Real-world evidence of improved healthcare utilization in patients with schizophrenia or schizoaffective disorder after early treatment of paliperidone palmitate once-monthly treatment in Hong Kong.

BACKGROUND: Very few data are available to demonstrate the economic benefit of early paliperidone palmitate once-monthly long-acting injectable (PP1M) treatment in patients with schizophrenia or schizoaffective disorder. METHODS AND MATERIALS: This study has retrospectively compared the healthcare utilization and associated costs of pre- and post-PPIM treatment in 413 patients with schizophrenia or schizoaffective disorder recruited from three major public hospitals providing psychiatric services in Hong Kong. Patients were categorized into early treatment (≤3 years since diagnosis) and chronic (>3 years) groups, and also whether they were receiving polypharmacy (POP). RESULTS: It was found that patients who were started on early therapy with no POP had the most favourable outcomes. Overall results of the entire cohort, including both early and late treatments, indicate that there was a slight increase in annual in-patient days (IP) per patient and outpatient visit (OP) by 3.18 and 1.87, respectively, and a decrease in emergency room visit (ER) of 0.9 (p < 0.05). For non-polypharmacy (NP) patients receiving early PP1M therapy, there was a significant decrease in IP and ER of 21.56 (p < 0.05) and 1.15 (p < 0.05), respectively, but an increase in OP of 1.88 (p < 0.05). For patients with POP, there was an all-across increase in IP and all-across decrease in OP and ER. In monetary terms, a NP patient receiving early therapy may have an overall saving of HKD40,878 (USD5,241, 1USD = 7.8HKD) per year compared to HKD6,224 (USD798) in patients where therapy was given after 3 years. For patients with POP, there was an all-across increase in overall spending despite reductions in OP and ER. CONCLUSIONS: From the 413 patients studied, potential annual savings is higher by early administration of PPIM in patients with NP. Analysis using multivariate linear regression based on generalized estimating equations and sensitivity analysis using a linear mixed model supported the findings.

Interdisciplinary pharmacometrics linking oseltamivir pharmacology, influenza epidemiology and health economics to inform antiviral use in pandemics.

AIMS: A modular interdisciplinary platform was developed to investigate the economic impact of oseltamivir treatment by dosage regimen under simulated influenza pandemic scenarios. METHODS: The pharmacology module consisted of a pharmacokinetic distribution of oseltamivir carboxylate daily area under the concentration-time curve at steady state (simulated for 75 mg and 150 mg twice daily regimens for 5 days) and a pharmacodynamic distribution of viral shedding duration obtained from phase II influenza inoculation data. The epidemiological module comprised a susceptible, exposed, infected, recovered (SEIR) model to which drug effect on the basic reproductive number (R0 ), a measure of transmissibility, was linked by reduction of viral shedding duration. The number of infected patients per population of 100 000 susceptible individuals was simulated for a series of pandemic scenarios, varying oseltamivir dose, R0 (1.9 vs. 2.7), and drug uptake (25%, 50%, and 80%). The number of infected patients for each scenario was entered into the health economics module, a decision analytic model populated with branch probabilities, disease utility, costs of hospitalized patients developing complications, and case-fatality rates. Change in quality-adjusted life years was determined relative to base case. RESULTS: Oseltamivir 75 mg relative to no treatment reduced the median number of infected patients, increased change in quality-adjusted life years by deaths averted, and was cost-saving under all scenarios; 150 mg relative to 75 mg was not cost effective in low transmissibility scenarios but was cost saving in high transmissibility scenarios. CONCLUSION: This methodological study demonstrates proof of concept that the disciplines of pharmacology, disease epidemiology and health economics can be linked in a single quantitative framework.

Chemical-assisted femtosecond laser writing of lab-in-fibers.

The lab-on-chip (LOC) platform has presented a powerful opportunity to improve functionalization, parallelization, and miniaturization on planar or multilevel geometries that has not been possible with fiber optic technology. A migration of such LOC devices into the optical fiber platform would therefore open the revolutionary prospect of creating novel lab-in-fiber (LIF) systems on the basis of an efficient optical transport highway for multifunctional sensing. For the LIF, the core optical waveguide inherently offers a facile means to interconnect numerous types of sensing elements along the optical fiber, presenting a radical opportunity for optimizing the packaging and densification of diverse components in convenient geometries beyond that available with conventional LOCs. In this paper, three-dimensional patterning inside the optical fiber by femtosecond laser writing, together with selective chemical etching, is presented as a powerful tool to form refractive index structures such as optical waveguides and gratings as well as to open buried microfluidic channels and optical resonators inside the flexible and robust glass fiber. In this approach, optically smooth surfaces (~12 nm rms) are introduced for the first time inside the fiber cladding that precisely conform to planar nanograting structures when formed by aberration-free focusing with an oil-immersion lens across the cylindrical fiber wall. This process has enabled optofluidic components to be precisely embedded within the fiber to be probed by either the single-mode fiber core waveguide or the laser-formed optical circuits. We establish cladding waveguides, X-couplers, fiber Bragg gratings, microholes, mirrors, optofluidic resonators, and microfluidic reservoirs that define the building blocks for facile interconnection of inline core-waveguide devices with cladding optofluidics. With these components, more advanced, integrated, and multiplexed fiber microsystems are presented demonstrating fluorescence detection, Fabry-Perot interferometric refractometry, and simultaneous sensing of refractive index, temperature, and bending strain. The flexible writing technique and multiplexed sensors described here open powerful prospects to migrate the benefits of LOCs into a more flexible and miniature LIF platform for highly functional and distributed sensing capabilities. The waveguide backbone of the LIF inherently provides an efficient exchange of information, combining sensing data that are attractive in telecom networks, smart catheters for medical procedures, compact sensors for security and defense, shape sensors, and low-cost health care products.

Histogram flow mapping with optical coherence tomography for in vivo skin angiography of hereditary hemorrhagic telangiectasia.

Speckle statistics of flowing scatterers have been well documented in the literature. Speckle variance optical coherence tomography exploits the large variance values of intensity changes in time caused mainly by the random backscattering of light resulting from translational activity of red blood cells to map out the microvascular networks. A method to map out the microvasculature malformation of skin based on the time-domain histograms of individual pixels is presented with results obtained from both normal skin and skin containing vascular malformation. Results demonstrated that this method can potentially map out deeper blood vessels and enhance the visualization of microvasculature in low signal regions, while being resistant against motion (e.g., patient tremor or internal reflex movements). The overall results are manifested as more uniform en face projection maps of microvessels. Potential applications include clinical imaging of skin vascular abnormalities and wide-field skin angiography for the study of complex vascular networks.

Temperature-compensated fiber-optic 3D shape sensor based on femtosecond laser direct-written Bragg grating waveguides.

Temperature-compensated 3D fiber shape sensing is demonstrated with femtosecond laser direct-written optical and Bragg grating waveguides that were distributed axially and radially inside a single coreless optical fiber. Efficient light coupling between the laser-written optical circuit elements and a standard single-mode fiber (SMF) was obtained for the first time by 3D laser writing of a 1 × 3 directional coupler to meet with the core waveguide in the fusion-spliced SMF. Simultaneous interrogation of nine Bragg gratings, distributed along three laterally offset waveguides, is presented through a single waveguide port at 1 kHz sampling rate to follow the Bragg wavelength shifts in real-time and thereby infer shape and temperature profile unambiguously along the fiber length. This distributed 3D strain and thermal sensor is freestanding, flexible, compact, lightweight and opens new directions for creating fiber cladding photonic devices for a wide range of applications from shape and thermal sensing to guidance of biomedical catheters and tools in minimally invasive surgery.

The Health Economic Impact of Universal Infant Vaccination with the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine as Compared with 13-Valent Pneumococcal Conjugate Vaccine in Hong Kong.

BACKGROUND: Pneumococcal universal vaccination in Hong Kong was introduced in 2009. OBJECTIVES: We assessed the health and economic impact of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PCV-10) compared with the current 13-valent pneumococcal conjugate vaccine (PCV-13) recommended for Hong Kong in 2011, providing new elements to be considered by public health authorities in the future decision-making process for pneumococcal vaccines in this country. METHODS: An analytical model was used to estimate the annual economic and health outcomes of invasive pneumococcal disease (IPD), community-acquired pneumonia, and acute otitis media (AOM), including nontypeable H. influenzae-related AOM, for a birth cohort in Hong Kong from the payer perspective with a 10-year horizon. Clinical impact including morbidity-mortality, quality-adjusted life-years (QALYs), incremental costs, and cost-effectiveness comparing PCV-10 and PCV-13 were estimated. Probabilistic sensitivity analyses by using alternate scenarios were performed. RESULTS: Model projections indicate that PCV-13 and PCV-10 have approximately equivalent impact on the prevention of deaths caused by IPD and pneumonia. PCV-13 is projected to prevent 6 additional cases of IPD, whereas PCV-10 is projected to prevent 13,229 additional AOM cases and 101 additional QALYs. For the base case, PCV-10 vaccination is estimated to save 44.6 million Hong Kong dollars (34.1 million Hong Kong dollars discounted). Sensitivity analysis indicated that PCV-10 would generate more QALYs and save costs as compared with PCV-13. CONCLUSIONS: Universal infant vaccination with new available pneumococcal vaccines is expected to generate a significant additional impact on reducing the burden of pneumococcal diseases in Hong Kong. PCV-10 vaccination would be potentially a cost-saving strategy compared with PCV-13 vaccination, generating better cost offsets and higher QALY gains.

In vivo feasibility of endovascular Doppler optical coherence tomography.

Feasibility of detecting intravascular flow using a catheter based endovascular optical coherence tomography (OCT) system is demonstrated in a porcine carotid model in vivo. The effects of A-line density, radial distance, signal-to-noise ratio, non-uniform rotational distortion (NURD), phase stability of the swept wavelength laser and interferometer system on Doppler shift detection limit were investigated in stationary and flow phantoms. Techniques for NURD induced phase shift artifact removal were developed by tracking the catheter sheath. Detection of high flow velocity (~51 cm/s) present in the porcine carotid artery was obtained by phase unwrapping techniques and compared to numerical simulation, taking into consideration flow profile distortion by the eccentrically positioned imaging catheter. Using diluted blood in saline mixture as clearing agent, simultaneous Doppler OCT imaging of intravascular flow and structural OCT imaging of the carotid artery wall was feasible. To our knowledge, this is the first in vivo demonstration of Doppler imaging and absolute measurement of intravascular flow using a rotating fiber catheter in carotid artery.

Combined antibiotic/corticosteroid cream in the empirical treatment of moderate to severe eczema: friend or foe?

BACKGROUND: Eczema is a common atopic disease associated with pruritus, sleep disturbance, and impaired quality of life. Staphylococcus aureus colonization/infection is important in its pathophysiology. AIM: To evaluate the prevalence of S aureus colonization/infection and the efficacy and acceptability of a combined antibiotic/corticosteroid cream in the empirical treatment of eczema. METHODS: Consecutive patients with moderate to severe eczema were recruited. Swab and cultures from the right antecubital fossa and the worst eczematous area, disease severity (SCORAD) and quality of life (Children's Dermatology Life Quality Index, CDLQI), skin hydration (SH), and transepidermal water loss (TEWL) were obtained prior to and following a two week twice-daily course of treatment with a fucidin/corticosteroid cream. General acceptability of treatment (GAT) was documented at completion. RESULTS: Thirty-five patients (63% males; mean age 13.5, standard deviation 3.6 years; with 21 moderate and 14 severe disease) were recruited. At start, S aureus was isolated from the right antecubital fossa and the worst affected areas in 66% and 71% of these patients, respectively. At completion, S aureus was isolated in 23% and 40% at the antecubital fossae and worst affected areas (P=0.001 and P=0.003, respectively). No methicillin-resistant S aureus was isolated in this series, but the percentage of fucidin-resistant S aureus increased from 8% to 58% (P<0.001). Disease severity and quality of life were significantly improved (pre-Objective SCORAD and post-Objective SCORAD were 38.4±13.7 and 29.7±14.2, P<0.001; pre-CDLQI and post-CDLQI were 9.4±5.2 and 7.1±4.8, P<0.001). At the right antecubital fossa, skin hydration improved from 30.8±14.2 to 36.7±15.2 (P=0.015); and TEWL from 10.7±2.3 to 9.4±2.2 (P<0.001). Eighty percent of patients found the treatment good or very good, and only one (3%) patient found it unacceptable. CONCLUSIONS: The most prevalent organism in moderate to severe eczema was S aureus. Usage of the combined fucidin/corticosteroid cream is convenient and associated with a reduction in disease severity, improvement in quality of life, SH, and TEWL, but caution has to be taken with emergence of fucidin-resistant S aureus.

Real-time speckle variance swept-source optical coherence tomography using a graphics processing unit.

Advances in swept source laser technology continues to increase the imaging speed of swept-source optical coherence tomography (SS-OCT) systems. These fast imaging speeds are ideal for microvascular detection schemes, such as speckle variance (SV), where interframe motion can cause severe imaging artifacts and loss of vascular contrast. However, full utilization of the laser scan speed has been hindered by the computationally intensive signal processing required by SS-OCT and SV calculations. Using a commercial graphics processing unit that has been optimized for parallel data processing, we report a complete high-speed SS-OCT platform capable of real-time data acquisition, processing, display, and saving at 108,000 lines per second. Subpixel image registration of structural images was performed in real-time prior to SV calculations in order to reduce decorrelation from stationary structures induced by the bulk tissue motion. The viability of the system was successfully demonstrated in a high bulk tissue motion scenario of human fingernail root imaging where SV images (512 × 512 pixels, n = 4) were displayed at 54 frames per second.

Intraoperative handheld optical coherence tomography forward-viewing probe: physical performance and preliminary animal imaging.

A prototype intraoperative hand-held optical coherence tomography (OCT) imaging probe was developed to provide micron resolution cross-sectional images of subsurface tissue during open surgery. This new ergonomic probe was designed based on electrostatically driven optical fibers, and packaged into a catheter probe in the form factor of clinically accepted Bayonet shaped neurosurgical probes. Optical properties of the probe were measured to have a ~20 µm spot size, 5 mm working distance and 4 mm field of view. Feasibility of this probe for structural and Doppler shift imaging was tested on porcine femoral blood vessel imaging.

Speckle variance optical coherence tomography of the rodent spinal cord: in vivo feasibility.

Optical coherence tomography (OCT) has the combined advantage of high temporal (µsec) and spatial (<10µm) resolution. These features make it an attractive tool to study the dynamic relationship between neural activity and the surrounding blood vessels in the spinal cord, a topic that is poorly understood. Here we present work that aims to optimize an in vivo OCT imaging model of the rodent spinal cord. In this study we image the microvascular networks of both rats and mice using speckle variance OCT. This is the first report of depth resolved imaging of the in vivo spinal cord using an entirely endogenous contrast mechanism.

Endovascular optical coherence tomography intensity kurtosis: visualization of vasa vasorum in porcine carotid artery.

Application of speckle variance optical coherence tomography (OCT) to endovascular imaging faces difficulty of extensive motion artifacts inherently associated with arterial pulsations in addition to other physiological movements. In this study, we employed a technique involving a fourth order statistical method, kurtosis, operating on the endovascular OCT intensity images to visualize the vasa vasorum of carotid artery in vivo and identify its flow dynamic in a porcine model. The intensity kurtosis technique can distinguish vasa vasorum from the surrounding tissues in the presence of extensive time varying noises and dynamic motions of the arterial wall. Imaging of vasa vasorum and its proliferation, may compliment the growing knowledge of structural endovascular OCT in assessment and treatment of atherosclerosis in coronary and carotid arteries.

Microstructuring of polypyrrole by maskless direct femtosecond laser ablation.

Ultrafast laser micromachining was optimized for microstructuring polypyrrole as a facile new approach towards tailoring electrochemical and mechanical responses desirable for microactuator, sensors, neural probing, and nerve conduit applications. Laser perforation of high-density and high aspect ratio through-holes generated greater than 5-fold increase in surface area. The flexible machining technique offers micron-size resolution and fast prototyping capability for optimizing properties and opening new directions for polypyrrole-based devices.