Cost and cost-effectiveness of tuberculosis treatment shortening: a model-based analysis.

BACKGROUND: Despite improvements in treatment success rates for tuberculosis (TB), current six-month regimen duration remains a challenge for many National TB Programmes, health systems, and patients. There is increasing investment in the development of shortened regimens with a number of candidates in phase 3 trials. METHODS: We developed an individual-based decision analytic model to assess the cost-effectiveness of a hypothetical four-month regimen for first-line treatment of TB, assuming non-inferiority to current regimens of six-month duration. The model was populated using extensive, empirically-collected data to estimate the economic impact on both health systems and patients of regimen shortening for first-line TB treatment in South Africa, Brazil, Bangladesh, and Tanzania. We explicitly considered 'real world' constraints such as sub-optimal guideline adherence. RESULTS: From a societal perspective, a shortened regimen, priced at USD1 per day, could be a cost-saving option in South Africa, Brazil, and Tanzania, but would not be cost-effective in Bangladesh when compared to one gross domestic product (GDP) per capita. Incorporating 'real world' constraints reduces cost-effectiveness. Patient-incurred costs could be reduced in all settings. From a health service perspective, increased drug costs need to be balanced against decreased delivery costs. The new regimen would remain a cost-effective option, when compared to each countries' GDP per capita, even if new drugs cost up to USD7.5 and USD53.8 per day in South Africa and Brazil; this threshold was above USD1 in Tanzania and under USD1 in Bangladesh. CONCLUSION: Reducing the duration of first-line TB treatment has the potential for substantial economic gains from a patient perspective. The potential economic gains for health services may also be important, but will be context-specific and dependent on the appropriate pricing of any new regimen.

Isolation demand from carbapenemase-producing Enterobacteriaceae screening strategies based on a West London hospital network.

OBJECTIVE: To estimate the isolation demands arising from high-risk specialty-based screening for carbapenemase-producing Enterobacteriaceae (CPE), and the potential fraction of CPE burden detected. METHODS: Clinical specialty groups from three London hospitals were ranked by incidence of carbapenem resistance among Escherichia coli and Klebsiella spp. Contact precaution bed-days were estimated for three screening strategies: Strategy 1, 'circulation science and renal medicine'; Strategy 2, Strategy 1 plus 'specialist services'; and Strategy 3, Strategy 2 plus 'private patients'. Isolation bed occupancy rates and potential CPE detection rates were estimated. RESULTS: Of 99,105 admissions to the three hospitals in Financial Year 2014/15, Strategies 1, 2 and 3 would have screened 4371 (4.4%), 7482 (7.6%), and 13,542 (13.7%) patients, respectively. The specialties' isolation bed occupancy rates varied between 3% and 696% depending on strategy, number of consecutive tests, and whether or not pre-emptive isolation had been applied. Expected detection rates of the potential CPE burden in the hospital network would have varied between 17.1% and 47.5%. CONCLUSIONS: High-risk specialty-based screening has the potential to detect nearly half of the potential CPE burden, and would be more pragmatic than patient-level risk-factor-based screening. Pre-emptive isolation increases isolation requirements substantially. CPE screening strategies need to balance risk and resources.

The complex evolution of antibiotic resistance in Mycobacterium tuberculosis.

Multidrug-resistant and extensively drug-resistant tuberculosis (TB) represent a major threat to the control of the disease worldwide. The mechanisms and pathways that result in the emergence and subsequent fixation of resistant strains of Mycobacterium tuberculosis are not fully understood and recent studies suggest that they are much more complex than initially thought. In this review, we highlight the exciting new areas of research within TB resistance that are beginning to fill these gaps in our understanding, whilst also raising new questions and providing future directions.

Clinical evaluation of diamine silver fluoride/potassium iodide as a dentine desensitizing agent. A pilot study.

BACKGROUND: The aim of the present study was to compare the efficacy of an experimental diamine silver fluoride/potassium iodide product with an oxalic acid-based preparation in reducing dentine hypersensitivity. METHODS: The study was conducted as a double-blind, randomized clinical trial. A total of 19 subjects with dentine hypersensitivity on both sides of their upper arch were selected. The most sensitive tooth in each quadrant was identified and received a cold stimulus. The response was recorded on a visual analogue scale (VAS). The tooth thus selected was treated with one of the treatment agents. One week later the level of dentine sensitivity was assessed. Participants were also asked for their subjective assessment of treatment effects. RESULTS: The mean difference between VAS at baseline and seven days for teeth treated with diamine silver fluoride/potassium iodide was greater than that for teeth treated with the oxalic acid-based preparation (p = 0.0134). The subjects' subjective assessment of changes in dentine hypersensitivity indicated that more obtained relief with the diamine silver fluoride/potassium iodide treatment (p = 0.0129). CONCLUSIONS: It was concluded that an experimental diamine silver fluoride/potassium iodide product has potential as a treatment for dentine hypersensitivity.

The inability of Streptococcus mutans and Lactobacillus acidophilus to form a biofilm in vitro on dentine pretreated with ozone.

BACKGROUND: The use of ozone therapy in the treatment of dental caries is equivocal. The aim of this study was to use an in vitro model to determine the effects of prior ozone application to dentine on biofilm formation and to measure any associated reduction in bacteria viability. METHODS: Twenty dentine discs were bonded to the bases of 5 mL polycarbonate screw top vials. Ten dentine discs were infused with ozone for 40 seconds, 10 samples remained untreated as a control. The vials were filled with nutrient medium, sterilized and placed into the outflow from a continuous chemostat culture of Streptococcus mutans and Lactobacillus acidophilus for four weeks. At the conclusion of the experiment bacterial growth was monitored by taking optical density readings of the growth medium in each vial and the outer surface of the dentine specimens were examined by scanning electron microscopy as shown by SEM analysis. RESULTS: Ozone infusion prevented biofilm formation on all the treated samples while there was substantial biofilm present on the control specimens. While the average optical density of the control specimens was almost twice that of the ozone infused dentine (0.710 for the control with a SD of 0.288 and 0.446 for the ozonated samples with a SD of 0.371), the results were not significant (p > 0.05). CONCLUSIONS: This preliminary study has shown that the infusion of ozone into non-carious dentine prevented biofilm formation in vitro from S. mutans and L. acidophilus over a four-week period. The possibility exists that ozone treatment may alter the surface wettability of dentine through reaction with organic constituents.

An in vitro investigation of marginal dentine caries abutting composite resin and glass ionomer cement restorations.

BACKGROUND: There are a number of studies citing the primary reason for replacing auto cure glass ionomer cements was due to recurrent caries. The purpose of this study was to use an in vitro model to measure caries at the dentine restoration interface of bonded composite resin and auto cure glass ionomer cement restorations and to measure the amount of surface degradation occurring in the restorative materials. METHODS: Specimens of auto cure glass ionomer cements (Riva Fast, Fuji IX Fast, Ketac Molar Quick and Fuji VII) and bonded composite resin restorations (Ice, SDI) were placed separately at the dentino-enamel junction of 10 recently extracted human third molar teeth, disinfected and placed into the overflow from a continuous culture of S. mutans for two weeks. Restorations were sectioned and prepared for scanning electron microscopy (SEM) and electron probe microanalysis (EPMA). Restoration tooth interfaces were photographed and the distance from the surface of the teeth to the surface of the restorations measured. EPMA of percentage weights of calcium, phosphorous and fluoride were made outwards from the restoration surface 130pm at a depth of 10 microm below the surface of the dentine. RESULTS: There were significant differences between the surface heights of composite resin, auto cure glass ionomer cements compared to teeth surfaces. Percentage weights of calcium and phosphorus levels were similar to non-demineralized dentine in the auto cure glass ionomer cement samples but there were significant reductions in mineral content of dentine adjacent to bonded composite resin restorations. Fluoride levels were mixed. CONCLUSIONS: This study shows that placing a bonded composite resin restoration into dentine affords little protection to the surrounding tooth from caries attack although insignificant degradation of the restorative surface occurs. Placing a glass ionomer cement restoration into dentine protects the surrounding tooth from caries but degradation of the restoration surface occurs.

Electron probe microanalysis of ion exchange of selected elements between dentine and adhesive restorative materials.

BACKGROUND: There have been numerous attempts to demonstrate the phenomenon of ion exchange between auto cure glass ionomer cements (GICs) and dentine. The purpose of this study was to employ an electron probe microanalysis (EPMA) technique to examine the interchange of elements between non-demineralized dentine and two types of restorative material, auto cure GICs and a resin composite. METHODS: Restorations of auto cure GICs (Riva Fast, Fuji IX Fast, Ketac Molar Quick and Fuji VII) and a bonded composite resin were placed in each of 10 recently extracted human third molar teeth. After two weeks the restorations were sectioned and prepared for EPMA. Percentage weights of calcium, phosphorus aluminum, strontium and fluoride were calculated in the restorations 200 microm from the restorative interface and 200 microm into the dentine at 5 microm intervals. RESULTS: There was evidence of calcium and phosphorus in all five auto cure GICs to a depth of 50 microm. Aluminum and strontium ions were also present in dentine except subjacent to Ketac Molar restorations. There was evidence of element transfer into composite resin and resin-bonded dentine. CONCLUSIONS: The findings of this paper support the concept of ion exchange as a bonding mechanism between auto cure GIC and dentine. Element penetration into tooth structure and GIC exceeded beyond the "ion exchange layer" observed in scanning electron microscopy studies. Penetration of calcium and phosphorus into composite resin from dentine likely occurred as a result of the self-etching process dissolving calcium and phosphorus and incorporating these elements into the hybrid layer. The presence of Al and Sr ions in dentine were likely to be associated with resin tags extending into the dentine.

Differences between normal and demineralized dentine pretreated with silver fluoride and potassium iodide after an in vitro challenge by Streptococcus mutans.

BACKGROUND: The application of diamine silver fluoride (Ag(NH3)2F) and potassium iodide (KI) to demineralized dentine has been shown to inhibit the growth of Streptococcus mutans. The purpose of this study was to observe the differences between demineralized and non-demineralized dentine treated with AgF/KI. METHODS: Thirty-five dentine discs were bonded to the bases of 5 mL polycarbonate screw top vials which were filled with nutrient medium, sterilized and placed into the overflow from a continuous culture of S. mutans. Samples were divided as follows: 10 samples of demineralized dentine; 10 samples of demineralized dentine treated with AgF/KI; 5 samples of non-demineralized dentine; and 10 samples of non-demineralized dentine treated with AgF/KI. Following two weeks connected to the Chemostat, an electron probe microanalysis (EPMA) of percentage weights and penetration depths of calcium, phosphorous silver and fluoride was conducted. Bacterial growth was monitored by taking optical density readings of the growth medium in each vial and outer surfaces of the specimens were examined by scanning electron microscopy (SEM). RESULTS: AgF/KI treatment of demineralized and non-demineralized dentine prevented biofilm formation and reduced further demineralization by S. mutans. AgF/KI treatment of demineralized dentine was more effective in reducing dentine breakdown and the growth of S. mutans. Significantly higher levels of silver and fluoride were deposited within demineralized dentine. CONCLUSIONS: A topical treatment with AgF/KI on dentine reduced in vitro caries development and inhibited surface biofilm formation. Reduction of in vitro caries development and viability of S. mutans was more pronounced on the dentine samples that had been demineralized prior to the application of

Ion uptake into demineralized dentine from glass ionomer cement following pretreatment with silver fluoride and potassium iodide.

BACKGROUND: Diamine silver fluoride (Ag(NH3)2F), referred to as AgF, has been shown to provide a pronounced antimicrobial action against caries. The clinical application of this material has been limited by the staining associated with both teeth and tooth coloured restorative materials. The application of potassium iodide (KI) after AgF eliminates stain formation. The purpose of this study was to determine if a prior application of silver fluoride and potassium iodine to demineralized dentine affected the uptake of strontium and fluoride from a glass ionomer cement restoration. METHOD: Three cavities were prepared in each of five recently extracted human third molars. The cavities were demineralized and treated as follows. In each tooth, one cavity was left as a control, one cavity was restored with glass ionomer cement and one cavity was treated with 1.8M AgF and a saturated KI solution and then restored with glass ionomer cement. The penetration of the various elements into demineralized dentine was measured by their relative percentage weights using electron probe microanalysis (EPMA). RESULTS: Fluoride uptake was significantly higher in the AgF and KI treated samples compared to the other two samples and significantly higher in the glass ionomer restored sample compared to the control. The application of AgF and KI did not significantly interfere with the transfer of strontium from glass ionomer cement into dentine. Silver and iodine deposits were present in the demineralized dentine treated with AgF and KI. CONCLUSIONS: The application of AgF and KI onto dentine prior to the placement of glass ionomer cement did not significantly affect the strontium uptake into the subjacent demineralized dentine and the fluoride levels in this zone were significantly increased.

Bond strengths between composite resin and auto cure glass ionomer cement using the co-cure technique.

BACKGROUND: The clinical technique for sandwich restorations prescribes etching initially set auto cure glass ionomer cement (GIC) prior to placing a layer of resin bond to develop a weak mechanical bond between composite resin and GIC. Co-curing a resin modified glass ionomer cement (RMGIC) bond and composite resin to GIC may create a chemical bond and improve the bond strengths between these two materials. METHODS: A total of 48 specimens were prepared, 12 in each of four categories. Capsulated GIC was placed into a mould and allowed to set for four minutes, etched for five seconds followed by placement of a resin bond and photo cured for five seconds over which a composite resin was puddled onto the resin bond and photo cured for 10 seconds. Capsulated GIC was placed into a mould and allowed to set for four minutes after which a sample of RMGIC (Riva LC) was prepared using twice the liquid powder ratio and painted over the surface of the set GIC using a micro brush. An increment of composite resin was added over the RMGIC and both materials were photo co-cured for 10 seconds. Capsulated GIC was placed into a mould and RMGIC (Riva LC) that had been prepared using twice the liquid powder was brushed over the GIC (prior to initial set) followed by the placement of a layer of composite resin and photo co-cured for 10 seconds. Capsulated GIC was placed into a mould and RMGIC (Fuji II LC) that had been prepared using twice the liquid powder was brushed over the GIC (prior to initial set) followed by the placement of a layer of composite resin and photo co-cured for 10 seconds. Shear testing of each of the samples was carried out and specimens were examined to determine the nature of the fracture. Selected samples were prepared for SEM investigation to observe the interfaces between the GIC and composite resin. RESULTS: There were significantly lower bond strengths (P < 0.05) amongst samples that had been etched and bonded (2.42MPa) compared to the other samples that had been co-cure bonded with RMGIC (6.48-7.05MPa). There were no significant differences amongst the bond strengths of the samples co-cure bonded with RMGIC. Specimens prepared by the 'etch and bond' technique failed adhesively and co-cured specimens failed cohesively within the GIC. SEM investigation showed chemical bonds between RMGIC bond and GIC and composite resin. CONCLUSIONS: The co-cured RMGIC bonding system eliminates several placement steps and produces a significantly stronger chemical bond between GIC and composite resin than the 'etch and bond' technique. RMGIC bond and composite resin may be co-cured to GIC either before or after initial set has occurred.

The effect of silver fluoride and potassium iodide on the bond strength of auto cure glass ionomer cement to dentine.

BACKGROUND: Diamine silver fluoride (Ag(NH3)2F), referred to as AgF, has been shown to reduce the incidence of caries in primary dentitions. The clinical application of this material has been limited by staining associated with both teeth and restorative materials. The application of potassium iodide (KI) after AgF eliminates stain formation. There is a lack of information as to how the addition of AgF followed by KI may affect the bond strength to dentine. The purpose of this study was to compare the bond strengths of auto cure glass ionomer cement to dentine surfaces that had been treated with AgF and KI and without treatment. METHODS: Ten recently extracted human third molars were embedded into methyl methacrylate resin and sliced to form a square block of exposed dentine surfaces. Each of the four surfaces were treated by one of the following procedures: (a) etching with 37 per cent phosphoric acid; (b) applying GC dentine conditioner; (c) etching, followed by application of AgF/KI then washing off the precipitate and air drying; and (d) etching, applying AgF/KI and air drying the reaction products on the surface. Fuji VII auto cure glass ionomer cement was bonded onto each sample and fracture tested. RESULTS: The dentine samples treated with AgF/KI followed by washing away the precipitate and air drying had bond strengths (2.83 MPa) not significantly different from samples that had been conditioned (2.40 MPa). Samples where the AgF/KI precipitate had been air dried onto the dentine surface had significantly lower bond strengths (1.49 MPa) than the washed samples. Samples that were etched had significantly lower bond strengths (1.91MPa) than the conditioned samples. CONCLUSIONS: This study found that the application of AgF/KI to etched dentine samples followed by washing off the precipitate, created bond strengths that were not significantly different to conditioned samples. Leaving the AgF/KI precipitate on the dentine surface significantly reduced the bond strength of auto cured glass ionomer cement to dentine. Washing away the reaction products and air drying is recommended as the clinical protocol for using AgF and KI on dentine surfaces prior to application of an auto cure glass ionomer cement.

An in vitro model to measure the effect of a silver fluoride and potassium iodide treatment on the permeability of demineralized dentine to Streptococcus mutans.

BACKGROUND: Diamine silver fluoride (Ag(NH3)2F), referred to as AgF, has been used to reduce the incidence of caries in primary dentitions but has been limited by the associated staining of both teeth and restorative materials. The application of potassium iodide (KI), following AgF prevents staining but its effects on the ability of AgF to reduce caries are not known. The aim of this study was to develop an in vitro model that would provide an indication of the permeability of demineralized dentine to Streptococcus mutans after treatment of the dentine with AgF followed by KI. METHODS: Forty dentine discs were bonded to the base of forty 5mL polycarbonate screw top vials (that had had their bases removed), filled with nutrient medium, sterilized and placed into a continuous culture of S. mutans. Samples were divided into four groups as follows: 10 samples of demineralized dentine as a control, 10 samples of demineralized dentine treated with AgF/KI, 10 samples of demineralized dentine treated with KI and 10 samples of demineralized dentine treated with AgF. After two weeks the optical density of the growth medium chambers was measured to determine bacterial penetration and growth. Cultures were plated out to determine migration through the discs by S. mutans. RESULTS: S. mutans migrated through all dentine discs. However, the samples treated with AgF and AgF/KI had significantly lower optical densities than the corresponding controls. The range of optical densities was least amongst demineralized samples treated with AgF/KI. CONCLUSIONS: Under the conditions of this study, treatment of demineralized dentine discs with AgF followed by KI allowed the penetration of S. mutans. Based on optical density measurements, the treatment resulted in significantly fewer microorganisms being present subjacent to the discs treated with AgF and KI than the control discs at the end of the experimental period.

The co-cured, light-activated glass-ionomer cement-composite resin restoration.

The simultaneous curing of unpolymerized composite resin and inactivated light-curing glass-ionomer cement appears to offer a number of clinical improvements to the laminated glass-ionomer cement-composite resin restoration. The observation that composite resin cures before the glass-ionomer cement suggests that the polymerization shrinkage of the resin may be taken up by the uncured glass-ionomer cement, reducing the internal stress of the restoration. A procedure is described for the placement of this type of laminate restoration that reduces both technique sensitivity and placement time, by eliminating a number of the steps required for a conventional "sandwich" restoration. The apparent clinical success of this technique indicates the need for laboratory testing to evaluate the potential of this procedure.

The tunnel restoration--nine years of clinical experience using capsulated glass ionomer cements. Case report.

The clinical potential of the tunnel restoration is restrained by perceived difficulties of access to proximal caries and lack of long-term clinical data. This paper describes a technique that affords proximal access similar to that of a standard Class II cavity preparation and provides an evaluation of a technique, using capsulated glass ionomer cements. It is supported by more than nine years of clinical experience that confirms the viability of this procedure as an alternative to conventional Class II cavity restorations for initial proximal lesions.