Peto Odds Ratio Research Articles

Abstract 4138662: Mineralocorticoid receptor antagonist in patients with acute myocardial infarction: An updated systematic review and meta-analysis of randomized trials

Background: While mineralocorticoid antagonists (MRA) reduce mortality in patients developing heart failure post myocardial infarction (MI), it is unclear whether they are beneficial in an unselected post-MI population. Aims: Using a systematic review and meta-analysis, we aim to determine the effect of MRA treatment versus no MRA treatment on all-cause mortality in unselected post-MI patients from randomized data, simultaneously with the presentation of the largest randomized controlled trial on the topic, the CLEAR SYNERGY trial. Methods/Approach: We completed a systematic review of all randomized controlled trials comparing MRA treatment to no MRA treatment in post-MI patients. We will perform our primary analysis using fixed effects with the Peto odds ratio method and use random effects as a sensitivity analysis. The primary outcome will be all-cause mortality, and secondary outcomes will include cardiovascular mortality, new or worsening heart failure, recurrent myocardial infarction and stroke. Results/Data: Our systematic review of Pubmed, Embase, and CENTRAL from inception until April 30, 2024, yielded 456 records. A total of 11,199 participants from 11 randomized clinical trials will be included in addition to the late-breaking CLEAR SYNERGY trial. The CLEAR SYNERGY trial is a 2 x 2 factorial randomized controlled trial of low-dose colchicine 0.5mg daily versus placebo and spironolactone 25mg daily versus placebo in 7,062 post-MI patients who were within 72h of the index percutaneous coronary intervention. The results of the spironolactone factorial will be presented in the fall of 2024 with an expected median follow-up of 3.5 years. As the investigators of the CLEAR SYNERGY trial, we will combine our data with the other 11 trials for a total of 12 trials and 18,261 participants. Conclusions: CLEAR SYNERGY is the largest randomized controlled trial with the longest follow-up of spironolactone in the post-MI population. Our meta-analysis will provide updated effect estimates of post-MI MRA treatment, leveraging the late-breaking CLEAR SYNERGY data to reflect the totality of the evidence.

Efficacy and Safety of Modafinil for Treatment of Amphetamine-Type Stimulant Use Disorder: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials: Efficacité et innocuité du modafinil pour le traitement des troubles liés à l'usage de stimulants de type amphétamine : revue systématique et méta-analyse d'essais randomisés contrôlés par placebo.

Amphetamine-type stimulants (ATSs) are related to significant harm worldwide, with limited effective pharmacological treatments for ATS use disorder (ATSUD). Modafinil has been explored as a potential treatment for ATSUD. This systematic review and meta-analysis (PROSPERO ID: CRD42023388487) aimed to evaluate the efficacy and safety of modafinil for the treatment of ATSUD. A comprehensive search of major indexing sources and trial registries, from inception to search date, was conducted on February 15, 2023, and updated on October 31, 2023. Eligible studies were randomized placebo-controlled trials (RCTs) of modafinil in individuals meeting the criteria for the Diagnostic and Statistical Manual of Mental Disorders, fourth and fifth editions, diagnoses of ATSUD. Eligible studies were assessed for risk of bias, using the Cochrane Risk of Bias tool. The primary outcome included the effect of modafinil on ATS use. Secondary outcomes included retention in treatment, ATS craving, treatment discontinuation due to adverse events (AEs), and serious AEs. Subgroup analysis by modafinil dose was conducted where appropriate. Risk ratio (RR) or Peto's odds ratio (OR) was calculated for the meta-analysis of dichotomous variables and standardized mean difference (SMD) was calculated for the random-effect meta-analysis of continuous variables. Five RCTs (N = 451 participants) were included. Modafinil did not significantly impact ATS use (RR = 0.99; 95% CI, 0.97 to 1.02; p = 0.655), retention in treatment (RR = 1.02; 95% CI, 0.91 to 1.14; p = 0.799), ATS craving (SMD = -0.36; 95% CI, -1.19 to 0.47; p = 0.398), or treatment discontinuation due to AEs (Peto's OR = 0.48; 95% CI, 0.20 to 1.14; p = 0.100). These results were consistent across subgroup analyses. More episodes of serious AEs were reported in the modafinil group than in the placebo group, at higher doses (Peto's OR = 4.80; 95% CI, 1.18 to 19.56, p = 0.029). There is currently no evidence suggesting that modafinil has a statistically significant effect on efficacy outcomes in populations with ATSUD. Continued research into effective treatments and harm reduction strategies for ATSUD is essential.

Appendectomy versus antibiotic treatment for acute appendicitis.

Acute appendicitis is one of the most common emergency general surgical conditions worldwide. Uncomplicated/simple appendicitis can be treated with appendectomy or antibiotics. Some studies have suggested possible benefits with antibiotics with reduced complications, length of hospital stay, and the number of days off work. However, surgery may improve success of treatment as antibiotic treatment is associated with recurrence and future need for surgery. To assess the effects of antibiotic treatment for uncomplicated/simple acute appendicitis compared with appendectomy for resolution of symptoms and complications. We searched CENTRAL, MEDLINE, Embase, and two trial registers (World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov) on 19 July 2022. We also searched for unpublished studies in conference proceedings together with reference checking and citation search. There were no restrictions on date, publication status, or language of publication. We included parallel-group randomised controlled trials (RCTs) only. We included studies where most participants were adults with uncomplicated/simple appendicitis. Interventions included antibiotics (by any route) compared with appendectomy (open or laparoscopic). We used standard methodology expected by Cochrane. We used GRADE to assess the certainty of evidence for each outcome. Primary outcomes included mortality and success of treatment, and secondary outcomes included number of participants requiring appendectomy in the antibiotic group, complications, pain, length of hospital stay, sick leave, malignancy in the antibiotic group, negative appendectomy rate, and quality of life. Success of treatment definitions were heterogeneous although mainly based on resolution of symptoms rather than incorporation of long-term recurrence or need for surgery in the antibiotic group. We included 13 studies in the review covering 1675 participants randomised to antibiotics and 1683 participants randomised to appendectomy. One study was unpublished. All were conducted in secondary care and two studies received pharmaceutical funding. All studies used broad-spectrum antibiotic regimens expected to cover gastrointestinal bacteria. Most studies used predominantly laparoscopic surgery, but some included mainly open procedures. Six studies included adults and children. Almost all studies aimed to exclude participants with complicated appendicitis prior to randomisation, although one study included 12% with perforation. The diagnostic technique was clinical assessment and imaging in most studies. Only one study limited inclusion by sex (male only). Follow-up ranged from hospital admission only to seven years. Certainty of evidence was mainly affected by risk of bias (due to lack of blinding and loss to follow-up) and imprecision. Primary outcomes It is uncertain whether there was any difference in mortality due to the very low-certainty evidence (Peto odds ratio (OR) 0.51, 95% confidence interval (CI) 0.05 to 4.95; 1 study, 492 participants). There may be 76 more people per 1000 having unsuccessful treatment in the antibiotic group compared with surgery, which did not reach our predefined level for clinical significance (risk ratio (RR) 0.91, 95% CI 0.87 to 0.96; I2 = 69%; 7 studies, 2471 participants; low-certainty evidence). Secondary outcomes At one year, 30.7% (95% CI 24.0 to 37.8; I2 = 80%; 9 studies, 1396 participants) of participants in the antibiotic group required appendectomy or, alternatively, more than two-thirds of antibiotic-treated participants avoided surgery in the first year, but the evidence is very uncertain. Regarding complications, it is uncertain whether there is any difference in episodes of Clostridium difficile diarrhoea due to very low-certainty evidence (Peto OR 0.97, 95% CI 0.24 to 3.89; 1 study, 1332 participants). There may be a clinically significant reduction in wound infections with antibiotics (RR 0.25, 95% CI 0.09 to 0.68; I2 = 16%; 9 studies, 2606 participants; low-certainty evidence). It is uncertain whether antibiotics affect the incidence of intra-abdominal abscess or collection (RR 1.58, 95% CI 0.61 to 4.07; I2 = 19%; 6 studies, 1831 participants), or reoperation (Peto OR 0.13, 95% CI 0.01 to 2.16; 1 study, 492 participants) due to very low-certainty evidence, mainly due to rare events causing imprecision and risk of bias. It is uncertain if antibiotics prolonged length of hospital stay by half a day due to the very low-certainty evidence (MD 0.54, 95% CI 0.06 to 1.01; I2 = 97%; 11 studies, 3192 participants). The incidence of malignancy was 0.3% (95% CI 0 to 1.5; 5 studies, 403 participants) in the antibiotic group although follow-up was variable. Antibiotics probably increased the number of negative appendectomies at surgery (RR 3.16, 95% CI 1.54 to 6.49; I2 = 17%; 5 studies, 707 participants; moderate-certainty evidence). Antibiotics may be associated with higher rates of unsuccessful treatment for 76 per 1000 people, although differences may not be clinically significant. It is uncertain if antibiotics increase length of hospital stay by half a day. Antibiotics may reduce wound infections. A third of the participants initially treated with antibiotics required subsequent appendectomy or two-thirds avoided surgery within one year, but the evidence is very uncertain. There were too few data from the included studies to comment on major complications.

Cardioprotective Effects of PARP Inhibitors: A Re-Analysis of a Meta-Analysis and a Real-Word Data Analysis Using the FAERS Database.

Objective: This study aimed to assess the potential of PARP inhibitors to prevent cardiotoxicity. Methods: First, a re-analysis and update of a previously published study was conducted. Additional searches were conducted of the PubMed and Cochrane Central Register of Controlled Trials databases on 2 June 2023. After the selection process, the pooled odds ratio (OR) for cardiac adverse events (AEs) was calculated. Second, the FAERS database was examined for 10 frequently co-administered anticancer agents. The reporting odds ratio (ROR) was calculated based on the occurrence of cardiac AEs depending on the co-administration of PARP inhibitors. Results: Seven studies were selected for the meta-analysis. Although not statistically significant, co-administration of PARP inhibitors with chemotherapy/bevacizumab decreased the risk of cardiac AEs (Peto OR = 0.61; p = 0.36), while co-administration with antiandrogens increased the risk of cardiac AEs (Peto OR = 1.83; p = 0.18). A total of 19 cases of cardiac AEs were reported with co-administration of PARP inhibitors in the FAERS database. Co-administration of PARP inhibitors with chemotherapy/bevacizumab significantly decreased the risk of cardiac AEs (ROR = 0.352; 95% confidence interval (CI), 0.194-0.637). On the other hand, for antiandrogens co-administered with PARP inhibitors, the ROR was 3.496 (95% CI, 1.539-7.942). The ROR for immune checkpoint inhibitors co-administered with PARP inhibitors was 0.606 (95% CI, 0.151-2.432), indicating a non-significant effect on cardiac AEs. Conclusion: This study reports that PARP inhibitors show cardioprotective effects when used with conventional anticancer agents.

Transjugular intrahepatic portosystemic shunts for adults with hepatorenal syndrome.

Transjugular intrahepatic portosystemic shunts for adults with hepatorenal syndrome.

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

ST waveform analysis vs cardiotocography alone for intrapartum fetal monitoring: An updated systematic review and meta-analysis of randomized trials.

ST waveform analysis (STAN) was introduced as an adjunct to cardiotocography (CTG) to improve neonatal and maternal outcomes. The aim of the present study was to quantify the efficacy of STAN vs CTG and assess the quality of the evidence using GRADE. We performed systematic literature searches to identify randomized controlled trials and assessed included studies for risk of bias. We performed meta-analyses, calculating pooled risk ratio (RR) or Peto odds ratio (OR). We also performed post hoc trial sequential analyses for selected outcomes to assess the risk of false-positive results and the need for additional studies. Nine randomized controlled trials including 28 729 women were included in the meta-analysis. There were no differences between the groups in operative deliveries for fetal distress (10.9 vs 11.1%; RR 0.96; 95% confidence interval [CI] 0.82-1.11). STAN was associated with a significantly lower rate of metabolic acidosis (0.45% vs 0.68%; Peto OR 0.66; 95% CI 0.48-0.90). Accordingly, 441 women need to be monitored with STAN instead of CTG alone to prevent one case of metabolic acidosis. Women allocated to STAN had a reduced risk of fetal blood sampling compared with women allocated to conventional CTG monitoring (12.5% vs 19.6%; RR 0.62; 95% CI 0.49-0.80). The quality of the evidence was high to moderate. Absolute effects of STAN were minor and the clinical significance of the observed reduction in metabolic acidosis is questioned. There is insufficient evidence to state that STAN as an adjunct to CTG leads to important clinical benefits compared with CTG alone.

The efficacy and safety of tranexamic acid in transforaminal lumbar interbody fusion: a systematic review and meta-analysis.

This meta-analysis aimed to assess the efficacy and safety of tranexamic acid (TXA) in transforaminal lumbar interbody fusion (TLIF), focusing on its impact on intraoperative blood loss and related outcomes. The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, EMBASE, Medline, and Cochrane Library databases to identify all literature related with TXA and TLIF. Finally, five trials ultimately meeting the inclusion criteria. Continuous variables were analyzed using mean difference and categorical variables were analyzed using Peto odds ratio, via random effects models. The meta-analysis revealed a significant reduction in intraoperative blood loss associated with TXA use during TLIF, as confirmed by the RCTs. However, the impact of TXA on other outcomes, such as postoperative drainage volume, total blood loss, and length of hospital stay, remains inconclusive due to limited data. No severe complications related to TXA use were reported, providing preliminary evidence of its safety in TLIF. TXA appears to effectively reduce intraoperative blood loss in TLIF, based on the available RCT evidence. However, further research is needed to provide a comprehensive assessment of TXA's overall impact on various outcomes in this context. This meta-analysis underscores the importance of ongoing investigation to establish the full potential and safety profile of TXA in TLIF procedures.

Inhaled nitric oxide in acute bronchiolitis: A systematic review and meta-analysis.

Until date there is lack of effective therapies in acute bronchiolitis in infants. The aim was to analyze inhaled nitric oxide efficacy in acute bronchiolitis. Systematic review and meta-analysis of randomized controlled trials. Pediatric specialized healthcare. All infants (age less than 2 years) having acute bronchiolitis, which requires emergency room visit or hospitalization. Inhaled nitric oxide. Need for intensive care unit admission. Secondary outcomes were length of hospital stay and adverse events. Risk ratios (RR) and mean differences with 95% confidence intervals (CI) calculated by random-effects DerSimonian and Laird inverse variance method. Peto Odds ratios were used for rare outcomes. Evidence certainty assessed according to GRADE. 186 studies were screened and three included for analysis. Two had low risk of bias and one had some concerns. Three studies (166 infants) analyzed length of hospital stay and the duration was -11.3 h (CI: -26.8 to +4.2 h) shorter in the nitric oxide group. Evidence certainty was ranked as low. Overall adverse event rates were similar (3 studies, 166 infants, RR: 0.94, CI: 0.70-1.26), but treatment related harms were more common in nitric oxide group (2 studies, 98 infants, OR: 3.86, CI: 1.04-14.40). Evidence certainty in both was rated as low. Low certainty evidence suggests that inhaled nitric oxide does not reduce length of hospital stay but may have higher rate of treatment associated harms. Future studies with larger sample sizes are needed to better estimate both the efficacy and adverse events.

Antibiotics for otitis media with effusion (OME) in children.

Antibiotics for otitis media with effusion (OME) in children.

Efficacy of Polyhexamethylene Biguanide in Reducing Post-Operative Infections: A Systematic Review and Meta-Analysis.

Background: Post-operative infections are a substantial cause of morbidity and mortality worldwide. Polyhexamethylene biguanide (PHMB) is an antimicrobial agent that has been used in various surgical settings to prevent infections. However, the literature on its efficacy in reducing post-operative infections remains unclear. Materials and Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of PHMB in reducing post-operative infections. The risk of bias and methodologic quality of the included studies were also assessed. Results: The systematic review included nine RCTs, and eight were included in the meta-analysis that showed that the use of PHMB was associated with a reduction in the rate of post-operative infections. The overall effect size was statistically significant, with moderate heterogeneity across the included studies (log Peto's odds ratio [OR], -0.890; 95% confidence interval [CI], -1.411 to -0.369; I2 = 41.89%). However, the diversity in the application of PHMB and the potential influence of other factors, such as adherence to infection prevention protocols and organizational-level variables, underscore the need for further primary studies. Conclusions: Polyhexamethylene biguanide appears to be a promising intervention for reducing post-operative infections. However, more high-quality, well-designed RCTs are needed to confirm these findings and to explore the most effective ways to use PHMB within specific infection prevention bundles. Future research should also aim to control for potential confounding factors to provide a more comprehensive understanding of the efficacy of PHMB in reducing post-operative infections.

Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery.

Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery.

Pharmacological interventions for the prevention of bleeding in people undergoing definitive fixation or joint replacement forhip, pelvic and long bone fractures.

Pharmacological interventions for the prevention of bleeding in people undergoing definitive fixation or joint replacement forhip, pelvic and long bone fractures.

RENIN-ANGIOTENSIN SYSTEM INHIBITOR IS BETTER IN SLOWING PROGRESSION OF MILD COGNITIVE IMPAIRMENT (MCI): A META-ANALYSIS ON ANTIHYPERTENSIVE DRUG AND RISK OF DEMENTIA IN MCI PATIENT

Objective: Antihypertensive drugs has been known to reduce risk of mild cognitive impairment (MCI) and dementia in hypertensive patients. The current meta-analysis aims to assess association of antihypertensive drugs and risk of dementia in MCI patients. Design and method: PubMed, Embase and Web of Science were searched for articles from database inception until October, 2022. Longitudinal cohort studies in subjects aged 18 or above with MCI at baseline involving (1) comparison of use of antihypertensive drugs and non-user, or (2) comparison among classes of antihypertensive drugs were included. Primary outcome was risk of dementia. Reported risk of dementia was extracted as hazard ratio or odds ratio. Peto fixed effects meta-analysis was performed to estimate the pooled effect size of antihypertensive drugs on risk of dementia. Results: Eight studies were included in current analysis. One was post-hoc analysis of randomised controlled trial, while the others were observational cohort study. A total number of 1,107 dementia cases were identified. Use of antihypertensive drugs, regardless of therapeutic class, reduced risk of dementia by 27% (Peto odds ratio (OR) 0.73, 95% confidence interval (CI) 0.62-0.86). Use of renin-angiotensin system (RAS) inhibitor, including angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB), reduced risk of dementia by 47% (Peto OR 0.53, 95% CI 0.39-0.72), while use of non-RAS antihypertensives reduced risk of dementia by 28% (Peto OR 0.72, 95% CI 0.57-0.91). When directly comparing use of RAS and non-RAS antihypertensives, RAS inhibitor further reduced 20% risk of dementia (Peto OR 0.80, 95% CI 0.68-0.94). Among RAS inhibitor, ARBs showed trend of reducing dementia risk but could not achieve statistical significance (Peto OR 0.85, 95% CI 0.69-1.06). Conclusions: Antihypertensive drug reduced risk of dementia in MCI patients. Among different classes of antihypertensive drugs, RAS inhibitor performed better than other non-RAS antihypertensive drug in slowing progression of mild cognitive impairment to dementia, while ARB and ACEI were comparable in this aspect.

Effects of morphine and P2Y inhibitor amongst patients with acute coronary syndrome: A meta-analysis of comparative studies

BackgroundP2Y inhibitor and morphine are widely used in caring for patients with the acute coronary syndrome (ACS), but there are some concerns about the combination use due to interaction in metabolism. Therefore, this study aimed to examine whether using morphine with antiplatelets in patients with ACS affects the clinical outcomes based on currently available evidence. MethodsThree databases were searched for comparative studies on this topic by using relevant keywords of ACS and morphine. Two authors independently extracted study information, mortality, major adverse cardiac event (MACE), major bleeding, and length of hospital stay. Then, they evaluated the quality of evidence independently. Meta-analysis was planned to be conducted in random-effects model. Risk ratio (RR) was used for most outcomes except hospital stay, and Peto odds ratio (POR) was used if there were any zero cells. Pooled estimate was presented with 95% confidence interval (CI). ResultsFourteen studies (n = 73,033) met eligibility criteria, and there was non-significant difference in mortality between antiplatelet with and without morphine (RR = 1.13, 95%CI: 0.78 to 1.64). Antiplatelet therapy without morphine significantly reduced the risk of MACE (RR = 0.78, 95%CI: 0.67 to 0.89; I-square = 0%), but increased the odds of major bleeding (POR = 1.87, 95%CI: 1.04 to 3.35; I-square = 0%) as compared with the combined use of antiplatelet therapy and morphine. ConclusionIn conclusion, there is no statistically significant difference in mortality in patients with ACS using morphine or not, but clinicians ought to make a trade-off between a lower risk of MACE and a higher risk of major bleeding before adding morphine to antiplatelet therapy.

Incidence of second primary malignancies in patients with multiple myeloma receiving anti-CD38 monoclonal antibodies: A systematic review and meta-analysis

Anti-CD38 monoclonal antibodies (mAbs) are commonly used for treating newly diagnosed and relapsed/refractory (r/r) multiple myeloma (MM). However, concerns have been raised about the occurrence of second primary malignancies (SPMs) in patients receiving anti-CD38 mAbs. Assessing the safety data for rare adverse events like SPMs is challenging because individual clinical trials are typically focused on the primary endpoint. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) published between January 2005 and April 2022, including patients with newly diagnosed or r/r MM. Our aim was to compare SPM rate with the use of anti-CD38 mAb-based regimens with other anti-myeloma regimens. After a median follow-up of 35.3 months (range: 8.2–56.2), we found that exposure to anti-CD38 mAbs was associated with an increased risk of developing SPMs compared to the control group (6.8% vs. 5.2%; Peto odds ratio [OR]: 1.53 [95% confidence interval (CI): 1.20–1.95]; I2= 0%, p-value for heterogeneity= 0.44). This increased risk was primarily driven by non-melanoma cutaneous cancers (92 vs. 47; Peto OR: 1.77 [95% CI: 1.25–2.51]; I2 = 0%, p-value for heterogeneity = 0.54). However, there was no significant difference in the incidence of solid tumors (including malignant melanoma) (OR: 1.28 [95% CI: 0.85–1.95]) or hematologic SPMs (OR: 1.86; [95% CI: 0.81–4.27]). In conclusion, the use of anti-CD38 mAb-based combination regimens is associated with a higher risk of non-invasive cutaneous SPMs, but not solid tumors or hematologic SPMs. The increased occurrence of non-invasive cutaneous SPMs may be due to enhanced monitoring resulting from longer treatment duration with anti-CD38 mAbs.

Subclinical atherosclerosis in Behcet's disease and its inverse relation to azathioprine use: an updated meta-analysis.

To evaluate the intima media thickness of carotid arteries (IMT) and its clinical, laboratory and treatment correlates in Behcet's disease (BD). Systematic search of EMBASE and PubMed databases from January 2016 to October 2022; we employed random effect meta-analyses for continuous outcomes and Peto's odds ratio for rare events. The meta-analysis included 36 case control studies: the IMT was greater in BD (n = 1103) than in controls (n = 832) (p < 0.0001) with wide heterogeneity (I2 = 86.9%); a sensitivity analysis that included mean age of BD participants, gender, disease duration and activity, atherogenic index of plasma, blood pressure, C-reactive protein, ethnicity, smoking status, anti-inflammatory and immune suppressive agents, revealed that male gender, mean age of participants and azathioprine use (the latter two in inverse fashion) partly explained the heterogeneity variance (p = 0.02, p = 0.005, and p = 0.01). The IMT was greater in vascular (n = 114) than in non-vascular BD (n = 214) (p = 0.006). BD patients (n = 782) had a greater pooled prevalence of carotid plaques than controls (n = 537) (13.1% vs. 2.97%, p < 0.0001). Subclinical carotid artery atherosclerosis represents a vascular feature of BD, independently of the traditional cardiovascular risk factors. The inverse correlations between IMT, age and azathioprine use suggest that thicker carotid arteries at disease onset eventually regress with immune suppressive treatment: this assumption needs verification on adequately designed clinical trials.

Interstitial lung disease in patients treated with poly (ADP-ribose) polymerase inhibitors (PARPi): analysis of results from clinical trials and the FDA Adverse Events Reporting System database

ObjectiveTo evaluate the risk of interstitial lung disease associated with poly (ADP-ribose) polymerase inhibitors (PARPi) and characterize its clinical features.MethodsWe systematically reviewed phase III randomized clinical trials of interstitial lung...

Oral Class I and III antiarrhythmic drugs for maintaining sinus rhythm after catheter ablation of atrial fibrillation.

Oral Class I and III antiarrhythmic drugs for maintaining sinus rhythm after catheter ablation of atrial fibrillation.

Major adverse cardiac events and cardiovascular toxicity with PARP inhibitors-based therapy for solid tumors: a systematic review and safety meta-analysis

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) provided significant antitumor activity in various tumors, mainly carrying deleterious mutations of BRCA1/BRCA2 genes. Only few data are available regarding the cardiac and vascular safety profile of this drug class. We carried out a meta-analysis for assessing the incidence and relative risk (RR) of major adverse cardiovascular events (MACEs), hypertension, and thromboembolic events in patients with solid tumors treated with PARPi-based therapy. Prospective studies were identified by searching the Medline/PubMed, Cochrane Library, and ASCO Meeting abstracts. Data extraction was conducted according to the Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) statement. Combined odds ratios (ORs), RRs, and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods, depending on studies heterogeneity. RevMan software for meta-analysis (v.5.2.3) was used to carry out statistical analyses. Thirty-two studies were selected for the final analysis. The incidence of PARPi-related MACEs of any and high grade was 5.0% and 0.9%, respectively, compared with 3.6% and 0.9% in the control arms, corresponding to a significant increased risk of MACEs of any grade (Peto OR 1.62; P= 0.0009) but not of high grade (P= 0.49). The incidence of hypertension of any grade and high grade was 17.5% and 6.0% with PARPi, respectively, compared with 12.6% and 4.4% in the controls. Treatment with PARPi significantly increased the risk of hypertension of any grade (random-effects, RR= 1.53; P= 0.03) but not of high grade (random-effects, RR= 1.47; P= 0.09) compared with controls. Finally, PARPi-based therapies significantly increased the risk of thromboembolic events of any grade (Peto OR= 1.49, P= 0.004) and not of high grade (Peto OR= 1.31; P= 0.13) compared with controls. PARPi-based therapy is associated with a significantly increased risk of MACEs, hypertension, and thromboembolic events of any grade compared with controls. The lack of a significant increased risk of high-grade events together with the absolute low incidence of these adverse events led not to consider routine cardiovascular monitoring as recommended in asymptomatic patients.