Evaluating Palin Stammering Therapy for School Children (Palin STSC 8-14): protocol for a feasibility randomised controlled trial comparing Palin STSC(8-14) with usual treatment.

BACKGROUND: Having a stammer can have a significant effect on a child's social, emotional and educational development. With approximately 66,000 children in the UK having a stammer, there is a need to establish an adequate evidence base to inform clinical practice. We describe a feasibility trial to explore the effectiveness of a new therapy programme for children aged 8-14: Palin Stammering Therapy for School Children (Palin STSC(8-14)). Preliminary data from the Michael Palin Centre, where the programme was developed, indicate that Palin STSC(8-14) is effective in reducing stammering frequency and impact for children, with beneficial effects for parents too. We will investigate the feasibility of the methods required for a definitive randomised controlled trial to investigate the application of this therapy by NHS speech and language therapists (SLTs), compared with 'treatment as usual' (TAU), beyond the specialist context in which it was developed. METHODS: This is a two-arm feasibility cluster-randomised controlled trial of Palin STSC(8-14) with TAU control arm, and randomisation at the level of the SLT. Quantitative and qualitative data will be collected to examine the following: the recruitment and retention of therapists and families, the acceptability of the research processes and the therapeutic intervention and the appropriateness of the therapy outcome measures. Assessments will be completed by children and parents at baseline and 6 months later, including measures of stammering severity; the impact of child's stammering on both children and parents; child temperament, behaviour and peer relations, anxiety; quality of life; and economic outcomes. There will also be a qualitative process evaluation, including interviews with parents, children, SLTs and SLT managers to explore the acceptability of both the research and therapy methods. Treatment fidelity will be examined through analysis of therapy session records and recordings. DISCUSSION: The findings of this feasibility trial will inform the decision as to whether to progress to a full-scale randomised controlled trial to explore the effectiveness of Palin STSC(8-14) when compared to Treatment as Usual in NHS SLT services. There is a strong need for an evidence-based intervention for school age children who stammer. TRIAL REGISTRATION: ISRCTN. ISRCTN17058884 . Registered on 18 December 2019.

Identifying joint-specific gait mechanisms causing impaired gait in alkaptonuria patients.

BACKGROUND: Alkaptonuria is a rare genetic disease that leads to structural joint damage and impaired movement function. Previous research indicates that alkaptonuria affects gait, however the detailed mechanisms are unknown. RESEARCH QUESTION: What are the joint-specific gait mechanisms which contribute to impaired gait in alkaptonuria patients? METHODS: The gait of 36 alkaptonuria patients were compared to those of 21 unimpaired controls. The AKU patients were split into three age groups (young 16-29 years, n = 9, middle 30-49 years, n = 16 and old 50 + years, n = 11), and the kinematic and kinetic gait profiles were compared to speed-matched controls using a spm1d two-sample t-test. RESULTS: The young AKU group showed significant differences in the sagittal plane of the knee joint compared to speed-matched controls. The middle group showed deviations in the knee and hip joints. The old group showed significant differences in multiple joints and planes and exhibited gait mechanisms which may be compensation strategies. SIGNIFICANCE: This study is the first to identify and describe joint-specific mechanisms during gait in alkaptonuria patients. Gait deviations were evident even in young AKU patients, including a 16-year-old, much earlier than previously thought. The knee joint is an important focus of future research and potential interventions as deviations were found across all three AKU age groups.

Leaving hip rotation out of a conventional 3D gait model improves discrimination of pathological gait in cerebral palsy: A novel neural network analysis.

BACKGROUND: Complex clinical gait analysis results can be expressed as single number gait deviations by applying multivariate processing methods. The original Movement Deviation Profile (MDP) quantifies the deviation of abnormal gait using the most trusted nine dynamic joint angles of lower limbs. RESEARCH QUESTION: Which subset of joint angles maximises the ability of the MDP to separate abnormal gait from normality? What is the effect of using the best subset in a large group of patients, and in individuals? METHODS: A self-organising neural network was trained using normal gait data from 166 controls, and then the MDP of 1923 patients with cerebral palsy (3846 legs) was calculated. The same procedure was repeated with 511 combinations of the nine joint angles. The standardised distances of abnormal gait from normality were then calculated as log-transformed Z-scores to select the best combination. A mixed design ANOVA was used to assess how removing the least discriminating angle improved the separation of patients from controls. The effect of using the optimal subset of angles was also quantified for each individual leg by comparing the change in MDP to the independent FAQ levels of patients. RESULTS: Removal of hip rotation significantly (p<0.0005) increased the separation of the patient group from normality (ΔZ-score 0.24) and also at FAQ levels 7-10 (ΔZ-score 0.38, 0.27, 0.22, 0.14). The MDP of individual patients changed in a wider range of -4.65 to 1.12 Z-scores and their change matched their independent FAQ scores, with less functional patients moving further from, and more functional patients moving closer to normality. SIGNIFICANCE: In existing gait databases we recommend excluding hip rotation from data used to calculate the MDP. Alternatively, the calculation of hip rotation can be improved by post-hoc correction, but the ultimate solution is to use more accurate and reliable models of hip rotation.

Use of plumage and gular pouch color to evaluate condition of oil spill rehabilitated California brown pelicans (Pelecanus occidentalis californicus) post-release.

Sublethal effects of oil spills may dampen seabird rehabilitation success due to lingering negative impacts of contamination and stress on reproduction and long-term survival. These effects can be difficult to measure while birds are in care as well as once birds are released. Expression of sexually selected traits that are sensitive to condition can provide information on physiological status of birds. We evaluated plumage molt and gular pouch skin color of California brown pelicans (Pelecanus occidentalis californicus) following oil contamination and rehabilitation to test for differences between previously oiled and rehabilitated (post-spill) and presumably uncontaminated pelicans. Post-spill pelicans released with either color leg bands alone, or bands plus harness-mounted satellite GPS tags, were relocated and visually assessed in the field at non-breeding communal roosts and compared to surrounding unmarked pelicans in the general population. Non-oiled pelicans bearing GPS tags were also included in the study. Post-spill pelicans lagged the general population in molt of ornamental yellow crown feathers but hind neck transition into white plumage was not significantly different. Both post-spill and non-oiled pelicans wearing GPS tags had lower gular redness scores than the unmarked, non-oiled population. Pre-breeding gular pouch redness of post-spill pelicans was more strongly influenced by wearing of a GPS tag than a history of oil contamination and rehabilitation. Gular pouch redness of post-spill pelicans in the first 18 months after release was positively correlated with long term survivorship. If gular pouch color is a condition-dependent sexual signal and overall health influences plumage molt progression, our results indicate that many post-spill pelicans marked with bands alone were in relatively good condition going into the next breeding season, but those released with electronic tags experienced additional stress due to wearing the equipment, introducing a confounding variable to the post-release study.

Sensitivity of EQ-5D-3L, HUI2, HUI3, and SF-6D to changes in speech reception and tinnitus associated with cochlear implantation.

PURPOSE: There is concern that some generic preference-based measures (GPMs) of health-related quality of life may be insensitive to interventions that improve hearing. Establishing where sensitivity arises could contribute to the design of improved measures. Accordingly, we compared the sensitivity of four widely used GPMs to a clinically effective treatment-cochlear implantation-which restores material degrees of hearing to adults with little or no functional hearing. METHODS: Participants (N = 147) received implants in any of 13 hospitals in the UK. One month before implantation and 9 months after, they completed the HUI2, HUI3, EQ5D3L, and SF-6D questionnaires, together with the EuroQoL visual-analogue scale as a direct measure of health, a performance test of speech reception, and a self-report measure of annoyance due to tinnitus. RESULTS: Implantation was associated with a large improvement in speech reception and a small improvement in tinnitus. HUI2 and HUI3 were sensitive to the improvement in speech reception through their Sensation and Hearing dimensions; EQ5D3L was sensitive to the improvement in tinnitus through its Anxiety/Depression dimension; SF-6D was sensitive to neither. Participants reported no overall improvement in health. Variation in health was associated with variation in tinnitus, not variation in speech reception. CONCLUSIONS: None of the four GPMs was sensitive to the improvements in both speech reception and tinnitus that were associated with cochlear implantation. To capture fully the benefits of interventions for auditory disorders, developments of current GPMs would need to be sensitive to both the health-related and non-health-related aspects of auditory dysfunction.

Data on items of AKUSSI in Alkaptonuria collected over three years from the United Kingdom National Alkaptonuria Centre and the impact of nitisinone.

Alkaptonuria is a rare genetic disorder characterized by a high level of circulating (and urine) homogentisic acid (HGA), which contributes to ochronosis when it is deposited in connective tissue as a pigmented polymer. In an observational study carried out by National AKU Centre (NAC) in Liverpool, a total of thirty-nine AKU patients attended yearly visits in varying numbers. At each visit a mixture of clinical, joint and spinal assessments were carried out and the results calculated to yield an AKUSSI (Alkaptonuria Severity Score Index), see "Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre" (Ranganath at el., 2018). The aim of this data article is to produce visual representation of the change in the components of AKUSSI over 3 years, through radar charts. The metabolic effect of nitisinone is shown through box plots.

Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: Evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre.

QUESTION: Does Nitisinone prevent the clinical progression of the Alkaptonuria? FINDINGS: In this observational study on 39 patients, 2 mg of daily nitisinone inhibited ochronosis and significantly slowed the progression of AKU over a three-year period. MEANING: Nitisinone is a beneficial therapy in Alkaptonuria. BACKGROUND: Nitisinone decreases homogentisic acid (HGA), but has not been shown to modify progression of Alkaptonuria (AKU). METHODS: Thirty-nine AKU patients attended the National AKU Centre (NAC) in Liverpool for assessments and treatment. Nitisinone was commenced at V1 or baseline. Thirty nine, 34 and 22 AKU patients completed 1, 2 and 3 years of monitoring respectively (V2, V3 and V4) in the VAR group. Seventeen patients also attended a pre-baseline visit (V0) in the VAR group. Within the 39 patients, a subgroup of the same ten patients attended V0, V1, V2, V3 and V4 visits constituting the SAME Group. Severity of AKU was assessed by calculation of the AKU Severity Score Index (AKUSSI) allowing comparison between the pre-nitisinone and the nitisinone treatment phases. RESULTS: The ALL (sum of clinical, joint and spine AKUSSI features) AKUSSI rate of change of scores/patient/month, in the SAME group, was significantly lower at two (0.32 ±â€¯0.19) and three (0.15 ±â€¯0.13) years post-nitisinone when compared to pre-nitisinone (0.65 ±â€¯0.15) (p < .01 for both comparisons). Similarly, the ALL AKUSSI rate of change of scores/patient/month, in the VAR group, was significantly lower at one (0.16 ±â€¯0.08) and three (0.19 ±â€¯0.06) years post-nitisinone when compared to pre-nitisinone (0.59 ±â€¯0.13) (p < .01 for both comparisons). Combined ear and ocular ochronosis rate of change of scores/patient/month was significantly lower at one, two and three year's post-nitisinone in both VAR and SAME groups compared with pre-nitisinone (p < .05). CONCLUSION: This is the first indication that a 2 mg dose of nitisinone slows down the clinical progression of AKU. Combined ocular and ear ochronosis progression was arrested by nitisinone.

Substrate and flow characteristics associated with White Sturgeon recruitment in the Columbia River Basin.

A study was conducted to identify habitat characteristics associated with age 0+ White Sturgeon (Acipenser transmontanus Richardson, 1863) recruitment in three reaches of the Columbia River Basin: Skamania reach (consistent recruitment), John Day reach (intermittent/inconsistent recruitment), and Kootenai reach (no recruitment). Our modeling approach involved numerous steps. First, we collected information about substrate, embeddedness, and hydrodynamics in each reach. Second, we developed a set of spatially explicit predictor variables. Third, we built two habitat (probability) models with Skamania reach training data where White Sturgeon recruitment was consistent. Fourth, we created spawning maps of each reach by populating the habitat models with in-reach physical metrics (substrate, embeddedness, and hydrodynamics). Fifth, we examined model accuracy by overlaying spawning locations in Skamania and Kootenai reaches with habitat predictions obtained from probability models. Sixth, we simulated how predicted habitat changed in each reach after manipulating physical conditions to more closely match Skamania reach. Model verification confirmed White Sturgeon generally spawned in locations with higher model probabilities in Skamania and Kootenai reaches, indicating the utility of extrapolating the models. Model simulations revealed significant gains in White Sturgeon habitat in all reaches when spring flow increased, gravel/cobble composition increased, or embeddedness decreased. The habitat models appear well suited to assist managers when identifying reach-specific factors limiting White Sturgeon recruitment in the Columbia River Basin or throughout its range.

Economic evidence for nonpharmacological asthma management interventions: A systematic review.

Asthma management, education and environmental interventions have been reported as cost-effective in a previous review (Pharm Pract (Granada), 2014;12:493), but methods used to estimate costs and outcomes were not discussed in detail. This review updates the previous review by providing economic evidence on the cost-effectiveness of studies identified after 2012, and a detailed assessment of the methods used in all identified studies. Twelve databases were searched from 1990 to January 2016, and studies included economic evaluations, asthma subjects and nonpharmacological interventions written in English. Sixty-four studies were included. Of these, 15 were found in addition to the earlier review; 53% were rated fair in quality and 47% high. Education and self-management interventions were the most cost-effective, in line with the earlier review. Self-reporting was the most common method used to gather resource-use data, accompanied by bottom-up approaches to estimate costs. Main outcome measures were asthma-related hospitalizations (69%), quality of life (41%) and utility (38%), with AQLQ and the EQ-5D being the most common questionnaires measured prospectively at fixed time points. More rigorous costing methods are needed with a more common quality of life tool to aid greater replicability and comparability amongst asthma studies.

A pilot randomized controlled trial comparing effectiveness of prism glasses, visual search training and standard care in hemianopia.

OBJECTIVE: Pilot trial to compare prism therapy and visual search training, for homonymous hemianopia, to standard care (information only). METHODS: Prospective, multicentre, parallel, single-blind, three-arm RCT across fifteen UK acute stroke units. PARTICIPANTS: Stroke survivors with homonymous hemianopia. INTERVENTIONS: Arm a (Fresnel prisms) for minimum 2 hours, 5 days per week over 6 weeks. Arm b (visual search training) for minimum 30 minutes, 5 days per week over 6 weeks. Arm c (standard care-information only). INCLUSION CRITERIA: Adult stroke survivors (>18 years), stable hemianopia, visual acuity better than 0.5 logMAR, refractive error within ±5 dioptres, ability to read/understand English and provide consent. OUTCOMES: Primary outcomes were change in visual field area from baseline to 26 weeks and calculation of sample size for a definitive trial. Secondary measures included Rivermead Mobility Index, Visual Function Questionnaire 25/10, Nottingham Extended Activities of Daily Living, Euro Qual, Short Form-12 questionnaires and Radner reading ability. Measures were post-randomization at baseline and 6, 12 and 26 weeks. RANDOMIZATION: Randomization block lists stratified by site and partial/complete hemianopia. BLINDING: Allocations disclosed to patients. Primary outcome assessor blind to treatment allocation. RESULTS: Eighty-seven patients were recruited: 27-Fresnel prisms, 30-visual search training and 30-standard care; 69% male; mean age 69 years (SD 12). At 26 weeks, full results for 24, 24 and 22 patients, respectively, were compared to baseline. Sample size calculation for a definitive trial determined as 269 participants per arm for a 200 degree2 visual field area change at 90% power. Non-significant relative change in area of visual field was 5%, 8% and 3.5%, respectively, for the three groups. Visual Function Questionnaire responses improved significantly from baseline to 26 weeks with visual search training (60 [SD 19] to 68.4 [SD 20]) compared to Fresnel prisms (68.5 [SD 16.4] to 68.2 [18.4]: 7% difference) and standard care (63.7 [SD 19.4] to 59.8 [SD 22.7]: 10% difference), P=.05. Related adverse events were common with Fresnel prisms (69.2%; typically headaches). CONCLUSIONS: No significant change occurred for area of visual field area across arms over follow-up. Visual search training had significant improvement in vision-related quality of life. Prism therapy produced adverse events in 69%. Visual search training results warrant further investigation.

Supervised pharmacy student-led medication review in primary care for patients with type 2 diabetes: a randomised controlled pilot study.

OBJECTIVE: To pilot and feasibility-test supervised final year undergraduate pharmacy student-led medication reviews for patients with diabetes to enable definitive trial design. METHOD: Third year pharmacy students were recruited from one UK School of Pharmacy and trained to review patient's medical records and provide face-to-face consultations under supervision while situated within the patient's medical practice. Patients with type 2 diabetes were recruited by postal invitation letter from their medical practice and randomised via automated system to intervention or usual care. Diabetes-related clinical data, quality of life, patient reported beliefs, adherence and satisfaction with medicines information were collected with validated tools at baseline and 6 months postintervention. The process for collecting resource utilisation data was tested. Stakeholder meetings were held before and after intervention to develop study design and learn from its implementation. Recruitment and attrition rates were determined plus the quality of the outcome data. Power calculations for a definitive trial were performed on the different outcome measures to identify the most appropriate primary outcome measure. RESULTS: 792 patients were identified as eligible from five medical practices. 133 (16.8%) were recruited and randomised to control (n=66) or usual care (n=67). 32 students provided the complete intervention to 58 patients. Initial data analysis showed potential for impact in the right direction for some outcomes measured including glycated haemoglobin, quality of life and patient satisfaction with information about medicines. The intervention was found to be feasible and acceptable to patients. The pilot and feasibility study enabled the design of a future full randomised controlled trial. CONCLUSIONS: Student and patient recruitment are possible. The intervention was well received and demonstrated some potential benefits. While the intervention was relatively inexpensive and provided an experiential learning opportunity for pharmacy students, its cost-effectiveness remains to be determined. TRIAL REGISTRATION NUMBER: ISRCTN26445805; Results.

Cost Effectiveness of Using Array-CGH for Diagnosing Learning Disability.

OBJECTIVE: To undertake a cost-effectiveness analysis of using microarray comparative genomic hybridisation (array-CGH) as a first-line test versus as a second-line test for the diagnosis of causal chromosomal abnormalities in patients referred to a NHS clinical genetics service in the U.K. with idiopathic learning disability, developmental delay and/or congenital anomalies. METHODS: A cost-effectiveness study was conducted. The perspective is that of a U.K. NHS clinical genetics service provider (with respect to both costs and outcomes). A cohort of patients (n = 1590) referred for array-CGH testing of undiagnosed learning disability and developmental delay by a single NHS regional clinical genetics service (South East Thames Regional Genetics Service), were split into a before-and-after design where 742 patients had array-CGH as a second-line test (before group-comparator intervention) and 848 patients had array-CGH as a first-line test (after group-evaluated intervention). The mean costs were calculated from the clinical genetics testing pathway constructed for each patient including the costs of genetic testing undertaken and clinical appointments scheduled. The outcome was the number of diagnoses each intervention produced so that a mean cost-per-diagnosis could be calculated. The cost effectiveness of the two interventions was calculated as an incremental cost-effectiveness ratio to produce an incremental cost-per-diagnosis (in 2013 GBP). Sensitivity analyses were conducted by altering both costs and effects to check the validity of the outcome. RESULTS: The incremental mean cost of testing patients using the first-line testing strategy was -GBP241.56 (95% CIs -GBP256.93 to -GBP226.19) and the incremental mean gain in the percentage diagnoses was 0.39% (95% CIs -2.73 to 3.51%), which equates to an additional 1 diagnosis per 256 patients tested. This cost-effectiveness study comparing these two strategies estimates that array-CGH first-line testing dominates second-line testing because it was both less costly and as effective. The sensitivity analyses conducted (adjusting both costs and effects) supported the dominance of the first-line testing strategy (i.e. lower cost and as effective). CONCLUSIONS: The first-line testing strategy was estimated to dominate the second-line testing strategy because it was both less costly and as effective. These findings are relevant to the wider UK NHS clinical genetics service, with two key strengths of this study being the appropriateness of the comparator interventions and the direct applicability of the patient cohort within this study and the wider UK patient population.

A cohort study of influences, health outcomes and costs of patients' health-seeking behaviour for minor ailments from primary and emergency care settings.

OBJECTIVES: To compare health-related and cost-related outcomes of consultations for symptoms suggestive of minor ailments in emergency departments (EDs), general practices and community pharmacies. DESIGN: Observational study; prospective cohort design. SETTING: EDs (n=2), general practices (n=6) and community pharmacies (n=10) in a mix of rural/urban and deprived/affluent areas across North East Scotland and East Anglia. Participants Adults (≥18 years) presenting between 09:00 and 18:00 (Monday-Friday) in general practices and 09:00-18:00 (Monday-Saturday) in pharmacies and EDs with ≥1 of the following: musculoskeletal pain; eye discomfort; gastrointestinal disturbance; or upper respiratory tract-related symptoms. INTERVENTIONS: Participants completed three questionnaires: baseline (prior to index consultation); satisfaction with index consultation and follow-up (2 weeks after index consultation). MAIN OUTCOME MEASURES: Symptom resolution, quality of life, costs, satisfaction and influences on care-seeking behaviour. RESULTS: 377 patients participated, recruited from EDs (81), general practices (162) and community pharmacies (134). The 2-week response rate was 70% (264/377). Symptom resolution was similar across all three settings: ED (37.3%), general practice (35.7%) and pharmacy (44.3%). Mean overall costs per consultation were significantly lower for pharmacy (£29.30 (95% CI £21.60 to £37.00)) compared with general practice (£82.34 (95% CI £63.10 to £101.58)) and ED (£147.09 (95% CI £125.32 to £168.85)). Satisfaction varied across settings and by measure used. Compared with pharmacy and general practice use, ED use was significantly (p<0.001) associated with first episode and short duration of symptom(s), as well as higher levels of perceived seriousness and urgency for seeking care. Convenience of location was the most common reason for choice of consultation setting. CONCLUSIONS: These results suggest similar health-related outcomes and substantially lower costs with pharmacy consultations for minor ailments. Effective strategies are now needed to shift demand for minor ailment management away from EDs and general practices to the community pharmacy setting.

Quantitative proteomics in resected renal cancer tissue for biomarker discovery and profiling.

BACKGROUND: Proteomics-based approaches for biomarker discovery are promising strategies used in cancer research. We present state-of-art label-free quantitative proteomics method to assess proteome of renal cell carcinoma (RCC) compared with noncancer renal tissues. METHODS: Fresh frozen tissue samples from eight primary RCC lesions and autologous adjacent normal renal tissues were obtained from surgically resected tumour-bearing kidneys. Proteins were extracted by complete solubilisation of tissues using filter-aided sample preparation (FASP) method. Trypsin digested proteins were analysed using quantitative label-free proteomics approach followed by data interpretation and pathways analysis. RESULTS: A total of 1761 proteins were identified and quantified with high confidence (MASCOT ion score threshold of 35 and P-value <0.05). Of these, 596 proteins were identified as differentially expressed between cancer and noncancer tissues. Two upregulated proteins in tumour samples (adipose differentiation-related protein and Coronin 1A) were further validated by immunohistochemistry. Pathway analysis using IPA, KOBAS 2.0, DAVID functional annotation and FLink tools showed enrichment of many cancer-related biological processes and pathways such as oxidative phosphorylation, glycolysis and amino acid synthetic pathways. CONCLUSIONS: Our study identified a number of differentially expressed proteins and pathways using label-free proteomics approach in RCC compared with normal tissue samples. Two proteins validated in this study are the focus of on-going research in a large cohort of patients.

Food for thought: pilot randomized controlled trial of lay health trainers supporting dietary change to reduce cardiovascular disease in deprived communities.

BACKGROUND: Cardiovascular disease (CVD) accounts for 30% of UK deaths. It is associated with modifiable lifestyle factors, including insufficient consumption of fruit and vegetables (F&V). Lay health trainers (LHTs) offer practical support to help people develop healthier behaviour and lifestyles. Our two-group pilot randomized controlled trial (RCT) investigated the effectiveness of LHTs at promoting a heart-healthy lifestyle among adults with at least one risk factor for CVD to inform a full-scale RCT. METHODS: Eligible adults (aged 21-78 years), recruited from five practices serving deprived populations, were randomized to health information leaflets plus LHTs' support for 3 months (n = 76) versus health information leaflets alone (n = 38). RESULTS: We recruited 114 participants, with 60% completing 6 month follow-up. Both groups increased their self-reported F&V consumption and we found no evidence for LHTs' support having significant added impact. Most participants were relatively less deprived, as were the LHTs we were able to recruit and train. CONCLUSIONS: Our pilot demonstrated that an LHT's RCT whilst feasible faces considerable challenges. However, to justify growing investment in LHTs, any behaviour changes and sustained impact on those at greatest need should be demonstrated in an independently evaluated, robust, fully powered RCT.

Digitise this! A quick and easy remote sensing method to monitor the daily extent of dredge plumes.

Technological advancements in remote sensing and GIS have improved natural resource managers' abilities to monitor large-scale disturbances. In a time where many processes are heading towards automation, this study has regressed to simple techniques to bridge a gap found in the advancement of technology. The near-daily monitoring of dredge plume extent is common practice using Moderate Resolution Imaging Spectroradiometer (MODIS) imagery and associated algorithms to predict the total suspended solids (TSS) concentration in the surface waters originating from floods and dredge plumes. Unfortunately, these methods cannot determine the difference between dredge plume and benthic features in shallow, clear water. This case study at Barrow Island, Western Australia, uses hand digitising to demonstrate the ability of human interpretation to determine this difference with a level of confidence and compares the method to contemporary TSS methods. Hand digitising was quick, cheap and required very little training of staff to complete. Results of ANOSIM R statistics show remote sensing derived TSS provided similar spatial results if they were thresholded to at least 3 mg L(-1). However, remote sensing derived TSS consistently provided false-positive readings of shallow benthic features as Plume with a threshold up to TSS of 6 mg L(-1), and began providing false-negatives (excluding actual plume) at a threshold as low as 4 mg L(-1). Semi-automated processes that estimate plume concentration and distinguish between plumes and shallow benthic features without the arbitrary nature of human interpretation would be preferred as a plume monitoring method. However, at this stage, the hand digitising method is very useful and is more accurate at determining plume boundaries over shallow benthic features and is accessible to all levels of management with basic training.

A marker based kinematic method of identifying initial contact during gait suitable for use in real-time visual feedback applications.

A gait cycle is typically defined as being from heel strike or initial contact (IC) to the next ipsilateral IC using kinetic data. When these data are not available other methods of event definition are required. An algorithm based upon sagittal plane kinematics of the hip, which defines IC at contralateral peak hip extension (PHE) is presented. Kinematic and kinetic data were recorded while 10 unimpaired participants each completed a minimum of 25 overground gait cycles. The accuracy of 551 IC events was evaluated by comparing the agreement of PHE to other kinematic and kinetic algorithms. The mean temporal difference in IC between the PHE algorithm and a kinetic algorithm was +0.0006±0.008 s. The 95% Limits of Agreement was ±0.018 s. This new PHE algorithm provides simple to implement and accurate gait events for use when kinetic data are not available.

A study of the safety and harms of antidepressant drugs for older people: a cohort study using a large primary care database.

OBJECTIVES: The aim of this study was to establish the relative safety and balance of risks for antidepressant treatment in older people. The study objectives were to (1) determine relative and absolute risks of predefined adverse events in older people with depression, comparing classes of antidepressant drugs [tricyclic and related antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and other antidepressants] and commonly prescribed individual drugs with non-use of antidepressant drugs; (2) directly compare the risk of adverse events for SSRIs with TCAs; (3) determine associations with dose and duration of antidepressant medication; (4) describe patterns of antidepressant use in older people with depression; and (5) estimate costs of antidepressant medication and primary care visits. DESIGN: A cohort study of patients aged 65 years and over diagnosed with depression. SETTING: The study was based in 570 general practices in the UK supplying data to the QResearch database. PARTICIPANTS: Patients diagnosed with a new episode of depression between the ages of 65 and 100 years, from 1 January 1996 to 31 December 2007. Participants were followed up until 31 December 2008. INTERVENTIONS: The exposure of interest was treatment with antidepressant medication. Antidepressant drugs were grouped into the major classes and commonly prescribed individual drugs were identified. MAIN OUTCOME MEASURES: There were 13 predefined outcome measures: all-cause mortality, sudden cardiac death, suicide, attempted suicide/self-harm, myocardial infarction, stroke/transient ischaemic attack (TIA), falls, fractures, upper gastrointestinal bleeding, epilepsy/seizures, road traffic accidents, adverse drug reactions and hyponatraemia. RESULTS: In total, 60,746 patients were included in the study cohort. Of these, 54,038 (89.0%) received at least one prescription for an antidepressant during follow-up. The associations with the adverse outcomes were significantly different between the classes of antidepressant drugs for seven outcomes. SSRIs were associated with the highest adjusted hazard ratios (HRs) for falls [1.66, 95% confidence interval (CI) 1.58 to 1.73] and hyponatraemia (1.52, 95% CI 1.33 to 1.75), and the group of other antidepressants was associated with the highest HRs for all-cause mortality (1.66, 95% CI 1.56 to 1.77), attempted suicide/self-harm (5.16, 95% CI 3.90 to 6.83), stroke/TIA (1.37, 95% CI 1.22 to 1.55), fracture (1.63, 95% CI 1.45 to 1.83) and epilepsy/seizures (2.24, 95% CI 1.60 to 3.15) compared with when antidepressants were not being used. TCAs did not have the highest HR for any of the outcomes. There were also significantly different associations between the individual drugs for seven outcomes, with trazodone, mirtazapine and venlafaxine associated with the highest rates for several of these outcomes. The mean incremental cost (for all antidepressant prescriptions) ranged between £51.58 (amitriptyline) and £641.18 (venlafaxine) over the 5-year post-diagnosis period. CONCLUSIONS: This study found associations between use of antidepressant drugs and a number of adverse events in older people. There was no evidence that SSRIs or drugs in the group of other antidepressants were associated with a reduced risk of any of the adverse outcomes compared with TCAs; however, they may be associated with an increased risk for certain outcomes. Among individual drugs trazodone, mirtazapine and venlafaxine were associated with the highest rates for some outcomes. Indication bias and residual confounding may explain some of the study findings. The risks of prescribing antidepressants need to be weighed against the potential benefits of these drugs. FUNDING: The National Institute for Health Research Health Technology Assessment programme.