35 research outputs found
Veillonella montpellierensis Endocarditis
Veillonella spp. rarely cause infections in humans. We report a case of Veillonella endocarditis documented by isolating a slow-growing, gram-negative microbe in blood cultures. This microbe was identified as the newly recognized species Veillonella montpellierensis (100% homology) by 16S RNA gene sequence analysis
Epidemiological study of E. coli O157:H7 isolated in Northern Ireland using pulsed-field gel electrophoresis (PFGE)
In Northern Ireland over the last 7 years, there is a mean of 41.9 laboratory reports per annum of human gastrointestinal infection (range 19-54) caused by Escherichia coli O157:H7. In the preceding years 1992-1996, reports were 5.4 per annum, whereas in 1997-2000, reports increased from 30 to 54 per annum. This high level has continued on an annual basis to date. The aim of this study was therefore to retrospectively examine this period of exponential increase in reports to help ascertain the genetic relatedness of strains employing pulsed-field gel electrophoresis (PFGE), as no data on the molecular epidemiology of E. coli O157:H7 in Northern Ireland has yet been published. Clinical isolates (n=84) were PFGE typed employing Xba I digestion and resulting band profiles demonstrated the presence of 13, 9 and 16 clonal types, for 1997, 1998 and 1999, respectively. In 1998, five clonal types remained from 1997 with the introduction of 4 new clonal types, whereas in 1999, 10 new clonal types were observed, accounting for over half (58%) of the E. coli O157 isolates for that year. These data suggest that, unlike gastrointestinal infections due to thermophilic campylobacters, there was considerable genetic evolution of PFGE clonal types of E. coli O157, through the displacement and emergence of genotypes. Further studies are now required to find the environmental reservoirs of these common clonal types of clinical E. coli O157:H7 in Northern Ireland to help define sources and routes of transmission of this infection locally
Runx1 deficiency protects against adverse cardiac remodeling following myocardial infarction
Background: Myocardial infarction (MI) is a leading cause of heart failure and death worldwide. Preservation of contractile function and protection against adverse changes in ventricular architecture (cardiac remodeling) are key factors to limiting progression of this condition to heart failure. Consequently, new therapeutic targets are urgently required to achieve this aim. Expression of the Runx1 transcription factor is increased in adult cardiomyocytes after MI; however, the functional role of Runx1 in the heart is unknown.
Methods: To address this question, we have generated a novel tamoxifen-inducible cardiomyocyte-specific Runx1-deficient mouse. Mice were subjected to MI by means of coronary artery ligation. Cardiac remodeling and contractile function were assessed extensively at the whole-heart, cardiomyocyte, and molecular levels.
Results: Runx1-deficient mice were protected against adverse cardiac remodeling after MI, maintaining ventricular wall thickness and contractile function. Furthermore, these mice lacked eccentric hypertrophy, and their cardiomyocytes exhibited markedly improved calcium handling. At the mechanistic level, these effects were achieved through increased phosphorylation of phospholamban by protein kinase A and relief of sarco/endoplasmic reticulum Ca2+-ATPase inhibition. Enhanced sarco/endoplasmic reticulum Ca2+-ATPase activity in Runx1-deficient mice increased sarcoplasmic reticulum calcium content and sarcoplasmic reticulum–mediated calcium release, preserving cardiomyocyte contraction after MI.
Conclusions: Our data identified Runx1 as a novel therapeutic target with translational potential to counteract the effects of adverse cardiac remodeling, thereby improving survival and quality of life among patients with MI
A randomized, embedded trial of pre-notification of trial participation did not increase recruitment rates to a falls prevention trial
Objectives: To design and evaluate the effectiveness of a pre-notification leaflet about research to increase recruitment to a randomised controlled trial (RCT). Methods: A methodological, two arm, randomised controlled trial was conducted, embedded within an existing cohort RCT (REFORM). Participants were randomised for the embedded trial, using a 1:2 (intervention:control) allocation ratio, prior to being randomised for the REFORM RCT. Controls received a trial recruitment pack. The intervention group received an additional pre-notification leaflet 2 to 3 weeks before the recruitment pack. Primary and secondary analyses were conducted using relative risk, the Cox Proportional Hazards Model and Incremental Cost Effectiveness Ratios. Results: Of the 1,436 intervention group participants, 73 (5.1%) were randomised into the REFORM trial compared to 126 (4.4%) of the 2,878 control group participants. The associated relative risk (1.16) was not statistically significant (95% CI 0.88 - 1.56). The leaflet did not significantly increase return rate (RR 1.10, 95% CI 0.92 -1.28) or decrease time to return (Hazard Ratio: 1.11, 95% CI 0.93 -1.33). Incremental Cost Effectiveness Ratios indicated that the intervention may be cost-effective if the true estimate of effect were close to the upper bound of the associated 95% CI. Conclusion: A pre-notification leaflet to potential trial participants demonstrated a small difference in favour of the intervention with regards randomisation (0.7% difference) and return rates (1.1% difference).Results should however be interpreted with caution as confidence intervals for these estimates cross the point of no effect. Nevertheless, this research enhances existing evidence for pre-notification to increase recruitment rates, with further development and assessment of this potentially cost-effective intervention being recommended
Medial longitudinal arch development of school children : The College of Podiatry Annual Conference 2015: meeting abstracts
Background Foot structure is often classified into flat foot, neutral and high arch type based on the variability of the Medial Longitudinal Arch (MLA). To date, the literature provided contrasting evidence on the age when MLA development stabilises in children. The influence of footwear on MLA development is also unknown. Aim This study aims to (i) clarify whether the MLA is still changing in children from age 7 to 9 years old and (ii) explore the relationship between footwear usage and MLA development, using a longitudinal approach. Methods We evaluated the MLA of 111 healthy school children [age = 6.9 (0.3) years] using three parameters [arch index (AI), midfoot peak pressure (PP) and maximum force (MF: % of body weight)] extracted from dynamic foot loading measurements at baseline, 10-month and 22-month follow-up. Information on the type of footwear worn was collected using survey question. Linear mixed modelling was used to test for differences in the MLA over time. Results Insignificant changes in all MLA parameters were observed over time [AI: P = .15; PP: P = .84; MF: P = .91]. When gender was considered, the AI of boys decreased with age [P = .02]. Boys also displayed a flatter MLA than girls at age 6.9 years [AI: mean difference = 0.02 (0.01, 0.04); P = .02]. At baseline, subjects who wore close-toe shoes displayed the lowest MLA overall [AI/PP/MF: P < .05]. Subjects who used slippers when commencing footwear use experienced higher PP than those who wore sandals [mean difference = 31.60 (1.44, 61.75) kPa; post-hoc P = .04]. Discussion and conclusion Our findings suggested that the MLA of children remained stable from 7 to 9 years old, while gender and the type of footwear worn during childhood may influence MLA development. Clinicians may choose to commence therapy when a child presents with painful flexible flat foot at age 7 years, and may discourage younger children from wearing slippers when they commence using footwear
Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received
Background
The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy.
Objective
To report outcomes according to treatment received in men in randomised and treatment choice cohorts.
Design, setting, and participants
This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy.
Intervention
Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment.
Outcome measurements and statistical analysis
Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores.
Results and limitations
According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa.
Conclusions
Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group.
Patient summary
More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common