Organic Solvent Nanofiltration in Pharmaceutical Applications.

Separation and purification in organic solvents are indispensable procedures in pharmaceutical manufacturing. However, they still heavily rely on the conventional separation technologies of distillation and chromatography, resulting in high energy and massive solvent consumption. As an alternative, organic solvent nanofiltration (OSN) offers the benefits of low energy consumption, low solid waste generation, and easy scale-up and incorporation into continuous processes. Thus, there is a growing interest in employing membrane technology in the pharmaceutical area to improve process sustainability and energy efficiency. This Review comprehensively summarizes the recent progress (especially the last 10 years) of organic solvent nanofiltration and its applications in the pharmaceutical industry, including the concentration and purification of active pharmaceutical ingredients, homogeneous catalyst recovery, solvent exchange and recovery, and OSN-assisted peptide/oligonucleotide synthesis. Furthermore, the challenges and future perspectives of membrane technology in pharmaceutical applications are discussed in detail.

Mild Strategy for the Preparation of Alkyl Sulfonyl Fluorides from Alkyl Bromides and Alcohols Using Photoredox Catalysis and Flow Chemistry.

Facile access to sp3-rich scaffolds containing a sulfonyl fluoride group is still limited. Herein, we describe a mild and scalable strategy for the preparation of alkyl sulfonyl fluorides from readily available alkyl bromides and alcohols using photoredox catalysis. This approach is based on halogen atom transfer (XAT), followed by SO2 capture and fluorination. The method features mild conditions enabling fast access to high-value derivatives and has been scaled up to 5 g using a continuous stirred tank reactor cascade.

Living with a person with young onset dementia - spousal experience.

PURPOSE: Being of working age while at the same time needing to help a partner with young onset dementia has specific consequences for spouses. Research to date has been sparse concerning this particular group of spouses. The aim of the study was to explore spouses' everyday experiences when living with a person with young onset dementia. METHOD: The study had a descriptive qualitative design with semi-structured interviews with nine spouses. The interviews were analysed using content analysis. RESULT: The interviewed spouses experienced emotions that varied from feelings of loneliness, frustration, and worry to peace of mind. They said that they used coping strategies, which included adopting a positive mindset, adapting to inabilities, adopting an avoidant approach, and finding ways to recharge. Spouses also felt that they could use more support, both formal and informal. CONCLUSION: The spouse of a person with young onset dementia has a range of emotional experiences and has resourceful ways of handling everyday life. Various types of support are offered to spouses, however, they seemed to desire more from health care services.

Parents' Experiences of Communication With School Nurses About Their Child's Weight Development in Sweden.

This study aimed to describe parents' experiences of communication with school nurses concerning the growth data and weight development of their children aged 8 and 10 years old in Sweden. Eighteen interviews with parents were conducted and analyzed through qualitative content analysis. The result showed a need for improved dialogue where the parents viewed the health visit's purpose as unclear and lacked feedback. The parents desired access to their child's growth data and described the need for an improved channel for receiving information. The parents moreover experienced the lack of a child-centered perspective, described the child's context as not in focus, and desired collaboration around their child. This study shows the need for the development of evidence-based methods for communicating growth data and weight development between School Health Service (SHS) and parents, as well as the need for a reformed SHS perspective towards parents and children.

The influence of the Covid-19 pandemic on municipal meeting places arranging group exercise for older persons.

PURPOSE: Many municipalities today, together with other stakeholders, offer group exercises for the older population via municipal meeting places, focusing on promoting good health. During the Covid-19 pandemic, these group exercises either continued in a modified form or ceased. The aim of this study was to explore involved stakeholders' experiences of group exercises for older persons arranged via municipal meeting places during the Covid-19 pandemic. METHODS: Six online focus group interviews were conducted with 25 stakeholders, such as decision-makers and representatives from the non-profit sector, from seven municipalities in Sweden. Data were analysed using thematic analysis. FINDINGS: The collaboration around the group exercises was challenged due to affected communication and decision-making. The stakeholders described the importance of adapting and finding new ways to offer group exercise. Furthermore, the re-arranging of group exercises created concerns about the well-being of the older persons but also happiness with the older persons ability to act for their own well-being during the pandemic. CONCLUSIONS: This study highlights the importance of the municipalities exchanging experiences, making the older persons more involved in the decision-making process, enabling a person-centred encounter with the older persons when exercising in groups, and strengthening supportive environments by sharing the ownership of arranging the group exercises with the older persons.

Restoring Balance-A Woman's Expressions of Lived Experience of Everyday Life During a Period of Aging: A Case Study.

Bereaved older people face stressors from the changes in roles associated with the death of a spouse. To illustrate the lived experience of everyday life during a period of aging after a woman's loss of her spouse. One woman born in 1918 was followed between 74 and 80 years of age after her husband died. Data consisted of daily diary. The text from the diaries were analyzed with a phenomenological hermeneutical approach. Everyday life after becoming a widow is characterized by balancing between personal resources to manage everyday life and vulnerability. In health and social care, it is important to identify experiences of vulnerability because these are associated with poor health.

School nurses' experience of communicating growth data and weight development to parents of children 8 and 10 years of age.

INTRODUCTION: The prevalence of overweight and obesity among children has risen sharply during recent decades. School nurses are key health professionals in interventions targeting the early onset of overweight and obesity during childhood. Understanding how school nurses experience communication with parents concerning their child´s growth and weight development are essential. The aim of the study is to describe school nurses' experience of communicating growth data and weight development to parents of school children ages 8 and 10 years. METHOD: The design of the study is a descriptive, qualitative design with purposive and snowball sampling. Sixteen interviews with school nurses were conducted and analysed with qualitative content analysis. RESULT: The analysis resulted in three main categories including subcategories. In Challenges in the professional role, the school nurses expressed a lack of knowledge, skills and tools in communication, described a perception of parental responsibility and stated using several different approaches in communicating growth data and weight development to parents. In Sustainable communication with parents, the school nurses described the value of creating a dialogue, a supportive approach to the parents, and the building of a relation between them and the parents as essential. In Barriers in communicating the child´s weight, the school nurses described the experience of stigma concerning the subject of overweight and obesity, increased concern when they detected underweight as well as an ambivalence towards measuring weight. CONCLUSION: The study highlights an educational challenge concerning the need for training, skills, and strategies for communication with parents. A variety of ways in school nurses' communication with parents were identified in the present study and this shows an inconsistency in how School health services was offered and a need for the development of evidence-based procedures for communicating growth data and weight development to parents.

Approaches to Synthesis and Isolation of Enantiomerically Pure Biologically Active Atropisomers.

Atropisomerism is a stereochemical phenomenon exhibited by molecules containing a rotationally restricted σ bond. Contrary to classical point chirality, the two atropisomeric stereoisomers exist as a dynamic mixture and can be interconverted without the requirement of breaking and reforming a bond. Although this feature increases structural complexity, atropisomers have become frequent targets in medicinal chemistry projects. Their axial chirality, e.g., from axially chiral biaryl motifs, gives access to unique 3D structures. It is often desirable to have access to both enantiomers of the atropisomers via a nonselective reaction during the early discovery phase as it allows the medicinal chemistry team to probe the structure activity relationship in both directions. However, once a single atropisomer is selected, it presents several problems. First, the pure single atropisomer may interconvert to the undesired stereoisomer under certain conditions. Second, separation of atropisomers is nontrivial and often requires expensive chiral stationary phases using chromatography or additives if a salt resolution approach is chosen. Other options can be kinetic resolution using enzymes or chiral catalysts. However, apart from the high cost often associated with the two latter methods, a maximum yield of only 50% of the desired atropisomer can be obtained. The ideal approach is to install the chiral atropisomeric axis enantioselectively or employing a dynamic kinetic resolution approach. In theory, both approaches have the potential to provide a single atropisomer in quantitative yield. This Account will discuss the successes/failures and challenges we have experienced in developing methods for resolution/separation and asymmetric synthesis of atropisomeric drug candidates in one of our early phase drug development projects. Suitability for the different methods at various stages of the drug development phase is discussed. Depending on the scale and time available, a separation of a mixture of atropisomers by chromatography was sometimes preferred, whereas asymmetric- or resolution approaches were desired for long-term supply. With the use of chromatography, the impact on separation efficiency and solvent consumption, depending on the nature of the substrate, is discussed. We hope that with this Account the readers will get a better view on the challenges medicinal and process chemists meet when designing new atropisomeric drug candidates and developing processes for manufacture of a single atropisomer.

Weighted Blankets' Effect on the Health of Older People Living in Nursing Homes.

BACKGROUND: An increasingly aging population is a global phenomenon. While considered a positive step forward, vulnerability to age-related health problems increases along with the ageing population. The aim of the study was to investigate weighted blankets' effect on health regarding quality of life (QoL), sleep, nutrition, cognition, activities of daily living ADL and medication in older people living in nursing homes. METHODS: In total, 110 older people were involved in an intervention with weighted blankets, and 68 older people completed the intervention. Measures before and after were performed regarding quality of life; QoL-AD, EQ-VAS, sleep; MISS, nutrition; MNA, cognition; S -MMSE (ADL) and medication. Comparative statistical analyses were applied. RESULTS: After intervention with weighted blankets, health in general, such as QoL, improved. Sleep also improved significantly, especially with respect to waking up during the night. Nutrition was enhanced, health as a cognitive ability improved, and medication in the psychoanaleptic group decreased. The effect size varied between small and large. CONCLUSIONS: A weighted blanket seems to be an effective and safe intervention for older people in nursing homes, as several improvements were made regarding the health of older people.

Nursing staff's experiences of how weighted blankets influence resident's in nursing homes expressions of health.

PURPOSE: The most common treatment for resident's health problems is pharmacological. Little research has been done on how an intervention with a non-pharmacological method, such as a weighted blanket, Through the nursing staff view, we can learn how weighted blankets influence resident's health in nursing homes. The aim of this study was to explore nursing staff's experiences of how an intervention with weighted blankets influenced resident's expressions of health. METHODS: The study had a descriptive qualitative design with semi-structured interviews with 20 nursing staff working in nursing homes, and an inductive content analysis was applied. RESULTS: The nursing staff expressed that the weighted blanket positively influenced resident's health in the areas of sleep, physical activity, and psychological behaviour. The weighted blanket made them fall asleep faster, sleep was uninterrupted andthey felt more rested in the morning. The nursing staff observed an increased level of activity as the resident became more energetic . The nursing staff also experienced reduced negative psychological behaviours like anxiety and worrying. CONCLUSION: This study indicated that the weighted blanket changed the health expression of resident in several crucial areas. Deep pressure treatment indicates an alternative health-improved treatment for resident in nursing homes.

The impact of dance activities on the health of persons with Parkinson's disease in Sweden.

Purpose: Parkinson's disease (PD) is associated with motor and non-motor symptoms that negatively influence the person's quality of life. To reduce illness and increase quality of life, alternative treatments of PD such as dance might be experienced as beneficial. The aim of this study was to explore experiences of how a dance program in Sweden influences perceived physical, social, and emotional wellbeing in persons with PD.Method: A qualitative method with semi-structured interviews and content analysis was used, and 10 participants with variations in age, gender, and how long they had been diagnosed with the disease were interviewed.Results: The results showed that dancing was experienced as improving health, which implied feeling both calmed and excited, getting better sleep, and being able to move with more focus and freedom. The dance program was experienced as a social context through the importance of community, feelings of togetherness, and being able to compare oneself with others. Experiences of self-support included experiencing increased self-esteem and joy, but also a sense of being confirmed and having structure, which gave meaning to everyday life.Conclusions: To reduce illness and increase quality of life in persons with PD, it is important to investigate alternative treatment methods, and this study shows the importance of participating in a dance program in Sweden for the life situation and health of people with PD.

Welfare technology, ethics and well-being a qualitative study about the implementation of welfare technology within areas of social services in a Swedish municipality.

Purpose: Digitalization and e-health have potential to generate good quality, equal health, well-being and to develop and strengthen individuals' resources with the goal of increased independence and participation in society. The implementation of welfare technology requires knowledge of digitalization, as well as an awareness of its meaning in terms of ethical principles and ethical analysis. The purpose of this study was to describe ethical analysis concerning the implementation of welfare technology, in terms of both strategies and tools, within areas of social services in a Swedish municipality. Method: We followed a working model that focused on increased knowledge and experience in the implementation of welfare technology from an ethical perspective. In the data collection were observations, a questionnaire with open-ended questions and focus group discussions used. Results: The analysis showed that when welfare technology was introduced and implemented within the area of social services in a municipality, ethical awareness resulting from the conflicts between various interests and values had to be addressed. Conclusions: The ethical analysis improved implementation of strategies and tools in terms of facts and values, and invisible underlying values to the concept of well-being.

Novel Chemical Series of 5-Lipoxygenase-Activating Protein Inhibitors for Treatment of Coronary Artery Disease.

5-Lipoxygenase (5-LO)-activating protein (FLAP) inhibitors have proven to attenuate 5-LO pathway activity and leukotriene production in human clinical trials. However, previous clinical candidates have been discontinued and the link between FLAP inhibition and outcome in inflammatory diseases remains to be established. We here describe a novel series of FLAP inhibitors identified from a screen of 10k compounds and the medicinal chemistry strategies undertaken to progress this series. Compound 4i showed good overall properties and a pIC50 hWBfree of 8.1 and an lipophilic ligand efficiency of 5.2. Target engagement for 4i was established in dogs using ex vivo measurement of leukotriene B4 (LTB4) levels in blood with good correlation to in vitro potency. A predicted human dose of 280 mg b.i.d. suggests a wide margin to any identified in vitro off-target effects and sufficient exposure to achieve an 80% reduction of LTB4 levels in humans. Compound 4i is progressed to preclinical in vivo safety studies.

Experiences of living with persisting post-stroke dysphagia and of dysphagia management - a qualitative study.

PURPOSE: The aim of this study was to investigate people's experiences of living with dysphagia after stroke, and their experiences of dysphagia management. METHODS: The study design was qualitative, and an open-ended approach to data collection was used, with follow-up probing questions to gain more information as needed. Personal interviews were conducted with five persons who had persisting moderate to severe dysphagia after stroke, living in the south-west part of Sweden. The data were analysed with qualitative content analysis. RESULTS: When analysing the data, the following theme emerged; "Dysphagia impacts life situations negatively and requires individually adapted, long term support from skilled health care professionals". The theme consists of three categories: "Learning to manage dysphagia and its complications", "Professional support with dysphagia varies" and "Finding small moments of joy despite large restrictions in life situations". CONCLUSIONS: Findings indicated that people with dysphagia experienced a lack of support from health care professionals. Better health care support following discharge from hospital is required to ensure an optimal quality of life. Actions to achieve this may include developing national guidelines for adequate dysphagia follow-up and establishing multidisciplinary dysphagia teams in hospitals and long-term care facilities.

Subpixel x-ray imaging with an energy-resolving detector.

The detector pixel size can be a severe limitation in x-ray imaging of fine details in the human body. We demonstrate a method of using spectral x-ray measurements to image the spatial distribution of the linear attenuation coefficient on a length scale smaller than one pixel, based on the fact that interfaces parallel to the x-ray beam have a unique spectral response, which distinguishes them from homogeneous materials. We evaluate the method in a simulation study by simulating projection imaging of the border of an iodine insert with [Formula: see text] in a soft tissue phantom. The results show that the projected iodine profile can be recovered with an RMS resolution of 5% to 34% of the pixel size, using an ideal energy-resolving detector. We also validate this method in an experimental study by imaging an iodine insert in a polyethylene phantom using a photon-counting silicon-strip detector. The results show that abrupt and gradual transitions can be distinguished based on the transmitted x-ray spectrum, in good agreement with simulations. The demonstrated method may potentially be used for improving visualization of blood vessel boundaries, e.g., in acute stroke care.

Utilisation of formal and informal care and services at home among persons with dementia: a cross-sectional study.

BACKGROUND: The progression of dementia disease implies increasing needs for both informal and formal care and services but also risk of institutionalisation. To better adjust care and services in the phase preceding institutionalisation it is important to find out whether utilisation of formal and informal care and services is determined by increased needs and by who meets the needs. AIM: The aim was to compare persons with dementia (65+) with different levels of cognitive impairment, regarding utilisation of formal and informal care and service at home. METHODS: The participants consisted of 177 persons with dementia ≥65 years old and at risk of nursing home admission, divided into groups according to their cognitive function. Structured interviews were conducted based on questionnaires about type and amount of formal and informal care utilised, as well as questions regarding cognitive impairment, dependency in activities of daily living (ADLs) and neuropsychiatric symptoms. To analyse the data, descriptive and comparative statistics were used. RESULTS: The findings revealed that the group with severe dementia used significantly more help with ADLs and supervision in terms of time (number of hours and days) provided by the informal caregiver, compared with the group with moderate dementia. Utilisation of formal care and services was highest in the group with the most severe cognitive impairments (Standardized Mini-Mental State Examination score of <9). The group with severe dementia were more dependent in ADLs and had more neuropsychiatric symptoms (hallucinations and motor disturbances). They were younger and more often cohabitated with the informal caregiver, compared with the group with moderate dementia. CONCLUSION: This study shows that in the phase preceding institutionalisation the ADL and supervision needs due to progression of dementia appear to tend to be met first and foremost by the informal caregivers.

Trends in treatment with antipsychotic medication in relation to national directives, in people with dementia - a review of the Swedish context.

BACKGROUND: The aim of this study was to explore trends in treatment with antipsychotic medication in Swedish dementia care in nursing homes as reported in the most recent empirical studies on the topic, and to relate these trends to directives from the national authorities. METHODS: The study included two scoping review studies based on searches of electronic databases as well as the Swedish directives in the field. RESULTS: During the past decade, directives have been developed for antipsychotic medication in Sweden. These directives were generic at first, but have become increasingly specific and restrictive with time. The scoping review showed that treatment with antipsychotic drugs varied between 6% and 38%, and was higher in younger older persons and in those with moderate cognitive impairment and living in nursing homes for people with dementia. A decreasing trend in antipsychotic use has been seen over the last 15 years. CONCLUSIONS: Directives from the authorities in Sweden may have had an impact on treatment with antipsychotic medication for people with dementia. Treatment with antipsychotic medication has decreased, while treatment with combinations of psychotropic medications is common. National directives may possibly be even more effective, if applied in combination with systematic follow-ups.

Significance of quality of care for quality of life in persons with dementia at risk of nursing home admission: a cross-sectional study.

BACKGROUND: Quality of life in persons with dementia is, in large part, dependent on the quality of care they receive. Investigating both subjective and objective aspects of quality of care may reveal areas for improvement regarding their care, which information may ultimately enable persons with dementia to remain living in their own homes while maintaining quality of life. The aim of this study was to 1) describe self-reported quality of life in persons with dementia at risk of nursing home admission. 2) describe subjective and objective aspects of quality of care, 3) investigate the significance of quality of care for quality of life. METHODS: A cross-sectional interview study design was used, based on questionnaires about quality of life (QoL-AD) and different aspects of quality of care (CLINT and quality indicators). The sample consisted of 177 persons with dementia living in urban and rural areas in Skåne County, Sweden. Descriptive and comparative statistics (Mann-Whitney U-test) were used to analyse the data. RESULTS: Based upon Lawton's conceptual framework for QoL in older people, persons with pain showed significantly lower quality of life in the dimensions behavioural competence (p = 0.026) and psychological wellbeing (p = 0.006) compared with those without pain. Satisfaction with care seemed to have a positive effect on quality of life. The overall quality of life was perceived high even though one-third of the persons with dementia had daily pain and had had a weight loss of ≥4% during the preceding year. Furthermore, 23% of the persons with dementia had fallen during the last month and 40% of them had sustained an injury when falling. CONCLUSION: This study indicates need for improvements in home care and services for persons with dementia at risk for nursing home admission. Registered nurses are responsible for nursing interventions related to pain, patient safety, skin care, prevention of accidents, and malnutrition. Therefore, it is of great importance for nurses to have knowledge about areas that can be improved to be able to tailor interventions and thereby improve quality of care outcomes such as quality of life in persons with dementia living at home.