Plasmodium sporozoite

Credit: Ute Frevert

and Margaret Shear

In a new study, genetically altered viruses produced long-lasting antimalaria antibodies in mice and protected many of them from the disease.

The approach, known as vector immunoprophylaxis (VIP), produced antibodies against the Plasmodium falciparum circumsporozoite protein (CSP) and prevented malaria infection in 10% to 100% of mice, depending on the dose and type of viral vector used.

Researchers recounted these results in PNAS.

“We need better ways to fight malaria,” said study author Gary Ketner, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. “And our research suggests [VIP] could be a promising approach.”

To test the approach, Dr Ketner and his colleagues constructed adeno-associated virus (AAV) vectors encoding human immunoglobulin G (hIgG) specific for the P falciparum CSP central repeat by inserting the variable regions of mouse monoclonal antibodies (mAbs) 2A10 and 2C11 into the hIgG framework of the VIP expression plasmid.

The team then injected mice with 1 x 10¹¹ genome copies (GC) of 2A10-AAV, 2C11-AAV, b12-AAV (which protects against HIV), or with buffer.

Within a week, the AAV-transduced mice expressed hIgG at 50 μg/mL to 500 μg/mL in serum. The expression increased until about the 4-week mark, when it reached 1000 μg/mL in some mice.

The mice that received 2A10-AAV or 2C11-AAV expressed antibodies that bound recombinant CSP and recognized whole P falciparum sporozoites. The b12-AAV-transduced mice and buffer-transduced mice did not.

In all AAV-transduced mice, serum antibody concentrations plateaued at 4 to 8 weeks and remained at that level through the end of the study, which was 52 weeks after transduction.

At the 8-week mark, the researchers tested the efficacy of VIP. They introduced—either intravenously or through a mosquito-bite challenge—transgenic Plasmodium berghei rodent sporozoites that incorporate the P falciparum target of the antibody in their CSP.

In the intravenously challenged group, 70% of 2A10-AAV-transduced mice were protected from malaria. In the mosquito-bite-challenged group, 60% of 2A10-AAV-transduced mice and 30% of 2C11-AAV-transduced mice were protected from malaria.

Role of dose and antibody level

To examine the effects of vector dose on mAb production and malaria protection, the researchers compared varying doses of 2A10-AAV to b12-AAV. They tested mice transduced with 3 x 10¹¹ GC of b12-AAV or doses of 2A10-AAV ranging from 3 x 10⁹ GC to 3 x 10¹¹ GC.

The team conducted a mosquito-bite challenge at 11 weeks after transduction. And they found that 70% of the mice that received the highest AAV dose (1 x 10¹¹ GC) were protected, as were 40% of mice that received 3 x 10¹⁰ GC and 10% of mice that received 1 x 10¹⁰ GC.

All mice transduced with 3 x 10⁹ GC were parasitemic by day 7, and all b12-AAV mice were parasitemic by day 6. There was a signficant correlation between 2A10 antibody concentration and day to parasitemia.

In a subset of mice that produced higher levels of antibodies, the antimalaria protection was 100%. These mice expressed CSP-specific mAb 2A10 at 1 mg/mL or more.

So it seems the protection from malaria is dose-dependent, said study author Cailin Deal, PhD, of the Ragon Institute of MGH, MIT and Harvard in Cambridge, Massachusetts.

“Of course, we don’t know what the human dosage would be,” she added, “but it’s conceivable that the right dosage could completely protect against malaria.”

Plasmodium sporozoite

Credit: Ute Frevert

and Margaret Shear

In a new study, genetically altered viruses produced long-lasting antimalaria antibodies in mice and protected many of them from the disease.

The approach, known as vector immunoprophylaxis (VIP), produced antibodies against the Plasmodium falciparum circumsporozoite protein (CSP) and prevented malaria infection in 10% to 100% of mice, depending on the dose and type of viral vector used.

Researchers recounted these results in PNAS.

“We need better ways to fight malaria,” said study author Gary Ketner, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. “And our research suggests [VIP] could be a promising approach.”

To test the approach, Dr Ketner and his colleagues constructed adeno-associated virus (AAV) vectors encoding human immunoglobulin G (hIgG) specific for the P falciparum CSP central repeat by inserting the variable regions of mouse monoclonal antibodies (mAbs) 2A10 and 2C11 into the hIgG framework of the VIP expression plasmid.

The team then injected mice with 1 x 10¹¹ genome copies (GC) of 2A10-AAV, 2C11-AAV, b12-AAV (which protects against HIV), or with buffer.

Within a week, the AAV-transduced mice expressed hIgG at 50 μg/mL to 500 μg/mL in serum. The expression increased until about the 4-week mark, when it reached 1000 μg/mL in some mice.

The mice that received 2A10-AAV or 2C11-AAV expressed antibodies that bound recombinant CSP and recognized whole P falciparum sporozoites. The b12-AAV-transduced mice and buffer-transduced mice did not.

In all AAV-transduced mice, serum antibody concentrations plateaued at 4 to 8 weeks and remained at that level through the end of the study, which was 52 weeks after transduction.

At the 8-week mark, the researchers tested the efficacy of VIP. They introduced—either intravenously or through a mosquito-bite challenge—transgenic Plasmodium berghei rodent sporozoites that incorporate the P falciparum target of the antibody in their CSP.

In the intravenously challenged group, 70% of 2A10-AAV-transduced mice were protected from malaria. In the mosquito-bite-challenged group, 60% of 2A10-AAV-transduced mice and 30% of 2C11-AAV-transduced mice were protected from malaria.

Role of dose and antibody level

To examine the effects of vector dose on mAb production and malaria protection, the researchers compared varying doses of 2A10-AAV to b12-AAV. They tested mice transduced with 3 x 10¹¹ GC of b12-AAV or doses of 2A10-AAV ranging from 3 x 10⁹ GC to 3 x 10¹¹ GC.

The team conducted a mosquito-bite challenge at 11 weeks after transduction. And they found that 70% of the mice that received the highest AAV dose (1 x 10¹¹ GC) were protected, as were 40% of mice that received 3 x 10¹⁰ GC and 10% of mice that received 1 x 10¹⁰ GC.

All mice transduced with 3 x 10⁹ GC were parasitemic by day 7, and all b12-AAV mice were parasitemic by day 6. There was a signficant correlation between 2A10 antibody concentration and day to parasitemia.

In a subset of mice that produced higher levels of antibodies, the antimalaria protection was 100%. These mice expressed CSP-specific mAb 2A10 at 1 mg/mL or more.

So it seems the protection from malaria is dose-dependent, said study author Cailin Deal, PhD, of the Ragon Institute of MGH, MIT and Harvard in Cambridge, Massachusetts.

“Of course, we don’t know what the human dosage would be,” she added, “but it’s conceivable that the right dosage could completely protect against malaria.”

Plasmodium sporozoite

Credit: Ute Frevert

and Margaret Shear

In a new study, genetically altered viruses produced long-lasting antimalaria antibodies in mice and protected many of them from the disease.

The approach, known as vector immunoprophylaxis (VIP), produced antibodies against the Plasmodium falciparum circumsporozoite protein (CSP) and prevented malaria infection in 10% to 100% of mice, depending on the dose and type of viral vector used.

Researchers recounted these results in PNAS.

“We need better ways to fight malaria,” said study author Gary Ketner, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. “And our research suggests [VIP] could be a promising approach.”

To test the approach, Dr Ketner and his colleagues constructed adeno-associated virus (AAV) vectors encoding human immunoglobulin G (hIgG) specific for the P falciparum CSP central repeat by inserting the variable regions of mouse monoclonal antibodies (mAbs) 2A10 and 2C11 into the hIgG framework of the VIP expression plasmid.

The team then injected mice with 1 x 10¹¹ genome copies (GC) of 2A10-AAV, 2C11-AAV, b12-AAV (which protects against HIV), or with buffer.

Within a week, the AAV-transduced mice expressed hIgG at 50 μg/mL to 500 μg/mL in serum. The expression increased until about the 4-week mark, when it reached 1000 μg/mL in some mice.

The mice that received 2A10-AAV or 2C11-AAV expressed antibodies that bound recombinant CSP and recognized whole P falciparum sporozoites. The b12-AAV-transduced mice and buffer-transduced mice did not.

In all AAV-transduced mice, serum antibody concentrations plateaued at 4 to 8 weeks and remained at that level through the end of the study, which was 52 weeks after transduction.

At the 8-week mark, the researchers tested the efficacy of VIP. They introduced—either intravenously or through a mosquito-bite challenge—transgenic Plasmodium berghei rodent sporozoites that incorporate the P falciparum target of the antibody in their CSP.

In the intravenously challenged group, 70% of 2A10-AAV-transduced mice were protected from malaria. In the mosquito-bite-challenged group, 60% of 2A10-AAV-transduced mice and 30% of 2C11-AAV-transduced mice were protected from malaria.

Role of dose and antibody level

To examine the effects of vector dose on mAb production and malaria protection, the researchers compared varying doses of 2A10-AAV to b12-AAV. They tested mice transduced with 3 x 10¹¹ GC of b12-AAV or doses of 2A10-AAV ranging from 3 x 10⁹ GC to 3 x 10¹¹ GC.

The team conducted a mosquito-bite challenge at 11 weeks after transduction. And they found that 70% of the mice that received the highest AAV dose (1 x 10¹¹ GC) were protected, as were 40% of mice that received 3 x 10¹⁰ GC and 10% of mice that received 1 x 10¹⁰ GC.

All mice transduced with 3 x 10⁹ GC were parasitemic by day 7, and all b12-AAV mice were parasitemic by day 6. There was a signficant correlation between 2A10 antibody concentration and day to parasitemia.

In a subset of mice that produced higher levels of antibodies, the antimalaria protection was 100%. These mice expressed CSP-specific mAb 2A10 at 1 mg/mL or more.

So it seems the protection from malaria is dose-dependent, said study author Cailin Deal, PhD, of the Ragon Institute of MGH, MIT and Harvard in Cambridge, Massachusetts.

“Of course, we don’t know what the human dosage would be,” she added, “but it’s conceivable that the right dosage could completely protect against malaria.”

Micrograph showing DLBCL

The US Food and Drug Administration (FDA) has granted orphan designation for the histone deacetylase (HDAC) inhibitor mocetinostat to treat diffuse large B-cell lymphoma (DLBCL). The drug already had orphan designation as a treatment for myelodysplastic syndrome (MDS).

The FDA grants orphan status to support the development of drugs for underserved patient populations or rare disorders affecting fewer than 200,000 people in the US.

Orphan designation provides the drug’s developer, Mirati Therapeutics, Inc., with certain benefits, including market exclusivity upon regulatory approval, exemption of FDA application fees, and tax credits for qualified clinical trials.

Mocetinostat works by reversing aberrant acetylation resulting from mutations in histone acetyltransferases (HATs).

The drug is being developed as a single-agent treatment for patients with DLBCL or bladder cancer characterized by HAT mutations that Mirati believes are critical in the pathogenesis and progression of these cancers.

“We have identified genetic alterations in histone acetylation pathways (CREBBP and EP300) in approximately one-third of DLBCL and bladder tumors,” said Charles Baum, MD, PhD, president and CEO of Mirati.

He added that nonclinical tumor models with these mutations have proven responsive to mocetinostat, so  Mirati predicts the HDAC inhibitor will halt tumor progression and reduce tumor burden in patients.

Mocetinostat is also under investigation in phase 2 studies in combination with azacitidine (Vidaza) as a treatment for intermediate- and high-risk MDS.

Mocetinostat previously demonstrated activity, as well as toxicity, in patients with Hodgkin lymphoma.

Micrograph showing DLBCL

The US Food and Drug Administration (FDA) has granted orphan designation for the histone deacetylase (HDAC) inhibitor mocetinostat to treat diffuse large B-cell lymphoma (DLBCL). The drug already had orphan designation as a treatment for myelodysplastic syndrome (MDS).

The FDA grants orphan status to support the development of drugs for underserved patient populations or rare disorders affecting fewer than 200,000 people in the US.

Orphan designation provides the drug’s developer, Mirati Therapeutics, Inc., with certain benefits, including market exclusivity upon regulatory approval, exemption of FDA application fees, and tax credits for qualified clinical trials.

Mocetinostat works by reversing aberrant acetylation resulting from mutations in histone acetyltransferases (HATs).

The drug is being developed as a single-agent treatment for patients with DLBCL or bladder cancer characterized by HAT mutations that Mirati believes are critical in the pathogenesis and progression of these cancers.

“We have identified genetic alterations in histone acetylation pathways (CREBBP and EP300) in approximately one-third of DLBCL and bladder tumors,” said Charles Baum, MD, PhD, president and CEO of Mirati.

He added that nonclinical tumor models with these mutations have proven responsive to mocetinostat, so  Mirati predicts the HDAC inhibitor will halt tumor progression and reduce tumor burden in patients.

Mocetinostat is also under investigation in phase 2 studies in combination with azacitidine (Vidaza) as a treatment for intermediate- and high-risk MDS.

Mocetinostat previously demonstrated activity, as well as toxicity, in patients with Hodgkin lymphoma.

Micrograph showing DLBCL

The US Food and Drug Administration (FDA) has granted orphan designation for the histone deacetylase (HDAC) inhibitor mocetinostat to treat diffuse large B-cell lymphoma (DLBCL). The drug already had orphan designation as a treatment for myelodysplastic syndrome (MDS).

The FDA grants orphan status to support the development of drugs for underserved patient populations or rare disorders affecting fewer than 200,000 people in the US.

Orphan designation provides the drug’s developer, Mirati Therapeutics, Inc., with certain benefits, including market exclusivity upon regulatory approval, exemption of FDA application fees, and tax credits for qualified clinical trials.

Mocetinostat works by reversing aberrant acetylation resulting from mutations in histone acetyltransferases (HATs).

The drug is being developed as a single-agent treatment for patients with DLBCL or bladder cancer characterized by HAT mutations that Mirati believes are critical in the pathogenesis and progression of these cancers.

“We have identified genetic alterations in histone acetylation pathways (CREBBP and EP300) in approximately one-third of DLBCL and bladder tumors,” said Charles Baum, MD, PhD, president and CEO of Mirati.

He added that nonclinical tumor models with these mutations have proven responsive to mocetinostat, so  Mirati predicts the HDAC inhibitor will halt tumor progression and reduce tumor burden in patients.

Mocetinostat is also under investigation in phase 2 studies in combination with azacitidine (Vidaza) as a treatment for intermediate- and high-risk MDS.

Mocetinostat previously demonstrated activity, as well as toxicity, in patients with Hodgkin lymphoma.

Atopic dermatitis remains a challenging condition.

The 2014 guidelines of care for the management of atopic dermatitis (AD) are being published by the American Academy of Dermatology in a series of four parts. Each part begins with a disclaimer stating that, "the ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient and the known variability and biologic behavior of the disease." The disclaimer continues, "This guideline reflects the best available data at the time the guideline was prepared. The results of future studies may require revisions to the recommendations in this guideline to reflect new data."

• Section 1: Diagnosis and assessment of atopic dermatitis. This section includes risk factors for the development of AD, diagnostic and monitoring techniques, assessment and outcomes, and clinical associations in AD patients (J. Am. Acad. Dermatol. 2014;70:338-51).

• Section 2: Management and treatment of atopic dermatitis with topical therapies. This section focuses on recommendations for the use of nonpharmacologic and topical therapies in the management of AD (J. Am. Acad. Dermatol. 2014;71:116-32).

• Section 3: Management and treatment with phototherapy and systemic agents. This section reviews indications for the use of phototherapy and systemic immunomodulators for treating AD, including side-effect profiles and clinical considerations for treating children (J. Am. Acad. Dermatol. 2014;71:327-49).

• Section 4: The fourth and final section of the guidelines is expected to be published in the September 2014 issue of the Journal of the American Academy of Dermatology.

No outside funding sources were involved in the creation of the guidelines. Disclosures of members of the guidelines committee are available following full text of each guidelines section in print and online.

[email protected]

Atopic dermatitis remains a challenging condition.

The 2014 guidelines of care for the management of atopic dermatitis (AD) are being published by the American Academy of Dermatology in a series of four parts. Each part begins with a disclaimer stating that, "the ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient and the known variability and biologic behavior of the disease." The disclaimer continues, "This guideline reflects the best available data at the time the guideline was prepared. The results of future studies may require revisions to the recommendations in this guideline to reflect new data."

• Section 1: Diagnosis and assessment of atopic dermatitis. This section includes risk factors for the development of AD, diagnostic and monitoring techniques, assessment and outcomes, and clinical associations in AD patients (J. Am. Acad. Dermatol. 2014;70:338-51).

• Section 2: Management and treatment of atopic dermatitis with topical therapies. This section focuses on recommendations for the use of nonpharmacologic and topical therapies in the management of AD (J. Am. Acad. Dermatol. 2014;71:116-32).

• Section 3: Management and treatment with phototherapy and systemic agents. This section reviews indications for the use of phototherapy and systemic immunomodulators for treating AD, including side-effect profiles and clinical considerations for treating children (J. Am. Acad. Dermatol. 2014;71:327-49).

• Section 4: The fourth and final section of the guidelines is expected to be published in the September 2014 issue of the Journal of the American Academy of Dermatology.

No outside funding sources were involved in the creation of the guidelines. Disclosures of members of the guidelines committee are available following full text of each guidelines section in print and online.

[email protected]

Atopic dermatitis remains a challenging condition.

The 2014 guidelines of care for the management of atopic dermatitis (AD) are being published by the American Academy of Dermatology in a series of four parts. Each part begins with a disclaimer stating that, "the ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient and the known variability and biologic behavior of the disease." The disclaimer continues, "This guideline reflects the best available data at the time the guideline was prepared. The results of future studies may require revisions to the recommendations in this guideline to reflect new data."

• Section 1: Diagnosis and assessment of atopic dermatitis. This section includes risk factors for the development of AD, diagnostic and monitoring techniques, assessment and outcomes, and clinical associations in AD patients (J. Am. Acad. Dermatol. 2014;70:338-51).

• Section 2: Management and treatment of atopic dermatitis with topical therapies. This section focuses on recommendations for the use of nonpharmacologic and topical therapies in the management of AD (J. Am. Acad. Dermatol. 2014;71:116-32).

• Section 3: Management and treatment with phototherapy and systemic agents. This section reviews indications for the use of phototherapy and systemic immunomodulators for treating AD, including side-effect profiles and clinical considerations for treating children (J. Am. Acad. Dermatol. 2014;71:327-49).

• Section 4: The fourth and final section of the guidelines is expected to be published in the September 2014 issue of the Journal of the American Academy of Dermatology.

No outside funding sources were involved in the creation of the guidelines. Disclosures of members of the guidelines committee are available following full text of each guidelines section in print and online.

[email protected]

"Mrs. Jones in ED room 12? Septic with severe multilobar pneumonia and hypoxemic respiratory failure? Got it. I’m on my way down to the ED now." The heart races in anticipation of caring for this critically ill patient near death’s door. But it’s okay. You know exactly what you have to do. You have done it many times before. No problem. Just as you are about to hang up the phone you learn more ...

"What’s that? She is 22 weeks pregnant? Uh, all right."

©Paul Hakimata/thinkstockphotos.com

Suddenly, what initially seemed to be a routine case takes a complicated twist. You are no longer caring for one life, you are caring for two (or more), and one of those is extremely frail and vulnerable. The bugs, the drugs, maintaining adequate perfusion of vital organs – both hers and her baby’s – the questions of "What if ... ?" and "Should I ... ?" race through your mind. Should you get infectious disease and pulmonary consultations for an added layer of protection or should you treat her as you have treated so many others before her, the caveat, of course, being the need to check every single drug for its teratogenicity.

If you have ever felt at least a little queasiness in the pit of your stomach when called upon to care for an expectant mother, you are notalone. I think it is natural to feel a bit uneasy when we care for pregnant patients because most of us do it rather infrequently and there may not be room for a do-over even if you make the tiniest mistake. Each drug we order has the potential to do harm and any missed or delayed diagnosis may be tolerated well by mom, but maybe not much by the tiny baby growing inside her. Get it right and the family may live a storybook fantasy. Yet, a single miscalculation, an honest mistake, and that innocent child’s future may be compromised or destroyed.

Fortunately, these days, horror stories seem to be less frequent than in the past. But we must remain vigilant to not only optimally treat our patient (mommy), but also to protect our patients (mommy and baby) from future complications of treatment. If there is any doubt, go ahead and call an infectious disease and pulmonary consultation. Sometimes, everyone sleeps better when we do.

Dr. A. Maria Hester is a hospitalist with Baltimore-Washington Medical Center, Glen Burnie, Md., who has a passion for empowering patients to partner in their health care. She is the creator of the Patient Whiz, a patient-engagement app for iOS.

"Mrs. Jones in ED room 12? Septic with severe multilobar pneumonia and hypoxemic respiratory failure? Got it. I’m on my way down to the ED now." The heart races in anticipation of caring for this critically ill patient near death’s door. But it’s okay. You know exactly what you have to do. You have done it many times before. No problem. Just as you are about to hang up the phone you learn more ...

"What’s that? She is 22 weeks pregnant? Uh, all right."

©Paul Hakimata/thinkstockphotos.com

Suddenly, what initially seemed to be a routine case takes a complicated twist. You are no longer caring for one life, you are caring for two (or more), and one of those is extremely frail and vulnerable. The bugs, the drugs, maintaining adequate perfusion of vital organs – both hers and her baby’s – the questions of "What if ... ?" and "Should I ... ?" race through your mind. Should you get infectious disease and pulmonary consultations for an added layer of protection or should you treat her as you have treated so many others before her, the caveat, of course, being the need to check every single drug for its teratogenicity.

If you have ever felt at least a little queasiness in the pit of your stomach when called upon to care for an expectant mother, you are notalone. I think it is natural to feel a bit uneasy when we care for pregnant patients because most of us do it rather infrequently and there may not be room for a do-over even if you make the tiniest mistake. Each drug we order has the potential to do harm and any missed or delayed diagnosis may be tolerated well by mom, but maybe not much by the tiny baby growing inside her. Get it right and the family may live a storybook fantasy. Yet, a single miscalculation, an honest mistake, and that innocent child’s future may be compromised or destroyed.

Fortunately, these days, horror stories seem to be less frequent than in the past. But we must remain vigilant to not only optimally treat our patient (mommy), but also to protect our patients (mommy and baby) from future complications of treatment. If there is any doubt, go ahead and call an infectious disease and pulmonary consultation. Sometimes, everyone sleeps better when we do.

Dr. A. Maria Hester is a hospitalist with Baltimore-Washington Medical Center, Glen Burnie, Md., who has a passion for empowering patients to partner in their health care. She is the creator of the Patient Whiz, a patient-engagement app for iOS.

"Mrs. Jones in ED room 12? Septic with severe multilobar pneumonia and hypoxemic respiratory failure? Got it. I’m on my way down to the ED now." The heart races in anticipation of caring for this critically ill patient near death’s door. But it’s okay. You know exactly what you have to do. You have done it many times before. No problem. Just as you are about to hang up the phone you learn more ...

"What’s that? She is 22 weeks pregnant? Uh, all right."

©Paul Hakimata/thinkstockphotos.com

Suddenly, what initially seemed to be a routine case takes a complicated twist. You are no longer caring for one life, you are caring for two (or more), and one of those is extremely frail and vulnerable. The bugs, the drugs, maintaining adequate perfusion of vital organs – both hers and her baby’s – the questions of "What if ... ?" and "Should I ... ?" race through your mind. Should you get infectious disease and pulmonary consultations for an added layer of protection or should you treat her as you have treated so many others before her, the caveat, of course, being the need to check every single drug for its teratogenicity.

If you have ever felt at least a little queasiness in the pit of your stomach when called upon to care for an expectant mother, you are notalone. I think it is natural to feel a bit uneasy when we care for pregnant patients because most of us do it rather infrequently and there may not be room for a do-over even if you make the tiniest mistake. Each drug we order has the potential to do harm and any missed or delayed diagnosis may be tolerated well by mom, but maybe not much by the tiny baby growing inside her. Get it right and the family may live a storybook fantasy. Yet, a single miscalculation, an honest mistake, and that innocent child’s future may be compromised or destroyed.

Fortunately, these days, horror stories seem to be less frequent than in the past. But we must remain vigilant to not only optimally treat our patient (mommy), but also to protect our patients (mommy and baby) from future complications of treatment. If there is any doubt, go ahead and call an infectious disease and pulmonary consultation. Sometimes, everyone sleeps better when we do.

Dr. A. Maria Hester is a hospitalist with Baltimore-Washington Medical Center, Glen Burnie, Md., who has a passion for empowering patients to partner in their health care. She is the creator of the Patient Whiz, a patient-engagement app for iOS.

A tree species belonging to the Rosaceae family and native to the Middle East and South Asia, Prunus dulcis (also called Prunus amygdalus), popularly known as almond, is cultivated widely in warm, arid locations and used primarily for its edible seeds (J. Agric. Food Chem. 2007;55:8498-507; J. Agric. Food Chem. 2006;54:312-8). Almonds and almond skins are rich in polyphenols and are an important source of these phytonutrients, particularly flavan-3-ols and flavonols (J. Proteome Res. 2010;9:5859-67). Almonds also are known to contain an abundance of fiber (Anaerobe 2014;26:1-6). Almond extracts are used in cosmetic formulations because of their high concentration of polyphenols, particularly flavonoids and phenolic acids (Int. J. Curr. Pharm. Res. 2011;3:57-9).

Key components

In 2006, Milbury et al. determined that the main flavonoids and phenolic acids in Prunus dulcis skins and kernels are isorhamnetin-3-O-rutinoside and isorhamnetin-3-O-glucoside (in combination), catechin, kaempferol-3-O-rutinoside, epicatechin, quercetin-3-O-galactoside, and isorhamnetin-3-O-galactoside (J. Agric. Food Chem. 2006;54:5027-33).

Wikimedia Commons/PikiWiki_Israel_7025_Amond_blossom.jpg

In a separate study that year, Wijeratne et al. identified quercetin, isorhamnetin, quercitrin, kaempferol 3-O-rutinoside, isorhamnetin 3-O-glucoside, and morin as the primary flavonoids in various whole-seed, brown, skin, and green-shell-cover almond extracts (J. Agric. Food Chem. 2006;54:312-8). Almond seed skin also has been shown to contain highly polymerized polyphenols that exhibit potent alpha-amylase inhibitory activity, thus slowing the absorption of carbohydrate (J. Agric. Food Chem. 2013;61:4570-6).

In 2010, Bartolomé et al. identified A- and B-type procyanidin, propelargonidin, and prodelphinidin polymers in almond skins. In human plasma and urine samples taken after consumption of almond skin polyphenols, the investigators detected O-methyl glucuronide sulfate and O-methyl sulfate derivatives of (epi)catechin; the glucuronide conjugates of naringenin and isorhamnetin; and sulfate conjugates of isorhamnetin, together with conjugates of hydroxyphenylvalerolactones. They also identified various microbial-derived metabolites, including hydroxyphenylpropionic, hydroxyphenylacetic, hydroxycinnamic, hydroxybenzoic, and hydroxyhippuric acids (Arch. Biochem. Biophys. 2010;501:124-33).

A functional food: Antioxidant constituents and activity

In a study of two human subjects conducted in 2009, Urpi-Sarda et al. profiled microbial-derived phenolic metabolites in plasma and urine samples before and after the consumption of almond skins. They detected glucuronide, O-methyl glucuronide sulfate, and O-methyl sulfate derivatives of epicatechin, the glucuronide conjugates of naringenin and glucuronide, and sulfate conjugates of isorhamnetin. The researchers also detected, in their glucuronide and sulfate forms, microbial-derived metabolites of flavanols, including 5-(dihydroxyphenyl)-gamma-valerolactone and 5-(hydroxymethoxyphenyl)-gamma-valerolactone (J. Agric. Food Chem. 2009;57:10134-42).

A 2010 study with 24 volunteers conducted by Llorach et al. investigated urinary metabolome changes during the 24-hour period following ingestion of a single dose of almond skin extract. The participants, who were following a polyphenol-free diet for 48 hours, were divided into two groups: the almond skin group or a placebo group. Thirty-four metabolites were linked to the consumption of the almond extract (J. Proteome Res. 2010;9:5859-67).

Monagas et al. previously led a comprehensive investigation of the phenolic composition of almond skins to elucidate its potential as a functional food. They identified 33 compounds, including flavanols, flavonols, dihydroflavonols, and flavanones, as well as nonflavonoid substances. The most abundant phenols were flavanols (38%-57%) and flavonol glycosides (14%-35%). Further, the researchers measured the oxygen radical absorbance capacity of almond skins at 0.398-0.500 mmol Trolox/g, a range that suggests its antioxidant potency (J. Agric. Food Chem. 2007;55:8498-507).

In 2008, Garrido et al. investigated the phenolic composition and antioxidant activity of almond skins (Prunus dulcis) obtained from three almond varieties and through various industrial processes, including blanching, blanching and drying, as well as roasting. Identified were 31 phenolic compounds, including flavan-3-ols, flavonol glycosides, hydroxybenzoic acids and aldehydes, flavonol aglycones, flavanone glycosides, flavanone aglycones, hydroxycinnamic acids, and dihydroflavonol aglycones. Phenolic content as well as antioxidant activity were significantly higher in the roasted samples (J. Food Sci. 2008;73:C106-15).

In 2014, Liu et al. conducted a study in healthy humans of the potential prebiotic effects of consuming almonds and almond skins. For 6 weeks, 48 adult volunteers ingested a daily dose of roasted almonds, almond skins, or a positive control (commercial fructo-oligosaccharides). The investigators collected fecal samples and analyzed them for microbiota composition. They observed significant increases in populations of Bifidobacterium spp. and Lactobacillus spp. in fecal samples after almond or almond skin supplementation; substantial inhibition of the growth of the pathogen Clostridium perfringens; and favorable changes in bacterial enzyme activities. They concluded that almonds and almond skins appear to exhibit potential prebiotic qualities (Anaerobe 2014;26:1-6).

Topical antiaging potential

In 2011, Sachdeva and Katyal assessed the antioxidant and antiwrinkle effects of almond skin extracts in UV-induced photoaging in mice. Twenty-five mice were used as an unirradiated control, receiving neither UV exposure nor almond skin treatment. A second group of 24 mice received only UV exposure of 5 minutes twice a day, and served as an irradiated control. Further groups of 24 mice received both UV radiation and treatment with prepared formulation. The treatment groups received various topical almond skin extract doses 2 hours prior to the same level of UV exposure. Significant decreases in malondialdehyde and increases in glutathione levels, respectively, suggested to the investigators that the almond skin extracts effectively scavenged free radicals while also enhancing moisturization. They concluded that almond skin extracts display potential as antiaging ingredients in topical cosmetic formulations (Int. J. Curr. Pharm. Res. 2011;3:57-9).

Conclusion

Almonds are believed to be a healthy addition to the human diet, with their regular consumption thought to confer cardiovascular benefits. The healthful effects of dietary intake of almonds are often attributed to the presence of several polyphenolic constituents. While it is speculated that such ingredients also play a role in imparting cutaneous benefits, the body of evidence supporting such claims remains sparse to date. Nevertheless, P. dulcis is incorporated in various cosmetic formulations. More research is necessary to ascertain whether such inclusion is warranted.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in Miami Beach. She founded the cosmetic dermatology center at the University of Miami in 1997. Dr. Baumann wrote the textbook "Cosmetic Dermatology: Principles and Practice" (McGraw-Hill, April 2002), and a book for consumers, "The Skin Type Solution" (Bantam, 2006). She has contributed to the Cosmeceutical Critique column in Skin & Allergy News since January 2001. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Galderma, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Stiefel, Topix Pharmaceuticals, and Unilever.

A tree species belonging to the Rosaceae family and native to the Middle East and South Asia, Prunus dulcis (also called Prunus amygdalus), popularly known as almond, is cultivated widely in warm, arid locations and used primarily for its edible seeds (J. Agric. Food Chem. 2007;55:8498-507; J. Agric. Food Chem. 2006;54:312-8). Almonds and almond skins are rich in polyphenols and are an important source of these phytonutrients, particularly flavan-3-ols and flavonols (J. Proteome Res. 2010;9:5859-67). Almonds also are known to contain an abundance of fiber (Anaerobe 2014;26:1-6). Almond extracts are used in cosmetic formulations because of their high concentration of polyphenols, particularly flavonoids and phenolic acids (Int. J. Curr. Pharm. Res. 2011;3:57-9).

Key components

In 2006, Milbury et al. determined that the main flavonoids and phenolic acids in Prunus dulcis skins and kernels are isorhamnetin-3-O-rutinoside and isorhamnetin-3-O-glucoside (in combination), catechin, kaempferol-3-O-rutinoside, epicatechin, quercetin-3-O-galactoside, and isorhamnetin-3-O-galactoside (J. Agric. Food Chem. 2006;54:5027-33).

Wikimedia Commons/PikiWiki_Israel_7025_Amond_blossom.jpg

In a separate study that year, Wijeratne et al. identified quercetin, isorhamnetin, quercitrin, kaempferol 3-O-rutinoside, isorhamnetin 3-O-glucoside, and morin as the primary flavonoids in various whole-seed, brown, skin, and green-shell-cover almond extracts (J. Agric. Food Chem. 2006;54:312-8). Almond seed skin also has been shown to contain highly polymerized polyphenols that exhibit potent alpha-amylase inhibitory activity, thus slowing the absorption of carbohydrate (J. Agric. Food Chem. 2013;61:4570-6).

In 2010, Bartolomé et al. identified A- and B-type procyanidin, propelargonidin, and prodelphinidin polymers in almond skins. In human plasma and urine samples taken after consumption of almond skin polyphenols, the investigators detected O-methyl glucuronide sulfate and O-methyl sulfate derivatives of (epi)catechin; the glucuronide conjugates of naringenin and isorhamnetin; and sulfate conjugates of isorhamnetin, together with conjugates of hydroxyphenylvalerolactones. They also identified various microbial-derived metabolites, including hydroxyphenylpropionic, hydroxyphenylacetic, hydroxycinnamic, hydroxybenzoic, and hydroxyhippuric acids (Arch. Biochem. Biophys. 2010;501:124-33).

A functional food: Antioxidant constituents and activity

In a study of two human subjects conducted in 2009, Urpi-Sarda et al. profiled microbial-derived phenolic metabolites in plasma and urine samples before and after the consumption of almond skins. They detected glucuronide, O-methyl glucuronide sulfate, and O-methyl sulfate derivatives of epicatechin, the glucuronide conjugates of naringenin and glucuronide, and sulfate conjugates of isorhamnetin. The researchers also detected, in their glucuronide and sulfate forms, microbial-derived metabolites of flavanols, including 5-(dihydroxyphenyl)-gamma-valerolactone and 5-(hydroxymethoxyphenyl)-gamma-valerolactone (J. Agric. Food Chem. 2009;57:10134-42).

A 2010 study with 24 volunteers conducted by Llorach et al. investigated urinary metabolome changes during the 24-hour period following ingestion of a single dose of almond skin extract. The participants, who were following a polyphenol-free diet for 48 hours, were divided into two groups: the almond skin group or a placebo group. Thirty-four metabolites were linked to the consumption of the almond extract (J. Proteome Res. 2010;9:5859-67).

Monagas et al. previously led a comprehensive investigation of the phenolic composition of almond skins to elucidate its potential as a functional food. They identified 33 compounds, including flavanols, flavonols, dihydroflavonols, and flavanones, as well as nonflavonoid substances. The most abundant phenols were flavanols (38%-57%) and flavonol glycosides (14%-35%). Further, the researchers measured the oxygen radical absorbance capacity of almond skins at 0.398-0.500 mmol Trolox/g, a range that suggests its antioxidant potency (J. Agric. Food Chem. 2007;55:8498-507).

In 2008, Garrido et al. investigated the phenolic composition and antioxidant activity of almond skins (Prunus dulcis) obtained from three almond varieties and through various industrial processes, including blanching, blanching and drying, as well as roasting. Identified were 31 phenolic compounds, including flavan-3-ols, flavonol glycosides, hydroxybenzoic acids and aldehydes, flavonol aglycones, flavanone glycosides, flavanone aglycones, hydroxycinnamic acids, and dihydroflavonol aglycones. Phenolic content as well as antioxidant activity were significantly higher in the roasted samples (J. Food Sci. 2008;73:C106-15).

In 2014, Liu et al. conducted a study in healthy humans of the potential prebiotic effects of consuming almonds and almond skins. For 6 weeks, 48 adult volunteers ingested a daily dose of roasted almonds, almond skins, or a positive control (commercial fructo-oligosaccharides). The investigators collected fecal samples and analyzed them for microbiota composition. They observed significant increases in populations of Bifidobacterium spp. and Lactobacillus spp. in fecal samples after almond or almond skin supplementation; substantial inhibition of the growth of the pathogen Clostridium perfringens; and favorable changes in bacterial enzyme activities. They concluded that almonds and almond skins appear to exhibit potential prebiotic qualities (Anaerobe 2014;26:1-6).

Topical antiaging potential

In 2011, Sachdeva and Katyal assessed the antioxidant and antiwrinkle effects of almond skin extracts in UV-induced photoaging in mice. Twenty-five mice were used as an unirradiated control, receiving neither UV exposure nor almond skin treatment. A second group of 24 mice received only UV exposure of 5 minutes twice a day, and served as an irradiated control. Further groups of 24 mice received both UV radiation and treatment with prepared formulation. The treatment groups received various topical almond skin extract doses 2 hours prior to the same level of UV exposure. Significant decreases in malondialdehyde and increases in glutathione levels, respectively, suggested to the investigators that the almond skin extracts effectively scavenged free radicals while also enhancing moisturization. They concluded that almond skin extracts display potential as antiaging ingredients in topical cosmetic formulations (Int. J. Curr. Pharm. Res. 2011;3:57-9).

Conclusion

Almonds are believed to be a healthy addition to the human diet, with their regular consumption thought to confer cardiovascular benefits. The healthful effects of dietary intake of almonds are often attributed to the presence of several polyphenolic constituents. While it is speculated that such ingredients also play a role in imparting cutaneous benefits, the body of evidence supporting such claims remains sparse to date. Nevertheless, P. dulcis is incorporated in various cosmetic formulations. More research is necessary to ascertain whether such inclusion is warranted.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in Miami Beach. She founded the cosmetic dermatology center at the University of Miami in 1997. Dr. Baumann wrote the textbook "Cosmetic Dermatology: Principles and Practice" (McGraw-Hill, April 2002), and a book for consumers, "The Skin Type Solution" (Bantam, 2006). She has contributed to the Cosmeceutical Critique column in Skin & Allergy News since January 2001. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Galderma, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Stiefel, Topix Pharmaceuticals, and Unilever.

A tree species belonging to the Rosaceae family and native to the Middle East and South Asia, Prunus dulcis (also called Prunus amygdalus), popularly known as almond, is cultivated widely in warm, arid locations and used primarily for its edible seeds (J. Agric. Food Chem. 2007;55:8498-507; J. Agric. Food Chem. 2006;54:312-8). Almonds and almond skins are rich in polyphenols and are an important source of these phytonutrients, particularly flavan-3-ols and flavonols (J. Proteome Res. 2010;9:5859-67). Almonds also are known to contain an abundance of fiber (Anaerobe 2014;26:1-6). Almond extracts are used in cosmetic formulations because of their high concentration of polyphenols, particularly flavonoids and phenolic acids (Int. J. Curr. Pharm. Res. 2011;3:57-9).

Key components

In 2006, Milbury et al. determined that the main flavonoids and phenolic acids in Prunus dulcis skins and kernels are isorhamnetin-3-O-rutinoside and isorhamnetin-3-O-glucoside (in combination), catechin, kaempferol-3-O-rutinoside, epicatechin, quercetin-3-O-galactoside, and isorhamnetin-3-O-galactoside (J. Agric. Food Chem. 2006;54:5027-33).

Wikimedia Commons/PikiWiki_Israel_7025_Amond_blossom.jpg

In a separate study that year, Wijeratne et al. identified quercetin, isorhamnetin, quercitrin, kaempferol 3-O-rutinoside, isorhamnetin 3-O-glucoside, and morin as the primary flavonoids in various whole-seed, brown, skin, and green-shell-cover almond extracts (J. Agric. Food Chem. 2006;54:312-8). Almond seed skin also has been shown to contain highly polymerized polyphenols that exhibit potent alpha-amylase inhibitory activity, thus slowing the absorption of carbohydrate (J. Agric. Food Chem. 2013;61:4570-6).

In 2010, Bartolomé et al. identified A- and B-type procyanidin, propelargonidin, and prodelphinidin polymers in almond skins. In human plasma and urine samples taken after consumption of almond skin polyphenols, the investigators detected O-methyl glucuronide sulfate and O-methyl sulfate derivatives of (epi)catechin; the glucuronide conjugates of naringenin and isorhamnetin; and sulfate conjugates of isorhamnetin, together with conjugates of hydroxyphenylvalerolactones. They also identified various microbial-derived metabolites, including hydroxyphenylpropionic, hydroxyphenylacetic, hydroxycinnamic, hydroxybenzoic, and hydroxyhippuric acids (Arch. Biochem. Biophys. 2010;501:124-33).

A functional food: Antioxidant constituents and activity

In a study of two human subjects conducted in 2009, Urpi-Sarda et al. profiled microbial-derived phenolic metabolites in plasma and urine samples before and after the consumption of almond skins. They detected glucuronide, O-methyl glucuronide sulfate, and O-methyl sulfate derivatives of epicatechin, the glucuronide conjugates of naringenin and glucuronide, and sulfate conjugates of isorhamnetin. The researchers also detected, in their glucuronide and sulfate forms, microbial-derived metabolites of flavanols, including 5-(dihydroxyphenyl)-gamma-valerolactone and 5-(hydroxymethoxyphenyl)-gamma-valerolactone (J. Agric. Food Chem. 2009;57:10134-42).

A 2010 study with 24 volunteers conducted by Llorach et al. investigated urinary metabolome changes during the 24-hour period following ingestion of a single dose of almond skin extract. The participants, who were following a polyphenol-free diet for 48 hours, were divided into two groups: the almond skin group or a placebo group. Thirty-four metabolites were linked to the consumption of the almond extract (J. Proteome Res. 2010;9:5859-67).

Monagas et al. previously led a comprehensive investigation of the phenolic composition of almond skins to elucidate its potential as a functional food. They identified 33 compounds, including flavanols, flavonols, dihydroflavonols, and flavanones, as well as nonflavonoid substances. The most abundant phenols were flavanols (38%-57%) and flavonol glycosides (14%-35%). Further, the researchers measured the oxygen radical absorbance capacity of almond skins at 0.398-0.500 mmol Trolox/g, a range that suggests its antioxidant potency (J. Agric. Food Chem. 2007;55:8498-507).

In 2008, Garrido et al. investigated the phenolic composition and antioxidant activity of almond skins (Prunus dulcis) obtained from three almond varieties and through various industrial processes, including blanching, blanching and drying, as well as roasting. Identified were 31 phenolic compounds, including flavan-3-ols, flavonol glycosides, hydroxybenzoic acids and aldehydes, flavonol aglycones, flavanone glycosides, flavanone aglycones, hydroxycinnamic acids, and dihydroflavonol aglycones. Phenolic content as well as antioxidant activity were significantly higher in the roasted samples (J. Food Sci. 2008;73:C106-15).

In 2014, Liu et al. conducted a study in healthy humans of the potential prebiotic effects of consuming almonds and almond skins. For 6 weeks, 48 adult volunteers ingested a daily dose of roasted almonds, almond skins, or a positive control (commercial fructo-oligosaccharides). The investigators collected fecal samples and analyzed them for microbiota composition. They observed significant increases in populations of Bifidobacterium spp. and Lactobacillus spp. in fecal samples after almond or almond skin supplementation; substantial inhibition of the growth of the pathogen Clostridium perfringens; and favorable changes in bacterial enzyme activities. They concluded that almonds and almond skins appear to exhibit potential prebiotic qualities (Anaerobe 2014;26:1-6).

Topical antiaging potential

In 2011, Sachdeva and Katyal assessed the antioxidant and antiwrinkle effects of almond skin extracts in UV-induced photoaging in mice. Twenty-five mice were used as an unirradiated control, receiving neither UV exposure nor almond skin treatment. A second group of 24 mice received only UV exposure of 5 minutes twice a day, and served as an irradiated control. Further groups of 24 mice received both UV radiation and treatment with prepared formulation. The treatment groups received various topical almond skin extract doses 2 hours prior to the same level of UV exposure. Significant decreases in malondialdehyde and increases in glutathione levels, respectively, suggested to the investigators that the almond skin extracts effectively scavenged free radicals while also enhancing moisturization. They concluded that almond skin extracts display potential as antiaging ingredients in topical cosmetic formulations (Int. J. Curr. Pharm. Res. 2011;3:57-9).

Conclusion

Almonds are believed to be a healthy addition to the human diet, with their regular consumption thought to confer cardiovascular benefits. The healthful effects of dietary intake of almonds are often attributed to the presence of several polyphenolic constituents. While it is speculated that such ingredients also play a role in imparting cutaneous benefits, the body of evidence supporting such claims remains sparse to date. Nevertheless, P. dulcis is incorporated in various cosmetic formulations. More research is necessary to ascertain whether such inclusion is warranted.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in Miami Beach. She founded the cosmetic dermatology center at the University of Miami in 1997. Dr. Baumann wrote the textbook "Cosmetic Dermatology: Principles and Practice" (McGraw-Hill, April 2002), and a book for consumers, "The Skin Type Solution" (Bantam, 2006). She has contributed to the Cosmeceutical Critique column in Skin & Allergy News since January 2001. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Galderma, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Stiefel, Topix Pharmaceuticals, and Unilever.

Medical imaging was the first taste of digital health technology for physicians and most health care providers. The technology provides prompt high-quality information which improves efficiency and is mobile. Then came electronic health records (EHRs). EHRs were mandated as part of the Health Information Technology for Economic and Clinical Health (HITECH) Act of 2009. The goals of EHRs are to improve patient safety, decrease costs, and allow for the seamless exchange of information among providers and providing entities. As a proponent of digital health technologies, I submit that they are patient advocacy tools. The debate over the "effectiveness"of EHRs continues. It is too early to evaluate the true impact of EHRs on patient care at this juncture. Stage 1 of Meaningful Use (MU) of EHRs pertains solely to data capture. It is with Stages 2 and 3 that patient engagement and clinical decision support tools are incorporated in processes around the EHR. These stages have not been fully implemented and won’t be for a few years to come. Therefore those attributes of MU potentially having the most impact on patients are not in use today. What we do know is that: A) Physicians are spending more time looking at computer screens than into the faces of the people they are treating. B) That much of the data entered is to satisfy regulations of the HITECH Act and not directly related to patient care. C) That EHRs were designed for billing and regulatory purposes and do not in any way reflect clinical work flow. D) EHRs do not integrate well with medical devices or disparate digital health technology systems. However some excellent progress has been made in developing true interoperability among systems.

The EHR does not represent the face of digital technology in health care. Mobile health technologies, wearable sensor technologies, aging at home technologies, and ingestible medication sensor technology populate today’s digital health landscape. These are developments which will contribute directly to more efficient and improved patient care. They will address gaps in care. Having a mother who is ill and requiring significant help at home has taken me on a journey riddled with frustration and pain that is also experienced by my patients and their caregivers daily. It has made me a better physician, who realizes that the most important aspect of care is empathy. Most people view technology as a something that creates a divide between provider and patient. Effective technology can actually bring them closer. It can deliver trending data (which must be accurate, filtered, and actionable in order to be useful), drastically altering care recommendations and preventing hospitalizations and medical emergencies. While there remains much to be proven with regards to digital technologies, I expect them to become a backbone of the health care landscape.

Another digital health technology sector making its way into advanced health care enterprises is analytics. These tools take health care "big data" and make it relevant to treating individual patients as well as populations. Use cases for health care analytics demonstrate that EHRs, while being innately clumsy can be transformed into powerful sources of useful information.

Patients as consumers are demanding mobile tools long utilized in the retail and finance sectors . Examples can be seen in patient-physician video conferencing, mobile appointment schedulers, and even a smartphone ECG rhythm monitor. Digital health also involves social media. Patients are now finding themselves in online patient support groups. There are significant advantages of online versus real life support groups. On the provider side, digital tools such as Doximity and Epocratesare widely used.

In summary, the digital health landscape is much broader and friendlier than the EHR of today. I look forward to EHRs becoming more user friendly and clinically rewarding.

Dr. Scher is an electrophysiologist with the Heart Group of Lancaster (Pa.) General Health. He is also director of DLS Healthcare Consulting, Harrisburg, Pa., and clinical associate professor of medicine at the Pennsylvania State University, Hershey.

Medical imaging was the first taste of digital health technology for physicians and most health care providers. The technology provides prompt high-quality information which improves efficiency and is mobile. Then came electronic health records (EHRs). EHRs were mandated as part of the Health Information Technology for Economic and Clinical Health (HITECH) Act of 2009. The goals of EHRs are to improve patient safety, decrease costs, and allow for the seamless exchange of information among providers and providing entities. As a proponent of digital health technologies, I submit that they are patient advocacy tools. The debate over the "effectiveness"of EHRs continues. It is too early to evaluate the true impact of EHRs on patient care at this juncture. Stage 1 of Meaningful Use (MU) of EHRs pertains solely to data capture. It is with Stages 2 and 3 that patient engagement and clinical decision support tools are incorporated in processes around the EHR. These stages have not been fully implemented and won’t be for a few years to come. Therefore those attributes of MU potentially having the most impact on patients are not in use today. What we do know is that: A) Physicians are spending more time looking at computer screens than into the faces of the people they are treating. B) That much of the data entered is to satisfy regulations of the HITECH Act and not directly related to patient care. C) That EHRs were designed for billing and regulatory purposes and do not in any way reflect clinical work flow. D) EHRs do not integrate well with medical devices or disparate digital health technology systems. However some excellent progress has been made in developing true interoperability among systems.

The EHR does not represent the face of digital technology in health care. Mobile health technologies, wearable sensor technologies, aging at home technologies, and ingestible medication sensor technology populate today’s digital health landscape. These are developments which will contribute directly to more efficient and improved patient care. They will address gaps in care. Having a mother who is ill and requiring significant help at home has taken me on a journey riddled with frustration and pain that is also experienced by my patients and their caregivers daily. It has made me a better physician, who realizes that the most important aspect of care is empathy. Most people view technology as a something that creates a divide between provider and patient. Effective technology can actually bring them closer. It can deliver trending data (which must be accurate, filtered, and actionable in order to be useful), drastically altering care recommendations and preventing hospitalizations and medical emergencies. While there remains much to be proven with regards to digital technologies, I expect them to become a backbone of the health care landscape.

Another digital health technology sector making its way into advanced health care enterprises is analytics. These tools take health care "big data" and make it relevant to treating individual patients as well as populations. Use cases for health care analytics demonstrate that EHRs, while being innately clumsy can be transformed into powerful sources of useful information.

Patients as consumers are demanding mobile tools long utilized in the retail and finance sectors . Examples can be seen in patient-physician video conferencing, mobile appointment schedulers, and even a smartphone ECG rhythm monitor. Digital health also involves social media. Patients are now finding themselves in online patient support groups. There are significant advantages of online versus real life support groups. On the provider side, digital tools such as Doximity and Epocratesare widely used.

In summary, the digital health landscape is much broader and friendlier than the EHR of today. I look forward to EHRs becoming more user friendly and clinically rewarding.

Dr. Scher is an electrophysiologist with the Heart Group of Lancaster (Pa.) General Health. He is also director of DLS Healthcare Consulting, Harrisburg, Pa., and clinical associate professor of medicine at the Pennsylvania State University, Hershey.

Medical imaging was the first taste of digital health technology for physicians and most health care providers. The technology provides prompt high-quality information which improves efficiency and is mobile. Then came electronic health records (EHRs). EHRs were mandated as part of the Health Information Technology for Economic and Clinical Health (HITECH) Act of 2009. The goals of EHRs are to improve patient safety, decrease costs, and allow for the seamless exchange of information among providers and providing entities. As a proponent of digital health technologies, I submit that they are patient advocacy tools. The debate over the "effectiveness"of EHRs continues. It is too early to evaluate the true impact of EHRs on patient care at this juncture. Stage 1 of Meaningful Use (MU) of EHRs pertains solely to data capture. It is with Stages 2 and 3 that patient engagement and clinical decision support tools are incorporated in processes around the EHR. These stages have not been fully implemented and won’t be for a few years to come. Therefore those attributes of MU potentially having the most impact on patients are not in use today. What we do know is that: A) Physicians are spending more time looking at computer screens than into the faces of the people they are treating. B) That much of the data entered is to satisfy regulations of the HITECH Act and not directly related to patient care. C) That EHRs were designed for billing and regulatory purposes and do not in any way reflect clinical work flow. D) EHRs do not integrate well with medical devices or disparate digital health technology systems. However some excellent progress has been made in developing true interoperability among systems.

The EHR does not represent the face of digital technology in health care. Mobile health technologies, wearable sensor technologies, aging at home technologies, and ingestible medication sensor technology populate today’s digital health landscape. These are developments which will contribute directly to more efficient and improved patient care. They will address gaps in care. Having a mother who is ill and requiring significant help at home has taken me on a journey riddled with frustration and pain that is also experienced by my patients and their caregivers daily. It has made me a better physician, who realizes that the most important aspect of care is empathy. Most people view technology as a something that creates a divide between provider and patient. Effective technology can actually bring them closer. It can deliver trending data (which must be accurate, filtered, and actionable in order to be useful), drastically altering care recommendations and preventing hospitalizations and medical emergencies. While there remains much to be proven with regards to digital technologies, I expect them to become a backbone of the health care landscape.

Another digital health technology sector making its way into advanced health care enterprises is analytics. These tools take health care "big data" and make it relevant to treating individual patients as well as populations. Use cases for health care analytics demonstrate that EHRs, while being innately clumsy can be transformed into powerful sources of useful information.

Patients as consumers are demanding mobile tools long utilized in the retail and finance sectors . Examples can be seen in patient-physician video conferencing, mobile appointment schedulers, and even a smartphone ECG rhythm monitor. Digital health also involves social media. Patients are now finding themselves in online patient support groups. There are significant advantages of online versus real life support groups. On the provider side, digital tools such as Doximity and Epocratesare widely used.

In summary, the digital health landscape is much broader and friendlier than the EHR of today. I look forward to EHRs becoming more user friendly and clinically rewarding.

Dr. Scher is an electrophysiologist with the Heart Group of Lancaster (Pa.) General Health. He is also director of DLS Healthcare Consulting, Harrisburg, Pa., and clinical associate professor of medicine at the Pennsylvania State University, Hershey.

The news last night was tragic: Robin Williams has died of an apparent suicide at the early age of 63. I saw the news and felt overwhelmingly sad. Really? He was a tremendous actor, a creative genius by any account, a man who I imagined had everything – talent, wealth, fame, the wonderful ability to make people laugh and to brighten lives. Such people also get draped with love and admiration, though certainly at a price. For what it’s worth, Robin Williams has been open about the fact that he’s struggled with both depression and addiction, but the complete story is never the one that gets told by the media.

Courtesy Wikimedia Commons/John J. Kruzel/Creative Commons License

Twitter started with 140-character links to suicide hotlines and suicide awareness, to statements about how depression is a treatable illness – Is it always? – and I hit retweet on a comment stating:" We’re never going to get anywhere till we take seriously that depression is an illness, not a weakness" and several people retweeted my retweet. I’m not sure why I did this; I don’t think that most people still think of mood disorders as a "weakness," or that those who do might change their minds because of a tweet. And I don’t think that suicide does anything to reduce stigma.

One psychiatrist friend tweeted a comment about how one should never ask someone why they are depressed, I guess because the "why?" implies something other than because biology dictated it, but if you’ve ever spoken to a person suffering from depression, you know that it comes in all shades of severity and that people often write a story to explain it. Sometimes that story is right: I’m depressed because of a breakup, or because I don’t have a job now, or because of ongoing work stress – and indeed, the person suffering often feels better after talking about the situation, after getting a new boyfriend or a new job, or after their boss moves to Zimbabwe.

I’m convinced that treatment works best when psychotherapy is combined with medication (if indicated), and while medicines are a miracle for some, they aren’t for others. As psychiatrists, we certainly see a good deal of treatment-resistant depression. And yes, the antipsychiatry faction may postulate that it is the treatment – the medications, specifically – that cause people to kill themselves and others, but I will leave you with the idea that the science just doesn’t support that. Certainly, they aren’t for everyone, but clinically, I have seen medications do more good than harm in clinical practice overall.

I know nothing about Robin Williams beyond what I’ve read in the media, and I know that the media reports are often incomplete and distorted. I do imagine that Mr. Williams had the resources to get good care and that he may well have had treatment for depression since he was open about his struggle. His story will be used to say: "Get help," and if you’re feeling suicidal and aren’t getting help, please do so. If you’re feeling suicidal and "help" isn’t making you feel better, please consider getting a second opinion or a different kind of help.

The tragic thing about suicide is that it’s a permanent answer to what is often a temporary problem.

Sometimes, I imagine that there are people who have tried and tried to get help and that their pain remains so unbearable for so long that suicide offers them the only possible relief – if such a thing is even to be had given that we don’t what comes next and some religions will say that suicide leads to nowhere good. Even if it provides relief to the person involved, it comes with the cost of leaving those who remain in horrible pain. Sadly, depressed people sometimes imagine that the world will be better off without them, and often that idea is just not true.

I hope that Robin Williams is in a better place, for his sake. I hope that before he ended his life, he tried every possible treatment option, and that this wasn’t an impulsive decision, or one based on an episodic relapse of either depression or substance abuse – a relapse that may have resolved and let him live for decades more. I hope his wife and children and all the people who knew and loved him will eventually find some peace. His death, however, is not simply a personal one because he touched us all with his talent and his charisma. What a tragic loss.

Dr. Miller also posted a version http://bit.ly/1kyO1a7 of this piece on the Shrink Rap News website. She is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: the Johns Hopkins University Press, 2011).

The news last night was tragic: Robin Williams has died of an apparent suicide at the early age of 63. I saw the news and felt overwhelmingly sad. Really? He was a tremendous actor, a creative genius by any account, a man who I imagined had everything – talent, wealth, fame, the wonderful ability to make people laugh and to brighten lives. Such people also get draped with love and admiration, though certainly at a price. For what it’s worth, Robin Williams has been open about the fact that he’s struggled with both depression and addiction, but the complete story is never the one that gets told by the media.

Courtesy Wikimedia Commons/John J. Kruzel/Creative Commons License

Twitter started with 140-character links to suicide hotlines and suicide awareness, to statements about how depression is a treatable illness – Is it always? – and I hit retweet on a comment stating:" We’re never going to get anywhere till we take seriously that depression is an illness, not a weakness" and several people retweeted my retweet. I’m not sure why I did this; I don’t think that most people still think of mood disorders as a "weakness," or that those who do might change their minds because of a tweet. And I don’t think that suicide does anything to reduce stigma.

One psychiatrist friend tweeted a comment about how one should never ask someone why they are depressed, I guess because the "why?" implies something other than because biology dictated it, but if you’ve ever spoken to a person suffering from depression, you know that it comes in all shades of severity and that people often write a story to explain it. Sometimes that story is right: I’m depressed because of a breakup, or because I don’t have a job now, or because of ongoing work stress – and indeed, the person suffering often feels better after talking about the situation, after getting a new boyfriend or a new job, or after their boss moves to Zimbabwe.

I’m convinced that treatment works best when psychotherapy is combined with medication (if indicated), and while medicines are a miracle for some, they aren’t for others. As psychiatrists, we certainly see a good deal of treatment-resistant depression. And yes, the antipsychiatry faction may postulate that it is the treatment – the medications, specifically – that cause people to kill themselves and others, but I will leave you with the idea that the science just doesn’t support that. Certainly, they aren’t for everyone, but clinically, I have seen medications do more good than harm in clinical practice overall.

I know nothing about Robin Williams beyond what I’ve read in the media, and I know that the media reports are often incomplete and distorted. I do imagine that Mr. Williams had the resources to get good care and that he may well have had treatment for depression since he was open about his struggle. His story will be used to say: "Get help," and if you’re feeling suicidal and aren’t getting help, please do so. If you’re feeling suicidal and "help" isn’t making you feel better, please consider getting a second opinion or a different kind of help.

The tragic thing about suicide is that it’s a permanent answer to what is often a temporary problem.

Sometimes, I imagine that there are people who have tried and tried to get help and that their pain remains so unbearable for so long that suicide offers them the only possible relief – if such a thing is even to be had given that we don’t what comes next and some religions will say that suicide leads to nowhere good. Even if it provides relief to the person involved, it comes with the cost of leaving those who remain in horrible pain. Sadly, depressed people sometimes imagine that the world will be better off without them, and often that idea is just not true.

I hope that Robin Williams is in a better place, for his sake. I hope that before he ended his life, he tried every possible treatment option, and that this wasn’t an impulsive decision, or one based on an episodic relapse of either depression or substance abuse – a relapse that may have resolved and let him live for decades more. I hope his wife and children and all the people who knew and loved him will eventually find some peace. His death, however, is not simply a personal one because he touched us all with his talent and his charisma. What a tragic loss.

Dr. Miller also posted a version http://bit.ly/1kyO1a7 of this piece on the Shrink Rap News website. She is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: the Johns Hopkins University Press, 2011).

The news last night was tragic: Robin Williams has died of an apparent suicide at the early age of 63. I saw the news and felt overwhelmingly sad. Really? He was a tremendous actor, a creative genius by any account, a man who I imagined had everything – talent, wealth, fame, the wonderful ability to make people laugh and to brighten lives. Such people also get draped with love and admiration, though certainly at a price. For what it’s worth, Robin Williams has been open about the fact that he’s struggled with both depression and addiction, but the complete story is never the one that gets told by the media.

Courtesy Wikimedia Commons/John J. Kruzel/Creative Commons License

Twitter started with 140-character links to suicide hotlines and suicide awareness, to statements about how depression is a treatable illness – Is it always? – and I hit retweet on a comment stating:" We’re never going to get anywhere till we take seriously that depression is an illness, not a weakness" and several people retweeted my retweet. I’m not sure why I did this; I don’t think that most people still think of mood disorders as a "weakness," or that those who do might change their minds because of a tweet. And I don’t think that suicide does anything to reduce stigma.

One psychiatrist friend tweeted a comment about how one should never ask someone why they are depressed, I guess because the "why?" implies something other than because biology dictated it, but if you’ve ever spoken to a person suffering from depression, you know that it comes in all shades of severity and that people often write a story to explain it. Sometimes that story is right: I’m depressed because of a breakup, or because I don’t have a job now, or because of ongoing work stress – and indeed, the person suffering often feels better after talking about the situation, after getting a new boyfriend or a new job, or after their boss moves to Zimbabwe.

I’m convinced that treatment works best when psychotherapy is combined with medication (if indicated), and while medicines are a miracle for some, they aren’t for others. As psychiatrists, we certainly see a good deal of treatment-resistant depression. And yes, the antipsychiatry faction may postulate that it is the treatment – the medications, specifically – that cause people to kill themselves and others, but I will leave you with the idea that the science just doesn’t support that. Certainly, they aren’t for everyone, but clinically, I have seen medications do more good than harm in clinical practice overall.

I know nothing about Robin Williams beyond what I’ve read in the media, and I know that the media reports are often incomplete and distorted. I do imagine that Mr. Williams had the resources to get good care and that he may well have had treatment for depression since he was open about his struggle. His story will be used to say: "Get help," and if you’re feeling suicidal and aren’t getting help, please do so. If you’re feeling suicidal and "help" isn’t making you feel better, please consider getting a second opinion or a different kind of help.

The tragic thing about suicide is that it’s a permanent answer to what is often a temporary problem.

Sometimes, I imagine that there are people who have tried and tried to get help and that their pain remains so unbearable for so long that suicide offers them the only possible relief – if such a thing is even to be had given that we don’t what comes next and some religions will say that suicide leads to nowhere good. Even if it provides relief to the person involved, it comes with the cost of leaving those who remain in horrible pain. Sadly, depressed people sometimes imagine that the world will be better off without them, and often that idea is just not true.

I hope that Robin Williams is in a better place, for his sake. I hope that before he ended his life, he tried every possible treatment option, and that this wasn’t an impulsive decision, or one based on an episodic relapse of either depression or substance abuse – a relapse that may have resolved and let him live for decades more. I hope his wife and children and all the people who knew and loved him will eventually find some peace. His death, however, is not simply a personal one because he touched us all with his talent and his charisma. What a tragic loss.

Dr. Miller also posted a version http://bit.ly/1kyO1a7 of this piece on the Shrink Rap News website. She is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: the Johns Hopkins University Press, 2011).

Updated recommendations for the diagnosis and treatment of non-neurogenic overactive bladder incorporate two new treatments approved since 2012 – oral mirabegron and intradetrusor injection of onabotulinumtoxinA.

The 2014 update from the American Urological Association and the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (AUA/SUFU) also recognizes the growing number of therapeutic options by stressing the need to take a methodical approach and give an adequate trial of individual treatments before combining them.

"As we have more and more options on the market, you don’t want to stack one on top of another," Dr. Emily Cole said in an interview.

"All of these methodologies have some side effects. What you don’t want to do is have added side effects if something is not working," said Dr. Cole, a urologist specializing in female pelvic medicine and reconstructive surgery in a group practice in San Diego.

Compared with the 2012 AUA/SUFU recommendations, the 2014 guideline on "Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults" adds the beta₃-adrenoceptor agonist mirabegron (Myrbetriq, Astellas Pharma) as a first- or second-line treatment option for some patients. OnabotulinumtoxinA (Botox, Allergan) has been upgraded to a "Standard Option" among third-line treatments instead of a nonapproved, off-label therapy.

The Food and Drug Administration approved mirabegron for adults with overactive bladder in June 2012. The FDA approved onabotulinumtoxinA (Botox, Allergan) in January 2013 for adults with overactive bladder who can’t use or don’t respond adequately to anticholinergics.

Clinicians always should start with first- and second-line therapies to reduce symptoms of overactive bladder, Dr. Cole said. By the time patients come to her, they typically have failed those options, but she offers them hope with third-line treatments.

"In most cases, we can really help patients. We may not make you completely dry," she said, but "we have enough tools now that we can make marked improvements."

That’s a big change in recent years, she added. "When I started out, we had two medications that had horrible side effects," she said. Dr. Cole was not involved in creation of the AUA/SUFU guideline.

The AUA/SUFU based the 2012 guideline on 151 articles on the treatment of overactive bladder and reviewed 72 more articles on treatment for the 2014 update.

The recommendations on diagnosis have not changed since 2012 and are based on expert opinion and clinical principles due to insufficient evidence for stronger recommendations.

First-line treatments are behavioral therapies such as bladder training and bladder control strategies or pelvic floor muscle training, which may be combined with pharmacologic management, the guideline states.

Second-line treatments include oral antimuscarinic drugs or mirabegron, preferably in an extended-release formulation if available to reduce the likelihood of dry mouth from immediate-release formulations. A transdermal patch that delivers the antimuscarinic drug oxybutynin became available to adult women over the counter (without a prescription) in 2013.

If a first antimuscarinic medication doesn’t work or causes unacceptable side effects, modify the dose or offer a different antimuscarinic or beta₃-adrenoceptor agonist, the guideline states. If an antimuscarinic is effective but causes constipation or dry mouth, don’t give up on that drug class without trying to manage side effects through bowel management, fluid management, modifying the dose, or trying another antimuscarinic.

Be extremely cautious in using antimuscarinics in patients with impaired gastric emptying or a history of urinary retention, and don’t use antimuscarinics in patients with narrow-angle glaucoma without approval from a treating ophthalmologist. If a patient is on other medications with anticholinergic properties, be cautious about prescribing antimuscarinics.

Patients who fail first- and second-line therapies should be evaluated by a specialist if they still desire treatment, according to the guideline.

Among third-line treatment options, sacral neuromodulation may be offered to patients with severe refractory overactive bladder or patients who are not candidates for second-line treatments and who are willing to undergo a surgical procedure. Peripheral tibial nerve stimulation is another option in carefully selected patients.

Intradetrusor injections of Botox may be appropriate for carefully selected and "thoroughly counseled" patients who failed first- and second-line treatments if they are able and willing to return for frequent postvoid residual evaluations and to perform self-catheterization if necessary.

The guideline does not recommend indwelling catheters for management of overactive bladder except as a last resort in some patients, and says that augmentation cystoplasty or urinary diversion may be considered in rare cases of severe, refractory, complicated overactive bladder.

Dr. Cole has been a speaker for Allergan, which markets Botox.

[email protected]

On Twitter @sherryboschert

Updated recommendations for the diagnosis and treatment of non-neurogenic overactive bladder incorporate two new treatments approved since 2012 – oral mirabegron and intradetrusor injection of onabotulinumtoxinA.

The 2014 update from the American Urological Association and the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (AUA/SUFU) also recognizes the growing number of therapeutic options by stressing the need to take a methodical approach and give an adequate trial of individual treatments before combining them.

"As we have more and more options on the market, you don’t want to stack one on top of another," Dr. Emily Cole said in an interview.

"All of these methodologies have some side effects. What you don’t want to do is have added side effects if something is not working," said Dr. Cole, a urologist specializing in female pelvic medicine and reconstructive surgery in a group practice in San Diego.

Compared with the 2012 AUA/SUFU recommendations, the 2014 guideline on "Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults" adds the beta₃-adrenoceptor agonist mirabegron (Myrbetriq, Astellas Pharma) as a first- or second-line treatment option for some patients. OnabotulinumtoxinA (Botox, Allergan) has been upgraded to a "Standard Option" among third-line treatments instead of a nonapproved, off-label therapy.

The Food and Drug Administration approved mirabegron for adults with overactive bladder in June 2012. The FDA approved onabotulinumtoxinA (Botox, Allergan) in January 2013 for adults with overactive bladder who can’t use or don’t respond adequately to anticholinergics.

Clinicians always should start with first- and second-line therapies to reduce symptoms of overactive bladder, Dr. Cole said. By the time patients come to her, they typically have failed those options, but she offers them hope with third-line treatments.

"In most cases, we can really help patients. We may not make you completely dry," she said, but "we have enough tools now that we can make marked improvements."

That’s a big change in recent years, she added. "When I started out, we had two medications that had horrible side effects," she said. Dr. Cole was not involved in creation of the AUA/SUFU guideline.

The AUA/SUFU based the 2012 guideline on 151 articles on the treatment of overactive bladder and reviewed 72 more articles on treatment for the 2014 update.

The recommendations on diagnosis have not changed since 2012 and are based on expert opinion and clinical principles due to insufficient evidence for stronger recommendations.

First-line treatments are behavioral therapies such as bladder training and bladder control strategies or pelvic floor muscle training, which may be combined with pharmacologic management, the guideline states.

Second-line treatments include oral antimuscarinic drugs or mirabegron, preferably in an extended-release formulation if available to reduce the likelihood of dry mouth from immediate-release formulations. A transdermal patch that delivers the antimuscarinic drug oxybutynin became available to adult women over the counter (without a prescription) in 2013.

If a first antimuscarinic medication doesn’t work or causes unacceptable side effects, modify the dose or offer a different antimuscarinic or beta₃-adrenoceptor agonist, the guideline states. If an antimuscarinic is effective but causes constipation or dry mouth, don’t give up on that drug class without trying to manage side effects through bowel management, fluid management, modifying the dose, or trying another antimuscarinic.

Be extremely cautious in using antimuscarinics in patients with impaired gastric emptying or a history of urinary retention, and don’t use antimuscarinics in patients with narrow-angle glaucoma without approval from a treating ophthalmologist. If a patient is on other medications with anticholinergic properties, be cautious about prescribing antimuscarinics.

Patients who fail first- and second-line therapies should be evaluated by a specialist if they still desire treatment, according to the guideline.

Among third-line treatment options, sacral neuromodulation may be offered to patients with severe refractory overactive bladder or patients who are not candidates for second-line treatments and who are willing to undergo a surgical procedure. Peripheral tibial nerve stimulation is another option in carefully selected patients.

Intradetrusor injections of Botox may be appropriate for carefully selected and "thoroughly counseled" patients who failed first- and second-line treatments if they are able and willing to return for frequent postvoid residual evaluations and to perform self-catheterization if necessary.

The guideline does not recommend indwelling catheters for management of overactive bladder except as a last resort in some patients, and says that augmentation cystoplasty or urinary diversion may be considered in rare cases of severe, refractory, complicated overactive bladder.

Dr. Cole has been a speaker for Allergan, which markets Botox.

[email protected]

On Twitter @sherryboschert

Updated recommendations for the diagnosis and treatment of non-neurogenic overactive bladder incorporate two new treatments approved since 2012 – oral mirabegron and intradetrusor injection of onabotulinumtoxinA.

The 2014 update from the American Urological Association and the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (AUA/SUFU) also recognizes the growing number of therapeutic options by stressing the need to take a methodical approach and give an adequate trial of individual treatments before combining them.

"As we have more and more options on the market, you don’t want to stack one on top of another," Dr. Emily Cole said in an interview.

"All of these methodologies have some side effects. What you don’t want to do is have added side effects if something is not working," said Dr. Cole, a urologist specializing in female pelvic medicine and reconstructive surgery in a group practice in San Diego.

Compared with the 2012 AUA/SUFU recommendations, the 2014 guideline on "Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults" adds the beta₃-adrenoceptor agonist mirabegron (Myrbetriq, Astellas Pharma) as a first- or second-line treatment option for some patients. OnabotulinumtoxinA (Botox, Allergan) has been upgraded to a "Standard Option" among third-line treatments instead of a nonapproved, off-label therapy.

The Food and Drug Administration approved mirabegron for adults with overactive bladder in June 2012. The FDA approved onabotulinumtoxinA (Botox, Allergan) in January 2013 for adults with overactive bladder who can’t use or don’t respond adequately to anticholinergics.

Clinicians always should start with first- and second-line therapies to reduce symptoms of overactive bladder, Dr. Cole said. By the time patients come to her, they typically have failed those options, but she offers them hope with third-line treatments.

"In most cases, we can really help patients. We may not make you completely dry," she said, but "we have enough tools now that we can make marked improvements."

That’s a big change in recent years, she added. "When I started out, we had two medications that had horrible side effects," she said. Dr. Cole was not involved in creation of the AUA/SUFU guideline.

The AUA/SUFU based the 2012 guideline on 151 articles on the treatment of overactive bladder and reviewed 72 more articles on treatment for the 2014 update.

The recommendations on diagnosis have not changed since 2012 and are based on expert opinion and clinical principles due to insufficient evidence for stronger recommendations.

First-line treatments are behavioral therapies such as bladder training and bladder control strategies or pelvic floor muscle training, which may be combined with pharmacologic management, the guideline states.

Second-line treatments include oral antimuscarinic drugs or mirabegron, preferably in an extended-release formulation if available to reduce the likelihood of dry mouth from immediate-release formulations. A transdermal patch that delivers the antimuscarinic drug oxybutynin became available to adult women over the counter (without a prescription) in 2013.

If a first antimuscarinic medication doesn’t work or causes unacceptable side effects, modify the dose or offer a different antimuscarinic or beta₃-adrenoceptor agonist, the guideline states. If an antimuscarinic is effective but causes constipation or dry mouth, don’t give up on that drug class without trying to manage side effects through bowel management, fluid management, modifying the dose, or trying another antimuscarinic.

Be extremely cautious in using antimuscarinics in patients with impaired gastric emptying or a history of urinary retention, and don’t use antimuscarinics in patients with narrow-angle glaucoma without approval from a treating ophthalmologist. If a patient is on other medications with anticholinergic properties, be cautious about prescribing antimuscarinics.

Patients who fail first- and second-line therapies should be evaluated by a specialist if they still desire treatment, according to the guideline.

Among third-line treatment options, sacral neuromodulation may be offered to patients with severe refractory overactive bladder or patients who are not candidates for second-line treatments and who are willing to undergo a surgical procedure. Peripheral tibial nerve stimulation is another option in carefully selected patients.

Intradetrusor injections of Botox may be appropriate for carefully selected and "thoroughly counseled" patients who failed first- and second-line treatments if they are able and willing to return for frequent postvoid residual evaluations and to perform self-catheterization if necessary.

The guideline does not recommend indwelling catheters for management of overactive bladder except as a last resort in some patients, and says that augmentation cystoplasty or urinary diversion may be considered in rare cases of severe, refractory, complicated overactive bladder.

Dr. Cole has been a speaker for Allergan, which markets Botox.

[email protected]

On Twitter @sherryboschert

In July 2011, I first had the opportunity to write a column on ethics for ACS Surgery News. That article, "Responding to Family/Patient Requests," explored possible responses to the family members’ requests to "do everything" for a critically ill patient. The article was published under the tag line, "The Right Choice."

Since that first article, I have had the opportunity to write 12 additional columns on different ethical issues in the care of surgical patients. The issues have ranged from considerations of informed consent and disclosure of information to the challenges of innovative techniques and scarce resources. Each of these columns has continued to be under the heading "The Right Choice." As I considered what to write about this month, I reviewed my previous articles and I was struck by a worrisome possibility. In the challenging surgical cases presented, is the suggestion that I know "the right choice" actually wrong?

Medical ethics has increasingly become an important topic in medical schools and the clinical care of patients since the late 1970s. Although the medical and surgical care of patients has always had an ethical dimension, it has only been in the last several decades that the ethical issues have been separately identified and analyzed. As the acceptance of surgeons making decisions about what is "best" for their patients has shifted to increasing respect for the patient as an autonomous decision maker, we have seen the importance of understanding patient preferences increase.

At the same time, as medical and surgical care has improved, we now have more options to prolong patients’ lives even when the quality of those lives may be dramatically diminished. These factors have led to the increased consideration of ethical dimensions of decisions that we must help our patients make.

Although many authors have suggested ways to proceed with the ethical analysis of cases, few methods have been as widely adopted as that suggested by Albert Jonsen, Mark Siegler, and William Winslade in their influential book, "Clinical Ethics: A Practical Approach to Ethical Decisions in Clinical Medicine," 7th edition (New York: Lange Clinical Science/McGraw Hill, 2010). These authors suggest that the analysis of a case should include attention to four sets of issues: medical indications, patient preferences, quality of life, and contextual features. By analyzing these issues for a difficult case, we are often able to see where the underlying principles of beneficence, nonmaleficence, respect for patient autonomy, and justice may be at odds.

For example, in the case that I discussed in the July 2011 issue, about the 80-year-old woman with extensive gangrenous bowel, a central concern was whether the surgical decision making should be altered by the family member’s request to "do everything you can." In this case, I suggested that requests from surrogate decision makers must be tempered by the realities of the case and the importance of not harming a patient by providing burdensome care that has minimal chance of success.

As I reread that prior article, I am struck by the fact that I suggest a way of thinking about the case and a series of considerations that are important. However, I am not comfortable saying that I have identified the single correct course of action. I believe that although ethical analysis of cases has tremendous value for doctors and patients, there is rarely one right answer. There may be several wrong answers, and there may be several acceptable answers, but there is rarely a single right choice. My goal in these columns that I wrote in the past and hope to write in the future is to raise awareness of the ethical dimensions of the case, to suggest important considerations, and perhaps even to identify some of the ethical principles that may be relevant. But I do not believe that I can identify "the right choice

In the very first edition of "Clinical Ethics" published in 1982, Jonsen, Siegler, and Winslade wrote in the preface, "We do not merely discuss or analyze the ethical problems; we offer counsel about decisions. Lest this be thought presumptuous, we do not consider our counsel the single and final answer. We offer it in the tradition of medical consultation: The consultant may bring to the practitioner’s view of the case not only broader information but another perspective."

I have tried to provide this type of information and perspective in the ACS Surgery News ethics columns and in view of the difficulty of determining the single right answer to many challenging cases, future columns will be found under the new heading, "The Right Choice?" By adding the critical question mark, I hope that readers will be reminded of the need for ongoing discussion of the challenging ethical questions that arise in the care of surgical patients.

Dr. Angelos is the Linda Kohler Anderson Professor of Surgery and Surgical Ethics; chief, endocrine surgery; and associate director, MacLean Center for Clinical Medical Ethics, at the University of Chicago.

In July 2011, I first had the opportunity to write a column on ethics for ACS Surgery News. That article, "Responding to Family/Patient Requests," explored possible responses to the family members’ requests to "do everything" for a critically ill patient. The article was published under the tag line, "The Right Choice."

Since that first article, I have had the opportunity to write 12 additional columns on different ethical issues in the care of surgical patients. The issues have ranged from considerations of informed consent and disclosure of information to the challenges of innovative techniques and scarce resources. Each of these columns has continued to be under the heading "The Right Choice." As I considered what to write about this month, I reviewed my previous articles and I was struck by a worrisome possibility. In the challenging surgical cases presented, is the suggestion that I know "the right choice" actually wrong?

Medical ethics has increasingly become an important topic in medical schools and the clinical care of patients since the late 1970s. Although the medical and surgical care of patients has always had an ethical dimension, it has only been in the last several decades that the ethical issues have been separately identified and analyzed. As the acceptance of surgeons making decisions about what is "best" for their patients has shifted to increasing respect for the patient as an autonomous decision maker, we have seen the importance of understanding patient preferences increase.

At the same time, as medical and surgical care has improved, we now have more options to prolong patients’ lives even when the quality of those lives may be dramatically diminished. These factors have led to the increased consideration of ethical dimensions of decisions that we must help our patients make.

Although many authors have suggested ways to proceed with the ethical analysis of cases, few methods have been as widely adopted as that suggested by Albert Jonsen, Mark Siegler, and William Winslade in their influential book, "Clinical Ethics: A Practical Approach to Ethical Decisions in Clinical Medicine," 7th edition (New York: Lange Clinical Science/McGraw Hill, 2010). These authors suggest that the analysis of a case should include attention to four sets of issues: medical indications, patient preferences, quality of life, and contextual features. By analyzing these issues for a difficult case, we are often able to see where the underlying principles of beneficence, nonmaleficence, respect for patient autonomy, and justice may be at odds.

For example, in the case that I discussed in the July 2011 issue, about the 80-year-old woman with extensive gangrenous bowel, a central concern was whether the surgical decision making should be altered by the family member’s request to "do everything you can." In this case, I suggested that requests from surrogate decision makers must be tempered by the realities of the case and the importance of not harming a patient by providing burdensome care that has minimal chance of success.

As I reread that prior article, I am struck by the fact that I suggest a way of thinking about the case and a series of considerations that are important. However, I am not comfortable saying that I have identified the single correct course of action. I believe that although ethical analysis of cases has tremendous value for doctors and patients, there is rarely one right answer. There may be several wrong answers, and there may be several acceptable answers, but there is rarely a single right choice. My goal in these columns that I wrote in the past and hope to write in the future is to raise awareness of the ethical dimensions of the case, to suggest important considerations, and perhaps even to identify some of the ethical principles that may be relevant. But I do not believe that I can identify "the right choice

In the very first edition of "Clinical Ethics" published in 1982, Jonsen, Siegler, and Winslade wrote in the preface, "We do not merely discuss or analyze the ethical problems; we offer counsel about decisions. Lest this be thought presumptuous, we do not consider our counsel the single and final answer. We offer it in the tradition of medical consultation: The consultant may bring to the practitioner’s view of the case not only broader information but another perspective."

I have tried to provide this type of information and perspective in the ACS Surgery News ethics columns and in view of the difficulty of determining the single right answer to many challenging cases, future columns will be found under the new heading, "The Right Choice?" By adding the critical question mark, I hope that readers will be reminded of the need for ongoing discussion of the challenging ethical questions that arise in the care of surgical patients.

Dr. Angelos is the Linda Kohler Anderson Professor of Surgery and Surgical Ethics; chief, endocrine surgery; and associate director, MacLean Center for Clinical Medical Ethics, at the University of Chicago.

In July 2011, I first had the opportunity to write a column on ethics for ACS Surgery News. That article, "Responding to Family/Patient Requests," explored possible responses to the family members’ requests to "do everything" for a critically ill patient. The article was published under the tag line, "The Right Choice."

Since that first article, I have had the opportunity to write 12 additional columns on different ethical issues in the care of surgical patients. The issues have ranged from considerations of informed consent and disclosure of information to the challenges of innovative techniques and scarce resources. Each of these columns has continued to be under the heading "The Right Choice." As I considered what to write about this month, I reviewed my previous articles and I was struck by a worrisome possibility. In the challenging surgical cases presented, is the suggestion that I know "the right choice" actually wrong?

Medical ethics has increasingly become an important topic in medical schools and the clinical care of patients since the late 1970s. Although the medical and surgical care of patients has always had an ethical dimension, it has only been in the last several decades that the ethical issues have been separately identified and analyzed. As the acceptance of surgeons making decisions about what is "best" for their patients has shifted to increasing respect for the patient as an autonomous decision maker, we have seen the importance of understanding patient preferences increase.

At the same time, as medical and surgical care has improved, we now have more options to prolong patients’ lives even when the quality of those lives may be dramatically diminished. These factors have led to the increased consideration of ethical dimensions of decisions that we must help our patients make.

Although many authors have suggested ways to proceed with the ethical analysis of cases, few methods have been as widely adopted as that suggested by Albert Jonsen, Mark Siegler, and William Winslade in their influential book, "Clinical Ethics: A Practical Approach to Ethical Decisions in Clinical Medicine," 7th edition (New York: Lange Clinical Science/McGraw Hill, 2010). These authors suggest that the analysis of a case should include attention to four sets of issues: medical indications, patient preferences, quality of life, and contextual features. By analyzing these issues for a difficult case, we are often able to see where the underlying principles of beneficence, nonmaleficence, respect for patient autonomy, and justice may be at odds.

For example, in the case that I discussed in the July 2011 issue, about the 80-year-old woman with extensive gangrenous bowel, a central concern was whether the surgical decision making should be altered by the family member’s request to "do everything you can." In this case, I suggested that requests from surrogate decision makers must be tempered by the realities of the case and the importance of not harming a patient by providing burdensome care that has minimal chance of success.

As I reread that prior article, I am struck by the fact that I suggest a way of thinking about the case and a series of considerations that are important. However, I am not comfortable saying that I have identified the single correct course of action. I believe that although ethical analysis of cases has tremendous value for doctors and patients, there is rarely one right answer. There may be several wrong answers, and there may be several acceptable answers, but there is rarely a single right choice. My goal in these columns that I wrote in the past and hope to write in the future is to raise awareness of the ethical dimensions of the case, to suggest important considerations, and perhaps even to identify some of the ethical principles that may be relevant. But I do not believe that I can identify "the right choice

In the very first edition of "Clinical Ethics" published in 1982, Jonsen, Siegler, and Winslade wrote in the preface, "We do not merely discuss or analyze the ethical problems; we offer counsel about decisions. Lest this be thought presumptuous, we do not consider our counsel the single and final answer. We offer it in the tradition of medical consultation: The consultant may bring to the practitioner’s view of the case not only broader information but another perspective."

I have tried to provide this type of information and perspective in the ACS Surgery News ethics columns and in view of the difficulty of determining the single right answer to many challenging cases, future columns will be found under the new heading, "The Right Choice?" By adding the critical question mark, I hope that readers will be reminded of the need for ongoing discussion of the challenging ethical questions that arise in the care of surgical patients.

Dr. Angelos is the Linda Kohler Anderson Professor of Surgery and Surgical Ethics; chief, endocrine surgery; and associate director, MacLean Center for Clinical Medical Ethics, at the University of Chicago.