Intussusception risk following oral monovalent rotavirus vaccination in 3 Asian countries: A self-control case series evaluation.

Rotavirus vaccines have substantially decreased rotavirus hospitalizations in countries where they have been implemented. In some high- and middle-income countries, a low-level of increased risk of intussusception, a type of acute bowel obstruction, has been detected following rotavirus vaccination. However, no increased risk of intussusception was found in India, South Africa, or a network of 7 other African countries. We assessed the association between a 2-dose monovalent rotavirus vaccine (Rotarix) and intussusception in 3 early-adopter low-income Asian countries -- Afghanistan, Myanmar, and Pakistan. Children <12 months of age admitted to a sentinel surveillance hospital with Brighton level 1 intussusception were eligible for enrollment. We collected information about each child's vaccination status and used the self-controlled case series method to calculate the relative incidence of intussusception 1-7 days, 8-21 days, and 1-21 days following each dose of vaccine and derived confidence intervals with bootstrapping. Of the 585 children meeting the analytic criteria, the median age at intussusception symptom onset was 24 weeks (IQR: 19-29). Overall, 494 (84 %) children received the first Rotarix dose and 398 (68 %) received the second dose. There was no increased intussusception risk during any of the risk periods following the first (1-7 days: 1.01 (95 %CI: 0.39, 2.60); 8-21 days: 1.37 (95 %CI: 0.81, 2.32); 1-21 days: 1.28 (95 %CI: 0.78, 2.11)) or second (1-7 days: 0.81 (95 %CI: 0.42, 1.54); 8-21 days: 0.77 (95 %CI: 0.53, 1.16); 1-21 days: 0.78 (95 %CI: 0.53, 1.16)) rotavirus vaccine dose. Our findings are consistent with other data showing no increased intussusception risk with rotavirus vaccination in low-income countries and add to the growing body of evidence demonstrating safety of rotavirus vaccines.

A novel bidirectional LSTM deep learning approach for COVID-19 forecasting.

COVID-19 has resulted in significant morbidity and mortality globally. We develop a model that uses data from thirty days before a fixed time point to forecast the daily number of new COVID-19 cases fourteen days later in the early stages of the pandemic. Various time-dependent factors including the number of daily confirmed cases, reproduction number, policy measures, mobility and flight numbers were collected. A deep-learning model using Bidirectional Long-Short Term Memory (Bi-LSTM) architecture was trained on data from 22nd Jan 2020 to 8 Jan 2021 to forecast the new daily number of COVID-19 cases 14 days in advance across 190 countries, from 9 to 31 Jan 2021. A second model with fewer variables but similar architecture was developed. Results were summarised by mean absolute error (MAE), root mean squared error (RMSE), mean absolute percentage error (MAPE), and total absolute percentage error and compared against results from a classical ARIMA model. Median MAE was 157 daily cases (IQR: 26-666) under the first model, and 150 (IQR: 26-716) under the second. Countries with more accurate forecasts had more daily cases and experienced more waves of COVID-19 infections. Among countries with over 10,000 cases over the prediction period, median total absolute percentage error was 33% (IQR: 18-59%) and 34% (IQR: 16-66%) for the first and second models respectively. Both models had comparable median total absolute percentage errors but lower maximum total absolute percentage errors as compared to the classical ARIMA model. A deep-learning approach using Bi-LSTM architecture and open-source data was validated on 190 countries to forecast the daily number of cases in the early stages of the COVID-19 outbreak. Fewer variables could potentially be used without impacting prediction accuracy.

Fabrication of polyvinyl pyrrolidone-K90/Eudragit RL100-based dissolving microneedle patches loaded with alpha-arbutin and resveratrol for skin depigmentation.

Alpha-arbutin (AA) and resveratrol (Res) are widely used in skin-lightening products. However, current topical formulations have minimal skin-lightening effects due to the low absorption and poor solubility of these active compounds. This study investigated the efficacy and safety of using dissolving microneedle (DMN) patches to improve the delivery of AA and Res for skin depigmentation. The DMN patches (F0-F3) fabricated from polyvinyl pyrrolidone-K90 (PVP-K90)/Eudragit RL100 blends successfully penetrated excised porcine skin and showed sufficient mechanical strength to resist compression forces. Loading DMNs with 10% AA and 2% Res at a ratio of 5 : 1 (F3) resulted in a synergistic interaction between the drugs with desirable dissolving ability, drug loading, and stability. Furthermore, both in vitro and in vivo studies revealed that the use of F3 DMN patches successfully enhanced the intradermal delivery of AA and Res over a 24 h period, with the delivered amount being higher (∼2.6 times) than that provided by a cream formulation (P < 0.05). After removing the DMN patches, the mice's skin was spontaneously and completely resealed within 12 h. In clinical studies, F3 DMN patches slightly decreased the melanin index of the participants without causing skin irritation or erythema at any time during the 24 h period when the patches were applied (P < 0.05). Moreover, application of the patches for 24 h was not found to affect skin hydration, transepidermal water loss, or skin elasticity. Therefore, AA/Res-loaded DMN patches could offer a promising approach for the effective local delivery of cosmetic agents for skin depigmentation.

Epidemiology of intussusception among children less than 2 years of age; findings from baseline surveillance before rotavirus vaccine introduction in Myanmar.

BACKGROUND: Rotavirus vaccine was planned to be introduced in the National Immunization Program of Myanmar in 2020. Reported potential association of a small increased risk of intussusception after rotavirus vaccination in some countries is a major safety concern and it is mandatory to collect baseline information before vaccine introduction. METHODS: Retrospective study reviewed medical records of intussusception cases for past 3 years (2015-2018) and prospective, active study was conducted from August 2018 to January 2020 at three tertiary children hospitals where pediatric surgical facility is present. Brighton Level 1 Criteria was used for confirmation of intussusception among children <2 years of age admitted to surgical wards. Demographic, clinical, diagnostic and treatment practices data were collected and descriptive data analysis was performed. RESULTS: A total of 697 (421 in retrospective and 276 in prospective) confirmed intussusception cases were identified. Majority of intussusception cases (550/697, 78.9%) were observed in the first year of life and most frequent between 5-7 months of age (292/697, 41.9%) with a peak at 6 months (114/697, 16.4%). The most common clinical presentations were vomiting and bloody diarrhea accounting 82.1% and 77.5% respectively. Regarding diagnosis and treatment, 458/697 (65.7%) required surgical intervention either manual reduction or intestinal resection and 34.4% by either air or barium enema. Overall mortality was 0.7% (5/697) and four out of five children died needed intestinal resection. Late arrival to hospital (>3days after onset) is significantly associated with requirement of surgery (61/85, 71.8%), which in turn is significantly associated with longer hospital stay (296/452, 65.5%) (p < 0.05). CONCLUSIONS: Intussusception occurrence is most frequent between 5-7 months age group which is old enough to be vaccinated under the schedule that has now been introduced in Myanmar. More than half of the cases were treated by surgery and late arrival to hospital enhances requirement of surgery and poor outcome. Findings of this baseline surveillance provide important facts for public health officials in balancing risks and benefits of rotavirus vaccine introduction, defining targeted age and dosage scheduling and facilitate monitoring system in post-vaccination.

Fabrication, characterization and comparison of α-arbutin loaded dissolving and hydrogel forming microneedles.

In this study, polyacrylic acid-co-maleic acid (PAMA) and polyvinyl alcohol (PVA) (1:4) were used to fabricate dissolving microneedles (DMNs) and hydrogel forming microneedles (HMNs) which incorporated α-arbutin. Αlpha-arbutin is commonly used as a skin lightening agent. However, it has poor penetration ability due to its hydrophilic properties. The purpose of this study was to compare the permeation of α-arbutin into the skin using DMNs and HMNs. Both types of microneedles (MNs) were sharp, strong with elegant appearance and approximately 100% penetrated the neonatal porcine skin. All needles of α-arbutin loaded DMNs were completely dissolved within 45 min, whereas maximum swelling of HMNs was observed at 4 h. In vitro permeation studies showed that α-arbutin loaded DMNs and HMNs provided significantly about 4.5 and 2.8 times, respectively, greater α-arbutin permeability than gel and commercial cream (P < 0.05). In vivo study also showed high intradermal delivery of α-arbutin levels using DMNs (5.33 µg/mL) and HMNs (1.47 µg/mL) when compared to that of commercial cream 0.15 µg/mL. Moreover, the micro-holes caused by applying MNs can reseal within 1 h. MNs were also stable at 25 °C for 3 months. The results suggested that DMNs and HMNs developed have a promising platform for transdermal delivery.

HPMC/PVP Dissolving Microneedles: a Promising Delivery Platform to Promote Trans-Epidermal Delivery of Alpha-Arbutin for Skin Lightening.

Alpha-arbutin is one of the most efficient skin lightener agents, which shows the effect on reducing the pigmentation by competitively inhibiting human tyrosinase. However, alpha-arbutin has difficulty in skin permeability due to its hydrophilic property. The objective of this study was, therefore, to develop alpha-arbutin-loaded dissolving microneedles (DMNs) for improving the delivery of alpha-arbutin into the skin. The DMN patch was prepared using Gantrez™ S-97, hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone K-90 (PVP), chitosan, and their combinations. The optimal 8% alpha-arbutin-loaded DMNs, aside from Gantrez™ S-97, was successfully formulated with combination of 8% w/w HPMC and 40% w/w PVP K-90 (HPMC/PVP) at the weight ratio of 1:1. Both DMNs had 100% of penetration into porcine skin. Over 12 h of skin permeation, the flux of Gantrez™ S-97 DMNs and the HPMC/PVP DMNs were 66.21 µg/cm2/h and 74.24 µg/cm2/h, respectively. The accumulation amount of alpha-arbutin in the skin from Gantrez™ S-97 DMNs and HPMC/PVP DMNs was 107.76 µg and 312.23 µg, respectively. In comparison to the gel formulations, Gantrez™ S-97 DMNs and HPMC/PVP DMNs increase the delivery of alpha-arbutin across the skin approximately 2 and 4.7 times, respectively. In vivo studies found that alpha-arbutin-loaded HPMC/PVP DMNs delivered more alpha-arbutin into the skin than commercial cream. Moreover, the skin can reseal naturally after removal of DMNs patch without any signs of infection and remain stable in accelerated conditions for 4 weeks. Accordingly, alpha-arbutin-loaded HPMC/PVP DMNs could be a promising delivery platform for promoting trans-epidermal delivery of alpha-arbutin for skin lightening.

Time series classification using a modified LSTM approach from accelerometer-based data: A comparative study for gait cycle detection.

BACKGROUND: Gait event detection (GED) is an important aspect in identifying and interpret a user's gait to assess gait abnormalities and design intelligent assistive devices. RESEARCH QUESTION: There is a need to develop robust GED models that can accurately detect various gait instances in different scenarios and environments. METHODS: This paper presents a novel method of detecting heel strikes (HS) and toe offs (TO) during the user's gait cycle using a modified Long Short-Term Memory (LSTM) networks approach. The method was tested on a database from Movement Analysis in Real-world Environments using Accelerometers (MAREA) (n = 20 healthy subjects) that consisted of walking and running in indoor and outdoor environments with accelerometers positioned on waist, wrist and both ankles. Modifications include oversampling, composite accelerations and optimizing the LSTM network architecture were made. RESULTS: Performance of our modified model was found to be better than six state-of-the-art GED algorithms, with a median F1 score of 0.98 for Heel Strikes and 0.98 for Toe Offs in the scenario of steady walking in an indoor environment, and a median F1 score of 0.94 for Heel Strikes and 0.68 for Toe-offs in the scenario of walking and running in an outdoor environment. SIGNIFICANCE: This paper highlights the potential of the single proposed model to be an alternative to the six GED models in gait detection under various conditions.