Clinical implementation of dynamic multileaf collimation for compensated bladder treatments.

BACKGROUND AND PURPOSE: To describe the clinical implementation of dynamic multileaf collimation (DMLC). Custom compensated four-field treatments of carcinoma of the bladder have been used as a simple test site for the introduction of intensity modulated radiotherapy.MATERIALS AND METHODS: Compensating intensity modulations are calculated from computed tomography (CT) data, accounting for scattered, as well as primary radiation. Modulations are converted to multileaf collimator (MLC) leaf and jaw settings for dynamic delivery on a linear accelerator. A full dose calculation is carried out, accounting for dynamic leaf and jaw motion and transmission through these components. Before treatment, a test run of the delivery is performed and an absolute dose measurement made in a water or solid water phantom. Treatments are verified by in vivo diode measurements and real-time electronic portal imaging. RESULTS: Seven patients have been treated using DMLC. The technique improves dose homogeneity within the target volume, reducing high dose areas and compensating for loss of scatter at the beam edge. A typical total treatment time is 20 min. CONCLUSIONS: Compensated bladder treatments have proven an effective test site for DMLC in an extremely busy clinic.

Application of atmospheric pressure nonthermal plasma for the in vitro eradication of bacterial biofilms

The use of atmospheric pressure nonthermal plasma represents an interesting and novel approach for the decontamination of surfaces colonized with microbial biofilms that exhibit enhanced tolerance to antimicrobial challenge. In this study, the influence of an atmospheric pressure nonthermal plasma jet, operated in a helium and oxygen gas mixture under ambient pressure, was evaluated against biofilms of Bacillus cereus,Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa. Within <4 min of plasma exposure, complete eradication of the two Gram-positive bacterial biofilms was achieved. Although Gram-negative biofilms required longer treatment time, their complete eradication was still possible with 10 min of exposure. Whilst this study provides useful proof of concept data on the use of atmospheric pressure plasmas for the eradication of bacterial biofilms in vitro, it also demonstrates the critical need for improved understanding of the mechanisms and kinetics related to such a potentially significant approach. © 2012 Federation of European Microbiological Societies.

Cost-effectiveness of ART restorations in elderly adults: a randomized clinical trial

BACKGROUND: As the world population ages, the requirement for cost-effective methods of treating chronic disease conditions increases. In terms of oral health, there is a rapidly increasing number of dentate elderly with a high burden of maintenance. Population surveys indicate that older individuals are keeping their teeth for longer and are a higher caries risk group. Atraumatic Restorative Treatment (ART) could be suitable for patients in nursing homes or house-bound elderly, but very little research has been done on its use in adults.

OBJECTIVES: To compare the cost-effectiveness of ART and a conventional technique (CT) for restoring carious lesions as part of a preventive and restorative programme for older adults.

METHODS: In this randomized clinical trial, 82 patients with carious lesions were randomly allocated to receive either ART or conventional restorations. Treatment costs were measured based on treatment time, materials and labour. For the ART group, the cost of care provided by a dentist was also compared to the cost of having a hygienist to provide treatment. Effectiveness was measured using percentage of restorations that survived after a year.

RESULTS: Eighty-two patients received 260 restorations, that is, 128 ART and 132 conventional restorations. 91.1% of the restorations were on one surface only. After a year, 252 restorations were assessed in 80 patients. The average cost for ART and conventional restorations was €16.86 and €28.71 respectively; the restoration survival percentages were 91.1% and 97.7%, respectively. This resulted in a cost-effectiveness ratio of 0.18 (ART) and 0.29 (CT). When the cost of a hygienist to provide ART was inserted in the analysis, the resulting ratio was 0.14.

CONCLUSIONS: Atraumatic restorative treatment was found to be a more cost-effective alternative to treat older adults after 1 year, compared to conventional restorations, especially in out of surgery facilities and using alternative workforce such as hygienists. Atraumatic restorative treatment can be a useful tool to provide dental care for frail and fearful individuals who might not access dental treatment routinely.

A preliminary report of the cost-effectiveness of tooth replacement strategies for partially dentate elders

OBJECTIVE: To compare the cost-effectiveness of conventional treatment using partial dentures with functionally orientated treatment to replace missing teeth for partially dentate elders using a randomised controlled clinical trial.

BACKGROUND: In many countries, including the Republic of Ireland, the only publically funded treatment option offered to partially dentate older patients is a removable partial denture. However, evidence suggests that these removable prostheses are unpopular with patients and can potentially increase the risk of further dental disease and subsequent tooth loss.

MATERIALS AND METHODS: Fourty-four partially dentate patients aged 65 years and older were recruited. Patients were randomly assigned to the two treatment arms of the study. The conventional treatment group received removable partial dentures to replace all missing natural teeth. The functionally orientated group was restored to a Shortened Dental Arch (SDA) of 10 occluding contacts using resin-bonded bridgework (RBB). The costs associated with each treatment were recorded. Effectiveness was measured in terms of the impact on oral health-related quality of life (OHRQoL) using OHIP-14.

RESULTS: Both groups reported improvements in OHRQoL 1 month after completion of treatment. The conventional treatment group required 8.3 clinic visits as compared to 4.4 visits for the functionally orientated group. The mean total treatment time was 183 min 19 s for the conventional group vs. 124 min 8 s for the functionally orientated group. The average cost of treatment for the conventional group was 487.74 Euros compared to 356.20 Euros for the functional group.

CONCLUSIONS: Functionally orientated treatment was more cost-effective than conventional treatment in terms of treatment effect and opportunity costs to the patients' time.

Cost Effectiveness of Tooth Replacement Strategies for Partially Dentate Elders

Objectives: This study aimed to compare the cost effectiveness of conventional treatment using partial dentures with functionally-orientated treatment based on the shortened dental arch concept to replace missing teeth for partially dentate elders.
Methods: 44 partially dentate patients aged 65 years and older were recruited following routine dental assessment at a university dental hospital. Patients consented to and were randomly assigned to the two treatment arms. The conventional treatment group received a removable partial denture to replace all missing natural teeth. The functionally-orientated group were restored to a shortened dental arch of 10 occluding contacts using resin bonded bridgework. The costs associated with each treatment were recorded including laboratory charges, treatment time and opportunity costs. The impact on quality of life (OHRQoL) was measured using the 14-item Oral Health Impact Profile.
Results: Both groups reported improvements in OHRQoL after completion of treatment. For the conventional group, the mean OHIP-14 score decreased from 12.4 pre-operatively to 3.3 post-operatively (p<0.001). In the functionally-orientated group the OHIP-14 score decreased from 11.4 to 1.8 following treatment (p<0.001). On average the conventional treatment group required 8.3 clinic visits as compared to 4.4 visits for the functionally-orientated group. The mean total treatment time was 183 minutes 19 seconds for the conventional group versus 124 minutes 8 seconds for the functionally-orientated group. The conventional treatment group had an average of 6.33 teeth replaced at a laboratory cost of 337.31 Euros. The functionally-orientated group had an average of 2.64 teeth replaced at a laboratory cost of 244.05 Euros.
Conclusions: Restoration to a shortened dental arch using functionally-orientated treatment resulted in a similar improvement in OHRQoL with fewer clinic visits, less operative time and at a lower laboratory cost compared with conventional treatment.

The influence of microbial factors on the susceptibility of bacteria to photocatalytic destruction

The role that bacterial factors play in determining how bacteria respond to photocatalytic degradation is becoming increasingly recognised. Fimbriae which are thin, proteinaceous cell surface structures produced by many enterobacteria are generally considered to be important bacterial virulence determinants in the host. Recent studies, however, suggest that their expression may be increased during times of environmental stress to protect them against factors such as nutrient depletion and oxidation. In this study bacteria were grown under defined culture conditions to promote the expression of type 1 fimbriae and subjected to photocatalytic treatment. Results showed that Escherichia coli grown under conditions to express type 1 fimbriae were more resistant to photocatalytic destruction than control cultures, taking 75 min longer to be destroyed. Curli fimbriae are also known to play a role in environmental protection of bacteria and they are associated with biofilm production. The ability of the E. coli strain to produce curli fimbriae was confirmed and biofilms were grown and subjected to photocatalytic treatment. Biofilm destruction by photocatalysis was assessed using a resazurin viability assay and a loss of cell viability was demonstrated within 30 min treatment time. This study suggests that intrinsic bacterial factors may play a role in determining an organism’s response to photocatalytic treatment and highlights their importance in this disinfection process.

Technological aids for the rehabilitation of memory and executive functioning in children and adolescents with acquired brain injury (Review).

Background The use of technology in healthcare settings is on the increase and may represent a cost-effective means of delivering rehabilitation. Reductions in treatment time, and delivery in the home, are also thought to be benefits of this approach. Children and adolescents with brain injury often experience deficits in memory and executive functioning that can negatively affect their school work, social lives, and future occupations. Effective interventions that can be delivered at home, without the need for high-cost clinical involvement, could provide a means to address a current lack of provision. We have systematically reviewed studies examining the effects of technology-based interventions for the rehabilitation of deficits in memory and executive functioning in children and adolescents with acquired brain injury. Objectives To assess the effects of technology-based interventions compared to placebo intervention, no treatment, or other types of intervention, on the executive functioning and memory of children and adolescents with acquired brain injury. Search methods We ran the search on the 30 September 2015. We searched the Cochrane Injuries Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), EMBASE Classic + EMBASE (OvidSP), ISI Web of Science (SCI-EXPANDED, SSCI, CPCI-S, and CPSI-SSH), CINAHL Plus (EBSCO), two other databases, and clinical trials registers. We also searched the internet, screened reference lists, and contacted authors of included studies. Selection criteria Randomised controlled trials comparing the use of a technological aid for the rehabilitation of children and adolescents with memory or executive-functioning deficits with placebo, no treatment, or another intervention. Data collection and analysis Two review authors independently reviewed titles and abstracts identified by the search strategy. Following retrieval of full-text manuscripts, two review authors independently performed data extraction and assessed the risk of bias. Main results Four studies (involving 206 participants) met the inclusion criteria for this review. Three studies, involving 194 participants, assessed the effects of online interventions to target executive functioning (that is monitoring and changing behaviour, problem solving, planning, etc.). These studies, which were all conducted by the same research team, compared online interventions against a 'placebo' (participants were given internet resources on brain injury). The interventions were delivered in the family home with additional support or training, or both, from a psychologist or doctoral student. The fourth study investigated the use of a computer program to target memory in addition to components of executive functioning (that is attention, organisation, and problem solving). No information on the study setting was provided, however a speech-language pathologist, teacher, or occupational therapist accompanied participants. Two studies assessed adolescents and young adults with mild to severe traumatic brain injury (TBI), while the remaining two studies assessed children and adolescents with moderate to severe TBI. Risk of bias We assessed the risk of selection bias as low for three studies and unclear for one study. Allocation bias was high in two studies, unclear in one study, and low in one study. Only one study (n = 120) was able to conceal allocation from participants, therefore overall selection bias was assessed as high. One study took steps to conceal assessors from allocation (low risk of detection bias), while the other three did not do so (high risk of detection bias). Primary outcome 1: Executive functioning: Technology-based intervention versus placebo Results from meta-analysis of three studies (n = 194) comparing online interventions with a placebo for children and adolescents with TBI, favoured the intervention immediately post-treatment (standardised mean difference (SMD) -0.37, 95% confidence interval (CI) -0.66 to -0.09; P = 0.62; I2 = 0%). (As there is no 'gold standard' measure in the field, we have not translated the SMD back to any particular scale.) This result is thought to represent only a small to medium effect size (using Cohen’s rule of thumb, where 0.2 is a small effect, 0.5 a medium one, and 0.8 or above is a large effect); this is unlikely to have a clinically important effect on the participant. The fourth study (n = 12) reported differences between the intervention and control groups on problem solving (an important component of executive functioning). No means or standard deviations were presented for this outcome, therefore an effect size could not be calculated. The quality of evidence for this outcome according to GRADE was very low. This means future research is highly likely to change the estimate of effect. Primary outcome 2: Memory One small study (n = 12) reported a statistically significant difference in improvement in sentence recall between the intervention and control group following an eight-week remediation programme. No means or standard deviations were presented for this outcome, therefore an effect size could not be calculated. Secondary outcomes Two studies (n = 158) reported on anxiety/depression as measured by the Child Behavior Checklist (CBCL) and were included in a meta-analysis. We found no evidence of an effect with the intervention (mean difference -5.59, 95% CI -11.46 to 0.28; I2 = 53%). The GRADE quality of evidence for this outcome was very low, meaning future research is likely to change the estimate of effect. A single study sought to record adverse events and reported none. Two studies reported on use of the intervention (range 0 to 13 and 1 to 24 sessions). One study reported on social functioning/social competence and found no effect. The included studies reported no data for other secondary outcomes (that is quality of life and academic achievement). Authors' conclusions This review provides low-quality evidence for the use of technology-based interventions in the rehabilitation of executive functions and memory for children and adolescents with TBI. As all of the included studies contained relatively small numbers of participants (12 to 120), our findings should be interpreted with caution. The involvement of a clinician or therapist, rather than use of the technology, may have led to the success of these interventions. Future research should seek to replicate these findings with larger samples, in other regions, using ecologically valid outcome measures, and reduced clinician involvement.

Fasciola hepatica: time-dependent disruption of spermatogenesis following in vivo treatment with triclabendazole

Sheep infected with the Cullompton isolate of Fasciola hepatica were treated with triclabendazole at a concentration of 10 mg/kg at 12 weeks post-infection. Adult flukes were recovered from the liver and, where present, from the gall bladder at 48, 72 and 96 h post-treatment (pt). Gross changes to the spermatogenic cells of the testis were examined by histology and ultrastructural alterations were visualised via transmission electron microscopy. Disruption was progressive in nature, with the testis tubules becoming shrunken, vacuolated and gradually more denuded of cellular content over the 96-h time period. From 48 h pt, the number of primary and secondary spermatogonia decreased and multinucleate spermatogonial cells were frequent. Later, developmental stages were uncommon, giving rise to much empty space within the tubules. By 72 h pt, the tubules contained many apoptotic and degraded cells and had an extremely disorganised appearance. At 96 h pt, the tubules were almost completely empty, with the exception of the remains of degraded spermatogenic cells. These results indicate that triclabendazole severely disrupts spermatogenesis in the liver fluke from 48 h pt in vivo.

Androgen deprivation results in time-dependent hypoxia in LNCaP prostate tumours; informed scheduling of the bioreductive drug AQ4N improves treatment response

Androgen withdrawal induces hypoxia in androgen-sensitive tissue; this is important as in the tumour microenvironment hypoxia is known to drive malignant progression. This study examined the time-dependent effect of androgen deprivation therapy (ADT) on tumour oxygenation and investigated the role of ADT-induced hypoxia on malignant progression in prostate tumours. LNCaP xenografted tumours were treated with anti-androgens and tumour oxygenation measured. Dorsal skin fold chambers (DSF) were used to image tumour vasculature in vivo. Quantitative PCR (QPCR) identified differential gene expression following treatment with bicalutamide. Bicalutamide and vehicle-only treated tumours were re-established in vitro and invasion and sensitivity to docetaxel were measured. Tumour growth delay was calculated following treatment with bicalutamide combined with the bioreductive drug AQ4N. Tumour oxygenation measurements showed a precipitate decrease following initiation of ADT. A clinically relevant dose of bicalutamide (2mg/kg/day) decreased tumour oxygenation by 45% within 24h, reaching a nadir of 0.09% oxygen (0.67±0.06 mmHg) by day 7; this persisted until day 14 when it increased up to day 28. Using DSF chambers, LNCaP tumours treated with bicalutamide showed loss of small vessels at days 7 and 14 with revascularization occurring by day 21. QPCR showed changes in gene expression consistent with the vascular changes and malignant progression. Cells from bicalutamide-treated tumours were more malignant than vehicle-treated controls. Combining bicalutamide with AQ4N (50mg/kg; single dose) caused greater tumour growth delay than bicalutamide alone. This study shows that bicalutamide-induced hypoxia selects for cells that show malignant progression; targeting hypoxic cells may provide greater clinical benefit.

The Adult Cystic Fibrosis Airway Microbiota Is Stable over Time and Infection Type, and Highly Resilient to Antibiotic Treatment of Exacerbations

Cystic fibrosis (CF) is characterized by defective mucociliary clearance and chronic airway infection by a complex microbiota. Infection, persistent inflammation and periodic episodes of acute pulmonary exacerbation contribute to an irreversible decline in CF lung function. While the factors leading to acute exacerbations are poorly understood, antibiotic treatment can temporarily resolve pulmonary symptoms and partially restore lung function. Previous studies indicated that exacerbations may be associated with changes in microbial densities and the acquisition of new microbial species. Given the complexity of the CF microbiota, we applied massively parallel pyrosequencing to identify changes in airway microbial community structure in 23 adult CF patients during acute pulmonary exacerbation, after antibiotic treatment and during periods of stable disease. Over 350,000 sequences were generated, representing nearly 170 distinct microbial taxa. Approximately 60% of sequences obtained were from the recognized CF pathogens Pseudomonas and Burkholderia, which were detected in largely non-overlapping patient subsets. In contrast, other taxa including Prevotella, Streptococcus, Rothia and Veillonella were abundant in nearly all patient samples. Although antibiotic treatment was associated with a small decrease in species richness, there was minimal change in overall microbial community structure. Furthermore, microbial community composition was highly similar in patients during an exacerbation and when clinically stable, suggesting that exacerbations may represent intrapulmonary spread of infection rather than a change in microbial community composition. Mouthwash samples, obtained from a subset of patients, showed a nearly identical distribution of taxa as expectorated sputum, indicating that aspiration may contribute to colonization of the lower airways. Finally, we observed a strong correlation between low species richness and poor lung function. Taken together, these results indicate that the adult CF lung microbiome is largely stable through periods of exacerbation and antibiotic treatment and that short-term compositional changes in the airway microbiota do not account for CF pulmonary exacerbations.

Optimisation of time/temperature treatment, for heat treated soft wheat flour

Chlorination of wheat flour in the EU countries has been replaced in recent years, to some extent, by heat treated flour which is used to produce high ratio cakes. Heat treated flour allows high ratio recipes to be developed which generate products with longer shelf life, finer texture, moist crumb and sweeter taste. The mechanism by which heat treatment improves the flour is not fully understood, but it is known that during the heat treatment process, protein denaturation and partial gelatinisation of the starch granules occurs, as well as an increase in batter viscosity. Therefore, it is important to optimize the flour heat treatment process, in order to enhance baking quality. Laboratory preparation of heat treated base wheat flour (culinary, soft, low protein) was carried out in a fluidised bed drier using a range of temperatures and times. The gluten was extracted from the final product and its quality was tested, to obtain objective and comparative information on the extent of protein denaturation. The results indicated that heat treatment of flour decreases gluten extensibility and partial gelatinisation of the starch granules occurred. After heat treatment the gluten appeared to retain moisture. The optimum time/temperature for the heat treatment of base flour was 120-130°C for 30 min with moisture content of ˜12.5%.© 2012 Elsevier Ltd. All rights reserved.

Time-dependent tegumental surface changes in juvenile Fasciola gigantica in response to triclabendazole treatment in goat

Triclabendazole (TCBZ), the anthelmintic drug active against both mature and immature liver flukes, was used to investigate the effect of in vivo treatment on the tegumental surface of juvenile Fasciola gigantica. Five goats were infected with 150 F. gigantica metacercariae each by oral gavage. Four of them were treated with single dose of TCBZ at 10mg/kg at four weeks post-infection. They were euthanized at 0 (untreated), 24, 48, 72 and 96h post treatment. Juvenile flukes were manually retrieved from the goat livers and processed for scanning electron microscopy. In control flukes, the anterior region was adorned with sharply pointed spines projecting away from the surface, while in the posterior region, spines become shorter and narrower, loosing serration and with the appearance of distinct furrows and papillae. The dorsal surface retained the same pattern of surface architecture similar to that of ventral surface. Flukes obtained from 24h post-treatment did not show any apparent change and were still very active. However, there were limited movements and some blebbing, swelling, deposition of tegumental secretions and some flattening displayed by the flukes of 48h post-treatment. All the worms were found dead 72h post-treatment and showed advanced level of tegumental disruptions, consisting of severe distortion of spines, sloughing off the tegument to expose the basal lamina, formation of pores and isolated patches of lesions. By 96h post-treatment, the disruption was extremely severe and the tegument was completely sheared off causing deeper lesions that exposed the underlying musculature. The disruption was more severe at posterior than anterior region and on ventral than dorsal surface. The present study further establishes the time-course of TCBZ action in vivo with 100% efficacy against the juvenile tropical liver fluke.

Combinations of ZAP-70, CD38 and IGHV mutational status as predictors of time to first treatment in CLL.

ZAP-70, CD38 and IGHV mutations have all been reported to have prognostic impact in chronic lymphocytic leukemia (CLL), both individually and in paired combinations. We aimed to determine whether the combination of all three factors provided more refined prognostic information concerning the treatment-free interval (TFI) from diagnosis. ZAP-70, CD38 and IGHV mutations were evaluated in 142 patients. Combining all three factors, the ZAP-70-/CD38-/Mutated group showed the longest median TFI (62 months, n = 37), ZAP-70+/CD38+/Unmutated cases the shortest (11 months, n = 37) and cases discordant for > or = 1 factor, an intermediate TFI (27 months, n = 68) (p = 0.006). Analysis of discordant cases revealed values that were otherwise masked when measuring single prognostic factors. The presence or absence of cytogenetic abnormalities did not explain the variability among discordant cases. Simultaneous analysis of ZAP-70, CD38 and IGHV mutations in CLL provides more discriminatory prediction of TFI than any factor alone.

Design, characterisation and preliminary clinical evaluation of a novel mucoadhesive topical formulation containing tetracycline for the treatment of periodontal disease

This study describes the formulation, characterisation and preliminary clinical evaluation of mucoadhesive, semi-solid formulations containing hydroxyethylcellulose (HEC, 1-5%, w/w), polyvinylpyrrolidine (PVP, 2 or 3%, w/w), poly carbophil (PC, 1 or 3%, w/w) and tetracycline (5%, w/w, as the hydrochloride). Each formulation was characterised in terms of drug release, hardness, compressibility, adhesiveness (using a texture analyser in texture profile analysis mode), syringeability (using a texture analyser in compression mode) and adhesion to a mucin disc (measured as a detachment force using the texture analyser in tensile mode). The release exponent for the formulations ranged from 0.78+/-0.02 to 1.27+/-0.07, indicating that drug release was non-diffusion controlled. Increasing the concentrations of each polymeric component significantly increased the time required for 10 and 30% release of the original mass of tetracycline, due to both increased viscosity and, additionally, the unique swelling properties of the formulations. Increasing concentrations of each polymeric component also increased the hardness, compressibility, adhesiveness, syringeability and mucoadhesion of the formulations. The effects on product hardness, compressibility and syringeability may be due to increased product viscosity and, hence, increased resistance to compression. Similarly, the effects of these polymers on adhesiveness/mucoadhesion highlight their mucoadhesive nature and, importantly, the effects of polymer state (particularly PC) on these properties. Thus, in formulations where the neutralisation of PC was maximally suppressed, adhesiveness and mucoadhesion were also maximal. Interestingly, statistical interactions were primarily observed between the effects of HEC and PC on drug release, mechanical and mucoadhesive properties. These were explained by the effects of HEC on the physical state of PC, namely swollen or unswollen. In the preliminary clinical evaluation, a formulation was selected that offered an appropriate balance of the above physical properties and contained 3% HEC, 3% PVP and 1% PC, in addition to tetracycline 5% (as the hydrochloride). The clinical efficacy of this (test) formulation was compared to an identical tetracycline-devoid (control) formulation in nine periodontal pockets (greater than or equal to 5 mm depth). One week following administration of the test formulation, there was a significant improvement in periodontal health as identified by reduced numbers of sub-gingival microbial pathogens. Therefore, it can be concluded that, when used in combination with mechanical plaque removal, the tetracycline-containing semi-solid systems described in this study would augment such therapy by enhancing the removal of pathogens, thus improving periodontal health. (C) 2000 Elsevier Science B.V. All rights reserved.