Long-term operation of a permeable reactive barrier with diffusive exchange.

In this study, we evaluate the long term operation of a bench-scale reactor which simulates a permeable reactive barrier with sulfidic diffusive exchange (SDES PRB) to treat acid mine drainage (AMD), considering that treatment costs are very sensitive to the useful life for passive reactors. Its functioning was evaluated for a much longer period of 591 days compared to previous SDES PRB studies, with two influents simulating moderately and highly acid groundwater contaminated by AMD. First, we fed water amended with 200 mg/L Zn2+ and 3300 mg/L SO42- at pH 4.9; and after, water with 450 mg/L Fe2+, 100 mg/L Zn2+, 10 mg/L Ni2+, 5 mg/L Cu2+ and 3600 mg/L SO42- at pH 2.5. Biologically produced sulfide and alkalinity were enough to remove both metals and acidity (~99%) from the moderately acidic water, while with the highly acidic water, they resulted in significant removal of the metals reaching up to 87% and 79% of total Fe and Zn, respectively. Furthermore, no inhibitory effect was apparent, as the sulfate reduction rates in the two experiments did not vary significantly (averages close to 0.2 mol/m3-d), despite the much higher acidity and metal load in the second case. Hence, the SDES PRB protected the microbial consortium from metal toxicity and acidity in the long-term, and thus is suitable for remediation of AMD contaminated groundwater with high concentrations of metals, extending the operational range of conventional biological PRBs. Furthermore, an economic evaluation shows that SDES costs can be competitive with the costs of conventional chemical precipitation if the enhanced reactivity that SDES technology offers is realized.

Long-Term Compassionate Use of Cefiderocol To Treat Chronic Osteomyelitis Caused by Extensively Drug-Resistant Pseudomonas aeruginosa and Extended-Spectrum-ß-Lactamase-Producing Klebsiella pneumoniae in a Pediatric Patient.

We report a 15 year-old Nigerian adolescent male with chronic osteomyelitis caused by an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain of sequence type 773 (ST773) carrying blaNDM-1 and an extended spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae strain. The patient developed neurological side effects in the form of circumoral paresthesia with polymyxin B and asymptomatic elevation of transaminases with aztreonam (used in combination with ceftazidime-avibactam). Cefiderocol treatment for 14 weeks plus bone implantation resulted in apparent cure and avoided amputation.

Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis.

BACKGROUND: More than 10 years have elapsed since human papillomavirus (HPV) vaccination was implemented. We did a systematic review and meta-analysis of the population-level impact of vaccinating girls and women against human papillomavirus on HPV infections, anogenital wart diagnoses, and cervical intraepithelial neoplasia grade 2+ (CIN2+) to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination. METHODS: In this updated systematic review and meta-analysis, we used the same search strategy as in our previous paper. We searched MEDLINE and Embase for studies published between Feb 1, 2014, and Oct 11, 2018. Studies were eligible if they compared the frequency (prevalence or incidence) of at least one HPV-related endpoint (genital HPV infections, anogenital wart diagnoses, or histologically confirmed CIN2+) between pre-vaccination and post-vaccination periods among the general population and if they used the same population sources and recruitment methods before and after vaccination. Our primary assessment was the relative risk (RR) comparing the frequency (prevalence or incidence) of HPV-related endpoints between the pre-vaccination and post-vaccination periods. We stratified all analyses by sex, age, and years since introduction of HPV vaccination. We used random-effects models to estimate pooled relative risks. FINDINGS: We identified 1702 potentially eligible articles for this systematic review and meta-analysis, and included 65 articles in 14 high-income countries: 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+. After 5-8 years of vaccination, the prevalence of HPV 16 and 18 decreased significantly by 83% (RR 0·17, 95% CI 0·11-0·25) among girls aged 13-19 years, and decreased significantly by 66% (RR 0·34, 95% CI 0·23-0·49) among women aged 20-24 years. The prevalence of HPV 31, 33, and 45 decreased significantly by 54% (RR 0·46, 95% CI 0·33-0·66) among girls aged 13-19 years. Anogenital wart diagnoses decreased significantly by 67% (RR 0·33, 95% CI 0·24-0·46) among girls aged 15-19 years, decreased significantly by 54% (RR 0·46, 95% CI 0.36-0.60) among women aged 20-24 years, and decreased significantly by 31% (RR 0·69, 95% CI 0·53-0·89) among women aged 25-29 years. Among boys aged 15-19 years anogenital wart diagnoses decreased significantly by 48% (RR 0·52, 95% CI 0·37-0·75) and among men aged 20-24 years they decreased significantly by 32% (RR 0·68, 95% CI 0·47-0·98). After 5-9 years of vaccination, CIN2+ decreased significantly by 51% (RR 0·49, 95% CI 0·42-0·58) among screened girls aged 15-19 years and decreased significantly by 31% (RR 0·69, 95% CI 0·57-0·84) among women aged 20-24 years. INTERPRETATION: This updated systematic review and meta-analysis includes data from 60 million individuals and up to 8 years of post-vaccination follow-up. Our results show compelling evidence of the substantial impact of HPV vaccination programmes on HPV infections and CIN2+ among girls and women, and on anogenital warts diagnoses among girls, women, boys, and men. Additionally, programmes with multi-cohort vaccination and high vaccination coverage had a greater direct impact and herd effects. FUNDING: WHO, Canadian Institutes of Health Research, Fonds de recherche du Québec - Santé.

Adherence stages measured by patient-reported outcome instruments in adults with asthma: a scoping review.

Objective: Individuals who are adherent to their asthma inhaled maintenance medication: (1) initiate their treatment (take the first dose); (2) implement it (take it as per prescribed dosing regimen); and persist with it (take it for the entire prescribing period). To avoid unnecessary hospitalizations and costs, patient adherence should be routinely assessed. To this end, we aimed to identify patient-reported outcome instruments (PROs) used for measurement of patient adherence to inhaled maintenance medication in asthmatic adults and to report on the adherence stage that these instruments measured. Data sources: We conducted a scoping review of six databases. Study selection: We searched for studies in which PROs were used to measure patient adherence to inhaled maintenance medication in asthmatic participants aged ≥18 years. We extracted and synthesized data in order to list the available PROs and to report the adherence stages that these instruments measured. Results: We included 186 studies (87 PROs). Among all 87 instruments, none were found to measure all three adherence stages. We found that 1 measured initiation, 2 evaluated initiation and implementation, 74 assessed implementation, 7 measured implementation and persistence. The most used instrument (n = 41 studies or 22%) was the Self-Reported Medication-Taking Scale, which was found to assess implementation only. Conclusion: Our results suggest that no single PRO exists to measure initiation, implementation and persistence with asthma inhaled maintenance medication. Results from this review could therefore guide the development or refinement of PROs that would aim to measure all three adherence stages.

Integrated probabilistic risk assessment in sites contaminated with arsenic and lead by long-term mining liabilities in San Luis Potosi, Mexico.

Mining environmental liabilities (MEL) in San Luis Potosi are the result of more than 450 years of mining activity, which has contaminated the soil mainly with arsenic (As) and lead (Pb) in several areas. Risk assessments are used to estimate the possibility of the occurrence of adverse effects on human health or on ecological receptors; and the most accessible way of performing them is through probabilistic estimates such as the Latin Hypercube Sampling (LHS) model. Therefore, the aim of this study was to carry out an Integrated Probabilistic Environmental Risk Assessment (IPERA) for the estimation of health risks in infants and rodents. The mean concentrations of As and Pb in soil were significantly higher (p<0.05) in all contaminated sites than in their respective reference sites. Villa de la Paz was the site with the highest mean concentration of As (1374 mg/kg), while Charcas was the one with the highest level of Pb (12,929 mg/kg). The Hazard Quotient (HQ) was calculated and Villa de la Paz had the highest values of As in both rodents (11.994) and children (39.32), and Charcas showed the highest values of Pb in both (24.971 and 31.668 for rodents and children respectively). The cumulative hazard Index (HI) reveals there is a very significant health risk due to As and Pb exposure for both rodents and children in contaminated areas of these mining communities.

Use of sawdust as pretreatment of photo-Fenton process in the depuration of landfill leachate.

A research of the depuration of landfill leachate using sawdust as activated carbon material to be applied in adsorption process as pretreatment of solar photo-Fenton and solar photo-Fenton + O3, was carried out. The activated sawdust shows very irregular shapes and pores, and a high capacity to remove ammonium (87.0%), iron (70.2%) and copper (61.1%). As well, it has the capacity to remove humic acid (18.3%), COD (33.7%) and colour (19.5%). Also, a removal of organic matter was obtained in terms of COD (76.4%), colour (74.9%), nitrate (50.0%), ammonium (12.8%) and humic acid (73.3%) due to the joint action of ozone and solar photo-Fenton process. The overall treatment (filtration, adsorption, photo-Fenton and photo-Fenton + ozone) carried out showed a very high removal of pollutants, with a reduction of COD, colour, ammonium and humic acid of 95.1%, 95.0%, 94.5% and 97.9%, respectively. With this enhancement in the landfill leachate (LL) quality, there is a reduction of toxicity, obtaining with the LL 50% diluted, a germination index for Lactuca sativa of 20% GI. This shows that the incorporation of sawdust is a useful pretreatment of photo-Fenton in the treatment of landfill leachate.

Imported Congenital Rubella Syndrome, United States, 2017.

Although transmission of rubella virus within the United States is rare, the risk for imported cases persists. We describe a rubella case in a newborn, conceived in Saudi Arabia, in Texas during 2017, highlighting the importance of active surveillance and early diagnosis of this disease.

Transverse Myelitis and Guillain-Barré Syndrome Associated with Cat-Scratch Disease, Texas, USA, 2011.

We describe a case of coexisting transverse myelitis and Guillain-Barré syndrome related to infection with Bartonella henselae proteobacterium and review similar serology-proven cases. B. henselae infection might be emerging as a cause of myelitis and Guillain-Barré syndrome and should be considered as an etiologic factor in patients with such clinical presentations.

Patient-reported outcome instruments that evaluate adherence behaviours in adults with asthma: a systematic review of measurement properties.

AIM: The aim of the present study was to identify systematically the measurement properties of patient-reported outcome instruments (PROs) that evaluate adherence to inhaled maintenance medication in adults with asthma. METHODS: We conducted a systematic review of six databases. Two reviewers independently included studies on the measurement properties of PROs that evaluated adherence in asthmatic participants aged ≥18 years. Based on the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN), the reviewers: (i) extracted data on internal consistency, reliability, measurement error, content validity, structural validity, hypotheses testing, cross-cultural validity, criterion validity and responsiveness; (ii) assessed the methodological quality of the included studies; (iii) assessed the quality of the measurement properties (positive or negative); and (iv) summarized the level of evidence (limited, moderate or strong). RESULTS: We screened 6068 records and included 15 studies (14 PROs). No studies evaluated measurement error or responsiveness. Based on methodological and measurement property quality assessments, we found limited positive evidence of: (i) internal consistency of the Adherence Questionnaire, Refined Medication Adherence Reason (MAR) scale, Medication Adherence Report Scale for Asthma (MARS-A) and Test of the Adherence to Inhalers (TAI); (ii) reliability of the TAI; and (iii) structural validity of the adherence questionnaire, MAR scale, MARS-A and TAI. We also found limited negative evidence of: (i) hypotheses testing of the Adherence Questionnaire; (ii) reliability of the MARS-A; and (iii) criterion validity of the MARS-A and TAI. CONCLUSIONS: Our results highlighted the need to conduct further high-quality studies to evaluate the reliability, validity and responsiveness of the available PROs.

Appropriateness of Ticagrelor Use at Initiation: A Population-Based Cohort Study.

PURPOSE: Ticagrelor is recommended following an acute coronary syndrome if used appropriately. Its use has not yet been well described in the context of ambulatory clinical practice. The objective of this study was to assess the proportion of ticagrelor new users who initiated this medication appropriately and explore associated factors. METHODS: A retrospective population-based inception cohort study was conducted using Quebec administrative databases. The study population included all Quebec residents aged ≥18 years who had a first ticagrelor prescription claim between 1 January, 2012, and 31 March, 2015, and had been continuously eligible in the Quebec public drug plan during the 365 days preceding the first ticagrelor claim. The initial ticagrelor prescription was considered appropriate if:1) it met the indication for use criterion, 2) the prescribed daily dose was 90 mg twice a day, and 3) there was a concomitant use of acetylsalicylic acid (ASA) 80-81 mg daily. Factors potentially associated with the ticagrelor appropriateness of use were included in a logistic log-binomial regression model. RESULTS: A total of 7,073 patients were included in the study, 6,013 (85.0%) had an appropriate indication, 6,895 (97.5%) were prescribed ticagrelor 90 mg twice a day, and 6,385 (90.3%) had a concomitant prescription of ASA. A total of 5,371 (75.9%) patients were prescribed ticagrelor in accordance with all criteria. Twelve factors were associated with prescription appropriateness. CONCLUSIONS: A large majority of patients initiated ticagrelor appropriately. Further improvement in appropriateness may come at targeting indication for use.

Angiostrongylus cantonensis Meningitis and Myelitis, Texas, USA.

Infection with Angiostrongylus cantonensis roundworms is endemic in Southeast Asia and the Pacific Basin. A. cantonensis meningitis and myelitis occurred in summer 2013 in a child with no history of travel outside of Texas, USA. Angiostrongyliasis is an emerging neurotropic helminthic disease in Texas and warrants increased awareness among healthcare providers.

Recent Thymus Emigrant CD4+ T Cells Predict HIV Disease Progression in Patients With Perinatally Acquired HIV.

BACKGROUND: Robust immune restoration in human immunodeficiency virus (HIV)-positive patients is dependent on thymic function. However, few studies have investigated thymic function and its correlation with disease progression over time in HIV-positive patients. METHODS: In this longitudinal prospective study, we followed 69 HIV-positive patients who were perinatally infected. Peripheral blood mononuclear cells were stained with monoclonal anti-CD4 and anti-CD31 and recent thymic emigrants (CD4+recently emigrated from the thymus (RTE), CD4+CD31+) quantified by flow cytometry. Statistical analysis used Wilcoxon rank sum test, Kruskal-Wallis, Spearman correlation, and Kaplan-Meier estimates; Cox regression models were performed for the longitudinal analysis. RESULTS: Median age of HIV positive patients enrolled was 13 years (interquartile range [IQR], 8.6). CD4+RTE% decreased with age and was higher in females. Median CD4+RTE% was 53.5%, IQR, 22.9. CD4+RTE% was closely related to CD4+% and absolute counts but independent of viral load and CD8+CD38+%. Antiretroviral compliance as well as higher nadir CD4+% were associated with higher CD4+RTE%. Low CD4+RTE% predicted poor progression of VL and CD4+% over time. CONCLUSIONS: CD4+RTE% predicts disease progression and may reflect history of disease in HIV-positive patients and adolescents. They are easy to measure in the clinical setting and may be helpful markers in guiding treatment decisions.

Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients.

This study aimed to investigate the pharmacokinetics (PK), safety, and tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A phase I, multicenter, open-label PK study was conducted in pediatric patients hospitalized with an infection and receiving systemic antibiotic therapy. Patients were enrolled into four age cohorts (cohort 1, ≥12 to <18 years; cohort 2, ≥6 to <12 years; cohort 3, ≥2 to <6 years; cohort 4, ≥3 months to <2 years). Patients received a single 2-h intravenous infusion of ceftazidime-avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [≥40 kg] or 50 to 12.5 mg/kg [<40 kg]; cohorts 3 and 4, 50 to 12.5 mg/kg). Blood samples were collected to describe individual PK characteristics for ceftazidime and avibactam. Population PK modeling was used to describe characteristics of ceftazidime and avibactam PK across all age groups. Safety and tolerability were assessed. Thirty-two patients received study drug. Mean plasma concentration-time curves, geometric mean maximum concentration (Cmax), and area under the concentration-time curve from time zero to infinity (AUC0-∞) were similar across all cohorts for both drugs. Six patients (18.8%) reported an adverse event, all mild or moderate in intensity. No deaths or serious adverse events occurred. The single-dose PK of ceftazidime and avibactam were comparable between each of the 4 age cohorts investigated and were broadly similar to those previously observed in adults. No new safety concerns were identified. (This study has been registered at ClinicalTrials.gov under registration no. NCT01893346.).

Effectiveness and Content Analysis of Interventions to Enhance Oral Antidiabetic Drug Adherence in Adults with Type 2 Diabetes: Systematic Review and Meta-Analysis.

OBJECTIVES: To estimate the pooled effect size of oral antidiabetic drug (OAD) adherence-enhancing interventions and to explore which of the behavior change techniques (BCTs) applied in the intervention groups modified this pooled intervention effect size. METHODS: We searched relevant studies published until September 3, 2013, on MEDLINE, Embase, PsycInfo, the Cochrane Library, CINAHL, Current Contents Connect, and Web of Science. Selected studies were qualitatively synthesized, and those of at least medium quality were included in the meta-analysis. A random-effects model was used to pool effectiveness (Hedges's g) and to examine heterogeneity (Higgins I(2)). We also explored the influence on the pooled effectiveness of unique intervention BCTs (those delivered to the intervention groups but not control groups in a trial) by estimating their modifying effects. RESULTS: Fourteen studies were selected for the qualitative synthesis and 10 were included in the meta-analysis. The pooled effectiveness of the interventions was 0.21 (95% confidence interval -0.05 to 0.47; I(2) = 82%). Eight unique BCTs were analyzed. "Cope with side effects" (P = 0.003) and "general intention formation" (P = 0.006) had a modifying effect on the pooled effectiveness. The pooled effectiveness of the interventions in which "cope with side effects" was applied was moderate (0.64; 95% confidence interval 0.31-0.96; I(2) = 56%). CONCLUSIONS: The overall effectiveness of OAD adherence-enhancing interventions that have been tested is small. Helping patients cope with side effects or formulate desired treatment outcomes could have an impact on the effectiveness of OAD adherence-enhancing interventions. Only those interventions that include helping patients to cope with side effects appear to be particularly effective in improving OAD adherence.

Occurrence of glyphosate in water bodies derived from intensive agriculture in a tropical region of southern Mexico.

Glyphosate is an agrochemical widely used to control weeds. However, glyphosate spreads to water bodies by spray-drift, run-off and leaching, potentially causing detrimental effects on non-target biota. There is no information on the occurrence of this herbicide in water bodies near crop fields in Mexico, although it is the most commonly used pesticide in this country. To fill this gap, we quantified glyphosate in water bodies from twenty-three locations, including natural protected areas and agricultural areas in southern Mexico, during the dry and the rainy seasons. We expected (1) higher concentrations during the dry season due to reduced dilution by precipitation and, (2) absence of glyphosate in the protected areas. In agreement with our expectation, concentration of glyphosate was higher during the dry season (up to 36.7 µg/L). Nonetheless, glyphosate was detected in all samples-including natural protected areas. These results emphasize the need for an evaluation of the impact of glyphosate on native species as well as regulate its use.

Prevalence and risk factors associated with resistance-associated mutations to etravirine in a cohort of perinatally HIV-infected children.

BACKGROUND: Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with reduced cross-resistance to first-generation NNRTIs. Because many perinatally HIV-infected patients have been treated with first-generation NNRTIs, they may have acquired resistance-associated mutations to etravirine (RAMe). METHODS: We determined for the interval 1998-2009 the prevalence and factors associated with the presence of RAMe. RESULTS: Twenty-three of 66 (34.8%) children had RAMe; the most common were 181C (19.6%), 190A (7.5%), 98G (6%), 106I (4.5%), 179D (4.5%), 100I (3%), 181I (1.5%), 138A (1.5%) and 179T (1.5%). Eleven children with RAMe (17%) had a mutation score between 2.5 and 3.5 and 1 (1.5%) a score ≥4, indicating an intermediate and reduced response to etravirine. For each 1% increase in CD4% there is a 7% decrease in the odds of RAMe (OR 0.93; 95% CI 0.88-0.97; P < 0.01). History of nevirapine use (OR 8.95; 95% CI 2.31-34.73; P < 0.01) and Hispanic ethnicity (OR 4.76; 95% CI 1.03-21.87; P = 0.04) are significantly associated with risk of RAMe. CONCLUSIONS: RAMe are present and common among antiretroviral-experienced perinatally HIV-infected children without previous exposure to etravirine. This could limit the efficacy of etravirine-based regimens. In addition, our results underscore the importance of taking previous history of nevirapine into account for combined antiretroviral therapy regimens that contain etravirine.

Use of vinasse and coffee waste as chelating agent of photo-Fenton landfill leachate treatment.

This research studies the use of vinasse (VS) coming from Pisco and caffeic acid (Caa) from solid coffee waste as chelating agents of this process, to carry out a photo-Fenton process using UVc lamps of 254-nm wavelength for 60 min, at the natural pH of the landfill leachate (8.9). Without the chelating agent, there was a removal of UV 254 and COD of 54.2% and 54.7%, respectively, when the photo-Fenton reaction was carried out at pH 3; at pH 6, the removal of UV 254 and COD was 13.1% and 39.2%, respectively, and at pH 8.9, the elimination of UV 254 and COD was 10.8% and 16.1%, respectively. When Caa was used in the landfill leachate (LL) for the photo-catalytic processes carried out at pH 8.9, a removal of 24.1%, 43.0%, and 47.4% of UV 254 was obtained using 5 mg/L, 50 mg/L, and 100 mg/L of Caa. The removal of UV 254 was 27.3%, 30.7%, and 36.3% using 5 mg/L, 50 mg/L, and 100 mg/L of VS, respectively, and the removal of COD was 32.2%, 35.4%, and 39.2% using 5 mg/L, 50 mg/L, and 100 mg/L of VS, respectively. When Caa was used in the LL at pH 8.9, the concentration of total Fe went from 37.5 to 33.2, from 40.2 to 36.8, and from 45.2 to 42.1, using 5 mg/L, 50 mg/L, and 100 mg/L of caffeic acid, respectively. Using VS in the LL at pH 8.9, the concentration of total Fe along the run went from 35.1 to 32.2, from 39.4 to 34.8, and from 42.1 to 40.2, using 5 mg/L, 50 mg/L, and 100 mg/L of VS, respectively. As a result of these processes, it was noted that the use of Caa and VS increases the solubility of Fe at a higher pH.

Pediatric Infectious Diseases Milestones: A Step in the Right Direction to Evaluate Subspecialty Learners.

We share the work of the ACGME Pediatric Infectious Diseases Working Group in creating the Pediatric Infectious Diseases-Specific Milestones and discuss key considerations that lead to the reformation of competencies to better assess learners in Pediatric Infectious Diseases.

Assessment of the levels of persistent organic pollutants and 1-hydroxypyrene in blood and urine samples from Mexican children living in an endemic malaria area in Mexico.

The aim of this study was to evaluate the exposure levels to persistent organic pollutants and 1-hydroxypyrene in children living in an endemic malaria zone in Mexico. The blood levels for 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and lindane ranged from 15.4 to 17,886.5 ng/g lipid, 6,624.3 to 100,119.0 ng/g lipid, and 351.1 to 6,153.8 ng/g lipid, respectively. For total polychlorinated biphenyls the blood levels ranged from 2,584.9 to 14,547.9 ng/g lipid. Regarding urinary 1-hydroxypyrene levels, the mean level was 2.9 ± 3.1 µmol/mol creatinine. In conclusion, the children in our study are exposed to levels higher than normal to mixtures of environmental contaminants.