Outcomes from a proof-of-concept specialist lymphoedema clinic in the community.

The Health and Safety Execultive lymphoedema model of care was published in 2018 highlighting the lack of dedicated lymphoedema services in Ireland. This led to the introduction of a proof-of-concept primary care specialist lymphoedema clinic. The clinic was responsible for all patients from their county. A comprehensive dataset was gathered which included the patient's history for 1 year prior to their presentation at clinic and then 6 monthly. A quality of life tool (LymQoL) and a patient satisfaction survey were completed. Completed 1-year data showed a significant reduction in GP and public health nurse visits as well as a reduction in the occurrence of cellulitis and associated hospital admissions. All areas of quality of life were improved and patient satisfaction was either excellent (89%) or very good (11%). The 1-year findings strongly support the roll-out of specialist clinics to all regional health areas.

The All-Ireland Guidelines for the diagnosis, assessment and management of lymphoedema.

The last decade has produced a plethora of lymphoedema-based research. As such, a new All-Ireland Guideline for lymphoedema diagnosis, assessment and management was required to replace the 2008 CREST Guideline. A research team was commissioned to work with healthcare staff and service users following international research standards practice. An evidence-based clinical practice guideline was developed to aid clinicians in the diagnosis, assessment, and management of lymphoedema. Recommendations were formulated based on the evidence available to answer each clinical question and were assigned a grade based on the strength of the evidence. In the absence of sufficient evidence and in an effort to maximise clinical applicability, recommendations were also based on expert opinion, which was gathered via guideline member consensus. The recommendations from the guideline, which aim to provide healthcare professionals with clear, evidence-based guidance on the diagnosis, assessment and management of patients with all types of lymphoedema, should be communicated at all levels regarding responsibility for implementation in clinical care and service development. Audit should be a core component of the implementation. A budget impact analysis should be completed to determine additional costs required to fully implement the guideline.

A Snapshot of Lymphedema in Ireland: Results from LIMPRINT.

Background: To estimate the prevalence and impact of chronic edema (CE) in two Irish health care settings as part of LIMPRINT, an international study developed and co-ordinated by the International Lymphoedema Framework (ILF), and researched in Ireland by the National Lymphoedema Framework Ireland (NLFI). Methods and Results: Data were collected using clinical assessment tools previously validated by the ILF. Three hospital settings were chosen, both an in-patient and out-patient oncology unit in Galway and a vascular out-patient unit in Dublin. Patients attending an oncology clinic or in an in-patient ward on a specified day were invited to participate as desired, and all patients attending vascular out-patients for a 4-week period were included in the study. All patients were assessed for the presence of CE, and if present, patients were asked to answer several questionnaires regarding diagnosis, available services, quality of life, and wound care where appropriate. The collection of data was anonymized and was inputted to a central database (Clindex). A total of 152 patients were assessed, 76 from the oncology service and 76 from the vascular service. Eighty-seven (57%) patients were female and 65 (43%) patients were male. The mean age was 65 years with a range 15-93 years. Twenty-five patients (16%) had CE, 8 (11%) in the oncology service and 17 (22%) in the vascular service. All the oncology patients were normal weight while almost 60% (n = 10) of the vascular patients were obese. Two (25%) of the oncology patients had a history of cellulitis, whereas seven (41%) of the vascular patients had a history of cellulitis. Four of the oncology patients (50%) received full lymphedema management whereas two oncology patients (20%) received no treatment at all. In contrast, in the vascular group, only two patients (12%) received full lymphedema management. Eight patients (47%) were receiving no treatment at all and seven (41%) were in compression garments and received skin care advice only. Conclusion: Though number of patients are small, these results highlight the high prevalence of CE in both oncology and vascular service patients as well as the disparities in management. In addition, there is a high incidence of cellulitis reported that is possibly not surprising given the low number of patients receiving full lymphedema care. Good data collection is essential if we are to provide and fund a comprehensive service in the future.

Double diastereoselective, nucleophile-catalyzed aldol lactonizations (NCAL) leading to beta-lactone fused carbocycles and extensions to beta-lactone fused tetrahydrofurans.

A double diastereoselective variant of the nucleophile-catalyzed aldol lactonization (NCAL) process is described. This strategy delivers beta-lactone-fused carbocycles with good to excellent diastereoselectivities using cinchona alkaloid catalysts with enantioenriched aldehyde acids, which gave low diastereoselectivity based on substrate control alone. beta-Lactone-fused tetrahydrofurans are also prepared for the first time via the NCAL process; however, diastereoselectivity was only modestly improved when applying double diastereodifferentiation to these systems.

Asymmetric synthesis, structure, and reactivity of unexpectedly stable spiroepoxy-beta-lactones including facile conversion to tetronic acids: application to (+)-maculalactone A.

A novel class of small spirocyclic heterocycles, spiroepoxy-beta-lactones (1,4-dioxaspiro[2.3]-hexan-5-ones), is described that exhibit a number of interesting reactivity patterns. These spiroheterocycles, including an optically active series, are readily synthesized by epoxidation of ketene dimers (4-alkylidene-2-oxetanones) available from homo- or heteroketene dimerization. An analysis of bond lengths in these systems by X-ray crystallography and comparison to data for known spirocycles and those determined computationally suggest that anomeric effects in these systems may be more pronounced due to their rigidity and may contribute to their surprising stability. The synthetic utility of spiroepoxy-beta-lactones was explored, and one facile rearrangement identified under several conditions provides a three-step route from acid chlorides to optically active tetronic acids, ubiquitous heterocycles in bioactive natural products. The addition of various nucleophiles to these spirocycles leads primarily to addition at C5 and C2. The utility of an optically active spiroepoxy-beta-lactone was demonstrated in the concise, enantioselective synthesis of the antifouling agent, (+)-maculalactone A, which proceeds in five steps from hydrocinnamoyl chloride by way of a tetronic acid intermediate.

Synthesis, structure, and reactivity of unexpectedly stable spiroepoxy-beta-lactones obtained by epoxidation of 4-alkylidene-2-oxetanones.

We describe the first synthesis of spiroepoxy-beta-lactones obtained via epoxidation of ketene dimers. These compounds display unexpected stability that may be due to a double anomeric effect garnered from analysis of bond lengths by X-ray crystallography of one spirocycle in comparison to calculated bond lengths of related structures. These new strained intermediates display interesting reactivity leading to a butenolide, an alpha-hydroxyketone, a triol, an alpha-chloroketone, and an alpha-azidoketone.

Total synthesis of cytotoxic anhydrophytosphingosine pachastrissamine (jaspine B).

Starting from L-serine, a stereoselective synthesis of pachastrissamine, a structurally novel anhydrosphingosine derivative, is reported in this Letter. [structure: see text]