Clinical effectiveness and safety of analogue glargine in type 1 diabetes : systematic review and meta-analysis

INTRODUCTION: The use of insulin analogues for the treatment of type 1 diabetes mellitus (T1DM) is widespread; however, the therapeutic benefits still require further evaluation given their higher costs. Objective: To evaluate the effectiveness and safety of Analogue Glargine (AG) compared to Recombinant DNA insulin (rDNA) in patients with DM1 in observational studies, building on previous reviews of RCTs comparing NPH insulin and AG. METHODS: A systematic review (SR) with meta-analysis. The SR included cohort studies and registries available on PUBMED, LILACS, and CENTRAL as well as manual and gray literature searches. The meta-analysis was conducted in Review Manager ® 5.2 software. The primary outcomes were: glycohemoglobin (Hb1Ac), weight gain and hypoglycemia. Methodological quality was assessed using the Newcastle-Ottawa scale. RESULTS: Out of 796 publications, 11 studies were finally included. The meta-analysis favored AG in Hb1Ac outcomes (adult patients) and hypoglycemic episodes (p <0.05), but without reaching glycemic control (Hb1Ac to approximately 7%). The methodological quality of the studies was moderate, noting that 45% of studies were funded by pharmaceutical companies. CONCLUSION: Given the high heterogeneity of the studies, the discrete value presented by the estimated effect on effectiveness and safety, potential conflicts of interest of the studies and the appreciable higher cost of AG, there is still no support for recommending first line therapy with analogues. The role of analogues in the treatment DM1 could be better determined by further observational studies of good methodological quality to assess their long-term effectiveness, safety as well as cost-effectiveness

Quality of Life of Patients with Type 1 Diabetes Mellitus Using Insulin Analog Glargine Compared with NPH Insulin: A Systematic Review and Policy Implications

INTRODUCTION: Insulin analogue glargine (GLA) has been available as one of the therapeutic options for patients with type 1 diabetes mellitus to enhance glycemic control. Studies have shown that a decrease in the frequency of hypoglycemia episodes improves the Quality of Life (QoL) of diabetic patients. However, there are appreciable acquisition cost differences between different insulins. Consequently, a need to assess their impact on QoL to provide future guidance to health authorities. METHOD: A Systematic review (SR) of multiple databases including Medline, LILACS, Cochrane and EMBASE databases with several combinations of agreed terms involving randomized controlled trials (RCTs) and cohorts, as well as manual searches and gray literature was undertaken. The primary outcome measure was a change in QoL. The quality of the studies and the risk of bias was also assessed. RESULTS: Eight studies were eventually included in the systematic review out of 634 publications. Eight different QoL instruments were used (2 generic, 2 mixed and 4 specific), in which the Diabetes Treatment Satisfaction Questionnaire (DTSQs) was the most used. The systematic review did not consistently show any significant difference overall in QoL scores whether as part of subsets or combined into a single score with the use of GLA versus NPH insulin. Only in patients’ satisfaction measured by DTSQ was a better result consistently seen with GLA versus NPH insulin but not using the WED scale. However, none of the cohort studies scored a maximum on the Newcastle-Ottawa scale for quality and they generally were of moderate quality with bias in the studies. CONCLUSION: There was no consistent difference in QoL or patient reported outcomes when the findings from the eight studies were collated. In view of this, we believe the current price differential between GLA and NPH insulin in Brazil cannot be justified by these findings

Early intervention for obsessive compulsive disorder : An expert consensus statement

© 2019 Elsevier B.V.and ECNP. All rights reserved.Obsessive-compulsive disorder (OCD) is common, emerges early in life and tends to run a chronic, impairing course. Despite the availability of effective treatments, the duration of untreated illness (DUI) is high (up to around 10 years in adults) and is associated with considerable suffering for the individual and their families. This consensus statement represents the views of an international group of expert clinicians, including child and adult psychiatrists, psychologists and neuroscientists, working both in high and low and middle income countries, as well as those with the experience of living with OCD. The statement draws together evidence from epidemiological, clinical, health economic and brain imaging studies documenting the negative impact associated with treatment delay on clinical outcomes, and supporting the importance of early clinical intervention. It draws parallels between OCD and other disorders for which early intervention is recognized as beneficial, such as psychotic disorders and impulsive-compulsive disorders associated with problematic usage of the Internet, for which early intervention may prevent the development of later addictive disorders. It also generates new heuristics for exploring the brain-based mechanisms moderating the ‘toxic’ effect of an extended DUI in OCD. The statement concludes that there is a global unmet need for early intervention services for OC related disorders to reduce the unnecessary suffering and costly disability associated with under-treatment. New clinical staging models for OCD that may be used to facilitate primary, secondary and tertiary prevention within this context are proposed.Peer reviewe

Avaliação da presença de Suberina em Minicenoura, durante a conservação refrigerada

Suberina é um polímero de natureza lipídica presente em paredes celulares da periderme de cenoura. Uma de suas principais funções é manter elevada resistência à difusão de vapor de água. Na confecção de minicenouras, o torneamento remove a periderme natural, facilitando a desidratação e esbranquecimento. Objetivou-se avaliar histoquimicamente a formação de periderme em minicenoura com revestimento comestível à base de amido e quitosana. Cenouras cv. Esplanada colhidas aos 90 dias, processadas na forma de minicenouras, foram imersas em suspensão contendo 3% de amido de milho, 1,5% de quitosana, 2% de glicerol e 0,4% de ácido acético glacial. Foram mantidas sob ventilação por três horas, embaladas em bandejas de polipropileno envoltas com filme de polivinilcloreto e mantidas a 5±1ºC. Aos 0; 10; 25 e 30 dias, amostras foram desidratadas, incluídas em historresina, cortadas em micrótomo manual, coradas com sudan vermelho, montadas em lâminas e fotografadas. Minicenouras que não foram imersas em suspensão e cenouras com periderme, serviram como controle. Nas minicenouras sem revestimento, foi nítido o esbranquecimento na superficie a partir do terceiro dia de conservação. Todavia, pouca diferença foi observada na perda de massa fresca entre minicenouras revestidas e o controle. Nas avaliações microscópicas, observou-se acúmulo de paredes celulares oriundas de células colapsadas e desidratadas na superfície de minicenoura com ou sem revestimento. Em minicenoura tratadas, foi observado, aos 30 dias, uma leve coloração avermelhada característica de reação positiva com sudan. Todavía, isso parece estar relacionado com componentes do revestimento, uma vez que não se observou reação positiva na região das paredes celulares, onde é característico a presença de suberina, como foi evidenciada em cenouras intactas, com periderme. Portanto, não houve evidências para formação de suberina em minicenouras, com ou sem recobrimento, durante o período de conservação estudado Apoio financeiro: CAPES, CNPq e FAPEMIG

The clinical effectiveness of insulin glargine in patients with Type I diabetes in Brazil: findings and implications

Aims: Published studies have challenged the cost-effectiveness of insulin glargine versus NPH insulins in Brazil with limited evidence of increased effectiveness despite considerably higher acquisition costs. However, still a controversy. Consequently, a need to address this. Methods: Retrospective cohort study of type 1 diabetes patients receiving insulin glargine in Brazil following NPH insulin who met the criteria. Results: 580 patients were enrolled. HbA1c varied from 8.80 ± 1.98% in NPH insulin users to 8.54 ± 1.88% after insulin glargine for six months, which is not clinically significant. Frequency of glycemic control varied from 22.6% with NPH insulin to 26.2% with insulin glargine. No statistically significant difference was observed between controlled and still uncontrolled groups for all analyzed factors including type and frequency of insulin use and carbohydrate counting. Conclusions: Limited differences between NPH insulins and insulin analogues in routine clinical care does not justify an appreciable cost difference

Chloroplast genome assembly of Serjania erecta Raldk: comparative analysis reveals gene number variation and selection in protein-coding plastid genes of Sapindaceae

Serjania erecta Raldk is an essential genetic resource due to its anti-inflammatory, gastric protection, and anti-Alzheimer properties. However, the genetic and evolutionary aspects of the species remain poorly known. Here, we sequenced and assembled the complete chloroplast genome of S. erecta and used it in a comparative analysis within the Sapindaceae family. S. erecta has a chloroplast genome (cpDNA) of 159,297 bp, divided into a Large Single Copy region (LSC) of 84,556 bp and a Small Single Copy region (SSC) of 18,057 bp that are surrounded by two Inverted Repeat regions (IRa and IRb) of 28,342 bp. Among the 12 species used in the comparative analysis, S. erecta has the fewest long and microsatellite repeats. The genome structure of Sapindaceae species is relatively conserved; the number of genes varies from 128 to 132 genes, and this variation is associated with three main factors: (1) Expansion and retraction events in the size of the IRs, resulting in variations in the number of rpl22, rps19, and rps3 genes; (2) Pseudogenization of the rps2 gene; and (3) Loss or duplication of genes encoding tRNAs, associated with the duplication of trnH-GUG in X. sorbifolium and the absence of trnT-CGU in the Dodonaeoideae subfamily. We identified 10 and 11 mutational hotspots for Sapindaceae and Sapindoideae, respectively, and identified six highly diverse regions (tRNA-Lys — rps16, ndhC – tRNA-Val, petA – psbJ, ndhF, rpl32 – ccsA, and ycf1) are found in both groups, which show potential for the development of DNA barcode markers for molecular taxonomic identification of Serjania. We identified that the psaI gene evolves under neutrality in Sapindaceae, while all other chloroplast genes are under strong negative selection. However, local positive selection exists in the ndhF, rpoC2, ycf1, and ycf2 genes. The genes ndhF and ycf1 also present high nucleotide diversity and local positive selection, demonstrating significant potential as markers. Our findings include providing the first chloroplast genome of a member of the Paullinieae tribe. Furthermore, we identified patterns in variations in the number of genes and selection in genes possibly associated with the family’s evolutionary history

Detecting Network Communities: An Application to Phylogenetic Analysis

This paper proposes a new method to identify communities in generally weighted complex networks and apply it to phylogenetic analysis. In this case, weights correspond to the similarity indexes among protein sequences, which can be used for network construction so that the network structure can be analyzed to recover phylogenetically useful information from its properties. The analyses discussed here are mainly based on the modular character of protein similarity networks, explored through the Newman-Girvan algorithm, with the help of the neighborhood matrix . The most relevant networks are found when the network topology changes abruptly revealing distinct modules related to the sets of organisms to which the proteins belong. Sound biological information can be retrieved by the computational routines used in the network approach, without using biological assumptions other than those incorporated by BLAST. Usually, all the main bacterial phyla and, in some cases, also some bacterial classes corresponded totally (100%) or to a great extent (>70%) to the modules. We checked for internal consistency in the obtained results, and we scored close to 84% of matches for community pertinence when comparisons between the results were performed. To illustrate how to use the network-based method, we employed data for enzymes involved in the chitin metabolic pathway that are present in more than 100 organisms from an original data set containing 1,695 organisms, downloaded from GenBank on May 19, 2007. A preliminary comparison between the outcomes of the network-based method and the results of methods based on Bayesian, distance, likelihood, and parsimony criteria suggests that the former is as reliable as these commonly used methods. We conclude that the network-based method can be used as a powerful tool for retrieving modularity information from weighted networks, which is useful for phylogenetic analysis

Progress toward standardized diagnosis of vascular cognitive impairment: Guidelines from the Vascular Impairment of Cognition Classification Consensus Study

INTRODUCTION: Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. METHODS: We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. RESULTS: Six survey rounds comprising 65-79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders-Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. DISCUSSION: The VICCCS-2 suggests standardized use of the National Institute of Neurological Disorders-Canadian Stroke Network recommendations on neuropsychological and imaging assessment for diagnosis of VCI so as to promote research collaboration