Digging out the evidence – how strong is the IDSA recommendation against antibiotic prophylaxis in basilar skull fracture and cerebrospinal fluid leakage?

Reply to Kuehl et al.

What’s New in Imaging for Gynecologic Cancer?

Abstract

Magnetic resonance imaging (MRI) is the optimal modality for local staging of gynecological tumors. Advances in functional MRI with diffusion-weighted and dynamic contrast-enhanced sequences provide more detailed information regarding tumor cellularity, vascularity, and viability. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) now has an established role in imaging for gynecological cancers, particularly staging of locally advanced cervical cancers and pre-salvage exenterative therapy in relapsed gynecologic tumors. Novel PET tracers, targeting other aspects of tumor biology, are being evaluated although none are currently in routine clinical use. New PET/MR scanners have the potential to combine the strengths of both modalities in one sitting. This review covers advances in gynecologic imaging concentrating on cervical, endometrial, and ovarian cancers.

Early participant-reported symptoms as predictors of adherence to anastrozole in the International Breast Cancer Intervention Studies II

Abstract

Background

Anastrozole reduces breast cancer risk in women at high risk, but implementing preventive therapy in clinical practice is difficult. Here, we evaluate adherence to anastrozole in the International Breast Cancer Intervention Study (IBIS) II prevention and Ductal Carcinoma in Situ (DCIS) trials, and its association with early symptoms.

Patients and methods

In the prevention trial, 3864 postmenopausal women were randomized to placebo vs. anastrozole. 2980 postmenopausal women with DCIS were randomized to tamoxifen vs. anastrozole. Adherence to trial medication was calculated using the Kaplan-Meier method and all P-values were two-sided.

Results

In the prevention trial, adherence was 65.8% (anastrozole (65.7%) vs. placebo (65.9%); HR = 0.97 (0.87-1.09), p=0.6). Adherence was lower for those reporting arthralgia in the placebo group (p=0.02) or gynecological symptoms in the anastrozole group (P=0.003), compared with those not reporting these symptoms at 6 months. In the DCIS study, adherence was 66.7% (anastrozole (67.5%) vs. tamoxifen (65.8%); HR = 1.06 (0.94-1.20), p=0.4). Hot flashes were associated with greater adherence in the anastrozole arm (p=0.02). In both studies, symptoms were mostly mild or moderately severe, and adherence decreased with increasing severity for most symptoms. Drop-outs were highest in the first 1.5 years of therapy in both trials.

Conclusions

In the IBIS-II prevention and DCIS trials, over two-thirds of women were adherent to therapy, with no differences by treatment groups. Participants who reported specific symptoms in the IBIS-II prevention trial had a small but significant effect on adherence, which strengthened as severity increased. Strategies to promote adherence should target the first year of preventive therapy.

Impact of Neoadjuvant Chemoradiotherapy on Health Related Quality of Life In Long-Term Survivors of Esophageal or Junctional Cancer: Results from the Randomized Cross Trial

Abstract

Background

Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard of care for patients with esophageal or junctional cancer, but the long-term impact of nCRT on health-related quality of life (HRQOL) is unknown. The purpose of this study is to compare very long-term HRQOL in long-term survivors of esophageal cancer who received nCRT plus surgery or surgery alone.

Patients and methods

Patients were randomly assigned to receive nCRT (carboplatin/paclitaxel with 41.4Gy radiotherapy) plus surgery or surgery alone. HRQOL was measured using EORTC-QLQ-C30, EORTC-QLQ-OES24 and K-BILD questionnaires after a minimum follow-up of 6 years. To allow for examination over time, EORTC-QLQ-C30 and QLQ-OES24 questionnaire scores were compared to pre-treatment and 12-months-postoperative questionnaire scores. Physical functioning (QLQ-C30), eating problems (QLQ-OES24) and respiratory problems (K-BILD) were predefined primary endpoints. Predefined secondary endpoints were global quality of life and fatigue (both QLQ-C30).

Results

After a median follow-up of 105 months, 123/368 included patients (33%) were still alive (70 nCRT plus surgery, 53 surgery alone). No statistically significant or clinically relevant differential effects in HRQOL-endpoints were found between both groups. Compared to one-year postoperative levels, eating problems, physical functioning, global quality of life and fatigue remained at the same level in both groups. Compared to pre-treatment levels, eating problems had improved (Cohen's d -0.37, p = 0.011) during long-term follow-up, whereas physical functioning and fatigue were not restored to pre-treatment levels in both groups (Cohen's d -0.56 and 0.51, resp., both p < 0.001).

Conclusion(s)

Although physical functioning and fatigue remain reduced after long-term follow-up, no adverse impact of nCRT is apparent on long-term HRQOL compared to patients who were treated with surgery alone. In addition to the earlier reported improvement in survival and the absence of impact on short-term HRQOL, these results support the view that nCRT according to CROSS can be considered as a standard of care.

CLINICAL TRIALS NUMBER

Trial registration number: Netherlands Trial Register NTR487

Infant Group B Streptococcal Disease Incidence and Serotypes Worldwide: Systematic Review and Meta-analyses

Abstract

Background

Group B Streptococcus (GBS) remains a leading cause of neonatal sepsis in high-income contexts, despite declines due to intrapartum antibiotic prophylaxis (IAP). Recent evidence suggests higher incidence in Africa, where IAP is rare. We investigated the global incidence of infant invasive GBS disease and the associated serotypes, updating previous estimates.

Methods

We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data regarding invasive GBS disease in infants aged 0–89 days. We conducted random-effects meta-analyses of incidence, case fatality risk (CFR), and serotype prevalence.

Results

We identified 135 studies with data on incidence (n = 90), CFR (n = 64), or serotype (n = 45). The pooled incidence of invasive GBS disease in infants was 0.49 per 1000 live births (95% confidence interval [CI], .43–.56), and was highest in Africa (1.12) and lowest in Asia (0.30). Early-onset disease incidence was 0.41 (95% CI, .36–.47); late-onset disease incidence was 0.26 (95% CI, .21–.30). CFR was 8.4% (95% CI, 6.6%–10.2%). Serotype III (61.5%) dominated, with 97% of cases caused by serotypes Ia, Ib, II, III, and V.

Conclusions

The incidence of infant GBS disease remains high in some regions, particularly Africa. We likely underestimated incidence in some contexts, due to limitations in case ascertainment and specimen collection and processing. Burden in Asia requires further investigation.

Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children: Why, What, and How to Undertake Estimates?

Abstract

Improving maternal, newborn, and child health is central to Sustainable Development Goal targets for 2030, requiring acceleration especially to prevent 5.6 million deaths around the time of birth. Infections contribute to this burden, but etiological data are limited. Group B Streptococcus (GBS) is an important perinatal pathogen, although previously focus has been primarily on liveborn children, especially early-onset disease. In this first of an 11-article supplement, we discuss the following: (1) Why estimate the worldwide burden of GBS disease? (2) What outcomes of GBS in pregnancy should be included? (3) What data and epidemiological parameters are required? (4) What methods and models can be used to transparently estimate this burden of GBS? (5) What are the challenges with available data? and (6) How can estimates address data gaps to better inform GBS interventions including maternal immunization? We review all available GBS data worldwide, including maternal GBS colonization, risk of neonatal disease (with/without intrapartum antibiotic prophylaxis), maternal GBS disease, neonatal/infant GBS disease, and subsequent impairment, plus GBS-associated stillbirth, preterm birth, and neonatal encephalopathy. We summarize our methods for searches, meta-analyses, and modeling including a compartmental model. Our approach is consistent with the World Health Organization (WHO) Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER), published in The Lancet and the Public Library of Science (PLoS). We aim to address priority epidemiological gaps highlighted by WHO to inform potential maternal vaccination.

Maternal Disease With Group B Streptococcus and Serotype Distribution Worldwide: Systematic Review and Meta-analyses

Abstract

Background

Infections such as group B Streptococcus (GBS) are an important cause of maternal sepsis, yet limited data on epidemiology exist. This article, the third of 11, estimates the incidence of maternal GBS disease worldwide.

Methods

We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data on invasive GBS disease in women pregnant or within 42 days postpartum. We undertook meta-analyses to derive pooled estimates of the incidence of maternal GBS disease. We examined maternal and perinatal outcomes and GBS serotypes.

Results

Fifteen studies and 1 unpublished dataset were identified, all from United Nations–defined developed regions. From a single study with pregnancies as the denominator, the incidence of maternal GBS disease was 0.38 (95% confidence interval [CI], .28–.48) per 1000 pregnancies. From 3 studies reporting cases by the number of maternities (pregnancies resulting in live/still birth), the incidence was 0.23 (95% CI, .09–.37). Five studies reported serotypes, with Ia being the most common (31%). Most maternal GBS disease was detected at or after delivery.

Conclusions

Incidence data on maternal GBS disease in developing regions are lacking. In developed regions the incidence is low, as are the sequelae for the mother, but the risk to the fetus and newborn is substantial. The timing of GBS disease suggests that a maternal vaccine given in the late second or early third trimester of pregnancy would prevent most maternal cases.

Neurodevelopmental Impairment in Children After Group B Streptococcal Disease Worldwide: Systematic Review and Meta-analyses

Group B Streptococcus (GBS) is a leading cause of invasive disease in infants, causing mortality and neurodevelopmental impairment (NDI) in survivors. This article estimates the percentage of survivors of infant GBS disease with NDI.

Background

Survivors of infant group B streptococcal (GBS) disease are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified. This is the 10th of 11 articles estimating the burden of GBS disease. Here we aimed to estimate NDI in survivors of infant GBS disease.

Methods

We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data on the risk of NDI after invasive GBS disease in infants <90 days of age. We did meta-analyses to derive pooled estimates of the percentage of infants with NDI following GBS meningitis.

Results

We identified 6127 studies, of which 18 met eligibility criteria, all from middle- or high-income contexts. All 18 studies followed up survivors of GBS meningitis; only 5 of these studies also followed up survivors of GBS sepsis and were too few to pool in a meta-analysis. Of meningitis survivors, 32% (95% CI, 25%–38%) had NDI at 18 months of follow-up, including 18% (95% CI, 13%–22%) with moderate to severe NDI.

Conclusions

GBS meningitis is an important risk factor for moderate to severe NDI, affecting around 1 in 5 survivors. However, data are limited, and we were unable to estimate NDI after GBS sepsis. Comparability of studies is difficult due to methodological differences including variability in timing of clinical reviews and assessment tools. Follow-up of clinical cases and standardization of methods are essential to fully quantify the total burden of NDI associated with GBS disease, and inform program priorities.

Stillbirth With Group B Streptococcus Disease Worldwide: Systematic Review and Meta-analyses

Abstract

Background

There are an estimated 2.6 million stillbirths each year, many of which are due to infections, especially in low- and middle-income contexts. This paper, the eighth in a series on the burden of group B streptococcal (GBS) disease, aims to estimate the percentage of stillbirths associated with GBS disease.

Methods

We conducted systematic literature reviews (PubMed/Medline, Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde, World Health Organization Library Information System, and Scopus) and sought unpublished data from investigator groups. Studies were included if they reported original data on stillbirths (predominantly ≥28 weeks' gestation or ≥1000 g, with GBS isolated from a sterile site) as a percentage of total stillbirths. We did meta-analyses to derive pooled estimates of the percentage of GBS-associated stillbirths, regionally and worldwide for recent datasets.

Results

We included 14 studies from any period, 5 with recent data (after 2000). There were no data from Asia. We estimated that 1% (95% confidence interval [CI], 0–2%) of all stillbirths in developed countries and 4% (95% CI, 2%–6%) in Africa were associated with GBS.

Conclusions

GBS is likely an important cause of stillbirth, especially in Africa. However, data are limited in terms of geographic spread, with no data from Asia, and cases worldwide are probably underestimated due to incomplete case ascertainment. More data, using standardized, systematic methods, are critical, particularly from low- and middle-income contexts where the highest burden of stillbirths occurs. These data are essential to inform interventions, such as maternal GBS vaccination.

Maternal Colonization With Group B Streptococcus and Serotype Distribution Worldwide: Systematic Review and Meta-analyses

Abstract

Background

Maternal rectovaginal colonization with group B Streptococcus (GBS) is the most common pathway for GBS disease in mother, fetus, and newborn. This article, the second in a series estimating the burden of GBS, aims to determine the prevalence and serotype distribution of GBS colonizing pregnant women worldwide.

Methods

We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus), organized Chinese language searches, and sought unpublished data from investigator groups. We applied broad inclusion criteria to maximize data inputs, particularly from low- and middle-income contexts, and then applied new meta-analyses to adjust for studies with less-sensitive sampling and laboratory techniques. We undertook meta-analyses to derive pooled estimates of maternal GBS colonization prevalence at national and regional levels.

Results

The dataset regarding colonization included 390 articles, 85 countries, and a total of 299924 pregnant women. Our adjusted estimate for maternal GBS colonization worldwide was 18% (95% confidence interval [CI], 17%–19%), with regional variation (11%–35%), and lower prevalence in Southern Asia (12.5% [95% CI, 10%–15%]) and Eastern Asia (11% [95% CI, 10%–12%]). Bacterial serotypes I–V account for 98% of identified colonizing GBS isolates worldwide. Serotype III, associated with invasive disease, accounts for 25% (95% CI, 23%–28%), but is less frequent in some South American and Asian countries. Serotypes VI–IX are more common in Asia.

Conclusions

GBS colonizes pregnant women worldwide, but prevalence and serotype distribution vary, even after adjusting for laboratory methods. Lower GBS maternal colonization prevalence, with less serotype III, may help to explain lower GBS disease incidence in regions such as Asia. High prevalence worldwide, and more serotype data, are relevant to prevention efforts.

Preterm Birth Associated With Group B Streptococcus Maternal Colonization Worldwide: Systematic Review and Meta-analyses

Abstract

Background

Preterm birth complications are the leading cause of deaths among children <5 years of age. Studies have suggested that group B Streptococcus (GBS) maternal rectovaginal colonization during pregnancy may be a risk factor for preterm delivery. This article is the fifth of 11 in a series. We aimed to assess the association between GBS maternal colonization and preterm birth in order to inform estimates of the burden of GBS.

Methods

We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups on the association of preterm birth (<37 weeks' gestation) and maternal GBS colonization (GBS isolation from vaginal, cervical, and/or rectal swabs; with separate subanalysis on GBS bacteriuria). We did meta-analyses to derive pooled estimates of the risk and odds ratios (according to study design), with sensitivity analyses to investigate potential biases.

Results

We identified 45 studies for inclusion. We estimated the risk ratio (RR) for preterm birth with maternal GBS colonization to be 1.21 (95% confidence interval [CI], .99–1.48; P = .061) in cohort and cross-sectional studies, and the odds ratio to be 1.85 (95% CI, 1.24–2.77; P = .003) in case-control studies. Preterm birth was associated with GBS bacteriuria in cohort studies (RR, 1.98 [95% CI, 1.45–2.69]; P < .001).

Conclusions

From this review, there is evidence to suggest that preterm birth is associated with maternal GBS colonization, especially where there is evidence of ascending infection (bacteriuria). Several biases reduce the chance of detecting an effect. Equally, however, results, including evidence for the association, may be due to confounding, which is rarely addressed in studies. Assessment of any effect on preterm delivery should be included in future maternal GBS vaccine trials.

Neonatal Encephalopathy With Group B Streptococcal Disease Worldwide: Systematic Review, Investigator Group Datasets, and Meta-analysis

Abstract

Background

Neonatal encephalopathy (NE) is a leading cause of child mortality and longer-term impairment. Infection can sensitize the newborn brain to injury; however, the role of group B streptococcal (GBS) disease has not been reviewed. This paper is the ninth in an 11-article series estimating the burden of GBS disease; here we aim to assess the proportion of GBS in NE cases.

Methods

We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups reporting GBS-associated NE. Meta-analyses estimated the proportion of GBS disease in NE and mortality risk. UK population-level data estimated the incidence of GBS-associated NE.

Results

Four published and 25 unpublished datasets were identified from 13 countries (N = 10436). The proportion of NE associated with GBS was 0.58% (95% confidence interval [CI], 0.18%–.98%). Mortality was significantly increased in GBS-associated NE vs NE alone (risk ratio, 2.07 [95% CI, 1.47–2.91]). This equates to a UK incidence of GBS-associated NE of 0.019 per 1000 live births.

Conclusions

The consistent increased proportion of GBS disease in NE and significant increased risk of mortality provides evidence that GBS infection contributes to NE. Increased information regarding this and other organisms is important to inform interventions, especially in low- and middle-resource contexts.

Intrapartum Antibiotic Chemoprophylaxis Policies for the Prevention of Group B Streptococcal Disease Worldwide: Systematic Review

Abstract

Background

Intrapartum antibiotic chemoprophylaxis (IAP) prevents most early-onset group B streptococcal (GBS) disease. However, there is no description of how IAP is used around the world. This article is the sixth in a series estimating the burden of GBS disease. Here we aimed to review GBS screening policies and IAP implementation worldwide.

Methods

We identified data through (1) systematic literature reviews (PubMed/Medline, Embase, Literature in the Health Sciences in Latin America and the Caribbean [LILACS], World Health Organization library database [WHOLIS], and Scopus) and unpublished data from professional societies and (2) an online survey and searches of policies from medical societies and professionals. We included data on whether an IAP policy was in use, and if so whether it was based on microbiological or clinical risk factors and how these were applied, as well as the estimated coverage (percentage of women receiving IAP where indicated).

Results

We received policy information from 95 of 195 (49%) countries. Of these, 60 of 95 (63%) had an IAP policy; 35 of 60 (58%) used microbiological screening, 25 of 60 (42%) used clinical risk factors. Two of 15 (13%) low-income, 4 of 16 (25%) lower-middle–income, 14 of 20 (70%) upper-middle–income, and 40 of 44 (91%) high-income countries had any IAP policy. The remaining 35 of 95 (37%) had no national policy (25/33 from low-income and lower-middle–income countries). Coverage varied considerably; for microbiological screening, median coverage was 80% (range, 20%–95%); for clinical risk factor–based screening, coverage was 29% (range, 10%–50%). Although there were differences in the microbiological screening methods employed, the individual clinical risk factors used were similar.

Conclusions

There is considerable heterogeneity in IAP screening policies and coverage worldwide. Alternative global strategies, such as maternal vaccination, are needed to enhance the scope of global prevention of GBS disease.

Estimates of the Burden of Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children

Abstract

Background

We aimed to provide the first comprehensive estimates of the burden of group B Streptococcus (GBS), including invasive disease in pregnant and postpartum women, fetal infection/stillbirth, and infants. Intrapartum antibiotic prophylaxis is the current mainstay of prevention, reducing early-onset infant disease in high-income contexts. Maternal GBS vaccines are in development.

Methods

For 2015 live births, we used a compartmental model to estimate (1) exposure to maternal GBS colonization, (2) cases of infant invasive GBS disease, (3) deaths, and (4) disabilities. We applied incidence or prevalence data to estimate cases of maternal and fetal infection/stillbirth, and infants with invasive GBS disease presenting with neonatal encephalopathy. We applied risk ratios to estimate numbers of preterm births attributable to GBS. Uncertainty was also estimated.

Results

Worldwide in 2015, we estimated 205000 (uncertainty range [UR], 101000–327000) infants with early-onset disease and 114000 (UR, 44000–326000) with late-onset disease, of whom a minimum of 7000 (UR, 0–19000) presented with neonatal encephalopathy. There were 90000 (UR, 36000–169000) deaths in infants <3 months age, and, at least 10000 (UR, 3000–27000) children with disability each year. There were 33000 (UR, 13000–52000) cases of invasive GBS disease in pregnant or postpartum women, and 57000 (UR, 12000–104000) fetal infections/stillbirths. Up to 3.5 million preterm births may be attributable to GBS. Africa accounted for 54% of estimated cases and 65% of all fetal/infant deaths. A maternal vaccine with 80% efficacy and 90% coverage could prevent 107000 (UR, 20000–198000) stillbirths and infant deaths.

Conclusions

Our conservative estimates suggest that GBS is a leading contributor to adverse maternal and newborn outcomes, with at least 409000 (UR, 144000–573000) maternal/fetal/infant cases and 147000 (UR, 47000–273000) stillbirths and infant deaths annually. An effective GBS vaccine could reduce disease in the mother, the fetus, and the infant.

Risk of Early-Onset Neonatal Group B Streptococcal Disease With Maternal Colonization Worldwide: Systematic Review and Meta-analyses

Abstract

Background

Early-onset group B streptococcal disease (EOGBS) occurs in neonates (days 0–6) born to pregnant women who are rectovaginally colonized with group B Streptococcus (GBS), but the risk of EOGBS from vertical transmission has not been systematically reviewed. This article, the seventh in a series on the burden of GBS disease, aims to estimate this risk and how it varies with coverage of intrapartum antibiotic prophylaxis (IAP), used to reduce the incidence of EOGBS.

Methods

We conducted systematic reviews (Pubmed/Medline, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups on maternal GBS colonization and neonatal outcomes. We included articles with ≥200 GBS colonized pregnant women that reported IAP coverage. We did meta-analyses to determine pooled estimates of risk of EOGBS, and examined the association in risk of EOGBS with IAP coverage.

Results

We identified 30 articles including 20328 GBS-colonized pregnant women for inclusion. The risk of EOGBS in settings without an IAP policy was 1.1% (95% confidence interval [CI], .6%–1.5%). As IAP increased, the risk of EOGBS decreased, with a linear association. Based on linear regression, the risk of EOGBS in settings with 80% IAP coverage was predicted to be 0.3% (95% CI, 0–.9).

Conclusions

The risk of EOGBS among GBS-colonized pregnant women, from this first systematic review, is consistent with previous estimates from single studies (1%–2%). Increasing IAP coverage was linearly associated with decreased risk of EOGBS disease.

Cover

Trust and Justice in Big Data Analytics: Bringing the Philosophical Literature on Trust to Bear on the Ethics of Consent

Abstract

Much bioethical literature and policy guidances for big data analytics in biomedical research emphasize the importance of trust. It is essential that potential participants trust so they will allow their data to be used to further research. However, comparatively, little guidance is offered as to what trustworthy oversight mechanisms are, or how policy should support them, as data are collected, shared, and used. Generally, "trust" is not characterized well enough, or meaningfully enough, for the term to be systematically applied in policy development. Yet points made in the philosophical literature on trust can help. They allow us, not only to better distinguish the different ways the term "trust" may be interpreted, but also to better determine how different approaches to trust can align with policy and governance—in what ways they may relate to key bioethical concepts and related laws, and in what ways they can help to balance individual and group interests in data sharing. This article draws from the philosophical literature on trust to identify a relationship among consent, trust, and justice. Specifically, parallels are drawn between "character-trustworthiness" and "natural justice," a set of widely held legal safeguards intended to ensure decision-makers follow a pattern of procedural fairness which protects the rights of the individual and thereby maintains public confidence in the decision-making process. Relevance to traditional bioethical principles, established laws, and consent procedures are addressed throughout. In conclusion, policy actions are suggested.

The crop-residue of fiber hemp cv. Futura 75: from a waste product to a source of botanical insecticides

Abstract

In the attempt to exploit the potential of the monoecious fiber hemp cv. Futura 75 in new fields besides textile, cosmetics and food industry, its crop-residue given by leaves and inflorescences was subjected to hydrodistillation to obtain the essential oils. These are niche products representing an ideal candidate for the development of natural insecticides for the control and management of mosquito vectors, houseflies and moth pests. After GC-MS analysis highlighting a safe and legal chemical profile (THC in the range 0.004–0.012% dw), the leaf and inflorescence essential oils were investigated for the insecticidal potential against three insect targets: the larvae of Culex quinquefasciatus and Spodoptera littoralis and the adults of Musca domestica. The essential oil from inflorescences, showing (E)-caryophyllene (21.4%), myrcene (11.3%), cannabidiol (CBD, 11.1%), α-pinene (7.8%), terpinolene (7.6%), and α-humulene (7.1%) as the main components, was more effective than leaf oil against these insects, with LD₅₀ values of 65.8 μg/larva on S. littoralis, 122.1 μg/adult on M. domestica, and LC₅₀ of 124.5 μl/l on C. quinquefasciatus larvae. The hemp essential oil moderately inhibited the acetylcholinesterase (AChE), which is a target enzyme in pesticide science. Overall, these results shed light on the future application of fiber hemp crop-residue for the development of effective, eco-friendly and sustainable insecticides.

Sustainable bioreduction of toxic levels of chromate in a denitrifying granular sludge reactor

Abstract

Biological removal of chromate [Cr(VI)] in the presence or absence of nitrate by granular sludge biofilms was investigated in batch experiments and in a sequencing batch reactor (SBR). Denitrifying granular sludge cultivated from activated sludge was able to directly reduce Cr(VI) in the presence of an electron donor. Bioreduction was dependent on the initial Cr(VI) and the granular sludge concentrations. Bioreduction of Cr(VI) was followed by Cr(III) precipitation or entrapment in the granular sludge which was corroborated with decrease in total soluble Cr and increase in inorganic content of biomass. Batch experiments revealed that Cr(VI) addition has no major influence on high-strength nitrate (3000 mg L⁻¹) denitrification, but nitrite denitrification was slowed-down. However, SBR experiment demonstrated successful denitrification as well as Cr(VI) removal due to enrichment of Cr(VI)-tolerant denitrifying bacteria. In fact, stable SBR performance in terms of complete and sustained removal of 0.05, 0.1, 0.2, 0.3, 0.5 and 0.75 mM Cr(VI) and denitrification of 3000 mg L⁻¹ was observed during 2 months of operation. Active biomass and electron donor-dependent Cr(VI) removal, detection of Cr(III) in the biomass and recovery of ~ 92% of the Cr from the granular sludge biofilms confirms bioreduction followed by precipitation or entrapment of Cr(III) as the principal chromate removal mechanism. Metagenomic bacterial community analysis showed enrichment of Halomonas sp. in denitrifying granular sludge performing either denitrification or simultaneous reduction of nitrate and chromate.

Issue Information

Traitement du lupus érythémateux par le bélimumab en pratique courante : étude rétrospective de 15 malades

Publication date: Available online 4 November 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): E. Garval, J.-L. Pennaforte, R. Jaussaud, A. Servettaz, P. Bernard, Z. Reguiai
IntroductionLe bélimumab (anticorps monoclonal anti-BLyS) a été récemment commercialisé dans le traitement du lupus érythémateux (LE) systémique. Le but de cette étude était d'en décrire l'efficacité, la tolérance, l'impact sur les paramètres sérologiques du LE et le rôle d'épargne des traitements de fond en pratique courante.Malades et méthodesCette étude rétrospective menée au CHU de Reims incluait tous les malades atteints de LE traités par bélimumab entre 2012 et 2016. L'efficacité du traitement était évaluée sur l'évolution clinique, la normalisation des concentrations d'anticorps anti-DNA et de complément, et l'épargne des autres traitements du LE.RésultatsUne réponse thérapeutique était obtenue chez 9 des 15 malades inclus (60 %), à type de rémission partielle pour 8 d'entre eux. La concentration médiane d'anti-DNA était de 50UI/mL (4 à 50) et celle de C3 sérique de 0,82g/L (0,36 à 1,23) à l'instauration du bélimumab, versus respectivement 25,5UI/mL (2 à 50) et 0,89g/L (0,34 à 1,22) à la date des dernières nouvelles (DDN), sans modification significative (respectivement p=0,12 et p=0,45). La posologie médiane de prednisone à l'instauration du bélimumab passait de 9,5mg/j (0 à 18) à 6mg/j (0 à 20) à la DDN. Huit malades (53 %) ont présenté des effets secondaires, toujours minimes.ConclusionLe bélimumab a eu chez 15 malades une efficacité modérée et une faible toxicité ; il a permis une épargne cortisonique modérée, en vue de limiter les effets secondaires de la corticothérapie au long cours.BackgroundBelimumab (an anti-BLyS monoclonal antibody) was recently approved for the treatment of systemic lupus erythematosus (SLE). The aim of the study was to describe efficacy and safety of the drug as well as its impact on serologic parameters and the role of long-term systemic sparing of treatment in clinical practice in LE.Patients and methodsWe conducted a retrospective study at Reims University Hospital between 2012 and 2016 including consecutive patients with LE treated with belimumab. Efficacy was evaluated in terms of clinical progression, and normalisation of laboratory factors (anti-DNA antibody and C3 serum levels) and sparing of associated long-term systemic therapies for LE.ResultsAmong the 15 patients included, a therapeutic response was obtained in 9 patients (60%), with partial remission in 8 of 9 cases. The median titre of anti-DNA antibody was 50IU/mL (range: 4–50) and the median C3 level was 0.82g/L (range: 0.36–1.23) before initiation of belimumab, vs. 25.5IU/mL (range: 2–50) and 0.89g/L (range: 0.34–1.22) at the last evaluation, respectively, without significant modification (P=0.12 and P=0.45). The median dose of prednisone at the time of the first belimumab infusion was reduced from 9.5mg/day (range: 0–18) to 6mg/day (range: 0–20) at the last clinical evaluation. Eight patients (53%) experienced adverse events, and these were very slight or moderate in all cases.ConclusionBelimumab appears to be an effective and well-tolerated treatment for moderately severe systemic LE, allowing sparing of maintenance corticosteroid therapy in order to decrease its frequent adverse events.

inside front cover (Editorial Board)

Publication date: December 2017
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 177

Texture-specific bag of visual words model and spatial cone matching-based method for the retrieval of focal liver lesions using multiphase contrast-enhanced CT images

Abstract

Purpose

The bag of visual words (BoVW) model is a powerful tool for feature representation that can integrate various handcrafted features like intensity, texture, and spatial information. In this paper, we propose a novel BoVW-based method that incorporates texture and spatial information for the content-based image retrieval to assist radiologists in clinical diagnosis.

Methods

This paper presents a texture-specific BoVW method to represent focal liver lesions (FLLs). Pixels in the region of interest (ROI) are classified into nine texture categories using the rotation-invariant uniform local binary pattern method. The BoVW-based features are calculated for each texture category. In addition, a spatial cone matching (SCM)-based representation strategy is proposed to describe the spatial information of the visual words in the ROI. In a pilot study, eight radiologists with different clinical experience performed diagnoses for 20 cases with and without the top six retrieved results. A total of 132 multiphase computed tomography volumes including five pathological types were collected.

Results

The texture-specific BoVW was compared to other BoVW-based methods using the constructed dataset of FLLs. The results show that our proposed model outperforms the other three BoVW methods in discriminating different lesions. The SCM method, which adds spatial information to the orderless BoVW model, impacted the retrieval performance. In the pilot trial, the average diagnosis accuracy of the radiologists was improved from 66 to 80% using the retrieval system.

Conclusion

The preliminary results indicate that the texture-specific features and the SCM-based BoVW features can effectively characterize various liver lesions. The retrieval system has the potential to improve the diagnostic accuracy and the confidence of the radiologists.

Evaluation of the quality and quantity of compost and leachate from household waterless toilets in France

Abstract

One of the most undesired wastes is the human excreta due to the socio-environmental pressure. Otherwise, the nutriments contained in human excreta could be used as fertilizers to enrich the soil. Familial waterless litter composting toilets (FWLCT) are an alternative for locations where a centralized sewerage network cannot be provided or where there is a lack of standard urban infrastructure including roads, electricity, and water supply. The scientific researches on the composting techniques, the methods of control of the composting processors, and the rate of produced leachate are very limited. In this research, the composting systems included a feces and urine collection device. In each passage, the litter (carbonaceous material) is added to the excreta. Regularly, the buckets were emptied into a composting device located outside the house to which an additional portion of carbonaceous materials can be added. Monitoring was carried out on five rural and one urban familial composting areas in France for 1.5 years. The physiochemical and microbiological properties of the compost and leachate have been monitored and measured in compliance with the protocols. The results show that one of the main problems of this system of human excreta treatment is that the composting process does not achieve a significant rise in temperature and does not allow reaching the optimum temperatures (> 50 °C). Otherwise, from an agronomic point of view, the obtained compost is not rich enough in nutriments to be a good compost as soil fertilizer. But it can be used as a soil conditioner. The average leachate flux from the composters is 1.79 L/day. Because of the very short stay time in the piles, the leachate is contaminated by harmful bacteria and should be treated by another sanitation system.

Is there any association between urinary metabolites of polycyclic aromatic hydrocarbons and thyroid hormone levels in children and adolescents?

Abstract

Considering the possible effects of polycyclic aromatic hydrocarbons (PAHs) on thyroid function, the current study aims to investigate the association of PAH urinary metabolites with the level of thyroid hormones in a sample of Iranian children and adolescents. This cross-sectional study was conducted from September 2015 to July 2016 in Isfahan, Iran. Participants were 150 students, aged 6–18 years, who were selected by multistage cluster random sampling from schools of Isfahan province. Blood and urine samples of participants were obtained for measurement of thyroid hormone levels (measured by immunoradiometric assay) and PAH urinary metabolites, including 1-hydroxynaphthalene, 2-hydroxynaphthalene, 9-hydroxyphenanthrene, and 1-hydroxypyrene. The association of serum thyroid-stimulating hormone (TSH) and PAH urinary metabolites was determined by correlation and regression analyses. Multivariate regression analysis revealed significant association between serum TSH and PAH urinary metabolites; this association remained significant after adjustment for gender and age. The corresponding figures were r = 0.85 for 1-naphthol, r = 0.86 for 2-naphthol, r = 0.87 for 1-hydroxypyrene, and r = 0.42 for 9-phenantrol, respectively, all p values < 0.001. The mean levels of 1-hydroxypyrene and 9-phenanthrol were higher in boys than those in girls (p < 0.05). The findings of this study indicated significant positive association between urinary PAH biomarkers and the TSH level in children and adolescents. It can be suggested that long-term exposure to PAHs might result in thyroid function impairment. The clinical implication of the current findings should be confirmed by future longitudinal studies.

An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 1: new molecules, metabolism, fate, and transport

Abstract

With the exponential number of published data on neonicotinoids and fipronil during the last decade, an updated review of literature has been conducted in three parts. The present part focuses on gaps of knowledge that have been addressed after publication of the Worldwide Integrated Assessment (WIA) on systemic insecticides in 2015. More specifically, new data on the mode of action and metabolism of neonicotinoids and fipronil, and their toxicity to invertebrates and vertebrates, were obtained. We included the newly detected synergistic effects and/or interactions of these systemic insecticides with other insecticides, fungicides, herbicides, adjuvants, honeybee viruses, and parasites of honeybees. New studies have also investigated the contamination of all environmental compartments (air and dust, soil, water, sediments, and plants) as well as bees and apicultural products, food and beverages, and the exposure of invertebrates and vertebrates to such contaminants. Finally, we review new publications on remediation of neonicotinoids and fipronil, especially in water systems. Conclusions of the previous WIA in 2015 are reinforced; neonicotinoids and fipronil represent a major threat worldwide for biodiversity, ecosystems, and all the services the latter provide.

Modifications in the structure of the lichen Cladonia thallus in the aftermath of habitat contamination and implications for its heavy-metal accumulation capacity

Abstract

Phenotypic traits of lichens can be greatly modified by environmental factors. Granulose thalli on soil and podetia, densely covered with granules, referring to common and widespread lichen Cladonia cervicornis subsp. verticillata were found near zinc smelter. The granules are stratified, filled with fungal medulla and heavily encrusted with calcium oxalate weddellite crystals, not observed on regularly developed thalli of the species. Phylogenetic analysis revealed that deformed granulose forms belong to this taxon, showing that the phenotypic plasticity of the lichens of Cladonia can lead to the emergence of features that do not coincide with the taxonomic definition of the species. The heavy-metal accumulation capacity of both granulose and regular form of primary and secondary lichen thallus, in relation to the element content in corresponding substrate, was determined. Granulose-modified thalli accumulate greater amounts of heavy metals than regular ones, meaning that the bioaccumulation property of a given species may be greatly affected by morphological modifications. The granulose forms are also characterised by considerably higher ratios of Cd, Pb and As concentrations in lichen samples in relation to the corresponding substrates than regular ones. This means that collection of variously formed thalli should be avoided in biomonitoring sampling procedures. The results indicate that a substantial part of the element load, in particular zinc, in the examined lichen thalli collected near the smelter originates from atmospheric fallout.

Enhanced bioreduction of nitrobenzene by reduced graphene oxide materials: effects of surface modification and coexisting soluble electron shuttles

Abstract

Reduced graphene oxide (rGO) can enhance the bioreduction of nitrobenzene by Shewanella oneidensis MR-1. The effects of surface modification and coexisting soluble electron shuttles on rGO-enhanced bioreduction of nitrobenzene were investigated here. The results showed that rGO enhanced the secretion of extracellular polymeric substance and the bioreduction of nitrobenzene of several folds. No inhibition effect on nitrobenzene bioreduction was observed even when the concentration of rGO was as high as 200 mg/L. The surface modification of rGO might affect the electrical conductivity which was assumed as one of the main factors that contributed to the enhancement of nitrobenzene bioreduction by rGO materials. Moreover, the coexisting electron shuttles further enhanced the rGO-mediated nitrobenzene bioreduction. After the simultaneous addition of flavin mononucleotide (10 μM) and rGO (50 mg/L), the reduction rate increased 7.8 times to 424.98 ± 7.84 mg (nitrobenzene)/(g (dry cell)∙h), which was higher than those ever reported.