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Evidence from clinical trials suggest anti-SARS-CoV-2 monoclonal antibodies (mABs) may reduce coronavirus disease 2019 (COVID-19)-related hospitalizations. The purpose of this study was to assess the real-world impact of mAB administration on COVID-19 hospitalization among patients 65 years or older. This was a retrospective, propensity-matched cohort study that included patients aged 65 years and older who presented to the emergency department (ED) within 10 days of symptom onset of mild to moderate COVID-19 infection. Outcomes were compared between those who did and did not receive mAB therapy. The primary endpoint was the rate of hospitalization for COVID-19 within 30 days of index ED visit. A total of 137 patients receiving mABs were matched to 137 controls. Hospitalization occurred in 2.9% of mAB-treated patients compared to 14.6% of patients of the standard of care (SOC) arm (odds ratio: 0.20 [95% CI: 0.07-0.59]). There were zero intubations and zero deaths compared to 3 (2.2%) and 2 (1.5%) in the SOC group. Among the 223 patients receiving mAB in the overall cohort, adverse drug events occurred in 10 (4.5%). Treatment with mAB therapy for mild to moderate COVID-19 was associated with a substantially reduced risk of hospitalization among patients at least 65 years of age.
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Tratamento Farmacológico da COVID-19 , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Antivirais , Estudos de Coortes , Hospitalização , Humanos , Estudos Retrospectivos , SARS-CoV-2RESUMO
AIMS: To evaluate the safety of irrigation water sources based on phenotypic antimicrobial resistance (AMR) in Enterococcus spp., a potential environmental reservoir for AMR determinants. METHODS AND RESULTS: Eleven sites representing fresh and brackish water rivers, ponds and reclaimed water, were sampled over 2 years. Samples (n = 333) yielded 198 unique isolates of Ent. faecalis and Ent. faecium which were tested for antimicrobial susceptibility by microbroth dilution. Species distribution was influenced by water type and season. Enterococcus faecalis was more likely found in freshwater rivers and in summer, and Ent. faecium in reclaimed water and in spring. Only 11% of isolates were pansusceptible, while 48.5% and 26.3% were single (SDR) and multidrug resistant (MDR), respectively. MDR was more likely detected in Ent. faecium than Ent. faecalis. Winter isolates were more likely than summer isolates to exhibit MDR than SDR. CONCLUSIONS: Enterococcus faecalis and Ent. faecium in surface and reclaimed water exhibited diverse phenotypic AMR and a low-level resistance to clinically important antimicrobials such as ampicillin, vancomycin and linezolid. SIGNIFICANCE AND IMPACT OF THE STUDY: Single and multidrug resistance in E. faecalis and E. faecium varied by season but not water type. Antimicrobial resistance prevalence can assist decisions on the safety of irrigation water sources for fresh produce crops.
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Enterococcus faecalis , Enterococcus faecium , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Estações do AnoRESUMO
BACKGROUND: Limited access to, understanding of, and trust in paper-based patient information is a key factor influencing paramedic decisions to transfer patients nearing end-of-life to hospital. Practical solutions to this problem are rarely examined in research. This paper explores the extent to which access to, and quality of, patient information affects the care paramedics provide to patients nearing end-of-life, and their views on a shared electronic record as a means of accessing up-to-date patient information. METHOD: Semi-structured interviews with paramedics (n = 10) based in the north of England, drawn from a group of health and social care professionals (n = 61) participating in a study exploring data recording and sharing practices in end-of-life care. Data were analysed using thematic analysis. RESULTS: Two key themes were identified regarding paramedic views of patient information: 1) access to information on patients nearing end-of-life, and 2) views on the proposed EPaCCS. Paramedics reported they are typically unable to access up-to-date patient information, particularly advance care planning documents, and consequently often feel they have little option but to actively treat and transport patients to hospital - a decision not always appropriate for, or desired by, the patient. While paramedics acknowledged a shared electronic record (such as EPaCCs) could support them to provide community-based care where desired and appropriate, numerous practical and technical issues must be overcome to ensure the successful implementation of such a record. CONCLUSIONS: Access to up-to-date patient information is a barrier to paramedics delivering appropriate end-of-life care. Current approaches to information recording are often inconsistent, inaccurate, and inaccessible to paramedics. Whilst a shared electronic record may provide paramedics with greater and timelier access to patient information, meaning they are better able to facilitate community-based care, this is only one of a series of improvements required to enable this to become routine practice.
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Pessoal Técnico de Saúde/psicologia , Registros Eletrônicos de Saúde/normas , Disseminação de Informação/métodos , Assistência Terminal/métodos , Pessoal Técnico de Saúde/educação , Inglaterra , Acessibilidade aos Serviços de Saúde/normas , Humanos , Entrevistas como Assunto/métodos , Pesquisa QualitativaRESUMO
OBJECTIVE: Few published studies have evaluated the clinical utility of new diagnostic criteria for avoidant/restrictive food intake disorder (ARFID), a DSM-5 reformulation of feeding and eating disorder of infancy or early childhood. We examined the prevalence of ARFID and inter-rater reliability of its diagnostic criteria in a pediatric gastrointestinal sample. METHOD: We conducted a retrospective chart review of 2,231 consecutive new referrals (ages 8-18 years) to 19 Boston-area pediatric gastroenterology clinics for evidence of DSM-5 ARFID. RESULTS: We identified 33 (1.5%) ARFID cases; 22 of whom (67%) were male. Most were characterized by insufficient intake/little interest in feeding (n = 19) or limited diet due to sensory features of the food (n = 7). An additional 54 cases (2.4%) met one or more ARFID criteria but there was insufficient information in the medical record to confer or exclude the diagnosis. Diagnostic agreement between coders was adequate (κ = 0.72). Common challenges were (i) distinguishing between diagnoses of ARFID and anorexia nervosa or anxiety disorders; (ii) determination of whether the severity of the eating/feeding disturbance was sufficient to warrant diagnosis in the presence of another medical or psychiatric disorder; and (iii) assessment of psychosocial impairment related to eating/feeding problems. DISCUSSION: In a pediatric treatment-seeking sample where ARFID features were common, cases meeting full criteria were rare, suggesting that the diagnosis is not over-inclusive even in a population where eating/feeding difficulties are expected.
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Manual Diagnóstico e Estatístico de Transtornos Mentais , Transtornos de Alimentação na Infância/diagnóstico , Transtornos de Alimentação na Infância/epidemiologia , Adolescente , Anorexia Nervosa/diagnóstico , Ansiedade/diagnóstico , Criança , Diagnóstico Diferencial , Feminino , Gastroenterologia , Humanos , Masculino , Prevalência , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
Our previous work demonstrated that the action encoding parietofrontal network, which is crucial in planning and executing motor tasks, is less active in prosthesis users who imitate movements of intact actors (mismatched limb) versus prosthesis users (matched limb). Such activation could have behavioral consequences in prosthesis users rehabilitating with intact therapists. The goal was to identify behavioral effects of matched versus mismatched limb action imitation in naïve users of prostheses. Intact subjects donned a specially adapted prosthetic device to simulate the wrist and forearm movement that transradial amputees experience. While electrogoniometry was recorded, non-amputated prosthesis users (NAPUs) observed and imitated demonstrations of a skillful motor task performed by either an intact actor or NAPU. We hypothesized that NAPUs would elicit less motion variability when performing matched versus mismatched imitation. Matched imitation resulted in a significant decrease in shoulder motion variability compared with mismatched imitation. The matched group also developed elbow motion patterns similar to the NAPU demonstrator, while the mismatched group attempted patterns similar to the intact demonstrator. This suggests a behavioral advantage to matched imitation when adapting to a prosthetic device, as it yielded more consistent movements and facilitated development of new motor patterns. Further, these results suggest that when prosthesis users are faced with the impossible task of imitating movements of an intact hand, they perform this action with greater variability and poorer technique. This work has implications on how prosthetic device operation is conveyed to persons with amputation as their clinical interactions often involve mismatched limb imitation.
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Membros Artificiais/psicologia , Movimento/fisiologia , Desempenho Psicomotor/fisiologia , Amplitude de Movimento Articular/fisiologia , Extremidade Superior/fisiologia , Adolescente , Adulto , Análise de Variância , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Fatores de Tempo , Extremidade Superior/inervação , Adulto JovemRESUMO
Introduction: Healthcare information is increasingly internet-based. Standards require websites to be 'perceivable, operable, understandable and robust' with relevant content for citizens in appropriate language. This study examined UK and international websites offering public healthcare information on advance care planning (ACP) using current recommendations for website accessibility and content and informed by a public engagement exercise. Methods: Google searches identified websites in English from health service providers, governmental or third sector organisations based in the UK and internationally. Target keywords that would be used by a member of the public informed the search terms. Data extraction used criterion-based assessment and web content analysis of the first two pages of each search result. Public patient representatives as key members of the multidisciplinary research team guided the development of the evaluation criteria. Results: A total of 1158 online searches identified 89 websites, reduced to 29 by inclusion/exclusion criteria. Most sites met international recommendations for knowledge/understanding about ACP. Differences in terminology, lack of information about ACP limitations and non-adherence to recommended reading levels, accessibility standards and translation options were apparent. Sites targeting members of the public used more positive, non-technical language than those for both professional and lay users. Conclusions: Some websites met accepted standards required to facilitate understanding and public engagement in ACP. Others could be improved significantly. Website providers have important roles and responsibilities in increasing people's understanding of their health conditions, future care options and ability to take an active role in planning for their health and care.
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Families, friends and communities have an important role to play in providing informal support when someone is faced with deteriorating health, caring responsibilities, death or bereavement. However, people can lack the confidence, skills and opportunities to offer this support. Public education is an example of a public health approach to palliative care that can help to develop individual skills and knowledge relating to these issues. In Scotland, the Scottish Partnership for Palliative Care (SPPC) has developed a new public education course called End of Life Aid Skills for Everyone (EASE) which aims to enable people to be more comfortable and confident supporting family/community members with issues they face during dying, death and bereavement. The aim was to design a course that imparts knowledge and skills while supporting development of social networks and avoids presenting professionals as the sole repository of expertise in the area of caring, dying and grieving. The intention was also to establish a sustainable delivery model that didn't rely too heavily on busy palliative care specialists and which had the potential to bring the course to a diversity of communities. This article outlines the development of the EASE course, from conception to delivery.
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This article critically examines how professional boundaries and hierarchies influence how end-of-life care is managed and negotiated between health and social care professionals. Our findings suggest there is uncertainty and lack of clarity amongst health and social care professionals regarding whose responsibility it is to engage, and document, the wishes of patients who are dying, which can lead to ambiguity in treatment decisions. We go on to explore the potential role of a new electronic system, designed to facilitate information sharing across professional boundaries, in shaping and bridging professional boundaries in the delivery of end-of-life care. We highlight potential negative impacts that may arise when health and social care groups are permitted varying levels of access to the system, and how this may be seen to reflect the value placed on their role in end-of-life care.
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Cuidados Paliativos na Terminalidade da Vida , Assistência Terminal , Humanos , Negociação , Papel Profissional , IncertezaRESUMO
OBJECTIVES: To explore current challenges in interdisciplinary management of end-of-life care in the community and the potential of an Electronic Palliative Care Co-ordination System (EPaCCS) to facilitate the delivery of care that meets patient preferences. DESIGN: Qualitative study using interviews and focus groups. SETTING: Health and Social Care Services in the North of England. PARTICIPANTS: 71 participants, 62 health and social care professionals, 9 patients and family members. RESULTS: Four key themes were identified: information sharing challenges; information sharing systems; perceived benefits of an EPaCCS and barriers to use and requirements for an EPaCCS. Challenges in sharing information were a source of frustration for health and social care professionals as well as patients, and were suggested to result in inappropriate hospital admissions. Current systems were perceived by participants to not work well-paper advance care planning (ACP) documentation was often unavailable or inaccessible, meaning it could not be used to inform decision-making at the point of care. Participants acknowledged the benefits of an EPaCCS to facilitate information sharing; however, they also raised concerns about confidentiality, and availability of the increased time and resources required to access and maintain such a system. CONCLUSIONS: EPaCCS offer a potential solution to information sharing challenges in end-of-life care. However, our findings suggest that there are issues in the initiation and documentation of end-of-life discussions that must be addressed through investment in training in order to ensure that there is sufficient information regarding ACP to populate the system. There is a need for further qualitative research evaluating use of an EPaCCS, which explores benefits and challenges, uptake and reasons for disparities in use to better understand the potential utility and implications of such systems.
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Cuidados Paliativos , Assistência Terminal , Eletrônica , Inglaterra , Humanos , Disseminação de Informação , Pesquisa QualitativaRESUMO
People's experiences of death, dying and bereavement are only partially determined by formal health and social care services. A broad-based alliance of organisations and individuals was established in Scotland in 2011 with the aim of influencing a wider range of social, cultural and other environmental factors which impact on people's experiences towards the end of life. Called Good Life, Good Death, Good Grief (GLGDGG) this alliance has grown and developed over the past 6 years, with a current diverse membership of over 1,100. A small central resource hosted by the Scottish Partnership for Palliative Care (SPPC) provides infrastructure, resources, promotion, events and advocacy for the alliance. GLGDGG's approach is primarily to engage, support and enhance the assets of communities, organisations and individuals who have the potential to improve the experience of death, dying and bereavement in Scotland. In addition to having very limited financial and staff resources the alliance has faced and responded to some other major challenges; the breadth and diversity of areas needing action; a lack of evidence to inform prioritisation and advocacy; how to operationalise theory in specific contexts; risk aversion on the part of some institutions in relation to death, dying and bereavement; how to measure change and demonstrate impact. The alliance has developed or used different frameworks for conceptualising and organising its work, but always with an emphasis on practical and adaptable approaches to action. Key successes of GLGDGG include growth in the size and diversity of the membership and the development of a portfolio of resources, activities and events. Amongst events developed is To Absent Friends, a people' festival of storytelling and remembrance which gives people across Scotland an excuse to remember, to tell stories, to celebrate and to reminisce about people who have died but who remain important to them. GLGDGG promotes the festival, encourages involvement, provides ideas and support, and organises a small number of events. However, the vast majority of the activity which takes place during the festival is conceptualised and carried out by individuals and organisations on their own initiative. GLGDGG has been successful in influencing public policies relating to death, dying and bereavement. The experience of GLGDGG suggests that: enthusiasm for action exists widely in Scottish society; local ownership is the key for local action; national infrastructure and off-the-shelf resources are valued by local actors; small resource can make a big difference to local work; national events can act as a catalyst for local action. The next phase of work is to scale up existing activities and initiatives and to base future plans on scoping work currently being undertaken.
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Colaboração Intersetorial , Cuidados Paliativos/organização & administração , Saúde Pública , Humanos , EscóciaRESUMO
Two experiments investigated the role of language in children's spatial recall performance. In particular, we assessed whether selecting an intrinsic reference frame could be improved through verbal encoding. Selecting an intrinsic reference frame requires remembering locations relative to nearby objects independent of one's body (egocentric) or distal environmental (allocentric) cues, and does not reliably occur in children under 5 years of age (Nardini, Burgess, Breckenridge, & Atkinson, 2006). The current studies tested the relation between spatial language and 4-year-olds' selection of an intrinsic reference frame in spatial recall. Experiment 1 showed that providing 4-year-olds with location-descriptive cues during (Exp. 1a) or before (Exp. 1b) the recall task improved performance both overall and specifically on trials relying most on an intrinsic reference frame. Additionally, children's recall performance was predicted by their verbal descriptions of the task space (Exp. 1a control condition). Non-verbally highlighting relations among objects during the recall task (Exp. 2) supported children's performance relative to the control condition, but significantly less than the location-descriptive cues. These results suggest that the ability to verbally represent relations is a potential mechanism that could account for developmental changes in the selection of an intrinsic reference frame during spatial recall.
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Idioma , Rememoração Mental/fisiologia , Desempenho Psicomotor/fisiologia , Percepção Espacial/fisiologia , Pré-Escolar , Feminino , Humanos , Masculino , Estimulação Luminosa/métodos , Distribuição AleatóriaRESUMO
Background Previous studies have demonstrated improved neurobehavioral outcomes when prosthesis users learn task-specific behaviors by imitating movements of prosthesis users (matched limb) compared with intact limbs (mismatched limb). Objective This study is the first to use a unique combination of neurophysiological and task performance methods to investigate prosthetic device training strategies from a cognitive motor control perspective. Intact nonamputated prosthesis users (NAPUs) donned specially adapted prosthetic devices to simulate the wrist and forearm movement that persons with transradial limb loss experience. The hypothesis is that NAPUs trained with matched limb imitation would show greater engagement of parietofrontal regions and reduced movement variability compared with their counterparts trained with a mismatched limb. Methods Training elapsed over 3 days comprised alternating periods of video demonstration observation followed by action imitation. At the beginning and end of the training protocol, participants performed a cued movement paradigm while electroencephalography and electrogoniometry data were collected to track changes in cortical activity and movement variability, respectively. Results Matched limb participants showed greater engagement of motor-related areas while mismatched limb participants showed greater engagement of the parietooccipital system. Matched limb participants also showed lower movement variability. Conclusions These results indicate that the type of limb imitated influences neural and behavioral strategies for novel prosthetic device usage. This finding is important, as customary prosthetic rehabilitation with intact therapists involves mismatched limb imitation that may exacerbate challenges in adapting to new motor patterns demanded by prosthesis use.
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Amputados/reabilitação , Movimento/fisiologia , Próteses e Implantes , Amplitude de Movimento Articular/fisiologia , Resultado do Tratamento , Extremidade Superior/inervação , Adolescente , Adulto , Análise de Variância , Fenômenos Biomecânicos , Eletroencefalografia , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Desempenho Psicomotor/fisiologia , Rotação , Adulto JovemRESUMO
INTRODUCTION: Public health palliative care is a term that can be used to encompass a variety of approaches that involve working with communities to improve people's experience of death, dying and bereavement. Recently, public health palliative care approaches have gained recognition and momentum within UK health policy and palliative care services. There is general consensus that public health palliative care approaches can complement and go beyond the scope of formal service models of palliative care. However, there is no clarity about how these approaches can be undertaken in practice or how evidence can be gathered relating to their effectiveness. Here we outline a scoping review protocol that will systematically map and categorise the variety of activities and programmes that could be classified under the umbrella term 'public health palliative care' and highlight the impact of these activities where measured. METHODS AND ANALYSIS: This review will be guided by Arksey and O'Malley's scoping review methodology and incorporate insights from more recent innovations in scoping review methodology. Sensitive searches of 9 electronic databases from 1999 to 2016 will be supplemented by grey literature searches. Eligible studies will be screened independently by two reviewers using a data charting tool developed for this scoping review. ETHICS AND DISSEMINATION: This scoping review will undertake a secondary analysis of data already collected and does not require ethical approval. The results will facilitate better understanding of the practical application of public health approaches to palliative care, the impacts these activities can have and how to build the evidence base for this work in future. The results will be disseminated through traditional academic routes such as conferences and journals and also policy and third sector seminars.
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Serviços de Saúde , Cuidados Paliativos , Saúde Pública , Assistência Terminal , Luto , Política de Saúde , Humanos , Projetos de Pesquisa , Reino UnidoRESUMO
BACKGROUND: Storytelling/remembrance can the reduce isolation of recently (and less recently) bereaved people, and are beneficial to participants. Traditional rituals and approaches which supported storytelling/remembrance are declining in Scotland. Pubs are hubs of social interaction and storytelling, especially for men. AIM: To explore the acceptability of beer mats in pubs as a prompt to storytelling and remembrance of people who have died, and to promote To Absent Friends, a peoples' festival of storytelling and remembrance. METHODS: 5 mats were designed - each had a carefully selected quotation or piece of trivia relating to loss or remembrance, plus a web link to www.toabsentfriends.org.uk. 20,000 mats were made available to order. Feedback regarding acceptability was elicited through conversation with bar tenders, direct observation and a questionnaire dispatched with some orders. A press release was issued. RESULTS: The mats were generally viewed as being acceptable. A local brewer distributed Approximately 15,000 mats to pubs across Edinburgh. The main Edinburgh newspaper ran a prominent article about the mats, the To Absent Friends Festival and the value of greater openness about death and dying. CONCLUSION: Beer mats are an acceptable way of introducing reflection on loss, grief and mortality into pubs. More research is needed to establish the effectiveness of the mats in prompting storytelling and remembrance.
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BACKGROUND: Social harms are caused in Scotland because of a cultural reluctance to be open about death, dying and bereavement, and there is growing recognition of the importance of promoting culture change relating to these issues. AIM: Good Life, Good Death, Good Grief (GLGDGG) was established to make Scotland a place where there is more openness about death, dying and bereavement. METHODS: Led and supported by the Scottish Partnership for Palliative Care, GLGDGG follows an "assets-based" approach-engaging, supporting and enhancing the assets of others. RESULTS: GLGDGG has: assisted in mobilising the assets of communities (eg through establishing small grants schemes and focal points of activity like To Absent Friends.) influenced policy (eg key messages incorporated within significant publications) found innovative ways of achieving impact on minimal resources (eg Death on the Fringe) CONCLUSION: A national alliance to encourage and guide activity is helpful in engaging communities and shaping policy.
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BACKGROUND: Communities play a key role in supporting members through difficult times, yet bereaved individuals often experience social isolation. Palliative care services should make efforts to develop community capacity to support bereaved people. Rituals of remembrance build solidarity. There are indications that many people would like to talk more openly about dead loved ones but are restricted by cultural norms. AIM: To create a time of year when remembering dead loved ones is socially accepted and supported within mainstream culture. METHODS: To Absent Friends, a People's Festival of Storytelling and Remembrance was held across Scotland, 1-7 November 2014. Efforts were made to promote the festival, but not to control the form of people's participation. RESULTS: A wide variety of events took place including community-based activities and high profile participation, for example from the Royal Scottish National Orchestra quartet, and the Scottish Rugby Union. CONCLUSION: A public festival in celebration and remembrance of dead loved ones has resonance for many people in Scotland and should grow in future years.
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Oxidised low density lipoprotein (LDL) may play a role in atherogenesis. We have investigated some of the mechanisms by which the thiol cysteine and the disulphide cystine can influence the oxidation of LDL by copper ions. Cysteine or cystine (100 microM) inhibited the oxidation of native LDL by copper in a simple phosphate buffer. One of the mechanisms by which cysteine (or more likely its oxidation products in the presence of copper) and cystine inhibited LDL oxidation was by decreasing the binding of copper to LDL (97% inhibition). Cysteine, but not cystine, rapidly reduced Cu(2+) to Cu(+). This may help to explain the antioxidant effect of cysteine as it may limit the amount of Cu(2+) that is available to convert alpha-tocopherol in LDL into the prooxidant alpha-tocopherol radical. Cysteine (but not cystine) had a prooxidant effect, however, toward partially oxidised LDL in the presence of a low copper concentration, which may have been due to the rapid breakdown of lipid hydroperoxides in partially oxidised LDL by Cu(+) generated by cysteine. To prove that cysteine can cause the rapid breakdown of lipid hydroperoxides in LDL, we enriched LDL with lipid hydroperoxides using an azo initiator in the absence of copper. Cysteine, but not cystine, increased the rate of lipid hydroperoxide decomposition to thiobarbituric acid-reactive substances (TBARS) in the presence of copper.
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Cobre/farmacologia , Lipoproteínas LDL/metabolismo , Antioxidantes/farmacologia , Cisteína/farmacologia , Cistina/farmacologia , Humanos , Técnicas In Vitro , Peroxidação de Lipídeos/efeitos dos fármacos , Oxidantes/farmacologia , Oxirredução/efeitos dos fármacosRESUMO
Canada is struggling with burgeoning health care access problems. At the same time, this nation may be overlooking an available resource to help address specific physician shortages. The services of more than 130 physician assistants in the Canadian Department of National Defense are used to off-set and amplify physician services. Their extensive education and training, along with their international experience in war-torn areas, dealing with wounded and ill military personnel, refugees, civilians, epidemics, and other health care problems make them particularly valuable assets. Yet, upon discharge from military service and reentry into the civilian sector, they are left without the legislation and formal recognition as a health care provider that would enable them to use these skills to help improve medical care access. This study provides the first description of the training and activity of Canadian physician assistants.
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Militares/educação , Assistentes Médicos/educação , Assistentes Médicos/tendências , Canadá , HumanosRESUMO
In this communication, we report the discovery of 1S (apremilast), a novel potent and orally active phosphodiesterase 4 (PDE4) and tumor necrosis factor-alpha inhibitor. The optimization of previously reported 3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-3-(3,4-dimethoxyphenyl)propionic acid PDE4 inhibitors led to this series of sulfone analogues. Evaluation of the structure-activity relationship of substitutions on the phthalimide group led to the discovery of an acetylamino analogue 1S, which is currently in clinical trials.