OBJECTIVE: The 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria score (≥20 points) has been associated with poor outcomes. We aimed to evaluate its utility as a predictor for mortality and hospitalisation and to derive and validate an ominosity score based on the SLE classification criteria set. METHODS: Incident patients with SLE in a population-based cohort were included. The association between the 2019 EULAR/ACR SLE score and mortality and hospitalisation was assessed using Cox regression adjusted for age, sex and calendar year. An ominosity score for mortality was developed based on the SLE criteria set. The least absolute shrinkage and selection operator method was used to estimate model coefficients. Concordance and calibration were assessed by cross-validation and by plotting the observed event rates against the deciles of predicted probabilities. RESULTS: Among 374 patients with incident SLE, a EULAR/ACR score ≥20 points was not associated with an increased risk of mortality (HR 1.17, 95% CI 0.67 to 2.03) or first hospitalisation (HR 1.14, 95% CI 0.79 to 1.64) compared with a score ≤19 points. The derived ominosity score for mortality included age, sex, thrombocytopaenia, neuropsychiatric manifestations, subacute cutaneous or discoid lupus, non-scarring alopecia, inflammatory arthritis, renal involvement, antiphospholipid antibodies and hypocomplementaemia. This model demonstrated a concordance=0.76 with adequate calibration. Age and sex were the main predictors, as seen in the model including just age, sex and year (concordance=0.77). CONCLUSION: The 2019 EULAR/ACR SLE criteria score was not associated with mortality and hospitalisation. The derived ominosity score for mortality presented good prediction for mortality but was not better than age and sex alone.

OBJECTIVE: To characterize presentation and care pathways of patients with systemic lupus erythematosus (SLE), and delays in access to SLE-specialized care. METHODS: We included patients with incident SLE from the Lupus Midwest Network registry. Time from the first medical encounter for SLE clinical manifestation to access to SLE-specialized care, physician diagnosis, and treatment was estimated. Delays were defined as ≥6 months to access specialized care. We compared SLE manifestations, disease activity (SLEDAI-2k), and SLICC/ACR damage indexes (SDI) between patients with and without delays. Logistic regression models assessed associations with delays. RESULTS: The study included 373 patients with SLE. The median time to access SLE-specialized care was 1.1 months (95% confidence interval [CI] 0.9-1.5); time to diagnosis 30.6 months (95% CI 18.9-48.1), and time to treatment initiation 4.7 months (95% CI 3.9-8.4). Approximately 25% (93/373) of patients experienced delays accessing specialized care, which were associated with fewer SLE manifestations at first SLE-related encounter (<2 SLE domains; 92% vs 72%, P < 0.001). Patients with mucocutaneous or musculoskeletal manifestations were less likely to experience delays, while hematologic (odds ratio [OR] 1.71, 95% CI 1.03-2.84) or antiphospholipid antibodies domains (OR 6.05, 95% CI 2.46-14.88) were associated with delays. Delays were associated with damage at first access to SLE-specialized care (SDI ≥1; 30% vs 7%, P < 0.001). CONCLUSIONS: Patients follow a heterogeneous pathway to receive care. One-fourth of patients experienced delays accessing SLE-specialized care, which was associated with damage. Fewer manifestations, hematologic, or antiphospholipid antibodies were associated with delays.

Aedes mosquito-borne viruses (ABVs) place a substantial strain on public health resources in the Americas. Vector control of Aedes mosquitoes is an important public health strategy to decrease or prevent spread of ABVs. The ongoing Targeted Indoor Residual Spraying (TIRS) trial is an NIH-sponsored clinical trial to study the efficacy of a novel, proactive vector control technique to prevent dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) infections in the endemic city of Merida, Yucatan, Mexico. The primary outcome of the trial is laboratory-confirmed ABV infections in neighborhood clusters. Despite the difficulties caused by the COVID-19 pandemic, by early 2021 the TIRS trial completed enrollment of 4,792 children aged 2-15 years in 50 neighborhood clusters which were allocated to control or intervention arms via a covariate-constrained randomization algorithm. Here, we describe the makeup and ABV seroprevalence of participants and mosquito population characteristics in both arms before TIRS administration. Baseline surveys showed similar distribution of age, sex, and socio-economic factors between the arms. Serum samples from 1,399 children were tested by commercially available ELISAs for presence of anti-ABV antibodies. We found that 45.1% of children were seropositive for one or more flaviviruses and 24.0% were seropositive for CHIKV. Of the flavivirus-positive participants, most were positive for ZIKV-neutralizing antibodies by focus reduction neutralization testing which indicated a higher proportion of participants with previous ZIKV than DENV infections within the cohort. Both study arms had statistically similar seroprevalence for all viruses tested, similar socio-demographic compositions, similar levels of Ae. aegypti infestation, and similar observed mosquito susceptibility to insecticides. These findings describe a population with a high rate of previous exposure to ZIKV and lower titers of neutralizing antibodies against DENV serotypes, suggesting susceptibility to future outbreaks of flaviviruses is possible, but proactive vector control may mitigate these risks.

OBJECTIVES: To assess the prevalence and incidence of multimorbidity and the association with the SLICC/ACR damage index (SDI) among patients with systemic lupus erythematosus (SLE). METHODS: Using prevalent and incident population-based cohorts of patients with SLE and their matched comparators, we assessed 57 chronic conditions. Chronic conditions were categorized as SDI-related or SDI-unrelated. Multimorbidity was defined as the presence of 2+ chronic conditions. Multimorbidity at prevalence and incidence/index was compared between cohorts using logistic regression. Cox models were used to examine development of multimorbidity after SLE incidence. RESULTS: The prevalent cohort included 449 patients with established SLE on January 1, 2015. They were three times more likely to have multimorbidity compared with non-SLE comparators (OR 2.98, 95% CI 2.18-4.11). The incident cohort included 270 patients with new-onset SLE. At SLE incidence, patients with SLE were more likely to have multimorbidity than comparators (OR 2.27, 95% CI 1.59-3.27). After incidence, the risk of developing multimorbidity was 2-fold higher among patients with SLE than comparators (hazard ratio (HR) 2.11, 95% CI 1.59-2.80). Development of multimorbidity was higher in patients with SLE based on SDI-related (HR 2.91, 95% CI 2.17-3.88) and SDI-unrelated conditions (HR 1.73, 95% CI, 1.32-2.26). CONCLUSION: Patients with SLE have a higher burden of multimorbidity, even before the onset of the disease. The risk disparity continues after SLE classification and is also seen in a prevalent SLE cohort. Multimorbidity is driven both by SDI-related and unrelated conditions.

One in six nursing home residents and staff with positive SARS-CoV-2 tests 90 days after initial infection had specimen cycle thresholds (Ct) <30. Individuals with specimen Ct<30 were more likely to report symptoms but were not different from individuals with high Ct value specimens by other clinical and testing data.

The genotypes referred to in this article were stated incorrectly. The genotype number 49 should have been stated as 48 and the number 27 should have been stated as 26. These errors occurred in the 'Abstract' section on page 1, in the ‘Discussion’ section on page 11, and within Fig. 5 on page 12. | | The sentence in the 'Abstract' should have read: | | ‘Using previously described 2× standard deviation (sd) criteria to group sequences into separate clusters, we expanded the number of genogroups to 10 (GI-GX) and the number of genotypes to 48 (9 GI, 26 GII, 3 GIII, 2 GIV, 2 GV, 2 GVI and 1 genotype each for GVII, GVIII, GIX [formerly GII.15] and GX).’ | | The sentence in the 'Discussion' section on page 11 should have read: | | ‘Viruses in these ten genogroups can be further divided into 48 confirmed capsid genotypes based on amino acids of the complete VP1 and 60 confirmed P-types based on partial nucleotide sequences of RdRp regions.’ | | Fig. 5 on page 12 erroneously stated ‘27+2T’. This should have been stated as ‘26+2T’.

OBJECTIVE: There is little information about the epidemiology and factors associated with opioid therapy in systemic lupus erythematosus (SLE). We aimed to assess the prevalence of opioid therapy and explore factors associated with long-term opioid therapy (LTOT) in patients with SLE. METHODS: Patients with SLE were matched with non-SLE controls in a population-based cohort on January 1, 2015. We captured demographics, manifestations of lupus, comorbidities (fibromyalgia, mood disorders, osteoarthritis, chronic low back pain [CLBP], chronic kidney disease, avascular necrosis, osteoporosis, fragility fractures, and cancer), and the area deprivation index (ADI). Opioid prescription data were used to assess prevalence of LTOT, defined as contiguous prescriptions (gaps of <30 days between prescriptions) and receiving opioid therapy ≥90 days or ≥10 prescriptions before index date. RESULTS: 465 SLE patients and 465 non-SLE controls were included; 13% of SLE patients and 3% of non-SLE controls were receiving opioid therapy (P<0.001), and 11% of SLE patients were on LTOT versus 1% of non-SLE controls. Among SLE patients, acute pericarditis (OR: 3.92; 95% CI: 1.78-8.66), fibromyalgia (OR: 7.78; 95% CI: 3.89-15.55), fragility fractures (OR: 3.72; 95% CI: 1.25-11.07), CLBP (OR: 4.00; 95% CI: 2.13-7.51), and mood disorders (OR: 2.76; 95% CI: 1.47-5.16) were associated with LTOT. We did not find an association between opioid therapy and ADI. CONCLUSION: Patients with SLE have higher LTOT than controls. Among patients with SLE, LTOT was associated with pericarditis and several comorbidities. However, LTOT was not associated with kidney disease despite the limited pain control options in these patients.

OBJECTIVE: The aim of this study was to determine inpatient health care utilization in an incident cohort of patients with systemic lupus erythematosus (SLE) compared with the general population. METHODS: This was a population-based cohort study in the upper Midwest, United States. We included patients fulfilling the European League Against Rheumatism/American College of Rheumatology SLE classification criteria between 1995 and 2018. They were 1:1 age-, sex-, county-matched with individuals without SLE. All hospital admissions and emergency department (ED) visits were electronically retrieved for 1995-2020. Rates for hospital admission, length of stay, readmission, ED visits, and discharge destination were compared between groups. RESULTS: Three hundred forty-one patients with SLE and 341 comparators without SLE were included (mean age, 48.6 years at diagnosis; 79.2% female). Rates of hospitalization for patients with SLE and comparators were 29.8 and 9.9 per 100 person-years, respectively. These differences were present across sexes and age groups. Hospitalization rates were higher in patients with SLE after diagnosis and remained higher than comparators for the first 15 years of the disease. Patients with SLE were more likely than comparators to visit the ED (hazard ratio, 2.71; 95% confidence interval, 2.05-3.59). Readmission rates (32% vs. 21%, p = 0.017) were higher in patients with SLE. Length of stay and discharge destination were similar between both groups. CONCLUSION: Patients with SLE were more likely to be hospitalized and to visit the ED than individuals without SLE, highlighting important inpatient care needs. Increased hospitalization rates were observed in both male and female patients and all age groups.

BACKGROUND: Systemic lupus erythematosus (SLE) is a disease that can lead to damage of multiple organs and, along with certain treatments, increase the risk of developing cancer, cardiovascular disease, diabetes, osteoporosis, and infections. Preventive services are particularly important in patients with SLE to mitigate the aforementioned risks. We aimed to evaluate the trends of preventive services utilization in patients with systemic lupus erythematosus, compared with non-SLE population. METHODS: All ≥19-year-old patients in the Lupus Midwest Network (LUMEN) registry, a population-based cohort, with SLE on January 1, 2015, were included and matched (1:1) by sex, age, race, and county to non-SLE comparators. Among both groups, we compared the rates of screenings for breast and cervical cancer, hypertension, hyperlipidemia, diabetes mellitus, and osteoporosis as well as immunizations. RESULTS: We included 440 SLE patients and 430 non-SLE comparators. The probability of breast cancer screening among women with SLE was similar to comparators (hazard ratio [HR] 1.09, 95% CI 0.85-1.39), while cervical cancer screening was lower (HR 0.75, 95% CI 0.58-0.96). Hypertension screening was higher among patients with SLE (HR 1.35, 95% CI 1.13-1.62); however, hyperlipidemia screening was similar to comparators (HR 1.16, 95% CI 0.96-1.41). Diabetes and osteoporosis screenings were more likely to be performed for SLE patients than for comparators (HR 2.46, 95% CI 2.11-2.87; and HR 3.19, 95% CI 2.31-4.41; respectively). Influenza and pneumococcal immunizations were higher among SLE patients (HR 1.31, 95% CI 1.12-1.54; and HR 2.06, 95% CI 1.38-3.09; respectively), while zoster vaccination was similar (HR 1.17, 95% CI 0.81-1.69). CONCLUSIONS: The trends of utilization of preventive services by SLE patients vary according to screening or vaccine compared with the general population. Considering these differences, we demonstrate an opportunity for improvement, particularly in cervical cancer, hyperlipidemia, and osteoporosis screenings and vaccinations.

The disruptions of the coronavirus disease 2019 (COVID-19) pandemic impacted the delivery and utilization of healthcare services with potential long-term implications for population health and the hospital workforce. Using electronic health record data from over 700 USacute care hospitals, we documented changes in admissions to hospital service areas (inpatient, observation, emergency room [ER], and same-day surgery) during 2019-2020 and examined whether surges of COVID-19 hospitalizations corresponded with increased inpatient disease severity and death rate. We found that in 2020, hospitalizations declined by 50% in April, with greatest declines occurring in same-day surgery (-73%). The youngest patients (0-17) experienced largest declines in ER, observation, and same-day surgery admissions; inpatient admissions declined the most among the oldest patients (65+). Infectious disease admissions increased by 52%. The monthly measures of inpatient case mix index, length of stay, and non-COVID death rate were higher in all months in 2020 compared with respective months in 2019.

OBJECTIVE: Systemic lupus erythematosus (SLE) patients are at higher risk of poor outcomes from coronavirus disease 2019 (COVID-19). The vaccination rate among such patients is unknown. We aimed to assess COVID-19 vaccine uptake among SLE patients. METHODS: We included 342 SLE patients from the Lupus Midwest Network and 350 age, sex, race, and county matched comparators. Vaccination uptake for influenza, pneumococcal, and zoster vaccines before pandemic restrictions began (up to February 29, 2020) was assessed. First-dose COVID-19 vaccine uptake was electronically retrieved and manually ascertained (December 15, 2020, to July 31, 2021). Time to COVID-19 vaccination, demographics, lupus manifestations, medications, comorbidity index, area deprivation index, and rurality measures were compared. RESULTS: On July 31, 2021, 83.3% of SLE patients and 85.5% of comparators were vaccinated against COVID-19. The COVID-19 vaccination rates were similar among SLE and comparators (hazard ratio: 0.93; 95% CI: 0.79-1.10). Non-vaccinated SLE patients were more likely to be men (27.3% versus 14.1% vaccinated), younger (mean 54.1 versus 58.8 years in vaccinated), have a shorter SLE duration (median 7.3 versus 10.7 years in vaccinated), and be less frequently vaccinated with influenza and pneumococcal vaccine. CONCLUSION: SLE patients in the Lupus Midwest Network had similar COVID-19 vaccination uptake as matched comparators, most of whom were vaccinated early when the vaccine became available. One in six remain unvaccinated.

Noroviruses are genetically diverse RNA viruses associated with acute gastroenteritis in mammalian hosts. Phylogenetically, they can be segregated into different genogroups as well as P (polymerase)-groups and further into genotypes and P-types based on amino acid diversity of the complete VP1 gene and nucleotide diversity of the RNA-dependent RNA polymerase (RdRp) region of ORF1, respectively. In recent years, several new noroviruses have been reported that warrant an update of the existing classification scheme. Using previously described 2x standard deviation (sd) criteria to group sequences into separate clusters, we expanded the number of genogroups to 10 (GI-GX) and the number of genotypes to 49 (9 GI, 27 GII, 3 GIII, 2 GIV, 2 GV, 2 GVI and 1 genotype each for GVII, GVIII, GIX [formerly GII.15] and GX). Viruses for which currently only one sequence is available in public databases were classified into tentative new genogroups (GNA1 and GNA2) and genotypes (GII.NA1, GII.NA2 and GIV.NA1) with their definitive assignment awaiting additional related sequences. Based on nucleotide diversity in the RdRp region, noroviruses can be divided into 60 P-types (14 GI, 37 GII, 2 GIII, 1 GIV, 2 GV, 2 GVI, 1 GVII and 1 GX), 2 tentative P-groups and 14 tentative P-types. Future classification and nomenclature updates will be based on complete genome sequences and will be coordinated and disseminated by the international norovirus classification-working group.

STUDY QUESTION: Are in-utero or peripubertal exposures to phthalates, parabens and other phenols found in personal care products associated with timing of pubertal onset in boys and girls? SUMMARY ANSWER: We found some associations of altered pubertal timing in girls, but little evidence in boys. WHAT IS KNOWN ALREADY: Certain chemicals in personal care and consumer products, including low molecular weight phthalates, parabens and phenols, or their precursors, are associated with altered pubertal timing in animal studies. STUDY DESIGN, SIZE, DURATION: Data were from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal cohort study which followed 338 children in the Salinas Valley, California, from before birth to adolescence. PARTICIPANTS/MATERIALS, SETTING, METHODS: Pregnant women were enrolled in 1999-2000. Mothers were mostly Latina, living below the federal poverty threshold and without a high school diploma. We measured concentrations of three phthalate metabolites (monoethyl phthalate [MEP], mono-n-butyl phthalate and mono-isobutyl phthalate), methyl and propyl paraben and four other phenols (triclosan, benzophenone-3 and 2,4- and 2,5-dichlorophenol) in urine collected from mothers during pregnancy and from children at age 9. Pubertal timing was assessed among 179 girls and 159 boys every 9 months between ages 9 and 13 using clinical Tanner staging. Accelerated failure time models were used to obtain mean shifts of pubertal timing associated with concentrations of prenatal and peripubertal biomarkers. MAIN RESULTS AND THE ROLE OF CHANCE: In girls, we observed earlier onset of pubic hair development with prenatal urinary MEP concentrations and earlier menarche with prenatal triclosan and 2,4-dichlorophenol concentrations. Regarding peripubertal biomarkers, we observed: earlier breast development, pubic hair development and menarche with methyl paraben; earlier menarche with propyl paraben; and later pubic hair development with 2,5-dichlorophenol. In boys, we observed no associations with prenatal urinary biomarker concentrations and only one association with peripubertal concentrations: earlier genital development with propyl paraben. LIMITATIONS, REASONS FOR CAUTION: These chemicals are quickly metabolized and one to two urinary measurements per developmental point may not accurately reflect usual exposure. Associations of peripubertal measurements with parabens may reflect reverse causality: children going through puberty early may be more likely to use personal care products. The study population was limited to Latino children of low socioeconomic status living in a farmworker community and may not be widely generalizable. WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to a growing literature that suggests that exposure to certain endocrine disrupting chemicals may impact timing of puberty in children. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Institute of Environmental Health Sciences and the US Environmental Protection Agency. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Background: The yeasts species determination is fundamental not only for an accurate diagnosis but also for establishing a suitable patient treatment. We performed a concordance study of five methodologies for the species identification of oral isolates of Candida in Colombia. Methods: Sixty-seven Candida isolates were tested by; API(R) 20C-AUX, Vitek(R)2 Compact, Vitek(R)MS, Microflex(R) and a molecular test (panfungal PCR and sequencing). The commercial cost and processing time of the samples was done by graphical analysis. Results: Panfungal PCR differentiated 12 species of Candida, Vitek(R)MS and Microflex(R) methods identified 9 species, and API(R) 20C-AUX and Vitek(R)2 Compact methods identified 8 species each. Weighted Kappa (wK) showed a high agreement between Panfungal PCR, Vitek(R)MS, Microflex(R) and API(R) 20C-AUX (wK 0.62-0.93). The wK that involved the Vitek(R)2 Compact method presented moderate or good concordances compared with the other methods (wK 0.56-0.73). Methodologies based on MALDI TOF MS required 4 minutes to generate results and the Microflex(R) method had the lowest selling price. Conclusion: The methods evaluated showed high concordance in their results, being higher for the molecular methods and the methodologies based on MALDI TOF. The latter are faster and cheaper, presenting as promising alternatives for the routine identification of yeast species of the genus Candida.

BACKGROUND: Animal studies suggest that phthalates and bisphenol A (BPA), endocrine-disrupting chemicals found in many consumer products, may impact the timing of puberty. OBJECTIVES: We aimed to determine the association of prenatal exposure to high-molecular-weight phthalates and BPA with pubertal timing in boys and girls participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal cohort study. METHODS: We quantified urinary concentrations of eight phthalate metabolites and BPA at two time points during pregnancy among participating mothers ([Formula: see text]) and conducted clinical Tanner staging of puberty on their children every 9 months between 9 and 13 y of age. We conducted accelerated failure time models and examined the role of child overweight/obese status in this association. RESULTS: The sum of urinary metabolites of di(2-ethylhexyl) phthalate [Formula: see text], monobenzyl phthalate (MBzP), and BPA were associated with later onset of at least one of the three outcomes assessed in girls (thelarche, pubarche, or menarche) and with earlier onset of at least one of the two outcomes assessed in boys (gondarche and pubarche). We found that monocarboxynonyl phthalate, monocarboxyoctyl phthalate, mono(3-carboxypropyl) phthalate, and BPA were associated with later pubarche and menarche mostly among normal-weight girls but not overweight/obese girls. MBzP was associated with later thelarche in all girls, and [Formula: see text] was associated with later thelarche and menarche in all girls. BPA and all phthalate biomarkers were associated with earlier gonadarche and pubarche in all boys as well as in overweight/obese boys when stratified by weight. Among normal-weight boys, associations with BPA were also inverse, whereas associations with phthalate metabolites were close to the null or positive. CONCLUSIONS: Several high-molecular-weight phthalates and BPA were associated with later puberty in girls and earlier puberty in boys included in the CHAMACOS cohort study. Childhood overweight/obesity may modify these associations. https://doi.org/10.1289/EHP3424.

Background: Candida auris is a multidrug-resistant yeast associated with hospital outbreaks worldwide. During 2015-2016, multiple outbreaks were reported in Colombia. We aimed to understand the extent of contamination in healthcare settings and to characterize the molecular epidemiology of C. auris in Colombia. Methods: We sampled patients, patient contacts, healthcare workers, and the environment in four hospitals with recent C. auris outbreaks. Using standardized protocols, people were swabbed at different body sites. Patient and procedure rooms were sectioned into four zones and surfaces were swabbed. We performed whole-genome sequencing (WGS) and antifungal susceptibility testing (AFST) on all isolates. Results: Seven (41%) of the 17 people swabbed were found to be colonized. C. auris was isolated from 37/322 (12%) environmental samples. These were collected from a variety of items in all four zones. WGS and AFST revealed that although isolates were similar throughout the country, isolates from the northern region were genetically distinct and more resistant to amphotericin B (AmB) than the isolates from central Colombia. Four novel non-synonymous mutations were found to be significantly associated with AmB resistance. Conclusions: Our results show that extensive C. auris contamination can occur and highlight the importance of adherence to appropriate infection control practices and disinfection strategies. Observed genetic diversity supports healthcare transmission and a recent expansion of C. auris within Colombia with divergent AmB susceptibility.

In 2004 the Brazilian National Cancer Institute (INCA) established breast cancer screening guidelines for women in Brazil: annual clinical breast exam for women age 40-49 and biennial mammogram for women age 50-69. Healthcare provider's adherence to these guidelines is currently unknown. The objective of this study is to describe the perceptions and practices related to breast cancer screening among physicians, nurses, and health unit coordinators working in the network of primary healthcare units (HCUs) in Brazil. In 2011, 1600 primary HCUs were randomly sampled from all regions in Brazil. At each HCU the coordinator and one health professional were asked to participate in a telephone survey to gathered information on their knowledge, attitudes, and practices related to breast cancer screening. Participation rates for coordinators, physicians, and nurses were 78%, 34%, and 65% respectively. Health unit coordinators identified numerous barriers that prevent patients from receiving appropriate screening, many (44%) were unaware of INCA cancer screening guidelines. Despite a high perceived impact of INCA guidelines, a majority of physicians and nurses did not follow them. Most physicians and nurses recommended mammograms on an annual basis (~75%) and 50.9% of nurses and 25.1% of physicians initiated routine breast cancer screening in women under age 40. Physicians and nurses in Brazil screen at younger ages and more frequently than recommended by INCA guidelines. Given that primary HCUs are the source of health care for many women, interventions that educate healthcare providers on the appropriate ages and intervals for breast cancer screening may prove useful.

BACKGROUND: Children are considered a potentially vulnerable population for Zika virus infection. However, data on paediatric Zika virus infection are sparse. METHODS: We analysed data from Colombia's national surveillance system during the 2015-2016 Zika virus outbreak on patients meeting the clinical case definition of Zika virus disease (ZVD) among children aged 1 month to 18 years to estimate incidence by demographic characteristics and characterize the occurrence of selected complications. RESULTS: Between August 14, 2015, and May 28, 2016, there were 18 576 reported cases of postnatal ZVD among children aged 1 month to 18 years. Laboratory testing was prioritized for high-risk patients (infants, pregnant women, adults aged ≥65 years, and persons with serious co-morbidities); among 1655 that were tested by real-time reverse transcriptase polymerase chain reaction, 1207 (72.9%) were positive. The cumulative incidence of reported ZVD was 114.4 per 100 000. The incidence differed by sex, depending on age group; the largest difference was observed for 15-18 year olds, with females having a higher incidence than males (cumulative incidence ratio 2.5, 95% confidence interval 2.3, 2.7). At the time of report to the surveillance system, 631 patients (3.4%) were hospitalised and 96 (0.5%) had a report of an accompanying neurological diagnosis, including Guillain-Barre syndrome in 40 patients. CONCLUSIONS: Only a small proportion of reported paediatric ZVD cases in Colombia were hospitalized or had reported neurological conditions following ZVD. However, the potential for some serious outcomes demonstrates the importance of preventing Zika virus infection in children.

OBJECTIVE: To evaluate fetal ultrasound and magnetic resonance imaging findings among a series of pregnant women with confirmed Zika virus infection to evaluate the signs of congenital Zika syndrome with respect to timing of infection. METHODS: We conducted a retrospective case series of pregnant women referred to two perinatal clinics in Barranquilla and Ibague, Colombia, who had findings consistent with congenital Zika syndrome and Zika virus infection confirmed in maternal, fetal, or neonatal samples. Serial ultrasound measurements, fetal magnetic resonance imaging results, laboratory results, and perinatal outcomes were evaluated. RESULTS: We describe 17 cases of confirmed prenatal maternal Zika virus infection with adverse fetal outcomes. Among the 14 symptomatic women, the median gestational age for maternal Zika virus symptoms was 10 weeks (range 7-14 weeks of gestation). The median time between Zika virus symptom onset and microcephaly (head circumference less than 3 standard deviations below the mean) was 18 weeks (range 15-24 weeks). The earliest fetal head circumference measurement consistent with microcephaly diagnosis was at 24 weeks of gestation. The earliest sign of congenital Zika syndrome was talipes equinovarus, which in two patients was noted first at 19 weeks of gestation. Common findings on fetal magnetic resonance imaging were microcephaly, ventriculomegaly, polymicrogyria, and calcifications. CONCLUSION: Our analysis suggests a period of at least 15 weeks between maternal Zika virus infection in pregnancy and development of microcephaly and highlights the importance of serial and detailed neuroimaging.

We report the results of pathologic examinations of 2 fetuses from women in Colombia with Zika virus infection during pregnancy that revealed severe central nervous system defects and potential associated abnormalities of the eye, spleen, and placenta. Amniotic fluid and tissues from multiple fetal organs tested positive for Zika virus.

Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections.

BACKGROUND: Polybrominated diphenyl ether (PBDE) flame retardants are endocrine-disrupting chemicals that exhibit estrogenic and androgenic properties and may affect pubertal timing. METHODS: Study subjects were participants between 1999 and 2013 in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal cohort study of predominantly Mexican origin families in Northern California. We measured serum concentrations of four PBDEs (BDE-47, -99, -100, -153) in blood collected from mothers during pregnancy (N=263) and their children at age 9years (N=522). We determined timing of pubertal onset in 309 boys and 314 girls using clinical Tanner staging every 9months between 9 and 13years of age, and timing of menarche by self-report. We used Poisson regression for relative risk (RR) of earlier puberty and parametric survival analysis for time ratios (TR) of pubertal milestones. RESULTS: Prenatal concentrations of all 4 congeners and PBDEs were associated with later menarche in girls (RRearlier menarche=0.5, 95% confidence interval (CI): 0.3, 0.9 for PBDEs) but earlier pubic hair development in boys (RRearlier pubarche=2.0, 95% CI: 1.3, 3.3 for PBDEs). No associations were seen between prenatal exposure and girls' breast or pubic hair development or boys' genital development. Childhood PBDE exposure was not associated with any measure of pubertal timing, except for an association of BDE-153 with later menarche. CONCLUSIONS: We found that prenatal PBDE exposure was associated with later menarche in girls but earlier pubarche in boys, suggesting opposite pubertal effects in girls and boys.

Oxidative stress has been linked to many obesity-related conditions among children including cardiovascular disease, diabetes mellitus and hypertension. Exposure to environmental chemicals such as phthalates, ubiquitously found in humans, may also generate reactive oxygen species and subsequent oxidative stress. We examined longitudinal changes of 8-isoprostane urinary concentrations, a validated biomarker of oxidative stress, and associations with maternal prenatal urinary concentrations of phthalate metabolites for 258 children at 5, 9 and 14 years of age participating in a birth cohort residing in an agricultural area in California. Phthalates are endocrine disruptors, and in utero exposure has been also linked to altered lipid metabolism, as well as adverse birth and neurodevelopmental outcomes. We found that median creatinine-corrected 8-isoprostane concentrations remained constant across all age groups and did not differ by sex. Total cholesterol, systolic and diastolic blood pressure were positively associated with 8-isoprostane in 14-year-old children. No associations were observed between 8-isoprostane and body mass index (BMI), BMI Z-score or waist circumference at any age. Concentrations of three metabolites of high molecular weight phthalates measured at 13 weeks of gestation (monobenzyl, monocarboxyoctyl and monocarboxynonyl phthalates) were negatively associated with 8-isoprostane concentrations among 9-year olds. However, at 14 years of age, isoprostane concentrations were positively associated with two other metabolites (mono(2-ethylhexyl) and mono(2-ethyl-5-carboxypentyl) phthalates) measured in early pregnancy. Longitudinal data on 8-isoprostane in this pediatric population with a high prevalence of obesity provides new insight on certain potential cardiometabolic risks of prenatal exposure to phthalates.

In Brazil, colorectal cancer (CRC) is the fourth most common cause of cancer-related death among men, and the third most common among women. We aimed to examine CRC screening-related knowledge, attitudes, and practices among physicians and nurses working in Brazil's network of health units, and to describe the capacity of these units for CRC screening. In 2011, 1,600 health units were randomly selected from all 26 states and the Federal District. One coordinator and one health care provider were selected for the interview. Response rates were 78% for coordinators, 34% for physicians, and 65% for nurses. The Brazilian National Cancer Institute (INCA) recommendations for CRC screening were not often used in the health units, but screening outreach and use of CRC exams were more common in units that were using them. Physicians and nurses differed in most characteristics, and in their knowledge, attitudes, and practices of CRC screening. Forty-seven percent of physicians reported not conducting CRC screening compared to 65% of nurses. Fecal occult blood test was most often used by physicians and nurses, but fewer physicians than nurses perceived this exam as very effective in reducing CRC mortality. Physicians' gender, years since graduation, and geographical region of practice in Brazil were associated to CRC screening practice. The findings may reflect the low influence of INCA CRC screening recommendations, physicians receiving their medical education when CRC burden in Brazil was of low concern, and the lack of CRC screening capacity in some regions of Brazil.

OBJECTIVES: To measure knowledge of current recommendations of physical activity and consequences of physical inactivity among healthcare providers throughout Brazil. METHODS: A phone survey of 1600 randomly selected primary healthcare units in Brazil was conducted between January and July 2011. At each unit, a physician, nurse or community healthcare worker (n = 798) responded to a 40-minute survey, eliciting information about demographics, knowledge, and health behaviors pertaining to physical activity. RESULTS: Among nurses and community healthcare workers, > 95% reported needing more information on physical activity guidelines. Among physicians this proportion was 80%. Nearly 40% of the professionals incorrectly believed 90-min of moderate-intensity physical activity per week is the recommended amount for health benefits; nearly 30% believed that 90-min of vigorous-intensity activity per week is needed for the same purpose. More than 75% of all groups reported that type II diabetes, hypertension, depression, and coronary heart disease might result from physical inactivity, but on average only 60% from each group are aware of osteoporosis as a possible consequence of physical inactivity. CONCLUSIONS: Training health professionals in how to convey all relevant information about physical activity to their patients is critical for health promotion within the primary care system in Brazil.

OBJECTIVE: Assessment of prevalence of health promotion programs in primary health care units within Brazil's health system. METHODS: We conducted a cross-sectional descriptive study based on telephone interviews with managers of primary care units. Of a total 42,486 primary health care units listed in the Brazilian Unified Health System directory, 1,600 were randomly selected. Care units from all five Brazilian macroregions were selected proportionally to the number of units in each region. We examined whether any of the following five different types of health promotion programs was available: physical activity; smoking cessation; cessation of alcohol and illicit drug use; healthy eating; and healthy environment. Information was collected on the kinds of activities offered and the status of implementation of the Family Health Strategy at the units. RESULTS: Most units (62.0%) reported having in place three health promotion programs or more and only 3.0% reported having none. Healthy environment (77.0%) and healthy eating (72.0%) programs were the most widely available; smoking and alcohol use cessation were reported in 54.0% and 42.0% of the units. Physical activity programs were offered in less than 40.0% of the units and their availability varied greatly nationwide, from 51.0% in the Southeast to as low as 21.0% in the North. The Family Health Strategy was implemented in most units (61.0%); however, they did not offer more health promotion programs than others did. CONCLUSIONS: Our study showed that most primary care units have in place health promotion programs. Public policies are needed to strengthen primary care services and improve training of health providers to meet the goals of the agenda for health promotion in Brazil.

OBJECTIVES: To explore the association between electronic media exposure (television viewing time, personal computer/video game use, total screen time), and waist circumference and body mass index, and study whether this association is independent of cardiorespiratory fitness, in a representative sample of adolescents from Monteria, Colombia. DESIGN: Cross-sectional study analyzing data from 546 students aged 11-18 years, from fourteen randomly selected schools. Z-scores for WC and BMI were calculated. METHODS: The physical activity module of the Global School Health Survey 2007 was used to determine EME, and the shuttle run test was used to assess CRF. Linear regression models adjusted by age, school location, physical activity level, type of institution (public or private), consumption of sweetened beverages, fast food, and fried food were used. RESULTS: Among boys, independently of cardiorespiratory fitness, high television viewing time (≥2h/day) (beta=+0.22; p<0.02), was positively associated with waist circumference. High total screen time (>3h/day) was positively associated with waist circumference (beta=+0.34; p<0.01), and body mass index (beta=+0.39; p<0.01). Among girls, sedentary behavior was not associated with adiposity, but cardiorespiratory fitness (beta=-0.04; p<0.02) was negatively associated with body mass index. CONCLUSIONS: These findings support the evidence on the negative impact of excessive electronic media exposure and low cardiorespiratory fitness, and highlight the need for interventions and prevention strategies.

The global health burden due to physical inactivity is enormous and growing. There is a need to consider new ways of generating evidence and to identify the role of government in promoting physical activity at the population level. In this paper, we summarize key findings from a large-scale cross-national collaboration to understand physical activity promotion in Brazil. We describe the main aspects of the partnership of Project GUIA (Guide for Useful Interventions for Activity in Brazil and Latin America) that sustained the collaborative effort for eight years and describe how the evidence gathered from the collaboration triggered political action in Brazil to scale up a physical activity intervention at the national level. Project GUIA is a cross-national multidisciplinary research partnership designed to understand and evaluate current efforts for physical activity promotion at the community level in Latin America. This example of scaling up is unprecedented for promoting health in the region and is an example that must be followed and evaluated.

CONTEXT: Systematic reviews of public health interventions are useful for identifying effective strategies for informing policy and practice. The goals of this review were to (1) update a previous systematic review of physical activity interventions in Latin America which found that only school-based physical education had sufficient evidence to recommend widespread adoption; (2) assess the reporting of external validity elements; and (3) develop and apply an evidence typology for classifying interventions. EVIDENCE ACQUISITION: In 2010-2011, community-level, physical activity intervention studies from Latin America were identified, categorized, and screened based on the peer-reviewed literature or Brazilian theses published between 2006 and 2010. Articles meeting inclusion criteria were evaluated using U.S. Community Guide methods. External validity reporting was assessed among a subset of articles reviewed to date. An evidence rating typology was developed and applied to classify interventions along a continuum based on evidence about their effectiveness in the U.S. context, reach, adoption, implementation, institutionalization, and benefits and costs. EVIDENCE SYNTHESIS: Thirteen articles published between 2006 and 2010 met inclusion criteria and were abstracted systematically, yet when combined with evidence from articles from the previous systematic review, no additional interventions could be recommended for practice. Moreover, the reporting of external validity elements was low among a subset of 19 studies published to date (median=21% of elements reported). By applying the expanded evidence rating typology, one intervention was classified as evidence-based, seven as promising, and one as emerging. CONCLUSIONS: Several physical activity interventions have been identified as promising for future research and implementation in Latin America. Enhanced reporting of external validity elements will inform the translation of research into practice.

OBJECTIVE: This study examined associations between time spent traveling in motor vehicles per week (TSTMV) and BMI and abdominal obesity (AO) among Colombian adults residing in urban areas who do not own car. METHOD: Secondary data analysis of the 2005 National Nutrition Survey of Colombia was conducted. TSTMV was assessed using the long International Physical Activity Questionnaire. Body composition was measured in 7900 adults. Polytomous and binary logistic regressions were conducted, stratified by gender and adjusted for confounders, including physical activity (PA). RESULTS: Forty-two percent of participants were either overweight or obese according to their BMI, and 22.4% had AO. Males in the middle (10 to 149min) and highest (>150min) TSTMV tertiles were more likely to be overweight (POR=1.58, 95% CI=1.13-2.21 and POR=1.55, 95% CI=1.12-2.15 respectively, p-trend=0.012), obese (POR=2.39, 95% CI=1.43-3.99 and POR=1.93, 95% CI=1.22-3.08 respectively, p trend=0.019) and to have AO (POR=1.81, 95% CI=1.18-2.78 and POR=1.73, 95% CI=1.18-2.54 respectively, p-trend=0.009). Associations were not significant in females. CONCLUSIONS: TSTMV was positively associated with overweight and AO in adult Colombian males even after adjusting for PA. These findings highlight the potential deleterious health effects of sedentary behaviors such as prolonged traveling time, independently of having met PA recommendations.