Omar Mohamed Mattar

Beclabuvir in combination with asunaprevir and daclatasvir for hepatitis C virus genotype 1 infection: A systematic review and meta‐analysis

Daclatasvir, asunaprevir (ASV), and beclabuvir (BCV) are direct‐acting antivirals (DAAs) for patients with hepatitis C virus genotype 1 infection. This systematic review and meta‐analysis investigating the efficacy and safety of this three‐drug combination in HCV genotype 1 infection. Eleven electronic search engines were searched for relevant publications. Studies were screened for eligibility and data was extracted. The outcomes were pooled as event rate and risk ratio (RR). The protocol was registered in PROSPERO (CRD42017054391). Among the included six studies, five studies were included for the meta‐analysis (n = 1261). The three‐drug combination showed a high response rate in naïve patients with sustained virologic response at week‐12 posttreatment (SVR12) rate = 95.7% (95%CI [93.8‐97.1]) and no difference detected by adding ribavirin (RBV) (the pooled RR = 0.98, 95%CI [0.90‐1.08], P = 0.70) or comparing with interferon‐experienced patients (RR = 1.02, 95%CI [0.98‐1.07], P = 0.31) regardless the genotype 1 subtypes or IL28B genotype. Treatment failure was minimal and showed no difference regarding the previous comparisons. Increasing the dose or the duration did not show a significant increase in the efficacy. In conclusion, this analysis showed high response rates in HCV genotype 1‐infected patients treated with daclatasvir, ASV, and BCV irrespective of RBV use, prior interferon‐based therapy, or restriction on non‐cirrhotic patients, IL28B genotype, or baseline resistance‐associated variants.

Denosumab versus bisphosphonates in patients with advanced cancers-related bone metastasis: systematic review and meta-analysis of randomized controlled trials

BackgroundBone metastasis is reported to be associated with poor quality of life, and increased risk of hospitalization. We aim to synthesize evidence from published randomized controlled trials (RCTs) which compared the efficacy of denosumab versus bisphosphonates in patients with advanced cancers.MethodsWe searched for all published RCTs in the following electronic databases: PubMed, Scopus, Web of Science, and Cochrane Central. Retrieved records were screened for eligibility. Time-to-event data were pooled as hazard ratio (HR) using the generic inverse-variance method and dichotomous data were pooled as relative risk (RR) in a random-effect model. We used Review Manager 5.3 for windows.ResultsSix unique RCTs with a total of 7722 patients were included. Overall effect estimates favored denosumab group in comparison to intravenous (IV) bisphosphonates in the following terms: time to first skeletal-related events (HR 0.92, 95% CI [0.86, 0.98], p = 0.01), time to subsequent skeletal-related event (RR 0.92, 95% CI [0.86, 0.99], p = 0.03), and radiation to bone (RR 0.81, 95% CI [0.71, 0.92], p = 0.02). Denosumab group was associated with increased risk of grade 3 or 4 hypocalcaemia (RR 1.99, 95% CI [1.11, 3.54], p = 0.02) and reduced risk of renal impairment or toxicity (RR 0.75, 95% CI [0.61, 0.91], p = 0.003) in comparison to IV bisphosphonates group. Pooled studies were homogenous.ConclusionDenosumab showed a favorable significant impact on delaying the time to first skeletal-related event and reducing the incidence of radiation to the bone event in comparison to bisphosphonates, with similar efficacy regarding overall survival and time to disease progression. Further large-scale and long-term studies are needed to clarify the long-term efficacy and safety of both regimens.

Quality of flow diagram in systematic review and/or meta-analysis

Systematic reviews and/or meta-analyses generally provide the best evidence for medical research. Authors are recommended to use flow diagrams to present the review process, allowing for better understanding among readers. However, no studies as of yet have assessed the quality of flow diagrams in systematic review/meta-analyses. Our study aims to evaluate the quality of systematic review/meta-analyses over a period of ten years, by assessing the quality of the flow diagrams, and the correlation to the methodological quality. Two hundred articles of “systematic review” and/or “meta-analysis” from January 2004 to August 2015 were randomly retrieved in Pubmed to be assessed for the flow diagram and methodological qualities. The flow diagrams were evaluated using a 16-grade scale corresponding to the four stages of PRISMA flow diagram. It composes four parts: Identification, Screening, Eligibility and Inclusion. Of the 200 articles screened, 154 articles were included and were assessed with AMSTAR checklist. Among them, 78 articles (50.6%) had the flow diagram. Over ten years, the proportion of papers with flow diagram available had been increasing significantly with regression coefficient beta = 5.649 (p = 0.002). However, the improvement in quality of the flow diagram increased slightly but not significantly (regression coefficient beta = 0.177, p = 0.133). Our analysis showed high variation in the proportion of articles that reported flow diagram components. The lowest proportions were 1% for reporting methods of duplicates removal in screening phase, followed by 6% for manual search in identification phase, 22% for number of studies for each specific/subgroup analysis, 27% for number of articles retrieved from each database, and 31% for number of studies included in qualitative analysis. The flow diagram quality was correlated with the methodological quality with the Pearson’s coefficient r = 0.32 (p = 0.0039). Therefore, this review suggests that the reporting quality of flow diagram is less satisfactory, hence not maximizing the potential benefit of the flow diagrams. A guideline with standardized flow diagram is recommended to improve the quality of systematic reviews, and to enable better reader comprehension of the review process.

Intralesional Immunotherapy for the Treatment of Warts: A Network Meta-analysis

Background: Without clear evidence, selecting among the existing immunotherapeutic options for warts remains challenging. Objective: Through network meta‐analyses, we aimed to evaluate the comparative efficacy of different intralesional immunotherapeutic modalities. Methods: We included randomized controlled trials comparing intralesional immunotherapeutic modalities to cryotherapy, placebo, or imiquimod. All outcomes were presented as odds ratios (ORs) with 95% confidence intervals. Both conventional and network meta‐analyses (with a frequentist approach) were conducted on R software. The P‐score was used to rank different treatments. Results: Network meta‐analysis of 17 randomized controlled trials (1676 patients) showed that PPD (purified protein derivative vaccine, OR 39.56), MMR (measles, mumps, rubella vaccine, OR 17.46) and interferon &bgr; (OR 15.55) had the highest efficacy in terms of complete recovery at the primary site compared with placebo. Regarding complete recovery at the distant site, autoinoculation (OR 79.95), PPD (OR 42.95), and MMR (OR 15.39) were all statistically superior to placebo. According to the P‐score, MMR was more effective than other modalities in reducing the recurrence rate at the same site. Limitations: Relatively small sample size in some comparisons and variability in baseline characteristics. Conclusion: PPD and MMR were the most effective in achieving complete primary and distant recovery (along with autoinoculation for distant recovery) and reducing the recurrence rate at the same site compared with cryotherapy and other immunotherapeutic modalities.

Lidocaine-prilocaine cream versus local infiltration anaesthesia in pain relief during repair of perineal trauma after vaginal delivery: a systematic review and meta-analysis.

Abstract Background: Perineal trauma is a common problem that may affect women during vaginal delivery; this trauma can be either spontaneous (tear) or intentional (episiotomy). When repair of perineal trauma is required, adequate analgesics must be obtained. Topical products as lidocaine-prilocaine (EMLA) cream is one of the suggested methods, but still there is lack of evidence with regard to its efficacy and safety. Objective: The aim of this review is to assess the evidence of utilizing EMLA cream in comparison to local perineal infiltration anesthesia for pain control during perineal repair after vaginal delivery. Data sources: Medline, Embase, Dynamed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov and the Cochrane Library were searched electronically from January 2006 to May 2018 for studies investigating the effect of lidocaine-prilocaine cream in relieving pain during repair of perineal trauma. Methods of study selection: All randomized controlled trials assessing effect of lidocaine-prilocaine cream versus local infiltration anesthesia in relieving pain during repair of perineal trauma were considered for this meta-analysis. Fifteen studies were identified of which four studies deemed eligible for this review. Quality and risk of bias assessment was performed for all studies. Data extraction: Two researchers independently extracted the data from the individual articles and entered into RevMan software. The weighted mean difference (WMD) and 95% confidence interval (CI) was calculated. Statistical heterogeneity between studies was assessed by the Higgins chi-square and (I2) statistics. When heterogeneity was significant, a random-effects model was used for meta-analysis. Otherwise, the fixed effect meta-analysis was used when there was no significant heterogeneity. Results: Pooled analysis of result in “pain score” was insignificant between the two groups (WMD −1.11; 95% CI (−2.55 to 0.33); p = .13). Furthermore, the use of additional analgesia showed no statistically significant difference between the two groups (WMD 1.34; 95% CI (0.66–2.71), p = .42). Regarding patient satisfaction, an overall analysis of three studies showed significant results favoring EMLA cream group users (WMD 4.65; 95% CI (1.96–11.03), p = .0005). The pooled analysis of the outcome “duration of repair” showed the significantly shorter duration of repair in EMLA cream users (n = 92) than local infiltration anesthesia (n = 95) (1.72 min; 95% CI (−2.76 to −0.67), p = .001). Conclusions: This meta-analysis suggests that topical lidocaine-prilocaine cream gives comparable results in reducing pain during perineal repair after vaginal delivery.

Tolerability and Efficacy of Ipragliflozin in The Management of Inadequately Controlled Type 2 Diabetes mellitus: A Systematic Review and Meta-analysis

AIM Ipragliflozin is a new antidiabetic agent that works through enhancing renal glucose excretion. We aim to synthesize evidence from published randomized controlled trials (RCTs) on the safety and efficacy of ipragliflozin in the management of type 2 diabetes mellitus (T2DM). METHODS We searched PubMed, Scopus, Web of Science, and Cochrane Central register of clinical trials using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager Version 5.3 for windows. Subgroup and sensitivity analyses were conducted. RESULTS We included 13 RCTs (N=2535 patients) in the final analysis. The overall effect estimates favoured ipragliflozin 50mg monotherapy group over placebo in terms of: HbA1c (Standardized mean difference (SMD)=-1.20%, 95% Confidence interval (95% CI)=[-1.47, -0.93]; p<0.001), fasting plasma glucose (SMD=-1.30 mg/dL, 95% CI [-1.93, -0.67]; p<0.001), fasting serum insulin (SMD=-1.64 μU/mL, 95% CI [-2.70, -0.59]; p=0.002), and body weight (SMD=-0.85 kg, 95% CI [-1.19, -0.51]; p<0.001). Similarly, better glycemic control and significant body weight reduction compared to placebo were attained in ipragliflozin 50 mg combination with metformin, insulin with/without dipeptidyl peptidase-4 inhibitor, sulfonylurea, and pioglitazone. Ipragliflozin, either alone or in combination, exhibits acceptable safety profile. CONCLUSION The presented meta-analysis provides class one evidence that ipragliflozin is safe and effective in the management of T2DM either as monotherapy or an add-on.

Safety and Efficacy of Rifaximin in Prophylaxis of Spontaneous Bacterial Peritonitis: Is this time to abandon fluoroquinolones for prevention of spontaneous bacterial peritonitis? : A Systematic Review.

AIM The role of rifaximin in the prevention of Spontaneous Bacterial Peritonitis (SBP) is not well studied. The aim of this meta-analysis was to evaluate the role of rifaximin in the prevention of SBP. METHODS A computerized literature search for relevant clinical trials was conducted during August 2017. Data on Frequency of SBP, the success rate of prevention of SBP, mortality rate, hepatorenal syndrome, septic shock, hepatic encephalopathy, and GIT bleeding were extracted and pooled as Risk Ratio (RR) with their 95% Confidence Interval (CI) in a meta-analysis model. Heterogeneity was assessed by Chi-square test. RESULTS Six studies involving 973 patients were included in the final analysis. The pooled effect estimate showed that the rifaximin plus norfloxacin group had less incidence of SBP (RR 0.58, 95% CI[0.37, 0.92], P=0.02) and hepatic encephalopathy (RR 0.38, 95% CI[0.17, 0.84], P=0.02) than the norfloxacin-based regimen group. No significant difference between rifaximin and norfloxacin in terms of frequency of SBP and success rate of primary prevention of SBP (RR 0.49, 95% CI [0.24, 1.01], P=0.05; RR1.21, 95% CI [0.95, 1.55], P=0.13, respectively). CONCLUSION Based on our analysis, Rifaximin is a promising drug and appears to be a good alternative to norfloxacin in the prevention of SBP.