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Biologic approved for moderate to severe psoriasis in adolescents
The Food and Drug Administration approval of ustekinumab has been expanded to include adolescents aged 12 and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, based on the results of a phase 3 study.
The manufacturer, Janssen Biotech, announced the expanded indication in a press release on Oct. 13.
Ustekinumab, an interleukin-12 and -23 antagonist administered subcutaneously, was first approved by the FDA in 2009 for the same indication in adults; it is also approved for adults with active psoriatic arthritis, and for adults with moderately to severely active Crohn’s disease.
Ustekinumab is marketed as Stelara.
The Food and Drug Administration approval of ustekinumab has been expanded to include adolescents aged 12 and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, based on the results of a phase 3 study.
The manufacturer, Janssen Biotech, announced the expanded indication in a press release on Oct. 13.
Ustekinumab, an interleukin-12 and -23 antagonist administered subcutaneously, was first approved by the FDA in 2009 for the same indication in adults; it is also approved for adults with active psoriatic arthritis, and for adults with moderately to severely active Crohn’s disease.
Ustekinumab is marketed as Stelara.
The Food and Drug Administration approval of ustekinumab has been expanded to include adolescents aged 12 and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, based on the results of a phase 3 study.
The manufacturer, Janssen Biotech, announced the expanded indication in a press release on Oct. 13.
Ustekinumab, an interleukin-12 and -23 antagonist administered subcutaneously, was first approved by the FDA in 2009 for the same indication in adults; it is also approved for adults with active psoriatic arthritis, and for adults with moderately to severely active Crohn’s disease.
Ustekinumab is marketed as Stelara.
Irregular Erythematous Patch on the Face of an Infant
The Diagnosis: Phakomatosis Pigmentovascularis With Sturge-Weber Syndrome
The erythematous patches were identified as capillary malformations (port-wine stains) and the slate gray pigmentary changes as dermal melanocytosis (Mongolian spots)(Figure). In fact, the diagnosis of phakomatosis pigmentovascularis (PPV) type II requires dermal melanocytosis and capillary malformation with and without nevus anemicus.1 In one case series, 46% (7/15) of patients with PPV had nevus anemicus2 but our patient did not.
Phakomatosis pigmentovascularis was divided into 4 types in 1985,3 then later 5 types.4 Subcategories of the 5 types include type A, which denotes a lack of extracutaneous involvement, and type B, which is used when internal manifestations have been exhibited. Since 1947, approximately 222 cases of PPV have been described in the literature.2
A case of PPV associated with Sturge-Weber syndrome (SWS) was reported in 1997.5 Since then, PPV occasionally has been linked with SWS,5-9 though there have been other syndromic associations including Klippel-Trenaunay-Weber syndrome and melanosis oculi.2 The incidence and prevalence of overlap of PPV and SWS is unknown but is likely to be rare. In our case, magnetic resonance imaging of the patient's brain did not reveal the characteristic tram-track appearance of SWS; however, the diagnosis of SWS type II only requires facial angioma with or without glaucoma.9,10 Most cases of PPV originate from Japan, Argentina, and Mexico.2 Interestingly, our patient's parents were both of Mexican ancestry. Phakomatosis pigmentovascularis type IIb is the most common, followed by type IIa.2 Most cases have been described as sporadic, though our patient's mother also exhibited a port-wine stain on the right neck, suggesting a possible genetic association.
The etiology of PPV has been postulated as twin spotting or didymosis (Greek for twin), most commonly seen in plants and animals. A previous review defined twin spotting as 2 mutant tissues situated adjacent to one another and unique from the normal tissue surrounding both of them.2 When the cell loses its heterozygosity, this phenomenon appears. An alternative etiology supplants that a drug or virus toxic to the nervous system causes aberrant angioblasts and melanoblasts.11,12 The etiology of SWS also is unknown, though vasomotor instability has been postulated as a cause.6,13
It is important to exclude associated internal organ involvement with both of these syndromes because approximately 50% of PPV cases have extracutaneous organ involvement.2,14 In fact, PPV is known to involve the brain, skeletal system, and eye, potentially manifesting as deafness, hydrocephalus, extremity overgrowth, scoliosis, cataracts, and more.2 Patients with SWS often exhibit brain and eye symptoms including seizures.1 To screen for extracutaneous involvement, multiple imaging studies should be performed. In our patient, an echocardiogram revealed a patent foramen ovale and normal cardiac anatomy for his age. Brain imaging revealed a hypoplastic left sigmoid and transverse sinus without venous thrombosis and unremarkable appearance of the brain. An ultrasound of the liver, spleen, kidneys, and pancreas revealed no evidence of solid, cystic, or vascular lesions, though the gallbladder exhibited hyperechoic areas.
To manage the skin lesions, some authors recommend Q-switched lasers for pigmented lesions and pulsed dye lasers for capillary malformations.15 Paller and Mancini1 cited evidence that pulsed dye laser treatment before the age of 1 year may offer a psychological advantage, while other views have been offered.16 Some physicians believe that no urgent treatment of capillary malformations is needed unless internal organs are involved.2,15
- Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 4th ed. New York, NY: Elsevier/Saunders; 2011.
- Fernández-Guarino M, Boixeda P, de Las Heras E, et al. Phakomatosis pigmentovascularis: clinical findings in 15 patients and review of the literature. J Am Acad Dermatol. 2008;58:88-93.
- Hasegawa Y, Yasuhara M. Phakomatosis pigmentovascularis type VIa. Arch Dermatol. 1985;121:651-655.
- Torrelo A, Zambrano A, Happle R. Cutis marmorata telangiectatica congenita and extensive Mongolian spots: type V phacomatosis pigmentovascularis. Br J Dermatol. 2003;148:342-345.
- Teekhasaenee C, Ritch R. Glaucoma in phakomatosis pigmentovascularis. Ophthalmology. 1997;104:150-157.
- Patil B, Sinha G, Nayak B, et al. Bilateral Sturge-Weber and phakomatosis pigmentovascularis with glaucoma, an overlap syndrome [published online May 6, 2015]. Case Rep Ophthalmol Med. 2015;2015:106932.
- Hagiwara K, Uezato H, Nonaka S. Phacomatosis pigmentovascularis type IIb associated with Sturge-Weber syndrome and pyogenic granuloma. J Dermatol. 1998;25:721-729.
- Al Robaee A, Banka N, Alfadley A. Phakomatosis pigmentovascularis type IIb associated with Sturge-Weber syndrome. Pediatr Dermatol. 2004;21:642-645.
- Yang Y, Guo X, Xu J, et al. Phakomatosis pigmentovascularis associated with Sturge-Weber syndrome, ota nevus, and congenital glaucoma. Medicine (Baltimore). 2015;94:E1025.
- Roach ES. Neurocutaneous syndromes. Pediatr Clin North Am. 1992;39:591-620.
- Happle R. Mosaicism in human skin, understanding the patterns and mechanisms. Arch Dermatol. 1993;129:1460-1470.
- Happle R. Loss of heterozygosity in human skin. J Am Acad Dermatol. 1999;85:355-358.
- Comi AM. Pathophysiology of Sturge-Weber syndrome. J Child Neurol. 2003;18:509-516.
- Kim YC, Park HJ, Cinn YW. Phakomatosis pigmentovascularis type IIa with generalized vitiligo. Br J Dermatol. 2002;147:1028-1029.
- Brittain P, Walsh EJ, Smidt AC. Blotchy baby: a case of phakomatosis pigmentovascularis [published online February 1, 2013]. J Pediatr. 2013;162:1293.
- Van der Horst CM, Koster PH, de Borgie CA, et al. Effect of the timing of treatment of port-wine stains with the flash-lamp-pumped pulsed-dye laser. N Engl J Med. 1998;338:1028-1033.
The Diagnosis: Phakomatosis Pigmentovascularis With Sturge-Weber Syndrome
The erythematous patches were identified as capillary malformations (port-wine stains) and the slate gray pigmentary changes as dermal melanocytosis (Mongolian spots)(Figure). In fact, the diagnosis of phakomatosis pigmentovascularis (PPV) type II requires dermal melanocytosis and capillary malformation with and without nevus anemicus.1 In one case series, 46% (7/15) of patients with PPV had nevus anemicus2 but our patient did not.
Phakomatosis pigmentovascularis was divided into 4 types in 1985,3 then later 5 types.4 Subcategories of the 5 types include type A, which denotes a lack of extracutaneous involvement, and type B, which is used when internal manifestations have been exhibited. Since 1947, approximately 222 cases of PPV have been described in the literature.2
A case of PPV associated with Sturge-Weber syndrome (SWS) was reported in 1997.5 Since then, PPV occasionally has been linked with SWS,5-9 though there have been other syndromic associations including Klippel-Trenaunay-Weber syndrome and melanosis oculi.2 The incidence and prevalence of overlap of PPV and SWS is unknown but is likely to be rare. In our case, magnetic resonance imaging of the patient's brain did not reveal the characteristic tram-track appearance of SWS; however, the diagnosis of SWS type II only requires facial angioma with or without glaucoma.9,10 Most cases of PPV originate from Japan, Argentina, and Mexico.2 Interestingly, our patient's parents were both of Mexican ancestry. Phakomatosis pigmentovascularis type IIb is the most common, followed by type IIa.2 Most cases have been described as sporadic, though our patient's mother also exhibited a port-wine stain on the right neck, suggesting a possible genetic association.
The etiology of PPV has been postulated as twin spotting or didymosis (Greek for twin), most commonly seen in plants and animals. A previous review defined twin spotting as 2 mutant tissues situated adjacent to one another and unique from the normal tissue surrounding both of them.2 When the cell loses its heterozygosity, this phenomenon appears. An alternative etiology supplants that a drug or virus toxic to the nervous system causes aberrant angioblasts and melanoblasts.11,12 The etiology of SWS also is unknown, though vasomotor instability has been postulated as a cause.6,13
It is important to exclude associated internal organ involvement with both of these syndromes because approximately 50% of PPV cases have extracutaneous organ involvement.2,14 In fact, PPV is known to involve the brain, skeletal system, and eye, potentially manifesting as deafness, hydrocephalus, extremity overgrowth, scoliosis, cataracts, and more.2 Patients with SWS often exhibit brain and eye symptoms including seizures.1 To screen for extracutaneous involvement, multiple imaging studies should be performed. In our patient, an echocardiogram revealed a patent foramen ovale and normal cardiac anatomy for his age. Brain imaging revealed a hypoplastic left sigmoid and transverse sinus without venous thrombosis and unremarkable appearance of the brain. An ultrasound of the liver, spleen, kidneys, and pancreas revealed no evidence of solid, cystic, or vascular lesions, though the gallbladder exhibited hyperechoic areas.
To manage the skin lesions, some authors recommend Q-switched lasers for pigmented lesions and pulsed dye lasers for capillary malformations.15 Paller and Mancini1 cited evidence that pulsed dye laser treatment before the age of 1 year may offer a psychological advantage, while other views have been offered.16 Some physicians believe that no urgent treatment of capillary malformations is needed unless internal organs are involved.2,15
The Diagnosis: Phakomatosis Pigmentovascularis With Sturge-Weber Syndrome
The erythematous patches were identified as capillary malformations (port-wine stains) and the slate gray pigmentary changes as dermal melanocytosis (Mongolian spots)(Figure). In fact, the diagnosis of phakomatosis pigmentovascularis (PPV) type II requires dermal melanocytosis and capillary malformation with and without nevus anemicus.1 In one case series, 46% (7/15) of patients with PPV had nevus anemicus2 but our patient did not.
Phakomatosis pigmentovascularis was divided into 4 types in 1985,3 then later 5 types.4 Subcategories of the 5 types include type A, which denotes a lack of extracutaneous involvement, and type B, which is used when internal manifestations have been exhibited. Since 1947, approximately 222 cases of PPV have been described in the literature.2
A case of PPV associated with Sturge-Weber syndrome (SWS) was reported in 1997.5 Since then, PPV occasionally has been linked with SWS,5-9 though there have been other syndromic associations including Klippel-Trenaunay-Weber syndrome and melanosis oculi.2 The incidence and prevalence of overlap of PPV and SWS is unknown but is likely to be rare. In our case, magnetic resonance imaging of the patient's brain did not reveal the characteristic tram-track appearance of SWS; however, the diagnosis of SWS type II only requires facial angioma with or without glaucoma.9,10 Most cases of PPV originate from Japan, Argentina, and Mexico.2 Interestingly, our patient's parents were both of Mexican ancestry. Phakomatosis pigmentovascularis type IIb is the most common, followed by type IIa.2 Most cases have been described as sporadic, though our patient's mother also exhibited a port-wine stain on the right neck, suggesting a possible genetic association.
The etiology of PPV has been postulated as twin spotting or didymosis (Greek for twin), most commonly seen in plants and animals. A previous review defined twin spotting as 2 mutant tissues situated adjacent to one another and unique from the normal tissue surrounding both of them.2 When the cell loses its heterozygosity, this phenomenon appears. An alternative etiology supplants that a drug or virus toxic to the nervous system causes aberrant angioblasts and melanoblasts.11,12 The etiology of SWS also is unknown, though vasomotor instability has been postulated as a cause.6,13
It is important to exclude associated internal organ involvement with both of these syndromes because approximately 50% of PPV cases have extracutaneous organ involvement.2,14 In fact, PPV is known to involve the brain, skeletal system, and eye, potentially manifesting as deafness, hydrocephalus, extremity overgrowth, scoliosis, cataracts, and more.2 Patients with SWS often exhibit brain and eye symptoms including seizures.1 To screen for extracutaneous involvement, multiple imaging studies should be performed. In our patient, an echocardiogram revealed a patent foramen ovale and normal cardiac anatomy for his age. Brain imaging revealed a hypoplastic left sigmoid and transverse sinus without venous thrombosis and unremarkable appearance of the brain. An ultrasound of the liver, spleen, kidneys, and pancreas revealed no evidence of solid, cystic, or vascular lesions, though the gallbladder exhibited hyperechoic areas.
To manage the skin lesions, some authors recommend Q-switched lasers for pigmented lesions and pulsed dye lasers for capillary malformations.15 Paller and Mancini1 cited evidence that pulsed dye laser treatment before the age of 1 year may offer a psychological advantage, while other views have been offered.16 Some physicians believe that no urgent treatment of capillary malformations is needed unless internal organs are involved.2,15
- Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 4th ed. New York, NY: Elsevier/Saunders; 2011.
- Fernández-Guarino M, Boixeda P, de Las Heras E, et al. Phakomatosis pigmentovascularis: clinical findings in 15 patients and review of the literature. J Am Acad Dermatol. 2008;58:88-93.
- Hasegawa Y, Yasuhara M. Phakomatosis pigmentovascularis type VIa. Arch Dermatol. 1985;121:651-655.
- Torrelo A, Zambrano A, Happle R. Cutis marmorata telangiectatica congenita and extensive Mongolian spots: type V phacomatosis pigmentovascularis. Br J Dermatol. 2003;148:342-345.
- Teekhasaenee C, Ritch R. Glaucoma in phakomatosis pigmentovascularis. Ophthalmology. 1997;104:150-157.
- Patil B, Sinha G, Nayak B, et al. Bilateral Sturge-Weber and phakomatosis pigmentovascularis with glaucoma, an overlap syndrome [published online May 6, 2015]. Case Rep Ophthalmol Med. 2015;2015:106932.
- Hagiwara K, Uezato H, Nonaka S. Phacomatosis pigmentovascularis type IIb associated with Sturge-Weber syndrome and pyogenic granuloma. J Dermatol. 1998;25:721-729.
- Al Robaee A, Banka N, Alfadley A. Phakomatosis pigmentovascularis type IIb associated with Sturge-Weber syndrome. Pediatr Dermatol. 2004;21:642-645.
- Yang Y, Guo X, Xu J, et al. Phakomatosis pigmentovascularis associated with Sturge-Weber syndrome, ota nevus, and congenital glaucoma. Medicine (Baltimore). 2015;94:E1025.
- Roach ES. Neurocutaneous syndromes. Pediatr Clin North Am. 1992;39:591-620.
- Happle R. Mosaicism in human skin, understanding the patterns and mechanisms. Arch Dermatol. 1993;129:1460-1470.
- Happle R. Loss of heterozygosity in human skin. J Am Acad Dermatol. 1999;85:355-358.
- Comi AM. Pathophysiology of Sturge-Weber syndrome. J Child Neurol. 2003;18:509-516.
- Kim YC, Park HJ, Cinn YW. Phakomatosis pigmentovascularis type IIa with generalized vitiligo. Br J Dermatol. 2002;147:1028-1029.
- Brittain P, Walsh EJ, Smidt AC. Blotchy baby: a case of phakomatosis pigmentovascularis [published online February 1, 2013]. J Pediatr. 2013;162:1293.
- Van der Horst CM, Koster PH, de Borgie CA, et al. Effect of the timing of treatment of port-wine stains with the flash-lamp-pumped pulsed-dye laser. N Engl J Med. 1998;338:1028-1033.
- Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 4th ed. New York, NY: Elsevier/Saunders; 2011.
- Fernández-Guarino M, Boixeda P, de Las Heras E, et al. Phakomatosis pigmentovascularis: clinical findings in 15 patients and review of the literature. J Am Acad Dermatol. 2008;58:88-93.
- Hasegawa Y, Yasuhara M. Phakomatosis pigmentovascularis type VIa. Arch Dermatol. 1985;121:651-655.
- Torrelo A, Zambrano A, Happle R. Cutis marmorata telangiectatica congenita and extensive Mongolian spots: type V phacomatosis pigmentovascularis. Br J Dermatol. 2003;148:342-345.
- Teekhasaenee C, Ritch R. Glaucoma in phakomatosis pigmentovascularis. Ophthalmology. 1997;104:150-157.
- Patil B, Sinha G, Nayak B, et al. Bilateral Sturge-Weber and phakomatosis pigmentovascularis with glaucoma, an overlap syndrome [published online May 6, 2015]. Case Rep Ophthalmol Med. 2015;2015:106932.
- Hagiwara K, Uezato H, Nonaka S. Phacomatosis pigmentovascularis type IIb associated with Sturge-Weber syndrome and pyogenic granuloma. J Dermatol. 1998;25:721-729.
- Al Robaee A, Banka N, Alfadley A. Phakomatosis pigmentovascularis type IIb associated with Sturge-Weber syndrome. Pediatr Dermatol. 2004;21:642-645.
- Yang Y, Guo X, Xu J, et al. Phakomatosis pigmentovascularis associated with Sturge-Weber syndrome, ota nevus, and congenital glaucoma. Medicine (Baltimore). 2015;94:E1025.
- Roach ES. Neurocutaneous syndromes. Pediatr Clin North Am. 1992;39:591-620.
- Happle R. Mosaicism in human skin, understanding the patterns and mechanisms. Arch Dermatol. 1993;129:1460-1470.
- Happle R. Loss of heterozygosity in human skin. J Am Acad Dermatol. 1999;85:355-358.
- Comi AM. Pathophysiology of Sturge-Weber syndrome. J Child Neurol. 2003;18:509-516.
- Kim YC, Park HJ, Cinn YW. Phakomatosis pigmentovascularis type IIa with generalized vitiligo. Br J Dermatol. 2002;147:1028-1029.
- Brittain P, Walsh EJ, Smidt AC. Blotchy baby: a case of phakomatosis pigmentovascularis [published online February 1, 2013]. J Pediatr. 2013;162:1293.
- Van der Horst CM, Koster PH, de Borgie CA, et al. Effect of the timing of treatment of port-wine stains with the flash-lamp-pumped pulsed-dye laser. N Engl J Med. 1998;338:1028-1033.
A newborn presented with an irregular and well-demarcated erythematous patch on the face, trunk, buttocks, and toes on the left foot. Another red patch was present on the right side of the face, while a slate gray patch covered the flanks and back. The limbs appeared symmetric and he exhibited no gross deformities. On close physical examination, he was noted to have a cloudy left eye. An ophthalmology consultation revealed a choroidal hemangioma and congenital glaucoma in the left eye.
Study supports prophylaxis in kids with ALL
Results of an observational study support targeted antibacterial prophylaxis in children undergoing induction therapy for acute lymphoblastic leukemia (ALL).
Prophylaxis effectively prevented febrile neutropenia and systemic infection in the children studied.
Prophylaxis with the drug levofloxacin reduced the use of treatment antibiotics and the incidence of Clostridium difficile infection.
“This research provides the first major evidence supporting targeted use of antibacterial prophylaxis for at-risk pediatric ALL patients, particularly use of the broad-spectrum antibiotic levofloxacin,” said study author Joshua Wolf, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“Prophylactic antibiotic therapy with levofloxacin is routine for at-risk adult ALL patients, but it has remained controversial in children. Until this study, evidence supporting the safety and efficacy of prophylactic antibiotic therapy in children with ALL has been sparse.”
Dr Wolf and his colleagues described their study in Clinical Infectious Diseases.
The study included 344 patients newly diagnosed with ALL who were enrolled in the St. Jude Total XVI clinical trial (NCT00549848). Patients were enrolled from 2007 to 2016.
Until July 2014, the patients received prophylactic antibiotic therapy at the discretion of their physicians. Patients typically received cefepime, ciprofloxacin, or vancomycin plus cefepime or ciprofloxacin. And prophylaxis was typically started at the onset of neutropenia after chemotherapy.
Beginning in August 2014, hospital treatment guidelines changed to recommend prophylactic levofloxacin during induction for ALL patients who develop neutropenia expected to last at least 7 days.
Dr Wolf and his colleagues used the change to compare infection rates and other questions in the following patient groups.
| Patient characteristics | No prophylaxis (n=173) | Levofloxacin prophylaxis (n=69) | Other prophylaxis (n=102) |
| Median age in years (range) | 5.8 (3-11.9) | 6.8 (3.9-11.1) | 7 (3.6-11.9) |
| B-ALL | 83% | 78% | 79% |
| Low-risk ALL | 51% | 54% | 50% |
| Standard-risk ALL | 47% | 41% | 42% |
| High-risk ALL | 2% | 6% | 8% |
| Median duration of neutropenia in days (range) | 17 (11-24) | 18 (12-23) | 20 (17-25) |
| Median duration of profound neutropenia in days (range) | 6 (2-13) | 7 (4-12) | 11 (5-16) |
Results
Researchers reported that patients with neutropenia who received any prophylactic therapy were far less likely than those who did not to develop fever, documented or likely infections, or bloodstream infections.
In a multivariate analysis, the adjusted odds ratios in patients who received prophylaxis, compared to those who did not, were as follows.
- Febrile neutropenia—0.23, P<0.001
- Febrile neutropenia with clinically documented infection—0.30, P=0.002
- Febrile neutropenia with microbiologically documented infection—0.25, P<0.001
- Clinically documented infection—0.54, P=0.02
- Microbiologically documented infection—0.40, P<0.001
- Bloodstream infection—0.30, P=0.008
- C difficile infection—0.38, P=0.04
- Likely bacterial infection—0.26, P<0.001
- Any enterocolitis—0.44, P=0.03.
Analysis also revealed that patients who received levofloxacin had a greater reduction in C difficile infection than patients who received other prophylaxis. The adjusted odds ratio was 0.04 (P<0.001).
However, there was no significant difference between the prophylaxis groups when it came to other infections.
Patients who received levofloxacin prophylaxis had significantly less exposure to other antibiotics than patients who received other prophylaxis or no prophylaxis.
This included exposure to cefepime/ceftazidime (P<0.001 for both comparisons), vancomycin (P<0.001 for both), meropenem (P<0.001 for both), and aminoglycosides (P=0.002 for no prophylaxis, P=0.04 for other prophylaxis).
The reduction in exposure to other antibiotics may partly explain why C difficile infections declined in levofloxacin-treated patients, Dr Wolf said.
He also noted that antibiotic resistance did not significantly increase in this study, despite the greater use of levofloxacin to prevent infections.
“We are cautiously optimistic that any impact of levofloxacin on antibacterial resistance will be balanced by the reduction in use of other antibiotics,” Dr Wolf said, “but long-term monitoring of antibiotic resistance patterns in young ALL patients will be needed to prove this.” 
Results of an observational study support targeted antibacterial prophylaxis in children undergoing induction therapy for acute lymphoblastic leukemia (ALL).
Prophylaxis effectively prevented febrile neutropenia and systemic infection in the children studied.
Prophylaxis with the drug levofloxacin reduced the use of treatment antibiotics and the incidence of Clostridium difficile infection.
“This research provides the first major evidence supporting targeted use of antibacterial prophylaxis for at-risk pediatric ALL patients, particularly use of the broad-spectrum antibiotic levofloxacin,” said study author Joshua Wolf, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“Prophylactic antibiotic therapy with levofloxacin is routine for at-risk adult ALL patients, but it has remained controversial in children. Until this study, evidence supporting the safety and efficacy of prophylactic antibiotic therapy in children with ALL has been sparse.”
Dr Wolf and his colleagues described their study in Clinical Infectious Diseases.
The study included 344 patients newly diagnosed with ALL who were enrolled in the St. Jude Total XVI clinical trial (NCT00549848). Patients were enrolled from 2007 to 2016.
Until July 2014, the patients received prophylactic antibiotic therapy at the discretion of their physicians. Patients typically received cefepime, ciprofloxacin, or vancomycin plus cefepime or ciprofloxacin. And prophylaxis was typically started at the onset of neutropenia after chemotherapy.
Beginning in August 2014, hospital treatment guidelines changed to recommend prophylactic levofloxacin during induction for ALL patients who develop neutropenia expected to last at least 7 days.
Dr Wolf and his colleagues used the change to compare infection rates and other questions in the following patient groups.
| Patient characteristics | No prophylaxis (n=173) | Levofloxacin prophylaxis (n=69) | Other prophylaxis (n=102) |
| Median age in years (range) | 5.8 (3-11.9) | 6.8 (3.9-11.1) | 7 (3.6-11.9) |
| B-ALL | 83% | 78% | 79% |
| Low-risk ALL | 51% | 54% | 50% |
| Standard-risk ALL | 47% | 41% | 42% |
| High-risk ALL | 2% | 6% | 8% |
| Median duration of neutropenia in days (range) | 17 (11-24) | 18 (12-23) | 20 (17-25) |
| Median duration of profound neutropenia in days (range) | 6 (2-13) | 7 (4-12) | 11 (5-16) |
Results
Researchers reported that patients with neutropenia who received any prophylactic therapy were far less likely than those who did not to develop fever, documented or likely infections, or bloodstream infections.
In a multivariate analysis, the adjusted odds ratios in patients who received prophylaxis, compared to those who did not, were as follows.
- Febrile neutropenia—0.23, P<0.001
- Febrile neutropenia with clinically documented infection—0.30, P=0.002
- Febrile neutropenia with microbiologically documented infection—0.25, P<0.001
- Clinically documented infection—0.54, P=0.02
- Microbiologically documented infection—0.40, P<0.001
- Bloodstream infection—0.30, P=0.008
- C difficile infection—0.38, P=0.04
- Likely bacterial infection—0.26, P<0.001
- Any enterocolitis—0.44, P=0.03.
Analysis also revealed that patients who received levofloxacin had a greater reduction in C difficile infection than patients who received other prophylaxis. The adjusted odds ratio was 0.04 (P<0.001).
However, there was no significant difference between the prophylaxis groups when it came to other infections.
Patients who received levofloxacin prophylaxis had significantly less exposure to other antibiotics than patients who received other prophylaxis or no prophylaxis.
This included exposure to cefepime/ceftazidime (P<0.001 for both comparisons), vancomycin (P<0.001 for both), meropenem (P<0.001 for both), and aminoglycosides (P=0.002 for no prophylaxis, P=0.04 for other prophylaxis).
The reduction in exposure to other antibiotics may partly explain why C difficile infections declined in levofloxacin-treated patients, Dr Wolf said.
He also noted that antibiotic resistance did not significantly increase in this study, despite the greater use of levofloxacin to prevent infections.
“We are cautiously optimistic that any impact of levofloxacin on antibacterial resistance will be balanced by the reduction in use of other antibiotics,” Dr Wolf said, “but long-term monitoring of antibiotic resistance patterns in young ALL patients will be needed to prove this.”
Results of an observational study support targeted antibacterial prophylaxis in children undergoing induction therapy for acute lymphoblastic leukemia (ALL).
Prophylaxis effectively prevented febrile neutropenia and systemic infection in the children studied.
Prophylaxis with the drug levofloxacin reduced the use of treatment antibiotics and the incidence of Clostridium difficile infection.
“This research provides the first major evidence supporting targeted use of antibacterial prophylaxis for at-risk pediatric ALL patients, particularly use of the broad-spectrum antibiotic levofloxacin,” said study author Joshua Wolf, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“Prophylactic antibiotic therapy with levofloxacin is routine for at-risk adult ALL patients, but it has remained controversial in children. Until this study, evidence supporting the safety and efficacy of prophylactic antibiotic therapy in children with ALL has been sparse.”
Dr Wolf and his colleagues described their study in Clinical Infectious Diseases.
The study included 344 patients newly diagnosed with ALL who were enrolled in the St. Jude Total XVI clinical trial (NCT00549848). Patients were enrolled from 2007 to 2016.
Until July 2014, the patients received prophylactic antibiotic therapy at the discretion of their physicians. Patients typically received cefepime, ciprofloxacin, or vancomycin plus cefepime or ciprofloxacin. And prophylaxis was typically started at the onset of neutropenia after chemotherapy.
Beginning in August 2014, hospital treatment guidelines changed to recommend prophylactic levofloxacin during induction for ALL patients who develop neutropenia expected to last at least 7 days.
Dr Wolf and his colleagues used the change to compare infection rates and other questions in the following patient groups.
| Patient characteristics | No prophylaxis (n=173) | Levofloxacin prophylaxis (n=69) | Other prophylaxis (n=102) |
| Median age in years (range) | 5.8 (3-11.9) | 6.8 (3.9-11.1) | 7 (3.6-11.9) |
| B-ALL | 83% | 78% | 79% |
| Low-risk ALL | 51% | 54% | 50% |
| Standard-risk ALL | 47% | 41% | 42% |
| High-risk ALL | 2% | 6% | 8% |
| Median duration of neutropenia in days (range) | 17 (11-24) | 18 (12-23) | 20 (17-25) |
| Median duration of profound neutropenia in days (range) | 6 (2-13) | 7 (4-12) | 11 (5-16) |
Results
Researchers reported that patients with neutropenia who received any prophylactic therapy were far less likely than those who did not to develop fever, documented or likely infections, or bloodstream infections.
In a multivariate analysis, the adjusted odds ratios in patients who received prophylaxis, compared to those who did not, were as follows.
- Febrile neutropenia—0.23, P<0.001
- Febrile neutropenia with clinically documented infection—0.30, P=0.002
- Febrile neutropenia with microbiologically documented infection—0.25, P<0.001
- Clinically documented infection—0.54, P=0.02
- Microbiologically documented infection—0.40, P<0.001
- Bloodstream infection—0.30, P=0.008
- C difficile infection—0.38, P=0.04
- Likely bacterial infection—0.26, P<0.001
- Any enterocolitis—0.44, P=0.03.
Analysis also revealed that patients who received levofloxacin had a greater reduction in C difficile infection than patients who received other prophylaxis. The adjusted odds ratio was 0.04 (P<0.001).
However, there was no significant difference between the prophylaxis groups when it came to other infections.
Patients who received levofloxacin prophylaxis had significantly less exposure to other antibiotics than patients who received other prophylaxis or no prophylaxis.
This included exposure to cefepime/ceftazidime (P<0.001 for both comparisons), vancomycin (P<0.001 for both), meropenem (P<0.001 for both), and aminoglycosides (P=0.002 for no prophylaxis, P=0.04 for other prophylaxis).
The reduction in exposure to other antibiotics may partly explain why C difficile infections declined in levofloxacin-treated patients, Dr Wolf said.
He also noted that antibiotic resistance did not significantly increase in this study, despite the greater use of levofloxacin to prevent infections.
“We are cautiously optimistic that any impact of levofloxacin on antibacterial resistance will be balanced by the reduction in use of other antibiotics,” Dr Wolf said, “but long-term monitoring of antibiotic resistance patterns in young ALL patients will be needed to prove this.”
W. Curt LaFrance Jr, MD
International parental attitudes of HPV vaccination have similarities, differences
A study comparing parental attitudes of the human papillomavirus (HPV) vaccine in three countries indicates both low and high HPV knowledge may be associated with lower rates of vaccination, and parents’ country and gender also impact the likelihood of adolescents being immunized, reported Brooke Nickel, of the University of Sydney, and associates.
Of 179 parents with a daughter aged 9-17 years from the United States, United Kingdom, or Australia who took part in an online HPV vaccine opinion survey in 2011, 59% reported that their daughters had received HPV vaccination – 43% in the United States cohort, 63% in the United Kingdom cohort, and 76% in the Australian cohort.
(P less than .001). Parents who had either low knowledge scores or high knowledge scores were less likely to have their daughters vaccinated; U.S. parents and men across all countries also were less likely to vaccinate their daughters.
Among the parents whose daughters did not receive the HPV vaccine, worry about the vaccine’s side effects was significantly more prevalent among the U.S. parents (61%) than among parents in the United Kingdom (36%) or among parents in Australia (15%) (P less than .05). U.S. parents who did not have their daughters get the HPV vaccine also were more likely to agree that getting all three HPV vaccine doses would be a “big hassle” (21%), compared with the United Kingdom cohort (0%) and the Australian cohort (8%) (P less than .05).
Parents from the United States also were significantly more likely to agree that the HPV vaccine was too new so they would want to wait before deciding to get it for their daughters (45%), compared with the parents in the United Kingdom (23%) and those in Australia (8%) (P less than .05).
“This finding was unexpected, given that advertising about HPV contributed to an increased awareness of HPV in the United States at the time of data collection. It is important to note, however, that this survey was conducted in 2011, and therefore attitudes of U.S. parents now may differ,” the researchers wrote.
Nonetheless, parents of unvaccinated daughters with higher knowledge scores overall were more likely to believe that they would want to be on the safe side and vaccinate their daughters at some time (74%) compared with parents who had lower knowledge scores (27%) (P less than .001).
“Parents from the United States with unvaccinated daughters more often believed that getting all three doses of the HPV vaccine would be a significant obstacle, not surprisingly as the HPV vaccine distribution in the United States is predominantly available through physicians’ clinics and medical centers, whereas in the United Kingdom and Australia, free school-based and catch-up programs are offered,” the investigators said.
Read more in Preventive Medicine Reports (2017 Oct 10. doi: 10.1016/j.pmedr.2017.10.005).
A study comparing parental attitudes of the human papillomavirus (HPV) vaccine in three countries indicates both low and high HPV knowledge may be associated with lower rates of vaccination, and parents’ country and gender also impact the likelihood of adolescents being immunized, reported Brooke Nickel, of the University of Sydney, and associates.
Of 179 parents with a daughter aged 9-17 years from the United States, United Kingdom, or Australia who took part in an online HPV vaccine opinion survey in 2011, 59% reported that their daughters had received HPV vaccination – 43% in the United States cohort, 63% in the United Kingdom cohort, and 76% in the Australian cohort.
(P less than .001). Parents who had either low knowledge scores or high knowledge scores were less likely to have their daughters vaccinated; U.S. parents and men across all countries also were less likely to vaccinate their daughters.
Among the parents whose daughters did not receive the HPV vaccine, worry about the vaccine’s side effects was significantly more prevalent among the U.S. parents (61%) than among parents in the United Kingdom (36%) or among parents in Australia (15%) (P less than .05). U.S. parents who did not have their daughters get the HPV vaccine also were more likely to agree that getting all three HPV vaccine doses would be a “big hassle” (21%), compared with the United Kingdom cohort (0%) and the Australian cohort (8%) (P less than .05).
Parents from the United States also were significantly more likely to agree that the HPV vaccine was too new so they would want to wait before deciding to get it for their daughters (45%), compared with the parents in the United Kingdom (23%) and those in Australia (8%) (P less than .05).
“This finding was unexpected, given that advertising about HPV contributed to an increased awareness of HPV in the United States at the time of data collection. It is important to note, however, that this survey was conducted in 2011, and therefore attitudes of U.S. parents now may differ,” the researchers wrote.
Nonetheless, parents of unvaccinated daughters with higher knowledge scores overall were more likely to believe that they would want to be on the safe side and vaccinate their daughters at some time (74%) compared with parents who had lower knowledge scores (27%) (P less than .001).
“Parents from the United States with unvaccinated daughters more often believed that getting all three doses of the HPV vaccine would be a significant obstacle, not surprisingly as the HPV vaccine distribution in the United States is predominantly available through physicians’ clinics and medical centers, whereas in the United Kingdom and Australia, free school-based and catch-up programs are offered,” the investigators said.
Read more in Preventive Medicine Reports (2017 Oct 10. doi: 10.1016/j.pmedr.2017.10.005).
A study comparing parental attitudes of the human papillomavirus (HPV) vaccine in three countries indicates both low and high HPV knowledge may be associated with lower rates of vaccination, and parents’ country and gender also impact the likelihood of adolescents being immunized, reported Brooke Nickel, of the University of Sydney, and associates.
Of 179 parents with a daughter aged 9-17 years from the United States, United Kingdom, or Australia who took part in an online HPV vaccine opinion survey in 2011, 59% reported that their daughters had received HPV vaccination – 43% in the United States cohort, 63% in the United Kingdom cohort, and 76% in the Australian cohort.
(P less than .001). Parents who had either low knowledge scores or high knowledge scores were less likely to have their daughters vaccinated; U.S. parents and men across all countries also were less likely to vaccinate their daughters.
Among the parents whose daughters did not receive the HPV vaccine, worry about the vaccine’s side effects was significantly more prevalent among the U.S. parents (61%) than among parents in the United Kingdom (36%) or among parents in Australia (15%) (P less than .05). U.S. parents who did not have their daughters get the HPV vaccine also were more likely to agree that getting all three HPV vaccine doses would be a “big hassle” (21%), compared with the United Kingdom cohort (0%) and the Australian cohort (8%) (P less than .05).
Parents from the United States also were significantly more likely to agree that the HPV vaccine was too new so they would want to wait before deciding to get it for their daughters (45%), compared with the parents in the United Kingdom (23%) and those in Australia (8%) (P less than .05).
“This finding was unexpected, given that advertising about HPV contributed to an increased awareness of HPV in the United States at the time of data collection. It is important to note, however, that this survey was conducted in 2011, and therefore attitudes of U.S. parents now may differ,” the researchers wrote.
Nonetheless, parents of unvaccinated daughters with higher knowledge scores overall were more likely to believe that they would want to be on the safe side and vaccinate their daughters at some time (74%) compared with parents who had lower knowledge scores (27%) (P less than .001).
“Parents from the United States with unvaccinated daughters more often believed that getting all three doses of the HPV vaccine would be a significant obstacle, not surprisingly as the HPV vaccine distribution in the United States is predominantly available through physicians’ clinics and medical centers, whereas in the United Kingdom and Australia, free school-based and catch-up programs are offered,” the investigators said.
Read more in Preventive Medicine Reports (2017 Oct 10. doi: 10.1016/j.pmedr.2017.10.005).
FROM PREVENTIVE MEDICINE REPORTS
Missed opportunities abound to give HPV vaccine to adolescent girls
, in a study of more than 14,000 fully insured teen girls, reported Claudia M. Espinosa, MD, of the division of pediatric infectious diseases, University of Louisville (Ky.), and her associates.
In a study of 14,588 girls in a fully insured commercial or Medicaid plan who turned 11 years old between Jan. 1, 2010, and Sept. 31, 2015, it was documented whether or not the girls received an HPV vaccine when they were given another adolescent vaccine – one or more doses of the Tdap vaccine and/or one or more doses of the 4-valent meningococcal conjugate vaccine (MenACWY vaccine).
Girls who started HPV vaccination were more likely than those who didn’t to receive the MenACWY (86% vs. 64%, respectively; P less than .0001) and Tdap (86% vs. 73%, respectively; P less than .0001) vaccines.
“A missed opportunity was defined as the absence of an HPV vaccine dose administered during any visit with a Tdap or MenACWY vaccine claim, any well-adolescent visit, or any encounter with a primary care provider, regardless of visit type,” the investigators said.
Of 10,987 visits when a Tdap or MenACWY vaccine dose was given, HPV vaccine was given at the same visit in only 37% of cases. An HPV vaccine was administered at only 26% of 12,621 of well-adolescent visits, and 42% of 14,195 other visits with primary care providers.
“The data also suggest that pediatricians and nonpediatricians alike are missing opportunities to administer the HPV vaccine when other adolescent vaccines are given,” Dr. Espinosa and her associates noted. “Future research should focus on communication strategies that might facilitate the conceptual ‘bundling’ of HPV vaccine with other adolescent vaccines in the provider’s office.”
Read more in the Journal of the Pediatric Infectious Diseases Society (2017 Sep 23. doi: 10.1093/jpids/pix067).
cnellist@frontlinemedcom.com
, in a study of more than 14,000 fully insured teen girls, reported Claudia M. Espinosa, MD, of the division of pediatric infectious diseases, University of Louisville (Ky.), and her associates.
In a study of 14,588 girls in a fully insured commercial or Medicaid plan who turned 11 years old between Jan. 1, 2010, and Sept. 31, 2015, it was documented whether or not the girls received an HPV vaccine when they were given another adolescent vaccine – one or more doses of the Tdap vaccine and/or one or more doses of the 4-valent meningococcal conjugate vaccine (MenACWY vaccine).
Girls who started HPV vaccination were more likely than those who didn’t to receive the MenACWY (86% vs. 64%, respectively; P less than .0001) and Tdap (86% vs. 73%, respectively; P less than .0001) vaccines.
“A missed opportunity was defined as the absence of an HPV vaccine dose administered during any visit with a Tdap or MenACWY vaccine claim, any well-adolescent visit, or any encounter with a primary care provider, regardless of visit type,” the investigators said.
Of 10,987 visits when a Tdap or MenACWY vaccine dose was given, HPV vaccine was given at the same visit in only 37% of cases. An HPV vaccine was administered at only 26% of 12,621 of well-adolescent visits, and 42% of 14,195 other visits with primary care providers.
“The data also suggest that pediatricians and nonpediatricians alike are missing opportunities to administer the HPV vaccine when other adolescent vaccines are given,” Dr. Espinosa and her associates noted. “Future research should focus on communication strategies that might facilitate the conceptual ‘bundling’ of HPV vaccine with other adolescent vaccines in the provider’s office.”
Read more in the Journal of the Pediatric Infectious Diseases Society (2017 Sep 23. doi: 10.1093/jpids/pix067).
cnellist@frontlinemedcom.com
, in a study of more than 14,000 fully insured teen girls, reported Claudia M. Espinosa, MD, of the division of pediatric infectious diseases, University of Louisville (Ky.), and her associates.
In a study of 14,588 girls in a fully insured commercial or Medicaid plan who turned 11 years old between Jan. 1, 2010, and Sept. 31, 2015, it was documented whether or not the girls received an HPV vaccine when they were given another adolescent vaccine – one or more doses of the Tdap vaccine and/or one or more doses of the 4-valent meningococcal conjugate vaccine (MenACWY vaccine).
Girls who started HPV vaccination were more likely than those who didn’t to receive the MenACWY (86% vs. 64%, respectively; P less than .0001) and Tdap (86% vs. 73%, respectively; P less than .0001) vaccines.
“A missed opportunity was defined as the absence of an HPV vaccine dose administered during any visit with a Tdap or MenACWY vaccine claim, any well-adolescent visit, or any encounter with a primary care provider, regardless of visit type,” the investigators said.
Of 10,987 visits when a Tdap or MenACWY vaccine dose was given, HPV vaccine was given at the same visit in only 37% of cases. An HPV vaccine was administered at only 26% of 12,621 of well-adolescent visits, and 42% of 14,195 other visits with primary care providers.
“The data also suggest that pediatricians and nonpediatricians alike are missing opportunities to administer the HPV vaccine when other adolescent vaccines are given,” Dr. Espinosa and her associates noted. “Future research should focus on communication strategies that might facilitate the conceptual ‘bundling’ of HPV vaccine with other adolescent vaccines in the provider’s office.”
Read more in the Journal of the Pediatric Infectious Diseases Society (2017 Sep 23. doi: 10.1093/jpids/pix067).
cnellist@frontlinemedcom.com
FROM THE JOURNAL OF THE PEDIATRIC INFECTIOUS DISEASES SOCIETY
Physical inactivity in youth is an independent risk factor for schizophrenia
PARIS – Low physical activity in childhood and adolescence was independently associated with later development of schizophrenia and other nonaffective psychotic disorders in the large, prospective, population-based Cardiovascular Risk in Young Finns cohort study, Jarmo Hietala, MD, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.
The key question now: Is this risk factor remediable? That is, will a pediatric exercise intervention that results in improved physical fitness also reduce the risk of later nonaffective psychosis? Given that there are really no downsides to physical activity, the Finnish data make a strong case for including exercise and physical activity interventions in investigational psychosis prevention programs targeting high-risk youth, according to Dr. Hietala, professor of psychiatry at the University of Turku (Finland).
Dr. Hietala and his coinvestigators tapped into comprehensive national registries in order to identify all study participants with a psychiatric diagnosis of sufficient severity to have resulted in hospitalization up to 2012. Forty-one patients were hospitalized for schizophrenia spectrum disorders, 47 for other forms of nonaffective psychosis, 43 for personality disorders, 111 for affective disorders, and 49 with alcohol and other substance use disorders.
In a multivariate analysis adjusted for sex, age, body mass index, birth weight, non-preterm birth, and maternal mental disorders, each 1-point decrement in the pediatric physical activity index was associated with a 26% increase in the risk of developing any nonaffective psychosis and, more specifically, a 43% increased risk of schizophrenia.
Moreover, nonparticipation in organized sports competitions was independently associated with a 2.58-fold increased risk of any nonaffective psychosis and a 4.88-fold increased risk of schizophrenia. And social isolation as reflected in spending less time in common activities with friends during leisure time was associated with a 71% increased risk of nonaffective psychosis and a 76% increased risk of schizophrenia.
Of note, schizophrenia was the only psychiatric disorder associated with low physical activity in childhood and adolescence. Sedentary youths were not at increased risk of later hospitalization for affective disorders or other forms of mental illness.
“Our results have relevance for preemptive psychiatry and provide rationale for including exercise in early interventions for psychosis,” the psychiatrist said.
Current programs aimed at preventing schizophrenia in youth at high risk because of family history typically emphasize avoidance of street drugs, the importance of seeking out constructive social interactions, stress reduction techniques, and cognitive-behavioral therapy aimed at promoting a positive world view.
Formal evaluation of physical activity as part of a preventive approach has a sound theoretic basis, according to Dr. Hietala. He cited an influential essay called “Rethinking Schizophrenia” by the then-director of the National Institute of Mental Health, Thomas R. Insel, MD. In that article, Dr. Insel highlights the past half-century of largely unsatisfactory results with pharmacotherapy and goes on to make the case for considering schizophrenia as a neurodevelopmental disorder in which, he argues, “psychosis is a late, potentially preventable stage of the illness” (Nature. 2010 Nov 11;468[7321]:187-93).
This view of schizophrenia as a neurodevelopmental disorder has quickly come to dominate thinking within the field. Dr. Hietala noted that the schizophrenia spectrum chapter in the DSM-5 includes a greater focus on abnormal behavior and catatonia as a core domain alongside classic features, such as delusions, hallucinations, negative symptoms, and disorganized speech.
“My view of schizophrenia is that the psychotic symptoms are a secondary phenomenon, a complication of the disease that has been going on for a while. It’s a pity that we focus so much on the psychotic symptoms rather than the cognitive or negative or affective symptoms,” he said.
The hope is that a long-term physical activity intervention in at-risk youth will stimulate neurodevelopmental catch-up, thereby thwarting their predisposition to schizophrenia.
“Human development is not a linear process; it happens in spurts of rapid growth followed by consolidation periods,” Dr. Hietala said.
However, even if it turns out that an early physical activity intervention does not reduce the risk of developing schizophrenia, it might favorably alter its course in important ways, according to Dr. Hietala.
Individuals with schizophrenia are known to be at increased risk for metabolic syndrome and premature death tied to cardiovascular disease. A recent meta-analysis of 16 prospective cohort studies totaling more than 1 million men and women found that mortality during follow-up was 59% greater in those who sat for more than 8 hours per day and were in the lowest quartile of physical activity, compared with those sitting for less than 4 hours per day who were in the top quartile of physical activity, at more than 35.5 metabolic equivalent hours per week.
But there was no increased risk of mortality among those who sat for more than 8 hours per day and were also in the highest quartile of physical activity. The implication is that high levels of moderate-intensity physical activity eliminates the increased risk of death associated with high sitting time (Lancet. 2016 Sep 24;388[10051]:1302-10). That’s a finding that could be applicable to patients with schizophrenia.
Dr. Hietala reported having no financial conflicts regarding the Cardiovascular Risk in Young Finns study, which is supported by the Academy of Finland, the Social Insurance Institution of Finland, and grants from nonprofit foundations.
PARIS – Low physical activity in childhood and adolescence was independently associated with later development of schizophrenia and other nonaffective psychotic disorders in the large, prospective, population-based Cardiovascular Risk in Young Finns cohort study, Jarmo Hietala, MD, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.
The key question now: Is this risk factor remediable? That is, will a pediatric exercise intervention that results in improved physical fitness also reduce the risk of later nonaffective psychosis? Given that there are really no downsides to physical activity, the Finnish data make a strong case for including exercise and physical activity interventions in investigational psychosis prevention programs targeting high-risk youth, according to Dr. Hietala, professor of psychiatry at the University of Turku (Finland).
Dr. Hietala and his coinvestigators tapped into comprehensive national registries in order to identify all study participants with a psychiatric diagnosis of sufficient severity to have resulted in hospitalization up to 2012. Forty-one patients were hospitalized for schizophrenia spectrum disorders, 47 for other forms of nonaffective psychosis, 43 for personality disorders, 111 for affective disorders, and 49 with alcohol and other substance use disorders.
In a multivariate analysis adjusted for sex, age, body mass index, birth weight, non-preterm birth, and maternal mental disorders, each 1-point decrement in the pediatric physical activity index was associated with a 26% increase in the risk of developing any nonaffective psychosis and, more specifically, a 43% increased risk of schizophrenia.
Moreover, nonparticipation in organized sports competitions was independently associated with a 2.58-fold increased risk of any nonaffective psychosis and a 4.88-fold increased risk of schizophrenia. And social isolation as reflected in spending less time in common activities with friends during leisure time was associated with a 71% increased risk of nonaffective psychosis and a 76% increased risk of schizophrenia.
Of note, schizophrenia was the only psychiatric disorder associated with low physical activity in childhood and adolescence. Sedentary youths were not at increased risk of later hospitalization for affective disorders or other forms of mental illness.
“Our results have relevance for preemptive psychiatry and provide rationale for including exercise in early interventions for psychosis,” the psychiatrist said.
Current programs aimed at preventing schizophrenia in youth at high risk because of family history typically emphasize avoidance of street drugs, the importance of seeking out constructive social interactions, stress reduction techniques, and cognitive-behavioral therapy aimed at promoting a positive world view.
Formal evaluation of physical activity as part of a preventive approach has a sound theoretic basis, according to Dr. Hietala. He cited an influential essay called “Rethinking Schizophrenia” by the then-director of the National Institute of Mental Health, Thomas R. Insel, MD. In that article, Dr. Insel highlights the past half-century of largely unsatisfactory results with pharmacotherapy and goes on to make the case for considering schizophrenia as a neurodevelopmental disorder in which, he argues, “psychosis is a late, potentially preventable stage of the illness” (Nature. 2010 Nov 11;468[7321]:187-93).
This view of schizophrenia as a neurodevelopmental disorder has quickly come to dominate thinking within the field. Dr. Hietala noted that the schizophrenia spectrum chapter in the DSM-5 includes a greater focus on abnormal behavior and catatonia as a core domain alongside classic features, such as delusions, hallucinations, negative symptoms, and disorganized speech.
“My view of schizophrenia is that the psychotic symptoms are a secondary phenomenon, a complication of the disease that has been going on for a while. It’s a pity that we focus so much on the psychotic symptoms rather than the cognitive or negative or affective symptoms,” he said.
The hope is that a long-term physical activity intervention in at-risk youth will stimulate neurodevelopmental catch-up, thereby thwarting their predisposition to schizophrenia.
“Human development is not a linear process; it happens in spurts of rapid growth followed by consolidation periods,” Dr. Hietala said.
However, even if it turns out that an early physical activity intervention does not reduce the risk of developing schizophrenia, it might favorably alter its course in important ways, according to Dr. Hietala.
Individuals with schizophrenia are known to be at increased risk for metabolic syndrome and premature death tied to cardiovascular disease. A recent meta-analysis of 16 prospective cohort studies totaling more than 1 million men and women found that mortality during follow-up was 59% greater in those who sat for more than 8 hours per day and were in the lowest quartile of physical activity, compared with those sitting for less than 4 hours per day who were in the top quartile of physical activity, at more than 35.5 metabolic equivalent hours per week.
But there was no increased risk of mortality among those who sat for more than 8 hours per day and were also in the highest quartile of physical activity. The implication is that high levels of moderate-intensity physical activity eliminates the increased risk of death associated with high sitting time (Lancet. 2016 Sep 24;388[10051]:1302-10). That’s a finding that could be applicable to patients with schizophrenia.
Dr. Hietala reported having no financial conflicts regarding the Cardiovascular Risk in Young Finns study, which is supported by the Academy of Finland, the Social Insurance Institution of Finland, and grants from nonprofit foundations.
PARIS – Low physical activity in childhood and adolescence was independently associated with later development of schizophrenia and other nonaffective psychotic disorders in the large, prospective, population-based Cardiovascular Risk in Young Finns cohort study, Jarmo Hietala, MD, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.
The key question now: Is this risk factor remediable? That is, will a pediatric exercise intervention that results in improved physical fitness also reduce the risk of later nonaffective psychosis? Given that there are really no downsides to physical activity, the Finnish data make a strong case for including exercise and physical activity interventions in investigational psychosis prevention programs targeting high-risk youth, according to Dr. Hietala, professor of psychiatry at the University of Turku (Finland).
Dr. Hietala and his coinvestigators tapped into comprehensive national registries in order to identify all study participants with a psychiatric diagnosis of sufficient severity to have resulted in hospitalization up to 2012. Forty-one patients were hospitalized for schizophrenia spectrum disorders, 47 for other forms of nonaffective psychosis, 43 for personality disorders, 111 for affective disorders, and 49 with alcohol and other substance use disorders.
In a multivariate analysis adjusted for sex, age, body mass index, birth weight, non-preterm birth, and maternal mental disorders, each 1-point decrement in the pediatric physical activity index was associated with a 26% increase in the risk of developing any nonaffective psychosis and, more specifically, a 43% increased risk of schizophrenia.
Moreover, nonparticipation in organized sports competitions was independently associated with a 2.58-fold increased risk of any nonaffective psychosis and a 4.88-fold increased risk of schizophrenia. And social isolation as reflected in spending less time in common activities with friends during leisure time was associated with a 71% increased risk of nonaffective psychosis and a 76% increased risk of schizophrenia.
Of note, schizophrenia was the only psychiatric disorder associated with low physical activity in childhood and adolescence. Sedentary youths were not at increased risk of later hospitalization for affective disorders or other forms of mental illness.
“Our results have relevance for preemptive psychiatry and provide rationale for including exercise in early interventions for psychosis,” the psychiatrist said.
Current programs aimed at preventing schizophrenia in youth at high risk because of family history typically emphasize avoidance of street drugs, the importance of seeking out constructive social interactions, stress reduction techniques, and cognitive-behavioral therapy aimed at promoting a positive world view.
Formal evaluation of physical activity as part of a preventive approach has a sound theoretic basis, according to Dr. Hietala. He cited an influential essay called “Rethinking Schizophrenia” by the then-director of the National Institute of Mental Health, Thomas R. Insel, MD. In that article, Dr. Insel highlights the past half-century of largely unsatisfactory results with pharmacotherapy and goes on to make the case for considering schizophrenia as a neurodevelopmental disorder in which, he argues, “psychosis is a late, potentially preventable stage of the illness” (Nature. 2010 Nov 11;468[7321]:187-93).
This view of schizophrenia as a neurodevelopmental disorder has quickly come to dominate thinking within the field. Dr. Hietala noted that the schizophrenia spectrum chapter in the DSM-5 includes a greater focus on abnormal behavior and catatonia as a core domain alongside classic features, such as delusions, hallucinations, negative symptoms, and disorganized speech.
“My view of schizophrenia is that the psychotic symptoms are a secondary phenomenon, a complication of the disease that has been going on for a while. It’s a pity that we focus so much on the psychotic symptoms rather than the cognitive or negative or affective symptoms,” he said.
The hope is that a long-term physical activity intervention in at-risk youth will stimulate neurodevelopmental catch-up, thereby thwarting their predisposition to schizophrenia.
“Human development is not a linear process; it happens in spurts of rapid growth followed by consolidation periods,” Dr. Hietala said.
However, even if it turns out that an early physical activity intervention does not reduce the risk of developing schizophrenia, it might favorably alter its course in important ways, according to Dr. Hietala.
Individuals with schizophrenia are known to be at increased risk for metabolic syndrome and premature death tied to cardiovascular disease. A recent meta-analysis of 16 prospective cohort studies totaling more than 1 million men and women found that mortality during follow-up was 59% greater in those who sat for more than 8 hours per day and were in the lowest quartile of physical activity, compared with those sitting for less than 4 hours per day who were in the top quartile of physical activity, at more than 35.5 metabolic equivalent hours per week.
But there was no increased risk of mortality among those who sat for more than 8 hours per day and were also in the highest quartile of physical activity. The implication is that high levels of moderate-intensity physical activity eliminates the increased risk of death associated with high sitting time (Lancet. 2016 Sep 24;388[10051]:1302-10). That’s a finding that could be applicable to patients with schizophrenia.
Dr. Hietala reported having no financial conflicts regarding the Cardiovascular Risk in Young Finns study, which is supported by the Academy of Finland, the Social Insurance Institution of Finland, and grants from nonprofit foundations.
AT THE ECNP CONGRESS
Key clinical point:
Major finding: Each 1-point decrement on a physical activity score recorded during childhood and adolescence was independently associated with a 43% increased risk of later development of schizophrenia.
Data source: The Cardiovascular Risk in Young Finns study is an ongoing prospective, population-based study of nearly 3,600 Finns who were aged 3-18 years old when the study began in 1980.
Disclosures: The presenter reported having no financial conflicts regarding the study, which is supported by the Academy of Finland, the Social Insurance Institution of Finland, and grants from nonprofit foundations.
Insulin pumps associated with lower risk of ketoacidosis and severe hypoglycemia in kids
Children with type 1 diabetes mellitus who use insulin pumps are at a lower risk for ketoacidosis and severe hypoglycemia, compared with those receiving insulin by injection, according to a population-based cohort study from the University of Ulm, Germany.
The study participants were all younger than 20 years of age and were divided into the following groups for data analysis: 1.5-5 years; 6-10 years; 11-15 years; or 16-19 years. The study evaluated both primary and secondary outcomes to analyze the effectiveness of insulin pumps vs. traditional insulin injections. The primary outcomes were the rates of ketoacidosis and hypoglycemia severe enough to require assistance from another person to administer intravenous carbohydrates or induce hypoglycemic coma. The secondary outcomes were serum levels of glycated hemoglobin (HbA1c), daily insulin dose, prandial to total insulin ratio, frequency of self-monitoring blood glucose level, and body mass index, according to Beate Karges, MD, of the University of Aachen (Germany), Division of Endocrinology and Diabetes, and her colleagues.
After applying selection criteria, 30,579 patients treated for type 1 diabetes were selected for analysis. Of the 30,579, a 1 to 1 matched cohort of 19,628 patients, split into equal sized groups, was created for propensity score analysis to compare the effect of treatment between insulin pumps and injects. The matched cohort was also included in the entire cohort for another propensity score analysis. Of the entire 30,579 patients, 14,119 used pump therapy and 16,460 used traditional daily insulin injections.
In the matched cohort, event rates for both severe hypoglycemia and hypoglycemic coma were much lower with insulin pumps than with traditional insulin injections (9.55 vs. 13.97 per 100 patient-years and 2.30 vs. 2.96 per 100 patient-years, respectively). The pattern of pump therapy lowering rates of severe hypoglycemia and hypoglycemic coma was observed in entire cohort as well, according to the investigators (JAMA. 2017 Oct 10;318[14]:1358-66).
The secondary outcomes of the matched cohort did not share as consistent a pattern as the primary outcomes. HbA1c levels were lower in pump users (8.04% vs. 8.22%). Total daily insulin doses were lower in pump users, but the prandial to total insulin ratio was higher. Daily frequency of self-monitoring blood glucose level was also elevated in pump users.
“These findings provide evidence for improved clinical outcomes associated with insulin pump therapy, compared with injection therapy, in children, adolescents, and young adults with type 1 diabetes,” Dr. Karges and her colleagues wrote.
The study was funded by both the Competence Network Diabetes Mellitus and the German Center for Diabetes Research. Thomas Kapellen, MD, had received funding from the European Commission concerning closed-loop systems as well as speaking fees for pharmaceuticals companies including Abbott, Medtronic, and Novo Nordisk. No other authors reported financial conflicts.
Children with type 1 diabetes mellitus who use insulin pumps are at a lower risk for ketoacidosis and severe hypoglycemia, compared with those receiving insulin by injection, according to a population-based cohort study from the University of Ulm, Germany.
The study participants were all younger than 20 years of age and were divided into the following groups for data analysis: 1.5-5 years; 6-10 years; 11-15 years; or 16-19 years. The study evaluated both primary and secondary outcomes to analyze the effectiveness of insulin pumps vs. traditional insulin injections. The primary outcomes were the rates of ketoacidosis and hypoglycemia severe enough to require assistance from another person to administer intravenous carbohydrates or induce hypoglycemic coma. The secondary outcomes were serum levels of glycated hemoglobin (HbA1c), daily insulin dose, prandial to total insulin ratio, frequency of self-monitoring blood glucose level, and body mass index, according to Beate Karges, MD, of the University of Aachen (Germany), Division of Endocrinology and Diabetes, and her colleagues.
After applying selection criteria, 30,579 patients treated for type 1 diabetes were selected for analysis. Of the 30,579, a 1 to 1 matched cohort of 19,628 patients, split into equal sized groups, was created for propensity score analysis to compare the effect of treatment between insulin pumps and injects. The matched cohort was also included in the entire cohort for another propensity score analysis. Of the entire 30,579 patients, 14,119 used pump therapy and 16,460 used traditional daily insulin injections.
In the matched cohort, event rates for both severe hypoglycemia and hypoglycemic coma were much lower with insulin pumps than with traditional insulin injections (9.55 vs. 13.97 per 100 patient-years and 2.30 vs. 2.96 per 100 patient-years, respectively). The pattern of pump therapy lowering rates of severe hypoglycemia and hypoglycemic coma was observed in entire cohort as well, according to the investigators (JAMA. 2017 Oct 10;318[14]:1358-66).
The secondary outcomes of the matched cohort did not share as consistent a pattern as the primary outcomes. HbA1c levels were lower in pump users (8.04% vs. 8.22%). Total daily insulin doses were lower in pump users, but the prandial to total insulin ratio was higher. Daily frequency of self-monitoring blood glucose level was also elevated in pump users.
“These findings provide evidence for improved clinical outcomes associated with insulin pump therapy, compared with injection therapy, in children, adolescents, and young adults with type 1 diabetes,” Dr. Karges and her colleagues wrote.
The study was funded by both the Competence Network Diabetes Mellitus and the German Center for Diabetes Research. Thomas Kapellen, MD, had received funding from the European Commission concerning closed-loop systems as well as speaking fees for pharmaceuticals companies including Abbott, Medtronic, and Novo Nordisk. No other authors reported financial conflicts.
Children with type 1 diabetes mellitus who use insulin pumps are at a lower risk for ketoacidosis and severe hypoglycemia, compared with those receiving insulin by injection, according to a population-based cohort study from the University of Ulm, Germany.
The study participants were all younger than 20 years of age and were divided into the following groups for data analysis: 1.5-5 years; 6-10 years; 11-15 years; or 16-19 years. The study evaluated both primary and secondary outcomes to analyze the effectiveness of insulin pumps vs. traditional insulin injections. The primary outcomes were the rates of ketoacidosis and hypoglycemia severe enough to require assistance from another person to administer intravenous carbohydrates or induce hypoglycemic coma. The secondary outcomes were serum levels of glycated hemoglobin (HbA1c), daily insulin dose, prandial to total insulin ratio, frequency of self-monitoring blood glucose level, and body mass index, according to Beate Karges, MD, of the University of Aachen (Germany), Division of Endocrinology and Diabetes, and her colleagues.
After applying selection criteria, 30,579 patients treated for type 1 diabetes were selected for analysis. Of the 30,579, a 1 to 1 matched cohort of 19,628 patients, split into equal sized groups, was created for propensity score analysis to compare the effect of treatment between insulin pumps and injects. The matched cohort was also included in the entire cohort for another propensity score analysis. Of the entire 30,579 patients, 14,119 used pump therapy and 16,460 used traditional daily insulin injections.
In the matched cohort, event rates for both severe hypoglycemia and hypoglycemic coma were much lower with insulin pumps than with traditional insulin injections (9.55 vs. 13.97 per 100 patient-years and 2.30 vs. 2.96 per 100 patient-years, respectively). The pattern of pump therapy lowering rates of severe hypoglycemia and hypoglycemic coma was observed in entire cohort as well, according to the investigators (JAMA. 2017 Oct 10;318[14]:1358-66).
The secondary outcomes of the matched cohort did not share as consistent a pattern as the primary outcomes. HbA1c levels were lower in pump users (8.04% vs. 8.22%). Total daily insulin doses were lower in pump users, but the prandial to total insulin ratio was higher. Daily frequency of self-monitoring blood glucose level was also elevated in pump users.
“These findings provide evidence for improved clinical outcomes associated with insulin pump therapy, compared with injection therapy, in children, adolescents, and young adults with type 1 diabetes,” Dr. Karges and her colleagues wrote.
The study was funded by both the Competence Network Diabetes Mellitus and the German Center for Diabetes Research. Thomas Kapellen, MD, had received funding from the European Commission concerning closed-loop systems as well as speaking fees for pharmaceuticals companies including Abbott, Medtronic, and Novo Nordisk. No other authors reported financial conflicts.
FROM JAMA
Key clinical point:
Major finding: Patients using insulin pumps had lower rates of hypoglycemia (9.55 per 100 patient-years) and severe ketoacidosis (3.64 per 100 patient-years).
Data source: Population cohort study of 30,579 patients from the Diabetes Prospective Follow-up Initiative Database.
Disclosures: The study was funded by both the Competence Network Diabetes Mellitus and the German Center for Diabetes Research. Thomas Kapellen, MD, had received funding from the European Commission concerning closed-loop systems as well as speaking fees for pharmaceutical companies including Abbott, Medtronic, and Novo Nordisk. No other authors reported financial conflicts.
Evidence is mixed on probiotics in pediatric patients
CHICAGO – Outside of that, things are less clear.
“In terms of diarrhea, the evidence is positive, but probiotics only provide about 25 hours of benefit. And treatment of antibiotic-associated diarrhea is really dependent on patient adherence,” said Michael D. Cabana, MD. When it comes to treating colic, there is a particular probiotic that looks promising, he added, but the research so far demonstrating effectiveness is limited to breastfed babies. Also, the probiotic therapy appears to work best when started relatively early.
You are very likely to be asked your take on probiotics for a wide range of conditions, Dr. Cabana said, Overall, however, skepticism is warranted. Advise patients and families to be aware of advertising that promotes many different products as “probiotic,” especially around claims of improved “gut health” or “balanced microbiota.” He emphasized: “Make sure what your patients are using has some evidence behind it.”
Knowing the particular probiotic strain is essential to researching the evidence around its use, said Dr. Cabana, professor of pediatrics at the University of California, San Francisco. “I used the Canis familiaris example. All dogs are C. familiaris. But there are different breeds. You want to make sure you match the right breed to the task. If you were in an avalanche in the Swiss Alps, you would want a St. Bernard to rescue you, not a Chihuahua,” he said. “Similarly, when you are using probiotics you want to make sure you have the right strain, not just the genus and species.” For example, if a product label states it contains Bifidobacterium breve C50, the “C50” is the strain.
Another tip is to look for labeling that lists probiotic concentrations in colony-forming units or CFUs, Dr. Cabana said. He’s seen concentrations listed in mg, a red flag that a product is not legitimate.
Families also might ask if it’s better to take a probiotic supplement or choose food that contains probiotics. “Food products offer additional nutritional benefits, but you can give a relatively higher dose with supplements with a much lower volume ingested,” Dr. Cabana said. “And supplements theoretically provide a more consistent dose.” Speaking of dose, it’s difficult to counsel patients on dosing and frequency in general because probiotics really vary by the indication and formulation.
“As a pediatrician, I also get this question: Should kids get a lower dose of probiotic?” Dr. Cabana said. There are no known reports of toxicity associated with probiotic use in either adults or children, he said. “Unless a dose modification has been documented in a clinical trial, it is not clear that this is necessary. You’re just giving less of the probiotic.”
Treating diarrhea and antibiotic-associated diarrhea
When it comes to probiotics for treating acute diarrhea in children, “the literature is actually fairly good here,” Dr. Cabana said. More than 60 studies with an excess of 8,000 participants, the majority with rotavirus infection, suggests probiotics are not associated with any adverse effects and generally shorten duration of diarrhea.
In fact, Dr. Cabana added, multiple meta-analyses support a shorter course of diarrhea. He added, “Look at the units here – it’s hours, not days. You can treat, but on average it’s only 25 hours.” He added that a day less of diarrhea can be significant for patients and parents, however.
In another meta-analysis probiotics, particularly Lactobacillus strains, were analyzed for prevention of antibiotic-associated diarrhea (JAMA. 2012 May 9;307[18]:1959-69). Researchers assessed 63 randomized controlled trials with nearly 12,000 participants. The pooled results showed a statistically significant positive reduction in antibiotic-associated diarrhea (relative risk, 0.58; P less than .001). “Note the number needed to treat to see the effect is 13, so it won’t work in every patient,” Dr. Cabana said.
“So prevention of antibiotic-associated diarrhea is well documented. However, it’s also highly dependent on patent adherence,” he emphasized.
The clinical evidence on colic
For treating babies with colic, the best evidence is behind use of Lactobacilus reuteri DSM 17938, Dr. Cabana said. It tends to work best in breastfed infants, babies not on any gastrointestinal meds, and babies that start therapy early in the course of symptoms. “Use in formula-fed infants is unknown, because there are not enough data so far,” he said.
In some cases, during a prenatal visit, soon-to-be-parents will ask if they should start a probiotic to prevent colic. Dr. Cabana has seen only one prophylaxis study for this indication (JAMA Pediatr. 2014 Mar;168[3]:228-33). In the study, 589 infants were randomly allocated to take L. reuteri DSM 17938 or placebo daily for 90 days. At 3 months of age, the researchers discovered a significantly shorter mean duration of daily crying in the probiotic group (38 vs. 71 minutes; P less than .01).
What’s known about efficacy for eczema
The evidence for treating a child who presents with eczema with probiotics does not support efficacy in general, Dr. Cabana said. And the evidence on prevention of atopic eczema is mixed.
For example, in a randomized, controlled study from Finland, investigators randomized mothers to receive Lactobacillus GG or placebo during the prenatal period (Lancet. 2001;357:1076-9). Of 132 of the children, 35% were later diagnosed with atopic eczema, and the rate in the probiotic group, 23%, was half the 46% rate in the placebo group.
In contrast, researchers found no benefit regarding prevention of atopic dermatitis when 105 pregnant women were randomized to Lactobacillus GG or placebo. At the age of 2 years, atopic dermatitis was diagnosed in 28% of the 50 children in the probiotic group and 27.3% of the 44 in the placebo group (Pediatrics. 2008;121:e850-6).
The region of Germany where the study was conducted was rural/agricultural, so the diet could be different, Dr. Cabana said. Also, the median duration of breastfeeding differed between the Finnish and German study population, 6.8 months versus 9.2 months, respectively. “So that could potentially explain it, or there are just differences that cannot be explained.”
For more information, Dr. Cabana recommended information provided by the International Scientific Association of Prebiotics & Probiotics (https://isappscience.org/infographics/). The association’s website has easy to understand infographics including: What are probiotics and what can they do for you?; What’s so special about fermented foods?; and How do you read a probiotic label?
Dr. Cabana reported he receives research support from the National Institutes of Health, Wyeth Nutrition, and Nestle; is on the speakers bureau for Merck; owns stocks or bonds in Abbot and AbbVie; and is a consultant for Mead Johnson, Abbott, Genentech, Biogaia, General Mills, and Nestle.
CHICAGO – Outside of that, things are less clear.
“In terms of diarrhea, the evidence is positive, but probiotics only provide about 25 hours of benefit. And treatment of antibiotic-associated diarrhea is really dependent on patient adherence,” said Michael D. Cabana, MD. When it comes to treating colic, there is a particular probiotic that looks promising, he added, but the research so far demonstrating effectiveness is limited to breastfed babies. Also, the probiotic therapy appears to work best when started relatively early.
You are very likely to be asked your take on probiotics for a wide range of conditions, Dr. Cabana said, Overall, however, skepticism is warranted. Advise patients and families to be aware of advertising that promotes many different products as “probiotic,” especially around claims of improved “gut health” or “balanced microbiota.” He emphasized: “Make sure what your patients are using has some evidence behind it.”
Knowing the particular probiotic strain is essential to researching the evidence around its use, said Dr. Cabana, professor of pediatrics at the University of California, San Francisco. “I used the Canis familiaris example. All dogs are C. familiaris. But there are different breeds. You want to make sure you match the right breed to the task. If you were in an avalanche in the Swiss Alps, you would want a St. Bernard to rescue you, not a Chihuahua,” he said. “Similarly, when you are using probiotics you want to make sure you have the right strain, not just the genus and species.” For example, if a product label states it contains Bifidobacterium breve C50, the “C50” is the strain.
Another tip is to look for labeling that lists probiotic concentrations in colony-forming units or CFUs, Dr. Cabana said. He’s seen concentrations listed in mg, a red flag that a product is not legitimate.
Families also might ask if it’s better to take a probiotic supplement or choose food that contains probiotics. “Food products offer additional nutritional benefits, but you can give a relatively higher dose with supplements with a much lower volume ingested,” Dr. Cabana said. “And supplements theoretically provide a more consistent dose.” Speaking of dose, it’s difficult to counsel patients on dosing and frequency in general because probiotics really vary by the indication and formulation.
“As a pediatrician, I also get this question: Should kids get a lower dose of probiotic?” Dr. Cabana said. There are no known reports of toxicity associated with probiotic use in either adults or children, he said. “Unless a dose modification has been documented in a clinical trial, it is not clear that this is necessary. You’re just giving less of the probiotic.”
Treating diarrhea and antibiotic-associated diarrhea
When it comes to probiotics for treating acute diarrhea in children, “the literature is actually fairly good here,” Dr. Cabana said. More than 60 studies with an excess of 8,000 participants, the majority with rotavirus infection, suggests probiotics are not associated with any adverse effects and generally shorten duration of diarrhea.
In fact, Dr. Cabana added, multiple meta-analyses support a shorter course of diarrhea. He added, “Look at the units here – it’s hours, not days. You can treat, but on average it’s only 25 hours.” He added that a day less of diarrhea can be significant for patients and parents, however.
In another meta-analysis probiotics, particularly Lactobacillus strains, were analyzed for prevention of antibiotic-associated diarrhea (JAMA. 2012 May 9;307[18]:1959-69). Researchers assessed 63 randomized controlled trials with nearly 12,000 participants. The pooled results showed a statistically significant positive reduction in antibiotic-associated diarrhea (relative risk, 0.58; P less than .001). “Note the number needed to treat to see the effect is 13, so it won’t work in every patient,” Dr. Cabana said.
“So prevention of antibiotic-associated diarrhea is well documented. However, it’s also highly dependent on patent adherence,” he emphasized.
The clinical evidence on colic
For treating babies with colic, the best evidence is behind use of Lactobacilus reuteri DSM 17938, Dr. Cabana said. It tends to work best in breastfed infants, babies not on any gastrointestinal meds, and babies that start therapy early in the course of symptoms. “Use in formula-fed infants is unknown, because there are not enough data so far,” he said.
In some cases, during a prenatal visit, soon-to-be-parents will ask if they should start a probiotic to prevent colic. Dr. Cabana has seen only one prophylaxis study for this indication (JAMA Pediatr. 2014 Mar;168[3]:228-33). In the study, 589 infants were randomly allocated to take L. reuteri DSM 17938 or placebo daily for 90 days. At 3 months of age, the researchers discovered a significantly shorter mean duration of daily crying in the probiotic group (38 vs. 71 minutes; P less than .01).
What’s known about efficacy for eczema
The evidence for treating a child who presents with eczema with probiotics does not support efficacy in general, Dr. Cabana said. And the evidence on prevention of atopic eczema is mixed.
For example, in a randomized, controlled study from Finland, investigators randomized mothers to receive Lactobacillus GG or placebo during the prenatal period (Lancet. 2001;357:1076-9). Of 132 of the children, 35% were later diagnosed with atopic eczema, and the rate in the probiotic group, 23%, was half the 46% rate in the placebo group.
In contrast, researchers found no benefit regarding prevention of atopic dermatitis when 105 pregnant women were randomized to Lactobacillus GG or placebo. At the age of 2 years, atopic dermatitis was diagnosed in 28% of the 50 children in the probiotic group and 27.3% of the 44 in the placebo group (Pediatrics. 2008;121:e850-6).
The region of Germany where the study was conducted was rural/agricultural, so the diet could be different, Dr. Cabana said. Also, the median duration of breastfeeding differed between the Finnish and German study population, 6.8 months versus 9.2 months, respectively. “So that could potentially explain it, or there are just differences that cannot be explained.”
For more information, Dr. Cabana recommended information provided by the International Scientific Association of Prebiotics & Probiotics (https://isappscience.org/infographics/). The association’s website has easy to understand infographics including: What are probiotics and what can they do for you?; What’s so special about fermented foods?; and How do you read a probiotic label?
Dr. Cabana reported he receives research support from the National Institutes of Health, Wyeth Nutrition, and Nestle; is on the speakers bureau for Merck; owns stocks or bonds in Abbot and AbbVie; and is a consultant for Mead Johnson, Abbott, Genentech, Biogaia, General Mills, and Nestle.
CHICAGO – Outside of that, things are less clear.
“In terms of diarrhea, the evidence is positive, but probiotics only provide about 25 hours of benefit. And treatment of antibiotic-associated diarrhea is really dependent on patient adherence,” said Michael D. Cabana, MD. When it comes to treating colic, there is a particular probiotic that looks promising, he added, but the research so far demonstrating effectiveness is limited to breastfed babies. Also, the probiotic therapy appears to work best when started relatively early.
You are very likely to be asked your take on probiotics for a wide range of conditions, Dr. Cabana said, Overall, however, skepticism is warranted. Advise patients and families to be aware of advertising that promotes many different products as “probiotic,” especially around claims of improved “gut health” or “balanced microbiota.” He emphasized: “Make sure what your patients are using has some evidence behind it.”
Knowing the particular probiotic strain is essential to researching the evidence around its use, said Dr. Cabana, professor of pediatrics at the University of California, San Francisco. “I used the Canis familiaris example. All dogs are C. familiaris. But there are different breeds. You want to make sure you match the right breed to the task. If you were in an avalanche in the Swiss Alps, you would want a St. Bernard to rescue you, not a Chihuahua,” he said. “Similarly, when you are using probiotics you want to make sure you have the right strain, not just the genus and species.” For example, if a product label states it contains Bifidobacterium breve C50, the “C50” is the strain.
Another tip is to look for labeling that lists probiotic concentrations in colony-forming units or CFUs, Dr. Cabana said. He’s seen concentrations listed in mg, a red flag that a product is not legitimate.
Families also might ask if it’s better to take a probiotic supplement or choose food that contains probiotics. “Food products offer additional nutritional benefits, but you can give a relatively higher dose with supplements with a much lower volume ingested,” Dr. Cabana said. “And supplements theoretically provide a more consistent dose.” Speaking of dose, it’s difficult to counsel patients on dosing and frequency in general because probiotics really vary by the indication and formulation.
“As a pediatrician, I also get this question: Should kids get a lower dose of probiotic?” Dr. Cabana said. There are no known reports of toxicity associated with probiotic use in either adults or children, he said. “Unless a dose modification has been documented in a clinical trial, it is not clear that this is necessary. You’re just giving less of the probiotic.”
Treating diarrhea and antibiotic-associated diarrhea
When it comes to probiotics for treating acute diarrhea in children, “the literature is actually fairly good here,” Dr. Cabana said. More than 60 studies with an excess of 8,000 participants, the majority with rotavirus infection, suggests probiotics are not associated with any adverse effects and generally shorten duration of diarrhea.
In fact, Dr. Cabana added, multiple meta-analyses support a shorter course of diarrhea. He added, “Look at the units here – it’s hours, not days. You can treat, but on average it’s only 25 hours.” He added that a day less of diarrhea can be significant for patients and parents, however.
In another meta-analysis probiotics, particularly Lactobacillus strains, were analyzed for prevention of antibiotic-associated diarrhea (JAMA. 2012 May 9;307[18]:1959-69). Researchers assessed 63 randomized controlled trials with nearly 12,000 participants. The pooled results showed a statistically significant positive reduction in antibiotic-associated diarrhea (relative risk, 0.58; P less than .001). “Note the number needed to treat to see the effect is 13, so it won’t work in every patient,” Dr. Cabana said.
“So prevention of antibiotic-associated diarrhea is well documented. However, it’s also highly dependent on patent adherence,” he emphasized.
The clinical evidence on colic
For treating babies with colic, the best evidence is behind use of Lactobacilus reuteri DSM 17938, Dr. Cabana said. It tends to work best in breastfed infants, babies not on any gastrointestinal meds, and babies that start therapy early in the course of symptoms. “Use in formula-fed infants is unknown, because there are not enough data so far,” he said.
In some cases, during a prenatal visit, soon-to-be-parents will ask if they should start a probiotic to prevent colic. Dr. Cabana has seen only one prophylaxis study for this indication (JAMA Pediatr. 2014 Mar;168[3]:228-33). In the study, 589 infants were randomly allocated to take L. reuteri DSM 17938 or placebo daily for 90 days. At 3 months of age, the researchers discovered a significantly shorter mean duration of daily crying in the probiotic group (38 vs. 71 minutes; P less than .01).
What’s known about efficacy for eczema
The evidence for treating a child who presents with eczema with probiotics does not support efficacy in general, Dr. Cabana said. And the evidence on prevention of atopic eczema is mixed.
For example, in a randomized, controlled study from Finland, investigators randomized mothers to receive Lactobacillus GG or placebo during the prenatal period (Lancet. 2001;357:1076-9). Of 132 of the children, 35% were later diagnosed with atopic eczema, and the rate in the probiotic group, 23%, was half the 46% rate in the placebo group.
In contrast, researchers found no benefit regarding prevention of atopic dermatitis when 105 pregnant women were randomized to Lactobacillus GG or placebo. At the age of 2 years, atopic dermatitis was diagnosed in 28% of the 50 children in the probiotic group and 27.3% of the 44 in the placebo group (Pediatrics. 2008;121:e850-6).
The region of Germany where the study was conducted was rural/agricultural, so the diet could be different, Dr. Cabana said. Also, the median duration of breastfeeding differed between the Finnish and German study population, 6.8 months versus 9.2 months, respectively. “So that could potentially explain it, or there are just differences that cannot be explained.”
For more information, Dr. Cabana recommended information provided by the International Scientific Association of Prebiotics & Probiotics (https://isappscience.org/infographics/). The association’s website has easy to understand infographics including: What are probiotics and what can they do for you?; What’s so special about fermented foods?; and How do you read a probiotic label?
Dr. Cabana reported he receives research support from the National Institutes of Health, Wyeth Nutrition, and Nestle; is on the speakers bureau for Merck; owns stocks or bonds in Abbot and AbbVie; and is a consultant for Mead Johnson, Abbott, Genentech, Biogaia, General Mills, and Nestle.
EXPERT ANALYSIS FROM AAP 2017
Tdap during pregnancy, or before, offers infants pertussis protection
during the early months of life, according to Tami H. Skoff of the Centers for Disease Control and Prevention, Atlanta, and her associates.
In an analysis of 240 infants younger than 2 months with pertussis cough onset between 2011 and 2015 and 535 control infants, 57% of case mothers and 67% of control mothers had at least one valid Tdap dose; 13% of vaccinated case mothers and 14% of vaccinated control mothers had more than one valid dose of Tdap reported.
Of Tdap doses received during pregnancy in 22 cases and 117 controls, 77% were received during the third trimester, most during the Advisory Committee on Immunization Practices’ recommended 27-36 weeks of gestation. Of the Tdap doses received before pregnancy in mothers of 24 cases and 67 controls, 25% of the case mothers and 67% of the control mothers received Tdap 2 or fewer years before pregnancy.
The effectiveness of Tdap vaccination during the third trimester of pregnancy was 78%, and effectiveness during the first or second trimester was 64%. Effectiveness of Tdap given 2 or fewer years before pregnancy was 83%. This study was not powered to determine a difference if the vaccine was administered in the ACIP-recommended time period during the third trimester.
A reported 49% of U.S. pregnant women received Tdap during the 2015-2016 flu season, an increase of 22% from the 2013-2014 season, according to a CDC Internet panel survey.
“While maternal immunization during pregnancy will help bridge the gap until next-generation pertussis vaccines are licensed and available for use, this highly effective strategy will likely remain an integral component of pertussis prevention and control, even in the setting of new vaccines,” the investigators said.
Read more in Clinical Infectious Diseases (2017 Sep 28. doi: 10.1093/cid/cix724).
during the early months of life, according to Tami H. Skoff of the Centers for Disease Control and Prevention, Atlanta, and her associates.
In an analysis of 240 infants younger than 2 months with pertussis cough onset between 2011 and 2015 and 535 control infants, 57% of case mothers and 67% of control mothers had at least one valid Tdap dose; 13% of vaccinated case mothers and 14% of vaccinated control mothers had more than one valid dose of Tdap reported.
Of Tdap doses received during pregnancy in 22 cases and 117 controls, 77% were received during the third trimester, most during the Advisory Committee on Immunization Practices’ recommended 27-36 weeks of gestation. Of the Tdap doses received before pregnancy in mothers of 24 cases and 67 controls, 25% of the case mothers and 67% of the control mothers received Tdap 2 or fewer years before pregnancy.
The effectiveness of Tdap vaccination during the third trimester of pregnancy was 78%, and effectiveness during the first or second trimester was 64%. Effectiveness of Tdap given 2 or fewer years before pregnancy was 83%. This study was not powered to determine a difference if the vaccine was administered in the ACIP-recommended time period during the third trimester.
A reported 49% of U.S. pregnant women received Tdap during the 2015-2016 flu season, an increase of 22% from the 2013-2014 season, according to a CDC Internet panel survey.
“While maternal immunization during pregnancy will help bridge the gap until next-generation pertussis vaccines are licensed and available for use, this highly effective strategy will likely remain an integral component of pertussis prevention and control, even in the setting of new vaccines,” the investigators said.
Read more in Clinical Infectious Diseases (2017 Sep 28. doi: 10.1093/cid/cix724).
during the early months of life, according to Tami H. Skoff of the Centers for Disease Control and Prevention, Atlanta, and her associates.
In an analysis of 240 infants younger than 2 months with pertussis cough onset between 2011 and 2015 and 535 control infants, 57% of case mothers and 67% of control mothers had at least one valid Tdap dose; 13% of vaccinated case mothers and 14% of vaccinated control mothers had more than one valid dose of Tdap reported.
Of Tdap doses received during pregnancy in 22 cases and 117 controls, 77% were received during the third trimester, most during the Advisory Committee on Immunization Practices’ recommended 27-36 weeks of gestation. Of the Tdap doses received before pregnancy in mothers of 24 cases and 67 controls, 25% of the case mothers and 67% of the control mothers received Tdap 2 or fewer years before pregnancy.
The effectiveness of Tdap vaccination during the third trimester of pregnancy was 78%, and effectiveness during the first or second trimester was 64%. Effectiveness of Tdap given 2 or fewer years before pregnancy was 83%. This study was not powered to determine a difference if the vaccine was administered in the ACIP-recommended time period during the third trimester.
A reported 49% of U.S. pregnant women received Tdap during the 2015-2016 flu season, an increase of 22% from the 2013-2014 season, according to a CDC Internet panel survey.
“While maternal immunization during pregnancy will help bridge the gap until next-generation pertussis vaccines are licensed and available for use, this highly effective strategy will likely remain an integral component of pertussis prevention and control, even in the setting of new vaccines,” the investigators said.
Read more in Clinical Infectious Diseases (2017 Sep 28. doi: 10.1093/cid/cix724).
FROM CLINICAL INFECTIOUS DISEASES