Care needs assessment of older adults with dementia in a semi-rural district in Vietnam: A community-based cross-sectional study.

BACKGROUND: The increasing needs of people living with dementia (PLWD) in Vietnam present an enormous public health challenge. Vietnam is an understudied country, and little is known regarding the overall unmet needs of caregivers or the demographic risk factors associated with unmet caregiving needs. This study aimed to determine the burden of unmet care needs of community-dwelling PLWD and identify sociodemographic risks associated with unmet care needs. METHODS: A cross-sectional study in a rural area facing urbanisation in Hanoi, Vietnam recruited PWLD-caregiver dyads with multistage sampling. We utilised the Camberwell Assessment of Need for the Elderly (CANE) instrument to evaluate care needs across four domains. Caregivers rated PLWD needs, with higher scores indicating greater unmet needs. The Mann-Whitney test was employed for comparing two groups, while the Kruskal-Wallis test was used for comparisons involving more than two groups in the analysis, and a P-value of less than 0.05 was considered statistically significant. RESULTS: Among 90 PLWD participating in the study, the overall mean care needs score was 11.6 ± 4.3, with only 16.2% of PLWD having their care needs met. Environmental and physical needs were more frequently met than psychological or social needs. Only 48.0% and 43.9% of environmental and physical needs were met respectively, and a meagre 20.9% and 23.6% for psychological and social needs. Unmet care needs were more frequent for PWLD who were female, single or divorced, had lower monthly household income, or who were in more advanced stages of dementia, as indicated by Clinical Dementia Rating scores ≥1. CONCLUSIONS: Unmet needs for PWLD are common. Increased caregiver education, resources, and services in Vietnam are urgently required to improve the quality of life for this population.

Elongated microparticles tuned for targeting hyaluronic acid delivery to specific skin strata.

OBJECTIVE: Microneedle or fractional laser applications are the most common topical delivery enhancement platforms. However, these methods of drug delivery are not skin strata specific. Drug delivery approaches which could target specific stratum of the skin remains a challenge. Elongated microparticles (EMPs) have been used in enhancing drug delivery into the skin. The aim of this study was to evaluate, for the first time, elongated silica microparticles with two different length profiles to enhance delivery of hyaluronic acid into different strata of human skin. METHODS: Two types of EMPs-long (milled EMPs) or short (etched EMPs) length ranges were characterized. A prototypical liquid formulation (Fluorescent hyaluronic acid) with and without EMP enhancement were evaluated for hyaluronic acid delivery in ex-vivo human skin. High performance liquid chromatography, Typhoon fluorescence scanning system, laser scanning confocal microscopy and reflectance confocal microscopy (RCM) were used to validate F-HA stability, visualize fluorescein in the skin, image the depth of F-HA delivery in the skin and define EMP penetration in skin strata, respectively. Statistical analysis was conducted using GraphPad Prism 6 software (GraphPad Software Inc, USA). RESULTS: Fluorescein-hyaluronic acid was stable and EMP enhanced skin penetration. RCM revealed that 'etched EMP' penetrated the skin to the stratum spinosum level. The vast majority (97.8%; p < 0.001) of the etched EMP did not penetrate completely through the viable epidermis and no obvious penetration into the dermis. In contrast, milled EMP showed 41-fold increase in penetration compared to the etched EMP but penetrated beyond the dermoepidermal junction. CONCLUSION: EMPs can enhance delivery of hyaluronic acid. Using EMPs with defined length distributions, which can be tuned for a specific stratum of the skin, can achieve targeted hyaluronic acid delivery.

OBJECTIF: Les microaiguilles ou le laser fractionné sont couramment utilisés pour augmenter l'absorption d'actif appliqué par voie topique. Toutefois, ces approches ne permettent de cibler une strate spécifique de la peau. Ainsi les méthodes permettant de cibler spécifiquement l'épiderme reste un défi. Les microparticules allongées (EMP) ont déjà été utilisé pour augmenter l'absorption cutanée. L'objectif de l'étude est d'évaluer pour la première fois, la capacité de microparticules allongées de silice (de deux longueurs différentes) à délivrer l'acide hyaluronique dans les différentes couches de la peau. MÉTHODES: Deux types d'EMP, longues (EMP broyé) ou courtes (EMP gravé), ont été caractérisées. Une formulation liquide contenant de l'acide hyaluronique marquée avec une sonde fluorescente (F-HA) a été évaluée avec et sans EMP sur peau humaine ex vivo. La chromatographie liquide haute performance, le scanner à fluorescence Typhoon, la microscopie laser confocal à balayage et la microscopie confocale par réflectance (RCM) ont été utilisées respectivement pour contrôler la stabilité de la F-HA, visualiser le signal de la fluorescéine dans la peau, imager l'absorption du F-HA dans la peau en fonction de la profondeur et caractériser la pénétration des EMP. Les analyses statistiques ont été réalisées avec le logiciel GraphPad Prims 6 (GraphPad Software Inc, USA). RÉSULTATS: L'acide hyaluronique marquée avec la fluorescéine est stable et les EMP permettent d'augmenter son absorption cutanée. Le RCM a montré que les EMP gravées pénètrent dans la peau jusqu'au niveau du stratum spinosum. La grande majorité des EMP gravés (97.8% ; p < 0,001) ne pénètre pas complétement dans l'épiderme viable et aucune pénétration mesurable dans le derme. Au contraire, les EMP broyées ont montrées une pénétration 41 fois plus importantes que les EMP gravées et peuvent aller au-delà de la jonction derme-épiderme. CONCLUSION: Les EMP peuvent augmenter l'absorption cutanée de l'acide hyaluronique. En utilisant des EMP de longueur définie et en ajustant celle-ci, il est même possible de cibler spécifiquement une strate cutanée.

Absorbent Microbiopsy Sampling and RNA Extraction for Minimally Invasive, Simultaneous Blood and Skin Analysis.

Conventional skin biopsy limits the clinical research that involves cosmetically sensitive areas or pediatric applications due to its invasiveness. Here, we describe the protocol for using an absorbent microneedle-based device, absorbent microbiopsy, for minimally invasive sampling of skin and blood mixture. Our goal is to help facilitate rapid progress in clinical research, the establishment of biomarkers for skin disease and reducing the risk for clinical research participants. In contrast to conventional skin biopsy techniques, the absorbent microbiopsy can be performed within seconds and does not require intensive training due to its simple design. In this report, we describe the use of absorbent microbiopsy, including loading and application, on a volunteer. Then, we show how to isolate RNA from the absorbed sample. Finally, we demonstrate the use of quantitative reverse transcription PCR (RT-qPCR) to quantify mRNA expression levels of both blood (CD3E and CD19) and skin (KRT14 and TYR). The methods that we describe utilize off the shelf kits and reagents. This protocol offers a minimally invasive approach for simultaneous sampling of skin and blood within the same absorbent microbiopsy matrix. We have found human ethics committees, clinicians and volunteers to be supportive of this approach to dermatological research.

Controlled delivery of the antiprotozoal agent (tinidazole) from intravaginal polymer matrices for treatment of the sexually transmitted infection, trichomoniasis.

Microporous polymeric matrices prepared from poly(ɛ-caprolactone) [PCL] were evaluated for controlled vaginal delivery of the antiprotozoal agent (tinidazole) in the treatment of the sexually transmitted infection, trichomoniasis. The matrices were produced by rapidly cooling co-solutions of PCL and tinidazole in acetone to -80 °C to induce crystallisation and hardening of the polymer. Tinidazole incorporation in the matrices increased from 1.4 to 3.9% (w/w), when the drug concentration in the starting PCL solution was raised from 10 to 20% (w/w), giving rise to drug loading efficiencies up to 20%. Rapid 'burst release' of 30% of the tinidazole content was recorded over 24 h when the PCL matrices were immersed in simulated vaginal fluid. Gradual drug release occurred over the next 6 days resulting in delivery of around 50% of the tinidazole load by day 7 with the released drug retaining antiprotozoal activity at levels almost 50% that of the 'non-formulated' drug in solution form. Basic modelling predicted that the concentration of tinidazole released into vaginal fluid in vivo from a PCL matrix in the form of an intravaginal ring would exceed the minimum inhibitory concentration against Trichomonas vaginalis. These findings recommend further investigation of PCL matrices as intravaginal devices for controlled delivery of antiprotozoal agents in the treatment and prevention of sexually transmitted infections.

Using elongated microparticles to enhance tailorable nanoemulsion delivery in excised human skin and volunteers.

This study demonstrates, for the first time, clinical testing of elongated silica microparticles (EMP) combined with tailorable nanoemulsions (TNE) to enhance topical delivery of hydrophobic drug surrogates. Likewise, this is the first report of 6-carboxyfluorescein (a model molecule for topically delivered hydrophobic drugs) AM1 & DAMP4 (novel short peptide surfactants) used in volunteers. The EMP penetrates through the epidermis and stop at the dermal-epidermal junction (DEJ). TNE are unusually stable and useful because the oil core allows high drug loading levels and the surface properties can be easily controlled. At first, we chose alginate as a crosslinking agent between EMP and TNE. We initially incorporated a fluorescent lipophilic dye, DiI, as a hydrophobic drug surrogate into TNE for visualization with microscopy. We compared four different coating approaches to combine EMP and TNE and tested these formulations in freshly excised human skin. The delivery profile characterisation was imaged by dye- free coherent anti-Stoke Raman scattering (CARS) microscopy to detect the core droplet of TNE that was packed with pharmaceutical grade lipid (glycerol) instead of DiI. These data show the EMP penetrating to the DEJ followed by controlled release of the TNE. Freeze-dried formulations with crosslinking resulted in a sustained release profile, whereas a freeze-dried formulation without crosslinking showed an immediate burst-type release profile. Finally, we tested the crosslinked TNE coated EMP formulation in volunteers using multiphoton microscopy (MPM) and fluorescence-lifetime imaging microscopy (FLIM) to document the penetration depth characteristics. These forms of microscopy have limitations in terms of image acquisition speed and imaging area coverage but can detect fluorescent drug delivery through the superficial skin in volunteers. 6-Carboxyfluorescein was selected as the fluorescent drug surrogate for the volunteer study based on the similarity of size, charge and hydrophobicity characteristics to small therapeutic drugs that are difficult to deliver through skin. The imaging data showed a 6-carboxyfluorescein signal deep in volunteer skin supporting the hypothesis that EMP can indeed enhance the delivery of TNE in human skin. There were no adverse events recorded at the time of the study or after the study, supporting the use of 6-carboxyfluorescein as a safe and detectable drug surrogate for topical drug research. In conclusion, dry formulations, with controllable release profiles can be obtained with TNE coated EMP that can effectively enhance hydrophobic payload delivery deep into the human epidermis.

Occurrence of antibiotic residues and antibiotic-resistant bacteria in effluents of pharmaceutical manufacturers and other sources around Hanoi, Vietnam.

Pharmaceutical manufacturers in Vietnam are producing a wide variety of antibiotics for human and veterinary use. Consequently, the water discharged from those facilities can contain residues of antibiotics, which could have adverse impact on the environment. However, studies on the occurrence of antibiotics in the wastewater from pharmaceutical manufacturers in Vietnam are almost non-existent. In this study, water samples were collected at around the outlets of four pharmaceutical manufacturing plants as well as from a hospital and an aquaculture farm around Hanoi in 2016 and 2017. Fifteen antibiotics from four major classes (ß-lactam, quinolones, macrolides, sulfonamides) were monitored, using a validated LC-MS/MS method, based on their number of registrations at the Ministry of Health. Ten antibiotics, ampicillin, cefuroxime, cefotaxime, clarithromycin, azithromycin, sulfamethoxazole, trimethoprim, ofloxacin, norfloxacin, and ciprofloxacin were detected in the samples at different concentrations. Notably, sulfonamides and quinolones were occasionally detected at very high concentration, such as sulfamethoxazole (252 µg/L), trimethoprim (107 µg/L), ofloxacin (85 µg/L), and ciprofloxacin (41 µg/L). In this study, concentrations of antibiotic residues in effluent of pharmaceutical plants were higher than those from other sources. The antibiotic-resistance tests indicated the widespread resistance to common antibiotics like quinolone and sulfonamides in the collected samples. This finding suggests that wastewater from pharmaceutical manufacturers could be an important source of antibiotics and antibiotic-resistant bacteria in the aquatic environment of Vietnam.

Antibiotics in the aquatic environment of Vietnam: Sources, concentrations, risk and control strategy.

The presence of antibiotics in the aquatic environment is a serious concern because it may lead to the emergence of antibiotic resistance, thus lowering the therapeutic effect of antibiotics. In Vietnam, the problem is aggravated by the irrational use of antibiotics in different sectors of agriculture and human health service. Moreover, the residues of antibiotics in the aquatic environment can be spread widely due to the lack of proper wastewater treatment systems. In this paper, we aim to comprehensively review all relevant sources that discharge antibiotics to the aquatic environment in Vietnam. Apart from the common source of antibiotics from aquaculture, other activities that release considerable amounts of antibiotics into water environment are also included. Environmental concentrations of antibiotics related to those sources are studied to demonstrate their contributions to the presence of antibiotics in the aquatic environment in Vietnam. As antibiotic-contained water may be used as water supply for irrigation and even human consumption in rural areas, the essence of wastewater treatment is highlighted. Finally, we also discuss the new National Action plan from the Ministry of Health for controlling the issue of antibiotic resistance in Vietnam.

The fractional laser-induced coagulation zone characterized over time by laser scanning confocal microscopy-A proof of concept study.

BACKGROUND: Ablative fractional laser (AFXL) is an acknowledged technique to increase uptake of topical agents in skin. Micro thermal ablation zones (MAZs) consist of ablated vertical channels surrounded by a coagulation zone (CZ). Laser scanning confocal microscopy (LSCM) images individual MAZs at 733 nm (reflectance confocal microscopy (RCM)). Further, LSCM can image sodium fluorescein (NaF) fluorescence with 488 nm excitation (fluorescence confocal microcopy (FCM)), a small hydrophilic test molecule (370 MW, log P -1.52), which may simulate uptake, bio-distribution and kinetics of small hydrophilic drugs. OBJECTIVES: To explore LSCM for combined investigations of CZ thickness and uptake, bio-distribution and kinetics of NaF in AFXL-exposed skin. STUDY DESIGNS/METHODS AND MATERIALS: Excised human abdominal skin samples were exposed to AFXL (15 mJ/microbeam, 2% density) and NaF gel (1000 µg/ml, 10 µl/cm2) in six repetitions, including untreated control samples. CZ thickness and spatiotemporal fluorescence intensities (FI) were quantified up to four hours after NaF application by RCM and FCM. Test sites were scanned to a depth of 200 µm, quantifying thickness of skin compartments (stratum corneum, epidermis, upper dermis), individual CZ thicknesses and FI in CZ and surrounding skin. RESULTS: RCM images established skin morphology to a depth of 200 µm. The CZ thickness measurements were feasible to a depth of 50 µm, and remained unchanged over time at 50 µm (P > 0.5). FI were detected to a depth of 160 µm and remained constant in CZ up to four hours after NaF application (15 minutes: 79 AU (73-92 AU), 60 minutes: 72 AU (58-82 AU), four hours: 78 AU (71-90 AU), P > 0.1). In surrounding skin, FI increased significantly over time, but remained lower than FI in CZ (15 minutes: 21 AU (17-22 AU), 60 minutes: 21 AU (19-26 AU), four hours: 42 (31- 48 AU), P = 0.03). AFXL-processed skin generated higher FI compared to non-laser processed skin in epidermis and upper dermis at 60 minutes and four hours (P = 0.03). CONCLUSIONS: By LSCM, assessment of the AFXL-induced CZ thickness was feasible to a depth of 50 µm, and assessment of FI from a small hydrophilic test molecule, NaF in CZ and surrounding skin feasible to a depth of 160 µm. Lasers Surg. Med. 50:70-77, 2018. © 2017 Wiley Periodicals, Inc.

Can wastewater-based epidemiology be used to evaluate the health impact of temperature? - An exploratory study in an Australian population.

Ambient temperature is known to have impact on population health but assessing its impact by the traditional cohort approach is resource intensive. Wastewater-based epidemiology (WBE) could be an alternative for the traditional approach. This study was to provide the first evaluation to see if WBE can be used to assess the impact of temperature exposure to a population in South East Queensland, Australia using selected pharmaceuticals and personal care products (PPCPs) as biomarkers. Daily loads of eight PPCPs in wastewater collected from a wastewater treatment plant were measured from February 2011 to June 2012. Corresponding daily weather data were obtained from the closest weather station. Missing data of PPCPs were handled using the multiple imputation (MI) method, then we used a one-way between-groups analysis of variance to examine the seasonal effect on daily variation of PPCPs by seasons. Finally, an MI estimate was performed to evaluate the continuous relationship between daily average temperature and each multiply-imputed PPCP using time-series regression analysis. The results indicated that an increase of 1°C in average temperature associated with decrease at 1.3g/d (95% CI: -2.2 to (-0.4), p<0.05) for atenolol, increase at 36.5g/d (95% CI: 25.2-47.8, p<0.01) for acesulfame, and increase at 0.8g/d (95% CI: 0.02-1.55, p=0.05) for naproxen. No significant association was observed between temperature and the remaining PPCPs, comprising: caffeine, carbamazepine, codeine, hydrochlorothiazide, and salicylic acid. The findings suggested that consumption of sweetened drinks, risk of worsening cardiovascular conditions and pains are associated with variation in ambient temperature. WBE can thus be used as a complementary method to traditional cohort studies in epidemiological evaluation of the association between environmental factors and health outcomes provided that specific biomarkers of such health outcomes can be identified.

Effective cutaneous vaccination using an inactivated chikungunya virus vaccine delivered by Foroderm.

Foroderm is a new cutaneous delivery technology that uses high-aspect ratio, cylindrical silica microparticles, that are massaged into the skin using a 3D-printed microtextured applicator, in order to deliver payloads across the epidermis. Herein we show that this technology is effective for delivery of a non-adjuvanted, inactivated, whole-virus chikungunya virus vaccine in mice, with minimal post-vaccination skin reactions. A single topical Foroderm-based vaccination induced T cell, Th1 cytokine and antibody responses, which provided complete protection against viraemia and disease after challenge with chikungunya virus. Foroderm vaccination was shown to deliver fluorescent, virus-sized beads across the epidermis, with beads subsequently detected in draining lymph nodes. Foroderm vaccination also stimulated the egress of MHC II(+) antigen presenting cells from the skin. Foroderm thus has potential as a simple, cheap, effective, generic, needle-free technology for topical delivery of vaccines.