Infectious Diseases

In Reply: We would like to thank Dr. Lichtenberg for giving us the opportunity to clarify and expand on questions regarding HPV vaccine efficacy.

Our statement “HPV immunization can prevent up to 70% of cases of cervical cancer due to HPV as well as 90% of genital warts” was based on a statement by Thaxton and Waxman, ie, that immunization against HPV types 16 and 18 has the potential to prevent 70% of cancers of the cervix plus a large percentage of other lower anogenital tract cancers.¹ This was meant to describe the prevention potential of the quadrivalent vaccine. The currently available Gardasil 9 targets the HPV types that account for 90% of cervical cancers,² with projected effectiveness likely to vary based on geographic variation in HPV subtypes, ranging from 86.5% in Australia to 92% in North America.³ It is difficult to precisely calculate the effectiveness of HPV vaccination alone, given that cervical cancer prevention is twofold, with primary vaccination and secondary screening (with several notable updates to US national screening guidelines during the same time frame as vaccine development).⁴

It is true that the 29% decrease in US cervical cancer incidence rates during the years 2011–2014 compared with 2003–2006 is less than the predicted 70%.⁵ However, not all eligible US females are vaccinated; according to reports from the US Centers for Disease Control and Prevention, 49% of adolescents were appropriately immunized against HPV in 2017, an increase over the rate of only 35% in 2014.⁶ Low vaccination rates undoubtedly negatively impact any benefits from herd immunity, though the exact benefits of this population immunity are difficult to quantify.⁷

In Australia, a national school-based HPV vaccination program was initiated in 2007, making the vaccine available for free. Over 70% of girls ages 12 and 13 were vaccinated, and follow-up within the same decade showed a greater than 90% reduction in genital warts, as well as a reduction in high-grade cervical lesions.⁸ In addition, the incidence of genital warts in unvaccinated heterosexual males during the prevaccination vs the vaccination period decreased by up to 81% (a marker of herd immunity).⁹

In the US, the HPV subtypes found in the quadrivalent vaccine decreased by 71% in those ages 14 to 19, within 8 years of vaccine introduction.¹⁰ An analysis of US state cancer registries between 2009 and 2012 showed that in Michigan, the rates of high-grade, precancerous lesions declined by 37% each year for women ages 15 to 19, thought to be due to changes in screening and vaccination guidelines.¹¹ Similarly, an analysis of 9 million privately insured US females showed that the presence of high-grade precancerous lesions significantly decreased between the years 2007 and 2014 in those ages 15 to 24 (vaccinated individuals), but not in those ages 25 to 39 (unvaccinated individuals).¹² Most recently, a study of 10,206 women showed a 21.9% decrease in cervical intraepithelial neoplasia grade 2 or worse lesions due to HPV subtypes 16 or 18 in those who have received at least 1 dose of the vaccine; reduced rates in unvaccinated women were also seen, representing first evidence of herd immunity in the United States.¹³ In contrast, the rates of high-grade lesions due to nonvaccine HPV subtypes remained constant. Given that progression to cervical cancer can take 10 to 15 years or longer after HPV infection, true vaccine benefits will emerge once increased vaccination rates are achieved and after at least a decade of follow-up.

We applaud Dr. Lichtenberg’s efforts to clarify vaccine efficacy for appropriate counseling, as this is key to ensuring patient trust. Immunization fears have fueled the re-emergence of vaccine-preventable illnesses across the world. Given the wave of vaccine misinformation on the Internet, we all face patients and family members skeptical of vaccine efficacy and safety. Those requesting more information deserve an honest, informed discussion with their provider. Interestingly, however, among 955 unvaccinated women, the belief of not being at risk for HPV was the most common reason for not receiving the vaccine.¹⁴ Effective education can be achieved by focusing on the personal risks of HPV to the patient, as well as the overall favorable risk vs benefits of vaccination. Quoting an exact rate of cancer reduction is likely a less effective counseling strategy, and these efficacy estimates will change as vaccination rates and HPV prevalence within the population change over time.

In Reply: We would like to thank Dr. Lichtenberg for giving us the opportunity to clarify and expand on questions regarding HPV vaccine efficacy.

Our statement “HPV immunization can prevent up to 70% of cases of cervical cancer due to HPV as well as 90% of genital warts” was based on a statement by Thaxton and Waxman, ie, that immunization against HPV types 16 and 18 has the potential to prevent 70% of cancers of the cervix plus a large percentage of other lower anogenital tract cancers.¹ This was meant to describe the prevention potential of the quadrivalent vaccine. The currently available Gardasil 9 targets the HPV types that account for 90% of cervical cancers,² with projected effectiveness likely to vary based on geographic variation in HPV subtypes, ranging from 86.5% in Australia to 92% in North America.³ It is difficult to precisely calculate the effectiveness of HPV vaccination alone, given that cervical cancer prevention is twofold, with primary vaccination and secondary screening (with several notable updates to US national screening guidelines during the same time frame as vaccine development).⁴

It is true that the 29% decrease in US cervical cancer incidence rates during the years 2011–2014 compared with 2003–2006 is less than the predicted 70%.⁵ However, not all eligible US females are vaccinated; according to reports from the US Centers for Disease Control and Prevention, 49% of adolescents were appropriately immunized against HPV in 2017, an increase over the rate of only 35% in 2014.⁶ Low vaccination rates undoubtedly negatively impact any benefits from herd immunity, though the exact benefits of this population immunity are difficult to quantify.⁷

In Australia, a national school-based HPV vaccination program was initiated in 2007, making the vaccine available for free. Over 70% of girls ages 12 and 13 were vaccinated, and follow-up within the same decade showed a greater than 90% reduction in genital warts, as well as a reduction in high-grade cervical lesions.⁸ In addition, the incidence of genital warts in unvaccinated heterosexual males during the prevaccination vs the vaccination period decreased by up to 81% (a marker of herd immunity).⁹

In the US, the HPV subtypes found in the quadrivalent vaccine decreased by 71% in those ages 14 to 19, within 8 years of vaccine introduction.¹⁰ An analysis of US state cancer registries between 2009 and 2012 showed that in Michigan, the rates of high-grade, precancerous lesions declined by 37% each year for women ages 15 to 19, thought to be due to changes in screening and vaccination guidelines.¹¹ Similarly, an analysis of 9 million privately insured US females showed that the presence of high-grade precancerous lesions significantly decreased between the years 2007 and 2014 in those ages 15 to 24 (vaccinated individuals), but not in those ages 25 to 39 (unvaccinated individuals).¹² Most recently, a study of 10,206 women showed a 21.9% decrease in cervical intraepithelial neoplasia grade 2 or worse lesions due to HPV subtypes 16 or 18 in those who have received at least 1 dose of the vaccine; reduced rates in unvaccinated women were also seen, representing first evidence of herd immunity in the United States.¹³ In contrast, the rates of high-grade lesions due to nonvaccine HPV subtypes remained constant. Given that progression to cervical cancer can take 10 to 15 years or longer after HPV infection, true vaccine benefits will emerge once increased vaccination rates are achieved and after at least a decade of follow-up.

We applaud Dr. Lichtenberg’s efforts to clarify vaccine efficacy for appropriate counseling, as this is key to ensuring patient trust. Immunization fears have fueled the re-emergence of vaccine-preventable illnesses across the world. Given the wave of vaccine misinformation on the Internet, we all face patients and family members skeptical of vaccine efficacy and safety. Those requesting more information deserve an honest, informed discussion with their provider. Interestingly, however, among 955 unvaccinated women, the belief of not being at risk for HPV was the most common reason for not receiving the vaccine.¹⁴ Effective education can be achieved by focusing on the personal risks of HPV to the patient, as well as the overall favorable risk vs benefits of vaccination. Quoting an exact rate of cancer reduction is likely a less effective counseling strategy, and these efficacy estimates will change as vaccination rates and HPV prevalence within the population change over time.

In Reply: We would like to thank Dr. Lichtenberg for giving us the opportunity to clarify and expand on questions regarding HPV vaccine efficacy.

Our statement “HPV immunization can prevent up to 70% of cases of cervical cancer due to HPV as well as 90% of genital warts” was based on a statement by Thaxton and Waxman, ie, that immunization against HPV types 16 and 18 has the potential to prevent 70% of cancers of the cervix plus a large percentage of other lower anogenital tract cancers.¹ This was meant to describe the prevention potential of the quadrivalent vaccine. The currently available Gardasil 9 targets the HPV types that account for 90% of cervical cancers,² with projected effectiveness likely to vary based on geographic variation in HPV subtypes, ranging from 86.5% in Australia to 92% in North America.³ It is difficult to precisely calculate the effectiveness of HPV vaccination alone, given that cervical cancer prevention is twofold, with primary vaccination and secondary screening (with several notable updates to US national screening guidelines during the same time frame as vaccine development).⁴

It is true that the 29% decrease in US cervical cancer incidence rates during the years 2011–2014 compared with 2003–2006 is less than the predicted 70%.⁵ However, not all eligible US females are vaccinated; according to reports from the US Centers for Disease Control and Prevention, 49% of adolescents were appropriately immunized against HPV in 2017, an increase over the rate of only 35% in 2014.⁶ Low vaccination rates undoubtedly negatively impact any benefits from herd immunity, though the exact benefits of this population immunity are difficult to quantify.⁷

In Australia, a national school-based HPV vaccination program was initiated in 2007, making the vaccine available for free. Over 70% of girls ages 12 and 13 were vaccinated, and follow-up within the same decade showed a greater than 90% reduction in genital warts, as well as a reduction in high-grade cervical lesions.⁸ In addition, the incidence of genital warts in unvaccinated heterosexual males during the prevaccination vs the vaccination period decreased by up to 81% (a marker of herd immunity).⁹

In the US, the HPV subtypes found in the quadrivalent vaccine decreased by 71% in those ages 14 to 19, within 8 years of vaccine introduction.¹⁰ An analysis of US state cancer registries between 2009 and 2012 showed that in Michigan, the rates of high-grade, precancerous lesions declined by 37% each year for women ages 15 to 19, thought to be due to changes in screening and vaccination guidelines.¹¹ Similarly, an analysis of 9 million privately insured US females showed that the presence of high-grade precancerous lesions significantly decreased between the years 2007 and 2014 in those ages 15 to 24 (vaccinated individuals), but not in those ages 25 to 39 (unvaccinated individuals).¹² Most recently, a study of 10,206 women showed a 21.9% decrease in cervical intraepithelial neoplasia grade 2 or worse lesions due to HPV subtypes 16 or 18 in those who have received at least 1 dose of the vaccine; reduced rates in unvaccinated women were also seen, representing first evidence of herd immunity in the United States.¹³ In contrast, the rates of high-grade lesions due to nonvaccine HPV subtypes remained constant. Given that progression to cervical cancer can take 10 to 15 years or longer after HPV infection, true vaccine benefits will emerge once increased vaccination rates are achieved and after at least a decade of follow-up.

We applaud Dr. Lichtenberg’s efforts to clarify vaccine efficacy for appropriate counseling, as this is key to ensuring patient trust. Immunization fears have fueled the re-emergence of vaccine-preventable illnesses across the world. Given the wave of vaccine misinformation on the Internet, we all face patients and family members skeptical of vaccine efficacy and safety. Those requesting more information deserve an honest, informed discussion with their provider. Interestingly, however, among 955 unvaccinated women, the belief of not being at risk for HPV was the most common reason for not receiving the vaccine.¹⁴ Effective education can be achieved by focusing on the personal risks of HPV to the patient, as well as the overall favorable risk vs benefits of vaccination. Quoting an exact rate of cancer reduction is likely a less effective counseling strategy, and these efficacy estimates will change as vaccination rates and HPV prevalence within the population change over time.

The “human microbiota” describes all microorganisms within the human body, including bacteria, viruses, and eukaryotes. The related term “microbiome” refers to the complete catalog of these microbes and their genes.¹ There is a growing awareness that the human microbiota plays an important role in maintaining mental health, and that a disruption in its composition can contribute to manifestations of psychiatric disorders. A growing body of evidence has also linked mental health outcomes to the gut microbiome, suggesting that the gut microbiota can modulate the gut-brain axis.²

Numerous neurotransmitters, including dopamine, serotonin, gamma-aminobutyric acid, and acetylcholine, are produced in the gastrointestinal (GI) tract, and our diet is vital in sustaining and replenishing them. At the same time, our brain regulates our GI tract by secretion of hormones such as oxytocin, leptin, ghrelin, neuropeptide Y, corticotrophin-releasing factor, and a plethora of others. Dysregulation of this microbiome can lead to both physical and mental illnesses. Symptoms of psychiatric disorders, such as depression, psychosis, anxiety, and autism, can be a consequence of this dysregulation.²

Our diet can also modify the gut micro­organisms and therefore many of its metabolic pathways. More attention has been given to pre- and probiotics and their effects on DNA by epigenetic changes. One can quickly start to appreciate how this intricate crosstalk can lead to a variety of pathologic and psychiatric problems that have an adverse effect on autoimmune, inflammatory, metabolic, cognitive, and behavioral processes.^2,3

Thus far, links have mostly been reported in animal models, and human studies are limited.⁴ Researchers are just beginning to elucidate how the microbiota affect gut-brain signaling in humans. Such mechanisms may include alterations in microbial composition, immune activation, vagus nerve signaling, alterations in tryptophan metabolism, production of specific microbial neuroactive metabolites, and bacterial cell wall sugars.⁵ The microbiota-gut-brain axis plays a part in regulating/programming the hypothalamic-pituitary-adrenal (HPA) axis throughout the life span.³ The interactions between the gut microbiome, the immune system, and the CNS are regulated through pathways that involve endocrine functions (HPA axis), the immune system, and metabolic factors.^3,4 Recent research focusing on the gut microbiome has also given rise to international projects such as the Human Microbiome Project (Human Microbiome Project Consortium, 2012).³

Several studies have looked into psychiatry and inflammatory/immune pathways. Here we review 3 recent studies that have focused on the gut-brain axis (Table^6-8).

1. Rudzki L, Pawlak D, Pawlak K, et al. Immune suppression of IgG response against dairy proteins in major depression. BMC Psychiatry. 2017;17(1):268.

The aim of this study was to evaluate immunoglobulin G (IgG) response against 40 food products in patients with depression vs those in a control group, along with changes in inflammatory markers, psychological stress, and dietary variables.⁶

Study design

• N = 63, IgG levels against 44 food products, cortisol levels, tumor necrosis factor (TNF)-alpha, interleukin 6 (IL-6), and IL-1 beta levels were recorded. The psychological parameters of 34 participants with depression and 29 controls were compared using the Hamilton Depression Rating scale, (HAM-D-17), Perceived Stress scale, and Symptom Checklist scale. The study was conducted in Poland.

Continue to: Outcomes

Outcomes

• Patients who were depressed had lower IgG levels against dairy products compared to controls when there was high dairy consumption. However, there was no overall difference between patients and controls in mean IgG concentration against food products. 
• Patients who were depressed had higher levels of cortisol. Levels of cortisol had a positive correlation with HAM-D-17 score. Patients with depression had lower levels of TNF-alpha.

Conclusion

• Patients with depression had lower levels of IgG against dairy protein. Patients with depression had high cortisol levels but decreased levels of TNF-alpha, which could explain an immune suppression of IgG in these patients. There were no differences in IL-6 or IL-1beta levels.

Hypercortisolemia is present in approximately 60% of patients with depression. Elevated cortisol levels have a negative effect on lymphocyte function. B-lymphocytes (CD 10+ and CD 19+) are sensitive to glucocorticoids. Studies in mice have demonstrated that elevated glucocorticoid levels are associated with a 50% decrease in serum B-lymphocytes, and this can be explained by downregulation of c-myc protein, which plays a role in cell proliferation and cell survival. Glucocorticoids also decrease levels of protein kinases that are vital for the cell cycle to continue, and they upregulate p27 and p21, which are cell cycle inhibitors. Therefore, if high cortisol suppresses B-lymphocyte production, this can explain how patients with depression have low IgG levels, since B-lymphocytes differentiate into plasma cells that will produce antibodies.⁶

Depression can trigger an inflammatory response by increasing levels of inflammatory cytokines, acute phase reactants, and oxidative molecules. The inflammatory response can lead to intestinal wall disruption, and therefore bacteria can migrate across the GI barrier, along with food antigens, which could then lead to food antigen hypersensitivity.⁶

The significance of diet

Many studies have looked into specific types of diets, such as the Mediterranean diet, the ketogenic diet, and the addition of supplements such as probiotics, omega-3 fatty acids, zinc, and multivitamins.⁷ The Mediterranean diet is high in fiber, nuts, legumes, and fish.⁷ The ketogenic diet includes a controlled amount of fat, but is low in protein and carbohydrates.⁷ The main point is that a balanced diet can have a positive effect on mental health.⁷ The Mediterranean diet has shown to decrease the incidence of cardiovascular disease and lower the risk of depression.⁷ In animal studies, the ketogenic diet has improved anxiety, depression, and autism.⁷ Diet clearly affects gut microbiota and, as a consequence, the body’s level of inflammation.⁷ 

Continue to: The following review...

The following review highlighted the significance of diet on gut microbiome and mental health.⁷

2. Mörkl S, Wagner-Skacel J, Lahousen T, et al. The role of nutrition and the gut- brain axis in psychiatry: a review of the literature. Neuropsychobiology. 2018;17: 1-9.

Study design

• These researchers provided a narrative review of the significance of a healthy diet and nutritional supplements on the gut microbiome and the treatment of patients with psychiatric illness. 

Outcomes

• This review suggested dietary coaching as a nonpharmacologic treatment for patients with psychiatric illness. 

Conclusion

• The utilization of nutritional advice, along with medication management, therapy, and physical activity, can provide a holistic approach to the biopsychosocial treatment of patients with psychiatric illness.

This review also emphasized the poor dietary trends of Westernized countries, which include calorie-dense, genetically altered, processed meals. As Mörkl et al⁷ noted, we are overfed but undernourished. Mörkl et al⁷ reviewed studies that involve dietary coaching as part of the treatment plan of patients with mental illness. In one of these studies, patients who received nutritional advice and coaching over 6 weeks had a 40% to 50% decrease in depressive symptoms. These effects persisted for 2 more years. Mörkl et al⁷ also reviewed an Italian study that found that providing nutritional advice in patients with affective disorders and psychosis helped improve symptom severity and sleep.⁷

Continue to: Mörkl et al...

Mörkl et al⁷ also reviewed dietary supplements. Some studies have linked use of omega-3 fatty acids with improvement in affective disorders, Alzheimer’s disease, and posttraumatic stress disorder, as well as cardiovascular conditions. Omega-3 fatty acids may exert beneficial effects by enhancing brain-derived neurotrophic factor and neurogenesis as well as by decreasing inflammation.⁷

Zinc supplementation can also improve depression, as it has been linked to cytokine variation and hippocampal neuronal growth. Vitamin B₉ deficiency and vitamin D deficiency also have been associated with depression. Mörkl et al⁷ emphasized that a balanced diet that incorporates a variety of nutrients is more beneficial than supplementation of any individual vitamin alone.

Researchers have long emphasized the importance of a healthy balanced diet when treating patients with medical conditions such as cardiovascular or cerebrovascular diseases. Based on the studies Mörkl et al⁷ reviewed, the same emphasis should be communicated to our patients who suffer from psychiatric conditions.

The gut and anxiety

The gut microbiome has also been an area of research when studying generalized anxiety disorder (GAD).⁸

3. Jiang HY, Zhang X, Yu ZH, et al. Altered gut microbiota profile in patients with generalized anxiety disorder. J Psychiatr Res. 2018;104:130-136.

The aim of the study was to determine if there were changes in the composition of the gut microbiome in patients with GAD compared with healthy controls.⁸

Continue to: Study design

Study design

• A cross-sectional study of 76 patients in Zhejiang, China. Forty patients with GAD in the active state and 36 healthy controls were compared in terms of composition of GI microbacterial flora.
• Researchers also examined a subgroup of 12 patients who were treatment-naïve and 17 controls. Stool samples were collected from the 12 patients who were treatment-naïve before initiating medication.
• Researchers also conducted a prospective study in a subgroup of 9 patients with GAD in both the active state and remissive state. Two stool samples were collected from each patient—one during the active state of GAD and one during the remissive state—for a total of 18 samples. Stool samples analyzed with the use of polymerase chain reaction and microbial analysis.
• Patients completed the Hamilton Anxiety Rating (HAM-A) scale and were classified into groups. Those with HAM-A scores >14 were classified as being in the active state of GAD, and those with scores <7 were classified as being in the remissive state. 

Outcomes

• Among the samples collected, 8 bacterial taxa were found in different amounts in patients with GAD and healthy controls. Bacteroidetes, Ruminococcus gnavus, and Fusobacterium were increased in patients with GAD compared with controls, while Faecalibacterium, Eubacterium rectale, Sutterella, Lachnospira, and Butyricicoccus were increased in healthy controls.
• Bacterial variety was notably lower in the 12 patients who were treatment-naïve compared with the control group.
• There was no notable difference in microbial composition between patients in the active vs remissive state.

Conclusion

• Patients with GAD had less short chain fatty acid–producing bacteria (Faecalibacterium, Eubacterium rectale, Sutterella, Lachnospira, and Butyricicoccus) compared with controls. Decreased formation of short chain fatty acids could lead to GI barrier disruption. Fusobacterium and Ruminococcus were increased in patients with GAD. Fusobacterium can cause disease and be invasive when it disseminates within the body. The inflammatory characteristics of Fusobacterium contribute to the immunologic activation in GAD. Ruminococcus breaks down mucin, which could then increase GI permeability by mucous degradation of the GI lumen.

Changes in food processing and manufacturing have led to changes in our diets. Changes in our normal GI microbacterial flora could lead to increased gut permeability, bacterial dissemination, and subsequent systemic inflammation. Research has shown that the composition of the microbiota changes across the life span.⁹ A balanced intake of nutrients is important for both our physical and mental health and safeguards the basis of gut microbiome regulation. A well-regulated gut microbiome ensures low levels of inflammation in the brain and body. Lifestyle modifications and dietary coaching could be practical interventions for patients with psychiatric conditions.⁵ Current advances in technology now offer precise analyses of thousands of metabolites, enabling metabolomics to offer the promise of discovering new drug targets and biomarkers that may help pave a way to precision medicine.

The “human microbiota” describes all microorganisms within the human body, including bacteria, viruses, and eukaryotes. The related term “microbiome” refers to the complete catalog of these microbes and their genes.¹ There is a growing awareness that the human microbiota plays an important role in maintaining mental health, and that a disruption in its composition can contribute to manifestations of psychiatric disorders. A growing body of evidence has also linked mental health outcomes to the gut microbiome, suggesting that the gut microbiota can modulate the gut-brain axis.²

Numerous neurotransmitters, including dopamine, serotonin, gamma-aminobutyric acid, and acetylcholine, are produced in the gastrointestinal (GI) tract, and our diet is vital in sustaining and replenishing them. At the same time, our brain regulates our GI tract by secretion of hormones such as oxytocin, leptin, ghrelin, neuropeptide Y, corticotrophin-releasing factor, and a plethora of others. Dysregulation of this microbiome can lead to both physical and mental illnesses. Symptoms of psychiatric disorders, such as depression, psychosis, anxiety, and autism, can be a consequence of this dysregulation.²

Our diet can also modify the gut micro­organisms and therefore many of its metabolic pathways. More attention has been given to pre- and probiotics and their effects on DNA by epigenetic changes. One can quickly start to appreciate how this intricate crosstalk can lead to a variety of pathologic and psychiatric problems that have an adverse effect on autoimmune, inflammatory, metabolic, cognitive, and behavioral processes.^2,3

Thus far, links have mostly been reported in animal models, and human studies are limited.⁴ Researchers are just beginning to elucidate how the microbiota affect gut-brain signaling in humans. Such mechanisms may include alterations in microbial composition, immune activation, vagus nerve signaling, alterations in tryptophan metabolism, production of specific microbial neuroactive metabolites, and bacterial cell wall sugars.⁵ The microbiota-gut-brain axis plays a part in regulating/programming the hypothalamic-pituitary-adrenal (HPA) axis throughout the life span.³ The interactions between the gut microbiome, the immune system, and the CNS are regulated through pathways that involve endocrine functions (HPA axis), the immune system, and metabolic factors.^3,4 Recent research focusing on the gut microbiome has also given rise to international projects such as the Human Microbiome Project (Human Microbiome Project Consortium, 2012).³

Several studies have looked into psychiatry and inflammatory/immune pathways. Here we review 3 recent studies that have focused on the gut-brain axis (Table^6-8).

1. Rudzki L, Pawlak D, Pawlak K, et al. Immune suppression of IgG response against dairy proteins in major depression. BMC Psychiatry. 2017;17(1):268.

The aim of this study was to evaluate immunoglobulin G (IgG) response against 40 food products in patients with depression vs those in a control group, along with changes in inflammatory markers, psychological stress, and dietary variables.⁶

Study design

• N = 63, IgG levels against 44 food products, cortisol levels, tumor necrosis factor (TNF)-alpha, interleukin 6 (IL-6), and IL-1 beta levels were recorded. The psychological parameters of 34 participants with depression and 29 controls were compared using the Hamilton Depression Rating scale, (HAM-D-17), Perceived Stress scale, and Symptom Checklist scale. The study was conducted in Poland.

Continue to: Outcomes

Outcomes

• Patients who were depressed had lower IgG levels against dairy products compared to controls when there was high dairy consumption. However, there was no overall difference between patients and controls in mean IgG concentration against food products. 
• Patients who were depressed had higher levels of cortisol. Levels of cortisol had a positive correlation with HAM-D-17 score. Patients with depression had lower levels of TNF-alpha.

Conclusion

• Patients with depression had lower levels of IgG against dairy protein. Patients with depression had high cortisol levels but decreased levels of TNF-alpha, which could explain an immune suppression of IgG in these patients. There were no differences in IL-6 or IL-1beta levels.

Hypercortisolemia is present in approximately 60% of patients with depression. Elevated cortisol levels have a negative effect on lymphocyte function. B-lymphocytes (CD 10+ and CD 19+) are sensitive to glucocorticoids. Studies in mice have demonstrated that elevated glucocorticoid levels are associated with a 50% decrease in serum B-lymphocytes, and this can be explained by downregulation of c-myc protein, which plays a role in cell proliferation and cell survival. Glucocorticoids also decrease levels of protein kinases that are vital for the cell cycle to continue, and they upregulate p27 and p21, which are cell cycle inhibitors. Therefore, if high cortisol suppresses B-lymphocyte production, this can explain how patients with depression have low IgG levels, since B-lymphocytes differentiate into plasma cells that will produce antibodies.⁶

Depression can trigger an inflammatory response by increasing levels of inflammatory cytokines, acute phase reactants, and oxidative molecules. The inflammatory response can lead to intestinal wall disruption, and therefore bacteria can migrate across the GI barrier, along with food antigens, which could then lead to food antigen hypersensitivity.⁶

The significance of diet

Many studies have looked into specific types of diets, such as the Mediterranean diet, the ketogenic diet, and the addition of supplements such as probiotics, omega-3 fatty acids, zinc, and multivitamins.⁷ The Mediterranean diet is high in fiber, nuts, legumes, and fish.⁷ The ketogenic diet includes a controlled amount of fat, but is low in protein and carbohydrates.⁷ The main point is that a balanced diet can have a positive effect on mental health.⁷ The Mediterranean diet has shown to decrease the incidence of cardiovascular disease and lower the risk of depression.⁷ In animal studies, the ketogenic diet has improved anxiety, depression, and autism.⁷ Diet clearly affects gut microbiota and, as a consequence, the body’s level of inflammation.⁷ 

Continue to: The following review...

The following review highlighted the significance of diet on gut microbiome and mental health.⁷

2. Mörkl S, Wagner-Skacel J, Lahousen T, et al. The role of nutrition and the gut- brain axis in psychiatry: a review of the literature. Neuropsychobiology. 2018;17: 1-9.

Study design

• These researchers provided a narrative review of the significance of a healthy diet and nutritional supplements on the gut microbiome and the treatment of patients with psychiatric illness. 

Outcomes

• This review suggested dietary coaching as a nonpharmacologic treatment for patients with psychiatric illness. 

Conclusion

• The utilization of nutritional advice, along with medication management, therapy, and physical activity, can provide a holistic approach to the biopsychosocial treatment of patients with psychiatric illness.

This review also emphasized the poor dietary trends of Westernized countries, which include calorie-dense, genetically altered, processed meals. As Mörkl et al⁷ noted, we are overfed but undernourished. Mörkl et al⁷ reviewed studies that involve dietary coaching as part of the treatment plan of patients with mental illness. In one of these studies, patients who received nutritional advice and coaching over 6 weeks had a 40% to 50% decrease in depressive symptoms. These effects persisted for 2 more years. Mörkl et al⁷ also reviewed an Italian study that found that providing nutritional advice in patients with affective disorders and psychosis helped improve symptom severity and sleep.⁷

Continue to: Mörkl et al...

Mörkl et al⁷ also reviewed dietary supplements. Some studies have linked use of omega-3 fatty acids with improvement in affective disorders, Alzheimer’s disease, and posttraumatic stress disorder, as well as cardiovascular conditions. Omega-3 fatty acids may exert beneficial effects by enhancing brain-derived neurotrophic factor and neurogenesis as well as by decreasing inflammation.⁷

Zinc supplementation can also improve depression, as it has been linked to cytokine variation and hippocampal neuronal growth. Vitamin B₉ deficiency and vitamin D deficiency also have been associated with depression. Mörkl et al⁷ emphasized that a balanced diet that incorporates a variety of nutrients is more beneficial than supplementation of any individual vitamin alone.

Researchers have long emphasized the importance of a healthy balanced diet when treating patients with medical conditions such as cardiovascular or cerebrovascular diseases. Based on the studies Mörkl et al⁷ reviewed, the same emphasis should be communicated to our patients who suffer from psychiatric conditions.

The gut and anxiety

The gut microbiome has also been an area of research when studying generalized anxiety disorder (GAD).⁸

3. Jiang HY, Zhang X, Yu ZH, et al. Altered gut microbiota profile in patients with generalized anxiety disorder. J Psychiatr Res. 2018;104:130-136.

The aim of the study was to determine if there were changes in the composition of the gut microbiome in patients with GAD compared with healthy controls.⁸

Continue to: Study design

Study design

• A cross-sectional study of 76 patients in Zhejiang, China. Forty patients with GAD in the active state and 36 healthy controls were compared in terms of composition of GI microbacterial flora.
• Researchers also examined a subgroup of 12 patients who were treatment-naïve and 17 controls. Stool samples were collected from the 12 patients who were treatment-naïve before initiating medication.
• Researchers also conducted a prospective study in a subgroup of 9 patients with GAD in both the active state and remissive state. Two stool samples were collected from each patient—one during the active state of GAD and one during the remissive state—for a total of 18 samples. Stool samples analyzed with the use of polymerase chain reaction and microbial analysis.
• Patients completed the Hamilton Anxiety Rating (HAM-A) scale and were classified into groups. Those with HAM-A scores >14 were classified as being in the active state of GAD, and those with scores <7 were classified as being in the remissive state. 

Outcomes

• Among the samples collected, 8 bacterial taxa were found in different amounts in patients with GAD and healthy controls. Bacteroidetes, Ruminococcus gnavus, and Fusobacterium were increased in patients with GAD compared with controls, while Faecalibacterium, Eubacterium rectale, Sutterella, Lachnospira, and Butyricicoccus were increased in healthy controls.
• Bacterial variety was notably lower in the 12 patients who were treatment-naïve compared with the control group.
• There was no notable difference in microbial composition between patients in the active vs remissive state.

Conclusion

• Patients with GAD had less short chain fatty acid–producing bacteria (Faecalibacterium, Eubacterium rectale, Sutterella, Lachnospira, and Butyricicoccus) compared with controls. Decreased formation of short chain fatty acids could lead to GI barrier disruption. Fusobacterium and Ruminococcus were increased in patients with GAD. Fusobacterium can cause disease and be invasive when it disseminates within the body. The inflammatory characteristics of Fusobacterium contribute to the immunologic activation in GAD. Ruminococcus breaks down mucin, which could then increase GI permeability by mucous degradation of the GI lumen.

Changes in food processing and manufacturing have led to changes in our diets. Changes in our normal GI microbacterial flora could lead to increased gut permeability, bacterial dissemination, and subsequent systemic inflammation. Research has shown that the composition of the microbiota changes across the life span.⁹ A balanced intake of nutrients is important for both our physical and mental health and safeguards the basis of gut microbiome regulation. A well-regulated gut microbiome ensures low levels of inflammation in the brain and body. Lifestyle modifications and dietary coaching could be practical interventions for patients with psychiatric conditions.⁵ Current advances in technology now offer precise analyses of thousands of metabolites, enabling metabolomics to offer the promise of discovering new drug targets and biomarkers that may help pave a way to precision medicine.

The “human microbiota” describes all microorganisms within the human body, including bacteria, viruses, and eukaryotes. The related term “microbiome” refers to the complete catalog of these microbes and their genes.¹ There is a growing awareness that the human microbiota plays an important role in maintaining mental health, and that a disruption in its composition can contribute to manifestations of psychiatric disorders. A growing body of evidence has also linked mental health outcomes to the gut microbiome, suggesting that the gut microbiota can modulate the gut-brain axis.²

Numerous neurotransmitters, including dopamine, serotonin, gamma-aminobutyric acid, and acetylcholine, are produced in the gastrointestinal (GI) tract, and our diet is vital in sustaining and replenishing them. At the same time, our brain regulates our GI tract by secretion of hormones such as oxytocin, leptin, ghrelin, neuropeptide Y, corticotrophin-releasing factor, and a plethora of others. Dysregulation of this microbiome can lead to both physical and mental illnesses. Symptoms of psychiatric disorders, such as depression, psychosis, anxiety, and autism, can be a consequence of this dysregulation.²

Our diet can also modify the gut micro­organisms and therefore many of its metabolic pathways. More attention has been given to pre- and probiotics and their effects on DNA by epigenetic changes. One can quickly start to appreciate how this intricate crosstalk can lead to a variety of pathologic and psychiatric problems that have an adverse effect on autoimmune, inflammatory, metabolic, cognitive, and behavioral processes.^2,3

Thus far, links have mostly been reported in animal models, and human studies are limited.⁴ Researchers are just beginning to elucidate how the microbiota affect gut-brain signaling in humans. Such mechanisms may include alterations in microbial composition, immune activation, vagus nerve signaling, alterations in tryptophan metabolism, production of specific microbial neuroactive metabolites, and bacterial cell wall sugars.⁵ The microbiota-gut-brain axis plays a part in regulating/programming the hypothalamic-pituitary-adrenal (HPA) axis throughout the life span.³ The interactions between the gut microbiome, the immune system, and the CNS are regulated through pathways that involve endocrine functions (HPA axis), the immune system, and metabolic factors.^3,4 Recent research focusing on the gut microbiome has also given rise to international projects such as the Human Microbiome Project (Human Microbiome Project Consortium, 2012).³

Several studies have looked into psychiatry and inflammatory/immune pathways. Here we review 3 recent studies that have focused on the gut-brain axis (Table^6-8).

1. Rudzki L, Pawlak D, Pawlak K, et al. Immune suppression of IgG response against dairy proteins in major depression. BMC Psychiatry. 2017;17(1):268.

The aim of this study was to evaluate immunoglobulin G (IgG) response against 40 food products in patients with depression vs those in a control group, along with changes in inflammatory markers, psychological stress, and dietary variables.⁶

Study design

• N = 63, IgG levels against 44 food products, cortisol levels, tumor necrosis factor (TNF)-alpha, interleukin 6 (IL-6), and IL-1 beta levels were recorded. The psychological parameters of 34 participants with depression and 29 controls were compared using the Hamilton Depression Rating scale, (HAM-D-17), Perceived Stress scale, and Symptom Checklist scale. The study was conducted in Poland.

Continue to: Outcomes

Outcomes

• Patients who were depressed had lower IgG levels against dairy products compared to controls when there was high dairy consumption. However, there was no overall difference between patients and controls in mean IgG concentration against food products. 
• Patients who were depressed had higher levels of cortisol. Levels of cortisol had a positive correlation with HAM-D-17 score. Patients with depression had lower levels of TNF-alpha.

Conclusion

• Patients with depression had lower levels of IgG against dairy protein. Patients with depression had high cortisol levels but decreased levels of TNF-alpha, which could explain an immune suppression of IgG in these patients. There were no differences in IL-6 or IL-1beta levels.

Hypercortisolemia is present in approximately 60% of patients with depression. Elevated cortisol levels have a negative effect on lymphocyte function. B-lymphocytes (CD 10+ and CD 19+) are sensitive to glucocorticoids. Studies in mice have demonstrated that elevated glucocorticoid levels are associated with a 50% decrease in serum B-lymphocytes, and this can be explained by downregulation of c-myc protein, which plays a role in cell proliferation and cell survival. Glucocorticoids also decrease levels of protein kinases that are vital for the cell cycle to continue, and they upregulate p27 and p21, which are cell cycle inhibitors. Therefore, if high cortisol suppresses B-lymphocyte production, this can explain how patients with depression have low IgG levels, since B-lymphocytes differentiate into plasma cells that will produce antibodies.⁶

Depression can trigger an inflammatory response by increasing levels of inflammatory cytokines, acute phase reactants, and oxidative molecules. The inflammatory response can lead to intestinal wall disruption, and therefore bacteria can migrate across the GI barrier, along with food antigens, which could then lead to food antigen hypersensitivity.⁶

The significance of diet

Many studies have looked into specific types of diets, such as the Mediterranean diet, the ketogenic diet, and the addition of supplements such as probiotics, omega-3 fatty acids, zinc, and multivitamins.⁷ The Mediterranean diet is high in fiber, nuts, legumes, and fish.⁷ The ketogenic diet includes a controlled amount of fat, but is low in protein and carbohydrates.⁷ The main point is that a balanced diet can have a positive effect on mental health.⁷ The Mediterranean diet has shown to decrease the incidence of cardiovascular disease and lower the risk of depression.⁷ In animal studies, the ketogenic diet has improved anxiety, depression, and autism.⁷ Diet clearly affects gut microbiota and, as a consequence, the body’s level of inflammation.⁷ 

Continue to: The following review...

The following review highlighted the significance of diet on gut microbiome and mental health.⁷

2. Mörkl S, Wagner-Skacel J, Lahousen T, et al. The role of nutrition and the gut- brain axis in psychiatry: a review of the literature. Neuropsychobiology. 2018;17: 1-9.

Study design

• These researchers provided a narrative review of the significance of a healthy diet and nutritional supplements on the gut microbiome and the treatment of patients with psychiatric illness. 

Outcomes

• This review suggested dietary coaching as a nonpharmacologic treatment for patients with psychiatric illness. 

Conclusion

• The utilization of nutritional advice, along with medication management, therapy, and physical activity, can provide a holistic approach to the biopsychosocial treatment of patients with psychiatric illness.

This review also emphasized the poor dietary trends of Westernized countries, which include calorie-dense, genetically altered, processed meals. As Mörkl et al⁷ noted, we are overfed but undernourished. Mörkl et al⁷ reviewed studies that involve dietary coaching as part of the treatment plan of patients with mental illness. In one of these studies, patients who received nutritional advice and coaching over 6 weeks had a 40% to 50% decrease in depressive symptoms. These effects persisted for 2 more years. Mörkl et al⁷ also reviewed an Italian study that found that providing nutritional advice in patients with affective disorders and psychosis helped improve symptom severity and sleep.⁷

Continue to: Mörkl et al...

Mörkl et al⁷ also reviewed dietary supplements. Some studies have linked use of omega-3 fatty acids with improvement in affective disorders, Alzheimer’s disease, and posttraumatic stress disorder, as well as cardiovascular conditions. Omega-3 fatty acids may exert beneficial effects by enhancing brain-derived neurotrophic factor and neurogenesis as well as by decreasing inflammation.⁷

Zinc supplementation can also improve depression, as it has been linked to cytokine variation and hippocampal neuronal growth. Vitamin B₉ deficiency and vitamin D deficiency also have been associated with depression. Mörkl et al⁷ emphasized that a balanced diet that incorporates a variety of nutrients is more beneficial than supplementation of any individual vitamin alone.

Researchers have long emphasized the importance of a healthy balanced diet when treating patients with medical conditions such as cardiovascular or cerebrovascular diseases. Based on the studies Mörkl et al⁷ reviewed, the same emphasis should be communicated to our patients who suffer from psychiatric conditions.

The gut and anxiety

The gut microbiome has also been an area of research when studying generalized anxiety disorder (GAD).⁸

3. Jiang HY, Zhang X, Yu ZH, et al. Altered gut microbiota profile in patients with generalized anxiety disorder. J Psychiatr Res. 2018;104:130-136.

The aim of the study was to determine if there were changes in the composition of the gut microbiome in patients with GAD compared with healthy controls.⁸

Continue to: Study design

Study design

• A cross-sectional study of 76 patients in Zhejiang, China. Forty patients with GAD in the active state and 36 healthy controls were compared in terms of composition of GI microbacterial flora.
• Researchers also examined a subgroup of 12 patients who were treatment-naïve and 17 controls. Stool samples were collected from the 12 patients who were treatment-naïve before initiating medication.
• Researchers also conducted a prospective study in a subgroup of 9 patients with GAD in both the active state and remissive state. Two stool samples were collected from each patient—one during the active state of GAD and one during the remissive state—for a total of 18 samples. Stool samples analyzed with the use of polymerase chain reaction and microbial analysis.
• Patients completed the Hamilton Anxiety Rating (HAM-A) scale and were classified into groups. Those with HAM-A scores >14 were classified as being in the active state of GAD, and those with scores <7 were classified as being in the remissive state. 

Outcomes

• Among the samples collected, 8 bacterial taxa were found in different amounts in patients with GAD and healthy controls. Bacteroidetes, Ruminococcus gnavus, and Fusobacterium were increased in patients with GAD compared with controls, while Faecalibacterium, Eubacterium rectale, Sutterella, Lachnospira, and Butyricicoccus were increased in healthy controls.
• Bacterial variety was notably lower in the 12 patients who were treatment-naïve compared with the control group.
• There was no notable difference in microbial composition between patients in the active vs remissive state.

Conclusion

• Patients with GAD had less short chain fatty acid–producing bacteria (Faecalibacterium, Eubacterium rectale, Sutterella, Lachnospira, and Butyricicoccus) compared with controls. Decreased formation of short chain fatty acids could lead to GI barrier disruption. Fusobacterium and Ruminococcus were increased in patients with GAD. Fusobacterium can cause disease and be invasive when it disseminates within the body. The inflammatory characteristics of Fusobacterium contribute to the immunologic activation in GAD. Ruminococcus breaks down mucin, which could then increase GI permeability by mucous degradation of the GI lumen.

Changes in food processing and manufacturing have led to changes in our diets. Changes in our normal GI microbacterial flora could lead to increased gut permeability, bacterial dissemination, and subsequent systemic inflammation. Research has shown that the composition of the microbiota changes across the life span.⁹ A balanced intake of nutrients is important for both our physical and mental health and safeguards the basis of gut microbiome regulation. A well-regulated gut microbiome ensures low levels of inflammation in the brain and body. Lifestyle modifications and dietary coaching could be practical interventions for patients with psychiatric conditions.⁵ Current advances in technology now offer precise analyses of thousands of metabolites, enabling metabolomics to offer the promise of discovering new drug targets and biomarkers that may help pave a way to precision medicine.

The Food and Drug Administration has approved glecaprevir/pibrentasvir tablets (Mavyret) for treating any of six identified genotypes of hepatitis C virus in children ages 12-17 years.

The agency noted in its press announcement that, although Mavyret is not the first treatment option for HCV in children, it is the first that can target any of six genotypes. Dosing information now will be provided for patients aged 12 years and older or weighing at least 99 lbs, without cirrhosis or who have compensated cirrhosis. It is not recommended for patients with moderate cirrhosis, and it is contraindicated in patients with severe cirrhosis, as well as patients taking atazanavir and rifampin.

In clinical trials of 47 patients with genotype 1, 2, 3, or 4 HCV without cirrhosis or with only mild cirrhosis, results at 12 weeks after 8 or 16 weeks’ treatment suggested patients’ infections had been cured – 100% had no virus detected in their blood. Adverse reactions observed were consistent with those previously observed in adults during clinical trials.

The most common reactions were headache and fatigue. Hepatitis B virus reactivation has been reported in coinfected adults during or after treatment with direct-acting antivirals, and in those who were not receiving HBV antiviral treatment. Full prescribing information can be found on the FDA website, and more information about this approval can be found in the agency’s announcement.

The Food and Drug Administration has approved glecaprevir/pibrentasvir tablets (Mavyret) for treating any of six identified genotypes of hepatitis C virus in children ages 12-17 years.

The agency noted in its press announcement that, although Mavyret is not the first treatment option for HCV in children, it is the first that can target any of six genotypes. Dosing information now will be provided for patients aged 12 years and older or weighing at least 99 lbs, without cirrhosis or who have compensated cirrhosis. It is not recommended for patients with moderate cirrhosis, and it is contraindicated in patients with severe cirrhosis, as well as patients taking atazanavir and rifampin.

In clinical trials of 47 patients with genotype 1, 2, 3, or 4 HCV without cirrhosis or with only mild cirrhosis, results at 12 weeks after 8 or 16 weeks’ treatment suggested patients’ infections had been cured – 100% had no virus detected in their blood. Adverse reactions observed were consistent with those previously observed in adults during clinical trials.

The most common reactions were headache and fatigue. Hepatitis B virus reactivation has been reported in coinfected adults during or after treatment with direct-acting antivirals, and in those who were not receiving HBV antiviral treatment. Full prescribing information can be found on the FDA website, and more information about this approval can be found in the agency’s announcement.

The Food and Drug Administration has approved glecaprevir/pibrentasvir tablets (Mavyret) for treating any of six identified genotypes of hepatitis C virus in children ages 12-17 years.

The agency noted in its press announcement that, although Mavyret is not the first treatment option for HCV in children, it is the first that can target any of six genotypes. Dosing information now will be provided for patients aged 12 years and older or weighing at least 99 lbs, without cirrhosis or who have compensated cirrhosis. It is not recommended for patients with moderate cirrhosis, and it is contraindicated in patients with severe cirrhosis, as well as patients taking atazanavir and rifampin.

In clinical trials of 47 patients with genotype 1, 2, 3, or 4 HCV without cirrhosis or with only mild cirrhosis, results at 12 weeks after 8 or 16 weeks’ treatment suggested patients’ infections had been cured – 100% had no virus detected in their blood. Adverse reactions observed were consistent with those previously observed in adults during clinical trials.

The most common reactions were headache and fatigue. Hepatitis B virus reactivation has been reported in coinfected adults during or after treatment with direct-acting antivirals, and in those who were not receiving HBV antiviral treatment. Full prescribing information can be found on the FDA website, and more information about this approval can be found in the agency’s announcement.

ORLANDO – Infections before the age of 4 are linked to the risk of nonaffective psychosis (NAP) in adulthood, according to a study presented at the annual congress of the Schizophrenia International Research Society. Researchers also found that a lower IQ seems to make the psychosis risk more likely.

It’s well-established in the literature that infections are tied to schizophrenia and that a premorbid IQ deficit is linked as well. Researchers looked to a huge data pool from the Swedish population to try to better define these risks.

“We know that there is an association between infection and schizophrenia,” said Golam Khandaker, MRCPsych, PhD, head of the inflammation and psychiatry research group at the University of Cambridge (England). “We know that there is premorbid IQ deficit in schizophrenia. So, we wanted to know, is there a sensitive period during childhood when exposure to infection is more harmful?”

Researchers analyzed data for 647,000 people in the Swedish population who were born between 1973 and 1997, and conscripted for military service through 2010. Exposure to infection was considered to be any hospitalization with any serious infection between birth and age 13. IQ measurements were taken during military conscription at the age of 18. And researchers looked for risk of nonaffective psychosis from the age of 18 on.

There was a significant increase in risk of nonaffective psychosis in adulthood among those who’d had an infection, with a hazard ratio of 1.16 (95% confidence interval, 1.08-1.24). But when researchers broke down this risk into smaller age spans, they found that only infection between birth and 1 year old (HR, 1.19; 95% CI, 1.06-1.33) and between age 2 and 4 (HR, 1.11; 95% CI, 1.02-1.22) was linked with a significantly elevated risk of NAP. Researchers also saw a link between infection and IQ.

“It seems that early childhood is a sensitive period with regards to the effects of infection on IQ and risk of psychosis in adult life,” Dr. Khandaker said.

Researchers assessed whether familial factors could be confounding this link. They looked at rates of NAP among those with an early infection and no early infection in the general population and found that it was no different statistically than among full siblings with an early infection, compared with those with no early infection. In other words, the infection-psychosis risk was the same – whether someone was a close family member or not.

Dr. Khandaker said the findings more definitively establish a link between infection and psychosis risk and suggest that the early years are when children are at their most vulnerable.

“The association between adult nonaffective psychosis with premorbid IQ and childhood infection are not explained by shared familial confounding,” he said. “So these associations could be causal.”

When they looked at the role of IQ and the link between infection and psychosis risk, researchers found an interaction: With every 1-point decrease in IQ score, there was a corresponding increased risk of NAP among those with childhood infections (odds ratio, 1.006; P = .02).

“Childhood infections,” Dr. Khandaker said, “increase psychosis risk partly by interfering with neurodevelopment, and partly by exaggerating the effects of cognitive vulnerability to psychosis.”

Dr. Khandaker disclosed no relevant financial relationships.

ORLANDO – Infections before the age of 4 are linked to the risk of nonaffective psychosis (NAP) in adulthood, according to a study presented at the annual congress of the Schizophrenia International Research Society. Researchers also found that a lower IQ seems to make the psychosis risk more likely.

It’s well-established in the literature that infections are tied to schizophrenia and that a premorbid IQ deficit is linked as well. Researchers looked to a huge data pool from the Swedish population to try to better define these risks.

“We know that there is an association between infection and schizophrenia,” said Golam Khandaker, MRCPsych, PhD, head of the inflammation and psychiatry research group at the University of Cambridge (England). “We know that there is premorbid IQ deficit in schizophrenia. So, we wanted to know, is there a sensitive period during childhood when exposure to infection is more harmful?”

Researchers analyzed data for 647,000 people in the Swedish population who were born between 1973 and 1997, and conscripted for military service through 2010. Exposure to infection was considered to be any hospitalization with any serious infection between birth and age 13. IQ measurements were taken during military conscription at the age of 18. And researchers looked for risk of nonaffective psychosis from the age of 18 on.

There was a significant increase in risk of nonaffective psychosis in adulthood among those who’d had an infection, with a hazard ratio of 1.16 (95% confidence interval, 1.08-1.24). But when researchers broke down this risk into smaller age spans, they found that only infection between birth and 1 year old (HR, 1.19; 95% CI, 1.06-1.33) and between age 2 and 4 (HR, 1.11; 95% CI, 1.02-1.22) was linked with a significantly elevated risk of NAP. Researchers also saw a link between infection and IQ.

“It seems that early childhood is a sensitive period with regards to the effects of infection on IQ and risk of psychosis in adult life,” Dr. Khandaker said.

Researchers assessed whether familial factors could be confounding this link. They looked at rates of NAP among those with an early infection and no early infection in the general population and found that it was no different statistically than among full siblings with an early infection, compared with those with no early infection. In other words, the infection-psychosis risk was the same – whether someone was a close family member or not.

Dr. Khandaker said the findings more definitively establish a link between infection and psychosis risk and suggest that the early years are when children are at their most vulnerable.

“The association between adult nonaffective psychosis with premorbid IQ and childhood infection are not explained by shared familial confounding,” he said. “So these associations could be causal.”

When they looked at the role of IQ and the link between infection and psychosis risk, researchers found an interaction: With every 1-point decrease in IQ score, there was a corresponding increased risk of NAP among those with childhood infections (odds ratio, 1.006; P = .02).

“Childhood infections,” Dr. Khandaker said, “increase psychosis risk partly by interfering with neurodevelopment, and partly by exaggerating the effects of cognitive vulnerability to psychosis.”

Dr. Khandaker disclosed no relevant financial relationships.

ORLANDO – Infections before the age of 4 are linked to the risk of nonaffective psychosis (NAP) in adulthood, according to a study presented at the annual congress of the Schizophrenia International Research Society. Researchers also found that a lower IQ seems to make the psychosis risk more likely.

It’s well-established in the literature that infections are tied to schizophrenia and that a premorbid IQ deficit is linked as well. Researchers looked to a huge data pool from the Swedish population to try to better define these risks.

“We know that there is an association between infection and schizophrenia,” said Golam Khandaker, MRCPsych, PhD, head of the inflammation and psychiatry research group at the University of Cambridge (England). “We know that there is premorbid IQ deficit in schizophrenia. So, we wanted to know, is there a sensitive period during childhood when exposure to infection is more harmful?”

Researchers analyzed data for 647,000 people in the Swedish population who were born between 1973 and 1997, and conscripted for military service through 2010. Exposure to infection was considered to be any hospitalization with any serious infection between birth and age 13. IQ measurements were taken during military conscription at the age of 18. And researchers looked for risk of nonaffective psychosis from the age of 18 on.

There was a significant increase in risk of nonaffective psychosis in adulthood among those who’d had an infection, with a hazard ratio of 1.16 (95% confidence interval, 1.08-1.24). But when researchers broke down this risk into smaller age spans, they found that only infection between birth and 1 year old (HR, 1.19; 95% CI, 1.06-1.33) and between age 2 and 4 (HR, 1.11; 95% CI, 1.02-1.22) was linked with a significantly elevated risk of NAP. Researchers also saw a link between infection and IQ.

“It seems that early childhood is a sensitive period with regards to the effects of infection on IQ and risk of psychosis in adult life,” Dr. Khandaker said.

Researchers assessed whether familial factors could be confounding this link. They looked at rates of NAP among those with an early infection and no early infection in the general population and found that it was no different statistically than among full siblings with an early infection, compared with those with no early infection. In other words, the infection-psychosis risk was the same – whether someone was a close family member or not.

Dr. Khandaker said the findings more definitively establish a link between infection and psychosis risk and suggest that the early years are when children are at their most vulnerable.

“The association between adult nonaffective psychosis with premorbid IQ and childhood infection are not explained by shared familial confounding,” he said. “So these associations could be causal.”

When they looked at the role of IQ and the link between infection and psychosis risk, researchers found an interaction: With every 1-point decrease in IQ score, there was a corresponding increased risk of NAP among those with childhood infections (odds ratio, 1.006; P = .02).

“Childhood infections,” Dr. Khandaker said, “increase psychosis risk partly by interfering with neurodevelopment, and partly by exaggerating the effects of cognitive vulnerability to psychosis.”

Dr. Khandaker disclosed no relevant financial relationships.

BALTIMORE – U.S. pediatricians feel comfortable providing patients with preventive information and travel advice related to Zika, but few feel prepared when it comes to testing and management of infants exposed prenatally to Zika infections, a study found.

Aunt_Spray/Thinkstock

“Areas where pediatricians were less likely to report preparedness included recommending testing, providing data to the Centers for Disease Control and Prevention’s Zika Pregnancy Registry, managing infants exposed to Zika prenatally, and informing parents of social services for Zika-infected infants,” senior author Amy J. Houtrow, MD, MPH, PhD, and colleagues reported at the Pediatric Academic Societies annual meeting.

“Results indicate that additional education efforts are needed to grow the overall Zika knowledge of pediatricians and boost preparedness, particularly around recommending Zika testing and providing data to CDC,” they concluded.

But these findings are not surprising given how rare congenital Zika virus syndrome is, explained Dr. Houtrow, an associate professor of physical medicine and rehabilitation and pediatrics at the University of Pittsburgh.

“For most rare conditions, pediatricians report better general than specific knowledge,” Dr. Houtrow said in an interview. “We expect pediatricians have a broad range of knowledge for a multitude of conditions and to be well versed in the care of infants and children with common conditions, coupled with the ability to access knowledge and expertise about rarer conditions such as congenital Zika syndrome.”

Dr. Houtrow and associates drew their findings from the 2018 AAP Periodic Survey of Fellows, which includes both primary care physicians and neonatologists. The survey’s response rate was 42%, with 672 of 1,599 surveys returned, but the researchers limited their analysis to 576 postresidency respondents who were providing direct patient care.

Overall, 39% of physicians reported being knowledgeable about Zika virus, and 47% said they wanted to learn more. More than half of responding doctors (57%) reported feeling moderately or very prepared when it came to informing patients of preventive measures to reduce risk of Zika infection, and nearly half (49%) felt confident about giving patients travel advice.

However, physicians’ preparedness gradually dropped for clinical situations requiring more direct experience with Zika. For example, 37% felt moderately or very prepared to provide clinical referrals for infant patients with an infection, and 33% felt prepared to talk with pregnant women about the risks of birth defects from Zika infection.

Just one in five physicians (22%) felt prepared for recommending Zika virus testing, and 16% felt prepared about providing data to the CDC’s U.S. Zika Pregnancy Registry or managing infants who had been prenatally exposed to Zika infection. Only 15% felt they had the preparedness to tell parents about social services for Zika-affected infants.

Preparedness did not differ by gender, specialty, practice setting, hours worked per week, or population density (urban, rural and suburban). However, differences did appear based on respondents’ age and U.S. region.

Older doctors reported greater knowledge about Zika than younger doctors. Compared with those aged 39 years or younger, those aged 40-49 and 50-59 reported feeling more knowledgeable (adjusted odds ratio, 1.74 and 1.72, respectively; P less than .05). The odds of feeling more knowledgeable was nearly triple among those aged at least 60 years, compared with those under 40 (aOR, 2.92; P less than .001).

Those practicing in the Northeast United States (aOR, 2.19; P less than .01) and in the South (aOR, 1.74; P less than .05) also reported feeling more knowledgeable than those in the West or Midwest.

“This makes sense because infants with a history of prenatal exposure to the Zika Virus are more likely to be seen in practices with more immigrants from the Caribbean and Latin America,” Dr. Houtrow said in an interview.

“There is definitely an opportunity to improve the dissemination of information about Zika virus to pediatricians, but the urgency of the need for education about Zika virus has diminished because the rates of new congenital Zika syndrome have dropped,” she continued.

Study limitations include the inability to generalize the findings beyond U.S. members of the AAP and the possibility that nonrespondents differed from respondents in terms of Zika knowledge and preparedness.

The research was funded by the AAP and CDC.

BALTIMORE – U.S. pediatricians feel comfortable providing patients with preventive information and travel advice related to Zika, but few feel prepared when it comes to testing and management of infants exposed prenatally to Zika infections, a study found.

Aunt_Spray/Thinkstock

“Areas where pediatricians were less likely to report preparedness included recommending testing, providing data to the Centers for Disease Control and Prevention’s Zika Pregnancy Registry, managing infants exposed to Zika prenatally, and informing parents of social services for Zika-infected infants,” senior author Amy J. Houtrow, MD, MPH, PhD, and colleagues reported at the Pediatric Academic Societies annual meeting.

“Results indicate that additional education efforts are needed to grow the overall Zika knowledge of pediatricians and boost preparedness, particularly around recommending Zika testing and providing data to CDC,” they concluded.

But these findings are not surprising given how rare congenital Zika virus syndrome is, explained Dr. Houtrow, an associate professor of physical medicine and rehabilitation and pediatrics at the University of Pittsburgh.

“For most rare conditions, pediatricians report better general than specific knowledge,” Dr. Houtrow said in an interview. “We expect pediatricians have a broad range of knowledge for a multitude of conditions and to be well versed in the care of infants and children with common conditions, coupled with the ability to access knowledge and expertise about rarer conditions such as congenital Zika syndrome.”

Dr. Houtrow and associates drew their findings from the 2018 AAP Periodic Survey of Fellows, which includes both primary care physicians and neonatologists. The survey’s response rate was 42%, with 672 of 1,599 surveys returned, but the researchers limited their analysis to 576 postresidency respondents who were providing direct patient care.

Overall, 39% of physicians reported being knowledgeable about Zika virus, and 47% said they wanted to learn more. More than half of responding doctors (57%) reported feeling moderately or very prepared when it came to informing patients of preventive measures to reduce risk of Zika infection, and nearly half (49%) felt confident about giving patients travel advice.

However, physicians’ preparedness gradually dropped for clinical situations requiring more direct experience with Zika. For example, 37% felt moderately or very prepared to provide clinical referrals for infant patients with an infection, and 33% felt prepared to talk with pregnant women about the risks of birth defects from Zika infection.

Just one in five physicians (22%) felt prepared for recommending Zika virus testing, and 16% felt prepared about providing data to the CDC’s U.S. Zika Pregnancy Registry or managing infants who had been prenatally exposed to Zika infection. Only 15% felt they had the preparedness to tell parents about social services for Zika-affected infants.

Preparedness did not differ by gender, specialty, practice setting, hours worked per week, or population density (urban, rural and suburban). However, differences did appear based on respondents’ age and U.S. region.

Older doctors reported greater knowledge about Zika than younger doctors. Compared with those aged 39 years or younger, those aged 40-49 and 50-59 reported feeling more knowledgeable (adjusted odds ratio, 1.74 and 1.72, respectively; P less than .05). The odds of feeling more knowledgeable was nearly triple among those aged at least 60 years, compared with those under 40 (aOR, 2.92; P less than .001).

Those practicing in the Northeast United States (aOR, 2.19; P less than .01) and in the South (aOR, 1.74; P less than .05) also reported feeling more knowledgeable than those in the West or Midwest.

“This makes sense because infants with a history of prenatal exposure to the Zika Virus are more likely to be seen in practices with more immigrants from the Caribbean and Latin America,” Dr. Houtrow said in an interview.

“There is definitely an opportunity to improve the dissemination of information about Zika virus to pediatricians, but the urgency of the need for education about Zika virus has diminished because the rates of new congenital Zika syndrome have dropped,” she continued.

Study limitations include the inability to generalize the findings beyond U.S. members of the AAP and the possibility that nonrespondents differed from respondents in terms of Zika knowledge and preparedness.

The research was funded by the AAP and CDC.

BALTIMORE – U.S. pediatricians feel comfortable providing patients with preventive information and travel advice related to Zika, but few feel prepared when it comes to testing and management of infants exposed prenatally to Zika infections, a study found.

Aunt_Spray/Thinkstock

“Areas where pediatricians were less likely to report preparedness included recommending testing, providing data to the Centers for Disease Control and Prevention’s Zika Pregnancy Registry, managing infants exposed to Zika prenatally, and informing parents of social services for Zika-infected infants,” senior author Amy J. Houtrow, MD, MPH, PhD, and colleagues reported at the Pediatric Academic Societies annual meeting.

“Results indicate that additional education efforts are needed to grow the overall Zika knowledge of pediatricians and boost preparedness, particularly around recommending Zika testing and providing data to CDC,” they concluded.

But these findings are not surprising given how rare congenital Zika virus syndrome is, explained Dr. Houtrow, an associate professor of physical medicine and rehabilitation and pediatrics at the University of Pittsburgh.

“For most rare conditions, pediatricians report better general than specific knowledge,” Dr. Houtrow said in an interview. “We expect pediatricians have a broad range of knowledge for a multitude of conditions and to be well versed in the care of infants and children with common conditions, coupled with the ability to access knowledge and expertise about rarer conditions such as congenital Zika syndrome.”

Dr. Houtrow and associates drew their findings from the 2018 AAP Periodic Survey of Fellows, which includes both primary care physicians and neonatologists. The survey’s response rate was 42%, with 672 of 1,599 surveys returned, but the researchers limited their analysis to 576 postresidency respondents who were providing direct patient care.

Overall, 39% of physicians reported being knowledgeable about Zika virus, and 47% said they wanted to learn more. More than half of responding doctors (57%) reported feeling moderately or very prepared when it came to informing patients of preventive measures to reduce risk of Zika infection, and nearly half (49%) felt confident about giving patients travel advice.

However, physicians’ preparedness gradually dropped for clinical situations requiring more direct experience with Zika. For example, 37% felt moderately or very prepared to provide clinical referrals for infant patients with an infection, and 33% felt prepared to talk with pregnant women about the risks of birth defects from Zika infection.

Just one in five physicians (22%) felt prepared for recommending Zika virus testing, and 16% felt prepared about providing data to the CDC’s U.S. Zika Pregnancy Registry or managing infants who had been prenatally exposed to Zika infection. Only 15% felt they had the preparedness to tell parents about social services for Zika-affected infants.

Preparedness did not differ by gender, specialty, practice setting, hours worked per week, or population density (urban, rural and suburban). However, differences did appear based on respondents’ age and U.S. region.

Older doctors reported greater knowledge about Zika than younger doctors. Compared with those aged 39 years or younger, those aged 40-49 and 50-59 reported feeling more knowledgeable (adjusted odds ratio, 1.74 and 1.72, respectively; P less than .05). The odds of feeling more knowledgeable was nearly triple among those aged at least 60 years, compared with those under 40 (aOR, 2.92; P less than .001).

Those practicing in the Northeast United States (aOR, 2.19; P less than .01) and in the South (aOR, 1.74; P less than .05) also reported feeling more knowledgeable than those in the West or Midwest.

“This makes sense because infants with a history of prenatal exposure to the Zika Virus are more likely to be seen in practices with more immigrants from the Caribbean and Latin America,” Dr. Houtrow said in an interview.

“There is definitely an opportunity to improve the dissemination of information about Zika virus to pediatricians, but the urgency of the need for education about Zika virus has diminished because the rates of new congenital Zika syndrome have dropped,” she continued.

Study limitations include the inability to generalize the findings beyond U.S. members of the AAP and the possibility that nonrespondents differed from respondents in terms of Zika knowledge and preparedness.

The research was funded by the AAP and CDC.

The CDC estimates that 1.7 million people in the United States acquire sepsis annually; sepsis accounts for nearly 270,000 patient deaths per year. 

Decreasing mortality and improving patient outcomes requires early detection and appropriate timely treatment. The Joint Commission Center for Transforming Healthcare’s recent sepsis project demonstrated this by analyzing root causes and reducing sepsis mortality with five leading hospitals by an aggregate of nearly 25%.

“Most organizations can tell you how they are doing with regard to whether or not they are ordering lactates or fluids, but many can’t tell you where in the process these elements are failing,” said Kelly Barnes, Black Belt III, Joint Commission Center for Transforming Healthcare. “For instance, is the issue in ordering lactates, drawing lactates, or getting the results of lactates in a timely manner? The key is to understand where in the process things are breaking down to identify what solutions an organization needs to put in place.”

During the Joint Commission project, one organization found that patients had inadequate fluid resuscitation due to staff fear of fluid overload, while another organization found they had issues with fluids being disconnected when patients were taken for tests and then not reconnected – different problems that needed different solutions. 

The Joint Commission Center for Transforming Healthcare is currently developing a Targeted Solutions Tool^® (TST^®), scheduled for release in 2019, to help organizations determine their issues with sepsis recognition and barriers to meeting sepsis bundle element requirements and implement targeted solutions to address their specific issues. The tool will be available free of charge to all Joint Commission-accredited customers.
 

Reference

1. “Hospital-Wide Sepsis Project Reduces Mortality by Nearly 25 Percent,” Kelly Barnes, The Joint Commission Center for Transforming Healthcare. 2018, Sep 25.

The CDC estimates that 1.7 million people in the United States acquire sepsis annually; sepsis accounts for nearly 270,000 patient deaths per year. 

Decreasing mortality and improving patient outcomes requires early detection and appropriate timely treatment. The Joint Commission Center for Transforming Healthcare’s recent sepsis project demonstrated this by analyzing root causes and reducing sepsis mortality with five leading hospitals by an aggregate of nearly 25%.

“Most organizations can tell you how they are doing with regard to whether or not they are ordering lactates or fluids, but many can’t tell you where in the process these elements are failing,” said Kelly Barnes, Black Belt III, Joint Commission Center for Transforming Healthcare. “For instance, is the issue in ordering lactates, drawing lactates, or getting the results of lactates in a timely manner? The key is to understand where in the process things are breaking down to identify what solutions an organization needs to put in place.”

During the Joint Commission project, one organization found that patients had inadequate fluid resuscitation due to staff fear of fluid overload, while another organization found they had issues with fluids being disconnected when patients were taken for tests and then not reconnected – different problems that needed different solutions. 

The Joint Commission Center for Transforming Healthcare is currently developing a Targeted Solutions Tool^® (TST^®), scheduled for release in 2019, to help organizations determine their issues with sepsis recognition and barriers to meeting sepsis bundle element requirements and implement targeted solutions to address their specific issues. The tool will be available free of charge to all Joint Commission-accredited customers.
 

Reference

1. “Hospital-Wide Sepsis Project Reduces Mortality by Nearly 25 Percent,” Kelly Barnes, The Joint Commission Center for Transforming Healthcare. 2018, Sep 25.

The CDC estimates that 1.7 million people in the United States acquire sepsis annually; sepsis accounts for nearly 270,000 patient deaths per year. 

Decreasing mortality and improving patient outcomes requires early detection and appropriate timely treatment. The Joint Commission Center for Transforming Healthcare’s recent sepsis project demonstrated this by analyzing root causes and reducing sepsis mortality with five leading hospitals by an aggregate of nearly 25%.

“Most organizations can tell you how they are doing with regard to whether or not they are ordering lactates or fluids, but many can’t tell you where in the process these elements are failing,” said Kelly Barnes, Black Belt III, Joint Commission Center for Transforming Healthcare. “For instance, is the issue in ordering lactates, drawing lactates, or getting the results of lactates in a timely manner? The key is to understand where in the process things are breaking down to identify what solutions an organization needs to put in place.”

During the Joint Commission project, one organization found that patients had inadequate fluid resuscitation due to staff fear of fluid overload, while another organization found they had issues with fluids being disconnected when patients were taken for tests and then not reconnected – different problems that needed different solutions. 

The Joint Commission Center for Transforming Healthcare is currently developing a Targeted Solutions Tool^® (TST^®), scheduled for release in 2019, to help organizations determine their issues with sepsis recognition and barriers to meeting sepsis bundle element requirements and implement targeted solutions to address their specific issues. The tool will be available free of charge to all Joint Commission-accredited customers.
 

Reference

1. “Hospital-Wide Sepsis Project Reduces Mortality by Nearly 25 Percent,” Kelly Barnes, The Joint Commission Center for Transforming Healthcare. 2018, Sep 25.

There have been 704 measles cases in the United States in 2019 as of April 26, the Centers for Disease Control and Prevention reported.

The updated figure adds 9 cases to the previous tally of 695 cases as of April 24, when the CDC announced that the number of cases in 2019 had surpassed the total for any year since the disease was considered effectively eliminated from the country in 2000.

Cases have been reported in 22 states, with the largest outbreaks in Washington and New York. The outbreak in Washington, which included 72 cases, was declared over last week. Two outbreaks in New York, however, are the largest and longest-lasting measles outbreaks since the disease was considered eliminated, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. The longer they continue, the “greater the chance that measles will again gain a foothold in the United States,” she said at CDC telebriefing on measles.

The outbreaks are linked to travelers who are exposed to measles abroad and bring it to the United States. The disease then may spread, especially in communities with high rates of unvaccinated people. “A significant factor contributing to the outbreaks in New York is misinformation in the communities about the safety of the measles/mumps/rubella vaccine,” according to the CDC.
 

National Infant Immunization Week

Until last week, 2014 – with 667 measles cases – had been the year with the most cases since the disease was effectively eliminated. The last time the United States had more measles cases was in 1994, when there were 963 cases for the year.

Health and Human Services Secretary Alex Azar, also at the telebriefing, pointed out that 1994 also was the year that the United States first observed National Infant Immunization Week, which is April 27–May 4 this year. The CDC is marking the 25th anniversary of the annual observance, which highlights “the importance of protecting infants from vaccine-preventable diseases” and celebrates “the achievements of immunization programs in promoting healthy communities,” Secretary Azar said.
 

Message to health care providers

CDC director Robert Redfield Jr., MD, noted that measles has “no treatment, no cure, and no way to predict how bad a case will be.”

Some patients may have mild symptoms, whereas others may have serious complications such as pneumonia or encephalitis. In 2019, 3% of the patients with measles have developed pneumonia, he said. No patients have died.

Dr. Redfield, a virologist, noted that the CDC is recommending that children aged 6-12 months receive 1 dose of the measles vaccine if traveling abroad.

“As CDC director and as a physician, I have and continue to wholeheartedly advocate for infant immunization,” he said in a statement. “More importantly, as a father and grandfather I have ensured all of my children and grandchildren are vaccinated on the recommended schedule. Vaccines are safe. Vaccines do not cause autism. Vaccine-preventable diseases are dangerous.”

More than 94% of parents vaccinate their children, Dr. Redfield added. “CDC is working to reach the small percentage of vaccine-hesitant individuals so they too understand the importance of vaccines. It is imperative that we correct misinformation and reassure fearful parents so they protect their children from illnesses with long-lasting health impacts.”

About 1.3%, or 100,000 children, in the United States under 2 years old have not been vaccinated, he said.

“I call upon health care providers to encourage parents and expectant parents to vaccinate their children for their own protection and to avoid the spread of vaccine-preventable diseases within their families and communities,” he said. “We must join together as a nation to once again eliminate measles and prevent future disease outbreaks.”

The CDC has a complete list of clinical recommendations for health care providers on its website.
 

The president weighs in

President Donald Trump said that children should receive vaccinations – his first public comment about vaccines since his inauguration. Previously, he had questioned the safety of vaccines.

Asked by reporters about the measles outbreaks and his message for parents about having their kids vaccinated, he said: “They have to get the shot. The vaccinations are so important. This is really going around now. They have to get their shots.”

[email protected]

There have been 704 measles cases in the United States in 2019 as of April 26, the Centers for Disease Control and Prevention reported.

The updated figure adds 9 cases to the previous tally of 695 cases as of April 24, when the CDC announced that the number of cases in 2019 had surpassed the total for any year since the disease was considered effectively eliminated from the country in 2000.

Cases have been reported in 22 states, with the largest outbreaks in Washington and New York. The outbreak in Washington, which included 72 cases, was declared over last week. Two outbreaks in New York, however, are the largest and longest-lasting measles outbreaks since the disease was considered eliminated, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. The longer they continue, the “greater the chance that measles will again gain a foothold in the United States,” she said at CDC telebriefing on measles.

The outbreaks are linked to travelers who are exposed to measles abroad and bring it to the United States. The disease then may spread, especially in communities with high rates of unvaccinated people. “A significant factor contributing to the outbreaks in New York is misinformation in the communities about the safety of the measles/mumps/rubella vaccine,” according to the CDC.
 

National Infant Immunization Week

Until last week, 2014 – with 667 measles cases – had been the year with the most cases since the disease was effectively eliminated. The last time the United States had more measles cases was in 1994, when there were 963 cases for the year.

Health and Human Services Secretary Alex Azar, also at the telebriefing, pointed out that 1994 also was the year that the United States first observed National Infant Immunization Week, which is April 27–May 4 this year. The CDC is marking the 25th anniversary of the annual observance, which highlights “the importance of protecting infants from vaccine-preventable diseases” and celebrates “the achievements of immunization programs in promoting healthy communities,” Secretary Azar said.
 

Message to health care providers

CDC director Robert Redfield Jr., MD, noted that measles has “no treatment, no cure, and no way to predict how bad a case will be.”

Some patients may have mild symptoms, whereas others may have serious complications such as pneumonia or encephalitis. In 2019, 3% of the patients with measles have developed pneumonia, he said. No patients have died.

Dr. Redfield, a virologist, noted that the CDC is recommending that children aged 6-12 months receive 1 dose of the measles vaccine if traveling abroad.

“As CDC director and as a physician, I have and continue to wholeheartedly advocate for infant immunization,” he said in a statement. “More importantly, as a father and grandfather I have ensured all of my children and grandchildren are vaccinated on the recommended schedule. Vaccines are safe. Vaccines do not cause autism. Vaccine-preventable diseases are dangerous.”

More than 94% of parents vaccinate their children, Dr. Redfield added. “CDC is working to reach the small percentage of vaccine-hesitant individuals so they too understand the importance of vaccines. It is imperative that we correct misinformation and reassure fearful parents so they protect their children from illnesses with long-lasting health impacts.”

About 1.3%, or 100,000 children, in the United States under 2 years old have not been vaccinated, he said.

“I call upon health care providers to encourage parents and expectant parents to vaccinate their children for their own protection and to avoid the spread of vaccine-preventable diseases within their families and communities,” he said. “We must join together as a nation to once again eliminate measles and prevent future disease outbreaks.”

The CDC has a complete list of clinical recommendations for health care providers on its website.
 

The president weighs in

President Donald Trump said that children should receive vaccinations – his first public comment about vaccines since his inauguration. Previously, he had questioned the safety of vaccines.

Asked by reporters about the measles outbreaks and his message for parents about having their kids vaccinated, he said: “They have to get the shot. The vaccinations are so important. This is really going around now. They have to get their shots.”

[email protected]

There have been 704 measles cases in the United States in 2019 as of April 26, the Centers for Disease Control and Prevention reported.

The updated figure adds 9 cases to the previous tally of 695 cases as of April 24, when the CDC announced that the number of cases in 2019 had surpassed the total for any year since the disease was considered effectively eliminated from the country in 2000.

Cases have been reported in 22 states, with the largest outbreaks in Washington and New York. The outbreak in Washington, which included 72 cases, was declared over last week. Two outbreaks in New York, however, are the largest and longest-lasting measles outbreaks since the disease was considered eliminated, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. The longer they continue, the “greater the chance that measles will again gain a foothold in the United States,” she said at CDC telebriefing on measles.

The outbreaks are linked to travelers who are exposed to measles abroad and bring it to the United States. The disease then may spread, especially in communities with high rates of unvaccinated people. “A significant factor contributing to the outbreaks in New York is misinformation in the communities about the safety of the measles/mumps/rubella vaccine,” according to the CDC.
 

National Infant Immunization Week

Until last week, 2014 – with 667 measles cases – had been the year with the most cases since the disease was effectively eliminated. The last time the United States had more measles cases was in 1994, when there were 963 cases for the year.

Health and Human Services Secretary Alex Azar, also at the telebriefing, pointed out that 1994 also was the year that the United States first observed National Infant Immunization Week, which is April 27–May 4 this year. The CDC is marking the 25th anniversary of the annual observance, which highlights “the importance of protecting infants from vaccine-preventable diseases” and celebrates “the achievements of immunization programs in promoting healthy communities,” Secretary Azar said.
 

Message to health care providers

CDC director Robert Redfield Jr., MD, noted that measles has “no treatment, no cure, and no way to predict how bad a case will be.”

Some patients may have mild symptoms, whereas others may have serious complications such as pneumonia or encephalitis. In 2019, 3% of the patients with measles have developed pneumonia, he said. No patients have died.

Dr. Redfield, a virologist, noted that the CDC is recommending that children aged 6-12 months receive 1 dose of the measles vaccine if traveling abroad.

“As CDC director and as a physician, I have and continue to wholeheartedly advocate for infant immunization,” he said in a statement. “More importantly, as a father and grandfather I have ensured all of my children and grandchildren are vaccinated on the recommended schedule. Vaccines are safe. Vaccines do not cause autism. Vaccine-preventable diseases are dangerous.”

More than 94% of parents vaccinate their children, Dr. Redfield added. “CDC is working to reach the small percentage of vaccine-hesitant individuals so they too understand the importance of vaccines. It is imperative that we correct misinformation and reassure fearful parents so they protect their children from illnesses with long-lasting health impacts.”

About 1.3%, or 100,000 children, in the United States under 2 years old have not been vaccinated, he said.

“I call upon health care providers to encourage parents and expectant parents to vaccinate their children for their own protection and to avoid the spread of vaccine-preventable diseases within their families and communities,” he said. “We must join together as a nation to once again eliminate measles and prevent future disease outbreaks.”

The CDC has a complete list of clinical recommendations for health care providers on its website.
 

The president weighs in

President Donald Trump said that children should receive vaccinations – his first public comment about vaccines since his inauguration. Previously, he had questioned the safety of vaccines.

Asked by reporters about the measles outbreaks and his message for parents about having their kids vaccinated, he said: “They have to get the shot. The vaccinations are so important. This is really going around now. They have to get their shots.”

[email protected]

BALTIMORE – Comprehensive respiratory pathogen panels (RPAN) cannot be relied on to detect pertussis, according to an investigation from the University of Michigan, Ann Arbor.

Respiratory pathogen panels are popular because they test for many things at once, but providers have to know their limits, said lead investigator Colleen Mayhew, MD, a pediatric emergency medicine fellow at the University of Michigan.

“Should RPAN be used to diagnosis pertussis? No,” she said at the Pediatric Academic Societies annual meeting. RPAN was negative for confirmed pertussis 44% of the time in the study.

“In our cohort, [it] was no better than a coin flip for detecting pertussis,” she said. Also, even when it missed pertussis, it still detected other pathogens, which raises the risk that symptoms might be attributed to a different infection. “This has serious public health implications.”

“The bottom line is, if you are concerned about pertussis, it’s important to use a dedicated pertussis PCR [polymerase chain reaction] assay, and to use comprehensive respiratory pathogen testing only if there are other, specific targets that will change your clinical management,” such as mycoplasma or the flu, Dr. Mayhew said.

In the study, 102 nasopharyngeal swabs positive for pertussis on standalone PCR testing – the university uses an assay from Focus Diagnostics – were thawed and tested with RPAN.

RPAN was negative for pertussis on 45 swabs (44%). “These are the potential missed pertussis cases if RPAN is used alone,” Dr. Mayhew said. RPAN detected other pathogens, such as coronavirus, about half the time, whether or not it tested positive for pertussis. “Those additional pathogens might represent coinfection, but might also represent asymptomatic carriage.” It’s impossible to differentiate between the two, she noted.

In short, “neither positive testing for other respiratory pathogens, nor negative testing for pertussis by RPAN, is reliable for excluding the diagnosis of pertussis. Dedicated pertussis PCR testing should be used for diagnosis,” she and her team concluded.

RPAN also is a PCR test, but with a different, perhaps less robust, genetic target.

The 102 positive swabs were from patients aged 1 month to 73 years, so “it’s important for all of us to keep pertussis on our differential diagnose” no matter how old patients are, Dr. Mayhew said.

Freezing and thawing the swabs shouldn’t have degraded the genetic material, but it might have; that was one of the limits of the study.

The team hopes to run a quality improvement project to encourage the use of standalone pertussis PCR in Ann Arbor. 
There was no industry funding. Dr. Mayhew didn’t report any disclosures.

[email protected]

BALTIMORE – Comprehensive respiratory pathogen panels (RPAN) cannot be relied on to detect pertussis, according to an investigation from the University of Michigan, Ann Arbor.

Respiratory pathogen panels are popular because they test for many things at once, but providers have to know their limits, said lead investigator Colleen Mayhew, MD, a pediatric emergency medicine fellow at the University of Michigan.

“Should RPAN be used to diagnosis pertussis? No,” she said at the Pediatric Academic Societies annual meeting. RPAN was negative for confirmed pertussis 44% of the time in the study.

“In our cohort, [it] was no better than a coin flip for detecting pertussis,” she said. Also, even when it missed pertussis, it still detected other pathogens, which raises the risk that symptoms might be attributed to a different infection. “This has serious public health implications.”

“The bottom line is, if you are concerned about pertussis, it’s important to use a dedicated pertussis PCR [polymerase chain reaction] assay, and to use comprehensive respiratory pathogen testing only if there are other, specific targets that will change your clinical management,” such as mycoplasma or the flu, Dr. Mayhew said.

In the study, 102 nasopharyngeal swabs positive for pertussis on standalone PCR testing – the university uses an assay from Focus Diagnostics – were thawed and tested with RPAN.

RPAN was negative for pertussis on 45 swabs (44%). “These are the potential missed pertussis cases if RPAN is used alone,” Dr. Mayhew said. RPAN detected other pathogens, such as coronavirus, about half the time, whether or not it tested positive for pertussis. “Those additional pathogens might represent coinfection, but might also represent asymptomatic carriage.” It’s impossible to differentiate between the two, she noted.

In short, “neither positive testing for other respiratory pathogens, nor negative testing for pertussis by RPAN, is reliable for excluding the diagnosis of pertussis. Dedicated pertussis PCR testing should be used for diagnosis,” she and her team concluded.

RPAN also is a PCR test, but with a different, perhaps less robust, genetic target.

The 102 positive swabs were from patients aged 1 month to 73 years, so “it’s important for all of us to keep pertussis on our differential diagnose” no matter how old patients are, Dr. Mayhew said.

Freezing and thawing the swabs shouldn’t have degraded the genetic material, but it might have; that was one of the limits of the study.

The team hopes to run a quality improvement project to encourage the use of standalone pertussis PCR in Ann Arbor. 
There was no industry funding. Dr. Mayhew didn’t report any disclosures.

[email protected]

BALTIMORE – Comprehensive respiratory pathogen panels (RPAN) cannot be relied on to detect pertussis, according to an investigation from the University of Michigan, Ann Arbor.

Respiratory pathogen panels are popular because they test for many things at once, but providers have to know their limits, said lead investigator Colleen Mayhew, MD, a pediatric emergency medicine fellow at the University of Michigan.

“Should RPAN be used to diagnosis pertussis? No,” she said at the Pediatric Academic Societies annual meeting. RPAN was negative for confirmed pertussis 44% of the time in the study.

“In our cohort, [it] was no better than a coin flip for detecting pertussis,” she said. Also, even when it missed pertussis, it still detected other pathogens, which raises the risk that symptoms might be attributed to a different infection. “This has serious public health implications.”

“The bottom line is, if you are concerned about pertussis, it’s important to use a dedicated pertussis PCR [polymerase chain reaction] assay, and to use comprehensive respiratory pathogen testing only if there are other, specific targets that will change your clinical management,” such as mycoplasma or the flu, Dr. Mayhew said.

In the study, 102 nasopharyngeal swabs positive for pertussis on standalone PCR testing – the university uses an assay from Focus Diagnostics – were thawed and tested with RPAN.

RPAN was negative for pertussis on 45 swabs (44%). “These are the potential missed pertussis cases if RPAN is used alone,” Dr. Mayhew said. RPAN detected other pathogens, such as coronavirus, about half the time, whether or not it tested positive for pertussis. “Those additional pathogens might represent coinfection, but might also represent asymptomatic carriage.” It’s impossible to differentiate between the two, she noted.

In short, “neither positive testing for other respiratory pathogens, nor negative testing for pertussis by RPAN, is reliable for excluding the diagnosis of pertussis. Dedicated pertussis PCR testing should be used for diagnosis,” she and her team concluded.

RPAN also is a PCR test, but with a different, perhaps less robust, genetic target.

The 102 positive swabs were from patients aged 1 month to 73 years, so “it’s important for all of us to keep pertussis on our differential diagnose” no matter how old patients are, Dr. Mayhew said.

Freezing and thawing the swabs shouldn’t have degraded the genetic material, but it might have; that was one of the limits of the study.

The team hopes to run a quality improvement project to encourage the use of standalone pertussis PCR in Ann Arbor. 
There was no industry funding. Dr. Mayhew didn’t report any disclosures.

[email protected]

BALTIMORE – While rates of surgical site infections after bariatric surgery have been reported in the low single digits, SSIs have continued to be a persistent complication.

Richard Kirkner/MDedge News

At the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons, researchers reported on two strategies to reduce SSI in bariatric surgery: a predictive tool that identifies risk factors for wound infection, allowing surgeons to employ protective measures before and during surgery, and a change in surgical practice leading to a 78% reduction in wound infection rates that resulted from a single-center study.

Jerry Dang, MD, of the University of Alberta, Edmonton, reported that the BariWound predictive tool designed to stratify patients into risk categories showed a high level of accuracy with an area under the curve of 0.73. Cynthia Weber, MD, of University Hospitals, Cleveland, reported that changing the method for performing circular-stapled gastrojejunostomy (GJ) from the transoral to the transabdominal approach along with more vigilant use of wound protection reduced wound infection rates from 6% to 1.3%.

Dr. Dang noted that SSI has been reported as the most common hospital-acquired complication in bariatric surgery, with reported rates of between 1% and 10%. A 2014 analysis of the American College of Surgeons National Surgical Quality Improvement Program database reported an SSI rate of 1.8% (Surg Endosc. 2014;28:3285-92). Although these rates are low, Dr. Dang explained that his group wanted to identify factors associated with SSI within 30 days of bariatric surgery. They analyzed outcomes data of 274,187 patients in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database who had bariatric surgery in 2015 and 2016 (196,608 by laparoscopic sleeve gastrectomy [SG] and 77,579 laparoscopic Roux-en-Y gastric bypass [RYGB]). Their analysis determined an incisional SSI rate of 0.47% (n = 1,291). “Incisional SSI rates were four times higher for laparoscopic RYGB: 1.04% vs. 0.25%,” Dr. Dang said.

On multivariable logistic regression, the adjusted odds ratio of SSI after RYGB vs. SG was 3.13 (P less than .001). Other significant risk factors were chronic steroid or immunosuppressant use (odds ratio, 1.75; P = .001), female sex (OR, 1.48; P less than .001) and history of gastroesophageal reflux disease (OR, 1.45; P less than .001). Other factors with a 21%-31% greater risk of SSI were white race (P = .002), history of diabetes (P less than .001), hypertension (P less than .001), obstructive sleep apnea (P = .001), and longer operation times (P less than .001). Each single-digit increase in body mass index increased risk by 3%, and older age actually had a protective effect for unknown reasons, Dr. Dang noted.

The BariWound tool assigns points to each risk factor. Each hour of operation time and each 10 kg/m² of weight carry a value of 1 point, with partial points allowed. RYGB equals 5 points, and chronic steroid/immunosuppressant use, 4 points. The tool assigns risk to four categories based on score and 30-day SSI rate:

• Low, less than 15 (1% risk of SSI).
• Moderate, 15-21.9 (1%-5%).
• High, 22-26.9 (5%-10%).
• Very high, greater than 27 (greater than 10%).

“The BariWound tool can help to inform clinical decision making so patients can know they’re at higher risk, and this could allow for us to target high-risk patients with preventive packages, such as the Cleveland Clinic Technique of wound protection, wound irrigation, and wound packing as a resource-saving measure,” Dr. Dang said. “Targeting high-risk populations can reduce cost and operating time.”

Richard Kirkner/MDedge NEws

Dr. Weber reported on her institution’s study of SSIs using two different methods for circular stapling of GJ that involved two different surgeons who performed 333 RYGB procedures from January 2016 to March 2018. Surgeon “A” had traditionally used the transoral technique without wound protection to insert the anvil of the stapler; surgeon “B” used wound protection and the transabdominal technique for stapler insertion. Wound protection involves draping of the stapler with sterile plastic.

“In a quarterly review, we detected a higher than expected wound complication rate of 6%,” Dr. Weber said. “Of particular concern was the development of five recent wound infection cases, which all occurred in the transoral group for a rate of 8.9% in that cohort.”

That left the quality team questioning the safety profile of the transoral technique, Dr. Weber said. “We wanted to know why and whether or not the main contributor to the development of a wound infection was the technique for the anvil introduction or was it the difference between surgeons using wound protection.”

Halfway through the study period, surgeon A made two modifications: He adopted the transabdominal technique for a subset of patients; and because of the surgeon’s comfort level and expertise with the transoral approach, he continued using that approach but added wound protection. Surgeon B continued with the transabdominal approach with wound protection. The share of transabdominal insertions in the study population increased from 69.2% before the change to 75% after. Demographics between the pre- and postchange patient populations were similar, as were the rates of revision surgery between the two groups.

“We noticed a significant reduction in total wound complications from 6% to 1.3%, and we noticed a complete elimination of surgical site infections after adding wound protection to the transoral technique,” Dr. Weber said.

Dr. Weber noted a number of limitations with the study: its retrospective nature; the lack of control for other intraoperative factors that contribute to SSIs; relatively low incidence of SSI; and surgeon’s choice to determine the technique of anvil insertion.

“We found that our quality improvement intervention was efficacious and decided that it was not the technique of anvil insertion, but it was the wound protection that was key to preventing wound infections, as we saw complete elimination after we added wound protection to the transoral technique,” Dr. Weber said. “Using proper precautions with the circular stapler and anastomosis can be done using either technique for anvil insertion. Overall self-assessment of outcomes leads to best practice.”

Dr. Dang had no financial relationships to disclose. Dr. Weber’s coauthor Leena Khatian, MD, MPH, disclosed relationships with Torax Medical, Medtronic, and Gore.

SOURCES: Weber C et al. SAGES 2109, Presentation S049; Dang J et al. SAGES 2019, Presentation S050.

BALTIMORE – While rates of surgical site infections after bariatric surgery have been reported in the low single digits, SSIs have continued to be a persistent complication.

Richard Kirkner/MDedge News

At the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons, researchers reported on two strategies to reduce SSI in bariatric surgery: a predictive tool that identifies risk factors for wound infection, allowing surgeons to employ protective measures before and during surgery, and a change in surgical practice leading to a 78% reduction in wound infection rates that resulted from a single-center study.

Jerry Dang, MD, of the University of Alberta, Edmonton, reported that the BariWound predictive tool designed to stratify patients into risk categories showed a high level of accuracy with an area under the curve of 0.73. Cynthia Weber, MD, of University Hospitals, Cleveland, reported that changing the method for performing circular-stapled gastrojejunostomy (GJ) from the transoral to the transabdominal approach along with more vigilant use of wound protection reduced wound infection rates from 6% to 1.3%.

Dr. Dang noted that SSI has been reported as the most common hospital-acquired complication in bariatric surgery, with reported rates of between 1% and 10%. A 2014 analysis of the American College of Surgeons National Surgical Quality Improvement Program database reported an SSI rate of 1.8% (Surg Endosc. 2014;28:3285-92). Although these rates are low, Dr. Dang explained that his group wanted to identify factors associated with SSI within 30 days of bariatric surgery. They analyzed outcomes data of 274,187 patients in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database who had bariatric surgery in 2015 and 2016 (196,608 by laparoscopic sleeve gastrectomy [SG] and 77,579 laparoscopic Roux-en-Y gastric bypass [RYGB]). Their analysis determined an incisional SSI rate of 0.47% (n = 1,291). “Incisional SSI rates were four times higher for laparoscopic RYGB: 1.04% vs. 0.25%,” Dr. Dang said.

On multivariable logistic regression, the adjusted odds ratio of SSI after RYGB vs. SG was 3.13 (P less than .001). Other significant risk factors were chronic steroid or immunosuppressant use (odds ratio, 1.75; P = .001), female sex (OR, 1.48; P less than .001) and history of gastroesophageal reflux disease (OR, 1.45; P less than .001). Other factors with a 21%-31% greater risk of SSI were white race (P = .002), history of diabetes (P less than .001), hypertension (P less than .001), obstructive sleep apnea (P = .001), and longer operation times (P less than .001). Each single-digit increase in body mass index increased risk by 3%, and older age actually had a protective effect for unknown reasons, Dr. Dang noted.

The BariWound tool assigns points to each risk factor. Each hour of operation time and each 10 kg/m² of weight carry a value of 1 point, with partial points allowed. RYGB equals 5 points, and chronic steroid/immunosuppressant use, 4 points. The tool assigns risk to four categories based on score and 30-day SSI rate:

• Low, less than 15 (1% risk of SSI).
• Moderate, 15-21.9 (1%-5%).
• High, 22-26.9 (5%-10%).
• Very high, greater than 27 (greater than 10%).

“The BariWound tool can help to inform clinical decision making so patients can know they’re at higher risk, and this could allow for us to target high-risk patients with preventive packages, such as the Cleveland Clinic Technique of wound protection, wound irrigation, and wound packing as a resource-saving measure,” Dr. Dang said. “Targeting high-risk populations can reduce cost and operating time.”

Richard Kirkner/MDedge NEws

Dr. Weber reported on her institution’s study of SSIs using two different methods for circular stapling of GJ that involved two different surgeons who performed 333 RYGB procedures from January 2016 to March 2018. Surgeon “A” had traditionally used the transoral technique without wound protection to insert the anvil of the stapler; surgeon “B” used wound protection and the transabdominal technique for stapler insertion. Wound protection involves draping of the stapler with sterile plastic.

“In a quarterly review, we detected a higher than expected wound complication rate of 6%,” Dr. Weber said. “Of particular concern was the development of five recent wound infection cases, which all occurred in the transoral group for a rate of 8.9% in that cohort.”

That left the quality team questioning the safety profile of the transoral technique, Dr. Weber said. “We wanted to know why and whether or not the main contributor to the development of a wound infection was the technique for the anvil introduction or was it the difference between surgeons using wound protection.”

Halfway through the study period, surgeon A made two modifications: He adopted the transabdominal technique for a subset of patients; and because of the surgeon’s comfort level and expertise with the transoral approach, he continued using that approach but added wound protection. Surgeon B continued with the transabdominal approach with wound protection. The share of transabdominal insertions in the study population increased from 69.2% before the change to 75% after. Demographics between the pre- and postchange patient populations were similar, as were the rates of revision surgery between the two groups.

“We noticed a significant reduction in total wound complications from 6% to 1.3%, and we noticed a complete elimination of surgical site infections after adding wound protection to the transoral technique,” Dr. Weber said.

Dr. Weber noted a number of limitations with the study: its retrospective nature; the lack of control for other intraoperative factors that contribute to SSIs; relatively low incidence of SSI; and surgeon’s choice to determine the technique of anvil insertion.

“We found that our quality improvement intervention was efficacious and decided that it was not the technique of anvil insertion, but it was the wound protection that was key to preventing wound infections, as we saw complete elimination after we added wound protection to the transoral technique,” Dr. Weber said. “Using proper precautions with the circular stapler and anastomosis can be done using either technique for anvil insertion. Overall self-assessment of outcomes leads to best practice.”

Dr. Dang had no financial relationships to disclose. Dr. Weber’s coauthor Leena Khatian, MD, MPH, disclosed relationships with Torax Medical, Medtronic, and Gore.

SOURCES: Weber C et al. SAGES 2109, Presentation S049; Dang J et al. SAGES 2019, Presentation S050.

BALTIMORE – While rates of surgical site infections after bariatric surgery have been reported in the low single digits, SSIs have continued to be a persistent complication.

Richard Kirkner/MDedge News

At the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons, researchers reported on two strategies to reduce SSI in bariatric surgery: a predictive tool that identifies risk factors for wound infection, allowing surgeons to employ protective measures before and during surgery, and a change in surgical practice leading to a 78% reduction in wound infection rates that resulted from a single-center study.

Jerry Dang, MD, of the University of Alberta, Edmonton, reported that the BariWound predictive tool designed to stratify patients into risk categories showed a high level of accuracy with an area under the curve of 0.73. Cynthia Weber, MD, of University Hospitals, Cleveland, reported that changing the method for performing circular-stapled gastrojejunostomy (GJ) from the transoral to the transabdominal approach along with more vigilant use of wound protection reduced wound infection rates from 6% to 1.3%.

Dr. Dang noted that SSI has been reported as the most common hospital-acquired complication in bariatric surgery, with reported rates of between 1% and 10%. A 2014 analysis of the American College of Surgeons National Surgical Quality Improvement Program database reported an SSI rate of 1.8% (Surg Endosc. 2014;28:3285-92). Although these rates are low, Dr. Dang explained that his group wanted to identify factors associated with SSI within 30 days of bariatric surgery. They analyzed outcomes data of 274,187 patients in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database who had bariatric surgery in 2015 and 2016 (196,608 by laparoscopic sleeve gastrectomy [SG] and 77,579 laparoscopic Roux-en-Y gastric bypass [RYGB]). Their analysis determined an incisional SSI rate of 0.47% (n = 1,291). “Incisional SSI rates were four times higher for laparoscopic RYGB: 1.04% vs. 0.25%,” Dr. Dang said.

On multivariable logistic regression, the adjusted odds ratio of SSI after RYGB vs. SG was 3.13 (P less than .001). Other significant risk factors were chronic steroid or immunosuppressant use (odds ratio, 1.75; P = .001), female sex (OR, 1.48; P less than .001) and history of gastroesophageal reflux disease (OR, 1.45; P less than .001). Other factors with a 21%-31% greater risk of SSI were white race (P = .002), history of diabetes (P less than .001), hypertension (P less than .001), obstructive sleep apnea (P = .001), and longer operation times (P less than .001). Each single-digit increase in body mass index increased risk by 3%, and older age actually had a protective effect for unknown reasons, Dr. Dang noted.

The BariWound tool assigns points to each risk factor. Each hour of operation time and each 10 kg/m² of weight carry a value of 1 point, with partial points allowed. RYGB equals 5 points, and chronic steroid/immunosuppressant use, 4 points. The tool assigns risk to four categories based on score and 30-day SSI rate:

• Low, less than 15 (1% risk of SSI).
• Moderate, 15-21.9 (1%-5%).
• High, 22-26.9 (5%-10%).
• Very high, greater than 27 (greater than 10%).

“The BariWound tool can help to inform clinical decision making so patients can know they’re at higher risk, and this could allow for us to target high-risk patients with preventive packages, such as the Cleveland Clinic Technique of wound protection, wound irrigation, and wound packing as a resource-saving measure,” Dr. Dang said. “Targeting high-risk populations can reduce cost and operating time.”

Richard Kirkner/MDedge NEws

Dr. Weber reported on her institution’s study of SSIs using two different methods for circular stapling of GJ that involved two different surgeons who performed 333 RYGB procedures from January 2016 to March 2018. Surgeon “A” had traditionally used the transoral technique without wound protection to insert the anvil of the stapler; surgeon “B” used wound protection and the transabdominal technique for stapler insertion. Wound protection involves draping of the stapler with sterile plastic.

“In a quarterly review, we detected a higher than expected wound complication rate of 6%,” Dr. Weber said. “Of particular concern was the development of five recent wound infection cases, which all occurred in the transoral group for a rate of 8.9% in that cohort.”

That left the quality team questioning the safety profile of the transoral technique, Dr. Weber said. “We wanted to know why and whether or not the main contributor to the development of a wound infection was the technique for the anvil introduction or was it the difference between surgeons using wound protection.”

Halfway through the study period, surgeon A made two modifications: He adopted the transabdominal technique for a subset of patients; and because of the surgeon’s comfort level and expertise with the transoral approach, he continued using that approach but added wound protection. Surgeon B continued with the transabdominal approach with wound protection. The share of transabdominal insertions in the study population increased from 69.2% before the change to 75% after. Demographics between the pre- and postchange patient populations were similar, as were the rates of revision surgery between the two groups.

“We noticed a significant reduction in total wound complications from 6% to 1.3%, and we noticed a complete elimination of surgical site infections after adding wound protection to the transoral technique,” Dr. Weber said.

Dr. Weber noted a number of limitations with the study: its retrospective nature; the lack of control for other intraoperative factors that contribute to SSIs; relatively low incidence of SSI; and surgeon’s choice to determine the technique of anvil insertion.

“We found that our quality improvement intervention was efficacious and decided that it was not the technique of anvil insertion, but it was the wound protection that was key to preventing wound infections, as we saw complete elimination after we added wound protection to the transoral technique,” Dr. Weber said. “Using proper precautions with the circular stapler and anastomosis can be done using either technique for anvil insertion. Overall self-assessment of outcomes leads to best practice.”

Dr. Dang had no financial relationships to disclose. Dr. Weber’s coauthor Leena Khatian, MD, MPH, disclosed relationships with Torax Medical, Medtronic, and Gore.

SOURCES: Weber C et al. SAGES 2109, Presentation S049; Dang J et al. SAGES 2019, Presentation S050.

BALTIMORE – Most infants prenatally exposed to Zika showed relatively normal neurodevelopment if their fetal MRI and birth head circumference were normal, but others with similarly initial normal measures appeared to struggle with social cognition and mobility as they got older, according to a new study.

“I think we need to be cautious with saying that these children are normal when these normal-appearing children may not be doing as well as we think,” lead author Sarah Mulkey, MD, of Children’s National Health System and George Washington University, Washington, said in an interview. “While most children are showing fairly normal development, there are some children who are … becoming more abnormal over time.”

Dr. Mulkey shared her findings at the Pediatric Academic Societies annual meeting. She and her colleagues had previously published a prospective study of 82 Zika-exposed infants’ fetal brain MRIs. In their new study, they followed up with the 78 Colombian infants from that study whose fetal neuroimaging and birth head circumstance had been normal.

The researchers used the Alberta Infant Motor Scale (AIMS) and the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA) to evaluate 72 of the children, 34 of whom underwent assessment twice. Forty of the children were an average 5.7 months old when evaluated, and 66 were an average 13.5 months old.

As the children got older, their overall WIDEA z-score and their subscores in the social cognition domain and especially in the mobility domain trended downward. Three of the children had AIMS scores two standard deviations below normal, but the rest fell within the normal range.

Their WIDEA communication z-score hovered relatively close to the norm, but self-care also showed a very slight slope downward, albeit not as substantially as in the social cognition and mobility domains.

The younger a child is, the fewer skills they generally show related to neurocognitive development, Dr. Mulkey explained. But as they grow older and are expected to show more skills, it becomes more apparent where gaps and delays might exist.

“We can see that there are a lot of kids doing well, but some of these kids certainly are not,” she said. “Until children have a long time to develop, you really can’t see these changes unless you follow them long-term.”

The researchers also looked separately at a subgroup of 19 children (26%) whose cranial ultrasounds showed mild nonspecific findings. These findings – such as lenticulostriate vasculopathy, choroid plexus cysts, subependymal cysts and calcifications – do not usually indicate any problems, but they appeared in a quarter of this population, considerably more than the approximately 5% typically seen in the general population, Dr. Mulkey said.

BALTIMORE – Most infants prenatally exposed to Zika showed relatively normal neurodevelopment if their fetal MRI and birth head circumference were normal, but others with similarly initial normal measures appeared to struggle with social cognition and mobility as they got older, according to a new study.

“I think we need to be cautious with saying that these children are normal when these normal-appearing children may not be doing as well as we think,” lead author Sarah Mulkey, MD, of Children’s National Health System and George Washington University, Washington, said in an interview. “While most children are showing fairly normal development, there are some children who are … becoming more abnormal over time.”

Dr. Mulkey shared her findings at the Pediatric Academic Societies annual meeting. She and her colleagues had previously published a prospective study of 82 Zika-exposed infants’ fetal brain MRIs. In their new study, they followed up with the 78 Colombian infants from that study whose fetal neuroimaging and birth head circumstance had been normal.

The researchers used the Alberta Infant Motor Scale (AIMS) and the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA) to evaluate 72 of the children, 34 of whom underwent assessment twice. Forty of the children were an average 5.7 months old when evaluated, and 66 were an average 13.5 months old.

As the children got older, their overall WIDEA z-score and their subscores in the social cognition domain and especially in the mobility domain trended downward. Three of the children had AIMS scores two standard deviations below normal, but the rest fell within the normal range.

Their WIDEA communication z-score hovered relatively close to the norm, but self-care also showed a very slight slope downward, albeit not as substantially as in the social cognition and mobility domains.

The younger a child is, the fewer skills they generally show related to neurocognitive development, Dr. Mulkey explained. But as they grow older and are expected to show more skills, it becomes more apparent where gaps and delays might exist.

“We can see that there are a lot of kids doing well, but some of these kids certainly are not,” she said. “Until children have a long time to develop, you really can’t see these changes unless you follow them long-term.”

The researchers also looked separately at a subgroup of 19 children (26%) whose cranial ultrasounds showed mild nonspecific findings. These findings – such as lenticulostriate vasculopathy, choroid plexus cysts, subependymal cysts and calcifications – do not usually indicate any problems, but they appeared in a quarter of this population, considerably more than the approximately 5% typically seen in the general population, Dr. Mulkey said.

BALTIMORE – Most infants prenatally exposed to Zika showed relatively normal neurodevelopment if their fetal MRI and birth head circumference were normal, but others with similarly initial normal measures appeared to struggle with social cognition and mobility as they got older, according to a new study.

“I think we need to be cautious with saying that these children are normal when these normal-appearing children may not be doing as well as we think,” lead author Sarah Mulkey, MD, of Children’s National Health System and George Washington University, Washington, said in an interview. “While most children are showing fairly normal development, there are some children who are … becoming more abnormal over time.”

Dr. Mulkey shared her findings at the Pediatric Academic Societies annual meeting. She and her colleagues had previously published a prospective study of 82 Zika-exposed infants’ fetal brain MRIs. In their new study, they followed up with the 78 Colombian infants from that study whose fetal neuroimaging and birth head circumstance had been normal.

The researchers used the Alberta Infant Motor Scale (AIMS) and the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA) to evaluate 72 of the children, 34 of whom underwent assessment twice. Forty of the children were an average 5.7 months old when evaluated, and 66 were an average 13.5 months old.

As the children got older, their overall WIDEA z-score and their subscores in the social cognition domain and especially in the mobility domain trended downward. Three of the children had AIMS scores two standard deviations below normal, but the rest fell within the normal range.

Their WIDEA communication z-score hovered relatively close to the norm, but self-care also showed a very slight slope downward, albeit not as substantially as in the social cognition and mobility domains.

The younger a child is, the fewer skills they generally show related to neurocognitive development, Dr. Mulkey explained. But as they grow older and are expected to show more skills, it becomes more apparent where gaps and delays might exist.

“We can see that there are a lot of kids doing well, but some of these kids certainly are not,” she said. “Until children have a long time to develop, you really can’t see these changes unless you follow them long-term.”

The researchers also looked separately at a subgroup of 19 children (26%) whose cranial ultrasounds showed mild nonspecific findings. These findings – such as lenticulostriate vasculopathy, choroid plexus cysts, subependymal cysts and calcifications – do not usually indicate any problems, but they appeared in a quarter of this population, considerably more than the approximately 5% typically seen in the general population, Dr. Mulkey said.