The association of high-intensity zones on MRI and low back pain: a systematic review

Background

Magnetic resonance imaging (MRI) of the lumbar spine is commonly used to identify the source of low back pain (LBP); however, its use has been questionable. Throughout the years, numerous lumbar phenotypes (e.g., endplate abnormalities, Modic changes, black disc) have been studied as possible pain generators. High-intensity zones (HIZs) are of particular interest as they may represent annular tears. However, for over three decades, there has been heated debate as to whether these imaging biomarkers are synonymous with LBP. Therefore, the following study addressed a systematic review of the reported literature addressing the relationship of HIZs and LBP.

Methods

A systematic review was conducted via MEDLINE, SCOPUS, Cochrane, PubMed, PubMed Central, EMBASE via Ovid, and Web of Science with the following search terms: “HIZ,” “high intensity zone,” or “high intensity zones” and “low back pain,” “pain,” “lumbago,” and/or “sciatica.” Specific exclusion criteria were also maintained. Two independent reviewers searched the literature, selected the studies, and extracted the data.

Results

We identified six studies from our search strategy that met the inclusion criteria from a total of 756 possible studies. One cross-sectional population-based study and five comparison studies were identified, which provided information regarding the prevalence of HIZs. The prevalence of HIZs was 3 to 61% in subjects with LBP and 2 to 3% in subjects without LBP. Only three studies suggested a significant association between the presence of HIZ and LBP with or without sciatica.

Conclusions

Our systematic review has found evidence that HIZs may be a possible risk factor for LBP; however, a mismatch of the clinical relevance of HIZs between studies still remains. The available evidence is limited by small sample size, heterogeneous study populations, and lack of standardized imaging methods for phenotyping. HIZs may be important lumbar biomarkers that demand further investigation and should be considered in the global imaging assessment of the spine, which may have immense clinical utility. Further large-scale studies with standardized imaging and classification techniques as well as the assessment of patterns of HIZs are necessary to better understand their role with LBP development.

     

Current clinical trials with non-coding RNA-based therapeutics in malignant diseases: A systematic review

This systematic review aimed to shed light on the trend of current clinical trials of non-coding RNA (ncRNA)-based therapeutics for malignant diseases. We conducted a database search for published literature and ongoing clinical trials using PubMed, clinicaltrials.gov, and University Medical Information Network (UMIN) clinical trial registry. To ensure that our review was based on up-to-date clinical trials, we limited our search to literature published within the last five years (January 2017–September 2022). Furthermore, due to the “clinical” nature of our review, we focused only on studies involving human participants. Among ncRNAs, microRNAs have been extensively explored in observational studies of malignant diseases as potential diagnostic markers and prognostic predictors, as well as for their therapeutic monitoring and profiling capabilities. As therapeutic agents, microRNA or siRNA were estimated in interventional human clinical trials and showed promising outcomes; however, the number of trials was small. Evidence and ongoing clinical trials in which ncRNAs other than microRNA or siRNA have been evaluated for their potential as therapeutic agents are limited. Here, we summarized microRNA as a potential therapeutic agent in malignant diseases, but most of the current evidence suggests that it is useful as a potential biomarker. siRNA is also a promising ncRNA technique in cancer, however more data from clinical trials are warranted for clinical use.     

Vitamin D for Treatment and Prevention of Infectious Diseases; A Systematic Review of Randomized Controlled Trials

ObjectiveTo review the existing human controlled intervention studies of vitamin D as adjunctive therapy in settings of infection and provide recommendations for design and implementation of future studies in this field on the basis of the evidence reviewed.MethodsWe conducted a systematic review of randomized controlled clinical trials that studied vitamin D for treatment or prevention of infectious diseases in humans. Studies from 1948 through 2009 were identified through search terms in PubMed and Ovid MEDLINE.ResultsThirteen published controlled trials were identified by our search criteria. Ten trials were placebo controlled, and 9 of the 10 were conducted in a rigorous double-blind design. The selected clinical trials demonstrated substantial heterogeneity in baseline patient demographics, sample size, and vitamin D intervention strategies. Serious adverse events attributable to vitamin D supplementation were rare across all studies. On the basis of studies reviewed to date, the strongest evidence supports further research into adjunctive vitamin D therapy for tuberculosis, influenza, and viral upper respiratory tract illnesses. In the selected studies, certain aspects of study design are highlighted to help guide future clinical research in the field.ConclusionMore rigorously designed clinical trials are needed for further evaluation of the relationship between vitamin D status and the immune response to infection as well as for delineation of necessary changes in clinical practice and medical care of patients with vitamin D deficiency in infectious disease settings. (Endocr Pract. 2009;15:438-449)     

Spinal manipulation epidemiology: Systematic review of cost effectiveness studies

BackgroundSpinal manipulative therapy (SMT) is frequently used by health professionals to manage spinal pain. With many treatments having comparable outcomes to SMT, determining the cost-effectiveness of these treatments has been identified as a high research priority.ObjectiveTo investigate the cost-effectiveness of SMT compared to other treatment options for people with spinal pain of any duration.MethodsWe searched eight clinical and economic databases and the reference lists of relevant systematic reviews. Full economic evaluations conducted alongside randomised controlled trials with at least one SMT arm were eligible for inclusion. Two authors independently screened search results, extracted data and assessed risk of bias using the CHEC-list.ResultsSix cost-effectiveness and cost–utility analysis were included. All included studies had a low risk of bias scoring ?16/19 on the CHEC-List. SMT was found to be a cost-effective treatment to manage neck and back pain when used alone or in combination with other techniques compared to GP care, exercise and physiotherapy.ConclusionsThis review supports the use of SMT in clinical practice as a cost-effective treatment when used alone or in combination with other treatment approaches. However, as this conclusion is primarily based on single studies more high quality research is needed to identify whether these findings are applicable in other settings.     

Diagnostic Accuracy of Lipopolysaccharide-Binding Protein as Biomarker for Sepsis in Adult Patients: A Systematic Review and Meta-Analysis

IntroductionLipopolysaccharide-binding protein (LBP) is widely reported as a biomarker to differentiate infected from non-infected patients. The diagnostic use of LBP for sepsis remains a matter of debate. We aimed to perform a systematic review and meta-analysis to assess the diagnostic accuracy of serum LBP for sepsis in adult patients.MethodsWe performed a systematic review and meta-analysis to assess the accuracy of LBP for sepsis diagnosis. A systematic search in PubMed and EMBASE for studies that evaluated the diagnostic role of LBP for sepsis through December 2015 was conducted. We searched these databases for original, English language, research articles that studied the diagnostic accuracy between septic and non-septic adult patients. Sensitivity, specificity, and other measures of accuracy, such as diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUC) of LBP were pooled using the Hierarchical Summary Receiver Operating Characteristic (HSROC) method.ResultsOur search returned 53 reports, of which 8 fulfilled the inclusion criteria, accounting for 1684 patients. The pooled sensitivity and specificity of LBP for diagnosis of sepsis by the HSROC method were 0.64 (95% CI: 0.56–0.72) and 0.63 (95% CI: 0.53–0.73), respectively. The value of the DOR was 3.0 (95% CI: 2.0–4.0) and the AUC was 0.68 (95% CI: 0.64–0.72). Meta-regression analysis revealed that cut-off values accounted for the heterogeneity of sensitivity and sample size (> = 150) accounted for the heterogeneity of specificity.ConclusionsBased on the results of our meta-analysis, LBP had weak sensitivity and specificity in the detection of sepsis. LBP may not be practically recommended for clinical utilization as a single biomarker.     

An investigation of the flexion relaxation ratio in adults with and without a history of self-reported low back pain and transient sitting-induced pain

It is unknown whether the presence of sitting-induced pain or a clinical history of low back pain (LBP) changes spine function outcomes such as the flexion relaxation ratio (FRR). The purpose of this investigation was to determine whether sitting-induced pain or a history of non-specific LBP results in a different FRR. Forty-seven participants were instrumented with surface electromyography over erector spinae at L1, and accelerometers at L1 and S2. Standing maximum lumbar flexion trials were taken preceding and following a 1-hour sitting trial. Pain ratings during sitting and history of LBP were used to group participants for analysis. FRR values taken after the sitting exposures were compared between those that did and did not develop pain during sitting. Baseline FRR values were compared participants with and without a history of LBP. No significant differences in FRR were found for either pain groups (p = 0.11) or clinical history (p = 0.85). Lack of differences may be due to participants not currently experiencing a clinical episode of pain when the ratio was measured and/or because 1-hour sitting exposure was not long enough to induce pain modulation. The findings suggest that neither sitting-induced pain development or clinical history need to be controlled to prevent confounding of FRR.     

Autologous adipose tissue grafting for the management of the painful scar

Background aimsThere is currently no definitive treatment for the painful scar. Autologous adipose tissue grafting (AATG) as a treatment option for scars has become increasingly popular and there is now an abundance of evidence in the literature that supports its application. Some studies suggest that human adipose tissue is a rich source of multipotent mesenchymal stromal cells. To our knowledge, there is currently no systematic literature review to date that examines the effectiveness of AATG for reducing pain in scars. Our novel systematic review aims to examine clinical studies on the use of AATG in the treatment of the painful scar.MethodsA literature search was performed using the following databases: PubMed, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Medline, Cochrane library and Embase. The following key words and search terms were used: adipose stem cells, scar, pain, autologous fat grafting, scar management and neuropathic pain. Human interventional studies using autologous adipose tissue grafting for the treatment of painful scars including case series, case-control, cohort studies and randomized controlled trials were reviewed.ResultsA total of 387 studies were found and 18 studies from January 1990 to January 2019 were identified as relevant for the purpose of this systematic review. Two studies were evidence level V, seven were evidence level IV, six were evidence level III, two were evidence level II and one was level I. A total of 337 scars were assessed in 288 patients for improvement in pain after scar treatment using adipose tissue grafting. An improvement in the analgesic effect was recorded in 12 of the 18 studies with adipose tissue grafting. A total of 233 of the 288 treated subjects responded with reduction in pain, whereas the rest did not. We carried out a pooled analysis of the studies and observed an odds ratio of 3.94 (P = 0.00001) when comparing pain reduction to no change in pain.ConclusionsWe conclude that AATG is a promising and safe modality for the treatment of the painful scar. There is an abundance of low-level evidence to support its use as an alternative treatment but there is a lack of high-level evidence at present to support its standard use. Future long-term randomized controlled trials with analgesic scores as the primary outcome measures are required to assess long-term efficacy.     

Key issues in recruitment to randomised controlled trials with very different interventions: a qualitative investigation of recruitment to the SPARE trial (CRUK/07/011)

Background

Low back pain (LBP) is a recognized public health problem, impacting up to 80% of US adults at some point in their lives. Patients with LBP are utilizing integrative health care such as spinal manipulation (SM). SM is the therapeutic application of a load to specific body tissues or structures and can be divided into two broad categories: SM with a high-velocity low-amplitude load, or an impulse "thrust", (HVLA-SM) and SM with a low-velocity variable-amplitude load (LVVA-SM). There is evidence that sensorimotor function in people with LBP is altered. This study evaluates the sensorimotor function in the lumbopelvic region, as measured by postural sway, response to sudden load and repositioning accuracy, following SM to the lumbar and pelvic region when compared to a sham treatment.

Methods/Design

A total of 219 participants with acute, subacute or chronic low back pain are being recruited from the Quad Cities area located in Iowa and Illinois. They are allocated through a minimization algorithm in a 1:1:1 ratio to receive either 13 HVLA-SM treatments over 6 weeks, 13 LVVA-SM treatments over 6 weeks or 2 weeks of a sham treatment followed by 4 weeks of full spine "doctor's choice" SM. Sensorimotor function tests are performed before and immediately after treatment at baseline, week 2 and week 6. Self-report outcome assessments are also collected. The primary aims of this study are to 1) determine immediate pre to post changes in sensorimotor function as measured by postural sway following delivery of a single HVLA-SM or LVVA-SM treatment when compared to a sham treatment and 2) to determine changes from baseline to 2 weeks (4 treatments) of HVLA-SM or LVVA-SM compared to a sham treatment. Secondary aims include changes in response to sudden loads and lumbar repositioning accuracy at these endpoints, estimating sensorimotor function in the SM groups after 6 weeks of treatment, and exploring if changes in sensorimotor function are associated with changes in self-report outcome assessments.

Discussion

This study may provide clues to the sensorimotor mechanisms that explain observed functional deficits associated with LBP, as well as the mechanism of action of SM.

Trial registration

This trial is registered in ClinicalTrials.gov, with the ID number of NCT00830596, registered on January 27, 2009. The first participant was allocated on 30 January 2009 and the final participant was allocated on 17 March 2011.     

Comparison of Discectomy versus Sequestrectomy in Lumbar Disc Herniation: A Meta-Analysis of Comparative Studies

Background

Lumbar disc removal is currently the standard treatment for lumbar disc herniation. No consensus has been achieved whether aggressive disc resection with curettage (discectomy) versus conservative removal of the offending disc fragment alone (sequestrectomy) provides better outcomes. This study aims to compare the reherniation rate and clinical outcomes between discectomy and sequestrectomy by literature review and a meta-analysis.

Methods

A systematic search of PubMed, Medline, Embase and the Cochrane Library was performed up to June 1, 2014. Outcomes of interest assessing the two techniques included demographic and clinical baseline characteristics, perioperative variables, complications, recurrent herniation rate and post-operative functional outcomes.

Results

Twelve eligible trials evaluating discectomy vs sequestrectomy were identified including one randomized controlled study, five prospective and six retrospective comparative studies. By contrast to discectomy, sequestrectomy was associated with significantly less operative time (p<0.001), lower visual analogue scale (VAS) for low back pain (p<0.05), less post-operative analgesic usage (p<0.05) and better patients’ satisfaction (p<0.05). Recurrent herniation rate, reoperation rate, intraoperative blood loss, hospitalization duration and VAS for sciatica were without significant difference.

Conclusions

According to our pooled data, sequestrectomy entails equivalent reherniation rate and complications compared with discectomy but maintains a lower incidence of recurrent low back pain and higher satisfactory rate. High-quality prospective randomized controlled trials are needed to firmly assess these two procedures.     

The CROWN Initiative: journal editors invite researchers to develop core outcomes in women’s health

Clinical trials, systematic reviews and guidelines compare beneficial and non-beneficial outcomes following interventions. Often, however, various studies on a particular topic do not address the same outcomes, making it difficult to draw clinically useful conclusions when a group of studies is looked at as a whole. This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention, which found that among 103 randomised trials, no fewer than 72 different outcomes were reported. There is a growing recognition among clinical researchers that this variability undermines consistent synthesis of the evidence, and that what is needed is an agreed standardised collection of outcomes - a "core outcomes set" - for all trials in a specific clinical area. Recognising that the current inconsistency is a serious hindrance to progress in our specialty, the editors of over 50 journals related to women's health have come together to support The CROWN (CoRe Outcomes in WomeN's health) Initiative.     

Uso de metadona en el anciano con dolor oncológico: una revisión sistemática

Objective

To identify the clinical use of methadone as an analgesic in the management of cancer pain in elderly patients.

Material and methods

We performed a systemic review of the literature on the specific use of methadone in elderly with cancer pain in MEDLINE, COCHRANE DATABASE and SCOPUS. A second search was conducted in MEDLINE to look for clinical trials and systematic review of the use of methadone in cancer pain, selecting only those in which the mean age of patients was ≥ 65 years old.

Results

Four articles were obtained in the first search, and from the second 7 clinical trials, none of them specific to methadone use in elderly patients with cancer.

Conclusions

There are insufficient data on the use of methadone as an analgesic in the elderly with cancer. Given its pharmacological characteristics it must be used by trained personnel. Several recommendations are proposed for its use as an analgesic in the treatment of cancer pain in the elderly.     

Tissue engineering strategies applied in the regeneration of the human intervertebral disk

Low back pain (LBP) is one of the most common painful conditions that lead to work absenteeism, medical visits, and hospitalization. The majority of cases showing signs of LBP are due to age-related degenerative changes in the intervertebral disk (IVD), which are, in fact, associated with multiple spine pathologies. Traditional and more conservative procedures/clinical approaches only treat the symptoms of disease and not the underlying pathology, thus limiting their long-term efficiency. In the last few years, research and development of new approaches aiming to substitute the nucleus pulposus and annulus fibrosus tissue and stimulate its regeneration has been conducted. Regeneration of the damaged IVD using tissue engineering strategies appears particularly promising in pre-clinical studies. Meanwhile, surgical techniques must be adapted to this new approach in order to be as minimally invasive as possible, reducing recovering time and side effects associated to traditional surgeries. In this review, the current knowledge on IVD, its associated pathologies and current surgical procedures are summarized. Furthermore, it also provides a succinct and up-to-date overview on regenerative medicine research, especially on the newest tissue engineering strategies for IVD regeneration.     

Evidence-based hydro- and balneotherapy in Hungary—a systematic review and meta-analysis

Balneotherapy is appreciated as a traditional treatment modality in medicine. Hungary is rich in thermal mineral waters. Balneotherapy has been in extensive use for centuries and its effects have been studied in detail. Here, we present a systematic review and meta-analysis of clinical trials conducted with Hungarian thermal mineral waters, the findings of which have been published by Hungarian authors in English. The 122 studies identified in different databases include 18 clinical trials. Five of these evaluated the effect of hydro- and balneotherapy on chronic low back pain, four on osteoarthritis of the knee, and two on osteoarthritis of the hand. One of the remaining seven trials evaluated balneotherapy in chronic inflammatory pelvic diseases, while six studies explored its effect on various laboratory parameters. Out of the 18 studies, 9 met the predefined criteria for meta-analysis. The results confirmed the beneficial effect of balneotherapy on pain with weight bearing and at rest in patients with degenerative joint and spinal diseases. A similar effect has been found in chronic pelvic inflammatory disease. The review also revealed that balneotherapy has some beneficial effects on antioxidant status, and on metabolic and inflammatory parameters. Based on the results, we conclude that balneotherapy with Hungarian thermal-mineral waters is an effective remedy for lower back pain, as well as for knee and hand osteoarthritis.     

Delivering the WISE (Whole Systems Informing Self-Management Engagement) training package in primary care: learning from formative evaluation

Background

Several studies document disparities in access to care and quality of care for depression for African Americans. Research suggests that patient attitudes and clinician communication behaviors may contribute to these disparities. Evidence links patient-centered care to improvements in mental health outcomes; therefore, quality improvement interventions that enhance this dimension of care are promising strategies to improve treatment and outcomes of depression among African Americans. This paper describes the design of the BRIDGE (Blacks Receiving Interventions for Depression and Gaining Empowerment) Study. The goal of the study is to compare the effectiveness of two interventions for African-American patients with depression--a standard quality improvement program and a patient-centered quality improvement program. The main hypothesis is that patients in the patient-centered group will have a greater reduction in their depression symptoms, higher rates of depression remission, and greater improvements in mental health functioning at six, twelve, and eighteen months than patients in the standard group. The study also examines patient ratings of care and receipt of guideline-concordant treatment for depression.

Methods/Design

A total of 36 primary care clinicians and 132 of their African-American patients with major depressive disorder were recruited into a cluster randomized trial. The study uses intent-to-treat analyses to compare the effectiveness of standard quality improvement interventions (academic detailing about depression guidelines for clinicians and disease-oriented care management for their patients) and patient-centered quality improvement interventions (communication skills training to enhance participatory decision-making for clinicians and care management focused on explanatory models, socio-cultural barriers, and treatment preferences for their patients) for improving outcomes over 12 months of follow-up.

Discussion

The BRIDGE Study includes clinicians and African-American patients in under-resourced community-based practices who have not been well-represented in clinical trials to improve depression care. The patient-centered and culturally targeted approach to depression care is a relatively new one that has not been tested in most previous studies. The study will provide evidence about whether patient-centered accommodations improve quality of care and outcomes to a greater extent than standard quality improvement strategies for African Americans with depression.

Trial Registration

ClinicalTrials.gov NCT00243425     

Statins and the Risk of Lung Cancer: A Meta-Analysis

Purpose

Several epidemiologic studies have evaluated the association between statins and lung cancer risk, whereas randomized controlled trials (RCTs) on cardiovascular outcomes provide relevant data as a secondary end point. We conducted a meta-analysis of all relevant studies to examine this association.

Methods

A systematic literature search up to March 2012 was performed in PubMed database. Study-specific risk estimates were pooled using a random-effects model.

Results

Nineteen studies (5 RCTs and 14 observational studies) involving 38,013 lung cancer cases contributed to the analysis. They were grouped on the basis of study design, and separate meta-analyses were conducted. There was no evidence of an association between statin use and risk of lung cancer either among RCTs (relative risk [RR] 0.91, 95% confidence interval [CI] 0.76–1.09), among cohort studies (RR 0.94, 95% CI 0.82–1.07), or among case-control studies (RR 0.82, 95% CI 0.57–1.16). Low evidence of publication bias was found. However, statistically significant heterogeneity was found among cohort studies and among case-control studies. After excluding the studies contributing most to the heterogeneity, summary estimates were essentially unchanged.

Conclusion

The results of our meta-analysis suggest that there is no association between statin use and the risk of lung cancer.     

Clinical outcomes and outcome measurement tools reported in randomised controlled trials of treatment for snakebite envenoming: A systematic review

BackgroundSnakebite is a priority neglected tropical disease and causes a range of complications that vary depending on the snake species. Randomised clinical trials have used varied outcome measures that do not allow results to be compared or combined. In accordance with the Core Outcomes Measurements in Effectiveness Trials (COMET) initiative, this systematic review aims to support the development of a globally relevant core outcome set for snakebite.MethodsAll randomised controlled trials, secondary analyses of randomised controlled trials and study protocols investigating the efficacy of therapeutics for human snakebite envenoming were eligible for inclusion. Study screening and data extraction were conducted in duplicate by two independent reviewers. All primary and secondary outcome measures were extracted and compiled, as were adverse event outcome measures. Similar outcome measures were grouped into domains. The study was prospectively registered with PROSPERO: CRD42020196160.ResultsThis systematic review included 43 randomised controlled trials, two secondary analyses and 13 study protocols. A total of 382 outcome measures were extracted and, after duplicates were merged, there were 153 unique outcomes. The most frequently used outcome domain (‘venom antigenaemia’) was included in less than one third of the studies. The unique outcomes were classified into 60 outcome domains. Patient-centred outcomes were used in only three of the studies.DiscussionSignificant heterogeneity in outcome measures exists in snakebite clinical trials. Consensus is needed to select outcome measures that are valid, reliable, patient-centred and feasible. The results of this systematic review strongly support the development of a core outcome set for use in snakebite clinical trials.     

The effects of clinical practice guidelines on patient outcomes in primary care: a systematic review

OBJECTIVE: To assess the evidence for the effectiveness of clinical practice guidelines (CPGs) in improving patient outcomes in primary care. DATA SOURCES: A search of the MEDLINE, HEALTHPLAN, CINAHL and FAMLI databases was conducted to identify studies published between Jan. 1, 1980, and Dec. 31, 1995, concerning the use of guidelines in primary medical care. The keywords used in the search were "clinical guidelines," "primary care," "clinical care," "intervention," "randomized controlled trial" and "effectiveness." STUDY SELECTION: Studies of the use of CPGs were selected if they involved a randomized experimental or quasi-experimental method, concerned primary care, were related to clinical care and examined patient outcomes. Of 91 trials of CPGs identified through the search, 13 met the criteria for inclusion in the critical appraisal. DATA EXTRACTION: The following data were extracted, when possible, from the 13 trials: country and setting, number of physicians, number of patients (and the proportion followed to completion), length of follow-up, study method (including random assignment method), type of intervention, medical condition treated and effect on patient outcomes (including clinical and statistical significance, with confidence intervals). DATA SYNTHESIS: The most common conditions studied were hypertension (7 studies), asthma (2 studies) and cigarette smoking (2 studies). Four of the studies followed nationally developed guidelines, and 9 used locally developed guidelines. Six studies involved computerized or automated reminder systems, whereas the others relied on small-group workshops and education sessions. Only 5 of the 13 trials (38%) produced statistically significant results. CONCLUSION: There is very little evidence that the use of CPGs improves patient outcomes in primary medical care, but most studies published to date have used older guidelines and methods, which may have been insensitive to small changes in outcomes. Research is needed to determine whether the newer, evidence-based CPGs have an effect on patient outcomes.     

The pharmacological activity of epigallocatechin-3-gallate (EGCG) on Alzheimer's disease animal model: A systematic review

BackgroundAlzheimer's disease (AD) is currently incurable and there is an urgent need to develop new AD drugs. Many studies have revealed the potential neuroprotective effect of Epigallocatechin-3-O-gallate (EGCG), the main antioxidant in green tea, on animal models of AD. However, a systematic review of these reports is lacking.PurposeTo assess the effectiveness of EGCG for AD treatment using systematic review and meta-analysis of pre-clinical trials.MethodsWe conducted a systematic search of all available randomized controlled trials (RCTs) performed up to November 2019 in the following electronic databases: ScienceDirect, Web of Science, and PubMed. 17 preclinical studies assessing the effect of EGCG on animal AD models have been identified. Meta-analysis and subgroup analysis was performed to evaluate cognition improvement of various types of AD models. The study quality was assessed using the CAMARADES checklist and the criteria of published studies.ResultsOur analysis shows that the methodological quality ranges from 3 to 5, with a median score of 4. According to meta-analysis of random-effects method, EGCG showed a positive effect in AD with shorter escape latency (SMD= -9.24, 95%CI= -12.05 to -6.42) and decreased Aβ₄₂ level (SD= -25.74,95%CI= -42.36 to -9.11). Regulation of α-, β-, γ-secretase activity, inhibition of tau phosphorylation, anti-oxidation, anti-inflammation, anti-apoptosis, and inhibition of AchE activity are reported as the main neuroprotective mechanisms. Though more than 100 clinical trials have been registered on the ClinicalTrials.gov, only one clinical trial has been conducted to test the therapeutic effects of EGCG on the AD progression and cognitive performance.ConclusionHere, we conducted this review to systematically describe the therapeutic potential of EGCG in animal models of AD and hope to provide a more comprehensive assessment of the effects in order to design future clinical trials. Besides, the safety, blood-brain barrier (BBB) penetration and bioavailability issues in conducting clinical trials were also discussed.     

Intramedullary Nail versus Dynamic Compression Plate Fixation in Treating Humeral Shaft Fractures: Grading the Evidence through a Meta-Analysis

There is a debate regarding the choice of operative intervention in humeral shaft fractures that require surgical intervention. The choices for operative interventions include intramedullary nailing (IMN) and dynamic compression plate (DCP). This meta-analysis was performed to compare fracture union, functional outcomes, and complication rates in patients treated with IMN or DCP for humeral shaft fractures and to develop GRADE (Grading of Recommendations, Assessment, Development, and Evaluation)-based recommendations for using the procedures to treat humeral shaft fractures. A systematic search of all the studies published through December 2012 was conducted using the Medline, Embase, Sciencedirect, OVID and Cochrane Central databases. The randomized controlled trials (RCTs) and quasi-RCTs that compared IMN with DCP in treating adult patients with humeral shaft fractures and provided data regarding the safety and clinical effects were identified. The demographic characteristics, adverse events and clinical outcomes were manually extracted from all of the selected studies. Ten studies that included a total of 448 patients met the inclusion criteria. The results of a meta-analysis indicated that both IMN and DCP can achieve similar fracture union with a similar incidence of radial nerve injury and infection. IMN was associated with an increased risk of shoulder impingement, more restriction of shoulder movement, an increased risk of intraoperative fracture comminution, a higher incidence of implant failure, and an increased risk of re-operation. The overall GRADE system evidence quality was very low, which reduces our confidence in the recommendations of this system. DCP may be superior to IMN in the treatment of humeral shaft fractures. Because of the low quality evidence currently available, high-quality RCTs are required.