Cholinesterase inhibitors in mild cognitive impairment: a systematic review of randomised trials

Background

Mild cognitive impairment (MCI) refers to a transitional zone between normal ageing and dementia. Despite the uncertainty regarding the definition of MCI as a clinical entity, clinical trials have been conducted in the attempt to study the role of cholinesterase inhibitors (ChEIs) currently approved for symptomatic treatment of mild to moderate Alzheimer disease (AD), in preventing progression from MCI to AD. The objective of this review is to assess the effects of ChEIs (donepezil, rivastigmine, and galantamine) in delaying the conversion from MCI to Alzheimer disease or dementia.

Methods and Findings

The terms “donepezil”, “rivastigmine”, “galantamine”, and “mild cognitive impairment” and their variants, synonyms, and acronyms were used as search terms in four electronic databases (MEDLINE, EMBASE, Cochrane, PsycINFO) and three registers: the Cochrane Collaboration Trial Register, Current Controlled Trials, and ClinicalTrials.gov. Published and unpublished studies were included if they were randomized clinical trials published (or described) in English and conducted among persons who had received a diagnosis of MCI and/or abnormal memory function documented by a neuropsychological assessment. A standardized data extraction form was used. The reporting quality was assessed using the Jadad scale. Three published and five unpublished trials met the inclusion criteria (three on donepezil, two on rivastigmine, and three on galantamine). Enrolment criteria differed among the trials, so the study populations were not homogeneous. The duration of the trials ranged from 24 wk to 3 y. No significant differences emerged in the probability of conversion from MCI to AD or dementia between the treated groups and the placebo groups. The rate of conversion ranged from 13% (over 2 y) to 25% (over 3 y) among treated patients, and from 18% (over 2 y) to 28% (over 3 y) among those in the placebo groups. Only for two studies was it possible to derive point estimates of the relative risk of conversion: 0.85 (95% confidence interval 0.64–1.12), and 0.84 (0.57–1.25). Statistically significant differences emerged for three secondary end points. However, when adjusting for multiple comparisons, only one difference remained significant (i.e., the rate of atrophy in the whole brain).

Conclusions

The use of ChEIs in MCI was not associated with any delay in the onset of AD or dementia. Moreover, the safety profile showed that the risks associated with ChEIs are not negligible. The uncertainty regarding MCI as a clinical entity raises the question as to the scientific validity of these trials.     

Growth assessment in children with Williams-Beuren syndrome: a systematic review

Journal of Applied Genetics - Williams-Beuren syndrome (WBS) is a rare genetic disease caused by a sporadic heterozygous microdeletion in 7q11.23. It is characterized by distinctive facial...     

Cognitive impairment and risk of future stroke: a systematic review and meta-analysis

Background:

Several studies have assessed the link between cognitive impairment and risk of future stroke, but results have been inconsistent. We conducted a systematic review and meta-analysis of cohort studies to determine the association between cognitive impairment and risk of future stroke.

Methods:

We searched MEDLINE and Embase (1966 to November 2013) and conducted a manual search of bibliographies of relevant retrieved articles and reviews. We included cohort studies that reported multivariable adjusted relative risks and 95% confidence intervals or standard errors for stroke with respect to baseline cognitive impairment.

Results:

We identified 18 cohort studies (total 121 879 participants) and 7799 stroke events. Pooled analysis of results from all studies showed that stroke risk increased among patients with cognitive impairment at baseline (relative risk [RR] 1.39, 95% confidence interval [CI] 1.24–1.56). The results were similar when we restricted the analysis to studies that used a widely adopted definition of cognitive impairment (i.e., Mini-Mental State Examination score < 25 or nearest equivalent) (RR 1.64, 95% CI 1.46–1.84). Cognitive impairment at baseline was also associated with an increased risk of fatal stroke (RR 1.68, 95% CI 1.21–2.33) and ischemic stroke (RR 1.65, 95% CI 1.41–1.93).

Interpretation:

Baseline cognitive impairment was associated with a significantly higher risk of future stroke, especially ischemic and fatal stroke.Cognitive impairment is a major contributor to disability and dependence worldwide. Globally, stroke is the leading cause of long-term disability among adults and the second leading cause of death.¹ The high cumulative risk of dementia or stroke or both conditions has been shown by the Framingham study,² and the urgent need to improve knowledge regarding cognition and vascular conditions has been emphasized in a specific meeting providing harmonized standards.³ Beyond their personal tolls, both of these conditions carry substantial social and economic burdens. These conditions also correlate strongly with increasing age. Given the projected substantial rise in the number of older people around the world, prevalence rates of cognitive impairment and stroke are expected to soar over the next several decades, especially in high-income countries.^4,5Shared pathophysiologic mechanisms seem to exist between cognitive impairment and cerebrovascular disease.⁶ Indeed, risk factors for stroke (hypertension, hyperlipidemia, diabetes, obesity and physical inactivity) have been shown to play a role in the onset and progression of cognitive impairment,⁷ and it is well established that stroke itself increases the risk of future cognitive impairment.⁸ However, whether cognitive impairment increases the risk of future stroke remains unclear. Early identification and regular surveillance for cognitive impairment could potentially enable prompt initiation of treatment aimed at not only potentially limiting further deterioration of cognitive function (if mild), but also possibly reducing the risk of future stroke through timely and optimal control of risk factors.Several published studies have assessed the association between cognitive impairment and subsequent risk of stroke, but the results have not been consistent. We performed a systematic review and meta-analysis to determine the qualitative and quantitative association between baseline cognitive impairment and risk of future stroke.     

Hearing impairment: a panoply of genes and functions

Research in the genetics of hearing and deafness has evolved rapidly over the past years, providing the molecular foundation for different aspects of the mechanism of hearing. Considered to be the most common sensory disorder, hearing impairment is genetically heterogeneous. The multitude of genes affected encode proteins associated with many different functions, encompassing overarching areas of research. These include, but are not limited to, developmental biology, cell biology, physiology, and neurobiology. In this review, we discuss the broad categories of genes involved in hearing and deafness. Particular attention is paid to a subgroup of genes associated with inner ear gene regulation, fluid homeostasis, junctional complex and tight junctions, synaptic transmission, and auditory pathways. Overall, studies in genetics have provided research scientists and clinicians with insight regarding practical implications for the hearing impaired, while heralding hope for future development of therapeutics.     

Protective effect of mangiferin on memory impairment: A systematic review

Memory impairment (MI) is one of the predominant criteria generally used to identify schizophrenia, dementia and amnesia that are associated with neurodegenerative disorders by evaluating patient’s cognitive symptoms. To date, there is no available treatment that can completely mitigate MI. Currently, there is a trend in recent investigations towards symptomatic therapy approaches using a variety of natural compounds. Mangiferin is one of them that have been investigated extensively. Mangiferin is a naturally occurring potent glucoxilxanthone and is mainly isolated from the Mangifera indica (Mango) plant. This review is aimed at providing a comprehensive overview on the efficacy of mangiferin on MI, based on in-vivo animal studies. After screening through articles identified from Scopus and PubMed based on the inclusion and exclusion criteria, a total of 11 articles between 2009 and 2019 were included. The minimum and maximum dose of mangiferin were 10 and 200 mg/kg respectively and administered over the period of 12–154 days. The results of 11 articles showed that mangiferin effectively improved spatial recognition, episodic aversive events, short- and long-term memories primarily occurring via its antioxidant and anti-inflammatory effects. The outcomes of the review revealed that mangiferin improves memory and cognitive impairment in different animal models, indicating that it has potential preventive and therapeutic roles in MI.     

Metformin in polycystic ovary syndrome: systematic review and meta-analysis

Objective To assess the effectiveness of metformin in improving clinical and biochemical features of polycystic ovary syndrome.Design Systematic review and meta-analysis.Data sources Randomised controlled trials that investigated the effect of metformin compared with either placebo or no treatment, or compared with an ovulation induction agent.Selection of studies 13 trials were included for analysis, including 543 women with polycystic ovary syndrome that was defined by using biochemical or ultrasound evidence.Main outcome measure Pregnancy and ovulation rates. Secondary outcomes of clinical and biochemical features of polycystic ovary syndrome.Results Meta-analysis showed that metformin is effective in achieving ovulation in women with polycystic ovary syndrome, with odds ratios of 3.88 (95% confidence interval 2.25 to 6.69) for metformin compared with placebo and 4.41 (2.37 to 8.22) for metformin and clomifene compared with clomifene alone. An analysis of pregnancy rates shows a significant treatment effect for metformin and clomifene (odds ratio 4.40, 1.96 to 9.85). Metformin has an effect in reducing fasting insulin concentrations, blood pressure, and low density lipoprotein cholesterol. We found no evidence of any effect on body mass index or waist:hip ratio. Metformin was associated with a higher incidence of nausea, vomiting, and other gastrointestinal disturbance.Conclusions Metformin is an effective treatment for anovulation in women with polycystic ovary syndrome. Its choice as a first line agent seems justified, and there is some evidence of benefit on variables of the metabolic syndrome. No data are available regarding the safety of metformin in long term use in young women and only limited data on its safety in early pregnancy. It should be used as an adjuvant to general lifestyle improvements and not as a replacement for increased exercise and improved diet.     

Linkage analysis for prenatal diagnosis in a familial case of Stickler syndrome

The Stickler syndrome is among the most common heritable disorders of connective tissue. The syndrome fully expressed clinical phenotype includes the degeneration of the vitreous gel and retina, frequently associated with myopia, accompanied by non-ocular features, such as craniofacial dysmorphisms or malformations, hearing impairment, skeletal dysplasia and progressive arthropathy. So far, mutations at three collagen loci, COL2A1, COL11A1 and COL11A2, have been found in Stickler syndrome patients, with about two thirds of investigated familial cases found to be associated to COL2A1 gene mutations. We report on a three generation family in which a diagnosis of Stickler syndrome was made and linkage analysis suggested COL2A1 to be the causing gene. These data permitted us to perform two prenatal diagnosis analysing the 3'VNTR polymorphism of the involved gene on amniocytes' DNA and to provide the family with genetic counselling and paediatric support at the delivery.     

应用益生菌对代谢综合征患者干预效果的系统评价

目的系统评价应用益生菌对代谢综合征患者干预的效果。方法应用计算机检索Web of Science、PubMed、Cochrane Library、EMBASE、中国知网、维普、万方和CBM数据库中应用益生菌干预代谢综合征患者的随机对照试验,对纳入文献采用Cochrane Handbook(5.1.0)进行质量评价,采用RevMan 5.3软件进行Meta分析。结果共纳入9项研究。评价结果为口服益生菌可以降低代谢综合征患者腰围[MD=-2.39,95%CI(-4.58,-0.19),P=0.03]和低密度脂蛋白水平[SMD=-0.41,95%CI(-0.78,-0.04),P=0.03],在一定程度上改善胰岛素抵抗水平,但对空腹血糖水平[SMD=-0.03,95%CI(-0.31,0.24),P=0.83]没有影响。结论应用益生菌干预代谢综合征患者可产生减肥效果,同时在一定程度上改善代谢综合征患者糖代谢紊乱状态,调节脂质代谢水平。但未来仍需要本土化、大样本、高质量的研究进一步探索益生菌干预代谢综合征患者的效果及最有效方案。     

Prostacyclin in sepsis: a systematic review

According to current literature, infective processes greatly modify both vascular hemodynamics and anti-oxidant properties of affected tissues, causing a change in homeostasis that regulates the correct functioning of all cells responsible for the physiological and metabolic balance of various organs. As a consequence, the response to the infection that has caused the change is also likely to be weaker and, in the case of septic shock, ineffective. In this review, we will take into consideration these mechanisms and then focus on a group of vasodilator drugs (prostacyclin and its analogs) which, though have been used for over 20 years mainly to treat obstructive vascular diseases, have such hemodynamic and anti-inflammatory properties which prevent homeostatic changes. It is obvious that prostacyclin does not definitively have anti-infective characteristics; however, in association with anti-infective drugs (antibiotics, etc.), the effectiveness of the latter appears improved, at least in some circumstances. Similarly, the fact that prostacyclin and its analogs have a cytoprotective effect on the liver and reduce the ischemia-reperfusion damage following liver transplant is not a novelty and evidence that they improve hepatic hemodynamics suggests their use in those pathologies characterized by possible reduced perfusion or ascertained ischemia of the liver.     

Transdiagnostic psychiatry: a systematic review

The usefulness of current psychiatric classification, which is based on ICD/DSM categorical diagnoses, remains questionable. A promising alternative has been put forward as the “transdiagnostic” approach. This is expected to cut across existing categorical diagnoses and go beyond them, to improve the way we classify and treat mental disorders. This systematic review explores whether self‐defining transdiagnostic research meets such high expectations. A multi‐step Web of Science literature search was performed according to an a priori protocol, to identify all studies that used the word “transdiagnostic” in their title, up to May 5, 2018. Empirical variables which indexed core characteristics were extracted, complemented by a bibliometric and conceptual analysis. A total of 111 studies were included. Most studies were investigating interventions, followed by cognition and psychological processes, and neuroscientific topics. Their samples ranged from 15 to 91,199 (median 148) participants, with a mean age from 10 to more than 60 (median 33) years. There were several methodological inconsistencies relating to the definition of the gold standard (DSM/ICD diagnoses), of the outcome measures and of the transdiagnostic approach. The quality of the studies was generally low and only a few findings were externally replicated. The majority of studies tested transdiagnostic features cutting across different diagnoses, and only a few tested new classification systems beyond the existing diagnoses. About one fifth of the studies were not transdiagnostic at all, because they investigated symptoms and not disorders, a single disorder, or because there was no diagnostic information. The bibliometric analysis revealed that transdiagnostic research largely restricted its focus to anxiety and depressive disorders. The conceptual analysis showed that transdiagnostic research is grounded more on rediscoveries than on true innovations, and that it is affected by some conceptual biases. To date, transdiagnostic approaches have not delivered a credible paradigm shift that can impact classification and clinical care. Practical “TRANSD”iagnostic recommendations are proposed here to guide future research in this field.     

Whispered voice test for screening for hearing impairment in adults and children: systematic review

Objective To determine the accuracy of the whispered voice test in detecting hearing impairment in adults and children.Design Systematic review of studies of test accuracy.Data sources Medline, Embase, Science Citation Index, unpublished theses, manual searching of bibliographies of known primary and review articles, and contact with authors.Study selection Two reviewers independently selected and extracted data on study characteristics, quality, and accuracy of studies. Studies were included if they had cross sectional designs, at least one of the index tests was the whispered voice test, and the reference test (audiometry) was performed on at least 80% of the participants.Data extraction Data were used to form 2×2 contingency tables with hearing impairment by audiometry as the reference standard.Data synthesis The eight studies that were found used six different techniques. The sensitivity in the four adult studies was 90% or 100% and the specificity was 70% to 87%. The sensitivity in the four childhood studies ranged from 80% to 96% and specificity ranged from 90% to 98%.Conclusion The whispered voice test is a simple and accurate test for detecting hearing impairment. There is some concern regarding the lower sensitivity in children and the overall reproducibility of the test, particularly in primary care settings. Further studies should be conducted in primary care settings to explore the influence of components of the testing procedure to optimise test sensitivity and to promote standardisation of the testing procedure.     

Tuberculosis incidence in prisons: a systematic review

Background

Transmission of tuberculosis (TB) in prisons has been reported worldwide to be much higher than that reported for the corresponding general population.

Methods and Findings

A systematic review has been performed to assess the risk of incident latent tuberculosis infection (LTBI) and TB disease in prisons, as compared to the incidence in the corresponding local general population, and to estimate the fraction of TB in the general population attributable (PAF%) to transmission within prisons. Primary peer-reviewed studies have been searched to assess the incidence of LTBI and/or TB within prisons published until June 2010; both inmates and prison staff were considered. Studies, which were independently screened by two reviewers, were eligible for inclusion if they reported the incidence of LTBI and TB disease in prisons. Available data were collected from 23 studies out of 582 potentially relevant unique citations. Five studies from the US and one from Brazil were available to assess the incidence of LTBI in prisons, while 19 studies were available to assess the incidence of TB. The median estimated annual incidence rate ratio (IRR) for LTBI and TB were 26.4 (interquartile range [IQR]: 13.0–61.8) and 23.0 (IQR: 11.7–36.1), respectively. The median estimated fraction (PAF%) of tuberculosis in the general population attributable to the exposure in prisons for TB was 8.5% (IQR: 1.9%–17.9%) and 6.3% (IQR: 2.7%–17.2%) in high- and middle/low-income countries, respectively.

Conclusions

The very high IRR and the substantial population attributable fraction show that much better TB control in prisons could potentially protect prisoners and staff from within-prison spread of TB and would significantly reduce the national burden of TB. Future studies should measure the impact of the conditions in prisons on TB transmission and assess the population attributable risk of prison-to-community spread. Please see later in the article for the Editors'' Summary     

The conservative treatment of longstanding adductor-related groin pain syndrome: a critical and systematic review

Longstanding (chronic) adductor-related groin pain syndrome is a widely common problem for athletes in many sports activities which often drastically reduces player activity and performance. The first choice in therapeutic treatment is conservative therapy. The objective of this study is to provide a systematic review regarding conservative treatment for longstanding adductor-related groin pain syndrome present in literature today. Furthermore, this study aims to give a critical vision of the current state of the art of the considered topic. After screening 234 articles, 19 studies following the inclusion criteria were included and summarized in this current systematic review and seven different types of therapeutic interventions were described. Compression clothing therapy, manual therapy together with strengthening exercise and prolotherapy were the therapeutic interventions which showed both the greatest level of strength of evidence (Moderate) and grade of recommendation (D). The remaining four types of therapeutic interventions i.e.: corticoid injection, platelet rich plasma therapy, intra-tissue percutaneous electrolysis and pulse-dose radiofrequency, showed both lower levels of strength of evidence (Conflicting) and grade of recommendation (C). In conclusion the literature available on the conservative treatment for longstanding adductor-related groin pain syndrome is limited and characterized by a low level of evidence. Therefore, our recommendation is to refer only to the few studies with higher level of evidence and at the same time to encourage further research in this area. The intervention showing the greater level of strength of evidence, and the greater grade of recommendation are compression clothing therapy, manual therapy and strengthening exercise, and prolotherapy. Other therapeutic interventions such as intra-tissue percutaneous electrolysis and pulse-dose radiofrequency seem promising but require further studies to confirm their efficacy.     

Efficacy of progesterone and progestogens in management of premenstrual syndrome: systematic review

ObjectiveTo evaluate the efficacy of progesterone and progestogens in the management of premenstrual syndrome.DesignSystematic review of published randomised, placebo controlled trials.ResultsOverall standardised mean difference for all trials that assessed efficacy of progesterone (by both routes of administration) was −0.028 (95% confidence interval −0.017 to −0.040). The odds ratio was 1.05 (1.03 to 1.08) in favour of progesterone, indicating no clinically important difference between progesterone and placebo. For progestogens the overall standardised mean was −0.036 (−0.014 to −0.060), which corresponds to an odds ratio of 1.07 (1.03 to 1.11) showing a statistically, but not clinically, significant improvement for women taking progestogens.ConclusionThe evidence from these meta-analyses does not support the use of progesterone or progestogens in the management of premenstrual syndrome.

What is already known on this topic

The premenstrual syndrome affects about 1.5 million women in the United KingdomThere are numerous treatment options, progesterone being one of the most strongly advocatedProgesterone and progestogens are among the most widely prescribed treatments for premenstrual syndrome in the United Kingdom and the United States

What this study adds

There is no evidence to support the claimed efficacy of progesterone in the management of premenstrual syndromeThere is insufficient evidence to make a definitive statement about progestogens, but current evidence suggests that they are not likely to be effective     

Alport syndrome: a review

Alport syndrome, a hereditary nephritis accompanied by high-tone sensorineural deafness and distinctive ocular signs was first noted in the literature during the early 1900s. This disease is caused by a genetic defect in Type IV collagen which makes up basement membranes in many body systems. The patient will usually have bilateral anterior lenticonus causing varied refractive errors. You may also note yellow-white to silver flecks within the macular and midperipheral regions of the retina. The treatment of the visual problems is an important but secondary concern due to the seriousness of the systemic disease. Dual sensory loss, however, creates an urgent need for appropriate vision care. Due to the high risk for developmental delay and decreased social integration, early intervention should be considered in the treatment plan. Coping strategies for the patient (and the family) need to be addressed because of the chronicity of this syndrome. The primary care optometrist will be challenged by the individual with Alport syndrome since a balance between oculo-visual, developmental/psycho-educational and systemic care is required. A multi-disciplinary approach by the healthcare management team will enhance the quality of life and positive outcomes for these patients.     

Machine learning application in soccer: a systematic review

Due to the chaotic nature of soccer, the predictive statistical models have become in a current challenge to decision-making based on scientific evidence. The aim of the present study was to systematically identify original studies that applied machine learning (ML) to soccer data, highlighting current possibilities in ML and future applications. A systematic review of PubMed, SPORTDiscus, and FECYT (Web of Sciences, CCC, DIIDW, KJD, MEDLINE, RSCI, and SCIELO) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. From the 145 studies initially identified, 32 were fully reviewed, and their outcome measures were extracted and analyzed. In summary, all articles were clustered into three groups: injury (n = 7); performance (n = 21), which was classified in match/league outcomes forecasting, physical/physiological forecasting, and technical/tactical forecasting; and the last group was about talent forecasting (n = 5). The development of technology, and subsequently the large amount of data available, has become ML in an important strategy to help team staff members in decision-making predicting dose-response relationship reducing the chaotic nature of this team sport. However, since ML models depend upon the amount of dataset, further studies should analyze the amount of data input needed make to a relevant predictive attempt which makes accurate predicting available.     

Oxidative stress involvement in psoriasis: a systematic review

Psoriasis is a skin chronic inflammatory disease with a complex aetiology. It is characterised by the imbalance of environmental, genetic, and immunologic factors. Reactive oxygen species (ROS) could damage the cell components. The antioxidant system defends the body against ROS; a malfunction of the antioxidant system, together with an increased production of ROS, is involved in the pathogenesis of several diseases such as psoriasis. The purpose of this systematic review is to give an updated scenario about oxidative stress involvement in the psoriatic disease to identify useful biomarkers and to propose innovative therapies. A total of 28 studies were identified. Although several molecules were demonstrated being associated with psoriasis, only a little group resulted being eligible as disease biomarker [malonyldialdehyde (MDA), total oxidative stress, and oxidative stress index]. However, only MDA seems to be the best candidate for a clinical screening of psoriasis patients since it is intimately linked to Psoriasis Area Severity Index. Data suggest that current therapies with drugs, a healthy lifestyle, and the integration of a diet rich in antioxidants help to reduce the damage of oxidative stress caused by psoriasis, especially at the level of the skin. As much as we know, this is the first systematic review evaluating the oxidative stress role in psoriasis.