PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia.

We examined putative microglial activation as a function of illness course in schizophrenia. Microglial activity was quantified using [11C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide (11C-(R)-PK11195) positron emission tomography (PET) in: (i) 10 individuals at ultra-high risk (UHR) of psychosis; (ii) 18 patients recently diagnosed with schizophrenia; (iii) 15 patients chronically ill with schizophrenia; and, (iv) 27 age-matched healthy controls. Regional-binding potential (BPND) was calculated using the simplified reference-tissue model with four alternative reference inputs. The UHR, recent-onset and chronic patient groups were compared to age-matched healthy control groups to examine between-group BPND differences in 6 regions: dorsal frontal, orbital frontal, anterior cingulate, medial temporal, thalamus and insula. Correlation analysis tested for BPND associations with gray matter volume, peripheral cytokines and clinical variables. The null hypothesis of equality in BPND between patients (UHR, recent-onset and chronic) and respective healthy control groups (younger and older) was not rejected for any group comparison or region. Across all subjects, BPND was positively correlated to age in the thalamus (r=0.43, P=0.008, false discovery rate). No correlations with regional gray matter, peripheral cytokine levels or clinical symptoms were detected. We therefore found no evidence of microglial activation in groups of individuals at high risk, recently diagnosed or chronically ill with schizophrenia. While the possibility of 11C-(R)-PK11195-binding differences in certain patient subgroups remains, the patient cohorts in our study, who also displayed normal peripheral cytokine profiles, do not substantiate the assumption of microglial activation in schizophrenia as a regular and defining feature, as measured by 11C-(R)-PK11195 BPND.

White matter connectivity disruptions in early and chronic schizophrenia.

BACKGROUND: White matter disruptions in schizophrenia have been widely reported, but it remains unclear whether these abnormalities differ between illness stages. We mapped the connectome in patients with recently diagnosed and chronic schizophrenia and investigated the extent and overlap of white matter connectivity disruptions between these illness stages. METHODS: Diffusion-weighted magnetic resonance images were acquired in recent-onset (n = 19) and chronic patients (n = 45) with schizophrenia, as well as age-matched controls (n = 87). Whole-brain fiber tracking was performed to quantify the strength of white matter connections. Connections were tested for significant streamline count reductions in recent-onset and chronic groups, relative to separate age-matched controls. Permutation tests were used to assess whether disrupted connections significantly overlapped between chronic and recent-onset patients. Linear regression was performed to test whether connectivity was strongest in controls, weakest in chronic patients, and midway between these extremities in recent-onset patients (controls > recent-onset > chronic). RESULTS: Compared with controls, chronic patients displayed a widespread network of connectivity disruptions (p < 0.01). In contrast, connectivity reductions were circumscribed to the anterior fibers of the corpus callosum in recent-onset patients (p < 0.01). A significant proportion of disrupted connections in recent-onset patients (86%) coincided with disrupted connections in chronic patients (p < 0.01). Linear regression revealed that chronic patients displayed reduced connectivity relative to controls, while recent-onset patients showed an intermediate reduction compared with chronic patients (p < 0.01). CONCLUSIONS: Connectome pathology in recent-onset patients with schizophrenia is confined to select tracts within a more extensive network of white matter connectivity disruptions found in chronic illness. These findings may suggest a trajectory of progressive deterioration of connectivity in schizophrenia.

Longitudinal employment outcomes of an early intervention vocational rehabilitation service for people admitted to rehabilitation with a traumatic spinal cord injury.

STUDY DESIGN: Longitudinal cohort design. OBJECTIVES: First, to explore the longitudinal outcomes for people who received early intervention vocational rehabilitation (EIVR); second, to examine the nature and extent of relationships between contextual factors and employment outcomes over time. SETTING: Both inpatient and community-based clients of a Spinal Community Integration Service (SCIS). METHODS: People of workforce age undergoing inpatient rehabilitation for traumatic spinal cord injury were invited to participate in EIVR as part of SCIS. Data were collected at the following three time points: discharge and at 1 year and 2+ years post discharge. Measures included the spinal cord independence measure, hospital anxiety and depression scale, impact on participation and autonomy scale, numerical pain-rating scale and personal wellbeing index. A range of chi square, correlation and regression tests were undertaken to look for relationships between employment outcomes and demographic, emotional and physical characteristics. RESULTS: Ninety-seven participants were recruited and 60 were available at the final time point where 33% (95% confidence interval (CI): 24-42%) had achieved an employment outcome. Greater social participation was strongly correlated with wellbeing (ρ=0.692), and reduced anxiety (ρ=-0.522), depression (ρ=-0.643) and pain (ρ=-0.427) at the final time point. In a generalised linear mixed effect model, education status, relationship status and subjective wellbeing increased significantly the odds of being employed at the final time point. Tertiary education prior to injury was associated with eight times increased odds of being in employment at the final time point; being in a relationship at the time of injury was associated with increased odds of being in employment of more than 3.5; subjective wellbeing, while being the least powerful predictor was still associated with increased odds (1.8 times) of being employed at the final time point. CONCLUSIONS: EIVR shows promise in delivering similar return-to-work rates as those traditionally reported, but sooner. The dynamics around relationships, subjective wellbeing, social participation and employment outcomes require further exploration.

ICARUSS, the Integrated Care for the Reduction of Secondary Stroke trial: rationale and design of a randomized controlled trial of a multimodal intervention to prevent recurrent stroke in patients with a recent cerebrovascular event, ACTRN = 12611000264987.

BACKGROUND: The majority of strokes, both ischaemic and haemorrhagic, are attributable to a relatively small number of risk factors which are readily manageable in primary care setting. Implementation of best-practice recommendations for risk factor management is calculated to reduce stroke recurrence by around 80%. However, risk factor management in stroke survivors has generally been poor at primary care level. A model of care that supports long-term effective risk factor management is needed. AIM: To determine whether the model of Integrated Care for the Reduction of Recurrent Stroke (ICARUSS) will, through promotion of implementation of best-practice recommendations for risk factor management reduce the combined incidence of stroke, myocardial infarction and vascular death in patients with recent stroke or transient ischaemic attack (TIA) of the brain or eye. DESIGN: A prospective, Australian, multicentre, randomized controlled trial. SETTING: Academic stroke units in Melbourne, Perth and the John Hunter Hospital, New South Wales. SUBJECTS: 1000 stroke survivors recruited as from March 2007 with a recent (<3 months) stroke (ischaemic or haemorrhagic) or a TIA (brain or eye). RANDOMIZATION: Randomization and data collection are performed by means of a central computer generated telephone system (IVRS). INTERVENTION: Exposure to the ICARUSS model of integrated care or usual care. PRIMARY OUTCOME: The composite of stroke, MI or death from any vascular cause, whichever occurs first. SECONDARY OUTCOMES: Risk factor management in the community, depression, quality of life, disability and dementia. STATISTICAL POWER: With 1000 patients followed up for a median of one-year, with a recurrence rate of 7-10% per year in patients exposed to usual care, the study will have at least 80% power to detect a significant reduction in primary end-points CONCLUSION: The ICARUSS study aims to recruit and follow up patients between 2007 and 2013 and demonstrate the effectiveness of exposure to the ICARUSS model in stroke survivors to reduce recurrent stroke or vascular events and promote the implementation of best practice risk factor management at primary care level.

Patient satisfaction following endoscopic endonasal dacryocystorhinostomy: a quality of life study.

PURPOSE: To assess the subjective success and quality of life of adult patients post endoscopic endonasal dacryocystorhinostomy (EE-DCR) for acquired nasolacrimal duct obstruction. DESIGN: Retrospective, questionnaire study performed at least 6 months post EE-DCR. PARTICIPANTS: Hundred and ten of the 282 consecutive patients who underwent EE-DCR. METHODS: A standardised questionnaire (Glasgow Benefit Inventory, GBI) was used to analyse the quality of life. The questionnaire examines four parameters, providing total, subscale, social, and physical scores. MAIN OUTCOME MEASURES: We aimed to assess patient experience following EE-DCR surgery. Total GBI scores range from -100 to +100, the former reflecting maximal negative benefit and corresponding to subjective worsening of tearing and impact on quality of life. Any positive score reflects a satisfactory surgical outcome and +100 represents maximal positive benefit. A score of zero is no perceived benefit. RESULTS: The average age was 62 years, 63% were female. In three of the parameters measured, there was a subjective improvement post surgery: subscale score 22.16 (95% CI: 15.23-29.09), total score 15.04 (95% CI: 9.74-20.35), and social support score 4.67 (95% CI: 0.93-8.42). Physical health scored -4.47 (95% CI: -10.25 to 1.32). Secondary analyses demonstrate no statistical significance with respect to outcome whether a trainee or consultant performed the procedure. Younger patients (under split median of 63.5) had a better total score 19.04 (95% CI: 11.35-27.74) than those older than 63.5 years (11.04, 95% CI: 3.61-18.47). DISCUSSION: This study shows that EE-DCR gave patients improvement in quality of life, proven by a validated questionnaire. The mean total score of 15.04 found in our study compares with the 18.7 recorded by Feretis et al in 2009. Results were irrespective of the grade of surgeon, similar to the findings of Fayers et al for functional successes. CONCLUSION: This study supports the use of EE-DCR for the improvement of quality of life in adult patients.

Reducing the length of stay for acute hospital patients needing admission into inpatient rehabilitation: a multicentre study of process barriers.

BACKGROUND: Patient flow is a major problem in hospitals. Delays in accessing inpatient rehabilitation have not been well studied. AIMS: Measure the time taken for key processes in the patient journey from acute hospital admission through to inpatient rehabilitation admission in order to identify opportunities for improvement. METHODS: Retrospective open cohort study. All patients admitted over 8- and 10-month periods during 2008 into two inpatient rehabilitation units in Melbourne, Australia. Main outcome measures were the duration of the following key processes: acute hospital admission until referral for rehabilitation, referral until assessment by the rehabilitation service, assessment until deemed ready for transfer to rehabilitation, ready for transfer until rehabilitation admission. RESULTS: Three hundred and sixty patients were in the study sample (females = 186; 51.7%); mean age = 58.4 (standard deviation = 15.0) years. There was a median of 7 (interquartile range [IQR] 4-13) days from acute hospital admission till referral for rehabilitation, a median of 1 (IQR 0-1) day from referral till assessment, a median of 0 (IQR 0-2) days from assessment till deemed ready for transfer and a median of 1 (IQR 0-3) day from ready till admission into rehabilitation. Overall, patients spent 12.0% (804/6682) of their acute hospital admission waiting for a rehabilitation bed. CONCLUSIONS: There are opportunities to improve the efficiency of key processes in the acute hospital journey for patients subsequently admitted to inpatient rehabilitation; in particular, reducing the time from acute hospital admission till referral for rehabilitation and from being deemed ready for transfer to rehabilitation till admission.

The lateral tarsal strip in ectropion surgery: is it effective when performed in isolation?

PURPOSE: The lateral tarsal strip (LTS) for involutional ectropion is often performed with a medial spindle (tarsoconjunctival diamond excision). We aimed to evaluate how well the LTS alone can achieve symptomatic relief. METHODS: A retrospective, comparative case series was performed on consecutive patients undergoing LTS alone or with medial spindle for involutional ectropion. Outcomes for LTS alone were clinically derived functional success (improvement in symptoms and aesthetic appearance) and anatomical success (judged by punctal position in the tear lake, punctal movement during blinking and absence of ectropion). We verified if these outcomes compared favourably with those of the patients who had undergone an LTS with medial spindle. Procedure selection was based on pre-operative clinical examination, especially the lateral pinch and twist test (this is described). Complications were also recorded. RESULTS: Of 67 eyes, 23 had LTS alone and 44 had LTS with a medial spindle. Of those having LTS alone the functional success rate was 87% (95% CI (66.4, 97.2%)). This did not differ significantly from a success rate of 89% (75.4, 96.2%) in LTS with a medial spindle (P=0.99). A total of 78% (56.9, 92.5%) of patients undergoing LTS had a good anatomical result compared with 82% (67.3, 91.8%) of those who had an additional medial spindle (P=0.75). Complication rates were similar between the groups. CONCLUSION: Where the lateral pinch and twist test returns the eyelid to a good position, the LTS alone can suffice for the management of involutional ectropion.

A clinical trial of endoscopic vs external dacryocystorhinostomy for partial nasolacrimal duct obstruction.

OBJECTIVE: A literature review revealed there is no outcome data for endoscopic endonasal dacryocystorhinostomy (EES-DCR) in the subgroup of patients with acquired partial nasolacrimal duct obstruction (NDO). This study aimed to compare the results of EES-DCR vs external DCR (ext-DCR) in the treatment of partial NDO. DESIGN: This study is designed as a prospective nonrandomised comparative clinical trial. PARTICIPANTS: In total, 46 adult patients with acquired partial NDO participated in this study. METHODS: Partial (sometimes called 'functional') NDO (epiphora in the presence of patent syringing) was confirmed by nuclear lacrimal scintigraphy or delayed drainage on dacryocystography. Patients with 'functional' epiphora from other causes were excluded. Post-operative outcome was assessed at 6 months. Overall, 21 (46%) patients had EES-DCR and 25 patients had (54%) ext-DCR. MAIN OUTCOME MEASURES: Subjective success was based on patient symptoms, objective success on patency with syringing and a functioning rhinostomy evaluated using the functional endoscopic dye test (FEDT). RESULTS: In total 18 out of 21 (86%) of EES-DCR patients had marked reduction (n=11) or complete resolution (n=7) and 25 out of 25 (100%) of ext-DCR had marked reduction (n=9) or complete resolution (n=16) of epiphora. In total 17 out of 18 (94%) of the EES-DCR patients with subjective success had a positive FEDT. All 25 out of 25 (100%) ext-DCR patients with subjective success had a positive FEDT. The three failed EES-DCR patients were all blocked on syringing. Statistically, EES-DCR does not achieve the same success rate as ext-DCR in this study (P=0.09, two-tailed Fisher's exact test, 0.045 one-tailed). CONCLUSIONS: Both endoscopic and external DCRs provide satisfactory outcomes in acquired partial NDO. The success rate is nevertheless higher in ext-DCR compared with EES-DCR.

Botulinum toxin assessment, intervention and aftercare for lower limb disorders of movement and muscle tone in adults: international consensus statement.

Lower limb disorders of movement and muscle tone in adults significantly impact quality of life. The management of the patient with hypertonia is complex and requires a multidisciplinary team working with the patient and family/carers. Botulinum neurotoxin type A (BoNT-A) has been used as a component of this management to reduce lower limb hypertonia, increase passive range of motion and reduce associated pain and requirements for bracing. Adjunctive treatments to augment the effect of BoNT-A include electrical muscle stimulation of the injected muscles and stretching. When determining suitability for injection, the patient's main goals for intervention need to be established. Muscle overactivity must be distinguished from contracture, and the effect of underlying muscle weakness taken into account. Explanation of the injection process, potential adverse effects and post-injection interventions is essential. Assessment at baseline and post-treatment of impairments such as hypertonia, range of motion and muscle spasm are appropriate; however, the Goal Attainment Scale and other validated patient-centred scales can also be useful to assess therapy outcomes. In the future, initiatives should be directed towards examining the effectiveness of BoNT treatment to assist with achievement of functional and participation goals in adults with hypertonia and dystonia affecting the lower limb.

Image guidance removal of a foreign body in the orbital apex.

Retrieval of foreign bodies lodged in the orbit present a challenging surgical problem. The trans-nasal approach when combined with image-guided navigation allows clear identification of structures and increased safety. We report a case of a successful removal of a foreign body under image-guidance using a trans-nasal approach.

Stroke rehab down under: can Rupert Murdoch, Crocodile Dundee, and an Aboriginal elder expect the same services and care?

Australia is the world's sixth largest country, has a relatively small population of 21.5 million, and a blended (public and private) health system. In this article, we explain the stroke rehabilitation infrastructure including consumer organisations, research networks, data collection systems, and registries. This represents a complex but fledgling set of organisations showing great promise for coordination of care and research. The article goes on to expose the inequalities in service provision by describing the paths of stroke survivors in three settings - in the city, in the country, and in remote settings. The complexities and difficulties in treating indigenous stroke survivors are described in a culturally sensitive narrative. The article then discusses the outcomes of the first Australian audit of post acute stroke services completed in December 2008, which describes the journeys of 2,119 stroke survivors at 68 rehabilitation units throughout Australia's 6 states and 2 territories. It demonstrates an average length of stay of 26 days, with 18% of survivors requiring nursing home or other supported accommodation. The article concludes with future directions for stroke rehabilitation in Australia, which include hyperacute rehabilitation trials, studies in 7-days-a-week rehabilitation, and the potential use of robotics.

British Oculoplastic Surgery Society (BOPSS) National Ptosis Survey.

AIM: To assess the results of primary aponeurotic ptosis surgery among UK ophthalmic oculoplastic surgeons, from both the surgeon's and patient's perspective; also to inform and encourage good clinical practice by generating outcomes for individual surgeons, units and for benchmarking purposes. METHODS: A prospective, web-based, non-comparative, interventional study was conducted over a period of 1 year commencing January 2005 and ending December 2005. The data-entry sheet for the preoperative, operative and postoperative data was completed and submitted online via the British Oculoplastic Surgery Society website. Surgical results were assessed objectively (by the surgeon) by measuring the upper lid margin reflex distance (uMRD) and the interlid difference in: MRD, lid show, skin crease and lid contour with the outcome graded as: success, partial success or failed. Surgical results were also assessed subjectively (by the patient) with the outcome graded as: completely satisfied, significantly improved, no change or worse than before the operation. RESULTS: Three hundred and sixty-five patients undergoing primary aponeurotic ptosis repair, from 40 different consultant-led teams with a declared oculoplastic interest and expertise, originating from 27 units across the UK were entered into the study. Using objective criteria, success was achieved in 128/223 (57%) cases, with significantly greater degrees of success seen in patients with mild ptosis and for surgeons who performed ptosis surgery more frequently. Using subjective criteria, 184/282 (65%) of patients were completely satisfied, with a further 89/282 (32%) judging themselves significantly improved. The patients' assessment of the surgery was less critical than that of the surgeons: 46/138 (33%) of patients who were completely satisfied and 37/72 (51%) of those who were significantly improved did not meet the criteria for a successful surgical outcome. The re-operation rate was 8/313 (2.6%). CONCLUSIONS: The authors have generated a valid series of surgical outcomes both for individuals, units and the UK as a whole, expressed in both objective and subjective terms for what we regard as the signature procedure for an oculoplastic surgeon: aponeurotic ptosis surgery. Individual results have been communicated to our members, which will allow them to compare their results with true peer-group-generated figures and will aid appraisal and ultimately revalidation.

Anterior cingulate activation in antipsychotic-naïve first-episode schizophrenia.

UNLABELLED: Anterior cingulate (ACC) hypo-activity is commonly observed in chronically ill schizophrenia patients. However, it is unclear whether this is secondary to persistent illness and/or medication. METHOD: We examined eight antipsychotic-naïve first-episode patients and matched healthy controls undergoing PET scanning while performing the Stroop task. RESULTS: Group-averaged and single-subject analyses showed ACC activation in both controls and patients, albeit in different sub-regions (paracingulate and cingulate respectively). A direct comparison revealed relative under-activity of the left paracingulate cortex in patients. CONCLUSION: These findings suggest that the more pervasive hypo-activation observed in chronic patients may be secondary to persistent illness and/or medication.

Masked orbital abscess in Wegener's granulomatosis.

Two patients with chronic Wegener's granulomatosis presented with worsening proptosis and visual acuity. Both patients had been maintained on long-term corticosteroids, which led to masking of the signs of orbital sepsis with potentially life-threatening implications.

Esophageal adenocarcinoma metastatic to the orbit.

A 75-year-old woman presented with orbital and ethmoidal metastases from an esophageal adenocarcinoma 6 months after diagnosis of the primary.