Detention of children and adolescents under mental health legislation: a scoping review of prevalence, risk factors, and legal frameworks.

BACKGROUND: For individuals with severe mental illness, involuntary assessment and/or treatment (hereafter detention) can be a necessary intervention to support recovery and may even be lifesaving. Despite this, little is known about how often these interventions are used for children and adolescents. METHODS: This global scoping review set out to: (1) map the current evidence around mental health detentions of children and adolescents (< 18 years); (2) identify the clinical, sociodemographic, and behavioural factors associated with detention; and (3) document the views of professionals and young people on the implementation of mental health legislation. RESULTS: After searching databases of peer-reviewed literature and citation chaining, 42 articles from 15 jurisdictions were included. About one fifth of psychiatric admissions in national register data were detentions, however trends were only available for a few high-income Western countries. The circumstances justifying detention and the criteria authorising detention varied between studies, with a mix of clinical factors and observed behaviours reported as the reason(s) warranting/precipitating a detention. Particular groups were more likely to experience detention, such as children and adolescents from minority ethnic communities and those with a documented history of abuse. There was a notable absence of qualitative research exploring the views of professionals or children and adolescents on detention. CONCLUSION: Further research is needed to explore the impact of detention on those aged < 18 years, including national register-based studies and qualitative studies. This is particularly relevant in nations currently undergoing legislative reform.

Length and associated characteristics of short-term detentions: an analysis of detentions under the Mental Health Act in Scotland, 2006-2018.

PURPOSE: The Mental Health Act in Scotland is under review. Previous iterations increased patients' rights but the maximum time for short-term detentions remains unchanged, despite evolving psychiatric treatment models. We explored length, mode of ending and factors of influence on the application of short-term detention certificates (STDCs), which can last up to 28 days, across Scotland between 2006 and 2018. METHODS: Data on age, gender, ethnicity, date of commencement and ending of the STDC and detention site from all 42,493 STDCs issued to 30,464 patients over 12 years were extracted from the national repository for detentions under the Mental Health (Care and Treatment) (Scotland) Act 2003 and analysed using mixed models. RESULTS: One in five STDCs lapsed on day 28. Two in five were revoked and the remainder extended to a treatment order. STDCs that were not extended averaged 19 days, and revoked STDCs 14 days. The probability of a detention lapsing varied across hospitals and increased with patient age. The odds of a detention lapsing on day 28 were 62% lower and revoked detentions 10% shorter in 2018 relative to 2006. The odds of a detention extending decreased significantly from 2012 to 2018. Extended STDCs were associated with increased patient age, male gender, and ethnicity other than White Scottish. There was little initiation of or active revocation of STDCs on weekend days. CONCLUSION: The length of STDCs reduced over time, fewer detentions lapsed, and weekday patterning was evident in each year. These data can inform legislative and service reviews.

Developing a new pediatric extracorporeal membrane oxygenation (ECMO) program.

OBJECTIVES: We aimed to critically evaluate the effectiveness of a designated ECMO team in our ECMO selection process and patient outcomes in the first 3 years of our low-volume pediatric ECMO program. METHODS: We conducted a retrospective chart review of patients who received an ECMO consultation between the start of our program in March 2015 and May 2018. We gathered clinical and demographic information on patients who did and did not receive ECMO, and described our selection process. We reflected on the processes used to initiate our program and our outcomes in the first 3 years. RESULTS: Sixty-nine patients received consultations, and of those, 50 patients were potential candidates. 19 (38%) of the candidates were ultimately placed on ECMO. There were statistically significant differences in oxygen saturation, paO2, oxygenation index, A-aDO2, lactate, and pH between the patients who went on ECMO and who did not. We improved our outcomes from 0% survival to discharge in 2015, to 60% in 2018, with an average of 63% survival to discharge over the first 3 years of our program. CONCLUSIONS: In a low-volume pediatric ECMO center, having a designated team to assist in the patient selection process and management can help provide safe and efficient care to these patients, and improve patient outcomes. Having a strict management protocol and simulation sessions involving all members of the medical team yields comfort for the providers and optimal care for patients. This study describes our novel structure, processes, and outcomes, which we hope will be helpful to others seeking to develop a new pediatric ECMO program.

Oxygenator impact on peramivir in extra-corporeal membrane oxygenation circuits.

INTRODUCTION: This study aims to determine the oxygenator impact on alterations of peramivir (PRV) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extra-corporeal membrane oxygenation (ECMO) circuit including the Quadrox-i® oxygenator. METHODS: 1/4-inch and 3/8-inch, simulated closed-loop ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of PRV was administered into the circuits and serial pre- and post-oxygenator concentrations were obtained at 5-min and 1-, 2-, 3-, 4-, 5-, 6-, 8-, 12-, and 24-h time points. PRV was also maintained in a glass vial, and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation. RESULTS: For the 1/4-in. circuit with an oxygenator, there was < 15% PRV loss, and for the 1/4-in. circuit without an oxygenator, there was < 3% PRV loss during the study period. For the 3/8-in. circuits with an oxygenator, there was < 15% PRV loss, and for the 3/8-in. circuits without an oxygenator, there was < 3% PRV loss during the study period. CONCLUSION: There was no significant PRV loss over the 24-h study period in either the 1/4-in. or 3/8-in circuit, regardless of the presence of the oxygenator. The concentrations obtained pre- and post-oxygenator appeared to approximate each other, suggesting there may be no drug loss via the oxygenator. This preliminary data suggests PRV dosing may not need to be adjusted for concern of drug loss via the oxygenator. Additional single and multiple dose studies are needed to validate these findings.

Oxygenator impact on meropenem/vaborbactam in extracorporeal membrane oxygenation circuits.

INTRODUCTION: To determine the oxygenator impact on alterations of meropenem (MEM)/vaborbactam (VBR) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extra corporeal membrane oxygenation (ECMO) circuit including the Quadrox-i® oxygenator. METHODS: 1/4-inch and 3/8-inch, simulated closed-loop ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of MEM/VBR was administered into the circuits and serial pre- and post-oxygenator concentrations were obtained at 5 minutes, 1, 2, 3, 4, 5, 6, 8, 12, and 24-hour time points. MEM/VBR was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation. RESULTS: For the 1/4-inch circuit, there was an approximate mean 55% MEM loss with the oxygenator in series and a mean 33%-40% MEM loss without an oxygenator in series at 24 hours. For the 3/8-inch circuit, there was an approximate mean 70% MEM loss with the oxygenator in series and a mean 30%-38% MEM loss without an oxygenator in series at 24 hours. For both the 1/4-inch circuit and 3/8-inch circuits with and without an oxygenator, there was <10% VBR loss for the duration of the experiment. CONCLUSIONS: This ex-vivo investigation demonstrated substantial MEM loss within an ECMO circuit with an oxygenator in series with both sizes of the Quadrox-i oxygenator at 24 hours and no significant VBR loss. Further evaluations with multiple dose in-vitro and in-vivo investigations are needed before specific MEM/VBR dosing recommendations can be made for clinical application with ECMO.

Experts' Consensus on Use of Long-Acting Nitroglycerine in the Management of Angina and Chronic Coronary Syndrome in India.

AIM: To address the existing gaps in knowledge about long-acting nitroglycerine (LA-NTG) and provide recommendations to address these issues. METHODOLOGY: Approved LA-NTG questionnaire that included 17 questions related to the role of LA-NTG in the management of angina and chronic coronary syndrome (CCS) was shared with 150 expert cardiologists from different regions from India. Results of these survey questionnaires were further discussed in 12 regional level meetings. The opinions and suggestions from all the meetings were compiled and analyzed. Further, recommendations were made with the help of attending national cardiology experts and a consensus statement was derived. RESULTS: This is the first consensus on LA-NTG, summarizing the clinical evidence from India and suggesting recommendations based on these data. The experts recommended early use of LA-NTG as a first-line antianginal therapy in combination with beta-blocker since it improves exercise tolerance in patients with CCS. A strong consensus was observed for using LA-NTG in patients with co-morbid hypertension, diabetes, chronic kidney disease and post-percutaneous coronary intervention angina. As a part of cardiac rehabilitation, LA-NTG allows patients with angina to exercise to a greater functional capacity. CONCLUSIONS: A national consensus was observed for several aspects of LA-NTG in the management of angina and CCS. The clinical experience of the experts confirmed an extremely satisfied patient perception about the efficacy of LA-NTG.

Limits of remote working: the ethical challenges in conducting Mental Health Act assessments during COVID-19.

COVID-19 has created additional challenges in mental health services, including the impact of social distancing measures on care and treatment. For situations where a detention under mental health legislation is required to keep an individual safe, psychiatrists may consider whether to conduct an assessment in person or using video technology. The Mental Health (Care and Treatment) (Scotland) Act 2003 does not stipulate that an assessment has to be conducted in person. Yet, the Code of Practice envisions that detention assessments would be conducted face to face in all circumstances. During the pandemic, the Mental Welfare Commission for Scotland, a statutory body with a duty to promote best practice of the Act, has been asked whether it may be acceptable and indeed preferable for some assessments to be conducted via video technology. Where an assessment is needed to determine if a patient needs to be detained, and where there is a need for social distancing or the need for 'shielding', remote assessments may in some circumstances be preferable. In this article, we outline the modification of the Mental Welfare Commission's previous outright rejection of virtual assessments as the pandemic progressed and discuss the ethical and legal issues the possibility of remote assessments has exposed. We also discuss the limits and when a virtual assessment is not considered ethical. As the pandemic moves from a state of emergency into a 'new normal' in psychiatric services during second, or subsequent, waves, the use and place (if any) of remote assessments for detention needs to be considered.

Oxygenator Impact on Ceftolozane and Tazobactam in Extracorporeal Membrane Oxygenation Circuits.

OBJECTIVES: To determine the oxygenator impact on alterations of ceftolozane/tazobactam in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extracorporeal membrane oxygenation circuit including the Quadrox-i oxygenator (Maquet, Wayne, NJ). DESIGN: A 1/4-inch and 3/8-inch, simulated closed-loop extracorporeal membrane oxygenation circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of ceftolozane/tazobactam was administered into the circuits and serial preoxygenator and postoxygenator concentrations were obtained at 5 minutes, 1, 2, 3, 4, 5, 6, and 24-hour time points. Ceftolozane/tazobactam was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation SETTING:: A free-standing extracorporeal membrane oxygenation circuit. PATIENTS: None. INTERVENTIONS: Single-dose administration of ceftolozane/tazobactam into closed-loop extracorporeal membrane oxygenation circuits prepared with and without an oxygenator in series with serial preoxygenator, postoxygenator, and reference samples obtained for concentration determination over a 24-hour study period. MEASUREMENTS AND MAIN RESULTS: For the 1/4-inch circuit, there was approximately 92% ceftolozane and 22-25% tazobactam loss with the oxygenator in series and 19-30% ceftolozane and 31-34% tazobactam loss without an oxygenator in series at 24 hours. For the 3/8-inch circuit, there was approximately 85% ceftolozane and 29% tazobactam loss with the oxygenator in series and 25-27% ceftolozane and 23-26% tazobactam loss without an oxygenator in series at 24 hours. The reference ceftolozane and tazobactam concentrations remained relatively constant during the entire study period demonstrating the drug loss in each size of the extracorporeal membrane oxygenation circuit with or without an oxygenator was not a result of spontaneous drug degradation. CONCLUSIONS: This ex vivo investigation demonstrated substantial ceftolozane loss within an extracorporeal membrane oxygenation circuit with an oxygenator in series with both sizes of the Quadrox-i oxygenator at 24 hours and significant ceftolozane loss in the absence of an oxygenator. Tazobactam loss was similar regardless of the presence of an oxygenator. Further evaluations with multiple dose in vitro and in vivo investigations are needed before specific drug dosing recommendations can be made for clinical application with extracorporeal membrane oxygenation.

Oxygenator impact on voriconazole in extracorporeal membrane oxygenation circuits.

INTRODUCTION: To determine the oxygenator impact on alterations of voriconazole in a contemporary neonatal/pediatric (1/4 inch) and adolescent/adult (3/8 inch) extracorporeal membrane oxygenation circuit including the Quadrox-i® oxygenator. METHODS: Simulated closed-loop extracorporeal membrane oxygenation circuits (1/4 and 3/8 inch) were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. In addition, 1/4- and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of voriconazole was administered into the circuits, and serial pre- and post-oxygenator concentrations were obtained at 5 minutes, 1, 2, 3, 4, 5, 6, and 24 hour time points. Voriconazole was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation. RESULTS: For the 1/4-inch circuit, there was an approximate mean of 64-67% voriconazole loss with the oxygenator in series and mean of 15-20% voriconazole loss without an oxygenator in series at 24 hours. For the 3/8-inch circuit, there was an approximate mean of 44-51% voriconazole loss with the oxygenator in series and a mean of 8-12% voriconazole loss without an oxygenator in series at 24 hours. The reference voriconazole concentrations remained relatively constant during the entire study period demonstrating that the drug loss in each size of the extracorporeal membrane oxygenation circuit with or without an oxygenator was not a result of spontaneous drug degradation. CONCLUSION: This ex vivo investigation demonstrated substantial voriconazole loss within an extracorporeal membrane oxygenation circuit with an oxygenator in series with both sizes of the Quadrox-i oxygenator at 24 hours and no significant voriconazole loss in the absence of an oxygenator. Further evaluations with multiple dose in vitro and in vivo investigations are needed before specific voriconazole dosing recommendations can be made for clinical application with extracorporeal membrane oxygenation.

National survey and analysis of barriers to the utilisation of the 2005 mental capacity act by people with bipolar disorder in England and Wales.

Background: The Mental Capacity Act (2005) (MCA) provides a legal framework for advance planning for both health and welfare in England and Wales for people if they lose mental capacity, for example, through mania or severe depression.Aims: To determine the proportion of people with bipolar disorder (BD) who utilise advance planning, their experience of using it and barriers to its implementation.Methods: National survey of people with clinical diagnosis of BD of their knowledge, use and experience of the MCA. Thematically analysed qualitative interviews with maximum variance sample of people with BD.Results: A total of 544 respondents with BD participated in the survey; 18 in the qualitative study. 403 (74.1%) believed making plans about their personal welfare if they lost capacity to be very important. A total of 199 (36.6%) participants knew about the MCA. A total 54 (10%), 62 (11%) and 21 (4%) participants made advanced decisions to refuse treatment, advance statements and lasting power of attorney, respectively. Barriers included not understanding its different forms, unrealistic expectations and advance plans ignored by services.Conclusion: In BD, the demand for advance plans about welfare with loss of capacity was high, but utilisation of the MCA was low with barriers at service user, clinician and organisation levels.

Pharmacokinetics of cefazolin delivery via the cardiopulmonary bypass circuit priming solution in infants and children.

OBJECTIVES: Our aim was to describe the pharmacokinetics of cefazolin in paediatric patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) who received cefazolin for peri-operative surgical prophylaxis in addition to having cefazolin added to the CPB circuit priming solution. Secondary aims were to determine the pharmacodynamic exposure associated with the addition of cefazolin to the CPB priming solution and to assess whether a target cefazolin concentration range for the CPB priming solution could be identified. METHODS: A multicentre, prospective, open-label pharmacokinetic study was carried out in children from birth to 16 years of age undergoing cardiac surgery. RESULTS: Forty-one patients met the inclusion criteria and accounted for 492 samples for analysis. Cefazolin concentrations were best described by a one-compartment model with weight as a covariate on the volume of distribution (Vd) with allometric scaling. The mean ± standard deviation (SD) total body CL for the birth-6 month cohort was 0.009 ± 0.006 mL/min/kg with a mean ± SD Vd of 0.59 ± 0.26 L/kg, the mean ± SD total body CL for the 7 month-3 year cohort was 0.01 ± 0.005 mL/min/kg with a mean ± SD Vd of 0.79 ± 0.15 L/kg, and the mean ± SD total body CL for the 4-16 year cohort was 0.007 ± 0.004 mL/min/kg with a mean ± SD Vd of 3.4 ± 0.94 L/kg. The median cefazolin loss in the CPB circuit ranged from 78% to 95% and the median patient cefazolin concentration after CPB circuit detachment ranged from 92 to 197 mg/L. CONCLUSIONS: These data demonstrate that mixing cefazolin in the CPB circuit priming solution was effective in maintaining cefazolin serum concentrations during surgery. If this practice is utilized, re-dosing of cefazolin during the CPB run and upon CPB circuit detachment is most probably not needed. Larger pharmacokinetic studies are warranted.

ß-lactam Therapeutic Drug Management in the PICU.

OBJECTIVES: To determine whether contemporary ß-lactam anti-infective dosing recommendations in critically ill children achieve concentrations associated with maximal anti-infective activity. The secondary objective was to describe the microbiological and clinical outcomes associated with ß-lactam therapeutic drug management. DESIGN: Electronic Medical Record Review. SETTING: A 189-bed, freestanding children's tertiary care teaching hospital in Philadelphia, PA. PATIENTS: Patients admitted to the PICU from September 1, 2014, to May 31, 2017, with sepsis and those receiving extracorporal therapy with either extracorporeal membrane oxygenation or continuous renal replacement therapy that had routine ß-lactam therapeutic drug management. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-two patients were in the total cohort and 23 patients in the infected cohort accounting for 248 samples for therapeutic drug management analysis. The median age was 1 year (range, 4 d to 18 yr) with a mean weight of 19.7 ± 22.3 kg (range, 2.7-116 kg). Twenty-three patients (28%) had growth of an identified pathogen from a normally sterile site. Seventy-eight of 82 patients (95%) had subtherapeutic anti-infective concentrations and did not attain the primary pharmacodynamic endpoint. All patients in the infected cohort achieved a microbiological response, and 22 of 23 (95.7%) had a positive clinical response. CONCLUSIONS: Overall, 95% of patients had subtherapeutic anti-infective concentrations and did not achieve the requisite pharmacodynamic exposure with current pediatric dosing recommendations. All patients achieved a microbiological response, and 95.7% achieved clinical response with active ß-lactam therapeutic drug management. These data suggest ß-lactam therapeutic drug management is a potentially valuable intervention to optimize anti-infective pharmacokinetics and the pharmacodynamic exposure. Further, these data also suggest the need for additional research in specific pediatric populations and assessing clinical outcomes associated with ß-lactam therapeutic drug management in a larger cohort of pediatric patients.

Ceftaroline for Suspected or Confirmed Invasive Methicillin-Resistant Staphylococcus aureus: A Pharmacokinetic Case Series.

OBJECTIVES: To describe the ceftaroline pharmacokinetics in critically ill children treated for suspected or confirmed methicillin-resistant Staphylococcus aureus infections, including blood stream infection and describe the microbiological and clinical outcomes. DESIGN: Retrospective electronic medical record review. SETTINGS: Free-standing tertiary/quaternary pediatric children's hospital. PATIENTS: Critically ill children receiving ceftaroline monotherapy or combination therapy for suspected or confirmed methicillin-resistant S. aureus infections in the PICU. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Seven patients, three females (43%), and four males (57%), accounted for 33 ceftaroline samples for therapeutic drug management. A median of four samples for therapeutic drug management was collected per patient (range, 2-9 samples). The median age was 7 years (range, 1-13 yr) with a median weight of 25.5 kg (range, 12.6-40.1 kg). Six of seven patients (86%) demonstrated an increase in volume of distribution, five of seven patients (71%) demonstrated an increase in clearance, and 100% of patients demonstrated a shorter half-life estimate as compared with the package insert estimate. Six of seven patients (85.7%) had documented methicillin-resistant S. aureus growth from a normally sterile site with five of six (83.3%) having documented BSI, allowing six total patients to be evaluated for the secondary objective of microbiological and clinical response. All six patients achieved a positive microbiological and clinical response for a response rate of 100%. CONCLUSIONS: These data suggest the pharmacokinetics of ceftaroline in PICU patients is different than healthy pediatric and adult patients, most notably a faster clearance and larger volume of distribution. A higher mg/kg dose and a more frequent dosing interval for ceftaroline may be needed in PICU patients to provide appropriate pharmacodynamic exposures. Larger pharmacokinetic, pharmacodynamic, and interventional treatment trials in the PICU population are warranted.

Oxygenator Impact on Ceftaroline in Extracorporeal Membrane Oxygenation Circuits.

OBJECTIVES: To determine the oxygenator impact on alterations of ceftaroline in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extracorporeal membrane oxygenation circuit including the Quadrox-i oxygenator (Maquet, Wayne, NJ). DESIGN: Quarter-inch and 3/8-inch, simulated closed-loop extracorporeal membrane oxygenation circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. An one-time dose of ceftaroline was administered into the circuits, and serial pre- and postoxygenator concentrations were obtained at 5 minutes, 1-, 2-, 3-, 4-, 5-, 6-, and 24-hour time points. Ceftaroline was also maintained in a glass vial, and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation. SETTING: A free-standing extracorporeal membrane oxygenation circuit. PATIENTS: None. INTERVENTION: Single dose administration of ceftaroline into closed-loop extracorporeal membrane oxygenation circuits prepared with and without an oxygenator in series with serial preoxygenator, postoxygenator, and reference samples obtained for concentration determination over a 24-hour study period. MEASUREMENTS AND MAIN RESULTS: For the 1/4-inch circuit with an oxygenator, there was 79.8% drug loss preoxygenator and 82.5% drug loss postoxygenator at 24 hours. There was a statistically significant difference (p < 0.01) in the amount of ceftaroline remaining at 24 hours when compared with each prior time point for the 1/4-inch circuit. For the 1/4-inch circuit without an oxygenator, there was no significant drug loss at any study time point. For the 3/8-inch circuit with an oxygenator, there was 76.2% drug loss preoxygenator and 77.6% drug loss postoxygenator at 24 hours. There was a statistically significant difference (p < 0.01) in the amount of ceftaroline remaining at 24 hours when compared with each prior time point for the 3/8-inch circuit. For the 3/8-inch circuit without an oxygenator, there was no significant drug loss at any study time point. The reference ceftaroline concentrations remained relatively constant during the entire study period demonstrating the ceftaroline loss in each size of the extracorporeal membrane oxygenation circuit with or without an oxygenator was not a result of spontaneous drug degradation and primarily the result of the oxygenator. CONCLUSIONS: This ex vivo investigation demonstrated significant ceftaroline loss within an extracorporeal membrane oxygenation circuit with an oxygenator in series with both sizes of the Quadrox-i oxygenator at 24 hours. Therapeutic concentrations of ceftaroline in the setting of extracorporeal membrane oxygenation may not be achieved with current U.S. Food and Drug Administration-recommended doses, and further evaluation is needed before specific drug dosing recommendations can be made for clinical application with extracorporeal membrane oxygenation.

Association of procalcitonin values and bacterial infections in pediatric patients receiving extracorporeal membrane oxygenation.

OBJECTIVE: There is increasing data in pediatrics demonstrating procalcitonin (PCT) is more sensitive and specific than other biomarkers in the setting of bacterial infections. However, the use of PCT in neonatal and pediatric extracorporeal membrane oxygenation (ECMO) is not well described. Therefore, the purpose of this study was to describe the clinical utility of PCT in determining the absence or presence of bacterial infections in neonatal and pediatric patients on ECMO. METHODS: This was a retrospective electronic medical record (EMR) review of data between January 1, 2010 to June 30, 2016 at a single, free-standing, children 's hospital. All patients on ECMO with ≥1 PCT level obtained while receiving ECMO support were eligible for inclusion. The EMR was searched for chest radiographs (CXR) and bacterial culture results (urine, blood, cerebrospinal fluid (CSF), bronchoalveolar lavage (BAL) and respiratory cultures). All bacterial and viral cultures obtained within 5 days of PCT levels being obtained were analyzed. PCT levels of 0.5, 0.9, 1.0, 1.4 and 2.0 were used as the initial cut-off values for the analysis. The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV) and likelihood ratios were calculated for each of the PCT levels. RESULTS: Twenty-seven patients met the inclusion criteria and contributed 193 PCT values for the analysis. The median age was 8 months (range 0 days to 18 years). Linear regression analysis demonstrated that a PCT cut-off of 0.5, 0.9 and 1.4 predicted the presence of a bacterial infection. The PCT value with the most utility was 0.5, with a sensitivity of 92%, a specificity of 43%, a positive predictive value of 60% and a negative predictive value (NPV) of 86%. CONCLUSION: This is the largest data set evaluating PCT in neonatal and pediatric patients on ECMO. A PCT value of 0.5 ng/mL had the most utility for determining the absence or presence of a bacterial infection in the setting of ECMO with a high sensitivity and NPV.

Impact of ex-vivo extracorporeal membrane oxygenation circuitry on daptomycin.

BACKGROUND: The objective was to determine the alterations of daptomycin (DAP) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extracorporeal membrane oxygenation (ECMO) circuit including the Quadrox-i® oxygenator. METHODS: Quarter-inch and 3/8-inch, simulated, closed-loop, ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. A one-time dose of DAP was administered into the circuit and serial pre- and post-oxygenator concentrations were obtained at 0-5 minutes and 1, 2, 3, 4, 5, 6 and 24-hour time points. DAP was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation. RESULTS: For both the 1/4-inch and 3/8-inch circuits, there was no significant DAP loss at 24 hours. Additionally, the reference DAP concentrations remained relatively constant during the entire 24-hour study period. CONCLUSION: This ex-vivo investigation demonstrated no significant DAP loss within an ECMO circuit with both sizes of the Quadrox-i oxygenator at 24 hours. Therapeutic concentrations of DAP in the setting of ECMO may be anticipated with current recommended doses, depending on the amount of extracorporeal volume needed for circuit maintenance in comparison to the patient's apparent volume of distribution. Additional studies with a larger sample size are needed to confirm these findings.

Organ Support After Death by Neurologic Criteria in Pediatric Patients.

OBJECTIVES: We sought to 1) evaluate how pediatricians approach situations in which families request continuation of organ support after declaration of death by neurologic criteria and 2) explore potential interventions to make these situations less challenging. DESIGN: A survey on management and personal experience with death by neurologic criteria was distributed electronically to pediatric intensivists and neurologists. We compared responses from individuals who practice in states with accommodation exceptions (accommodation states where religious or moral beliefs must be taken into consideration when declaring death: California, Illinois, New Jersey, New York) to those from non-accommodation states. SETTING: United States. SUBJECTS: The survey was opened by 254 recipients, with 186 meeting inclusion criteria and providing data about the region in which they practice; of these, 26% were from accommodation states. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: More than half of physicians (61% from both accommodation states and non-accommodation states) reported they cared for a pediatric patient whose family requested continuation of organ support after declaration of death by neurologic criteria (outside of organ donation; range, 1-17 times). Over half of physicians (53%) reported they would not feel comfortable handling a situation in which a pediatric patient's family requested care be continued after declaration of death by neurologic criteria. Nearly every physician (98%) endorsed that something needs to be done to make situations involving families who object to discontinuation of organ support after declaration of death by neurologic criteria easier to handle. Respondents felt that public education, physician education, and uniform state laws about these situations are warranted. CONCLUSIONS: It is relatively common for pediatricians who care for critically ill patients to encounter families who object to discontinuation of organ support after death by neurologic criteria. Management of these situations is challenging, and guidance for medical professionals and the public is needed.

Population Pharmacokinetics and Pharmacodynamic Target Attainment of Vancomycin in Neonates on Extracorporeal Life Support.

OBJECTIVES: To evaluate the population pharmacokinetics and pharmacodynamic target attainment of vancomycin in neonates with a contemporary »-inch extracorporeal life support circuit with a Quadrox-iD Pediatric oxygenator (Maquet Cardiovascular, LLC, Wayne, NJ). DESIGN: Retrospective medical record review. SETTING: Two free-standing tertiary/quaternary pediatric children's hospitals. PATIENTS: Neonates receiving either veno-arterial or veno-venous extracorporeal life support and vancomycin for empiric or definitive therapy with resulting serum concentrations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twelve patients with a median gestations age of 39 weeks (range 36-41 wk) and a median postnatal age of 9.5 days (range 0-28 d) accounted for 14 courses of vancomycin therapy while on extracorporeal life support and were included in the analysis. The median weight was 3.1 kg (range 2.2-4.41 kg) with five of 12 patients (41.7%) being female. Vancomycin concentrations were best described by an one-compartment model incorporating allometric scaling of estimated glomerular filtration rate on clearance. The mean total body clearance (mL/min/kg) for the population was 3.48 ± 1.31 mL/min/kg, and the mean total volume of distribution (L/kg) for the population was 1.2 ± 0.4 L/kg. The intermittent and continuous infusion dosing regimens that provided for the highest percentage of trough concentrations in the range of 10-20 mg/L were the 10 mg/kg/dose IV q8h, 12.5 mg/kg/dose IV q8-12h, 15 mg/kg/dose IV q12h, and 20 mg/kg/dose IV q12h, and the 20, 25, and 30 mg/kg/d continuous infusion regimens, respectively. All regimens allowed for an area under the concentration:minimum inhibitory concentration ratio of 400:1 for minimum inhibitory concentrations of less than or equal to 0.5 mg/L for a 90% PTA. None of the simulated regimens had a greater than 90% probability of achieving an area under the concentration:minimum inhibitory concentration ratio of 400:1 for vancomycin minimum inhibitory concentrations greater than or equal to 1 mg/L while maintaining trough concentrations in the range of 10-20 mg/L. CONCLUSIONS: To our knowledge, this is the first pharmacokinetic and pharmacodynamic study of neonates receiving vancomycin with a contemporary »-inch extracorporeal life support circuit including the Quadrox-iD Pediatric oxygenator (Maquet Cardiovascular, LLC). The data suggest differences in vancomycin pharmacokinetics compared with previous extracorporeal life support data, notably a more rapid clearance, which could result in lower vancomycin concentrations. Considering this, a more aggressive initial dosing regimen may need to be employed in infants on extracorporeal life support.

Continuous Infusion Vancomycin Through the Addition of Vancomycin to the Continuous Renal Replacement Therapy Solution in the PICU: A Case Series.

OBJECTIVES: To describe our experience with achieving therapeutic serum vancomycin concentrations in pediatric continuous renal replacement therapy by using continuous infusion vancomycin by mixing vancomycin into the continuous renal replacement therapy solution. DESIGN: Retrospective chart review. SETTING: A 189-bed, freestanding children's tertiary care teaching hospital in Philadelphia, PA. PATIENTS: Pediatric patients receiving continuous renal replacement therapy from April 1, 2009, through December 31, 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were a total of 21 patients who received continuous renal replacement therapy during the study period. Of these, 11 (52.3%) received vancomycin in the continuous renal replacement therapy solution. The median (range) concentration of vancomycin added to the continuous renal replacement therapy solution was 25 mg/L (18-35 mg/L). The mean vancomycin plateau level was 22.8 ± 3.3 mg/L. All patients achieved a serum vancomycin plateau level that was greater than 15 mg/L. There were no adverse events related to the addition of vancomycin to the continuous renal replacement therapy solution. CONCLUSIONS: The addition of vancomycin to the continuous renal replacement therapy solution(s) is an effective modality that is used for delivering vancomycin continuous infusion and for ensuring therapeutic vancomycin serum plateau levels in the setting of pediatric continuous renal replacement therapy. Further studies are required to evaluate whether this delivery method can lead to improved patient outcomes.

Dengue NS3, an RNAi suppressor, modulates the human miRNA pathways through its interacting partner.

RNAi acts as a host immune response against non-self molecules, including viruses. Viruses evolved to neutralize this response by expressing suppressor proteins. In the present study, we investigated dengue virus non structural protein 3 (dvNS3), for its RNAi-suppressor activity in human cell lines. Dengue virus (DV) NS3 reverts the GFP expression in GFP-silenced cell lines. Pull-down assays of dvNS3 revealed that it interacts with the host factor human heat shock cognate 70 (hHSC70). Down-regulation of hHSC70 resulted in accumulation of dengue viral genomic RNA. Also, the interaction of dvNS3 with hHSC70 perturbs the formation of RISC (RNA-induced silencing complex)-loading complex (RLC), by displacing TRBP (TAR RNA-binding protein) and possibly impairing the downstream activity of miRNAs. Interestingly, some of these miRNAs have earlier been reported to be down-regulated upon DV infection in Huh7 cells. Further studies on the miRNA-mRNA relationship along with mRNA profiling of samples overexpressing dvNS3 revealed up-regulation of TAZ (tafazzin) and SYNGR1 (synaptogyrin 1), known dengue viral host factors (DVHFs). Importantly, overexpression of dvNS3 in human embryonic kidney (HEK) 293T cells resulted in modulation of both mature and precursor miRNAs in human cell lines. Subsequent analysis suggested that dvNS3 induced stage-specific down-regulation of miRNAs. Taken together, these results suggest that dvNS3 affects biogenesis and function of host miRNAs to regulate DVHFs for favouring DV replication.