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OBJECTIVE: To describe the medical, socio-economic and geographical profiles of patients with rifampicin-resistant TB (RR-TB) and the implications for the provision of patient-centred care. SETTING: Thirteen districts across three South African provinces. DESIGN: This descriptive study examined laboratory and healthcare facility records of 194 patients diagnosed with RR-TB in the third quarter of 2016. RESULTS: The median age was 35 years; 120/194 (62%) of patients were male. Previous TB treatment was documented in 122/194 (63%) patients and 56/194 (29%) had a record of fluoroquinolone and/or second-line injectable resistance. Of 134 (69%) HIV-positive patients, viral loads were available for 68/134 (51%) (36/68 [53%] had viral loads of >1000 copies/ml) and CD4 counts were available for 92/134 (69%) (20/92 [22%] had CD4 <50 cells/mm3). Patients presented with varying other comorbidities, including hypertension (13/194, 7%) and mental health conditions (11/194, 6%). Of 194 patients, 44 (23%) were reported to be employed. Other socio-economic challenges included substance abuse (17/194, 9%) and ill family members (17/194, 9%). Respectively 13% and 42% of patients were estimated to travel more than 20 km to reach their diagnosing and treatment-initiating healthcare facility. CONCLUSIONS: RR-TB patients had diverse medical and social challenges highlighting the need for integrated, differentiated and patient-centred healthcare to better address specific needs and underlying vulnerabilities of individual patients.

OBJECTIF: Décrire les profils médicaux, socioéconomiques et géographiques des patients atteints de TB résistante à la rifampicine (RR-TB) et les implications en matière de soins centrés sur le patient. CONTEXTE: Treize districts de trois provinces d'Afrique du Sud. MÉTHODE: Cette étude descriptive a analysé les dossiers médicaux et de laboratoire de 194 patients ayant reçu un diagnostic de RR-TB au troisième trimestre de 2016. RÉSULTATS: L'âge médian était de 35 ans ; 120/194 (62%) patients étaient des hommes. Un traitement antituberculeux antérieur était documenté chez 122/194 (63%) patients, et 56/194 (29%) avaient une résistance à la fluoroquinolone et/ou à un agent injectable de deuxième ligne documentée. Sur 134 (69%) patients infectés par le VIH, les charges virales étaient disponibles pour 68/134 (51%) patients (36/68 [53%] avaient des charges virales >1 000 copies/ml) et les taux de CD4 étaient disponibles pour 92/134 (69%) patients (20/92 [22%] avaient un taux de CD4 <50 cellules/mm3). Les patients présentaient diverses autres comorbidités, dont hypertension (13/194, 7%) et troubles psychiques (11/194, 6%). Sur les 194 patients, 44 (23%) avaient un emploi. Les autres problèmes socioéconomiques comprenaient la toxicomanie (17/194, 9%) et le fait d'avoir un membre de sa famille malade (17/194, 9%). Respectivement 13% et 42% des patients parcouraient plus de 20 km pour se rendre à leur centre de diagnostic et au centre de soins responsable de l'instauration du traitement. CONCLUSIONS: Les patients atteints de RR-TB avaient divers problèmes médicaux et sociaux. Ces résultats soulignent le besoin de soins intégrés, différenciés et centrés sur le patient afin de mieux répondre aux besoins spécifiques et aux vulnérabilités sous-jacentes de chaque patient.

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Maternal death from haemorrhage is decreasing: in the last 15 years the number of deaths has been halved. This improvement demonstrates the progress made in hemorrhage management as a result of collective efforts. The number of deaths in this triennium is 22, representing 8.4% of maternal deaths and a maternal mortality ratio by haemorrhage of 1.0/100,000 live births. Nevertheless, there is a worrying proportion of deaths from occult haemorrhage. These occult haemorrhages most often occurred after caesarean sections. A lack of surveillance in the immediate follow-up was generally associated. One or more factors of sub-optimal care were present in 84% of the cases, and 88.9% of deaths were considered possibly or probably preventable. Delay in the diagnosis of haemorrhage, delay in surgical treatment, an insufficient transfusion strategy and inappropriate locations of care were the most frequently reported factors. The experts suggest that risk factors for haemorrhage should be identified in order to propose the most appropriate facility for childbirth. They encourage the strategies for early diagnosis of haemorrhage (attentive and regular monitoring, rapid haemoglobin measurement, abdominal ultrasound) and surgical intervention in case of hemoperitoneum.

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SETTING: Thirteen districts in Eastern Cape (EC), KwaZulu-Natal (KZN) and Western Cape (WC) Provinces, South Africa.OBJECTIVE: To pilot a methodology for describing and visualising healthcare journeys among drug-resistant tuberculosis (DR-TB) patients using routine laboratory records.DESIGN: Laboratory records were obtained for 195 patients with laboratory-detected rifampicin-resistant TB (RR-TB) during July-September 2016. Health facility visits identified from these data were plotted to visualise patient healthcare journeys. Data were verified by facility visits.RESULTS: In the 9 months after the index RR-TB sample was collected, patients visited a mean of 2.3 health facilities (95% CI 2.1-2.6), with 9% visiting ≥4 facilities. The median distance travelled by patients from rural areas (116 km, interquartile range [IQR] 50-290) was greater than for urban patients (51 km, IQR 9-140). A median of 21% of patient's time was spent under the care of primary healthcare facilities: this was respectively 6%, 37% and 39% in KZN, EC and WC. Journey patterns were generally similar within districts. Some reflected a semi-centralised model of care where patients were referred to regional hospitals; other journeys showed greater involvement of primary care.CONCLUSION: Routine laboratory data can be used to explore DR-TB patient healthcare journeys and show how the use of healthcare services for DR-TB varies in different settings.

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OBJECTIVE: To determine a minimum threshold of human resources (midwives, obstetricians and gynecologists, anesthesiology and intensive care units, pediatricians) to ensure the safety and quality of unplanned activities in Obstetrics and Gynecology. MATERIALS AND METHODS: Consultation of the MedLine database, the Cochrane Library and the recommendations of authorities. Meetings of representative members in different modes of practice (university, hospital, liberal) under the aegis of and belonging to the French College of Obstetricians and Gynecologists (CNGOF), the French Society of Anesthesia and Resuscitation (SFAR), the French Society of Neonatalogy (SFN), the French Society of Perinatal Medicine (SFMP), the French College of Midwives (CNSF), the French Federation of Perinatal Care Networks (FFRSP) with elaboration of a re-read text by external experts, in particular by the members of the Boards of Directors of these authorities and of Club of Anesthesiology-Intensive Care Medicine in Obstetrics (CARO). RESULTS: Different minimum thresholds for each category of caregivers were proposed based on the number of births/year. These proposed minimum thresholds can be modulated upwards according to the types (level I, IIA, IIB or III) or the activity (existence of an emergency reception service, maternal-fetal and/or surgical activity of resort or referral). Due to peak activity and the possibility of unpredictable concomitance of urgent medical procedures, it is necessary that organizations plan to use resource persons. The occupancy rate of the target beds of a maternity ward must be 85%. CONCLUSION: These proposed minimum thresholds are intended to help caregivers providing non-scheduled perinatal as well as Obstetrics and Gynecology care to make the most of the human resources allocated to institutional bodies to ensure their safety and quality.

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OBJECTIVE: In past studies, a lack of social support has been associated with cardiovascular disease (CVD) risk, particularly in black Africans. However, whether or not coping strategies have beneficial effects on blood pressure (BP) and emotional well-being is not clear. We therefore assessed the relationship between BP levels, depression and coping strategies. METHODS: A prospective bi-ethnic cohort followed 359 black and white South African school teachers (aged 20-65 years) over a three-year period. Data on ambulatory 24-hour blood pressure, depression, coping strategies (defensiveness, social support, avoidance) and culture-specific coping scores (cognitive/emotional debriefing, spiritual-, collectivistic and ritualcentred) were obtained. RESULTS: Over three years, chronic depression (38 vs 19%) and hypertension (68 vs 35%) were apparent in blacks ( d-values > 0.3) as opposed to whites. In both groups, depression was accompanied by more avoidance (loss-of-control) coping. Consistent spiritual and increasing collectivistic coping were apparent in whites. Over time, increasing defensiveness (OR 1.08, p ≤ 0.05) and ritual coping (OR 1.27, p ≤ 0.01; d-values > 0.5), predicted chronic depression in blacks. The change in their symptoms of depression predicted 24-hour hypertension (OR 1.11, p = 0.04). No similar associations existed in whites. CONCLUSIONS: Blacks showed increasing defensiveness and ritual- and spiritual-centred coping in an attempt to combat chronic depression, which may be costly, as reflected by their chronic hypertensive status. Whites showed consistent spiritual- centred coping while utilising avoidance or loss-of-control coping, with a trend of seeking less social support or isolation as a coping mechanism. During counselling of depressed patients with hypertension, the beneficial effects of social support and spiritual coping may be of great importance.

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Haemorrhage is the first cause of maternal mortality and morbidity in France and a quality of care marker. Haemorrhage rate in France is around 5 to 10% of deliveries. PPH is defined as a post-partum blood loss≥500mL whatever the delivery route and sometime blood can be concealed inside the pelvis. Between 2010 and 2012 in France, 29 deaths were related to haemorrhage giving a maternal mortality ratio of 1.2/100,000 live births (CI 95% 0.8-1.7). Haemorrhage cases decreased from last triennium (2007-2009) especially for uterine atony cases (12/29) but remains the first leading cause of direct maternal death. Patients with previous cesarean birth were more represented than in general obstetrical population (11/23). Substandard care were mainly due to delays in diagnosis of hemoperitoneum, delays in adequate resuscitation because of reassuring vital signs (normal blood pressure or normal hematocrite at the initial stage of bleeding) or organisational mistakes.

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Dye-decolorizing peroxidases (DyPs) were classified as a new family of heme peroxidase in 2007. Produced by various bacteria, they are the first bacterial enzymes known able to degrade lignin and dyes, for which their application in waste treatment and pretreatment of lignocellulosic biomass could be envisaged. In this work, a PCR primer pair was created and tested that enabled the detection and quantification of a wide range of bacterial genes of P class DyP in complex matrices. In addition, a phylogenetic tree was built with all available sequences of DyP genes available, offering a first overview of their presence in the bacteria kingdom.

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AIMS: To investigate the nitrogen-microbial community dynamics during composting of a mixture of nitrifying waste activated sludge (WAS) and fine organic fraction of residual household waste (RHW). To examine whether the addition of nitrifying sludge could promote ammonia oxidation and reduce ammonia emissions. METHODS AND RESULTS: The fine organic fraction of RHW was mixed with the WAS and homogenized. The mixture and each waste alone were loaded in aerobic cells under controlled conditions, respectively. Both nitrogen and microbial community dynamics were monitored during 50 days of composting. The ammonia oxidizers were quantified and identified in the sludge and compost. The changes in ammonia-oxidizing bacteria (AOB) concentrations corresponded to the ammonia oxidation rates calculated from nitrogen balance. The addition of WAS did not efficiently reduce ammonia emissions because the Nitrosomonas oligotropha-like AOB introduced declined during the active stage of composting. Ammonia oxidation was probably limited by the intense heterotrophic activities at the active stage. Nitrosomonas europaea/eutropha and Nitrosomonas nitrosa-like AOB were established only during the maturation stage. They were the main contributors to ammonia oxidation during composting. CONCLUSIONS: The mixing of nitrifying WAS with the RHW during the early stages of composting does not promote ammonia oxidation nor reduce ammonia emissions because of limiting biologic factors during the active stage of composting. SIGNIFICANCE AND IMPACT OF THE STUDY: The mixing of activated sludge with RHW before composting is a common practice on composting plants. This study proved the limitation of this practice to reduce ammonia emissions during composting via bioaugmentation of ammonia-oxidizing organisms. It correlated successfully the ammonia oxidation rate with different groups of ammonia oxidizers and explains the fail of promoting ammonia oxidation during the early stages of composting. It suggests Nit. europaea/eutropha and Nit. nitrosa-like AOB were the main contributors to ammonia oxidation during composting.

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A field plot experiment was carried out to evaluate the impact of spreading chicken manure containing enrofloxacin (ENR) and its metabolite ciprofloxacin (CIP), on the levels of CIP-resistant Enterobacteriaceae in soil. The manures from chickens treated with ENR and from untreated control chickens were applied on six plots. Total and CIP-resistant Enterobacteriaceae were counted on Violet Red Bile Glucose medium containing 0 to 16mg L(-1) of CIP. A total of 145 isolates were genotyped by enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR). The minimum inhibitory concentration (MIC) of CIP for the isolates of each ERIC-PCR profile was determined. The most frequently isolated Enterobacteriaceae included Escherichia coli, and to a lesser extent, Enterobacter and 5 other genera from environmental origin. The composition of the E. coli community differed between manure and manured soil suggesting that the E. coli genotypes determined by ERIC-PCR varied significantly in their ability to survive in soil. One of these genotypes, including both susceptible and resistant isolates, was detected up to 89 days after the manure was applied. Most of the E. coli isolated in soil amended with manure from treated chickens was resistant to CIP (with a MIC ranging between 2 and 32mg L(-1)). In contrast, despite the presence of ENR in soil at concentrations ranging from 13-518µg kg(-1), the environmental Enterobacteriaceae isolates had a CIP MIC≤0.064mg L(-1), except one isolate which had a MIC of 0.25mg L(-1), These results showed that spreading manure from ENR-treated chickens enabled CIP-resistant E. coli to persist for at least three months in the soil. However, neither the presence of fluoroquinolones, nor the persistence of CIP-resistant E. coli, increased the CIP-susceptibility of environmental Enterobacteriaceae.

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SETTING: Two paediatric hospitals in Cape Town, South Africa. OBJECTIVE: To investigate the incidence of and risk factors for severe liver injury in human immunodeficiency virus (HIV) infected children receiving long-term isoniazid preventive therapy (IPT). DESIGN: Randomised trial of IPT or placebo given daily or thrice weekly to HIV-infected children aged ≥8 weeks; placebo was discontinued early. Alanine transaminase (ALT) was measured at baseline, 6-monthly and during illness: an increase of ≥10 times the upper limit of normal defined severe liver injury. RESULTS: Of 324 children enrolled, 297 (91.6%) received IPT (559.1 person-years [py]). Baseline median age was 23 months (interquartile range [IQR] 9.5-48.6) and median CD4%, 20% (IQR 13.6-26.9). A total of 207 (63.9%) children received combination antiretroviral therapy: 19 developed severe liver injury, 16 while receiving IPT. Among these there were 8 cases of viral hepatitis (5 with hepatitis A), 2 antiretroviral-induced liver injuries and 1 case of abdominal tuberculosis. IPT-related severe liver injury occurred in 1.7% (5/297, 0.78/100 py). No child developed hepatic failure; one died of an unrelated cause. All surviving children subsequently tolerated IPT. CONCLUSIONS: This study suggests that long-term IPT has a low toxicity risk in HIV-infected children. In the absence of chronic viral hepatitis, IPT can be safely re-introduced following recovery from liver injury.

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We report here on a European cohort of 27 kidney transplant recipients displaying operational tolerance, compared to two cohorts of matched kidney transplant recipients under immunosuppression and patients who stopped immunosuppressive drugs and presented with rejection. We report that a lower proportion of operationally tolerant patients received induction therapy (52% without induction therapy vs. 78.3%[p = 0.0455] and 96.7%[p = 0.0001], respectively), a difference likely due to the higher proportion (18.5%) of HLA matched recipients in the tolerant cohort. These patients were also significantly older at the time of transplantation (p = 0.0211) and immunosuppression withdrawal (p = 0.0002) than recipients who rejected their graft after weaning. Finally, these patients were at lower risk of infectious disease. Among the 27 patients defined as operationally tolerant at the time of inclusion, 19 still display stable graft function (mean 9 ± 4 years after transplantation) whereas 30% presented slow deterioration of graft function. Six of these patients tested positive for pre-graft anti-HLA antibodies. Biopsy histology studies revealed an active immunologically driven mechanism for half of them, associated with DSA in the absence of C4d. This study suggests that operational tolerance can persist as a robust phenomenon, although eventual graft loss does occur in some patients, particularly in the setting of donor-specific alloantibody.

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Transplant glomerulopathy (TG), a form of chronic renal transplant rejection, carries a poor prognosis. It must be differentiated from the entity defined by the Banff '05 classification, interstitial fibrosis/tubular atrophy (IF/TA). Sequential transplant biopsies have shown that these lesions are subclinical long before clinical manifestations. The availability of biomarkers may provide an earlier diagnosis and subsequent treatment. The aim of our study was to identify serum biomarkers in kidney recipients showing TG compared with IF/TA or stable patients, using protein microarray technology. This technology detects auto- or alloantibodies in patient sera. With a high degree of statistical significance, we identified 18 antibody reactivities specific for TG; 11 for IF/TA; and 10 among stable patients. Target proteins were involved in signal transduction, transcription regulation, DNA replication and repair, cell cycle, endocytosis, cell redox, as well as glycolysis. Some markers, such as podocan and collagen XXIII among TG and tubular cell ion channels among IF/TA, possibly provide insights into the pathogenesis of the lesions.

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OBJECTIVE: To determine whether full elbow extension as assessed by the elbow extension test can be used in routine clinical practice to rule out bony injury in patients presenting with elbow injury. DESIGN: Adults: multicentre prospective interventional validation study in secondary care. Children: multicentre prospective observational study in secondary care. SETTING: Five emergency departments in southwest England. PARTICIPANTS: 2127 adults and children presenting to the emergency department with acute elbow injury. INTERVENTION: Elbow extension test during routine care by clinical staff to determine the need for radiography in adults and to guide follow-up in children. MAIN OUTCOME MEASURES: Presence of elbow fracture on radiograph, or recovery with no indication for further review at 7-10 days. RESULTS: Of 1740 eligible participants, 602 patients were able to fully extend their elbow; 17 of these patients had a fracture. Two adult patients with olecranon fractures needed a change in treatment. In the 1138 patients without full elbow extension, 521 fractures were identified. Overall, the test had sensitivity and specificity (95% confidence interval) for detecting elbow fracture of 96.8% (95.0 to 98.2) and 48.5% (45.6 to 51.4). Full elbow extension had a negative predictive value for fracture of 98.4% (96.3 to 99.5) in adults and 95.8% (92.6 to 97.8) in children. Negative likelihood ratios were 0.03 (0.01 to 0.08) in adults and 0.11 (0.06 to 0.19) in children. CONCLUSION: The elbow extension test can be used in routine practice to inform clinical decision making. Patients who cannot fully extend their elbow after injury should be referred for radiography, as they have a nearly 50% chance of fracture. For those able to fully extend their elbow, radiography can be deferred if the practitioner is confident that an olecranon fracture is not present. Patients who do not undergo radiography should return if symptoms have not resolved within 7-10 days.

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Radiochemical partitioning experiments using 203Hg have been undertaken with mixtures of river, seawater and sediment samples taken from three geochemically contrasting UK estuaries: the Plym, Beaulieu and Mersey. Species of dissolved Hg were determined using reversed-phase C18 chelating columns and particulate species were determined by sequential leaching with 1 M NH4OAc and 1 M HCl. Mercury had a high particle reactivity with partition coefficients, KDs, ranging from 10(4) to 5 x 10(5) ml g(-1), depending on salinity, the chemical composition of the end-member waters, and on the physico-chemical characteristics of the sediment. Dissolved organic matter present in the waters (humic substances and/or anthropogenic compounds) was found to be the main factor governing the forms of dissolved Hg and their reactivity. From the spiked 203Hg, up to 95% of the dissolved metal was retained on the C18 columns for the Mersey waters, whereas this fraction was < 60% in the Plym and Beaulieu waters. Quasi-irreversible adsorption of Hg onto particles from each estuary was observed over a time-scale of a few hours and < 20% of total particulate Hg was released by the sequential leach. In this paper, physico-chemical processes are proposed to explain the estuarine behaviour of Hg and the results are discussed in terms of Hg availability in estuarine systems.

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The sediment-water partitioning and speciation of inorganic mercury have been studied under simulated estuarine conditions by monitoring the hydrophobicity and uptake of dissolved 203Hg(II) in samples from a variety of estuarine environments. A persistent increase in the distribution coefficientwith increasing salinity is inconsistent with inorganic speciation calculations, which predict an increase in the concentration of the soluble HgCl4(2-) complex (or reduction in sediment-water distribution coefficient) with increasing salinity. Partition data are, however, defined by an empirical equation relating to the salting out of nonelectrolytes via electrostriction and are characterized by salting constants between about 1.4 and 2.0 L mol(-1). Salting out of the neutral, covalent chloro-complex, HgCl2(0), is predicted but cannot account for the magnitude of salting out observed. Since Hg(II) strongly complexes with dissolved (and particulate) organic matter in natural environments, of more significance appears to be the salting out of Hg(II)-organic complexes. Operational measurements of the speciation of dissolved Hg(II) using Sep-Pak C18 columns indicate a reduction in the proportion of hydrophobic (C18-retained) dissolved Hg(II) complexes with increasing salinity, both in the presence and absence of suspended particles. Ratios of hydrophobic Hg(ll) before and after particle addition suggest a coupled salting out-sorption mechanism, with the precise nature of Hg(II) species salted out being determined bythe characteristics and concentrations of dissolved and sediment organic matter.

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OBJECTIVE: Evidence-based medicine is a growing paradigm in health care. We conducted a prospective study to determine whether laparoscopic surgery is truly evidence-based in everyday practice. METHODS: A prospective regional survey was performed in 11 French hospitals (one university and 10 district hospitals) to ascertain how general laparoscopic surgery was conducted during the last 3 months of 1997. We also searched the electronic databases for original articles on laparoscopic procedures. The methodology of randomized trials was analyzed and procedures were classed by level of evidence. We assumed that an evidence-based procedure was which had been validated by well-designed randomized controlled or prospective trials giving homogeneous results. RESULTS: One half of the procedures performed had been evaluated by randomized controlled trials. Among the 428 laparoscopic procedures, 334 (78%) were found to be evidence-based (CI 74.1-81.9%). Twelve of the 18 indications for laparoscopy (67%) were evidence based (CI: 62.5%-71.5). There was no difference between university teaching hospitals and general district hospitals. CONCLUSION: Contrary to initial criticisms, the practice of laparoscopic surgery appears to be truly evidence-based in the majority of cases.

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To study the vasopressin receptor domains involved in the hormonal binding, we synthesized natural and modified fragments of V1a vasopressin receptor and tested their abilities to affect hormone-receptor interactions. Natural fragments mimicking the external loops one, two, and three were able to inhibit specific vasopressin binding to V1a receptor. In contrast, the natural N-terminal part of the V1a vasopressin receptor was found inactive. One fragment, derived from the external second loop and containing an additional C-terminal cysteine amide, was able to fully inhibit the specific binding of both labeled vasopressin agonist and antagonist to rat liver V1a vasopressin receptor and the vasopressin-sensitive phospholipase C of WRK1 cells. The peptide-mediated inhibition involved specific interactions between the V1a receptor and synthetic V1a vasopressin receptor fragment since 1) it was dependent upon the vasopressin receptor subtype tested (Ki(app) for the peptide: 3.7, 14.6, and 64.5 microM for displacing [3H]vasopressin from rat V1a, V1b, and V2 receptors, respectively; 2) it was specific and did not affect sarcosin 1-angiotensin II binding to rat liver membranes; 3) it was not mimicked by vasopressin receptor unrelated peptides exhibiting putative detergent properties; and 4) no direct interaction between [3H]vasopressin and synthetic peptide linked to an affinity chromatography column could be observed. Such an inhibition affected both the maximal binding capacity of the V1a vasopressin receptor and its affinity for the labeled hormone, depending upon the dose of synthetic peptide used and was partially irreversible. Structure-activity studies using a serie of synthetic fragments revealed the importance of their size and cysteinyl composition. These data indicate that some peptides mimicking extracellular loops of the V1a vasopressin receptor may interact with the vasopressin receptor itself and modify its coupling with phospholipase C.

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At present, laparoscopic cholecystectomy is the treatment of choice for gallbladder stones. The operating technique reported by most authors includes the use of four trocars. We report a group of 710 consecutive patients treated by an original three-trocar technique. The use of the fourth trocar was necessary in only 55 cases (8%). However, among 56 cases of acute cholecystitis the use of the fourth trocar was necessary in 14 cases (25%) (p < 0.01). Twenty-six laparoscopies were converted to open procedures (3.6%). Four common bile duct injuries were observed (0.5%): two of them among the 655 operations with three trocars (0.3%) and two after application of the fourth trocar at the beginning of the procedure because of dissection difficulties. Our results are similar to those using the "classic" four-trocar technique. Moreover, this technique is less expensive and allows one less scar.

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