Publications

BACKGROUND

A better understanding of case management practices is required to improve inpatient pediatric care in resource-limited settings. Here we utilize data from a unique health facility-based surveillance system at six Ugandan hospitals to evaluate the quality of pediatric case management and the factors associated with appropriate care.

METHODS

All children up to the age of 14 years admitted to six district or regional hospitals over 15 months were included in the study. Four case management categories were defined for analysis: suspected malaria, selected illnesses requiring antibiotics, suspected anemia, and diarrhea. The quality of case management for each category was determined by comparing recorded treatments with evidence-based best practices as defined in national guidelines. Associations between variables of interest and the receipt of appropriate case management were estimated using multivariable logistic regression.

RESULTS

A total of 30,351 admissions were screened for inclusion in the analysis. Ninety-two percent of children met criteria for suspected malaria and 81% received appropriate case management. Thirty-two percent of children had selected illnesses requiring antibiotics and 89% received appropriate antibiotics. Thirty percent of children met criteria for suspected anemia and 38% received appropriate case management. Twelve percent of children had diarrhea and 18% received appropriate case management. Multivariable logistic regression revealed large differences in the quality of care between health facilities. There was also a strong association between a positive malaria diagnostic test result and the odds of receiving appropriate case management for comorbid non-malarial illnesses - children with a positive malaria test were more likely to receive appropriate care for anemia and less likely for illnesses requiring antibiotics and diarrhea.

CONCLUSIONS

Appropriate management of suspected anemia and diarrhea occurred infrequently. Pediatric quality improvement initiatives should target deficiencies in care unique to each health facility, and interventions should focus on the simultaneous management of multiple diagnoses.

Interferon-gamma release assays have limited sensitivity for detecting latent tuberculosis infection. In this study, we determine if the addition of immunomodulators to the QuantiFERON-TB Gold In-Tube (QFT-GIT) increased test sensitivity without compromising specificity. We prospectively compared QFT-GIT results with and without incubation with 2 immunomodulators (lipopolysaccharide [LPS] and polyinosine-polycytidylic acid [PolyIC]) in 2 cohorts-113 culture-confirmed tuberculosis (TB) subjects in Hanoi, Vietnam, and 226 documented QFT-GIT-negative, low TB risk health care workers undergoing annual TB screening at a US academic institution. Sensitivity of the tests in TB subjects was 84.1% with the standard QFT-GIT and 85.8% and 74.3% after incubation with LPS and PolyIC, respectively. Specificity in low TB risk health care workers was 100% with the standard QFT-GIT by design and 86.7% with LPS and 63.3% with PolyIC. In conclusion, use of the 2 immunomodulators did not improve sensitivity of the QFT-GIT in TB patients and reduced specificity in low-risk health care workers.

Exposure to Plasmodium falciparum is associated with circulating "atypical" memory B cells (atMBCs), which appear similar to dysfunctional B cells found in HIV-infected individuals. Functional analysis of atMBCs has been limited, with one report suggesting these cells are not dysfunctional but produce protective antibodies. To better understand the function of malaria-associated atMBCs, we performed global transcriptome analysis of these cells, obtained from individuals living in an area of high malaria endemicity in Uganda. Comparison of gene expression data suggested down-modulation of B cell receptor signaling and apoptosis in atMBCs compared to classical MBCs. Additionally, in contrast to previous reports, we found upregulation of Fc receptor-like 5 (FCRL5), but not FCRL4, on atMBCs. Atypical MBCs were poor spontaneous producers of antibody ex vivo, and higher surface expression of FCRL5 defined a distinct subset of atMBCs compromised in its ability to produce antibody upon stimulation. Moreover, higher levels of P. falciparum exposure were associated with increased frequencies of FCRL5+ atMBCs. Together, our findings suggest that FCLR5+ identifies a functionally distinct, and perhaps dysfunctional, subset of MBCs in individuals exposed to P. falciparum.

BACKGROUND

The electrocardiographic T-wave peak to T-wave end interval (Tpe) correlates with dispersion of ventricular repolarization (DVR). Increased DVR increases propensity toward electrical reentry that can cause ventricular tachyarrhythmia. The baseline rate-corrected Tpe (Tpec) has been shown to predict ventricular tachyarrhythmia and death in multiple patient populations but not among cardiomyopathic patients undergoing insertion of an implantable cardioverter-defibrillator (ICD) for primary prevention.

OBJECTIVE

The purpose of this study was to assess the risk stratification ability of the Tpec in patients with systolic cardiomyopathy without prior ventricular tachyarrhythmia (ie, the primary prevention population).

METHODS

We performed prospective follow-up of 305 patients (73% men; left ventricular ejection fraction [LVEF] 23 ± 7%) with LVEF ≤35% and an ICD implanted for primary prevention. Baseline ECGs were analyzed with automated algorithms. Endpoints were ventricular tachycardia (VT)/ventricular fibrillation (VF), death, and a combined endpoint of VT/VF or death, assessed by device follow-up and Social Security Death Index query.

RESULTS

The average Tpec was 107 ± 22 ms. During device clinic follow-up of 31 ± 23 months, 82 patients (27%) had appropriate ICD therapy for VT/VF, and during mortality follow-up of 49 ± 21 months, 91 patients (30%) died. On univariable analysis, Tpec predicted VT/VF, death, and the combined endpoint of VT/VF or death (P < .05 for each endpoint). Multivariable analysis included univariable predictors among demographics, clinical data, laboratory data, medications used, and electrocardiography parameters. After correction, Tpec remained predictive of VT/VF (hazard ratio [HR] per 10-ms increase 1.16, P = .009), all-cause mortality (HR per 10 ms 1.13, P = .05), and the combined endpoint (HR per 10 ms 1.17, P = .001).

CONCLUSION

Tpec independently predicts both VT/VF and overall mortality in patients with systolic dysfunction and ICDs implanted for primary prevention.