Subarachnoid haemorrhage (SAH):long-term cognitive outcome in patients treated with surgical clipping or endovascular coiling

Purpose: To compare long-term cognitive outcomes of patients treated with surgical clipping or endovascular coiling after subarachnoid haemorrhage (SAH). Method: Retrospective matched cohort study assessed neuropsychological functioning at least 12 months after aneurysmal SAH treatment. Fourteen patients treated by endovascular coiling and nine patients treated by surgical clipping participated. After gaining written consent, a comprehensive neuropsychological battery was completed. Standardised tests were employed to assess pre-morbid and current intellectual functioning (IQ), attention, speed of information processing, memory and executive function as well as psychosocial functioning and affect. Results: Treatment groups were not significantly different in terms of age, pre-morbid IQ, time from injury to treatment or time since injury. A significant effect of treatment on full-scale IQ score (p = 0.025), performance IQ (p = 0.045) and verbal IQ score (p = 0.029), all favouring the coiled group was observed. A medium effect size between groups difference in immediate memory (p = 0.19, partial ?(2) = 0.08) was also observed. No significant between group differences on attention, executive functioning and speed of information processing measures or mood and psychosocial functioning were noted. Both groups reported increased anxiety and memory, attention and speed of information processing deficits relative to normative data. Conclusions: Study findings indicate fewer cognitive deficits following endovascular coiling. Cognitive deficits in the clipped group may be due in part to the invasive nature of neurosurgical clipping. Further prospective research with regard to long-term cognitive and emotional outcomes is warranted. [Box: see text].

Medical versus surgical interventions for open angle glaucoma.

BACKGROUND: Open angle glaucoma (OAG) is a common cause of blindness.

OBJECTIVES: To assess the effects of medication compared with initial surgery in adults with OAG.

SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2012), EMBASE (January 1980 to August 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2012), Biosciences Information Service (BIOSIS) (January 1969 to August 2012), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to August 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), Zetoc, the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 1 August 2012. The National Research Register (NRR) was last searched in 2007 after which the database was archived. We also checked the reference lists of articles and contacted researchers in the field.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing medications with surgery in adults with OAG.

DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for missing information.

MAIN RESULTS: Four trials involving 888 participants with previously untreated OAG were included. Surgery was Scheie's procedure in one trial and trabeculectomy in three trials. In three trials, primary medication was usually pilocarpine, in one trial it was a beta-blocker.The most recent trial included participants with on average mild OAG. At five years, the risk of progressive visual field loss, based on a three unit change of a composite visual field score, was not significantly different according to initial medication or initial trabeculectomy (odds ratio (OR) 0.74, 95% confidence interval (CI) 0.54 to 1.01). In an analysis based on mean difference (MD) as a single index of visual field loss, the between treatment group difference in MD was -0.20 decibel (dB) (95% CI -1.31 to 0.91). For a subgroup with more severe glaucoma (MD -10 dB), findings from an exploratory analysis suggest that initial trabeculectomy was associated with marginally less visual field loss at five years than initial medication, (mean difference 0.74 dB (95% CI -0.00 to 1.48). Initial trabeculectomy was associated with lower average intraocular pressure (IOP) (mean difference 2.20 mmHg (95% CI 1.63 to 2.77) but more eye symptoms than medication (P = 0.0053). Beyond five years, visual acuity did not differ according to initial treatment (OR 1.48, 95% CI 0.58 to 3.81).From three trials in more severe OAG, there is some evidence that medication was associated with more progressive visual field loss and 3 to 8 mmHg less IOP lowering than surgery. In the longer-term (two trials) the risk of failure of the randomised treatment was greater with medication than trabeculectomy (OR 3.90, 95% CI 1.60 to 9.53; hazard ratio (HR) 7.27, 95% CI 2.23 to 25.71). Medications and surgery have evolved since these trials were undertaken.In three trials the risk of developing cataract was higher with trabeculectomy (OR 2.69, 95% CI 1.64 to 4.42). Evidence from one trial suggests that, beyond five years, the risk of needing cataract surgery did not differ according to initial treatment policy (OR 0.63, 95% CI 0.15 to 2.62).Methodological weaknesses were identified in all the trials.

AUTHORS' CONCLUSIONS: Primary surgery lowers IOP more than primary medication but is associated with more eye discomfort. One trial suggests that visual field restriction at five years is not significantly different whether initial treatment is medication or trabeculectomy. There is some evidence from two small trials in more severe OAG, that initial medication (pilocarpine, now rarely used as first line medication) is associated with more glaucoma progression than surgery. Beyond five years, there is no evidence of a difference in the need for cataract surgery according to initial treatment.The clinical and cost-effectiveness of contemporary medication (prostaglandin analogues, alpha2-agonists and topical carbonic anhydrase inhibitors) compared with primary surgery is not known.Further RCTs of current medical treatments compared with surgery are required, particularly for people with severe glaucoma and in black ethnic groups. Outcomes should include those reported by patients. Economic evaluations are required to inform treatment policy.

Filtration procedures supplemented with mitomycin C in the management of childhood glaucoma

Aims - To evaluate the outcome of filtering procedures supplemented with mitomycin C in children with glaucoma. Methods - All patients aged 17 or younger with glaucoma who underwent filtering surgery supplemented with mitomycin C at a tertiary care centre (n = 21) during a 5 year interval (1992 and 1996) were included. One eye for each patient was entered into the analysis. The postoperative intraocular pressure (IOP), use of antiglaucoma medications, clinical stability of glaucoma, complications, and visual acuity were retrospectively evaluated. Kaplan-Meier survival curves were used to estimate the probability of success. Results - At the time of surgery mean age was 5.7 (SD 5.0) years. The most common diagnoses were trabeculodysgenesis (n = 6) and aphakic glaucoma (n = 8). Mean IOP before surgery was 35.7 (10.5) mmHg. Average length of follow up was 18.6 (14.7) months. The probability of having IOP less than 21 mmHg with no antiglaucoma medications and with clinically stable glaucoma 1 year after surgery was 76.9% in phakic eyes (n = 13) and 0% in aphakic eyes (n = 8). A phakic patient with Sturge-Weber's syndrome had choroidal effusion after surgery that resolved spontaneously. In the aphakic group one patient had retinal detachment and another developed an encapsulated bleb. Visual acuity deteriorated in one patient. Conclusion - A guarded filtration procedure with mitomycin C is relatively successful in phakic children with glaucoma, but unsuccessful in aphakic ones.

A systematic literature review of surgical interventions for limbal stem cell deficiency in humans

PURPOSE: To evaluate the relative benefits and to identify any adverse effects of surgical interventions for limbal stem cell deficiency (LSCD).

DESIGN: Systematic literature review.

METHODS: We searched the following electronic databases from January 1, 1989 through September 30, 2006: MEDLINE, EMBASE, Science citation index, BIOSIS, and the Cochrane Library. In addition, reference lists were scanned to identify any additional reports. The quality of published reports was assessed using standard methods. The main outcome measure was improvement in vision of at least two Snellen lines of best-corrected visual acuity (BCVA). Data on adverse outcomes also were collected.

RESULTS: Twenty-six studies met the inclusion criteria. There were no randomized controlled studies. All 26 studies were either prospective or retrospective case series. For bilateral severe LSCD, keratolimbal allograft was the most common intervention with systemic immunosuppression. Other interventions included eccentric penetrating keratolimbal allografts and cultivated autologous oral mucosal epithelial grafts. An improvement in BCVA of two lines or more was reported in 31% to 67% of eyes. For unilateral severe LSCD, the most common surgical intervention was contralateral conjunctival limbal autograft, with 35% to 88% of eyes gaining an improvement in BCVA of two lines or more. The only study evaluating partial LSCD showed an improvement in BCVA of two lines or more in 39% of eyes.

CONCLUSIONS: Studies to date have not provided strong evidence to guide clinical practice on which surgery is most beneficial to treat various types of LSCD. Standardized data collection in a multicenter LSCD register is suggested.

Medical versus surgical interventions for open angle glaucoma.

BACKGROUND: Open angle glaucoma (OAG) is the commonest cause of irreversible blindness worldwide. OBJECTIVES: To study the relative effects of medical and surgical treatment of OAG. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to February 2005), EMBASE (1988 to February 2005), and reference lists of articles. We also contacted researchers in the field. SELECTION CRITERIA: Randomised controlled trials comparing medications to surgery in adults. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted trial investigators for missing information. MAIN RESULTS: Four trials involving 888 participants with previously untreated OAG were included. Surgery was Scheie's procedure in one trial and trabeculectomy in three trials. In three trials, primary medication was usually pilocarpine, in one trial a beta-blocker.In the most recent trial, participants with mild OAG, progressive visual field (VF) loss, after adjustment for cataract surgery, was not significantly different for medications compared to trabeculectomy (Odds ratio (OR) 0.74; 95% CI 0.54 to 1.01). Reduction of vision, with a higher risk of developing cataract (OR 2.69, 95%% CI 1.64 to 4.42), and more patient discomfort was more likely with trabeculectomy than medication.There is some evidence, from three trials, for people with moderately advanced glaucoma that medication is associated with more progressive VF loss and 6 to 8 mmHg less intraocular pressure (IOP) lowering than surgery, either by a Scheie's procedure or trabeculectomy. There was a trend towards an increased risk of failed IOP control over time for initial pilocarpine treatment compared to trabeculectomy. In the longer-term (two trials) the risk of failure was significantly greater with medication than trabeculectomy (OR 3.90, 95% CI 1.60 to 9.53; HR 7.27, 95% CI 2.23 to 25.71). Medicine and surgery have evolved since these trials were undertaken, and additionally the evidence is potentially subject to detection and attrition bias. AUTHORS' CONCLUSIONS: Evidence from one trial suggests, for mild OAG, that VF deterioration up to five-years is not significantly different whether treatment is initiated with medication or trabeculectomy. Reduced vision, cataract and eye discomfort are more likely with trabeculectomy. There is some evidence, for more severe OAG, that initial medication (pilocarpine, now rarely used as first line medication) is associated with greater VF deterioration than surgery. In general, surgery lowers IOP more than medication.There was no evidence to determine the effectiveness of contemporary medication (prostaglandin analogues, alpha2-agonists and topical carbonic anhydrase inhibitors) compared to surgery in severe OAG, and in people of black African ethnic origin who have a greater risk of more severe open angle glaucoma. More research is required.

Surgical checklist for cataract surgery:progress with the initiative by the Royal College of Ophthalmologists to improve patient safety

PurposeThe World Health Organisation (WHO) identified patient safety in surgery as an important public health matter and advised the adoption of a universal peri-operative surgical checklist. An adapted version of the WHO checklist has been mandatory in the National Health Service since 2010. Wrong intraocular lens (IOL) implantation is a particular safety concern in ophthalmology. The Royal College of Ophthalmologists launched a bespoke checklist for cataract surgery in 2010 to reduce the likelihood of preventable errors. We sought to ascertain the use of checklists in cataract surgery in 2012.Patients and methodsA survey of members of the Royal College of Ophthalmologists seeking views on the use of checklists in cataract surgery. Four hundred and sixty-nine completed responses were received (18% response rate).ResultsRespondents worked in England (75%), Scotland (11%), Wales (5%), Northern Ireland (2%), the Republic of Ireland (1%), and overseas (6%). Ninety-four per cent of respondents support the use of a checklist for cataract surgery and 85% say that they always use a checklist before cataract surgery. Sixty-seven per cent of cataract surgeons stated they undertake a pre-operative team brief. Thirty-six per cent use a cataract surgery checklist developed locally, 18% use the college's bespoke cataract surgery checklist, 39% use a generic surgical checklist, and 4% reported that they do not use a checklist.ConclusionNinety-three per cent of cataract surgeons responding to the questionnaire report using a surgical checklist and 67% use a team brief. However, only 54% use a checklist, which addresses the selection of the correct intraocular implant. We recommend wider adoption of checklists, which address risks relevant to cataract surgery, in particular the possibility of selection of an incorrect IOL.Eye advance online publication, 24 May 2013; doi:10.1038/eye.2013.101.

The effect of polymer coatings on physicochemical properties of spray-dried liposomes for nasal delivery of BSA

This work describes the development of spray dried polymer coated liposomes composed of soy phosphatidylcholine (SPC) and phospholipid dimyristoyl phosphatidylglycerol (DMPG) coated with alginate, chitosan or trimethyl chitosan (TMC), that are able to penetrate through the nasal mucosa and offer enhanced penetration over uncoated liposomes when delivered as a dry powder. All the liposome formulations, loaded with BSA as model antigen, were spray-dried to obtain powder size and liposome size in a suitable range for nasal delivery. Although coating resulted in some reduction in encapsulation efficiency, levels were still maintained between 60% and 69% and the structural integrity of the entrapped protein and its release characteristics were maintained. Coating with TMC gave the best product characteristics in terms of entrapment efficiency, glass transition (Tg) and mucoadhesive strength, while penetration of nasal mucosal tissue was very encouraging when these liposomes were administered as dispersions although improved results were observed for the dry powders

Familial hypocalciuric hypercalcaemia as a differential diagnosis of hyperparathyroidism:studies in a large kindred and a review of surgical experience in the condition

We have studied 46 members of a large kindred with familial hypocalciuric hypercalcaemia (FHH) after a neck exploration failed to cure hypercalcaemia in an asymptomatic patient. Serum calcium, serum phosphate, plasma parathormone and vitamin D metabolites do not distinguish affected members from patients with hyperparathyroidism. Because of the continuing debate as to whether or not FHH is a variant of, or distinct from, hyperparathyroidism, we have carried out a review of surgical experience with subtotal parathyroidectomy in hyperparathyroidism secondary to parathyroid hyperplasia and in FHH. Whereas the procedure is successful in 90 per cent of the former cases only one case of FHH has been cured by it. This provides evidence for the two conditions being aetiologically distinct. Before patients with asymptomatic hypercalcaemia are referred for parathyroid surgery the calcium:creatinine clearance ratio should be measured using a 2 h urine sample collected after an overnight fast and a fasting blood sample. If this ratio is less than 0.01 then screening of first degree relations should be undertaken before any parathyroid surgery is performed. Unnecessary surgery can therefore be avoided.

Pharmacological characterization of a noninvasive, chronic, experimental dog model of nasal congestion

The present experiments were undertaken to pharmacologically characterize a noninvasive, chronic, experimental dog model of nasal congestion with the overall goal of developing an effective tool for studying the mechanism of action of nasal decongestant drugs.

Measurement of nasal patency in anesthetized and conscious dogs

Experiments were undertaken to characterize a noninvasive chronic, model of nasal congestion in which nasal patency is measured using acoustic rhinometry. Compound 48/80 was administered intranasally to elicit nasal congestion in five beagle dogs either by syringe (0.5 ml) in thiopental sodium-anesthetized animals or as a mist (0.25 ml) in the same animals in the conscious state. Effects of mast cell degranulation on nasal cavity volume as well as on minimal cross-sectional area (A(min)) and intranasal distance to A(min) (D(min)) were studied. Compound 48/80 caused a dose-related decrease in nasal cavity volume and A(min) together with a variable increase in D(min). Maximal responses were seen at 90-120 min. Compound 48/80 was less effective in producing nasal congestion in conscious animals, which also had significantly larger basal nasal cavity volumes. These results demonstrate the utility of using acoustic rhinometry to measure parameters of nasal patency in dogs and suggest that this model may prove useful in studies of the actions of decongestant drugs.

Acoustic rhinometry in the dog:a novel large animal model for studies of nasal congestion

The aim of this project was to develop and pharmacologically characterize an experimental dog model of nasal congestion in which nasal patency is measured using acoustic rhinometry. Solubilized compound 48/80 (0.3-3.0%) was administered intranasally to thiopental anesthetized beagle dogs to elicit nasal congestion via localized mast cell degranulation. Compound 48/80-induced effects on parameters of nasal patency were studied in vehicle-treated animals, as well as in the same animals pretreated 2 hours earlier with oral d-pseudoephedrine or chlorpheniramine. Local mast cell degranulation caused a close-related decrease in nasal cavity volume and minimal cross-sectional area (Amin) together with a highly variable increase in nasal secretions. Maximal responses were seen at 90-120 minutes after 48/80 administration. Oral administration of the adrenergic agonist, d-pseudoephedrine (3.0 mg/kg), significantly antagonized all of the nasal effects of compound 48/80 (3.0%). In contrast, oral administration of the histamine H1 receptor antagonist chlorpheniramine (10 mg/kg) appeared to reduce the increased nasal secretions but was without effect on the compound 48/ 80-induced nasal congestion (i.e., volume and Amin). These results show the effectiveness of using acoustic rhinometry in this anesthetized dog model. The observations that compound 48/80-induced nasal congestion was prevented by d-pseudoephedrine pretreatment, but not by chlorpheniramine, suggest that this noninvasive model system may provide an effective tool with which to study the actions of decongestant drugs in preclinical investigations.

Nasal Epithelial Cells Can Act as a Physiological Surrogate for Paediatric Asthma Studies

Introduction: Differentiated paediatric epithelial cells can be used to study the role of epithelial cells in asthma. Nasal epithelial cells are easier to obtain and may act as a surrogate for bronchial epithelium in asthma studies. We assessed the suitability of nasal epithelium from asthmatic children to be a surrogate for bronchial epithelium using air-liquid interface cultures.

Methods: Paired nasal and bronchial epithelial cells from asthmatic children (n = 9) were differentiated for 28 days under unstimulated and IL-13-stimulated conditions. Morphological and physiological markers were analysed using immunocytochemistry, transepithelial-electrical-resistance, Quantitative Real-time-PCR, ELISA and multiplex cytokine/chemokine analysis.

Results: Physiologically, nasal epithelial cells from asthmatic children exhibit similar cytokine responses to stimulation with IL-13 compared with paired bronchial epithelial cells. Morphologically however, nasal epithelial cells differed significantly from bronchial epithelial cells from asthmatic patients under unstimulated and IL-13-stimulated conditions. Nasal epithelial cells exhibited lower proliferation/differentiation rates and lower percentages of goblet and ciliated cells when unstimulated, while exhibiting a diminished and varied response to IL-13.

Conclusions: We conclude that morphologically, nasal epithelial cells would not be a suitable surrogate due to a significantly lower rate of proliferation and differentiation of goblet and ciliated cells. Physiologically, nasal epithelial cells respond similarly to exogenous stimulation with IL-13 in cytokine production and could be used as a physiological surrogate in the event that bronchial epithelial cells are not available.