RESUMO
Purpose: Immune imbalances in major depressive disorder (MDD) have been targeted by anti-inflammatory treatment approaches in clinical trials to increase responsiveness to therapy. However, even after several meta-analyses, no translation of evidence into clinical practice has taken place. We performed a systematic review to evaluate meta-analytic evidence of randomized controlled trials on the use of anti-inflammatory agents for MDD to summarize efficacy estimates and elucidate shortcomings. Methods: Pooled effect estimates and heterogeneity indices were primary outcomes. Characteristics of the included meta-analyses were extracted. Scientific quality of meta-analyses was assessed using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR). Results: N=20 meta-analyses met the eligibility criteria. Study characteristics like outcome scales, composition of patient populations, and add-on or monotherapy regimen varied very little for celecoxib studies, varied little for minocycline studies, and were rather variable for omega 3 fatty acids studies. R-AMSTAR scores ranged from 26 to 39 out of 44 points indicating variable quality, where a comprehensive literature search was the strongest and the consideration of scientific quality in the conclusions was the weakest domain across all meta-analyses. For minocycline and celecoxib, superiority was demonstrated with medium to large effect size with substantial heterogeneity and with large to very large effect size with negligible heterogeneity, respectively. For omega 3 fatty acids, superiority was also demonstrated with mainly small and medium effect sizes with substantial heterogeneity. However, for minocycline and omega 3 fatty acids, non-significant meta-analyses were found also. Conclusion: Even in our synthesized approach, no clear recommendations could be derived on the use of anti-inflammatory treatment for MDD due to several critical aspects like heterogeneity, diversity of patient populations, treatment regimen, and outcomes, and limited scientific quality. However, we observed clear inter-substance differences with meta-analytic evidence being strongest for celecoxib and weakest for omega 3 fatty acids.
RESUMO
Objective: The main aim is to compare the risk of severe hypoglycemia associated with the modified-release (MR) gliclazide against glimepiride in diabetic older adults. Methods: All older adult diabetic patients who attended the emergency department (ED) between the 1st of Aug. 2017 and the end of Mar 2020 on gliclazide MR or glimepiride are included in two cohorts. We compared baseline differences between cohorts in demographics, lab results, diabetes complications, comorbidities, and drugs using the chi-squared test for categorical variables and unpaired t-test for continuous variables. All the baseline variables are used in a logistic regression to produce the propensity scores for receiving gliclazide MR. The primary outcome was Severe Hypoglycemia requiring Emergency Admission (SHEA). We used documented hypoglycemia, falls, fractures, Cardiovascular ED Admission (CVEA), and recurrent ED admissions as secondary outcomes. We used a univariate logistic regression followed by a propensity score-adjusted logistic regression to identify the adjusted odds ratio. We did a subgroup analysis for low and moderate-high doses users. Results: We included 2320 patients, 1786 were on gliclazide MR while 534 were on glimepiride. The risk of SHEA (Adjusted Odds Ratio AOR 6.74, p=0.002), falls (AOR 1.43, p=0.003), fractures (AOR 1.43, p=0.01), CVEA (AOR 1.66, p<0.001), recurrent ED admission (AOR 1.39, p=0.002) were significantly higher. At the same time, documented hypoglycemia was insignificantly higher (AOR 1.17, p= 0.444) with gliclazide MR compared to glimepiride. The low doses of both treatments did not show any SHEA cases, while the results with higher doses showed the same pattern of increased risk with gliclazide MR as the principle analysis. Conclusion: Using gliclazide MR for older patients may not be a relatively safer alternative to avoid severe hypoglycemia and its possible consequences compared to glimepiride. It may be added to glimepiride in the Beers list of medications to be avoided in older adults.
RESUMO
PURPOSE: To assess the prevalence and associated risk of potentially inappropriate prescribing (PIP) in older adults. METHODS: This was a national 3-year retrospective study of outpatient older adults exposed to potentially inappropriate medication (PIM) or polypharmacy. We used the Beers Criteria 2019 list to identify PIM to be avoided in older adults. We define moderate polypharmacy (MoP) and major polypharmacy (MaP) as using 6-10 or >10 chronic medications, respectively. Determinants of PIP included patients' demographics, lab results, medications, comorbidities, and home healthcare services. We used Chi-square (for categorical variables), Unpaired t-test and ANOVA (for continuous variables as applicable) to assess the association of these determinants with PIP. Univariate followed by multivariate logistic regression models were used to get the crude and adjusted odds ratios of exposure to PIM or polypharmacy within patients who had emergency department (ED) admissions, bone fractures, falls, or constipation, compared to those who had not. RESULTS: 3537 patients were included. 62.6%, 40.4%, and 27.2% were exposed to PIM, MoP and MaP, respectively. Determinants of PIP included age, gender, ethnicity, weight, kidney function, sodium levels, hypertension, diabetes, heart failure, CAD, and home healthcare services (all with p-value < 0.05). PIM was associated with risk of ED admission, bone fracture and constipation with adjusted OR (p-values) of 1.27 (0.002), 1.33 (0.005), and 1.40 (<0.001), respectively. MoP was associated with the risk of ED admission, bone fracture, and constipation, with adjusted OR (p-values) of 1.27 (0.012), 1.34 (0.019), and 1.47 (<0.001), respectively. MaP was associated with a higher risk of ED admission, bone fracture, falls, and constipation with adjusted OR (p-values) of 1.46 (0.001), 1.59 (0.002), 1.39 (0.023), and 2.07 (<0.001), respectively. CONCLUSION: PIP is common and is associated with an increased risk of poor clinical outcomes in older adults.
