Increasing confidence and changing behaviors in primary care providers engaged in genetic counselling.

BackgroundScreening and counseling for genetic conditions is an increasingly important part of primary care practice, particularly given the paucity of genetic counselors in the United States. However, primary care physicians (PCPs) often have an inadequate understanding of evidence-based screening; communication approaches that encourage shared decision-making; ethical, legal, and social implication (ELSI) issues related to screening for genetic mutations; and the basics of clinical genetics. This study explored whether an interactive, web-based genetics curriculum directed at PCPs in non-academic primary care settings was superior at changing practice knowledge, attitudes, and behaviors when compared to a traditional educational approach, particularly when discussing common genetic conditions.MethodsOne hundred twenty one PCPs in California and Pennsylvania physician practices were randomized to either an Intervention Group (IG) or Control Group (CG). IG physicians completed a 6 h interactive web-based curriculum covering communication skills, basics of genetic testing, risk assessment, ELSI issues and practice behaviors. CG physicians were provided with a traditional approach to Continuing Medical Education (CME) (clinical review articles) offering equivalent information.ResultsPCPs in the Intervention Group showed greater increases in knowledge compared to the Control Group. Intervention PCPs were also more satisfied with the educational materials, and more confident in their genetics knowledge and skills compared to those receiving traditional CME materials. Intervention PCPs felt that the web-based curriculum covered medical management, genetics, and ELSI issues significantly better than did the Control Group, and in comparison with traditional curricula. The Intervention Group felt the online tools offered several advantages, and engaged in better shared decision making with standardized patients, however, there was no difference in behavior change between groups with regard to increases in ELSI discussions between PCPs and patients.ConclusionWhile our intervention was deemed more enjoyable, demonstrated significant factual learning and retention, and increased shared decision making practices, there were few differences in behavior changes around ELSI discussions. Unfortunately, barriers to implementing behavior change in clinical genetics is not unique to our intervention. Perhaps the missing element is that busy physicians need systems-level support to engage in meaningful discussions around genetics issues. The next step in promoting active engagement between doctors and patients may be to put into place the tools needed for PCPs to easily access the materials they need at the point-of-care to engage in joint discussions around clinical genetics

Selective cyclooxygenase-2 silencing mediated by engineered E. coli and RNA interference induces anti-tumour effects in human colon cancer cells

Colorectal cancer (CRC) has an elevated incidence worldwide and represents one of the most aggressive human tumours. Many experimental data provide the evidence of a strong association between cyclooxygenase-2 (COX-2) enzyme overexpression and colon tumorigenesis. Furthermore, it has been demonstrated that the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs, a class of COX-2 inhibitors), partially protects patients from CRC development and progression. Unfortunately, NSAIDs have been shown to induce severe side effects in chronically treated patients and, therefore, new strategies for selective COX-2 blockade are needed. In this paper we present an innovative COX-2 silencing approach mediated by RNA Interference (RNAi) which is a mechanism we have already described as a powerful tool to knockdown COX-2 protein in CRC cells. In particular, we developed an improved method to gain a highly selective COX-2 silencing in CRC cells by a tumour-dependent expression of anti-COX-2 short hairpin RNA (shCOX-2). Moreover, we efficiently delivered shCOX-2 expressing vectors in CRC cells, in vitro and ex vivo, by using engineered Escherichia coli strains, capable of infecting and invading human tumour cells (InvColi). Combining the highly selective shCOX-2 expression and the delivery of COX-2 silencers mediated by InvColi strains, we obtained a strong reduction of both proliferative and invasive behaviour of tumour cells and we also confirmed the pivotal role of COX-2 overexpression for the survival of CRC cells. Finally, ex vivo data showed a global anti-inflammatory and anti-tumour effect elicited by COX-2 silencing

Tracking antioxidant properties and color changes in low-sugar bilberry jam as effect of processing, storage and pectin concentration

<p>Abstract</p> <p>Background</p> <p>Recently, an increased interest in the identification of valuable possibilities for preserving the antioxidant properties of products obtained by thermal processing of fruits rich in bioactive compounds can be noticed. In this regard, an extensive analysis is necessary in terms of thermal processed products behavior in relation to various factors. The purpose of the present study was to assess the effect which processing and storage at 20°C has on the antioxidant properties and color quality of low-sugar bilberry jam with different low-methoxyl pectin (LMP) concentrations.</p> <p>Results</p> <p>For all measured parameters, it should be noted that thermal processing induced significant alterations reported to the values registered for fresh fruit. Most important losses due to thermal processing were recorded for total monomeric anthocyanins (TMA) (81-84%), followed by L-ascorbic acid (L-AsAc) content (53-58%), total phenolics (TP) content (42-51%) and FRAP (ferric reducing antioxidant power) values (36-47%). Moreover, depreciation of the investigated compounds occurred during storage at 20°C. Jam storage for 7 months resulted in severe losses in TMA content in the range 58-72% from the value recorded one day after processing. This coincided with marked increases in polymeric color percent of these products after 7 months of storage. Also, bilberry jam storage for 7 months resulted in a decrease in L-AsAc content of 40-53% from the value recorded one day after processing, 41-57% in TP content and 33-46% from the value recorded one day after processing for FRAP values. By decreasing of LMP concentration in the jam recipe from 1 to 0.3% there has been an increase in losses of investigated compounds.</p> <p>Conclusion</p> <p>Overall, the results indicated that bilberry jams can also represent a good source of antioxidant compounds, although compared to the fruit, important losses seem to occur. Practical application of this work is that this kind of information will be very useful in optimizing the jam processing technology and storage conditions, in order to improve the quality of these products.</p

Adjusting to life after treatment: distress and quality of life following treatment for breast cancer

Clinical and anecdotal findings suggest that the completion of cancer treatment may be marked by heightened distress and disrupted adjustment. The present study examined psychological adjustment during the 3 months following treatment among 89 women with stages 0–III breast cancer. Participants completed measures of depression, cancer-related anxiety, cancer concerns, and quality of life at three time points: during treatment, 3 weeks following the end of treatment, and 3 months post-treatment. Post-treatment scores were suggestive of good psychological adjustment among the majority of women. Moreover, distress did not increase following treatment; longitudinal analyses showed no significant changes in depression or recurrence worry, while intrusive thoughts decreased, and quality of life improved. Younger age predicted greater distress across measures. A history of depression or anxiety predicted greater depressive symptomatology, while more extensive treatment predicted greater cancer-related anxiety. Despite the lack of distress endorsed on general depression and anxiety indices, participants reported moderate distress associated with cancer-related concerns, including physical problems, fear of cancer recurrence, and resuming normal life. In sum, while breast cancer survivors demonstrate good adjustment on general distress indices following treatment, some women are at risk for sustained distress. Moreover, significant cancer-related concerns are prevalent and may be important intervention targets

Dopaminergic modulation of appetitive trace conditioning: the role of D1 receptors in medial prefrontal cortex

Rationale: Trace conditioning may provide a behavioural model suitable to examine the maintenance of ‘on line’ information and its underlying neural substrates. Objectives: Experiment la was run to establish trace conditioning in a shortened procedure which would be suitable to test the effects of dopamine (DA) D1 receptor agents administered by microinjection directly into the brain. Experiment lb examined the effects of the DA D1 agonist SKF81297 and the DA D1 antagonist SCH23390 following systemic administration in pre-trained animals. Experiment 2 went on to test the effects of systemically administered SKF81297 on the acquisition of trace conditioning. In experiment 3, SKF81297 was administered directly in prelimbic (PL) and infralimbic (IL) sub-regions of medial prefrontal cortex (mPFC) to compare the role of different mPFC sub-regions. Results: Whilst treatment with SCH23390 impaired motor responding and/or motivation, SKF81297 had relatively little effect in the pre-trained animals tested in experiment 1b. However, systemic SKF81297 depressed the acquisition function at the 2-s trace interval in experiment 2. Similarly, in experiment 3, SKF81297 (0.1 μg in 1.0 μl) microinjected into either PL or IL mPFC impaired appetitive conditioning at the 2-s trace interval. Conclusions: Impaired trace conditioning under SKF81297 is likely to be mediated in part (but not exclusively) within the IL and PL mPFC sub-regions. The finding that trace conditioning was impaired rather than enhanced under SKF81297 provides further evidence for the inverse U-function which has been suggested to be characteristic of mPFC DA function

Infective endocarditis in intravenous drug abusers: an update

Infective endocarditis despite advances in diagnosis remains a common cause of hospitalization, with high morbidity and mortality rates. Through literature review it is possible to conclude that polymicrobial endocarditis occurs mainly in intravenous drug abusers with predominance in the right side of the heart, often with tricuspid valve involvement. This fact can be associated with the type of drug used by the patients; therefore, knowledge of the patient's history is critical for adjustment of the therapy. It is also important to emphasize that the most common combinations of organisms in polymicrobial infective endocarditis are: Staphylococcus aureus, Streptococcus pneumonia and Pseudomonas aeruginosa, as well as mixed cultures of Candida spp. and bacteria. A better understanding of the epidemiology and associated risk factors are required in order to develop an efficient therapy, although PE studies are difficult to perform due to the rarity of cases and lack of prospective cohorts.This work was supported by Portuguese Foundation for Science and Technology (FCT) through the grants SFRH/BPD/47693/2008, SFRH/BPD/20987/2004 and SFRH/BPD/72632/2010 attributed to Claudia Sousa, Claudia Botelho and Diana Rodrigues, respectively

Contextual factors in shared decision making: a randomised controlled trial in women with a strong suspicion of breast cancer

Decision aids in North American breast cancer outpatients have been shown to assist with treatment decision making and reduce decisional conflict. To date, appropriate delivery formats to effectively increase patient participation in newly diagnosed breast cancer inpatients have not been investigated in the context of German health care provision. The impact of a decision aid intervention was studied in patients (n=111) with a strong suspicion of breast cancer in a randomised controlled trial. The primary outcome variable was decisional conflict. Participants were followed up 1 week post-intervention with a retention rate of 92%. Analyses revealed that the intervention group felt better informed (ηp2=0.06) but did not experience an overall reduction in decisional conflict as compared with the control group. The intervention had no effect on uptake rates of treatment options, length of consultation with the surgeon, time point of treatment decision making, perceived involvement in decision making, neither decision related nor general patient satisfaction. Patients who received the decision aid intervention experienced a small benefit with regards to how informed they felt about advantages and disadvantages of relevant treatment options. Results are discussed in terms of contextual factors and individual differences as moderators of treatment decision aid effectiveness

Regulation of ABCC6 trafficking and stability by a conserved C-terminal PDZ-like sequence

Mutations in the ABCC6 ABC-transporter are causative of pseudoxanthoma elasticum (PXE). The loss of functional ABCC6 protein in the basolateral membrane of the kidney and liver is putatively associated with altered secretion of a circulatory factor. As a result, systemic changes in elastic tissues are caused by progressive mineralization and degradation of elastic fibers. Premature arteriosclerosis, loss of skin and vascular tone, and a progressive loss of vision result from this ectopic mineralization. However, the identity of the circulatory factor and the specific role of ABCC6 in disease pathophysiology are not known. Though recessive loss-of-function alleles are associated with alterations in ABCC6 expression and function, the molecular pathologies associated with the majority of PXE-causing mutations are also not known. Sequence analysis of orthologous ABCC6 proteins indicates the C-terminal sequences are highly conserved and share high similarity to the PDZ sequences found in other ABCC subfamily members. Genetic testing of PXE patients suggests that at least one disease-causing mutation is located in a PDZ-like sequence at the extreme C-terminus of the ABCC6 protein. To evaluate the role of this C-terminal sequence in the biosynthesis and trafficking of ABCC6, a series of mutations were utilized to probe changes in ABCC6 biosynthesis, membrane stability and turnover. Removal of this PDZ-like sequence resulted in decreased steady-state ABCC6 levels, decreased cell surface expression and stability, and mislocalization of the ABCC6 protein in polarized cells. These data suggest that the conserved, PDZ-like sequence promotes the proper biosynthesis and trafficking of the ABCC6 protein. © 2014 Xue et al

‘Making the invisible visible’ through alcohol screening and brief intervention in community pharmacies: an Australian feasibility study

Background: Screening and brief interventions (SBI) for alcohol related problems have been shown to be effective in health settings such as general practice or emergency departments. Recent data from the United Kingdom and New Zealand suggest that SBI can be delivered through community pharmacies, but this approach has not been tested in Australia. This study assesses the feasibility of delivering alcohol SBI via community pharmacists. Method: We recruited five pharmacies and developed an SBI training package to be delivered by pharmacy staff, who screened consumers and delivered the brief intervention where appropriate. Consumers also completed a questionnaire on the process. At three months consumers were telephoned to enable ‘retention’ to be quantified. After completing recruitment, a semi-structured interview was conducted with pharmacists on the process of delivering the intervention, potential improvements and sustainability. Results: Fifty consumer participants were screened, ten from each pharmacy. There were 28 (57 %) men and 21 (43 %) women with one not responding. Most (67 %) were aged 25-55 years. Their AUDIT scores had a range of 0 to 39 (mean 10.9, SD 9.8) with 11 categorised as ‘hazardous (8-15)’, four as ‘harmful (16-19)’ and eight as ‘probably dependent (20+)’ consumers of alcohol. Reactions to the process of SBI were generally favourable: for example 75 % agreed that it was either appropriate or very appropriate being asked about their alcohol consumption. With respect to follow-up interviews, 23 (46 %) agreed that they could be contacted, including five from the highest AUDIT category. Subsequently 11 (48 %) were contactable at three months. Three of the five non-low risk drinkers had reduced their level of risk over the three months. Ten pharmacists participated in semi-structured telephone interviews. Overall these pharmacists were positive about the intervention and five main themes emerged from the interviews: 1) flexibility applied in recruitment of participants, 2) easiness in use of AUDIT score to facilitate discussions, 3) perceived positive intervention impact, 4) enhanced role of community pharmacists and 5) facilitators and challenges experienced. Conclusions: Pharmacy-based SBI appears to be acceptable to consumers and feasible for pharmacy staff to deliver. Challenges remain in translating this potential into actual services

Impact of vital signs screening & clinician prompting on alcohol and tobacco screening and intervention rates: a pre-post intervention comparison

<p>Abstract</p> <p>Background</p> <p>Though screening and intervention for alcohol and tobacco misuse are effective, primary care screening and intervention rates remain low. Previous studies have increased intervention rates using vital signs screening for tobacco misuse and clinician prompts for screen-positive patients for both alcohol and tobacco misuse. This pilot study's aims were: (1) To determine the feasibility of combined vital signs screening for tobacco and alcohol misuse, (2) To assess the impact of vital signs screening on alcohol and tobacco screening and intervention rates, and (3) To assess the additional impact of tobacco assessment prompts on intervention rates.</p> <p>Methods</p> <p>In five outpatient practices, nurses measuring vital signs were trained to routinely ask a single tobacco question, a prescreening question that identified current drinkers, and the single alcohol screening question for current drinkers. After 4-8 weeks, clinicians were trained in tobacco intervention and nurses were trained to give tobacco abusers a tobacco questionnaire which also served as a clinician intervention prompt. Screening and intervention rates were measured using patient exit interviews (n = 622) at baseline, during the "screening only" period, and during the tobacco prompting phase. Changes in screening and intervention rates were compared using chi square analyses and test of linear trends. Clinic staff were interviewed regarding patient and staff acceptability. Logistic regression was used to evaluate the impact of nurse screening on clinician intervention, the impact of alcohol intervention on concurrent tobacco intervention, and the impact of tobacco intervention on concurrent alcohol intervention.</p> <p>Results</p> <p>Alcohol and tobacco screening rates and alcohol intervention rates increased after implementing vital signs screening (p < .05). During the tobacco prompting phase, clinician intervention rates increased significantly for both alcohol (12.4%, p < .001) and tobacco (47.4%, p = .042). Screening by nurses was associated with clinician advice to reduce alcohol use (OR 13.1; 95% CI 6.2-27.6) and tobacco use (OR 2.6; 95% CI 1.3-5.2). Acceptability was high with nurses and patients.</p> <p>Conclusions</p> <p>Vital signs screening can be incorporated in primary care and increases alcohol screening and intervention rates. Tobacco assessment prompts increase both alcohol and tobacco interventions. These simple interventions show promise for dissemination in primary care settings.</p