Diagnosis Code and Health Care Utilization Patterns Associated With Diagnostic Uncertainty.

BACKGROUND AND OBJECTIVES: Diagnostic uncertainty is challenging to identify and study in clinical practice. This study compares differences in diagnosis code and health care utilization between a unique cohort of hospitalized children with uncertain diagnoses (UD) and matched controls. PATIENTS AND METHODS: This case-control study was conducted at Cincinnati Children's Hospital Medical Center. Cases were defined as patients admitted to the pediatric hospital medicine service and having UDs during their hospitalization. Control patients were matched on age strata, biological sex, and time of year. Outcomes included type of diagnosis codes used (ie, disease- or nondisease-based) and change in code from admission to discharge. Differences in diagnosis codes were evaluated using conditional logistic regression. Health care utilization outcomes included hospital length of stay (LOS), hospital transfer, consulting service utilization, rapid response team activations, escalation to intensive care, and 30-day health care reutilization. Differences in health care utilization were assessed using bivariate statistics. RESULTS: Our final cohort included 240 UD cases and 911 matched controls. Compared with matched controls, UD cases were 8 times more likely to receive a nondisease-based diagnosis code (odds ratio [OR], 8.0; 95% confidence interval [CI], 5.7-11.2) and 2.5 times more likely to have a change in their primary International Classification of Disease, 10th revision, diagnosis code between admission and discharge (OR, 2.5; 95% CI, 1.9-3.4). UD cases had a longer average LOS and higher transfer rates to our main hospital campus, consulting service use, and 30-day readmission rates. CONCLUSIONS: Hospitalized children with UDs have meaningfully different patterns of diagnosis code use and increased health care utilization compared with matched controls.

Light-Induced Opening of the TRP Channel in Isolated Membrane Patches Excised from Photosensitive Microvilli from Drosophila Photoreceptors.

Drosophila phototransduction occurs in light-sensitive microvilli arranged in a longitudinal structure of the photoreceptor, termed the rhabdomere. Rhodopsin (Rh), isomerized by light, couples to G-protein, which activates phospholipase C (PLC), which in turn cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) generating diacylglycerol (DAG), inositol trisphosphate and H+. This pathway opens the light-dependent channels, transient receptor potential (TRP) and transient receptor potential like (TRPL). PLC and TRP are held together in a protein assembly by the scaffold protein INAD. We report that the channels can be photoactivated in on-cell rhabdomeric patches and in excised patches by DAG. In excised patches, addition of PLC-activator, m-3M3FBS, or G-protein-activator, GTP-γ-S, opened TRP. These reagents were ineffective in PLC-mutant norpA and in the presence of PLC inhibitor U17322. However, DAG activated TRP even when PLC was pharmacologically or mutationally suppressed. These observations indicate that PLC, G-protein, and TRP were retained functional in these patches. DAG also activated TRP in the protein kinase C (PKC) mutant, inaC, excluding the possibility that PKC could mediate DAG-dependent TRP activation. Labeling diacylglycerol kinase (DGK) by fusion of fluorescent mCherry (mCherry-DGK) indicates that DGK, which returns DAG to dark levels, is highly expressed in the microvilli. In excised patches, TRP channels could be light-activated in the presence of GTP, which is required for G-protein activation. The evidence indicates that the proteins necessary for phototransduction are retained functionally after excision and that DAG is necessary and sufficient for TRP opening. This work opens up unique possibilities for studying, in sub-microscopic native membrane patches, the ubiquitous phosphoinositide signaling pathway and its regulatory mechanisms in unprecedented detail.

Parents Support Teach-back, Demonstration, and a Postdischarge Phone Call to Augment Discharge Education.

OBJECTIVES: To identify caregiver preferences for discharge education components, content, and techniques. METHODS: Before discharge education, a 9-question structured interview was performed with caregivers of children from 2 populations admitted to the hospital medicine service: patients with asthma (age 2-17 years) or children who were not dependent on technology (age <2 years). McNemar's tests were used to evaluate for significant differences between response options. Open coding was used for theme development to interpret qualitative responses about information caregivers wished to receive before leaving the hospital. RESULTS: The interview was administered to 100 caregivers. More than 90% of caregivers believed that instruction regarding follow-up appointments, medications, and reasons to call the pediatrician or return to the emergency department were important aspects of discharge education. Caregivers also identified a desire for education on their child's condition, care at home, and illness prevention. Most caregivers reported that teach-back, early discharge education, and a postdischarge phone call would be beneficial. Caregivers varied in their preferences for written, verbal, and video instruction, whereas live demonstration was rated almost universally as an effective method by 97% of caregivers (P < .0001). CONCLUSIONS: In our study, we provide insight into caregivers' perspectives on the content, timing, and style of education needed to promote a safe transition of care from the hospital to the home. These findings add caregiver support to the expert consensus in Project Improving Pediatric Patient-Centered Care Transitions and elucidate additional themes to aid in further study and optimization of discharge education.

Investigating the efficacy of monovalent and tetravalent dengue vaccine formulations against DENV-4 challenge in AG129 mice.

Dengue (DEN) is the most important mosquito-borne viral disease, with a major impact on global health and economics, caused by four serologically and distinct viruses termed DENV-1 to DENV-4. Currently, there is no licensed vaccine to prevent DEN. We have developed a live attenuated tetravalent DENV vaccine candidate (TDV) (formally known as DENVax) that has shown promise in preclinical and clinical studies and elicits neutralizing antibody responses to all four DENVs. As these responses are lowest to DENV-4 we have used the AG129 mouse model to investigate the immunogenicity of monovalent TDV-4 or tetravalent TDV vaccines, and their efficacy against lethal DENV-4 challenge. Since the common backbone of TDV is based on an attenuated DENV-2 strain (TDV-2) we also tested the efficacy of TDV-2 against DENV-4 challenge. Single doses of the tetravalent or monovalent vaccines elicited neutralizing antibodies, anti-NS1 antibodies, and cellular responses to both envelope and nonstructural proteins. All vaccinated animals were protected against challenge at 60 days post-immunization, whereas all control animals died. Investigation of DENV-4 viremias post-challenge showed that only the control animals had high viremias on day 3 post-challenge, whereas vaccinated mice had no detectable viremia. Overall, these data highlight the excellent immunogenicity and efficacy profile of our candidate dengue vaccine in AG129 mice.