Scale up of anaesthesia services in underserved rural Tanzania.

BACKGROUND: Because of critical shortage of physician anaesthesiologists, the government of Tanzania adopted a task shifting strategy for provision of anaesthesia services. This paper describes the results of an operational study designed to increase the number of anaesthesia providers for emergency obstetric surgeries in order to reduce maternal and perinatal mortality in underserved rural Tanzania. METHODS: In 2016 a before-after cohort study was conducted in seven health centres in rural Tanzania. Five health centres received an intervention and two were selected to track secular trends (control group). Ten associate clinicians, i.e. assistant medical officers, clinical officers, and nurse midwives, from five health centres were trained in anaesthesia skills for emergency obstetric surgeries for three months followed by quarterly supportive supervision, mentoring and teleconsultation to reinforce skills. Primary and secondary outcome measures included Caesarean delivery (CD) rate, quality and safety of anaesthesia, and uptake of the educational program for anaesthesia. RESULTS: Out of the 2,179 CDs performed in the intervention facilities from 2016 to 2019, two women died from complications of anaesthesia. The risk of death from anaesthetic complications was 0.9 per 1000 CD (95% CI 0.1-3.3. The risk of death was not established in the control group because of inadequate documentation and records keeping. The proportion of CD performed under spinal anaesthesia in intervention facilities doubled from 28% (60/214 with 95% CI 22-35) at baseline (July 2014 - June 2016) to 57% (558/971 with 95% CI of 54-61) in year three (July 2018 - June 2019), while in the control group increased by only 40% from 19% (92/475 with 95% CI of 16-23) at baseline and 27% (68/251 with 95% CI of 22-33) in year three. In 2020I, this educational training program was then adopted by the government with minor content changes and increasing duration of training to six months. CONCLUSIONS: This three month educational training program for associate clinicians in anaesthesia, complemented by supportive supervision, can increase the CD rate to one that fills the "unmet need" and the proportion of operations performed under spinal anaesthesia, the gold standard technique for CD. The program can be used to meet the urgent demand for anaesthesia services in other underserved areas in Africa.

Solvent effects on differentiation of mouse brain tissue using laser microdissection 'cut and drop' sampling with direct mass spectral analysis.

RATIONALE: Laser microdissection-liquid vortex capture/electrospray ionization mass spectrometry (LMD-LVC/ESI-MS) has potential for on-line classification of tissue but an investigation into what analytical conditions provide best spectral differentiation has not been conducted. The effects of solvent, ionization polarity, and spectral acquisition parameters on differentiation of mouse brain tissue regions are described. METHODS: Individual 40 × 40 µm microdissections from cortex, white, grey, granular, and nucleus regions of mouse brain tissue were analyzed using different capture/ESI solvents, in positive and negative ion mode ESI, using time-of-flight (TOF)-MS and sequential window acquisitions of all theoretical spectra (SWATH)-MS (a permutation of tandem-MS), and combinations thereof. Principal component analysis-linear discriminant analysis (PCA-LDA), applied to each mass spectral dataset, was used to determine the accuracy of differentiation of mouse brain tissue regions. RESULTS: Mass spectral differences associated with capture/ESI solvent composition manifested as altered relative distributions of ions rather than the presence or absence of unique ions. In negative ion mode ESI, 80/20 (v/v) methanol/water yielded spectra with low signal/noise ratios relative to other solvents. PCA-LDA models acquired using 90/10 (v/v) methanol/chloroform differentiated tissue regions with 100% accuracy while data collected using methanol misclassified some samples. The combination of SWATH-MS and TOF-MS data improved differentiation accuracy. CONCLUSIONS: Combined TOF-MS and SWATH-MS data differentiated white, grey, granular, and nucleus mouse tissue regions with greater accuracy than when solely using TOF-MS data. Using 90/10 (v/v) methanol/chloroform, tissue regions were perfectly differentiated. These results will guide future studies looking to utilize the potential of LMD-LVC/ESI-MS for tissue and disease differentiation.

Hyphenation of Production-Scale Free-Flow Electrophoresis to Electrospray Ionization Mass Spectrometry Using a Highly Conductive Background Electrolyte.

In this technical note, we demonstrate the hyphenation of production-scale free-flow electrophoresis (FFE) and sheathless electrospray ionization mass spectrometry (ESI-MS). In contrast to previous hyphenation approaches, we used a highly conductive background electrolyte (BGE) required for production-scale FFE. We found that this kind of BGE as well as a production-scale setup leads to significant electric interference between FFE and MS. This interference prevents steady-state FFE operation. We examine this interference in detail and discuss possible solutions to this issue. We demonstrate that the straightforward grounding of the transfer line removes the influence of ESI-MS on FFE, but creates a current leak from the ESI interface, which adversely affects the ESI spray. Furthermore, we show that only the electrical disconnection of the ESI probe from the FFE-MS transfer line suppresses this undesirable current. In order to facilitate the electrical disconnection we used a low conductivity, silica-based ESI probe with withdrawn inner capillary. This approach allowed the interference-free hyphenation of production-scale FFE (using a highly conductive BGE) with ESI-MS.

Kinetic size-exclusion chromatography with mass spectrometry detection: an approach for solution-based label-free kinetic analysis of protein-small molecule interactions.

Studying the kinetics of reversible protein-small molecule binding is a major challenge. The available approaches require that either the small molecule or the protein be modified by labeling or immobilization on a surface. Not only can such modifications be difficult to do but also they can drastically affect the kinetic parameters of the interaction. To solve this problem, we present kinetic size-exclusion chromatography with mass spectrometry detection (KSEC-MS), a solution-based label-free approach. KSEC-MS utilizes the ability of size-exclusion chromatography (SEC) to separate any small molecule from any protein-small molecule complex without immobilization and the ability of mass spectrometry (MS) to detect a small molecule without a label. The rate constants of complex formation and dissociation are deconvoluted from the temporal pattern of small molecule elution measured with MS at the exit from the SEC column. This work describes the concept of KSEC-MS and proves it in principle by measuring the rate constants of interaction between carbonic anhydrase and acetazolamide.

SpectraX: A Straightforward Tool for Principal Component Analysis-Based Spectral Analysis.

The analysis of complex spectra is an important component of direct/ambient mass spectrometry (MS) applications such as natural product screening. Unlike chromatography-based metabolomics or proteomics approaches, which rely on software and algorithms, the work of spectral screening is mostly performed manually in the initial stages of research and relies heavily on the experience of the analyst. As a result, throughput and spectral screening reliability are problematic when dealing with large amounts of data. Here, we present SpectraX, a MATLAB-based application, which can analyze MS spectra and quickly locate m/z features from them. Principal component analysis (PCA) is used to analyze the data set, and scoring plots are presented to help in understanding the clustering of data. The algorithm uses mass to charge (m/z) features to produce a list of potential natural products.

A restricted cubic spline approach to assess the association between high fat fish intake and red blood cell EPA + DHA content.

BACKGROUND AND AIMS: Fish, especially fatty fish, are the main contributor to eicosapentaenoic (EPA) and docosahexaenoic (DHA) intake. EPA and DHA concentrations in red blood cells (RBC) has been proposed as a cardiovascular risk factor, with <4% and >8% associated with the lowest and greatest protection, respectively. The relationship between high fat fish (HFF) intake and RBC EPA + DHA content has been little investigated on a wide range of fish intake, and may be non-linear. We aimed to study the shape of this relationship among high seafood consumers. METHODS AND RESULTS: Seafood consumption records and blood were collected from 384 French heavy seafood consumers and EPA and DHA were measured in RBC. A multivariate linear regression was performed using restricted cubic splines to consider potential non-linear associations. Thirty-six percent of subjects had an RBC EPA + DHA content lower than 4% and only 5% exceeded 8%. HFF consumption was significantly associated with RBC EPA + DHA content (P [overall association] = 0.021) adjusted for sex, tobacco status, study area, socioeconomic status, age, alcohol, other seafood, meat, and meat product intakes. This relationship was non-linear: for intakes higher than 200 g/wk, EPA + DHA content tended to stagnate. Tobacco status and fish contaminants were negatively associated with RBC EPA + DHA content. CONCLUSION: Because of the saturation for high intakes, and accounting for the concern with exposure to trace element contaminants, intake not exceeding 200 g should be considered.

Rapid Mass Spectrometric Calibration and Standard Addition Using Hydrophobic/Hydrophilic Patterned Surfaces and Discontinuous Dewetting.

The rapid calibration chip (RCC) is a device that uses the fast and reproducible wetting behavior of hydrophilic/hydrophobic patterned surfaces to confine a series of differently sized droplets on a substrate to obtain a calibration curve. Multiple series of droplets can be formed within seconds by dipping an RCC into a calibration solution. No pipetting, sequential droplet deposition, or advanced equipment is required. The performance and reproducibility of RCCs were evaluated with an electrospray ionization triple-quadrupole mass spectrometer equipped with a liquid microjunction-surface sampling probe (LMJ-SSP) that allows for fast sampling of surfaces. Using circular hydrophilic areas with diameters ranging from 0.25 to 2.00 mm, liquid volumes of 4.6-70.6 nL could be deposited. Furthermore, the use of a second hydrophobic/hydrophilic patterned transfer chip can be used to add internal standard solutions to each calibration spot of the RCC, allowing to transfer a liquid volume of 22.5 nL.

Dietary exposure and biomarkers of arsenic in consumers of fish and shellfish from France.

Seafood, especially fish, is considered as a major dietary source of arsenic (As). Seafood consumption is recommended for nutritional properties but contaminant exposure should be considered. The objectives were to assess As intake of frequent French seafood consumers and exposure via biomarkers. Consumptions of 996 high consumers (18 and over) of 4 coastal areas were assessed using a validated food frequency questionnaire. Seafood samples were collected according to a total diet study (TDS) sampling method and analyzed for total As, arsenite (AsIII), arsenate (AsV), arsenobetaïne (AsB), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). The average As dietary exposure is 94.7+/-67.5 microg/kg bw/week in females and 77.3+/-54.6 microg/kg bw/week in males (p<0.001) and the inorganic As dietary exposure is respectively 3.34+/-2.06 microg/kg bw/week and 3.04+/-1.86 microg/kg bw/week (p<0.05). Urine samples were collected from 382 of the subjects. The average urinary As concentration is 94.8+/-250 microg/g creatinine for females and 59.7+/-81.8 microg/g for males (p<0.001). Samples having an As concentration above 75 microg/g creatinine (n=101) were analyzed for inorganic As (As(III), As(V), MMA(V) and DMA(V)) which was 24.6+/-27.9 microg/g creatinine for males and 27.1+/-20.6 microg/g for females. Analyses do not show any correlation between dietary exposure and urinary As. These results show that biological results should be interpreted cautiously. Diet recording seems to be the best way to assess dietary As exposure. Seafood is a high source of As exposure but even among high consumers it is not the main source of toxic As. From a public health point of view these results should be interpreted carefully in the absence of international consensus on the health-based guidance value.

Organotin levels in seafood and its implications for health risk in high-seafood consumers.

Fish and fishery products are considered as the main source of organotin compounds (OTC). Unfortunately, little national contamination data is available to assess food exposure of organotins from French consumers. To provide a more accurate estimate of risks to human health, the butyltin, phenyltin and octyltin compounds sampling in four French coastal areas were measured in 159 composite samples (96 fresh and frozen fish, 28 mollusks, 14 crustaceans, 1 echinoderm, 11 canned foods, 4 smoked fish, 5 prepared seafood-based dishes) by capillary gas chromatography coupled with a microwave induced plasma atomic-emission spectrometer (CGC-MIP-AES). In these samples, butyltins were usually predominant and the range of the contamination levels was generally below those of earlier studies (fish: mean 5.6; min-max 1.1-23 microg/kg; fishery products: mean 6; min-max 0.8-14 microg/kg). Fish, especially tuna, salmon, mackerel, saithe/coalfish and cod were largely the main contributors (38%) to the total organotin exposure. With the supplementary contribution of great scallop, surimi, squid and oysters, the exposure exceeded 50% in all. However, the utmost OTC exposure was lesser than 47% of the provisional tolerable weekly intake [EFSA (European Food Safety Agency). Opinion of the Scientific Panel on Contaminants in the food chain on a request from the Commission to assess the health risks to consumers associated with exposure to organotins in foodstuffs. (Question N EFSA-Q-2003-110). The EFSA Journal, 102, 1-119, 2004. http://www.efsa.eu.int]. Nobody would exceed this limit. Finally, as this study has some limitations and since some other sources and health effects have not been clearly evaluated, it appears rational from public health and environmental viewpoints to continue to reduce the OTC levels in the environment.

Evaluation of certain food additives and contaminants.

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The Committee also evaluated the risk posed by two food contaminants, with the aim of advising on risk management options for the purpose of public health protection. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular flavouring agents) and contaminants. A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (acidified sodium chlorite, asparaginase from Aspergillus oryzae expressed in Aspergillus oryzae, carrageenan and processed Eucheuma seaweed, cyclotetraglucose and cyclotetraglucose syrup, isoamylase from Pseudomonas amyloderamosa, magnesium sulfate, phospholipase A1 from Fusarium venenatum expressed in Aspergillus oryzae, sodium iron(III) ethylenediaminetetraacetic acid (EDTA) and steviol glycosides); eight groups of related flavouring agents (linear and branched-chain aliphatic, unsaturated, unconjugated alcohols, aldehydes, acids and related esters; aliphatic acyclic and alicyclic terpenoid tertiary alcohols and structurally related substances; simple aliphatic and aromatic sulfides and thiols; aliphatic acyclic dials, trials and related substances; aliphatic acetals; sulfur-containing heterocyclic compounds; aliphatic and aromatic amines and amides; and aliphatic alicyclic linear alpha, beta -unsaturated di- and trienals and related alcohols, acids and esters); and two food contaminants (aflatoxin and ochratoxin A). Specifications for the following food additives were revised: maltol and ethyl maltol, nisin preparation, pectins, polyvinyl alcohol, and sucrose esters of fatty acids. Specifications for the following flavouring agents were revised: maltol and ethyl maltol, maltyl isobutyrate, 3-acetyl-2,5-dimethylfuran and 2,4,5-trimethyl-delta-oxazoline (Nos 1482, 1506 and 1559), and monomenthyl glutarate (No. 1414), as well as the method of assay for the sodium salts of certain flavouring agents. Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives and contaminants considered.

Unique epidemiology of nosocomial urinary tract infection in children.

BACKGROUND: Nosocomial urinary tract infection (NUTI) occurs with varying frequency in children and is thought to be associated with urethral instrumentation. In response to changing infection control resources at our facility, we reviewed NUTI to determine whether the frequency of NUTI, associated complications, or presence of a remediable risk factor (instrumentation) justified ongoing routine infection control surveillance. METHODS: Prospective surveillance was conducted on all wards 8 months per year from January 1991 through December 1997 by an infection control nurse coordinator. NUTI was defined by laboratory evidence according to Center for Disease Control and Prevention definitions and detected 48 hours after admission. Urinary catheterization in the previous 7 days was categorized as continuous/indwelling or intermittent. RESULTS: NUTI was the fifth most common nosocomial infection (129/1375; approximately 9%) and decreased in frequency during the decade from 0.9 to approximately 0.6 cases/1000 patient days. Incidence was equal among men and women. Only 50% of cases had prior instrumentation of the urinary tract. NUTI occurred disproportionately in newborns and infants (P <.001). The most common pathogen was Escherichia coli (28%; 38/132), followed by Candida sp (18%; 24/134), Enterococcus (13%; 18/134), gram-negative nonfermenters (13%; 17/132), Enterobacter (approximately 10%; 13/134), Pseudomonas (9.7%; 13/134), and other (16%; 22/134). Three cases of secondary bacteremia occurred (2.3%; 95% confidence interval 0.5-6.6); there was no mortality. CONCLUSIONS: NUTI poses a less significant burden of illness (incidence, associated morbidity) than other nosocomial infection in children. If resources do not permit hospital-wide surveillance, high-risk children with urethral instrumentation and newborns and infants could be targeted. Although E coli remains the most common cause of pediatric NUTI, fungi have become the second most common pathogen in this tertiary care population. Risk factors for NUTI in noncatheterized children remain to be delineated.

Comparison of a preliminary procedure for the general unknown screening of drugs and toxic compounds using a quadrupole-linear ion-trap mass spectrometer with a liquid chromatography-mass spectrometry reference technique.

Liquid chromatography-tandem mass spectrometry (LC-MS-MS) might be a complement to GC-MS and HPLC-diode array detection for the general unknown screening (GUS) of drugs and toxic compounds, particularly when using information- or data-dependent acquisition (IDA or DDA), an auto-adaptive MS-MS product-ion scan mode where, at each unit time, the m/z ratios above a given intensity threshold are selected for fragmentation. A new quadrupole-linear ion-trap mass spectrometer (LC-QqQlinear ion-trap) was evaluated for GUS using IDA. For the first detection step (so-called "survey scan") the single quadrupole "enhanced" MS mode (EMS), where ions are accumulated then filtered in the Q3-linear ion-trap, was used. The so-called "enhanced" parent ion scan mode (EPI) used at two alternated fragmentation energies gave the best signal intensity and the best mass spectral information when adding mass spectra obtained in low and high fragmentation conditions, respectively, both in the positive (+20 and +50 eV) and negative (-15 and -40 eV) modes. Solid-phase extracts of serum spiked with eight test compounds (chosen for their retention times distributed along the 30-min long chromatogram and for ionising in both the positive and negative modes) were analysed in parallel with this LC-MS-MS technique and with a reference LC-MS method run on a single-quadrupole instrument where low and high in-source fragmentation conditions in the positive and the negative ion modes are alternated. A C(18), 5 microm (150 x 1 mm I.D.) column and a gradient elution of acetonitrile in pH 3, 2 mM ammonium formate, were used for both. Higher signal-to-noise ratios were obtained with the LC-QqQlinear ion-trap instrument than with the reference technique, resulting in mass spectra devoid of contaminant ions and at least as informative as the reconstructed single-MS spectra. After optimisation of the IDA intensity threshold for the detection of tiny chromatographic peaks in noise, five out of the eight compounds (milrinone, lorazepam, fluometuron, piretanide and warfarin) could be unambiguously identified at the concentration of 0.1 mg/l in serum, in the positive or negative modes, or in both, versus only two by LC-MS. All of them could be identified at 1 mg/l by both techniques. These preliminary results show that the sensitivity and mass structural information brought by this new LC-QqQlinear ion-trap instrument may help design an efficient toxicological GUS procedure.

Nutritional intakes of vegetarian populations in France.

OBJECTIVE: To assess food behaviour and determine nutritional intakes of various vegetarian populations in France. DESIGN: A five-day self-administered food record which was mailed to members of the three principal French vegetarian organisations. SUBJECTS: 145 subjects, aged 7-87 y; 94 classical vegetarians (19% of those contacted), 34 Hindu lactovegetarians (17% of those contacted) and 17 macrobiotic (34% of those contacted). SETTING: The survey was conducted between March 1997 and July 1997 in France. RESULTS: Vegetarianism in France is represented by three main classes of food behaviour: ovolactovegetarian (AAV), lactovegetarian (KRI) and macrobiotic (MMK). The geometric mean intakes ranged from 1952 kcal/d (KRI), 2051 kcal/d (MMK) to 2384 kcal/d (AAV) for males and from 1302 kcal/d (MMK), 1675 kcal/d (AAV) to 1804 kcal/d (KRI) for females, after adjusting for age and BMI. The energy consumption in the MMK group was significantly lower than that in the AAV (P<0.05) and KRI groups (P<0.01), respectively. A difference among groups was observed for females (P=0.0002), but not for males. The MMK group consumed less lipid than the other two vegetarian groups, 46 g/d for men and 38 g/d for women vs 80 g/d for men and 61 g/d for women in the AAV group and 93 g/d for men and 81 g/d for women in the KRI group, respectively. Differences with AAV and MMK were statistically significant (P<0.001 for men and women for both groups). Mean protein consumption ranged from 60 g/d (AAV), 64 g/d (KRI) to 77 g/d (MMK) for males and from 46 g/d (MMK), 50 g/d (AAV) to 58 g/d (KRI) for females. Mean carbohydrate intakes ranged from 247 g/d (AAV), 321 g/d (KRI) to 338 g/d (MMK) in males and from 209 g/d (MMK), 228 g/d (AAV) to 242 g/d (KRI) in females. There were no significant differences in protein and carbohydrate intakes between the groups. Median calcium intakes ranged from 758.2 mg/d (MMK), 863 mg/d (AAV) to 989.3 mg/d (KRI) for the men and from 500.8 mg/d (MMK), 863 mg/d (AAV) to 934 mg/d (KRI) for the women. In the men, there was no differences in daily calcium intakes between the three vegetarian groups. However, we found a significant difference for women (P=0. 0041). The women in the MMK group presented significantly lower daily calcium intakes than the women in the AAV (P=0.013) and KRI (P=0.0032) groups. The AAV and KRI groups consumed dairy products supplying respectively 36% and 53% for the men and 39% and 59% for the women of total calcium against 0% for men and women in the MMK group. Median iron intakes ranged between 12.5 mg/d (KRI), 13.2 mg/d (AAV) and 22.5 mg/d (MMK) for the men and between 11.2 mg/d (KRI), 14.6 mg/d (AAV) and 16.9 mg/d (MMK) for the women. MMK (men P=0.0172 and women P=0.0131) and AAV (only in men P=0.037) groups consumed significantly higher quantities of iron than did the KRI group. The heme iron median intake in males and females of the three vegetarian groups was very low (<0.5%). Overall, the female vegetarians consumed 58.1 (MMK), 109 (AAV) and 127.4 (KRI) mg of vitamin C per day and the males 76.3 (MMK), 150.4 (AAV) and 150.4 (KRI) mg per day. Median vitamin B9 intakes ranged from 247.5 microg/d (KRI), 312 microg/d (MMK) to 390.4 microg/d (AAV) for the men and from 188.3 microg/d (MMK), 266.9 microg/d (KRI) to 323.8 microg/d (AAV) for the women. Vitamin B12 consumption ranged from 0.2 microg/d (MMK), 1.5 microg/d (AAV) to 1.7 microg/d (KRI) in the women and from 0.6 microg/d (MMK) to 1.0 microg/d (AAV and KRI) in the men. No differences in consumption were observed in the males. On the other hand, the women in the MMK group consumed significantly less vitamin C and B12 than did the women in the AAV (P=0.0006) and KRI (P=0. 0396) groups, while it was at the limit of significance for the females (P=0.0715) for vitamin B9. CONCLUSION: Our results suggest that vegetarians have a better understanding of dietary requirements than does the general population. (ABSTRACT TRUNCATED)

Calculation of the intake of three intense sweeteners in young insulin-dependent diabetics.

In 1994, European Directive 94/35/CE authorised the use as food additives of five intense sweeteners for which Acceptable Daily Intakes (ADI) were established. The same directive stipulated that member states should organise a monitoring system to determine the consumption of these substances. Diabetic children are normally considered to constitute a group with a high consumption of sweeteners (European Commission, 1998. Report on Methodology for the Monitoring of Food Additives Intake across the European Union. Report of the Scientific Cooperation, Task 4.2 SCOOP/INT/REPORT/2. European Commission Directorate General III, Brussels.). A stepwise approach to the food additive intake in the general population had shown that three of the five authorised intense sweeteners (aspartame, saccharin and acesulfame K) are used at particularly high levels in sugar-free foods and are also very commonly utilised as table-top sweeteners. This paper presents the results of a food intake survey conducted in a group of French, insulin-dependent children in 1997, aimed at estimating the Theoretical Maximum Daily Intake (TMDI) for these three sweeteners and comparing this with the relevant ADI values. A 5-day diary questionnaire was used to estimate the intake of sugar-free, artificially sweetened foods and table-top sweeteners. When assessing the intake of each additive, all sugar-free products were assumed to be sweetened using a single sweetener at its maximum authorised level. This study was performed in five age groups, and based on the mean and 97.5th percentile of the distribution of consumption, demonstrated that it was unlikely that total exposure could rise above the ADI.

Emergency department use by infants less than 14 days of age.

OBJECTIVE: To determine the factors associated with nonacute presentation to the emergency department (ED) by infants less than 14 days of age. METHODS: A prospective survey was conducted in the pediatric ED of a teaching hospital providing voluntary in-home follow-up for families discharged within 48 hours of delivery. Participants were families of infants less than 14 days of age presenting to the ED over a 1-year period. The main outcome measure was acuteness of presenting problem. Presenting problems were classified as nonacute if the following 4 criteria were met: (i) no physician referral; (ii) nonurgent triage code assigned by a triage nurse; (iii) no investigations performed in the ED; and (iv) discharge home. RESULTS: Of the 142 eligible infants, 70 (49%) infants presented with nonacute problems. Ninety-two (65%) returned questionnaires. There was no significant difference in the proportion of nonacute problems between infants discharged at less than 48 hours of age and those discharged at more than 48 hours (P = 0.7). The proportion of nonacute problems among infants of primiparous mothers was significantly higher (64%) than among infants of multiparous mothers (24%) (P < 0.001). Infants of mothers less than 25 years of age were more likely to present with nonacute problems (P = 0.002). CONCLUSIONS: Primiparity and maternal age less than 25 years were associated with nonacute ED presentation. Acuteness of presentation to the ED was not influenced by timing of neonatal discharge. Therefore, perinatal education might be best targeted at first time mothers and young mothers to reduce the number of nonacute ED visits.

A randomized double-blind placebo controlled trial of oral acyclovir in renal allograft recipients.

Fifty renal transplant patients were randomized to receive either 800 mg acyclovir by mouth four times daily or identical placebo tablets for prophylaxis of herpes simplex infection. Patients were followed weekly to assess reactivation of herpes simplex, varicella zoster virus, Epstein-Barr virus or cytomegalovirus (CMV) infections. The patients received standard immunosuppressive regimens including cyclosporine A. Acyclovir suppressed secretion of herpes simplex virus in treated patients (P=0.001). Three episodes of mucocutaneous herpes simplex virus occurred in placebo recipients and one in a noncompliant acyclovir recipient. A clinically important difference in graft survival was demonstrated, but because of sample size failed to reach statistical significance (P=0.11). No reactivation of varicella zoster virus, Epstein-Barr virus or CMV infection was detected in either group. Toxicity was limited to central nervous irritability. The authors conclude that high dose oral acyclovir provides effective prophylaxis for prevention of herpes simplex virus infections in renal transplantation and may be associated with increased graft survival, perhaps from suppression of CMV infection.

Assessment of infant exposure to food chemicals: the French Total Diet Study design.

As part of the previous French Total Diet Studies (TDS) focusing on exposure to food chemicals in the population aged 3 years and older, the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) launched a specific TDS on infants to complete its overall chemical food safety programme for the general population. More than 500 chemical substances were analysed in food products consumed by children under 3 years old, including nutrients, several endocrine disruptors resulting from human activities (polychlorinated biphenyls, dioxins and furans, brominated flame retardants, perfluoroalkyl acids, pesticide residues, etc.) or migrating from food contact materials such as bisphenol A or phthalates, but also natural substances such as mycotoxins, phytoestrogens and steroids. To obtain a representative and general view of infant food consumption, food items were selected based on results of a national consumption survey conducted specifically on this population. Moreover, a specific study on food was conducted on 429 households to determine which home-cooking practices are employed to prepare food consumed by infants. Overall, the targeted chemical substances were analysed in more than 450 food samples, representing the purchase and home-cooking practices of over 5500 food products. Foods included common foods such as vegetables, fruit or cakes as well as specific infant foods such as infant formula or jarred baby food. The sampling plan covered over 80% of the total diet. Specificities in infant food consumption and habits were therefore considered to define this first infant TDS. This study, conducted on a large scale and focusing on a particularly sensitive population, will provide accurate information on the dietary exposure of children under 3 years to food chemicals, especially endocrine disruptors, and will be particularly useful for risk assessment analysis under the remit of ANSES' expert committees.

Food risk assessment for perfluoroalkyl acids and brominated flame retardants in the French population: results from the second French total diet study.

To determine the exposure of the French population to toxic compounds contaminating the food chain, a total diet study was performed in France between 2007 and 2009. This study was designed to reflect the consumption habits of the French population and covered the most important foods in terms of consumption, selected nutrients and contribution to contamination. Based on French consumption data, the present study reports the dietary exposure to perfluoroalkyl acids (16 congeners) and brominated flame retardants (polybrominated diphenyl ethers, hexabromocyclododecane and polybrominated biphenyls). Comparison of the calculated dietary exposures with the generally accepted health-based guidance values revealed that most compounds do not pose any risk. There are however knowledge gaps for some congeners in these large chemical classes.

Dietary exposure to perfluoroalkyl acids of specific French adult sub-populations: high seafood consumers, high freshwater fish consumers and pregnant women.

Perfluoroalkyl acids (PFAAs) are globally found in various media, including food and especially fishery products. In the present study, the dietary exposure to 15 perfluoroalkyl acids was assessed for 3 French adult populations, namely high seafood consumers, high freshwater fish consumers, and pregnant women. Purified food extracts were analysed by LC-MS/MS and PFBA, PFPA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnA, PFTrDA, PFTeDA, PFBS, PFHxS, PFHpS, PFOS and PFDS were monitored and quantified according to the isotope dilution principle. Under lower bound (LB) hypothesis (i.e. contamination values

Development and validation of a specific and sensitive gas chromatography tandem mass spectrometry method for the determination of bisphenol A residues in a large set of food items.

BPA-containing products are widely used in foodstuffs packaging as authorized within the European Union (UE no. 10/2011). Therefore, foods and beverages are in contact with BPA which can migrate from food contact material to foodstuffs. An accurate assessment of the exposure of the consumers to BPA is crucial for a non-ambiguous risk characterization. In this context, an efficient analytical method using gas chromatography coupled to tandem mass spectrometry (GC-MS/MS), in the selected reaction monitoring (SRM) mode, was developed for the quantification of BPA in foodstuffs at very low levels (<0.5µgkg(-1)). A standard operating procedure, based on the combination of two successive solid phase extractions (SPE), was developed for various liquid and solid foodstuffs. The use of (13)C12-BPA as internal standard allowed accurate quantification of BPA by isotopic dilution. Control charts based on both blank and certified materials have been implemented to ensure analytical data quality. The developed analytical method has been validated according to in-house validation requirements. R(2) was better than 0.9990 within the range [0-100µgkg(-1)], the trueness was 4.2%. Repeatability and within-laboratory reproducibility ranged from 7.5% to 19.0% and 2.5% to 12.2%, respectively, at 0.5 and 5.0µgkg(-1) depending on the matrices tested for. The detection and quantification limits were 0.03 and 0.10µgkg(-1), respectively. The reporting limit was 0.35µgkg(-1), taking into account the mean of the laboratory background contamination. The global uncertainty was 22.2% at 95% confidence interval.