A Qualitative Exploration of the Impact of a Distressed Family Member on Pediatric Resuscitation Teams.

BACKGROUND AND OBJECTIVES: Family presence during resuscitation (FPDR) is commonplace in many hospitals today. Research has supported the positive effects it can have on family members; however, there is little research about how it may affect the resuscitation team's performance, especially in a pediatric population. Our objective was to identify how resuscitation team members perceive and respond to the presence of a distressed family member during a resuscitation. METHODS: This is a qualitative study in which we examine FPDR-related themes raised by pediatric resuscitation team members after a resuscitation simulation. As part of a team training educational intervention, pediatric resuscitation teams, composed of nurses, respiratory therapists, and resident physicians, participated in a video-recorded simulated event in which they attempted to resuscitate an infant. During the scenario, a confederate actor played the role of a distressed "parent." Video-recorded debriefs occurred immediately after each simulation. Video recordings were transcribed verbatim, and then transcripts were coded and analyzed via thematic analysis to saturation. RESULTS: Thirteen postevent video debriefs were analyzed. A total of 74 participants took part in these simulations and debriefs. Analysis revealed 15 major and 29 minor themes, which were mapped to 5 factors, namely resuscitation environment, affective responses, cognitive responses, behavioral responses, and team dynamics. CONCLUSIONS: FPDR has an impact on resuscitation team members' responses and influences their adaptive behavior. If not managed well, this may pose potential patient safety concerns. Policy and training of specific teamwork skills are ways in which we can better equip health care providers to effectively manage FPDR.

Activity and safety of CTLA-4 blockade combined with vaccines in cynomolgus macaques.

The immune modulatory molecule CTLA-4 (CD152), through interactions with the B7 costimulatory molecules, has been shown to be a negative regulator of T cell activation in various murine model systems. Abs that block CTLA-4 function can enhance immune responses that mediate potent antitumor activity. However, CTLA-4 blockade can also exacerbate autoimmune disease. The safety and activity of anti-CTLA-4 Abs in primates has not been addressed. To that end, we generated human Abs against CTLA-4 using transgenic mice expressing human Ig genes. A high affinity Ab (10D1) that blocked the binding of CTLA-4 to the B7-1 and B7-2 ligands and had cross-reactivity with macaque CTLA-4 was chosen for further development. Administration of 10D1 to cynomolgus macaques significantly enhanced Ab responses to hepatitis surface Ag and a human melanoma cell vaccine. Anti-self Ab responses as measured by immunoassays using lysate from melanocyte-rich tissues were elicited in those animals receiving the melanoma cell vaccine and anti-CTLA-4 Ab. Remarkably, chronic administration of 10D1 did not result in measurable polyclonal T cell activation, significant alteration of the lymphocyte subsets, or induce clinically observable autoimmunity. Repeated dosing of the 10D1 did not elicit monkey anti-human Ab responses in the monkeys. These observations support the development of CTLA-4 blockade for human immunotherapy.

Simultaneous determination of six urinary porphyrins using liquid chromatography-tandem mass spectrometry.

A liquid chromatographic-tandem mass spectrometric (LC-MS-MS) method without sample pretreatment was developed and validated for determination of porphyrins in samples of canine urine. Acidified urine samples were directly injected into the LC-MS system and a gradient elution program was applied. The mass spectrometer was operated in the multi-reaction monitoring (MRM) mode and six porphyrins were detected with excellent sensitivity and selectivity. The lower limits of quantification were 0.014 nmol/mL for mesoporphyrin IX, coproporphyrin I, 5-carboxylporphyrin, 6-carboxylporphyrin and 7-carboxylporphyrin, and 0.029 nmol/mL for uroporphyrin I. Good ln-quadratic responses of calibration standards over the range 0.01 to 1.0 nmol/mL for mesoporphyrin IX, coproporphyrin I, 5-carboxylporphyrin, 6-carboxylporphyrin and 7-carboxylporphyrin, and 0.02 to 1.0 nmol/mL for uroporphyrin I were demonstrated. This method should be easily adapted through cross-validation for use in determining the effects of chemicals and pharmaceuticals on the urinary excretion profile of porphyrins in preclinical studies with other species, and in assisting the diagnosis of porphyria in clinical studies.