Direct oral anticoagulants in the treatment of acute venous thromboembolism in patients with obesity: A systematic review with meta-analysis.

BACKGROUND: Direct oral anticoagulants' (DOAC) pharmacokinetics are affected by obesity. Their efficacy and safety in obesity (BMI≥30 kg/m2) and morbid obesity (BMI≥40 kg/m2) are still unclear in the treatment of venous thromboembolism (VTE). OBJECTIVES: To compare the efficacy/safety of DOAC versus vitamin K antagonist (VKA)/low molecular weight heparin (LMWH) for the treatment of VTE in patients with obesity and morbid obesity. The primary efficacy/safety outcomes were VTE recurrence and major bleeding (MB). Clinically relevant non-MB and mortality were also evaluated. METHODS: A systematic literature search (MEDLINE, EMBASE, CENTRAL, Web of Science) identified studies evaluating DOAC in the treatment of VTE in patients with obesity and reporting one of the outcomes. Relative risks (RR) and 95 % confidence intervals (CI) were estimated using the Mantel-Haenszel method. RESULTS: We included 21 studies (50,360pts) of which 16,150 patients had a BMI≥30 kg/m2 and 6443 patients had a BMI≥40 kg/m2. VTE recurrence was similar with DOAC compared to VKA/LMWH in patients with obesity (RR 1.03;95 %CI 0.93-1.15;p = 0.55) and morbid obesity (RR 1.06;95 %CI 0.94-1.19;p = 0.35). DOAC were also associated with a reduction in MB (RR 0.57;95 %CI 0.34-0.94;p = 0.03 and RR 0.71;95 %CI 0.50-1.00;p = 0.05 in patients with obesity and morbid obesity, respectively). Subgroup analyses comparing randomized controlled trials to observational studies showed consistent results. No difference was observed in regards of clinically relevant non-MB and mortality. CONCLUSION: There is no signal for differences in VTE recurrence in patients with obesity and morbid obesity treated with DOAC compared to VKA/LMWH, while DOAC likely reduce the risk of MB compared to VKA/LMWH.

DOAC compared to LMWH in the treatment of cancer related-venous thromboembolism: a systematic review and meta-analysis.

Low molecular weight heparins (LMWH) are the standard of care for the treatment of cancer-associated venous thromboembolism (CA-VTE). We performed a systematic review and meta-analysis to compare the effects of direct oral anticoagulants (DOAC) versus LMWH for the treatment of CA-VTE. The primary efficacy and safety outcomes were VTE recurrence and major bleeding (MB). The secondary outcomes were clinically relevant non-MB (CRNMB), all-cause mortality and the net clinical benefit. We searched MEDLINE, EMBASE, CENTRAL and Web of Science (inception-December 2019) and abstracts of relevant conferences (2000-2019) to identify randomized controlled trials comparing DOAC and LMWH for the treatment of CA-VTE. Relative risks (RR) and 95% confidence intervals were estimated (Mantel-Haenszel method, random-effects models). A non-inferiority analysis with a margin of 1.3 for the upper boundary of the RR was conducted for the primary outcomes. From 637 references, we included four publications which encompass three trials (1756 patients). Compared to LMWH, DOAC were associated with a trend for decreased VTE recurrence (RR 0.51; 95%CI 0.25-1.03; p = 0.06; I2 = 51%), whereas MB (RR 1.64; 95%CI 1.00-2.69; p = 0.05; I2 = 0%) and CRNMB (RR 1.83; 95%CI 1.04-3.20; p = 0.03; I2 = 50%) were significantly more frequent with DOAC. Conversely, all-cause mortality (RR 1.06; 95%CI 0.83-1.35; p = 0.64; I2 = 36%) and net clinical benefit (RR 0.74; 95%CI 0.38-1.42; p = 0.36; I2 = 65%) were comparable. DOAC were non-inferior to LMWH in preventing CA-VTE recurrence, but were associated with an increased risk of MB and CRNMB. Further studies are required to confirm these results and inform on the risk/benefit ratio for specific populations.

Canadian cancer screening disparities: a recent historical perspective.

Across Canada, introduction of the Pap test for cervical cancer screening, followed by mammography for breast cancer screening and, more recently, the fecal occult blood test for colorectal cancer screening, has contributed to a reduction in cancer mortality. However, another contribution of screening has been disparities in cancer mortality between certain populations. Here, we explore the disparities associated with breast and cervical cancer screening and preliminary data concerning disparities in colorectal cancer screening. Although some disparities in screening utilization have been successfully reduced over time (for example, mammography and Pap test screening in rural and remote populations), screening utilization data for other populations (for example, low-income groups) clearly indicate that disparities have existed and continue to exist across Canada. Organized screening programs in Canada have been able to successfully engage 80% of women for regular cervical cancer screening and 70% of women for regular mammography screening, but of the women who remain to be reached or engaged in regular screening, those with the least resources, those who are the most isolated, and those who are least culturally integrated into Canadian society as a whole are over-represented. Population differences are also observed for utilization of colorectal cancer screening services. The research literature on interventions to promote screening utilization provides some evidence about what can be done to increase participation in organized screening by vulnerable populations. Adaption and adoption of evidence-based screening promotion interventions can increase the utilization of available screening services by populations that have experienced the greatest burden of disease with the least access to screening services.

Recent trends in breast, cervical, and colorectal cancer screening test utilization in Canada, using self-reported data from 2008 and 2012.

In Canada, self-reported data from the Canadian Community Health Survey 2008 and 2012 provide an opportunity to examine overall utilization of breast, cervical, and colorectal cancer screening tests for both programmatic and opportunistic screening. Among women 50-74 years of age, utilization of screening mammography was stable (62.0% in 2008 and 63.0% in 2012). Pap test utilization for women 25-69 years of age remained high and stable across Canada in 2008 and 2012 (78.9% in 2012). The percentage of individuals 50-74 years of age who reporting having at least 1 fecal test within the preceding 2 years increased in 2012 (to 23.0% from 16.9% in 2008), but remains low. Stable rates of screening mammography utilization (about 30%) were reported in 2008 and 2012 among women 40-49 years of age, a group for which population-based screening is not recommended. Although declining over time, cervical cancer screening rates were high for women less than 25 years of age (for whom screening is not recommended). Interestingly, an increased percentage of women 70-74 years of age reported having a Pap test. In 2012, a smaller percentage of women 50-69 years of age reported having no screening test (5.9% vs. 8.5% in 2008), and more women reported having the three types of cancer screening tests (19.0% vs. 13.2%). Efforts to encourage use of screening within the recommended average-risk age groups are needed, and education for stakeholders about the possible harms of screening outside those age groups has to continue.

N-acyl homoserine lactone signaling modulates bacterial community associated with human dental plaque.

N-acyl homoserine lactones (AHLs) are small diffusible signaling molecules that mediate a cell density-dependent bacterial communication system known as quorum sensing (QS). AHL-mediated QS regulates gene expression to control many critical bacterial behaviors including biofilm formation, pathogenicity, and antimicrobial resistance. Dental plaque is a complex multispecies oral biofilm formed by successive colonization of the tooth surface by groups of commensal, symbiotic, and pathogenic bacteria, which can contribute to tooth decay and periodontal diseases. While the existence and roles of AHL-mediated QS in oral microbiota have been debated, recent evidence indicates that AHLs play significant roles in oral biofilm development and community dysbiosis. The underlying mechanisms, however, remain poorly characterized. To better understand the importance of AHL signaling in dental plaque formation, we manipulated AHL signaling by adding AHL lactonases or exogenous AHL signaling molecules. We find that AHLs can be detected in dental plaque grown under 5% CO2 conditions, but not when grown under anaerobic conditions, and yet anaerobic cultures are still responsive to AHLs. QS signal disruption using lactonases leads to changes in microbial population structures in both planktonic and biofilm states, changes that are dependent on the substrate preference of the used lactonase but mainly result in the increase in the abundance of commensal and pioneer colonizer species. Remarkably, the opposite manipulation, that is the addition of exogenous AHLs increases the abundance of late colonizer bacterial species. Hence, this work highlights the importance of AHL-mediated QS in dental plaque communities, its potential different roles in anaerobic and aerobic parts of dental plaque, and underscores the potential of QS interference in the control of periodontal diseases.

Deep brain stimulation and the role of astrocytes.

Deep brain stimulation (DBS) has emerged as a powerful surgical therapy for the management of treatment-resistant movement disorders, epilepsy and neuropsychiatric disorders. Although DBS may be clinically effective in many cases, its mode of action is still elusive. It is unclear which neural cell types are involved in the mechanism of DBS, and how high-frequency stimulation of these cells may lead to alleviation of the clinical symptoms. Neurons have commonly been a main focus in the many theories explaining the working mechanism of DBS. Recent data, however, demonstrates that astrocytes may be active players in the DBS mechanism of action. In this review article, we will discuss the potential role of reactive and neurogenic astrocytes (neural progenitors) in DBS.

Colorectal cancer screening in Canada: results from the first round of screening for five provincial programs.

BACKGROUND: Early implementation of programmatic colorectal cancer (crc) screening for average-risk individuals 50-74 years of age in Canada has used fecal occult blood tests [fts (guaiac or immunochemical)] and colonoscopy for follow-up of abnormal fts. This paper presents results of an evaluation of this crc screening. METHODS: Five Canadian provincial programs provided aggregated data for individuals with a first-round ft processed between January 1, 2009, and December 31, 2011. RESULTS: The 104,750 people who successfully completed a first round of screening represented 16.1% of those who had access to the programs between January 1, 2009, and December 31, 2011 (mean age: 61.2 years; men: 61.4 years; women: 61.1 years). Of those participants, 4661 had an abnormal ft (4.4%). Uptake of colonoscopy within 180 days after an abnormal ft was 80.5%, ranging from 67.8% to 89.5% by program. The positive predictive value (ppv) for adenoma was 35.9% for guaiac ft and 50.6% for immunochemical ft. Adenoma and crc detection rates were, respectively, 16.9 and 1.8 per 1000 screened. Of invasive crcs detected, 64.6% were stage i or ii. CONCLUSIONS: Considering the variation in characteristics and stage of implementation of each provincial program, the collaboration of the provinces leading to this report on the early performance of crc screening in Canada is a major milestone. Targets are met or nearly met for significant indicators such as ppv for adenoma and cancer detection rate. Participation is expected to increase as programs are fully implemented in the provinces. Additional effort may be needed to improve timely access to follow-up colonoscopy.

The national DBS brain tissue network pilot study: need for more tissue and more standardization.

Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51-92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post-mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to facilitate advanced molecular studies and progenitor cell retrieval.

Artificial Intelligence and Ethics in Dentistry: A Scoping Review.

Dentistry increasingly integrates artificial intelligence (AI) to help improve the current state of clinical dental practice. However, this revolutionary technological field raises various complex ethical challenges. The objective of this systematic scoping review is to document the current uses of AI in dentistry and the ethical concerns or challenges they imply. Three health care databases (MEDLINE [PubMed], SciVerse Scopus, and Cochrane Library) and 2 computer science databases (ArXiv, IEEE Xplore) were searched. After identifying 1,553 records, the documents were filtered, and a full-text screening was performed. In total, 178 studies were retained and analyzed by 8 researchers specialized in dentistry, AI, and ethics. The team used Covidence for data extraction and Dedoose for the identification of ethics-related information. PRISMA guidelines were followed. Among the included studies, 130 (73.0%) studies were published after 2016, and 93 (52.2%) were published in journals specialized in computer sciences. The technologies used were neural learning techniques for 75 (42.1%), traditional learning techniques for 76 (42.7%), or a combination of several technologies for 20 (11.2%). Overall, 7 countries contributed to 109 (61.2%) studies. A total of 53 different applications of AI in dentistry were identified, involving most dental specialties. The use of initial data sets for internal validation was reported in 152 (85.4%) studies. Forty-five ethical issues (related to the use AI in dentistry) were reported in 22 (12.4%) studies around 6 principles: prudence (10 times), equity (8), privacy (8), responsibility (6), democratic participation (4), and solidarity (4). The ratio of studies mentioning AI-related ethical issues has remained similar in the past years, showing that there is no increasing interest in the field of dentistry on this topic. This study confirms the growing presence of AI in dentistry and highlights a current lack of information on the ethical challenges surrounding its use. In addition, the scarcity of studies sharing their code could prevent future replications. The authors formulate recommendations to contribute to a more responsible use of AI technologies in dentistry.

The association between birth order and childhood brain tumors: a systematic review and meta-analysis.

The incidence of childhood brain tumors (CBT) has increased worldwide, likely resulting from the improvements of early diagnostics. We conducted a systematic review and meta-analysis to clarify the association between birth order and CBT. We followed established guidelines to systematically search Ovid Medline, PubMed, and the Cochrane Library for English language studies, published before March 2018. Quality assessment was performed using the Newcastle-Ottawa Scale. Meta-analysis provided pooled risk estimates and their 95% confidence intervals (CIs) for birth order and CBT. We identified 16 case-control studies with a total sample of 32 439 cases and 166 144 controls and three prospective cohort studies (i.e. 4515 incident cases of CBTs among 5 281 558 participants). Compared with first birth order, the meta-odds ratio for second birth order in case-control studies was 1.04 (95% CI: 1.01-1.07), that for third birth order was 0.98 (95% CI: 0.90-1.06), and that for fourth order was 0.85 (95% CI: 0.78-0.92). The meta-hazard ratio for second or higher birth order compared with first birth order in cohort studies was 1.00 (95% CI: 0.96-1.05). We found no association between birth order and CBT in both case-control and cohort study designs; the small association observed for fourth birth order deserves further consideration.

A Poincaré's approach for plasmonics: the plasmon localization.

A Poincaré's approach is employed to characterize the excitation of a plasmon, which in essence corresponds to a zero of a complex S-matrix. Throughout this work we study the plasmonic behaviour of gold, as this metal not only is frequently used in experimental arrays, but also requires an accurate dispersion model to properly excite plasmons. We investigate the plasmonic behaviour of gold nanogratings by means of Born's approximation and the Finite-Elements Method. Also, a method based on the Poincaré's approach is proposed to optimize this kind of structures.

The effects of a high-fruit and -vegetable, high-fiber, low-fat dietary intervention on serum concentrations of insulin, glucose, IGF-I and IGFBP-3.

OBJECTIVE: To determine the effects of dietary change on serum concentrations of insulin, glucose, IGF-I and IGFBP-3. SUBJECTS: From among participants in a randomized clinical trial of men and women without a history of diabetes who were 35 years old or older and who had at least one histologically confirmed colorectal adenoma removed during a qualifying colonoscopy within the 6 months before randomization, 750 subjects were selected for this analysis. METHODS: The authors analyzed fasting serum from 375 subjects with and 375 subjects without a recurrent polyp among participants in a randomized trial of a low-fat (20% of energy), high-fiber (18 g per 1000 kcals of energy intake) and high-fruit and -vegetable (5-8 servings per day) dietary intervention. RESULTS: After 4 years of follow-up, IGF-I concentration in the intervention group (N=248) declined by 8.86 ng/ml (initial mean of 133 ng/ml) and 7.74 ng/ml (initial mean value of 139 ng/ml) in the non-intervention group (N=502). Based on an unpaired t-test, these declines were both statistically significant, but the difference between groups for the decline in IGF-I (1.12 ng/ml ((95% confidence interval, -3.24 to 5.48)) was not. After 4 years, concentrations of IGFBP-3, insulin and glucose were not statistically different from values at baseline, and there were no differences in these serum measures between the intervention and control groups. In analysis restricted to lean (body mass index <25 kg/m(2)) subjects only, however, glucose concentrations in the intervention group decreased by 0.28 mmol/l, while they increased in the control group by 0.01 mmol/l (t-test for mean differences P=0.0003) over 4 years. CONCLUSIONS: A low-fat, high-fiber, high-fruit and -vegetable dietary intervention had minimal impact on serum concentrations of insulin, glucose, IGF-I and IGFBP-3 overall, but in lean subjects the intervention resulted in a significant reduction in serum glucose concentration.

Wound closure expectations after fasciotomy for paediatric compartment syndrome.

PURPOSE: Acute compartment syndrome often requires additional surgery to achieve wound closure. Little information exists regarding the expected number of surgeries, techniques and complications after closure in paediatric patients. METHODS: A retrospective chart review identified patients treated for acute compartment syndrome at four hospitals over a ten-year period. The cause of injury, type of dressing, number of surgeries, type of closure and complications were recorded. RESULTS: In all, 32 patients (mean 10.9 years, 1 to 17) who underwent 18 lower and 14 upper extremity fasciotomies met inclusion criteria. Definitive wound closure technique was delayed primary in 72%, split thickness skin graft in 25%, and primary in 3% of patients. Closure required a mean 2.4 surgeries (0 to 4) over a mean 7.7 days (0 to 34). Days to closure and number of surgeries required were not significantly affected by mechanism of injury, fasciotomy location or type of dressing used. A total of 23.1% of patients with upper extremity and 0% with lower extremity fasciotomies had concerns about the scar appearance. Other complications included neurapraxia (6.7%), stiffness (6.7%), swelling (3.3%), scar pain (3.3%) and weakness (3.3%). CONCLUSIONS: The most common complication after paediatric compartment syndrome is an unpleasant scar. Wound closure after upper or lower extremity fasciotomies in paediatric patients requires a split thickness skin graft in approximately one in four patients. However, avoiding a skin graft does not guarantee the absence of cosmetic concerns, which are more likely following upper extremity fasciotomies. LEVEL OF EVIDENCE: IV.

Ceramic prosthesis surfaces induce an inflammatory cell response and fibrotic tissue changes.

Aims: Early evidence has emerged suggesting that ceramic-on-ceramic articulations induce a different tissue reaction to ceramic-on-polyethylene and metal-on-metal bearings. Therefore, the aim of this study was to investigate the tissue reaction and cellular response to ceramic total hip arthroplasty (THA) materials in vitro, as well as the tissue reaction in capsular tissue after revision surgery of ceramic-on-ceramic THAs. Patients and Methods: We investigated tissue collected at revision surgery from nine ceramic-on-ceramic articulations. we compared our findings with tissue obtained from five metal-on-metal THA revisions, four ceramic-on-polyethylene THAs, and four primary osteoarthritis synovial membranes. The latter were analyzed to assess the amount of tissue fibrosis that might have been present at the time of implantation to enable evaluation, in relation to implantation time, of any subsequent response in the tissues. Results: There was a significant increase in tissue fibrosis with implantation time for all implant types tested. Interestingly, the tissue fibrosis in ceramic-on-ceramic THAs was significantly increased compared with metal-on-metal and ceramic-on-polyethylene. Additionally, we found ceramic wear particles in the periprosthetic tissue of ceramic implants. Fibroblasts responded with expression of cytokines when cultured on alumina-toughened zirconia (ATZ) and zirconia-toughened alumina (ZTA) ceramic surfaces. This response was more pronounced on ATZ ceramics compared with ZTA ceramics. The same inflammatory response was observed with peripheral blood mononuclear cells (PBMCs) cultured on ZTA and ATZ. Conclusion: Our findings therefore, corroborate the previous findings that ceramic-on-ceramic periprosthetic revision tissue is fibrous and offer an explanation for this observation. We detected a long-term inflammatory response of PBMCs and an inflammatory response of fibroblasts to ATZ and ZTA ceramic. These findings partially explain the fibrotic tissue change in periprosthetic tissue of ceramic-on-ceramic bearings. Cite this article: Bone Joint J 2018;100-B:882-90.

Environmental and health effects of the herbicide glyphosate.

The herbicide glyphosate, N-(phosphonomethyl) glycine, has been used extensively in the past 40years, under the assumption that side effects were minimal. However, in recent years, concerns have increased worldwide about the potential wide ranging direct and indirect health effects of the large scale use of glyphosate. In 2015, the World Health Organization reclassified glyphosate as probably carcinogenic to humans. A detailed overview is given of the scientific literature on the movement and residues of glyphosate and its breakdown product aminomethyl phosphonic acid (AMPA) in soil and water, their toxicity to macro- and microorganisms, their effects on microbial compositions and potential indirect effects on plant, animal and human health. Although the acute toxic effects of glyphosate and AMPA on mammals are low, there are animal data raising the possibility of health effects associated with chronic, ultra-low doses related to accumulation of these compounds in the environment. Intensive glyphosate use has led to the selection of glyphosate-resistant weeds and microorganisms. Shifts in microbial compositions due to selective pressure by glyphosate may have contributed to the proliferation of plant and animal pathogens. Research on a link between glyphosate and antibiotic resistance is still scarce but we hypothesize that the selection pressure for glyphosate-resistance in bacteria could lead to shifts in microbiome composition and increases in antibiotic resistance to clinically important antimicrobial agents. We recommend interdisciplinary research on the associations between low level chronic glyphosate exposure, distortions in microbial communities, expansion of antibiotic resistance and the emergence of animal, human and plant diseases. Independent research is needed to revisit the tolerance thresholds for glyphosate residues in water, food and animal feed taking all possible health risks into account.

Essential oils Constituents of the leaves of Amomum gagnepainii and Amomum repoense.

The chemical constituents identified in the essential oils hydrodistilled from the leaves of Amomum gagnepainii T.L.Wu, K.Larsen and Turland and Amomum repoense Pierre ex Gagnep (Zingiberaceae) of Vietnam origin are reported. The chemical analyses were performed by means of gas chromatography-flame ionisation detector (GC-FID) and gas chromatography coupled with mass spectrometry (GC-MS). The main compounds of A. gagnepainii were farnesyl acetate (18.5%), zerumbone (16.4%) and ß-caryophyllene (10.5%). On the other hand, Amomum repoense comprised of monoterpenes dominated by ß-pinene (33.5%), (E)-ß-ocimene (9.6%), γ-terpinene (9.1%) and α-pinene (8.4%). This is the first report on the essential oils of A. gagnepainii and A. repoense grown in Vietnam or elsewhere.

Cancer Care Ontario Colonoscopy Standards: standards and evidentiary base.

Colorectal cancer (CRC) is the most common cause of non-tobacco-related cancer deaths in Canadian men and women, accounting for 10% of all cancer deaths. An estimated 7800 men and women will be diagnosed with CRC, and 3250 will die from the disease in Ontario in 2007. Given that CRC incidence and mortality rates in Ontario are among the highest in the world, the best opportunity to reduce this burden of disease would be through screening. The present report describes the findings and recommendations of Cancer Care Ontario's Colonoscopy Standards Expert Panel, which was convened in March 2006 by the Program in Evidence-Based Care. The recommendations will form the basis of the quality assurance program for colonoscopy delivered in support of Ontario's CRC screening program.

Costs of providing tuberculosis diagnosis and treatment services in Viet Nam.

OBJECTIVE: To estimate the cost of providing tuberculosis (TB) diagnosis and treatment packages at different levels of health facilities in Viet Nam. DESIGN: This was a retrospective costing study from the providers' perspective using a standard costing approach. We included typical services for TB diagnosis and treatment based on standard protocols. RESULTS: The least expensive TB service was the 6-month isoniazid preventive therapy regimen for latent tuberculous infection provided by district health centres (US$7.20-14.30, accounting for 0.3-0.7% of Viet Nam's per capita gross domestic product [GDP] of US$2052.30 in 2014). The cost of diagnosing and treating a patient with drug-susceptible TB (the most common type of TB) ranged between US$51.20 and US$180.70, and represented 2.5-8.8% of Viet Nam's per capita GDP in 2014. The most expensive TB service was the diagnosis and treatment of a multidrug-resistant TB case (US$1568.20-2391.20), accounting for 76.4-116.5% of Viet Nam's per capita GDP in 2014). CONCLUSION: The cost of TB diagnosis and treatment services in Viet Nam varied according to level of health facility, type of TB, different costing options, and different staff cost scenarios.

Calcium phosphate supplementation increases faecal Lactobacillus spp. in a randomised trial of young adults.

The aim of the studies was to determine the effects of calcium carbonate and calcium phosphate supplementation on faecal Lactobacillus spp., with and without a probiotic supplement, in healthy adults. Study 1 comprised of a randomised, double-blind, crossover design; participants (n=15) received 2 capsules/d of 250 mg elemental calcium as calcium carbonate (Ca1) and calcium phosphate (Ca2) each for 2-week periods, with 2-week baseline and washout periods. Study 2 was a randomised, double-blind, crossover design; participants (n=17) received 2 capsules/d of Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011 (probiotic) alone, the probiotic with 2 capsules/d of Ca1, and probiotic with 2 capsules/d of Ca2 each for 2-week periods with 2-week baseline and washout periods. In both studies, stools were collected during the baseline, intervention and washout periods for Lactobacillus spp. quantification and qPCR analyses. Participants completed daily questionnaires of stool frequency and compliance. In Study 1, neither calcium supplement influenced viable counts of resident Lactobacillus spp., genome equivalents of lactic acid bacteria or stool frequency. In Study 2, faecal Lactobacillus spp. counts were significantly enhanced from baseline when the probiotic was administered with Ca2 (4.83±0.30, 5.79±0.31) (P=0.02), but not with Ca1 (4.98±0.31) or with the probiotic alone (5.36±0.31, 5.55±0.29) (not significant). Detection of L. helveticus R0052 and L. rhamnosus R0011 was significantly increased with all treatments, but did not differ among treatments. There were no changes in weekly stool frequency. Calcium phosphate co-administration may increase gastrointestinal survival of orally-administered Lactobacillus spp.