Growth hormone regimens in Australia: analysis of the first 3 years of treatment for idiopathic growth hormone deficiency and idiopathic short stature

Objective To investigate response to growth hormone (GH) in the first, second and third years of treatment for all idiopathic GH‐deficient (GHD) and idiopathic short stature (ISS) patients in Australia. Context Eligibility for subsidized GH treatment in Australia is determined on auxological criteria for the indication of Short Stature and Slow Growth (SSSG), which includes ISS (SSSG‐ISS). The biochemical GHD (BGHD, peak GH < 10 mU/l) and SSSG indications are treated similarly: starting dose of 4·5 mg/m²/week with provision for incremental dosing. Some ISS patients were specifically diagnosed with familial short stature (SSSG‐FSS). Design Responses for each year of treatment for BGHD, SSSG‐ISS and SSSG‐FSS cohorts were compared in relation to influencing variables and with international benchmarks. The effect of incremental dosing was assessed. Patients Australian BGHD, SSSG‐ISS and SSSG‐FSS patients who had completed 1, 2, or 3 years of treatment and were currently receiving GH. Measurements Growth hormone dose, change in height‐standard deviation score (ΔSDS) and growth velocity (GV). Results First‐year response was 2–3 times greater than that in subsequent years: ΔSDS_{1st year} = 0·92, 0·50 and 0·46 for BGHD, SSSG‐ISS and SSSG‐FSS, respectively. Responses were similar to international reports and inversely related to age at commencement of GH. First‐year GV‐for‐age for BGHD patients was similar to international standards for idiopathic GHD. However, girls had an inferior response to boys when treatment commenced at <6 years of age. First‐year GV‐for‐age for SSSG‐ISS/FSS patients was less than ISS standards. Dose increments attenuated the first‐ to second‐year decline in response to BGHD but marginally improved the responses for SSSG‐ISS/FSS. Conclusions The Australian auxology‐based GH programme produces comparable responses to international programmes. A lower starting dose is offset by the initiation of treatment at younger ages. Incremental dosing does not appear optimal. A first‐year dose of 6·4–6·9 mg/m²/week for GHD and 8·9 mg/m²/week for ISS with early commencement of GH treatment may be most efficacious.     

Ultrathin chitosan–poly(ethylene glycol) hydrogel films for corneal tissue engineering

Due to the high demand for donor corneas and their low supply, autologous corneal endothelial cell (CEC) culture and transplantation for treatment of corneal endothelial dysfunction would be highly desirable. Many studies have shown the possibility of culturing CECs in vitro, but lack potential robust substrates for transplantation into the cornea. In this study, we investigate the properties of novel ultrathin chitosan–poly(ethylene glycol) (PEG) hydrogel films (CPHFs) for corneal tissue engineering applications. Cross-linking of chitosan films with diepoxy-PEG and cystamine was employed to prepare ～50 μm (hydrated) hydrogel films. Through variation of the PEG content (1.5–5.9 wt.%) it was possible to tailor the CPHFs to have tensile strains and ultimate stresses identical to or greater than those of human corneal tissue while retaining similar tensile moduli. Light transmission measurements in the visible spectrum (400–700 nm) revealed that the films were >95% optically transparent, above that of the human cornea (maximum ～90%), whilst in vitro degradation studies with lysozyme revealed that the CPHFs maintained the biodegradable characteristics of chitosan. Cell culture studies demonstrated the ability of the CPHFs to support the attachment and proliferation of sheep CECs. Ex vivo surgical trials on ovine eyes demonstrated that the CPHFs displayed excellent characteristics for physical manipulation and implantation purposes. The ultrathin CPHFs display desirable mechanical, optical and degradation properties whilst allowing attachment and proliferation of ovine CECs, and as such are attractive candidates for the regeneration and transplantation of CECs, as well as other corneal tissue engineering applications.     

Accuracy of stimulating electrode placement in paediatric pallidal deep brain stimulation for primary and secondary dystonia

Background

Accuracy of electrode placement is an important determinant of outcome following deep brain stimulation (DBS) surgery. Data on accuracy of electrode placement into the globus pallidum interna (GPi) in paediatric patients is limited, particularly those with non-primary dystonia who often have smaller GPi. Pallidal DBS is known to be more effective in the treatment of primary dystonia compared with secondary dystonia.

Objectives

We aimed to determine if accuracy of pallidal electrode placement differed between primary, secondary and NBIA (neuronal degeneration and brain iron accumulation) associated dystonia and how this related to motor outcome following surgery.

Methods

A retrospective review of a consecutive cohort of children and young people undergoing DBS surgery in a single centre. Fused in frame preoperative planning magnetic resonance imaging (MRI) and postoperative computed tomography (CT) brain scans were used to determine the accuracy of placement of DBS electrode tip in Leskell stereotactic system compared with the planned target. The differences along X, Y, and Z coordinates were calculated, as was the Euclidean distance of electrode tip from the target. The relationship between proximity to target and change in Burke-Fahn-Marsden Dystonia Rating Scale at 1 year was also measured.

Results

Data were collected from 88 electrodes placed in 42 patients (14 primary dystonia, 18 secondary dystonia and 10 NBIA associated dystonia). Median differences between planned target and actual position were: left-side X-axis 1.05 mm, Y-axis 0.85 mm, Z-axis 0.94 mm and Euclidean difference 2.04 mm; right-side X-axis 1.28 mm, Y-axis 0.70 mm, Z-axis 0.70 mm and Euclidean difference 2.45 mm. Accuracy did not differ between left and right-sided electrodes. No difference in accuracy was seen between primary, secondary or NBIA associated dystonia. Dystonia reduction at 1 year post surgery did not appear to relate to proximity of implanted electrode to surgical target across the cohort.

Conclusions

Accuracy of surgical placement did not differ between primary, secondary or NBIA associated dystonia. Decreased efficacy of pallidal DBS in secondary and NBIA associated dystonia is unlikely to be related to difficulties in achieving the planned electrode placement.     

Retrospective review of rectal cancer surgery in northern Alberta

Introduction

Previous studies, including research published more than 10 years ago in Northern Alberta, have demonstrated improved outcomes with increased surgical volume and subspecialisation in the treatment of rectal cancer. We sought to examine contemporary rectal cancer care in the same region to determine whether practice patterns have changed and whether outcomes have improved.

Methods

We reviewed the charts of all patients with rectal adenocarcinoma diagnosed between 1998 and 2003 who had a potentially curative resection. The main outcomes examined were 5-year local recurrence (LR) and disease-specific survival (DSS). Surgeons were classified into 3 groups according to training and volume, and we compared outcome measures among them. We also compared our results to those of the previous study from our region.

Results

We included 433 cases in the study. Subspecialty-trained colorectal surgeons performed 35% of all surgeries in our study compared to 16% in the previous study. The overall 5-year LR rate and DSS in our study were improved compared to the previous study. On multivariate analysis, the only factor associated with increased 5-year LR was presence of obstruction, and the factors associated with decreased 5-year DSS were high-volume noncolorectal surgeons, presence of obstruction and increased stage.

Conclusion

Over the past 10 years, the long-term outcomes of treatment for rectal cancer have improved. We found that surgical subspecialization was associated with improved DSS but not LR. Increased surgical volume was not associated with LR or DSS.     

Biomechanical performance of different cable and wire cerclage configurations

Purpose

Cerclage technology is regaining interest due to the increasing number of periprosthetic fractures. Different wiring techniques have been formerly proposed and have hibernated over years. Hereby, they are compared to current cerclage technology.

Methods

Seven groups (n = 6) of different cable cerclage (Ø1.7 mm, crimp closure) configurations (one single cerclage looped once around the shells, one single cerclage looped twice, two cerclages each looped once) and solid wire cerclages (Ø1.5 mm, twist closure) (same configurations as cable cerclages, and two braided wires, twisted around each other looped once) fixed two cortical half shells of human femoral shaft mounted on a testing jig. Sinusoidal cyclic loading with constantly increasing force (0.1 N/cycle) was applied starting at 50 N peak load. Cerclage pretension (P), load leading to onset of plastic deformation (D) and load at total failure (T) were identified. Statistical differences between the groups were detected by univariate ANOVA.

Results

Double looped cables (P442N ± 129; D1334N ± 319; T2734N ± 330) performed significantly better (p < 0.05) than single looped cables (P292N ± 56; D646N ± 108; T1622N ± 171) and were comparable to two single cables (P392N ± 154; D1191N ± 334; T2675N ± 361). Double looped wires (P335N ± 49; D752N ± 119; T1359N ± 80) were significantly better (p < 0.05) than single looped wires (P181N ± 16; D343N ± 33; T606N ± 109) and performed similarly to single looped cables. Braided wires (P119N ± 26; D225N ± 55; T919N ± 197) exhibited early loss of pretension and plastic deformation.

Conclusion

Double looped cerclages provided a better fixation stability compared to a single looped cerclage. Double looped wires were comparable to a single looped cable. The use of braided wires could not be recommended mechanically.     

Fatigue performance of angle-stable tibial nail interlocking screws

Purpose

Tibial nail interlocking screw failure often occurs during delayed fracture consolidation or at early weight bearing of nailed unstable fractures, in general when high implant stress could not be reduced by other means. Is there a biomechanical improvement in long-term performance of angle stable locking screws compared to conventional locking screws for distal locking of intramedullary tibial nails?

Methods

Surrogate bones of human tibiae were cut in the distal third and distal locking of the 10 mm intramedullary tibial nail was performed with either two angle stable locking screws or two conventional locking screws in the mediolateral plane. Six specimens per group were mechanically tested under quasi-static and cyclic axial loading with constantly increasing force.

Results

Angle stable locking screw constructs exhibited significantly higher stiffness values (7,809 N/mm ± 647, mean ± SD) than conventional locking screw constructs (6,614 N/mm ± 859, p = 0.025). Angle stable locking screw constructs provided a longer fatigue life, expressed in a significantly higher number of cycles to failure (187,200 ± 18,100) compared to conventional locking screw constructs (128,700 ± 7,000, p = 0.004).

Conclusion

Fatigue performance of locking screws can be ameliorated by the use of angle stable locking screws, being especially important if the nail acts as load carrier and an improved stability during fracture healing is needed.     

A comparison between the clinical significance and growth mixture modelling early change methods at predicting negative outcomes

Abstract

Objective: Routine outcome monitoring benefits treatment by identifying potential no change and deterioration. The present study compared two methods of identifying early change and their ability to predict negative outcomes on self-report symptom and wellbeing measures. Method: 1467 voluntary day patients participated in a 10-day group Cognitive Behaviour Therapy (CBT) program and completed the symptom and wellbeing measures daily. Early change, as defined by (a) the clinical significance method and (b) longitudinal modelling, was compared on each measure. Results: Early change, as defined by the simpler clinical significance method, was superior at predicting negative outcomes than longitudinal modelling. The longitudinal modelling method failed to detect a group of deteriorated patients, and agreement between the early change methods and the final unchanged outcome was higher for the clinical significance method. Conclusions: Therapists could use the clinical significance early change method during treatment to alert them of patients at risk for negative outcomes, which in turn could allow therapists to prevent those negative outcomes from occurring.