Risk of Budd-Chiari Syndrome Associated with Factor V Leiden and G20210A Prothrombin Mutation: A Meta-Analysis

Background

Various studies have demonstrated that factor V Leiden (FVL) and G20210A prothrombin mutation contribute to the risk of Budd-Chiari syndrome (BCS), while other studies provided conflicting findings. In order to derive more precise estimations of the relationships, a meta-analysis was performed.

Methods

Eligible articles were identified through search of databases including Pubmed, Chinese Biomedical Database (CBM, Chinese), and Chinese National Knowledge Infrastructure (CNKI, Chinese). Odd ratios (ORs) with 95% confidence intervals (CIs) were calculated using random- or fixed- model.

Results

Finally, twelve studies were included for FVL and nine studies were included for G20210A prothrombin mutation. With respect to FVL, significantly increased BCS risk was found in the overall population (OR = 6.29, 95%CI = 4.23–9.36). Subgroup analyses suggested that FVL was associated with an increased risk of BCS in the population with high background mutation prevalence (>1% in the normal population). No significant association was found between BCS and G20210A prothrombin mutation (OR = 1.78, 95%CI = 0.77–4.11).

Conclusion

The presence of FVL should be evaluated in patients with BCS. Conversely, G20210A prothrombin mutation is not significantly associated with risk of BCS. Large-scale well designed studies are necessary to be conducted to further confirm or refute the observed association.     

Prevalence of Arthritis in Africa: A Systematic Review and Meta-Analysis

Objective

In this systematic review, we estimate the prevalence of six types of arthritis in Africa; namely rheumatoid arthritis, osteoarthritis, juvenile arthritis, psoriatic arthritis, gout, and ankylosing spondylitis.

Methods

We comprehensively searched literature on 31 August 2014 in MEDLINE, EMBASE, Web of Science and the Cochrane Library to identify eligible studies from 1975 up to 31 July 2014. Two review authors independently selected studies, extracted data, and appraised studies. We carried out random effects meta-analysis of prevalence of arthritis and assessed heterogeneity through subgroup analyses. We performed separate analyses for population- and hospital-based studies, as well as rural and urban settings.

Main Findings

We included 27 cross-sectional studies (20 population-based and 7 hospital-based) from Africa reporting on the prevalence of arthritis. The majority of the studies were from South Africa (44.4%, 12/27). Rheumatoid arthritis in urban settings ranged from 0.1% in Algeria, 0.6% in the DRC, to a meta-analysis overall prevalence of 2.5% in South Africa, and in rural settings ranged from a meta-analysis overall prevalence of 0.07% in South Africa, 0.3% in Egypt, to 0.4% in Lesotho. Osteoarthritis was the most prevalent form of arthritis and in urban settings it was 55.1% in South Africa and in rural settings, all in South Africa, ranged from 29.5%, 29.7%, up to 82.7% among adults aged over 65 years. Other results include highest prevalence of 33.1% for knee osteoarthritis in rural South Africa, 0.1% for ankylosing spondylitis in rural South Africa, 4.4% for psoriatic arthritis in urban South Africa, 0.7% for gout in urban South Africa, and 0.3% for juvenile idiopathic arthritis in urban Egypt. A third of the included studies had a low risk of bias (33.3%, 9/27), 40.8% (11/27) moderate risk, and 25.9% (7/27) had a high risk of bias.

Conclusions

In this systematic review, we have identified the paucity of latest prevalence data on arthritis in Africa. More studies are needed to address the prevalence and the true burden of this disease in Africa.     

Patients with Systemic Lupus Erythematosus Have Higher Prevalence of Thyroid Autoantibodies: A Systematic Review and Meta-Analysis

Background

Thyroid autoimmunity is considered the most common type of organ-specific autoimmune disorder and can be associated with other autoimmune endocrine disorders or non-endocrine diseases. Systemic lupus erythematosus is a prototypical autoimmune disorder with multifactorial etiology. The pathogenesis and development of the disease may result from a loss of immune tolerance and the resulting synthesis of autoantibodies against nuclear antigens. Autoimmune factors may be common features of both thyroid autoimmunity and systemic lupus erythematosus, making it likely that both conditions may coexist within some patients.

Methods and Findings

A number of studies have investigated whether an association between thyroid autoimmunity and systemic lupus erythematosus exists. However, the results of these studies have been inconsistent. Furthermore, most of these studies have had relatively small sample sizes, which have rendered them insufficiently powerful to determine whether there is an association between systemic lupus erythematosus and thyroid autoimmunity. The main objective of this meta-analysis is to provide reliable estimates of the extent of any association between thyroid autoimmunity and systemic lupus erythematosus by combining the primary data from all relevant studies. Literature databases were searched, including the Medline, Embase, Web of Science, Chinese Wanfang and CBM databases, from January 1970 to May 2014. A total of 1076 systemic lupus erythematosus cases and 1661 healthy controls were included in this study. From these data, the odds ratio (OR) and the corresponding 95% confidence interval (95% CI) were calculated. The meta-analysis results showed that the prevalence of thyroid autoantibody positivity in patients with systemic lupus erythematosus was higher than in healthy controls (TgAb: OR = 2.99, 95% CI = 1.83–4.89; TPOAb: OR = 2.20, 95% CI = 1.27–3.82, respectively).

Conclusion

The results of this meta-analysis suggest that thyroid autoimmunity is more prevalent in patients with systemic lupus erythematosus than in a control group.     

Trends in Prevalence of Hypertension in Brazil: A Systematic Review with Meta-Analysis

Background

The prevalence of hypertension in emerging nations was scarcely described to date. In Brazil, many population-based surveys evaluated the prevalence in cities throughout the country. However, there is no population-based nationwide study of prevalence of hypertension. In this study, we estimated the prevalence of hypertension for the country and analyzed the trends for the last three decades.

Methods

Cross-sectional and cohort studies conducted from 1980 to 2010 were independently identified by two reviewers, without language restriction, in the PubMed, Embase, LILACS, and Scielo electronic databases. Unpublished studies were identified in the Brazilian electronic database of theses and in annals of Cardiology congresses and meetings. In total, 40 studies were selected, comprising 122,018 individuals.

Results

Summary estimates of prevalence by the former WHO criteria (BP≥160/95 mmHg) in the 1980’s and 1990’s were 23.6% (95% CI 17.3–31.4%) and 19.6% (16.4–23.3%) respectively. The prevalence of hypertension by the JNC criteria (BP≥140/90 mmHg) in the 1980’s, 1990’s and 2000’s were 36.1% (95% CI 28.7–44.2%), 32.9% (29.9–36.0%), and 28.7% (26.2–31.4%), respectively (P<0.001). In the 2000’s, the pooled prevalence estimates of self-reported hypertension on telephone inquiries was 20.6% (19.0–22.4%), and of self-reported hypertension in home surveys was 25.2% (23.3–27.2%).

Conclusions

The prevalence of hypertension in Brazil seems to have diminished 6% in the last three decades, but it still is approximately 30%. Nationwide surveys by self-reporting by telephone interviews underestimate the real prevalence. Rates of blood pressure control decreased in the same period, corresponding currently to only one quarter of individuals with hypertension.     

Antiphospholipid Antibody and Risk of Retinal Vein Occlusion: A Systematic Review and Meta-Analysis

Background

Retinal vein occlusion (RVO) is a common retinal vascular disease and it is one of the most frequently reported causes of visual damage and blindness in the elderly. The current study investigated the potential association between antiphospholipid antibodies (APLA) and RVO risk by conducting a meta-analysis of case–control studies.

Methods

A systematic literature search of Pubmed and Embase databases was conducted in August 1^st, 2014. Odds ratios (ORs) were used to evaluate the associations between APLA and the incidence of RVO. A random-effects model was obtained for the quantitative synthesis.

Results

A total of 11 studies were included in this meta-analysis. A meta-analysis of all studies assessing the risk of RVO revealed that APLA was associated with a statistically increased risk of RVO incidence (OR = 5.18, 95% CI = [3.37, 7.95]). The association between anticardiolipin antibodies (ACA) and the risk of RVO was significant (n =8, OR = 4.59, 95% CI = [2.75, 7.66]). However, the association between lupus anticoagulants (LA) and risk of RVO was non-significant (n = 5, OR = 3.90, 95% CI = [0.99, 15.37]). No significant publication bias was found in the 11 selected studies.

Conclusion

APLA was significantly associated with the risk of RVO. Advanced analyses showed that ACA rather than LA affected the risk of RVO. Additional well-designed and well-conducted epidemiological studies are required to further our understanding of the relationship between APLA and RVO risk.     

Risk of Venous Thromboembolism in Patients with Cancer: A Systematic Review and Meta-Analysis

Background

People with cancer are known to be at increased risk of venous thromboembolism (VTE), and this risk is believed to vary according to cancer type, stage of disease, and treatment modality. Our purpose was to summarise the existing literature to determine precisely and accurately the absolute risk of VTE in cancer patients, stratified by malignancy site and background risk of VTE.

Methods and Findings

We searched the Medline and Embase databases from 1 January 1966 to 14 July 2011 to identify cohort studies comprising people diagnosed with one of eight specified cancer types or where participants were judged to be representative of all people with cancer. For each included study, the number of patients who developed clinically apparent VTE, and the total person-years of follow-up were extracted. Incidence rates of VTE were pooled across studies using the generic inverse variance method. In total, data from 38 individual studies were included. Among average-risk patients, the overall risk of VTE was estimated to be 13 per 1,000 person-years (95% CI, 7 to 23), with the highest risk among patients with cancers of the pancreas, brain, and lung. Among patients judged to be at high risk (due to metastatic disease or receipt of high-risk treatments), the risk of VTE was 68 per 1,000 person-years (95% CI, 48 to 96), with the highest risk among patients with brain cancer (200 per 1,000 person-years; 95% CI, 162 to 247). Our results need to be considered in light of high levels of heterogeneity, which exist due to differences in study population, outcome definition, and average duration of follow-up between studies.

Conclusions

VTE occurs in greater than 1% of cancer patients each year, but this varies widely by cancer type and time since diagnosis. The absolute VTE risks obtained from this review can aid in clinical decision-making about which people with cancer should receive anticoagulant prophylaxis and at what times. Please see later in the article for the Editors'' Summary.     

Effect of Methylphenidate in Patients with Cancer-Related Fatigue: A Systematic Review and Meta-Analysis

Background

Cancer-related fatigue (CRF) is a common symptom affecting patients with cancer. There are an increasing number of trials examining potential treatments for CRF. Methylphenidate represents one of the most researched drugs and an up-to-date assessment of the evidence for its use is needed. Trials of methylphenidate for CRF provided inconsistent results. This meta-analysis was aimed at assessing the effect and safety of methylphenidate on CRF.

Methods

We comprehensively searched the Pubmed, EMBASE, PSYCHInfo and the Cochrane databases in order to identify published studies on the effect of methylphenidate on CRF. Primary outcomes included fatigue. Secondary outcomes included depression, cognition and adverse effects.

Findings

A meta-analysis was conducted on five randomized controlled trials and 498 patients were enrolled. Despite a large placebo effect observed in the studies included, pooled data suggested therapeutic effect of methylphenidate on CRF. Subgroup Analyses showed that the efficacy of methylphenidate on CRF is getting better with prolonging treatment duration, with a MD of −3.70 (95% CI −7.03– −0.37, p = 0.03) for long-time group and a MD of −2.49 (95% CI −6.01–1.03, p = 0.17) for short-time group. In general, there was no impact of methylphenidate on depression and cognition associated with CRF. Adverse events were similar between methylphenidate and placebo groups except that more patients reported vertigo, anxiety, anorexia and nausea in methylphenidate group compared to placebo group.

Conclusion

Existing trials of methylphenidate on CRF provided limited evidence for the use of methylphenidate to treat CRF. The absolute numbers still remain small, and further confirmation is needed before firm recommendations on their usage and safety can be made in the treatment of CRF.     

Radiotherapy Versus Radiosurgery in Treating Patients with Acromegaly: A Systematic Review and Meta-Analysis

Objective: When patients with acromegaly have residual disease following surgery, adjuvant radiation therapy is considered. Both stereotactic radiosurgery (SRS) and conventional fractionated radiotherapy (RT) are utilized. We conducted a systematic review and meta-analysis to synthesize the existing evidence and compare outcomes for SRS and RT in patients with acromegaly.Methods: We searched Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through April 2014 for studies in which SRS or RT were used in patients with acromegaly. Outcomes evaluated were serum insulin-like growth factor-I (IGF-I) and growth hormone (GH) levels, biochemical remission, all-cause mortality, hypopituitarism, headaches, and secondary malignancies. We pooled outcomes using a random-effects model.Results: The final search yielded 30 eligible studies assessing 2,464 patients. Compared to RT, SRS was associated with a nonsignificant increase in remission rate at the latest follow-up period (52% vs. 36%; P = .14) and a significantly lower follow-up IGF-I level (-409.72 μg/L vs. -102 μg/L, P = .002). SRS had a lower incidence of hypopituitarism than RT; however, the difference was not statistically significant (32% vs. 51%, respectively; P = .05).Conclusion: SRS may be associated with better biochemical remission, and it had a lower risk of hypopituitarism with at least 1 deficient axis when compared with RT; however, the confidence in such evidence is very low due to the noncomparative nature of the studies, high heterogeneity, and imprecision.Abbreviations: GH = growth hormone GKRS = gamma-knife radio-surgery IGF-I = insulin-like growth factor-I LINAC = linear accelerator RT = conventional radiotherapy SRS = stereotactic radiosurgery     

Factors Predicting Malignancy in Patients with Polymyositis and Dermatomyostis: A Systematic Review and Meta-Analysis

Objective

To define potential factors that could predict concomitant neoplastic diseases in patients diagnosed with PM/DM, which could inform screening decisions.

Methods

Two researchers independently reviewed articles from Pubmed (MEDLINE), EMBASE, Cochrane Plus Library and ISI Web of Knowledge with no restrictions on study design or language. Given that some of the studies combined PM and DM patients as research subjects while others included only DM patients, data were subjected to meta-analyses for all combined PM/DM studies and studies that included only DM patients to obtain informative results.

Results

For PM/DM patients, the following factors are all associated with an increased risk of malignancy: older age, age greater than 45, male sex, dysphagia, cutaneous necrosis, cutaneous vasculitis, rapid onset of myostis (<4 weeks), elevated CK, higher ESR, higher CRP levels. Several factors were associated with lower-than-average risk, including the presence of ILD, arthritis/arthralgia, Raynaud''s syndrome, or anti-Jo-1 antibody. For DM patients, results indicated an increased risk of malignancy with older age, male sex, the presence of cutaneous necrosis, elevated ESR (>35 mm/hr), higher CRP levels, or anti-p155 antibody. In addition, the presence of anti-ENA antibodies seem to be related to reduced risk of malignancy.

Conclusion

Awareness and implementation of early-stage cancer screening in PM/DM patients who have these identified factors – such as being older than 45, male sex, cutaneous necrosis, cutaneous vasculitis – are of crucial importance from public health and clinical perspectives and provide insight into the etiopathogenesis of CAM.     

Prognostic Value of Procalcitonin in Adult Patients with Sepsis: A Systematic Review and Meta-Analysis

Procalcitonin (PCT) has been widely investigated for its prognostic value in septic patients. However, studies have produced conflicting results. The purpose of the present meta-analysis is to explore the diagnostic accuracy of a single PCT concentration and PCT non-clearance in predicting all-cause sepsis mortality. We searched PubMed, Embase, Web of Knowledge and the Cochrane Library. Articles written in English were included. A 2 × 2 contingency table was constructed based on all-cause mortality and PCT level or PCT non-clearance in septic patients. Two authors independently evaluated study eligibility and extracted data. The diagnostic value of PCT in predicting prognosis was determined using a bivariate meta-analysis model. We used the Q-test and I² index to test heterogeneity. Twenty-three studies with 3,994 patients were included. An elevated PCT level was associated with a higher risk of death. The pooled relative risk (RR) was 2.60 (95% confidence interval (CI), 2.05–3.30) using a random-effects model (I² = 63.5%). The overall area under the summary receiver operator characteristic (SROC) curve was 0.77 (95% CI, 0.73–0.80), with a sensitivity and specificity of 0.76 (95% CI, 0.67–0.82) and 0.64 (95% CI, 0.52–0.74), respectively. There was significant evidence of heterogeneity for the PCT testing time (P = 0.020). Initial PCT values were of limited prognostic value in patients with sepsis. PCT non-clearance was a prognostic factor of death in patients with sepsis. The pooled RR was 3.05 (95% CI, 2.35–3.95) using a fixed-effects model (I² = 37.9%). The overall area under the SROC curve was 0.79 (95% CI, 0.75–0.83), with a sensitivity and specificity of 0.72 (95% CI, 0.58–0.82) and 0.77 (95% CI, 0.55–0.90), respectively. Elevated PCT concentrations and PCT non-clearance are strongly associated with all-cause mortality in septic patients. Further studies are needed to define the optimal cut-off point and the optimal definition of PCT non-clearance for accurate risk assessment.     

Prognostic Value of SPARC in Patients with Pancreatic Cancer: A Systematic Review and Meta-Analysis

Objective

There is a heated debate on whether the prognostic value of SPARC is favorable or unfavorable. Thus, we carried out a meta-analysis evaluating the relationship between SPARC expression and the prognosis of patients with pancreatic cancer.

Methods

We searched PubMed, EMBASE and Web of Science for relevant articles. The pooled hazard ratios (HRs) and corresponding 95%CI of overall survival (OS) were calculated to evaluate the prognostic value of SPARC expression in patients with pancreatic cancer. We also performed subgroup analyses.

Results

With 1623 patients pooled from 10 available studies, the incorporative HR showed an unfavorable prognosis of patients with pancreatic cancer in the multivariate analysis (HR = 1.55, 95%CI: 1.11–2.17, P = 0.01), but not in univariate analysis (HR = 1.41, 95%CI: 0.47–4.21, P = 0.54) and estimate (HR = 1.24, 95%CI: 0.72–2.13, P = 0.44). And this adverse impact could also be found in the subgroup analyses in multivariate analysis, especially in the stroma (HR = 1.53, 95%CI: 1.05–2.24, P = 0.03). However, the combined HR had the highly significant heterogeneity. No obvious publication bias was found.

Conclusions

SPARC might be an unfavorable indicator in patients with pancreatic cancer, especially in the stroma. More and further researches should be conducted to reveal the prognostic value of SPARC.     

Prognostic Value of Survivin in Patients with Gastric Cancer: A Systematic Review with Meta-Analysis

Objective

The prognostic significance of survivin for the survival of patients with gastric cancer remains controversial. Thus, the objective of this study was to conduct a systematic review of the literature evaluating survivin expression in gastric cancer as a prognostic indicator.

Methods

Relevant literature was searched using PubMed, EMBASE, and Chinese biomedicine databases. A meta-analysis of the association between survivin expression and overall survival in patients with gastric cancer was performed. Studies were pooled and summary hazard ratios (HRs) were calculated. Subgroup analyses were also conducted.

Results

Final analysis of 1365 patients from 16 eligible studies was performed. Combined HR suggested that survivin expression had an unfavorable impact on survival of gastric cancer patients (HR=1.39, 95% CI: 1.16-1.68). The unfavorable impact also appeared significant when stratified according to the studies categorized by patients’ ethnicity, detection methods, type of sample, and HR estimate. The combined HR in the English literature showed an inverse effect on survival (HR=1.40, 95% CI: 1.13-1.75), while HR in the non-English literature did not (HR=1.38, 95% CI: 0.93-2.05). When stratified according to the location of survivin expression, combined HR showed that expression in cytoplasm was significantly associated with poor prognosis of gastric cancer patients (HR=1.46, 95% CI: 1.12-1.90). While expression in nucleus was not significantly associated with poor prognosis (HR=1.29, 95% CI: 0.72-2.31), the heterogeneity was highly significant (chi-squared=11.5, I²=74%, p=0.009).

Conclusions

This study showed that survivin expression was associated with a poor prognosis in patients with gastric cancer. Cytoplasmic expression of survivin may be regarded as a prognostic factor for gastric cancer patients. In contrast, survivin expression in nucleus did not have a significant impact on patients’ overall survival.     

Prevalence of Hypertension in Indian Tribes: A Systematic Review and Meta-Analysis of Observational Studies

Introduction

In India there is an increasing trend in hypertension prevalence among the general population. Studies have shown that tribal populations in India are also experiencing this burden.

Objective

The aim was to estimate the pooled prevalence of primary hypertension among adult tribal populations of India.

Methods

A systematic search was conducted in MEDLINE, IndMed, Web of Science, Google Scholar and major journals for studies published between 1981 and 2011. Two authors independently reviewed the studies, did quality assessment and extracted data in pre-coded spread-sheets. Pooled estimates of prevalence of hypertension were calculated using DerSimonian-Laird random effects model. Subgroup and sensitivity analyses and meta-regression were performed.

Results

Twenty studies or 53 subpopulations with 64 674 subjects were included in final review. The pooled estimate of hypertension prevalence was 16.1% (95% CI: 13.5, 19.2). There was significant heterogeneity among the studies (I² = 99% and Q = 4624.0, df  = 53, p<0.001). Subgroup analyses showed that year of study, acculturation status, special features, and BP measurement techniques significantly influenced prevalence, but after meta-regression analyses, ‘decade of study’ remained the only covariate that significantly and independently influenced prevalence (R² = 0.57, Q = 119.2, df  = 49, p value <0.001).

Conclusion

An increasing trend was found in the prevalence of hypertension in adult tribal populations across three decades. Although acculturation was probably the underlying agent that caused this increase, other unmeasured factors that need further research were also important. Concerned policy makers should focus on the changing health needs of tribal communities.     

Significantly Increased Risk of Cancer in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis

ObjectiveTo conduct a review and meta-analysis of the effect of diabetes mellitus on the incidence of and mortality attributable to cancer at any anatomic site.MethodsWe performed a search of MEDLINE and the Cochrane Library for pertinent articles published from the origin of these databases to July 5, 2010, and included them in a qualitative review and meta-analysis of the risk of all-cancer incidence and mortality in patients with diabetes.ResultsAmong patients with diabetes (n = 257,222) in 12 cohort studies, the cancer incidence was about 7%. The cancer mortality was approximately 3% among patients with diabetes (n = 152,091) in 19 cohort studies. The pooled adjusted risk ratio (RR) of all-cancer incidence was significantly elevated—RR, 1.10 (95% confidence interval [CI], 1.04 to 1.17) overall; RR, 1.14 (CI, 1.06 to 23) for men; and RR, 1.18 (CI, 1.08 to 1.28) for women. Diabetes was also associated with an increased RR of mortality across all cancer types—RR, 1.16 (CI, 1.03 to 1.30) overall; RR, 1.10 (CI, 0.98 to 1.23) for men; and RR, 1.24 (CI, 1.11 to 1.40) for women.ConclusionCancer prevention and early detection by appropriate screening methods in patients with diabetes should be important components of clinical management and investigation, inasmuch as the exponentially increasing prevalence of diabetes will translate into substantial clinical and public health consequences on a global scale. (Endocr Pract. 2011;17:616-628)     

Prognosis of Differentiated Thyroid Carcinoma in Patients with Graves Disease: A Systematic Review and Meta-Analysis

Objective: It is still controversial whether differentiated thyroid carcinoma (DTC) in patients with Graves disease (GD) can be more aggressive than non-Graves DTC. We conducted a systematic review and meta-analysis to examine the association between GD and prognosis in patients with DTC.Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to March 2019. We included published studies that compared the risk of mortality and prognosis between DTC patients with GD and those with non-GD. Data from each study were combined using the random-effects model.Results: Twenty-five studies from February 1988 to May 2018 were included (987 DTC patients with GD and 2,064 non-Graves DTC patients). The DTC patients with GD had a significantly higher risk of associated multifocality/multicentricity (odds ratio, 1.45; 95% confidence interval, 1.04 to 2.02; I², 6.5%; P =.381) and distant metastasis at the time of cancer diagnosis (odds ratio, 2.19; 95% confidence interval, 1.08 to 4.47; I², 0.0%; P =.497), but this was not associated with DTC-related mortality and recurrence/persistence during follow-up.Conclusion: Our meta-analysis demonstrates a statistically significant increased risk of multifocality/multicentricity and distant metastasis at the time of cancer diagnosis in DTC patients with GD than those without GD.Abbreviations: CI = confidence interval; DTC = differentiated thyroid carcinoma; GD = Graves disease; LN = lymph node; OR = odds ratio; PTC = papillary thyroid carcinoma; TC = thyroid carcinoma; TSAb = thyroid-stimulating antibody; TSH = thyroid-stimulating hormone     

Molecular Characterization of Factor V Leiden G1691A and Prothrombin G20210A Mutations in Saudi Newborns with Stroke

This study examined a possible association between the mutations related to Factor V Leiden and Factor II (prothrombin) and stroke in Saudi neonates. A multiplex PCR was established to detect Factor V Leiden G1691A and prothrombin G20210A mutations in 72 neonatal stroke subjects and 70 healthy adult controls with no family history of thromboembolic diseases. The frequency of the homozygous normal genotype (GG) of both genes was found to be significantly lower in the stroke subjects than in the controls (P < 0.0001). The stroke cases also had higher frequencies of the combined Factor II heterozygous mutant form (GA) and the homozygous normal Factor V (GG) (P < 0.0001) and of the combined heterozygous Factor V and the homozygous normal Factor II genotypes (GG) (P = 0.0) than controls. The study concluded that prothrombin and Factor V Leiden may be important risk factors for neonatal stroke in Saudi children.     

Efficacy of Hospital at Home in Patients with Heart Failure: A Systematic Review and Meta-Analysis

Background

Heart failure (HF) is the commonest cause of hospitalization in older adults. Compared to routine hospitalization (RH), hospital at home (HaH)—substitutive hospital-level care in the patient’s home—improves outcomes and reduces costs in patients with general medical conditions. The efficacy of HaH in HF is unknown.

Methods and Results

We searched MEDLINE, Embase, CINAHL, and CENTRAL, for publications from January 1990 to October 2014. We included prospective studies comparing substitutive models of hospitalization to RH in HF. At least 2 reviewers independently selected studies, abstracted data, and assessed quality. We meta-analyzed results from 3 RCTs (n = 203) and narratively synthesized results from 3 observational studies (n = 329). Study quality was modest. In RCTs, HaH increased time to first readmission (mean difference (MD) 14.13 days [95% CI 10.36 to 17.91]), and improved health-related quality of life (HrQOL) at both, 6 months (standardized MD (SMD) -0.31 [-0.45 to -0.18]) and 12 months (SMD -0.17 [-0.31 to -0.02]). In RCTs, HaH demonstrated a trend to decreased readmissions (risk ratio (RR) 0.68 [0.42 to 1.09]), and had no effect on all-cause mortality (RR 0.94 [0.67 to 1.32]). HaH decreased costs of index hospitalization in all RCTs. HaH reduced readmissions and emergency department visits per patient in all 3 observational studies.

Conclusions

In the context of a limited number of modest-quality studies, HaH appears to increase time to readmission, reduce index costs, and improve HrQOL among patients requiring hospital-level care for HF. Larger RCTs are necessary to assess the effect of HaH on readmissions, mortality, and long-term costs.     

The Prognostic Value of BRAF Mutation in Colorectal Cancer and Melanoma: A Systematic Review and Meta-Analysis

Background

Mutation of BRAF is a predominant event in cancers with poor prognosis such as melanoma and colorectal cancer. BRAF mutation leads to a constitutive activation of mitogen activated protein kinase pathway which is essential for cell proliferation and tumor progression. Despite tremendous efforts made to target BRAF for cancer treatment, the correlation between BRAF mutation and patient survival is still a matter of controversy.

Methods/Principal Findings

Clinical studies on the correlation between BRAF mutation and patient survival were retrieved from MEDLINE and EMBASE databases between June 2002 and December 2011. One hundred twenty relevant full text studies were categorized based on study design and cancer type. Publication bias was evaluated for each category and pooled hazard ratio (HR) with 95% confidence interval (CI) was calculated using random or fixed effect meta-analysis based on the percentage of heterogeneity. Twenty six studies on colorectal cancer (11,773 patients) and four studies on melanoma (674 patients) were included in our final meta-analysis. The average prevalence of BRAF mutation was 9.6% in colorectal cancer, and 47.8% in melanoma reports. We found that BRAF mutation increases the risk of mortality in colorectal cancer patients for more than two times; HR = 2.25 (95% CI, 1.82–2.83). In addition, we revealed that BRAF mutation also increases the risk of mortality in melanoma patients by 1.7 times (95% CI, 1.37–2.12).

Conclusions

We revealed that BRAF mutation is an absolute risk factor for patient survival in colorectal cancer and melanoma.     

High-Maintenance-Dose Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

Background

Despite routine use of clopidogrel, adverse cardiovascular events recur among some patients undergoing percutaneous coronary intervention (PCI). To optimize antiplatelet therapies, we performed a meta-analysis to quantify the efficacy of high versus standard-maintenance-dose clopidogrel in these patients.

Methods

Randomized controlled trials (RCTs) comparing high (>75 mg) and standard maintenance doses of clopidogrel in patients undergoing PCI were included. The primary efficacy and safety end-points were major adverse cardiovascular/cerebrovascular events (MACE/MACCE) and major bleeding. The secondary end-points were other ischemic and bleeding adverse effects. The pooled odds ratio (OR) for each outcome was estimated.

Results

14 RCTs with 4424 patients were included. Compared with standard-maintenance-dose clopidogrel, high-maintenance-dose clopidogrel significantly reduced the incidence of MACE/MACCE (OR 0.60; 95% CI 0.43 to 0.83), stent thrombosis (OR 0.56; 95% CI 0.32 to 0.99) and target vessel revascularization (OR 0.38; 95% CI 0.20 to 0.74), without significant decrease of the risk of cardiovascular death (OR 0.92; 95% CI 0.74 to 1.13) and myocardial infarction (OR 0.83; 95% CI 0.51 to 1.33). For safety outcomes, it did not significantly increase the risk of major bleeding (OR 0.73; 95% CI 0.41 to 1.32), minor bleeding (OR 1.29; 95% CI 1.00 to 1.66) and any bleeding (OR 1.14; 95% CI 0.91 to 1.43).

Conclusion

High-maintenance-dose clopidogrel reduces the recurrence of most ischemic events in patients post-PCI without increasing the risk of bleeding complications.