Screening for poverty and related social determinants to improve knowledge of and links to resources (SPARK): development and cognitive testing of a tool for primary care.

BACKGROUND: Healthcare organizations are increasingly exploring ways to address the social determinants of health. Accurate data on social determinants is essential to identify opportunities for action to improve health outcomes, to identify patterns of inequity, and to help evaluate the impact of interventions. The objective of this study was to refine a standardized tool for the collection of social determinants data through cognitive testing. METHODS: An initial set of questions on social determinants for use in healthcare settings was developed by a collaboration of hospitals and a local public health organization in Toronto, Canada during 2011-2012. Subsequent research on how patients interpreted the questions, and how they performed in primary care and other settings led to revisions. We administered these questions and conducted in-depth cognitive interviews with all the participants, who were from Saskatchewan, Manitoba, Ontario, and Newfoundland and Labrador. Cognitive interviewing was used, with participants invited to verbalize thoughts and feelings as they read the questions. Interview notes were grouped thematically, and high frequency themes were addressed. RESULTS: Three hundred and seventy-five individuals responded to the study advertisements and 195 ultimately participated in the study. Although all interviews were conducted in English, participants were diverse. For many, the value of this information being collected in typical healthcare settings was unclear, and hence, we included descriptors for each question. In general, the questions were understood, but participants highlighted a number of ways the questions could be changed to be even clearer and more inclusive. For example, more response options were added to the question of sexual orientation and the "making ends meet" question was completely reworded in light of challenges to understand the informal phrasing cited by English as a Second Language (ESL) users of the tool. CONCLUSION: In this work we have refined an initial set of 16 sociodemographic and social needs questions into a simple yet comprehensive 18-question tool. The changes were largely related to wording, rather than content. These questions require validation against accepted, standardized tools. Further work is required to enable community data governance, and to ensure implementation of the tool as well as the use of its data is successful in a range of organizations.

Acceptability of a short list of essential medicines to patients and prescribers: Multimethod study.

OBJECTIVE: To determine the acceptability of providing free access to only a short list of medicines used in the Carefully seLected and Easily Accessible at No charge Medications (CLEAN Meds) trial. DESIGN: A multimethod explanatory sequential design including interviews with trial participants and focus groups with prescribers. SETTING: Ontario. PARTICIPANTS: Participants in the intervention arm of the CLEAN Meds trial and primary care providers who prescribed medicines to those in the intervention arm of the trial. MAIN OUTCOME MEASURES: The number of trial participants in each prescription category (ie, prescribed no off-list medicine, prescribed 1 off-list medicine, or prescribed 2 or more off-list medicines) and the acceptability of the list to both participants and prescribers. RESULTS: There were 395 participants in the intervention group of the CLEAN Meds trial, but 16 participants withdrew consent or were not prescribed any medicines during the first 12 months of the trial, resulting in a total of 379 participants in the quantitative component of this study. Of the 2648 total prescriptions, 2349 (89%) were for medications that were on or had an equivalent covered by the list. Random sampling was used to select 5 participants to interview from each prescription category. A total of 19 prescribers participated in the focus groups. Themes from participant interviews included the following: having access to medicines on the list was a relief, participants trusted health care professionals to switch medicines and to decide which medicines should be on a publicly funded list, and a short list of essential medicines should be publicly funded. Major themes from the prescribers' focus groups related to the process of developing the list, support for the list, and publicly funding a short list of essential medicines in Canada. CONCLUSION: The consensus among trial participants and prescribers is that the short list of medicines used in the trial is comprehensive and provides access to medicines commonly prescribed.

Comparison of antibiotics included in national essential medicines lists of 138 countries using the WHO Access, Watch, Reserve (AWaRe) classification: a cross-sectional study.

BACKGROUND: The WHO Model List of Essential Medicines classified antibiotics into Access, Watch, and Reserve (AWaRe) categories for the treatment of 31 priority bacterial infections as a tool to facilitate antibiotic stewardship and optimal use. We compared the listing of antibiotics on national essential medicines lists (NEMLs) to those in the 2019 WHO Model List and the AWaRe classification database to determine the degree to which NEMLs are in alignment with the AWaRe classification framework recommended by WHO. METHODS: In this cross-sectional study, we obtained up-to-date (data after 2017) NEMLs from our Global Essential Medicines (GEM) database, WHO online resources, and individual countries' websites. From the 2019 WHO Model List we extracted, as a reference standard, a list of 37 antibiotics (44 unique antibiotics after accounting for combination drugs or therapeutically equivalent drugs as specified by WHO) that were considered essential in treating 31 of the most common and severe clinical infectious syndromes (priority infections). From the WHO AWaRe Classification Database, which contains commonly used antibiotics globally, we extracted a list of 122 AWaRe antibiotics listed by at least one country in the GEM database. We then assessed individual countries' NEMLs for listing of the 44 essential and 122 commonly used antibiotics, overall and according to AWaRe classification group. We also evaluated and summarised the listing of both first-choice and second-choice treatments for the 31 priority infections. A total coverage score was calculated for each country by assigning a treatment score of 0-3 for each priority infection on the basis of whether first-choice and second-choice treatments, according to the 2019 WHO Model List, were included in the country's NEML. Coverage scores were then compared against the score of the 2019 WHO Model List and across World Bank income groups and WHO regions. FINDINGS: As of July 7, 2020, we had up-to-date NEMLs for 138 countries. Of the 44 unique essential antibiotics, 24 were Access, 15 were Watch, and five were Reserve. The median number of total essential antibiotics listed across the 138 NEMLs was 26 (IQR 21-32). 102 (74%) countries listed at least 22 (50%) of the 44 essential antibiotics. The median number of total AWaRe antibiotics listed by the 138 countries was 35 (IQR 29-46), of Access antibiotics was 18 (16-21), of Watch antibiotics was 16 (11-22), and of Reserve antibiotics was one (0-2). 56 (41%) countries did not list any essential Reserve antibiotics. 131 (95%) countries had coverage scores of at least 60, equivalent to at least 75% of the score of the 2019 WHO Model List, which was 80. Nine (7%) countries listed fewer than 12 of 24 essential Access antibiotics, and seven (5%) did not list sufficient first-choice and second-choice treatments for priority infections (ie, they had coverage scores lower than 60). Of the 31 priority infections, acute neonatal meningitis and high-risk febrile neutropenia did not have enough listed treatments, with 82 (59%) countries listing no treatment for acute neonatal meningitis and 84 (61%) countries listing only a first-choice treatment, only a second-choice treatment, or no treatment for high-risk febrile neutropenia. Coverage scores differed between countries on the basis of World Bank income groups (p=0·025). INTERPRETATION: Our findings highlight potential changes to the antibiotics included in NEMLs that would increase adherence to international guidance aimed at effectively treating infectious diseases while addressing antimicrobial resistance. FUNDING: Canadian Institutes of Health Research and Ontario Strategy for Patient Oriented Research Support Unit.

Exploring the experiences of people in Ontario, Canada who have trouble affording medicines: a qualitative concept mapping study.

OBJECTIVES: The experiences of people who report cost-related medicine non-adherence are not well documented. We aimed to present experiences relating to accessing medicines reported by the participants in a randomised controlled trial of free medicine distribution. METHODS: The trial consisted of primary care patients from a large urban family practice and three rural family practices who reported cost-related medicine non-adherence. Participants were randomly allocated to continue their poor access (control) or to receive free and easily accessible medicines (intervention). As part of data collection for the first year of the trial, participants were asked closed and open-ended questions to assess their adherence to medication, health outcomes and their experiences in relation to medicine accessibility. We conducted a qualitative concept mapping study in which we analysed and summarised participants' responses to the open-ended question on a concept map to visually present their experiences relating to accessing medicines. RESULTS: Of the 524 trial participants contacted, 198 (38%) responded to the open-ended question. The concept map contains clusters that represent eight types of experiences of participants related to medicine access including stress, relationship with doctor, health impact, quality of life, sacrificing other essentials, medicines are expensive, financial impact and adherence. These experiences fall under two major themes, experiences relating to personal finances and experiences relating to well-being, which are bridged by a central cluster of adherence. CONCLUSIONS: The experiences shared by the participants demonstrate that access to medicines impacts people's finances and well-being as well as their adherence to prescribed medicines. These results indicate that effects on personal finances and general well-being should be measured for interventions and policy changes aimed at improving medicine access. TRIAL REGISTRATION NUMBER: This article is linked to the Carefully Selected and Easily Accessible at No Charge Medicines (CLEAN Meds) randomised controlled trial (trial registration number: NCT02744963).

d-Glycero-ß-d-Manno-Heptose 1-Phosphate and d-Glycero-ß-d-Manno-Heptose 1,7-Biphosphate Are Both Innate Immune Agonists.

d-Glycero-ß-d-manno-heptose 1,7-biphosphate (ß-HBP) is a novel microbial-associated molecular pattern that triggers inflammation and thus has the potential to act as an immune modulator in many therapeutic contexts. To better understand the structure-activity relationship of this molecule, we chemically synthesized analogs of ß-HBP and tested their ability to induce canonical TIFA-dependent inflammation in human embryonic kidney cells (HEK 293T) and colonic epithelial cells (HCT 116). Of the analogs tested, only d-glycero-ß-d-manno-heptose 1-phosphate (ß-HMP) induced TIFA-dependent NF-κB activation and cytokine production in a manner similar to ß-HBP. This finding expands the spectrum of metabolites from the Gram-negative ADP-heptose biosynthesis pathway that can function as innate immune agonists and provides a more readily available agonist of the TIFA-dependent inflammatory pathway that can be easily produced by synthetic methods.

Alternate synthesis to d-glycero-ß-d-manno-heptose 1,7-biphosphate.

d-glycero-ß-d-manno-heptose 1,7-biphosphate (HBP) is an enzymatic intermediate in the biosynthesis of the heptose component of lipopolysaccharide (LPS), and was recently revealed to be a pathogen-associated molecular pattern (PAMP) that allows detection of Gram-negative bacteria by the mammalian immune system. Cellular detection of HBP depends upon its stimulation of a cascade that leads to the phosphorylation and assembly of the TRAF-interacting with forkhead-associated domain protein A (TIFA), which activates the transcription factor NF-κB. In this note, an alternate chemical synthesis of HBP is described and its biological activity is established, providing pure material for further assessing and exploiting the biological activity of this compound.

O-Aminobenzoyl-S-nitrosoglutathione: A fluorogenic, cell permeable, pseudo-substrate for S-nitrosoglutathione reductase.

S-nitrosoglutathione reductase (GSNOR) is a multifunctional enzyme. It can catalyze NADH-dependent reduction of S-nitrosoglutathione (GSNO); as well as NAD+-dependent oxidation of hydroxymethylglutathione (HMGSH; an adduct formed by the spontaneous reaction between formaldehyde and glutathione). While initially recognized as the enzyme that is involved in formaldehyde detoxification, increasing amount of evidence has shown that GSNOR also plays a significant role in nitric oxide mediated signaling through its modulation of protein S-nitrosothiol signaling. In humans, GSNOR/S-nitrosothiols have been implicated in the etiology of several diseases including lung cancer, cystic fibrosis, asthma, pulmonary hypertension, and neuronal dysfunction. Currently, it is not possible to monitor the activity of GSNOR in live cells. In this article, we present a new compound, O-aminobenzoyl-S-nitrosoglutathione (OAbz-GSNO), which acts as a fluorogenic pseudo-substrate for GSNOR with an estimated Km value of 320µM. The weak OAbz-GSNO fluorescence increases by approximately 14 fold upon reduction of its S-NO moiety. In live cell imaging studies, OAbz-GSNO is readily taken up by primary pulmonary endothelial cells and localizes to the same perinuclear region as GSNOR. The perinuclear OAbz-GSNO fluorescence increases in a time dependent manner and this increase in fluorescence is abolished by siRNA knockdown of GSNOR or by treatment with GSNOR-specific inhibitors N6022 and C3. Taken together, these data demonstrate that OAbz-GSNO can be used as a tool to monitor the activity of GSNOR in live cells.