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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., (© 2023. The Author(s).)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests. TG continues to work in an advisory capacity with the Department of Health and Social Care on its work relating to incorporating advance choice documents into the upcoming revisions of the Mental Health Act 1983 (England and Wales). AF and AC have no competing interests to declare.

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, paO 2 , oxygenation index, A-aDO 2 , 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., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

There is currently no specific guidance addressing vaccine hesitancy in those with mental health difficulties in the United Kingdom. This is particularly problematic when one considers that individuals with serious mental illnesses are at greater risk of infection and have poorer health outcomes for a range of reasons. There are also many individual and system level barriers to vaccination in this group. When an affected adult lacks the capacity to make a decision for themselves, it often falls to healthcare professionals to make a decision on that person's behalf and in their best interests. This article explores this matter with regard to the law in practice in the English and Welsh, and Scottish, jurisdictions and consider this with relevance to the safest approach that doctors and other healthcare professionals should take in working with patients for whom mental disorder may impact on decision-making capacity. The article focuses on psychiatric inpatients, including those who are detained involuntarily, to consider whether, and in what circumstances, COVID-19 vaccination should be given to individuals who cannot or do not consent.

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., (© Journal of the Association of Physicians of India 2011.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Outcomes in neonates receiving extracorporeal membrane oxygenation (ECMO) for meconium aspiration syndrome (MAS) and/or persistent pulmonary hypertension (PPHN) are favorable. Infants with preserved perfusion are often offered venovenous (VV) support to spare morbidities of venoarterial (VA) ECMO. Worsening perfusion or circuit complications can prompt conversion from VV-to-VA support. We examined whether outcomes in infants requiring VA ECMO for MAS/PPHN differed if they underwent VA support initially versus converting to VA after a VV trial, and what factors predicted conversion., Methods: We reviewed the Extracorporeal Life Support Organization registry from 2007 to 2017 for neonates with primary diagnoses of MAS/PPHN. Propensity score analysis matched VA single-runs (controls) 4:1 against VV-to-VA conversions based on age, pre-ECMO pH, and precannulation arrests. Primary outcomes were complications and survival. Data were analyzed using Mann-Whitney U and Fisher's exact testing. Multivariate regression identified independent predictors of conversion for VV patients., Results: 3831 neonates underwent ECMO for MAS/PPHN, including 2129 (55%) initially requiring VA support. Of 1702 patients placed on VV ECMO, 98 (5.8%) required VV-to-VA conversion. Compared with 364 propensity-matched isolated VA controls, conversion runs were longer (190 vs. 127 h, P < 0.001), were associated with more complications, and decreased survival to discharge (70% vs. 83%, P = 0.01). On multivariate regression, conversion was more likely if neonates on VV ECMO did not receive surfactant (OR = 1.7;95%CI = 1.1-2.7;P = 0.03) or required high-frequency ventilation (OR = 1.9;95%CI = 1.2-3.3;P = 0.01) before ECMO., Conclusion: Conversion from VV-to-VA ECMO in infants with MAS/PPHN conveys increased morbidity and mortality compared to similar patients placed initially onto VA ECMO. VV patients not receiving surfactant or requiring high-frequency ventilation before cannulation may have increased risk of conversion. While conversions remain rare, decisions to offer VV ECMO for MAS/PPHN must be informed by inferior outcomes observed should conversion be required., Level of Evidence: Level of evidence 3 Retrospective comparative study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To describe the characteristics of hospitalized children with severe acute respiratory syndrome coronavirus 2 in New York City metropolitan area., Patients and Methods: This was a multicenter, retrospective cohort study at 4 hospitals comprising 82 hospitalized children (0-21 years) who tested positive for severe acute respiratory syndrome coronavirus 2 after symptoms and risk screening between March 1 and May 10, 2020. We subdivided patients on the basis of their admission to acute or critical care units and by age groups. Further subanalyses were performed between patients requiring respiratory support or no respiratory support., Results: Twenty-three (28%) patients required critical care. Twenty-nine (35%) patients requiring respiratory support, with 9% needing mechanical ventilation, and 1 required extracorporeal support. All patients survived to discharge. Children with any comorbidity were more likely to require critical care (70% vs 37%, P = .008), with obesity as the most common risk factor for critical care (63% vs 28%, P = .02). Children with asthma were more likely to receive respiratory support (28% vs 8%, P = .02), with no difference in need for critical care ( P = .26). Children admitted to critical care had higher rates of renal dysfunction at presentation (43% vs 10%, P = .002)., Conclusions: Children with comorbidities (obesity and asthma in particular) were at increased risk for critical care admission and/or need for respiratory support. Children with renal dysfunction at presentation were more likely to require critical care., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Background: To determine if receiving targeted antimicrobial (AM) prophylaxis has an effect on the rate of postoperative infections in patient's colonized with a multidrug resistant organism (MDRO) undergoing cardiothoracic surgery (CTS)., Methods: Single-center, retrospective medical record review of pediatric patients from birth to 18 years of age undergoing CTS from January 2013 to September 2018. Demographic data collected included age, specific MDRO, site of MDRO colonization, type of surgery, perioperative AM agent and type of infection. Patients were stratified into 2 groups, MDRO+ and MDRO-. Demographic and clinical characteristics were compared between groups with a Student's t test for continuous variables and a χ2, Fisher exact test or Mann-Whitney U test for noncontinuous variables. A 2-sided significance level of α = 0.05 was used to determine statistical significance. All analyses were performed using IBM SPSS Version 24 (SPSS Inc., Chicago, IL)., Results: Fifty patients (26 males/24 females) were included in the MDRO (+) group and 295 patients (168 males/127 females) in the MDRO (-) group. The median age was 0.48 years (interquartile range 0.24-1 year) and 0.9 years (interquartile range 0.19-8 years) in the MDRO (+) and MDRO (-) groups, P = 0.003. 2 of 50 (4%) MDRO (+) patients and 15 of 295 (5.1 %) MDRO (-) patients developed an infection, P = 1. 10 of 50 (20%) MDRO (+) patients received targeted AM toward the MDRO and none developed an infection. Of the 2 MDRO (+) patients with infection, 1 was infected with the MDRO. For MDRO (+) patients, there was no difference in the rate of infection whether targeted AM therapy was received, P = 1., Conclusions: There was no difference in the rate of postoperative infection between MDRO (+) and MDRO (-) patients. Additionally, these preliminary pediatric data suggest targeting AM agents to a specific MDRO does not impact the rate of postoperative infection in children undergoing CTS. Larger studies are warranted to confirm these findings.

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.

Background: In ST-elevation myocardial infarction (STEMI), prehospital delay is a significant factor, decreasing likelihood of revascularization and increasing mortality. Prehospital delays are substantive in Indian patients with STEMI. Our study aimed to investigate factors associated with prehospital delay in patients with STEMI., Methods: A multicentric prospective analysis was conducted at five major cardiac care referral centers in Punjab including a tertiary care teaching hospital over a period of 1 year from January 2015 to December 2015. Patients presenting with STEMI were included in the study. A structured questionnaire was used to gather patient characteristics and factors responsible for prehospital delay., Results: Of the 619 patients included in the study, 42% presented with more than 6 h of prehospital delay. On univariate analysis, delay was significantly higher among elderly (p = 0.01), illiterate patients (p = 0.02), and patients residing in rural areas (p = 0.04). Recognizing symptoms as cardiac in origin (p < 0.001), hospital as initial medical contact, and availability of prehospital electrocardiogram (ECG) (p = 0.001) were associated with shorter delays. On multivariate analysis, prehospital delay was significant in elderly patients, initial point of care as outpatient clinic, and patients without access to prehospital ECG., Conclusion: Our study concludes that demographic and socioeconomic barriers exist that impede rapid care seeking and highlights the need for utilization of prehospital ECG to decrease prehospital delay. Possibilities include, educating the public on the importance of early emergency medical services contact or creating emergency stations in rural areas with ECG capabilities. Our study also invites further research, regarding role of telemedicine to triage patients derived from prehospital ECGs to decrease prehospital delay., (Copyright © 2018 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

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.

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.

Background: Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia., Methods: We performed a systematic review to summarize the evidence related to our questions. When evidence was not sufficient, we used data from the New York University Familial Dysautonomia Patient Registry, a database containing ongoing prospective comprehensive clinical data from 670 cases. The evidence was summarized and discussed by a multidisciplinary panel of experts. Evidence-based and expert recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system., Results: Recommendations were formulated for or against specific diagnostic tests and clinical interventions. Diagnostic tests reviewed included radiological evaluation, dysphagia evaluation, gastroesophageal evaluation, bronchoscopy and bronchoalveolar lavage, pulmonary function tests, laryngoscopy and polysomnography. Clinical interventions and therapies reviewed included prevention and management of aspiration, airway mucus clearance and chest physical therapy, viral respiratory infections, precautions during high altitude or air-flight travel, non-invasive ventilation during sleep, antibiotic therapy, steroid therapy, oxygen therapy, gastrostomy tube placement, Nissen fundoplication surgery, scoliosis surgery, tracheostomy and lung lobectomy., Conclusions: Expert recommendations for the diagnosis and management of respiratory disease in patients with familial dysautonomia are provided. Frequent reassessment and updating will be needed., (Copyright © 2018. Published by Elsevier Ltd.)

Objectives: There is a lack of standardization and supporting data regarding the duration preassembled and preprimed extracorporeal membrane oxygenation (ECMO) circuits are expected to be sterile. Therefore, the purpose of this study was to prospectively evaluate whether preassembled and preprimed ECMO circuits could maintain sterility for a period up to 65 days., Design: Four ECMO circuits (2 neonatal/pediatric¼" and 2 adolescent/adult ⅜ ") were assembled and primed under sterile conditions and maintained at room temperature. Culture samples were obtained from each circuit and plated within 1 hour. Culture samples were obtained on day 0 when assembled and primed then every 5 days up to day 65. Samples were plated on several different media including the following: blood agar plate: trypticase soy agar with 5% sheep blood, MacConkey agar, and thioglycollate broth then incubated at 35°C for 3 days., Results: All cultures obtained from the priming solution from of the¼" and ⅜ " ECMO circuits produced no microbial or fungal growth for the 65-day study period., Conclusion: These pilot data suggest preprimed ECMO circuits may maintain sterility for a period up to 65 days. Additional studies evaluating a larger number of ECMO circuits are needed to confirm these findings., Competing Interests: Disclosure Jeffrey J. Cies PharmD, MPH is a consultant for Atlantic Diagnostic Laboratories and has received grants and/or honoraria from Allergan, Merck, and Thermo Fisher Scientific. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data and take responsibility for the integrity and accuracy of the data analysis.

Aims and method To determine features associated with better perceived quality of training for psychiatrists on advance decision-making in the Mental Capacity Act 2005 (MCA), and whether the quality or amount of training were associated with positive attitudes or use of advance decisions to refuse treatment (ADRTs) by psychiatrists in people with bipolar disorder. An anonymised national survey of 650 trainee and consultant psychiatrists in England and Wales was performed. Results Good or better quality of training was associated with use of case summaries, role-play, ADRTs, assessment of mental capacity and its fluctuation. Good or better quality and two or more sessions of MCA training were associated with more positive attitudes and reported use of ADRTs, although many psychiatrists would never discuss them clinically with people with bipolar disorder. Clinical implications Consistent delivery of better-quality training is required for all psychiatrists to increase use of ADRTs in people with bipolar disorder., Competing Interests: Declaration of interest None.

Objectives: To evaluate the population pharmacokinetics and pharmacodynamic target attainment of vancomycin in neonates with a contemporary ¼-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 ¼-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.

Objective: This study aims to describe the population pharmacokinetics and pharmacodynamic target attainment of meropenem in critically ill children., Methods: The study involved a retrospective medical record review from a 189-bed, freestanding children's tertiary care teaching hospital of patients ages 1 to 9 years who received meropenem with concurrent therapeutic drug monitoring., Results: There were 9 patients ages 1 to 9 years (mean age, 3.1 ± 2.9 years) with a mean weight of 17.1 ± 11.9 kg who met the inclusion/exclusion criteria and were included in the pharmacokinetic analysis. Meropenem concentrations were best described by a 2-compartment model with first-order elimination, with an R 2 and bias of 0.91 and 13.2 mg/L, respectively, for the observed versus population predicted concentrations, and an R 2 , bias, and imprecision of 1, 0.0675, and 1 mg/L, respectively, for the observed versus individual predicted concentrations. The mean total body drug clearance for the population was 6.99 ± 2.5 mL/min/kg, and V c was 0.57 ± 0.47 L/kg. The calculated population estimate for the total volume of distribution was 0.78 ± 0.73 L/kg. Standard 0.5-hour meropenem infusions did not provide for appropriate pharmacodynamic exposures of 40% free time > minimum inhibitory concentration (40% f T > MIC) for Gram-negative organisms with susceptible MICs. Dosage regimens employing prolonged and continuous infusion regimens did provide appropriate pharmacodynamic exposures of 40% f T > MIC for Gram-negative organisms up to the break point for Pseudomonas aeruginosa of 4 mg/L., Conclusion: These data suggest the reference dosage regimens for meropenem (20-40 mg/kg per dose every 8 hours) do not meet an appropriate pharmacodynamic target attainment in critically ill children ages 1 to 9 years. Based on these data, only the 3- to 4-hour prolonged infusion and 24-hour continuous infusion regimens were able to achieve an optimal probability of target attainment against all susceptible Gram-negative bacteria in critically ill children for 40% f T > MIC. Dosage regimens of 120 and 160 mg/kg/day as continuous infusion regimens may be necessary to achieve an optimal probability of target attainment against all susceptible Gram-negative bacteria in critically ill children for 80% f T > MIC. Based on these findings, confirmation with a larger, prospective investigation in critically ill children is warranted., Competing Interests: Disclosure Dr Cies is a consultant for Atlantic Diagnostic Laboratories and has received grants or honoraria from Allergan, Merck, and Thermo Fisher Scientific. Drs Moore and Chopra declare no conflicts or financial interests, and neither does Ms Enache. The authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Background: The PANARrhythMia and Heart Failure Registry (PANARM HF) characterized demographic, clinical and interventional therapy indication profiles of cardiac arrhythmia (CA) and heart failure (HF) patients in India., Methods: Consulting Physicians (CP) who medically manage CA and HF patients enrolled patients with one or more of the following: syncope, pre-syncope, dyspnea, palpitation, fatigue and LV dysfunction. The CPs were trained by interventional cardiologists (IC) to identify CA/HF patients indicated for implantable device/radiofrequency ablation (RFA). 59 CP's, 16 IC's & 2205 patients from 12 cities participated. Demographic, clinical, device/RFA indication and referral-consultation profiles were created. IC's provided device/RFA recommendations based on these profiles., Results: The CA/HF distribution of patients was: HF - 58%, bradyarrhythmia - 15%, atrial fibrillation - 15%, other supraventricular tachyarrhythmia - 10% and ventricular tachycardia/fibrillation - 4.5%. 62% of the CA/HF population was male and 45% were below age 60. Coronary artery disease (52%), hypertension (44%), diabetes (30%) & myocardial infarction (20%) were prominent. 1011 (46%) of the CA/HF population were potential device/RFA candidates according to the IC's. However, only 700 (69%) of these patients were referred to the IC by the CP. Of referred patients, only 177 (25%) consulted the IC and were recommended therapy. Thus, 824 (83%) of patients indicated for interventional therapy were not advised therapy or did not opt for it., Conclusion: The India PANARM HF study provides new information and insights into the demographic, clinical, interventional therapy, referral and consultation pattern profiles of CA/HF patients in India., (Copyright © 2016. Published by Elsevier B.V.)

The present study aimed to develop and optimize a nanoemulsifying preconcentrate formulation of curcumin with good emulsification ability and optimal globule size, for controlled targeting in colon. Content of formulation variables, namely, X1 (Peceol), X2 (Cremophor-EL), and X3 (Transcutol HP), were optimized by Box-Behnken design of experiments for its impact on mean globule size (Y1), emulsification time (Y2), and time required for drug release (85%) in phosphate buffer (pH 7.2), t 85% (Y3). Transmission electron micrographs confirmed that there is no coalescence among globules, with size range concordant with the globule size analysis by dynamic light scattering technique (100 nm). 3D plots indicated that concentration of formulation ingredients significantly influences the formulation properties (globule size, emulsification time, and drug release). In vitro release profile (in phosphate buffer; pH 7.2) represents the fact that more than 50% of the drug was released within initial 15 min whereas in vivo release showed limited systemic absorption (C max 200 ng/mL) of curcumin. Stability study ensures the protection of drug in alkaline media which may further confirm the localised delivery of drug to colonic region. Study demonstrated that the nanoemulsifying preconcentrate can be a promising system for the colon specific delivery of curcumin to treat local pathologies.

Background: Clopidogrel has been the only available antiplatelet drug used along with aspirin in patients of ACS. In recent years 2 new antiplatelet drugs (Prasugrel and Ticagrelor) have become available. Prasugrel in the dose of 10 mg OD has been found to be more efficacious but with increased risk of major bleeding. For this reason it has not gained widespread usage in ACS patients undergoing PCI. There are no systematic data on the use of Prasugrel in Indian population., Method: This is a prospective, multicentric, hospital registry of 1000 patients with ACS undergoing PCI who were administered Prasugrel. The primary safety endpoint of this study was major and minor bleeding while the efficacy endpoint is the composite of CV death, nonfatal MI, nonfatal stroke up to 30 days after PCI. Patients with high bleeding risk were excluded., Results: Most patients (91%) received loading dose of Prasugrel along with the maintenance dose getting according to the defined protocol. Patients were followed up to 30 days post procedure. Primary efficacy end point was reached in 3 patients only with two of them dying due to possible stent thrombosis and the third requiring revascularization of the target vessel for stent thrombosis. One major and 19 minor bleeding complications were recorded, with access site bleeding in 0.7% & non-access site bleeding in 1.2% of the subjects., Conclusion: Prasugrel was found to be effective & not associated with a high incidence of bleeding in the high risk ACS patients when those at a high bleeding risk were excluded., (Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

A variety of ion channels are regulated by cholesterol, a major lipid component of the plasma membrane whose excess is associated with multiple pathological conditions. However, the mechanism underlying cholesterol sensitivity of ion channels is unknown. We have recently shown that an increase in membrane cholesterol suppresses inwardly rectifying K(+) (Kir2) channels that are responsible for maintaining membrane potential in a variety of cell types. Here we show that cholesterol sensitivity of Kir2 channels depends on a specific region of the C terminus of the cytosolic domain of the channel, the CD loop. Within this loop, the L222I mutation in Kir2.1 abrogates the sensitivity of the channel to cholesterol whereas a reverse mutation in the corresponding position in Kir2.3, I214L, has the opposite effect, increasing cholesterol sensitivity. Furthermore, the L222I mutation has a dominant negative effect on cholesterol sensitivity of Kir2.1 WT. Mutations of 2 additional residues in the CD loop in Kir2.1, N216D and K219Q, partially affect the sensitivity of the channel to cholesterol. Yet, whereas these mutations have been shown to affect activation of the channel by the membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)], other mutations outside the CD loop that have been previously shown to affect activation of the channel by PI(4,5)P(2) had no effect on cholesterol sensitivity. Mutations of the lipid-facing residues of the outer transmembrane helix also had no effect. These findings provide insights into the structural determinants of the sensitivity of Kir2 channels to cholesterol, and introduce the critical role of the cytosolic domain in cholesterol dependent channel regulation.

Objective: To determine whether schizophrenia is a commonly used 'illness as metaphor', to compare the use of schizophrenia and cancer as illnesses as metaphor, and to determine if there is a difference in such usage between the UK and USA., Design: An examination of articles published in the British press., Setting: 600 articles from six British newspapers: the Times, the Daily Telegraph, the Guardian, the Mirror, the Sun and the Daily Mail., Main Outcome Measures: Use of schizophrenia and cancer as metaphors., Results: Schizophrenia was more likely to be metaphorized than cancer (P<0.001) in the UK press, but was less likely to be used as metaphor in the UK press than in the US press (P<0.001). 11% of articles containing the term schizophrenia used the word as a metaphor., Conclusions: Clinicians need to be aware that patients, carers and the public might have a different understanding of the word we use as a diagnosis.