Antiresorptive Agents Increase the Effects of Exercise on Preventing Postmenopausal Bone Loss in Women: A Meta-Analysis

Background and Objectives

It remains unknown whether the combination of antiresorptive agents and exercise would generate additive effects on bone mineral density (BMD) in postmenopausal women, though their separate roles in preventing bone loss have been well established. This meta-analysis aimed to evaluate the combined impact of antiresorptive treatment and exercise on the lumbar spine and femoral neck BMD in postmenopausal women compared with an exercise-only intervention.

Methods

A systematic literature search of PubMed, EMBASE, SportDiscus and ProQuest up to Jun 2014 was conducted to identify the influence of antiresorptive agents and exercise on BMD in postmenopausal women. The study quality of the included trials was evaluated. The effect sizes were estimated by calculating the standardized mean difference (SMD). Subgroup analyses were conducted by pharmacological regimens and exercise categories.

Results

Nine studies with a total of 1,248 postmenopausal women met the inclusion criteria. The heterogeneity between the studies was evident at the spine (I² = 78.7%) and hip (I² = 41.7%) measurements; random-effects models were used in the data analysis. The pooled effect sizes associated with the combined interventions of antiresorptive agents and exercise were significant at the lumbar spine BMD (SMD = 0.511, 95% CI = 0.118-0.904, p = 0.011). Combining hormone replacement therapy (HRT) and exercise training generated greater beneficial effects on lumbar spine (SMD = 0.729, 95% CI = 0.186-1.273, p = 0.009) and femoral neck BMD (SMD = 0.220, 95% CI = 0.0110-429, p = 0.039) than the exercise-only intervention. Impact exercise was sensitive to antiresorptive agents in preventing postmenopausal bone loss both at the spine (SMD = 1.252, 95%CI = 0.465-2.039, p = 0.002) and hips (SMD = 0.414, 95%CI = 0.106-0.723, p = 0.008).

Conclusions

Our findings indicate that antiresorptive agents significantly increase the impact of exercise on the prevention of bone loss in postmenopausal women, which implies that the combination of antiresorptive agents and exercise may generate additive effects.     

A Cross-Sectional Randomised Study of Fracture Risk in People with HIV Infection in the Probono 1 Study

Objective

To determine comparative fracture risk in HIV patients compared with uninfected controls.

Design

A randomised cross-sectional study assessing bone mineral density (BMD), fracture history and risk factors in the 2 groups.

Setting

Hospital Outpatients.

Subbbjects

222 HIV infected patients and an equal number of age-matched controls. Assessments: Fracture risk factors were assessed and biochemical, endocrine and bone markers measured. BMD was assessed at hip and spine. 10-year fracture probability (FRAX) and remaining lifetime fracture probability (RFLP) were calculated.

Main Outcome Measures

BMD, and history of fractures.

Results

Reported fractures occurred more frequently in HIV than controls, (45 vs. 16; 20.3 vs. 7%; OR=3.27; p=0.0001), and unsurprisingly in this age range, non-fragility fractures in men substantially contributed to this increase. Osteoporosis was more prevalent in patients with HIV (17.6% vs. 3.6%, p<0.0001). BMD was most reduced, and predicted fracture rates most increased, at the spine. Low BMD was associated with antiretroviral therapy (ART), low body mass index and PTH. 10-year FRAX risk was <5% for all groups. RLFP was greater in patients with HIV (OR=1.22; p=0.003) and increased with ART (2.4 vs. 1.50; OR= 1.50; p=0.03).

Conclusions

The increased fracture rate in HIV patients in our relatively youthful population is partly driven by fractures, including non-fragility fractures, in men. Nonetheless, these findings may herald a rise in osteoporotic fractures in HIV patients. An appropriate screening and management response is required to assess these risks and identify associated lifestyle factors that are also associated with other conditions such as cardiovascular disease and diabetes.     

Genetic Analysis of the Relationship between Bone Mineral Density and Low-Density Lipoprotein Receptor-Related Protein 5 Gene Polymorphisms

Background

A number of studies have examined the association between the polymorphisms of the low-density lipoprotein receptor-related protein 5 gene (LRP5), but previous results have been inconclusive. Thus we performed a meta-analysis of studies on the association between the LRP5 polymorphisms and bone mineral density (BMD) to assess their pooled effects.

Methods

Published literature from PubMed, EMBASE and ISI web of science were searched for eligible publications. Weighted mean difference (WMD) and 95% confidence interval (CI) was calculated using fixed- or random-effects model.

Results

A total of 19 studies with 25773 subjects were considered in this meta-analysis. Of them, 17 examined the association between the A1330V polymorphism and BMD, 8 were focused on the V667M polymorphism, and 2 analyzed the Q89R polymorphism. Individuals with the A1330V AA genotype showed significantly higher BMD than those with the AV/VV genotypes [at lumbar spine (LS): WMD = 0.02g/cm², 95% CI = 0.01-0.03, P < 10^-4; at femur neck (FN): WMD = 0.01g/cm², 95% CI = 0.00-0.02, P = 0.01] or VV genotype (at LS: WMD = 0.02g/cm², 95% CI = 0.01-0.04, P = 0.01). Significant associations were also detected in the analysis for V667M (VV vs. VM/MM: WMD at LS = 0.02g/cm², 95% CI = 0.02-0.03, P < 10^-5; WMD at FN = 0.01g/cm², 95% CI = 0.01-0.02, P = 0.0002). As for Q89R, subjects with the QQ genotype tended to have higher BMD than those with the QR/RR genotypes at FN (WMD = 0.03g/cm², 95% CI = 0.01-0.05, P = 0.005).

Conclusion

This meta-analysis demonstrated that the LRP5 polymorphisms may be modestly associated with BMD of LS and FN.     

Testosterone,Sex Hormone-Binding Globulin and the Metabolic Syndrome in Men: An Individual Participant Data Meta-Analysis of Observational Studies

Background

Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably.

Objectives

We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components.

Data sources

Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE.

Study Eligibility Criteria

Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men.

Methods

We conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT) with MetS and its individual components. Multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) were calculated and effect modification by age and BMI was studied.

Results

Men with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95% CI 1.60-1.77), 1.73 (95% CI 1.62-1.85) and 1.46 (95% CI 1.36-1.57) for TT, SHBG and FT, respectively) and incident MetS (HRs per quartile decrease were 1.25 (95% CI 1.16-1.36), 1.44 (95% 1.30-1.60) and 1.14 (95% 1.01-1.28) for TT, SHBG and FT, respectively). Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension.

Conclusions

Associations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk.     

Dietary Methionine Intake and Risk of Incident Colorectal Cancer: A Meta-Analysis of 8 Prospective Studies Involving 431,029 Participants

Background

Methionine is one of the key components of one carbon metabolism. Experimental studies indicate that methionine may reduce inflammation-induced colon cancer. However, epidemiologic findings as to whether dietary methionine intake influences colorectal cancer incidence in humans are inconsistent.

Objective

To investigate the relationship between dietary methionine intake and risk of colorectal cancer by performing a meta-analysis of prospective studies.

Methods

Eligible studies were identified by searching PubMed and Embase and by reviewing the bibliographies of the retrieved publications. The summary risk estimates were computed using both a random- effects and a fixed-effects model.

Results

Eight eligible prospective cohort studies involving 431,029 participants and 6,331 colorectal cancer cases were identified. According to the random-effects model, the summary relative risks (RRs) for the highest compared with the lowest intake of methionine were 0.89 (95% confidence interval [CI] = 0.77-1.03) for colorectal cancer, 0.77 (95% CI = 0.64 - 0.92) for colon cancer, and 0.88 (95% CI = 0.55-1.42) for rectal cancer. In the stratified analysis, a significant inverse association between dietary methionine intake and risk of colorectal cancer was observed in studies with longer follow-up time (RR=0.81, 95% CI= 0.70- 0.95), in Western studies (RR= 0.83, 95% CI = 0.73 - 0.95) and in men (RR = 0.75, 95% CI= 0.57-0.99). We found no indication of publication bias.

Conclusion

This meta-analysis indicates that dietary methionine intake may be associated with decreased risk of colorectal cancer, especially colon cancer. More prospective studies with long follow-up time are needed to confirm these findings.     

Patterns of Bisphosphonates Utilization in Patients under Age 45 in a Large Cohort of Commercial Insurance Beneficiaries in the United States

Background

The effectiveness and safety of bisphosphonates treatment used in the young population have not been well studied. Despite insufficient data on effectiveness and safety of bisphosphonates in young patients, bisphosphonates are still considered in younger patients at high risk for osteoporosis or fracture. The objectives of this study were to identify bisphosphonate initiators aged 10–45 years and describe their clinical characteristics and to assess time trends of bisphosphonate use over the past decade in a large U.S. population-based cohort.

Methods

Using the medical and pharmacy claims data from a U.S. commercial insurance (2003–2012), patients aged 10–45 years without malignancy who initiated an oral or intravenous bisphosphonate after at least 1 year of insurance enrollment were selected. Baseline demographics, comorbidities, medications and health care utilization were assessed in the year prior to initiating a bisphosphonate. The trend of bisphosphonate use over time was examined.

Results

There were 9,082 bisphosphonate initiators (0.02% of the same age group in the population). The mean age was 38.1 years and 79.6% female. Osteoporosis was the most common diagnosis (41.2%). At baseline, 10.8% had a diagnosis of fracture and 29.0% had a bone mineral density measured. Of those who used glucocorticoids (39%) at baseline, the mean 1-year cumulative prednisone-equivalent dose was 2,669 milligrams. The use of bisphosphonates in the young population significantly decreased over the past decade (p<0.001).

Conclusions

Among young patients aged 10–45, the use of bisphosphonates was uncommon and significantly decreased over the past decade in the U.S. While most patients initiating bisphosphonates had a diagnosis of osteoporosis and fracture in the preceding year, some had no recorded claims with a diagnosis of fracture, osteoporosis, or long-term glucocorticoids use at baseline. Future research is needed to examine the effectiveness and safety of bisphosphonates in young patients at risk for osteoporosis.     

Meta-Analysis of Anti-Muscarinic Receptor Type 3 Antibodies for the Diagnosis of Sj?gren Syndrome

Purpose

To conduct a meta-analysis to evaluate the diagnostic value of anti-muscarinic receptor type 3 (M3R) antibodies in Sjögren syndrome (SS).

Methods

Two databases, PUBMED and the Cochrane Library, were systematically searched. Approximately 2,000 participants from several studies were included in this research. STATA 11.2 software and Meta-DiSc 1.4 was used to conduct the meta-analysis.

Results

Eleven studies were included in the meta-analysis. The pooled DOR was 13.00 (95% CI, 6.00–26.00). The sensitivity was 0.43 (95% CI, 0.28–0.58) and the specificity was 0.95 (95%CI, 0.91–0.97). The LR+ and LR- were 7.90 (95% CI, 4.70–13.40), 0.61 (95% CI, 0.46–0.79), respectively. The AUC was 0.89 (95% CI, 0.86–0.92).

Conclusion

The anti-M3R antibody had high specificity but relatively low sensitivity for the diagnosis of SS.     

Influences of Endplate Removal and Bone Mineral Density on the Biomechanical Properties of Lumbar Spine

Purpose

To investigate (1) effects of endplate removal and bone mineral density (BMD) on biomechanical properties of lumbar vertebrae (2) whether the distributions of mechanical strength and stiffness of endplate are affected by BMD.

Methods

A total of thirty-one lumbar spines (L1-L5) collected from fresh cadavers were used in this study. Bone density was measured using lateral DEXA scans and parts of samples were performed with partial or entire endplate removal. All the specimens were divided into three BMD groups. According to endplate integrity of the lumbar vertebrae, each BMD group was then divided into three subgroups: subgroup A: intact endplate; subgroup B: central region of endplate removal; subgroup C: entire endplate removal. The axial compression test was conducted with material testing system at a speed of 2mm/min. The experimental results were statistically analyzed using SPSS 17.0.

Results

(1) Significant differences of biomechanical properties occurred among normal BMD, osteoporotic and serious osteoporotic group (P<0.05). (2) Spearman analysis showed that BMD was positively correlated with the failure load and stiffness of lumbar vertebrae. (3) For each BMD group, significant differences of biomechanical properties were found between subgroup A and C, and between subgroup B and C (P<0.05). (4) For each BMD group, there was no statistical difference of biomechanical properties between subgroup A and B (P>0.05).

Conclusions

Entire endplate removal can significantly decrease the structural properties of lumbar vertebrae with little change in biomechanical properties by preservation of peripheral region of the endplate. BMD is positively correlated to the structural properties of the lumbar vertebrae.     

High Postoperative Serum Cortisol Level Is Associated with Increased Risk of Cognitive Dysfunction Early after Coronary Artery Bypass Graft Surgery: A Prospective Cohort Study

Context

Stress response induced by surgery is proposed to play an important role in the pathogenesis of postoperative cognitive dysfunction.

Objective

To investigate the association between postoperative serum cortisol level and occurrence of cognitive dysfunction early after coronary artery bypass graft surgery.

Design

Prospective cohort study.

Setting

Two teaching hospitals.

Patients

One hundred and sixth-six adult patients who were referred to elective coronary artery bypass graft surgery from March 2008 to December 2009.

Intervention

None.

Main Outcome Measures

Neuropsychological tests were completed one day before and seven days after surgery. Cognitive dysfunction was defined using the same definition as used in the ISPOCD1-study. Blood samples were obtained in the first postoperative morning for measurement of serum cortisol concentration. Multivariate Logistic regression analyses were performed to assess the relationship between serum cortisol level and occurrence of postoperative cognitive dysfunction.

Results

Cognitive dysfunction occurred in 39.8% (66 of 166) of patients seven days after surgery. Multivariate Logistic regression analysis showed that high serum cortisol level was significantly associated with the occurrence of postoperative cognitive dysfunction (odds ratio [OR] 2.603, 95% confidence interval [CI] 1.371-4.944, P = 0.003). Other independent predictors of early postoperative cognitive dysfunction included high preoperative New York Heart Association functional class (OR 0.402, 95% CI 0.207-0.782, P = 0.007), poor preoperative Grooved Pegboard test score of nondominant hand (OR 1.022, 95% CI 1.003-1.040, P = 0.020), use of penehyclidine as premedication (OR 2.565, 95% CI 1.109-5.933, P = 0.028), and occurrence of complications within seven days after surgery (OR 2.677, 95% CI 1.201-5.963, P = 0.016).

Conclusions

High serum cortisol level in the first postoperative morning was associated with increased risk of cognitive dysfunction seven days after coronary artery bypass graft surgery.     

The Prognostic Value of Phosphorylated AKT Expression in Non-Small Cell Lung Cancer: A Meta-Analysis

Objectives

Phosphorylated AKT (p-AKT), constitutive activation of AKT, is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). However, the available results of p-AKT expression in NSCLC are heterogeneous. Therefore, a meta-analysis of published researches investigating the prognostic relevance of p-AKT expression in patients with NSCLC was performed.

Materials and Methods

A literature search via PubMed, EMBASE and CNKI (China National Knowledge Infrastructure) databases was conducted. Data from eligible studies were extracted and included into meta-analysis using a random effects model.

Results

A total of 1049 patients from nine studies were included in the meta-analysis. Nine studies investigated the relationship between p-AKT expression and overall survival using univariate analysis, and five of these undertook multivariate analysis. The pooled hazard ratio (HR) for overall survival was 1.49 (95% confidence interval (CI): 1.01-2.20) by univariate analysis and 1.02 (95% CI: 0.54-1.95) by multivariate analysis.

Conclusion

Our study shows that positive expression of p-AKT is associated with poor prognosis in patients with NSCLC. However, adequately designed prospective studies need to perform.     

Incidence and Risk Factors of C5 Palsy following Posterior Cervical Decompression: A Systematic Review

Background

C5 palsy is a serious but poorly understood complication after posterior cervical decompression that could lead to muscle weakness, brachialgia and numbness of the upper limbs. The incidence of C5 palsy varies greatly between studies. The risk factors are inconclusive and even conflicting.

Object

To perform a systematic review on the incidence and risk factors of C5 palsy after posterior cervical decompression.

Materials and Methods

Four databases, PubMed, Embase, Web of Science and Cochrane CENTRAL, were searched to identify eligible studies. Either a fixed- or a random-effects model was used to calculate the pooled odd ratio (RR) or standardized mean difference (SMD) with its 95% confidence interval (95%CI).

Results

Of the 589 pre-recruited studies, 25 were included in this study for systematic review. The pooled incidence of C5 palsy after posterior decompression was 5.8% (95%CI: 4.4–7.2%). The incidence after open-door laminoplasty, double-door laminoplasty and laminectomy was 4.5%, 3.1% and 11.3%, respectively. The significant risk factors of C5 palsy were OPLL (OR, 2.188; 95%CI, 1.307–3.665), narrower intervertebral foramen (SMD, −0.972; 95%CI, −1.398 to −0.545), laminectomy (vs. open-door laminoplasty, OR, 2.988; 95%CI, 1.298–6.876), excessive spinal cord drift (SMD, 1.289, 95%CI, 0,197–2.381) and male gender (OR, 1.54; 95%CI, 1.036–2.301).

Conclusions

The results of this systematic review suggest that patients with excessive spinal cord drift, preexisting intervertebral foramenal stenosis, OPLL, laminectomy and male gender are at high risk for postoperative C5 palsy, and risk-reduction options should be considered for such patients.     

The Effects of Postmenopausal Hormone Use on Cataract: A Meta-Analysis

Background

Cataract is the leading cause of blindness worldwide. Many observational studies assessed the relationship between postmenopausal hormone replacement therapy (HRT) and risk of cataract development, but the reported results were controversial. The aim of present meta-analysis was to evaluate the association of postmenopausal hormone replacement therapy with risk of cataract development.

Methods

The eligible observational studies, including cross-sectional, case–control and cohort studies, were identified by searching PubMed and Embase during March of 2013. Either a fixed- or a random-effects model was used to calculate the pooled odds ratio (OR) with its 95% confidence interval (95%CI). Subgroup analysis on cataract types was performed.

Results

A total of four cohort and five case-control or cross-sectional studies were finally included into this meta-analysis. Overall, a significant decreased risk of developing any type of cataract was found in ever HRT group as compared with non-HRT group among cohort studies (OR 0.83; 95%CI: 0.71,0.97) and case-control or cross-sectional studies (OR 0.74; 95%CI: 0.59,0.93). Subgroup analysis on cataract types determined that the significantly decreased risk of nuclear cataract in current HRT group (OR 0.72; 95%CI: 0.61,0.85) and also a critically reduced risk of nuclear cataract in ever HRT group (OR 0.80; 95% CI: 0.64,1.01) were found among case-control or cross-sectional studies, as compared with non-HRT group. No association of HRT with risk of cortical and posterior subcapsular cataract was observed.

Conclusions

The results of present meta-analysis indicate that postmenopausal hormone use may play a protective role in cataract development.     

Periodontal Disease and Risk of Head and Neck Cancer: A Meta-Analysis of Observational Studies

Background

Many epidemiological studies have found a positive association of periodontal disease (PD) with risk of head and neck cancer (HNC), but the findings are varied or even contradictory. In this work, we performed a meta-analysis to ascertain the relationship between PD and HNC risk.

Methods

We searched the PubMed, Embase, and Cochrane Library databases for relevant observational studies on the association between PD and HNC risk published up to March 23, 2013. Data from the included studies were extracted and analyzed independently by two authors. Meta-analysis was performed using RevMan 5.2 software.

Results

We obtained seven observational studies involving two cohort and six case-control studies. Random-effects meta-analysis indicated a significant association between PD and HNC risk (odds ratio = 2.63, 95% confidence interval = 1.1.68 - 4.14; p < 0.001), with sensitivity analysis showing that the result was robust. Subgroup analyses based on adjustment for covariates, study design, PD assessment, tumor site, and ethnicity also revealed a significant association.

Conclusions

Based on currently evidence, PD is probably a significant and independent risk factor of HNC.     

Association of Trichomonas vaginalis and Cytological Abnormalities of the Cervix in Low Risk Women

Objective

Is Trichomonas vaginalis (TV) an inducing factor for the development of (pre-)cancerous lesions of the cervix?

Design

Cross sectional study.

Setting

Screening healthy Belgian women with low infection risk.

Sample

63,251 consecutive liquid based cervical samples.

Methods

Real time quantitative PCR for presence of TV, 18 HPV types and Pap smear analysis of cytologic abnormalities.

Main Outcome Measures

Association of TV and HPV with cervix dysplasia

Results

The overall prevalence of TV DNA was 0.37%, of low risk HPV 2%, of high risk HPV 13.2%, and 8.8 % had cytological abnormalities. Both LR-HPV and HR-HPV were significantly associated with all cytological abnormalities. Presence of TV was associated with LR- and HR-HPV, ASC-US and HSIL, but not with other abnormalities. All women with TV and HSIL also had HR-HPV, while the latter was present in only 59% of women with TV and ASC-US. Amongst HPV negative women, TV was found in 1.3% of women with ASC-US, but only in 0.03% of women with normal cytology (OR 4.2, CL95% 2.1-8.6). In HR-HPV positive women, presence of TV increased the likelihood of cytological abnormalities somewhat (P=0.05), mainly due to an increase in ASC-US and LSIL, but not HSIL.

Conclusions

We conclude that TV infection is associated with both LR and HR-HPV infection of the cervix, as well as with ASC-US and HSIL. TV is a concomitant STI, but is not thought to be a co-factor in the causation of HSIL and cervical cancer. However, TV may cause false positive diagnoses of ASC-US.     

Hypertension and Risk of Cataract: A Meta-Analysis

Background

Cataract is the major cause of blindness across the world. Many epidemiologic studies indicated that hypertension might play an important role in the development of cataract, while others not. We therefore conducted this meta-analysis to determine the relationship between risk of cataract and hypertension.

Methods

Retrieved studies on the association of hypertension with cataract risk were collected from PubMed, Web of Science and the Cochrane Library during June 2014 and were included into the final analysis according to the definite inclusion criteria. Odds ratio (OR) or risk ratio (RR) were pooled with 95% confidence interval (CI) to evaluate the relationship between hypertension and cataract risk. Subgroup analyses were carried out on the basis of cataract type, race and whether studies were adjusted for main components of metabolic syndrome (MS).

Results

The final meta-analysis included 25 studies (9 cohort, 5 case-control and 11 cross-sectional) from 23 articles. The pooled results showed that cataract risk in populations with hypertension significantly increased among cohort studies (RR 1.08; 95% CI: 1.05–1.12) and case-control or cross-sectional studies (OR 1.28; 95% CI: 1.12–1.45). This association was proved to be true among both Mongolians and Caucasians, and the significance was not altered by the adjustment of main components of MS. Subgroup analysis on cataract types indicated that an increased incidence of posterior subcapsular cataract (PSC) resulted among cohort studies (RR 1.22; 95% CI: 1.03–1.46) and cross-sectional/case-control studies (OR 1.23; 95% CI: 1.09–1.39). No association of hypertension with risk of nuclear cataract was found.

Conclusions

The present meta-analysis suggests that hypertension increases the risk of cataract, especially PSC. Further efforts should be made to explore the potential biological mechanisms.     

Strategies for Rapid Muscle Fatigue Reduction during FES Exercise in Individuals with Spinal Cord Injury: A Systematic Review

Background

Rapid muscle fatigue during functional electrical stimulation (FES)-evoked muscle contractions in individuals with spinal cord injury (SCI) is a significant limitation to attaining health benefits of FES-exercise. Delaying the onset of muscle fatigue is often cited as an important goal linked to FES clinical efficacy. Although the basic concept of fatigue-resistance has a long history, recent advances in biomedical engineering, physiotherapy and clinical exercise science have achieved improved clinical benefits, especially for reducing muscle fatigue during FES-exercise. This review evaluated the methodological quality of strategies underlying muscle fatigue-resistance that have been used to optimize FES therapeutic approaches. The review also sought to synthesize the effectiveness of these strategies for persons with SCI in order to establish their functional impacts and clinical relevance.

Methods

Published scientific literature pertaining to the reduction of FES-induced muscle fatigue was identified through searches of the following databases: Science Direct, Medline, IEEE Xplore, SpringerLink, PubMed and Nature, from the earliest returned record until June 2015. Titles and abstracts were screened to obtain 35 studies that met the inclusion criteria for this systematic review.

Results

Following the evaluation of methodological quality (mean (SD), 50 (6) %) of the reviewed studies using the Downs and Black scale, the largest treatment effects reported to reduce muscle fatigue mainly investigated isometric contractions of limited functional and clinical relevance (n = 28). Some investigations (n = 13) lacked randomisation, while others were characterised by small sample sizes with low statistical power. Nevertheless, the clinical significance of emerging trends to improve fatigue-resistance during FES included (i) optimizing electrode positioning, (ii) fine-tuning of stimulation patterns and other FES parameters, (iii) adjustments to the mode and frequency of exercise training, and (iv) biofeedback-assisted FES-exercise to promote selective recruitment of fatigue-resistant motor units.

Conclusion

Although the need for further in-depth clinical trials (especially RCTs) was clearly warranted to establish external validity of outcomes, current evidence was sufficient to support the validity of certain techniques for rapid fatigue-reduction in order to promote FES therapy as an integral part of SCI rehabilitation. It is anticipated that this information will be valuable to clinicians and other allied health professionals administering FES as a treatment option in rehabilitation and aid the development of effective rehabilitation interventions.     

Short-Term Consequences of Angiographically-Confirmed Coronary Stent Thrombosis

Objectives

To conduct a meta-analysis to quantify the real-world incidence of in-hospital or 30-day death or myocardial infarction (MI), and angiographically-confirmed ST-related treatment costs.

Background

The short-term clinical and economic consequences of coronary stent thrombosis (ST) are thought to be significant.

Methods

We searched MEDLINE, Embase and Scopus from January 2000-July 2012 to identify observational/registry studies that evaluated a cohort of ≥25 patients experiencing angiographically-confirmed thrombosis of a drug-eluting or bare-metal stent, required the use of dual-antiplatelet therapy for guideline-recommended durations, and reported incidences of in-hospital or 30-day death or MI and/or ST-related treatment costs. Incidences and costs from each study were pooled using random-effects meta-analysis.

Results

Twenty-three studies were included. Of the 13 studies reporting in-hospital outcomes, 12 (N=8,832 STs) reported mortality data, with the pooled incidence rate estimated to be 7.9%, 95%CI=5.4%-11.3%, I²=86%. Ten studies (N=1,294 STs) reported 30-day death, with a pooled incidence of 11.6%, 95%CI=8.8%-15.1%, I²=55%. Patients experiencing early ST (within 30-days of implant) had higher in-hospital and 30-day mortality than those experiencing very-late ST (interaction p<0.04 for both). Stent type had no significant effect on in-hospital or 30-day mortality. In the 5 studies (N=542 STs) and 3 studies (N=180 STs) reporting in-hospital and 30-day MI, respectively, the pooled incidence rates were 6.1%, 95%CI=2.1%-16.2%, I²=88% and 9.5%, 95%CI=3.8%-22.0%, I²=65%. One study reported costs associated with ST, estimating the median/patient cost of hospitalization to treat early ST at $11,134 (in 2000US$).

Conclusions

Regardless of stent type used, the short-term consequences of coronary ST appear significant.     

Prognosis and Risk Factors for Deterioration in Patients Admitted to a Medical Emergency Department

Objective

Patients that initially appear stable on arrival to the hospital often have less intensive monitoring of their vital signs, possibly leading to excess mortality. The aim was to describe risk factors for deterioration in vital signs and the related prognosis among patients with normal vital signs at arrival to a medical emergency department (MED).

Design and setting

Single-centre, retrospective cohort study of all patients admitted to the MED from September 2010-August 2011.

Subjects

Patients were included when their vital signs (systolic blood pressure, pulse rate, respiratory rate, Glasgow Coma Scale, oxygen saturation and temperature) were within the normal range at arrival. Deterioration was defined as a deviation from the defined normal range 2–24 hours after arrival.

Results

4292 of the 6257 (68.6%) admitted to the MED had a full set of vital signs at first presentation, 1440/4292 (33.6%) had all normal vital signs and were included in study, 44.0% were male, median age 64 years (5th/95th percentile: 21–90 years) and 446/1440 (31.0%) deteriorated within 24 hours. Independent risk factors for deterioration included age 65–84 years odds ratio (OR): 1.79 (95% confidence interval [CI]: 1.27–2.52), 85+ years OR 1.67 (95% CI: 1.10–2.55), Do-not-attempt-to-resuscitate order OR 3.76 (95% CI: 1.37–10.31) and admission from the open general ED OR 1.35 (95% CI: 1.07–1.71). Thirty-day mortality was 7.9% (95% CI: 5.5–10.7%) among deteriorating patients and 1.9% (95% CI: 1.2–3.0%) among the non-deteriorating, hazard ratio 4.11 (95% CI: 2.38–7.10).

Conclusions

Among acutely admitted medical patients who arrive with normal vital signs, 31.0% showed signs of deterioration within 24 hours. Risk factors included old age, Do-not-attempt-to-resuscitate order, admission from the open general ED. Thirty-day mortality among patients with deterioration was four times higher than among non-deteriorating patients. Further research is needed to determine whether intensified monitoring of vital signs can help to prevent deterioration or mortality among medical emergency patients.     

FTO Gene Variant and Risk of Overweight and Obesity among Children and Adolescents: a Systematic Review and Meta-Analysis

Objective

The fat mass and obesity associated gene (FTO) polymorphisms have been implicated in the susceptibility of overweight/obesity in children and adolescents. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of FTO gene polymorphisms with overweight/obesity risk among children and adolescents.

Methods

PubMed and Embase were used to search for eligible published literatures. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effect models.

Results

A total of 21 articles containing 23 studies (11208cases and 35015controls) were included in our analysis. The results indicated that variant in FTO gene was significantly associated with increased risk of overweight/obesity in children and adolescents (OR=1.35; 95%CI: 1.27-1.44; P<0.001). The overall pooled ORs for risk obesity and overweight were 1.34 (95%CI: 1.21-1.48) and 1.35 (95%CI: 1.25-1.47), respectively. Subgroup analyses also showed similar trends in most subgroups of adjustment for covariates and unadjustment, different ethnicities (Caucasians, Asians, and Amerindians), and each of three investigated polymorphisms (rs9939609, rs1421085, and rs1558902).

Conclusions

The present meta-analysis suggested a positive association between FTO gene polymorphism and overweight/obesity risk among children and adolescents. Further prospective studies should be recommended to confirm the observed association, and underlying mechanism should be investigated to clarify the association of FTO gene polymorphism with overweight/obesity.