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Abstract Background Potentially inappropriate medication use is prevalent among older adults in primary care, leading to increased morbidity, adverse drug reactions, hospitalizations, and mortality. This study aimed to develop and validate a tool for identifying PIMs in older adults within the primary care setting. The tool is composed of a list of criteria and was created based on consensus among experts from three Spanish-speaking countries, including two from Latin America. Methods A literature review was conducted to identify existing tools, and prescription patterns were evaluated in a cohort of 36,111 older adults. An electronic Delphi method, consisting of two rounds, was used to reach a formal expert consensus. The panel included 18 experts from Spain, Colombia, and Argentina. The content validity index, validity of each content item, and Kappa Fleiss statistical measure were used to establish reliability. Results Round one did not yield a consensus, but a definitive consensus was reached in round two. The resulting tool consisted of a list of 5 general recommendations per disease, along with 33 criteria related to potential problems, recommendations, and alternative therapeutic options. The overall content validity of the tool was 0.87, with a Kappa value of 0.69 (95% CI 0.64—0.73; Substantial). Conclusions The developed criteria provide a novel list that allows for a comprehensive approach to pharmacotherapy in older adults, intending to reduce inappropriate medication use, ineffective treatments, prophylactic therapies, and treatments with an unfavorable risk–benefit ratio for the given condition. Further studies are necessary to evaluate the impact of these criteria on health outcomes.

As the United Nations General Assembly prepares to convene its second high-level meeting on antimicrobial resistance (AMR) in September 2024, it is crucial to reflect on the progress made since the first meeting in 2016 and the urgent need for immediate action [...]

The spread of antimicrobial resistance (AMR) is a global challenge. Close and continuous surveillance for quick detection of AMR can be difficult, especially in remote places. This narrative review focuses on the contributions of pharmacovigilance (PV) as an auxiliary tool for identifying and monitoring the ineffectiveness, resistance, and inappropriate use of antibiotics (ABs). The terms “drug ineffective”, “therapeutic failure”, “drug resistance”, “pathogen resistance”, and “multidrug resistance” were found in PV databases and dictionaries, denoting ineffectiveness. These terms cover a range of problems that should be better investigated because they are useful in warning about possible causes of AMR. “Medication errors”, especially those related to dose and indication, and “Off-label use” are highlighted in the literature, suggesting inappropriate use of ABs. Hence, the included studies show that the terms of interest related to AMR and use are not only present but frequent in PV surveillance programs. This review illustrates the feasibility of using PV as a complementary tool for antimicrobial stewardship activities, especially in scenarios where other resources are scarce.

Abstract Hepatic injury has been documented in patients with coronavirus disease 2019 (COVID-19). However, pharmacotherapy can frequently impact liver alterations, given the known hepatotoxic potential of drugs not effective to treat COVID-19. The objective of the present study was to evaluate reports of suspected liver reactions to drugs used for treating COVID-19, compare their use for other indications among patients with COVID-19, and assess possible interactions between them. We obtained reports on drugs used to treat COVID-19 (tocilizumab, remdesivir, hydroxychloroquine, and/or lopinavir/ritonavir), registered on June 30, 2020, from the Food and Drug Administration Adverse Event Reporting System (FAERS) Public Dashboard. We then analyzed the risk of developing liver events with these drugs by calculating the reported odds ratios (ROR). We identified 662, 744, and 1381 reports related to tocilizumab, lopinavir/ ritonavir, and hydroxychloroquine use, respectively. The RORs (95% confidence intervals) were 6.32 (5.28-7.56), 6.12 (5.22-7.17), and 9.07 (8.00-10.29), respectively, demonstrating an increased risk of liver events among patients with COVID-19 when compared with uninfected patients. The elevated risk of reporting adverse liver events in patients with COVID-19 who receive these drugs, alone or in combination, highlights the need for careful drug selection and efforts to reduce drug combinations without notable benefits. Similar to any other condition, the use of drugs without established efficacy should be avoided.

Abstract Background In 2008, in the context of a complete computerisation of medical records, the Institut Català de la Salut (ICS, Catalan Health Institute) implemented a system in its electronic clinical workstation (ECW) to assist decision-making at the prescription level. This system is known as Self Audit, and it supports physicians in reviewing the medication of their patients. Self Audit provides lists of patients presenting medication-related problems (MRPs) that have potential for improvement, and provides therapeutic recommendations that are easy to apply from the system itself. The aim of this study was to analyse the main results derived from the use of Self Audit in primary care (PC) in Catalonia, and the effect of an incentive-based safety indicator on the results obtained. Methods A descriptive cross-sectional study was carried out to analyse variations in the MRPs detected by Self Audit during 2016, 2017, and 2018 in PC in Catalonia. The effect of a safety indicator on the results obtained was also studied. This safety indicator includes the most clinically relevant MRPs (i.e., therapeutic duplications, safety alerts from the Spanish Medicines Agency, and incidences of polymedication in patients over 65 years of age). Variation in the MRPs was measured using the differences between two evaluation points (initial and final). An MRP was considered resolved if the recommendation specified in the alert was followed. The prescriptions of 6411 PC doctors of the ICS who use the ECW and provide their services to 5.8 million Catalans through 288 PC teams were analysed. Results Analysis of the total safety-based MRPs detected by Self Audit gave overall resolutions from April to December of 9% (21,547) in 2016, 7% (15,924) in 2017, and 1% (2392) in 2018 out of the total number of MRPs recorded in April each year. Examination of the 3 types of MRPs with the highest clinical relevance that were linked to the safety indicator gave overall resolutions of 41% in 2016 (17,358), 20% in 2017 (7655), and 21% in 2018 (8135). Conclusions The ICS Self Audit tool assists in reducing the number of safety-based MRPs in a systematic manner, and yields superior results for the MRPs linked to a safety indicator included in the incentives of PC physicians.

Abstract Warfarin has been associated with bleeding and venous thromboembolism. Objective: This study aimed to estimate the association between bleeding and concomitant self-medication, and the incidence of adverse drug reactions in patients using warfarin. Setting: the public health network of Ijuí, a municipality in southern Brazil. This was an open prospective cohort, conducted for a period of 18 months with users of warfarin, treated at the public health service. The association between bleeding and self-medication was evaluated by means of the Cox Model with left truncation, using the time variable. Main outcome measurement: bleeding reported in the follow-up. Cases of thromboembolism and death were also registered. All patients treated with warfarin in the public health system of the municipality (98) were identified. Sixty-eight were interviewed and followed up, of whom 63 completed follow-up and five died during the study. Bleeding rates of 37.7 /100 patients/year, thromboembolism of 4.8/100 patients / year and deaths of 4.8 /100 patients / year were observed. The results showed that patients, who take warfarin and self-medicated present a two-fold increased bleeding, compared with those who do not self-medicate. The bleeding risk associated with self-medication ranged from 2.001 to 2.685; those values maintained their significance even when adjusted for number of interactions, CYP polymorphism, TTR and age in COX analysis. These results greatly suggest the need for providing greater assistance to patients who take anticoagulant medications with the purpose of reducing self-medication and consequently, adverse reactions.

Abstract Background In 2008, the Institut Català de la Salut (ICS, Catalan Health Institute) implemented a prescription decision support system in its electronic clinical workstation (ECW), which automatically generates online alerts for general practitioners when a possible medication-related problem (MRP) is detected. This tool is known as PREFASEG, and at the time of beginning a new treatment, it automatically assesses the suitability of the treatment for the individual patient. This analysis is based on ongoing treatments, demographic characteristics, existing pathologies, and patient biochemical variables. As a result of the assessment, therapeutic recommendations are provided. The objective of this study is to present the PREFASEG tool, analyse the main alerts that it generates, and determine the degree of alert acceptance. Methods A cross-sectional descriptive study was carried out to analyse the generation of MRP-related alerts detected by PREFASEG during 2016, 2017, and 2018 in primary care (PC) in Catalonia. The number of MRP alerts generated, the drugs involved, and the acceptance/rejection of the alerts were analysed. An alert was considered "accepted" when the medication that generated the alert was not prescribed, thereby following the recommendation given by the tool. The MRP alerts studied were therapeutic duplications, safety alerts issued by the Spanish Medicines Agency, and drugs not recommended for use in geriatrics. The prescriptions issued by 6411 ICS PC physicians who use the ECW and provide their services to 5.8 million Catalans through 288 PC teams were analysed. Results During the 3 years examined, 67.2 million new prescriptions were analysed, for which PREFASEG generated 4,379,866 alerts (1 for every 15 new treatments). A total of 1,222,159 alerts (28%) were accepted. Pharmacological interactions and therapeutic duplications were the most detected alerts, representing 40 and 30% of the total alerts, respectively. The main pharmacological groups involved in the safety alerts were nonsteroidal anti-inflammatory drugs and renin-angiotensin system inhibitors. Conclusions During the period analysed, 28% of the prescriptions wherein a toxicity-related PREFASEG alert was generated led to treatment modification, thereby helping to prevent the generation of potential safety MRPs. However, the tool should be further improved to increase alert acceptance and thereby improve patient safety.

Background: The introduction of new drugs that increase the usage of repurposed medicines for managing drug-resistant tuberculosis (DR-TB) comes with challenges of understanding, properly managing, and predicting adverse drug reactions (ADRs). In addition to the health consequences of ADRs for the individual, ADRs can reduce treatment adherence, thus contributing to resistance. This study aimed to describe the magnitude and characteristics of DR-TB-related ADRs through an analysis of ADRs reported to the WHO database (VigiBase) in the period from January 2018 to December 2020. Methods: A descriptive analysis was performed on selected reports from VigiBase on the basis of medicine-potential ADR pairs. The ADRs were stratified by sex, age group, reporting country, seriousness, outcome of the reaction, and dechallenge and rechallenge. Results: In total, 25 medicines reported to be suspected individual medicines or as a fixed-dose combination in the study period were included the study. Pyrazinamide (n = 836; 11.2%) was the most commonly reported medicine associated with ADRs, followed by ethionamide (n = 783; 10.5%) and cycloserine (n = 696; 9.3%). From the report included in this analysis, 2334 (31.2%) required complete withdrawal of the suspected medicine(s), followed by reduction of the dose (77; 1.0%) and an increased dose (4; 0.1%). Almost half of the reports were serious ADRs mainly caused by bedaquiline, delamanid, clofazimine, linezolid, and cycloserine that are the backbone of the DR-TB treatment currently in use. Conclusions: A third of the reports required medication withdrawal, which impacts treatment adherence and ultimately leads to drug resistance. Additionally, more than 40% of the reports indicated that ADRs appeared two months after the commencement of treatment, thus it’s important to remain alert for the potential ADRs for the entire duration of the treatment.

Abstract Background Previous studies in Europe and the USA have reported a high prevalence of adverse drug reactions (ADRs), but data on local ADRs in Myanmar are sparse. Objective Our objective was to study ADRs in patients admitted to selected wards of Yangon General Hospital (YGH) and Yangon Specialty Hospital (YSH), Myanmar. Methods This was a prospective observational study in three hospital wards during the first quarter of 2019. Suspected ADRs were carefully investigated in a face-to-face interview with each patient and via review of clinical records. Patients transferred to other wards or discharged were followed-up by the researchers until day 28 after admission. ADRs were divided into those that (1) led to the admission and (2) occurred during the hospital stay or after discharge (up to day 28 after admission). Results A total of 65 ADRs were identified, with 47 (29.4%) of 160 patients experiencing at least one ADR. Among these, 16 (24.6%) had led to hospital admission and 49 (75.4%) occurred in 31 patients during their hospital stay. Of 160 patients, 21 had taken at least one herbal remedy and six of these developed an ADR. Five ADR–drug associations (hypokalaemia with methylprednisolone, increased transaminase levels with standard antituberculosis drugs, upper gastrointestinal bleeding with nonsteroidal anti-inflammatory drugs, constipation with tramadol, and increased transaminase levels with herbal remedies) represented 18 (27.7%) of the 65 ADRs in this study. According to the Schumock and Thornton preventability scale, more than half of these ADRs (35 [53.9%]) were preventable. Conclusion The present study highlights the existence of ADRs among patients attending these hospitals. The implementation of active pharmacovigilance in hospitals could be a helpful first step to improving the awareness of unwanted effects of medicines and patient safety, as well as a way to strengthen the national pharmacovigilance system in countries such as Myanmar.

BackgroundA better understanding of COVID-19 immunopathology is needed to identify the most vulnerable patients and improve treatment options.ObjectiveWe aimed to identify immune system cell populations, cytokines, and inflammatory markers related to severity in COVID-19.Methods139 hospitalized patients with COVID-19−58 mild/moderate and 81 severe/critical—and 74 recovered patients were included in a prospective longitudinal study. Clinical data and blood samples were obtained on admission for laboratory markers, cytokines, and lymphocyte subsets study. In the recovered patients, lymphocyte subsets were analyzed 8–12 weeks after discharge.ResultsA National Early Warning Score 2 >2 (OR:41.4; CI:10.38–167.0), ferritin >583 pg/mL (OR:16.3; CI: 3.88–69.9), neutrophil/lymphocyte ratio >3 (OR: 3.5; CI: 1.08–12.0), sIL-2rα (sCD25) >512 pg/mL (OR: 3.3; CI: 1.48–7.9), IL-1Ra >94 pg/mL (OR: 3.2; IC: 1.4–7.3), and IL-18 >125 pg/mL (OR: 2.4; CI: 1.1–5.0) were associated with severe/critical COVID-19 in the multivariate models used. Lower absolute values of CD3, CD4, CD8, and CD19 lymphocytes together with higher frequencies of NK cells, a CD4 and CD8 activated (CD38+HLA-DR+) memory T cell and effector memory CD45RA+ (EMRA) phenotype, and lower T regulatory cell frequencies were found in severe/critical patients relative to mild/moderate and recovered COVID-19 patients. A significant reduction in Th1, Tfh1, and Tc1 with higher Th2, Tfh2, Tc2, and plasma cell frequencies was found in the most severe cases.ConclusionA characteristic hyperinflammatory state with significantly elevated neutrophil/lymphocyte ratio and ferritin, IL-1Ra, sIL-2rα, and IL-18 levels together with a “low T1 lymphocyte signature” was found in severe/critical COVID-19 patients.

Abstract: The U.S. Food and Drug Administration (FDA) has stated that the prescription of remdesivir should be cautious for patients with estimated glomerular filtration rate (eGFR) < 30 and some studies reported risk of adverse renal events. The available information on the renal safety profile for remdesivir is limited, thus we analyzed the renal and urinary adverse reactions attributed to remdesivir reported in a large open pharmacovigilance database. We obtained reports of remdesivir and other drugs used to treat COVID-19 (tocilizumab, hydroxychloroquine, lopinavir/ritonavir) registered by September 30 2020, from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). We analyzed the reporting odds ratios (RORs) for reports of adverse renal and urinary events for remdesivir and other drugs. We found 2,922 reports with remdesivir registered in FAERS for COVID-19. Among these, 493 renal and urinary adverse effects (16.9%) were reported. The most frequent events were acute kidney injury (338; 11.6%), renal impairment (86; 2.9%), and renal failure (53; 1.8%). Versus hydroxychloroquine, lopinavir/ritonavir, or tocilizumab, the use of remdesivir was associated with an increased chance of reporting renal and urinary disorders regardless of gender and age of patients (2.53; 95%CI: 2.10-3.06). The ROR remained significant when we restricted the analysis to hydroxychloroquine (4.31; 95%CI: 3.25-5.71) or tocilizumab (3.92; 95%CI: 2.51-6.12). Our results reinforce this already reported signal, emphasizing that it could be extremely useful for health professionals who prescribe this new antiviral to treat COVID-19, mainly knowing its low efficacy.

Mechanisms involved in thyroid dysfunction in critically ill coronavirus disease 2019 (COVID-19) patients are not clear. Our objective was to correlate the thyroid response with the pro- and anti-inflammatory cytokines profile in critically ill COVID-19 patients. This was a prospective single-center study. We studied the relationship between continuous variables by using Pearson correlation and simple linear regression. Multiple logistic regression analysis was performed to analyze the factors independently associated with mortality. Seventy-eight patients were included in the study at intensive care unit (ICU) admission and 72 had a measurement of the thyroid and inflammatory profile at day 5. No significant correlations were found between thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) and inflammatory cytokines at ICU admission. At day 5, fT4, was inversely correlated with IL-10 (p = 0.035). IL-10 was associated with maximum lactate (p < 0.001) and SOFA score values (p = 0.012). The multiple logistic regression analysis showed that there was a significant relationship between IL-10 (day 5) and in-hospital mortality after adjusting by age and severity of illness. In conclusion, we found that the thyroid hormone profile and inflammatory cytokines had a weak correlation at ICU admission. Associations of interest between fT4 and IL-10 were found at day 5. IL-10 at day 5 was found to be correlated with low fT4 and markers of organ failure and death.

To evaluate the clinical outcomes of daptomycin therapy and adherence to treatment recommendations, a retrospective cohort study was conducted with patients that received daptomycin during the period of the study. The adherence and nonadherence to clinical guidelines were assessed through organism identification, dose and time of treatment, management of bacteremia, and vancomycin treatment failure. A multiple logistic regression model analyzed the association between independent variables and clinical success (dependent variable), considering 5% of statistical significance. The study presented 52 patients who received daptomycin for the treatment of bacteremia (21.1%) or infections (osteomyelitis [63.5%], synovial fluid [15.4%]). Most patients (86.5%) received daptomycin as the second line of treatment, and 51.9% achieved clinical success. The patients had a better chance of clinical success when they followed the guideline indications (OR = 16.86; 95% CI = 1.45-195.88) and the medication was prescribed by a specialist in infectious diseases (OR = 4.84; 95% CI = 1.11-21.09). The study demonstrated lower clinical success than that described in the literature because of patients who were not eligible according to the clinical guidelines. Adherence to recommendations and appropriate prescription of reserve antibiotics is important in limiting early resistance, and avoiding clinical failure and unnecessary expenditure.

Every two years, the World Health Organization (WHO) updates its Model List of Essential Medicines, intended as a guide for countries to adopt or adapt in accordance with local priorities and treatment guidelines, for the development of national essential medicines lists. When more than one therapeutic option is available for a given indication, the WHO Model List often includes a single medicine as representative of a group of equivalent and interchangeable medicines. The representative medicine of that group is listed with an accompanying ‘square box’ symbol. The intended purpose of the square box is to highlight pharmacological classes or groups of medicines for which countries, institutions and health professionals can assume homogeneous therapeutic efficacy and safety and select the most appropriate single medicine based on price, local availability, and acceptability. Though this concept of therapeutic equivalence within a therapeutic class has been endorsed by most authoritative textbooks of pharmacology since Goodman & Gilman’s The Pharmacological Basis of Therapeutics and evidence-based guidelines, marketing forces have often made claims on individual drugs to distinguish them beyond relevant differences shown by reliable evidence: this has generated the concept of “me-too drugs” with its double meaning—i.e., market latecomers differing minimally from products preceding them and whose marketing budgets have significant opportunity costs, or medicines which may be useful to substitute for equivalent products in the event of shortages. The square box concept is applied in the context of a comprehensive list: therapeutic equivalence or interchangeability cannot always be easily established. Different interpretations have been applied to different groups of medicines over the 40+ year history of the Model List. This paper presents the concept of the square box, provides key examples and guidance on how square box listings should be practically interpreted in the development and implementation of national essential medicine lists, considers the applicability of a square box listing concept to biologic medicines and proposes that an updated review of the square box concept and listings is warranted.

(1) Background: Antimicrobial resistance (AMR) requires urgent multidisciplinary solutions, and pharmacovigilance has the potential to strengthen current antimicrobial stewardship strategies. This study aimed to characterize AMR-relevant adverse drug reaction (ADR) reports submitted to The Netherlands Pharmacovigilance Centre; (2) Methods: We carried out a descriptive analysis of ADR reports submitted to Lareb, coded with AMR-relevant MedDRA Preferred Terms (PTs); (3) Results: Between 1998 and January 2019, 252 AMR-relevant ADR reports were submitted to Lareb. The most frequent antibiotics were tobramycin (n = 89; 35%), colistin (n = 30; 11.9%), cipro-floxacin (n = 16; 6.3%), doxycycline (n = 14; 5.5%), and aztreonam (n = 12; 4.8%). The PTs used included off label use (n = 91; 36.1%), drug ineffective (n = 71; 28.2%), product use in unapproved indication (n = 28; 11.1%), pathogen resistance (n = 14; 5.6%), and drug resistance (n = 13; 5.2%). 54% of the reports were on Watch antibiotics and 19% were involved in the Reserve group. In the Watch group, “off label use” and “product use in unapproved indication” were the most frequent PTs and the majority of reports on Reserve antibiotics were coded as “Off label”. A sharp increase in the number of reports was observed in the three consecutive years with 21 in 2013, 54 in 2014, and 83 in 2015; (4) Conclusions: In addition to existing AMR monitoring strategies, pharmacovigilance databases can serve as a source of data on suspected resistance and inappropriate use. Future research should explore how these AMR-relevant MedDRA Terms are used in resource-limited settings with less capacity to generate laboratory-confirmed resistance data.

Objective: The aim of this study was to develop and validate a stepwise tool to aid primary health care professionals in the process of deprescribing potentially inappropriate medication in older persons. Methods: We carried out a systematic review to identify previously published tools. A composite proposal of algorithm was made by following the steps from clinical experience to deprescribe medications. A 2-round electronic Delphi method was conducted to establish consensus. Eighteen experts from different countries (Colombia, Spain and Argentina) accepted to be part of the panel representing geriatricians, internists, endocrinologist, general practitioners, pharmacologists, clinical pharmacists, family physicians and nurses. Panel members were asked to mark a Likert Scale from 1 to 9 points (1= strongly disagree, 9= strongly agree). The content validity‏ ratio, item-level content validity, and Fleiss’ Kappa statistics was measured to establish reliability. The same voting method was used for round 2. Results: A 7-question algorithm was proposed. Each question was part of a domain and conduct into a decision. In round 1, a consensus was not reached but statements were grouped and organized. In round 2, the tool met consensus. The inter-rater reliability was between substantial and almost perfect for questions with Kappa=0.77 (95% CI 0.60-0.93), for domains with Kappa= 0.73 (95%CI 0.60-0.86) and for decisions with Kappa= 0.97 (95%CI 0.90-1.00). Conclusions: This is a novel tool that captures and supports healthcare professionals in clinical decision-making for deprescribing potentially inappropriate medication. This includes patient’s and caregiver’s preferences about medication. This tool will help to standardize care and provide guidance on the prescribing/deprescribing process of older persons’ medications. Also, it provides a holistic way to reduce polypharmacy and inappropriate medications in clinical practice.

Background: In Uganda, national tuberculosis (TB) treatment guidelines were revised to include the newer generation fluoroquinolones among the second-line treatment options for multidrug-resistant TB. This study was designed to analyze if the prescription of these quinolones is compliant with country recommendations. Methods: This was an observational retrospective study of consumption data for 2017 and 2018 across four selected regional referral hospitals. The sources of consumption data were hospital pharmacy stock cards and the dispensing register. The medical files of patients who had been prescribed fluoroquinolones were also assessed to study compliance with the Uganda Clinical Guidelines and the British National Formulary (BNF). Results: None of the 371 levofloxacin prescriptions analyzed complied with the Uganda Clinical Guidelines, although 250 (67.3%) were prescribed for indications included in the BNF. According to WHO prescription indicators, only 220 (59.3%) prescriptions were appropriate. Conclusion: The prescription of levofloxacin and moxifloxacin increased in the hospitals studied, but in a high proportion of cases, they were not compliant with country recommendations. The findings call for the strengthening of national antimicrobial stewardship programs.

This pilot study was conducted to analyze the quality of the antimicrobials sold in the street markets in Port-au-Prince, Haiti. A total of 258 packs containing antimicrobials were bought in 28 street markets in Port-au-Prince (Haiti). Tablets and contents of capsules included in 196 packs were analyzed using a Raman handheld spectrometer (NanoRAM of BWTEK, Model: BWS456-785) during the first quarter of 2019. Three out of 11 antimicrobials (Amoxicillin, Metronidazole, and Cotrimoxazole) had a high spectral match with an HQI ≥ 90 to the respective authentic medicine for more than 95% of their tablets/capsules. For six antimicrobials (Tetracycline, Erythromycin, Cloxacillin, Azithromycin, Clarithromycin, and the combination Amoxicillin + Clavulanic Acid) none of their tablets/capsules showed a sufficient spectral match with the authentic medicine. This finding indicates that these products sold in the markets did not contain the labeled drug and/or contained a degraded drug. In addition to the fact that prescription antimicrobials can be purchased in street markets, the present field study found that for most of them (including “Watch” antimicrobials according to the AWaRe classification) were substandard, which contributes to the present antimicrobials resistance epidemic.

The use of antibiotics is the most important modifiable risk factor for the development of microorganism resistance. A cross-sectional study of outpatients receiving antibiotic prescriptions registered in a population database in Colombia was conducted. The characteristics of the consumption in capital cities and small municipalities was studied and the AWaRe classification was used. AWaRe classifies antibiotics into three stewardship groups: Access, Watch and Reserve, to emphasize the importance of their optimal use and potential harms of antimicrobial resistance. A total of 182,397 patients were prescribed an antibiotic; the most common were penicillins (38.6%), cephalosporins (30.2%) and fluoroquinolones (10.9%). ‘Access’ antibiotics (86.4%) were the most frequently prescribed, followed by ‘Watch’ antibiotics (17.0%). Being 18 or older, being male, living in a municipality, having one or more comorbidities and urinary, respiratory or gastrointestinal disorders increased the probability of receiving ‘Watch’ or ‘Reserve’ antibiotics. Penicillin and urinary antiseptic prescriptions predominated in cities, while cephalosporin and fluoroquinolone prescriptions predominated in municipalities. This analysis showed that the goal set by the WHO Access of mainly using Access antibiotics is being met, although the high use of Watch antibiotics in municipalities should be carefully studied to determine if it is necessary to design specific campaigns to improve antibiotics use.

BACKGROUND:Being aware of consumption patterns of antimicrobials is the first step in designing and implementing strategies to change behaviors and, thus, to reduce the occurrence of antimicrobial resistance. The present survey was carried out to identify and describe the use of antimicrobials without prescription in riverside dwellers of the Brazilian Amazon Basin. METHODS:A cross-sectional study was carried out from a conglomerate stratified sample in the rural municipality of Coari, Amazonas State, Brazil, between April and July 2016. The survey was conducted in the riverside dwellers' homes, and information was collected on all antimicrobials taken with and without medical or dental prescription for a 30-day period, together with indications of their use before the interview. RESULTS:A total of 492 riverside dwellers were included in the present survey; 346 (70.3%) had taken at least one medication during the previous month, and 74 (21.3% of those taking a medicine) used an antimicrobial. Two-thirds of the patients treated with an antimicrobial (49; 66.2%) obtained it without a prescription. Additionally, one-third of the antimicrobials consumed by the study sample (25) were used for non-infectious or non-bacterial conditions. DISCUSSION:The present survey showed not only that inappropriate use of antimicrobials is present in remote places such as the Amazon Basin, but also that one-third of those antimicrobials were taken to treat non-infectious or non-bacterial conditions. In addition to an unnecessary risk of adverse effects to the exposed populations, the inappropriate use of antibiotics without prescription helps to increase antibiotic-resistant strains. In the present case, this was happening near one of Latin America's most important water supplies, which could contribute to the global impact of antimicrobial resistance.

Understanding antimicrobials (AM) on offer in a pharmaceutical market, with a particular reference to drugs categorized as “Watch” active ingredients, is one of the important first steps to prevent their potentially inappropriate use. The March 2019 data of all AM containing registered brands and presentations currently being sold in the country for the J01 Anatomical Therapeutic Chemical (ATC) subgroup from IQVIA Pakistan was used. Each AM was categorized as “Access,” “Watch,” or “Reserve,” according to the WHO AWaRe classification. There were 59 single chemical entities and 14 combinations with 1869 brands and 4648 presentations. The WHO Essential Medicines List included 35 J01 AM while an additional 38 single and combination AM with 425 brands and 977 presentations were present in the country. Looking at the whole list of marketed AM, 8 of the 10 AM with more than 60 brands were classified as “Watch”, offering 962 brands and 2418 presentations. Most AM marketed in Pakistan, of which there are an excessive number of brands, belong to the “Watch” AWaRe category. The higher the number of brands, the higher the marketing pressure on prescribers and pharmacists will be which implies more potential confusion. One vital step to rationalize the use of AM lies in reviewing their market offer.

The objective of this study was to analyze the level of evidence regarding the efficacy, effectiveness and safety of over-the-counter (OTC) cough medications registered in Brazil. The National Health Surveillance Agency database was used to identify the drugs. Clinical trials, systematic reviews, meta-analyses, and studies on safety were searched on the Medline baseline, the Cochrane Library and SIETES (System of Essential Information in Therapeutics and Health; database in Spanish). Most drugs (62.5%) were sold as a fixed-dose combination of two or more drugs. Randomized clinical trials were found for only three drugs: bromhexine, dextromethorphan and guaifenesin. No clinical trials were found for fixed-dose combinations. Systematic reviews on Cochrane did not report any evidence in favor of or against the effectiveness of cough drugs. Efficacy is also unclear, especially regarding fixed-dose combinations. The evidence for the efficacy of OTC cough medications available in Brazil is poor due to the lack of quality studies. Pharmacovigilance of OTC cough medications should be encouraged.O objetivo deste trabalho foi analisar o nível de evidências sobre a eficácia, a efetividade e a segurança dos medicamentos para tosse registrados no Brasil. A base de dados da Agência Nacional de Vigilância Sanitária foi empregada para identificar os medicamentos. Os ensaios clínicos, as revisões sistemáticas, as metanálises e os estudos de segurança foram pesquisados no Medline, the Cochrane Library e SIETES (Sistema de Informações Essenciais em Terapêutica e Saúde, base de dados em espanhol). A maioria dos medicamentos (62,5%) eram comercializados como associação em dose fixa com dois ou mais fármacos. Ensaios clínicos randomizados foram encontrados apenas para três fármacos: bromexina, dextrometorfano e guaifenesina; para associações a dose fixa não foram encontrados ensaios clínicos. Revisões sistemáticas publicadas pela Cochrane não encontraram evidências favoráveis ou contrárias à efetividade dos medicamentos para tosse. Essa eficácia não é clara, especialmente a das associações a dose fixa. As evidências sobre a eficácia dos medicamentos para tosse isentos de prescrição disponíveis no mercado brasileiro são fracas, devido à falta de pesquisas de boa qualidade. A farmacovigilância de medicamentos para tosse isentos de prescrição deve ser incentivada.

A partir do momento que os medicamentos entraram no mercado e se converteram num bem de consumo como qualquer outro, são frequentes fenómenos como a comercialização de produtos com pouca ou sem eficácia demonstrada, a minimização dos riscos ou a promoção de alternativas terapêuticas cujas únicas diferenças com outras opções bem conhecidas, são um preço mais elevado e uma segurança incerta. Neste contexto, para assegurar a utilização mais apropriada e segura dos medicamentos e uma óptima qualidade de cuidados de saúde às pessoas é essencial: (1) aplicar a lógica clínica em todo o circuito do medicamento, desde o registo de novas substâncias até ao consumo; (2) promover a prescrição racional dos medicamentos em detrimento de prescrição puramente comercial; (3) fortalecer sistemas de farmacovigilância eficazes e activos; e (4) proporcionar, aos profissionais de saúde, programas de formação contínua independentes, assim como, uma formação sanitária sólida.