Comparing Catastrophic Costs: Active vs. Passive Tuberculosis Case Finding in Urban Vietnam.

Active case finding (ACF) is a strategy that aims to identify people with tuberculosis (TB) earlier in their disease. This outreach approach may lead to a reduction in catastrophic cost incurrence (costs exceeding 20% of annual household income), a main target of WHO's End TB Strategy. Our study assessed the socio-economic impact of ACF by comparing patient costs in actively and passively detected people with TB. Longitudinal patient cost surveys were prospectively fielded for people with drug-sensitive pulmonary TB, with 105 detected through ACF and 107 passively detected. Data were collected in four Vietnamese cities between October 2020 and March 2022. ACF reduced pre-treatment (USD 10 vs. 101, p < 0.001) and treatment costs (USD 888 vs. 1213, p < 0.001) in TB-affected individuals. Furthermore, it reduced the occurrence of job loss (15.2% vs. 35.5%, p = 0.001) and use of coping strategies (28.6% vs. 45.7%, p = 0.004). However, catastrophic cost incurrence was high at 52.8% and did not differ between cohorts. ACF did not significantly decrease indirect costs, the largest contributor to catastrophic costs. ACF reduces costs but cannot sufficiently reduce the risk of catastrophic costs. As income loss is the largest driver of costs during TB treatment, social protection schemes need to be expanded.

Safety and immunogenicity of Nanocovax, a SARS-CoV-2 recombinant spike protein vaccine: Interim results of a double-blind, randomised controlled phase 1 and 2 trial.

Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant. Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients. Findings: For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 [CI95%: 51·12-71·55], 49·11 [41·26-58·46], 57·18 [48·4-67·5] compared to 7·10 [6·32-13·92] of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 [52·2-152·3], 80·0 [50·8-125.9] and 95·1 [63·1-143·6], compared to 55·1 [33·4-91·0] of the convalescent group. Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. Funding: This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC.

Electric field and charged impurity doping effects on the Schottky anomaly of ß12-borophene.

Due to the coexistence of Dirac and triplet fermions, monolayer ß12-borophene has recently attracted both experimental and theoretical researchers. In particular, various phase transitions have been recently reported in the structure, in the presence of dilute charged impurity and a perpendicular electric field, leading to interesting electronic heat capacity (HC). In this paper, we systematically examine the effects of charged impurity doping and electric field on the HC of monolayer ß12-borophene. To do this, we utilize the five-band tight-binding Hamiltonian model, the Green's function, T-matrix, and the Born approximation for different models considering the substrate effects. Numerical analysis reveals that the inversion symmetric model is the proper model in the pristine and perturbed metallic ß12-borophene, leading to a regular reduction of HC with both charged impurity and electric field. Moreover, the pristine and perturbed Schottky anomaly alterations are fully addressed. Unforeseeably, HC irregularly fluctuates with impurity in the homogeneous model. We believe that our results provide new physical insights into the thermal properties of monolayer ß12-borophene.

Lung transplant programs in developing countries: challenges, solutions, and outcomes.

PURPOSE OF REVIEW: The majority of lung transplants (LT) performed are in developed countries. In contrast, little is known about the status of LT in developing nations. The objective is to summarize the challenges, present solutions, and review outcomes of LT in developing countries. We hope this review will guide healthcare providers in such countries that are contemplating embarking on this journey. RECENT FINDINGS: The key challenges that programs in developing countries encountered included shortage and marginal quality of donated organs, lack of dedicated multi-disciplinary LT team, limited availability of advanced technology and high risk of post-transplant infections. Education and collaboration among government, public, and healthcare sectors was seen as fundamental to building and maintaining a successful program. Despite minimal resources and huge challenges, LT survival rates in developing countries improved and were comparable with outcomes reported by the International Society for Heart and Lung Transplantation (ISHLT) Registry. SUMMARY: Starting a new LT program is a daunting task that is complex and resource intensive, especially in developing countries. Improving outcomes indeed provide impetus to continue to persevere in this endeavor with support from all sectors. The findings presented here could help new programs to better anticipate and tackle challenges.

Genetic structure of farmer-managed varieties in clonally-propagated crops.

The relative role of sexual reproduction and mutation in shaping the diversity of clonally propagated crops is largely unknown. We analyzed the genetic diversity of yam-a vegetatively-propagated crop-to gain insight into how these two factors shape its diversity in relation with farmers' classifications. Using 15 microsatellite loci, we analyzed 485 samples of 10 different yam varieties. We identified 33 different genotypes organized in lineages supported by high bootstrap values. We computed the probability that these genotypes appeared by sexual reproduction or mutation within and between each lineage. This allowed us to interpret each lineage as a product of sexual reproduction that has evolved by mutation. Moreover, we clearly noted a similarity between the genetic structure and farmers' classifications. Each variety could thus be interpreted as being the product of sexual reproduction having evolved by mutation. This highly structured diversity of farmer-managed varieties has consequences for the preservation of yam diversity.

Functional correlates of fundus autofluorescence abnormalities in patients with RPGR or RIMS1 mutations causing cone or cone rod dystrophy.

AIM: The aim of this study was to establish the functional significance of annular macular abnormalities present on fundus autofluorescence imaging (AF) in patients with cone or cone-rod dystrophy. METHODS: Fundus AF was performed on ten subjects (age range 18-82 years) with cone or cone-rod dystrophy consequent upon RPGR or RIMS1 mutation. International-standard full-field and pattern electroretinograms (ERGs) were performed in all cases. Photopic and scotopic fine matrix mapping (FMM) and multifocal ERG were performed on selected cases. RESULTS: Subjects had annuli of high density AF that bordered central areas of low density in older RPGR cases and most RIMS1 cases. The size of the AF ring correlated with age and enlarged with time in two subjects. High-density rings were associated with a gradient of scotopic and photopic sensitivity loss. Pattern electroretinogram (PERG) P50 amplitude, when detectable, was inversely related to the size of the AF ring. Multifocal ERGs in two subjects showed widespread reduction with relative sparing over the foveal area, in keeping with FMM data. CONCLUSIONS: Some patients with cone-rod dystrophy have a parafoveal ring of increased autofluorescence that may enlarge with time. Increased autofluorescence is associated with reduced rod and cone sensitivity, rather than photoreceptor cell death, and AF imaging may help identify viable areas of retina amenable to future therapeutic intervention.

Diabetic macular oedema: pilot randomised trial of pars plana vitrectomy vs macular argon photocoagulation.

INTRODUCTION: Focal macular photocoagulation for clinically significant macular oedema (CSME) is the proven method for treatment of this condition, but with little chance of visual improvement. Pars plana vitrectomy (PPV) may produce resolution of macular oedema and improvement in visual acuity. However, there have been no randomised trials to ascertain role of vitrectomy in the management of persistent CSME. METHODS: Patients with persistent CSME despite previous macular photocoagulation and Snellen visual acuity 6/15 to 6/60 were recruited. Dilated fundoscopy, best-corrected visual acuity including Early Treatment Diabetic Retinopathy Study (ETDRS) vision, ocular coherence tomography and fundus fluorescein angiography (FFA) at baseline and up to 12 months post-treatment was performed. Exclusion criteria were signs of posterior vitreous detachment, macular traction or the taut posterior hyaloid face syndrome, or macular ischaemia on FFA. In all, 20 patients were randomised (10 in each arm) to either standard macular photocoagulation or PPV and removal of the posterior hyaloid face. RESULTS: Of the 20 patients recruited, seven patients completed the protocol in the vitrectomy and eight in the laser arms, respectively. There was little evidence of any difference in the foveal thickness at 12 months between the two treatment arms despite a gradual improvement. Only one patient, from the vitrectomy arm, suffered moderate visual loss (defined as loss of 15 ETDRS letters) (our primary outcome). DISCUSSION: In this pilot RCT, standard PPV provides little visual benefit compared to macular photocoagulation, but a larger definitive study is required to confirm this early appraisal.

Pars plana vitrectomy for diabetic macular oedema: OCT and functional correlations.

PURPOSE: A prospective study to evaluate the macular structural and functional effects of pars plana vitrectomy (PPV) for persistent diffuse clinically significant macular oedema (CSMO). METHOD: A total of 12 patients with persistent diffuse CSMO were recruited and underwent assessment including best-corrected visual acuity, fundus fluorescein angiography, optical coherence tomography (OCT) and fine matrix mapping (FMM) at baseline and over a period of a year poststandard three-port PPV. RESULTS: The median baseline ETDRS letters score for all 12 patients was 52 (range 41-63) while at 12 months it had increased to 65 (range of 27-68), an improvement of two complete ETDRS lines (P=0.037). Similarly, there was an improvement in the perifoveal cone thresholds (P=0.02). The foveal thickening for all 12 patients ranged from a median of 183 to 751 microm (normal range 126-180 microm) and the macular volume ranged from a median of 2.13 to 6.42 mm(3) (normal <1.66 mm(3)). After surgery, both the median foveal thickness (from 334 to 280 microm) and median macular volume (from 3.24 to 2.61 mm(3)) demonstrated decreases over 12 months (P=0.01). On baseline OCT, the patients fell into two anatomically distinct groups: Group 1 (n=4) had a dome-shaped thickened macula with a partial posterior hyaloid separation and a significantly higher foveal thickness and macular volume than Group 2 (n=8) which had a diffuse low-elevation profile of the thickened macula (P=0.007). CONCLUSIONS: In this prospective study of PPV for persistent fovea-involving CSMO there was structural and functional improvement.

En face optical coherence tomography: a new method to analyse structural changes of the optic nerve head in rat glaucoma.

AIM: To investigate en face optical coherence tomography (eOCT) and its use as an effective objective technique for assessing changes in the glaucomatous rat optic nerve head (ONH) in vivo, and compare it with confocal scanning laser ophthalmoscopy (cSLO). METHODS: 18 Dark Agouti (DA) rats with surgically induced ocular hypertension were imaged with eOCT and cSLO at regular intervals. Assessment included three dimensional (3D) topographic reconstructions, intensity z-profile plots, a new method of depth analysis to define a "multilayered" structure, and scleral canal measurements, in relation to the degree of intraocular pressure (IOP) exposure. RESULTS: The increased depth resolution of the eOCT compared to the cSLO was apparent in all methods of analysis, with better discrimination of tissue planes. This was validated histologically. eOCT demonstrated several significant changes in imaged rat ONH which correlated with IOP exposure, including the area of ONH (p<0.01), separation between retinal vessel and scleral layers (p<0.05), and anterior scleral canal opening expansion (p<0.05). CONCLUSION: eOCT appears to be effective in assessing rat ONH, allowing detailed structural analysis of the multilayered ONH structure. As far as the authors are aware, this is the first report of scleral canal expansion in a rat model. They suggest eOCT as a novel method for the detection of early changes in the ONH in glaucoma.

One year recurrence of trachomatous trichiasis in routinely operated Cuenod Nataf procedure cases in Vietnam.

BACKGROUND: Recurrence of trichiasis following surgery remains unacceptably high, regardless of the surgical procedure. Few prospective studies of sufficient size are available to assess the rate of recurrence and the factors contributing to recurrence. A prospective study of the modified Cuenod Nataf surgical procedure was conducted in Vietnam to determine recurrence and co-factors. METHODS: The prospective study of Cuenod Nataf surgery for trachomatous trichiasis took place in four districts of Vietnam. All patients from identified villages who had surgery were followed for a period of 1 year. 10 Surgeons using standard techniques and recording procedures carried out the surgery. The presence of an eyelash touching the eyeball in the operated eye was considered as recurrence. Information on all subjects was recorded preoperatively, intraoperatively, and postoperatively. An independent examiner recorded postoperative information. Relative risks were calculated to assess the contribution of various risk factors to recurrence (by eye and by person). Cox proportional hazards modelling was used to assess the independent contribution of relevant factors to the outcome. RESULTS: 471 individuals had trichiasis surgery; 463 were followed for a period of 1 year. Overall, the recurrence rate was 10.8% (95% CI 8.0 to 13.6). Among people having surgery recurrence (one or both eyes) was most common in the most elderly (relative risk (RR) 2.49) and among those with a history of previous surgery (RR = 2.49). Cox proportional hazards analysis (by eye) revealed that visual acuity, conjunctival scarring, and suture adjustment were associated with recurrence at 1 year. CONCLUSION: The Cuenod Nataf procedure, which is well accepted in the community and by eye care providers in Vietnam, has an acceptable 1 year success rate. Individuals with severe conjunctival scarring have the highest rate of recurrence suggesting that other surgical approaches are needed to manage these patients or that these patients need to be educated regarding the risk of recurrence. Active follow up of these patients would be warranted. The association with suture adjustment requires further investigation.

Aging, carotid artery distensibility, and the Ser422Gly elastin gene polymorphism in humans.

Elastin is a protein of the extracellular matrix that forms the major component of elastic fibers from the arterial wall thickness and plays an important role in elastic properties of large blood vessels. To study the relationships between the Ser422Gly polymorphism in exon 16 of the gene-encoding elastin and the distensibility of 2 different arteries, the radial artery (a muscular artery) and the common carotid artery (an elastic artery), we studied a cohort of 320 subjects (49+/-12 years of age) without evidence of cardiovascular disease and who had never been treated with cardiovascular drugs. Distensibility and elastic modulus were evaluated for the common carotid and the radial arteries with high-resolution echo-tracking devices (NIUS-02 and Wall Track System). The A-to-G nucleotide change corresponding to the Ser422Gly amino acid change was studied by digestion of polymerase chain reaction products with BstNI. Results indicate that genotype frequencies (AA=10%, AG=51%, GG=39%) were in agreement with the Hardy-Weinberg equilibrium. For the carotid artery, a significant decrease in distensibility was observed in subjects carrying the A allele (with AA+AG genotypes) compared with subjects with the GG genotype (13.8+/-6.4 kPa(-1). 10(-3) versus 15.9+/-6.2 kPa(-1). 10(-3), P<0.01), assuming a dominant effect of the A allele. Moreover, the presence of the A allele was associated with a significant increase in elastic modulus (0.98+/-0.40 kPa. 10(3) in subjects with AA+AG genotypes versus 0.83+/-0.41 kPa. 10(3) in subjects with GG genotypes, P<0.01). Multivariate analysis indicated that these results were observed after adjustment for age, gender, and mean arterial blood pressure (P<0.01). In contrast, no association was found between arterial parameters and genotypes for the radial artery. The 2-way analysis of covariance adjusted for mean arterial blood pressure indicated that the association between the A allele and distensibility of the carotid artery was observed only in subjects >50 years of age, assuming for carotid distensibility a significant age effect (P<0.01), genotype effect (P=0.01), and age-genotype interaction (P=0.04). The present results indicate a relationship between the Ser422Gly polymorphism and the distensibility of elastic arteries but not of muscular arteries and suggest that there is an age-genotype interaction for carotid artery distensibility.

Association between the apolipoprotein E polymorphism and arterial wall thickness in asymptomatic adults.

OBJECTIVES: The polymorphism of the apolipoprotein E gene (epsilon2, epsilon3, epsilon4) affects plasma cholesterol but the relationship with artery wall thickness has indicated contradictory results. This study investigated the relationship between apolipoprotein E polymorphism and vascular phenotypes of the carotid and radial arteries, two arterial sites differently affected by atherosclerosis. METHODS: We studied a cohort of 320 Caucasian subjects (age 49 +/- 12 years) without evidence of cardiovascular disease. Structural (internal diameter and wall thickness) and functional phenotypes (compliance, distensibility) were evaluated for the common carotid and the radial arteries using high resolution echo-tracking devices. Genotypes of apolipoprotein E were determined by allele-specific oligonucleotides hybridization. Because of the relative low frequency of some apolipoprotein E genotypes, they were designated as E2 (epsilon2/epsilon2, epsilon2/epsilon3), E3 (epsilon3/epsilon3), and E4 (epsilon4/epsilon4, epsilon3/epsilon4). RESULTS: Apolipoprotein E allele frequencies were epsilon2 = 0.08, epsilon3 = 0.79, epsilon4 = 0.13. Subjects with epsilon4 allele had the highest levels of total serum cholesterol and low density lipoprotein cholesterol; subjects with epsilon2 allele had the lowest levels (P < 0.001). Considering carotid hypertrophy as intima-media thickness > 660 microm, and radial hypertrophy as intima-media thickness > 260 microm, a logistic regression model testing determinants of arterial hypertrophy (age, gender, weight, systolic blood pressure, smoking habits, and total serum cholesterol) observed a significant and positive association between carotid hypertrophy and epsilon2 allele carriers (P= 0.03). In contrast, no association was found between hypertrophy and apolipoprotein E genotypes for the radial artery. No association was observed between the apolipoprotein E genotypes and functional artery parameters. CONCLUSIONS: In subjects without any evidence of cardiovascular disease, the presence of the epsilon2 allele is related to wall hypertrophy in carotid artery despite favourable effect on the lipid profile.

Determination of copper in environmental matrices following vapor generation.

Copper was determined in environmental matrices following generation, separation, and atomization of a volatile species formed by the merging of an acidified sample solution with an aqueous sodium tetrahydroborate solution at room temperature. The copper species, as yet unidentified, was phase separated in a conventional gas-liquid separator and directed via a stream of Ar carrier gas to an inductively coupled plasma atomic emission detection system. Optimum conditions for generation were investigated. The efficiency of generation/transfer was estimated to be 50%, and no interference from the presence of 1000 mg/L concentration of As, Cd, Co, Ni, Fe, Cr, Mn, Pb, Se, and Zn concomitants was evident. Simple aqueous standards were used for calibration purposes, and good agreement was obtained with certified values in the analysis of National Research Council of Canada marine sediment BCSS-1 and lobster hepatopancreas tissue TORT-1.

Screening donor blood for malaria by polymerase chain reaction.

In countries where malaria is endemic, its transmission is a hazard of blood transfusion. The microscopical and immunological methods in current use for malaria diagnosis are unsatisfactory for low levels of parasitaemia in blood donations. The polymerase chain reaction (PCR) can be 100-fold more sensitive than thick blood film examination when appropriate primers are used and can detect and distinguish Plasmodium falciparum and P. vivax in a single tube. A study of 1506 blood donations in Ho Chi Minh City (3 of which were positive) suggests that PCR can provide an effective screen for P. falciparum under local conditions. Studies in a region of Viet Nam where malaria is common showed that PCR detects many more cases of low-level parasitaemia (19/30) than thick blood films (4/30).

Skeletal muscle form and function after 4 hr ischemia-hypothermia.

The purpose of this study was to examine the use of hypothermia to protect skeletal muscle from the effects of 4 hr of tourniquet ischemia. Muscle recovery was investigated at 6 weeks. Four hours of tourniquet ischemia was induced in two groups (n = 8 per group) of male, Wistar rats (344 +/- 15 g). In the ischemia-only group (IO), the ischemic leg was exposed to room temperature. In the ischemic-hypothermic group (IH), the ischemic leg was cooled to 5-8 degrees C throughout the ischemic period. The contralateral leg served as control. After 6 weeks, the isometric contractile function of the gastrocnemii of both the ischemic and nonischemic legs was determined. Following the functional assessment, the soleus and plantaris muscles were removed and weighed, and biopsies were taken for muscle fiber composition, mean fiber area, and myosin heavy chains (MHC) analysis. Differences between groups (P < 0.05) were determined using ANOVA. Muscle wet weight, tetanic forces, fiber area, fiber type, and MHC composition of IH group were the same as the control group. Yet, twitch tension and relaxation time were lower and longer in the IH group than control group. The tetanic force at 100 Hz of the IH group (12.62 +/- 0.73 N/g) was significantly greater than that of the IO group (2.12 +/- 0.84 N/g). The type 1 muscle fiber areas of plantaris in the IH (1.84 +/- 0.04 x 1000 microns 2) were significantly greater than those of the IO group (1.56 +/- 0.42 x 1000 microns 2).(ABSTRACT TRUNCATED AT 250 WORDS)