Maturational, comorbid, maternal and discharge domain impact on preterm rehospitalizations: a comparison of planned and unplanned rehospitalizations.

OBJECTIVE: To determine the predictive value of (1) maternal, (2) maturational, (3) comorbid and (4) discharge domains associated with preterm infant rehospitalization. STUDY DESIGN: Retrospective, cohort study of preterm infants discharged home from a level IV neonatal intensive care unit. Rates of unplanned and planned 6-month readmissions were assessed. The four domains were modeled incrementally and separately to predict relative and combined contributions to the readmission risk. RESULT: Out of 504 infants, 5% had 30-day readmissions (22 unplanned, three planned). By 6 months, 13% were rehospitalized (52 unplanned, 15 planned). Sixty-seven infants had 96 readmission events with 30% of readmission events elective. The four domains together predicted 78% of total 1-month, all 6-month and unplanned 6-month readmissions. Discharge complexity was as predictive as comorbidity in all models. CONCLUSION: These four-domain models were more predictive than single domains. Many total readmission events were planned, suggesting parsing planned and unplanned rehospitalizations may benefit quality-improvement efforts.

Effects of sodium bicarbonate correction of metabolic acidosis on regional tissue oxygenation in very low birth weight neonates.

OBJECTIVE: To determine the effects of sodium bicarbonate (NaHCO3) correction of metabolic acidosis on cardiopulmonary, laboratory, and cerebral, renal and splanchnic regional oxygen saturation (rSO2) and fractional tissue oxygen extraction (FTOE) in extremely premature neonates during the first postnatal week. STUDY DESIGN: Observational cohort data were collected from 500 to 1250 g neonates who received NaHCO3 'half' corrections (0.3 * Weight (kg) * Base Deficit (mmol l(-1))) for presumed renal losses. RESULT: Twelve subjects with normal blood pressure and heart rate received 17 NaHCO3 corrections. Mean (±s.d.) gestational age was 27±2 week and birth weight was 912±157 g. NaHCO3 corrections provided a mean (±s.d.) 4.5±1.0 ml kg(-1) fluid bolus, shifted mean (±s.d.) base deficit from 7.6±1.8 to 3.4±2.1 mmol l(-1) (P<0.05), and increased median (±s.d.) pH from 7.23±0.06 to 7.31±0.05 (P<0.05). No significant changes in blood pressure, pulse oximetry, PCO2, lactate, sodium, blood urea nitrogen, creatinine or hematocrit were observed. Cerebral, renal and splanchnic rSO2 (74%, 66% and 44%, respectively, at baseline) and FTOE (0.21, 0.29 and 0.52, respectively, at baseline) were unchanged following NaHCO3 correction. CONCLUSION: NaHCO3 infusions decreased base deficits and increased pH though produced no discernible effects or benefits on cardiopulmonary parameters including rSO2 and FTOE. These findings warrant further prospective evaluation in larger populations with more significant metabolic acidosis to determine the utility of tissue oxygenation monitoring in differentiating metabolic acidosis due to oxygen delivery/consumption imbalance versus renal bicarbonate losses.

Quiescent variability of cerebral, renal, and splanchnic regional tissue oxygenation in very low birth weight neonates.

OBJECTIVE: In extremely premature neonates, data concerning the normal baseline variability of near-infrared spectroscopy (NIRS)-derived regional oxygen saturation (rSO2) are lacking. We sought to determine: 1) the quiescent variability of cerebral, renal, and splanchnic rSO2 in clinically stable, undisturbed very low birth weight neonates and 2) the effects of different data averaging epochs on site-specific variability. STUDY DESIGN: In this prospective, observational study, neonates between 500 and 1250 g underwent seven days of continuous, real-time cerebral, renal, and splanchnic NIRS monitoring starting within the first seventy-two postnatal hours. Demographic, cardiopulmonary, bedside care, and rSO2 data were collected. rSO2 variability was analyzed utilizing data from quiescent periods identified using pre-specified stability criteria. Between- and within-monitoring site comparisons of data averaging methods were made utilizing ANOVA. RESULT: Twenty-four subjects (GA 27 ± 0.3 wk, birth weight 988 ± 34 g; mean ± SEM) were monitored. Coefficients of variation (CoVar = SD/mean) were calculated for each monitoring site using varied data averaging epochs. CoVar was lowest for cerebral, intermediate for renal, and highest for splanchnic rSO2 (P < 0.01). For renal and splanchnic sites, shorter epochs (5- and 15-min) resulted in significantly smaller CoVars [P < 0.01 and P < 0.05, respectively]. Splanchnic variability was highly dependent on epoch length, ranging from 16% over 5 min to 23% over 60 min. CONCLUSION: 1) rSO2 variability differs significantly between monitoring sites and 2) shorter data sampling epochs decrease rSO2 variability. These observations may assist clinicians in operationally defining minimally significant departures to enable medical decision making utilizing this monitoring technique.

Monitoring regional tissue oxygen extraction in neonates <1250 g helps identify transfusion thresholds independent of hematocrit.

OBJECTIVE: We sought to characterize the effects of "booster" packed red blood cell transfusions on multisite regional oxygen saturation in very low birth weight neonates during the first postnatal week and to examine the utility of fractional tissue oxygen extraction as an estimate of tissue oxygenation adequacy. STUDY DESIGN: Data were collected in an observational near-infrared spectroscopy (NIRS) pilot survey of 500-1250 g neonates during the first postnatal week. A before-after analysis of "booster" transfusions, defined as empiric 15 mL/kg transfusion following 10 mL/kg cumulative phlebotomy losses, was conducted upon cardiopulmonary, laboratory, and spectroscopy data. RESULT: Ten neonates (gestational age 26 ± 0 wk; birth weight 879 ± 49 g) received 14 transfusions at 3 ± 0 postnatal days. Mean hematocrit increased from 35.2 ± 1.2 to 38.5 ± 1.2 % (P < 0.05) following transfusion; pH, base deficit, lactate, creatinine, and cardiopulmonary parameters were unchanged. Cerebral, renal, and splanchnic tissue oxygenation increased 10, 18, and 16%, with concomitant decreases in calculated oxygen extraction of 27, 30, and 9% (all P < 0.05), consistent with enhanced tissue oxygenation. These findings were not observed in a non-transfused comparison group of nine patients. CONCLUSION: "Booster" transfusions improved indices of regional tissue oxygenation while no departures were observed in conventional cardiovascular assessments. We speculate that NIRS-derived oxygenation parameters can provide an objective, graded, and continuous estimate of oxygen delivery-consumption balance not evident using standard monitoring techniques.

Healing the schism: medicine and public health in Pakistan.

BACKGROUND: The relationship between medicine and public health has a long and complex co-evolution. In developing countries where the health needs are greatest and resources are few, this relationship is of critical importance. DEVELOPMENT OF MEDICINE AND PUBLIC HEALTH AT THE AGA KHAN UNIVERSITY: This paper provides a case study of the development of the relationship between medical and public health at the Aga Khan University (AKU), a leading educational institution in Pakistan, which was founded with a vision of reuniting medicine and public health. Rapid growth and development have led to successful medicine and public health programs, but have fallen short in creating the synergies needed to address the population health problems of the country. THE WAY FORWARD: In a twenty-five year history of strong growth and development, the AKU has recreated the schism that marked US institutional development in the 20th century, despite strategic consideration to address population health in the design of the University. We recommend the creation of public health schools that focus on leadership to renew an emphasis on unifying health concepts and actions following successful examples to bring medicine and public health together.

Mapping ganciclovir resistance in the human herpesvirus-6 U69 protein kinase.

Human herpesvirus-6 (HHV-6) is a growing concern in immunocompromised individuals, such as in the transplant setting. Alone, or in concert with human cytomegalovirus (HCMV), infections with HHV-6 are often severe enough to require antiviral therapy, generally in the form of ganciclovir (GCV). GCV resistance in HCMV is well documented, both clinically and in the laboratory, and has been shown to result from mutations in the UL97 protein kinase and/or UL54 DNA polymerase. GCV resistance in HHV-6 has been documented. However, to date, it has only been investigated to a limited extent. The baculovirus system has previously been shown to be useful in studying GCV resistance with respect to herpesvirus protein kinase mutations. Using the baculovirus system, we created recombinant baculoviruses expressing either a wild-type HHV-6 U69 protein kinase or a mutated form containing homologous mutations to those documented in the UL97 protein kinase of GCV resistant HCMV isolates. The recombinant baculoviruses were used to infect Sf-9 cells and cultured in the presence of GCV to determine the effect of the HHV-6 U69 protein kinase mutations on GCV susceptibility. Mutations in the HHV-6 U69 protein kinase, homologous to those in the HCMV UL97 protein kinase documented to cause GCV resistance, result in GCV resistance in the recombinant baculoviruses.