Comprehension of Pictograms Demonstrating the Risk of Medication Use During Pregnancy: A Systematic Review.

OBJECTIVE: This study aimed to summarize the comprehension of a pictogram about the risk of medication use during pregnancy. METHODS: A systematic review was performed using the PRISMA checklist of the PubMed, Embase, Cochrane Central Register of Controlled Trials, CINAHL, PsycInfo, LILACS, Academic Search Premier, Scopus, and Web of Science databases, grey literature (Google Scholar and OpenAIRE), ClinicalTrials.gov website, and design journals and congresses. The search was performed since the database inception, without language or year of publication restrictions. RESULTS: Twelve studies met the inclusion criteria for this review, 2 of which were randomized clinical trials. The pictograms and methods used varied widely among studies. The comprehension of the pregnancy pictograms had a complex communication outcome with a variation of 21-96%. CONCLUSIONS FOR PRACTICE: The lack of a standard pictogram and uniform methods to evaluate the comprehension of the pregnancy pictogram made it challenging to reach a conclusion with the studies available to date on the safety and efficacy of the pregnancy pictogram to alert the risk of medication use.

Comparative efficacy of amitriptyline, duloxetine and pregabalin for treating fibromyalgia in adults: an overview with network meta-analysis.

Treatment recommendations for fibromyalgia (FM) include a range of predominantly pharmacological treatment options designed to ensure the maintenance of symptoms and improvement in the quality of life of these patients. Our aim is to identify and compare the efficacy of amitriptyline (AMT), duloxetine (DLX), and pregabalin (PGB) for reducing pain intensity by 30% (R30%) and 50% (R50%) in adult patients with fibromyalgia. The review was conducted in the Medline/PubMed, Cochrane Library, and Embase databases up to February 2022. This study included systematic reviews (SR) of randomized clinical trials (RCTs) targeting adult patients over 18 years of age diagnosed with fibromyalgia according to the criteria of scientific societies, which include the basic clinical diagnosis characterized by the presence of pressure sensitivity in at least 11 of the 18 tender points, in addition to the presence of widespread musculoskeletal pain for a period longer than 3 months and a general assessment of the patient's health status. Pregnant women and children or adolescents were excluded. The Rob 2.0 tool from the Cochrane Collaboration was used to assess the risk of bias in RCTs. The quality of evidence of the reviews included was assessed according to the Grading of Recommendations Assessment, Development and Evaluation-GRADE. A meta-analysis for the evidence network was performed using the Bayesian approach, which allows simultaneous comparison of all treatment options (medication and dose). The different treatments were ranked according to the response rate according to the surface under the curve (SUCRA), which was expressed as a percentage. The results were presented in tables and figures. The protocol with the detailed methods was registered in PROSPERO (CRD42021229264). Eight systematic reviews were identified, and, from these, 15 clinical trials comparing AMT (n = 273), DLX (n = 2595), and PGB (n = 3,506) against placebo were selected. For the outcome R30%, PGB 450 mg was superior to DLX 30 mg and PGB 150 mg, while DLX 20 mg and 30 mg were not superior to placebo. For the outcome R50%, AMT 25 mg was superior to all other alternatives evaluated. The calculation of the SUCRA indicated that PGB 450 mg was the best performance option for R30% and AMT 25 mg for R50%. PGB 150 mg was the drug with the worst performance in the two outcomes evaluated. The drugs evaluated showed benefits for pain reduction in patients with fibromyalgia. In the absence of direct comparison studies, indirect comparison meta-analyses are an important resource for assisting in clinical decision-making. Our data only provide an indicator of the effectiveness of the three drugs evaluated, but as with other health conditions, tolerability and safety are important for the decision-making process and clinical management. In this regard, we encourage caution in interpreting our data.

Prevalence of drug interactions in hospitalised elderly patients: a systematic review.

BACKGROUND: The prevalence of drug-drug interactions (DDIs) in hospital settings is variable, and elderly patients are considered a high risk population for DDIs. There are no systematic reviews describing the prevalence of DDIs in hospitalised elderly patients. OBJECTIVES: To assess and summarise the available data on the prevalence of DDIs in hospitalised elderly patients and to describe which drugs, drug classes and drug combinations are most commonly involved in DDIs. DATA SOURCE: A systematic electronic literature search was conducted on Medline/PubMed, Embase, Lilacs, SciElo, Web of Science, Cinahl, Scopus, Cochrane, OpenGrey, Capes Thesis Bank, OasisBR, OpenAire and abstracts from scientific events, without limitation on language or period of publication. Study selection was completed on 21 September 2018. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Original observational studies that reported the prevalence of actual or potential DDIs during hospitalisation in patients aged 60 years or older were included. The main outcome measure was prevalence of DDIs and number of DDIs per patient. Subgroup analysis was performed in studies that reported the prevalence of DDIs in geriatric units. STUDY APPRAISAL AND SYNTHESIS METHODS: Study quality was assessed using the Agency for Healthcare Research and Quality methodological checklist for cross sectional and prevalence studies. RESULTS: 34 studies were included, involving 9577 patients. The prevalence of DDIs ranged from 8.34% to 100%. In studies conducted in geriatric units, the prevalence ranged from 80.5% to 90.5%. The number of DDIs per patient ranged from 1.2 to 30.6. Single drugs most commonly involved in DDIs were furosemide, captopril, warfarin and dipyrone. Drug classes mostly involved were potassium sparing diuretics and angiotensin converting enzyme inhibitors. LIMITATIONS: The main limitation is the heterogeneity between the included studies that precluded a meta-analysis. Several different methods were used to identify DDIs, majorly, and potential DDIs. Few studies have reported measures to control the quality of the collected data. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The prevalence of DDIs ranged widely, and the variation may reflect differences in the conditions of the elderly patients and level of attention (or complexity of care), as well as methodological differences, especially the methods and/or software used to identify DDIs. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42018096720.

Comparing the efficacy and safety of duloxetine and amitriptyline in the treatment of fibromyalgia: overview of systematic reviews.

BACKGROUND: Duloxetine and amitriptyline are antidepressants used in the treatment of fibromyalgia. In published systematic reviews, there is no agreement about which drug is more effective and safer. This study aimed to compare evidence of the efficacy and safety of duloxetine compared with amitriptyline in the treatment of adult patients with fibromyalgia. This work contributes to guiding clinicians on the use of duloxetine or amitriptyline for the treatment of fibromyalgia and provides information for public health decision-makers. METHODS: Overview of systematic reviews of clinical trials comparing duloxetine and amitriptyline in the treatment of fibromyalgia. The reviews were screened in Cochrane, PubMed, EMBASE, and SRDR with no restrictions on language and year of publication, considering that the research was conducted in July 2018 and updated until May 2020. The selection was based on the following criteria: adult patients with a diagnosis of fibromyalgia treated with duloxetine or amitriptyline, comparing the efficacy and safety in pain, fatigue, sleep, and mood disorder symptoms and quality of life, in addition to the acceptability of these antidepressants. The methodological quality and strength of evidence were assessed using the AMSTAR and GRADE instruments. RESULTS: Eight systematic reviews were selected. Amitriptyline had low evidence for pain, moderate evidence for sleep and fatigue, and high evidence for quality of life. Duloxetine had high quality of evidence in patients with mood disorders. With low evidence, duloxetine has higher acceptability, but is safer in older patients, while amitriptyline is safer for non-elderly individuals. CONCLUSION: Both antidepressants are effective in the treatment of fibromyalgia, differing according to the patient's symptoms and profile. REGISTRATION: PROSPERO: CRD42019116101.

Correction: Analgesic use among the Brazilian population: Results from the National Survey on Access, Use and Promotion of Rational Use of Medicines (PNAUM).

[This corrects the article DOI: 10.1371/journal.pone.0214329.].

Associations of acetaminophen use during pregnancy and the first year of life with neurodevelopment in early childhood.

BACKGROUND: Over-the-counter analgesic use during pregnancy, particularly acetaminophen, may be associated with negative developmental outcomes in children. OBJECTIVE: Estimate associations of prenatal and early-life exposure to acetaminophen in early childhood with cognitive, motor, and language skills in two birth cohorts. METHODS: The American Project Viva cohort (1217 mother-child pairs enrolled 1999-2002) assessed cognition at approximately 3 years using the Peabody Picture Vocabulary Test and the Wide Range Achievement of Visual Motor Abilities (WRAVMA). The Brazilian 2015 Pelotas Birth Cohort (3818 mother-child pairs) assessed cognition at 2 years using the INTERGROWTH-21st Neurodevelopment Assessment. We used linear regression to estimate associations of acetaminophen use during pregnancy (Project Viva and Pelotas) and infancy (Project Viva) with children's cognitive scores adjusted for maternal age, pre-pregnancy body mass index, education, parity, race/ethnicity, smoking and alcohol use during pregnancy, depression during pregnancy, antibiotic and ibuprofen use during pregnancy, household income, and child's sex. RESULTS: In Project Viva, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was associated with lower WRAVMA drawing scores (ß -1.51, 95% CI -2.92, -0.10). However, in Pelotas, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was not associated with INTER-NDA motor scores (ß 0.02; 95% CI -0.05, 0.09) and was associated with higher INTER-NDA total scores (ß 0.08, 95% CI 0.01, 0.16). Other comparisons did not show evidence for any associations. CONCLUSIONS: Inconsistencies and lack of specificity of the findings did not clarify the research question considering that we still have a large variability and uncertainty to define the risk or safety in the use of acetaminophen related to cognition in early childhood. More studies using better exposure assessment and better confounding variables are needed to clarify these associations.

The use of folic acid, iron salts and other vitamins by pregnant women in the 2015 Pelotas birth cohort: is there socioeconomic inequality?

BACKGROUND: Many low- and middle-income countries recommend micronutrient supplements for pregnant women to improve their nutritional status, prevent possible deficiencies and avoid fetal healgth consequences. This study evaluated the influence of socioeconomic status on the use of folic acid, iron salts and other vitamins and minerals among pregnant women in the 2015 Pelotas Birth Cohort. METHODS: This population-based birth cohort study was carried out with 4270 women. Participants were interviewed during pregnancy and at the maternity hospital about the antenatal period; including the use of iron salts, vitamins and other minerals. Descriptive analyses were performed to characterize the sample. The analyses were adjusted according to socioeconomic variables (maternal education, ethnicity, household income). RESULTS: The overall prevalence of the use of folic acid, iron salts or other vitamins and minerals was 91.0% (95% CI: 90.1-91.8). Specifically, 70.9% (95% CI: 69.5-72.3) used folic acid, 72.9% (95% CI: 71.5-74.3) used iron compounds, and 31.8% (95% CI: 30.3-33.2) used other vitamins or minerals. In the adjusted analysis, the use of iron salts was associated with nonwhite mothers, with ≤4 years of education and whose family income was less than or equal to the monthly minimum wage. The use of folic acid and other vitamins and minerals was associated with white mothers who were more highly educated and had a higher family income. CONCLUSION: Although folic acid and other vitamins and minerals were more frequently used in white, richer and more educated mothers, which indicates inequality, iron supplements were more frequently used in the poorer, less educated nonwhite mothers, suggesting the opposite association for this supplement.

Correction: Analgesic use among the Brazilian population: Results from the National Survey on Access, Use and Promotion of Rational Use of Medicines (PNAUM).

[This corrects the article DOI: 10.1371/journal.pone.0214329.].

Analgesic use among the Brazilian population: Results from the National Survey on Access, Use and Promotion of Rational Use of Medicines (PNAUM).

PURPOSE: To estimate the prevalence of use of analgesics in Brazil; and to characterize this use, according to sociodemographic and health-related characteristics. METHODS: A cross-sectional population-based study (National Survey on Access, Use and Promotion of Rational Use of Medicines, PNAUM) was conducted between September 2013 and February 2014. A total of 41,433 people of all ages in Brazilian urban households were interviewed. Occasional use (within the last 15 days) and continuous use of non-opioid analgesics, opioid analgesics and non-steroidal anti-inflammatory drugs were investigated, regardless of whether this use occurred through prescription or self-medication. The main outcome was the use of at least one analgesic. RESULTS: The majority of the individuals were female (52.8%), aged between 20 and 59 years (57.2%), with 1 to 8 years of schooling (45.6%). The overall prevalence of analgesic use was 22.8% [95% CI: 21.4-24.2]. The use of analgesics was significantly higher among women, adults and elderly (20 years or more), highly educated individuals and respondents who referred: diagnosis of one or more chronic diseases, using three or more medications, possession of health insurance and with one or more emergency care admittances or hospitalizations within the last year. Non-opioid analgesics were the agents most used (18.5% of the sample), followed by non-steroidal anti-inflammatory drugs (6.9%) and opioid analgesics (0.5%). The most commonly used drugs were metamizole (37.8% of all analgesics), paracetamol (25.3%) and diclofenac (10.7%). These drugs were used mainly to manage occasional health conditions, particularly pain. CONCLUSION: One in five Brazilians used some analgesic, especially non-opioid analgesics, to manage acute health problems such as painful conditions.

Effect of different formats for information on side effects regarding medicine users' understanding: A randomized controlled trial.

OBJECTIVE: The objective of this randomized controlled trial was to evaluate the efficacy of presenting information on the risks of side effects from a medicine, presented in different formats. METHODS: A randomized, parallel-group, single-center controlled trial was conducted among adult users of a training pharmacy. The information was categorized into the following groups: verbal descriptors+percentage range, percentage range and absolute percentage. The main outcomes were gist understanding and verbatim understanding, classified either as adequate or inadequate. The analyses were performed using ANOVA and Pearson's chi-square test. RESULTS: A total of 393 participants were recruited from June to October 2015. Adequate levels of gist understanding and verbatim understanding were respectively 65.6% and 53.9% for the verbal descriptors+percentage range (n=128), 63.4% and 44.3% for percentage range (n=131), and 62.3% and 48.5% for absolute percentage (n=131), with no statistically significant difference between the groups (p=0.852 and p=0.299, respectively). CONCLUSION: The understanding of the information was similar in all three formats, but the percentages of adequate understanding were low. PRACTICAL IMPLICATIONS: The percentage of inadequate understanding demonstrated in this study indicates that alternative formats for reporting adverse reactions need to be evaluated.

Drug information center: challenges of the research process to answer enquiries in hospital pharmaceutical practices.

OBJECTIVE: To characterise information requests (IRs) from hospitals received by a drug information center (DIC-RS) according to the resolution of the inquiries. METHOD: The sample consisted of all requestors and their respective IRs registered in the DIC-RS database from January 2012 to December 2016. Request without information in the consulted literature (RWI) were categorised according to the institution of origin. IRs from hospitals were classified by the information source, topic and subtopic of the questions, and the number of drugs and the pharmacological or therapeutic group. RESULTS: A total of 2,500 IRs were analysed. Of those, 25% did not exhibit conclusive information in the consulted sources. RWI from hospitals represented 51% of all RWI, followed by those from community pharmacies (13%) and health centres (9%). Tertiary literature was the most commonly used source (73%) for IRs from hospitals. The greatest difficulties in finding information were related to off-label drug administration and indication issues (52% of RWI). The most common type of off-label use was related to changes in the original pharmaceutical form of the drug. Furthermore, 61% of RWI were directed at a specific drug, mostly systemic anti-infectives. CONCLUSION: We found that a quarter of the answers did not exhibit conclusive information in the consulted sources. Answers to IRs from the hospital environment exhibited the greatest extent of limited information, and off-label use was responsible for most cases.

Use of medicines with unknown fetal risk among parturient women from the 2004 Pelotas Birth Cohort (Brazil).

BACKGROUND: To estimate the exposure to medicines with unknown fetal risk during pregnancy and to analyze the maternal characteristics associated with it. METHODS: A questionnaire was administered to 4,189 mothers of children belonging to the 2004 Pelotas (Brazil) birth cohort study about use of any medicine during gestation. We evaluated the associations between use of medicines with unknown fetal risk and the independent variables through logistic regression models. Unknown fetal risk was defined as medicines in which studies in animals have revealed adverse effects on the fetus, and no controlled studies in women, or studies in women and animals, are available. RESULTS: Out of the 4,189 women, 52.5% used at least one medicine from unknown fetal risk. Use of these medicines was associated with white skin color, high schooling, high income, six or more antenatal care consultations, hospital admission during pregnancy, and morbidity during gestation. CONCLUSION: The use of unknown fetal risk medicines is high, suggesting that their use must be addressed with caution with the aim of restricting their use to cases in which the benefits are greater than the potential risks.

Dipyrone use during pregnancy and adverse perinatal events.

OBJECTIVE: To evaluate the risk of adverse perinatal events among newborns exposed to dipyrone during gestation. DESIGN AND SETTING: The present study is a secondary analysis of Brazilian study of gestational diabetes (EBDG), a cohort of women attended at healthcare units of the Brazilian national health system (SUS) located in six Brazilian state capitals, between February 1991 and June 1995. SAMPLE: A total number of 5,564 women aged 20 years and over who were between their 21st and 28th week of pregnancy were followed up. METHODS: A structured questionnaire was used to obtain data on the pregnant women, their pregnancies, and their use of medications. Other data and the outcomes congenital abnormalities, intrauterine death, preterm birth, or low birth weight were obtained from the medical records. To estimate the odds ratios after adjustment for the potential confounding factors, logistic regression modeling was developed. MAIN OUTCOME MEASURES: Congenital abnormalities, intrauterine death, preterm birth, and low birth weight. RESULTS: Dipyrone use was reported by 555 pregnant women (11.5%). Their exposure to this medication did not present any association with the outcomes of congenital abnormalities (OR 1.11; 95% CI, 0.58-2.10), intrauterine death (OR 0.69; 95% CI, 0.33-1.43), preterm birth (OR 0.94; 95% CI, 0.73-1.20), or low birth weight (OR 0.88; 95% CI, 0.64-1.22), in the crude analysis. This absence of associations was maintained after performing logistic regression analysis. CONCLUSIONS: The data suggest that the exposure to dipyrone during pregnancy does not increase the risk of congenital abnormalities and other adverse events as outcomes from pregnancy.

Prenatal exposure to misoprostol and congenital anomalies: systematic review and meta-analysis.

The present systematic review was proposed with the objective of estimating the risk of congenital anomalies and other adverse events in children exposed to misoprostol during fetal life. The data source consisted of case-control studies that analyzed the effect of prenatal exposure to misoprostol on the pregnancy outcome, which were located in electronic databases and published up to June 2005. The outcomes of interest included congenital anomalies, fetal death, low birth weight and prematurity. The odds ratios (OR) for the individual studies were pooled by meta-analysis. Sensitivity tests and heterogeneity analysis were performed. Four studies involving 4899 cases of congenital anomalies and 5742 controls were included in accordance with the selection criteria. None of the studies analyzed other adverse effects from misoprostol on the outcome from gestation. Increased risks of congenital anomalies related to misoprostol use were found for any congenital defect (OR=3.56; 95% CI: 0.98-12.98), Möbius sequence (OR=25.31; 95% CI: 11.11-57.66) and terminal transverse limb defects (OR=11.86; 95% CI: 4.86-28.90). In conclusion, prenatal exposure to misoprostol is associated with an increased risk of Möbius sequence and terminal transverse limb defects.