STUDY OF ENHANCED ANTI-INFLAMMATORY POTENTIAL OF NIGELLA SATIVA IN TOPICAL NANOFORMULATION

Objective: Formulate a nanocarrier for enhancing the anti-inflammatory activity of thymoquinone (Tq), a major active constituent of Nigella sativa.Methods: Nanoformulation of Tq was developed by low energy emulsification techniques. NanoTqs were pre-screened by different thermodynamic stability tests, followed by in vitro release, zeta potential, viscosity, the transmittance (%), globule size distribution and ex vivo studies. The morphology of the optimized NanoTq was determined by transmission electron microscopy (TEM) which revealed fairly spherical shape and good correlation with particle size distribution study. The formulation used for assessment of the anti-inflammatory potential and permeability enhancement contained mixture of essential oil of Nigella sativa: Capryol 90 (3:7, 10%, v/v), Tween 80 (21.75%, v/v), PEG 400 (7.25%, v/v) and double distilled water (61%, v/v).Results: The in vitro permeation of Tq from optimized formulations was found extremely significant (p<0.001) in comparison to apiTq. The steady state flux (Jss), the permeability coefficient (Kp) and enhancement ratio (Er) of NanoTq gel was determined and compared with apiTq. The comparative anti-inflammatory effects of the optimized formulations NanoTq, apiTq and DicloGel was assessed on the edema in the carrageenan-induced paw model in Wistar rats. Therapeutic potential of NanoTq was found statistically extremely significant (P<0.0001) compared to apiTq and insignificant comparable with standard DicloGel. Storage stability of NanoTq showed insignificant changes in the zeta potential, droplet size and was free from any physical instability.Conclusion: The optimized nano formulation with a lower dose of Tq showed better anti-inflammatory effects, indicating greater absorption capability through the stratum corneum

Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermally applied nanoemulsion

<p>Abstract</p> <p>Background</p> <p>Celecoxib, a selective cyclo-oxygenase-2 inhibitor has been recommended orally for the treatment of arthritis and osteoarthritis. Long term oral administration of celecoxib produces serious gastrointestinal side effects. It is a highly lipophilic, poorly soluble drug with oral bioavailability of around 40% (Capsule). Therefore the aim of the present investigation was to assess the skin permeation mechanism and bioavailability of celecoxib by transdermally applied nanoemulsion formulation. Optimized oil-in-water nanoemulsion of celecoxib was prepared by the aqueous phase titration method. Skin permeation mechanism of celecoxib from nanoemulsion was evaluated by FTIR spectral analysis, DSC thermogram, activation energy measurement and histopathological examination. The optimized nanoemulsion was subjected to pharmacokinetic (bioavailability) studies on Wistar male rats.</p> <p>Results</p> <p>FTIR spectra and DSC thermogram of skin treated with nanoemulsion indicated that permeation occurred due to the disruption of lipid bilayers by nanoemulsion. The significant decrease in activation energy (2.373 kcal/mol) for celecoxib permeation across rat skin indicated that the stratum corneum lipid bilayers were significantly disrupted (p < 0.05). Photomicrograph of skin sample showed the disruption of lipid bilayers as distinct voids and empty spaces were visible in the epidermal region. The absorption of celecoxib through transdermally applied nanoemulsion and nanoemulsion gel resulted in 3.30 and 2.97 fold increase in bioavailability as compared to oral capsule formulation.</p> <p>Conclusion</p> <p>Results of skin permeation mechanism and pharmacokinetic studies indicated that the nanoemulsions can be successfully used as potential vehicles for enhancement of skin permeation and bioavailability of poorly soluble drugs.</p

Intellectual disability in children with attention deficit hyperactivity disorder

Objective: To determine whether children with attention deficit hyperactivity disorder (ADHD) and mild intellectual disability (ID) are a clinically distinct ADHD subgroup. Study design: This was a cross-sectional study comparing clinical characteristics (ADHD subtypes, total number of symptoms, and rates of common comorbidities) between children with ADHD and mild ID and those with ADHD and IQ test scores >70, and also between children with ADHD and ID and a general population sample of children with ID alone. The sample comprised a clinical sample of children with ADHD with ID (n = 97) and without ID (n = 874) and a general population sample of children with ID and without ADHD (n = 58). Results: After correcting for multiple statistical tests, no differences were found between the 2 ADHD groups on any measure except the presence of conduct disorder (CD) symptoms and diagnoses. Children with ADHD and ID had higher rates of both (OR, 2.38; 95% CI, 1.71-3.32 and OR, 2.69; 95% CI, 1.69-4.28, respectively). Furthermore, children with ADHD and ID had significantly higher rates of oppositional defiant disorder (OR, 5.54; 95% CI, 2.86-10.75) and CD (OR, 13.66; 95% CI, 3.25-57.42) symptoms and a higher incidence of oppositional defiant disorder diagnoses (OR, 30.99; 95% CI, 6.38-150.39) compared with children with ID without ADHD. Conclusion: Children with ADHD and mild ID appear to be clinically typical of children with ADHD except for more conduct problems. This finding has implications for clinicians treating these children in terms of acknowledging the presence and impact of ADHD symptoms above and beyond ID and dealing with a comorbid CD

Optimizing an adolescent hybrid telemedical mental health service: Staff scheduling using mathematical programming

Background: According to the World Health Organization, globally, one in seven 10- to 19-year-olds experiences a mental disorder, accounting for 13% of the global burden of disease in this age group. Half of all mental illnesses begin by the age of 14 years and some teenagers with severe presentations must be admitted to the hospital and assessed by highly skilled mental health care practitioners. Digital telehealth solutions can be useful for the assessment of young individuals remotely. Ultimately, this technology can save travel costs for the health service rather than assessing adolescents in person at the corresponding hospital. Especially in rural regions, where travel times can be high, this innovative approach can make a difference to patients by providing quicker assessments. Objective: The aim of this study is to share insights on how we developed a decision support tool to assign staff to days and locations where adolescent mental health patients are assessed face to face. Where possible, patients are seen through video consultation. The model not only seeks to reduce travel times and consequently carbon emissions but also can be used to find a minimum number of staff to run the service. Methods: To model the problem, we used integer linear programming, a technique that is used in mathematical modeling. The model features 2 objectives: first, we aim to find a minimum coverage of staff to provide the service and second, to reduce travel time. The constraints that are formulated algebraically are used to ensure the feasibility of the schedule. The model is implemented using an open-source solver backend. Results: In our case study, we focus on real-world demand coming from different hospital sites in the UK National Health Service (NHS). We incorporate our model into a decision support tool and solve a realistic test instance. Our results reveal that the tool is not only capable of solving this problem efficiently but also shows the benefits of using mathematical modeling in health services. Conclusions: Our approach can be used by NHS managers to better match capacity and location-dependent demands within an increasing need for hybrid telemedical services, and the aims to reduce traveling and the carbon footprint within health care organizations

Interviewer versus self-administered health-related quality of life questionnaires - Does it matter?

<p>Abstract</p> <p>Background</p> <p>Patient-reported outcomes are measured in many epidemiologic studies using self- or interviewer-administered questionnaires. While in some studies differences between these administration formats were observed, other studies did not show statistically significant differences important to patients. Since the evidence about the effect of administration format is inconsistent and mainly available from cross-sectional studies our aim was to assess the effects of different administration formats on repeated measurements of patient-reported outcomes in participants with AIDS enrolled in the Longitudinal Study of Ocular Complications of AIDS.</p> <p>Methods</p> <p>We included participants enrolled in the Longitudinal Study of Ocular Complications in AIDS (LSOCA) who completed the Medical Outcome Study [MOS] -HIV questionnaire, the EuroQol, the Feeling Thermometer and the Visual Function Questionnaire (VFQ) 25 every six months thereafter using self- or interviewer-administration. A large print questionnaire was available for participants with visual impairment. Considering all measurements over time and adjusting for patient and study site characteristics we used linear models to compare HRQL scores (all scores from 0-100) between administration formats. We defined adjusted differences of ≥0.2 standard deviations [SD]) to be quantitatively meaningful.</p> <p>Results</p> <p>We included 2,261 participants (80.6% males) with a median of 43.1 years of age at enrolment who provided data on 23,420 study visits. The self-administered MOS-HIV, Feeling Thermometer and EuroQol were used in 70% of all visits and the VFQ-25 in 80%. For eight domains of the MOS-HIV differences between the interviewer- and self- administered format were < 0.1 SD. Differences in scores were highest for the social and role function domains but the adjusted differences were still < 0.2 SD. There was no quantitatively meaningful difference between administration formats for EuroQol, Feeling Thermometer and VFQ-25 domain scores. For ocular pain (VFQ-25), we found a statistically significant difference of 3.5 (95% CI 0.2, 6.8), which did, however, not exceed 0.2 SD. For all instruments scores were similar for the large and standard print formats with all adjusted differences < 0.2 SD.</p> <p>Conclusions</p> <p>Our large study provides evidence that administration formats do not have a meaningful effect on repeated measurements of patient-reported outcomes. As a consequence, longitudinal studies may not need to consider the effect of different administration formats in their analyses.</p

Virtual consultation (VC) in fertility and obstetrics and gynaecology services: An analysis of patient and clinician satisfaction

Objective: To assess patient and clinician satisfaction and identify any differences between the two with the use of video consulting (VC) in the fields of obstetrics and gynaecology (O&G) and fertility in Wales. Design: A retrospective electronic survey study. Setting: All public hospitals in Wales that used virtual methods for delivery of fertility and/or O&G appointments during and after the COVID‐19 pandemic between August 2020 and March 2022. Population: Patients awaiting an appointment on the National Health Service, who have attended virtual fertility or O&G appointments in Wales, and fertility and O&G clinicians who have conducted appointments virtually. Methods: Analysis of patient and clinician responses to a VC satisfaction survey delivered after their consultation taking place between August 2020 and March 2022. Main Outcome Measures: Patient and clinician satisfaction rates with the use of virtual consultation in fertility and O&G appointments. Results: In satisfaction data collected from 420 patients and 161 clinicians, 83% of patients and 63% of clinicians reported their VC quality to be ‘very good’ or ‘excellent’. Difficulties when using VC were experienced by a minority of patients (1%–9%) and clinicians (1%–8%) and most patients (52v82%) and clinicians (34%–67%) found several aspects of VC to be ‘very beneficial’. Fertility patients rated their VC experience more positively than O&G patients. Conclusions: Most patients and clinicians were satisfied with their VC experience. Patients were more satisfied with the use of VC than clinicians. Fertility patients were more satisfied with the use of VC than O&G patients

Three-dimensional measurement of intervertebral kinematics in vitro using optical motion analysis

Measurement of the stiffness of spinal motion segments is widely used for evaluating the stability of spinal implant constructs. A three-dimensional motion analysis technique has been developed that allows accurate measurement of the relative movement of the vertebral bodies about a well-defined anatomical axis system. The position of marker clusters on each vertebra is tracked using digital infrared cameras (Qualisys AB, Gothenburg). Landmarks are identified using a marked pointer, and an anatomical coordinate system is defined for each vertebra. The transformation relating the upper and lower vertebrae is calculated, using the joint coordinate system approach of Grood and Suntay to find the rotations and translations in each anatomical plane. The stiffness of vertebrectomy constructs was investigated using a Synex vertebral body replacement and an anterior rod with one or two screws in each vertebral body, with or without damage to the posterior longitudinal ligament (PLL). A moment of 2 N m was applied about each anatomical axis, and the range of motion about each axis was calculated. The range of motion in flexion-extension and lateral bending was significantly greater with only one screw. When the PLL was cut, there was no significant increase in the range of motion

Capacity planning of virtual wards for frail and elderly patients

This paper investigates the planning of virtual ward (VW) capacity including the remote monitoring of frail and elderly patients. The main objective is to optimize VW hub locations across a region in the United Kingdom. Furthermore, assigning the optimal number of clinicians to different regions needs to be considered. We develop a mathematical model that minimizes the setup and travel costs of VW hubs and staff. Our experimental analysis evaluates different levels of demand considering postcode areas within different Trusts, also known as Health Boards, in the National Health Service (NHS). Furthermore, our experiments provide insights into how many hub locations should be deployed and staffed. This can be used to individually find the number of remote monitors and clinicians for each facility as well as the system overall

Understanding the support experiences of families of children with autism and sensory processing difficulties: A qualitative study.

Background: Support, such as information, advice and therapies, can play a vital role in the lives of families of autistic children. However, little is known about the support experiences of UK parents and carers. Aim: To explore experiences of and access to support for families of children with autism and sensory processing difficulties, from the perspective of parents and carers. Methods: Semi‐structured, timeline‐assisted interviews were conducted with parents/carers of 30 children aged 5–11, exploring experiences of support. Framework analysis was used to identify themes in the interview data. Results: Support varied widely and was not accessed equitably. Specialist autism support, together with support from other parents and voluntary organizations, was perceived as more useful than statutory and nonspecialist provision. Unmet support needs included an ongoing point of contact for information and advice for parents, and access to direct therapy and specialist mental health provision for children

Dizajn, razvoj i vrednovanje novih nanoemulzija za transdermalnu primjenu celekoksiba

The aim of the present study was to investigate the potential of nanoemulsion formulations for transdermal delivery of celecoxib (CXB). The in vitro skin permeation profile of optimized formulations was compared with CXB gel and nanoemulsion gel. Significant increase in the steady state flux (Jss), permeability coefficient (Kp) and enhancement ratio (Er) was observed in nanoemulsion formulations T1 and T2 (p < 0.05). The highest value of these permeability parameters was obtained in formulation T2, which consisted of 2% m/m of CXB, 10% m/m of oil phase (Sefsol 218 and Triacetin), 50% m/m of surfactant mixture (Tween-80 and Transcutol-P) and 40% m/m of water. The anti-inflammatory effects of formulation T2 showed a significant increase (p < 0.05) in inhibition after 24 h compared to CXB gel and nanoemulsion gel on carrageenean-induced paw edema in rats. These results suggested that nanoemulsions are potential vehicles for improved transdermal delivery of CXB.U radu su opisana ispitivanja nanoemulzija za transdermalnu primjenu celekoksiba (CXB). Profil permeacije kroz kožu ispitivan je in vitro i uspoređivan sa CXB gelom i nanoemulzijskim gelom. U formulacijama T1 i T2 postignuto je značajno povećanje ustaljenog fluksa (Jss), koeficijenta permeabilnosti (Kp) i povećanje omjera (Er) (p < 0.05). Najveće vrijednosti parametara permeabilnosti dobivene su u formulaciji T2 koja je sadržala 2% m/m CXB, 10% m/m uljne faze (Sefsol 218 i Triacetin), 50% m/m površinski-aktivnih tvari (Tween-80 i Transcutol-P) i 40% m/m vode. Protuupalno djelovanje formulacije T2 na edem šape štakora uzrokovan karageninom značajno je povećano (p < 0.05) poslije 24 h u usporedbi sa CXB gelom i nanoemulzijskim gelom. Rezultati ukazuju na poboljšanu isporuku celekoksiba putem nanoemulzija