, 0.39-0.84) and for MI (HR, 0.50; CI, 0.26-0.96), compared with benazepril plus HCTZ.

So, how do we put these findings into practice?

The evidence here supports the hypothesis that hypertension may be mediated by different mechanisms in obese patients (i.e., increased plasma volume) and nonobese patients (i.e., vasoconstriction). Drug selection, therefore, has a different impact on outcome based upon body weight.

Thus, CCB-based antihypertensive therapy may be the best first-line treatment for patients who are nonobese.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author. Reply via e-mail at [email protected].

The treatment of hypertension is the most common reason in the United States for the use of prescription medications and for office visits by nonpregnant adults. Effective treatments get us the numbers that we need and assure us that we are reducing patient risk for future adverse cardiovascular and cerebrovascular events.

Interestingly, epidemiologic studies have shown that lean patients with hypertension have a higher incidence of adverse cardiovascular outcomes, compared with obese individuals. This has been associated with a so-called "obesity paradox."

Most of us are aware of the decreased clinical efficacy of particular drug agents in certain racial groups. But how many of us are making decisions about antihypertensives based upon body weight?

To explore this question, investigators conducted a subgroup analysis with data from the ACCOMPLISH (Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension) trial (Lancet 2013;381:537-45).

ACCOMPLISH was a transnational, multicenter trial designed to compare combination angiotensin-converting enzyme (ACE) inhibitor (benazepril) and calcium channel blocker (CCB) (amlodipine) therapy with the effects of benazepril plus hydrochlorothiazide (HCTZ). The primary endpoint was reduction of a composite endpoint of cardiac death, nonfatal myocardial infarction, or nonfatal stroke among patients at risk for cardiovascular disease.

In the current analysis, patients were divided into obese (body mass index at least 30 kg/m²), overweight (from 25 to less than 30), or normal weight (less than 25).

Among obese subjects, no differences in risk for any outcome were observed between benazepril plus amlodipine or benazepril plus HCTZ. Within the overweight group, benazepril plus amlodipine was associated with a lower risk for the composite endpoint (hazard ratio, 0.76; 95% confidence interval, 0.59-0.94).

Within the normal-weight category, benazepril plus amlodipine was associated with significantly decreased risk for the composite endpoint (HR 0.57; CI, 0.39-0.84) and for MI (HR, 0.50; CI, 0.26-0.96), compared with benazepril plus HCTZ.

So, how do we put these findings into practice?

The evidence here supports the hypothesis that hypertension may be mediated by different mechanisms in obese patients (i.e., increased plasma volume) and nonobese patients (i.e., vasoconstriction). Drug selection, therefore, has a different impact on outcome based upon body weight.

Thus, CCB-based antihypertensive therapy may be the best first-line treatment for patients who are nonobese.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author. Reply via e-mail at [email protected].

In primary care, the sun never sets on a day in which we are not managing a rheumatologic or orthopedic issue. Obesity seems to be making knee pain an epidemic, and most patients seem to complain about knee pain at some point or another.

Knee osteoarthritis (OA) is one of the most common complaints we see. In addition to knee pain, the clinical diagnosis of knee OA can be secured with at least three of the following six clinical characteristics: age greater than 50 years; morning stiffness for less than 30 minutes; crepitus on active knee motion; bony tenderness; bony enlargement; and lack of palpable warmth.

These criteria result in a sensitivity and specificity for OA of 95% and 69%, respectively.

Once the diagnosis has been made, the easy part is over. Many of us may suggest stretching exercises from the patient information racks. And we may recommend steroid injections, physical therapy, or weight loss. Unfortunately, many patients instead may "settle on" long-term narcotics to manage knee OA pain.

But clinicians are nothing if not creative and enterprising. So what else can we try?

Investigators from Egypt evaluated the efficacy of duloxetine for pain and function management in older adults with knee OA. Duloxetine is a serotonin and norepinephrine reuptake inhibitor that has a proposed centrally acting analgesic effect.

In this study, 288 patients aged at least 65 years were randomized to 60 mg/day of duloxetine or placebo for 16 weeks (Age Ageing 2012;41:646-52). To enroll, patients had to have clinical and radiologic criteria of primary knee OA. The researchers excluded patients with a body mass index greater than 32 kg/m² or inflammatory arthritides. Patients could continue on their usual NSAIDs but could not increase the dose. Primary outcome measures included pain reduction and improved physical function.

Of 411 screened patients, 288 patients were randomized. Mean patient age was 68.5 years; 84% were female. Mean BMI was 26.5. NSAIDs were used by 89% of subjects.

At 16 weeks, 48% of subjects in the duloxetine group had a 20% reduction in pain or physical function, compared with 9% in the placebo group (P less than .05). After 16 weeks, duloxetine was associated with a significant reduction in pain, improvement in physical function, decreased depression, and reduced NSAID use. Side effects included constipation, nausea, hyperhidrosis, cough, myalgia, arthralgia, and palpitations.

Thus, duloxetine may be an appropriate step in selected older patients with knee OA before considering more aggressive and risky medications such as narcotic analgesics.

This column, What Matters, appears regularly in Internal Medicine News. Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author. Reply via e-mail at [email protected].

In primary care, the sun never sets on a day in which we are not managing a rheumatologic or orthopedic issue. Obesity seems to be making knee pain an epidemic, and most patients seem to complain about knee pain at some point or another.

Knee osteoarthritis (OA) is one of the most common complaints we see. In addition to knee pain, the clinical diagnosis of knee OA can be secured with at least three of the following six clinical characteristics: age greater than 50 years; morning stiffness for less than 30 minutes; crepitus on active knee motion; bony tenderness; bony enlargement; and lack of palpable warmth.

These criteria result in a sensitivity and specificity for OA of 95% and 69%, respectively.

Once the diagnosis has been made, the easy part is over. Many of us may suggest stretching exercises from the patient information racks. And we may recommend steroid injections, physical therapy, or weight loss. Unfortunately, many patients instead may "settle on" long-term narcotics to manage knee OA pain.

But clinicians are nothing if not creative and enterprising. So what else can we try?

Investigators from Egypt evaluated the efficacy of duloxetine for pain and function management in older adults with knee OA. Duloxetine is a serotonin and norepinephrine reuptake inhibitor that has a proposed centrally acting analgesic effect.

In this study, 288 patients aged at least 65 years were randomized to 60 mg/day of duloxetine or placebo for 16 weeks (Age Ageing 2012;41:646-52). To enroll, patients had to have clinical and radiologic criteria of primary knee OA. The researchers excluded patients with a body mass index greater than 32 kg/m² or inflammatory arthritides. Patients could continue on their usual NSAIDs but could not increase the dose. Primary outcome measures included pain reduction and improved physical function.

Of 411 screened patients, 288 patients were randomized. Mean patient age was 68.5 years; 84% were female. Mean BMI was 26.5. NSAIDs were used by 89% of subjects.

At 16 weeks, 48% of subjects in the duloxetine group had a 20% reduction in pain or physical function, compared with 9% in the placebo group (P less than .05). After 16 weeks, duloxetine was associated with a significant reduction in pain, improvement in physical function, decreased depression, and reduced NSAID use. Side effects included constipation, nausea, hyperhidrosis, cough, myalgia, arthralgia, and palpitations.

Thus, duloxetine may be an appropriate step in selected older patients with knee OA before considering more aggressive and risky medications such as narcotic analgesics.

This column, What Matters, appears regularly in Internal Medicine News. Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author. Reply via e-mail at [email protected].

In primary care, the sun never sets on a day in which we are not managing a rheumatologic or orthopedic issue. Obesity seems to be making knee pain an epidemic, and most patients seem to complain about knee pain at some point or another.

Knee osteoarthritis (OA) is one of the most common complaints we see. In addition to knee pain, the clinical diagnosis of knee OA can be secured with at least three of the following six clinical characteristics: age greater than 50 years; morning stiffness for less than 30 minutes; crepitus on active knee motion; bony tenderness; bony enlargement; and lack of palpable warmth.

These criteria result in a sensitivity and specificity for OA of 95% and 69%, respectively.

Once the diagnosis has been made, the easy part is over. Many of us may suggest stretching exercises from the patient information racks. And we may recommend steroid injections, physical therapy, or weight loss. Unfortunately, many patients instead may "settle on" long-term narcotics to manage knee OA pain.

But clinicians are nothing if not creative and enterprising. So what else can we try?

Investigators from Egypt evaluated the efficacy of duloxetine for pain and function management in older adults with knee OA. Duloxetine is a serotonin and norepinephrine reuptake inhibitor that has a proposed centrally acting analgesic effect.

In this study, 288 patients aged at least 65 years were randomized to 60 mg/day of duloxetine or placebo for 16 weeks (Age Ageing 2012;41:646-52). To enroll, patients had to have clinical and radiologic criteria of primary knee OA. The researchers excluded patients with a body mass index greater than 32 kg/m² or inflammatory arthritides. Patients could continue on their usual NSAIDs but could not increase the dose. Primary outcome measures included pain reduction and improved physical function.

Of 411 screened patients, 288 patients were randomized. Mean patient age was 68.5 years; 84% were female. Mean BMI was 26.5. NSAIDs were used by 89% of subjects.

At 16 weeks, 48% of subjects in the duloxetine group had a 20% reduction in pain or physical function, compared with 9% in the placebo group (P less than .05). After 16 weeks, duloxetine was associated with a significant reduction in pain, improvement in physical function, decreased depression, and reduced NSAID use. Side effects included constipation, nausea, hyperhidrosis, cough, myalgia, arthralgia, and palpitations.

Thus, duloxetine may be an appropriate step in selected older patients with knee OA before considering more aggressive and risky medications such as narcotic analgesics.

This column, What Matters, appears regularly in Internal Medicine News. Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author. Reply via e-mail at [email protected].

Benign prostatic hyperplasia is an uncommon cause of mortality but a common cause of morbidity.

More than 80% of men aged older than 80 years have histologic evidence of benign prostatic hyperplasia (BPH). As most of us know, the most common symptoms of BPH are urinary frequency, nocturia, hesitancy, and weak urine stream. But it seems like nocturia is the source of most complaints in my panel.

Interestingly, many men will experience stabilization or improvement over time without therapy. We likely do not remember this, because men who present to us are not typically enamored with the idea of "watchful waiting" when they are up all night standing at the latrine. But in fact, 38% of men will have symptom improvement over 2.6 to 5 years of follow-up without intervention.

Treatment is symptom driven. Treatment modality selections are cost and convenience driven. Many of us will reach for an alpha-adrenergic antagonist or a 5-alpha-reductase inhibitor as first-line therapy for patients with mild but annoying symptoms.

But how many of us consider NSAIDs in this setting?

Dr. Arman Kahokehr and colleagues conducted a systematic review of the literature examining the effects of NSAIDs in the treatment of men with BPH. Trials were included if they were randomized and included objective outcomes such as urologic symptom scales or urodynamics (BJU Int. 2013;111:304-11).

Three randomized trials enrolling 183 men and lasting 4-24 weeks were included in the meta-analysis. The trials used rofecoxib plus finasteride, celecoxib, and tenoxicam plus doxazosin. NSAIDs improved scores on the International Prostate Symptom Score (IPSS; P less than .001) and increased urine flow (0.89 mL/s; P = .01). No increased side effects were observed.

The authors highlight that inflammatory infiltration is seen in 43%-98% of BPH tissue, and men with acute or chronic inflammation have larger prostate volumes.

COX-2 inhibitors were used in the included studies, but nonselective NSAIDs may have as powerful an effect on the inflammatory process associated with BPH – and may be associated with less concern for adverse cardiovascular outcomes. The long-term effects of NSAIDs on kidney function and the gastrointestinal mucosa, especially in older patients, need to be considered.

But the use of NSAIDs in combination with other BPH pharmacologic agents before changing doses, medications, or intervention approach may be an attractive short-term clinical option.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author.

Benign prostatic hyperplasia is an uncommon cause of mortality but a common cause of morbidity.

More than 80% of men aged older than 80 years have histologic evidence of benign prostatic hyperplasia (BPH). As most of us know, the most common symptoms of BPH are urinary frequency, nocturia, hesitancy, and weak urine stream. But it seems like nocturia is the source of most complaints in my panel.

Interestingly, many men will experience stabilization or improvement over time without therapy. We likely do not remember this, because men who present to us are not typically enamored with the idea of "watchful waiting" when they are up all night standing at the latrine. But in fact, 38% of men will have symptom improvement over 2.6 to 5 years of follow-up without intervention.

Treatment is symptom driven. Treatment modality selections are cost and convenience driven. Many of us will reach for an alpha-adrenergic antagonist or a 5-alpha-reductase inhibitor as first-line therapy for patients with mild but annoying symptoms.

But how many of us consider NSAIDs in this setting?

Dr. Arman Kahokehr and colleagues conducted a systematic review of the literature examining the effects of NSAIDs in the treatment of men with BPH. Trials were included if they were randomized and included objective outcomes such as urologic symptom scales or urodynamics (BJU Int. 2013;111:304-11).

Three randomized trials enrolling 183 men and lasting 4-24 weeks were included in the meta-analysis. The trials used rofecoxib plus finasteride, celecoxib, and tenoxicam plus doxazosin. NSAIDs improved scores on the International Prostate Symptom Score (IPSS; P less than .001) and increased urine flow (0.89 mL/s; P = .01). No increased side effects were observed.

The authors highlight that inflammatory infiltration is seen in 43%-98% of BPH tissue, and men with acute or chronic inflammation have larger prostate volumes.

COX-2 inhibitors were used in the included studies, but nonselective NSAIDs may have as powerful an effect on the inflammatory process associated with BPH – and may be associated with less concern for adverse cardiovascular outcomes. The long-term effects of NSAIDs on kidney function and the gastrointestinal mucosa, especially in older patients, need to be considered.

But the use of NSAIDs in combination with other BPH pharmacologic agents before changing doses, medications, or intervention approach may be an attractive short-term clinical option.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author.

Benign prostatic hyperplasia is an uncommon cause of mortality but a common cause of morbidity.

More than 80% of men aged older than 80 years have histologic evidence of benign prostatic hyperplasia (BPH). As most of us know, the most common symptoms of BPH are urinary frequency, nocturia, hesitancy, and weak urine stream. But it seems like nocturia is the source of most complaints in my panel.

Interestingly, many men will experience stabilization or improvement over time without therapy. We likely do not remember this, because men who present to us are not typically enamored with the idea of "watchful waiting" when they are up all night standing at the latrine. But in fact, 38% of men will have symptom improvement over 2.6 to 5 years of follow-up without intervention.

Treatment is symptom driven. Treatment modality selections are cost and convenience driven. Many of us will reach for an alpha-adrenergic antagonist or a 5-alpha-reductase inhibitor as first-line therapy for patients with mild but annoying symptoms.

But how many of us consider NSAIDs in this setting?

Dr. Arman Kahokehr and colleagues conducted a systematic review of the literature examining the effects of NSAIDs in the treatment of men with BPH. Trials were included if they were randomized and included objective outcomes such as urologic symptom scales or urodynamics (BJU Int. 2013;111:304-11).

Three randomized trials enrolling 183 men and lasting 4-24 weeks were included in the meta-analysis. The trials used rofecoxib plus finasteride, celecoxib, and tenoxicam plus doxazosin. NSAIDs improved scores on the International Prostate Symptom Score (IPSS; P less than .001) and increased urine flow (0.89 mL/s; P = .01). No increased side effects were observed.

The authors highlight that inflammatory infiltration is seen in 43%-98% of BPH tissue, and men with acute or chronic inflammation have larger prostate volumes.

COX-2 inhibitors were used in the included studies, but nonselective NSAIDs may have as powerful an effect on the inflammatory process associated with BPH – and may be associated with less concern for adverse cardiovascular outcomes. The long-term effects of NSAIDs on kidney function and the gastrointestinal mucosa, especially in older patients, need to be considered.

But the use of NSAIDs in combination with other BPH pharmacologic agents before changing doses, medications, or intervention approach may be an attractive short-term clinical option.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author.

Recently, a healthy 43-year-old male presented to me complaining of a several-month history of "food getting stuck." He delivered a progressive history of solid-food dysphagia frequently uncomfortable enough for him to excuse himself from table company to deal with matters. He was a nonsmoker, and no other red flag symptoms were identified.

The esophagram was consistent with eosinophilic esophagitis (EoE) and also suggested a Schatzki’s ring. An EGD was obtained for possible ring dilatation, during which a biopsy confirmed the diagnosis of esophageal eosinophilia. I dutifully updated myself on the disorder, talked to the patient, and called in a prescription for fluticasone. As it would happen, I knew the gastroenterologist performing the EGD and phoned him to discuss the biopsy.

I told him my plan, and he said, "Try a PPI first."

Indeed, a recent study by Dr. Fouad J. Moawad and his colleagues evaluated the comparative efficacy of the histological and clinical response of patients with esophageal eosinophilia treated with swallowed fluticasone or esomeprazole (Am. J. Gastroenterol. 2013;108:366-72).

In this study, 42 patients with a new diagnosis of esophageal eosinophilia were randomized to fluticasone 440 mcg twice daily (21 patients) or esomeprazole 40 mg once daily (21 patients) for 8 weeks. Patients underwent repeat endoscopies and biopsy. The primary outcome was histological response of esophageal eosinophilia. Patients were also stratified by the presence of GERD (eight patients, with four in each treatment arm).

Overall, no significant differences in resolution of esophageal eosinophilia were observed between the fluticasone group and the esomeprazole group. That pattern was mirrored in the 36 patients who didn’t have GERD: There was no significant difference in esophageal eosinophilia resolution between the two treatment groups.

However, differences did emerge in the presence of GERD. While none of the four patients with GERD who took fluticasone demonstrated resolution of esophageal eosinophilia, all four GERD patients on esomeprazole saw their esophageal eosinophilia resolve.

My patient improved. He could be one of the patients who are now recognized by the more recent and updated EoE consensus statement as having "PPI-responsive esophageal eosinophilia." Another win for phoning the expert.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author.

Recently, a healthy 43-year-old male presented to me complaining of a several-month history of "food getting stuck." He delivered a progressive history of solid-food dysphagia frequently uncomfortable enough for him to excuse himself from table company to deal with matters. He was a nonsmoker, and no other red flag symptoms were identified.

The esophagram was consistent with eosinophilic esophagitis (EoE) and also suggested a Schatzki’s ring. An EGD was obtained for possible ring dilatation, during which a biopsy confirmed the diagnosis of esophageal eosinophilia. I dutifully updated myself on the disorder, talked to the patient, and called in a prescription for fluticasone. As it would happen, I knew the gastroenterologist performing the EGD and phoned him to discuss the biopsy.

I told him my plan, and he said, "Try a PPI first."

Indeed, a recent study by Dr. Fouad J. Moawad and his colleagues evaluated the comparative efficacy of the histological and clinical response of patients with esophageal eosinophilia treated with swallowed fluticasone or esomeprazole (Am. J. Gastroenterol. 2013;108:366-72).

In this study, 42 patients with a new diagnosis of esophageal eosinophilia were randomized to fluticasone 440 mcg twice daily (21 patients) or esomeprazole 40 mg once daily (21 patients) for 8 weeks. Patients underwent repeat endoscopies and biopsy. The primary outcome was histological response of esophageal eosinophilia. Patients were also stratified by the presence of GERD (eight patients, with four in each treatment arm).

Overall, no significant differences in resolution of esophageal eosinophilia were observed between the fluticasone group and the esomeprazole group. That pattern was mirrored in the 36 patients who didn’t have GERD: There was no significant difference in esophageal eosinophilia resolution between the two treatment groups.

However, differences did emerge in the presence of GERD. While none of the four patients with GERD who took fluticasone demonstrated resolution of esophageal eosinophilia, all four GERD patients on esomeprazole saw their esophageal eosinophilia resolve.

My patient improved. He could be one of the patients who are now recognized by the more recent and updated EoE consensus statement as having "PPI-responsive esophageal eosinophilia." Another win for phoning the expert.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author.

Recently, a healthy 43-year-old male presented to me complaining of a several-month history of "food getting stuck." He delivered a progressive history of solid-food dysphagia frequently uncomfortable enough for him to excuse himself from table company to deal with matters. He was a nonsmoker, and no other red flag symptoms were identified.

The esophagram was consistent with eosinophilic esophagitis (EoE) and also suggested a Schatzki’s ring. An EGD was obtained for possible ring dilatation, during which a biopsy confirmed the diagnosis of esophageal eosinophilia. I dutifully updated myself on the disorder, talked to the patient, and called in a prescription for fluticasone. As it would happen, I knew the gastroenterologist performing the EGD and phoned him to discuss the biopsy.

I told him my plan, and he said, "Try a PPI first."

Indeed, a recent study by Dr. Fouad J. Moawad and his colleagues evaluated the comparative efficacy of the histological and clinical response of patients with esophageal eosinophilia treated with swallowed fluticasone or esomeprazole (Am. J. Gastroenterol. 2013;108:366-72).

In this study, 42 patients with a new diagnosis of esophageal eosinophilia were randomized to fluticasone 440 mcg twice daily (21 patients) or esomeprazole 40 mg once daily (21 patients) for 8 weeks. Patients underwent repeat endoscopies and biopsy. The primary outcome was histological response of esophageal eosinophilia. Patients were also stratified by the presence of GERD (eight patients, with four in each treatment arm).

Overall, no significant differences in resolution of esophageal eosinophilia were observed between the fluticasone group and the esomeprazole group. That pattern was mirrored in the 36 patients who didn’t have GERD: There was no significant difference in esophageal eosinophilia resolution between the two treatment groups.

However, differences did emerge in the presence of GERD. While none of the four patients with GERD who took fluticasone demonstrated resolution of esophageal eosinophilia, all four GERD patients on esomeprazole saw their esophageal eosinophilia resolve.

My patient improved. He could be one of the patients who are now recognized by the more recent and updated EoE consensus statement as having "PPI-responsive esophageal eosinophilia." Another win for phoning the expert.

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reports having no conflicts of interest. The opinions expressed are those of the author.

Recently, I was critically reminded of the effect that certain medications have on the QT interval. My longtime patient with a history of depression and insomnia presented to me with chest pain symptoms. An ECG was ordered. Within an hour, our QT prolongation warning system notified me that her corrected QT interval (QTc) had prolonged to 530 milliseconds. Her previous QTc was 479 milliseconds. Electrolytes were normal. She was taking paroxetine for depression and trazodone for insomnia. Both were tapered and discontinued over the next several days, with return of her QTc to 473 milliseconds. Crisis averted.

A prolonged QT interval reflects abnormal repolarization (electrical recharging) and may lead to torsades de pointes and sudden cardiac death. A long QT interval can be associated with congenital long QT syndrome, electrolyte abnormalities, or medications. The greatest risk factors for an adverse event such as sudden death or aborted cardiac arrest are associated with a QTc of more than 500 milliseconds and a history of nonvasovagal syncope.

In my patient population surviving into their later years, iatrogenic causes of prolonged QTc are far and away the most common etiologies. And with my patient population either becoming more depressed – or me becoming more adept at diagnosing it – antidepressants are high on the list of offenders.

So which ones are the ones that we should be most concerned about? And is there a dose effect?

Dr. Victor M. Castro and his team published a case-control study (BMJ 2013;346:f288) quantifying the impact of citalopram and other selective serotonin reuptake inhibitors on the QT interval. Patients were at least 18 years of age with at least one prescription of an antidepressant or methadone between 1990 and 2011. Methadone is known to prolong the QT interval and was used to verify the sensitivity of the analysis.

The antidepressants analyzed were citalopram, escitalopram, fluoxetine, paroxetine, sertraline, amitriptyline, bupropion, duloxetine, mirtazapine, nortriptyline, and venlafaxine. Patients’ ECGs were selected for analysis if they occurred at least 14 days after a prescription. Of the study patients receiving a medication of interest, 38,397 patients had an ECG in the specified 14- to 90-day window. Analyses of QTc were adjusted for potential confounders such as preexisting cardiovascular disease.

In this population, 20.4% of individuals were characterized as having abnormal or high QTc values. Methadone predictably increased QTc. Dose was observed to be a significant predictor of QTc with citalopram (10-20 mg), escitalopram (5-10 mg and 10-20 mg), and amitriptyline (25-50 mg). Bupropion was found to significantly decrease QTc (P less than .05). Notably, 13.1% of patients who started citalopram with a QTc in the normal range shifted to abnormal after a dose increase.

In this study, one-fifth of patients had an abnormal QTc. But QTc is only considered a proxy measure for torsades de pointes. So, whether we should be routinely ordering ECGs for patients started on citalopram, escitalopram, or amitriptyline, or for whom the dose of these drugs has been changed, remains uncertain.

When my patient’s depression ferociously returned, I restarted paroxetine. This time, I ordered a follow-up ECG, which showed no QT prolongation. Crisis averted.

Recently, I was critically reminded of the effect that certain medications have on the QT interval. My longtime patient with a history of depression and insomnia presented to me with chest pain symptoms. An ECG was ordered. Within an hour, our QT prolongation warning system notified me that her corrected QT interval (QTc) had prolonged to 530 milliseconds. Her previous QTc was 479 milliseconds. Electrolytes were normal. She was taking paroxetine for depression and trazodone for insomnia. Both were tapered and discontinued over the next several days, with return of her QTc to 473 milliseconds. Crisis averted.

A prolonged QT interval reflects abnormal repolarization (electrical recharging) and may lead to torsades de pointes and sudden cardiac death. A long QT interval can be associated with congenital long QT syndrome, electrolyte abnormalities, or medications. The greatest risk factors for an adverse event such as sudden death or aborted cardiac arrest are associated with a QTc of more than 500 milliseconds and a history of nonvasovagal syncope.

In my patient population surviving into their later years, iatrogenic causes of prolonged QTc are far and away the most common etiologies. And with my patient population either becoming more depressed – or me becoming more adept at diagnosing it – antidepressants are high on the list of offenders.

So which ones are the ones that we should be most concerned about? And is there a dose effect?

Dr. Victor M. Castro and his team published a case-control study (BMJ 2013;346:f288) quantifying the impact of citalopram and other selective serotonin reuptake inhibitors on the QT interval. Patients were at least 18 years of age with at least one prescription of an antidepressant or methadone between 1990 and 2011. Methadone is known to prolong the QT interval and was used to verify the sensitivity of the analysis.

The antidepressants analyzed were citalopram, escitalopram, fluoxetine, paroxetine, sertraline, amitriptyline, bupropion, duloxetine, mirtazapine, nortriptyline, and venlafaxine. Patients’ ECGs were selected for analysis if they occurred at least 14 days after a prescription. Of the study patients receiving a medication of interest, 38,397 patients had an ECG in the specified 14- to 90-day window. Analyses of QTc were adjusted for potential confounders such as preexisting cardiovascular disease.

In this population, 20.4% of individuals were characterized as having abnormal or high QTc values. Methadone predictably increased QTc. Dose was observed to be a significant predictor of QTc with citalopram (10-20 mg), escitalopram (5-10 mg and 10-20 mg), and amitriptyline (25-50 mg). Bupropion was found to significantly decrease QTc (P less than .05). Notably, 13.1% of patients who started citalopram with a QTc in the normal range shifted to abnormal after a dose increase.

In this study, one-fifth of patients had an abnormal QTc. But QTc is only considered a proxy measure for torsades de pointes. So, whether we should be routinely ordering ECGs for patients started on citalopram, escitalopram, or amitriptyline, or for whom the dose of these drugs has been changed, remains uncertain.

When my patient’s depression ferociously returned, I restarted paroxetine. This time, I ordered a follow-up ECG, which showed no QT prolongation. Crisis averted.

Recently, I was critically reminded of the effect that certain medications have on the QT interval. My longtime patient with a history of depression and insomnia presented to me with chest pain symptoms. An ECG was ordered. Within an hour, our QT prolongation warning system notified me that her corrected QT interval (QTc) had prolonged to 530 milliseconds. Her previous QTc was 479 milliseconds. Electrolytes were normal. She was taking paroxetine for depression and trazodone for insomnia. Both were tapered and discontinued over the next several days, with return of her QTc to 473 milliseconds. Crisis averted.

A prolonged QT interval reflects abnormal repolarization (electrical recharging) and may lead to torsades de pointes and sudden cardiac death. A long QT interval can be associated with congenital long QT syndrome, electrolyte abnormalities, or medications. The greatest risk factors for an adverse event such as sudden death or aborted cardiac arrest are associated with a QTc of more than 500 milliseconds and a history of nonvasovagal syncope.

In my patient population surviving into their later years, iatrogenic causes of prolonged QTc are far and away the most common etiologies. And with my patient population either becoming more depressed – or me becoming more adept at diagnosing it – antidepressants are high on the list of offenders.

So which ones are the ones that we should be most concerned about? And is there a dose effect?

Dr. Victor M. Castro and his team published a case-control study (BMJ 2013;346:f288) quantifying the impact of citalopram and other selective serotonin reuptake inhibitors on the QT interval. Patients were at least 18 years of age with at least one prescription of an antidepressant or methadone between 1990 and 2011. Methadone is known to prolong the QT interval and was used to verify the sensitivity of the analysis.

The antidepressants analyzed were citalopram, escitalopram, fluoxetine, paroxetine, sertraline, amitriptyline, bupropion, duloxetine, mirtazapine, nortriptyline, and venlafaxine. Patients’ ECGs were selected for analysis if they occurred at least 14 days after a prescription. Of the study patients receiving a medication of interest, 38,397 patients had an ECG in the specified 14- to 90-day window. Analyses of QTc were adjusted for potential confounders such as preexisting cardiovascular disease.

In this population, 20.4% of individuals were characterized as having abnormal or high QTc values. Methadone predictably increased QTc. Dose was observed to be a significant predictor of QTc with citalopram (10-20 mg), escitalopram (5-10 mg and 10-20 mg), and amitriptyline (25-50 mg). Bupropion was found to significantly decrease QTc (P less than .05). Notably, 13.1% of patients who started citalopram with a QTc in the normal range shifted to abnormal after a dose increase.

In this study, one-fifth of patients had an abnormal QTc. But QTc is only considered a proxy measure for torsades de pointes. So, whether we should be routinely ordering ECGs for patients started on citalopram, escitalopram, or amitriptyline, or for whom the dose of these drugs has been changed, remains uncertain.

When my patient’s depression ferociously returned, I restarted paroxetine. This time, I ordered a follow-up ECG, which showed no QT prolongation. Crisis averted.