Search

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.

Introduction: Health care providers face a multitude of challenges in providing care to patients with diabetes who are experiencing homelessness. Considering the unique circumstance faced by this population, mainstream services must be adapted and tailored to meet patients’ needs. The objective of this study was to explore both the barriers faced by providers and programs in offering comprehensive diabetes care to these patients, and their suggested areas for improvement. Methods: We conducted semi-structured interviews with providers who care for patients who have diabetes and/or who experience homelessness. Participants included primary care providers, specialist physicians, dietitians, shelter staff, outreach workers, and diabetes educators in five Canadian centres (n=96). Responses were analyzed using qualitative thematic analysis. Results: Barriers most frequently cited by providers were a lack of resources for staff. Other challenges included policy barriers (restrictions on billing codes, care professionals’ scope of practice, and the structure of financial support for this population), duplication of services, and alternative priorities of care. Participants identified several strategies to improve care, which targeted the following spheres: location of service provision and coordination of care, policy changes, and extending funding and resources for staff, such as augmented funding to hire allied health professionals in outpatient settings and increasing outreach capabilities. Conclusion: Programs that strive to address the unique needs of clients experiencing homelessness face numerous challenges. Unique potential solutions to these barriers, such as service provision in a convenient location involving social and health services, incorporating allied health care providers in care to a greater extent, and updating policies to reflect the social complexity of the population can improve diabetes care.

Summary 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.

To compare national essential medicines lists (NEMLs) from countries in the Region of the Americas and to identify potential opportunities for improving those lists.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, 20The 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).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.Comparar las listas nacionales de medicamentos esenciales (LNME) de países de la Regi delas Américas e identificar oportunidades potenciales de mejorarlas.En junio de 2017, se extrajeron las LNME de 31 países de la Regi de documentos incluidos en un repositorio de la Organizaci Mundial de la Salud (OMS). Se compararon estas listas entre sí y con listas de fuera de la Regi, así como con la Lista Modelo de Medicamentos Esenciales de la OMS (20El nero de diferencias entre las LNME de la Regi y la Lista Modelo de la OMS fue similar dentro de esos países (mediana: 295; rango intercuartil (RIC): 265 a 347). Las LNME de la Regi en general fueron similares entre sí. Si bien las LNME de la Regi mostraron una coincidencia adecuada con la lista del Fondo Rotatorio, algunos medicamentos no estaban incluidos en ninguna de las primeras. Todas las LNME de la Regi incluían algunos medicamentos que habían sido retirados del mercado por las autoridades regulatorias nacionales debido a efectos adversos (mediana: 8 medicamentos retirados en cada lista; RIC: 4 a 12).Las LNME en la Región de las Américas son bastante similares entre sí y con la Lista Modelo de la OMS y la lista del Fondo Rotatorio de la OPS. Sin embargo, se identificaron algunas áreas terapéuticas y algunos medicamentos específicos que los países deberían reevaluar al revisar sus LNME.Comparar as listas nacionais de medicamentos essenciais (LNME) dos países da Região das Américas e identificar oportunidades potenciais de melhoria.Em junho de 2017, as LNME de 31 países das Américas foram obtidas de documentos incluídos em um repositio da Organização Mundial da Sae (OMS). As listas foram comparadas entre si, com listas de fora da Região, com a Lista Modelo de Medicamentos Essenciais da OMS (20As LNME dos países das Américas eram semelhantes entre si e apresentaram um nero semelhante de diferenças em relação à Lista Modelo da OMS (mediana: 295; intervalo interquartil: 265-347). Embora as LNME nas Américas fossem altamente consistentes com a lista do Fundo Estratégico, alguns dos medicamentos do Fundo não apareciam em nenhuma dessas LNME. Todas as LNME nas Américas incluíam medicamentos retirados do mercado por algum organismo regulador nacional devido a efeitos adversos (mediana: 8 medicamentos retirados por LNME; intervalo interquartil: 4-12).As LNME nas Américas são bastante semelhantes entre si e próximas da Lista Modelo da OMS e da lista do Fundo Estratégico. Contudo, foram identificadas algumas áreas terapêuticas e alguns medica mentos específicos que os países deveriam reavaliar ao rever as suas LNME.

Background: Opioid overdoses have been an increasing public health problem in North America for several years. Supervised consumption sites (SCSs) – hygienic and medically supervised spaces to use illicit substances – are one harm reduction strategy intended to decrease morbidity and mortality, with literature suggesting they reduce emergency department (ED) visits, overdoses, and deaths. Calgary’s sole SCS opened in 2017 and received over 6000 monthly visits prior to the COVID-19 pandemic, but recent provincial policy has jeopardized its longevity. To our knowledge, there has not been an evaluation of its effectiveness, so we sought to investigate its impact on opioid-related ED visits. Methods: Calgary’s SCS was not implemented in our institution specifically. It was implemented for the Calgary region by Safeworks, an outreach program under the Alberta Health Services (AHS) umbrella, after obtaining a Health Canada exemption and funding from the provincial government. Implementation also required close collaboration with public services (e.g., Calgary Police Services) and the municipal government. The Safeworks SCS opened on October 30, 2017 and remains the only supervised consumption facility in the Calgary region. It is currently located in the Sheldon Chumir Health Centre in downtown Calgary. In addition to supervised consumption, the SCS also offers all clients harm reduction supplies (e.g., naloxone kits), health services (e.g., testing and counselling for sexually transmitted infections, referral to Calgary Opioid Dependency Program), education (e.g., vein care), and access to social services (e.g., housing supports). Evaluation Methods: This was a retrospective observational study examining the impact of the SCS on two markers of opioid related morbidity (EMS responses and ED visits). Calgary EMS responses, wherein the opioid overdose protocol was activated or naloxone was administered, were queried from the Alberta Health Services (AHS) information management database. ED visits due to opioid toxicity were queried from AHS using ICD-10 codes T40.0-T40.4 and T40.6. Data was collected from January 2014 to February 2020. The impact of Calgary’s SCS was analyzed with an interrupted time series using ordinary least squares regression with Newey-West standard errors. Results: Our data query yielded 9208 EMS responses and 8442 ED visits related to opioid use over the 74-month period. There were no months with missing data. Prior to the opening of Calgary’s SCS, monthly EMS responses and ED visits increased significantly by 3.69 [3.08, 4.30] and 7.09 [5.92, 8.26] visits/month, respectively (p

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 ± 0.2 μM and 0.42 ± 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.

ObjectivesThe 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.MethodsThe 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.ResultsOf 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.ConclusionsThe 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 numberThis article is linked to the Carefully Selected and Easily Accessible at No Charge Medicines (CLEAN Meds) randomised controlled trial (trial registration number: NCT02744963).