Variation of codons 1961 and 2177 of the Stargardt disease gene is not associated with age-related macular degeneration.

OBJECTIVES: To investigate the role of 2 specific alleles of the Stargardt disease gene (ABCA4) in the pathogenesis of age-related macular degeneration (AMD). Secondary objectives were to investigate differences in frequency of the G1961E allele in selected ethnic groups as well as to examine the segregation of both G1961E and D2177N alleles in 5 multiplex families with AMD. METHODS: Five hundred forty-four patients with AMD and 689 controls were ascertained from 3 continents. Blood samples from 62 normal individuals of Somalian ancestry were also obtained. Participants were screened for the presence of these ABCA4 alleles with a combination of restriction digestion and single-strand conformation polymorphism analysis of polymerase chain reaction amplification products. Detected alleles were confirmed by DNA sequencing. The number of subjects exhibiting the G1961E or D2177N variants were compared between AMD and control groups using a 2-tailed Fisher exact test. RESULTS: There was no significant difference (P >.1) in the frequency of the G1961E and D2177N alleles in patients with AMD (2.2%) vs controls (1.0%). In contrast, there was a significant difference (P< .001) in the frequency of the G1961E alleles between normal individuals of Somali ancestry (11.3%) and normal individuals from other populations (0.4%). There was no evidence of cosegregation of these alleles and the AMD phenotype in the 5 multiplex families with AMD examined. These two ABCA4 alleles were slightly more frequent in patients with AMD with choroidal neovascularization (2.7%) than those without this complication (2.5%). CONCLUSIONS: Somali ancestry is more than 100 times more strongly associated with presence of the G1961E allele than the AMD phenotype. This study did not find any statistically significant evidence for involvement of the G1961E or D2177N alleles of the ABCA4 gene in AMD. CLINICAL RELEVANCE: The ABCA4 gene is definitively involved in the pathogenesis of Stargardt disease and some cases of photoreceptor degeneration. However, it does not seem to be involved in a statistically significant fraction of AMD cases.

The Westmead head injury project: Outcome prediction in acute subdural haematoma.

A prospective two year study of a consecutive sample of patients with an acute subdural haematoma who were admitted to Westmead Hospital, New South Wales, Australia was undertaken. There were 103 patients with an acute subdural haematoma admitted in the period. Twenty-four of these scored 9 or greater on the Glasgow Coma Scale (GCS) and of these all made a functional recovery, i.e. Glasgow Outcome Scale (GOS 1 or 2). The remaining 79 patients scored 8 or less on admission and of these 30% made a functional recovery. Of the 70% remaining, 4% were moderately or severely disabled (GOS 3 or 4) while 66% died (GOS 5). Age, hypoxia, hypotension, response to intracranial pressure control and two CT scan features, midline shift as measured from the septum pellucidum and cerebral oedema, were all significant in predicting outcome. Time from injury to treatment, initial pupil response, lucid interval and compression of brainstem cisterns on CT scans statistically failed to predict outcome. The data were analysed using logistic regression which showed age and midline shift to predict death or disability with an accuracy of 80% at twelve months after the injury (sensitivity 58%, specificity 89%).

The Westmead Head Injury Project outcome in severe head injury. A comparative analysis of pre-hospital, clinical and CT variables.

A prospective study of 315 consecutive patients with a severe head injury was undertaken to study factors contributing to mortality and morbidity, both in the pre-hospital and hospital phases. Entry criteria were a Glasgow Coma Scale (GCS) score of 8 or less after non-surgical resuscitation within 6 h of the injury, or a deterioration to that level within 48 h. Patients with gunshot wounds or who were dead on arrival were excluded. End points of the study were either death or at 6 months after the injury. Predictors of mortality were increasing age, the presence of hypotension, a low GCS, abnormal motor responses and pupillary non-reactivity. In the 167 patients in whom intracranial pressure (ICP) was measured, raised ICP and failure to respond to treatment for raised ICP also predicted mortality. Three CT predictors of mortality were the presence of cerebral oedema, intraventricular blood and the degree of midline shift. When analysed using logistic regression, the most accurate model (accuracy 84.4%) included increasing age, abnormal motor responses and the three CT indicators. Analysis of the data for 'good' (Glasgow Outcome Score (GOS) 1 and 2) vs 'poor' (GOS 3 and 4) survival at 6 months was also performed using logistic regression. The model which provided the most accurate prediction of poor outcome included age, hypotension and three different CT characteristics, subarachnoid blood, intracerebral haematoma or intracerebral contusion (accuracy 72.5%).

Objective evaluation of the quality of palliation in patients with oesophageal cancer comparing surgery, radiotherapy and intubation.

The objective of this study was to prospectively evaluate the quality of palliation of 103 patients presenting to a joint oesophageal cancer clinic while recording the outcome in terms of treatment, morbidity, mortality and long-term survival. Twenty-five patients underwent surgical resection (S), 22 radical radiotherapy (RR), 30 palliative radiotherapy (PR), 13 intubation (I) and 13 had no treatment (NT). The quality of palliation was quantified by plotting a score out of 100 on a graph at each visit for Karnofsky performance, severity of pain and swallowing ability, then calculating the area under each curve created using an algorithm, Simpson's discrete approximation. Efficiency of palliation was estimated by comparing the area calculated to the maximum that could be achieved during the time frame being studied. The incidence of stricture (benign and malignant) was 16% after surgery and 50% after radical radiotherapy. Treatment mortality was as follows: RR, 0; S, 1 (4%); PR, 3 (7%); and I, 0. The median survival was 26 months after surgery and 16 months after radical radiotherapy. It was 6 months for palliative radiotherapy, 4 months for intubation and 4 months for no treatment. The difference in swallowing was the only statistical difference in the quality of palliation of patients having surgery and radical radiotherapy, there being no differences in patients having palliative measures.

The hospital trauma team: a model for trauma management.

A triage system was established as the initiating mechanism for a trauma team response to assist the assessment and early management of patients presenting to an accident and emergency department. A checklist of triage criteria was used. During a 6-month period, 342 patients (29.7% of trauma admissions) satisfied the triage criteria, which should have resulted in an average of 1.9 trauma team calls per day. Staff compliance with the triage tool was 75.4%. The overtriage rate for the checklist criteria was 52.7%. The triage tool identified patients with severe injuries who were not initially considered sufficiently injured to justify initiation of the trauma team response. The sensitivity of the triage tool in identifying patients with serious injury was 95.0%. Comparison of the review with a similar review performed 12 months earlier demonstrated that staff compliance with initiating the trauma team response had improved. Using data from 564 patients from both series, logistic regression analysis of the power of the triage criteria to predict serious injury contributed to a revision of the triage criteria. This trauma triage tool and trauma team response constitute a valid approach to the early hospital management of trauma patients. This system may be more appropriate or achievable in many hospitals than the construction of dedicated trauma reception units or permanent surgical staffing of general Accident and Emergency departments.

Interhospital transfer in the management of acute trauma.

During an 8-month period, 538 injured patients were transferred from primary hospitals to a referral hospital for further management of their injuries. Delay at the primary hospital was identified in 20% of all transfers and in 40% of patients transferred for management of head injury or multisystem injury. Delay at the primary hospital resulted in a median time from injury to arrival at the second hospital of 4 h. Defects in clinical management during transport included inexperienced escorts, inadequate airway control, ventilation, fluid resuscitation and stabilization of chest injuries. Nearly half of transfers were inappropriate because of the relatively minor nature of the injuries. Most of these had solitary musculoskeletal injuries to the extremities. These patients reflect the marked deficiency of specialist orthopaedic services in western Sydney during the study. Development of a metropolitan regional system of trauma care in western Sydney requires urgent action towards reducing the frequency of transfer, minimizing delays in transfer and maximizing basic resuscitation of seriously injured patients. Some designation of hospital roles is required and needs to be accompanied by a prehospital triage process. The population also has a right to expect adequate specialty services at suburban hospitals to enable treatment of minor and moderate single system injuries. Future trauma system developments should adequately reflect population growth and technological advances in clinical care.