Direct health‐care cost utilization in Hong Kong inflammatory bowel disease patients in the initial 2 years following diagnosis

Background and Aim

There are scanty data on the health‐care utilization from Asia where the incidence of inflammatory bowel disease (IBD) is rising rapidly. We aim to determine the direct health‐care costs in the first 2 years of diagnosis in an IBD cohort from Hong Kong and the factors associated with high cost outliers.

Methods

This is a retrospective cohort study that included patients newly diagnosed with IBD in a territory‐wide IBD registry. Patients' clinical information, hospitalization records, investigations, and IBD treatments were retrieved for up to 2 years following diagnosis of IBD.

Results

Four hundred and thirty‐five newly diagnosed IBD patients were included: 198 with Crohn's disease and 237 with ulcerative colitis. Total direct medical expenditure for this cohort 2 years after the IBD diagnosis was $7 072 710: hospitalizations (33%), 5‐aminosalicylic acid (23%), imaging and endoscopy (17%), outpatient visits (10%), surgery (8%), and biologics (6%). Mean direct medical costs per patient‐year were significantly higher for Crohn's disease ($9918) than ulcerative colitis ($6634; P, 0.001). The total direct health‐care cost decreased significantly after transition to the second year (P < 0.01). High cost (> 90th percentile) outliers were associated with surgery (OR 7.1, 95% CI 2.9–17.2) and low hemoglobin on presentation (OR 0.83, 95% CI 0.70–0.96).

Conclusions

Hospitalization and 5‐aminosalicylic acid usage accounted for 56% of total direct medical costs in the first 2 years of our newly diagnosed IBD patients. Direct health‐care costs were higher in the first year compared with the second year of diagnosis. Surgery and low hemoglobin on presentation were associated with high cost outliers.     

Coronary artery bypass grafting versus percutaneous coronary intervention in patients with noninsulin treated type 2 diabetes mellitus: A meta‐analysis of randomized controlled trials

Background

The outcomes and prognosis of revascularization by either coronary artery bypass grafting (CABG) surgery or percutaneous coronary intervention (PCI) in patients with noninsulin‐treated type 2 diabetes mellitus (NITDM) have not yet been well established.

Methods

Randomized controlled trials (RCTs) were identified by searching Pubmed, EMBASE, and Cochrane library from inception until May 2016. Heterogeneity was evaluated, and the pooled hazard ratio (HR) was calculated by using a fixed‐effect model. A random‐effect model was used when statistically significant heterogeneity was observed (I² ≥ 50%). All data analyses were carried out by using RevMan 5.3 and STATA software 12.0.

Results

A total of 4 RCTs involving 5 studies, consisting of 2270 patients with noninsulin‐treated type 2 diabetes mellitus, were identified. Compared with CABG‐treated patients, PCI‐treated patients had significantly higher all‐cause mortality (HR 1.39; 95% CI 1.01 to 1.91; P = .04), myocardial infarction (HR 2.14; 95% CI 1.40 to 3.27; P = .0004), repeated revascularization (HR 2.52; 95% CI 1.77 to 3.57; P < .00001), and major adverse cardiovascular and cerebrovascular events (HR 1.50; 95% CI 1.20‐1.87; P = .0004). However, PCI was associated with lower incidence of stoke (HR 0.47; 95% CI 0.24 to 0.90; P = .02).

Conclusions

In NITDM patients, our study suggests that CABG surgery is associated with reduced risk of mortality and morbidity, although with increased incidence of stroke compared with percutaneous coronary intervention. The decision if to have percutaneous coronary intervention or CABG surgery should factor the risk for stroke of the patients when considering CABG over percutaneous coronary intervention. Adequately powered RCTs are needed to confirm the results of this meta‐analysis.     

Thiazolidinedione therapy and breast cancer risk in diabetic women: A systematic review and meta‐analysis

Rising experimental evidence suggests that thiazolidinediones (TZDs) exert a protective effect on breast cancer. However, studies concerning this issue were inconsistent and limited. Hence, we performed a meta‐analysis with data from currently available studies to evaluate the effect of TZDs on breast cancer risk among diabetic women. We comprehensively searched for all pertinent studies addressing TZDs use and breast cancer risk published before January 1, 2016, in PubMed, Clinical Trials, and Cochrane Library. Data synthesis was performed in a random‐effects model using Stata version 12.0 (Stata Corp, College Station, Texas). Fourteen independent studies were eventually selected in this meta‐analysis, including 5 randomized controlled clinical trials (RCTs), 7 cohort studies, and 2 case‐control studies. No significant associations of TZD use and risk of breast cancer were observed in the RCTs (pooled risk ratio [RR]: 0.77, 95% confidence interval (CI), 0.39‐1.53, I² = 26%) or case‐control studies (pooled odds ratio, 0.99, 95% CI, 0.76‐1.28, I² = 31%). A 19% reduction in breast cancer risk (pooled RR: 0.81, 95% CI, 0.66‐0.99, I² = 72%) was found in the cohort studies. However, after removing the study with the smallest event number and the greatest effect size, the association became nonsignificant with greatly decreased heterogeneity (pooled RR: 0.94, 95% CI, 0.86‐1.03, I² = 16%). This meta‐analysis did not find any significant association between TZDs use and risk of breast cancer among diabetic women.     

Use of the RenalGuard system to prevent contrast‐induced AKI: A meta‐analysis

Background

Contrast‐induced kidney injury (CI‐AKI) following cardiovascular interventions results in increased morbidity and mortality. RenalGuard (RG) is a novel, closed loop system which balances volume administration with forced diuresis to maintain a high urine output. We performed a meta‐analysis of the existing data comparing use of RG to conventional volume expansion.

Methods

Ten studies were found eligible, of which four were randomized controlled trials. Of an aggregate sample size (N) of 1585 patients, 698 were enrolled in the four RCTs and 887 belonged to the remaining registries included in this meta‐analysis. Primary outcomes included CI‐AKI incidence and relative risk. Mortality, dialysis, and major adverse cardiovascular events (MACCE) were secondary outcomes. A random effects model was used and data were evaluated for publication bias.

Results

RG was associated with significant risk reduction in CI‐AKI compared to control (RR: 0.30, 95%CI: 0.18‐0.50, P < 0.01). CI‐AKI in RG was found to be 7.7% versus 23.6% in the control group (P < 0.01). Use of RG was associated with decreased mortality (RR: 0.43, 95%CI: 0.18‐0.99, P = 0.05), dialysis (RR: 0.20, 95%CI: 0.06‐0.61, P = 0.01), and MACCE (RR: 0.42, 95%CI: 0.27‐0.65, P < 0.01) compared to control.

Conclusions

RG significantly reduces rates of CI‐AKI compared to standard volume expansion and is also associated with decreased rates of death, dialysis, and MACCE.

     

Therapeutic effects of hyaluronate injections in patients with chronic painful shoulder: A meta‐analysis of randomized controlled trials

Objective

To elucidate the therapeutic efficacy and safety of injection of hyaluronate (HA) for chronic painful shoulder.

Methods

The meta‐analysis comprised randomized controlled trials (RCTs) that compared the efficacy of HA injections with that of a placebo. Articles were retrieved through systematic searches of databases, including Medline, EMBase, and Japana Centra Revuo Medicina. The outcome end points were classified into 5 categories: pain, shoulder range of motion (ROM), total functional score, comparison between HA and steroid injections, and HA safety. The primary outcome measures of the efficacy of HA injections were the standardized mean differences (SMDs) and the relative risk (RR) or odds ratio (OR) between HA and placebo groups.

Results

Nineteen RCTs (2,120 participants) were pooled for the meta‐analysis. Injection of HA can decrease symptoms of chronic painful shoulder. An improvement was found in pain outcomes (SMD 0.39; 95% confidence interval [95% CI] 0.26, 0.53 and OR 1.84; 95% CI 1.49, 2.26) and total functional scores (SMD 0.36; 95% CI 0.01, 0.71), with few adverse events (RR 1.01; 95% CI 0.57, 1.77). Improvement in shoulder ROM was not effectively achieved. HA injection was modestly more effective than steroid injection, as estimated by the total functional score (SMD 0.36; 95% CI 0.02, 0.70), which indicated a likely benefit of injection of HA over steroid injection.

Conclusion

This meta‐analysis confirms that HA injection is effective in relief of pain and is a safe alternative therapy for chronic painful shoulder.     

Comparative efficacy and safety of low‐intensity warfarin therapy in preventing unprovoked recurrent venous thromboembolism: A systematic review and meta‐analysis

Background

Although there exists potential risk of bleeding, extended ‘lifelong’ conventional‐intensity [international normalized ratio (INR): 2.0‐3.0] warfarin anticoagulation is recommended for unprovoked venous thromboembolism (VTE) patients because of risk of recurrent VTE. Whether long‐term low‐intensity (INR: 1.5‐2.0) warfarin therapy reduced the risk of major bleeding without substantially lowered antithrombotic efficacy is not well understood. The aim of this study was to perform a systematic review and meta‐analysis to evaluate the risk‐benefits of low‐intensity warfarin therapy.

Methods

We conducted a comprehensive search of electronic databases and included randomized control trials (RCTs) that reported efficacy (recurrent VTE) and safety (bleeding episodes) of low‐intensity warfarin therapy compared with conventional‐intensity warfarin or placebo from inception through Jun 2016.

Results

Four RCTs reporting high GRADE quality evidence were included. Although the relative risk of recurrent VTE with low‐intensity therapy was significantly increased [2.96 (95% CI: 1.40 to 6.24), P < .004] compared to conventional‐intensity warfarin, there was significant decrease of relative risk when compared with placebo [0.37 (95% CI: 0.24 to 0.56), P < .00001]. As per included publications, no significant major bleeding episodes were observed in low‐intensity warfarin group.

Conclusions

Although less effective than conventional‐intensity warfarin therapy this meta‐analysis indicates that long‐term low‐intensity warfarin therapy is highly effective for preventing recurrent VTE than placebo, along with reduced risks of major bleeding and minimizing potential complications.     

Serum uric acid levels and decreased estimated glomerular filtration rate in patients with type 2 diabetes: A cohort study and meta‐analysis

Background

Epidemiological studies suggest that elevated serum uric acid (SUA) is associated with heightened incident kidney disease in both the general population and the type 2 diabetes (T2D) cases, although the results were not entirely consistent.

Methods

We investigated prospective association between SUA levels and estimated glomerular filtration (eGFR) decline risk (eGFR <60 mL min^–1 1.73 m^–2) among 3123 T2D in the Dongfeng‐Tongji cohort and further examined this association with a meta‐analysis. Generalize linear model was used to assess the associations of SUA with eGFR decline in the cohort. In the meta‐analysis, we used both fix‐effects and random‐effects models to calculate the overall effect estimate.

Results

During 5‐year follow‐up, 303 (9.7%) patients developed eGFR decline. After multiple adjustments, the relative risk (RR) (95% CI) of eGFR decline was 1.55 (1.07, 2.26) when comparing the highest with the lowest sex‐specific uric acid quartile. A 100 μmol/L increment of SUA level was significantly associated with 21% increased risk of eGFR decline. The SUA‐eGFR decline association was more evident in men, but not in women. In meta‐analysis, the pooled RR (95% CI) was 2.33 (1.66, 3.25) for developing eGFR decline when comparing the highest with the lowest levels of uric acid. A 100 μmol/L increment of SUA level was significantly associated with a 33% increased risk of eGFR decline.

Conclusions

Our results indicate an independent and significant positive association between higher SUA and increased risk of developing eGFR decline among T2D cases.     

Angioplasty Guided by Intravascular Ultrasound: Meta-Analysis of Randomized Clinical Trials

Background

The impact of intravascular ultrasound (IVUS) use on stenting has shown inconclusive results.

Objective

Systematic review and meta-analysis of the impact of IVUS on stenting regarding the clinical and angiographic evolution.

Methods

A search was performed in Medline/Pubmed, CENTRAL, Embase, Lilacs, Scopus and Web of Science databases. It included randomized clinical trials (RCTs) that evaluated the implantation of stents guided by IVUS, compared with those using angiography alone (ANGIO). The minimum follow-up duration was six months and the following outcomes were assessed: thrombosis, mortality, myocardial infarction, percutaneous and surgical revascularization, major adverse cardiovascular events (MACE) and restenosis. The binary outcomes were presented considering the number of events in each group; the estimates were generated by a random effects model, considering Mantel-Haenszel statistics as weighting agent and magnitude of effect for the relative risk (RR) with its respective 95% confidence interval (95%CI). Higgins I² test was used to quantify the consistency between the results of each study.

Results

A total of 2,689 articles were evaluated, including 8 RCTs. There was a 27% reduction in angiographic restenosis (RR: 0.73, 95% CI: 0.54-0.97, I² = 51%) and statistically significant reduction in the rates of percutaneous revascularization and overall (RR: 0.88; 95% CI: 0.51 to 1.53, I² = 61%, RR: 0.73, 95% CI: 0.54 to 0.99, I² = 55%), with no statistical difference in surgical revascularization (RR: 0.95, 95% CI: 0.52-1.74, I² = 0%) in favor of IVUS vs. ANGIO. There were no differences regarding the other outcomes in the comparison between the two strategies.

Conclusion

Angioplasty with stenting guided by IVUS decreases the rates of restenosis and revascularization, with no impact on MACE, acute myocardial infarction, mortality or thrombosis outcomes.     

Male circumcision for the prevention of heterosexually acquired HIV infection: a meta-analysis of randomized trials involving 11,050 men

Objectives

Observational studies and a small collection of randomized controlled trials (RCTs) suggest that male circumcision may significantly reduce HIV transmission between sero‐discordant contacts. The Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization have recently announced recommendations to scale up male circumcision in countries with generalized epidemics and low levels of male circumcision. However, no meta‐analysis has been conducted to determine the effectiveness of this intervention.

Methods

We conducted a systematic review of medical literature, and included any RCTs assessing male circumcision to prevent heterosexually acquired HIV infection among males. We used the DerSimonian–Laird random effects method to pool study outcomes. We calculated the relative risk (RR), risk difference, number needed to treat (NNT) and I², all with 95% confidence intervals (CIs).

Results

We identified three RCTs that met our inclusion criteria, involving a total of 11 050 men. The pooled RR was 0.44 (95% CI 0.33–0.60, P<0.0001, I²=0%, 95% CI 0–35%). The risk difference was 0.014 (95% CI 0.07–0.21), yielding a NNT of 72 (95% CI 50–143).

Conclusions

Male circumcision is an effective strategy for reducing new male HIV infections. Its impact on a population level will require consistently safe sexual practices to maintain the protective benefit.     

Long‐term tolerability,immunogenicity and efficacy of Nuwiq® (human‐cl rhFVIII) in children with severe haemophilia A

Introduction

Nuwiq^® (human‐cl rhFVIII, simoctocog alfa) is a 4th generation recombinant human FVIII, without chemical modification or fusion with any other protein, produced in a human cell line.

Aim/Methods

This study (GENA‐13) was an extension of the GENA‐03 study in which previously treated children aged 2‐12 years with severe haemophilia A received Nuwiq^® prophylaxis for ≥6 months. GENA‐13 examined long‐term tolerability, immunogenicity and efficacy of Nuwiq^® prophylaxis in children.

Results

Of 59 patients enrolled in GENA‐03, 49 continued Nuwiq^® prophylaxis in GENA‐13 for a median (range) of 30.0 (9.5‐52.0) months. No patient withdrew due to drug‐related adverse events or developed inhibitors. Only 2 of 20 518 infusions were associated with possibly related adverse events (dyspnoea, fever). The estimated annualized bleeding rate (ABR) was 0.67 (95% CI: 0.44, 1.02) for spontaneous and 2.88 (95% CI: 1.86, 4.46) for all bleeds. Younger children (2‐5 years) had lower ABRs than children aged 6‐12 years. Annualized bleeding rates were reduced in GENA‐13 vs GENA‐03, especially for spontaneous bleeds in younger children (71% reduction; ABR ratio 0.29 [95% CI: 0.11, 0.74]). Nuwiq^® efficacy was rated as excellent/good in the treatment of 83.0% of 305 evaluated breakthrough bleeds. Surgical prophylaxis with Nuwiq^® was rated as excellent for all 17 assessed procedures.

Conclusion

Long‐term treatment with Nuwiq^® for the prevention of bleeds in children with severe haemophilia A was well tolerated, effective and reduced spontaneous bleeding by up to 70% compared with GENA‐03.     

Post‐transplant consolidation plus lenalidomide maintenance vs lenalidomide maintenance alone in multiple myeloma: A systematic review

Background

In newly diagnosed multiple myeloma (NDMM), autologous stem cell transplantation (ASCT) remains the standard approach for transplant‐eligible patients. To control the inevitable relapse, post‐transplant consolidation/maintenance strategies are commonly used. However, the benefit of post‐transplant consolidation is still uncertain

Method

We conducted a systematic review of phase II/III studies to compare the efficacy of post‐ASCT consolidation plus lenalidomide maintenance (CON+LEN) vs lenalidomide maintenance alone (LEN alone) in NDMM. A meta‐analysis using fixed and random effects models was performed.

Results

Fourteen studies were included with 2275 participants with NDMM treated with ASCT and lenalidomide maintenance. Two groups were identified: CON+LEN group (n = 1102) and LEN alone group (n = 1173). There was no statistically significant difference in the complete response rate between the two groups [RR = 1.1; 95% CI: 0.83‐1.44; P = .490]. Interestingly, we found that very good partial response or better rate is around 1.5‐fold significantly higher in the CON+LEN group compared to LEN alone group [RR: 1.46; 95% CI: 1.25‐1.70; P < .0001]. However, there was no significant difference between the two groups regarding PFS [RR: 1.0; 95% CI: 0.92‐1.08, P = .929] and OS [RR: 0.9; 95% CI: 0.92‐1.01; P = .148] at 3‐4 years follow‐up. The risk of secondary primary malignancy (SPM) was also similar between the two groups (RR: 1.2; 95% CI: 0.84‐1.92; P = .2). Data on adverse events were limited.

Conclusion

Our data suggest that, in NDMM patients treated with upfront ASCT, post‐transplant consolidation may improve depth of response, but does not add to OS or PFS, compared to lenalidomide maintenance alone. However, data in this context are still immature.     

Association between colonic diverticulosis and prevalence of colorectal polyps

Introduction

Diverticulosis and colorectal polyps increase in frequency as the population ages. Proposed common mechanisms for both include lack of dietary fiber, increased saturated fats, and slow colonic transit time. The association of diverticulosis and colorectal polyps has been previously reported with conflicting results. Despite sharing common epidemiologic predisposing factors, the association between diverticulosis and colon polyps remains unclear and needs better clarification.

Aim

The primary aim of our study is to evaluate if there is any association between diverticular disease and colorectal polyps.

Materials and methods

This is a retrospective cohort study. All consecutive patients who underwent colonoscopy between January 2009 and December 2011 were included, except those with history of inflammatory bowel disease, polyposis syndrome, and poor bowel preparation. Univariate and multivariate logistic regression analysis was conducted to analyze the association between colon polyps and diverticulosis. Hyperplastic polyps were excluded from the statistical analysis, and only pre-cancerous adenomas were included.

Results

A total of 2,223 patients met the inclusion criteria. The prevalence of colorectal polyps in patients with diverticulosis was significantly higher than those without diverticulosis (odds ratio (OR) 1.54; 95 % confidence interval (CI) 1.27–1.80, p?=?0.001). This association was found significant for all locations of polyps and all histological subtypes. There was also a statistically significant association between age, presence of diverticulosis, and colorectal polyps (OR 1.03; 95 % CI 1.02–1.04). The incidence of colorectal polyps increases as age advances in patients with diverticulosis, with the highest association in patients >70 years of age (OR 3.55; 95 % CI 2.50–5.04). There was no significant association between indication for colonoscopy and presence of colorectal polyps in patients with diverticulosis (OR 0.98; 95 % CI 0.95–1.01). The incidence of diverticulitis was low (<1 %), and there was no association between diverticulitis and colon polyps.

Conclusion

There is a significant association between diverticulosis and synchronous pre-cancerous colorectal polyps (adenomas). Patients with diverticulosis have a higher risk of colorectal polyps as compared to those without. This observation needs further validation by a large prospective cohort study.     

Selective association of nonaspirin NSAIDs with risk of diverticulitis

Purpose

The purpose of this study is to investigate the association of intake of nonsteroidal anti-inflammatory drugs (NSAIDs) and in particular nonaspirin NSAIDs and compare it with other risk factors for the progression of diverticulosis to diverticulitis in patients who underwent colonoscopy.

Methods

A total of 194 patients who underwent complete colonoscopy in our center between 2012 and 2016 were recruited: 144 with diverticulosis without prior diverticulitis (median age 71 years, 59.7% men) and 50 with diverticulitis (median age 64 years, 54.0% men). Data concerning current and previous medication as well as concomitant diseases were collected using a structured questionnaire and by revision of patients medical charts.

Results

Patients with diverticulitis were significantly (p?<?0.001) younger as compared to individuals with plain diverticulosis (median age 64 versus 71 years, respectively). The intake of NSAIDs significantly (p?=?0.002) increased the risk of prior diverticulitis (OR 3.2, 95% CI 1.5–6.9). In the multivariate model, both age (p?<?0.001) and NSAIDs (p?=?0.03) proved to be independent determinants of diverticulitis. When analyzing aspirin intake, it was not associated with diverticulitis.

Conclusions

Our study demonstrates, in line with previous reports, that intake of NSAIDs is associated with diverticulitis. We show in particular that nonaspirin NSAIDs might be selectively associated with diverticulitis. These results point to divergent role of aspirin and nonaspirin NSAIDs in the development of diverticulitis.

     

Perforated sigmoid diverticulitis: Hartmann’s procedure or resection with primary anastomosis—a systematic review and meta-analysis of randomised control trials

Introduction

The surgical management of perforated sigmoid diverticulitis and generalised peritonitis is challenging. Surgical resection is the established standard of care. However, there is debate as to whether a primary anastomosis (PA) or a Hartmann’s procedure (HP) should be performed. The aim of the present study was to perform a review of the literature comparing HP to PA for the treatment of perforated sigmoid diverticulitis with generalised peritonitis.

Methods

A systematic literature search was performed for articles published up to March 2018. We considered only randomised control trials (RCTs) comparing the outcomes of sigmoidectomy with PA versus HP in adults with perforated sigmoid diverticulitis and generalised peritonitis (Hinchey III or IV). Primary outcomes were mortality and permanent stoma rate. Outcomes were pooled using a random-effects model to estimate the risk ratio and 95% confidence intervals.

Results

Of the 1,204 potentially relevant articles, 3 RCTs were included in the meta-analysis with 254 patients in total (116 and 138 in the PA and HP groups, respectively). All three RCTs had significant limitations including small size, lack of blinding and possible selection bias. There was no statistically significant difference in mortality or overall morbidity. Although 2 out of the 3 trials reported a lower permanent stoma rate in the PA arm, the difference in permanent stoma rates was not statistically significant (RR?=?0.40, 95% CI 0.14–1.16). The incidence of anastomotic leaks, including leaks after stoma reversal, was not statistically different between PA and HP (RR?=?1.42, 95% CI 0.41–4.87, p?=?0.58) while risk of a postoperative intra-abdominal abscess was lower after PA than after HP (RR?=?0.34, 95% CI 0.12–0.96, p?=?0.04).

Conclusions

PA and HP appear to be equivalent in terms of most outcomes of interest, except for a lower intra-abdominal abscess risk after PA. The latter finding needs further investigation as it was not reported in any of the individual trials. However, given the limitations of the included RCTs, no firm conclusion can be drawn on which is the best surgical option in patients with generalised peritonitis due to diverticular perforation.

     

Systematic review and meta-analysis: anti-tumor necrosis factor α therapy and cardiovascular events in rheumatoid arthritis

Objective

Control of rheumatoid arthritis (RA) may reduce the risk of cardiovascular events. We sought to systematically assess the association between anti–tumor necrosis factor α (anti‐TNFα) therapy in RA and cardiovascular event rates.

Methods

Observational cohorts and randomized controlled trials (RCTs) reporting on cardiovascular events (all events, myocardial infarction [MI], congestive heart failure, and cerebrovascular accident [CVA]) in RA patients treated with anti‐TNFα therapy compared to traditional disease‐modifying antirheumatic drugs were identified from a search of PubMed (1950 to November 2009), EMBase (1980 to November 2009), and conference abstracts. Relative risks (RRs) or hazard ratios and 95% confidence intervals (95% CIs) were extracted. If the incidence was reported, additional data were extracted to calculate an incidence density ratio and its variance.

Results

The systematic review and meta‐analysis include 16 and 11 publications, respectively. In cohort studies, anti‐TNFα therapy was associated with a reduced risk for all cardiovascular events (pooled adjusted RR 0.46; 95% CI 0.28, 0.77), MI (pooled adjusted RR 0.81; 95% CI 0.68, 0.96), and CVA (pooled adjusted RR 0.69; 95% CI 0.53, 0.89). Meta‐analysis of RCTs also produced a point estimate indicating lower risk of cardiovascular events, but this was not statistically significant (pooled RR 0.85; 95% CI 0.28, 2.59).

Conclusion

Anti‐TNFα therapy is associated with a reduced risk of all cardiovascular events, MI, and CVA in observational cohorts. There was heterogeneity among cohort studies and possible publication bias. The point estimate of the effect from RCTs is underpowered with wide 95% CIs, and cardiovascular events were secondary outcomes, but RCTs also demonstrated a trend toward decreased risk.     

Maternal viral load and hepatitis B virus mother‐to‐child transmission risk: A systematic review and meta‐analysis

Aim

The aim of this study was to assess the relationship between maternal viral load and mother‐to‐child transmission (MTCT) risk in hepatitis B envelope antigen (HBeAg)‐positive mothers.

Methods

PubMed and Web of Science were systematically searched. We compared MTCT incidence between maternal hepatitis B virus (HBV)‐DNA‐positive and HBV‐DNA‐negative groups. We also examined the dose–response effect of this relationship.

Results

Twenty‐one studies with 10 142 mother–child pairs were included in the studies. The mean MTCT incidence was 13.1% in the maternal HBV‐DNA‐positive group, compared with 4.2% in the negative group. The summary MTCT odds ratio of maternal HBV‐DNA positive compared with negative was 9.895 (95% confidence interval [CI], 5.333 to 18.359; Z = 7.27, P < 0.00001) by random‐effects model. In maternal HBV‐DNA <6 log10 copies/mL, 6–8 log10 copies/mL, and >8 log₁₀ copies/mL level stratifications, the pooled MTCT incidences were 2.754% (95% CI, 1.198–4.310%; Z = 3.47, P = 0.001), 9.932% (95% CI, 6.349–13.516%; Z = 5.43, P < 0.00001), and 14.445% (95% CI, 8.317–20.572%; Z = 4.62, P < 0.00001), respectively. A significant linear dose–response association was found between maternal viral load and MTCT risk, with the points estimate of increased MTCT risk 2.705 (95% CI, 1.808–4.047) at 6 log10 copies/mL compared with reference (3 log10 copies/mL), and 7.316 (95% CI, 3.268–16.378) at 9 log₁₀ copies/mL. A significant non‐linear dose–response association was also found between maternal viral load and HBV MTCT risk (model χ² = 23.43, P < 0.00001).

Conclusion

Our meta‐analysis indicated that maternal viral load was an important risk factor for MTCT in HBeAg‐positive mothers, and maternal viral load was dose‐dependent with HBV MTCT incidence.     

Risk factors for recurrence of right colonic uncomplicated diverticulitis after first attack

Purpose

Most patients with acute right colonic uncomplicated diverticulitis can be managed conservatively. The aim of this study was to assess the clinical and radiologic risk factors for recurrence in patients with right colonic uncomplicated diverticulitis.

Methods

The present survey included 469 patients who were successfully managed conservatively for the first episode of right colonic uncomplicated diverticulitis between 2002 and 2012 in a referral center, and records were reviewed from collected data. Patients were divided into two groups: a nonrecurrent and a recurrent group. The clinical and radiologic features of all patients were analyzed to identify possible risk factors for recurrence. The Kaplan-Meier method and Cox regression were used.

Results

Seventy-four (15.8 %) patients had recurrence, and 15 (3.2 %) received surgery at recurrence within a median follow-up of 59 months. The mean recurrence interval after the first attack was 29 months. In univariate and multivariate analyses, risk factors for recurrence were confirmed multiple diverticula (relative risk [RR], 2.62; 95 % confidence interval [CI], 1.56–4.40) and intraperitoneally located diverticulitis (RR, 3.73; 95 % CI, 2.13–6.52). Of 66 patients with two risk factors, 36 (54.5 %) had recurrence and 10 (15.2 %) received surgery at recurrence.

Conclusions

In patients with right colonic uncomplicated diverticulitis who have multiple diverticula and intraperitoneally located diverticulitis, the possibility of recurrence and surgical rate are high. Poor outcome may be cautioned in these patients.     

Efficacy and safety of intravenous vernakalant for the rapid conversion of recent‐onset atrial fibrillation: A meta‐analysis

Background

Atrial fibrillation is a common cardiac arrhythmia with increasing prevalence in the aging population. It is a major cause of emergency department visits worldwide. Vernakalant, a relatively new antiarrhythmic drug with selectively preferential effects on the atrial tissue is currently used in many European countries for the termination of recent‐onset atrial fibrillation. Presently, the drug is still not approved by the United States Food and Drug Administration due to safety concerns. We evaluate the efficacy and safety of vernakalant for the conversion of recent‐onset atrial fibrillation or atrial flutter into normal sinus rhythm (NSR).

Methods

PubMed/MEDLINE (1993–2017), the Cochrane Central Register of Controlled Trials (2000–2017), and reference lists of relevant articles were searched for randomized controlled trials (RCTs) comparing vernakalant to a control drug and extracted subsequently.

Results

Nine RCTs were identified and included in the meta‐analysis. Pooled analysis of events extracted for a total of 1421 patients with recent‐onset atrial fibrillation showed a statistically significant increase in cardioversion within 90 minutes from drug infusion (Relative Risk [RR], 6.61; 95% Confidence Interval [CI], 2.78 – 15.71; p < .00001). In terms of adverse events, vernakalant was considered safe in comparison to control drugs (RR, 0.80; 95% CI, 0.61–1.05; p = .11).

Conclusion

Vernakalant is effective for rapid conversion of recent‐onset atrial fibrillation into NSR. However, although it showed a safe profile in terms of side effects in this analysis, we are still hesitant about this conclusion and few safety issues should be addressed within specific patients’ subgroups.

     

Novel Oral Anticoagulants in Atrial Fibrillation: A Meta‐analysis of Large,Randomized, Controlled Trials vs Warfarin

Background:

Warfarin reduces ischemic stroke in atrial fibrillation, but has numerous limitations. Novel oral anticoagulants provide more predictable anticoagulation with fewer shortcomings.

Hypothesis:

Novel oral anticoagulants are superior to warfarin to prevent stroke or systemic embolism.

Methods:

Phase III randomized warfarin‐controlled trials enrolling >3000 patients that reported clinical efficacy and safety of novel oral anticoagulants in patients with atrial fibrillation were identified from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through October 2012. Two reviewers extracted data; differences were resolved by consensus. The end points analyzed were stroke or systemic embolism (primary efficacy composite); all‐cause mortality, ischemic stroke, systemic embolism (individually, secondary efficacy); and hemorrhagic stroke, major bleeding (individually, safety). The Mantel‐Haenszel method was used to calculate pooled relative risk (RR) and 95% confidence intervals (CI) from fixed‐effects (if homogenous) or random‐effects models (if heterogeneous).

Results:

In 5 studies of 51895 patients, the composite of stroke or systemic embolism (RR: 0.82; 95% CI: 0.69–0.98; P = 0.03) and all‐cause mortality (RR: 0.91; 95% CI: 0.85‐0.96; P = 0.0026, respectively) were reduced with the novel agents. Factor Xa inhibitors significantly reduced the primary composite (RR: 0.84; 95% CI: 0.74‐0.94; P = 0.004) and all‐cause mortality (RR: 0.91; 95% CI: 0.84 ‐ 0.98; P = 0.01). Direct thrombin inhibitor achieved results similar to the overall meta‐analysis (drug class–outcome interactions P = 0.47 for primary outcome, P = 1.00 for mortality). Compared with warfarin, novel anticoagulants markedly reduced hemorrhagic stroke (RR: 0.51; 95% CI: 0.41‐0.64; P < 0.0001).

Conclusions:

Novel oral anticoagulants may be superior to warfarin in patients with atrial fibrillation, reducing the composite of stroke or systemic embolism and lowering all‐cause mortality. The benefit is largely due to fewer hemorrhagic strokes. Ernesto Paolasso, MD, is a national lead investigator for a clinical trial sponsored by Daiichi‐Sankyo investigating a novel oral anticoagulant. Robert Giugliano, MD, SM, is a member of the TIMI Study Group, which has received research grant support from Johnson & Johnson and from Daiichi‐Sankyo related to clinical trials of anticoagulants. Dr. Giugliano has received honoraria for consultation/lectures from Bristol‐Myers Squibb, Daiichi‐Sankyo, Johnson & Johnson, and Sanofi‐Aventis. The authors have no other funding, financial relationships, or conflicts of interest to disclose.     

Diabetes mellitus and risk of dementia: A meta‐analysis of prospective observational studies

Aims/Introduction

The aim of the present study was to investigate the association between diabetes and the risk of all type dementia (ATD), Alzheimer's disease (AD) and vascular dementia (VaD).

Materials and Methods

Prospective observational studies describing the incidence of ATD, AD and VaD in patients with diabetes mellitus were extracted from PubMed, EMBASE and other databases up to January 2012. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random‐effects model. Subgroup analyses and sensitivity analysis were also carried out.

Results

A total of 28 studies contributed to the analysis. Pooled RR of developing ATD (n = 20) was 1.73 (1.65–1.82, I² = 71.2%), AD (n = 20) was 1.56 (1.41–1.73, I² = 9.8%) and VaD (n = 13) was 2.27 (1.94–2.66, I² = 0%) in patients with diabetes mellitus. Higher and medium quality studies did not show any significant difference for pooled RR for ATD, AD or VaD. Sensitivity analyses showed robustness of pooled RR among ATD, AD and VaD, showing no single study had a major impact on pooled RR.

Conclusions

The results showed a 73% increased risk of ATD, 56% increase of AD and 127% increase of VaD in diabetes patients.