Analgosedation in paediatric severe traumatic brain injury (TBI): practice, pitfalls and possibilities

Analgosedation is a fundamental part of traumatic brain injury (TBI) treatment guidelines, encompassing both first and second tier supportive strategies. Worldwide analgosedation practices continue to be heterogeneous due to the low level of evidence in treatment guidelines (level III) and the choice of analgosedative drugs is made by the treating clinician. Current practice is thus empirical and may result in unfavourable (often hemodynamic) side effects. This article presents an overview of current analgosedation practices in the paediatric intensive care unit (PICU) and addresses pitfalls both in the short and long term. We discuss innovative (pre-)clinical research that can provide the framework for initiatives to improve our pharmacological understanding of analgesic and sedative drugs used in paediatric severe TBI and ultimately facilitate steps towards evidence-based and precision pharmacotherapy in this vulnerable patient group

Quality of life and health status of Indonesian women with breast cancer symptoms before the definitive diagnosis

__Objectives__ Breast cancer (BC) is prevalent in low and middle-income countries (LMICs) where the majority of cases are diagnosed in late stages. The aims of this study were: (1) to assess quality of life (QOL) and health status of Indonesian women with BC symptoms before definitive diagnosis; (2) to compare QOL and health status between women with BC symptoms before definitive diagnosis and Indonesian women in general; (3) to evaluate the association between demographic variables (age, residence, social economic status and education level) and QOL within the Indonesian women with BC symptoms before definitive diagnosis. __Methods__ We used WHOQOL-BREF to measure QOL and EQ-5D-5L for health status. Multivariate analysis of covariance (MANCOVA) was used to compare QOL and health status between women with BC symptoms and women from the general Indonesian population in order to control for confounders. Regression analyses were used for testing the association between the demographic variables, QOL, and health status. __Results__ In comparison with the data from the women from the general population (n = 471), the women with BC symptoms (n = 132) reported lower QOL, especially in physical and psychological domains. They also reported more problems in all dimensions of health status. Higher education and monthly income were positively associated with QOL and health status among the women with BC symptoms. __Conclusion__ Before receiving a definitive diagnosis, women who visit hospitals with symptoms of BC, report a lower QOL and health status than women in general. Our results suggest that healthcare providers should provide targeted strategies for women with BC symptoms to improve their QOL

Pregnant women with bronchial asthma benefit from progressive muscle relaxation: A randomized, prospective, controlled trial

Background: Asthma is a serious medical problem in pregnancy and is often associated with stress, anger and poor quality of life. The aim of this study was to determine the efficacy of progressive muscle relaxation (PMR) on change in blood pressure, lung parameters, heart rate, anger and health-related quality of life in pregnant women with bronchial asthma. Methods: We treated a sample of 64 pregnant women with bronchial asthma from the local population in an 8-week randomized, prospective, controlled trial. Thirty-two were selected for PMR, and 32 received a placebo intervention. The systolic blood pressure, forced expiratory volume in the first second, peak expiratory flow and heart rate were tested, and the State-Trait Anger Expression Inventory and Health Survey (SF-36) were employed. Results: According to the intend-to-treat principle, a significant reduction in systolic blood pressure and a significant increase in both forced expiratory volume in the first second and peak expiratory flow were observed after PMR. The heart rate showed a significant increase in the coefficient of variation, root mean square of successive differences and high frequency ranges, in addition to a significant reduction in low and middle frequency ranges. A significant reduction on three of five State-Trait Anger Expression Inventory scales, and a significant increase on seven of eight SF-36 scales were observed. Conclusions: PMR appears to be an effective method to improve blood pressure, lung parameters and heart rate, and to decrease anger levels, thus enhancing health-related quality of life in pregnant women with bronchial asthma. Copyright (c) 2006 S. Karger AG, Basel

Population Pharmacokinetic Model and Pharmacokinetic Target Attainment of Micafungin in Intensive Care Unit Patients

_Objective:_ To study the pharmacokinetics of micafungin in intensive care patients and assess pharmacokinetic (PK) target attainment for various dosing strateg

Safe use of proton pump inhibitors in patients with cirrhosis

Aims: Proton pump inhibitors (PPIs) belong to the most frequently used drugs, also in patients with cirrhosis. PPIs are extensively metabolized by the liver, but practice guidance on prescribing in cirrhosis is lacking. We aim to develop practical guidance on the safe use of PPIs in patients with cirrhosis. Methods: A systematic literature search identified studies on the safety (i.e. adverse events) and pharmacokinetics of PPIs in cirrhotic patients. This evidence and data from the product information was reviewed by an expert panel who classified drugs as safe; no additional risks known; additional risks known; unsafe; or unknown. Guidance was aimed at the oral use of PPIs and categorized by the severity of cirrhosis, using the Child–Turcotte–Pugh (CTP) classification. Results: A total of 69 studies were included. Esomeprazole, omeprazole and rabeprazole were classified as having ‘no additional risks known’. A reduction in maximum dose of omeprazole and rabeprazole is recommended for CTP A and B patients. For patients with CTP C cirrhosis, the only PPI advised is esomeprazole at a maximum dosage of 20 mg per day. Pantoprazole and lansoprazole were classified as unsafe because of 4- to 8-fold increased exposure. The use of PPIs in cirrhotic patients has been associated with the development of infections and hepatic encephalopathy and should be carefully considered. Conclusions: We suggest using esomeprazole, omeprazole or rabeprazole in patients with CTP A or B cirrhosis and only esomeprazole in patients with CTP C. Pharmacokinetic changes are also important to consider when prescribing PPIs to vulnerable, cirrhotic patients

Long-term multidisciplinary follow-up programs in pediatric cardiac arrest survivors

Long-term outcome studies after pediatric cardiac arrest (CA) are few. They require a CA registry and dedicated outcome teams. Learning about the long-term outcomes is very important for developing prognostication guidelines, improving post-cardiac care, counseling caregivers about the future of their child, and creating opportunities for therapeutic intervention studies to improve outcomes. Few PICUs worldwide provide a multidisciplinary follow-up program as routine practice at an outpatient clinic with standardized measurements, using validated instruments including neuropsychological assessments by psychologists. The primary goal of such a follow-up program should be to provide excellent care to children and their caregivers, thereby resulting in a high attendance. Pediatric psychologists, neurologists and pediatricians/pediatric intensivists should ideally be involved to screen for delayed development and psychosocial problems and offer appropriate care at the same time. Preferably, outcomes should consist of evaluation of morbidity (physical and neuropsychological), functional health and Health Related Quality Of Life (QoL) of the patient and their caregivers.</p

Long-term multidisciplinary follow-up programs in pediatric cardiac arrest survivors

Long-term outcome studies after pediatric cardiac arrest (CA) are few. They require a CA registry and dedicated outcome teams. Learning about the long-term outcomes is very important for developing prognostication guidelines, improving post-cardiac care, counseling caregivers about the future of their child, and creating opportunities for therapeutic intervention studies to improve outcomes. Few PICUs worldwide provide a multidisciplinary follow-up program as routine practice at an outpatient clinic with standardized measurements, using validated instruments including neuropsychological assessments by psychologists. The primary goal of such a follow-up program should be to provide excellent care to children and their caregivers, thereby resulting in a high attendance. Pediatric psychologists, neurologists and pediatricians/pediatric intensivists should ideally be involved to screen for delayed development and psychosocial problems and offer appropriate care at the same time. Preferably, outcomes should consist of evaluation of morbidity (physical and neuropsychological), functional health and Health Related Quality Of Life (QoL) of the patient and their caregivers.</p

Borrelia valaisiana resist complement-mediated killing independently of the recruitment of immune regulators and inactivation of complement components

Spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato complex differ in their resistance to complement-mediated killing, particularly in regard to human serum. In the present study, we elucidate the serum and complement susceptibility of B. valaisiana, a genospecies with the potential to cause Lyme disease in Europe as well as in Asia. Among the investigated isolates, growth of ZWU3 Ny3 was not affected while growth of VS116 and Bv9 was strongly inhibited in the presence of 50% human serum. Analyzing complement activation, complement components C3, C4 and C6 were deposited on the surface of isolates VS116 and Bv9, and similarly the membrane attack complex was formed on their surface. In contrast, no surface-deposited components and no aberrations in cell morphology were detected for serum-resistant ZWU3 Ny3. While further investigating the protective role of bound complement regulators in mediating complement resistance, we discovered that none of the B. valaisiana isolates analyzed bound complement regulators Factor H, Factor H-like protein 1, C4b binding protein or C1 esterase inhibitor. In addition, B. valaisiana also lacked intrinsic proteolytic activity to degrade complement components C3, C3b, C4, C4b, and C5. Taken together, these findings suggest that certain B. valaisiana isolates differ in their capability to resist complement-mediating killing by human serum. The molecular mechanism utilized by B. valaisiana to inhibit bacteriolysis appears not to involve binding of the key host complement regulators of the alternative, classical, and lectin pathways as already known for serum-resistant Lyme disease or relapsing fever borreliae