Genotype-Specific Measles Transmissibility: A Branching Process Analysis.

Background: Substantial heterogeneity in measles outbreak sizes may be due to genotype-specific transmissibility. Using a branching process analysis, we characterize differences in measles transmission by estimating the association between genotype and the reproduction number R among postelimination California measles cases during 2000-2015 (400 cases, 165 outbreaks). Methods: Assuming a negative binomial secondary case distribution, we fit a branching process model to the distribution of outbreak sizes using maximum likelihood and estimated the reproduction number R for a multigenotype model. Results: Genotype B3 is found to be significantly more transmissible than other genotypes (P = .01) with an R of 0.64 (95% confidence interval [CI], .48-.71), while the R for all other genotypes combined is 0.43 (95% CI, .28-.54). This result is robust to excluding the 2014-2015 outbreak linked to Disneyland theme parks (referred to as "outbreak A" for conciseness and clarity) (P = .04) and modeling genotype as a random effect (P = .004 including outbreak A and P = .02 excluding outbreak A). This result was not accounted for by season of introduction, age of index case, or vaccination of the index case. The R for outbreaks with a school-aged index case is 0.69 (95% CI, .52-.78), while the R for outbreaks with a non-school-aged index case is 0.28 (95% CI, .19-.35), but this cannot account for differences between genotypes. Conclusions: Variability in measles transmissibility may have important implications for measles control; the vaccination threshold required for elimination may not be the same for all genotypes or age groups.

The impact of BMI on non-malignant respiratory symptoms and lung function in arsenic exposed adults of Northern Chile.

BACKGROUND: Elevated body mass index (BMI) and arsenic are both associated with cancer and with non-malignant lung disease. Using a unique exposure situation in Northern Chile with data on lifetime arsenic exposure, we previously identified the first evidence of an interaction between arsenic and BMI for the development of lung cancer. OBJECTIVES: We examined whether there was an interaction between arsenic and BMI for the development of non-malignant lung disease. METHODS: Data on lifetime arsenic exposure, respiratory symptoms, spirometry, BMI, and smoking were collected from 751 participants from cities in Northern Chile with varying levels of arsenic water concentrations. Spirometry values and respiratory symptoms were compared across subjects in different categories of arsenic exposure and BMI. RESULTS: Adults with both a BMI above the 90th percentile (>33.9kg/m2) and arsenic water concentrations ≥11µg/L exhibited high odds ratios (ORs) for cough (OR = 10.7, 95% confidence interval (CI): 3.03, 50.1), shortness of breath (OR = 14.2, 95% CI: 4.79, 52.4), wheeze (OR = 14.4, 95% CI: 4.80, 53.7), and the combined presence of any respiratory symptom (OR = 9.82, 95% CI: 4.22, 24.5). In subjects with lower BMIs, respiratory symptom ORs for arsenic water concentrations ≥11µg/L were markedly lower. In never-smokers, reductions in forced vital capacity associated with arsenic increased as BMI increased. Analysis of the FEV1/FVC ratio in never-smokers significantly increased as BMI and arsenic concentrations increased. Similar trends were not observed for FEV1 alone or in ever-smokers. CONCLUSIONS: This study provides preliminary evidence that BMI may increase the risk for arsenic-related non-malignant respiratory disease.

The role of vaccination coverage, individual behaviors, and the public health response in the control of measles epidemics: an agent-based simulation for California.

BACKGROUND: Measles cases continue to occur among susceptible individuals despite the elimination of endemic measles transmission in the United States. Clustering of disease susceptibility can threaten herd immunity and impact the likelihood of disease outbreaks in a highly vaccinated population. Previous studies have examined the role of contact tracing to control infectious diseases among clustered populations, but have not explicitly modeled the public health response using an agent-based model. METHODS: We developed an agent-based simulation model of measles transmission using the Framework for Reconstructing Epidemiological Dynamics (FRED) and the Synthetic Population Database maintained by RTI International. The simulation of measles transmission was based on interactions among individuals in different places: households, schools, daycares, workplaces, and neighborhoods. The model simulated different levels of immunity clustering, vaccination coverage, and contact investigations with delays caused by individuals' behaviors and/or the delay in a health department's response. We examined the effects of these characteristics on the probability of uncontrolled measles outbreaks and the outbreak size in 365 days after the introduction of one index case into a synthetic population. RESULTS: We found that large measles outbreaks can be prevented with contact investigations and moderate contact rates by having (1) a very high vaccination coverage (≥ 95%) with a moderate to low level of immunity clustering (≤ 0.5) for individuals aged less than or equal to 18 years, or (2) a moderate vaccination coverage (85% or 90%) with no immunity clustering for individuals (≤ 18 years of age), a short intervention delay, and a high probability that a contact can be traced. Without contact investigations, measles outbreaks may be prevented by the highest vaccination coverage with no immunity clustering for individuals (≤ 18 years of age) with moderate contact rates; but for the highest contact rates, even the highest coverage with no immunity clustering for individuals (≤ 18 years of age) cannot completely prevent measles outbreaks. CONCLUSIONS: The simulation results demonstrated the importance of vaccination coverage, clustering of immunity, and contact investigations in preventing uncontrolled measles outbreaks.

Identifying postelimination trends for the introduction and transmissibility of measles in the United States.

The continued elimination of measles requires accurate assessment of its epidemiology and a critical evaluation of how its incidence is changing with time. National surveillance of measles in the United States between 2001 and 2011 provides data on the number of measles introductions and the size of the resulting transmission chains. These data allow inference of the effective reproduction number, Reff, and the probability of an outbreak occurring. Our estimate of 0.52 (95% confidence interval: 0.44, 0.60) for Reff is smaller than prior results. Our findings are relatively insensitive to the possibility that as few as 75% of cases were detected. Although we confirm that measles remains eliminated, we identify an increasing trend in the number of measles cases with time. We show that this trend is likely attributable to an increase in the number of disease introductions rather than a change in the transmissibility of measles. However, we find that transmissibility may increase substantially if vaccine coverage drops by as little as 1%. Our general approach of characterizing the case burden of measles is applicable to the epidemiologic assessment of other weakly transmitting or vaccine-controlled pathogens that are either at risk of emerging or on the brink of elimination.

A randomized clinical trial comparing methotrexate and mycophenolate mofetil for noninfectious uveitis.

OBJECTIVE: To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis. DESIGN: Multicenter, block-randomized, observer-masked clinical trial. PARTICIPANTS: Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. INTERVENTION: Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. MAIN OUTCOME MEASURES: Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. RESULTS: Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31). CONCLUSIONS: There was no statistically significant difference in corticosteroid-sparing control of inflammation between patients receiving methotrexate or mycophenolate mofetil. However, there was a 22% difference in treatment success favoring methotrexate.

The epidemiology and surveillance response to pandemic influenza A (H1N1) among local health departments in the San Francisco Bay Area.

BACKGROUND: Public health surveillance and epidemiologic investigations are critical public health functions for identifying threats to the health of a community. Very little is known about how these functions are conducted at the local level. The purpose of the Epidemiology Networks in Action (EpiNet) Study was to describe the epidemiology and surveillance response to the 2009 pandemic influenza A (H1N1) by city and county health departments in the San Francisco Bay Area in California. The study also documented lessons learned from the response in order to strengthen future public health preparedness and response planning efforts in the region. METHODS: In order to characterize the epidemiology and surveillance response, we conducted key informant interviews with public health professionals from twelve local health departments in the San Francisco Bay Area. In order to contextualize aspects of organizational response and performance, we recruited two types of key informants: public health professionals who were involved with the epidemiology and surveillance response for each jurisdiction, as well as the health officer or his/her designee responsible for H1N1 response activities. Information about the organization, data sources for situation awareness, decision-making, and issues related to surge capacity, continuity of operations, and sustainability were collected during the key informant interviews. Content and interpretive analyses were conducted using ATLAS.ti software. RESULTS: The study found that disease investigations were important in the first months of the pandemic, often requiring additional staff support and sometimes forcing other public health activities to be put on hold. We also found that while the Incident Command System (ICS) was used by all participating agencies to manage the response, the manner in which it was implemented and utilized varied. Each local health department (LHD) in the study collected epidemiologic data from a variety of sources, but only case reports (including hospitalized and fatal cases) and laboratory testing data were used by all organizations. While almost every LHD attempted to collect school absenteeism data, many respondents reported problems in collecting and analyzing these data. Laboratory capacity to test influenza specimens often aided an LHD's ability to conduct disease investigations and implement control measures, but the ability to test specimens varied across the region and even well-equipped laboratories exceeded their capacity. As a whole, the health jurisdictions in the region communicated regularly about key decision-making (continued on next page) (continued from previous page) related to the response, and prior regional collaboration on pandemic influenza planning helped to prepare the region for the novel H1N1 influenza pandemic. The study did find, however, that many respondents (including the majority of epidemiologists interviewed) desired an increase in regional communication about epidemiology and surveillance issues. CONCLUSION: The study collected information about the epidemiology and surveillance response among LHDs in the San Francisco Bay Area that has implications for public health preparedness and emergency response training, public health best practices, regional public health collaboration, and a perceived need for information sharing.

Factors Influencing Parent and Guardian Decisions on Vaccinating Their Children Against SARS-CoV-2: A Qualitative Study.

This qualitative analysis sought to explore factors that influenced parent/guardian intentions to vaccinate their children against SARS-CoV-2 in San Francisco, California, USA in order to inform San Francisco Department of Public Health's (SFDPH) youth vaccine rollout program. 30-minute, semi-structured telephone interviews were conducted with parents and guardians in either Spanish or English. Respondents shared their perspectives on vaccinating their children against SARS-CoV-2. Interviews were conducted over the telephone and recorded on Zoom. Participants (n = 40) were parents/guardians responding on behalf of their adolescent children (age 13+) and parents/guardians identified from the SFDPH COVID-19 testing database who tested for SARS-CoV-2 within the last 2 weeks. Interviews were conducted, audio recorded, transcribed, translated into English as appropriate, and rapidly analyzed in REDCap according to matrix analysis methodology to develop parent study themes. Perspectives on child vaccination were then explored through thematic analysis. Three themes were identified from the thematic analysis: (1) parental desires for children to return to school safely, (2) unclear messaging and information on COVID-19 prevention and vaccination, and (3) consideration of child's desires or opinions on receiving the vaccine. This study highlights specific factors influencing parent/guardian decisions on whether to vaccinate their children against SARS-CoV-2. The analysis also illustrates a potential role for children to play in influencing household vaccine decision-making.

San Francisco's Citywide COVID-19 Response: Strategies to Reduce COVID-19 Severity and Health Disparities, March 2020 Through May 2022.

San Francisco implemented one of the most intensive, comprehensive, multipronged COVID-19 pandemic responses in the United States using 4 core strategies: (1) aggressive mitigation measures to protect populations at risk for severe disease, (2) prioritization of resources in neighborhoods highly affected by COVID-19, (3) timely and adaptive data-driven policy making, and (4) leveraging of partnerships and public trust. We collected data to describe programmatic and population-level outcomes. The excess all-cause mortality rate in 2020 in San Francisco was half that seen in 2019 in California as a whole (8% vs 16%). In almost all age and race and ethnicity groups, excess mortality from COVID-19 was lower in San Francisco than in California overall, with markedly diminished excess mortality among people aged >65 years. The COVID-19 response in San Francisco highlights crucial lessons, particularly the importance of community responsiveness, joint planning, and collective action, to inform future pandemic response and advance health equity.

Outdoor Activities Associated with Lower Odds of SARS-CoV-2 Acquisition: A Case-Control Study.

Access to recreational physical activities, particularly in outdoor spaces, has been a crucial outlet for physical and mental health during the COVID-19 pandemic. There is a need to understand how conducting these activities modulates the risk of SARS-CoV-2 infection. In this case-control study of unvaccinated individuals conducted in San Francisco, California, the odds of testing positive to SARS-CoV-2 were lower for those who conducted physical activity in outdoor locations (adjusted odds ratio [aOR]: 0.16, 95% confidence interval [CI]: 0.05, 0.40) in the two weeks prior to testing than for those who conducted no activity or indoor physical activity only. Individuals who visited outdoor parks, beaches, or playgrounds also had lower odds of testing positive to SARS-CoV-2 (aOR: 0.28, 95% CI: 0.11, 0.68) as compared with those who did not visit outdoor parks, beaches, or playgrounds. These findings, albeit in an unvaccinated population, offer observational data to support pre-existing ecological studies that suggest that activity in outdoor spaces lowers COVID-19 risk.

Evaluating the Impact of Language Concordance on Coronavirus Disease 2019 Contact Tracing Outcomes Among Spanish-Speaking Adults in San Francisco Between June and November 2020.

We evaluated the impact of language concordance-clinician or public health worker fluency in a patient's primary language-on coronavirus disease 2019 (COVID-19) contact tracing outcomes among 2668 Spanish-speaking adults in San Francisco. Language concordance was associated with 20% greater odds of COVID-19 testing and 53% greater odds of support service referrals.

COVID-19 Susceptibility and Outcomes Among People Living With HIV in San Francisco.

INTRODUCTION: Studies to examine whether HIV predisposes to a higher incidence of COVID-19 or more severe disease are accumulating. Initial studies from New York City suggested more severe disease among people living with HIV (PLWH), but this was during a time when hospitals were over-capacity and health systems stretched. This report presents the incidence and outcomes among PLWH with COVID-19 in San Francisco over the first 6 months of the pandemic. METHODS: Community transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first reported in San Francisco on March 5, 2020. This report examines the match of the San Francisco Department of Public Health COVID-19 testing database and the San Francisco Department of Public Health HIV Surveillance case registry from March 24, 2020, to September 3, 2020. RESULTS: Among 4252 COVID-19 tests performed among PLWH, 4.5% (N = 193) were positive for COVID-19, compared with a 3.5% (N = 9626) positivity rate among the 272,555 people without HIV tested for COVID-19 (P < 0.001). The mean age of those infected with HIV/COVID-19 was 48 years (20-76), 38.9% White, 38.3% Latinx, 11.9% Black, and 91.2% were men. Only 54.6% of coinfected PLWH were housed, with the remainder marginally housed. The rate of severe illness with COVID-19 was not increased among PLWH. DISCUSSION: In San Francisco, susceptibility to COVID-19 was increased among PLWH over the first 6 months of the pandemic, although clinical outcomes were similar to those without HIV. Homelessness and higher rates of congregate living situations among PLWH likely accounted for this disparity. Special efforts to house patients with marginal housing during the COVID-19 pandemic are needed.

Informatics response to address the COVID-19 pandemic in a safety net healthcare system.

In service of particularly vulnerable populations, safety net healthcare systems must nimbly leverage health information technology (IT), including electronic health records (EHRs), to coordinate the medical and public health response to the novel coronavirus (COVID-19). Six months after the San Francisco Department of Public Health implemented a new EHR across its hospitals and citywide clinics, California declared a state of emergency in response to COVID-19. This paper describes how the IT and informatics teams supported San Francisco Department of Public Health's goals of expanding the safety net healthcare system capacity, meeting the needs of specific vulnerable populations, increasing equity in COVID-19 testing access, and expanding public health analytics and research capacity. Key enabling factors included critical partnerships with operational leaders, early identification of priorities, a clear governance structure, agility in the face of rapidly changing circumstances, and a commitment to vulnerable populations.

The SARS-CoV-2 pandemic: the race to trace: contact tracing scale-up in San Francisco-early lessons learned.

In order to effectively control spread of coronavirus 2019 (COVID-19), it is essential that jurisdictions have the capacity to rapidly trace close contacts of each and every case. Best practice guidance on how to implement such programs is urgently needed. We describe the early experience in the City and County of San Francisco (CCSF), where the City's Department of Health expanded contact tracing capability in anticipation of changes in San Francisco's 'shelter in place' order between April and June 2020. Important prerequisites to successful scale-up included a rapid expansion of the COVID-19 response workforce, expansion of testing capability, and other containment resources. San Francisco's scale-up offers a model for how other jurisdictions can rapidly mobilize a workforce. We underscore the importance of an efficient digital case management system, effective training, and expansion of supportive service programs for those in quarantine or isolation, and metrics to ensure continuous performance improvement.

Measles transmission during a large outbreak in California.

A large measles outbreak in 2014-2015, linked to Disneyland theme parks, attracted international attention, and led to changes in California vaccine policy. We use dates of symptom onset and known epidemic links for California cases in this outbreak to estimate time-varying transmission in the outbreak, and to estimate generation membership of cases probabilistically. We find that transmission declined significantly during the course of the outbreak (p = 0.012), despite also finding that estimates of transmission rate by day or by generation can overestimate temporal decline. We additionally find that the outbreak size and duration alone are sufficient in this case to distinguish temporal decline from time-invariant transmission (p = 0.014). As use of a single large outbreak can lead to underestimates of immunity, however, we urge caution in interpretation of quantities estimated from this outbreak alone. Further research is needed to distinguish causes of temporal decline in transmission rates.

Relapse of Juvenile Idiopathic Arthritis-Associated Uveitis after Discontinuation of Immunomodulatory Therapy.

Purpose: To assess treatment outcomes in juvenile idiopathic arthritis (JIA)-associated uveitis and relapse rates upon discontinuation of immunomodulatory therapy (IMT). Methods: Medical records of patients with JIA-associated uveitis seen at the University of Illinois at Chicago and the F.I. Proctor Foundation uveitis clinics from September 14, 1988 to January 5, 2011 were reviewed. The main outcome was time to relapse after attempting to discontinue IMT.Results: Of 66 patients with JIA-associated uveitis, 51 (77%) received IMT as either sole or combination therapy. Of a total of 51, 41 (80%) patients achieved corticosteroid-sparing control. Attempts were made to discontinue treatment in 19/51 (37%) patients. Of a total of 19 patients, 13 (68%) attempting to discontinue IMT relapsed, with a median time to relapse of 288 days from the time of attempted taper/discontinuation (IQR: 108-338).Conclusions: Corticosteroid-sparing control of inflammation was achieved in the majority of patients; however, attempts to stop IMT were often unsuccessful. Close follow-up of patients after discontinuation of therapy is warranted.

Effectiveness of the polysaccharide pneumococcal vaccine among HIV-infected persons in Brazil: a case control study.

BACKGROUND: Polysaccharide pneumococcal vaccine is recommended for use in HIV-infected adults in Brazil but there is uncertainty about its effectiveness in this patient population. The main objective of this study was to assess the effectiveness of the 23-valent polysaccharide pneumococcal vaccine against invasive pneumococcal infection among HIV-infected adult patients in São Paulo, Brazil. METHODS: A case-control study of 79 cases and 242 controls matched on CD4+ cell count and health care setting was conducted. Among HIV-infected adults in São Paulo, Brazil, with and without S. pneumoniae recovered from a normally sterile site; prior receipt of 23 valent polysaccharide pneumococcal vaccine was determined by review of medical records and patient interview. RESULTS: After adjustment for confounding factors, the point estimate for the effectiveness of 23 valent polysaccharide vaccine among HIV-infected adults against all invasive pneumococcal infection was 18% (95% CI: <0 to 62%). CONCLUSION: We were unable to demonstrate a statistically significant protective effect of 23 valent polysaccharide against invasive pneumococcal infection vaccine among HIV-infected adults in Brazil.While the vaccine is relatively inexpensive and safe, its effectiveness among HIV-infected adults in Brazil is uncertain.

Early prediction of median survival among a large AIDS surveillance cohort.

BACKGROUND: For individuals with AIDS, data exist relatively soon after diagnosis to allow estimation of "early" survival quantiles (e.g., the 0.10, 0.15, 0.20 and 0.30 quantiles, etc.). Many years of additional observation must elapse before median survival, a summary measure of survival, can be estimated accurately. In this study, a new approach to predict AIDS median survival is presented and its accuracy tested using AIDS surveillance data. METHODS: The data consisted of 96,373 individuals who were reported to the HIV/AIDS Reporting System of the California Department of Health Services Office of AIDS as of December 31, 1996. We defined cohorts based on quarter year of diagnosis (e.g., the "931" cohort consists of individuals diagnosed with AIDS in the first quarter of 1993). We used early quantiles (estimated using the Inverse Probability of Censoring Weighted estimator) of the survival distribution to estimate median survival by assuming a linear relationship between the earlier quantiles and median survival. From this model, median survival was predicted for cohorts for which a median could not be estimated empirically from the available data. This prediction was compared with the actual medians observed when using updated survival data reported at least five years later. RESULTS: Using the 0.15 quantile as the predictor and the data available as of December 31, 1996, we were able to predict the median survival of four cohorts (933, 934, 941, and 942) to be 34, 34, 31, and 29 months. Without this approach, there were insufficient data with which to make any estimate of median survival. The actual median survival of these four cohorts (using data as of December 31, 2001) was found to be 32, 40, 46, and 80 months, suggesting that the accuracy for this approach requires a minimum of three years to elapse from diagnosis to the time an accurate prediction can be made. CONCLUSION: The results of this study suggest that early and accurate prediction of median survival time after AIDS diagnosis may be possible using early quantiles of the survival distribution. The methodology did not seem to work well during a period of significant change in survival as observed with highly active antiretroviral treatment, but results suggest that it may work well in a time of more gradual improvement in survival.

Clinical Presentation and Outcomes among Children with Sepsis Presenting to a Public Tertiary Hospital in Tanzania.

BACKGROUND: Pediatric sepsis causes significant global morbidity and mortality and low- and middle-income countries (LMICs) bear the bulk of the burden. International sepsis guidelines may not be relevant in LMICs, especially in sub-Saharan Africa (SSA), due to resource constraints and population differences. There is a critical lack of pediatric sepsis data from SSA, without which accurate risk stratification tools and context-appropriate, evidence-based protocols cannot be developed. The study's objectives were to characterize pediatric sepsis presentations, interventions, and outcomes in a public Emergency Medicine Department (EMD) in Tanzania. METHODS: Prospective descriptive study of children (28 days to 14 years) with sepsis [suspected infection with ≥2 clinical systemic inflammatory response syndrome (SIRS) criteria] presenting to a tertiary EMD in Dar es Salaam, Tanzania (July 1 to September 30, 2016). Outcomes included: in-hospital mortality (primary), EMD mortality, and hospital length of stay. We report descriptive statistics using means and SDs, medians and interquartile ranges, and counts and percentages as appropriate. Predictive abilities of SIRS criteria, the Alert-Verbal-Painful-Unresponsive (AVPU) score and the Lambaréné Organ Dysfunction Score (LODS) for in-hospital, early and late mortality were tested. RESULTS: Of the 2,232 children screened, 433 (19.4%) met inclusion criteria, and 405 were enrolled. There were 247 (61%) subjects referred from an outside facility. Approximately half (54.1%) received antibiotics in the EMD, and some form of microbiologic culture was collected in 35.8% (n = 145) of subjects. In-hospital and EMD mortality were 14.2 and 1.5%, respectively, median time to death was 3 days (IQR 1-6), and median length of stay was 6 days (IQR 1-12). SIRS criteria, the AVPU score, and the LODS had low positive (17-27.1, 33.3-43.9, 18.3-55.6%, respectively) and high negative predictive values (88.6-89.8, 86.5-91.2, 86.8-90.5%, respectively) for in-hospital mortality. CONCLUSION: This pediatric sepsis cohort had high and early in-hospital mortality. Current criteria and tested clinical scores were inadequate for risk-stratification and mortality prediction in this population and setting. Pediatric sepsis management must take into account the local patient population, etiologies of sepsis, healthcare system, and resource availability. Only through studies such as this that generate regional data in LMICs can accurate risk stratification tools and context-appropriate, evidence-based guidelines be developed.

External Validation of the Liverpool Uveal Melanoma Prognosticator Online.

PURPOSE: To validate the Liverpool Uveal Melanoma Prognosticator Online (LUMPO) in a cohort of patients treated at the University of California-San Francisco (UCSF). METHODS: A retrospective chart review was performed of 390 patients treated between 2002 and 2007 for choroidal melanoma at UCSF. Similar patients (n = 1175) treated at the Liverpool Ocular Oncology Centre (LOOC) were included in the study. The data were analyzed using the model previously developed for LUMPO, an online prognostication tool combining multiple prognostic factors. Main outcome measures included all-cause mortality and melanoma-specific mortality. Reliability of the survival estimates in each group of patients was indicated by the C-indices of discrimination and Hosmer-Lemeshow test. RESULTS: Patients treated at UCSF tended to be younger with thicker tumors, and were more likely to receive proton beam radiotherapy as primary treatment compared to patients at LOOC. There were no significance differences with respect to ciliary body involvement, melanoma cytomorphology, and mitotic counts between the two groups. Death occurred in 140/390 (35%) patients from UCSF and 409/1175 (34%) patients from LOOC, with no difference in overall mortality by Kaplan-Meier analysis (log rank test, P = 0.503). For all-cause mortality and melanoma-specific mortality, the C-index of discrimination and Hosmer-Lemeshow test at 5 years after treatment indicated good discrimination performance of the model, with no statistically significant difference between observed and predicted survival. CONCLUSIONS: Despite differences between the two cohorts, external validation in patients treated at UCSF indicates that LUMPO estimated the all-cause and melanoma-specific mortality well.