Conflicts of interest in electrophysiology and devices presentations.

AIMS: Industry collaboration with arrhythmia and devices research is common. However, this results in conflicts of interest (CoI) for researchers that should be disclosed. This study aimed to examine the quality of CoI disclosures in arrhythmia and devices presentations. METHODS: Recorded presentations from the Arrhythmia & Devices section of the ESC Annual Congress 2016-2020 were assessed. The number of words, conflicts, and time displayed was documented for CoI declarations. Meta-data including sponsorship by an industry partner, presenter sex, and institution were obtained. RESULTS: Of 1153 presentations assessed, 999 were suitable for inclusion. CoI statements were missing from 7.2% of presentations, and 58% reported ≥1 conflict. Those with conflicts spent less time-per-word on their disclosures (median 150 ms, interquartile range [IQR] 83-273 ms) compared with those without conflicts (median 250 ms, IQR 125-375 ms). One-in-eight presentations were sponsored (12.8%, n = 128). CoI statements were more likely to be missing in sponsored presentations (14.8%, n = 19) compared with non-sponsored presentations (6.1%, n = 53), P = 0.0003. Sponsored presentations contained a greater median number of CoIs (10, IQR 6-18) compared with non-sponsored sessions (1, IQR 0-5), P < 0.0001. Time-per-word spent on COI disclosures was 50% lower in sponsored sessions (125 ms, IQR 75-231 ms) compared with non-sponsored sessions (250 ms, IQR 125-375 ms), P < 0.0001. CONCLUSION: The majority of those presenting arrhythmia and devices research have CoIs to declare. Declarations were often missing or displayed for short periods of time. Presenters in sponsored sessions, while being more conflicted, had a lower standard of declaration suggesting a higher risk of potential bias which viewers had insufficient opportunity to assess.

Excluding familial hypocalciuric hypercalcaemia before surgery for primary hyperparathyroidism - a practical evaluation of urinary calcium using a retrospective cohort design.

INTRODUCTION: Familial hypocalciuric hypercalcaemia (FHH) and primary hyperparathyroidism (PHPT) are both associated with raised serum calcium and parathyroid hormone (PTH) levels; the former should be excluded in patients undergoing surgery for the latter. Twenty-four-hour urinary calcium collections (24UCA) can be performed to quantify total calcium excreted; however, results of this method do not take into account factors such as kidney function. Current guidelines suggest measuring urine calcium to creatinine clearance ratio (CCCR) as the initial step. The aim of this study was to evaluate the use of CCCR and 24UCA in a cohort design, to reliably exclude FHH patients before surgery for PHPT. METHODS: A retrospective cohort study of all patients having urine calcium investigations in a single centre, over a 2-year period was performed. Relevant biochemical data and recorded diagnoses were collected. RESULTS: In total, 296 urine calcium measurements were included from 199 patients. Ten (5%) had genetically confirmed or suspected FHH, 171 (85.9%) had surgically proven or suspected PHPT and the remainder had other diagnoses. At a CCCR cut-off of ≤0.020, positive and negative predictive values (PPV and NPV) were 2.33% and 100%, respectively. At a cut-off of ≤0.015, NPV was maintained at 100% and PPV increased to 3.28%. Low 24UCA measurements (<2.5mmol/L/24h) generated a NPV for FHH of 95.2%. CONCLUSION: A CCCR measurement below 0.020 should raise the possibility of FHH and genetic screening should be considered. 24UCA had a lower predictive power to exclude FHH (NPV), and measurements should be interpreted in the context of renal function.

Spontaneous thyroid abscesses without underlying malignancy: a differential diagnosis for recent onset or rapidly growing thyroid masses.

Thyroid abscess is a rare cause of neck swelling in patients. The rich iodine environment, good vasculature and protective capsule make bacterial growth suboptimal. We present two cases of thyroid abscess without underlying thyroid cancer in immunocompromised patients presenting to a thyroid unit. The demographics, clinical details, investigation, management and outcomes of two patients with thyroid abscess were reviewed. Two octogenarian women were referred with neck lumps originating in the thyroid gland. Ultrasound demonstrated fluid collection in the thyroid, aspiration of which demonstrated Escherichia coli. The patients had underlying diabetes mellitus and raised inflammatory markers at presentation. Both were treated with antibiotics and follow-up demonstrated complete resolution of infection with no underlying thyroid neoplasm. Thyroid abscesses are an important differential diagnosis in rapidly growing thyroid masses due to the potential for rapid deterioration, especially in patients with conditions or medications causing immunosuppression. Urgent admission should be considered to facilitate prompt intervention and rapid recovery.

How can Never Event data be used to reflect or improve hospital safety performance?

The absolute number of Never Events is used by UK regulators to help assess hospital safety performance, without account of hospital workload. We applied funnel plots, as an established means of taking workload into account, to published Never Event data for 151 acute Trusts in NHS England, matched to finished consultant episodes for 3 years, 2017-2020. Trusts with excess event rates should have the most Never Events if absolute number is a valid way to judge performance. The absolute number of Never Events was correlated with workload (r2 = 0.51, p < 0.001), but the five Trusts above the upper 95% confidence limit did not have the highest number of Never Events. However, a limitation to interpretation was that the data were skewed; 12 out of 151 Trusts lay below the lower 95% limit. This skew probably arises because funnel plots pool all Never Events and workload data; whereas, ideally, different Never Events should use as denominator only the relevant workload actions that could cause them. We conclude that the manner in which Never Event data are currently used by regulators, in part to judge or rate hospitals, is mathematically invalid. The focus should shift from identifying 'outlier' hospitals to reducing the overall national mean Never Event rate through shared learning and an integrated system-wide approach.

MR Elastography demonstrates reduced white matter shear stiffness in early-onset hydrocephalus.

INTRODUCTION: Hydrocephalus that develops early in life is often accompanied by developmental delays, headaches and other neurological deficits, which may be associated with changes in brain shear stiffness. However, noninvasive approaches to measuring stiffness are limited. Magnetic Resonance Elastography (MRE) of the brain is a relatively new noninvasive imaging method that provides quantitative measures of brain tissue stiffness. Herein, we aimed to use MRE to assess brain stiffness in hydrocephalus patients compared to healthy controls, and to assess its associations with ventricular size, as well as demographic, shunt-related and clinical outcome measures. METHODS: MRE was collected at two imaging sites in 39 hydrocephalus patients and 33 healthy controls, along with demographic, shunt-related, and clinical outcome measures including headache and quality of life indices. Brain stiffness was quantified for whole brain, global white matter (WM), and lobar WM stiffness. Group differences in brain stiffness between patients and controls were compared using two-sample t-tests and multivariable linear regression to adjust for age, sex, and ventricular volume. Among patients, multivariable linear or logistic regression was used to assess which factors (age, sex, ventricular volume, age at first shunt, number of shunt revisions) were associated with brain stiffness and whether brain stiffness predicts clinical outcomes (quality of life, headache and depression). RESULTS: Brain stiffness was significantly reduced in patients compared to controls, both unadjusted (p ≤ 0.002) and adjusted (p ≤ 0.03) for covariates. Among hydrocephalic patients, lower stiffness was associated with older age in temporal and parietal WM and whole brain (WB) (beta (SE): -7.6 (2.5), p = 0.004; -9.5 (2.2), p = 0.0002; -3.7 (1.8), p = 0.046), being female in global and frontal WM and WB (beta (SE): -75.6 (25.5), p = 0.01; -66.0 (32.4), p = 0.05; -73.2 (25.3), p = 0.01), larger ventricular volume in global, and occipital WM (beta (SE): -11.5 (3.4), p = 0.002; -18.9 (5.4), p = 0.0014). Lower brain stiffness also predicted worse quality of life and a higher likelihood of depression, controlling for all other factors. CONCLUSIONS: Brain stiffness is reduced in hydrocephalus patients compared to healthy controls, and is associated with clinically-relevant functional outcome measures. MRE may emerge as a clinically-relevant biomarker to assess the neuropathological effects of hydrocephalus and shunting, and may be useful in evaluating the effects of therapeutic alternatives, or as a supplement, of shunting.

Organ Culture and Grafting of Choroid Plexus into the Ventricular CSF of Normal and Hydrocephalic HTx Rats.

Choroid plexus (CP) may aid brain development and repair by secreting growth factors and neurotrophins for CSF streaming to ventricular and subventricular zones. Disrupted ventricular/subventricular zone progenitors and stem cells lead to CNS maldevelopment. Exploring models, we organ cultured the CP and transplanted fresh CP into a lateral ventricle of postnatal hydrocephalic (hyHTx) and nonhydrocephalic (nHTx) rats. After 60 days in vitro, the cultured choroid ependyma formed spherical rings with beating cilia. Cultured CP expressed endocytotic caveolin 1 and apical aquaporin 1 and absorbed horseradish peroxidase from medium. Transthyretin secretory protein was secreted by organ-cultured CP into medium throughout 60 days in vitro. Fresh CP, surviving at 1 week after lateral ventricle implantation of nHTx or hyHTx did not block CSF flow. Avascular 1-week transplants in vivo expressed caveolin 1, aquaporin 1, and transthyretin, indicating that grafted CP may secrete trophic proteins but not CSF. Our findings encourage further exploration on CP organ culture and grafting for translational strategies. Because transplanted CP, though not producing CSF, may secrete beneficial molecules for developing brain injured by hydrocephalus, we propose that upon CP removal in hydrocephalus surgery, the fractionated tissue could be transplanted back (ventricular autograft).

Efficacy of robotic versus open transversus abdominis release in a porcine model.

PURPOSE: Transversus abdominis muscle release (TAR) combines retromuscular mesh placement with posterior component separation and muscle release. TAR is usually an open technique for abdominal wall reconstruction; however, several centers have performed this operation robotically and claim better clinical outcomes when compared to open surgery. We sought to compare robotic versus open TAR utilizing a porcine model. METHODS: Animals were randomized to open versus robotic TAR with mesh placement, survived for 4 weeks, then underwent diagnostic laparoscopy to assess adhesive burden and adhesion tenacity. T-peel testing was utilized to assess mesh ingrowth. The primary outcome was adhesive burden; secondary outcomes included mesh incorporation, contraction, and operative time. RESULTS: Nine robotic and eight open TARs were performed. Mean operative time was significantly shorter for the open cases compared to robotic cases (88.6 ± 12.9 min versus 228.3 ± 46.2, p < 0.01). Operative time in the robotic arm of the study decreased over time, from 300 to 165 min. No difference was seen in the mean adhesion area between the two groups. Adhesion tenacity and mesh flatness were similar. The work required to peel the mesh off surrounding tissue was significantly higher in the open TAR than in the robotic TAR group: 52.6 ± 15.5 and 32.9 ± 10.6 mJ/cm2, respectively (p < 0.01). CONCLUSIONS: There were no differences in adhesions between the robotic and open approaches, but greater mesh contraction and ingrowth was observed in the open TAR group. Though operative time was longer in the robotic group, time dropped by about 40% from the first case to the last.

Next generation of ventricular catheters for hydrocephalus based on parametric designs.

BACKGROUND: The flow pattern of the cerebrospinal fluid is probably the most important factor related to obstruction of ventricular catheters during the normal treatment of hydrocephalus. To better comprehend the flow pattern, we have carried out a parametric study via numerical models of ventricular catheters. In previous studies, the flow was studied under steady and, recently, in pulsatile boundary conditions by means of computational fluid dynamics (CFD) in three-dimensional catheter models. OBJECTIVE: This study aimed to bring in prototype models of catheter CFD flow solutions as well to introduce the theory behind parametric development of ventricular catheters. METHODS: A preceding study allowed deriving basic principles which lead to designs with improved flow patterns of ventricular catheters. The parameters chosen were the number of drainage segments, the distances between them, the number and diameter of the holes on each segment, as well as their relative angular position. RESULTS: CFD results of previously unreleased models of ventricular catheter flow solutions are presented in this study. Parametric development guided new designs with better flow distribution while lowering the shear stress of the catheters holes. High-resolution 3D printed catheter solutions of three models and basic benchmark testing are introduced as well. CONCLUSIONS: The next generation of catheter with homogeneous flow patterns based on parametric designs may represent a step forward for the treatment of hydrocephalus, by possibly broadening their lifespan.

Protocol for an open-label, single-arm trial of HIV pre-exposure prophylaxis (PrEP) among people at high risk of HIV infection: the NSW Demonstration Project PRELUDE.

INTRODUCTION: Despite a number of HIV prevention strategies, the number of new HIV infections remains high. In Australia, over three-quarters of new HIV diagnoses are in gay and bisexual men (GBM). Pre-exposure prophylaxis (PrEP) has been shown to be effective at preventing new HIV infections in several randomised trials. The PRELUDE study aims to evaluate the implementation of PrEP in healthcare settings in New South Wales (NSW), Australia, among a sample of high-risk adults. METHODS AND ANALYSIS: PRELUDE is an ongoing open-label, single-arm demonstration project, conducted in public and private clinics across NSW, Australia. Enrolment began in November 2014. The study is designed for 300 high-risk participants-mainly GBM and heterosexual women. Participants receive daily oral PrEP, composed of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), for up to 2.5 years. Quarterly study visits include testing for HIV and sexually transmitted infections (STIs), assessment of ongoing eligibility and side effects, and self-reported adherence. Following each study visit, online behavioural surveys are administered to collect information on medication adherence, risk behaviours and attitudes. Blood samples will be collected in a subset of patients 1, 6 and 12 months after PrEP initiation to measure FTC/TDF concentrations. Analyses using longitudinal regression models will focus on feasibility, adherence, safety, tolerability and effects of PrEP on behaviour. This study will inform PrEP policy and guide the implementation of PrEP in Australia in people at high risk of HIV. ETHICS AND DISSEMINATION: The study will be conducted in accordance with the Declaration of Helsinki. All patients will provide written informed consent prior to participation in the study. Publications relating to each of the primary end points will be gradually released after 12 months of follow-up is complete. TRIAL REGISTRATION NUMBER: NCT02206555; Pre-results.

Raltegravir-emtricitabine-tenofovir as HIV nonoccupational post-exposure prophylaxis in men who have sex with men: safety, tolerability and adherence.

OBJECTIVES: Three-drug nonoccupational post-exposure prophylaxis (NPEP) typically includes co-formulated emtricitabine-tenofovir (FTC-TDF) and a protease inhibitor. However, protease inhibitors can cause significant toxicities, can interact with prescribed and illicit drugs, and work late in the viral cycle. Agents that act before viral integration into host DNA may have efficacy advantages. Raltegravir (RAL) is a good candidate for NPEP as it has few side effects or drug interactions and acts prior to HIV integration. The objective of this study was to investigate the use of RAL in 3-drug NPEP in terms of safety, adherence and tolerability. METHODS: We evaluated 28 days of RAL-FTC-TDF treatment in 86 men and FTC-TDF treatment in 34 men eligible for three- and two-drug NPEP, respectively. We assessed adherence (compared between groups and with nonstudy controls) and clinical and adverse events at weeks 1, 2 and 4, and efficacy at week 12. Analyses were by intention to treat, excluding from the adherence analysis subjects who ceased NPEP because their source was HIV-uninfected. RESULTS: No participant became infected with HIV. For RAL-FTC-TDF and FTC-TDF, regimen completion rates were 92% and 91% and medication adherence rates were 89% and 90%, respectively. Eight (9%) RAL recipients developed mild myalgias, with four developing transient grade 4 elevations in creatine kinase (two developed both), all of which improved to grade 2 or less by week 4 without RAL discontinuation. Eight prescribed and 37 potential illicit drug interactions with a protease inhibitor were avoided by use of RAL. CONCLUSIONS: RAL-FTC-TDF is well tolerated as NPEP, results in high levels of adherence and avoids potential drug-drug interactions. Patients and clinicians should be aware of the potential for acute muscle toxicity when RAL is used as NPEP.

Financial stress is associated with reduced treatment adherence in HIV-infected adults in a resource-rich setting.

OBJECTIVES: Financial stress has been identified as a barrier to antiretroviral adherence, but only in resource- limited settings. Almost half of HIV-infected Australian adults earn no regular income and, despite highly subsidised antiretroviral therapy and universal health care, 3% of HIV-infected Australians cease antiretroviral therapy each year. We studied the relationship between financial stress and treatment adherence in a resource-rich setting. METHODS: Out-patients attending the HIV clinic at St Vincent's Hospital between November 2010 and May 2011 were invited to complete an anonymous survey including questions relating to costs and adherence. RESULTS: Of 335 HIV-infected patients (95.8% male; mean age 52 years; hepatitis coinfection 9.2%), 65 patients (19.6%) stated that it was difficult or very difficult to meet pharmacy dispensing costs, 49 (14.6%) reported that they had delayed purchasing medication because of pharmacy costs, and 30 (9.0%) reported that they had ceased medication because of pharmacy costs. Of the 65 patients with difficulties meeting pharmacy costs, 19 (29.2%) had ceased medication vs. 11 (4.1%) of the remaining 270 patients (P < 0.0001). In addition, 19 patients (5.7%) also stated that it was difficult or very difficult to meet travel costs to the clinic. Treatment cessation and interruption were both independently associated with difficulty meeting both pharmacy and clinic travel costs. Only 4.9% had been asked if they were having difficulty paying for medication. CONCLUSIONS: These are the first data to show that pharmacy dispensing and clinic travel costs may affect treatment adherence in a resource-rich setting. Patients should be asked if financial stress is limiting their treatment adherence.

Novel proximal 14q deletion: clinical and diffusion tensor imaging tractography findings in a patient with lissencephaly, agenesis of the corpus callosum, and septo-optic dysplasia.

We report the unique CNS findings in a patient with a proximal chromosome 14q interstitial deletion. Conventional MR imaging allowed the clear delineation of agenesis of the corpus callosum, SOD, and diffuse lissencephaly. DTI tractography played a significant role in the evaluation of the proximal 14q deletion-associated abnormalities, delineating the extent of the dysmorphic connections of the Probst bundles and clarifying that apparent areas of heterotopias were the corticospinal tracts.

The effect of sodium fluoride on the stability of cyanide in postmortem blood samples from fire victims.

Assigning a level of significance to cyanide concentrations found in the blood of fire victims is often hampered by the fact that cyanide is inherently unstable in cadavers and in stored blood samples. A few researchers have proposed that sodium fluoride can be used to minimize the instability of cyanide in blood samples; however, controlled studies have not been performed to support validation of this hypothesis. To test the sodium fluoride hypothesis, both treated and control blood samples from 14 autopsied fire victims were tested over a 25-30 day period. A 2% concentration of sodium fluoride was added to the blood samples at the start of testing and the samples were refrigerated between testing intervals. Cyanide concentrations in the treated and control samples were measured between 9 and 11 days post treatment and between 25 and 30 days post treatment. A statistically significant difference was not present between blood cyanide concentrations in treated and control samples between 9 and 11 days. During this time period, although there were small statistically significant increases in both treated and untreated samples the fluctuations were minor. Since the treated and control samples did not exhibit instability between 9 and 11 days, it is not surprising that the sodium fluoride appeared to have no effect. However, a statistically significant difference between blood cyanide concentrations in treated and control samples was observed between 25 and 30 days. Those samples treated with sodium fluoride showed a reduction in blood cyanide variability with virtually no overall change, over a 25-30 day period when compared to control samples, while unconditioned samples showed a significant, average increase of 35%. Based on the findings of this study, it is recommended that 2% sodium fluoride be added to blood samples obtained from fire victims to reduce cyanide instability due to bacteriological activity.

Transmission of triple-class, drug-resistant HIV-1 in Australia.

We report the first two cases of transmitted triple-class, drug-resistant HIV-1 in Australia. Baseline testing of a newly diagnosed man showed four reverse transcriptase resistance mutations (affecting two drug classes) and six protease resistance mutations. A source patient was identified, and a likely second case newly infected 1 year later, suggesting sequential transmission. This raises therapeutic implications for the individual patients, as well as public health concerns.

Principles of antidote pharmacology: an update on prophylaxis, post-exposure treatment recommendations and research initiatives for biological agents.

The use of biological agents has generally been confined to military-led conflicts. However, there has been an increase in non-state-based terrorism, including the use of asymmetric warfare, such as biological agents in the past few decades. Thus, it is becoming increasingly important to consider strategies for preventing and preparing for attacks by insurgents, such as the development of pre- and post-exposure medical countermeasures. There are a wide range of prophylactics and treatments being investigated to combat the effects of biological agents. These include antibiotics (for both conventional and unconventional use), antibodies, anti-virals, immunomodulators, nucleic acids (analogues, antisense, ribozymes and DNAzymes), bacteriophage therapy and micro-encapsulation. While vaccines are commercially available for the prevention of anthrax, cholera, plague, Q fever and smallpox, there are no licensed vaccines available for use in the case of botulinum toxins, viral encephalitis, melioidosis or ricin. Antibiotics are still recommended as the mainstay treatment following exposure to anthrax, plague, Q fever and melioidosis. Anti-toxin therapy and anti-virals may be used in the case of botulinum toxins or smallpox respectively. However, supportive care is the only, or mainstay, post-exposure treatment for cholera, viral encephalitis and ricin - a recommendation that has not changed in decades. Indeed, with the difficulty that antibiotic resistance poses, the development and further evaluation of techniques and atypical pharmaceuticals are fundamental to the development of prophylaxis and post-exposure treatment options. The aim of this review is to present an update on prophylaxis and post-exposure treatment recommendations and research initiatives for biological agents in the open literature from 2007 to 2009.

Elevated CSF outflow resistance associated with impaired lymphatic CSF absorption in a rat model of kaolin-induced communicating hydrocephalus.

BACKGROUND: We recently reported a lymphatic cerebrospinal fluid (CSF) absorption deficit in a kaolin model of communicating hydrocephalus in rats with ventricular expansion correlating negatively with the magnitude of the impediment to lymphatic function. However, it is possible that CSF drainage was not significantly altered if absorption at other sites compensated for the lymphatic defect. The purpose of this study was to investigate the impact of the lymphatic absorption deficit on global CSF absorption (CSF outflow resistance). METHODS: Kaolin was injected into the basal cisterns of Sprague Dawley rats. The development of hydrocephalus was assessed using magnetic resonance imaging (MRI). In one group of animals at about 3 weeks after injection, the movement of intraventricularly injected iodinated human serum albumin (125I-HSA) into the olfactory turbinates provided an estimate of CSF transport through the cribriform plate into nasal lymphatics (n = 18). Control animals received saline in place of kaolin (n = 10). In a second group at about 3.5 weeks after kaolin injection, intraventricular pressure was measured continuously during infusion of saline into the spinal subarachnoid space at various flow rates (n = 9). CSF outflow resistance was calculated as the slope of the steady-state pressure versus flow rate. Control animals for this group either received no injections (intact: n = 11) or received saline in place of kaolin (n = 8). RESULTS: Compared to saline injected controls, lateral ventricular volume in the kaolin group was significantly greater (0.087 +/- 0.013 ml, n = 27 versus 0.015 +/- 0.001 ml, n = 17) and lymphatic function was significantly less (2.14 +/- 0.72% injected/g, n = 18 versus 6.38 +/- 0.60% injected/g, n = 10). Additionally, the CSF outflow resistance was significantly greater in the kaolin group (0.46 +/- 0.04 cm H2O microL(-1) min, n = 9) than in saline injected (0.28 +/- 0.03 cm H2O microL(-1) min, n = 8) or intact animals (0.18 +/- 0.03 cm H2O microL(-1) min, n = 11). There was a significant positive correlation between CSF outflow resistance and ventricular volume. CONCLUSIONS: The data suggest that the impediment to lymphatic CSF absorption in a kaolin-induced model of communicating hydrocephalus has a significant impact on global CSF absorption. A lymphatic CSF absorption deficit would appear to play some role (either direct or indirect) in the pathogenesis of ventriculomegaly.

Combined intravitreal anti-VEGF and verteporfin photodynamic therapy for juxtafoveal and extrafoveal choroidal neovascularization as an alternative to laser photocoagulation.

PURPOSE: To evaluate anti-VEGF and photodynamic therapy (PDT) for juxtafoveal and extrafoveal choroidal neovascularization (CNV) due to age-related macular degeneration (ARMD), ocular histoplasmosis syndrome (OHS), and degenerative myopia. METHODS: A total of 10 eyes with juxtafoveal or extrafoveal choroidal neovascularization underwent intravitreal anti-VEGF therapy combined with verteporfin PDT (689 nm). Most treatments consisted of PDT every 12 weeks and either ranibizumab 0.5 mg every 4 weeks or bevacizumab 1.25 mg every 6 weeks, initiated concurrently. Retreatment criteria were persistent exudative signs on optical coherence tomography or fluorescein angiography. RESULTS: Presenting visual acuity (VA) ranged from 20/20 to 20/60 (mean log MAR+/-SD, 0.338+/-0.16 (20/44 equivalent)). After a mean follow-up of 17.5 months, it ranged from 20/15 to 20/40 (mean log MAR+/-SD, 0.150+/-0.14 (20/28 equivalent); P=0.027, paired t-test). Six eyes improved by > or = 2 lines and four remained within 2 lines of initial VA. Non-ARMD eyes required much fewer treatments than ARMD eyes. All five non-ARMD eyes and three of five ARMD eyes showed no CNV activity at least 5 months after last treatment. CONCLUSIONS: Anti-VEGF therapy and PDT can preserve good visual function and may be suited to some cases of nonfoveal CNV. ARMD eyes require longer courses of treatment than non-ARMD eyes.

Reconstructing foveal pit morphology from optical coherence tomography imaging.

AIM: The aim of this study was to describe an automated method for extracting quantitative measures of foveal morphology from optical coherence tomography (OCT) images of the human retina. METHODS: We performed a methodological study and retrospective investigation of selected cases. Sixty-five human subjects were included: 61 healthy subjects and four female carriers of blue-cone monochromacy (BCM). Thickness data from B-scans traversing the foveal pit were fitted to a mathematical model designed to capture the contour of the foveal surface. From this model, various metrics of foveal morphology were extracted (pit depth, diameter and slope). RESULTS: Mathematical descriptions of foveal morphology enabled quantitative and objective evaluation of foveal dimensions from archived OCT data sets. We found a large variation in all aspects of the foveal pit (depth, diameter and slope). In myopes and BCM carriers, foveal pits were slightly less deep and had a more shallow slope, although these differences were not significant. CONCLUSIONS: Offline analysis of OCT data sets enables quantitative assessment of foveal morphology. The algorithm works on the Stratus and Cirrus macular thickness protocols, as well as the Spectralis and Bioptigen radial-line scan protocols, and can be objectively applied to existing data sets. These metrics will be useful in following changes associated with diseases such as retinopathy of prematurity and high myopia, as well as in studying normal postnatal development of the human fovea.

Ventricular dilation and elevated aqueductal pulsations in a new experimental model of communicating hydrocephalus.

In communicating hydrocephalus (CH), explanations for the symptoms and clear-cut effective treatments remain elusive. Pulsatile flow through the cerebral aqueduct is often significantly elevated, but a clear link between abnormal pulsations and ventriculomegaly has yet to be identified. We sought to demonstrate measurement of pulsatile aqueductal flow of CSF in the rat, and to characterize the temporal changes in CSF pulsations in a new model of CH. Hydrocephalus was induced by injection of kaolin into the basal cisterns of adult rats (n = 18). Ventricular volume and aqueductal pulsations were measured on a 9.4 T MRI over a one month period. Half of the animals developed ventricular dilation, with increased ventricular volume and pulsations as early as one day post-induction, and marked chronic elevations compared to intact controls (volume: 130.15 +/- 83.21 microl vs. 15.52 +/- 2.00 microl; pulsations: 114.51 nl +/- 106.29 vs. 0.72 +/- 0.13 nl). Similar to the clinical presentation, the relationship between ventricular size and pulsations was quite variable. However, the pulsation time-course revealed two distinct sub-types of hydrocephalic animals: those with markedly elevated pulsations which persisted over time, and those with mildly elevated pulsations which returned to near normal levels after one week. These groups were associated with severe and mild ventriculomegaly respectively. Thus, aqueductal flow can be measured in the rat using high-field MRI and basal cistern-induced CH is associated with an immediate change in CSF pulsatility. At the same time, our results highlight the complex nature of aqueductal pulsation and its relationship to ventricular dilation.

Cost-effectiveness of HIV nonoccupational post-exposure prophylaxis in Australia.

OBJECTIVE: The aim of the study was to determine the cost-effectiveness of HIV nonoccupational post-exposure prophylaxis (NPEP) in Australia. METHODS: A retrospective cost analysis of a population-based observational cohort of 1601 participants eligible for NPEP in Australia between 1998 and 2004 was carried out. We modelled NPEP treatment costs and combined them with effectiveness outcomes to calculate the cost per seroconversion avoided. We estimated the cost-utility of the programme, and sensitivity and threshold analysis was performed on key variables. RESULTS: The average NPEP cost per patient was A$1616, of which A$848 (52%) was for drugs, A$331 (21%) for consultations, A$225 (14%) for pathology and A$212 (13%) for other costs. The cost per seroconversion avoided in the cohort was A$1 647,476 in our base case analysis, and A$512,410 when transmission rates were set at their maximal values. The cost per quality-adjusted life-year (QALY) was between A$40,673 and A$176,772, depending on the risks of HIV transmission assumed. CONCLUSIONS: In our base case, NPEP was not a cost-effective intervention compared with the widely accepted Australian threshold of A$50,000 per QALY. It was only cost-effective after receptive unprotected anal intercourse exposure to an HIV-positive source. Although NPEP was a relatively well-targeted intervention in Australia, its cost-effectiveness could be improved by further targeting high-risk exposures.