Gene Therapy for Lysosomal Storage Disorders: Ongoing Studies and Clinical Development

Rare monogenic disorders such as lysosomal diseases have been at the forefront in the development of novel treatments where therapeutic options are either limited or unavailable. The increasing number of successful pre-clinical and clinical studies in the last decade demonstrates that gene therapy represents a feasible option to address the unmet medical need of these patients. This article provides a comprehensive overview of the current state of the field, reviewing the most used viral gene delivery vectors in the context of lysosomal storage disorders, a selection of relevant pre-clinical studies and ongoing clinical trials within recent years

Are ethnic disparities in HbA1c levels explained by mental wellbeing? Analysis of population-based data from the Health Survey for England

Aims: It is unclear how ethnic differences in HbA1c levels are affected by individual variations in mental wellbeing. Thus, the aim of this study was to assess the extent to which HbA1c disparities between Caucasian and South Asian adults are mediated by various aspects of positive psychological functioning. Methods: Data from the 2014 Health Survey for England was analysed using bootstrapping methods. A total of 3894 UK residents with HbA1c data were eligible to participate. Mental wellbeing was assessed using the Warwick-Edinburgh Mental Well-Being Scale. To reduce bias BMI, blood pressure, diabetes status, and other factors were treated as covariates. Results: Ethnicity directly predicted blood sugar control (unadjusted coefficient -2.15; 95% CI -3.64, -0.67), with Caucasians generating lower average HbA1c levels (37.68 mmol/mol (5.6%)) compared to South Asians (39.87 mmol/mol (5.8%)). This association was mediated by positive mental wellbeing, specifically concerning perceived vigour (unadjusted effect 0.30; 95% CI 0.13, 0.58): South Asians felt more energetic than Caucasians (unadjusted coefficient -0.32; 95% CI -0.49, -0.16), and greater perceived energy predicted lower HbA1c levels (unadjusted coefficient -0.92; 95% CI -1.29, -0.55). This mediator effect accounted for just over 14% of the HbA1c variance, and was negated after adjusting for BMI. Conclusions: Caucasian experience better HbA1c levels compared with their South Asian counterparts. However, this association is partly confounded by individual differences in perceived energy levels, which is implicated in better glycaemic control, and appears to serve a protective function in South Asians

Modifiable risk factors predicting major depressive disorder at four year follow-up: a decision tree approach

<p>Abstract</p> <p>Background</p> <p>Relative to physical health conditions such as cardiovascular disease, little is known about risk factors that predict the prevalence of depression. The present study investigates the expected effects of a reduction of these risks over time, using the decision tree method favoured in assessing cardiovascular disease risk.</p> <p>Methods</p> <p>The PATH through Life cohort was used for the study, comprising 2,105 20-24 year olds, 2,323 40-44 year olds and 2,177 60-64 year olds sampled from the community in the Canberra region, Australia. A decision tree methodology was used to predict the presence of major depressive disorder after four years of follow-up. The decision tree was compared with a logistic regression analysis using ROC curves.</p> <p>Results</p> <p>The decision tree was found to distinguish and delineate a wide range of risk profiles. Previous depressive symptoms were most highly predictive of depression after four years, however, modifiable risk factors such as substance use and employment status played significant roles in assessing the risk of depression. The decision tree was found to have better sensitivity and specificity than a logistic regression using identical predictors.</p> <p>Conclusion</p> <p>The decision tree method was useful in assessing the risk of major depressive disorder over four years. Application of the model to the development of a predictive tool for tailored interventions is discussed.</p

Anxiety and depressive symptoms related to parenthood in a large Norwegian community sample: the HUNT2 study

The study compared anxiety and depression prevalence between parents and non-parents in a society with family- and parenthood-friendly social politics, controlling for family status and family history, age, gender, education and social class. All participants aged 30–49 (N&nbsp;=&nbsp;24,040) in the large, non-sampled Norwegian HUNT2 community health study completed the Hospital Anxiety and Depression Scales. The slightly elevated anxiety and depression among non-parents compared to parents in the complete sample was not confirmed as statistically significant within any subgroups. Married parents and (previously unmarried) cohabiting parents did not differ in portraying low anxiety and depression prevalence. Anxiety was associated with single parenthood, living alone or being divorced, while elevated depression was found only among those living alone. Burdening selection and cultural/political context are suggested as interpretative perspectives on the contextual and personal influences on the complex relationship between parenthood and mental health

Intolerance of uncertainty and mental wellbeing: serial mediation by rumination and fear of COVID-19

The novel coronavirus-2019 (COVID-19) pandemic has become globally widespread with millions of confirmed cases and many countries implementing various levels of quarantine. Therefore, it is important to investigate the psychological consequences of this process, given the unique situation that has been experienced globally. Therefore, the present study examined whether intolerance of uncertainty was related to mental wellbeing and whether this relationship was mediated by rumination and fear of COVID-19. The sample comprised 1772 Turkish individuals (aged between 18 and 73 years) from 79 of 81 cities in Turkey, who completed measures of mental wellbeing, intolerance of uncertainty, rumination, and fear of COVID-19. Results of serial mediation analyses showed that intolerance of uncertainty had a significant direct effect on mental wellbeing. Rumination and fear of COVID-19, in combination, serially mediated the association between intolerance of uncertainty and mental wellbeing. The findings are discussed within the framework of the psychological consequences of the COVID-19 pandemic and related literature

A randomized controlled trial of an online, compassion-based intervention for maternal psychological well-being in the first year postpartum

Objectives New self-help interventions have been called for to promote psychological well-being amongst mothers in the first year postpartum, with compassion-based interventions having potential in this regard. The present study developed and evaluated a low-intensity, online, compassion-based intervention for this population called Kindness for Mums Online (KFMO). Methods UK mothers of infants under one year (N = 206) participated in a pragmatic randomized controlled trial, comparing KFMO with a waitlist control. Results The effect of the intervention on well-being (the primary outcome) was small and was sensitive to the way missing data were treated. However, KFMO robustly increased self-compassion relative to control, from baseline (week 0) to post-intervention (week 6), and from baseline to follow-up (week 12). No effects were observed on other secondary outcomes. Conclusions The findings suggest that self-compassion can be increased in postpartum mothers via an accessible, low-intensity, web-based, self-help program. However, this did not translate into robust improvements in well-being. Study limitations include relatively high attrition rates and limited generalizability to more diverse samples

How do we improve men’s mental health via primary care? An evaluation of the Atlas Men’s Well-being Pilot Programme for stressed/distressed men

Background Over three-quarters of all suicides are men (England and Wales), this is despite higher levels of anxiety and depression being reported by women. This disparity may in part be explained by atypical presentations of distress in men, and gendered issues around help-seeking. Consequently, the Atlas Men’s Well-being Programme was designed to engage stressed/distressed men who were patients at a London-based GP surgery. Atlas encouraged GPs to identify and refer men for counselling and/or acupuncture by raising their awareness of men’s distress. The aim of this pilot study was to evaluate Atlas in terms of patients’ characteristics, service utilisation, patient outcomes and cost implications. Methods All patients using the Programme were asked to complete a questionnaire before and after their Atlas sessions. Outcome measures included the Hospital Anxiety and Depression scale, Perceived Stress Scale, Warwick-Edinburgh Mental Well-being Scale, a 11-point scale measuring physical health, and the Psychological Outcome Profiles (PSYCHLOPS), a patient-generated outcome measure. Additionally, for cost calculations, participants were asked about their employment, number of days off work due to illness, and their health and social care service use. Results 102 participants were recruited, 82 completed pre- and post-treatment questionnaires. Comparisons pre- and post-treatment revealed a statistically significant improvement in anxious mood (p <0.001), perceived stress (p < 0.001), positive well-being (p = <0.001), PSYCHLOPS (p = <0.001) and physical health (p = 0.001), though not depressed mood (p = 0.660). Additionally, reductions in costs related to lost employment and health and social care use, exceeded the cost of Atlas counselling and acupuncture sessions, with an average saving of nearly £700 per patient. Conclusions Atlas attendance was associated with improvements in patients’ mental and physical health, and demonstrated likely cost savings. It is now important to understand patient and stakeholder perspectives. Further research could compare usual care with the Atlas approach, and investigate full cost-effectiveness

Comparison of participants and non-participants to the ORISCAV-LUX population-based study on cardiovascular risk factors in Luxembourg

BACKGROUND: Poor response is a major concern in public health surveys. In a population-based ORISCAV-LUX study carried out in Grand-Duchy of Luxembourg to assess the cardiovascular risk factors, the non-response rate was not negligible. The aims of the present work were: 1) to investigate the representativeness of study sample to the general population, and 2) to compare the known demographic and cardiovascular health-related profiles of participants and non-participants. METHODS: For sample representativeness, the participants were compared to the source population according to stratification criteria (age, sex and district of residence). Based on complementary information from the "medical administrative database", further analysis was carried out to assess whether the health status affected the response rate. Several demographic and morbidity indicators were used in the univariate comparison between participants and non-participants. RESULTS: Among the 4452 potentially eligible subjects contacted for the study, there were finally 1432 (32.2%) participants. Compared to the source population, no differences were found for gender and district distribution. By contrast, the youngest age group was under-represented while adults and elderly were over-represented in the sample, for both genders. Globally, the investigated clinical profile of the non-participants was similar to that of participants. Hospital admission and cardiovascular health-related medical measures were comparable in both groups even after controlling for age. The participation rate was lower in Portuguese residents as compared to Luxembourgish (OR = 0.58, 95% CI: 0.48-0.69). It was also significantly associated with the professional status (P < 0.0001). Subjects from the working class were less receptive to the study than those from other professional categories. CONCLUSION: The 32.2% participation rate obtained in the ORISCAV-LUX survey represents the realistic achievable rate for this type of multiple-stage, nationwide, population-based surveys. It corresponds to the expected rate upon which the sample size was calculated. Given the absence of discriminating health profiles between participants and non-participants, it can be concluded that the response rate does not invalidate the results and allows generalizing the findings for the population

Promotion, prevention and protection: interventions at the population- and community-levels for mental, neurological and substance use disorders in low- and middle-income countries

Background In addition to services within the health system, interventions at the population and community levels are also important for the promotion of mental health, primary prevention of mental, neurological and substance use (MNS) disorders, identification and case detection of MNS disorders; and to a lesser degree treatment, care and rehabilitation. This study aims to identify “best practice” and “good practice” interventions that can feasibly be delivered at these population- and community-levels in low- and middle-income countries (LMICs), to aid the identification of resource efficiencies and allocation in LMICs. Methods A narrative review was conducted given the wide range of relevant interventions. Expert consensus was used to identify “best practice” at the population-level on the basis of existing quasi-experimental natural experiments and cost effectiveness, with small scale emerging and promising evidence comprising “good practice”. At the community-level, using expert consensus, the ACE (Assessing Cost-Effectiveness in Prevention Project) grading system was used to differentiate “best practice” interventions with sufficient evidence from “good practice” interventions with limited but promising evidence. ResultsAt the population-level, laws and regulations to control alcohol demand and restrict access to lethal means of suicide were considered “best practice”. Child protection laws, improved control of neurocysticercosis and mass awareness campaigns were identified as “good practice”. At the community level, socio-emotional learning programmes in schools and parenting programmes during infancy were identified as “best practice”. The following were all identified as “good practice”: Integrating mental health promotion strategies into workplace occupational health and safety policies; mental health information and awareness programmes as well as detection of MNS disorders in schools; early child enrichment/preschool educational programs and parenting programs for children aged 2–14 years; gender equity and/or economic empowerment programs for vulnerable groups; training of gatekeepers to identify people with MNS disorders in the community; and training non-specialist community members at a neighbourhood level to assist with community-based support and rehabilitation of people with mental disorders. Conclusion Interventions provided at the population- and community-levels have an important role to play in promoting mental health, preventing the onset, and protecting those with MNS disorders. The importance of inter-sectoral enga