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The aim of the current study was to develop membrane-based transdermal patches of lornoxicam gel using oleic acid (OA)and propylene glycol (PG) as penetration enhancers to improve drug delivery across the skin and to evaluate in vivo analgesic and anti-inflammatory activity. For this purpose, nine formulations were developed in accordance with 32 factorial design using Design Expert® 11. The concentration of propylene glycol (X1) and oleic acid (X2) were selected as independent variable whereas Q10 (Y1), flux (Y2) and lag time (Y3) were considered as the response variables. The impact of drug loading, surface area, gel concentration, membrane variation and agitation speed on drug release and permeation was also studied. The skin sensitivity reaction, analgesic activity and anti-inflammatory action of the optimized patch were also determined in Albino Wistar rats. Stability studies were performed for three months at three different temperature conditions. The result suggests that a membrane-based system with controlled zero-order drug release of 95.8 ± 1.121% for 10 h exhibiting flux of 126.51±1.19 μg/cm2/h and lag time of 0.908 ±0.57h was optimized with the desired analgesic and anti-inflammatory effect can be obtained by using propylene glycol and oleic acid co-solvents as a penetration enhancer. The patch was also found stable at 4˚C for a period of 6.44 months. Formulation F9 comprising of 10% PG and 3% OA was selected as an optimized formulation. The study demonstrates that the fabricated transdermal system of lornoxicam can deliver the drug through the skin in a controlled manner with desired analgesic and anti-inflammatory activity and can be considered as a suitable alternative of the oral route.

The study is based on applying Artificial Neural Network (ANN) based machine learning and Response Surface Methodology (RSM) as simultaneous bivariate approaches in developing controlled-release rivaroxaban (RVX) osmotic tablets. The influence of different types of polyethylene oxide, osmotic agents, coating membrane thickness, and orifice diameter on RVX release profiles was investigated. After obtaining the trial formulation data sets from Central Composite Design (CCD), an ANN-based model was trained to get the optimized formulations. The Physiological-based Pharmacokinetic (PBPK) modeling of the predicted formulation was performed by GastroPlus™ to simulate in vivo plasma profiles under fasting and fed conditions. In vitro release tests showed zero-order RVX release for up to 12 h. Using graphical and numerical methods, the predicted formulation generated by the prediction profiler was cross-validated by the CCD-based optimized formulation. Analysis of Variance (ANOVA) findings revealed no significant difference between the predicted and optimized formulations and these formulations have a shelf life of 22.47 and 17.87 months, respectively. The PBPK modeling of RVX push-pull osmotic pump (PPOP) tablets suggested enhanced bioavailability in the fasted (up to 82%) and fed (up to 98.5%) state compared to immediate-release tablets. The results indicated that ANN can be effectively used for osmotic systems due to their complex nature and nonlinear interactions between dependent and independent variables.

Metoclopramide is an antiemetic agent prescribed for motion sickness, cancer chemotherapy, and pregnancy. The present work aimed to design a metoclopramide-loaded halloysite nanotubes (HNTs) drug-in-adhesive transdermal drug delivery system. Four formulations F1, F2, and F3 with different ratios of HNTs to metoclopramide and a F4 without HNTs were developed using acrylic adhesive DURO-TAK 387–2510 by the solvent casting method. These formulated patches were thoroughly evaluated and in-vitro release and permeation studies were performed. The optimized formulation was analyzed using skin irritation, SEM, DSC, and FTIR studies. The GASTROPLUS TCAT model was used to predict the in-vivo performance. HNT-based formulations exhibited controlled drug release, achieving approximately 60% in 4 h, compared to over 80% release in the same period from the formulation without HNT. The optimized formulation (F3) demonstrated a lag time of 1.802 h with a flux of 0.103 mg/cm 2 /hr. The shelf life was 19.279 months at 5 ± 3 °C. The C max , T max , AUC t , and AUC inf were predicted as 40.84 ng/mL, 6.32 h, 561.51 ng/mL×h and 599.61 ng/mL×h for a 30 mg patch. The study demonstrated that metoclopramide can be effectively loaded into HNTs and proved safe and effective in drug-in-adhesive type transdermal systems using HNTs as a drug carrier.

Clozapine is a potent serotonin receptor antagonist and commonly used for the treatment of Schizophrenia. The study aimed to develop and optimize the transdermal matrix patch of clozapine. A 3-level, 3-factor Central Composite Design was applied to examine and validate the impact of various formulation variables, Eudragit, PEG, and oleic acid on in vitro drug release, flux, and tensile strength (TS). Different formulation characteristics were studied in terms of physico-chemical characterization, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), drug release performance, and in vitro permeability. The numerical and graphical optimization was based on the desirability function and the optimized formulation obtained from the polynomial equation was further validated and evaluated for the targeted critical attributes. The optimized patch was further evaluated for skin irritation, in vivo pharmacodynamics, in silico prediction, and simulation using the GastroPlus TCAT® model and stability. The experimental results of the optimized formulation, such as tensile strength 1.220 kg/cm 2 , flux 147.376 μg/cm 2 /h and Q24 94.874%, showed similarity with the values predicted by numerical and graphical optimization. In vivo Neuro-pharmacological studies showed that the results were comparable to the standard. The C max , T max , AUC t, and AUC inf were predicted as 38.396 ng/mL, 28.960 h, 1625.500 ng-h/mL, and 1175.700 ng-h/mL for a 50 mg patch. No skin irritation was found for the optimized transdermal patch as per the Draize score method. The shelf life of the optimized formulation was 30.41 months under accelerated conditions. The study showed that the matrix-type transdermal patch of clozapine can be used for the management of schizophrenia in terms of improved patient compliance.

A taste-masked chewable tablet of ciprofloxacin using ion exchange resin Kyron T-134 for enhancing compliance for the paediatric population was developed. The drug-to-resin ratio was optimized for maximum taste masking by studying the effects of soaking time (X1) and mixing time (X2) on complexation (%) using Central Composite Rotatable Design (CCRD). The resin complexes were characterized by bitterness score, DSC, FTIR, and PXRD. The complex was further formulated and optimized into chewable tablets through full factorial design, The optimized formulation was subjected to a bioequivalence study, and a virtual approach of PBPK modelling was adapted to predict the pharmacokinetics of the drug in the paediatric group. The drug resin ratio of 1:1.5 yielded an optimum drug loading of 99.05%. The optimized formulation shows minimum disintegration time with more than 99% drug release within 30 min. The formulation F-9 was found to be bioequivalent with a geometric mean ratio of C max , T max , AUC 0–t , and AUC 0–∞ within 90% CI. It was concluded that quality by design approach can successfully be applied to optimize the drug resin ratio and PBPK modeling is a successful predictive tool for estimating the pharmacokinetics of ciprofloxacin HCl in the paediatric population.

Monkeypox, a viral disease caused by the monkeypox virus is well known for its characteristic rash with macular, papular, and vesicular stages. Although the skin is one of the most affected organs by monkeypox, the virus can also impact the respiratory, ophthalmologic, genitourinary, and gastrointestinal systems, among others. It is extremely common for the disease to begin with flu-like symptoms in the prodromal phase before cutaneous manifestations emerge. Here, we describe a unique case of monkeypox infection in which a patient first presented with periorbital cellulitis before any characteristic skin findings appeared. The source of the infection was unknown and the patient recovered without any complications to date. This odd presentation of monkeypox reiterates the need for a detailed evaluation of patients with a similar presentation.

Older adults aged 65 years and above have a disproportionately higher utilization of emergency healthcare, of which Emergency Department (ED) visits are a key component. They experience higher degree of multimorbidity and mobility issues compared to younger patients, and are consequently more likely to experience a health event which requires an ED visit. During their visit, older adults tend to require more extensive workup, therefore spending a greater amount of time in the ED. Compared to the younger population, older adults are more susceptible to adverse events following discharge. Considering these factors, investigating the determinants of ED utilisation would be valuable. In this paper, we present a protocol for a systematic review of the determinants of ED utilisation among communitydwelling older adults aged 65 years and above, applying Andersen and Newman's model of healthcare utilisation. Furthermore, we aim to present other conceptual frameworks for healthcare utilisation and propose a holistic approach for understanding the determinants of ED utilisation by older persons. The protocol is developed in accordance with the standards of Campbell Collaboration guidelines for systematic reviews, with reference to the Cochrane Handbook for Systematic Review of Interventions. Medline, Embase and Scopus will be searched for studies published from 2000 to 2020. Studies evaluating more than one determinant for ED utilisation among older adults aged 65 years and above will be included. Search process and selection of studies will be presented in a PRISMA flow chart. Statistically significant (p < 0.05) determinants of ED utilisation will be grouped according to individual and societal determinants. Quality of the studies will be assessed using Newcastle Ottawa Scale (NOS). In Andersen and Newman's model, individual determinants include predisposing factors, enabling and illness factors, and societal determinants include technology and social norms. Additional conceptual frameworks for healthcare utilisation include Health Belief Model, Social Determinants of Health and Big Five personality traits. By incorporating the concepts of these models, we hope to develop a holistic approach of conceptualizing the factors that influence ED utilisation among older people. This protocol is registered on 8 May 2021 with PROSPERO's International Prospective Register of Systematic Reviews (CRD42021253770).

BackgroundWhile much progress was made throughout the Millennium Development Goals era in reducing maternal and neonatal mortality, both remain unacceptably high, especially in areas affected by humanitarian crises. While valuable guidance on interventions to improve maternal and neonatal health in both non-crisis and crisis settings exists, guidance on how best to deliver these interventions in crisis settings, and especially in conflict settings, is still limited. This systematic review aimed to synthesise the available literature on the delivery on maternal and neonatal health interventions in conflict settings.MethodsWe searched MEDLINE, Embase, CINAHL and PsycINFO databases using terms related to conflict, women and children, and maternal and neonatal health. We searched websites of 10 humanitarian organisations for relevant grey literature. Publications reporting on conflict-affected populations in low-income and middle-income countries and describing a maternal or neonatal health intervention delivered during or within 5 years after the end of a conflict were included. Information on population, intervention, and delivery characteristics were extracted and narratively synthesised. Quantitative data on intervention coverage and effectiveness were tabulated but no meta-analysis was undertaken.Results115 publications met our eligibility criteria. Intervention delivery was most frequently reported in the sub-Saharan Africa region, and most publications focused on displaced populations based in camps. Reported maternal interventions targeted antenatal, obstetric and postnatal care; neonatal interventions focused mostly on essential newborn care. Most interventions were delivered in hospitals and clinics, by doctors and nurses, and were mostly delivered through non-governmental organisations or the existing healthcare system. Delivery barriers included insecurity, lack of resources and lack of skilled health staff. Multi-stakeholder collaboration, the introduction of new technology or systems innovations, and staff training were delivery facilitators. Reporting of intervention coverage or effectiveness data was limited.DiscussionThe relevant existing literature focuses mostly on maternal health especially around the antenatal period. There is still limited literature on postnatal care in conflict settings and even less on newborn care. In crisis settings, as much as in non-crisis settings, there is a need to focus on the first day of birth for both maternal and neonatal health. There is also a need to do more research on how best to involve community members in the delivery of maternal and neonatal health interventions.PROSPERO registration numberCRD42019125221.

Purpose. The aim of this review is to summarize and evaluate the relevant literature regarding the different ways how polyetheretherketone (PEEK) can be modified to overcome its limited bioactivity, and thereby making it suitable as a dental implant material. Study Selection. An electronic literature search was conducted via the PubMed and Google Scholar databases using the keywords “PEEK dental implants,” “nano,” “osseointegration,” “surface treatment,” and “modification.” A total of 16 in vivo and in vitro studies were found suitable to be included in this review. Results. There are many viable methods to increase the bioactivity of PEEK. Most methods focus on increasing the surface roughness, increasing the hydrophilicity and coating osseoconductive materials. Conclusion. There are many ways in which PEEK can be modified at a nanometer level to overcome its limited bioactivity. Melt-blending with bioactive nanoparticles can be used to produce bioactive nanocomposites, while spin-coating, gas plasma etching, electron beam, and plasma-ion immersion implantation can be used to modify the surface of PEEK implants in order to make them more bioactive. However, more animal studies are needed before these implants can be deemed suitable to be used as dental implants.

BackgroundOver 240 million children live in countries affected by conflict or fragility, and such settings are known to be linked to increased psychological distress and risk of mental disorders. While guidelines are in place, high-quality evidence to inform mental health and psychosocial support (MHPSS) interventions in conflict settings is lacking. This systematic review aimed to synthesise existing information on the delivery, coverage and effectiveness of MHPSS for conflict-affected women and children in low-income and middle-income countries (LMICs).MethodsWe searched Medline, Embase, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Psychological Information Database (PsycINFO)databases for indexed literature published from January 1990 to March 2018. Grey literature was searched on the websites of 10 major humanitarian organisations. Eligible publications reported on an MHPSS intervention delivered to conflict-affected women or children in LMICs. We extracted and synthesised information on intervention delivery characteristics, including delivery site and personnel involved, as well as delivery barriers and facilitators, and we tabulated reported intervention coverage and effectiveness data.ResultsThe search yielded 37 854 unique records, of which 157 were included in the review. Most publications were situated in Sub-Saharan Africa (n=65) and Middle East and North Africa (n=36), and many reported on observational research studies (n=57) or were non-research reports (n=53). Almost half described MHPSS interventions targeted at children and adolescents (n=68). Psychosocial support was the most frequently reported intervention delivered, followed by training interventions and screening for referral or treatment. Only 19 publications reported on MHPSS intervention coverage or effectiveness.DiscussionDespite the growing literature, more efforts are needed to further establish and better document MHPSS intervention research and practice in conflict settings. Multisectoral collaboration and better use of existing social support networks are encouraged to increase reach and sustainability of MHPSS interventions.PROSPERO registration numberCRD42019125221.