The Development of a Conceptual Framework for Providing Tailored Diabetes Care for Individuals Experiencing Homelessness: A Qualitative Study.

Homelessness results in barriers to effective diabetes self-management. Programs targeting individuals facing homelessness have refined strategies to address these barriers. We sought to develop a framework to characterize these strategies that could help multidisciplinary providers to better support these individuals. Semi-structured interviews were conducted with a purposive sample of health and social care providers working in diabetes or homelessness in five Canadian cities (n=96). Interview transcripts were analyzed through qualitative thematic analysis. Providers described three groups of approaches that enabled care for this population. Person-centered provider behaviours: This included tailoring care plans to accommodate individuals' situational constraints. Lower-barrier organizational structure: Providers developed specialized organizational processes to increase accessibility. Bridging to larger care systems: Strategies included providing access to support workers. Across diverse program structures, similar approaches are used to enhance diabetes care for individuals who are experiencing homelessness, highlighting tangible opportunities for mainstream services to better engage with this population.

Systematic Review and Meta-Analysis: Pearls for Interpretation, Appraisal, and Application in Clinical Practice.

Systematic reviews (SR) are a category of literature review that presents a comprehensive synthesis and analysis of all available literature evidence addressing a specific clinical question. Meta-analysis (MA) is a quantitative technique that is applied to data collected through SR that provides an estimate of an effect across a larger population. By synthesizing data from a large number of sources SR and MA often provide insights that cannot be obtained from single studies and can aid in clinical decision-making. However, these techniques are subject to important limitations. Both the validity and the usefulness of the results of an SR/MA depend on the methodological rigor used in preparing the review and the quality of included studies. In applying SR/MA to clinical decision-making the reader should be able to assess these features. Here we present an overview of important concepts in understanding SR and MA. We provide a general approach to interpretation and evaluation of an SR/MA, model the use of a critical appraisal tool for SR, and discuss the applications of SR and MA to clinical practice.

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.

A comparison of national essential medicines lists in the Americas.

OBJECTIVES: To compare national essential medicines lists (NEMLs) from countries in the Region of the Americas and to identify potential opportunities for improving those lists. METHODS: In June of 2017, NEMLs from 31 countries in the Americas were abstracted from documents included in a World Health Organization (WHO) repository. The lists from the Americas were compared to each other and to NEMLs from outside of the Americas, as well as with the WHO Model List of Essential Medicines, 20th edition ("WHO Model List") and the list of the Pan American Health Organization (PAHO) Regional Revolving Fund for Strategic Public Health Supplies ("Strategic Fund"). RESULTS: The number of differences between the NEMLs from the Americas and the WHO Model List were similar within those countries (median: 295; interquartile range (IQR): 265 to 347). The NEMLs from the Americas were generally similar to each other. While the NEMLs from the Americas coincided well with the Strategic Fund list, some medicines were not included on any of those NEMLs. All the NEMLs in the Americas included some medicines that were withdrawn due to adverse effects by a national regulatory body (median: 8 withdrawn medicines per NEML; IQR: 4 to 12). CONCLUSIONS: The NEMLs in the Americas were fairly similar to each other and to the WHO Model List and the Strategic Fund list. However, some areas of treatment and some specific medicines were identified that the countries should reassess when revising their NEMLs.

Acute poisoning in pregnancy: a province-wide perspective from a poison center.

Background: Poisoning in pregnancy can cause maternal and neonatal morbidity and mortality, but few data detail such events. Herein, we describe poisoning exposures in pregnant women identified by a large Canadian Poison Centre.Methods: This retrospective study evaluated poisoning exposures in pregnant women aged 12-60 years, reported to the Ontario Poison Centre from 2010 to 2017. Exposures were identified from the Poison Centre database by calls received, in which the patient was also reported to be pregnant. We collected patient demographics (age, trimester, and location), as well as information about the poisoning exposure (number and type of substances, route of exposure, reason for exposure, decontamination, and treatment recommendations).Results: There were 1716 cases of poisoning exposures during pregnancy over the eight-year study period, representing 0.28% of all 619,539 calls over the period. Median maternal age was 29 years (IQR 25-33), and exposures were most frequent in the second trimester of pregnancy (41%). Unintentional exposures (n = 1397) accounted for 81% of all calls. Of the 18% of calls (n = 305) for intentional exposures, 71% (n = 219) were suspected attempted suicides. Intentional exposures were more frequent in the first (OR 2.64, 95% CI 1.85-3.76) and second trimesters (OR 1.61, 95% CI 1.13-2.28), relative to third trimester. The associated risk of intentional exposures was more likely in women aged ≤19 years (OR 21.41, 95% CI 12.75-35.94) and 20-29 years (OR 3.72, 95% CI 2.70-5.14), relative to women ≥30 years old.Conclusions: Intentional poisoning exposures in pregnancy most commonly involve young women in the first two trimesters. Population-based studies are needed to further examine risk factors for overdose, poisoning, and self-harm in pregnancy, as well as perinatal outcomes.

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).

Potent dialkyl substrate-product analogue inhibitors and inactivators of α-methylacyl-coenzyme A racemase from Mycobacterium tuberculosis by rational design.

Rational approaches for the design of enzyme inhibitors furnish powerful strategies for developing pharmaceutical agents and tools for probing biological mechanisms. A new strategy for the development of gem-disubstituted substrate-product analogues as inhibitors of racemases and epimerases is elaborated using α-methylacyl-coenzyme A racemase from Mycobacterium tuberculosis (MtMCR) as a model enzyme. MtMCR catalyzes the epimerization at C2 of acyl-CoA substrates, a key step in the metabolism of branched-chain fatty acids. Moreover, the human enzyme is a potential target for the development of therapeutic agents directed against prostate cancer. We show that rationally designed, N,N-dialkylcarbamoyl-CoA substrate-product analogues inactivate MtMCR. Binding greatly exceeds that of the substrate, (S)-ibuprofenoyl-CoA, up to ∼250-fold and is proportional to the alkyl chain length (4-12 carbons) with the N,N-didecyl and N,N-didodecyl species having competitive inhibition constants with values of 1.9 ±â€¯0.2 µM and 0.42 ±â€¯0.04 µM, respectively. The presence of two decyl chains enhanced binding over a single decyl chain by ∼204-fold. Overall, the results reveal that gem-disubstituted substrate-product analogues can yield extremely potent inhibitors of an epimerase with a capacious active site.