Disconnected relationships between primary care and community-based health and social services and system navigation for older adults: a qualitative descriptive study.

BACKGROUND: There are gaps in knowledge and understanding about the relationships between primary care and community-based health and social services in the context of healthy aging at home and system navigation. This study examined provider perspectives on: a) older adults' health and social needs; b) barriers to accessing services; c) the nature of relationships between primary care and health and social services; and d) ways to facilitate primary care and health and social services navigation to optimize older adults' health. METHODS: Four focus groups were conducted involving providers (n = 21) in: urban primary care clinics and health and social services organizations serving older adults in Hamilton, Ontario, Canada. Purposive sampling was employed to recruit community health and social services managers, directors or supervisors and primary health care providers in a Family Health Team via email. RESULTS: Health and social services needs were exacerbated for community-dwelling older adults with multiple chronic conditions. Strong family/caregiver social support and advocacy was often lacking. Access barriers for older adults included: financial challenges; lack of accessible transportation; wait times and eligibility criteria; and lack of programs to address older adults' needs. Having multiple providers meant that assessments among providers and older adults resulted in contradictory care pathways. Primary care and health and social services linkages were deficient and complicated by poor communication with patients and health literacy barriers. Primary care had stronger links with other health services than with community-based health and social services; primary care providers were frustrated by the complex nature of health and social services navigation; and care coordination was problematic. Health and social services referred older adults to primary care for medical needs and gathered patient information to gauge program eligibility, but not without challenges. CONCLUSIONS: Results point to strategies to strengthen primary care and health and social services system navigation for older adults including: using a person-focused approach; employing effective primary care and health and social services communication strategies; applying effective system navigation; building trust between primary care and health and social services providers; advocating for improved program access; and adapting services/programs to address access barriers and meet older adults' needs.

Experiences of integrating community volunteers as extensions of the primary care team to help support older adults at home: a qualitative study.

BACKGROUND: Increasing the integration of community volunteers into primary health care delivery has the potential to improve person-focused, coordinated care, yet the use of volunteers in primary care is largely unexplored. Health Teams Advancing Patient Experience: Strengthening Quality (Health TAPESTRY) is a multi-component intervention involving trained community volunteers functioning as extensions of primary care teams, supporting care based on older adults' health goals and needs. This study aimed to gain an understanding of volunteer experiences within the program and client and health care provider perspectives on the volunteer role. METHODS: This study used a qualitative descriptive approach embedded in a pragmatic randomized controlled trial. Participants included Health TAPESTRY volunteers, health care providers, volunteer coordinator, and program clients, all connected to two primary care practice sites in a large urban setting in Ontario, Canada. Data collection included semi-structured focus groups and interviews with all participants, and the completion of a measure of attitudes toward older adults and self-efficacy for volunteers. Qualitative data were inductively coded and analyzed using a constant comparative approach. Quantitative data were summarized using descriptive statistics. RESULTS: Overall, 30 volunteers and 64 other participants (clients, providers, volunteer coordinator) were included. Themes included: 1. Volunteer training: "An investment in volunteers"; 2. Intergenerational volunteer pairing: "The best of both worlds"; 3. Understanding the volunteer role and its scope: "Lay people involved in care"; 4. Volunteers as extensions of primary care teams: "Being the eyes where they live"; 5. The disconnect between volunteers and the clinical team: "Is something being done?"; 6. "Learning… all the time": Impacts on volunteers; and 7. Clients' acceptance of volunteers. CONCLUSIONS: This study showed that it is possible to integrate community volunteers into the primary care setting, adding human connections to deepen the primary care team's understanding of their patients. Program implementation suggestions that emerged included: using role play in training, making volunteer role boundaries and specifications clear, and making efforts to connect volunteers and the primary care team they are supporting. This exploration of stakeholder voices has the potential to help improve volunteer program uptake and acceptability, as well as volunteer recruitment, retention, and training. TRIAL REGISTRATION: For RCT: https://clinicaltrials.gov/ct2/show/NCT02283723, November 5, 2014.

Examining Interprofessional teams structures and processes in the implementation of a primary care intervention (Health TAPESTRY) for older adults using normalization process theory.

BACKGROUND: Many countries are engaged in primary care reforms to support older adults who are living longer in the community. Health Teams Advancing Patient Experience: Strengthening Quality [Health TAPESTRY] is a primary care intervention aimed at supporting older adults that involves trained volunteers, interprofessional teams, technology, and system navigation. This paper examines implementation of Health TAPESTRY in relation to interprofessional teamwork including volunteers. METHODS: This study applied Normalization Process Theory (NPT) and used a descriptive qualitative approach [1] embedded in a mixed-methods, pragmatic randomized controlled trial. It was situated in two primary care practice sites in a large urban setting in Ontario, Canada. Focus groups and interviews were conducted with primary care providers, clinical managers, administrative assistants, volunteers, and a volunteer coordinator. Data was collected at 4 months (June-July 2015) and 12 months (February-March 2016) after intervention start-up. Patients were interviewed at the end of the six-month intervention. Field notes were taken at weekly huddle meetings. RESULTS: Overall, 84 participants were included in 17 focus groups and 13 interviews; 24 field notes were collected. Themes were organized under four NPT constructs of implementation: 1) Coherence- (making sense/understanding of the program's purpose/value) generating comprehensive assessments of older adults; strengthening health promotion, disease prevention, and self-management; enhancing patient-focused care; strengthening interprofessional care delivery; improving coordination of health and community services. 2) Cognitive Participation- (enrolment/buy-in) tackling new ways of working; attaining role clarity. 3) Collective Action- (enactment/operationalizing) changing team processes; reconfiguring resources. 4) Reflective Monitoring- (appraisal) improving teamwork and collaboration; reconfiguring roles and processes. CONCLUSIONS: This study contributes key strategies for effective implementation of interventions involving interprofessional primary care teams. Findings indicate that regular communication among all team members, the development of procedures and/or protocols to support team processes, and ongoing review and feedback are critical to implementation of innovations involving primary care teams. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT02283723 November 5, 2014. Prospectively registered.

Navigation delivery models and roles of navigators in primary care: a scoping literature review.

BACKGROUND: Systems navigation provided by individuals or teams is emerging as a strategy to reduce barriers to care. Complex clients with health and social support needs in primary care experience fragmentation and gaps in service delivery. There is great diversity in the design of navigation and a lack of consensus on navigation roles and models in primary care. METHODS: We conducted a scoping literature review following established methods to explore the existing evidence on system navigation in primary care. To be included, studies had to be published in English between 1990 and 2013, and include a navigator or navigation process in a primary care setting that involves the community- based social services beyond the health care system. RESULTS: We included 34 papers in our review, most of which were descriptive papers, and the majority originated in the US. Most of the studies involved studies of individual navigators (lay person or nurse) and were developed to meet the needs of specific patient populations. We make an important contribution to the literature by highlighting navigation models that address both health and social service navigation. The emergence and development of system navigation signals an important shift in the recognition that health care and social care are inextricably linked especially to address the social determinants of health. CONCLUSIONS: There is a high degree of variance in the literature, but descriptive studies can inform further innovation and development of navigation interventions in primary care.

Managing multiple chronic conditions in the community: a Canadian qualitative study of the experiences of older adults, family caregivers and healthcare providers.

BACKGROUND: The prevalence of multiple chronic conditions (MCC) among older persons is increasing worldwide and is associated with poor health status and high rates of healthcare utilization and costs. Current health and social services are not addressing the complex needs of this group or their family caregivers. A better understanding of the experience of MCC from multiple perspectives is needed to improve the approach to care for this vulnerable group. However, the experience of MCC has not been explored with a broad sample of community-living older adults, family caregivers and healthcare providers. The purpose of this study was to explore the experience of managing MCC in the community from the perspectives of older adults with MCC, family caregivers and healthcare providers working in a variety of settings. METHODS: Using Thorne's interpretive description approach, semi-structured interviews (n = 130) were conducted in two Canadian provinces with 41 community-living older adults (aged 65 years and older) with three or more chronic conditions, 47 family caregivers (aged 18 years and older), and 42 healthcare providers working in various community settings. Healthcare providers represented various disciplines and settings. Interview transcripts were analyzed using Thorne's interpretive description approach. RESULTS: Participants described the experience of managing MCC as: (a) overwhelming, draining and complicated, (b) organizing pills and appointments, (c) being split into pieces, (d) doing what the doctor says, (e) relying on family and friends, and (f) having difficulty getting outside help. These themes resonated with the emotional impact of MCC for all three groups of participants and the heavy reliance on family caregivers to support care in the home. CONCLUSIONS: The experience of managing MCC in the community was one of high complexity, where there was a large gap between the needs of older adults and caregivers and the ability of health and social care systems to meet those needs. Healthcare for MCC was experienced as piecemeal and fragmented with little focus on the person and family as a whole. These findings provide a foundation for the design of care processes to more optimally address the needs-service gap that is integral to the experience of managing MCC.

Implementation and maintenance of patient navigation programs linking primary care with community-based health and social services: a scoping literature review.

BACKGROUND: Since the early 90s, patient navigation programs were introduced in the United States to address inequitable access to cancer care. Programs have since expanded internationally and in scope. The goals of patient navigation programs are to: a) link patients and families to primary care services, specialist care, and community-based health and social services (CBHSS); b) provide more holistic patient-centred care; and, c) identify and resolve patient barriers to care. This paper fills a gap in knowledge to reveal what is known about motivators and factors influencing implementation and maintenance of patient navigation programs in primary care that link patients to CBHSS. It also reports on outcomes from these studies to help identify gaps in research that can inform future studies. METHODS: This scoping literature review involved: i) electronic database searches; ii) a web site search; iii) a search of reference lists from literature reviews; and, iv) author follow up. It included papers from Canada, the United States, the United Kingdom, Australia, New Zealand, and/or Western Europe published between January 1990 and June 2013 if they discussed navigators or navigation programs in primary care settings that linked patients to CBHSS. RESULTS: Of 34 papers, most originated in the United States (n = 29) while the remainder were from the United Kingdom, Canada and Australia. Motivators for initiating navigation programs were to: a) improve delivery of health and social care services; b) support and manage specific health needs or specific population needs, and; c) improve quality of life and wellbeing of patients. Eleven factors were found to influence implementation and maintenance of these patient navigation programs. These factors closely aligned with the Diffusion of Innovation in Service Organizations model, thus providing a theoretical foundation to support them. Various positive outcomes were reported for patients, providers and navigators, as well as the health and social care system, although they need to be considered with caution since the majority of studies were descriptive. CONCLUSIONS: This study contributes new knowledge that can inform the initiation and maintenance of primary care patient navigation programs that link patients with CBHSS. It also provides directions for future research.

N-myristoyltransferase inhibitors as new leads to treat sleeping sickness.

African sleeping sickness or human African trypanosomiasis, caused by Trypanosoma brucei spp., is responsible for approximately 30,000 deaths each year. Available treatments for this disease are poor, with unacceptable efficacy and safety profiles, particularly in the late stage of the disease when the parasite has infected the central nervous system. Here we report the validation of a molecular target and the discovery of associated lead compounds with the potential to address this lack of suitable treatments. Inhibition of this target-T. brucei N-myristoyltransferase-leads to rapid killing of trypanosomes both in vitro and in vivo and cures trypanosomiasis in mice. These high-affinity inhibitors bind into the peptide substrate pocket of the enzyme and inhibit protein N-myristoylation in trypanosomes. The compounds identified have promising pharmaceutical properties and represent an opportunity to develop oral drugs to treat this devastating disease. Our studies validate T. brucei N-myristoyltransferase as a promising therapeutic target for human African trypanosomiasis.

Quality-based procedures in Ontario: exploring health-care leaders' responses.

AIM: To examine health-care leaders' initial response to the implementation of orthopaedic quality based procedures (QBPs) in hospitals across Ontario, Canada. BACKGROUND: In 2012, Ontario, Canada shifted 91 hospitals to a patient-based funding (PBF) approach. This approach funds health-care organisations based on the number of patients treated with select procedures known as QBPs. METHODS: An exploratory descriptive design was employed to better understand health-care leaders' early implementation experiences. Seventy organisational leaders from 20 hospitals participated in six focus groups and four interviews to discuss their initial responses to the implementation of two QBPs (primary unilateral hip replacement and primary unilateral knee replacement). Qualitative data underwent content analysis. FINDINGS: Three key major themes emerged; (1) responding to change, (2) leading the change and (3) managing the change. Within each of these themes, barriers and benefits were identified. CONCLUSION: Leaders are accepting of PBF and QBPs. However, challenges exist that require further exploration including the need for a strong infrastructure, accurate and timely clinical and financial data, and policies to prevent unintended consequences. IMPLICATIONS FOR NURSING MANAGEMENT: Implementing QBPs requires careful planning, adequate and appropriate resources, vertical and horizontal communication strategies, and policies to ensure that unintended consequences are avoided and positive outcomes achieved.

Respiratory flexibility in response to inhibition of cytochrome C oxidase in Mycobacterium tuberculosis.

We report here a series of five chemically diverse scaffolds that have in vitro activities on replicating and hypoxic nonreplicating bacilli by targeting the respiratory bc1 complex in Mycobacterium tuberculosis in a strain-dependent manner. Deletion of the cytochrome bd oxidase generated a hypersusceptible mutant in which resistance was acquired by a mutation in qcrB. These results highlight the promiscuity of the bc1 complex and the risk of targeting energy metabolism with new drugs.

Moving the agenda forward for cancer patient navigation: understanding volunteer and peer navigation approaches.

Across Canada, individuals diagnosed with cancer have identified concerns about access to services before, during, and following treatment, highlighting a very real uncertainty that exists about where to turn for information and assistance. Cancer patient navigation programs are emerging as effective interventions, well-equipped to meet these patients' diverse needs. While many provinces have initiated professionally led navigation services, little is known about the potential for volunteer-led navigation. This article highlights pilot programs in British Columbia, Ontario, and Newfoundland, where volunteers are engaged as lay or peer providers of cancer patient navigation services. By describing the recruitment, training, and role of the navigators within each program, the paper underscores the capacity for unique programs to work within current care frameworks across distinct communities. These programs provide an innovative approach to overcoming barriers and augmenting access to supportive care for cancer patients and their family members.

Peptidyl tRNA Hydrolase Is Required for Robust Prolyl-tRNA Turnover in Mycobacterium tuberculosis.

Enzymes involved in rescuing stalled ribosomes and recycling translation machinery are ubiquitous in bacteria and required for growth. Peptidyl tRNA drop-off is a type of abortive translation that results in the release of a truncated peptide that is still bound to tRNA (peptidyl tRNA) into the cytoplasm. Peptidyl tRNA hydrolase (Pth) recycles the released tRNA by cleaving off the unfinished peptide and is essential in most bacteria. We developed a sequencing-based strategy called copper sulfate-based tRNA sequencing (Cu-tRNAseq) to study the physiological role of Pth in Mycobacterium tuberculosis (Mtb). While most peptidyl tRNA species accumulated in a strain with impaired Pth expression, peptidyl prolyl-tRNA was particularly enriched, suggesting that Pth is required for robust peptidyl prolyl-tRNA turnover. Reducing Pth levels increased Mtb's susceptibility to tRNA synthetase inhibitors that are in development to treat tuberculosis (TB) and rendered this pathogen highly susceptible to macrolides, drugs that are ordinarily ineffective against Mtb. Collectively, our findings reveal the potency of Cu-tRNAseq for profiling peptidyl tRNAs and suggest that targeting Pth would open new therapeutic approaches for TB. IMPORTANCE Peptidyl tRNA hydrolase (Pth) is an enzyme that cuts unfinished peptides off tRNA that has been prematurely released from a stalled ribosome. Pth is essential in nearly all bacteria, including the pathogen Mycobacterium tuberculosis (Mtb), but it has not been clear why. We have used genetic and novel biochemical approaches to show that when Pth levels decline in Mtb, peptidyl tRNA accumulates to such an extent that usable tRNA pools drop. Thus, Pth is needed to maintain normal tRNA levels, most strikingly for prolyl-tRNAs. Many antibiotics act on protein synthesis and could be affected by altering the availability of tRNA. This is certainly true for tRNA synthetase inhibitors, several of which are drug candidates for tuberculosis. We find that their action is potentiated by Pth depletion. Furthermore, Pth depletion results in hypersensitivity to macrolides, drugs that are not active enough under ordinary circumstances to be useful for tuberculosis.

Development of a 2,4-Diaminothiazole Series for the Treatment of Human African Trypanosomiasis Highlights the Importance of Static-Cidal Screening of Analogues.

While treatment options for human African trypanosomiasis (HAT) have improved significantly, there is still a need for new drugs with eradication now a realistic possibility. Here, we report the development of 2,4-diaminothiazoles that demonstrate significant potency against Trypanosoma brucei, the causative agent of HAT. Using phenotypic screening to guide structure-activity relationships, potent drug-like inhibitors were developed. Proof of concept was established in an animal model of the hemolymphatic stage of HAT. To treat the meningoencephalitic stage of infection, compounds were optimized for pharmacokinetic properties, including blood-brain barrier penetration. However, in vivo efficacy was not achieved, in part due to compounds evolving from a cytocidal to a cytostatic mechanism of action. Subsequent studies identified a nonessential kinase involved in the inositol biosynthesis pathway as the molecular target of these cytostatic compounds. These studies highlight the need for cytocidal drugs for the treatment of HAT and the importance of static-cidal screening of analogues.

Lysyl-tRNA synthetase, a target for urgently needed M. tuberculosis drugs.

Tuberculosis is a major global cause of both mortality and financial burden mainly in low and middle-income countries. Given the significant and ongoing rise of drug-resistant strains of Mycobacterium tuberculosis within the clinical setting, there is an urgent need for the development of new, safe and effective treatments. Here the development of a drug-like series based on a fused dihydropyrrolidino-pyrimidine scaffold is described. The series has been developed against M. tuberculosis lysyl-tRNA synthetase (LysRS) and cellular studies support this mechanism of action. DDD02049209, the lead compound, is efficacious in mouse models of acute and chronic tuberculosis and has suitable physicochemical, pharmacokinetic properties and an in vitro safety profile that supports further development. Importantly, preliminary analysis using clinical resistant strains shows no pre-existing clinical resistance towards this scaffold.

A Web-Based Social Network Tool (GENIE) for Supporting Self-management Among High Users of the Health Care System: Feasibility and Usability Study.

BACKGROUND: Primary care providers are well positioned to foster self-management through linking patients to community-based health and social services (HSSs). This study evaluated a web-based tool-GENIE (Generating Engagement in Network Involvement)-to support the self-management of adults. GENIE empowers patients to leverage their personal social networks and increase their access to HSSs. GENIE maps patients' personal social networks, elicits preferences, and filters local HSSs from a community service directory based on patient's interests. Trained volunteers (an extension of the primary care team) conducted home visits and conducted surveys related to life and health goals in the context of the Health TAPESTRY (Teams Advancing Patient Experience: Strengthening Quality) program, in which the GENIE tool was implemented. GENIE reports were uploaded to an electronic medical record for care planning by the team. OBJECTIVE: This study aims to explore patients', volunteers', and clinicians' perceptions of the feasibility, usability, and perceived outcomes of GENIE-a tool for community-dwelling adults who are high users of the health care system. METHODS: This study involved 2 primary care clinician focus groups and 1 clinician interview (n=15), 1 volunteer focus group (n=3), patient telephone interviews (n=8), field observations that captured goal-action sequences to complete GENIE, and GENIE utilization statistics. The patients were enrolled in a primary care program-Health TAPESTRY-and Ontario's Health Links Program, which coordinates care for the highest users of the health care system. NVivo 11 (QSR International) was used to support qualitative data analyses related to feasibility and perceived outcomes, and descriptive statistics were used for quantitative data. RESULTS: Most participants reported positive overall perceptions of GENIE. However, feasibility testing showed that participants had a partial understanding of the tool; volunteer facilitation was critical to support the implementation of GENIE; clinicians perceived their navigation ability as superior to that of GENIE supported by volunteers; and tool completion took 39 minutes, which made the home visit too long for some. Usability challenges included difficulties completing some sections of the tool related to medical terminology and unclear instructions, limitations in the quality and quantity of HSSs results, and minor technological challenges. Almost all patients identified a community program or activity of interest. Half of the patients (4/8, 50%) followed up on HSSs and added new members to their network, whereas 1 participant lost a member. Clinicians' strengthened their understanding of patients' personal social networks and needs, and patients felt less social isolation. CONCLUSIONS: This study demonstrated the potential of GENIE, when supported by volunteers, to expand patients' social networks and link them to relevant HSSs. Volunteers require training to implement GENIE for self-management support, which may help overcome the time limitations faced by primary care clinicians. Refining the filtering capability of GENIE to address adults' needs may improve primary care providers' confidence in using such tools.

Spirocycle MmpL3 Inhibitors with Improved hERG and Cytotoxicity Profiles as Inhibitors of Mycobacterium tuberculosis Growth.

With the emergence of multi-drug-resistant strains of Mycobacterium tuberculosis, there is a pressing need for new oral drugs with novel mechanisms of action. A number of scaffolds with potent anti-tubercular in vitro activity have been identified from phenotypic screening that appear to target MmpL3. However, the scaffolds are typically lipophilic, which facilitates partitioning into hydrophobic membranes, and several contain basic amine groups. Highly lipophilic basic amines are typically cytotoxic against mammalian cell lines and have associated off-target risks, such as inhibition of human ether-à-go-go related gene (hERG) and IKr potassium current modulation. The spirocycle compound 3 was reported to target MmpL3 and displayed promising efficacy in a murine model of acute tuberculosis (TB) infection. However, this highly lipophilic monobasic amine was cytotoxic and inhibited the hERG ion channel. Herein, the related spirocycles (1-2) are described, which were identified following phenotypic screening of the Eli Lilly corporate library against M. tuberculosis. The novel N-alkylated pyrazole portion offered improved physicochemical properties, and optimization led to identification of a zwitterion series, exemplified by lead 29, with decreased HepG2 cytotoxicity as well as limited hERG ion channel inhibition. Strains with mutations in MmpL3 were resistant to 29, and under replicating conditions, 29 demonstrated bactericidal activity against M. tuberculosis. Unfortunately, compound 29 had no efficacy in an acute model of TB infection; this was most likely due to the in vivo exposure remaining above the minimal inhibitory concentration for only a limited time.

Perceptions of older adults in Ontario, Canada on the implementation and impact of a primary care programme, Health Teams Advancing Patient Experience: Strengthening Quality (Health TAPESTRY): a descriptive qualitative study.

OBJECTIVES: The aim of the study was to explore the perceptions of older adults on the implementation and impact of Health Teams Advancing Patient Experience: Strengthening Quality (Health TAPESTRY), a multicomponent primary care programme that seeks to improve care coordination for individuals through health-related goal-setting supported by trained lay volunteers who are an extension of an interprofessional team, and the use of technology to support communication among the team. DESIGN: This study used a qualitative descriptive design. SETTING: The setting for this study was two primary care practice sites located in a large urban area in Ontario, Canada. PARTICIPANTS: The sample consisted of community-dwelling older adults aged 70 years and older. Participants were recruited from a convenience sample obtained from 360 clients who participated in the 12-month Health TAPESTRY randomised controlled trial. METHODS: Semistructured interviews were conducted with 32 older adults either face-to-face or by telephone. Interviews were transcribed verbatim. Data were analysed using a constant comparative approach to develop themes. RESULTS: Older adults' perceptions about the Health TAPESTRY programme included (1) the lack of a clear purpose and understanding of how information was shared among providers, (2) mixed positive and negative perceptions of goal-setting and provider follow-up after inhome visits by volunteers, (3) positive impacts such as satisfaction with the primary care team, and (4) the potential for the programme to become a regular programme and applied to other communities and groups. CONCLUSIONS: Older adults living in the community may benefit from greater primary care support provided through enhanced team-based approaches. Programmes such as Health TAPESTRY facilitate opportunities for older adults to work with primary care providers to meet their self-identified needs. By exploring perceptions of clients, primary care programmes can be further refined and expanded for various populations.

Identification of GSK3186899/DDD853651 as a Preclinical Development Candidate for the Treatment of Visceral Leishmaniasis.

The leishmaniases are diseases that affect millions of people across the world, in particular visceral leishmaniasis (VL) which is fatal unless treated. Current standard of care for VL suffers from multiple issues and there is a limited pipeline of new candidate drugs. As such, there is a clear unmet medical need to identify new treatments. This paper describes the optimization of a phenotypic hit against Leishmania donovani, the major causative organism of VL. The key challenges were to balance solubility and metabolic stability while maintaining potency. Herein, strategies to address these shortcomings and enhance efficacy are discussed, culminating in the discovery of preclinical development candidate GSK3186899/DDD853651 (1) for VL.

Feasibility study of goal setting discussions between older adults and volunteers facilitated by an eHealth application: development of the Health TAPESTRY approach.

BACKGROUND: In keeping with the changing needs of the Canadian population, primary care systems need to become more person-focused in providing quality care to older adults. As part of Health TAPESTRY, a complex intervention to strengthen primary care for older adults, a goal setting exercise was developed and tested in an initial feasibility study, intended to foster collaboration between patients and providers. METHODS: Participants-clinic clients-were recruited from the McMaster Family Health Team in Hamilton, Ontario. Five participants took part in the goal setting feasibility study phase I, which tested the functionality of a technology-enabled goal setting exercise between older adults and volunteers. Based on observations and feedback from volunteers, interprofessional team members, and older adults, the exercise was refined to include a guided survey and goals report. The goal setting survey is a list of probing questions designed based on SMART (specific, measurable, attainable, relevant, timely) goal setting strategies and goal attainment scaling (GAS). This was used in phase II, carried out with 16 participants, where the feasibility of goal setting and goal attainment with support from volunteers and interprofessional teams was tested. Volunteers carried out the goal setting survey via a tablet computer, a report of client goals was generated and sent to interprofessional teams, and client goals were discussed during clinic huddles. At 6 months of follow-up, clients self-evaluated their progress using GAS. RESULTS AND DISCUSSION: The goal setting exercise in phase I took an average of 24:45 (SD 11:42) minutes and yielded a diverse set of life and health goals. Goals identified by older adults were primarily focused on the maintenance of a certain level of activity or health state. Phase I work resulted in important changes to the goal setting process (e.g., asking about goal setting later in conversation, changing wording of questions) and development of a summary report of goals sent to the interprofessional team. In phase II, 44 goals were set by 16 participants during an average 7:23 (SD 4:26) minute discussion. Of these goals, 43.9% were characterized as health goals while 63.4% were characterized as life goals. Under the umbrella of Life goals, productivity featured most prominently at 22.9% of all goals. Goal attainment was not measured in phase I. In phase II, clients had an average weighted goal attainment score of 51.5. Considering client preferences for one goal over another, 68.8% of clients, on average, at least partially achieved the goals they had set. CONCLUSION: Goal setting as part of the Health TAPESTRY approach was feasible and provided interprofessional teams with client narratives that helped improve care management for older adults. The overall intervention-including the refined goal setting component-is being scaled and evaluated in a pragmatic randomized controlled trial.

Identification of Morpholino Thiophenes as Novel Mycobacterium tuberculosis Inhibitors, Targeting QcrB.

With the emergence of multidrug-resistant strains of Mycobacterium tuberculosis there is a pressing need for new oral drugs with novel mechanisms of action. Herein, we describe the identification of a novel morpholino-thiophenes (MOT) series following phenotypic screening of the Eli Lilly corporate library against M. tuberculosis strain H37Rv. The design, synthesis, and structure-activity relationships of a range of analogues around the confirmed actives are described. Optimized leads with potent whole cell activity against H37Rv, no cytotoxicity flags, and in vivo efficacy in an acute murine model of infection are described. Mode-of-action studies suggest that the novel scaffold targets QcrB, a subunit of the menaquinol cytochrome c oxidoreductase, part of the bc1-aa3-type cytochrome c oxidase complex that is responsible for driving oxygen-dependent respiration.