The effectiveness and safety of introducing condom-catheter uterine balloon tamponade for postpartum haemorrhage at secondary level hospitals in Uganda, Egypt and Senegal: a stepped wedge, cluster-randomised trial.

OBJECTIVE: To assess the effectiveness of introducing condom-catheter uterine balloon tamponade (UBT) for postpartum haemorrhage (PPH) management in low- and middle-income settings. DESIGN: Stepped wedge, cluster-randomised trial. SETTING: Eighteen secondary-level hospitals in Uganda, Egypt and Senegal. POPULATION: Women with vaginal delivery from October 2016 to March 2018. METHODS: Use of condom-catheter UBT for PPH management was introduced using a half-day training and provision of pre-packaged UBT kits. Hospitals were randomised to when UBT was introduced. The incident rate (IR) of study outcomes was compared in the control (i.e. before UBT) and intervention (i.e. after UBT) periods. Mixed effects regression models accounted for clustering (random effect) and time period (fixed effect). MAIN OUTCOME MEASURES: Combined IR of PPH-related invasive surgery and/or maternal death. RESULTS: There were 28 183 and 31 928 deliveries in the control and intervention periods, respectively. UBT was used for 9/1357 and 55/1037 women diagnosed with PPH in control and intervention periods, respectively. PPH-related surgery or maternal death occurred in 19 women in the control period (IR = 6.7/10 000 deliveries) and 37 in the intervention period (IR = 11.6/10 000 deliveries). The adjusted IR ratio was 4.08 (95% confidence interval 1.07-15.58). Secondary outcomes, including rates of transfer and blood transfusion, were similar in the trial periods. CONCLUSIONS: Introduction of condom-catheter UBT in these settings did not improve maternal outcomes and was associated with an increase in the combined incidence of PPH-related surgery and maternal death. The lack of demonstrated benefit of UBT introduction with respect to severe outcomes warrants reflection on its role. TWEETABLE ABSTRACT: Stepped wedge trial shows UBT introduction does not reduce the combined incidence of PPH-related surgery or death.

Exploring genotype concordance in epidemiologically linked cases of tuberculosis in New York City.

Comparing genotype results of tuberculosis (TB) isolates from individuals diagnosed with TB can support or refute transmission; however, these conclusions are based upon the criteria used to define a genotype match. We used a genotype-match definition which allowed for variation in IS6110 restriction fragment length polymorphism (RFLP) to support transmission between epidemiologically linked persons. Contacts of individuals with infectious TB (index cases) diagnosed in New York City from 1997 to 2003 who subsequently developed TB (contact cases) from 1997 to 2007 were identified. For each contact case and index case (case-pair), isolate genotypes (spoligotype and RFLP results) were evaluated. Isolates from case-pairs were classified as exact or non-exact genotype match. Genotypes from non-exact match case-pairs were reviewed at the genotyping laboratory to determine if the isolates met the near-genotype-match criteria (exactly matching spoligotype and similar RFLP banding patterns). Of 118 case-pairs identified, isolates from 83 (70%) had exactly matching genotypes and 14 (12%) had nearly matching genotypes (supporting transmission), while the remaining 21 (18%) case-pairs had discordant genotypes (refuting transmission). Using identical genotype-match criteria for isolates from case-pairs epidemiologically linked through contact investigation may lead to underestimation of transmission. TB programmes should consider the value of expanding genotype-match criteria to more accurately assess transmission between such cases.

Misoprostol for primary versus secondary prevention of postpartum haemorrhage: a cluster-randomised non-inferiority community trial.

OBJECTIVE: To assess whether secondary prevention, which preemptively treats women with above-average postpartum bleeding, is non-inferior to universal prophylaxis. DESIGN: A cluster-randomised non-inferiority community trial. SETTING: Health sub-centres and home deliveries in the Bijapur district of Karnataka, India. POPULATION: Women with low-risk pregnancies who were eligible for delivery with an Auxiliary Nurse Midwife at home or sub-centre and who consented to be part of the study. METHODS: Auxiliary Nurse Midwifes were randomised to secondary prevention using 800 mcg sublingual misoprostol administered to women with postpartum blood loss ≥350 ml or to universal prophylaxis using 600 mcg oral misoprostol administered to all women during the third stage of labour. MAIN OUTCOME MEASURES: Postpartum haemoglobin ≤7.8 g/dl, mean postpartum blood loss and postpartum haemoglobin, postpartum haemorrhage rate, transfer to higher-level facilities, acceptability and feasibility of the intervention. RESULTS: Misoprostol was administered to 99.7% of women as primary prevention. In secondary prevention, 92 (4.7%) women had postpartum bleeding ≥350 ml, of which 90 (97.8%) received misoprostol. The proportion of women with postpartum haemoglobin ≤7.8 g/dl was 5.9 and 8.8% in secondary and primary prevention clusters, respectively [difference -2.9%, one-sided 95% confidence interval (CI) <1.3%]. Postpartum transfer and haemorrhage rates were low (<1%) in both groups. Shivering was more common in primary prevention clusters (P = 0.013). CONCLUSION: Secondary prevention of postpartum haemorrhage with misoprostol is non-inferior to universal prophylaxis based on the primary outcome of postpartum haemoglobin. Secondary prevention could be a good alternative to universal prophylaxis as it medicates fewer women and is an acceptable and feasible strategy at the community level. TWEETABLE ABSTRACT: Secondary prevention of postpartum haemorrhage with misoprostol is non-inferior to universal prophylaxis.

HIV-positive patients treated for multidrug-resistant tuberculosis: clinical outcomes in the HAART era.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) and the human immunodeficiency virus (HIV) pose two of the greatest threats to global tuberculosis (TB) control. Given expanding global access to antiretroviral therapy (ART) and second-line TB drugs, more data are needed on experiences treating MDR-TB and HIV co-infection in resource-poor settings. OBJECTIVE: To describe the clinical characteristics, management, outcomes, and factors associated with survival among HIV-positive individuals receiving treatment for MDR-TB. DESIGN: This was a retrospective case series of 52 HIV-positive individuals receiving treatment for MDR-TB in Lima, Peru. We used Cox proportional hazards regression models to identify risk factors for mortality. RESULTS: A total of 31 (57%) of the cohort died on treatment, with the majority of deaths due to MDR-TB. Low baseline weight predicted a three-fold increased rate of death (aHR 3.1, 95%CI 1.5-6.7), while individuals receiving highly active ART experienced a significantly lower rate of death compared to those who were not (aHR 0.4, 95%CI 0.2-0.9). CONCLUSION: Early ART is likely a key component of effective MDR-TB management in co-infected individuals.

Degradation of pectins with different degrees of esterification by Bacteroides thetaiotaomicron isolated from human gut flora.

A complete human fecal flora and cultures of defined species obtained from fecal flora were investigated in vitro to determine their ability to ferment the dietary fiber pectin. Bacteroides thetaiotaomicron was tested as a pectin-degrading microorganism alone and in coculture with Escherichia coli. Macromolecular pectins with different degrees of esterification were used as substrates in microbial degradation studies. The levels of oligogalacturonic acids formed in batch cultures were estimated during a 24- or 48-h incubation period by using high-performance thin-layer chromatography and high-performance anion-exchange chromatography. The spectrum and the amount of unsaturated oligogalacturonic acids formed as intermediate products of pectin fermentation changed permanently in the culture media during incubation with the complete fecal flora. After 24 h, no oligogalacturonic acids were detected. The pectin-degrading activities of pure cultures of B. thetaiotaomicron were lower than the pectin-degrading activity of a complete fecal flora. Cocultures of B. thetaiotaomicron and E. coli exhibited intermediate levels of degradation activity. In pure cultures of E. coli no pectin-degrading activity was found. Additionally, the rate of pectin degradation was affected by the degree of esterification of the substrate. Saturated oligogalacturonic acids were not found during pectin fermentation. The disappearance of oligogalacturonic acids in the later stages of fermentation with both the complete fecal flora and B. thetaiotaomicron was accompanied by increased formation of short-chain fatty acids.

Effects of resistant starch on the colon in healthy volunteers: possible implications for cancer prevention.

Recent evidence suggests that resistant starch (RS) is the single most important substrate for bacterial carbohydrate fermentation in the human colon. During two 4-wk periods. 12 healthy volunteers consumed a controlled basal diet enriched with either amylomaize starch (55.2 +/- 3.5 g RS/d; high-RS diet) or available cornstarch (7.7 +/- 0.3 g RS/d; low-RS diet). Approximately 90% of the RS consumed disappeared during intestinal passage; increased fermentation was verified by elevated breath-hydrogen excretion. During the high-RS diet, fecal wet and dry weight increased 49% and 56%, respectively (P < or = 0.005), whereas stool water content did not change significantly. Fecal concentrations and daily excretion of short-chain fatty acids were not different in the two study periods. During the high-RS diet, bacterial beta-glucosidase activity decreased by 26% (P < or = 0.05). Fecal concentrations of total and secondary bile acids were significantly lower during the high-RS than during the low-RS period [a decrease of 30% (P < or = 0.05) and 32% (P < or = 0.01), respectively, in total and secondary bile acids] whereas concentrations of primary bile acids were unaffected by RS consumption. During the high-RS diet, fecal concentrations of total neutral sterols decreased by 30% (P < or = 0.005) and fecal concentrations of 4-cholesten-3-one decreased by 36% (P < or = 0.05). These data suggest that RS has potentially important effects on bacterial metabolism in the human colon that may be relevant for cancer prevention.

Interaction between food components and drugs. Part 6: Influence of starch degradation products on propranolol transport.

Interactions between different starch degradation products and propranolol (P) were studies using permeation experiments and affinity capillary electrophoresis (ACE). In the presence of maltooligosaccharides (MO), the transport of P across artificial lipid membranes was retarded. The most intensive interaction with the drug was found in the presence of the not-debranched MO from maize starch. The electrophoretic mobility mu of the drug was decreased in dependence of the MO concentration. However calculation of equilibrium binding constants from the ACE experiments was not possible because of the relatively weak influence of starch degradation products on the electrophoretic behaviour of the drug. With both methods the same tendency in strength of interactions between the different MO and P was found. Molecular parameters of the MO and their viscosity play a role in the interactions and in the decreased permeation of the drug.

Squash Yellow Leaf Curl Virus: A New Whitefly-Transmitted Poty-Like Virus.

A severe yellow and leaf curl disease affecting field squash was found in the Batinah region of the Sultanate of Oman. The symptoms appear as small yellow spots, diffuse veinal yellowing, and leaf curling of young leaves. The inciting virus was easily transmitted by mechanical inoculation and by the whitefly Bemisia tabaci in a semi-persistent manner. The host range of the virus was restricted to two cucurbit species. Leaf dip preparations contained few flexuous particles about 700 to 750 nm long. Pinwheel-like inclusion bodies were observed in thin sections of diseased squash tissues. Serological tests by enzyme-linked immunosorbent assay showed that the virus is serologically related to watermelon mosaic virus-2, but not to zucchini yellow mosaic virus or papaya ring spot virus (watermelon strain). In view of these properties, this virus is considered to be a newly described virus and is tentatively named squash yellow leaf curl virus.

Characterization of fat replacers.

Effects of commercial fat replacers on rheological properties of emulsions have been studied under a second-order design. The corresponding functions of regression have been calculated to describe the measured effects mathematically. On the basis of a figured three-dimensional plan of response, combinations of variables (fat, fat replacer, water) could be determined showing a similar consistency to the corresponding full-fat foodstuff.

[Biotinidase deficiency--a progressive metabolic disease in children with seizures and ataxia]. / Der Biotinidasemangel--Eine progrediente Stoffwechselerkrankung des Kindesalter mit Krampfanfällen und Ataxie.

Biotinidase deficiency is the primary biochemical defect in late-onset multiple carboxylase deficiency and an autosomal recessive disorder and characterized by seizures, ataxia, alopecia and skin rash. We describe a colorimetric semiquantitative method for screening for biotinidase activity from dried samples of whole blood spotted on filter papers. The administration of biotin to affected children can be a lifesaving procedure and can prevent irreversible neurologic damage.

Interaction of iloprost and indomethacin with the cardiac effects of isoprenaline, ouabain and trapidil.

Investigations in isolated heart preparations of guinea pigs showed, that iloprost enhanced the increase of cardiac performance by isoprenaline, but inhibit the positive inotropic effect of ouabain. On the other side pretreatment with indomethacin induced a significant rise of the cardiac effects of both isoprenaline and ouabain. The efficacy of trapidil and oxyfedrine remained uninfluenced. The results indicate, that prostanoids and cyclooxygenase inhibitors influence the effects of the investigated cardiac drugs. This is possibly be due to changes in the cellular membrane and the intracellular calcium content and should be considered in the therapeutic use of these substances.

Growth of Mycoplasma bovis in organ cultures of bovine foetal trachea and comparison with Mycoplasma dispar.

Inoculation of tracheal organ cultures from bovine foetuses with Mycoplasma bovis resulted in a loss of cellular structure of the lamina propria, followed 20-22 days later by lifting and detachment of overlying epithelium. The effect was associated with large numbers of M. bovis, identified by immunoperoxidase labelling and electromicroscopy, infiltrating between the epithelial cells and amassing in the lamina propria, especially in the region of the basement membrane of the epithelium. Ciliary activity was undiminished for up to 18 days following inoculation and little or no cytopathic effect on the ciliated epithelium was seen in spite of the close proximity of large numbers of organisms. In contrast, M. dispar was restricted to the margin of the ciliated epithelium where, as previously reported, it caused pyknosis, sloughing and flattening of the epithelium with consequent loss of ciliary activity. The cytopathology observed for each mycoplasma bore a close similarity to the behaviour of the two mycoplasmas in vivo and it is suggested that the organ culture system may be a useful and relevant system to elucidate the pathogenic mechanisms for each mycoplasma.

Emigration of polymorphonuclear leucocytes into the intestinal lumen of the neonatal piglet in response to challenge with K88-positive Escherichia coli.

The emigration of neutrophils from the blood of neonatal piglets into the intestinal lumen in response to a K88-positive strain of Escherichia coli was investigated. The pig herd used was of known genetic susceptibility to K88-positive E coli and had recently experienced an outbreak of neonatal diarrhoea. Neutrophil emigration depended on certain factors. Neutrophils emigrated into ligated loops in susceptible piglets sucking immune colostrum from susceptible dams but not into loops in colostrum deprived resistant piglets or piglets sucking non-immune colostrum from resistant dams. In susceptible, colostrum deprived piglets neutrophils in intestinal contents were only associated with severe lesions. Large numbers of neutrophils which appeared at several foci on the villi were observed in three of six resistant piglets that sucked immune colostrum from susceptible dams. It was concluded that neutrophil emigration into the intestinal lumen of piglets could occur in response to K88-positive E coli and resulted not from the presence or absence of the intestinal K88-receptor but from the ingestion of immune colostrum.

Aclarubicin (aclacinomycin A) in the treatment of relapsing acute leukaemias.

Forty patients with relapsing acute leukaemias were treated with aclacinomycin A (aclarubicin, ACM), 25 mg/m2 i.v. daily for 7 days. Twenty-nine patients with acute myeloid (AML) and five with acute lymphoblastic (ALL) leukaemia were evaluable. The overall response rate was 29.5%. Eight complete (CR) and one partial (PR) remissions were achieved in AML (31%). A high CR rate was induced in patients treated at first relapse without prior reinduction (6/12 patients). A small proportion of leukaemias resistant to daunorubicin or doxorubicin responded to ACM (3/17 patients). Median remission duration was 5.5 months (range: 2-9 months). The most common toxic effects were nausea, vomiting, stomatitis and diarrhoea. Acute cardiotoxic effects were documented in three patients. Congestive cardiomyopathy was not observed despite prior treatment with anthracyclines. We conclude that the present dose scheduling of ACM is effective in the treatment of relapsing AML and that it should be introduced in combined chemotherapy in phase III trials to compare its activity to that of daunorubicin or doxorubicin.