Randomized clinical trials (RCT) are accepted as the gold-standard approaches to measure effects of intervention or treatment on outcomes. They are also the designs of choice for health technology ...assessment (HTA). Randomization ensures comparability, in both measured and unmeasured pretreatment characteristics, of individuals assigned to treatment and control or comparator. However, even adequately powered RCTs are not always feasible for several reasons such as cost, time, practical and ethical constraints, and limited generalizability. RCTs rely on data collected on selected, homogeneous population under highly controlled conditions; hence, they provide evidence on efficacy of interventions rather than on effectiveness. Alternatively, observational studies can provide evidence on the relative effectiveness or safety of a health technology compared to one or more alternatives when provided under the setting of routine health care practice. In observational studies, however, treatment assignment is a non-random process based on an individual's baseline characteristics; hence, treatment groups may not be comparable in their pretreatment characteristics. As a result, direct comparison of outcomes between treatment groups might lead to biased estimate of the treatment effect. Propensity score approaches have been used to achieve balance or comparability of treatment groups in terms of their measured pretreatment covariates thereby controlling for confounding bias in estimating treatment effects. Despite the popularity of propensity scores methods and recent important methodological advances, misunderstandings on their applications and limitations are all too common. In this article, we present a review of the propensity scores methods, extended applications, recent advances, and their strengths and limitations.
ObjectiveWe aimed to develop and validate a new instrument called Questionnaire for the assessment of the knowledge, management and reporting ADR in Paediatrics by Healthcare teams ...(QUESA-P).DesignThis is a cross-sectional study.Settings and participantsTeams of healthcare professionals (HCP) that lead with pharmacological therapy in Paediatrician’s sector (Paediatric-HCP) in seven public hospitals in Brazil.OutcomeAn assessment of the knowledge and current management of ADR in Paediatric-HCP.MethodsWe developed and validated QUESA-P, using a standardised procedure which included item development and psychometric prevalidation using Cronbach’s Alpha, item-total correlation and test–retest validity for internal consistency and reliability. External criterion was used as criterion validation (the instrument was applied to the focus group expert vs focus group team of Paediatric-HCP in hospitals). The focus group of experts who participated in psychometrics was asked to respond to the QUESA-P twice in order to assess test-retest reliability. The content validity of the initial questionnaire was assessed by the Delphi method and pilot test. Subsequently, we made minor revisions and finalized the QUESA-PResultsSelection of domains and facets were based on literature review made in duplicate by authors. Content validity was done by trial of different examiners (panellists, n=16), conducting analysis through Delphi method (three rounds). The QUESA-P was constructed with three domains. The intraclass correlations (0.80) and the Cronbach’s alpha coefficient (0.82), indicated adequate test–retest reliability and internal consistency for each domain. The application of the QUESA to 61 Paediatric-HCP in hospital resulted in lower mean score of 42.1 ± 3.4 in all domains when compared with expert teams (n= 46) 48.2 ± 3.7 (p <0.001) indicating that the instrument is valid to discriminate QUESA experts and Paediatric-HCP.ConclusionThe selected domains can be used to check weaknesses in the identification, management and reporting of suspected ADR by Paediatric-HCP in Brazil.
Abstract
Background
The use of atypical antipsychotics for the treatment of schizophrenia and other mental disorders in populations under 18 years of age is increasing worldwide. Little is known ...about treatment patterns and the influence of gender differences, which may be a predictor of clinical outcomes. The aim of this study was to investigate gender differences in the use of atypical antipsychotics in patients with early-onset schizophrenia (EOS) assisted by the public health system in Brazil.
Methods
We conducted a cross-sectional study of outpatients with EOS aged 10 to 17 years who received at least one provision of atypical antipsychotics (clozapine, olanzapine, risperidone, quetiapine or ziprasidone) from a large Brazilian pharmaceutical assistance programme. Data were retrieved from a nationwide administrative database from 2008 to 2017.
Results
Of the 49,943 patients with EOS, 63.5% were males, and the mean age was 13.6 years old. The patients were using risperidone (62.5%), olanzapine (19.6%), quetiapine (12.4%), ziprasidone (3.3%) and clozapine (2.2%). We found gender differences, especially in the 13–17 year age group (65.1% for males vs. 34.9% for females,
p
< 0.001), in the use of risperidone (72.1% for males vs. 27.9% for females,
p
< 0.001) and olanzapine (66.5% for males vs. 33.5% for females,
p
< 0.001). Only in the 13 to 17 years age group were the prescribed doses of olanzapine (
p
= 0.012) and quetiapine (
p
= 0.041) slightly higher for males than for females.
Conclusions
Our findings showed gender differences among patients diagnosed with EOS and who received atypical antipsychotics. More attention should be devoted to gender differences in research and clinical practice.
The use of psychotropic drugs by elderly people is widely spread around the world, given that prevalence of inappropriate medication is frequent. Strictly speaking, in Brazil, the vulnerable ...population of elderly people is more likely to use Potentially Inappropriate Psychotropic (PIP) due to the impact of social-economic characteristics, to the Brazilian Public Health System, and to the lack of patient monitoring. However, neither the use pattern nor the prevalence rate of PIP have been studied in Brazil so far. The objectives of this study were to determine the prevalence of PIP in elderly outpatients taking antidepressants, and to compare the performance of two different tools (Beers, STOPP).
This cross-sectional study involved all the aged outpatients (≥ 60 years of age) taking antidepressants attended by the public health system in a city of the State of São Paulo, Brazil. Data were obtained from a pharmacy database and medical records. All psychotropic drugs evaluated included: antidepressants, antipsychotics, anti-epileptics and benzodiazepines. STOPP and Beers criteria were applied to detect PIP.
One thousand one hundred forty prescriptions from 174 outpatients were subjected to two different screening tools. The average patient age was 67 (interquartile range 63-74) and the median number of drugs used was 3.0 (interquartile 2-4) per patient. The overall prevalence of PIP was 121 (69.5%). The levels of PIP observed according to tools were 39.6% (STOPP) and 29.9% (Beers).The long-term use of benzodiazepines was the most common PIP recognized, and the one which contributed more significantly to higher levels of PIP than other medications.
The prevalence of PIP was high among the elderly. STOPP criteria identified more PIP than Beers criteria. Knowledge of PIP prevalence should gear efforts to reduce the level of inappropriate prescriptions and may provide the need for developing national criteria.
Evidence on the use of non-steroidal anti-inflammatory drugs (NSAIDs) and corticoids for rheumatoid arthritis (RA) is inconclusive and is not up to date. This systematic review assessed the ...effectiveness and safety of these anti-inflammatories (AI) in the treatment of RA. COCHRANE (CENTRAL), MEDLINE, EMBASE, CINAHL, Web of Science and Virtual Health Library were searched to identify randomized controlled trials (RCT) with adults which used AI (dose represented in mg/day) compared with placebo or active controls and was carried out up to December of 2019. Reviewers, in pairs and independently, selected studies, performed the data extraction and assessed the risk of bias. The quality of the evidence was assessed by GRADE. Network meta-analyses were performed using the Stata v.14.2. Twenty-six articles were selected (NSAIDs = 21 and corticoids = 5). Naproxen 1,000 improved physical function, reduced pain and the number of painful joints compared to placebo. Etoricoxib 90 reduced the number of painful joints compared to placebo. Naproxen 750 reduced the number of swollen joints, except for etoricoxib 90. Naproxen 1,000, etoricoxib 90 and diclofenac 150 were better than placebo regarding patient assessment. Assessment physician showed that NSAIDs were better than placebo. Meta-analyses were not performed for prednisolone and prednisone. Naproxen 1,000 was the most effective drug and celecoxib 200 showed fewer adverse events. However, the low quality of the evidence observed for the outcomes with NSAIDs, the absence of meta-analyses to assess the outcomes with corticoids, as well as the risk of bias observed, indicate that future RCT can confirm such findings.
Objective:
Switching between second-generation antipsychotics (SGAs) is a common clinical practice in the treatment of schizophrenia and schizoaffective disorders due to differences in the drugs’ ...tolerability and safety profiles as well as the challenge of obtaining an ideal response. However, the factors associated with SGA switching remain uncertain and related real-world data are scarce. The main objective was to identify the factors associated with the switching of SGAs in patients with schizophrenia or schizoaffective disorder.
Methods:
We conducted a retrospective cohort study of outpatients with schizophrenia or schizoaffective disorder, who were aged ≥18 years and received a SGA (clozapine, olanzapine, risperidone, quetiapine or ziprasidone) from a Brazilian pharmaceutical assistance program for at least 3 months. We identified SGA users from 2008 to 2017 by using a national administrative database (Ambulatory Information System-SIA/SUS). The factors associated with the switches were evaluated by Cox proportional hazards regression and adjusted for sex and age; the confidence interval was set at 95% (95% CI).
Results:
In total, 563,765 patients were included. Female sex, advanced age of ≥70 years, residence in the Brazilian northeast region, and the type of antipsychotic used were associated with an increased risk of switching (
p
< 0.001). The incidence of switching ranged from 37.6/100 person-years for clozapine users to 58.2/100 person-years for risperidone users. Compared to the adjusted hazard ratio, for clozapine users, the corresponding ratios for risperidone, ziprasidone, quetiapine and olanzapine were 1.59 (95% CI, 1.57–1.61), 1.41 (95% CI, 1.39–1.44), 1.25 (95% CI, 1.23–1.26) and 1.11 (95% CI, 1.10–1.12) respectively.
Conclusion:
The groups most susceptible to SGA switching in real-life setting were older individuals, women, and those living in the Brazilian northeast region. Risperidone was associated with the highest risk of switching and as expected, clozapine was associated with the lowest risk of switching than that associated with the other SGAs.
Chronic kidney disease-mineral and bone disorder (CKD-MBD), a complication of chronic kidney disease, has been linked to reduced quality and length of life. High serum phosphate levels that result ...from CKD-MBD require phosphate-lowering agents, also known as phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on laboratory outcomes in patients with CKD-MBD.
Data sources included MEDLINE and EMBASE from January 1996 to April 2016, and the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD and randomized them to receive calcium-based phosphate binders (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet (diet), placebo or no treatment and reported effects on serum levels of phosphate, calcium and parathyroid hormone. We performed Bayesian network meta-analyses (NMA) to calculate the effect estimates (mean differences) and 95% credible intervals for serum levels of phosphate, calcium and parathyroid hormone. We calculated direct, indirect and network meta-analysis estimates using random-effects models. We applied the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each pairwise comparison.
Our search yielded 1108 citations; 71 RCTs were retrieved for full review and 16 proved eligible. Including an additional 13 studies from a previous review, 29 studies that enrolled 8335 participants proved eligible; 26 trials provided data for quantitative synthesis. Sevelamer, lanthanum, calcium, iron, diet and combinations of active treatments (calcium or sevelamer or lanthanum and combination of calcium and sevelamer) resulted in significantly lower serum phosphate as compared to placebo (moderate to very low quality of evidence). We found no statistically significant differences between active treatment categories in lowering serum phosphate. Sevelamer, lanthanum and diet resulted in lower serum calcium compared to calcium (moderate quality evidence for lanthanum and diet; low quality evidence for Sevelamer). Iron, sevelamer and calcium yielded lower parathyroid hormone levels as compared to lanthanum. Meta-regression analyses did not yield a statistically significant association between treatment effect and trial duration.
We found few differences between treatments in impact on phosphate and differences in parathyroid hormone. Relative to calcium, sevelamer, lanthanum and diet showed significant reduction in serum calcium from baseline. Treatment recommendations should be based on impact on patient-important outcomes rather than on surrogate outcomes. Systematic review registration: PROSPERO CRD-42016032945.
ObjectiveTo examine the relative impact of three management options in patients aged <60 years with cryptogenic stroke and a patent foramen ovale (PFO): PFO closure plus antiplatelet therapy, ...antiplatelet therapy alone and anticoagulation alone.DesignSystematic review and network meta-analysis (NMA) supported by complementary external evidence.Data sourcesMedline, EMBASE and Cochrane CENTRAL.Study selectionRandomised controlled trials (RCTs) addressing PFO closure and/or medical therapies in patients with PFO and cryptogenic stroke.Review methodsWe conducted an NMA complemented with external evidence and rated certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.ResultsTen RCTs in eight studies proved eligible (n=4416). Seven RCTs (n=3913) addressed PFO closure versus medical therapy. Of these, three (n=1257) addressed PFO closure versus antiplatelet therapy, three (n=2303) addressed PFO closure versus mixed antiplatelet and anticoagulation therapies and one (n=353) addressed PFO closure versus anticoagulation. The remaining three RCTs (n=503) addressed anticoagulant versus antiplatelet therapy. PFO closure versus antiplatelet therapy probably results in substantial reduction in ischaemic stroke recurrence (risk difference per 1000 patients over 5 years (RD): −87, 95% credible interval (CrI) −100 to −33; moderate certainty). Compared with anticoagulation, PFO closure may confer little or no difference in ischaemic stroke recurrence (low certainty) but probably has a lower risk of major bleeding (RD −20, 95% CrI −27 to −2, moderate certainty). Relative to either medical therapy, PFO closure probably increases the risk of persistent atrial fibrillation (RD 18, 95% CI +5 to +56, moderate certainty) and device-related adverse events (RD +36, 95% CI +23 to +50, high certainty). Anticoagulation, compared with antiplatelet therapy, may reduce the risk of ischaemic stroke recurrence (RD −71, 95% CrI −100 to +17, low certainty), but probably increases the risk of major bleeding (RD +12, 95% CrI −5 to +65, moderate certainty).ConclusionsIn patients aged <60 years, PFO closure probably confers an important reduction in ischaemic stroke recurrence compared with antiplatelet therapy alone but may make no difference compared with anticoagulation. PFO closure incurs a risk of persistent atrial fibrillation and device-related adverse events. Compared with alternatives, anticoagulation probably increases major bleeding.PROSPERO registration numberCRD42017081567.
BackgroundDeprescribing is the planned and supervised process of dose reduction or stopping of medication that might be causing harm, or no longer be of benefit. It is an activity that should be a ...normal part of care/the prescribing cycle. Although now broadly recognised, there are still challenges in its effective implementation.ObjectivesTo develop and validate an instrument to measure Brazilian healthcare professionals’ knowledge, attitudes and practices towards deprescribing.MethodsThis study will include the following steps: (1) development of the preliminary instrument; (2) content validation; (3) pilot study; (4) evaluation of psychometric characteristics. After the elaboration of items of the instrument through the literature review, we will use a hybrid Delphi method to develop and establish the content validity of the instrument. Further, a pilot survey will be performed with 30 healthcare professionals. Finally, for the evaluation of psychometric characteristics, a cross-sectional study will be accomplished with a representative sample of different healthcare professionals from different Brazilian states using respondent-driven sampling. Exploratory factor analysis and confirmatory factor analysis will be performed. For assessing the model fit, we will use the ratio of χ2 and df (χ2/df), comparative fit index, the goodness of fit index and root mean square error of approximation. In addition, the reliability of the instrument will be estimated by test–retest reproducibility and Cronbach’s alpha coefficient (α).Ethics and disseminationThe Ethics Committee for Research at the University of Sorocaba (ethics approval number: 3.848.916) approved the study. Study findings will be circulated to healthcare professionals and scientists in the field through publication in peer-reviewed journals and conference presentations.
Current tobacco treatment guidelines have established the efficacy of available interventions, but they do not provide detailed guidance for common implementation questions frequently faced in the ...clinic. An evidence-based guideline was created that addresses several pharmacotherapy-initiation questions that routinely confront treatment teams.
Individuals with diverse expertise related to smoking cessation were empaneled to prioritize questions and outcomes important to clinicians. An evidence-synthesis team conducted systematic reviews, which informed recommendations to answer the questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in the estimated effects and the strength of recommendations.
The guideline panel formulated five strong recommendations and two conditional recommendations regarding pharmacotherapy choices. Strong recommendations include using varenicline rather than a nicotine patch, using varenicline rather than bupropion, using varenicline rather than a nicotine patch in adults with a comorbid psychiatric condition, initiating varenicline in adults even if they are unready to quit, and using controller therapy for an extended treatment duration greater than 12 weeks. Conditional recommendations include combining a nicotine patch with varenicline rather than using varenicline alone and using varenicline rather than electronic cigarettes.
Seven recommendations are provided, which represent simple practice changes that are likely to increase the effectiveness of tobacco-dependence pharmacotherapy.
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