Multimorbidity and Evidence Generation

Most people with a chronic disease actually have more than one, a condition known as multimorbidity. Despite this, the evidence base to prevent adverse disease outcomes has taken a disease-specific approach. Drawing on a conference, Improving Guidelines for Multimorbid Patients, the goal of this paper is to identify challenges to the generation of evidence to support the care of people with multimorbidity and to make recommendations for improvement. We identified three broad categories of challenges: 1) challenges to defining and measuring multimorbidity; 2) challenges related to the effects of multimorbidity on study design, implementation and analysis; and 3) challenges inherent in studying heterogeneity of treatment effects in patients with differing comorbid conditions. We propose a set of recommendations for consideration by investigators and others (reviewers, editors, funding agencies, policymaking organizations) involved in the creation of evidence for this common type of person that address each of these challenges. The recommendations reflect a general approach that emphasizes broader inclusion (recruitment and retention) of patients with multimorbidity, coupled with more rigorous efforts to measure comorbidity and comorbidity burden and the influence of multimorbidity on outcomes and the effects of therapy. More rigorous examination of heterogeneity of treatment effects requires careful attention to prioritizing the most important comorbid-related questions, and also requires studies that provide greater statistical power than conventional trials have provided. Relatively modest changes in the orientation of current research along these lines can be helpful in pointing to and partially addressing selected knowledge gaps. However, producing a robust evidence base to support patient-centered decision making in complex individuals with multimorbidity, exposed to many different combinations of potentially interacting factors that can modify the risks and benefits of therapies, is likely to require a clinical research enterprise fundamentally restructured to be more fully integrated with routine clinical practice.     

Synthesis and Anticholinesterase Activity Evaluation of Asymmetric Azines

Pharmaceutical Chemistry Journal - Azines or di-imines are compounds containing R1R2C=N-N=CR3R4 fragment in its structure. These compounds have received special attention due to their importance as...     

Detection of the gubernacular canal and its attachment to the dental follicle may indicate an abnormal eruption status

Objectives:To evaluate and compare the detection of gubernacular canals (GC) and their characteristics in normal and abnormal tooth eruption.Materials and Methods:Patients with unerupted teeth were classified according to sex and age. Each tooth was classified according to dental group, eruption status, formation status, angulation, and GC detection. The opening of the GC in the alveolar crest and the attachment sites in relation to the dental follicle were assessed. Data were analyzed by the chi-square and Kruskal-Wallis tests, with a significance level of 5%.Results:Cone-beam computed tomography scans of 159 patients were evaluated. The final sample (N = 598) consisted of 423 teeth with normal eruption, 140 impacted teeth, and 35 teeth with delayed eruption. The overall detection rate of GC was 90.6%. These rates were 94.1%, 87.1%, and 62.9% for normal eruption, impacted teeth, and delayed eruption, respectively. GC detection rates were higher in the early stages of tooth formation in normal tooth eruption and in impacted teeth. The rate of GC detection was even lower in delayed teeth when they were angulated. Unusual attachment sites of the GC to the dental follicle were associated with abnormal eruption status.Conclusions:The results of the present study suggest that GC characteristics may indicate an abnormal eruption status.     

Timing of clamping and factors associated with iron stores in full-term newborns

OBJECTIVE

To analyze the impact of timing of clamping and obstetric, biological and socioeconomic factors on the iron stores of full-term newborns.

METHODS

Cross-sectional study between October 2011 and July 2012 in which hematological parameters were evaluated for newborns in Viçosa, MG, Southeastern Brazil. It involved collecting 7 mL of umbilical cord blood from 144 full-term not underweight newborns. The parameters investigated were complete blood count, serum iron, ferritin and C-reactive protein. The time of umbilical cord clamping was measured using a digital timer without interfering in the procedures of childbirth. The birth data were collected from Live Birth Certificates and other information was obtained from the mother through a questionnaire applied in the first month postpartum. Analysis of multiple linear regression was then used to estimate the influence of biological, obstetrics and socioeconomic factors on the ferritin levels at birth.

RESULTS

The median ferritin was 130.3 µg/L (n = 129, minimum = 16.4; maximum = 420.5 µg/L), the mean serum iron was 137.9 μg/dL (n = 144, SD = 39.29) and mean hemoglobin was 14.7 g/dL (n = 144, SD = 1.47). The median time of cord clamping was 36 seconds, ranging between 7 and 100. The bivariate analysis detected an association between ferritin levels and color of the child, timing clamping of 60 seconds, type of delivery, the presence of gestational diabetes and per capita family income. In multivariate analysis, the variables per capita income, number of antenatal visits and length at birth accounted for 22.0% of variation in ferritin levels.

CONCLUSIONS

Iron stores at birth were influenced by biological, obstetric and social characteristics. Tackling anemia should involve creating policies aimed at reducing social inequalities, improving the quality of antenatal care, as well as implementing a criterion of delayed clamping of the umbilical cord within the guidelines of labor.     

The exposure of the nursing profession in online and print media

Objective

to describe the coverage of news concerning the nursing profession in the Portuguese media: informative sites on the Internet and in print media.

Method

a total of 1,271 health news items were collected in September and October of 2011 (956 online news items and 325 news items originating from the press review of the Portuguese Order of Nurses). Statistical analysis was used to characterize the variables.

Results

nurses were the sources of information in 6.6% of cases, suggesting limited media exposure. The health news collected is characterized by a production based on limited information sources, that is, male and official sources, on information disseminated by news agencies focused on economic and political issues in the health field.

Conclusion

the presence of nurses in the news concerning nursing health is reduced. We suggest that nurses develop public communication skills to disseminate the importance of their profession in society and their relationship with the media.     

Multidrug-Resistant Nontuberculous Mycobacteria Isolated from Cystic Fibrosis Patients

Worldwide, nontuberculous mycobacteria (NTM) have become emergent pathogens of pulmonary infections in cystic fibrosis (CF) patients, with an estimated prevalence ranging from 5 to 20%. This work investigated the presence of NTM in sputum samples of 129 CF patients (2 to 18 years old) submitted to longitudinal clinical supervision at a regional reference center in Rio de Janeiro, Brazil. From June 2009 to March 2012, 36 NTM isolates recovered from 10 (7.75%) out of 129 children were obtained. Molecular identification of NTM was performed by using PCR restriction analysis targeting the hsp65 gene (PRA-hsp65) and sequencing of the rpoB gene, and susceptibility tests were performed that followed Clinical and Laboratory Standards Institute recommendations. For evaluating the genotypic diversity, pulsed-field gel electrophoresis (PFGE) and/or enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR) was performed. The species identified were Mycobacterium abscessus subsp. bolletii (n = 24), M. abscessus subsp. abscessus (n = 6), Mycobacterium fortuitum (n = 3), Mycobacterium marseillense (n = 2), and Mycobacterium timonense (n = 1). Most of the isolates presented resistance to five or more of the antimicrobials tested. Typing profiles were mainly patient specific. The PFGE profiles indicated the presence of two clonal groups for M. abscessus subsp. abscessus and five clonal groups for M. abscesssus subsp. bolletii, with just one clone detected in two patients. Given the observed multidrug resistance patterns and the possibility of transmission between patients, we suggest the implementation of continuous and routine investigation of NTM infection or colonization in CF patients, including countries with a high burden of tuberculosis disease.     

The use of NaOCl in combination with CHX produces cytotoxic product

Objectives

The combination of sodium hypochlorite (NaOCl) and chlorhexidine (CHX) yields a “precipitate potentially toxic” (PPT). The aim of this study was to evaluate the tissue response to implanted polyethylene tubes filled with PPT-soaked fibrin sponge.

Methods

Forty rats received four polyethylene tubes each; each tube was filled with fibrin sponge soaked by 2.5 % NaOCl, 2.0 % CHX, PPT (2.5 % NaOCl plus 2.0 % CHX), or not soaked (control). The observation time points were 7, 15, 30, 60, and 90 days. At each time point, eight animals were killed, and the tubes and surrounding tissues were removed, fixed, and prepared for light microscopic analysis by performing glycol methacrylate embedding, serial cutting into 3-μm sections, and hematoxylin–eosin staining. Qualitative and quantitative evaluations of the reactions were performed. Results were statistically analyzed by Kruskal–Wallis test (p?<?0.05).

Results

All chemical solutions caused moderate reactions at 7 days. On day 30, PPT group was more cytotoxic than the control group and the CHX group (p?<?0.05). On days 15 and 60, PPT group was more cytotoxic than the control group (p?<?0.05). On day 90, there was no statistically significant difference between the different groups.

Conclusion

PPT is more cytotoxic than NaOCl and CHX alone, particularly in the short term.

Clinical significance

Protocols which suggest the use of CHX and NaOCl must be revised because this mixture produces cytotoxic product.     

Characterization of a Parkinson’s disease rat model using an upgraded paraquat exposure paradigm

Animal models of human diseases are crucial experimental tools to investigate the mechanisms involved in disease pathogenesis and to develop new therapies. In spite of the numerous animal models currently available that reproduce several neuropathological features of Parkinson disease (PD), it is challenging to have one that consistently recapitulates human PD conditions in both motor behaviors and biochemical pathological outcomes. Given that, we have implemented a new paradigm to expose rats to a chronic low dose of paraquat (PQ), using osmotic minipumps and characterized the developed pathologic features over time. The PQ exposure paradigm used lead to a rodent model of PD depicting progressive nigrostriatal dopaminergic neurodegeneration, characterized by a 41% significant loss of dopaminergic neuron in the substantia nigra pars compacta (SNpc), a significant decrease of 18% and 40% of dopamine levels in striatum at week 5 and 8, respectively, and a significant 1.5‐fold decrease in motor performance. We observed a significant increase of microglia activation state, sustained levels of α‐synucleinopathy and increased oxidative stress markers in the SNpc. In summary, this is an explorative study that allowed to characterize an improved PQ‐based rat model that recapitulates cardinal features of PD and may represent an attractive tool to investigate several mechanisms underlying the various aspects of PD pathogenesis as well as for the validation of the efficacy of new therapeutic approaches that targets different mechanisms involved in PD neurodegeneration.     

Radiotherapy-induced malignancies in breast cancer patients with TP53 pathogenic germline variants (Li–Fraumeni syndrome)

Familial Cancer - The risk of radiotherapy-induced malignancies (RIMs) is a concern when treating Li–Fraumeni syndrome (LFS) or Li–Fraumeni Like (LFL) patients. However, the type of...