Sensomotoric Orthoses, Ankle-Foot Orthoses, and Children with Cerebral Palsy: The Bigger Picture

Ankle–foot orthoses (AFOs) and sensomotoric orthoses (SMotOs) are two—clinically relevant, yet under researched—types of lower limb orthoses used in children with cerebral palsy (CP). Quality of life is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity. Evaluating the effect of these two types of orthoses on quality of life in children with CP has not been reported on. The aim of this case study series was to synthesise and enrich the volume of evidence reported to inform real world applications of SMotO use in children with CP. Participants recruited were children with CP who performed the Berg Balance Scale, Timed Up-and-Go, the Gross Motor Function Measure and/or the Edinburgh Visual Gait Score in AFOs, SMotOs and barefoot where able. Qualitative data included videos of gait, a questionnaire and pedographs. Eight participants completed 39 quantitative and six qualitative measures, with the Edinburgh Visual Gait Score (EVGS) reporting the highest response. A general improvement was seen in gross motor skills and gait when wearing the SMotOs compared to AFOs and some parents reported that SMotOs were preferred. The reader is able to correlate the quantitative results with the qualitative evidence presented

Patient perceptions regarding benefits of single visit scale and polish : a randomised controlled trial

Peer reviewedPublisher PD

Clinical outcomes of Single-Visit oral Prophylaxis: A practice-based randomised controlled trial

Peer reviewedPublisher PD

High cut-off microdialysis catheters to clinically investigate cytokine changes following flap transfer

Background: ‘Choke vessels’ are thought to dilate in the first 72 h when blood flow to an area is disrupted. This study used ‘high cut-off’ microdialysis catheters in clinical research to investigate factors mediating circulatory change within free flaps. Methods: Six patients undergoing DIEP flap breast reconstruction each had three ‘high cut-off’ microdialysis catheters, with a membrane modification allowing molecules as large as 100 kDa to pass, inserted into Hartrampf zones 1, 2 and 4 to assess multiple vascular territories. Microdialysis continued for 72 h post-operatively. Samples were analysed for interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα) and fibroblast growth factor basic (FGFβ). Results: Three hundred and twenty-four samples were analysed for IL-6, FGFβ and TNFα totalling 915 analyses. IL-6 showed an increasing trend until 36 h post-operatively before remaining relatively constant. Overall, there was an increase (p < 0.001) over the time period from 4 to 72 h, fitting a linear trend. TNFα had a peak around 20–24 h before a gradual decrease. There was a significant linear time trend (p = 0.029) between 4 and 76 h, decreasing over the time period. FGFβ concentrations did not appear to have any overall difference in concentration with time. The concentration however appeared to oscillate about a horizontal trend line. There were no differences between the DIEP zones in concentrations of cytokines collected. Conclusion: This study uses high-cut off microdialysis catheters to evaluate changes in cytokines, and requires further research to be undertaken to add to our knowledge of choke vessels and flap physiology

Comparison of DC Bead-irinotecan and DC Bead-topotecan drug eluting beads for use in locoregional drug delivery to treat pancreatic cancer

DC Bead is a drug delivery embolisation system that can be loaded with doxorubicin or irinotecan for the treatment of a variety of liver cancers. In this study we demonstrate that the topoisomerase I inhibitor topotecan hydrochloride can be successfully loaded into the DC Bead sulfonate-modified polyvinyl alcohol hydrogel matrix, resulting in a sustained-release drug eluting bead (DEBTOP) useful for therapeutic purposes. The in vitro drug loading capacity, elution characteristics and the effects on mechanical properties of the beads are described with reference to our previous work with irinotecan hydrochloride (DEBIRI). Results showed that drug loading was faster when the solution was agitated compared to static loading and a maximum loading of ca. 40–45 mg topotecan in 1 ml hydrated beads was achievable. Loading the drug into the beads altered the size, compressibility moduli and colour of the bead. Elution was shown to be reliant on the presence of ions to perform the necessary exchange with the electrostatically bound topotecan molecules. Topotecan was shown by MTS assay to have an IC50 for human pancreatic adenocarcinoma cells (PSN-1) of 0.22 and 0.27 lM compared to 28.1 and 19.2 lM for irinotecan at 48 and 72 h, respectively. The cytotoxic efficacy of DEBTOP on PSN-1 was compared to DEBIRI. DEPTOP loaded at 6 & 30 mg ml-1, like its free drug form, was shown to be more potent than DEBIRI of comparable doses at 24, 48 & 72 h using a slightly modified MTS assay. Using a PSN-1 mouse xenograft model, DEBIRI doses of 3.3–6.6 mg were shown to be well tolerated (even with repeat administration) and effective in reducing the tumour size. DEBTOP however, was lethal after 6 days at doses of 0.83–1.2 mg but demonstrated reasonable efficacy and tolerability (again with repeat injection possible) at 0.2–0.4 mg doses. Care must therefore be taken when selecting the dose of topotecan to be loaded into DC Bead given its greater potency and potential toxicity

Argon behaviour in an inverted Barrovian sequence, Sikkim Himalaya: the consequences of temperature and timescale on ⁴⁰Ar/³⁹Ar mica geochronology

40Ar/39Ar dating of metamorphic rocks sometimes yields complicated datasets which are difficult to interpret in terms of timescales of the metamorphic cycle. Single-grain fusion and step-heating data were obtained for rocks sampled through a major thrust-sense shear zone (the Main Central Thrust) and the associated inverted metamorphic zone in the Sikkim region of the eastern Himalaya. This transect provides a natural laboratory to explore factors influencing apparent 40Ar/39Ar ages in similar lithologies at a variety of metamorphic pressure and temperature (P–T) conditions. The 40Ar/39Ar dataset records progressively younger apparent age populations and a decrease in within-sample dispersion with increasing temperature through the sequence. The white mica populations span ~ 2–9 Ma within each sample in the structurally lower levels (garnet grade) but only ~ 0–3 Ma at structurally higher levels (kyanite-sillimanite grade). Mean white mica single-grain fusion population ages vary from 16.2 ± 3.9 Ma (2σ) to 13.2 ± 1.3 Ma (2σ) from lowest to highest levels. White mica step-heating data from the same samples yields plateau ages from 14.27 ± 0.13 Ma to 12.96 ± 0.05 Ma. Biotite yield older apparent age populations with mean single-grain fusion dates varying from 74.7 ± 11.8 Ma (2σ) at the lowest structural levels to 18.6 ± 4.7 Ma (2σ) at the highest structural levels; the step-heating plateaux are commonly disturbed. Temperatures > 600 °C at pressures of 0.4–0.8 GPa sustained over > 5 Ma, appear to be required for white mica and biotite ages to be consistent with diffusive, open-system cooling. At lower temperatures, and/or over shorter metamorphic timescales, more 40Ar is retained than results from simple diffusion models suggest. Diffusion modelling of Ar in white mica from the highest structural levels suggests that the high-temperature rocks cooled at a rate of ~ 50–80 °C Ma− 1, consistent with rapid thrusting, extrusion and exhumation along the Main Central Thrust during the mid-Miocene

Tolerance, adherence, and acceptability of a ketogenic 2.5:1 ratio, nutritionally complete, medium chain triglyceride-containing liquid feed in children and adults with drug-resistant epilepsy following a ketogenic diet

Objective: To investigate incorporating a ready-to-use 2.5:1 ratio liquid feed into a ketogenic diet (KD) in children and adults with drug-resistant epilepsy. Methods: Following a three-day baseline, patients (n = 19; age: 19 years [SD 13], range: 8–46 years) followed a KD for 28 days (control period), then incorporated ≥200 mL/day of a ready-to-use liquid feed, made with a ratio of 2.5 g of fat to 1 g of protein plus carbohydrate and including medium chain triglycerides ([MCTs]; 25.6% of total fat/100 mL) for 28 days as part of their KD (intervention period). Outcome measures (control vs intervention period) included gastrointestinal (GI) tolerance, adherence to KD and intervention feed, dietary intake, blood ß-hydroxybutyrate (BHB) concentration, seizure outcomes, health-related quality of life (HRQoL), acceptability and safety. Results: Compared to the control period, during the intervention period, the percentage of patients reporting no GI symptoms increased (+5% [SD 5], p = 0.02); adherence to the KD prescription was similar (p = 0.92) but higher in patients (n = 5) with poor adherence (&lt;50%) to KD during the control period (+33% [SD 26], p = 0.049); total MCT intake increased (+12.1 g/day [SD 14.0], p = 0.002), driven by increases in octanoic (C8; +8.3 g/day [SD 6.4], p &lt; 0.001) and decanoic acid (C10; +5.4 g/day [SD 5.4], p &lt; 0.001); KD ratio decreased (p = 0.047), driven by a nonsignificant increase in protein intake (+11 g/day [SD 44], p = 0.29); seizure outcomes were similar (p ≥ 0.63) but improved in patients (n = 6) with the worst seizure outcomes during the control period (p = 0.04); and HRQoL outcomes were similar. The intervention feed was well adhered to (96% [SD 8]) and accepted (≥88% of patients confirmed). Significance: These findings provide an evidence-base to support the effective management of children and adults with drug-resistant epilepsy following a KD with the use of a ready-to-use, nutritionally complete, 2.5:1 ratio feed including MCTs. Plain language summary: This study examined the use of a ready-to-use, nutritionally complete, 2.5:1 ratio (2.5 g of fat to 1 g of protein plus carbohydrate) liquid feed, including medium chain triglycerides (MCTs), into a ketogenic diet (KD) in children and adults with drug-resistant epilepsy. The results show that the 2.5:1 ratio feed was well tolerated, adhered to, and accepted in these patients. Increases in MCT intake (particularly C8 and C10) and improvements in seizure outcomes (reduced seizure burden and intensity) and KD adherence also occurred with the 2.5:1 ratio feed in patients with the worst seizures and adherence, respectively.</p