Hospital care for children and young adults in the last year of life: a population-based study

BACKGROUND: To help design population-based pediatric palliative care services, we sought to describe the hospital care received in the last year of life by children and young adults who died. We also determined the proportion with complex chronic conditions (CCCs) and tested whether the use of hospital services increased as the date of death drew nearer. METHODS: For all deaths occurring under 25 years of age from 1990 to 1996 in Washington State, USA, we linked death certificate information to hospital utilization records and analyzed the timing and duration of hospitalizations and the nature of hospital procedures during the year prior to death. RESULTS: Of the 8 893 deaths, 25 % had CCCs. Among infants with CCCs, 84 % were hospitalized at the time of death and 50 % had been mechanically ventilated during their terminal admission. Among the 458 CCC neonates dying under a week of age, 92% of all days of life were spent in the hospital; among the 172 CCC neonates dying during the second to fourth weeks of life, 85 % of all days of life were spent hospitalized; among the 286 CCC infants dying during the second to twelfth month of life, 41 % of all days of life were spent hospitalized. Among children and young adults with CCCs, 55 % were hospitalized at the time of death, and 19 % had been mechanically ventilated during their terminal admission. For these older patients, the median number of days spent in the hospital during the year preceding death was 18, yet less than a third of this group was hospitalized at any point in time until the last week of their lives. The rate of hospital use increased as death drew near. For subjects who had received hospital care, 44 % had governmental insurance as the source of primary payment. CONCLUSIONS: Infants who died spent a substantial proportion of their lives in hospitals, whereas children and adolescents who died from CCCs predominantly lived outside of the hospital during the last year of life. To serve these patients, pediatric palliative and end-of-life care will have to be provided in an integrated, coordinated manner both in hospitals and home communities

EspA Acts as a Critical Mediator of ESX1-Dependent Virulence in Mycobacterium tuberculosis by Affecting Bacterial Cell Wall Integrity

Mycobacterium tuberculosis (Mtb) requires the ESX1 specialized protein secretion system for virulence, for triggering cytosolic immune surveillance pathways, and for priming an optimal CD8+ T cell response. This suggests that ESX1 might act primarily by destabilizing the phagosomal membrane that surrounds the bacterium. However, identifying the primary function of the ESX1 system has been difficult because deletion of any substrate inhibits the secretion of all known substrates, thereby abolishing all ESX1 activity. Here we demonstrate that the ESX1 substrate EspA forms a disulfide bonded homodimer after secretion. By disrupting EspA disulfide bond formation, we have dissociated virulence from other known ESX1-mediated activities. Inhibition of EspA disulfide bond formation does not inhibit ESX1 secretion, ESX1-dependent stimulation of the cytosolic pattern receptors in the infected macrophage or the ability of Mtb to prime an adaptive immune response to ESX1 substrates. However, blocking EspA disulfide bond formation severely attenuates the ability of Mtb to survive and cause disease in mice. Strikingly, we show that inhibition of EspA disulfide bond formation also significantly compromises the stability of the mycobacterial cell wall, as does deletion of the ESX1 locus or individual components of the ESX1 system. Thus, we demonstrate that EspA is a major determinant of ESX1-mediated virulence independent of its function in ESX1 secretion. We propose that ESX1 and EspA play central roles in the virulence of Mtb in vivo because they alter the integrity of the mycobacterial cell wall

Cognitive Behavior Therapy for Anxious Adolescents: Developmental Influences on Treatment Design and Delivery

Anxiety disorders in adolescence are common and disruptive, pointing to a need for effective treatments for this age group. Cognitive behavior therapy (CBT) is one of the most popular interventions for adolescent anxiety, and there is empirical support for its application. However, a significant proportion of adolescent clients continue to report anxiety symptoms post-treatment. This paper underscores the need to attend to the unique developmental characteristics of the adolescent period when designing and delivering treatment, in an effort to enhance treatment effectiveness. Informed by the literature from developmental psychology, developmental psychopathology, and clinical child and adolescent psychology, we review the ‘why’ and the ‘how’ of developmentally appropriate CBT for anxious adolescents. ‘Why’ it is important to consider developmental factors in designing and delivering CBT for anxious adolescents is addressed by examining the age-related findings of treatment outcome studies and exploring the influence of developmental factors, including cognitive capacities, on engagement in CBT. ‘How’ clinicians can developmentally tailor CBT for anxious adolescents in six key domains of treatment design and delivery is illustrated with suggestions drawn from both clinically and research-oriented literature. Finally, recommendations are made for research into developmentally appropriate CBT for anxious adolescents

Cognitive evolutionary therapy for depression: a case study

KEY CLINICAL MESSAGE: We present an evolutionary-driven cognitive–behavioral intervention for a moderately depressed patient. Standard cognitive and behavioral therapy techniques focused on the patient's perfectionistic and self-downing beliefs, while novel, evolutionary-informed techniques were used to guide behavioral activation and conceptualize secondary emotional problems related to anger. The treatment reduced depressive symptomatology and increased evolutionary fitness