Management of chronic heart failure in the community: role of a hospital based open access heart failure service

Objective: To evaluate the role of an open access heart failure service based at a teaching hospital for the diagnosis and treatment optimisation of patients with heart failure in the community and to identify measures that may further enhance the effectiveness of such a service.

Subjects: 963 patients with suspected heart failure seen over an eight year period referred by their general practitioners to the cardiology department at a district general hospital.

Main outcome measures: Presence or absence of left ventricular systolic dysfunction (LVSD) (left ventricular ejection fraction < 50% on echocardiography), and determination of the risk factors and predictors of LVSD.

Results: The majority of the patients were women (60% v 40%) and elderly (mean age 68.8 years). On echocardiography, only 30.8% were found to have LVSD. Patients were more likely to have LVSD if they were men (42.3% v 23.1%, p < 0.001, relative risk (RR) 1.8), were > 60 years of age (33.5% v 20.8%, p < 0.001, RR 1.6), or had a history of diabetes (49.4% v 29.1%, p < 0.001, RR 1.7), ischaemic heart disease (36.5% v 29.1%, p = 0.04, RR 1.3), or atrial fibrillation (52.6% v 27.8%, p < 0.001, RR 1.9). An abnormal ECG (48.4% v 19.5%, p < 0.001, RR 2.5) and cardiothoracic ratio > 0.5 on chest radiograph (44.3% v 17.8%, p < 0.001, RR 2.5) were found to be good predictors of LVSD. A normal ECG (negative predictive value 80.5%) and a cardiothoracic ratio of < 0.5 (negative predictive value 82.2%) can be used as baseline measures to identify patients with lower risk of developing LVSD (combined negative predictive value 87.9%).

Conclusions: An open access heart failure clinic is effective for the diagnosis and management of chronic heart failure in community based patients. The presence of risk factors and simple baseline tests can be used to identify patients with LVSD in the community. The introduction of a protocol based on these findings into a referral system can improve the efficiency and cost effectiveness of such a service.

     

Osteonecrosis of the jaw in a Crohn’s disease patient following a course of Bisphosphonate and Adalimumab therapy: a case report

Background

Cyclooxygenase-2 (COX-2, PTGS2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of biologic processes such as inflammation, cell proliferation and angiogenesis. COX-2 over-expression was reported in many (pre) malignant tissues, but data strongly vary and seem to depend on the methodology used.

Methods

Normal colorectal mucosa and paired cancerous tissue from 60 patients with colorectal cancer was investigated for the levels of COX-2 mRNA by real-time quantitative Polymerase Chain Reaction (qPCR). COX-2 levels were expressed relative to either: tissue weight or levels of the housekeeping genes beta-2 microglobulin (B2M) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

Results

COX-2 mRNA levels, normalized with respect to tissue weight or mRNA levels of the housekeeping genes B2M or GAPDH, were over-expressed in 80%, 70% and 40% of the colorectal tumor tissues, as compared to the paired adjacent normal colorectal mucosa samples, respectively. Highest mRNA COX-2 ratios tumor/normal were measured when expressed per mg tissue (mean ratio 21.6). When normalized with respect to the housekeeping genes B2M or GAPDH, mean tumor/normal ratios were 16.1 and 7.5, respectively.

Conclusion

Expression of COX-2 mRNA levels per mg tissue is most simple in comparison to normalization with respect to the housekeeping genes B2M or GAPDH. Levels of COX-2 mRNA are found over-expressed in almost 80% of the colorectal tumors, compared to paired adjacent normal colorectal mucosa, suggesting a role of COX-2 as a potential biomarker for cancer risk, whereas inhibitors of COX-2 could be of value in chemoprevention of colon cancer.     

Caffeine Inhibits EGF-Stimulated Trophoblast Cell Motility through the Inhibition of mTORC2 and Akt

Impaired trophoblast invasion is associated with pregnancy disorders such as early pregnancy loss and preeclampsia. There is evidence to suggest that the consumption of caffeine during pregnancy may increase the risk of pregnancy loss; however, little is known about the direct effect of caffeine on normal trophoblast biology. Our objectives were to examine the effect of caffeine on trophoblast migration and motility after stimulation with epidermal growth factor (EGF) and to investigate the intracellular signaling pathways involved in this process. Primary first-trimester extravillous trophoblasts (EVT) and the EVT-derived cell line SGHPL-4 were used to study the effect of caffeine on EGF-stimulated cellular motility using time-lapse microscopy. SGHPL-4 cells were further used to study the effect of caffeine and cAMP on EGF-stimulated invasion of fibrin gels. The influence of caffeine and cAMP on EGF-stimulated intracellular signaling pathways leading to the activation of Akt were investigated by Western blot analysis. Caffeine inhibits both EGF-stimulated primary EVT and SGHPL-4 cell motility. EGF stimulation activates phosphatidylinositol 3-kinase, and Akt and caffeine inhibit this activation. Although cAMP inhibits both motility and invasion, it does not inhibit the activation of Akt, indicating that the effects of caffeine seen in this study are independent of cAMP. Further investigation indicated a role for mammalian target of rapamycin complex 2 (mTORC2) as a target for the inhibitory effect of caffeine. In conclusion, we demonstrate that caffeine inhibits EGF-stimulated trophoblast invasion and motility in vitro and so could adversely influence trophoblast biology in vivo.     

Changes in nerve growth factor level and symptom severity following antibiotic treatment for refractory overactive bladder

Introduction and hypothesis

Overactive bladder (OAB) has a multifactorial aetiology, and for some women symptoms may be associated with chronic urothelial inflammation secondary to bacterial colonisation. One marker of such inflammation may be urinary nerve growth factor (NGF). We hypothesised that for women with OAB and urothelial inflammation, urinary NGF would be reduced following antibiotic therapy.

Methods

Women with overactive bladder and urodynamic diagnosis of detrusor overactivity who were refractory to anticholinergics, and had histological evidence of urothelial inflammation were treated with a 6-week course of rotating antibiotics. Urinary NGF was measured by ELISA before and after treatment. Three-day bladder diaries, the Patients’ Perception of Intensity of Urgency Scale, the King’s Health Questionnaire and the Patients’ Perception of Bladder Condition questionnaire were used to assess subjective and objective outcomes of therapy.

Results

Thirty-nine women with refractory DO were recruited. The NGF levels decreased significantly after antibiotic therapy (Wilcoxon signed rank test; p?=?0.015). There were significant improvements in daytime frequency, nocturia and urgency (p?<?0.05), and 74 % of women reported improvement in perception of their bladder condition.

Conclusions

Urinary NGF is responsive to antibiotic therapy. Women with refractory overactive bladder and elevated NGF may benefit from antibiotic treatment.     

Nerve cross-sectional area in extremes of age

Introduction: Nerve cross-sectional area reference values have been reported for many nerves, but there have been few studies in pediatric and geriatric populations. This study was conducted to determine the influence of age on nerve cross-sectional area. Methods: Thirty-two children (3 months to 16 years) and 20 geriatric adults (67–92 years) without known neurologic conditions underwent bilateral ultrasound to measure the area of the following nerves: median at the wrist and forearm; ulnar at the wrist and elbow; radial in the spiral groove; sciatic in the distal thigh; fibular at the knee; tibial at the knee and ankle; and sural at the ankle. Results: In general, nerve cross-sectional area increased with age. Nerve size correlated most closely with age, but a correlation was also seen with body mass index. Conclusions: Nerve cross-sectional area increases with age, which is important to note when using ultrasound to evaluate children and geriatric patients. Muscle Nerve 47: 890–893, 2013     

Validity and reliability of nerve and muscle ultrasound

Introduction: Nerve and muscle ultrasound has been studied in several conditions, but validity and reliability have not been assessed systematically. Methods: Nerve cross‐sectional area and muscle thickness were measured ultrasonographically at several sites in 4 cadavers, which were then dissected, and actual measurements were obtained. To assess intrarater and interrater reliability, between 3 and 5 ultrasonographers, with varying experience levels, made repeated measurements on healthy volunteers. Results: Correlation coefficients for nerve and muscle validity were >0.968 (P < 0.001), and for intrarater reliability were >0.901 (P < 0.001) for still and real‐time images. Correlation coefficients for interrater reliability were more varied, but for still images they were all significant at the P < 0.001 (0.542–0.998) level, and for real‐time images they were significant at the P < 0.05 level for half the sites (0.243–0.981). Conclusion: Overall, nerve and muscle ultrasound is a valid and reliable diagnostic imaging technique. Muscle Nerve, 2013     

Adjunctive Parental Support Within Manualized Parent Training for Children with Autism Spectrum Disorder

Parent training is a central focus of behavioral intervention, with emphasis on teaching parents to become change agents for their children by using behavioral management skills. However, its effectiveness is limited by a parent’s ability to engage in the learning process. Parents managing external stressors, psychopathology, or poverty often do not gain the skills and thus, the treatment may minimally impacts parent and child behavior. In order to increase a parent’s ability to acquire and implement new skills accurately, referred to as parent treatment integrity, the current study added a parent-support component to the RUBI Autism Network’s Parent Training for Disruptive Behaviors protocol. The parent-support component was intended to remove barriers to skill acquisition during the parent training session by alleviating some of the interfering parental stress. In an alternating treatments design, a community-based sample of five parent-child dyads (average age of child?=?32 months) participated in the parent-training protocol; half of the intervention sessions included a 15-min parent-support component. The addition of the parent-support component increased parent engagement, treatment integrity, and learned parenting skills, like parent praise. Results support a model of change for parenting behavior. Inclusion of a parent-support component is supported as an effective practice for parent training.

     

Association between joint hypermobility and pelvic organ prolapse in women: a systematic review and meta-analysis

Introduction and hypothesis

Abnormalities of common collagen proteins have been noted in individuals affected by POP and JHM, suggesting a common aetiology. We assessed strength, consistency and potential for bias in pooled associations of the relationship between JHM and POP.

Methods

We searched MEDLINE, EMBASE and CINAHL, as well as International Continence Society (ICS) and International Urogynaecologic Association (IUGA) annual meeting abstracts, including reference lists, without language restrictions. We included case–control and cohort studies and applied strict criteria for choosing eligible studies. Methodologically trained reviewers independently screened abstracts and full texts to confirm eligibility. We extracted data on study and patient characteristics, clinical assessment tools, and methodology. We assessed comparability and representativeness of source populations, confidence in the assessment of JHM and POP and adjustment for confounding and missing data. Meta-analysis was performed using a random effects model.

Results

We retrieved 39 full texts, of which 14 were used in the meta-analysis. Overall pooled odds ratio (OR) was 2.37 [95 % confidence interval (CI) 1.54–3.64, I²?=?77.0 %]. We identified no significant factors in meta-regression, and there was no evidence of publication bias; six studies were at high risk of bias with frequent differences in sampling frames, limited validity for clinical assessments and failure to match for important prognostic variables.

Conclusions

We found a strong association between POP and JHM, with an effect size that is clinically relevant. Our findings are limited by high heterogeneity and the potential for residual confounding factors. JHM is an important early indicator for POP risk, and future longitudinal studies should explore the shared aetiology.