Appropriate follow up to detect potential adverse events after initiation of select contraceptive methods: a systematic review

Abstract Background Biochemical markers of bone turnover (BTMs), such as the bone alkaline phosphatase (bALP), procollagen type I N propeptide (PINP), serum cross-linked C-telopeptides of type I collagen (bCTx), and urinary cross-linked N-telopeptides of type I collagen (NTx), are used to manage therapy monitoring in osteoporotic patients. This systematic review analyzed the potential of these BMTs in predicting the clinical outcomes in terms of BMD, t-score, rate of fractures, and adverse events during the therapy setting in postmenopausal osteoporosis. Methods All randomized clinical trials (RCTs) reporting data on biomarkers for postmenopausal osteoporosis were accessed. Only articles reporting quantitative data on the level of biomarkers at baseline and on the outcomes of interest at the last follow-up were eligible. Results A total of 36,706 patients were retrieved. Greater values of bALP were associated with a greater rate of vertebral (P = 0.001) and non-vertebral fractures (P = 0.0001). Greater values of NTx at baseline were associated with a greater rate of adverse events at the last follow-up (P = 0.02). Greater values of CTx at baseline were associated with a greater rate of adverse events leading to discontinuation (P = 0.04), gastrointestinal adverse events (P = 0.0001), musculoskeletal adverse events (P = 0.04), and mortality (P = 0.04). Greater values of PINP at baseline were associated with greater rates of gastrointestinal adverse events (P = 0.02) at the last follow-up. Conclusion The present analysis supports the adoption of BMTs during pharmacological therapy setting of patients suffering from osteoporosis. Level of evidence I, systematic review of RCTs

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Outcomes of operative versus non-operative interventions on rectus abdominis diastasis: a combination of a retrospective analysis and a systematic review

10.21203/rs.2.18930/v1 ◽

2019 ◽

Author(s):

sue yuan ◽

Yunxia Li ◽

Qi Li ◽

Lu Fan ◽

Jie Zhou

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Rectus Abdominis ◽

Operative Intervention ◽

Abdominal Hernia ◽

Cochrane Library ◽

Abdominal Muscles ◽

Recurrence Rates ◽

Mesh Placement

Abstract Background There is no current consensus on the treatment of Rectus abdominis diastasis (RAD). This study aimed to assess the recurrence rates and adverse events after operative or non-operative intervention.Methods We performed a retrospective study and a systematic review. Patients with a diagnosis of RAD who underwent the mesh placement procedure were eligible. Data were collected from The Research Patient Data Registry. Then, a systematic literature search of Pubmed, Embase, and The Cochrane Library databases was performed. A modified Downs and Black checklist for randomized and non-randomized studies of healthcare interventions (DB) was used to evaluate the methodological quality of the studies.Results Data of 82 patients was collected. The 5-year cumulative incidence of recurrence of abdominal hernia was high (females 37.0% vs males 43.4%, P = 0.557). Of 3908 citations, 27 studies describing 2,372 patients were included into the systematic review. In non-operative group, seven studies (25.93%) with a total of 603 subjects reported no patient relapsed after a follow-up of 12 months; a 40% recurrence rate was reported after a follow-up of 5 years in one study, the adverse events associated with operation mainly included seroma (5.13%), a sensibility disorder of the abdominal skin (2.26%), and minor scarring (1.56%). Muscle strength training, such as training of the pelvic floor muscles, abdominal muscles, rectus abdominis, internal/external oblique, or transverse abdominal muscles, was performed in all included non-surgery studies, neither adverse events nor recurrence was reported.Conclusion Operative intervention may be effective at restoring the functions of the rectus muscles and at improving the stability of abdominal wall in the short-term, while non-operative intervention has a limited effect, especially for those RAD combined with hernia.

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Efficacy and safety of rituximab in adult frequent-relapsing or steroid-dependent minimal change disease or focal segmental glomerulosclerosis: a systematic review and meta-analysis

Clinical Kidney Journal ◽

10.1093/ckj/sfaa191 ◽

2020 ◽

Author(s):

Cheng Xue ◽

Bo Yang ◽

Jing Xu ◽

Chenchen Zhou ◽

Liming Zhang ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Focal Segmental Glomerulosclerosis ◽

Minimal Change Disease ◽

Meta Analysis ◽

Minimal Change ◽

Efficacy And Safety ◽

Segmental Glomerulosclerosis ◽

Steroid Dependent

Abstract Background The efficacy and safety of rituximab (RTX) in adult frequent-relapsing (FR) or steroid-dependent (SD) nephrotic syndrome (NS), including minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS), are still inconclusive. Methods We performed a systematic review and meta-analysis registered in PROSPERO (CRD42019148102) by pooling data of cohort studies or case series on adult patients with difficult-to-treat NS. Steroid-resistant NS was excluded. The primary outcomes were the complete remission (CR) rate and the relapse rate. Partial remission (PR) rate, no response (NR) rate and adverse events were the secondary outcomes. A random-effects model was performed for all the outcomes. Results We included 21 studies involving 382 adult MCD/FSGS subjects with a median follow-up duration from 12 to 43 months. RTX treatment induced a pooled 84.2% CR rate [95% confidence interval (CI): 67.7–96.3%], while MCD patients had a high 91.6% CR rate and FSGS patients a moderate 43% CR rate. However, 27.4% (95% CI 20.7–34.5%) of the patients relapsed during the follow-up. The pooled PR and NR rates were 5.8% (95% CI 1.2–12.5%) and 5.2% (95% CI 0.0–15.0%), respectively. RTX was associated with trivial adverse events and good tolerance. Conclusions In summary, by pooling results of current pilot studies, RTX may be an effective and relatively safe alternative for most adult FR or SD MCD/FSGS to displace calcineurin inhibitors or prednisone in the hierarchy of treatment. More clinical trials comparing RTX with other immunosuppressants and concerning the long-term adverse events are needed.

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Comparative Safety of Bevacizumab, Ranibizumab, and Aflibercept for Treatment of Neovascular Age-Related Macular Degeneration (AMD): A Systematic Review and Network Meta-Analysis of Direct Comparative Studies

Journal of Clinical Medicine ◽

10.3390/jcm9051522 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1522 ◽

Cited By ~ 1

Author(s):

Anna A. Plyukhova ◽

Maria V. Budzinskaya ◽

Kirill M. Starostin ◽

Robert Rejdak ◽

Claudio Bucolo ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Macular Degeneration ◽

Pigment Epithelium ◽

Meta Analysis ◽

Retinal Pigment ◽

Age Related Macular Degeneration ◽

Macular Atrophy ◽

Age Related

Background: Since the efficacy of ranibizumab (RBZ), bevacizumab (BVZ) and aflibercept (AFB) is comparable in neovascular age-related macular degeneration (AMD), we conducted a systematic review and meta-analysis to evaluate the long-term safety profiles of these agents, including ocular safety. Methods: Systematic review identifying randomized controlled trials (RCTs) comparing RBZ, BVZ and AFB directly published before March 2019. Serious ocular adverse events (SOAE) of special interest were endophthalmitis, pseudo-endophthalmitis, retinal pigment epithelium tear and newly identified macular atrophy. Results: Thirteen RCTs selected for meta-analysis (4952 patients, 8723 people-years follow-up): 10 compared RBZ vs. BVZ and three RBZ vs. AFB. There were no significant differences in almost all adverse events (systemic and ocular) between BVZ, RBZ and AFB in up to two years’ follow-up. Macular atrophy was reported heterogeneously and not reported as SOAE in most trials. Conclusions: Direct comparison of RBZ, BVZ and AFB safety profiles in the RCT network meta-analytical setting have not revealed a consistent benefit of these three commonly used anti-vascular endothelial growth factor (anti-VEGF) agents in AMD. Network model ranking highlighted potential benefits of RBZ in terms of a systemic safety profile; however, this appears a hypothesis rather than a conclusion. Newly identified macular atrophy is underestimated in RCTs—future real-world data should be focused on SOAE.

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Exercise for patients with major depression: a systematic review with meta-analysis and trial sequential analysis

BMJ Open ◽

10.1136/bmjopen-2016-014820 ◽

2017 ◽

Vol 7 (9) ◽

pp. e014820 ◽

Cited By ~ 34

Author(s):

Jesper Krogh ◽

Carsten Hjorthøj ◽

Helene Speyer ◽

Christian Gluud ◽

Merete Nordentoft

Keyword(s):

Quality Of Life ◽

Systematic Review ◽

Adverse Events ◽

Sequential Analysis ◽

Trial Sequential Analysis ◽

Depression Severity ◽

Serious Adverse Events ◽

Secondary Outcomes

ObjectivesTo assess the benefits and harms of exercise in patients with depression.DesignSystematic reviewData sourcesBibliographical databases were searched until 20 June 2017.Eligibility criteria and outcomesEligible trials were randomised clinical trials assessing the effect of exercise in participants diagnosed with depression. Primary outcomes were depression severity, lack of remission and serious adverse events (eg, suicide) assessed at the end of the intervention. Secondary outcomes were quality of life and adverse events such as injuries, as well as assessment of depression severity and lack of remission during follow-up after the intervention.ResultsThirty-five trials enrolling 2498 participants were included. The effect of exercise versus control on depression severity was −0.66 standardised mean difference (SMD) (95% CI −0.86 to −0.46; p<0.001; grading of recommendations assessment, development and evaluation (GRADE): very low quality). Restricting this analysis to the four trials that seemed less affected of bias, the effect vanished into −0.11 SMD (−0.41 to 0.18; p=0.45; GRADE: low quality). Exercise decreased the relative risk of no remission to 0.78 (0.68 to 0.90; p<0.001; GRADE: very low quality). Restricting this analysis to the two trials that seemed less affected of bias, the effect vanished into 0.95 (0.74 to 1.23; p=0.78). Trial sequential analysis excluded random error when all trials were analysed, but not if focusing on trials less affected of bias. Subgroup analyses found that trial size and intervention duration were inversely associated with effect size for both depression severity and lack of remission. There was no significant effect of exercise on secondary outcomes.ConclusionsTrials with less risk of bias suggested no antidepressant effects of exercise and there were no significant effects of exercise on quality of life, depression severity or lack of remission during follow-up. Data for serious adverse events and adverse events were scarce not allowing conclusions for these outcomes.Systematic review registrationThe protocol was published in the journalSystematic Reviews: 2015; 4:40.

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Long-term and serious harms of medical cannabis and cannabinoids for chronic pain: A systematic review of non-randomized studies

10.1101/2021.05.27.21257921 ◽

2021 ◽

Author(s):

Dena Zeraatkar ◽

Matthew Cooper ◽

Arnav Agarwal ◽

Robin Vernooij ◽

Gareth Leung ◽

...

Keyword(s):

Systematic Review ◽

Chronic Pain ◽

Adverse Events ◽

Cochrane Central Register ◽

Medical Cannabis ◽

Management Options ◽

Serious Adverse Events ◽

Randomized Studies

Objective: To establish the risk and prevalence of long-term and serious harms of medical cannabis and cannabinoids for chronic pain. Design: Systematic review and meta-analysis. Data sources: MEDLINE, EMBASE, PsycInfo, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 1, 2020. Study selection: Non-randomized studies reporting on harms of medical cannabis or cannabinoids in people living with chronic pain with ≥4 weeks of follow-up. Data extraction and synthesis: A parallel guideline panel provided input on the design and interpretation of the systematic review, including selection of adverse events for consideration. Two reviewers, working independently and in duplicate, screened the search results, extracted data, and assessed risk of bias. We used random-effects models for all meta-analyses and the GRADE approach to evaluate the certainty of evidence. Results: We identified 39 eligible studies that enrolled 12,143 patients with chronic pain. Very low certainty evidence suggests that adverse events are common (prevalence: 26.0%; 95% CI 13.2 to 41.2) among users of medical cannabis or cannabinoids for chronic pain, particularly any psychiatric adverse events (prevalence: 13.5%; 95% CI 2.6 to 30.6). However, very low certainty evidence indicates serious adverse events, adverse events leading to discontinuation, cognitive adverse events, accidents and injuries, and dependence and withdrawal syndrome are uncommon and typically occur in fewer than one in 20 patients. We compared studies with <24 weeks and ≥ 24 weeks cannabis use and found more adverse events reported among studies with longer follow-up (test of interaction p < 0.01). Palmitoylethanolamide was usually associated with few to no adverse events. We found insufficient evidence addressing the harms of medical cannabis compared to other pain management options, such as opioids. Conclusions: There is very low certainty evidence that adverse events are common among people living with chronic pain who use medical cannabis or cannabinoids, but that few patients experience serious adverse events. Future research should compare long-term and serious harms of medical cannabis with other management options for chronic pain, including opioids.

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The Efficacy of Acupuncture Treatment for Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-Analysis

Complementary Medicine Research ◽

10.1159/000513655 ◽

2021 ◽

pp. 1-11

Author(s):

Yi-Chen Chen ◽

Li-Kung Wu ◽

Ming-Shinn Lee ◽

Yen-Lun Kung

Keyword(s):

Systematic Review ◽

Attention Deficit Hyperactivity Disorder ◽

Adverse Events ◽

Acupuncture Treatment ◽

Meta Analysis ◽

Effective Rate ◽

Controlled Trials ◽

Hyperactivity Disorder ◽

Randomized Controlled

Background: This study aimed to assess the efficacy of acupuncture for treating attention deficit hyperactivity disorder (ADHD) in children and adolescents. Patients and Methods: Systematic review and meta-analysis including randomized controlled trials that compared the effects of acupuncture treatment (AT) with pharmacotherapy (methylphenidate hydrochloride, MPH) among patients with ADHD. A total of 12 electronic databases were searched from inception until February 3, 2020. The main outcomes were the effective rate and post-treatment hyperactivity scores. We also assessed the incidence of adverse events and follow-up course. Results: A total of 10 studies involving 876 patients were included in this study. The meta-analysis revealed that AT yielded a significantly higher effective rate than MPH (odds ratio 2.239, 95% CI 1.438–3.487, p < 0.001, 8 studies), and that AT can reduce the hyperactivity scores to a lesser degree than MPH (standardized mean difference = –0.882, 95% CI –1.295 to –0.469, p < 0.001, 3 studies). Two studies reported no adverse events in the AT group, while one study suggested that AT can reduce adverse drug reactions. Furthermore, 3 studies concluded that the effects of AT were maintained, even after completion of treatment. Conclusion: This study suggests that AT may be more beneficial than MPH therapy for ADHD patients. However, the evidence may be highly limited, especially considering the outcome of hyperactivity scores with the high risk of bias, very low GRADE, and small number of studies. Thus, further studies of rigorous design and high quality are needed to confirm and strengthen the results, especially in the Western part of the world. Additionally, well-designed randomized controlled trials that evaluate adverse events and include a long-term follow-up should be conducted to determine the efficacy, safety, and side effects of AT for ADHD in children and adolescents.

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Efficacy and Safety of Probiotics, Prebiotics and Synbiotics in the Treatment of Irritable Bowel Syndrome: A systematic review and meta-analysis

Sultan Qaboos University Medical Journal [SQUMJ] ◽

10.18295/squmj.2020.20.01.003 ◽

2020 ◽

Vol 20 (1) ◽

pp. 13 ◽

Cited By ~ 3

Author(s):

Mohammad Z. Asha ◽

Sundos F. H. Khalil

Keyword(s):

Systematic Review ◽

Irritable Bowel Syndrome ◽

Adverse Events ◽

Meta Analysis ◽

Group Differences ◽

Significant Heterogeneity ◽

Efficacy And Safety ◽

Gastrointestinal Microbiome ◽

Irritable Bowel

Treatments that target alterations in gut microbiota may be beneficial for patients with irritable bowel syndrome (IBS). A systematic review and meta-analysis was conducted of randomised clinical trials (RCTs) evaluating the efficacy and safety of probiotics, prebiotics and synbiotics. Factors considered in the analysis included global IBS symptoms and/or abdominal pain, secondary symptoms and the frequency of adverse events. A total of 33 RCTs involving 4,321 patients were identified. Overall, probiotics significantly improved global IBS symptoms compared to placebos (standardised mean difference = −0.32, 95% confidence interval: −0.48 to −0.15; P <0.001), with significant heterogeneity between studies (I2 = 72%; P <0.001). This remained apparent in both single- and multi-strain probiotic interventions as well as synbiotic formulations. However, evidence regarding prebiotics was scarce. There were no significant inter-group differences in terms of the frequency of adverse events. Future RCTs should address methodological limitations, including short follow-up periods and patient adherence.Keywords: Irritable Bowel Syndrome; Gastrointestinal Microbiome; Dietary Supplements; Probiotics; Prebiotics; Synbiotics; Meta-Analysis; Systematic Review.

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Newer-generation antihistamines and the risk of adverse events in children: a systematic review

10.22541/au.160680607.70423821/v1 ◽

2020 ◽

Author(s):

Michael Miligkos ◽

Maria Dakoutrou ◽

Eleni Statha ◽

Nikoletta Theochari ◽

Ilektra Antonia Mavroeidi ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Pediatric Population ◽

Indirect Evidence ◽

Allergic Diseases ◽

Tolerability Profile ◽

Eligibility Criteria ◽

Safety Parameters ◽

Comparative Safety

Background: H1-antihistamines (AHs) are widely used for the treatment of allergic diseases, being one of the most commonly prescribed classes of medications in Pediatrics. Newer-generation AHs are associated with fewer adverse effects compared to first-generation. However, their relative harms in the pediatric population still need scrutiny. Methods: We performed a systematic review of randomized controlled trials (RCTs) which included comparisons of safety parameters between an orally administered newer-generation AH with another AH (first- or second- generation), montelukast or placebo in children aged≤12 years. We searched MEDLINE and CENTRAL, independently extracted data on study population, interventions, adverse events (AEs) and treatment discontinuations, and assessed the methodological quality of the included RCTs using the Cochrane’s risk of bias tool. Results: Fourty-five RCTs published between 1989 and 2017 met eligibility criteria. The majority of RCTs included school-aged children with allergic rhinitis and had a follow-up period of up to a month. Four RCTs reported serious AEs in patients receiving a newer-generation AH, but only two patients experienced a possibly drug-related serious AE. The occurrence of AEs, drug-related AEs and treatment discontinuations due to AEs varied between RCTs. Most AEs reported were of mild intensity. Indirect evidence indicates that cetirizine is more sedating than the other newer-generation AHs. Conclusion: Our findings confirm that newer-generation AHs have a favorable safety and tolerability profile. However, we could not draw firm conclusions regarding the comparative safety profile of the newer-generation AHs due to the paucity of head-to-head RCTs, variation in definitions and reporting of AEs, and short follow-up duration.

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Outcomes evaluated in controlled clinical trials on the management of COVID-19: A methodological systematic review

10.1101/2020.10.26.20218370 ◽

2020 ◽

Author(s):

Alexander G. Mathioudakis ◽

Markus Fally ◽

Rola Hashad ◽

Ahmed Kouta ◽

Ali Sina Hadi ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Outcome Measurement ◽

Treatment Success ◽

Community Setting ◽

Significant Heterogeneity ◽

Measurement Instruments ◽

Life Saving

AbstractIt is crucial that randomized controlled trials (RCTs) on the management of coronavirus disease 2019 (COVID-19) evaluate the outcomes that are critical to patients and clinicians, to facilitate relevance, interpretability, and comparability.This methodological systematic review describes the outcomes evaluated in 415 RCTs on the management of COVID-19, that were registered with ClinicalTrials.gov, by 5/5/2020.Significant heterogeneity was observed in the selection of outcomes and the instruments used to measure them. Mortality, adverse events and treatment success or failure are only evaluated in 64.4%, 48.4% and 43% of the included studies, respectively, while other outcomes are selected less often. Studies focusing on more severe presentations (hospitalized patients or requiring intensive care) most frequently evaluate mortality and adverse events, while hospital admission and viral detection/load are most frequently assessed in the community setting. Outcome measurement instruments are poorly reported and heterogeneous. In general, simple instruments that can control for important sources of bias are favoured. Follow-up does not exceed one month in 64.3% of these earlier trials, and long-term COVID-19 burden is rarely assessed.The methodological issues identified could delay the introduction of potentially life-saving treatments in clinical practice. Our findings demonstrate the need for consensus in the design of RCTs.Take home message@ERSpublications: This systematic review describes the heterogeneity in outcomes evaluated in 415 RCTs on COVID-19 management and the instruments used to measure them. Our findings reveal a need for consensus in the design of future RCTs.

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