Enhancing departmental preparedness for COVID-19 using rapid-cycle in-situ simulation.

In response to coronavirus disease 2019 (COVID-19), a rapid-cycle in-situ simulation (ISS) programme was developed to facilitate identification and resolution of systems-based latent safety threats. The simulation involved a possible COVID-19 case in respiratory failure, using a mannequin modified to aerosolize phosphorescent secretions. Thirty-six individuals participated in five ISS sessions over 6 weeks, and a further 20 individuals observed these sessions. Debriefing identified latent safety threats from four domains: personnel, personal protective equipment, supply/environment and communication. These threats were addressed and resolved in later iterations. Ninety-four percent of participants felt more prepared to care for a potential case of COVID-19 after the ISS.

Prevention of mother-to-child transmission of HIV: a cross-sectional study in Malawi.

OBJECTIVE: To estimate the use and outcomes of the Malawian programme for the prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). METHODS: In a cross-sectional analysis of 33 744 mother-infant pairs, we estimated the weighted proportions of mothers who had received antenatal HIV testing and/or maternal antiretroviral therapy and infants who had received nevirapine prophylaxis and/or HIV testing. We calculated the ratios of MTCT at 4-26 weeks postpartum for subgroups that had missed none or at least one of these four steps. FINDINGS: The estimated uptake of antenatal testing was 97.8%; while maternal antiretroviral therapy was 96.3%; infant prophylaxis was 92.3%; and infant HIV testing was 53.2%. Estimated ratios of MTCT were 4.7% overall and 7.7% for the pairs that had missed maternal antiretroviral therapy, 10.7% for missing both maternal antiretroviral therapy and infant prophylaxis and 11.4% for missing maternal antiretroviral therapy, infant prophylaxis and infant testing. Women younger than 19 years were more likely to have missed HIV testing (adjusted odds ratio, aOR: 4.9; 95% confidence interval, CI: 2.3-10.6) and infant prophylaxis (aOR: 6.9; 95% CI: 1.2-38.9) than older women. Women who had never started maternal antiretroviral therapy were more likely to have missed infant prophylaxis (aOR: 15.4; 95% CI: 7.2-32.9) and infant testing (aOR: 13.7; 95% CI: 4.2-83.3) than women who had. CONCLUSION: Most women used the Malawian programme for the prevention of MTCT. The risk of MTCT increased if any of the main steps in the programme were missed.

Characteristics and outcomes of women initiating ART during pregnancy versus breastfeeding in Option B+ in Malawi.

BACKGROUND: Malawi adopted the PMTCT strategy 'Option B+' in 2011, providing life-long ART for all HIV-infected pregnant and breastfeeding women. We explored differences in characteristics and outcomes of women initiating ART during pregnancy versus breastfeeding. METHODS: We conducted a retrospective cohort analysis of women in Zomba District, southern Malawi, from January 2012- September 2013. Data were extracted from the Zomba District Observational Cohort Study, a surveillance project collecting data from standardized Ministry of Health ART monitoring tools. RESULTS: 1986 (67.2 %) women initiated ART during pregnancy and 969 (32.8 %) during breastfeeding. Women initiating ART in breastfeeding were more likely to be > 30 years (aOR = 1.33, 95 % CI1.11-1.59, p = 0.003) and have WHO Stage 3/4 (aOR = 2.74, 95 % CI1.94-3.87, p < 0.001). Eighteen (0.6 %) deaths occurred and 942 (31.9 %) women defaulted ART. 'Early' death (< 30 days) occurred in 3 (0.1 %) women and 449 (16.4 %) women defaulted early. Death/default < 30 days was more likely among women initiating ART during pregnancy (aOR 1.62, 95 % CI1.28-2.05, p < 0.001) or < 30 years old (aOR 1.27, 95 % CI 1.02-1.57, p = 0.03) and was less likely among those with WHO Stage 3/4 (aOR 0.30, 95 % CI 0.15-0.60, p < 0.001). Using Kaplan-Meier estimators to investigate time to death/default, we showed a sharp drop in death/default-free survival probability at time zero, yet survival probability decreased in a nearly linear manner after this initial period of high default. Women under 30 years had increased rates of death/default over time (log rank test: p < 0.001), however no significant differences were observed in death/default over time associated with timing of ART initiation, documented clinical stage at initiation, health clinic size or adherence rates. CONCLUSIONS: Many women in Malawi started ART during breastfeeding within Option B+ and were older and had more advanced WHO Clinical Staging. This represents a missed PMTCT opportunity to initiate treatment early in pregnancy. Early defaulting is identified as a challenge within Option B+, and was more likely among younger women and those initiating ART in pregnancy. Targeted research to understand factors associated with uptake of ART during pregnancy and retention in care could improve the efficacy of Option B+ in Malawi.

Volcanology. A large magmatic sill complex beneath the Toba caldera.

An understanding of the formation of large magmatic reservoirs is a key issue for the evaluation of possible strong volcanic eruptions in the future. We estimated the size and level of maturity of one of the largest volcanic reservoirs, based on radial seismic anisotropy. We used ambient-noise seismic tomography below the Toba caldera (in northern Sumatra) to observe the anisotropy that we interpret as the expression of a fine-scale layering caused by the presence of many partially molten sills in the crust below 7 kilometers. This result demonstrates that the magmatic reservoirs of present (non-eroded) supervolcanoes can be formed as large sill complexes and supports the concept of the long-term incremental evolution of magma bodies that lead to the largest volcanic eruptions.

Hepatitis B or hepatitis C coinfection in HIV-infected pregnant women in Europe.

OBJECTIVES: The aim of the study was to investigate the prevalence of and risk factors for hepatitis C or B virus (HCV or HBV) coinfection among HIV-infected pregnant women, and to investigate their immunological and virological characteristics and antiretroviral therapy use. METHODS: Information on HBV surface antigen (HBsAg) positivity and HCV antibody (anti-HCV) was collected retrospectively from the antenatal records of HIV-infected women enrolled in the European Collaborative Study and linked to prospectively collected data. RESULTS: Of 1050 women, 4.9% [95% confidence interval (CI) 3.6-6.3] were HBsAg positive and 12.3% (95% CI 10.4-14.4) had anti-HCV antibody. Women with an injecting drug use(r) (IDU) history had the highest HCV-seropositivity prevalence (28%; 95% CI 22.8-35.7). Risk factors for HCV seropositivity included IDU history [adjusted odds ratio (AOR) 2.92; 95% CI 1.86-4.58], age (for > or =35 years vs. <25 years, AOR 3.45; 95% CI 1.66-7.20) and HBsAg carriage (AOR 5.80; 95% CI 2.78-12.1). HBsAg positivity was associated with African origin (AOR 2.74; 95% CI 1.20-6.26) and HCV seropositivity (AOR 6.44; 95% CI 3.08-13.5). Highly active antiretroviral therapy (HAART) use was less likely in HIV/HCV-seropositive than in HIV-monoinfected women (AOR 0.34; 95% CI 0.20-0.58). HCV seropositivity was associated with a higher adjusted HIV RNA level (+0.28 log(10) HIV-1 RNA copies/mL vs. HIV-monoinfected women; P=0.03). HIV/HCV-seropositive women were twice as likely to have detectable HIV in the third trimester/delivery as HIV-monoinfected women (AOR 1.95; P=0.049). CONCLUSIONS: Although HCV serostatus impacted on HAART use, the association between HCV seropositivity and uncontrolled HIV viraemia in late pregnancy was independent of HAART.

Comparative kinetic analysis of cholinesterase methods in rat and human erythrocytes and plasma.

A kinetic analysis of the substitution of 6,6'-dithiodinicotinic acid (DTNA) for 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) for the determination of rat and human erythrocyte acetylcholinesterase (AChE; EC 3.1.1.7) and plasma butyrylcholinesterase (BuChE; EC 3.1.1.8) is presented. Increasing concentrations of DTNB, but not DTNA, significantly increased Km for the substrate acetylthiocholine but had little or no effect on Vmax for rat or human AChE. The coupling agent DTNA was more efficient than DTNB, as demonstrated by the higher Vmax/Km ratio for the former. DTNB, more so than DTNA, caused linear mixed-type inhibition of rat AChE. Poor precision was observed for the DTNB versus DTNA method. Reagent blanks were a significant component of rat, but not human, AChE activity. The use of DTNA in place of DTNB is recommended for quantitative mechanistic investigations of cholinesterases. The most practical aspect of the DTNA method is that it can be adapted to automated instruments which can monitor the change in absorbance at 340 nm, away from the hemoglobin peak.

Pretreatment of rats with anticollagen IgG renders them resistant to active type II collagen arthritis.

Intravenous administration of 24 mg of affinity-purified rat anticollagen IgG induced a polyarthritis in recipient rats within 48 hr. This polyarthritis was transient and hind paw diameters returned to normal values within 12 days. IgG and C3 could be detected on the articular cartilage by immunofluorescence up to 16 days after antibody administration. Administration of 24 mg of rat anticollagen IgG to these antibody-treated rats did not induce a second phase of polyarthritis. In addition, recovered rats that had been pretreated with antibody were resistant to arthritis when Type II collagen was administered intradermally. In these rats, serum anticollagen IgG levels were significantly lower than in control rats which were not treated with antibody. Pretreatment of rats with anticollagen IgG did not have an effect on the severity or the incidence of adjuvant-induced arthritis. In addition, pretreatment of rats with anticollagen IgG did not have an effect on the development of a humoral response to ovalbumin.

Suppression of type II collagen-induced arthritis by the intravenous administration of type II collagen or its constituent peptide alpha 1 (II) CB10.

Intravenous administration of Type II collagen to rats prior to immunization with Type II collagen suppresses hind paw inflammation, humoral response to Type II collagen, and the severity of the arthritic lesion. Suppression of inflammation and its severity as well as the humoral response can also be induced by the prior intravenous administration of alpha 1 (II) CB10 a cyanogen bromide peptide derived from Type II collagen. Suppression of arthritis is disease specific; intravenous administration of either Type II collagen or alpha 1 (II) CB10 does not have an effect on adjuvant-induced arthritis. These studies indicate that structural determinants of alpha 1 (II) CB10 (Mr 30,000), a peptide located near the carboxy terminus of the collagen molecule, can induce suppression and suggest that these determinants may be responsible for the suppression of arthritis when Type II collagen is administered intravenously.

Induction of collagenase synthesis in chondrocytes by a factor synthesized by inflamed synovial tissue.

Rabbit inflamed synovial tissue grown in culture synthesizes a factor that induces collagenase synthesis in chondrocytes and in cartilage. Synthesis of this factor by the synovial tissue is inhibited by cycloheximide but not by indomethacin. The factor has an apparent molecular weight of 30,000, is stable to heat and to trypsin treatment but is inactivated by acid. Induction of collagenase synthesis in chondrocytes occurs after a lag period of 6 hours.

Type II collagen-induced arthritis. Studies with purified anticollagen immunoglobulin.

Immunization of rats with native bovine type II collagen results in a polyarthritis by day 21 in approximately 40% of the rats. Sera of these rats contained anticollagen IgG, principally IgG2a. Small amounts of IgG2b were also detected, but IgG1 and IgG2c were absent. By enzyme-linked immunosorbent assay, the paw tissue of these polyarthritic rats was shown to contain anticollagen IgG, the principal subclass being IgG2a, with minor amounts of IgG2b. Immunofluorescence examination of the paws from polyarthritic rats demonstrated deposition of both IgG and C3 on the articular surface. Passive transfer of disease was accomplished by injection of affinity-purified anticollagen immunoglobulin into naive recipients; paw swelling and histopathologic changes were detected 24 hours after transfer, and by immunofluorescence techniques IgG and C3 deposits were demonstrable on the articular cartilage. On passive transfer, neutrophils invaded the joint space and became juxtaposed to the surface of the articular cartilage. Passive transfer of the disease with anticollagen immunoglobulin was unsuccessful after rats were decomplemented with cobra venom factor; immunofluorescence demonstrated IgG but not C3 on the articular cartilage of these decomplemented rats. In rats decomplemented with cobra venom factor, neutrophils did not accumulate in the joint and erosion of articular cartilage was not detected.

Anti-inflammatory and analgesic profile of amidines of 3-amino-1,2,4-benzotriazine and 3-amino-1,2,4-benzotriazine-1-oxide.

Several formamidine and acetamidine derivatives prepared from 3-amino-1,2,4-benzotriazine and 3-amino-1,2,4-benzotriazine-1-oxide displayed an aspirin-like anti-inflammatory and analgesic profile. The test systems include adjuvant-induced arthritis in rats, carrageenan-induced edema in rats, UV-induced erythema in guinea pigs, the analgesic gait test, the antipyretic test, and GI ulcer studies.

Destruction of articular cartilage by arthritic synovium in vitro: mechanism of breakdown and effect of indomethacin and prednisolone.

Arthritic synovial tissue when cultured with normal articular cartilage induces a breakdown of articular cartilage proteoglycans. No collagen breakdown occurs unless the macroglobulins are inactivated by pretreatment with acid. Proteoglycan breakdown is most likely due to the continuous secretion of hydrolases by the synovium. A proteolytic enzyme has been found in the culture medium which has a pH optimum around 7.6, and is Ca++ dependent. Both indomethacin and hydrocortisone are inhibitors of proteoglycan breakdown.