The Diagnosis: Acquired Acrodermatitis Enteropathica

Acquired acrodermatitis enteropathica (AAE) is a rare disorder caused by severe zinc deficiency. Although acrodermatitis enteropathica is an autosomal-recessive disorder that typically manifests in infancy, AAE also can result from poor zinc intake, impaired absorption, or accelerated losses. There are reports of AAE in patients with zinc-deficient diets,¹ eating disorders,² bariatric and other gastrointestinal surgeries,³ malabsorptive diseases,⁴ and nephrotic syndrome.⁵

Zinc plays an important role in DNA and RNA synthesis, reactive oxygen species attenuation, and energy metabolism, allowing for proper wound healing, skin differentiation, and proliferation.⁶ Zinc is found in most foods, but animal protein contains higher concentrations (Table).⁷ Approximately 85% of zinc is stored in muscles and bones, with only a small amount of accessible zinc available in the liver. Liver stores can be depleted as quickly as 1 week.⁸ Total parenteral nutrition without trace element supplementation can quickly predispose patients to AAE.

Diagnosis of this condition requires triangulation of clinical presentation, histopathology examination, and laboratory findings. Acrodermatitis enteropathica typically is characterized by dermatitis, diarrhea, and epidermal appendage findings. In its early stages, the dermatitis often manifests with angular cheilitis and paronychia.⁹ Patients then develop erythema, erosions, and occasionally vesicles or psoriasiform plaques in periorificial, perineal, and acral sites (Figure 1). Epidermal appendage effects include generalized alopecia and thinning nails with white transverse ridges. Although dermatologic and gastrointestinal manifestations are the most obvious, severe AAE may cause other symptoms, including mental slowing, hypogonadism, and impaired immune function.⁹

Histopathology of AAE skin lesions is similar to other nutritional deficiencies. Early changes are more specific to deficiency dermatitis and include cytoplasmic pallor and ballooning degeneration of keratinocytes in the stratum spinosum and granulosum.⁹ Necrolysis results in confluent keratinocyte necrosis developing into subcorneal bulla. Later in the disease course, the presentation becomes psoriasiform with keratinocyte dyskeratosis and confluent parakeratosis¹⁰ (Figure 2). Dermal edema with dilated tortuous vessels and a neutrophilic infiltrate may be present throughout disease progression.

Common laboratory abnormalities used to confirm zinc deficiency are decreased plasma zinc and alkaline phosphatase levels. Plasma zinc levels should be drawn after fasting because zinc levels decrease after food intake.⁹ Concurrent albumin levels should be drawn to correct for low levels caused by hypoalbuminemia. Acquired acrodermatitis enteropathica has been seen in patients with only mildly decreased plasma zinc levels or even zinc levels within reference range.¹¹ Alkaline phosphatase metalloenzyme synthesis requires zinc and a decreased level suggests zinc deficiency even with a plasma zinc level within reference range. Alkaline phosphatase levels usually can be ascertained in a matter of hours, while the zinc levels take much longer to result.

Acquired acrodermatitis enteropathica is treated with oral elemental zinc supplementation at 1 to 2 mg/kg daily.¹² Diarrhea typically resolves within 24 hours, but skin lesions heal in 1 to 2 weeks or longer. Although there is no consensus on when to discontinue zinc replacement therapy, therapy generally is not lifelong. Once the patient is zinc replete and the inciting factor has resolved, patients can discontinue supplementation without risk for recurrence.

Trace elements had not been added to our patient’s total parenteral nutrition prior to admission. Basic nutrition laboratory results and zinc levels returned markedly low: 14 μg/dL (reference range, 60–120 μg/dL). Alkaline phosphatase, a zinc-dependent protein, also was low at 12 U/L (reference range, 40–150 U/L). We added trace elements and vitamins and began empiric zinc replacement with 440 mg oral zinc sulfate daily (100 mg elemental zinc). Cephalexin was prescribed for impetiginized skin lesions. The patient noted skin improvement after 3 days on zinc replacement therapy.

The Diagnosis: Acquired Acrodermatitis Enteropathica

Acquired acrodermatitis enteropathica (AAE) is a rare disorder caused by severe zinc deficiency. Although acrodermatitis enteropathica is an autosomal-recessive disorder that typically manifests in infancy, AAE also can result from poor zinc intake, impaired absorption, or accelerated losses. There are reports of AAE in patients with zinc-deficient diets,¹ eating disorders,² bariatric and other gastrointestinal surgeries,³ malabsorptive diseases,⁴ and nephrotic syndrome.⁵

Zinc plays an important role in DNA and RNA synthesis, reactive oxygen species attenuation, and energy metabolism, allowing for proper wound healing, skin differentiation, and proliferation.⁶ Zinc is found in most foods, but animal protein contains higher concentrations (Table).⁷ Approximately 85% of zinc is stored in muscles and bones, with only a small amount of accessible zinc available in the liver. Liver stores can be depleted as quickly as 1 week.⁸ Total parenteral nutrition without trace element supplementation can quickly predispose patients to AAE.

Diagnosis of this condition requires triangulation of clinical presentation, histopathology examination, and laboratory findings. Acrodermatitis enteropathica typically is characterized by dermatitis, diarrhea, and epidermal appendage findings. In its early stages, the dermatitis often manifests with angular cheilitis and paronychia.⁹ Patients then develop erythema, erosions, and occasionally vesicles or psoriasiform plaques in periorificial, perineal, and acral sites (Figure 1). Epidermal appendage effects include generalized alopecia and thinning nails with white transverse ridges. Although dermatologic and gastrointestinal manifestations are the most obvious, severe AAE may cause other symptoms, including mental slowing, hypogonadism, and impaired immune function.⁹

Histopathology of AAE skin lesions is similar to other nutritional deficiencies. Early changes are more specific to deficiency dermatitis and include cytoplasmic pallor and ballooning degeneration of keratinocytes in the stratum spinosum and granulosum.⁹ Necrolysis results in confluent keratinocyte necrosis developing into subcorneal bulla. Later in the disease course, the presentation becomes psoriasiform with keratinocyte dyskeratosis and confluent parakeratosis¹⁰ (Figure 2). Dermal edema with dilated tortuous vessels and a neutrophilic infiltrate may be present throughout disease progression.

Common laboratory abnormalities used to confirm zinc deficiency are decreased plasma zinc and alkaline phosphatase levels. Plasma zinc levels should be drawn after fasting because zinc levels decrease after food intake.⁹ Concurrent albumin levels should be drawn to correct for low levels caused by hypoalbuminemia. Acquired acrodermatitis enteropathica has been seen in patients with only mildly decreased plasma zinc levels or even zinc levels within reference range.¹¹ Alkaline phosphatase metalloenzyme synthesis requires zinc and a decreased level suggests zinc deficiency even with a plasma zinc level within reference range. Alkaline phosphatase levels usually can be ascertained in a matter of hours, while the zinc levels take much longer to result.

Acquired acrodermatitis enteropathica is treated with oral elemental zinc supplementation at 1 to 2 mg/kg daily.¹² Diarrhea typically resolves within 24 hours, but skin lesions heal in 1 to 2 weeks or longer. Although there is no consensus on when to discontinue zinc replacement therapy, therapy generally is not lifelong. Once the patient is zinc replete and the inciting factor has resolved, patients can discontinue supplementation without risk for recurrence.

Trace elements had not been added to our patient’s total parenteral nutrition prior to admission. Basic nutrition laboratory results and zinc levels returned markedly low: 14 μg/dL (reference range, 60–120 μg/dL). Alkaline phosphatase, a zinc-dependent protein, also was low at 12 U/L (reference range, 40–150 U/L). We added trace elements and vitamins and began empiric zinc replacement with 440 mg oral zinc sulfate daily (100 mg elemental zinc). Cephalexin was prescribed for impetiginized skin lesions. The patient noted skin improvement after 3 days on zinc replacement therapy.

The Diagnosis: Acquired Acrodermatitis Enteropathica

Acquired acrodermatitis enteropathica (AAE) is a rare disorder caused by severe zinc deficiency. Although acrodermatitis enteropathica is an autosomal-recessive disorder that typically manifests in infancy, AAE also can result from poor zinc intake, impaired absorption, or accelerated losses. There are reports of AAE in patients with zinc-deficient diets,¹ eating disorders,² bariatric and other gastrointestinal surgeries,³ malabsorptive diseases,⁴ and nephrotic syndrome.⁵

Zinc plays an important role in DNA and RNA synthesis, reactive oxygen species attenuation, and energy metabolism, allowing for proper wound healing, skin differentiation, and proliferation.⁶ Zinc is found in most foods, but animal protein contains higher concentrations (Table).⁷ Approximately 85% of zinc is stored in muscles and bones, with only a small amount of accessible zinc available in the liver. Liver stores can be depleted as quickly as 1 week.⁸ Total parenteral nutrition without trace element supplementation can quickly predispose patients to AAE.

Diagnosis of this condition requires triangulation of clinical presentation, histopathology examination, and laboratory findings. Acrodermatitis enteropathica typically is characterized by dermatitis, diarrhea, and epidermal appendage findings. In its early stages, the dermatitis often manifests with angular cheilitis and paronychia.⁹ Patients then develop erythema, erosions, and occasionally vesicles or psoriasiform plaques in periorificial, perineal, and acral sites (Figure 1). Epidermal appendage effects include generalized alopecia and thinning nails with white transverse ridges. Although dermatologic and gastrointestinal manifestations are the most obvious, severe AAE may cause other symptoms, including mental slowing, hypogonadism, and impaired immune function.⁹

Histopathology of AAE skin lesions is similar to other nutritional deficiencies. Early changes are more specific to deficiency dermatitis and include cytoplasmic pallor and ballooning degeneration of keratinocytes in the stratum spinosum and granulosum.⁹ Necrolysis results in confluent keratinocyte necrosis developing into subcorneal bulla. Later in the disease course, the presentation becomes psoriasiform with keratinocyte dyskeratosis and confluent parakeratosis¹⁰ (Figure 2). Dermal edema with dilated tortuous vessels and a neutrophilic infiltrate may be present throughout disease progression.

Common laboratory abnormalities used to confirm zinc deficiency are decreased plasma zinc and alkaline phosphatase levels. Plasma zinc levels should be drawn after fasting because zinc levels decrease after food intake.⁹ Concurrent albumin levels should be drawn to correct for low levels caused by hypoalbuminemia. Acquired acrodermatitis enteropathica has been seen in patients with only mildly decreased plasma zinc levels or even zinc levels within reference range.¹¹ Alkaline phosphatase metalloenzyme synthesis requires zinc and a decreased level suggests zinc deficiency even with a plasma zinc level within reference range. Alkaline phosphatase levels usually can be ascertained in a matter of hours, while the zinc levels take much longer to result.

Acquired acrodermatitis enteropathica is treated with oral elemental zinc supplementation at 1 to 2 mg/kg daily.¹² Diarrhea typically resolves within 24 hours, but skin lesions heal in 1 to 2 weeks or longer. Although there is no consensus on when to discontinue zinc replacement therapy, therapy generally is not lifelong. Once the patient is zinc replete and the inciting factor has resolved, patients can discontinue supplementation without risk for recurrence.

Trace elements had not been added to our patient’s total parenteral nutrition prior to admission. Basic nutrition laboratory results and zinc levels returned markedly low: 14 μg/dL (reference range, 60–120 μg/dL). Alkaline phosphatase, a zinc-dependent protein, also was low at 12 U/L (reference range, 40–150 U/L). We added trace elements and vitamins and began empiric zinc replacement with 440 mg oral zinc sulfate daily (100 mg elemental zinc). Cephalexin was prescribed for impetiginized skin lesions. The patient noted skin improvement after 3 days on zinc replacement therapy.

High coffee consumption decreased the odds of developing multiple sclerosis (MS) in two separate case-control studies conducted by Dr. Anna K. Hedström of the Karolinska Institute, Stockholm, and her associates.

The investigators analyzed coffee consumption across certain ages among 1,620 cases and 2,788 controls in the Swedish Epidemiological Investigation of Multiple Sclerosis (EIMS) and 1,159 cases and 1,172 controls in the Kaiser Permanente Medical Care Plan, Northern California Region (KPNC).

s-photo/iStockphoto.com

In EIMS, the adjusted odds ratio (OR) was 0.70 (95% confidence interval, 0.49-0.99; P = .04) among participants who drank six or more cups of coffee (greater than 900 mL) daily at the index year, which was defined as the year of the initial appearance of symptoms indicative of MS. The corresponding OR for those who reported high coffee consumption at 5 and 10 years before the study was 0.72 and 0.71, respectively, but neither comparison reached statistical significance.

In KPNC, those who consumed four or more cups of coffee (more than 948 mL in this study) daily were significantly less likely to develop MS than were those who never drank coffee (OR, 0.69; 95% CI, 0.50-0.96; P = .05). And the cohorts who drank four or more cups of coffee daily at least 5 years prior to the study were associated with significantly reduced odds of MS (OR, 0.64).

The combined results of the two studies in a meta-analysis found a significant, 29% reduction in the likelihood of developing MS among the highest drinkers of coffee (greater than 900 mL daily in EIMS and greater than 948 mL in KPNC). The investigators adjusted all the analyses for many demographic and environmental risk factors for MS, including age, gender, residential area, ancestry, smoking habits, exposure to passive smoking, sun exposure habits, and body mass index at age 20 years.

No evidence was found for associations between increased amounts of tea or soda intake and MS.

“Further studies are required to establish if it is in fact caffeine, or if there is another molecule in coffee underlying the findings, to longitudinally assess the association between consumption of coffee and disease activity in MS, and to evaluate the mechanisms by which coffee may be acting, which could thus lead to new therapeutic targets,” the researchers concluded.

Find the full study in the Journal of Neurology, Neurosurgery & Psychiatry (doi: 10.1136/jnnp-2015-312176).

[email protected]

High coffee consumption decreased the odds of developing multiple sclerosis (MS) in two separate case-control studies conducted by Dr. Anna K. Hedström of the Karolinska Institute, Stockholm, and her associates.

The investigators analyzed coffee consumption across certain ages among 1,620 cases and 2,788 controls in the Swedish Epidemiological Investigation of Multiple Sclerosis (EIMS) and 1,159 cases and 1,172 controls in the Kaiser Permanente Medical Care Plan, Northern California Region (KPNC).

s-photo/iStockphoto.com

In EIMS, the adjusted odds ratio (OR) was 0.70 (95% confidence interval, 0.49-0.99; P = .04) among participants who drank six or more cups of coffee (greater than 900 mL) daily at the index year, which was defined as the year of the initial appearance of symptoms indicative of MS. The corresponding OR for those who reported high coffee consumption at 5 and 10 years before the study was 0.72 and 0.71, respectively, but neither comparison reached statistical significance.

In KPNC, those who consumed four or more cups of coffee (more than 948 mL in this study) daily were significantly less likely to develop MS than were those who never drank coffee (OR, 0.69; 95% CI, 0.50-0.96; P = .05). And the cohorts who drank four or more cups of coffee daily at least 5 years prior to the study were associated with significantly reduced odds of MS (OR, 0.64).

The combined results of the two studies in a meta-analysis found a significant, 29% reduction in the likelihood of developing MS among the highest drinkers of coffee (greater than 900 mL daily in EIMS and greater than 948 mL in KPNC). The investigators adjusted all the analyses for many demographic and environmental risk factors for MS, including age, gender, residential area, ancestry, smoking habits, exposure to passive smoking, sun exposure habits, and body mass index at age 20 years.

No evidence was found for associations between increased amounts of tea or soda intake and MS.

“Further studies are required to establish if it is in fact caffeine, or if there is another molecule in coffee underlying the findings, to longitudinally assess the association between consumption of coffee and disease activity in MS, and to evaluate the mechanisms by which coffee may be acting, which could thus lead to new therapeutic targets,” the researchers concluded.

Find the full study in the Journal of Neurology, Neurosurgery & Psychiatry (doi: 10.1136/jnnp-2015-312176).

[email protected]

High coffee consumption decreased the odds of developing multiple sclerosis (MS) in two separate case-control studies conducted by Dr. Anna K. Hedström of the Karolinska Institute, Stockholm, and her associates.

The investigators analyzed coffee consumption across certain ages among 1,620 cases and 2,788 controls in the Swedish Epidemiological Investigation of Multiple Sclerosis (EIMS) and 1,159 cases and 1,172 controls in the Kaiser Permanente Medical Care Plan, Northern California Region (KPNC).

s-photo/iStockphoto.com

In EIMS, the adjusted odds ratio (OR) was 0.70 (95% confidence interval, 0.49-0.99; P = .04) among participants who drank six or more cups of coffee (greater than 900 mL) daily at the index year, which was defined as the year of the initial appearance of symptoms indicative of MS. The corresponding OR for those who reported high coffee consumption at 5 and 10 years before the study was 0.72 and 0.71, respectively, but neither comparison reached statistical significance.

In KPNC, those who consumed four or more cups of coffee (more than 948 mL in this study) daily were significantly less likely to develop MS than were those who never drank coffee (OR, 0.69; 95% CI, 0.50-0.96; P = .05). And the cohorts who drank four or more cups of coffee daily at least 5 years prior to the study were associated with significantly reduced odds of MS (OR, 0.64).

The combined results of the two studies in a meta-analysis found a significant, 29% reduction in the likelihood of developing MS among the highest drinkers of coffee (greater than 900 mL daily in EIMS and greater than 948 mL in KPNC). The investigators adjusted all the analyses for many demographic and environmental risk factors for MS, including age, gender, residential area, ancestry, smoking habits, exposure to passive smoking, sun exposure habits, and body mass index at age 20 years.

No evidence was found for associations between increased amounts of tea or soda intake and MS.

“Further studies are required to establish if it is in fact caffeine, or if there is another molecule in coffee underlying the findings, to longitudinally assess the association between consumption of coffee and disease activity in MS, and to evaluate the mechanisms by which coffee may be acting, which could thus lead to new therapeutic targets,” the researchers concluded.

Find the full study in the Journal of Neurology, Neurosurgery & Psychiatry (doi: 10.1136/jnnp-2015-312176).

[email protected]

SCOTTSDALE, ARIZ. – Oncologists should consider not only age, but also comorbidities and disease extent when deciding whether to offer concurrent chemoradiation to older adults with locally advanced head and neck cancer, suggests a cohort study using data from the National Cancer Data Base.

The study of 4,042 patients aged 71 years or older found that adding chemotherapy to radiation therapy (RT) reduced the risk of death by at least one-fourth overall, according to results reported in a poster session and related press briefing at the Multidisciplinary Head and Neck Cancer Symposium.

In further analysis, benefit was limited to those who were aged 81 years or younger with low comorbidity and more advanced disease.

“Does age matter? The answer to that question is yes and no,” commented senior author Dr. Sana Karam of the University of Colorado at Denver, Aurora. “The physician needs to use his or her clinical judgment.”

“Don’t just look at the age of the patient,” she advised. “In this day and age where patients are healthier and living longer, give them the benefit of curative intent with the addition of chemo. Assess the patient clinically. If they are not healthy; their comorbidity score, KPS, ECOG, whatever you are using in your practice, is poor; or if they have earlier-stage disease, early T, no bulky nodes, then it’s okay to just give RT alone. But the addition of chemotherapy can improve survival dramatically” for other patients.

The new findings are likely to temper those of the pivotal MACH-NC (Meta-Analysis of Chemotherapy in Head and Neck Cancers). That analysis found little to no survival benefit from adding concurrent chemotherapy to radiation therapy in patients aged 71 years or older, but only 4% of the included patients fell into this age-group.

“So it was very underpowered, but yet, it has set our clinical practice guidelines,” Dr. Karam noted at the meeting cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology. “And we know from many of our clinical trials this is a patient population that’s generally heavily underrepresented on clinical trials.”

Press briefing moderator Dr. Christine Gourin of Johns Hopkins University, Baltimore, commented, “Your data are very important because we all know the MACH-NC meta-analysis is used by our colleagues in Europe to support not using chemotherapy in elderly patients,” she added. “And in fact your data suggest it’s really not age, but comorbidity” that should be considered.

Dr. Gourin and colleagues performed a similar analysis, but instead used the Surveillance, Epidemiology, and End Results (SEER) Medicare database. Their results suggested that the impact of adding concurrent chemotherapy to radiation depended on the site: Patients with oropharynx cancer benefited, but those with larynx cancer actually fared worse because of late toxicity.

“Did you find any difference when you drilled down between larynx and hypopharynx and oropharynx?” she asked.

“We found that the overall survival benefit was regardless of the subsite,” Dr. Karam replied, noting that the patient populations in the two cohorts differed somewhat. “Unfortunately, we don’t have clear-cut variables for toxicity, but what we did look at is time to completion of RT, and we found that patients who did get concurrent chemoradiation had a longer time to completion of RT, suggesting perhaps more treatment breaks maybe. … But still, despite the treatment breaks, even after controlling for that, we still found an overall survival advantage, regardless of the subsite.”

At her institution, patients are already being treated with a tailored approach, Dr. Gourin commented. “We have young patients who are so sick that they are not great candidates for chemotherapy, and then we have old patients who are healthier than I am who are great candidates for chemotherapy. So I would say that we have been doing what Dr. Karam suggests, which is looking at age not as a number, but rather comorbidity and the overall functional status of the patient.”

“That’s why I really liked your study: It’s great to see that in writing, because I know that colleagues in other countries that I talk to about health care reform and how to cut costs, they actually use the MACH-NC to define who gets treated and who doesn’t,” she added.

For their analysis, Dr. Karam and colleagues identified patients in the database given a diagnosis of locally advanced cancer of the oropharynx, larynx, or hypopharynx between 1998 and 2011 who were treated with radiation therapy.

Overall, 53% received chemotherapy concurrently, defined as starting it in the 14 days before or 14 days after initiation of the radiation therapy, according to Dr. Karam.

The specific agents given could not be ascertained, she acknowledged. “Unfortunately, the NCDB does not give us data in regard to the type of chemotherapy, and they only started collecting cetuximab data in 2013.”

With a median follow-up of 19 months, the unadjusted 5-year overall survival rate was 15.2% with radiation therapy alone and 30.3% with concurrent chemoradiation (hazard ratio, 0.59; P less than .001). Benefit fell only slightly after multivariate adjustment (HR, 0.63; P less than .001).

Findings were similar in a propensity-matched analysis, which showed an 18.1% survival with radiation therapy alone versus 26.4% with concurrent chemoradiation (HR, 0.73; P less than .001).

On recursive partitioning analysis, chemoradiation was associated with better survival among patients 81 years of age or younger who had low comorbidity based on Charlson-Deyo score and either T1-2,N2-3 disease or T3-4,N0-3 disease.

There was no survival benefit in patients older than age 81. And among patients aged 71-80, there was no benefit for those having less advanced disease (stage T1-2,N1) and low comorbidity, or having more advanced disease (T3-4,N1+ disease) and high comorbidity.

SCOTTSDALE, ARIZ. – Oncologists should consider not only age, but also comorbidities and disease extent when deciding whether to offer concurrent chemoradiation to older adults with locally advanced head and neck cancer, suggests a cohort study using data from the National Cancer Data Base.

The study of 4,042 patients aged 71 years or older found that adding chemotherapy to radiation therapy (RT) reduced the risk of death by at least one-fourth overall, according to results reported in a poster session and related press briefing at the Multidisciplinary Head and Neck Cancer Symposium.

In further analysis, benefit was limited to those who were aged 81 years or younger with low comorbidity and more advanced disease.

“Does age matter? The answer to that question is yes and no,” commented senior author Dr. Sana Karam of the University of Colorado at Denver, Aurora. “The physician needs to use his or her clinical judgment.”

“Don’t just look at the age of the patient,” she advised. “In this day and age where patients are healthier and living longer, give them the benefit of curative intent with the addition of chemo. Assess the patient clinically. If they are not healthy; their comorbidity score, KPS, ECOG, whatever you are using in your practice, is poor; or if they have earlier-stage disease, early T, no bulky nodes, then it’s okay to just give RT alone. But the addition of chemotherapy can improve survival dramatically” for other patients.

The new findings are likely to temper those of the pivotal MACH-NC (Meta-Analysis of Chemotherapy in Head and Neck Cancers). That analysis found little to no survival benefit from adding concurrent chemotherapy to radiation therapy in patients aged 71 years or older, but only 4% of the included patients fell into this age-group.

“So it was very underpowered, but yet, it has set our clinical practice guidelines,” Dr. Karam noted at the meeting cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology. “And we know from many of our clinical trials this is a patient population that’s generally heavily underrepresented on clinical trials.”

Press briefing moderator Dr. Christine Gourin of Johns Hopkins University, Baltimore, commented, “Your data are very important because we all know the MACH-NC meta-analysis is used by our colleagues in Europe to support not using chemotherapy in elderly patients,” she added. “And in fact your data suggest it’s really not age, but comorbidity” that should be considered.

Dr. Gourin and colleagues performed a similar analysis, but instead used the Surveillance, Epidemiology, and End Results (SEER) Medicare database. Their results suggested that the impact of adding concurrent chemotherapy to radiation depended on the site: Patients with oropharynx cancer benefited, but those with larynx cancer actually fared worse because of late toxicity.

“Did you find any difference when you drilled down between larynx and hypopharynx and oropharynx?” she asked.

“We found that the overall survival benefit was regardless of the subsite,” Dr. Karam replied, noting that the patient populations in the two cohorts differed somewhat. “Unfortunately, we don’t have clear-cut variables for toxicity, but what we did look at is time to completion of RT, and we found that patients who did get concurrent chemoradiation had a longer time to completion of RT, suggesting perhaps more treatment breaks maybe. … But still, despite the treatment breaks, even after controlling for that, we still found an overall survival advantage, regardless of the subsite.”

At her institution, patients are already being treated with a tailored approach, Dr. Gourin commented. “We have young patients who are so sick that they are not great candidates for chemotherapy, and then we have old patients who are healthier than I am who are great candidates for chemotherapy. So I would say that we have been doing what Dr. Karam suggests, which is looking at age not as a number, but rather comorbidity and the overall functional status of the patient.”

“That’s why I really liked your study: It’s great to see that in writing, because I know that colleagues in other countries that I talk to about health care reform and how to cut costs, they actually use the MACH-NC to define who gets treated and who doesn’t,” she added.

For their analysis, Dr. Karam and colleagues identified patients in the database given a diagnosis of locally advanced cancer of the oropharynx, larynx, or hypopharynx between 1998 and 2011 who were treated with radiation therapy.

Overall, 53% received chemotherapy concurrently, defined as starting it in the 14 days before or 14 days after initiation of the radiation therapy, according to Dr. Karam.

The specific agents given could not be ascertained, she acknowledged. “Unfortunately, the NCDB does not give us data in regard to the type of chemotherapy, and they only started collecting cetuximab data in 2013.”

With a median follow-up of 19 months, the unadjusted 5-year overall survival rate was 15.2% with radiation therapy alone and 30.3% with concurrent chemoradiation (hazard ratio, 0.59; P less than .001). Benefit fell only slightly after multivariate adjustment (HR, 0.63; P less than .001).

Findings were similar in a propensity-matched analysis, which showed an 18.1% survival with radiation therapy alone versus 26.4% with concurrent chemoradiation (HR, 0.73; P less than .001).

On recursive partitioning analysis, chemoradiation was associated with better survival among patients 81 years of age or younger who had low comorbidity based on Charlson-Deyo score and either T1-2,N2-3 disease or T3-4,N0-3 disease.

There was no survival benefit in patients older than age 81. And among patients aged 71-80, there was no benefit for those having less advanced disease (stage T1-2,N1) and low comorbidity, or having more advanced disease (T3-4,N1+ disease) and high comorbidity.

SCOTTSDALE, ARIZ. – Oncologists should consider not only age, but also comorbidities and disease extent when deciding whether to offer concurrent chemoradiation to older adults with locally advanced head and neck cancer, suggests a cohort study using data from the National Cancer Data Base.

The study of 4,042 patients aged 71 years or older found that adding chemotherapy to radiation therapy (RT) reduced the risk of death by at least one-fourth overall, according to results reported in a poster session and related press briefing at the Multidisciplinary Head and Neck Cancer Symposium.

In further analysis, benefit was limited to those who were aged 81 years or younger with low comorbidity and more advanced disease.

“Does age matter? The answer to that question is yes and no,” commented senior author Dr. Sana Karam of the University of Colorado at Denver, Aurora. “The physician needs to use his or her clinical judgment.”

“Don’t just look at the age of the patient,” she advised. “In this day and age where patients are healthier and living longer, give them the benefit of curative intent with the addition of chemo. Assess the patient clinically. If they are not healthy; their comorbidity score, KPS, ECOG, whatever you are using in your practice, is poor; or if they have earlier-stage disease, early T, no bulky nodes, then it’s okay to just give RT alone. But the addition of chemotherapy can improve survival dramatically” for other patients.

The new findings are likely to temper those of the pivotal MACH-NC (Meta-Analysis of Chemotherapy in Head and Neck Cancers). That analysis found little to no survival benefit from adding concurrent chemotherapy to radiation therapy in patients aged 71 years or older, but only 4% of the included patients fell into this age-group.

“So it was very underpowered, but yet, it has set our clinical practice guidelines,” Dr. Karam noted at the meeting cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology. “And we know from many of our clinical trials this is a patient population that’s generally heavily underrepresented on clinical trials.”

Press briefing moderator Dr. Christine Gourin of Johns Hopkins University, Baltimore, commented, “Your data are very important because we all know the MACH-NC meta-analysis is used by our colleagues in Europe to support not using chemotherapy in elderly patients,” she added. “And in fact your data suggest it’s really not age, but comorbidity” that should be considered.

Dr. Gourin and colleagues performed a similar analysis, but instead used the Surveillance, Epidemiology, and End Results (SEER) Medicare database. Their results suggested that the impact of adding concurrent chemotherapy to radiation depended on the site: Patients with oropharynx cancer benefited, but those with larynx cancer actually fared worse because of late toxicity.

“Did you find any difference when you drilled down between larynx and hypopharynx and oropharynx?” she asked.

“We found that the overall survival benefit was regardless of the subsite,” Dr. Karam replied, noting that the patient populations in the two cohorts differed somewhat. “Unfortunately, we don’t have clear-cut variables for toxicity, but what we did look at is time to completion of RT, and we found that patients who did get concurrent chemoradiation had a longer time to completion of RT, suggesting perhaps more treatment breaks maybe. … But still, despite the treatment breaks, even after controlling for that, we still found an overall survival advantage, regardless of the subsite.”

At her institution, patients are already being treated with a tailored approach, Dr. Gourin commented. “We have young patients who are so sick that they are not great candidates for chemotherapy, and then we have old patients who are healthier than I am who are great candidates for chemotherapy. So I would say that we have been doing what Dr. Karam suggests, which is looking at age not as a number, but rather comorbidity and the overall functional status of the patient.”

“That’s why I really liked your study: It’s great to see that in writing, because I know that colleagues in other countries that I talk to about health care reform and how to cut costs, they actually use the MACH-NC to define who gets treated and who doesn’t,” she added.

For their analysis, Dr. Karam and colleagues identified patients in the database given a diagnosis of locally advanced cancer of the oropharynx, larynx, or hypopharynx between 1998 and 2011 who were treated with radiation therapy.

Overall, 53% received chemotherapy concurrently, defined as starting it in the 14 days before or 14 days after initiation of the radiation therapy, according to Dr. Karam.

The specific agents given could not be ascertained, she acknowledged. “Unfortunately, the NCDB does not give us data in regard to the type of chemotherapy, and they only started collecting cetuximab data in 2013.”

With a median follow-up of 19 months, the unadjusted 5-year overall survival rate was 15.2% with radiation therapy alone and 30.3% with concurrent chemoradiation (hazard ratio, 0.59; P less than .001). Benefit fell only slightly after multivariate adjustment (HR, 0.63; P less than .001).

Findings were similar in a propensity-matched analysis, which showed an 18.1% survival with radiation therapy alone versus 26.4% with concurrent chemoradiation (HR, 0.73; P less than .001).

On recursive partitioning analysis, chemoradiation was associated with better survival among patients 81 years of age or younger who had low comorbidity based on Charlson-Deyo score and either T1-2,N2-3 disease or T3-4,N0-3 disease.

There was no survival benefit in patients older than age 81. And among patients aged 71-80, there was no benefit for those having less advanced disease (stage T1-2,N1) and low comorbidity, or having more advanced disease (T3-4,N1+ disease) and high comorbidity.

One in every seven infections in acute care hospitals related to catheters and surgeries was caused by antibiotic-resistant bacteria. In long-term acute care hospitals, that number increased to one in four.

Those are key findings from a study published March 3 in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report that is the first to combine national data on antibiotic-resistant (AR) bacteria threats with progress on health care–associated infections (HAIs).

“Antibiotic resistance threatens to return us to a time when a simple infection could kill,” CDC Director Thomas Frieden said during a March 3 telebriefing. “The more people who get infected with resistant bacteria, the more people who suffer complications, the more who, tragically, may die from preventable infections. On any given day about one in 25 hospitalized patients has at least one health care–associated infection that they didn’t come in with. No one should get sick when they’re trying to get well.”

For the study, researchers led by Dr. Clifford McDonald of the CDC’s Division of Healthcare Quality Promotion, collected data on specific infections that were reported to the National Healthcare Safety Network in 2014 by approximately 4,000 short-term acute care hospitals, 501 long-term acute care hospitals, and 1,135 inpatient rehabilitation facilities in all 50 states (MMWR. 2016 Mar 3. doi: 10.15585/mmwr.mm6509e1er). Next, they determined the proportions of AR pathogens and HAIs caused by any of six resistant bacteria highlighted by the CDC in 2013 as urgent or serious threats: CRE (carbapenem-resistant Enterobacteriaceae), MRSA (methicillin-resistant Staphylococcus aureus), ESBL-producing Enterobacteriaceae (extended-spectrum beta-lactamases), VRE (vancomycin-resistant enterococci), multidrug-resistant pseudomonas, and multidrug-resistant Acinetobacter.

The researchers found that, compared with historical data from 5-8 years earlier, central line–associated bloodstream infections decreased by 50% and surgical site infections (SSIs) by 17% in 2014.

© CDC

“There is encouraging news here,” Dr. Frieden said. “Doctors, nurses, hospitals, health care systems and other partners have made progress preventing some health care–associated infections.” However, the study found that one in six remaining central line-associated bloodstream infections were caused by urgent or serious antibiotic-resistant bacteria, while one in seven remaining surgical site infections were caused by urgent or serious antibiotic-resistant bacteria.

While catheter-associated urinary tract infections appear unchanged from baseline, there have been recent decreases, according to the study. In addition, C. difficile infections in hospitals decreased 8% between 2011 and 2014.

Dr. McDonald and his associates determined that in 2014, one in seven infections in acute care hospitals related to catheters and surgeries was caused by one of the six antibiotic-resistance threat bacteria, “which is deeply concerning,” Dr. Frieden said. That number increased to one in four infections in long-term acute care hospitals, a proportion that he characterized as “chilling.”

The CDC recommends three strategies that doctors, nurses, and other health care providers should take with every patient, to prevent HAIs and stop the spread of antibiotic resistance:

• Prevent the spread of bacteria between patients. Dr. Peter Pronovost, who participated in the telebriefing, said that he and his associates at Johns Hopkins University in Baltimore “do this by practicing good hand hygiene techniques by wearing sterile equipment when inserting lines.”

• Prevent surgery-related infections and/or placement of a catheter. “Check catheters frequently and remove them when you no longer need them,” advised Dr. Pronovost, director of the Armstrong Institute for Patient Safety and Quality at Johns Hopkins. “Ask if you actually need them before you even place them.”

• Improve antibiotic use through stewardship. This means using “the right antibiotics for the right duration,” Dr. Pronovost said. “Antibiotics could be lifesaving and are necessary for critically ill patients, especially those with septic shock. But these antibiotics need to be adjusted based on lab results and new information about the organisms that are causing these infections. Forty-eight hours after antibiotics are initiated, take a ‘time out.’ Perform a brief but focused assessment to determine if antibiotic therapy is still needed, or if it should be refined. A common mistake we make is to continue vancomycin when there is no presence of MRSA. We often tell our staff at Johns Hopkins, ‘if it doesn’t grow, let it go.’ ”

Dr. Frieden concluded his remarks by noting that physicians and other clinicians on the front lines “need support of their facility leadership,” to prevent HAIs. “Health care facilities, CEOs, and administrators are a major part of the solution. It’s important that they make a priority of infection prevention, sepsis prevention, and antibiotic stewardship. Know your facility’s data and target prevention efforts to ensure improvements in patient safety.”

[email protected]

One in every seven infections in acute care hospitals related to catheters and surgeries was caused by antibiotic-resistant bacteria. In long-term acute care hospitals, that number increased to one in four.

Those are key findings from a study published March 3 in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report that is the first to combine national data on antibiotic-resistant (AR) bacteria threats with progress on health care–associated infections (HAIs).

“Antibiotic resistance threatens to return us to a time when a simple infection could kill,” CDC Director Thomas Frieden said during a March 3 telebriefing. “The more people who get infected with resistant bacteria, the more people who suffer complications, the more who, tragically, may die from preventable infections. On any given day about one in 25 hospitalized patients has at least one health care–associated infection that they didn’t come in with. No one should get sick when they’re trying to get well.”

For the study, researchers led by Dr. Clifford McDonald of the CDC’s Division of Healthcare Quality Promotion, collected data on specific infections that were reported to the National Healthcare Safety Network in 2014 by approximately 4,000 short-term acute care hospitals, 501 long-term acute care hospitals, and 1,135 inpatient rehabilitation facilities in all 50 states (MMWR. 2016 Mar 3. doi: 10.15585/mmwr.mm6509e1er). Next, they determined the proportions of AR pathogens and HAIs caused by any of six resistant bacteria highlighted by the CDC in 2013 as urgent or serious threats: CRE (carbapenem-resistant Enterobacteriaceae), MRSA (methicillin-resistant Staphylococcus aureus), ESBL-producing Enterobacteriaceae (extended-spectrum beta-lactamases), VRE (vancomycin-resistant enterococci), multidrug-resistant pseudomonas, and multidrug-resistant Acinetobacter.

The researchers found that, compared with historical data from 5-8 years earlier, central line–associated bloodstream infections decreased by 50% and surgical site infections (SSIs) by 17% in 2014.

© CDC

“There is encouraging news here,” Dr. Frieden said. “Doctors, nurses, hospitals, health care systems and other partners have made progress preventing some health care–associated infections.” However, the study found that one in six remaining central line-associated bloodstream infections were caused by urgent or serious antibiotic-resistant bacteria, while one in seven remaining surgical site infections were caused by urgent or serious antibiotic-resistant bacteria.

While catheter-associated urinary tract infections appear unchanged from baseline, there have been recent decreases, according to the study. In addition, C. difficile infections in hospitals decreased 8% between 2011 and 2014.

Dr. McDonald and his associates determined that in 2014, one in seven infections in acute care hospitals related to catheters and surgeries was caused by one of the six antibiotic-resistance threat bacteria, “which is deeply concerning,” Dr. Frieden said. That number increased to one in four infections in long-term acute care hospitals, a proportion that he characterized as “chilling.”

The CDC recommends three strategies that doctors, nurses, and other health care providers should take with every patient, to prevent HAIs and stop the spread of antibiotic resistance:

• Prevent the spread of bacteria between patients. Dr. Peter Pronovost, who participated in the telebriefing, said that he and his associates at Johns Hopkins University in Baltimore “do this by practicing good hand hygiene techniques by wearing sterile equipment when inserting lines.”

• Prevent surgery-related infections and/or placement of a catheter. “Check catheters frequently and remove them when you no longer need them,” advised Dr. Pronovost, director of the Armstrong Institute for Patient Safety and Quality at Johns Hopkins. “Ask if you actually need them before you even place them.”

• Improve antibiotic use through stewardship. This means using “the right antibiotics for the right duration,” Dr. Pronovost said. “Antibiotics could be lifesaving and are necessary for critically ill patients, especially those with septic shock. But these antibiotics need to be adjusted based on lab results and new information about the organisms that are causing these infections. Forty-eight hours after antibiotics are initiated, take a ‘time out.’ Perform a brief but focused assessment to determine if antibiotic therapy is still needed, or if it should be refined. A common mistake we make is to continue vancomycin when there is no presence of MRSA. We often tell our staff at Johns Hopkins, ‘if it doesn’t grow, let it go.’ ”

Dr. Frieden concluded his remarks by noting that physicians and other clinicians on the front lines “need support of their facility leadership,” to prevent HAIs. “Health care facilities, CEOs, and administrators are a major part of the solution. It’s important that they make a priority of infection prevention, sepsis prevention, and antibiotic stewardship. Know your facility’s data and target prevention efforts to ensure improvements in patient safety.”

[email protected]

One in every seven infections in acute care hospitals related to catheters and surgeries was caused by antibiotic-resistant bacteria. In long-term acute care hospitals, that number increased to one in four.

Those are key findings from a study published March 3 in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report that is the first to combine national data on antibiotic-resistant (AR) bacteria threats with progress on health care–associated infections (HAIs).

“Antibiotic resistance threatens to return us to a time when a simple infection could kill,” CDC Director Thomas Frieden said during a March 3 telebriefing. “The more people who get infected with resistant bacteria, the more people who suffer complications, the more who, tragically, may die from preventable infections. On any given day about one in 25 hospitalized patients has at least one health care–associated infection that they didn’t come in with. No one should get sick when they’re trying to get well.”

For the study, researchers led by Dr. Clifford McDonald of the CDC’s Division of Healthcare Quality Promotion, collected data on specific infections that were reported to the National Healthcare Safety Network in 2014 by approximately 4,000 short-term acute care hospitals, 501 long-term acute care hospitals, and 1,135 inpatient rehabilitation facilities in all 50 states (MMWR. 2016 Mar 3. doi: 10.15585/mmwr.mm6509e1er). Next, they determined the proportions of AR pathogens and HAIs caused by any of six resistant bacteria highlighted by the CDC in 2013 as urgent or serious threats: CRE (carbapenem-resistant Enterobacteriaceae), MRSA (methicillin-resistant Staphylococcus aureus), ESBL-producing Enterobacteriaceae (extended-spectrum beta-lactamases), VRE (vancomycin-resistant enterococci), multidrug-resistant pseudomonas, and multidrug-resistant Acinetobacter.

The researchers found that, compared with historical data from 5-8 years earlier, central line–associated bloodstream infections decreased by 50% and surgical site infections (SSIs) by 17% in 2014.

© CDC

“There is encouraging news here,” Dr. Frieden said. “Doctors, nurses, hospitals, health care systems and other partners have made progress preventing some health care–associated infections.” However, the study found that one in six remaining central line-associated bloodstream infections were caused by urgent or serious antibiotic-resistant bacteria, while one in seven remaining surgical site infections were caused by urgent or serious antibiotic-resistant bacteria.

While catheter-associated urinary tract infections appear unchanged from baseline, there have been recent decreases, according to the study. In addition, C. difficile infections in hospitals decreased 8% between 2011 and 2014.

Dr. McDonald and his associates determined that in 2014, one in seven infections in acute care hospitals related to catheters and surgeries was caused by one of the six antibiotic-resistance threat bacteria, “which is deeply concerning,” Dr. Frieden said. That number increased to one in four infections in long-term acute care hospitals, a proportion that he characterized as “chilling.”

The CDC recommends three strategies that doctors, nurses, and other health care providers should take with every patient, to prevent HAIs and stop the spread of antibiotic resistance:

• Prevent the spread of bacteria between patients. Dr. Peter Pronovost, who participated in the telebriefing, said that he and his associates at Johns Hopkins University in Baltimore “do this by practicing good hand hygiene techniques by wearing sterile equipment when inserting lines.”

• Prevent surgery-related infections and/or placement of a catheter. “Check catheters frequently and remove them when you no longer need them,” advised Dr. Pronovost, director of the Armstrong Institute for Patient Safety and Quality at Johns Hopkins. “Ask if you actually need them before you even place them.”

• Improve antibiotic use through stewardship. This means using “the right antibiotics for the right duration,” Dr. Pronovost said. “Antibiotics could be lifesaving and are necessary for critically ill patients, especially those with septic shock. But these antibiotics need to be adjusted based on lab results and new information about the organisms that are causing these infections. Forty-eight hours after antibiotics are initiated, take a ‘time out.’ Perform a brief but focused assessment to determine if antibiotic therapy is still needed, or if it should be refined. A common mistake we make is to continue vancomycin when there is no presence of MRSA. We often tell our staff at Johns Hopkins, ‘if it doesn’t grow, let it go.’ ”

Dr. Frieden concluded his remarks by noting that physicians and other clinicians on the front lines “need support of their facility leadership,” to prevent HAIs. “Health care facilities, CEOs, and administrators are a major part of the solution. It’s important that they make a priority of infection prevention, sepsis prevention, and antibiotic stewardship. Know your facility’s data and target prevention efforts to ensure improvements in patient safety.”

[email protected]

The ED physician suspected necrotizing fasciitis (NF) and immediately called for a surgical consult. This patient had type II NF, which can be caused by common skin organisms, such as Streptococcus pyogenes and Staphylococcus aureus.

Surgical debridement is the primary therapeutic modality. If the first debridement occurs within 24 hours of the onset of symptoms, there is a significantly improved chance of survival. Extensive, definitive debridement should be the goal with the first surgery. This may require amputation of an extremity to control the disease. Surgical debridement is repeated until all infected devitalized tissue is removed.

Antibiotics are the main adjunctive therapy to surgery. Broad-spectrum empiric antibiotics should be started immediately when NF is suspected and should include coverage of Gram-positive, Gram-negative, and anaerobic organisms. Antimicrobial therapy must be directed at the known or suspected pathogens and used in appropriate doses until repeated operative procedures are no longer needed. Empiric vancomycin should be considered while awaiting culture results to cover for the increasing incidence of methicillin-resistant Staphylococcus aureus (MRSA). Aggressive fluid resuscitation is often necessary because of massive capillary leak syndrome.

In this case, the patient was started on empiric broad-spectrum intravenous antibiotics to cover Gram-positive, Gram-negative, and anaerobic organisms. The surgical team then rapidly admitted the patient to the operating room (OR) for debridement. From the OR, she was transferred to the surgical intensive care unit where she received ongoing supportive and postoperative care. The intraoperative tissue cultures grew out MRSA.

The patient in this case was fortunate. She survived because of the speed with which she received a proper diagnosis and treatment.

Photo courtesy of Michael Babcock, MD. Text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Franklin J. Necrotizing fasciitis. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:702-706.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The ED physician suspected necrotizing fasciitis (NF) and immediately called for a surgical consult. This patient had type II NF, which can be caused by common skin organisms, such as Streptococcus pyogenes and Staphylococcus aureus.

Surgical debridement is the primary therapeutic modality. If the first debridement occurs within 24 hours of the onset of symptoms, there is a significantly improved chance of survival. Extensive, definitive debridement should be the goal with the first surgery. This may require amputation of an extremity to control the disease. Surgical debridement is repeated until all infected devitalized tissue is removed.

Antibiotics are the main adjunctive therapy to surgery. Broad-spectrum empiric antibiotics should be started immediately when NF is suspected and should include coverage of Gram-positive, Gram-negative, and anaerobic organisms. Antimicrobial therapy must be directed at the known or suspected pathogens and used in appropriate doses until repeated operative procedures are no longer needed. Empiric vancomycin should be considered while awaiting culture results to cover for the increasing incidence of methicillin-resistant Staphylococcus aureus (MRSA). Aggressive fluid resuscitation is often necessary because of massive capillary leak syndrome.

In this case, the patient was started on empiric broad-spectrum intravenous antibiotics to cover Gram-positive, Gram-negative, and anaerobic organisms. The surgical team then rapidly admitted the patient to the operating room (OR) for debridement. From the OR, she was transferred to the surgical intensive care unit where she received ongoing supportive and postoperative care. The intraoperative tissue cultures grew out MRSA.

The patient in this case was fortunate. She survived because of the speed with which she received a proper diagnosis and treatment.

Photo courtesy of Michael Babcock, MD. Text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Franklin J. Necrotizing fasciitis. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:702-706.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The ED physician suspected necrotizing fasciitis (NF) and immediately called for a surgical consult. This patient had type II NF, which can be caused by common skin organisms, such as Streptococcus pyogenes and Staphylococcus aureus.

Surgical debridement is the primary therapeutic modality. If the first debridement occurs within 24 hours of the onset of symptoms, there is a significantly improved chance of survival. Extensive, definitive debridement should be the goal with the first surgery. This may require amputation of an extremity to control the disease. Surgical debridement is repeated until all infected devitalized tissue is removed.

Antibiotics are the main adjunctive therapy to surgery. Broad-spectrum empiric antibiotics should be started immediately when NF is suspected and should include coverage of Gram-positive, Gram-negative, and anaerobic organisms. Antimicrobial therapy must be directed at the known or suspected pathogens and used in appropriate doses until repeated operative procedures are no longer needed. Empiric vancomycin should be considered while awaiting culture results to cover for the increasing incidence of methicillin-resistant Staphylococcus aureus (MRSA). Aggressive fluid resuscitation is often necessary because of massive capillary leak syndrome.

In this case, the patient was started on empiric broad-spectrum intravenous antibiotics to cover Gram-positive, Gram-negative, and anaerobic organisms. The surgical team then rapidly admitted the patient to the operating room (OR) for debridement. From the OR, she was transferred to the surgical intensive care unit where she received ongoing supportive and postoperative care. The intraoperative tissue cultures grew out MRSA.

The patient in this case was fortunate. She survived because of the speed with which she received a proper diagnosis and treatment.

Photo courtesy of Michael Babcock, MD. Text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Franklin J. Necrotizing fasciitis. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:702-706.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The ED physician suspected necrotizing fasciitis (NF), a rapidly progressive infection of the deep fascia with necrosis of the subcutaneous tissues. It usually occurs after surgery or trauma. Patients have erythema and pain disproportionate to the physical findings.

This patient had type I NF, a polymicrobial infection with aerobic and anaerobic bacteria. It is frequently caused by enteric Gram-negative pathogens including Enterobacteriaceae organisms and Bacteroides. It can also occur with Gram-positive organisms such as non–group A streptococci and Peptostreptococcus.

Risk factors for type I NF include diabetes, severe peripheral vascular disease, obesity, alcoholism, cirrhosis, intravenous drug use, decubitus ulcers, poor nutritional status, surgery, and penetrating trauma. Early recognition based on signs and symptoms is potentially lifesaving. Although lab tests and imaging studies can confirm one’s clinical impression, rapid treatment with antibiotics and surgery are crucial to improving survival.

The patient in this case was taken to the operating room for debridement of her NF. Broad-spectrum antibiotics were started, but the infection continued to quickly advance. The patient died the following day. Her wound culture later grew Escherichia coli, Proteus vulgaris, Corynebacterium, Enterococcus, Staphylococcus sp., and Peptostreptococcus.


Adapted from: Dufel S, Martino M. Simple cellulitis or a more serious infection? J Fam Pract. 2006;55:396-400.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The ED physician suspected necrotizing fasciitis (NF), a rapidly progressive infection of the deep fascia with necrosis of the subcutaneous tissues. It usually occurs after surgery or trauma. Patients have erythema and pain disproportionate to the physical findings.

This patient had type I NF, a polymicrobial infection with aerobic and anaerobic bacteria. It is frequently caused by enteric Gram-negative pathogens including Enterobacteriaceae organisms and Bacteroides. It can also occur with Gram-positive organisms such as non–group A streptococci and Peptostreptococcus.

Risk factors for type I NF include diabetes, severe peripheral vascular disease, obesity, alcoholism, cirrhosis, intravenous drug use, decubitus ulcers, poor nutritional status, surgery, and penetrating trauma. Early recognition based on signs and symptoms is potentially lifesaving. Although lab tests and imaging studies can confirm one’s clinical impression, rapid treatment with antibiotics and surgery are crucial to improving survival.

The patient in this case was taken to the operating room for debridement of her NF. Broad-spectrum antibiotics were started, but the infection continued to quickly advance. The patient died the following day. Her wound culture later grew Escherichia coli, Proteus vulgaris, Corynebacterium, Enterococcus, Staphylococcus sp., and Peptostreptococcus.


Adapted from: Dufel S, Martino M. Simple cellulitis or a more serious infection? J Fam Pract. 2006;55:396-400.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The ED physician suspected necrotizing fasciitis (NF), a rapidly progressive infection of the deep fascia with necrosis of the subcutaneous tissues. It usually occurs after surgery or trauma. Patients have erythema and pain disproportionate to the physical findings.

This patient had type I NF, a polymicrobial infection with aerobic and anaerobic bacteria. It is frequently caused by enteric Gram-negative pathogens including Enterobacteriaceae organisms and Bacteroides. It can also occur with Gram-positive organisms such as non–group A streptococci and Peptostreptococcus.

Risk factors for type I NF include diabetes, severe peripheral vascular disease, obesity, alcoholism, cirrhosis, intravenous drug use, decubitus ulcers, poor nutritional status, surgery, and penetrating trauma. Early recognition based on signs and symptoms is potentially lifesaving. Although lab tests and imaging studies can confirm one’s clinical impression, rapid treatment with antibiotics and surgery are crucial to improving survival.

The patient in this case was taken to the operating room for debridement of her NF. Broad-spectrum antibiotics were started, but the infection continued to quickly advance. The patient died the following day. Her wound culture later grew Escherichia coli, Proteus vulgaris, Corynebacterium, Enterococcus, Staphylococcus sp., and Peptostreptococcus.


Adapted from: Dufel S, Martino M. Simple cellulitis or a more serious infection? J Fam Pract. 2006;55:396-400.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The physician recognized that his patient had a neck abscess that was likely related to a dental abscess (odontogenic abscess). The patient’s alcoholism most likely weakened his ability to fight the infection, causing it to become potentially life-threatening. Risk factors for abscess formation include intravenous drug abuse, alcoholism, homelessness, dental disease, contact sports, and incarceration.

The physician transferred the patient to the local emergency department for hospitalization under the care of the ear, nose, and throat (ENT) service. The ENT physicians drained the abscess in the operating room without any complications. They cultured the abscess and started the patient on appropriate antibiotics, including penicillin G for dental aerobes and anaerobes.

The hospital team observed the patient for signs of alcohol withdrawal, but there were no complications because the patient hadn’t been drinking for the 5 days prior to hospitalization. Social Services was consulted and the patient was discharged to a respite bed in a local shelter that also had an alcohol and drug rehabilitation program. Arrangements were made for dental work in a charity dental clinic.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Abscess. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill;2013:698-701.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The physician recognized that his patient had a neck abscess that was likely related to a dental abscess (odontogenic abscess). The patient’s alcoholism most likely weakened his ability to fight the infection, causing it to become potentially life-threatening. Risk factors for abscess formation include intravenous drug abuse, alcoholism, homelessness, dental disease, contact sports, and incarceration.

The physician transferred the patient to the local emergency department for hospitalization under the care of the ear, nose, and throat (ENT) service. The ENT physicians drained the abscess in the operating room without any complications. They cultured the abscess and started the patient on appropriate antibiotics, including penicillin G for dental aerobes and anaerobes.

The hospital team observed the patient for signs of alcohol withdrawal, but there were no complications because the patient hadn’t been drinking for the 5 days prior to hospitalization. Social Services was consulted and the patient was discharged to a respite bed in a local shelter that also had an alcohol and drug rehabilitation program. Arrangements were made for dental work in a charity dental clinic.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Abscess. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill;2013:698-701.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The physician recognized that his patient had a neck abscess that was likely related to a dental abscess (odontogenic abscess). The patient’s alcoholism most likely weakened his ability to fight the infection, causing it to become potentially life-threatening. Risk factors for abscess formation include intravenous drug abuse, alcoholism, homelessness, dental disease, contact sports, and incarceration.

The physician transferred the patient to the local emergency department for hospitalization under the care of the ear, nose, and throat (ENT) service. The ENT physicians drained the abscess in the operating room without any complications. They cultured the abscess and started the patient on appropriate antibiotics, including penicillin G for dental aerobes and anaerobes.

The hospital team observed the patient for signs of alcohol withdrawal, but there were no complications because the patient hadn’t been drinking for the 5 days prior to hospitalization. Social Services was consulted and the patient was discharged to a respite bed in a local shelter that also had an alcohol and drug rehabilitation program. Arrangements were made for dental work in a charity dental clinic.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Abscess. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill;2013:698-701.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

Electroconvulsive therapy increased illness-free intervals and reduced manic and depressive episodes in bipolar patients, reported Dr. Gian Paolo Minnai of the psychiatry unit at San Martino Hospital in Oristano, Italy, and coauthors.

In a retrospective study of 41 patients with bipolar disorder, the investigators analyzed the number of episodes and admissions 5 years before and after ECT treatment. The duration of free intervals before and after ECT was also studied.

wildpixel/Thinkstock.com

The results showed “significantly longer” free intervals after treatment (13.2 ± 9.0 months before ECT to 25.1 ± 19.1 months after treatment [t = 3.8; P less than .0001]), Dr. Minnai and colleagues reported. In addition, the analysis found “significant reductions” in the number of manic and depressive episodes (5.9 ± 3.0 before ECT to 1.0 ± 1.7 after treatment [t = 9.3; P less than .0001]) and admissions (2.2 ± 1.3 before ECT to 0.2 ± 0.5 after treatment [t = 9.4; P less than .0001]).

The study suggests that “it is plausible that ECT, along with suspending antidepressant treatment, might carry intrinsic stabilizing effect on the course of [bipolar disorder],” the authors concluded.

No financial conflicts of interest were disclosed.

Read the full article in the Journal of Affective Disorders (May 2016;195:180-4).

[email protected]

Electroconvulsive therapy increased illness-free intervals and reduced manic and depressive episodes in bipolar patients, reported Dr. Gian Paolo Minnai of the psychiatry unit at San Martino Hospital in Oristano, Italy, and coauthors.

In a retrospective study of 41 patients with bipolar disorder, the investigators analyzed the number of episodes and admissions 5 years before and after ECT treatment. The duration of free intervals before and after ECT was also studied.

wildpixel/Thinkstock.com

The results showed “significantly longer” free intervals after treatment (13.2 ± 9.0 months before ECT to 25.1 ± 19.1 months after treatment [t = 3.8; P less than .0001]), Dr. Minnai and colleagues reported. In addition, the analysis found “significant reductions” in the number of manic and depressive episodes (5.9 ± 3.0 before ECT to 1.0 ± 1.7 after treatment [t = 9.3; P less than .0001]) and admissions (2.2 ± 1.3 before ECT to 0.2 ± 0.5 after treatment [t = 9.4; P less than .0001]).

The study suggests that “it is plausible that ECT, along with suspending antidepressant treatment, might carry intrinsic stabilizing effect on the course of [bipolar disorder],” the authors concluded.

No financial conflicts of interest were disclosed.

Read the full article in the Journal of Affective Disorders (May 2016;195:180-4).

[email protected]

Electroconvulsive therapy increased illness-free intervals and reduced manic and depressive episodes in bipolar patients, reported Dr. Gian Paolo Minnai of the psychiatry unit at San Martino Hospital in Oristano, Italy, and coauthors.

In a retrospective study of 41 patients with bipolar disorder, the investigators analyzed the number of episodes and admissions 5 years before and after ECT treatment. The duration of free intervals before and after ECT was also studied.

wildpixel/Thinkstock.com

The results showed “significantly longer” free intervals after treatment (13.2 ± 9.0 months before ECT to 25.1 ± 19.1 months after treatment [t = 3.8; P less than .0001]), Dr. Minnai and colleagues reported. In addition, the analysis found “significant reductions” in the number of manic and depressive episodes (5.9 ± 3.0 before ECT to 1.0 ± 1.7 after treatment [t = 9.3; P less than .0001]) and admissions (2.2 ± 1.3 before ECT to 0.2 ± 0.5 after treatment [t = 9.4; P less than .0001]).

The study suggests that “it is plausible that ECT, along with suspending antidepressant treatment, might carry intrinsic stabilizing effect on the course of [bipolar disorder],” the authors concluded.

No financial conflicts of interest were disclosed.

Read the full article in the Journal of Affective Disorders (May 2016;195:180-4).

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A new practice pathway provides primary care providers with evidence-based steps in assessing and addressing irritability and problem behavior in patients at least 3 years old who have been diagnosed with an autism spectrum disorder (ASD).

“As the medical professionals whom children with ASD will probably encounter first and most frequently, pediatric primary care providers need a breadth of knowledge to enable them to identify contributing factors to irritability and problem behavior, decide when and how to initiate treatment, and judge when to refer to specialists,” reported Dr. Kelly McGuire of Columbia University Medical Center and New York State Psychiatric Institute, and her associates (Pediatrics. 2016 Feb;137 Suppl 2:S136-48). “Therefore, this practice pathway can be viewed more as a comprehensive rather than an exhaustive recommendation for [primary care physicians], who must weigh their expertise and resources when addressing the range of issues that a child with ASD and irritability and problem behavior may present.”

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The Irritability Workgroup comprised eight child psychiatrists, a developmental pediatrician, and a behavioral psychologist who met regularly to define irritability and problem behavior, and then to review the evidence base on assessing and treating factors that contribute to irritability and problem behavior. They grouped these factors into five domains: “co-occurring medical conditions, lack of functional communication, psychosocial stressors, maladaptive reinforcement patterns, and co-occurring psychiatric conditions.”

Then the group developed a consensus in determining each step in the practice pathway and when it should occur, along with opportunities for a primary care provider to refer the patient to a specialist or to collaborate with school and community providers. The 10 steps in the practice pathway are:

1. Assess the patient for irritability and problem behavior based on the presence of tantrums, meltdowns or rages; property destruction; aggression toward others; and self-injury.

2. Assess the safety of the patient and others in the home, enlisting home-based crisis services or considering hospitalization if safety is threatened.

3. Review the patient’s medical, developmental, communication, environmental, and psychiatric history before and after the problem behavior. Include information on the caretaker’s characteristics, any loss of skills by patient, and any interference occurring with functioning or relationships.

4. Prioritize the behaviors to address based on safety, severity, and impact on daily life.

5. Consider all contributing factors to the problem behavior, including medical problems, difficulties functionally communicating, psychosocial stressors, maladaptive reinforcement patterns (reducing inadvertent triggers), and comorbid psychiatric disorders.

6. Consider possible medication treatments, such as N-acetylcysteine, clonidine, risperidone or aripiprazole, depending on circumstances.

7. Develop an individualized treatment and safety plan.

8. Implement and monitor the treatment plan, setting clear and measurable treatment goals.

9. Follow up at 3 months to assess whether symptoms are continuing and a reassessment is needed.

10. Reevaluate every 3 months.

The article provides a useful and extensive checklist with a variety of specific things to consider when implementing the 10 steps.

“No other provider in the patient’s life combines the medical expertise and first-hand knowledge of the individual patient’s health and development” than the primary care provider, the authors wrote. “The practice pathway is most likely to be efficient and effective in generating a treatment plan if it is systematically followed and the specific combination of individual contributing factors is identified for each patient.”

The research was conducted through the Autism Speaks Autism Treatment Network and funded by the U.S. Department of Health and Human Services with the Autism Intervention Research Network on Physical Health and by Marilyn and James Simons Family Giving. Dr. Jeremy Veenstra-VanderWeele has received research funding from Seaside Therapeutics, Roche, Novartis, Forest, Sunovion, and SynapDx and has consulted with Roche, Novartis and SynapDx.

A new practice pathway provides primary care providers with evidence-based steps in assessing and addressing irritability and problem behavior in patients at least 3 years old who have been diagnosed with an autism spectrum disorder (ASD).

“As the medical professionals whom children with ASD will probably encounter first and most frequently, pediatric primary care providers need a breadth of knowledge to enable them to identify contributing factors to irritability and problem behavior, decide when and how to initiate treatment, and judge when to refer to specialists,” reported Dr. Kelly McGuire of Columbia University Medical Center and New York State Psychiatric Institute, and her associates (Pediatrics. 2016 Feb;137 Suppl 2:S136-48). “Therefore, this practice pathway can be viewed more as a comprehensive rather than an exhaustive recommendation for [primary care physicians], who must weigh their expertise and resources when addressing the range of issues that a child with ASD and irritability and problem behavior may present.”

©Devonyu/thinkstockphotos.com

The Irritability Workgroup comprised eight child psychiatrists, a developmental pediatrician, and a behavioral psychologist who met regularly to define irritability and problem behavior, and then to review the evidence base on assessing and treating factors that contribute to irritability and problem behavior. They grouped these factors into five domains: “co-occurring medical conditions, lack of functional communication, psychosocial stressors, maladaptive reinforcement patterns, and co-occurring psychiatric conditions.”

Then the group developed a consensus in determining each step in the practice pathway and when it should occur, along with opportunities for a primary care provider to refer the patient to a specialist or to collaborate with school and community providers. The 10 steps in the practice pathway are:

1. Assess the patient for irritability and problem behavior based on the presence of tantrums, meltdowns or rages; property destruction; aggression toward others; and self-injury.

2. Assess the safety of the patient and others in the home, enlisting home-based crisis services or considering hospitalization if safety is threatened.

3. Review the patient’s medical, developmental, communication, environmental, and psychiatric history before and after the problem behavior. Include information on the caretaker’s characteristics, any loss of skills by patient, and any interference occurring with functioning or relationships.

4. Prioritize the behaviors to address based on safety, severity, and impact on daily life.

5. Consider all contributing factors to the problem behavior, including medical problems, difficulties functionally communicating, psychosocial stressors, maladaptive reinforcement patterns (reducing inadvertent triggers), and comorbid psychiatric disorders.

6. Consider possible medication treatments, such as N-acetylcysteine, clonidine, risperidone or aripiprazole, depending on circumstances.

7. Develop an individualized treatment and safety plan.

8. Implement and monitor the treatment plan, setting clear and measurable treatment goals.

9. Follow up at 3 months to assess whether symptoms are continuing and a reassessment is needed.

10. Reevaluate every 3 months.

The article provides a useful and extensive checklist with a variety of specific things to consider when implementing the 10 steps.

“No other provider in the patient’s life combines the medical expertise and first-hand knowledge of the individual patient’s health and development” than the primary care provider, the authors wrote. “The practice pathway is most likely to be efficient and effective in generating a treatment plan if it is systematically followed and the specific combination of individual contributing factors is identified for each patient.”

The research was conducted through the Autism Speaks Autism Treatment Network and funded by the U.S. Department of Health and Human Services with the Autism Intervention Research Network on Physical Health and by Marilyn and James Simons Family Giving. Dr. Jeremy Veenstra-VanderWeele has received research funding from Seaside Therapeutics, Roche, Novartis, Forest, Sunovion, and SynapDx and has consulted with Roche, Novartis and SynapDx.

A new practice pathway provides primary care providers with evidence-based steps in assessing and addressing irritability and problem behavior in patients at least 3 years old who have been diagnosed with an autism spectrum disorder (ASD).

“As the medical professionals whom children with ASD will probably encounter first and most frequently, pediatric primary care providers need a breadth of knowledge to enable them to identify contributing factors to irritability and problem behavior, decide when and how to initiate treatment, and judge when to refer to specialists,” reported Dr. Kelly McGuire of Columbia University Medical Center and New York State Psychiatric Institute, and her associates (Pediatrics. 2016 Feb;137 Suppl 2:S136-48). “Therefore, this practice pathway can be viewed more as a comprehensive rather than an exhaustive recommendation for [primary care physicians], who must weigh their expertise and resources when addressing the range of issues that a child with ASD and irritability and problem behavior may present.”

©Devonyu/thinkstockphotos.com

The Irritability Workgroup comprised eight child psychiatrists, a developmental pediatrician, and a behavioral psychologist who met regularly to define irritability and problem behavior, and then to review the evidence base on assessing and treating factors that contribute to irritability and problem behavior. They grouped these factors into five domains: “co-occurring medical conditions, lack of functional communication, psychosocial stressors, maladaptive reinforcement patterns, and co-occurring psychiatric conditions.”

Then the group developed a consensus in determining each step in the practice pathway and when it should occur, along with opportunities for a primary care provider to refer the patient to a specialist or to collaborate with school and community providers. The 10 steps in the practice pathway are:

1. Assess the patient for irritability and problem behavior based on the presence of tantrums, meltdowns or rages; property destruction; aggression toward others; and self-injury.

2. Assess the safety of the patient and others in the home, enlisting home-based crisis services or considering hospitalization if safety is threatened.

3. Review the patient’s medical, developmental, communication, environmental, and psychiatric history before and after the problem behavior. Include information on the caretaker’s characteristics, any loss of skills by patient, and any interference occurring with functioning or relationships.

4. Prioritize the behaviors to address based on safety, severity, and impact on daily life.

5. Consider all contributing factors to the problem behavior, including medical problems, difficulties functionally communicating, psychosocial stressors, maladaptive reinforcement patterns (reducing inadvertent triggers), and comorbid psychiatric disorders.

6. Consider possible medication treatments, such as N-acetylcysteine, clonidine, risperidone or aripiprazole, depending on circumstances.

7. Develop an individualized treatment and safety plan.

8. Implement and monitor the treatment plan, setting clear and measurable treatment goals.

9. Follow up at 3 months to assess whether symptoms are continuing and a reassessment is needed.

10. Reevaluate every 3 months.

The article provides a useful and extensive checklist with a variety of specific things to consider when implementing the 10 steps.

“No other provider in the patient’s life combines the medical expertise and first-hand knowledge of the individual patient’s health and development” than the primary care provider, the authors wrote. “The practice pathway is most likely to be efficient and effective in generating a treatment plan if it is systematically followed and the specific combination of individual contributing factors is identified for each patient.”

The research was conducted through the Autism Speaks Autism Treatment Network and funded by the U.S. Department of Health and Human Services with the Autism Intervention Research Network on Physical Health and by Marilyn and James Simons Family Giving. Dr. Jeremy Veenstra-VanderWeele has received research funding from Seaside Therapeutics, Roche, Novartis, Forest, Sunovion, and SynapDx and has consulted with Roche, Novartis and SynapDx.