Copper-Mediated Dehydrogenative C(sp3)-H Borylation of Alkanes.

Borylations of inert carbon-hydrogen bonds are highly useful for transforming feedstock chemicals into versatile organoboron reagents. Catalysis of these reactions has historically relied on precious-metal complexes, which promote dehydrogenative borylations with diboron reagents under oxidant-free conditions. Recently, photoinduced radical-mediated borylations involving hydrogen atom transfer pathways have emerged as attractive alternatives because they provide complimentary regioselectivities and proceed under metal-free conditions. However, these net oxidative processes require stoichiometric oxidants and therefore cannot compete with the high atom economy of their precious-metal-catalyzed counterparts. Herein, we report that CuCl2 catalyzes radical-mediated, dehydrogenative C(sp3)-H borylations of alkanes with bis(catecholato)diboron under oxidant-free conditions. This is a result of an unexpected dual role of the copper catalyst, which promotes oxidation of the diboron reagent to generate an electrophilic bis-boryloxide that acts as an effective borylating agent in subsequent redox-neutral photocatalytic C-H borylations.

De Novo Synthesis of Dihydrobenzofurans and Indolines and Its Application to a Modular, Asymmetric Synthesis of Beraprost.

Dihydrobenzofurans and indolines are important constituents of pharmaceuticals. Herein, we describe a novel strategy for their construction in which the aromatic ring is created de novo through an inverse-electron demand Diels-Alder reaction and cheletropic extrusion sequence of a 2-halothiophene-1,1-dioxide with an enol ether/enamide, followed by aromatization. Unusually, the aromatization process proved to be highly challenging, but it was discovered that treatment of the halocyclohexadienes with a base effected an α-elimination-aromatization reaction. Mechanistic investigation of this step using deuterium-labeling studies indicated the intermediacy of a carbene which undergoes a 1,2-hydrogen shift and subsequent aromatization. The methodology was applied to a modular and stereoselective total synthesis of the antiplatelet drug beraprost in only 8 steps from a key enal-lactone. This lactone provided the core of beraprost to which both its sidechains could be appended through a 1,4-conjugate addition process (lower ω-sidechain), followed by de novo construction of beraprost's dihydrobenzofuran (upper α-sidechain) using our newly developed methodology. Additionally, we have demonstrated the breadth of our newly established protocol in the synthesis of functionalized indolines, which occurred with high levels of regiocontrol. According to density-functional theory (DFT) calculations, the high selectivity originates from attractive London dispersion interactions in the TS of the Diels-Alder reaction.

C-H Insertion in Dirhodium Tetracarboxylate-Catalyzed Reactions despite Dynamical Tendencies toward Fragmentation: Implications for Reaction Efficiency and Catalyst Design.

Rh-catalyzed C-H insertion reactions to form ß-lactones suffer from post-transition state bifurcations, with the same transition states leading to ketones and ketenes via fragmentation in addition to ß-lactones. In such a circumstance, traditional transition state theory cannot predict product selectivity, so we employed ab initio molecular dynamics simulations to do so and provide a framework for rationalizing the origins of said selectivity. Weak interactions between the catalyst and substrate were studied using energy decomposition and noncovalent interaction analyses, which unmasked an important role of the 2-bromophenyl substituent that has been used in multiple ß-lactone-forming C-H insertion reactions. Small and large catalysts were shown to behave differently, with the latter providing a means of overcoming dynamically preferred fragmentation by lowering the barrier for the recombination of the product fragments in the grip of the large catalyst active site cavity.

The Development of an International Oncofertility Competency Framework: A Model to Increase Oncofertility Implementation.

BACKGROUND: Despite international evidence about fertility preservation (FP), several barriers still prevent the implementation of equitable FP practice. Currently, oncofertility competencies do not exist. The aim of this study was to develop an oncofertility competency framework that defines the key components of oncofertility care, develops a model for prioritizing service development, and defines the roles that health care professionals (HCPs) play. MATERIALS AND METHOD: A quantitative modified Delphi methodology was used to conduct two rounds of an electronic survey, querying and synthesizing opinions about statements regarding oncofertility care with HCPs and patient and family advocacy groups (PFAs) from 16 countries (12 high and 4 middle income). Statements included the roles of HCPs and priorities for service development care across ten domains (communication, oncofertility decision aids, age-appropriate care, referral pathways, documentation, oncofertility training, reproductive survivorship care and fertility-related psychosocial support, supportive care, and ethical frameworks) that represent 33 different elements of care. RESULTS: The first questionnaire was completed by 457 participants (332 HCPs and 125 PFAs). One hundred and thirty-eight participants completed the second questionnaire (122 HCPs and 16 PFAs). Consensus was agreed on 108 oncofertility competencies and the roles HCPs should play in oncofertility care. A three-tier service development model is proposed, with gradual implementation of different components of care. A total of 92.8% of the 108 agreed competencies also had agreement between high and middle income participants. CONCLUSION: FP guidelines establish best practice but do not consider the skills and requirements to implement these guidelines. The competency framework gives HCPs and services a structure for the training of HCPs and implementation of care, as well as defining a model for prioritizing oncofertility service development. IMPLICATIONS FOR PRACTICE: Despite international evidence about fertility preservation (FP), several barriers still prevent the implementation of equitable FP practice. The competency framework gives 108 competencies that will allow health care professionals (HCPs) and services a structure for the development of oncofertility care, as well as define the role HCPs play to provide care and support. The framework also proposes a three-tier oncofertility service development model which prioritizes the development of components of oncofertility care into essential, enhanced, and expert services, giving clear recommendations for service development. The competency framework will enhance the implementation of FP guidelines, improving the equitable access to medical and psychological oncofertility care.

Prediction of 19F NMR Chemical Shifts for Fluorinated Aromatic Compounds.

Scaling factors are reported for use in predicting 19F NMR chemical shifts for fluorinated (hetero)aromatic compounds with relatively low levels of theory. Our recommended scaling factors were developed using a curated data set of 52 compounds, with 100 individual 19F shifts spanning a range of 153 ppm. With a maximum deviation of 6.5 ppm between experimental and computed shifts, or 4% of the range tested, these scaling factors allow for the assignment of chemical shifts to specific fluorines in multifluorinated aromatics. The utility of this approach is highlighted by several structural reassignments.

Home care in Australia: an integrative review.

The home care sector comprises one of Australia's fastest growing workforces, yet few papers capture the overall landscape of Australian home care. This integrative review investigates home care with the aim of better understanding care recipients and their needs, funding, and regulation; care worker skills, tasks, demographics, employment conditions, and training needs. Over 2,700 pieces of literature were analyzed to inform this review. Results suggest sector fragmentation and a home care workforce who, although well-placed to improve outcomes for care recipients, are in need of better training and employment support. Suggestions for future research regarding Australian home care include studies that combine both aged and disability aspects of care, more research around care recipients, priority needs and strategies for addressing them, and how best to prepare home care workers for their roles.

Chronic disease management support in Australian workplaces-low base, rising need.

ISSUE ADDRESSED: This study investigates the current nature, levels and perceived need for workplace support among mature age Australian workers with chronic illness. METHODS: A cross-sectional population survey was conducted via a double opt-in panel sample of Australian workers aged 45 years and older with one or more of six major chronic diseases (diabetes and/or chronic heart, kidney, lung, mental health and/or musculoskeletal conditions). RESULTS: Three hundred and fourteen respondents reported being in the workforce and having at least one of the chronic conditions under investigation, of which almost one third reported having more than one of the conditions. The findings reveal a number of considerable gaps in Australian workplace support for employees 45 years and older with chronic illness, including workplace flexibility, supportive policies and co-worker support. CONCLUSIONS: This research adds to a scarce existing literature base on workplace support for workers with chronic illness in Australia. Future research is needed to identify opportunities for effective public policy and implementation of workplace interventions to better support this cohort. SO WHAT?: If timely progress is not made in this area, the projected increase in the aged population and scheduled public policy changes impacting retirement age will multiply potential adverse effects on the health of employees with chronic illness and Australia's labour market productivity.

The Patient's Voice: Australian Health Care Quality and Safety Regulation from the Perspective of the Public.

The quality and safety of health care is a topic of permanent debate in the field of health services policy and regulation. Often absent from this debate, however, are the views and values of the public. These are excluded by a dominant narrative of health care regulation which understands the regulation of quality and safety in health care as principally a technical and instrumental undertaking. This approach constrains the application of law and legal regulation, devaluing their normative and expressive function in this field. In-part as a form of corrective, we offer an analysis based on recent survey data, of the attitudes and perceptions held by the Australian public towards stakeholder responsibility for, and the regulation of, health care quality and safety.

Application of Computational Chemical Shift Prediction Techniques to the Cereoanhydride Structure Problem-Carboxylate Complications.

Despite the vast array of techniques available to modern-day chemists, structural misassignments still occur. These misassignments are often only realized upon attempted synthesis, when the spectra of synthesized products do not match previously reported spectra. This was the case with marine natural product cereoanhydride. The originally proposed 7-membered ring anhydride (1) was shown to be incorrect, although a likely precursor to the correct structure (2) in both its laboratory synthesis and biosynthesis. Herein, in addition to showing how NMR computations could have been used to arrive at the correct structure, we show that the conversion of 1 to 2 is indeed energetically viable, and we highlight complications in predicting NMR chemical shifts for molecules with acidic protons.

Is health systems integration being advanced through Local Health District planning?

Objective Delivering genuine integrated health care is one of three strategic directions in the New South Wales (NSW) Government State Health Plan: Towards 2021. This study investigated the current key health service plan of each NSW Local Health District (LHD) to evaluate the extent and nature of health systems integration strategies that are currently planned. Methods A scoping review was conducted to identify common key principles and practices for successful health systems integration to enable the development of an appraisal tool to content assess LHD strategic health service plans. Results The strategies that are planned for health systems integration across LHDs focus most often on improvements in coordination, health care access and care delivery for complex at-risk patients across the care continuum by both state- and commonwealth-funded systems, providers and agencies. The most common reasons given for integrated activities were to reduce avoidable hospitalisation, avoid inappropriate emergency department attendance and improve patient care. Conclusions Despite the importance of health systems integration and finding that all NSW LHDs have made some commitment towards integration in their current strategic health plans, this analysis suggests that health systems integration is in relatively early development across NSW. What is known about the topic? Effective approaches to managing complex chronic diseases have been found to involve health systems integration, which necessitates sound communication and connection between healthcare providers across community and hospital settings. Planning based on current health systems integration knowledge to ensure the efficient use of scarce resources is a responsibility of all health systems. What does this paper add? Appropriate planning and implementation of health systems integration is becoming an increasingly important expectation and requirement of effective health systems. The present study is the first of its kind to assess the planned activity in health systems integration in the NSW public health system. NSW health districts play a central role in health systems integration; each health service plan outlines the strategic directions for the development and delivery of all state-funded services across each district for the coming years, equating to hundreds of millions of dollars in health sector funding. The inclusion of effective health systems integration strategies allows Local Health Districts to lay the foundation for quality patient outcomes and long-term financial sustainability despite projected increases in demand for health services. What are the implications for practice? Establishing robust ongoing mechanisms for effective health systems integration is now a necessary part of health planning. The present study identifies several key areas and strategies that are wide in scope and indicative of efforts towards health systems integration, which may support Local Health Districts and other organisations in systematic planning and implementation.

Right care, right place, right time: improving the timeliness of health care in New South Wales through a public-private hospital partnership.

Objective The overall aim of the study was to investigate and assess the feasibility of improving the timeliness of public hospital care through a New South Wales (NSW)-wide public-private hospital partnership. Methods The study reviewed the academic and professional grey literature, and undertook exploratory analyses of secondary data acquired from two national health data repositories informing in-patient access and utilisation across NSW public and private hospitals. Results In 2014-15, the NSW public hospital system was unable to deliver care within the medically recommended time frame for over 27400 people who were awaiting elective surgery. Available information indicates that the annual commissioning of 15% of public in-patient rehabilitation bed days to the private hospital system would potentially free up enough capacity in the NSW public hospital system to enable elective surgery for all public patients within recommended time frames. Conclusions The findings of the study justify a strategic whole-of-health system approach to reducing public patient wait times in NSW and highlight the need for research efforts aimed at securing a better understanding of available hospital capacity across the public and private hospital systems, and identifying and testing workable models that improve the timeliness of public hospital care. What is known about the topic? There are very few studies available to inform public-private hospital service partnerships and the opportunities available to improve timely health care access through such partnerships. What does this paper add? This paper has the potential to open and prompt timely discussion and debate, and generate further fundamental investigation, on public-private hospital service partnerships in Australia where opportunity is available to address elective surgery wait times in a reliable and effective manner. What are the implications for practitioners? The NSW Ministry of Health and its Local Health Districts have the potential to realise a key objective, namely to deliver the 'right care, in the right place, at the right time', through the core value of collaboration, using available infrastructure.

Cancer patient experience measures: An evidence review.

OBJECTIVES: This research investigates the instruments currently available to measure the cancer patient experience of health care. An investigation of the number of instruments, the domains covered by the instruments, and the structure and psychometric performance of instruments is undertaken. METHODS: A narrative synthesis approach is used to gather evidence from multiple studies and explain the findings. Purposely broad search terms and strategies are used to capture studies with cancer patients at all stages of disease and across a range of cancer types and health care settings. RESULTS: The majority of identified instruments were originally designed for the oncology field. Twelve of the studies developed new cancer patient measures; eight studies adapted existing or utilized items from existing instruments, and seven studies assessed the psychometric properties of existing instruments or assessed validated tools under different conditions (e.g., cross-cultural adaptation). The number of instruments assessing cancer patient experience that have sound psychometric properties across items was found to be low. The properties least tested are test-retest reliability, construct, convergent and discriminant validity, scale variability (floor/ceiling effects), and interpretability. CONCLUSION: This review examined 10 years of research on the development of instruments to measure the cancer patient experience of health care. It found that research in this area is still in early stages of development. Further inquiry based on development and validation of cancer patient experience measures is required to support improvements in cancer care based on the perspective of cancer patients.

Neonatal abstinence syndrome: evaluating the effectiveness of an evidence-based multidisciplinary care approach.

An evidence-based, multidisciplinary neonatal abstinence syndrome protocol was developed using a stepwise continuous quality improvement (CQI) approach with the goal of standardizing care procedures for these infants. A retrospective secondary data analysis was performed to evaluate the differential effects of each step of the CQI project on 4 key clinical outcome measures: length of stay (total and post-opioid wean), weaning time from opioids, and use of adjunct medications. Data were analyzed from 386 newborn infants with a diagnosis of neonatal abstinence syndrome undergoing treatment in a level III neonatal intensive care unit. After implementation of a pharmacologic weaning protocol as a foundational first step of the CQI project, the weaning time from opioids remained stable throughout each of the subsequent CQI steps (P = .905). The overall total neonatal intensive care unit length of stay was reduced by 10.35 days (P = .002), and the length of neonatal intensive care unit stay after completing wean from opioids was reduced by 2.79 days (P < .001). Use of adjunct medications also decreased from 30.1% of infants at the initiation of the CQI project to 24.5% at the completion of the project (P = .020). These findings indicate that this multidisciplinary treatment approach led to an overall improved efficiency of both opioid weaning and symptom management for these infants.

Selective hydroboration of electron-rich isocyanates by an NHC-copper(I) alkoxide.

The (IPr)CuOtBu catalysed reduction of 11 aryl and alkyl isocyanates with pinacolborane gave only the boraformamides, pinBN(R)C(O)H, in most cases. Overreduction, which hampers almost all isocyanate hydroborations, was restricted to electron poor aryl isocyanates (4-NC-C6H4NCO, 4-F3C-C6H4NCO, 3-O2N-C6H4NCO). Computational analysis showed stability of [(IPr)CuH]2, which was proposed to be the catalyst resting state, drives selectivity, suggesting an approach to prevent overreduction in future work. In the case of iPrNCO, formation of this species renders overreduction kinetically inaccessible. For 4-NC-C6H4NCO, however, the barrier height for the first step of over-reduction is much lower, even relative to [(IPr)CuH]2, resulting in unselective reduction.

Enriching health research through consumer involvement--learning through atypical exemplars.

OBJECTIVE: The goal of this exploratory study was to identify and describe notable cases of consumer involvement in Australian health research to generate insights and concepts, and assist others to develop and build capacity in this area. METHODS: In-depth interviews were conducted with nine organisations known to be active in this area. The interviews were supplemented with content analysis of relevant documentation to further examine involvement strategies. RESULTS: Key attributes that aid consumer involvement competence and contribute to success in this area are identified, including the availability of time, resources and supporting policies, principles and attitudes that securely back opportunities for consumers to be involved in meaningful ways. CONCLUSION: This study provides an important contribution to our knowledge and understanding of consumer involvement practice in Australian health research. The examples do not offer definitive approaches but rather highlights and lessons drawn from experiences in consumer involvement across a diverse range of organisations.

Status, challenges and facilitators of consumer involvement in Australian health and medical research.

BACKGROUND: The emergent international practice of involving consumers in health research is driven, in part, by the growing share of health research that can only be applied in and emerge from knowledge that is shaped by human values and societal contexts. This is the first investigation of its kind to identify the current prevalence, challenges, enabling factors and range of approaches to consumer involvement in health and medical research in Australia. METHODS: A nation-wide survey of research funding organisations and organisations that conduct research was performed during 2008-2009. RESULTS: Marked variation in consumer involvement experience and perceptions exists between research funders and researchers. Research funders were over eight times more likely than organisations conducting research to involve consumers in identifying research needs and prioritising research topics. Across both groups, practical and time constraints were reported as key challenges to involving consumers, while guidelines on consumer involvement and evidence of effect were the most important potential enablers. More than a third of research organisations indicated that when consumer involvement was a condition of research funding, it was an important facilitator of involvement. CONCLUSION: It is no longer simply enough to keep society informed of important scientific breakthroughs. If Australian health research is to take into account important social contexts and consequences, it must involve consumers. A set of minimum consumer involvement standards and associated guidelines, that are agreed and routinely adopted, could ensure that consumers and the Australian community they represent, are given an opportunity to shed light on experiences and local circumstance, and express views and concerns relevant to health research.

Primary care experience of older Australians with chronic illness.

This large (>1000) cross-sectional study investigates patient-reported primary care experiences of older people with chronic illness. Previous research has found that approximately half of patients with chronic illness receive optimal chronic illness care and outcomes in Australian general practice. A survey was administered via a double opt-in panel method to people aged ≥55 years who have one or more self-reported major chronic diseases (diabetes and/or chronic heart, kidney, lung, mental health and/or musculoskeletal conditions). Health professionals were found to be important to the majority of Australians surveyed. Well-known chronic illness support resources such as care plans and recalls/reminders were reported to be wanting by up to 50 per cent of respondents. Across all chronic illness groups, <42 per cent of respondents reported the provision of information on community resources and 25 per cent reported not having a sound understanding about their medications. Regular local surveys for older people with chronic illness would allow a timely understanding of primary care experiences, needs and preferences of this group, to support quality improvement and drive enhanced patient outcomes.