CASE CORRESPONDENCE
Endocarditis caused by Streptococcus infantarius subsp. infantarius: a report of two cases To the Editor:
Introduction Streptococcus infantarius, formerly known as Streptococcus bovis biotype II/1, is a member of S. bovis/equinus complex, associated with several human and animal infections with low clinical impact. Streptococcus infantarius comprises two subspecies genetically closely related, S. infantarius subsp. coli and S. infantarius subsp. infantarius. S. infantarius subsp. infantarius has been recovered from traditionally fermented dairy and plant products but rarely has been isolated in human specimens. We describe herein two cases of endocarditis caused by Streptococcus infantarius subsp. infantarius which, to our knowledge, are the first reported cases of endocarditis.
Case 1 An 88-year-old man was admitted to our hospital with 15-day history of dyspnoea and general malaise. Fourteen years previously, the patient had undergone aortic valve replacement (biological valve) because of aortic valve insufficiency. Physical examination revealed a temperature of 37.5 °C, a grade III/VI systolic murmur and basal lung crackles. Laboratory studies showed a haemoglobin of 10.5 g/dl, sedimentation rate of 55 mm, C-reactive protein of 32. Urinalysis revealed microscopic haematuria and red cell casts. A chest X-ray revealed signs of cardiac failure. Two blood cultures were positive for Streptococcus bovis (MIC, minimum inhibitory
concentration of penicillin: 0.094 lg/ml). Transesophageal echocardiographic evaluation showed an aortic vegetation with severe aortic regurgitation. The patient was treated with diuretics and antibiotic therapy was started with ceftriaxone 2 g/24 h i.v. (6 weeks) plus gentamicin 240 mg/24 h i.v. (2 weeks), which resulted in recovery. Surgery was rejected in this patient because of his advanced age. A colonoscopy showed diverticula. Nine months later, the patient died of cardiac failure.
Case 2 A 66-year-old man was admitted on the hospital because of weakness, low-grade fever, diffuse myalgia and weight loss of 1-month duration. There was a previous history of diabetes mellitus, and surgery for ampulla of Vater carcinoma 2 years earlier. Eight years prior to admission, he had undergone mitral valve replacement (mechanical valve) for mitral insufficiency. Examination showed a temperature of 37.4 °C, a systolic murmur consistent with mitral regurgitation with petechiae on his legs. Laboratory testing showed a white blood cell count of 10,400/ mm3, haemoglobin of 12.3 g/dl. Six blood cultures were all positive for S. bovis (MIC of penicillin: 0.047 lg/ml). A transesophageal echocardiogram showed vegetations in the mitral and aortic valves with severe mitral regurgitation. The patient responded well to an antimicrobial therapy of penicillin 3 million U/4 h i.v. (6 weeks) and gentamicin 240 mg/24 h i.v. (2 weeks). Colonoscopy was normal. Seven months later, the patient died
of liver and lung metastasis of his ampullary carcinoma. Microbiology: We have followed up prospectively all episodes of significant bacteremia caused by S. bovis group during the period 1990–2011 in our institution. Isolates were stored in skim milk DifcoTM (Becton Dickinson, Sparks, MD, USA) at 70 °C and were identified by a combination of conventional phenotypic tests, using the API 20 Strep and/or GP card Vitek 2 system (both from bioMerieux, Marcy l’Etoile, France) and molecular methods by analysis of the complete rRNA gene sequence and the polymorphism of manganese-dependent superoxide dismutase gene (sodA). Both isolates of this report were initially identified as S. bovis II/1 by the API 20 Strep system V6.0. SodA was used for molecular identification according to the indications of Poyart et al. (1). The sequences obtained were compared with those of the corresponding genes available in GenBank by using Blast sequence software (http://www.ncbi.nlm.nih. gov/) and showed 100% similarity with Streptococcus infantarius subsp. infantarius. The MIC of penicillin was determined by E-test (AB Biodisk, Solna, Sweden) on MuellerHinton agar plates supplemented with 5% sheep blood. The type of infection and underlying diseases associated with S. infantarius are poorly understood, but appear to be associated with biliary tract infections and non-bowel digestive cancer (2,3). Little is known about the infections associated with the two subspecies: S. infantarius subsp. coli and S. infantarius subsp. infantarius; the former has been associ-
Table 1 Reported cases of endocarditis caused by Streptococcus bovis group
Author (Ref.)
Biotype II/1* Endocarditis/bacteremia
Biotype II/2† Endocarditis/bacteremia
Biotype I‡ Endocarditis/bacteremia
Ruoff et al. (2) Claridge et al. (10) Tripodi et al. (12) Beck et al. (9) Vaska and Faoagali (13) Romero et al. (6) Gomez-Garces et al. (7) Lazarovitch et al. (8) Our series Total
1/10 1/2 0/1 4/14 0/1 0/7 2/5 0/5 4/47 12/92 (13%)
2/7 3/10 4/4 0/11 1/5 6/24 2/24 3/13 0/27 21/125 (17%)
16/17 1/1 18/20 9/21 6/10 1/14 10/15 2/6 86/107 149/211 (71%)
*Streptococcus bovis biotype II/1 now S. infantarius; †Streptococcus bovis biotype II/2 now S. gallolyticus subsp. pasteurianus; ‡Streptococcus bovis biotype I now S. gallolyticus subsp. gallolyticus.
ª 2014 John Wiley & Sons Ltd Int J Clin Pract, May 2014, 68, 5, 653–654. doi: 10.1111/ijcp.12376
653
654
Letter
ated with endocarditis in otters and the latter has been isolated from dairy milk products (4,5). Streptococcus infantarius subsp. infantarius is rarely isolated from humans (6–8). In the largest published series of bacteriemia caused by S. infantarius (9), all isolates belonged to S. infantarius subsp. coli. We have only found in the literature a report of human infection with S. infantarius subsp. infantarius from a neutropenic patient with metastasic colon cancer (8). During the period of study, a total of 185 isolates of S. bovis group were recovered (47 S. infantarius) and we would like to remark that during this period, two of the four endocarditis caused by S. infantarius diagnosed in our hospital were caused by S. infantarius subsp. infantarius, while only one of 43 bacteremia without endocarditis was caused by this subspecies (2/4 vs. 1/43; p = 0.01 Yates’ v2 test). These four cases of endocarditis accounted for the 4% of all endocarditis caused by S. bovis group in our institution (4/90). Although we had only four cases, their characteristics do not seem different from those caused by S. gallolyticus subsp. gallolyticus (86 cases), formerly S. bovis biotype I, except for its lower association with colorectal neoplasms (1/4 vs. 56/78; p = 0.002 Yates’ v2 test), including only patients who underwent colonoscopy, and with a high percentage of prosthetic valve endocarditis (3/4 vs. 10/86 p < 0.001 Yates’ v2 test). Endocarditis caused by S. infantarius is rarely found. To our knowledge, there are only eight cases of endocarditis caused by S. infantarius published in the literature (Table 1), all of them as a part of a series of endocarditis and bacteremia (2,7,9,10). In a French multicentre study (11), S. infantarius was responsible of the 7% (5/74) of endocarditis caused by S. bovis group. Only Beck et al. (9) specified which subspecies caused their four cases of endocarditis and all were caused by S. infantarius subsp. coli; however, they employed 16S rRNA gene sequencing to identify their strains. A study conducted by Poyart et al. (1) showed that 16S rDNA sequences of the S. bovis group type strains have a percentage of homology ranging from 97.1% to 99.8% and to differentiate such strains, the sodA gene is a more discriminative target sequence than the 16S rRNA gene. We have identified all 47 strains of S. infantarius by both methods and all of them were assigned as S. infantarius subsp. coli using 16S
rRNA method, whereas three of them were identified as S. infantarius subsp. infantarius by sodA gene sequencing. Romero et al. (6) also detected differences in isolate identification between the 16S rRNA and sodA gene sequencing methods, considering the latter the most accurate method of identification. In conclusion, the association of S. infantarius with endocarditis appears to be low, in contrast to S. gallolyticus subsp. gallolyticus (14). Streptococcus gallolyticus subsp. gallolyticus forms biofilms on collagen types I and IV and this is crucial for explaining the specific association with endocarditis (15); however, S. infantarius is not able to form biofilms on collagen. More studies are needed to determine the clinical profile of these infections and if the two subspecies may be associated with different types of infection. J. Corredoira Sanchez,1 F. Garcıa-Garrote,2 M. J. Garcıa-Paıs,1 A. Testa Fernandez,3 C. Gonzalez-Juanatey,3 M. P. Alonso Garcıa,2 1 Infectious Disease Unit, Hospital Lucus Augusti, Lugo, Spain 2 Department of Clinical Microbiology Hospital Lucus Augusti, Lugo, Spain 3 Department of Cardiology, Hospital Lucus Augusti, Lugo, Spain E-mail: [email protected]
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References 1 Poyart C, Quesne G, Trieu-Cuot P. Taxonomic dissection of the Streptococcus bovis group by analysis of manganese-dependent superoxidase dismutase gene (sodA) sequences: reclassification of ‘Streptococcus subsp. coli’ as Streptococcus lutetiensis sp. nov. and of Streptococcus bovis biotype II.2 as Streptococcus pasteurianus sp. nov. Int J Syst Evol Microbiol 2002; 52: 1247–55. 2 Ruoff K, Miller S, Garner C et al. Bacteraemia with Streptococcus bovis and Streptococcus salivarius: clinical correlates of more accurate identification of isolates. J Clin Microbiol 1989; 27: 305–8. 3 Corredoira J, Alonso P, Coira A et al. Association between Streptococcus infantarius (formerly S. bovis II/1) bacteraemia and noncolonic cancer. J Clin Microbiol 2008; 46: 1570. 4 Counihan-Edgar K, Gill V, Doroff A et al. Genotypic characterization of Streptococus infantarius subsp. coli isolates from sea otters with infective endocarditis and/or septicemia and from environmental mussel samples. J Clin Microbiol 2012; 50: 4131–3. 5 Abdelgabir W, Nielsen D, Hamad S, Jakobsen M. A traditional Sudanese fermented camel’s milk prod-
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14
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uct, Gariss, as a habitat of Streptococcus infantarius subsp. infantarius. Int J Food Microbiol 2008; 127: 215–9. Romero B, Morosini M, Loza E et al. Reidentification of Streptococcus bovis isolates causing bacteremia according to the new taxonomy criteria: still an issue? J Clin Microbiol 2011; 49: 3228–33. Gomez-Garces J, Gil Y, Burillo A, Wilhelmi I, Palomo M. Diseases associated with bloodstream infections caused by the new species included in the old Streptococcus bovis group. Enferm Infecc Microbiol Clin 2012; 30: 175–9. Lazarovitch T, Shango M, Levine M et al. The relationship between the new taxonomy of Streptococcus bovis and its clonality to colon cancer, endocarditis, and biliary disease. Infection 2013; 41: 329–37. Beck M, Frodl R, Funke G. Comprehensive study of strains previously designated Streptococcus bovis consecutively isolated from human blood cultures and emended description of Streptococcus gallolyticus and Streptococcus infantarius subsp. coli. J Clin Microbiol 2008; 46: 2966–72. Claridge J, Attori S, Zhang Q, Bartell J. 16S ribosomal DNA sequence analysis distinguishes biotypes of Streptococcus bovis: Streptococcus bovis biotype II/2 is a separate genospecies and the predominant clinical isolate in adult males. J Clin Microbiol 2001; 39: 1549–52. Giannisoti E, Chirouze C, Buvet A et al. Characteristics and regional variations of group D streptococcal endocarditis in France. Clin Microbiol Infect 2007; 13: 770–6. Tripodi M, Fortunato R, Utilli R, Triassi M, Zarilli R. Molecular epidemiology of Streptococcus bovis causing endocarditis and bacteremia in Italian patients. Clin Microbiol Infect 2005; 11: 814–9. Vaska V, Faoagali J. Streptococcus bovis bacteraemia: identification within organism complex and association with endocarditis and colonic malignancy. Pathology 2009; 41: 183–6. Corredoira J, Garcıa Garrote F, Rabu~ nal R et al. Association between bacteraemia due to Streptococcus gallolyticus subsp. gallolyticus (S. bovis I) and colorectal cancer: a prospective study of 109 cases. Clin Infect Dis 2012; 55: 491–6. Boleij A, Muytjens C, Bukjari S et al. Novel clues on the specific association of Streptococcus gallolyticus subsp. gallolyticus with colorectal cancer. J Infect Dis 2011; 203: 1101–9.
Disclosures The authors have nothing to disclose. doi: 10.1111/ijcp.12376
ª 2014 John Wiley & Sons Ltd Int J Clin Pract, May 2014, 68, 5, 653–654
Endocarditis caused by Streptococcus infantarius subsp. infantarius: a report of two cases To the Editor:
Introduction Streptococcus infantarius, formerly known as Streptococcus bovis biotype II/1, is a member of S. bovis/equinus complex, associated with several human and animal infections with low clinical impact. Streptococcus infantarius comprises two subspecies genetically closely related, S. infantarius subsp. coli and S. infantarius subsp. infantarius. S. infantarius subsp. infantarius has been recovered from traditionally fermented dairy and plant products but rarely has been isolated in human specimens. We describe herein two cases of endocarditis caused by Streptococcus infantarius subsp. infantarius which, to our knowledge, are the first reported cases of endocarditis.
Case 1 An 88-year-old man was admitted to our hospital with 15-day history of dyspnoea and general malaise. Fourteen years previously, the patient had undergone aortic valve replacement (biological valve) because of aortic valve insufficiency. Physical examination revealed a temperature of 37.5 °C, a grade III/VI systolic murmur and basal lung crackles. Laboratory studies showed a haemoglobin of 10.5 g/dl, sedimentation rate of 55 mm, C-reactive protein of 32. Urinalysis revealed microscopic haematuria and red cell casts. A chest X-ray revealed signs of cardiac failure. Two blood cultures were positive for Streptococcus bovis (MIC, minimum inhibitory
concentration of penicillin: 0.094 lg/ml). Transesophageal echocardiographic evaluation showed an aortic vegetation with severe aortic regurgitation. The patient was treated with diuretics and antibiotic therapy was started with ceftriaxone 2 g/24 h i.v. (6 weeks) plus gentamicin 240 mg/24 h i.v. (2 weeks), which resulted in recovery. Surgery was rejected in this patient because of his advanced age. A colonoscopy showed diverticula. Nine months later, the patient died of cardiac failure.
Case 2 A 66-year-old man was admitted on the hospital because of weakness, low-grade fever, diffuse myalgia and weight loss of 1-month duration. There was a previous history of diabetes mellitus, and surgery for ampulla of Vater carcinoma 2 years earlier. Eight years prior to admission, he had undergone mitral valve replacement (mechanical valve) for mitral insufficiency. Examination showed a temperature of 37.4 °C, a systolic murmur consistent with mitral regurgitation with petechiae on his legs. Laboratory testing showed a white blood cell count of 10,400/ mm3, haemoglobin of 12.3 g/dl. Six blood cultures were all positive for S. bovis (MIC of penicillin: 0.047 lg/ml). A transesophageal echocardiogram showed vegetations in the mitral and aortic valves with severe mitral regurgitation. The patient responded well to an antimicrobial therapy of penicillin 3 million U/4 h i.v. (6 weeks) and gentamicin 240 mg/24 h i.v. (2 weeks). Colonoscopy was normal. Seven months later, the patient died
of liver and lung metastasis of his ampullary carcinoma. Microbiology: We have followed up prospectively all episodes of significant bacteremia caused by S. bovis group during the period 1990–2011 in our institution. Isolates were stored in skim milk DifcoTM (Becton Dickinson, Sparks, MD, USA) at 70 °C and were identified by a combination of conventional phenotypic tests, using the API 20 Strep and/or GP card Vitek 2 system (both from bioMerieux, Marcy l’Etoile, France) and molecular methods by analysis of the complete rRNA gene sequence and the polymorphism of manganese-dependent superoxide dismutase gene (sodA). Both isolates of this report were initially identified as S. bovis II/1 by the API 20 Strep system V6.0. SodA was used for molecular identification according to the indications of Poyart et al. (1). The sequences obtained were compared with those of the corresponding genes available in GenBank by using Blast sequence software (http://www.ncbi.nlm.nih. gov/) and showed 100% similarity with Streptococcus infantarius subsp. infantarius. The MIC of penicillin was determined by E-test (AB Biodisk, Solna, Sweden) on MuellerHinton agar plates supplemented with 5% sheep blood. The type of infection and underlying diseases associated with S. infantarius are poorly understood, but appear to be associated with biliary tract infections and non-bowel digestive cancer (2,3). Little is known about the infections associated with the two subspecies: S. infantarius subsp. coli and S. infantarius subsp. infantarius; the former has been associ-
Table 1 Reported cases of endocarditis caused by Streptococcus bovis group
Author (Ref.)
Biotype II/1* Endocarditis/bacteremia
Biotype II/2† Endocarditis/bacteremia
Biotype I‡ Endocarditis/bacteremia
Ruoff et al. (2) Claridge et al. (10) Tripodi et al. (12) Beck et al. (9) Vaska and Faoagali (13) Romero et al. (6) Gomez-Garces et al. (7) Lazarovitch et al. (8) Our series Total
1/10 1/2 0/1 4/14 0/1 0/7 2/5 0/5 4/47 12/92 (13%)
2/7 3/10 4/4 0/11 1/5 6/24 2/24 3/13 0/27 21/125 (17%)
16/17 1/1 18/20 9/21 6/10 1/14 10/15 2/6 86/107 149/211 (71%)
*Streptococcus bovis biotype II/1 now S. infantarius; †Streptococcus bovis biotype II/2 now S. gallolyticus subsp. pasteurianus; ‡Streptococcus bovis biotype I now S. gallolyticus subsp. gallolyticus.
ª 2014 John Wiley & Sons Ltd Int J Clin Pract, May 2014, 68, 5, 653–654. doi: 10.1111/ijcp.12376
653
654
Letter
ated with endocarditis in otters and the latter has been isolated from dairy milk products (4,5). Streptococcus infantarius subsp. infantarius is rarely isolated from humans (6–8). In the largest published series of bacteriemia caused by S. infantarius (9), all isolates belonged to S. infantarius subsp. coli. We have only found in the literature a report of human infection with S. infantarius subsp. infantarius from a neutropenic patient with metastasic colon cancer (8). During the period of study, a total of 185 isolates of S. bovis group were recovered (47 S. infantarius) and we would like to remark that during this period, two of the four endocarditis caused by S. infantarius diagnosed in our hospital were caused by S. infantarius subsp. infantarius, while only one of 43 bacteremia without endocarditis was caused by this subspecies (2/4 vs. 1/43; p = 0.01 Yates’ v2 test). These four cases of endocarditis accounted for the 4% of all endocarditis caused by S. bovis group in our institution (4/90). Although we had only four cases, their characteristics do not seem different from those caused by S. gallolyticus subsp. gallolyticus (86 cases), formerly S. bovis biotype I, except for its lower association with colorectal neoplasms (1/4 vs. 56/78; p = 0.002 Yates’ v2 test), including only patients who underwent colonoscopy, and with a high percentage of prosthetic valve endocarditis (3/4 vs. 10/86 p < 0.001 Yates’ v2 test). Endocarditis caused by S. infantarius is rarely found. To our knowledge, there are only eight cases of endocarditis caused by S. infantarius published in the literature (Table 1), all of them as a part of a series of endocarditis and bacteremia (2,7,9,10). In a French multicentre study (11), S. infantarius was responsible of the 7% (5/74) of endocarditis caused by S. bovis group. Only Beck et al. (9) specified which subspecies caused their four cases of endocarditis and all were caused by S. infantarius subsp. coli; however, they employed 16S rRNA gene sequencing to identify their strains. A study conducted by Poyart et al. (1) showed that 16S rDNA sequences of the S. bovis group type strains have a percentage of homology ranging from 97.1% to 99.8% and to differentiate such strains, the sodA gene is a more discriminative target sequence than the 16S rRNA gene. We have identified all 47 strains of S. infantarius by both methods and all of them were assigned as S. infantarius subsp. coli using 16S
rRNA method, whereas three of them were identified as S. infantarius subsp. infantarius by sodA gene sequencing. Romero et al. (6) also detected differences in isolate identification between the 16S rRNA and sodA gene sequencing methods, considering the latter the most accurate method of identification. In conclusion, the association of S. infantarius with endocarditis appears to be low, in contrast to S. gallolyticus subsp. gallolyticus (14). Streptococcus gallolyticus subsp. gallolyticus forms biofilms on collagen types I and IV and this is crucial for explaining the specific association with endocarditis (15); however, S. infantarius is not able to form biofilms on collagen. More studies are needed to determine the clinical profile of these infections and if the two subspecies may be associated with different types of infection. J. Corredoira Sanchez,1 F. Garcıa-Garrote,2 M. J. Garcıa-Paıs,1 A. Testa Fernandez,3 C. Gonzalez-Juanatey,3 M. P. Alonso Garcıa,2 1 Infectious Disease Unit, Hospital Lucus Augusti, Lugo, Spain 2 Department of Clinical Microbiology Hospital Lucus Augusti, Lugo, Spain 3 Department of Cardiology, Hospital Lucus Augusti, Lugo, Spain E-mail: [email protected]
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References 1 Poyart C, Quesne G, Trieu-Cuot P. Taxonomic dissection of the Streptococcus bovis group by analysis of manganese-dependent superoxidase dismutase gene (sodA) sequences: reclassification of ‘Streptococcus subsp. coli’ as Streptococcus lutetiensis sp. nov. and of Streptococcus bovis biotype II.2 as Streptococcus pasteurianus sp. nov. Int J Syst Evol Microbiol 2002; 52: 1247–55. 2 Ruoff K, Miller S, Garner C et al. Bacteraemia with Streptococcus bovis and Streptococcus salivarius: clinical correlates of more accurate identification of isolates. J Clin Microbiol 1989; 27: 305–8. 3 Corredoira J, Alonso P, Coira A et al. Association between Streptococcus infantarius (formerly S. bovis II/1) bacteraemia and noncolonic cancer. J Clin Microbiol 2008; 46: 1570. 4 Counihan-Edgar K, Gill V, Doroff A et al. Genotypic characterization of Streptococus infantarius subsp. coli isolates from sea otters with infective endocarditis and/or septicemia and from environmental mussel samples. J Clin Microbiol 2012; 50: 4131–3. 5 Abdelgabir W, Nielsen D, Hamad S, Jakobsen M. A traditional Sudanese fermented camel’s milk prod-
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14
15
uct, Gariss, as a habitat of Streptococcus infantarius subsp. infantarius. Int J Food Microbiol 2008; 127: 215–9. Romero B, Morosini M, Loza E et al. Reidentification of Streptococcus bovis isolates causing bacteremia according to the new taxonomy criteria: still an issue? J Clin Microbiol 2011; 49: 3228–33. Gomez-Garces J, Gil Y, Burillo A, Wilhelmi I, Palomo M. Diseases associated with bloodstream infections caused by the new species included in the old Streptococcus bovis group. Enferm Infecc Microbiol Clin 2012; 30: 175–9. Lazarovitch T, Shango M, Levine M et al. The relationship between the new taxonomy of Streptococcus bovis and its clonality to colon cancer, endocarditis, and biliary disease. Infection 2013; 41: 329–37. Beck M, Frodl R, Funke G. Comprehensive study of strains previously designated Streptococcus bovis consecutively isolated from human blood cultures and emended description of Streptococcus gallolyticus and Streptococcus infantarius subsp. coli. J Clin Microbiol 2008; 46: 2966–72. Claridge J, Attori S, Zhang Q, Bartell J. 16S ribosomal DNA sequence analysis distinguishes biotypes of Streptococcus bovis: Streptococcus bovis biotype II/2 is a separate genospecies and the predominant clinical isolate in adult males. J Clin Microbiol 2001; 39: 1549–52. Giannisoti E, Chirouze C, Buvet A et al. Characteristics and regional variations of group D streptococcal endocarditis in France. Clin Microbiol Infect 2007; 13: 770–6. Tripodi M, Fortunato R, Utilli R, Triassi M, Zarilli R. Molecular epidemiology of Streptococcus bovis causing endocarditis and bacteremia in Italian patients. Clin Microbiol Infect 2005; 11: 814–9. Vaska V, Faoagali J. Streptococcus bovis bacteraemia: identification within organism complex and association with endocarditis and colonic malignancy. Pathology 2009; 41: 183–6. Corredoira J, Garcıa Garrote F, Rabu~ nal R et al. Association between bacteraemia due to Streptococcus gallolyticus subsp. gallolyticus (S. bovis I) and colorectal cancer: a prospective study of 109 cases. Clin Infect Dis 2012; 55: 491–6. Boleij A, Muytjens C, Bukjari S et al. Novel clues on the specific association of Streptococcus gallolyticus subsp. gallolyticus with colorectal cancer. J Infect Dis 2011; 203: 1101–9.
Disclosures The authors have nothing to disclose. doi: 10.1111/ijcp.12376
ª 2014 John Wiley & Sons Ltd Int J Clin Pract, May 2014, 68, 5, 653–654
