<em>Per Os</em> Administered Modified-Release Solid Formulations of Melatonin: A Review of the Latest Developments Including the Design of Experiments (DoE) Approach

The pineal hormone melatonin (MLT) is a derivative of the amino acid L-tryptophan and controls the circadian diurnal rhythm and the seasonal biorhythm. Exogenous administration is aimed at alleviating sleep-related dysfunctions and jet lag, as it decreases sleep-onset latency, increases total sleep time and improves overall sleep quality. Besides these indications, MLT has been shown to have other actions, such as antioxidant, immune enhancement and anticancer. It has also been shown to be useful against cardiovascular, neurological and psychiatric diseases. In the context of this work, a review of the related literature on the modified release of MLT from its per os administered formulations is presented, including the utilization of the design of experiments (DoE) for the selection of the optimal composition of melatonin formulations. The chapter offers an account of the recent advantages on MLT’s solid dosage forms suitable for treating sleep disorders, referring either to its onset or maintenance

Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development

A novel chaotropic chromatography method for the quantitative determination of bupropion and its impurities, following analytical quality-by-design (AQbD) principles, is presented. The analytical target profile (ATP) was defined on the basis of the efficient separation and reliable determination of bupropion and its five impurities in tablets. Preliminary experiments revealed the need for the addition of a gradient elution part. A screening fractional factorial experimental design was employed to select the critical method parameters (CMPs) and a Box–Behnken design (BBD) was utilized to investigate their influence on predefined critical method attributes (CMAs). In order to compute the design space (DS), where CMPs meet predefined acceptance limits with a high level of probability (π ≥ 85%), Monte Carlo simulations were performed. The working point selected from the DS corresponded to the following conditions: 37.5% acetonitrile at the start of the gradient program (up to 70% at the end of the gradient program), 45 mM of potassium hexafluorophosphate in the water phase, and the start of the linear gradient step in the gradient program at 10 min. The method was validated according to ICH guidelines and applied to the analysis of Wellbutrin® tablets containing bupropion hydrochloride

Trajectories of housing affordability and mental health problems: a population-based cohort study

PURPOSE: With housing costs increasing faster than incomes and a limited supply of social housing options, many households face unaffordable housing. Housing affordability problems may negatively impact mental health; however, longitudinal evidence is limited. This study investigates the association between trajectories of housing affordability problems and mental health. METHODS: We used data from 30,025 households from Understanding Society, a longitudinal household survey from the UK. Participants spending 30% or more of household income on housing were categorised as facing housing affordability problems. We estimated group-based trajectories of housing affordability problems from 9 waves of data (2009-2019). We used linear regression to calculate the association between the trajectories and mental health problems, as measured by General Health Questionnaire (GHQ) score in Wave 10 (2018-2020). RESULTS: We found six distinct trajectories of housing affordability problems. Those in the 'stable low' group had a consistently low probability of affordability problems, whilst those in 'high falling' group had a sustained high probability in the earlier waves of the study, subsequently decreasing over time. The adjusted analysis showed that trajectory group membership over the first nine waves of data predicted GHQ score in 2018-2020 (Wave 10). Compared to the 'stable low' group, those in the 'high falling' group had a GHQ score that was 1.06 (95% CI 0.53-1.58) points higher. CONCLUSION: This study provides evidence that sustained exposure to housing affordability problems is associated with long-term worse mental health, even in the absence of more recent problems

INVESTIGATING STUDENTS' - FUTURE TEACHERS' VIEWS ON THEIR INTERNSHIP: BENEFITS AND CHALLENGES

In several countries worldwide, the internship is part of teacher education programs and aims at the professional and personal development of teachers. In Greece, the Pedagogical Departments of Primary Education (PPT) include in their curriculum the students’ practical education which is an internship supervised and supported by teachers - mentors. Through this process, students gain the opportunity to acquire more knowledge of teaching and improve the needed skills, attitudes and values associated with the efficient performance of their job. This case study seeks to unearth the benefits of the internship program and also intends to explore the potential obstacles encountered by students - future teachers during their internship. The qualitative method of research using the semi-directed interview tool was adopted to study the opinion of students - future teachers about the internship program. The survey involved eleven students - future teachers of the Department of Education and Social Work of the University of Patras, who participated in internships in schools in the region of Patras. The results showed that students - future teachers benefited from the development of integrated teaching skills with the proper guidance and support of mentors, yet they simultaneously indicated some potential inhibitory aspects and challenges which arise through their relationship with mentors.  Article visualizations

Baseline Correction for HPLC Chromatograms by Using Free Open-Source Software

Chromatograms with overlapping peaks and a baseline rise or upset constitute a great challenge for analysts. Such a case regarding the analysis of bupropion hydrochloride and its 5 impurities in a tablet formulation was used as a model. A baseline correction technique for liquid chromatography coupled with diode array detection is described by using Rstudio. The asymmetry least squares (ALS) algorithm was used as implemented in the “baseline” package, with parameters lambda and p set to 4 and 0.05, respectively. Peak deconvolution and subsequent integration and area quantification were accomplished through Fytik software. Chromatographic data from the validation procedure were utilized to demonstrate the feasibility of the suggested method and whether this correction affects the outcome of the validation study. Finally, a robustness study was carried out in order to shed light on the factors that have a more significant influence on the baseline correction, showing the reliability of this procedure through random changes in its parameters

The gender dimensions of mental health during the Covid-19 pandemic: A path analysis

BACKGROUND: The Covid-19 pandemic has had a substantial population mental health impact, with evidence indicating that mental health has deteriorated in particular for women. This gender difference could be explained by the distinct experiences of women during the pandemic, including the burden of unpaid domestic labour, changes in economic activity, and experiences of loneliness. This study investigates potential mediators in the relationship between gender and mental health during the first wave of the Covid-19 pandemic in the UK. METHODS: We used data from 9,351 participants of Understanding Society, a longitudinal household survey from the UK. We conducted a mediation analysis using structural equation modelling to estimate the role of four mediators, measured during the first lockdown in April 2020, in the relationship between gender and mental health in May and July 2020. Mental health was measured with the 12-item General Health Questionnaire (GHQ-12). Standardized coefficients for each path were obtained, as well as indirect effects for the role of employment disruption, hours spent on housework, hours spent on childcare, and loneliness. RESULTS: In a model controlling for age, household income and pre-pandemic mental health, we found that gender was associated with all four mediators, but only loneliness was associated with mental health at both time points. The indirect effects showed strong evidence of partial mediation through loneliness for the relationship between gender and mental health problems; loneliness accounted for 83.9% of the total effect in May, and 76.1% in July. No evidence of mediation was found for housework, childcare, or employment disruption. CONCLUSION: The results suggest that the worse mental health found among women during the initial period of the Covid-19 pandemic is partly explained by women reporting more experiences of loneliness. Understanding this mechanism is important for prioritising interventions to address gender-based inequities that have been exacerbated by the pandemic

A novel HPLC method for the simultaneous determination of empagliflozin and dapagliflozin: Development, validation, robustness testing and greenness assessment

Empagliflozin (EMPA) and Dapagliflozin (DAPA) are mainly recommended for the treatment of type 2 diabetes mellitus and heart failure. Based on the principles of green analytical chemistry, a simple, rapid and robust HPLC method was developed for the determination of both analytes in bulk. An isocratic protocol was developed using a C18 column, with a mobile phase consisting of just 30% organic modifier (ACN), while the remaining 70% was HPLC water. The run was completed within 4 min, with a flow rate of 1.20 mL/min, while UV detection took place at 230 nm. The method was then validated according to the ICH Q2 (R1) guidelines, and all the parameters examined were within the specified limits. Furthermore, the robustness of the method was evaluated by employing a factorial experimental design. Finally, the environmental friendliness of the proposed method was assessed by using the Analytical GREEness (AGREE) metric tool. The proposed method can be used for analysis of EMPA and DAPA in bulk, with potential application to the relevant pharmaceuticals

The impact of comorbid severe mental illness and common chronic physical health conditions on hospitalisation: A systematic review and meta-analysis

BACKGROUND: People with severe mental illness (SMI) are at higher risk of physical health conditions compared to the general population, however, the impact of specific underlying health conditions on the use of secondary care by people with SMI is unknown. We investigated hospital use in people managed in the community with SMI and five common physical long-term conditions: cardiovascular diseases, COPD, cancers, diabetes and liver disease. METHODS: We performed a systematic review and meta-analysis (Prospero: CRD42020176251) using terms for SMI, physical health conditions and hospitalisation. We included observational studies in adults under the age of 75 with a diagnosis of SMI who were managed in the community and had one of the physical conditions of interest. The primary outcomes were hospital use for all causes, physical health causes and related to the physical condition under study. We performed random-effects meta-analyses, stratified by physical condition. RESULTS: We identified 5,129 studies, of which 50 were included: focusing on diabetes (n = 21), cardiovascular disease (n = 19), COPD (n = 4), cancer (n = 3), liver disease (n = 1), and multiple physical health conditions (n = 2). The pooled odds ratio (pOR) of any hospital use in patients with diabetes and SMI was 1.28 (95%CI:1.15-1.44) compared to patients with diabetes alone and pooled hazard ratio was 1.19 (95%CI:1.08-1.31). The risk of 30-day readmissions was raised in patients with SMI and diabetes (pOR: 1.18, 95%CI:1.08-1.29), SMI and cardiovascular disease (pOR: 1.27, 95%CI:1.06-1.53) and SMI and COPD (pOR:1.18, 95%CI: 1.14-1.22) compared to patients with those conditions but no SMI. CONCLUSION: People with SMI and five physical conditions are at higher risk of hospitalisation compared to people with that physical condition alone. Further research is warranted into the combined effects of SMI and physical conditions on longer-term hospital use to better target interventions aimed at reducing inappropriate hospital use and improving disease management and outcomes

A Qualitative Study Exploring Access to Mental Health and Substance Use Support among Individuals Experiencing Homelessness during COVID-19

People experiencing homelessness have higher rates of mental ill-health and substance use and lower access to health services compared to the general population. The COVID-19 pandemic led to changes in service delivery across health and social care services, with many adopting virtual or telephone support for service users. This paper explores the experiences of access to community-based mental health and substance use support for people experiencing homelessness during the COVID-19 pandemic. Qualitative telephone interviews were conducted with 10 women and 16 men (ages 25 to 71) who self-identified as experiencing homelessness in North East England between February and May 2021. With five individuals with lived experience, results were analysed using inductive reflexive thematic analysis. Reactive changes to support provision often led to inadvertent exclusion. Barriers to access included: physical locations, repetition of recovery stories, individual readiness, and limited availability. Participants suggested creating services reflective of need and opportunities for choice and empowerment. Community mental health and substance use support for people experiencing homelessness should ensure the support is personalised, responsive to need, inclusive, and trauma-informed. The findings of this research have important implications for mental health and substance use policy and practice for individuals who experience homelessness during a public health crisis