Fit for Purpose? The Suitability of Oral Health Outcome Measures to Inform Policy.

KNOWLEDGE TRANSFER STATEMENT: Oral health research and program evaluation should consider alternative outcome measures for population oral health other than the DMFT index.

Adjunctive Dexamethasone for Tuberculous Meningitis in HIV-Positive Adults.

BACKGROUND: Adjunctive glucocorticoids are widely used to treat human immunodeficiency virus (HIV)-associated tuberculous meningitis despite limited data supporting their safety and efficacy. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving HIV-positive adults (≥18 years of age) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomly assigned to receive a 6-to-8-week tapering course of either dexamethasone or placebo in addition to 12 months of antituberculosis chemotherapy. The primary end point was death from any cause during the 12 months after randomization. RESULTS: A total of 520 adults were randomly assigned to receive either dexamethasone (263 participants) or placebo (257 participants). The median age was 36 years; 255 of 520 participants (49.0%) had never received antiretroviral therapy, and 251 of 484 participants (51.9%) with available data had a baseline CD4 count of 50 cells per cubic millimeter or less. Six participants withdrew from the trial, and five were lost to follow-up. During the 12 months of follow-up, death occurred in 116 of 263 participants (44.1%) in the dexamethasone group and in 126 of 257 participants (49.0%) in the placebo group (hazard ratio, 0.85; 95% confidence interval, 0.66 to 1.10; P = 0.22). Prespecified analyses did not reveal a subgroup that clearly benefited from dexamethasone. The incidence of secondary end-point events, including cases of immune reconstitution inflammatory syndrome during the first 6 months, was similar in the two trial groups. The numbers of participants with at least one serious adverse event were similar in the dexamethasone group (192 of 263 participants [73.0%]) and the placebo group (194 of 257 participants [75.5%]) (P = 0.52). CONCLUSIONS: Among HIV-positive adults with tuberculous meningitis, adjunctive dexamethasone, as compared with placebo, did not confer a benefit with respect to survival or any secondary end point. (Funded by the Wellcome Trust; ACT HIV ClinicalTrials.gov number, NCT03092817.).

Histological and electron microscopic features of the extracellular matrix of invasive breast ductal carcinoma of no special type. Report of 5 cases and literature review.

Invasive ductal carcinoma of no special type is the most common type of breast cancer. In light of the above, many authors have reported the histological and electron microscopic characteristics of these tumors. On the other hand, a limited number of works exist where the authors have concentrated on investigating the extracellular matrix. This article presents data received as the results of light and electron microscopic examination of the extracellular matrix, angiogenesis, and cellular microenvironment of invasive breast ductal carcinoma of no special type. The authors have shown that the processes of stroma formation in the IDC NOS type are associated with the presence of fibroblasts, macrophages, dendritic cells, lymphocytes, and other cells. It was also shown the detailed interaction of the above cells with each other, as well as with vessels and fibrillar proteins such as collagen and elastin. The microcirculatory component is characterized by histophysiological heterogeneity, which manifests as the activation of angiogenesis, relative vascular differentiation, and regression of individual microcirculation components.

The impact of preoperative sarcopenia on postoperative ileus following colorectal cancer surgery.

PURPOSE: Sarcopenia is associated with poor short- and long-term patient outcomes following colorectal surgery. Despite postoperative ileus (POI) being a major complication following colorectal surgery, the predictive value of sarcopenia for POI is unclear. We assessed the association between sarcopenia and POI in patients with colorectal cancer. METHODS: Elective colorectal cancer surgery patients were retrospectively included (2018-2022). The cross-sectional psoas area was calculated using preoperative staging imaging at the level of the 3rd lumbar vertebrae. Sarcopenia was determined using gender-specific cut-offs. The primary outcome POI was defined as not achieving GI-2 by day 4. Demographics, operative characteristics, and complications were compared via univariate and multivariate analyses. RESULTS: Of 297 patients, 67 (22.6%) were sarcopenic. Patients with sarcopenia were older (median 74 (IQR 67-82) vs. 69 (58-76) years, p < 0.001) and had lower body mass index (median 24.4 (IQR 22.2-28.6) vs. 28.8 (24.9-31.9) kg/m2, p < 0.001). POI was significantly more prevalent in patients with sarcopenia (41.8% vs. 26.5%, p = 0.016). Overall rate of complications (85.1% vs. 68.3%, p = 0.007), Calvien-Dindo grade > 3 (13.4% vs. 10.0%, p = 0.026) and length of stay were increased in patients with sarcopenia (median 7 (IQR 5-12) vs. 6 (4-8) days, p = 0.013). Anastomotic leak rate was higher in patients with sarcopenia although the difference was not statistically significant (7.5% vs. 2.6%, p = 0.064). Multivariate analysis demonstrated sarcopenia (OR 2.0, 95% CI 1.1-3.8), male sex (OR 1.9, 95% CI 1.0-3.5), postoperative hypokalemia (OR 3.2, 95% CI 1.6-6.5) and increased opioid use (OR 2.4, 95% CI 1.3-4.3) were predictive of POI. CONCLUSION: Sarcopenia demonstrates an association with POI. Future research towards truly identifying the predictive value of sarcopenia for postoperative complications could improve informed consent and operative planning for surgical patients.

Cost-effectiveness analysis of silver diamine fluoride to divert dental general anaesthesia compared to standard care.

BACKGROUND: The aim is to perform a model-based cost-effectiveness analysis of a silver diamine fluoride (SDF) protocol intervention to divert dental general anaesthesia (DGA) among Victorian children aged 2-10 years. METHODS: Data inputs were based on an Australian single-cohort 2017/18 study. Intervention costs for standard care were derived from two subgroups of children: (1) children who received standard care without DGA, and (2) children who received standard care with DGA. Two scenarios were modelled due to limited post-follow-up data: (1) children receiving SDF had standard care without DGA (base-case scenario), and (2) children receiving SDF did not receive standard care without DGA (alternative scenario). A simple decision-tree model with probabilistic sensitivity analysis (PSA) estimated the incremental costs per diverted DGA. RESULTS: The probability of children requiring specialist referral and offered SDF, but the primary carer opted for DGA is 0.124 (SD 0.034), and the probability of children requiring DGA in standard care is 0.346 (SD 0.036). For both the base-case and alternative scenario, the incremental cost-effectiveness ratio outcome is dominant and their cost-effectiveness being either 74.8% or 100% respectively. CONCLUSIONS: The SDF protocol intervention is cost-effective dental caries management option for young children where referral for DGA is considered. © 2022 Australian Dental Association.

Dental Restrictions to Clinical Practice during the COVID-19 Pandemic: An Australian Perspective.

KNOWLEDGE TRANSFER STATEMENT: The reportedly low COVID-19 transmission occurring in dental settings highlight achievements made by the dental profession. There are valid reasons to reconsider risk-based essential oral healthcare during the COVID-19 pandemic.

Transverse facial artery: Its role in blindness after cosmetic filler and botulinum toxin injections.

Masseter injections for cosmetic or pathological reasons are increasingly common, as are filler injections using dual or multiplane techniques in the lateral facial regions or for jawline contouring. The occurrence of blindness following these procedures often remains unexplained. This study aimed to determine the anatomical explanation for this debilitating complication by investigating the transverse facial artery and its relation to the masseter. For this purpose, we dissected 35 cheek specimens with latex injections and 10 specimens without latex. The external carotid artery was dissected up to its bifurcation into the maxillary and superficial temporal arteries. Results showed that the transverse facial artery arose from the superficial temporal or external carotid artery that runs between the zygomatic arch and the parotid duct. Three types of transverse facial arteries were observed: type I: a short artery that did not extend beyond the masseter muscle; type II: a transverse artery that ran to the nasolabial fold and anastomosed to the facial artery; and type III: a sizable transverse artery that substituted the hypoplastic facial artery, continued as the angular artery, and then anastomosed to the dorsal nasal artery. Knowledge of these three types of transverse facial arteries is a prerequisite to study the vascular territory. Type III provides an explanation for the occurrence of blindness after lateral face injections. We consequently define a line that runs from the tragus to the outer quarter of the upper lip as the risk area, while the safe zone is located on either side of this line.

Superiority of a Novel Mp1p Antigen Detection Enzyme Immunoassay Compared to Standard BACTEC Blood Culture in the Diagnosis of Talaromycosis.

BACKGROUND: Talaromycosis is an invasive mycosis endemic in Southeast Asia and causes substantial morbidity and mortality in individuals with advanced human immunodeficiency virus (HIV) disease. Current diagnosis relies on isolating Talaromyces marneffei in cultures, which takes up to 14 days and is detectable only during late-stage infection, leading to high mortality. METHODS: In this retrospective case-control study, we assessed the accuracy of a novel Mp1p antigen-detecting enzyme immunoassay (EIA) in stored plasma samples of 372 patients who had culture-proven talaromycosis from blood or sterile body fluids (reference standard) and 517 individuals without talaromycosis (338 healthy volunteers; 179 with other infections). All participants were recruited between 2011 and 2017 in Vietnam. RESULTS: Of cases and controls, 66.1% and 75.4%, respectively, were male; the median age was 33 and 37, respectively. All cases were HIV infected; median CD4 count was 10 cells/µL. At an optical density cutoff of 0.5, the specificity was 98.1% (95% CI, 96.3%-99.0%); the sensitivity was superior to blood culture (86.3% [95% CI, 82.3%-89.5%] vs 72.8% [95% CI, 68.0%-77.2%]) (P < .001, McNemar test). The time to diagnosis was 6 hours vs 6.6 ± 3.0 days for blood culture. Paired plasma and urine testing in the same patients (n = 269) significantly increased sensitivity compared to testing plasma alone or testing urine alone (P < .001 and P = .02, respectively, McNemar test). CONCLUSIONS: The Mp1p EIA is highly specific and is superior in sensitivity and time to diagnosis compared to blood culture for the diagnosis of talaromycosis. Paired plasma and urine testing further increases sensitivity, introducing a new tool for rapid diagnosis, enabling early treatment and potentially reducing mortality.

Characterizations and Fibrinolytic Activity of Serine Protease from Bacillus subtilis C10.

BACKGROUND: Fibrinolytic enzymes, such as Nattokinases from Bacillus species are known to degrade the fibrin blood clots. They belong to serine protease group having commercial applications, such as therapeutic agents and functional food formulation. OBJECTIVE: The present study reports some characteristics and fibrinolytic activity of serine protease from B. subtilis C10 strain that was isolated from shrimp shell. METHODS: Extracellular enzyme from B. subtilis C10 culture was harvested and partially purified by ammonium sulphate precipitation. Fibrinolytic activity of the enzyme was determined by zymography and measured by spectrophotometry with fibrinogen and thrombin used as substrates. The optimal temperature and pH for fibrinolytic activity were studied in the range of 31-43ºC and 5-10, respectively. The thermal and pH stability of enzyme was studied by incubating enzyme for 30 min in the same range of temperature and pH as above. The effect of some metal ions and reagents on fibrinolytic activity of enzyme was evaluated by concentrations of 5 mM and 5%, respectively. RESULTS: Zymogram analysis indicated the presence of four fibrinolytic enzymes with molecular weights of approximately 69, 67, 39 and 36 kDa. The optimal temperature and pH for enzyme activity were 37°C and 9, respectively. The thermal and pH stability ranged from 35-39°C and 8-10, respectively. Fibrinolytic activity reached a maximum value of about 400 U/mg protein after 16 h of C10 strain culture. Enzyme has been drastically inhibited by PMSF and SDS, and partially inhibited by EDTA, while Triton X-100 has significantly increased enzyme activity. Effects of ions such as Mg2+, Ca2+ and Mn2+ on enzyme were negligible, except Cu2+ and Zn2+ have strongly decreased its activity. CONCLUSION: Results from the present study suggested that enzyme obtained from B. subtilis C10 could be serine protease that has a high fibrinolytic activity up to about 400 U/mg protein at the most appropriate temperature and pH of 37ºC and 9. This activity can be improved up to 142% by incubating enzyme with 5% Triton X-100 for 30 min.

Diversity and Distribution of Rice Blast (Pyricularia oryzae Cavara) Races in Vietnam.

A total of 239 isolates of blast (Pyricularia oryzae Cavara) collected from northern and central Vietnam showed a wide variation in pathogenicity based on the reaction patterns to 25 differential varieties (DVs) harboring 23 resistance genes and susceptible cultivar Lijiangxintuanheigu (LTH). The frequencies of isolates virulent toward DVs for Pish, Pik-m, Pi1, Pik-h, Pik, Pik-p, Pi7(t), Pi9(t), Piz-5, Pita-2, and Pita were low, but they were high for DVs for Pib, Pit, Pia, Pii, Pi3, Pi5(t), Pik-s, Piz, Piz-t, Pi12(t), Pi19(t), and Pi20(t). Isolates were classified into three cluster groups Ia, Ib, and II based on reaction patterns to DVs and LTH. The frequencies of isolates virulent toward 11 DVs for Pik-m, Pi1, Pik-h, Pik, Pik-p, Pi7(t), Pi9(t), Piz, Piz-5, Pita-2, and Pita in cluster II and DV for Piz-t were higher and lower than those of Ia and Ib, respectively. The frequencies to DVs for Pii, Pi3, Pi5(t), and Piz-t were different between clusters Ia and Ib. Clusters Ia and Ib were distributed with similar frequencies in the northeast, north central, and south central coast regions, but the frequencies among three cluster groups in the Red River Delta and northwest regions were different. This means that the blast races in these two regions were different from the others. Overall, the blast isolates were categorized into 153 races. Among them, 26 were selected as a set of standard differential blast isolates for characterizing 23 resistance genes and developing a differential system in Vietnam.

Antibiofilm activity of alpha-mangostin loaded nanoparticles against Streptococcus mutans

Objective: To investigate the antibiofilm activity of alpha-mangostin (AMG) loaded nanoparticle (nanoAMG) against dental caries pathogen Streptococcus mutans. Methods: AMG was isolated from the peels of Garcinia mangostana L. using silica gel columns and chemically analysed by high performance liquid chromatography and nuclear magnetic resonance. NanoAMG was prepared using the solvent evaporation method combined with high-speed homogenization. The nanoparticles were characterized using dynamic light scattering, field emission scanning electron microscopy (FE-SEM) and Fourier transform infrared spectroscopy (FTIR). The toxicity of nanoAMG in fibroblast NIH/3T3 cell line was determined using MTT method. The antibiofilm effect of nanoAMG was determined through the evaluation of biofilm formation by Streptococcus mutans using a 96-well plate. Biofilm biomass was quantified using crystal violet. Cell viability was observed under confocal microscopy using LIVE/DEAD BacLight staining. Moreover, gene expression was determined by quantitative real-time PCR and membrane permeabilization activity by measuring the uptake of o-nitrophenol-β-D-galactoside. Results: NanoAMG size was in a range of 10-50 nm with a polydispersity index of < 0.3 and zeta potential value of -35.2 mV. The size and the incorporation of AMG in the nanoparticles were confirmed by FE-SEM and FTIR analyses. The IC50 values of the test agents on NIH/3T3 cells were (9.80 ± 0.63) μg/mL for AMG and (8.70 ± 0.81) μg/mL for nanoAMG, while no toxicity was generated from excipients used to prepare nanoparticles. In the early stage of biofilm formation, treatment with 6.25 μmol/L nanoAMG caused a reduction in biofilm biomass up to 49.1％, compared to 33.4％ for AMG. In contrast, biofilms at the late stage were more resistant to the test agents. At 96 μmol/L (= 10 × MIC), nanoAMG reduced only 20.7％ of biofilm biomass while AMG did not show any effect. Expressions of gtfB and gtfC genes involved in biofilm formation were down-regulated 3.3 and 12.5 folds, respectively, compared to AMG (2.4 and 7.6 folds, respectively). LIVE/DEAD BacLight fluorescence staining and microscopy observation indicated that biofilm cells were killed by both nanoAMG andAMG at 48 μmol/L (= 5 × MIC). In addition, membrane permeabilization activity was increased in a time dependent manner and higher in nanoAMG treated cells compared toAMG.Conclusions: AMG coated nanoparticle can enhance AMG bioactivity and can be used as a new and promising antibiofilm agent.

Distribution of Virulence Genes among Salmonella Serotypes Isolated from Pigs in Southern Vietnam.

This study was carried out to evaluate the prevalence of Salmonella serogroups and serotypes and their virulence gene carriage in pig fecal samples from farms and slaughterhouses in some southern provinces of Vietnam. The presence of Salmonella was assessed based on culture enrichment of the collected samples and biochemical and serological analyses; 27.7% (51) of 184 samples were posititve for Salmonella. Based on the availability of antisera, serogroups were determined for 61% (31) of 51 isolates. Twenty isolates belonging to Salmonella serotypes Typhimurium (10 isolates), Anatum (8 isolates), Senftenberg (7 isolates), Paratyphi B (3 isolates), Paratyphi A (1 isolate), Montevideo (1 isolate), and Saintpaul (1 isolate) were further characterized by a multiplex PCR protocol targeting Salmonella invasion A and virulence plasmid C genes ( invA and spvC, respectively). Individual PCR assays were developed to detect genes for Salmonella enterotoxin ( stn) , Salmonella outer protein B ( sopB), and Salmonella fimbriae ( pef). Various carriage patterns were identified among tested isolates. The invA and sopB genes were found in all isolates, and the stn gene was found in 95% of the isolates. The spvC gene was found in only 5% of the Salmonella Typhimurium isolates. None of the isolates were positive for the pef gene. Among all isolates, the predominant genotypic virulence profile (virulotype) was characterized by the concomitant presence of invA, sopB, and stn in carrier strains. In contrast, two virulotypes comprising either invA, sopB, spvC, and stn or invA and sopB were identified for the Salmonella Typhimurium isolates. Virulotypes made up of multiple virulence genes were predominant in most Salmonella strains tested in this study, indicating that pigs might act as a reservoir for these virulent strains.

Systematic review with meta-analysis: prevalence, risk factors and costs of aminosalicylate use in Crohn's disease.

BACKGROUND: Aminosalicylates are the most frequently prescribed drugs for patients with Crohn's disease (CD), yet evidence to support their efficacy as induction or maintenance therapy is controversial. AIMS: To quantify aminosalicylate use in CD clinical trials, identify factors associated with use and estimate direct annual treatment costs of therapy. METHODS: MEDLINE, Embase and CENTRAL were searched to April 2017 for placebo-controlled trials in adults with CD treated with corticosteroids, immunosuppressants or biologics. The proportion of patients co-prescribed aminosalicylates in placebo arms was pooled using a random-effects model. Meta-regression was used to identify factors associated with aminosalicylate use. Annual treatment costs were estimated using the 2016 Ontario Drug Benefit Program. RESULTS: Forty-two induction and 10 maintenance trials were included. The pooled proportion of patients co-prescribed aminosalicylates was 44% [95% CI: 39%-49%] in induction trials and 49% [95% CI: 35%-64%] in maintenance trials. There was substantial to considerable heterogeneity (I2  = 86.0%, 91.8% for induction and maintenance trials, respectively). In multivariable meta-regression, aminosalicylate use has decreased over time in induction trials (OR 0.50 [95% CI: 0.34-0.74] per 10-year increment). While a decline has been seen over time, 35% of CD patients were still using aminosalicylates in contemporary trials from the last 5 years. The estimated annual cost for the lowest price mesalazine (mesalamine) formulation is approximately $32 million for the Canadian CD population. CONCLUSIONS: Over one-third of CD patients entering clinical trials are still co-prescribed aminosalicylates. A definitive trial is needed to inform the conventional practice of using aminosalicylates as CD maintenance therapy.

A subperiosteal maxillary implant causing severe osteolysis.

Subperiosteal implant denture therapy was initially introduced in 1942 in Sweden and was subsequently used worldwide for the treatment of fully edentulous maxillary or mandibular arches with advanced bone atrophy. Most authors describe decent success rates for mandibular subperiosteal implants in cases with major bone atrophy but follow-up studies for maxillary subperiosteal implants are not available. Here, we report a case of severe maxillary osteolysis secondary to the placement of a subperiosteal in-house implant. Subperiosteal implants are rarely used today but patients still carrying these devices can be challenging to manage when severe complications occur. New technical advances, including the use of surgical planification and additive manufacturing, may lead to a new interest in subperiosteal implants.

Systematic review with meta-analysis: endoscopic and histologic placebo rates in induction and maintenance trials of ulcerative colitis.

BACKGROUND: Regulatory requirements for claims of mucosal healing in ulcerative colitis (UC) will require demonstration of both endoscopic and histologic healing. Quantifying these rates is essential for future drug development. AIMS: To meta-analyse endoscopic and histologic placebo response and remission rates in UC randomised controlled trials (RCTs) and identify factors influencing these rates. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched from inception to March 2017 for placebo-controlled trials of pharmacological interventions for UC. Endoscopic and histologic placebo rates were pooled by random effects. Mixed effects univariable and multivariable meta-regression was used to evaluate the influence of patient, intervention and trial-related study-level covariates on these rates. RESULTS: Fifty-six induction (placebo n = 4171) and 8 maintenance trials (placebo n = 1011) were included. Pooled placebo endoscopic remission and response rates for induction trials were 23% [95 confidence interval (CI) 19-28%] and 35% [95% CI 27-42%] respectively, and 20% [95% CI 16-24%] for maintenance of remission. The pooled histologic placebo remission rate was 14% [95% CI 8-22%] for induction trials. High heterogeneity was observed for all outcomes (I2 56.2%-88.3%). On multivariable meta-regression, central endoscopy reading was associated with significantly lower endoscopic placebo remission rates (16% vs 25%; OR = 0.52, [95% CI 0.29-0.92], P = 0.03). On univariable meta-regression, higher histologic placebo remission was associated with concomitant corticosteroids (OR = 1.17 [95% CI 1.08-1.26], P < 0.0001, per 10% increase in corticosteroid use). CONCLUSIONS: Placebo endoscopic and histologic rates range from 14% to 35% in UC RCTs but are highly heterogeneous. Outcome standardisation may reduce heterogeneity and is needed in this field.

Economic Evaluation of a Pilot School-Based Dental Checkup Program.

The objectives of this study were to perform an economic evaluation of a targeted school-based dental checkup program in northern metropolitan Melbourne, Victoria. A 12-mo retrospective case-control cohort analysis using the decision tree method evaluated the incremental cost-utility and cost-effectiveness ratio (ICUR/ICER) for passive standard care dental services and an outreach pilot intervention completed in 2013. A societal perspective was adopted. A total of 273 children ( n = 273) aged between 3 and 12 y met the inclusion/exclusion criteria: 128 in the standard care group and 145 in the intervention group. The total society costs included health sector costs, patient/family costs, and productivity losses in 2014 Australian dollars. Outcome measures were evaluated using quality-adjusted tooth years (QATY) and the combined deciduous and permanent decayed, missing, and filled teeth prevented (DMFT-prevented). A generic outcome variable was created to determine the impact of the intervention to reach underserved populations based on government concession eligibility (cardholder status). Uncertainties were incorporated using 95% confidence intervals. The mean total society cost per child is $463 and $291 ( P = 0.002), QATY utility difference is 0.283 and 0.293 ( P = 0.937), effectiveness difference is 0.16 and 0.10 ( P = 0.756), and cardholder status is 50.0% and 66.2% ( P = 0.007), respectively, for the standard care and intervention groups. On average per child, there was a cost saving of $172 and improvement of 0.01 QATY, with an additional proportion of 16.2% of cardholder children reached. The calculated ICER was $3,252 per DMFT-prevented. The intervention dominates standard care for QATY and per 1% cardholder reached outcome measures. Our study found the pilot checkup program was largely less costly and more effective compared with the current standard care. Further research is needed to quantify the value of outreach interventions to prevent dental caries development and progression in populations from low socioeconomic status. Knowledge Transfer Statement: The findings of this research demonstrated that an outreach dental program can be less costly and more effective than standard models of dental care. It showed that a school-based dental checkup program is beneficial despite other opinions that dental screening is ineffective as a method to improve public dental health. There is fiscal economic evidence to support broader expansion of similar programs locally and internationally to reduce dental caries for children from low-income families.

The role of macroscopic sputum quality assessments to optimise sputum testing for tuberculosis.

SETTING: Community-wide active case finding for tuberculosis (TB) using Xpert® MTB/RIF as the primary screening tool, Ca Mau Province, Viet Nam. OBJECTIVES: To determine whether macroscopic sputum quality characteristics (sputum colour and volume) can be used to predict Xpert MTB-negative sputum and hence exclude sputum samples from testing. DESIGN: Field staff conducted household visits to approximately 51,200 adults in 58 villages randomly selected from throughout the province. Sputum samples from all screened participants who were able to produce ⩾1 ml sputum underwent macroscopic sputum assessment and were tested with Xpert. RESULTS: Of the 21,624 sputum samples tested, 159 (0.74%) were Xpert MTB-positive; 93% of the samples were 1-2 ml and nearly all were mucoid (93%) or mucopurulent (5.7%). One salivary sample was Xpert MTB-positive (2.0% of all salivary samples). The lowest positive predictive value for any sputum volume or colour characteristic was 0.66%. This was not substantially different from the overall prevalence of positive sputum Xpert MTB (0.74%). CONCLUSION: Sputum colour and volume cannot be used to predict the presence or absence of M. tuberculosis in sputum detected using Xpert. These sputum quality parameters cannot therefore be used to exclude sputum samples from testing for TB.

Spatial relationships between bone formation and mechanical stress within cancellous bone.

Bone adapts to mechanical stimuli. While in vivo mechanical loading has been shown to increase the density of cancellous bone, theory suggests that the relationship between tissue stress/strain and subsequent bone formation occurs at the scale of individual trabeculae. Here we examine bone formation one week following mechanical stimulus. Three bouts of cyclic loading (300 cycles/day on 3 consecutive days) were applied to caudal vertebrae of female rats (n=7). Bone formation was determined using three-dimensional images of fluorescent markers of bone formation (0.7×0.7×5.0µm(3)) and local tissue stress/strain was determined using high-resolution finite element models. Three days of mechanical stimuli resulted in an increase in mineralizing surface (loaded: 17.68±2.17%; control: 9.05±3.20%; mean±SD) and an increase in the volume of bone formed (loaded: 7.09±1.97%; control: 1.44±0.50%). The number of bone formation sites was greater in loaded animals (650.71±118.54) than pinned not loaded controls (310.71±91.55), a difference that was explained by the number of formation sites at regions with large local tissue strain energy density (SED). In addition, the probability of observing bone formation was greater at locations of the microstructure experiencing greater SED, but did not exceed 32%, consistent with prior work. Our findings demonstrate that bone formation in the week following a short term mechanical stimulus occurs near regions of bone tissue experiencing high tissue SED, although the ability of finite element models to predict the locations of bone formation remains modest and further improvements may require accounting for additional factors such as osteocyte distribution or fluid flow.