Procalcitonin performance in detecting serious and invasive bacterial infections in children with fever without apparent source: a systematic review and meta-analysis

ABSTRACT Introduction: The management of children with fever without apparent sources (FWAS) is difficult. This study aimed to evaluate the diagnostic accuracy of procalcitonin (PCT) in detecting serious or invasive bacterial infection (SBI or IBI) in children with FWAS. Areas covered: A systematic review of literature from 2007 to 2017 was performed on Medline. Twelve studies were included, involving 7,260 children with FWAS and analyzing the diagnostic performance of PCT. Four meta-analyses were performed to calculate pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve for PCT in detecting SBI and IBI, at two different thresholds. Considering IBI, PCT sensitivity and specificity at a threshold of 0.5 ng/mL were 0.82 and 0.86, respectively; at a threshold of 2 ng/mL sensitivity and specificity were 0.61 and 0.94, respectively. In detecting SBI, PCT performance was lower, with 55% sensitivity and 85% specificity at a threshold of 0.5 ng/mL, and 30% sensitivity and 95% specificity at a threshold of 2 ng/mL. Expert commentary: Considering IBI, results showed high diagnostic accuracy for PCT. Conversely, PCT performance in diagnosis of SBI was poor. These findings suggest that PCT level determination could be helpful in detecting meningitis, bacteremia and sepsis in children with FWAS.

[1]  P. Diggle,et al.  Predicting Risk of Serious Bacterial Infections in Febrile Children in the Emergency Department , 2017, Pediatrics.

[2]  Kate Dorney,et al.  Febrile infant update , 2017, Current opinion in pediatrics.

[3]  F. D. De Rosa,et al.  Current use and potential role of procalcitonin in the diagnostic work up and follow up of febrile neutropenia in hematological patients , 2017, Expert review of hematology.

[4]  S. Kilic,et al.  Is colchicine more effective to prevent periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis episodes in Mediterranean fever gene variants? , 2017, Pediatrics international : official journal of the Japan Pediatric Society.

[5]  Y. Kim,et al.  Clinical usefulness of serum procalcitonin level in distinguishing between Kawasaki disease and other infections in febrile children , 2017, Korean journal of pediatrics.

[6]  M. Boubaya,et al.  New parameters on the hematology analyzer XN‐10 (SysmexTM) allow to distinguish childhood bacterial and viral infections , 2017, International journal of laboratory hematology.

[7]  B. Gomez,et al.  Validation of a predictive model for identifying febrile young infants with altered urinalysis at low risk of invasive bacterial infection , 2017, European Journal of Clinical Microbiology & Infectious Diseases.

[8]  Ruixi Liu,et al.  Relationship between IL-27 and coronary arterial lesions in children with Kawasaki disease , 2017, Clinical and Experimental Medicine.

[9]  B. Phillips,et al.  Prospective cohort study of procalcitonin levels in children with cancer presenting with febrile neutropenia , 2017, BMC Pediatrics.

[10]  N. Radhakrishnan,et al.  Serum Procalcitonin for Predicting Significant Infections and Mortality in Pediatric Oncology. , 2016, Indian pediatrics.

[11]  N. Zhao,et al.  Comparison of the diagnostic power of cytokine patterns and procalcitonin for predicting infection among paediatric haematology/oncology patients. , 2016, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[12]  S. Pon,et al.  The Diagnostic Accuracy of Serum Procalcitonin for Bacteremia in Critically Ill Children , 2016, Infectious diseases in clinical practice.

[13]  J. R. Contreras,et al.  Lack of Accuracy of Biomarkers and Physical Examination to Detect Bacterial Infection in Febrile Infants , 2016, Pediatric emergency care.

[14]  Chengcheng Hu,et al.  Procalcitonin as a Marker of Bacteremia in Patients With Fever and Acute Lymphoblastic Leukemia , 2016, Pediatric emergency care.

[15]  A. Gervaix,et al.  Validation of the “Step-by-Step” Approach in the Management of Young Febrile Infants , 2016, Pediatrics.

[16]  S. Mintegi,et al.  Outpatient management of selected young febrile infants without antibiotics , 2016, Archives of Disease in Childhood.

[17]  B. Koes,et al.  C-Reactive Protein Level as Diagnostic Marker in Young Febrile Children Presenting in a General Practice Out-of-Hours Service , 2016, The Journal of the American Board of Family Medicine.

[18]  J. Haagsma,et al.  Procalcitonin-guided therapy for the initiation of antibiotics in the ED: a systematic review. , 2016, The American journal of emergency medicine.

[19]  M. Vakili,et al.  Early prediction of renal parenchymal injury with serum procalcitonin , 2016, Journal of renal injury prevention.

[20]  I. Cinel,et al.  The diagnostic value of soluble urokinase plasminogen activator receptor compared with C-reactive protein and procalcitonin in children with febrile neutropenia , 2016, Pediatric hematology and oncology.

[21]  L. Szenborn,et al.  Procalcitonin and C-reactive protein-based decision tree model for distinguishing PFAPA flares from acute infections , 2016, Bosnian journal of basic medical sciences.

[22]  Lirong Lin,et al.  Diagnostic value of serum procalcitonin for acute pyelonephritis in infants and children with urinary tract infections: an updated meta-analysis , 2016, World Journal of Urology.

[23]  C. Muñoz-Almagro,et al.  Clinical, biochemical and microbiological factors associated with the prognosis of pneumococcal meningitis in children. , 2016, Enfermedades infecciosas y microbiologia clinica.

[24]  K. Tullus Low urinary bacterial counts: do they count? , 2016, Pediatric Nephrology.

[25]  C. Marcello,et al.  Procalcitonin and community-acquired pneumonia (CAP) in children. , 2015, Clinica chimica acta; international journal of clinical chemistry.

[26]  D. Foell,et al.  Increased serum concentrations of neutrophil-derived protein S100A12 in heterozygous carriers of MEFV mutations. , 2015, Clinical and experimental rheumatology.

[27]  A. Heidarzadeh,et al.  Diagnostic value of IL-6, CRP, WBC, and absolute neutrophil count to predict serious bacterial infection in febrile infants. , 2015, Acta medica Iranica.

[28]  D. Streiner,et al.  Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study , 2015, PloS one.

[29]  H. Ekmekçi,et al.  Adrenomedullin—A New Marker in Febrile Neutropenia: Comparison With CRP and Procalcitonin , 2015, Pediatric hematology and oncology.

[30]  Chester Ni,et al.  Comparison of biomarkers for systemic juvenile idiopathic arthritis , 2015, Pediatric Research.

[31]  N. Bošnjak,et al.  Lab-score is a valuable predictor of serious bacterial infection in infants admitted to hospital , 2015, Wiener klinische Wochenschrift.

[32]  F. Kee,et al.  Clinical and Cost-Effectiveness of Procalcitonin Test for Prodromal Meningococcal Disease–A Meta-Analysis , 2015, PloS one.

[33]  R. Hankard,et al.  High procalcitonin and thrombocytopenic purpura in a case of Kikuchi-Fujimoto disease. , 2015, Archives de pediatrie : organe officiel de la Societe francaise de pediatrie.

[34]  O. Rajas,et al.  Review of Non-bacterial Infections in Respiratory Medicine: Viral Pneumonia , 2015, Archivos de Bronconeumología (English Edition).

[35]  A. Chen,et al.  Burkholderia gladioli infection isolated from the blood cultures of newborns in the neonatal intensive care unit , 2015, European Journal of Clinical Microbiology & Infectious Diseases.

[36]  Jong-seo Yoon,et al.  Pentraxin 3 as a clinical marker in children with lower respiratory tract infection , 2015, Pediatric pulmonology.

[37]  B. Tarai,et al.  Hemophilus influenzae meningitis and septicaemia in a 14-month-old child after primary immunisation , 2015, Indian journal of medical microbiology.

[38]  R. Mozun,et al.  Febrile Young Infants With Altered Urinalysis at Low Risk for Invasive Bacterial Infection. A Spanish Pediatric Emergency Research Network’s Study , 2015, The Pediatric infectious disease journal.

[39]  A. Gervaix,et al.  Impact of the Lab-Score on Antibiotic Prescription Rate in Children with Fever without Source: A Randomized Controlled Trial , 2014, PloS one.

[40]  S. Aronoff,et al.  Use of serum procalcitonin in evaluation of febrile infants: a meta-analysis of 2317 patients. , 2014, The Journal of emergency medicine.

[41]  Susan Mallett,et al.  QUADAS-2: A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies , 2011, Annals of Internal Medicine.

[42]  A. Gervaix,et al.  C-reactive Protein, Procalcitonin and the Lab-Score for Detecting Serious Bacterial Infections in Febrile Children at the Emergency Department: A Prospective Observational Study , 2014, The Pediatric infectious disease journal.

[43]  Dimitris Mavridis,et al.  A hands-on practical tutorial on performing meta-analysis with Stata , 2014, Evidence-Based Mental Health.

[44]  H. Wong,et al.  Biomarkers of sepsis and their potential value in diagnosis, prognosis and treatment , 2014, Expert review of clinical immunology.

[45]  K. Karavanaki,et al.  Clinical and laboratory indices of severe renal lesions in children with febrile urinary tract infection , 2014, Acta paediatrica.

[46]  Pooneh Nabavizadeh,et al.  Can Procalcitonin Reduce Unnecessary Voiding Cystoureterography in Children with First Febrile Urinary Tract Infection? , 2014, Iranian journal of pediatrics.

[47]  M. Bigham,et al.  Use of procalcitonin for the prediction and treatment of acute bacterial infection in children , 2014, Current opinion in pediatrics.

[48]  H. Otukesh,et al.  Serum procalcitonin level for prediction of high-grade vesicoureteral reflux in urinary tract infection. , 2014, Iranian journal of kidney diseases.

[49]  K. Lue,et al.  Comparison of procalcitonin and different guidelines for first febrile urinary tract infection in children by imaging , 2014, Pediatric Nephrology.

[50]  S. Testa,et al.  Febrile urinary tract infections: clinical and laboratory diagnosis, imaging, and prognosis. , 2014, Seminars in nuclear medicine.

[51]  M. Alarcon,et al.  Afebrile Very Young Infants With Urinary Tract Infection and the Risk for Bacteremia , 2014, The Pediatric infectious disease journal.

[52]  M. Grzybowski,et al.  Procalcitonin as a marker of serious bacterial infections in febrile children younger than 3 years old. , 2014, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[53]  G. Haeusler,et al.  An Updated Systematic Review and Meta-analysis of the Predictive Value of Serum Biomarkers in the Assessment of Fever During Neutropenia in Children With Cancer , 2013, The Pediatric infectious disease journal.

[54]  K. Lue,et al.  Role of Procalcitonin in Predicting Dilating Vesicoureteral Reflux in Young Children Hospitalized With a First Febrile Urinary Tract Infection , 2013, The Pediatric infectious disease journal.

[55]  S. Mintegi,et al.  Accuracy of a sequential approach to identify young febrile infants at low risk for invasive bacterial infection , 2013, Emergency Medicine Journal.

[56]  N. Bošnjak,et al.  CD15s is a potential biomarker of serious bacterial infection in infants admitted to hospital , 2013, European Journal of Pediatrics.

[57]  P. Schlattmann,et al.  Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. , 2013, Lancet. Infectious Diseases (Print).

[58]  B. Freyne,et al.  Field Testing the Utility of Procalcitonin and the Acute Infantile Observation Score in Febrile Infants 6 to 36 Months Old Presenting to the Pediatric Emergency Department With No Obvious Focus of Infection , 2013, Clinical pediatrics.

[59]  Chien-Chang Lee,et al.  The use of procalcitonin in the diagnosis of bone and joint infection: a systemic review and meta-analysis , 2013, European Journal of Clinical Microbiology & Infectious Diseases.

[60]  Rishi Kapoor,et al.  Serum Procalcitonin in Septic Meningitis , 2013, The Indian Journal of Pediatrics.

[61]  S. Mintegi,et al.  Diagnostic Performance of the Lab-score in Predicting Severe and Invasive Bacterial Infections in Well-appearing Young Febrile Infants , 2012, The Pediatric infectious disease journal.

[62]  S. Mintegi,et al.  Diagnostic Value of Procalcitonin in Well-Appearing Young Febrile Infants , 2012, Pediatrics.

[63]  Chien-Chang Lee,et al.  Comparison of the test characteristics of procalcitonin to C-reactive protein and leukocytosis for the detection of serious bacterial infections in children presenting with fever without source: a systematic review and meta-analysis. , 2012, Annals of emergency medicine.

[64]  N. Akar,et al.  The value of procalcitonin measurements in children with familial Mediterranean fever , 2012, Rheumatology International.

[65]  H. Wong,et al.  Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children , 2012, Critical Care.

[66]  J. D. Ozeran,et al.  Serial Procalcitonin Levels to Detect Bacteremia in Febrile Neutropenia , 2012, Clinical pediatrics.

[67]  A. Bhutta,et al.  Biomarkers for risk stratification of febrile neutropenia among children with malignancy: A pilot study , 2012, Pediatric blood & cancer.

[68]  Shu-guang Lin,et al.  Role of Procalcitonin in the Diagnosis of Severe Infection in Pediatric Patients With Fever and Neutropenia—A Systemic Review and Meta-analysis , 2012, The Pediatric infectious disease journal.

[69]  R. Oostenbrink Implementation of procalcitonin in the management of febrile children. , 2012, The Pediatric infectious disease journal.

[70]  D. Mant,et al.  Systematic review and validation of prediction rules for identifying children with serious infections in emergency departments and urgent-access primary care. , 2012, Health technology assessment.

[71]  J. García-García,et al.  Procalcitonin to Detect Invasive Bacterial Infection in Non–Toxic-appearing Infants With Fever Without Apparent Source in the Emergency Department , 2012, The Pediatric infectious disease journal.

[72]  A. Gervaix Commentary: procalcitonin to detect invasive bacterial infection in febrile infants. , 2012, The Pediatric infectious disease journal.

[73]  K. Lue,et al.  Diagnostic performance of procalcitonin for hospitalised children with acute pyelonephritis presenting to the paediatric emergency department , 2012, Emergency Medicine Journal.

[74]  K. Powell,et al.  Serum Procalcitonin Concentration in the Evaluation of Febrile Infants 2 to 60 Days of Age , 2012, Pediatric emergency care.

[75]  A. Gervaix,et al.  Procalcitonin measurement for detection of serious bacterial infection in febrile children: comparison between two automated immunoassays. , 2012, Clinical biochemistry.

[76]  E. Nahum,et al.  Procalcitonin level as an aid for the diagnosis of bacterial infections following pediatric cardiac surgery. , 2012, Journal of critical care.

[77]  I. O. Ipek,et al.  Relationship between procalcitonin levels and presence of vesicoureteral reflux during first febrile urinary tract infection in children. , 2012, Urology.

[78]  S. Erdoğan,et al.  Procalcitonin is More Useful Than C-reactive Protein in Differentiation of Fever in Patients With Sickle Cell Disease , 2012, Journal of pediatric hematology/oncology.

[79]  A. Tsertsvadze,et al.  Diagnosis and management of febrile infants (0-3 months). , 2012, Evidence report/technology assessment.

[80]  L. Stewart,et al.  Systematic review and meta-analysis of the value of initial biomarkers in predicting adverse outcome in febrile neutropenic episodes in children and young people with cancer , 2012, BMC Medicine.

[81]  G. Breart,et al.  Prediction of moderate and high grade vesicoureteral reflux after a first febrile urinary tract infection in children: construction and internal validation of a clinical decision rule. , 2011, The Journal of urology.

[82]  K. Lue,et al.  The role of procalcitonin for acute pyelonephritis and subsequent renal scarring in infants and young children. , 2011, The Journal of urology.

[83]  D. Mant,et al.  Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review , 2011, BMJ : British Medical Journal.

[84]  A. Gervaix,et al.  Markers for bacterial infection in children with fever without source , 2011, Archives of Disease in Childhood.

[85]  A. Gervaix,et al.  Procalcitonin: A Key Marker in Children with Urinary Tract Infection , 2011, Advances in urology.

[86]  A. Gervaix,et al.  Identifying severe bacterial infection in children with fever without source , 2010, Expert review of anti-infective therapy.

[87]  Xi-rong Guo,et al.  The accuracy of the procalcitonin test for the diagnosis of neonatal sepsis: A meta-analysis , 2010, Scandinavian journal of infectious diseases.

[88]  E. Bilavsky,et al.  Should complete blood count be part of the evaluation of febrile infants aged ≤2 months? , 2010, Acta paediatrica.

[89]  A. Gervaix,et al.  Validation of a laboratory risk index score for the identification of severe bacterial infection in children with fever without source , 2010, Archives of Disease in Childhood.

[90]  B. Pourakbari,et al.  Evaluation of procalcitonin and neopterin level in serum of patients with acute bacterial infection. , 2010, The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases.

[91]  M. Hatzistilianou,et al.  Procalcitonin as an early marker of bacterial infection in neutropenic febrile children with acute lymphoblastic leukemia , 2010, Inflammation Research.

[92]  R. Nikfar,et al.  Usefulness of procalcitonin rapid test for the diagnosis of acute pyelonephritis in children in the emergency department , 2010, Pediatrics international : official journal of the Japan Pediatric Society.

[93]  Frank Buntinx,et al.  Diagnostic value of clinical features at presentation to identify serious infection in children in developed countries: a systematic review , 2010, The Lancet.

[94]  D. Karageorgopoulos,et al.  Serum procalcitonin for prediction of renal parenchymal involvement in children with urinary tract infections: a meta-analysis of prospective clinical studies. , 2009, The Journal of pediatrics.

[95]  J. Cappelleri,et al.  Understanding heterogeneity in meta‐analysis: the role of meta‐regression , 2009, International journal of clinical practice.

[96]  R. Troyo-Sanromán,et al.  PROCALCITONIN AND C-REACTIVE PROTEIN SERUM LEVELS AS MARKERS OF INFECTION IN A PEDIATRIC POPULATION WITH FEBRILE NEUTROPENIA AND CANCER , 2009, Pediatric hematology and oncology.

[97]  G. Perilongo,et al.  Procalcitonin as a predictor of renal scarring in infants and young children , 2009, Pediatric Nephrology.

[98]  J. Emparanza,et al.  Markers that predict serious bacterial infection in infants under 3 months of age presenting with fever of unknown origin , 2009, Archives of Disease in Childhood.

[99]  A. Dauber,et al.  Procalcitonin Levels in Febrile Infants After Recent Immunization , 2008, Pediatrics.

[100]  T. Tan Procalcitonin in Young Febrile Infants for the Detection of Serious Bacterial Infections: Is This the “Holy Grail”? , 2008, Pediatrics.

[101]  Andrew Dauber,et al.  Procalcitonin in Young Febrile Infants for the Detection of Serious Bacterial Infections , 2008, Pediatrics.

[102]  S. Sanders,et al.  Systematic review of the diagnostic accuracy of C-reactive protein to detect bacterial infection in nonhospitalized infants and children with fever. , 2008, Jornal de Pediatria.

[103]  G. Valerio,et al.  Hyponatremia in pediatric community-acquired pneumonia , 2008, Pediatric Nephrology.

[104]  F. Valent,et al.  The value of clinical features in differentiating between viral, pneumococcal and atypical bacterial pneumonia in children , 2008, Acta paediatrica.

[105]  A. Gervaix,et al.  The Search for Adenovirus 14 in Children in Houston, Texas , 2008, The Pediatric infectious disease journal.

[106]  A. King,et al.  Predictors of Severe Sepsis Not Clinically Apparent During the First Twenty-Four Hours of Hospitalization in Children With Cancer, Neutropenia, and Fever: A Prospective, Multicenter Trial , 2008, The Pediatric infectious disease journal.

[107]  A. Gervaix,et al.  Streptococcus pneumoniae bacteraemia in children. , 2007, International journal of antimicrobial agents.

[108]  M. Plebani,et al.  Procalcitonin and C-Reactive Protein as Diagnostic Markers of Severe Bacterial Infections in Febrile Infants and Children in the Emergency Department , 2007, The Pediatric infectious disease journal.

[109]  John Attia,et al.  Moving beyond sensitivity and specificity: using likelihood ratios to help interpret diagnostic tests , 2003 .

[110]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[111]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.

[112]  M. Svaldi,et al.  Procalcitonin‐reduced sensitivity and specificity in heavily leucopenic and immunosuppressed patients , 2001, British journal of haematology.

[113]  D. Gendrel,et al.  Procalcitonin as a marker of bacterial infection. , 2000, The Pediatric infectious disease journal.

[114]  I. Olkin,et al.  Meta-analysis of observational studies in epidemiology - A proposal for reporting , 2000 .

[115]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[116]  C. Begg,et al.  Operating characteristics of a rank correlation test for publication bias. , 1994, Biometrics.

[117]  L E Moses,et al.  Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. , 1993, Statistics in medicine.

[118]  J A Swets,et al.  Measuring the accuracy of diagnostic systems. , 1988, Science.

[119]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[120]  G. Rodríguez-Caravaca,et al.  Usefulness of analytical parameters in the management of paediatric patients with suspicion of acute pyelonephritis. Is procalcitonin reliable? , 2017, Revista espanola de medicina nuclear e imagen molecular.

[121]  C. Tascini,et al.  A high PCT level correlates with disease severity in Plasmodium falciparum malaria in children. , 2017, The new microbiologica.

[122]  E. Chiappini,et al.  Use, abuse and misuse of biomarkers in paediatrics. , 2016, Journal of biological regulators and homeostatic agents.

[123]  N. Kuppermann,et al.  Role of Serum Procalcitonin in Identifying Young Febrile Infants With Invasive Bacterial Infections: One Step Closer to the Holy Grail? , 2016, JAMA pediatrics.

[124]  J. Bouyer,et al.  Use of Procalcitonin Assays to Predict Serious Bacterial Infection in Young Febrile Infants. , 2016, JAMA pediatrics.

[125]  V. Gajdos,et al.  Use of Procalcitonin Assays to Predict Serious Bacterial Infection in Young Febrile Infants-Reply. , 2016, JAMA pediatrics.

[126]  M. Emiroğlu,et al.  High-risk febrile neutropenia and its management in children with solid tumors and lymphoma. , 2015, Turkish journal of medical sciences.

[127]  Javier Zamora,et al.  Meta-DiSc : a software for meta-analysis of test accuracy data , 2015 .

[128]  T. Jackowska,et al.  Soluble urokinase plasminogen activator receptor: an indicator of pneumonia severity in children. , 2015, Advances in experimental medicine and biology.

[129]  M. Ghojazadeh,et al.  Usefulness of serum procalcitonin level for prediction of vesicoureteral reflux in pediatric urinary tract infection. , 2014, Iranian journal of kidney diseases.

[130]  Susana Ferrando-Monleón,et al.  Predictive factors for kidney damage in febrile urinary tract infection. Usefulness of procalcitonin. , 2014, Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia.

[131]  J. Bouyer,et al.  Stability of procalcitonin at room temperature. , 2014, Clinical laboratory.

[132]  S. Hojker,et al.  Diagnostic accuracy of lipopolysaccharide-binding protein for predicting bacteremia/clinical sepsis in children with febrile neutropenia: comparison with interleukin-6, procalcitonin, and C-reactive protein , 2013, Supportive Care in Cancer.

[133]  M. Franchini,et al.  Is serum procalcitonin able to predict long-term kidney morbidity from urinary tract infections in children? , 2008, Clinical chemistry and laboratory medicine.

[134]  I. Olkin,et al.  Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. , 2000, JAMA.