Multiethnic involvement in autosomal-dominant optic atrophy in Singapore.

PurposeAutosomal-dominant optic atrophy (ADOA), often associated with mutations in the OPA1 gene (chromosome 3q28-q29) is rarely reported in Asia. Our aim was to identify and describe this condition in an Asian population in Singapore.Patients and methodsPreliminary cross-sectional study at the Singapore National Eye Centre, including patients with clinical suspicion of ADOA, who subsequently underwent genetic testing by direct sequencing of the OPA1 gene.ResultsAmong 12 patients (10 families) with clinically suspected ADOA, 7 patients (5 families) from 3 different ethnic origins (Chinese, Indian, and Malay) carried a heterozygous pathogenic variant in the OPA1 gene. The OPA1 mutations were located on exons 8, 9, 11, and 17: c.869G>A (p.Arg290Glu), c.892A>G (p.Ser298Gly), c.1140G>A (splicing mutation), and c.1669C>T (p.Arg557*), respectively. One splicing mutation (c.871-1G>A) was identified in intron 8. We also identified a novel mutation causing optic atrophy and deafness (c.892A>G (p.Ser298Gly)). Among the phenotypic features, colour pupillometry disclosed a dissociation between low vision and preserved pupillary light reflex in ADOA.ConclusionWe report the first cases of genetically confirmed OPA1-related ADOA from Singapore, including a novel mutation causing 'ADOA plus' syndrome. Further epidemiological studies are needed in order to determine the prevalence of ADOA in South-East Asia.

Clinical value of electrophysiology in determining the diagnosis of visual dysfunction in neuro-ophthalmology patients.

PURPOSE: To assess clinical value of visual electrophysiology in identifying causes of visual dysfunction in patients referred from neuro-ophthalmology clinics. METHODS: A review of 410 subjects (aged 0.3-88 years) referred for visual electrophysiology from neuro-ophthalmologists between 2009 and 2013 was performed. Subjects were divided into those with unexplained poor vision, visual field defects, visual symptoms or other reasons (e.g. monitoring for drug toxicity or known conditions). Subjects underwent pattern, full-field and multifocal electroretinography (ERG) and pattern visual evoked potential (VEP) tests. Flash and multifocal VEP were included where indicated. RESULTS: Most subjects referred for poor vision (n = 158) had electrophysiology findings suggestive of retinopathy (37 %) or post-retinal pathology (34 %). Those with poorer vision (worse than 6/24) were more likely to have abnormal recordings (86 vs. 62 %, p = 0.002). Among subjects with unexplained visual field defects (n = 102), findings of retinopathy, post-retinal pathology and normal recordings were noted in 31, 24 and 28 %, respectively. Most subjects with other visual symptoms (n = 97) had normal findings (69 %). The multifocal ERG was most sensitive for detecting retinopathy (96 %) and maculopathy (95 %), while pattern VEP was most sensitive for post-retinal pathology (94 %). An indeterminate result was noted in 9 %. CONCLUSION: Electrophysiology was effective in differentiating between retinopathy, post-retinal pathology and normality in 91 % of subjects. Pre-testing provisional diagnoses of retinopathy and post-retinal pathology were revised in 30 and 42 %, respectively, after electrophysiology. Appreciation of characteristics of each test, correlation with the clinical picture and interpretation of results in totality are required to localize the site of pathology.

End-of-life hospital costs in cancer patients: do advance directives or routes of hospital admission make a difference?

OBJECTIVE: End-of-life cancer care is costly. The current study explored whether advance directives or route of hospital admission reduced cancer patients' terminal hospitalization costs. METHODS: This single-institution study focused on solid tumor patients who died on an inpatient oncology service in 2008 and 2009. Patients' total costs were compared based on advance directives and route of hospitalization. RESULTS: Among 120 patients, all except 4 had an incurable malignancy. Forty-six (38%) had an advance directive. Sixteen (13%) were admitted after an oncology clinic visit and 6 (5%) from hospice; others were admitted via other routes, most commonly from the emergency department. The median total cost for hospitalization (range) per patient was USD 12,962 (1,244-138,877). Patients with advance directives had no statistically significant difference in cost (p = 0.30), even after adjusting for age and time in the hospital. Those admitted after an oncology clinic or from hospice also had no difference in cost compared to those admitted via another route. Use of cardiopulmonary resuscitation, intensive care unit monitoring and intubation were similar between all compared groups. CONCLUSION: Advance directives and route of admission do not appear to impact the cost of terminal hospitalization for cancer patients.

If you hold it off-hours, will they come? Results from a feasibility project intended to stimulate interest in the physician-investigator career path among medical oncology trainees.

BACKGROUND: An "endangered species," the physician-scientist faces challenges in oncology. The authors thus implemented a series of voluntary off-hours sessions on academic development for their trainees. METHODS: Numerous workday interruptions among trainees led the authors to conclude that off-hours sessions would be preferable. Thus, this feasibility project was conducted. All 34 trainees were invited to a session and were surveyed thereafter. An attendance rate of >or=34% was to be a "success." RESULTS: Seventy percent of trainees attended, and over 90% said they would do so again. Write-in comments were mostly favorable. CONCLUSIONS: Off-hours sessions to discuss academic career development are feasible among medical oncology trainees.

Optic neuritis in Singapore.

INTRODUCTION: Optic neuritis (ON) is the commonest optic neuropathy encountered in the younger group of patients from the Singapore Neuro-Ophthalmology Study Group. Previous surveys in Asia and our study suggest that ON in Singapore differs from that in Western populations where the majority of cases are associated with multiple sclerosis (MS). METHODS: Patients satisfying our entry criteria for ON seen between September 2002 and June 2004 were enrolled in the study. The data collected was recorded in a central database and analysed two years later. RESULTS: The majority (60 percent) of our patients had anterior ON with optic disc swelling (papillitis), were idiopathic in 49.1 percent, and associated with MS in only 25.5 percent. Bilateral cases comprised 16.4 percent of our series and were usually of the anterior variety and mostly idiopathic, although it is still essential to rule out secondary causes. Recurrent ON is indicative of an underlying disease process. CONCLUSION: The pattern of ON as seen in Singapore differs from that reported in Caucasian studies and from the seminal Optic Neuritis Treatment Trial. We found a higher incidence of optic disc swelling, i.e. anterior ON (papillitis), and a lesser association with MS; visual recovery is similarly good but our recurrence rate is lower.

An update on advance directives in the medical record: findings from 1186 consecutive patients with unresectable exocrine pancreas cancer.

BACKGROUND: The Terri Schiavo case and other recent events underscore the importance of advance directives. Yet, in the past, only a small subgroup has utilized them. This study from a large tertiary medical center was undertaken to assess current rates of advance directives among patients with incurable pancreas cancer. METHODS/RESULTS: The medical records of 1,186 consecutive patients with unresectable pancreas cancer were reviewed over a 4-year span. Only 174 patients (15%) had an advance directive in the medical record. Older age and having cancer therapy at our institution were associated with a greater likelihood of having an advance directive with odds ratios (95% confidence intervals) of 8.26 (2.81, 24.93) and 2.86 (2.03, 4.02), respectively, in multivariate analyses. Importantly, 42 patients (24%) had a different person designated as their healthcare agent in their advanced directive than what appeared in the medical record as the "contact person." CONCLUSION: These findings underscore the ongoing need to discuss advance directives with patients with incurable malignancies and to clarify patients' wishes when seemingly contradictory information appears in other parts of the medical record.

The presentation, aetiology, management and outcome of optic neuritis in an Asian population.

PURPOSE: To analyse the presentation, aetiology, management and outcome of patients with optic neuritis (ON) in Singapore. METHODS: This was a retrospective study involving consecutive patients with ON presentng at the Singapore National Eye Centre between January 1997 and May 1999. The presenting features, investigatons, treatment and visual outcome after 6 months were studied. RESULTS: A total of 31 patents (39 eyes) presented with ON during this period, 17 of whom had anterior ON. No aetiology was found in 26 patients (83.9%), two patients (6.5%) had multiple sclerosis, one had active syphilis, one had rheumatoid arthritis and another had pan-sinusitis. Seventeen patients (54.8%) were treated with intravenous methyl-prednisolone followed by oral prednisolone. Within the follow-up period 26 of 31 eyes (83.9%) wth idiopathic ON attained visual acuity of 6/12 or better with 12 (38.7%) recovering to 6/6 or better and only one eye ending with less than 6/60 visual acuity. The one patient with syphilis recovered 6/6 visual acuity bilaterally. Both patients with multiple sclerosis also had good visual recovery at 6 months. The visual outcome in those cases of ON associated with rheumatoid arthritis and pan-sinusitis was poor with visual acuity of less than 6/60 at 6 months follow up in each instance. CONCLUSION: The majority of the cases of ON in this study were idiopathic. There was a low association with multiple sclerosis. Most patients had good visual recovery within 6 months.

Amniotic membrane transplantation in entropion surgery.

PURPOSE: To evaluate the role of amniotic membrane transplantation in the management of cicatricial eyelid entropion. DESIGN: Prospective, noncomparative interventional case series. PARTICIPANTS: Eighteen consecutive patients with cicatricial entropion. METHODS: A gray line lid split procedure with vertical anterior lamella repositioning was performed on 25 eyelids (upper or lower) of 18 patients with moderate to severe cicatricial entropion. Preserved human amniotic membrane (AM) was used to cover the bare tarsus up to the lid margin and secured with running 7-0 Vicryl. Impression cytology of the AM was performed at various stages postoperatively to study the epithelialization process. MAIN OUTCOME MEASURES: (1) Reepithelialization of bare tarsus, (2) extent of tarsal shrinkage, (3) recurrence of entropion. RESULTS: All the AM grafts took well. The most common complication was hemorrhage below the graft, which occurred in six cases. Complete success with no lashes touching the globe was achieved in 22 of 25 (88%) lids after a minimum follow-up of 12.0 months. The mean follow-up was 17.8 months. Two cases (qualified success) had recurrent trichiasis treated successfully with electrolysis. One case with severe trachomatous upper lid entropion recurred 14 months after surgery. The AM accelerated the epithelialization of bare tarsus; this was demonstrated by lack of fluorescein staining and reversion to skin color within 2 to 3 weeks. However, AM could not prevent tarsal shrinkage. Impression cytology demonstrated that features of conjunctival epithelium were present for the first postoperative month, but this was gradually replaced by squamous metaplasia, with keratinization appearing as early as 3 weeks postoperatively. CONCLUSIONS: The use of AM in a lid split procedure for correction of cicatricial entropion helps the bare tarsus epithelialize rapidly and improves the initial cosmetic result of surgery.

Using metadata to create navigation paths in the HealthInsite Internet gateway.

The objective of this study was to evaluate the HealthInsite topic query technique, which uses a dynamic database search to assign resources to a topic. It is an alternative to the explicit classification technique, which relies on the classification of each resource using a predefined classification scheme. We performed a recall-precision analysis on all topics within the broad topic area of Child Health. Recall and precision errors were checked to determine which part of the information retrieval process was at fault. We then compared the topic query technique with the explicit classification technique. The results show errors or problems at every stage of the information retrieval process. This has initiated a review of all the tools used in the process, from indexing guidelines to the search engine. While many errors could be corrected, there were still features of the explicit classification technique that could not be achieved by the topic query technique. In conclusion, the topic query technique has the advantage of flexibility, but close co-operation between the different information retrieval specialists is needed to get the best results. The HealthInsite topic navigation structure should be regarded as an organized set of predefined searches rather than a full classified listing.

Combined phacoemulsification, intraocular lens implantation and trabeculectomy for chronic angle closure glaucoma.

PURPOSE: To investigate the results of combined phacoemulsification, intraocular lens implantation and trabeculectomy in Asian patients with chronic angle closure glaucoma (CACG). METHODS: This was a retrospective non-comparative case series of 55 consecutive patients (57 eyes) who underwent phacoemulsification, posterior chamber intraocular lens implantation and trabeculectomy for CACG at the Singapore National Eye Centre between 1997-1998. The surgical outcome was assessed in terms of intraocular pressure (IOP), the incidence of complications and the visual acuity at last follow-up. Success was defined as final IOP < or = 21 mmHg without medication and qualified success as final IOP < or = 21 mmHg with medication. Patients with final IOP > 21 mmHg who required further glaucoma surgery, lost light perception or became pthisical, were classified as failures. The eyes were further categorized into two groups according to whether single-site or separate-site surgery was performed. The outcome was also compared among eyes in which per-operative antimetabolites were applied to the trabeculectomy site and those without antimetabolites. RESULTS: The mean follow up was 22.0 +/- 5.6 months (mean +/- SD). Success was achieved in 46 (81%) eyes, qualified success in 10 (17%) eyes, and failure in 1 (2%) eye. In terms of IOP outcome, the success rate was similar in the two surgical groups (single-site or separate-site). There was no significant difference in IOP outcome among eyes in which per-operative antimetabolites were used and eyes with no per-operative antimetabolites use. Forty-one eyes (72%) had 6/12 or better vision. There were no cases of intraoperative complications and the incidence of postoperative complications was low. CONCLUSIONS: Combined phacoemulsification, intraocular lens implantation and trabeculectomy is associated with good intraocular pressure control and visual outcome in patients with CACG.

Trabeculectomy for acute primary angle closure.

OBJECTIVE: To analyze the results of trabeculectomy performed for all cases of acute primary angle closure (APAC). DESIGN: Retrospective, noncomparative case series PARTICIPANTS: Fifty-six consecutive patients who underwent trabeculectomy for APAC at two Singapore centers from 1993 through 1995. METHODS: The conventional treatment for APAC is to lower intraocular pressure (IOP) medically, after which laser peripheral iridotomy (PI) is performed. However, in Asian eyes, the acute attack is often refractory to standard treatment. Trabeculectomy is occasionally performed on eyes that do not respond to medical therapy, as well as eyes with APAC that respond to medical therapy but are assessed as having underlying chronic angle-closure glaucoma. In such cases, laser PI is not performed before trabeculectomy. MAIN OUTCOME MEASURES: The surgical outcome was assessed in terms of final IOP and the incidence of complications. Success was defined as final IOP less than 21 mmHg without medication, and qualified success was defined as final IOP less than 21 mmHg with medication. Patients whose IOP was more than 21 mmHg, required further glaucoma surgery, lost light perception, or whose eye became phthisical were classified as failures. RESULTS: The mean follow up was 22 months (range, 6-42 months). In group A, the medical failure group (n = 32), success in IOP control was obtained in 18 patients (56.2%), qualified success was achieved in 3 patients (9.4%), and failure resulted in 11 patients (34.4%). Ten patients (31.3%) encountered early postoperative complications such as shallow anterior chamber. In group B, the medical success group (n = 24), success in IOP control was achieved in 21 patients (87.5%), qualified success was achieved in 3 patients (12.5%), and there were no cases of failure. The incidence of postoperative complications was low (4 eyes [16.7%]). In terms of IOP outcome, trabeculectomy outcome was significantly worse in group A (P<0.001, Fisher's exact test). CONCLUSIONS: Because there is a high risk of surgical failure and complications, trabeculectomy may not be the procedure of choice in medically unresponsive cases of APAC.

The risk of midline catheterization in hospitalized patients. A prospective study.

OBJECTIVE: To assess the risk associated with midline catheter use in hospitalized patients. DESIGN: Prospective, consecutive enrollment. SETTING: A 719-bed university-affiliated hospital. PATIENTS: Patients were enrolled if they were likely to require at least 7 days of intravascular catheterization while hospitalized. MEASUREMENTS: Patients were monitored for adverse reactions. Catheter segment, insertion site, hub, infusate, and blood cultures were assessed. RESULTS: From February 1993 through June 1994, 251 Landmark midline catheters were inserted in 238 patients. One hundred forty catheter cultures were obtained from 130 patients who remained hospitalized for the duration of catheterization. For these 130 patients, the mean duration of catheterization was 9 days, the incidence of catheter colonization was 5.0 per 1000 catheter days, and the incidence of catheter-related bloodstream infection was 0.8 per 1000 catheter days. During the study period, two severe, unexpected adverse reactions occurred that may have been associated with the use of Landmark midline catheters; no such reactions were associated with the insertion of 58,580 Teflon peripheral catheters (P < 0.00001; exact 95% lower bound of the odds ratio, 68.9). Fifty-three similar reactions associated with Landmark midline catheters, including two deaths, have been reported to the Food and Drug Administration through June 1994. CONCLUSION: The risk for midline catheter-related infection is low. However, Landmark midline catheters are associated with life-threatening adverse reactions that are probably attributable to the catheter material itself.

Isobolographic assessment of the effects of combinations of phenylpropanolamine and fenfluramine on food intake in rats.

Phenylpropanolamine (PPA) suppresses appetite in rats via activation of alpha 1-adrenergic receptors within the paraventricular hypothalamus (PVN). The serotonergic (5-HT) agonist fenfluramine (FEN) is thought to suppress appetite via stimulation of 5-HT release within the PVN rather than activation of adrenergic receptors. Whether a mixture of these neurochemically distinct anorexic drugs will serve as an effective appetite suppressant is unknown. In the present experiment, drug-drug interactions between PPA and FEN were explored using an isobologram technique. Fixed doses of PPA (0 vs. 5 mg/kg) were combined with various doses of FEN (1.25, 2.5, and 5.0 mg/kg) and fixed doses of FEN (0 vs. 2.5 mg/kg) were combined with various doses of PPA (0, 5, 10, and 15 mg/kg). Drug combinations were injected IP 30 min before a 1-h feeding trial in 16-h food-deprived rats. PPA and FEN were dose-additive in this paradigm, an outcome that supports the feasibility of a new appetite suppressant composed of a mixture of PPA and FEN.

Malignant mesenchymoma of the retropharyngeal space.

Malignant mesenchymoma is a very rare head and neck tumour. To date only 15 cases have been reported in world literature and all in children under 16 years of age. We present here a case of a 40-year-old man with malignant mesenchymoma of the retropharyngeal space. The clinical picture is that of progressive dysphagia, voice change, snoring and dyspnoea. CT scan showed a soft tissue space-occupying lesion of the retropharyngeal space which enhanced very well with intravenous contrast. The tumour was excised in toto and the patient given post-operative radiotherapy. Histopathology showed two unrelated differentiated tissue types (bone and fat) in addition to the fibrosarcomatous element thus satisfying Stout's criteria (Stout, 1948) for a diagnosis of malignant mesenchymoma.

Enhancement of phenylpropanolamine anorexia by proglumide in rats.

Although a number of studies have characterized the anorectic state induced by phenylpropanolamine (PPA), the mechanism by which this drug suppresses appetite remains elusive. PPA inhibits gastric emptying at doses that also suppress appetite as does the gut hormone cholecystokinin (CCK). To evaluate whether PPA anorexia results via an action on gut CCK activity, rats in the present study were treated (IP) with either 0.9% saline or 150 mg/kg proglumide, a CCK receptor antagonist, 30 minutes before a 15 min feeding trial and then injected (IP) 5 min prior to the trial with either 0.9% saline, 5 mg/kg PPA, 10 mg/kg PPA, 8 ug/kg CCK or 16 ug/kg CCK. Although 150 mg/kg proglumide antagonized CCK anorexia, this dose of proglumide significantly enhanced the anorectic action of PPA. These results suggest that PPA does not act via an endogenous CCK system to suppress feeding.