Murad, Mohammad Hassan

Summary Objective The outcomes of patients with metastatic phaeochromocytoma (PHEO) and paraganglioma (PGL) are unclear. We performed a systematic review and meta‐analysis of baseline characteristics and mortality rates of patients with metastatic PHEO and PGL (PPGL). Design Ovid MEDLINE In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Scopus, Web of Science, and references of key articles were searched from inception to 2016. Patients Studies comprised ≥20 patients with metastatic PPGL and reported baseline characteristics and follow‐up data. Measurements Reviewers extracted standardized data and assessed risk of bias using a modified Newcastle‐Ottawa tool. Random‐effects meta‐analysis was used to pool event rates across studies. Results Twenty retrospective noncomparative studies reported on 1338 patients with metastatic PHEO (685/1296, 52.9%) and PGL (611/1296, 47.1%), diagnosed at a mean age of 43.9 ± 5.2 years. Mean follow‐up was 6.3 ± 3.2 years. Of 532 patients with reported data, 40.4% had synchronous metastases. Five‐year (7 studies, n = 738) and 10‐year (2 studies, n = 55) mortality rates for patients with metastatic PPGL were 37% (95% CI, 24%‐51%) and 29% (95% CI, 17%‐42%), respectively. Higher mortality was associated with male sex (RR 1.50; 95% CI, 1.11‐2.02) and synchronous metastases (RR 2.43; 95% CI, 1.01‐5.85). Conclusions Available low‐quality evidence from heterogeneous studies suggests low mortality rates of patients with metastatic PPGL. Male sex and synchronous metastases correlated with increased mortality. The outcomes of patients with metastatic PPGL have been inadequately assessed, indicating the need for carefully planned prospective studies.

AbstractBackgroundThe acquisition of intravenous (IV) access in the actively convulsing patient is difficult. This often delays the administration of the IV benzodiazepine (BDZ) necessary for seizure cessation. Delays in seizure cessation are associated with increased pharmacoresistance, increased risk of neuronal injury, worse patient outcomes, and increased morbidity.ObjectiveThe objective was to assess whether the delay imposed by IV access acquisition is justified by improved outcomes. We compared IV versus non‐IV BDZ efficacy in the real world with regard to failure rates (primary outcome), interval to seizure control, and observed complications (secondary outcomes).MethodsA systematic review was performed using Medline, Embase, and the Cochrane Library. All studies published or in press from the inception of the respective database to July 2016 were included. Only randomized and quasi‐randomized controlled trials directly comparing IV to non‐IV (buccal, rectal, intranasal, or intramuscular) BDZ were included.ResultsOur search strategy retrieved 2,604 citations for review. A total of 11 studies were finally included in qualitative synthesis and 10 in quantitative analysis. Only one was of high quality. For treatment failure, non‐IV BDZ was superior to IV BDZ (odd ratio [OR] = 0.72; 95% confidence interval [CI] = 0.56–0.92). However, no significant difference was found between the two treatments in the pediatric subgroup (OR = 1.16; 95% CI = 0.74–1.81). Non‐IV BDZ was administered faster than IV BDZ and therefore controlled seizures faster (mean difference = 3.41 minutes; 95% CI = 1.69–5.13 minutes) despite a longer interval between drug administration and seizure cessation (mean difference = 0.74 minutes; 95% CI = 0.52–0.95 minutes). Respiratory complications requiring intervention were similar between non‐IV BDZ and IV BDZ, regardless of administration route (risk difference = 0.00; 95% CI = –0.02 to 0.01).ConclusionNon‐IV BDZ, compared to IV BDZ, terminate seizures faster and have a superior efficacy and side effect profile. Higher‐quality studies and further evaluation in different age groups are warranted.

AbstractObjectivesWe performed a systematic review and meta‐regression analysis of randomized control trials to investigate the association between response to initial treatment and survival outcomes in patients with newly diagnosed multiple myeloma (MM).MethodsResponse outcomes included complete response (CR) and the combined outcome of CR or very good partial response (VGPR), while survival outcomes were overall survival (OS) and progression‐free survival (PFS). We used random‐effect meta‐regression models and conducted sensitivity analyses based on definition of CR and study quality.ResultsSeventy‐two trials were included in the systematic review, 63 of which contributed data in meta‐regression analyses. There was no association between OS and CR in patients without autologous stem cell transplant (ASCT) (regression coefficient: .02, 95% confidence interval [CI] −0.06, 0.10), in patients undergoing ASCT (−.11, 95% CI −0.44, 0.22) and in trials comparing ASCT with non‐ASCT patients (.04, 95% CI −0.29, 0.38). Similarly, OS did not correlate with the combined metric of CR or VGPR, and no association was evident between response outcomes and PFS. Sensitivity analyses yielded similar results.ConclusionsThis meta‐regression analysis suggests that there is no association between conventional response outcomes and survival in patients with newly diagnosed MM.