A Temperature- and Age-Adjusted Shock Index for Emergency Department Identification of Pediatric Sepsis.

OBJECTIVE: To empirically derive a novel temperature- and age-adjusted mean shock index (TAMSI) for early identification of sepsis and septic shock in children with suspected infection. METHODS: We performed a retrospective cohort study of children aged 1 month to <18 years presenting to a single emergency department with suspected infection over a 10-year period. TAMSI was defined as (pulse rate - 10 × [temperature - 37])/(mean arterial pressure). The primary outcome was sepsis, and the secondary outcome was septic shock. In the two-thirds training set, we determined TAMSI cutoffs for each age group using a minimum sensitivity of 85% and Youden Index. In the one-third validation data set, we calculated test characteristics for the TAMSI cutoffs and compared them with those for the Pediatric Advanced Life Support (PALS) tachycardia or systolic hypotension cutoffs. RESULTS: In the sepsis validation data set, the sensitivity-targeting TAMSI cutoff yielded a sensitivity of 83.5% (95% confidence interval [CI] 81.7% to 85.4%) and specificity of 42.8% (95% CI 42.4% to 43.3%) versus a sensitivity of 77.7% (95% CI 75.7% to 79.8%) and specificity of 60.0% (95% CI 59.5% to 60.4%) for PALS. For septic shock, the sensitivity-targeting TAMSI cutoff achieved a sensitivity of 81.3% (95% CI 75.2% to 87.4%) and a specificity of 83.5% (95% CI 83.2% to 83.8%) versus a sensitivity of 91.0% (95% CI 86.5% to 95.5%) and a specificity of 58.8% (95% CI 58.4% to 59.3%) for PALS. TAMSI yielded an increased positive likelihood ratio and similar negative likelihood ratio versus PALS. CONCLUSIONS: TAMSI achieved a similar negative likelihood ratio and improved positive likelihood ratio compared with PALS vital sign cutoffs for the prediction of septic shock, but it did not improve on PALS for sepsis prediction, among children with suspected infection.

Balanced resuscitation: application to the paediatric trauma population.

PURPOSE OF REVIEW: Trauma is the leading cause of death in children over 5 years old. Early mortality is associated with trauma-induced coagulopathy (TIC), with balanced resuscitation potentially mitigating the effects of TIC. We review TIC, balanced resuscitation and the best evidence for crystalloid fluid versus early blood products, massive transfusion protocol (MTP) and the optimal ratio for blood products. RECENT FINDINGS: Crystalloid fluids have been associated with adverse events in paediatric trauma patients. However, the best way to implement early blood products remains unclear; MTP has only shown improved time to blood products without clear clinical improvement. The indications to start blood products are also currently under investigation with several scoring systems and clinical indications being studied. Current studies on the blood product ratio suggest a 1 : 1 ratio for plasma:pRBC is likely ideal, but prospective studies are needed to further support its use. SUMMARY: Balanced resuscitation strategies of minimal crystalloid use and early administration of blood products are associated with improved morbidity in paediatric trauma patients but unclear mortality benefit. Current evidence suggests that the utilization of MTPs with 1 : 1 plasma:pRBC ratio may improve morbidity, but more research is needed.

Derivation and validation of an improved pediatric shock index for predicting need for early intervention and outcomes in pediatric trauma.

BACKGROUND: Shock index, pediatric age adjusted (SIPA), has been widely applied in pediatric trauma but has limited precision because of the reference ranges used in its derivation. We hypothesized that a pediatric shock index (PSI) equation based on age-based vital signs would outperform SIPA. METHODS: A retrospective cohort of trauma patients aged 1 to 18 years from Trauma Quality Programs - Participant Use File 2010 to 2018 was performed. A random 70% training subset was used to derive Youden index-optimizing shock index (SI) cutoffs by age for blood transfusion within 4 hours. We used linear regression to derive equations representing the PSI cutoff for children 12 years or younger and 13 years or older. For children 13 years or older, the well-established SI of 0.9 remained optimal, consistent with SIPA and other indices. For children 12 years or younger in the 30% validation subset, we compared our age-based PSI to SIPA as predictors of early transfusion, mortality, pediatric intensive care unit admission, and injury severity score of ≥25. For bedside use, a simplified "rapid" pediatric shock index (rPSI) equation was also derived and compared with SIPA. RESULTS: A total of 439,699 patients aged 1 to 12 years met the inclusion criteria with 2,718 (1.3% of those with available outcome data) requiring transfusion within 4 hours of presentation. In the validation set, positive predictive values for early transfusion were higher for PSI (8.3%; 95% confidence interval [CI], 7.5-9.1%) and rPSI (6.3%; 95% CI, 5.7-6.9%) than SIPA (4.3%; 95% CI, 3.9-4.7%). For early transfusion, negative predictive values for both PSI (99.3%; 95% CI, 99.2-99.3%) and rPSI (99.3%; 95% CI, 99.2-99.4%) were similar to SIPA (99.4%; 95% CI, 99.3-99.4%). CONCLUSION: We derived the PSI and rPSI for use in pediatric trauma using empiric, age-based SI cutoffs. The PSI and rPSI achieved higher positive predictive values and similar negative predictive values to SIPA in predicting the need for early blood transfusion and mortality. LEVEL OF EVIDENCE: Prognostic/Epidemiological; level III.

Alternative shock index cutoffs for pediatric patients outperform the Shock Index Pediatric Age-adjusted (SIPA) on strength of association with adverse outcomes in pediatric trauma patients.

BACKGROUND: The shock index is a tool for evaluating critically ill patients that is defined as the ratio of their heart rate divided by systolic blood pressure. The SI is associated with outcomes in adult trauma patients. The Shock Index Pediatric Age-adjusted was developed as a pediatric-specific tool to account for the physiologic differences of children of varying ages. There is growing interest in Shock Index Pediatric Age-adjusted, which is associated with adverse outcomes in pediatric trauma. We hypothesized that alternative shock index cutoffs based on the Advanced Trauma Life Support or the Pediatric Advanced Life Support vital sign reference ranges would outperform Shock Index Pediatric Age-adjusted. METHODS: We analyzed a retrospective cohort of pediatric trauma patients (age 1 to 16 years old) in the American College of Surgeons Trauma Quality Programs Participant Use File from 2010 to 2018. The primary outcome measure was in-hospital mortality. The Shock Index Pediatric Age-adjusted was compared to an Advanced Trauma Life Support-based and a Pediatric Advanced Life Support-based shock index cutoff system. Our findings were subsequently confirmed with a separate, internal validation data set. RESULTS: A total of 598,830 Trauma Quality Programs Participant Use File patients were included, 0.9% (n = 5,471) of whom died. For mortality, the Advanced Trauma Life Support-based system yielded the highest positive predictive value (15.8%; 95% confidence interval 15.0%-16.7%) compared with the Pediatric Advanced Life Support-based system (4.3%; 95% confidence interval 4.1%-4.5%). Both the Advanced Trauma Life Support-based and Pediatric Advanced Life Support-based systems achieved higher positive predictive values compared to Shock Index Pediatric Age-adjusted (2.6%; 95% confidence interval 2.5%-2.7%). The negative predictive values were not clinically different. Our findings were validated using a separate internal trauma database, in which the positive predictive value for mortality of the Advanced Trauma Life Support-based system was significantly higher than Shock Index Pediatric Age-adjusted (18.2% [95% confidence interval: 8.2%-32.7%] vs 2.9% [95% confidence interval: 1.6%-5.0%], P < .05). CONCLUSION: Advanced Trauma Life Support and Pediatric Advanced Life Support-based shock index cutoffs achieved higher positive predictive values and similar negative predictive values compared to Shock Index Pediatric Age-adjusted for adverse outcomes in pediatric trauma.

Higher Crystalloid Volume During Initial Pediatric Trauma Resuscitation is Associated With Mortality.

BACKGROUND: Historically, aggressive fluid resuscitation has been a cornerstone of management of hemorrhagic shock in pediatrics. Adult data suggest this strategy may be harmful. We sought to determine whether aggressive fluid resuscitation within the first hour of presentation to the emergency department in pediatric patients with trauma is associated with worse clinical outcomes. MATERIALS AND METHODS: We performed a retrospective cohort study from 2012 to 2017 at a single pediatric level 1 trauma center. We defined three patient cohorts: ≤ 20 cc/kg (reference), 20-40 (20.01 to 39.99) cc/kg, and ≥40 cc/kg of intravenous fluid (IVF) given in the first in-hospital hour. Covariates included age, injury severity score, shock index (adjusted for age), and mechanism of injury and were adjusted for with multivariable regression. The primary outcome was in-hospital mortality. RESULTS: A total of 1479 consecutive injured children were eligible for inclusion. One hundred ninety-four patients were excluded for missing IVF data, aged ≥16 y, having primary burns, or arriving pulseless. A total of 1285 patients met inclusion criteria (mean age 8.1 ± 5.5 y, male 64.5%). Higher rates of IVF administration were associated with mortality for both the 20-40 cc/kg (adjusted odds ratio (aOR) 2.96; 95% confidence interval (CI) 1.02-8.55; P = 0.045) and ≥40 cc/kg groups (aOR 6.26; 95% CI 1.79-21.83; P = 0.004). The ≥40 cc/kg group was associated with increased pediatric intensive care unit length of stay (aOR 2.20; 95% CI: 1.05-4.61; P = 0.036) and increased need for mechanical ventilation (aOR 3.79; 95% CI 1.62-8.87; P = 0.002). CONCLUSIONS: Greater than one 20 cc/kg IVF bolus in the first emergency department hour was associated with mortality with a dose-response relationship, even after adjusting for injury severity and initial hemodynamics. These results encourage further investigation into initial resuscitation strategies for injured children.

Impact of a clinical program using weekly Short Message Service (SMS) on antiretroviral therapy adherence support in South Africa: a retrospective cohort study.

BACKGROUND: In randomized controlled trials, short message service (SMS) programs have improved adherence to HIV antiretroviral therapy (ART). In response, the World Health Organization recommended use of SMS programs to support ART. However, there is limited data on real-world implementations of SMS programs. METHODS: We conducted a retrospective cohort study of an SMS program to improve ART adherence in a government-run HIV clinic in rural South Africa. We analyzed data from all adult patients who 1) enrolled at the clinic before the observation period (July 2013 through June 2014), 2) had ≥1 ART prescriptions in the observation period, and 3) had data on phone number availability (N = 2255). Our main outcome measure was prescription coverage, defined as the presence of a valid ART prescription for each day observed. We fit generalized linear mixed models adjusted for pre-program prescription coverage, demographics, and ART duration, dosing, and regimen. RESULTS: Exposure to the SMS program was independently associated with greater prescription coverage (AOR = 1.23, 95% CI 1.13-1.34, P < 0.001) compared with non-exposure, although the absolute increase in prescription coverage was small (4.7 days of ART prescription coverage per average patient per year). Among a subset of patients (n = 725) whose pre-program prescription coverage was <100%, the corresponding mean expected absolute increase in prescription coverage was 8.2 days per year. CONCLUSIONS: Our primary finding was that an SMS reminder program implemented in routine clinical care was associated with a small increase in prescription coverage of uncertain clinical significance.

The Acceptability and Perceived Usefulness of a Weekly Clinical SMS Program to Promote HIV Antiretroviral Medication Adherence in KwaZulu-Natal, South Africa.

Short message service (SMS) text messages have been used to remind and encourage patients to take ART in research studies. However, few studies have assessed the feasibility and acceptability of SMS in routine clinical practice. We report patient perspectives on a weekly SMS adherence support program after implementation into clinical care at an HIV clinic in KwaZulu-Natal, South Africa. We conducted structured interviews with a cross-sectional convenience sample of 100 adult patients who were invited to join the program, 88 of whom had received a program SMS. Of these respondents, 81 (92 %) would recommend the program to a friend. Sixty-eight (77 %) felt the program helped them remember clinic appointments, a response associated with male gender [odds ratio (OR) 5.88, 95 % confidence interval (CI) 1.52-23.26, P = 0.011] and HIV disclosure outside the home [OR 3.40, 95 %CI 1.00-11.60, P = 0.050]. This clinical SMS adherence program was found to have high patient-perceived usefulness.

No clinically significant drug-resistance mutations in HIV-1 subtype C-infected women after discontinuation of NRTI-based or PI-based HAART for PMTCT in Botswana.

Risk of developing drug resistance after stopping antiretroviral regimens to prevent mother-to-child HIV-1 transmission is unknown. The Mma Bana Study randomized treatment-naive pregnant women with CD4 ≥200 cells per cubic millimeter to receive either abacavir/zidovudine/lamivudine [triple nucleoside reverse transcriptase inhibitor (NRTI) arm] or lopinavir/ritonavir/zidovudine/lamivudine [protease inhibitor (PI) arm]. Drugs were discontinued after 6 months of breastfeeding. One month after discontinuation, 29 NRTI arm samples and 25 PI arm samples were successfully genotyped. No clinically significant antiretroviral resistance mutations were detected. Eight minor resistance mutations were found among 11 (20%) women (3 from NRTI arm and 8 from PI arm), occurring at similar frequencies to those reported in HIV-1 subtype C treatment-naive cohorts.

Predicting the herd immunity threshold during an outbreak: a recursive approach.

BACKGROUND: The objective was to develop a novel algorithm that can predict, based on field survey data, the minimum vaccination coverage required to reduce the mean number of infections per infectious individual to less than one (the Outbreak Response Immunization Threshold or ORIT) from up to six days in the advance. METHODOLOGY/PRINCIPAL FINDINGS: First, the relationship between the rate of immunization and the ORIT was analyzed to establish a link. This relationship served as the basis for the development of a recursive algorithm that predicts the ORIT using survey data from two consecutive days. The algorithm was tested using data from two actual measles outbreaks. The prediction day difference (PDD) was defined as the number of days between the second day of data input and the day of the prediction. The effects of different PDDs on the prediction error were analyzed, and it was found that a PDD of 5 minimized the error in the prediction. In addition, I developed a model demonstrating the relationship between changes in the vaccination coverage and changes in the individual reproduction number. CONCLUSIONS/SIGNIFICANCE: The predictive algorithm for the ORIT generates a viable prediction of the minimum number of vaccines required to stop an outbreak in real time. With this knowledge, the outbreak control agency may plan to expend the lowest amount of funds required stop an outbreak, allowing the diversion of the funds saved to other areas of medical need.