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

The Effect of Anandamide on Uterine Nitric Oxide Synthase Activity Depends on the Presence of the Blastocyst

Nitric oxide production, catalyzed by nitric oxide synthase (NOS), should be strictly regulated to allow embryo implantation. Thus, our first aim was to study NOS activity during peri-implantation in the rat uterus. Day 6 inter-implantation sites showed lower NOS activity (0.19±0.01 pmoles L-citrulline mg prot−1 h−1) compared to days 4 (0.34±0.03) and 5 (0.35±0.02) of pregnancy and to day 6 implantation sites (0.33±0.01). This regulation was not observed in pseudopregnancy. Both dormant and active blastocysts maintained NOS activity at similar levels. Anandamide (AEA), an endocannabinoid, binds to cannabinoid receptors type 1 (CB1) and type 2 (CB2), and high concentrations are toxic for implantation and embryo development. Previously, we observed that AEA synthesis presents an inverted pattern compared to NOS activity described here. We adopted a pharmacological approach using AEA, URB-597 (a selective inhibitor of fatty acid amide hydrolase, the enzyme that degrades AEA) and receptor selective antagonists to investigate the effect of AEA on uterine NOS activity in vitro in rat models of implantation. While AEA (0.70±0.02 vs 0.40±0.04) and URB-597 (1.08±0.09 vs 0.83±0.06) inhibited NOS activity in the absence of a blastocyst (pseudopregnancy) through CB2 receptors, AEA did not modulate NOS on day 5 pregnant uterus. Once implantation begins, URB-597 decreased NOS activity on day 6 implantation sites via CB1 receptors (0.25±0.04 vs 0.40±0.05). While a CB1 antagonist augmented NOS activity on day 6 inter-implantation sites (0.17±0.02 vs 0.27±0.02), a CB2 antagonist decreased it (0.17±0.02 vs 0.12±0.01). Finally, we described the expression and localization of cannabinoid receptors during implantation. In conclusion, AEA levels close to and at implantation sites seems to modulate NOS activity and thus nitric oxide production, fundamental for implantation, via cannabinoid receptors. This modulation depends on the presence of the blastocyst. These data establish cannabinoid receptors as an interesting target for the treatment of implantation deficiencies

Low prevalence of H. pylori Infection in HIV-Positive Patients in the Northeast of Brazil

<p>Abstract</p> <p>Background</p> <p>This study conducted in Northeastern Brazil, evaluated the prevalence of <it>H. pylori </it>infection and the presence of gastritis in HIV-infected patients.</p> <p>Methods</p> <p>There were included 113 HIV-positive and 141 age-matched HIV-negative patients, who underwent upper gastrointestinal endoscopy for dyspeptic symptoms. <it>H. pylori </it>status was evaluated by urease test and histology.</p> <p>Results</p> <p>The prevalence of <it>H. pylori </it>infection was significantly lower (p < 0.001) in HIV-infected (37.2%) than in uninfected (75.2%) patients. There were no significant differences between <it>H. pylori </it>status and gender, age, HIV viral load, antiretroviral therapy and the use of antibiotics. A lower prevalence of <it>H. pylori </it>was observed among patients with T CD4 cell count below 200/mm³; however, it was not significant. Chronic active antral gastritis was observed in 87.6% of the HIV-infected patients and in 780.4% of the control group (p = 0.11). <it>H. pylori </it>infection was significantly associated with chronic active gastritis in the antrum in both groups, but it was not associated with corpus chronic active gastritis in the HIV-infected patients.</p> <p>Conclusion</p> <p>We demonstrated that the prevalence of <it>H. pylori </it>was significantly lower in HIV-positive patients compared with HIV-negative ones. However, corpus gastritis was frequently observed in the HIV-positive patients, pointing to different mechanisms than <it>H. pylori </it>infection in the genesis of the lesion.</p

Decreased production of TNF-alpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats

Experimental autoimmune encephalomyelitis (EAE) is mediated by CD4+ Th1 cells that mainly secrete IFN-&#947; and TNF-&#945;, important cytokines in the pathophysiology of the disease. Spontaneous remission is, in part, attributed to the down regulation of IFN-&#947; and TNF-&#945; by TGF-&#946;. In the current paper, we compared weight, histopathology and immunological parameters during the acute and recovery phases of EAE to establish the best biomarker for clinical remission. Female Lewis rats were immunised with myelin basic protein (MBP) emulsified with complete Freund's adjuvant. Animals were evaluated daily for clinical score and weight prior to euthanisation. All immunised animals developed the expected characteristics of EAE during the acute phase, including significant weight loss and high clinical scores. Disease remission was associated with a significant reduction in clinical scores, although immunised rats did not regain their initial weight values. Brain inflammatory infiltrates were higher during the acute phase. During the remission phase, anti-myelin antibody levels increased, whereas TNF-&#945; and IFN-&#947; production by lymph node cells cultured with MBP or concanavalin A, respectively, decreased. The most significant difference observed between the acute and recovery phases was in the induction of TNF-&#945; levels in MBP-stimulated cultures. Therefore, the in vitro production of this cytokine could be used as a biomarker for EAE remission

Ancestry of the Brazilian TP53 c.1010G>A (p.Arg337His, R337H) founder mutation : clues from haplotyping of short tandem repeats on Chromosome 17p

Rare germline mutations in TP53 (17p13.1) cause a highly penetrant predisposition to a specific spectrum of early cancers, defining the Li-Fraumeni Syndrome (LFS). A germline mutation at codon 337 (p.Arg337His, c1010G>A) is found in about 0.3% of the population of Southern Brazil. This mutation is associated with partially penetrant LFS traits and is found in the germline of patients with early cancers of the LFS spectrum unselected for familial his- tory. To characterize the extended haplotypes carrying the mutation, we have genotyped 9 short tandem repeats on chromosome 17p in 12 trios of Brazilian p.Arg337His carriers. Results confirm that all share a common ancestor haplotype of Caucasian/Portuguese-Ibe- ric origin, distant in about 72–84 generations (2000 years assuming a 25 years intergenera- tional distance) and thus pre-dating European migration to Brazil. So far, the founder p. Arg337His haplotype has not been detected outside Brazil, with the exception of two resi- dents of Portugal, one of them of Brazilian origin. On the other hand, increased meiotic recombination in p.Arg337His carriers may account for higher than expected haplotype diversity. Further studies comparing haplotypes in populations of Brazil and of other areas of Portuguese migration are needed to understand the historical context of this mutation in Brazil.This study was funded by grant # 478430/2012-4 from CNPq (RFA MCT/CNPq - No 14/2012; Universal), Brazil.We would like to thank UFRGS, UFPA, AC Camargo, HC Barretos and University of Minho for their support during this work

Understanding the barriers to successful adoption and use of a mobile health information system in a community health center in São Paulo, Brazil: a cohort study

BACKGROUND: Mobile technology to support community health has surged in popularity, yet few studies have systematically examined usability of mobile platforms for this setting. METHODS: We conducted a mixed-methods study of 14 community healthcare workers at a public healthcare clinic in São Paulo, Brazil. We held focus groups with community healthcare workers to elicit their ideas about a mobile health application and used this input to build a prototype app. A pre-use test survey was administered to all participants, who subsequently use-tested the app on three different devices (iPhone, iPad mini, iPad Air). Usability was assessed by objectively scored data entry errors and through a post-use focus group held to gather open-ended feedback on end-user satisfaction. RESULTS: All of the participants were women, ranging from 18–64 years old. A large percentage (85.7%) of participants had at least a high school education. Internet (92.8%), computer (85.7%) and cell phone (71.4%) use rates were high. Data entry error rates were also high, particularly in free text fields, ranging from 92.3 to 100%. Error rates were comparable across device type. In a post-use focus group, participants reported that they found the app easy to use and felt that its design was consistent with their vision. The participants raised several concerns, including that they did not find filling out the forms in the app to be a useful task. They also were concerned about an app potentially creating more work for them and personal security issues related to carrying a mobile device in low-income areas. CONCLUSION: In a cohort of formally educated community healthcare workers with high levels of personal computer and cell phone use, we identified no technological barriers to adapting their existing work to a mobile device based system. Transferring current data entry work into a mobile platform, however, uncovered underlying dissatisfaction with some data entry tasks. This dissatisfaction may be a more significant barrier than the data entry errors our testing revealed. Our results highlight the fact that without a deep understanding of local process to optimize usability, technology-based solutions in health may fail. Developing such an understanding must be a central component in the design of any mHealth solution in global health