Effectiveness of community-based DOTS strategy on tuberculosis treatment success rates in Namibia.

DOTS is a key pillar of the global strategy to end tuberculosis (TB). To assess the effectiveness of community-based compared with facility-based DOTS on TB treatment success rates in Namibia. Annual TB treatment success, cure, completion and case notification rates were compared between 1996 and 2015 using interrupted time series analysis. The intervention was the upgrading by the Namibian government of the TB treatment strategy from facility-based to community-based DOTS in 2005. The mean annual treatment success rate during the pre-intervention period was 58.9% (range 46-66) and increased significantly to 81.3% (range 69-87) during the post-intervention period. Before the intervention, there was a non-significant increase (0.3%/year) in the annual treatment success rate. After the intervention, the annual treatment success rate increased abruptly by 12.9% (P < 0.001) and continued to increase by 1.1%/year thereafter. The treatment success rate seemed to have stagnated at ∼85% at the end of the observation period. Expanding facility-based DOTS to community-based DOTS increased annual treatment success rates significantly. However, the treatment success rate at the end of the observation period had stagnated below the targeted 95% success rate. .

Correction to: Biodentine™ material characteristics and clinical applications: a 3 year literature review and update.

Owing to a misunderstanding on the part of the authors, the name of the last author, Prof. R. M. H. Verbeeck, was omitted from this article.

Addition of bioactive glass to glass ionomer cements: Effect on the physico-chemical properties and biocompatibility.

OBJECTIVES: Glass ionomer cements (GICs) are a subject of research because of their inferior mechanical properties, despite their advantages such as fluoride release and direct bonding to bone and teeth. Recent research aims to improve the bioactivity of the GICs and thereby improve mechanical properties on the long term. In this study, two types of bioactive glasses (BAG) (45S5F and CF9) are combined with GICs to evaluate the physico-chemical properties and biocompatibility of the BAG-GIC combinations. The effect of the addition of Al3+ to the BAG composition and the use of smaller BAG particles on the BAG-GIC properties was also investigated. MATERIALS AND METHODS: Conventional aluminosilicate glass (ASG) and (modified) BAG were synthesized by the melt method. BAG-GIC were investigated on setting time, compressive strength and bioactivity. Surface changes were evaluated by Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), EDS and PO43- -and Ca2+ uptake in SBF. Biocompatibility of selected BAG-GICs was determined by a direct toxicity assay. RESULTS: The addition of BAG improves the bioactivity of the GIC, which can be observed by the formation of an apatite (Ap) layer, especially in CF9-containing GICs. More BAG leads to more bioactivity but decreases strength. The addition of Al3+ to the BAG composition improves strength, but decreases bioactivity. BAGs with smaller particle sizes have no effect on bioactivity and decrease strength. The formation of an Ap layer seems beneficial to the biocompatibility of the BAG-GICs. SIGNIFICANCE: Bioactive GICs may have several advantages over conventional GICs, such as remineralization of demineralized tissue, adhesion and proliferation of bone- and dental cells, allowing integration in surrounding tissue. CF9 BAG-GIC combinations containing maximum 10mol% Al3+ are most promising, when added in ≤20wt% to a GIC.

Bioactivity and biocompatibility of two fluoride containing bioactive glasses for dental applications.

OBJECTIVE: Bioactive glasses (BAG) form, in contrast to formerly used implant materials, a stable bond with tissues, especially bone, when implanted. Nowadays BAGs are often mixed with a cement/composite that hardens in situ to broaden its applications in dentistry or orthopedics. The bioactivity and biocompatibility of possible BAG candidates for BAG-cement/composite development were evaluated. METHODS: Two fluoride containing BAGs were tested: a Na+-containing (45S5F), based on the first commercial BAG, and a Na+-free BAG (CF9), with a higher Ca2+ and PO43- content. BAGs were tested on their bioactivity upon immersion in SBF for 7days by evaluating the surface changes by FT-IR, SEM, EDS and PO43- and Ca2+ uptake and/or release from SBF. Moreover, the biocompatibility of the BAGs was investigated with a direct contact cell viability study with HFF cells and a cell adhesion study with MG-63 cells. RESULTS: The Na+-free BAG, CF9, showed the highest potential to bioactivate cements because of its high Ca2+-release and apatite (Ap) formation, as evidenced by SEM pictures and corresponding EDX patterns. FT-IR confirmed the formation of an Ap layer. Moreover CF9 had a higher biocompatibility than 45S5F. SIGNIFICANCE: For the bioactivation of GICs/composites in order to enhance bonding and remineralization of surrounding tissues, fluoride containing BAG may have advantages over other BAGs as a more stable fluorapatite can be formed. CF9 may be an excellent candidate therefore.

The influence of particle size and fluorine content of aluminosilicate glass on the glass ionomer cement properties.

OBJECTIVE: Glass ionomer cements (GIC) are clinically accepted dental restorative materials mainly due to their direct chemical adhesion to both enamel and dentin and their ability to release fluoride. However, their mechanical properties are inferior compared to those of amalgam and composite. The aim of this study is to investigate if combinations of nano- and macrogranular glass with different compositions in a glass ionomer cement can improve the mechanical and physical properties. METHODS: Glasses with the composition 4.5 SiO2-3 Al2O3-1.5 P2O5-(5-x) CaO-x CaF2 (x=0 and x=2) were prepared. Of each type of glass, particles with a median size of about 0.73 µm and 6.02 µm were made. RESULTS: The results show that the setting time of GIC decreases when macrogranular glass particles are replaced by nanogranular glass particles, whereas the compressive strength and Young's modulus, measured after 24 h setting, increase. The effects are more pronounced when the nanogranular glass particles contain fluoride. After thermocycling, compressive strength decreases for nearly all formulations, the effect being most pronounced for cements containing nanogranular glass particles. Hence, the strength of the GIC seems mainly determined by the macrogranular glass particles. Cumulative F--release decreases when the macrogranular glass particles with fluoride are replaced by nanogranular glass particles with(out) fluoride. SIGNIFICANCE: The present study thus shows that replacing macro- by nanogranular glass particles with different compositions can lead to cements with approximately the same physical properties (e.g. setting time, consistency), but with different physicochemical (e.g. F--release, water-uptake) and initial mechanical properties. On the long term, the mechanical properties are mainly determined by the macrogranular glass particles.

Biodentine™ material characteristics and clinical applications: a review of the literature.

INTRODUCTION: Biodentine™ is a new version of calcium silicate-based inorganic cement. AIM: The aim of this review is to provide a detailed analysis of the physical and biological properties of Biodentine™ and to compare these properties with those of other tricalcium silicate cements viz. mineral trioxide aggregate (MTA) and Bioaggregate™ (Bioaggregate). STUDY DESIGN: A comprehensive systematic literature search for all publications to date was performed on 20th November 2013 by two independent reviewers in Medline (PubMed), Embase, Web of Science, CENTRAL (Cochrane), SIGLE, SciELO, Scopus, Lilacs and clinicaltrials.gov using the search terms Biodentine, "tricalcium silicate", Ca3SiO5, "dentine substitute", "dentin substitute" and RD 94. In addition to the electronic search, hand searches and reference searches were performed to include articles published in journals that were not indexed in Medline. Randomised control trials (RCT), case control studies, case series, case reports, in vitro studies, animal studies and short communications in English language were considered for this review. CONCLUSIONS: Considering the superior physical and biologic properties, Biodentine™ could be an efficient alternative to MTA to be used in a variety of clinical applications. There appears to be a wide range of clinical applications where Biodentine™ could be used in the field of endodontics, dental traumatology, restorative dentistry and pediatric dentistry. Although it seems to be good clinical practice, currently there is little clinical evidence to support all potential indications.

Population pharmacokinetic analysis of tacrolimus in the first year after pediatric liver transplantation.

PURPOSES: Tacrolimus (TAC) is the most widely used immunosuppressant for the prevention of acute rejection after solid organ transplantation. Its pharmacokinetics (PK) show considerable variability, making TAC a good candidate for therapeutic drug monitoring (TDM). The principal aim of the study was to describe the PK of TAC in pediatric patients during the first year after transplantation. METHODS: Routine TDM trough levels of TAC were obtained from 42 pediatric liver allograft recipients during the first year after transplantation. A population PK model was developed using nonlinear mixed-effects modeling to describe TAC PK during this period and to explain the observed variability by means of patients' demographics, biochemical test results and physiological characteristics. RESULTS: The PK of TAC were best described by a two-compartment model with first-order elimination. Apparent volumes of the central compartment, intercomparmental clearance and maximum blood clearance estimates were 253 L, 115 L/day and 314 L/day, respectively. The absorption first-order rate and volume of peripheral compartment were fixed to 4.5 h(-1) and 100 L, respectively. While hematocrit levels, time after transplantation and bodyweight influenced TAC clearance, bodyweight was the only covariate retained on volume of distribution. CONCLUSIONS: We developed a TAC population PK model in pediatrics covering the first year after liver transplantation that may serve as a tool for TAC dose individualization as part of TDM.

Fracture resistance of bone samples filled with fibre-reinforced composite posts: an ex vivo model.

AIM: To evaluate the strengthening effect of two different types of fibre-reinforced composite (FRC) posts in an ex vivo experimental model. METHODOLOGY: Compact and hollow bone samples from bovine femurs were used as standardized samples. A total of 80 hollow samples were divided into two groups and filled either with a prefabricated FRC post or with individually adapted FRC posts. For each group, half of the samples were subjected to thermocycling (5-55 °C, 5000×). The remaining samples were kept for 24 h at 37 °C at 100% relative humidity. All samples were loaded diametrically until fracture. The null hypothesis tested was that the fracture resistance of standardized bone samples is not influenced by the type of FRC post, independently of the exposure to thermocycling. Results were evaluated by anova, and subsequent multiple comparisons were performed. RESULTS: The samples filled with the individually adapted FRC posts were more resistant to fracture than the prefabricated ones (P < 0.001), but this difference was not apparent in the thermocycled groups. Detachment of the posts upon fracture was highest after thermocycling for both groups, amounting to 55% and 95% for the individual adapted posts and the prefabricated posts, respectively. CONCLUSIONS: Initially, the samples filled with the individually adapted FRC posts were more resistant to fracture than those filled with the prefabricated ones. However, after ageing of the samples, both types of posts had similar strengthening effects.

Pulpal regeneration and root development after subcutaneous transplantation of cryopreserved immature teeth in rats.

The purpose of this in vivo study was to investigate revascularization and root growth after autotransplantation of cryopreserved immature teeth. Immature molar teeth were extracted in 4-week-old Wistar rats. In the test group, teeth were cryopreserved for 1 week and transplanted subcutaneously to the abdomen. In the control group, teeth were transplanted subcutaneously immediately after extraction. Material was collected in test and control animals at intervals of 1, 2, 4 and 10 weeks post-transplantation and histological and microradiographical examination was performed. Results showed that during the first weeks after transplantation, pulpal repair was similar in both groups although degenerated pulpal tissue was replaced slower in cryopreserved teeth and some differences in types of hard tissue formation were found between test and control teeth. After 10 weeks, the differences in the regenerated pulpal tissue between cryopreserved and control teeth observed during the first weeks were no longer detectable. No root growth was detected microradiographically 10 weeks after transplantation in any of the transplanted teeth. The presence of dentin-like tissue in the pulp cavity of some autotransplanted cryopreserved teeth, suggests survival of pulpal tissue after cryopreservation.

Application of dermal microdialysis for the determination of bioavailability of clobetasol propionate applied to the skin of human subjects.

Dermal microdialysis was used to assess the bioavailability of a topical corticosteroid, clobetasol propionate, following application onto the skin of human subjects. The penetration of clobetasol propionate from a 4% m/v ethanolic solution applied onto 4 sites on one forearm of healthy human volunteers was studied. A lipid emulsion, Intralipid®, was used as the perfusate and linear microdialysis probes with a 2-kDa cutoff were inserted intradermally at the designated sites. The results indicated that Intralipid could be used as a suitable perfusate for in vivo microdialysis of this lipophilic drug of interest. Furthermore, the study clearly demonstrated the application of dermal microdialysis as a valuable tool to assess the bioavailability/bioequivalence of clobetasol propionate penetration into the skin following topical application.

The addition of calcium ions to starch/Carbopol mixtures enhances the nasal bioavailability of insulin.

To evaluate the influence of calcium poly(acrylates) on the nasal absorption of insulin in rabbits, starch/poly(acrylic acid) (ratio 25/75) (SD 25/75) was neutralised with NaOH and/or Ca(OH)(2). After neutralisation, a mixture of sodium and/or calcium carboxylate was formed depending on the Ca(OH)(2) concentration in the formulation. IR spectroscopy confirmed that most of the calcium molecules in the formulation interacted with acid groups of the acrylic acid polymer. Addition of Ca(OH)(2) to aqueous dispersions containing starch/poly(acrylic acid) yielded powders with an enhanced absorption of insulin after nasal delivery to rabbits in comparison with the equivalent powder without Ca(OH)(2). A mixture of SD 25/75 and Ca(OH)(2) at a ratio of 90/10 neutralised to pH 7.4 with NaOH induced the highest absorption of insulin, obtaining a bioavailability of +/-29% (vs. 19% for an equivalent formulation without Ca(OH)(2)). This increase in nasal delivery was possibly due to a higher elasticity after dispersing this formulation in nasal fluid and to a higher water absorbing capacity. Furthermore, after nasal delivery of (SD 25/75)/Ca(OH)(2) 90/10, a decrease in t(max) was observed, possibly due to a progressive dissociation of Ca(2+)-ions after hydration of the powder resulting in the closing of the tight junctions.

The tibialis tendon as a valuable anterior cruciate ligament allograft substitute: biomechanical properties.

The study evaluates the biomechanical properties of single-strand and single-loop tibialis (anterior and posterior) tendon allografts. A comparison was made with bone-patellar tendon-bone (BPTB) allografts. Sixty-four tendon allografts were evaluated in this study. Sixteen of these were single-strand tibialis anterior (TA) and 16 single-strand tibialis posterior (TP) tendons. Sixteen single-loop TA and TP tendons were also tested. The fourth group was composed of 16 BPTB allografts. The biomechanical properties determined were maximal load, stiffness, cross-sectional area and elongation. The results of this study showed that the maximal load of the single-loop tibialis tendons (1,553 +/- 62 N) was greater than of the BPTB (1,139 +/- 99 N), TA (776 +/- 43 N) and TP (888 +/- 64 N) tendons. The stiffness of the single-loop tibialis tendons (236 +/- 10 N/mm) was also greater than of the BPTB (168 +/- 13 N/mm), TA (60 +/- 2 N/mm) and TP (73 +/- 5 N/mm) tendons. The cross-sectional area of the BPTB tendons was 67 +/- 5 mm(2), of the single-loop tibialis tendons 36 +/- 2 mm(2), of the TA tendons 20 +/- 1 mm(2), and of the TP tendons 23 +/- 1 mm(2). The elongation of the single-loop tibialis tendons and of the BPTB tendons was almost similar (7 +/- 0.4 mm). The same applied to the TA and TP tendons (14 +/- 0.6 mm). The results of this in vitro mechanical study suggest that fresh-frozen single-loop TA and TP tendons, and BPTB allografts are an acceptable substitute for hamstrings in anterior cruciate ligament reconstruction.

The effect of ageing on cytochrome p450 enzymes: consequences for drug biotransformation in the elderly.

Ageing is an aggravating factor leading to alterations in the biotransformation of drugs, and therefore their therapeutic efficacy and safety. In this review we discuss the influence of ageing on drug metabolizing enzymes in male Wistar rats. We report that drug metabolizing enzymes can be affected by ageing either by post-translational modifications or by transcriptional modifications. The post-translational modifications could be due to an increase of oxidative stress during ageing. Although it is now well established that transcriptional modifications are due to a change in the GH secretion profile in senescent rats, the intracellular mechanisms underlying these modifications are still unclear. In addition to the strong decrease in the activity of the main CYPs of male rats, we discuss the potential consequences on human drug metabolism in the elderly.

Review: finishing and polishing procedures of (resin-modified) glass ionomers and compomers in paediatric dentistry.

BACKGROUND: A smooth surface has a beneficial effect on the aesthetic quality and longevity of a dental restoration, as well as on its biocompatibility with oral tissues. In this review studies on glass-ionomer cements (GIC), resin-modified glass-ionomer cements (RM-GIC), and compomers or polyacid-modified resin composites (PAM-C) were assessed as these are currently used in paediatric dentistry. METHOD: Medline databases (USA National Library of Medicine) was searched using WinSpirs and Pubmed. This search used a keyword filter including dental materials, polishing procedures, and instrumentation including influencing factors. FINDINGS: Although the literature shows different commercially available tools it seems that the ideal polishing instrumentation in paediatric dentistry for GIC and compomers is not yet on the market. Furthermore, the constant development of dental materials and polishing products impose a need for continuous scientific research.

Seckel syndrome associated with oligodontia, microdontia, enamel hypoplasia, delayed eruption, and dentin dysmineralization: a new variant?

Seckel syndrome (SCKL) [OMIM Entry 210600] is a rare, autosomal recessive syndrome, characterized by severe intrauterine and postnatal growth retardation, microcephaly, mental retardation, and typical facial appearance with beaklike protrusion of the midface (bird-headed). Associated findings may include limb anomalies, dislocation of femoral heads, scoliosis, and gastrointestinal malformation. A 14-year-old boy is presented with brain hypoplasia, pachygyria, hydrocephaly, enamel hypoplasia and root dysplasia in the temporary dentition, and oligodontia, severe microdontia, and delayed eruption of the permanent dentition. The association of SCKL with the above unusual dental findings may represent a new phenotype.

Generic substitution: the use of medicinal products containing different salts and implications for safety and efficacy.

In their quest to gain early entry of new generic products into the market prior to patent expiration, one of the strategies pursued by generic drug product manufacturers is to incorporate different salts of an approved active pharmaceutical ingredient (API) in a brand company's marketed dosage form and subject such dosage forms to bioequivalence assessment. These initiatives present challenges to regulatory authorities where the decision to approve bioequivalent products containing such pharmaceutical alternatives must be considered in the light of safety and efficacy, and more particularly, with respect to their substitutability. This article describes the various issues and contentions associated with the concept of pharmaceutical alternatives, specifically with respect to the uses of different salts and the implications for safety, efficacy and generic substitution.

Biowaiver monographs for immediate release solid oral dosage forms based on biopharmaceutics classification system (BCS) literature data: chloroquine phosphate, chloroquine sulfate, and chloroquine hydrochloride.

Literature data on the properties of chloroquine phosphate, chloroquine sulfate, and chloroquine hydrochloride related to the Biopharmaceutics Classification System (BCS) are reviewed. The available information indicates that these chloroquine salts can be classified as highly soluble and highly permeable, i.e., BCS class I. The qualitative composition of immediate release (IR) tablets containing these Active Pharmaceutical Ingredients (APIs) with a Marketing Authorization (MA) in Belgium (BE), Germany (DE), Finland (FI), and The Netherlands (NL) is provided. In view of these MA's and the critical therapeutic indication of chloroquine, it is assumed that the registration authorities had evidence that these formulations are bioequivalent to the innovator. It is concluded that IR tablets formulated with these excipients are candidates for a biowaiver.

In vivo tolerance assessment of skin after insertion of subcutaneous and cutaneous microdialysis probes in the rat.

The purpose of the study was to evaluate the trauma induced by insertion of the linear microdialysis probe in the subcutaneous and dermal tissue in the rat and to check if the microdialysis probe insertion affects transdermal drug delivery. Non-invasive bioengineering methods (TEWL, Laser Doppler Velocimeter, Chromameter) as well as histology were combined to characterize these effects. The results showed that the dermal and subcutaneous insertion of microdialysis probes did not change skin permeability, blood flow and color, confirming the safety of this technique. The probe depth did not influence the trauma. No significant physical damage after probe insertion was noticed. Thus, the present work validates the use of microdialysis in dermatopharmacokinetics studies after topical or systemic drug delivery.