TLR2-TLR4/CD14 polymorphisms and predisposition to severe invasive infections by Neisseria meningitidis and Streptococcus pneumoniae.

PURPOSE: Streptococcus pneumoniae and Neisseria meningitidis are major causes of severe invasive bacterial infections in some individuals. Apparently the genetic is a major susceptibility determinant to these infectious diseases. We study if the functional polymorphisms within genes of the innate immune system (TLR2-TLR4 and CD14) are related to the predisposition to severe invasive infections caused by S. pneumoniae and N. meningitidis. MATERIAL AND METHODS: Prospective descriptive study. Sixty-six Caucasian healthy children and 173 consecutive Caucasian children with invasive bacterial infections by N. meningitidis (n=59) and S. pneumoniae (n=114) were enrolled between January 1, 2008 and December 31, 2010. All blood samples were genotyped with description of the coding polymorphisms in p.R753Q of TLR2 gene and p.D299G of TLR4 gene as well as the promotor polymorphism c.-159C>T of the CD14 gene. RESULTS: Compared to the controls the p.753Q allele of TLR2 and the allele c.-159T of CD14 were more frequent in patients with S. pneumoniae (p<0.0001 and p=0.0167) and meningococcal infections (p=0.0003 and p=0.0276 respectively). CONCLUSIONS: Genetical variations in the innate immune system by polymorphisms in the TLR2 and CD14, could be related with an increases susceptibility to severe invasive infections by S. pneumoniae and N. meningitidis.

[Falls from heights in Pediatrics. Epidemiology and evolution of 54 patients]. / Caídas desde grandes alturas en Pediatría. Epidemiología y evolución de 54 pacientes.

OBJECTIVE: Falls from heights are a major preventable cause of morbidity and mortality in children. The aims of this study are to describe the evolution and long-term prognosis of such patients, to identify the pediatric population at greatest risk of falling from heights in our setting, and to define the variables at admission capable of predicting mortality. DESIGN: A retrospective patient cohort review was carried out. SETTING: Pediatric patients. POPULATION: Pediatric patients admitted to the pediatric intensive care unit following a fall from a height of over two meters, in the last 10 years. RESULTS: Ninety-two percent of the patients fell from buildings. Out of a total of 54 patients suffering falls, 51% were preschoolers. Fifty percent of the adolescents cases corresponded to attempted suicide. Fifty-two percent of the children were immigrants. Head injuries were the most common type of traumatism. The mortality rate was 12%. Eighty-two percent of the patients with a follow-up period of two years were leading an independent life. The independent predictors of mortality were the height of the fall, the Glasgow coma score and pediatric trauma index score upon admission, the presence of anemia, acidosis and hypotension upon admission, the need for vasoactive drugs, and the presence of severe head injury with the development of intracranial hypertension. CONCLUSIONS: Falls from heights occur mainly in unsupervised preschool children and teenagers attempting suicide. These patients have a high number of injuries, a high mortality rate, and important care needs. Most survivors are able to lead an independent life over the long term. Preventive measures should be implemented in risk populations.

[Breathing difficulties in children with cancer]. / Dificultad respiratoria en el niño con cáncer.

Respiratory distress is a common phenomenon in children with cancer. It is the most frequent cause of admission to the pediatric intensive care unit (PICU) in this group of patients. Its etiology is varied, and early and appropriate treatment is required. This review describes the most prevalent forms of respiratory distress in children with cancer without bone marrow transplantation. The symptoms, diagnosis and treatment are commented.

[Breathing difficulties in children subjected to bone marrow transplantation]. / Dificultad respiratoria en el niño sometido a trasplante de médula ósea.

Up to 60% of all children that receive to bone marrow transplantation (BMT) develop respiratory distress. It constitutes a common complication in this kind of patients, due to the increasing number of therapeutic applications of BMT and to improvement in the therapeutic approach to the problems associated with this procedure. We describe the different causes of respiratory distress after BMT in relation to its initiation or the presence of infection in its origin. The diagnosis and treatment are also reviewed.

Respiratory and pharmacological management in severe acute bronchiolitis: Were clinical guidelines not written for critical care?

PURPOSE: The treatment applied for children admitted to the pediatric intensive care unit (PICU) for severe acute bronchiolitis may differ from general recommendations. The first objective of our study was to describe the treatments offered to these children in a Spanish tertiary PICU. The second objective was to analyse the changes in management derived from the publication of the American Academy of Pediatrics (AAP) bronchiolitis guideline in 2014. METHODS: This was a retrospective-prospective observational study conducted during two epidemic waves (2014-2015 and 2015-2016). The AAP guidelines were distributed and taught to PICU staff between both epidemic waves. RESULTS: A total of 138 children were enrolled (78 male). In the first period, 78 children were enrolled. The median age was 1.8 months (IQR 1.1-3.6). There were no differences between the management in the two periods, except for the use of high-flow oxygen therapy (HFOT); its use increased in the second period. Overall, 83% of patients received non-invasive ventilation or HFOT. Children older than 12 months received HFOT exclusively. In comparison, continuous positive airway pressure and bi-level positive airway pressure were used less during the period 2015-2016 (P=0.036). Regarding pharmacological therapy, 70% of patients received antibiotics, 23% steroids, 33% salbutamol, 31% adrenaline, and 7% hypertonic saline. The mortality rate was zero. CONCLUSIONS: Our PICU did not follow the AAP recommendations. There were no differences between the two periods, except in the use of HFOT. All children older than 12 months received HFOT exclusively. The rate of using invasive mechanical ventilation was also low.

[Severe child abuse admitted to paediatric ICU]. / Maltrato infantil grave en la unidad de cuidados intensivos pediátricos.

OBJECTIVE: To describe cases of severe child abuse admitted to PICU. METHODS AND PATIENTS: It is a retrospective study (2000-2008) in which patients diagnosed with physical child abuse admitted to PICU were included. Other abuse patterns were excluded (severe negligence, sexual abuse or scalding). RESULTS: There were 8 patients included (3 boys and 5 girls). The median age was 5.2 months, with 6 patients were less than 7 months old. The most frequent sign was neurological symptoms: seizures (4 patients), subdural haematoma (2 patients), traumatic brain injury (1 patient). Other: haemothorax (1 patient) and cardiac arrest of no known aetiology (1 patient). The CT showed a subdural haematoma in 5 patients, 3 of which needed surgical drainage. Child abuse was confirmed using the social history and the presence of inflicted injuries. There were long bones fractures (tibia, ulna and radius, bilateral rib fractures) in 3 patients and 4 patients had retinal haemorrhages. There was one death and 3 had severe neurological after effects. CONCLUSION: Severely abused children can be falsely diagnosed with a casual neurological disease. The most frequent injury is subdural haematoma with or without another injury associated to child abuse. It very important to diagnose child abuse in order to prevent recurrent injuries.

[Pleural effusion in children with pneumonia: a study of 63 cases]. / Derrame pleural en niños con neumonía. Estudio de 63 casos.

INTRODUCTION: An increase in the number and severity of pleural effusions has been observed in the last few years. The aim of the study is to describe the epidemiological characteristics, clinical findings and the treatment of this disease. MATERIAL AND METHODS: This is a retrospective study of patients admitted into the PICU in Hospital Niño Jesús with parapneumonic pleural effusion from January 2005 to May 2006. RESULTS: Sixty-three patients were included in the study. An increase of 29 % was observed in the number of patients admitted with parapneumonia effusion from 2005 to 2006. The most common aetiology was Streptococcus pneumoniae. In 65 % of patients pleural effusion was an empyema and in 33 % it was an exudate. In all patients with C-reactive protein below 100 mg/L the effusion was an exudate, whereas 81 % of patients with C-reactive protein above 170 mg/L had an empyema, p < 0.05. The patients who had an exudate needed lower doses of fibrinolytics than those who had an empyema (1.6 vs. 4.5, p < 0.05). The number of days having a chest tube or admitted in PICU was lower in patients with exudate (3 days each) than those with empyema (7 and 9 days respectively) (p < 0.05). CONCLUSIONS: An increase in the number of complicated pneumonias is observed amongst children in our country, S. pneumoniae being the main aetiology. Using laboratory techniques such as C-reactive protein can help to distinguish between complicated and uncomplicated pneumonia. Pleural effusion characteristics seem to have an influence on the need for fibrinolytic and the length of chest tube treatment.

[Attitudes and needs of pediatric intensivists in relation to the death of their patients]. / Actitudes y necesidades de los intensivistas pediátricos ante la muerte de sus pacientes.

INTRODUCTION: Most deaths in infants and children occur in hospitals and especially in pediatric and neonatal intensive care units. OBJECTIVES: To determine 1) how often pediatric intensivists have to manage dying patients, 2) their approach to these patients, and 3) their knowledge of this field and their needs. MATERIAL AND METHOD: A 28-item questionnaire was sent by surface mail to each physician, as well as another questionnaire with general questions on the work of the pediatric intensive care unit (PICU) in 2000. RESULTS: Responses were obtained from 20 PICUs (54 %) from different parts of Spain. There where 373 deaths. More of the half of the deaths (62 %) were due to acute events or occurred during the neonatal period. Ninety-four physicians completed the questionnaire. Each physician attended four deaths (SD = 3.1; range 0-20). Sixty-eight percent of the physicians believed that families were helped by knowing the possibility that the child might die. Intensivists believed that pediatric patients should not be informed that they were dying. In 64 % of deaths, the physicians were with their patients at the moment of death. More than half of the patients died without physical contact with their parents. Forty-six percent of the physicians interpreted death among their patients as a personal or professional failure and most (92 %) wanted training. Only three PICUs allowed parents to stay all day with their children. CONCLUSIONS: Almost half the physicians experienced death as a personal or professional failure and most wanted training to help them deal with death in their professional work. Most PICUs restrict the time parents are allowed to stay with their children.

[Severe bronchiolitis. Epidemiology and clinical course of 284 patients]. / Bronquiolitis grave. Epidemiología y evolución de 284 pacientes.

INTRODUCTION: Bronchiolitis is the leading cause of hospital admission and a frequent cause of pediatric intensive care unit (PICU) admission among infants during the winter months. The objective of this study was to analyze the characteristics and clinical course of patients admitted to the PICU for bronchiolitis. PATIENTS AND METHOD: We performed a descriptive, observational study by clinical chart review of all patients admitted to the PICU for severe bronchiolitis from November 1994 to March 2006. RESULTS: A total of 284 patients were included. Most were admitted during December and January and 74% had respiratory syncytial virus (RSV) infection. At least one risk factor for severe disease was present in 68% of the patients: the most frequent risk factor was age < 6 weeks (45%), followed by prematurity (30%). Mechanical ventilation was required in 64 of the 284 patients (24%). Mortality was 1.8% and was associated with chronic pre-existing illness (p < 0.001). The factors associated with a greater risk of mechanical ventilation and a longer PICU stay were the association of two or more risk factors (42/284; 15%), the presence of apnea (73/284; 25.7%), and images of pulmonary consolidation or atelectasis on admission chest X-ray (157/284; 55%). CONCLUSIONS: Most patients admitted for severe bronchiolitis to the PICU are healthy infants whose principal risk factor is young age. The main predictors of severe clinical course during PICU stay are the association of two or more risk factors, the presence of apnea, and pulmonary consolidation on admission chest X-ray. Bronchiolitis-associated mortality is low and is associated with pre-existing chronic illness.

Subclavian vein catheterization in critically ill children: analysis of 322 cannulations.

Complications in 322 percutaneous subclavian vein catheters placed in 272 children by the infraclavicular approach were investigated prospectively. Ages ranged from 4 days to 15 years. Incidents during catheter introduction occurred in 13 cases, and were more common when insertion was on the right side (p less than 0.01). Nine (2.8%) required urgent treatment: (6 pneumothorax, 1 hydrothorax, and 2 hemothorax). Anomalous lodging of the catheter tip was more common when insertion was on the right side (p less than 0.05). Complications during catheter maintenance were 3 venous thromboses, 3 catheter obstructions, and 7 migrations out of position. There was no significant difference in complications related to age. Catheter cultures were positive in 33 (17%) of 190 catheters cultured (27 through colonization and 6 through catheter-related sepsis). Staph. epidermidis was the organism most frequently isolated (19 cases; 58%). Catheterization time of more than 5 days and catheter-related sepsis were statistically associated (p less than 0.05). Staph. epidermidis isolation and duration of cannula use were statistically related (p less than 0.01). No catheter-related deaths occurred. We conclude that subclavian vein catheterization is a simple and useful procedure that entails relatively few serious complications when performed by experienced pediatricians.

Complications of central venous catheterization in critically ill children.

OBJECTIVE: Analysis of central venous catheterization complications in different access sites with the Seldinger technique. Patients and Methods: A prospective study (May 1992 through December 1996) of 308 central venous catheterizations in children of different ages in a pediatric intensive care unit. RESULTS: Access sites were the subclavian vein (76.3%), femoral vein (20.4%), and jugular vein (3.2%). The frequency of catheter placement-related complications was 22%, and the frequency of serious catheter placement-related complications was 2.9% (pneumothorax 1.9%, hemothorax 1%). Catheter placement-related complications were more common in the subclavian than in the femoral vein (chi-square, p =.02) for the larger bore catheters (chi-square, p =.01) and for the higher number of attempts (Student's t -test, p <.001). Catheter placement-related complications were not related to the age, weight, or whether the procedure was performed by the staff physician or resident. The overall complication rate for maintenance-related complications was 36%. Maintenance-related complications were more common in younger children (Student's t -test, p =.03). The most frequent maintenance-related complications were mechanical complications (catheter obstruction and central venous thrombosis), and these were higher for femoral access (chi-square, p <.01) and for catheters indwelling for a longer period of time. Infection was found in 5.8% of patients, mainly due to Staphylococcus epidermidis. Infection was not related to the site of venous access or to the length of time the catheter was left indwelling. CONCLUSIONS: Central venous catheterization can be performed readily in children of all ages with an acceptable degree of risk. The immediate complications were more frequent and severe for subclavian vein catheterization, and the highest risk factor was the number of attempts at catheter insertion. Although the most frequent late complications were mechanical, which were higher for the femoral access and long-indwelling catheters, femoral catheters can be left indwelling for longer periods if routine ultrasound follow-up is performed. Infectious complications were independent of the venous access site or the duration of catheterization.

[Meningococcal sepsis in pediatrics. Parameters associated with poor outcome]. / Sepsis meningocócica en pediatría. Parámetros asociados a mala evolución.

BACKGROUND: Mortality due to meningococcal sepsis continues to be extremely high. Patients with a poor prognosis require aggressive therapy and should be identified early. OBJECTIVE: To investigate the clinical and biological factors associated with poor outcome. PATIENTS AND METHOD: Seventy-one children aged 2 months to 13 years with meningococcal sepsis were studied. Inclusion criteria were meningococcus isolation in cultures or characteristic clinical features with purpuric exanthema. METHODS: A correlational descriptive study was performed. In all patients we evaluated the Pediatric Risk of Mortality (PRISM), the Glasgow Scale for Meningococcal Sepsis (GSMS), polymorphonuclear (PMN) count and prolactin (PRL), leptin (LPT) and C-reactive protein (CRP) levels. RESULTS: Fourteen children (19.7 %) died. Death was associated with multiple organ dysfunction syndrome (MODS) (p = 0.0001), high GSMS and PRISM scores (p = 0.0001) and to a lesser extent with shock (p = 0.01). In patients who died, the determinations showing greatest alteration at admission were PRL levels (p = 0.0009) and PMN count (p = 0.0005). CRP levels were not associated with differences in mortality but were high in patients with shock (p = 0.008). Children with high body weight percentiles were at greater risk of death and showed higher levels of PRL, PCT (p = 0.006) and LPT (p = 0.006), without differences in GSMS or PRISM scores. Age did not influence mortality or PRL levels but did influence GMSM and PRISM scores and PMN and CRP levels. These differences disappeared after the age of 2-3 years. In patients with MODS or shock, the only differences found were reduced PMN count (p = 0.0001) and elevated PRL levels (p = 0.0001). CONCLUSIONS: In meningococcal sepsis, death is more frequent in children with high body weight percentiles. Moreover, these children present elevated PRL and LPT levels, although whether these variables act independently remains to be elucidated.

[Gastric tonometry as monitoring system in abdominal surgery]. / Tonometría gástrica como sistema de monitorización en cirugía abdominal.

OBJECTIVE: The aim of this study is the evolution of the intramucosal pH (pHi) during the quirurgic and the immediate postoperative process in pediatric patients, operated in abdominal surgery longer than 90 minutes. MATERIAL AND METHODS: A prospective study including 25 patients was done. In all of them intraabdominal surgery was performed. The mean age was 5.6 +/- 3 years, range from 9 months to 13 years. The operative time was 207 +/- 76 minutes. The pHi was measured by means of a sigmoid tonometer introduced in the stomach. A tonometry was done hourly during the operative procedure, and every 8 hours during the postoperative period. RESULTS: 157 determinations of pHi were made with an average of 6.28 per patient. During the operative period the pHi decreased from 7.36 +/- 0.11 (30') to 7.22 +/- 0.11 (210'). During the postoperative, the pHi increased to 7.36 +/- 0.05, 24 hours later (p < 0.005). CONCLUSIONS: During the surgery there was a significant reduction of the pHi, which recovered 16 hours after in the postoperative.

[Extreme reactive thrombocytosis in a healthy 6 year-old child]. / Trombocitosis extrema reactiva en un niño sano de 6 años.

Thrombocytosis is usually a casual finding in children. Reactive or secondary thrombocytosis is the more common form, being the infections diseases the most prevalent cause of it. Regarding the number of platelets there are four degrees of thrombocytosis; in its extreme degree the number of platelets exceeds 1,000,000/mm(3). We describe a case of extreme reactive thrombocytosis in a healthy 6-year-old child. He required critical care admission for diagnosis and treatment (maximum number of platelets 7,283,000/mm(3)). We review the different causes of thrombocytosis in childhood, the differential diagnosis, and the available treatments in case of extreme thrombocytosis.

Extreme reactive thrombocytosis in a healthy 6 year-old child.

Thrombocytosis is usually found by chance in children. Reactive or secondary thrombocytosis is the more common form, with infectious diseases being the most prevalent cause of it. Regarding the number of platelets there are four degrees of thrombocytosis; in its extreme degree the number of platelets exceeds 1,000,000/mm3. We describe a case of extreme reactive thrombocytosis in a healthy 6-year-old child. He required critical care admission for diagnosis and treatment (maximum number of platelets 7,283,000/mm3). We review the different causes of thrombocytosis in childhood, the differential diagnosis, and the available treatments in case of extreme thrombocytosis.

La trombocitosis es un hallazgo casual frecuente en pediatría. En niños, predominan las formas secundarias, siendo las infecciones su causa más prevalente. Se distinguen 4 grados de trombocitosis en función del número de plaquetas; en la forma extrema, se supera el 1.000.000/mm3. Se presenta un caso de trombocitosis extrema reactiva en un niño sano de 6 años, que requirió ingreso en cuidados intensivos para tratamiento y diagnóstico (cifra máxima de plaquetas de 7.283.000/mm3). Se revisan las diferentes causas de trombocitosis en la infancia, se describe el diagnóstico diferencial y se discute sobre los diferentes tratamientos disponibles ante un caso como el descrito.

[Staphylococcus aureus infections in the intensive care unit: clinical and epidemiological characteristics]. / Infecciones por Staphylococcus aureus en cuidados intensivos: características clínicas y epidemiológicas.

INTRODUCTION: There has been an increase in invasive Staphylococcus Aureus infections over the last few years, which have required admission to the pediatric intensive care unit (PICU). PATIENTS AND METHODS: All patients with S. aureus infection who were admitted to PICU were enrolled in a retrospective study (January 2006-June 2010). The patients were classified into 2 groups: community-acquired infection (Group 1) and nosocomial infection (Group 2). We recorded epidemiological data, type of S. aureus (methicillin-susceptible S. aureus [MSSA], methicillin-resistant S. aureus [MRSA]), risk factors, site of infection, presence of hemodynamic instability, respiratory support, and mortality. RESULTS: A total of 51 patients were enrolled, 21 belonging to Group 1 and 30 to Group 2. The median age was lower in Group 1 (1.6 years vs 3.2 years; P=.009). MSSA was isolated in 88% of cases. MRSA was detected in 6/51 (12%) of cases, which were isolated in the later study period (January 2009-June 2010). The risk factors for infection were: immunosuppression, venous catheter, institutionalization, mechanical ventilation, previous surgery, previous trauma and chronic osteomyelitis. A large majority (83%) of the patients with MRSA infection had risk factors. The type of infection was varied, with respiratory tract infection being the most common (75%). Hemodynamic instability was observed in 43% of patients. Most patients (86%) required respiratory support. One patient in Group 1 died of necrotizing pneumonia caused by MSSA. CONCLUSIONS: Infections by S. aureus in children are severe and have a high morbidity. Respiratory infection was the most common in our series. Isolation of MSSA is common in these infections, although, an increase in the number of infections by MRSA was observed during the latter part of the study.

[Severe bronchiolitis. Changes in epidemiology and respiratory support]. / Bronquiolitis grave. Cambios epidemiológicos y de soporte respiratorio.

INTRODUCTION: Bronchiolitis generates lots of admissions during the cold months in the paediatric intensive care units (PICU). New forms of respiratory support are being used and could improve the care of these patients. OBJECTIVES: To analyse the epidemiological and respiratory support changes of children admitted to the PICU. PATIENTS AND METHODS: An observational, retrospective, descriptive and analytical study of patients with the diagnosis of bronchiolitis admitted to the PICU of a tertiary hospital during the respiratory syncytial virus (RSV) epidemic months between 2005 and 2010. RESULTS: A total of 229 patients were admitted, of whom 83% were infected with RSV. The mean age was 1.48 months, with children under 3 months being the greatest number of admissions (73.3%). December was the month with the highest number of admissions (52%). Mortality was 0.9%. The mean time of stay in the PICU and on respiratory assistance were 4 and 3 days, respectively (no significant differences between the periods studied). Patients with RSV bronchiolitis were younger than the negative RSV (mean 2.61 months and 4.05 months, P=.023). Active respiratory support was required in 73% of cases. The percentage of patients who required active respiratory support increased over the years (Z=3.81, P=.00014), especially high flow nasal oxygen therapy (Z=3.62, P=.00028). An inverse relationship was observed between patient age and length of stay in PICU (Beta=-0.245, P ≤.0001) and days on respiratory support (Beta=-0.167, P=.039). CONCLUSIONS: Most patients admitted to the PICU are less than 3 months old. Mortality was 0.9%. Respiratory support (especially non-invasive mechanical ventilation and high flow nasal oxygen therapy) is used increasingly often. The youngest patients need more days in PICU and more respiratory support.

Relationship between serotypes, age, and clinical presentation of invasive pneumococcal disease in Madrid, Spain, after introduction of the 7-valent pneumococcal conjugate vaccine into the vaccination calendar.

To assess invasive pneumococcal disease (IPD) clinical presentations and relationships with age and serotype in hospitalized children (<15 years) after PCV7 implementation in Madrid, Spain, a prospective 2-year (May 2007 to April 2009) laboratory-confirmed (culture and/or PCR) IPD surveillance study was performed (22 hospitals). All isolates (for serotyping) and culture-negative pleural/cerebrospinal fluids were sent to the reference laboratory for pneumolysin (ply) and autolysin (lyt) gene PCR analysis. A total of 330 IPDs were identified: 263 (79.7%) confirmed by culture and 67 (20.3%) confirmed by PCR. IPD distribution by age (months) was as follows: 23.6% (<12), 15.8% (12 to 23), 15.5% (24 to 35), 22.4% (36 to 59), and 22.7% (>59). Distribution by clinical presentation was as follows: 34.5% bacteremic pneumonia, 30.3% pediatric parapneumonic empyema (PPE), 13.6% meningitis, 13.3% primary bacteremia, and 8.2% others. Meningitis and primary bacteremia were the most frequent IPDs in children <12 months old, and bacteremic pneumonia and PPE were most frequent in those >36 months old. Frequencies of IPD-associated serotypes were as follows: 1, 26.1%; 19A, 18.8%; 5, 15.5%; 7F, 8.5%; 3, 3.9%; nontypeable/other 30 serotypes, 27.3%. Serotype 1 was linked to respiratory-associated IPD (38.6% in bacteremic pneumonia and 38.0% in PPE) and children of >36 months (51.4% for 36 to 59 months and 40.0% for >59 months), while serotype 19A was linked to nonrespiratory IPDs (31.1% in meningitis, 27.3% in primary bacteremia, and 51.9% in others) and children of <24 months (35.9% for children of <12 months and 36.5% for those 12 to 23 months old), with high nonsusceptibility rates for penicillin, cefotaxime, and erythromycin. After PCV7 implementation, non-PCV7 serotypes caused 95.5% of IPDs. The new 13-valent conjugate vaccine would provide 79.1% coverage of serotypes responsible for IPDs in this series.