“Clinical features of women with gout arthritis.” A systematic review

Clinically, gout is generally considered as a preferential male disease. However, it definitely does not occur exclusively in males. Our aim was to assess differences in the clinical features of gout arthritis between female and male patients. Five electronic databases were searched to identify relevant original studies published between 1977 and 2007. The included studies had to focus on adult patients with primary gout arthritis and on sex differences in clinical features. Two reviewers independently assessed eligibility and quality of the studies. Out of 355 articles, 14 were selected. Nine fulfilled the quality and score criteria. We identified the following sex differences in the clinical features of gout in women compared to men: the onset of gout occurs at a higher age, more comorbidity with hypertension or renal insufficiency, more often use of diuretics, less likely to drink alcohol, less often podagra but more often involvement of other joints, less frequent recurrent attacks. We found interesting sex differences regarding the clinical features of patients with gout arthritis. To diagnose gout in women, knowledge of these differences is essential, and more research is needed to understand and explain the differences , especially in the general population

Challenges for drug checking services in Scotland: a qualitative exploration of police perceptions.

Background The impact of policing practices on the engagement of people who use drugs (PWUD) with harm reduction services is well evidenced. Although the police have traditionally taken an enforcement role in responding to drug use, it is increasingly clear that they can play an important part in multiagency delivery of harm reduction interventions. Despite this, there have been no studies exploring police officer perceptions of drug checking services (DCS), which provide analytical testing of client drug samples alongside harm reduction support and advice. Methods Semi-structured interviews were conducted with 10 police officers to explore the policing and legal challenges which could be encountered in the delivery of DCS in Scotland. Results Participants expressed general support for DCS and described this support as part of a wider organisational shift towards public health-oriented policing. Participants also discussed different potential approaches to the policing of areas surrounding DCS including: formal limits on police presence around the service and/or stop and search powers in relation to personal possession; the effective decriminalisation of personal possession within a specified boundary around the service; and informal agreements between local divisions and DCS outlining expected policing practices. Any formal limitation on the capacity of police officers to respond to community concerns was viewed as problematic and as having the potential to erode public confidence in policing. Participants also highlighted the potential for frontline officers to utilise discretion in ways which could undermine public health goals. Legislative change, or national strategic guidance from relevant stakeholders, was seen as a means of providing 'cover', enabling local divisions to support the operation of drug checking. Conclusions Despite a small sample of participants, this study summarises key challenges to be addressed in the implementation and operation of DCS in Scotland, and more widely. The paper concludes with suggested opportunities to develop approaches to policing that can facilitate rather than impede implementation and operation of these services

Planning and implementing community-based drug checking services in Scotland: a qualitative exploration using the consolidated framework for implementation research

Background: Drug checking services (DCS) provide harm reduction support and advice to individuals based on chemical analysis of submitted substances of concern. Whilst there are currently no DCS in Scotland, community-based services are being planned in three cities. Methods: In this paper, we report qualitative findings based on interviews with 43 participants, focused on perceptions of DCS and their implementation. Participants were relevant professionals, those with experience of drug use, and family members of those with experience of drug use. The Consolidated Framework for Implementation Research (CFIR) was used to inform data collection and analysis. We report findings under nine constructs/themes across the five CFIR domains. Results: Participants noted the importance of DCS being implemented in low-threshold, trusted services with a harm reduction ethos, and outlined a range of further service design considerations such as speed of testing, and information provided through the analysis process. In relation to the ‘inner setting’, a key finding related to the potential value of leveraging existing resources in order to expand both reach and effectiveness of drug trend communication. The approach of local and national police to DCS, and the attitudes of the public and local community, were described as important external factors which could influence the success (or otherwise) of implementation. Bringing together a range of stakeholders in dialogue and developing tailored communication strategies were seen as ways to build support for DCS. Overall, we found high levels of support and perceived need for DCS amongst all stakeholder groups. Conclusions: Our findings present initial implementation considerations for Scotland which could be further explored as DCS are operationalised. Further, our focus on implementation contexts is relevant to research on DCS more generally, given the minimal consideration of such issues in the literature

“It would really support the wider harm reduction agenda across the board”: A qualitative study of the potential impacts of drug checking service delivery in Scotland

Drug checking services (DCS) enable individuals to voluntarily submit a small amount of a substance for analysis, providing information about the content of the substance along with tailored harm reduction support and advice. There is some evidence suggesting that DCS may lead to behaviour and system change, with impacts for people who use drugs, staff and services, and public health structures. The evidence base is still relatively nascent, however, and several evidence gaps persist. This paper reports on qualitative interviews with forty-three participants across three Scottish cities where the implementation of community-based DCS is being planned. Participants were drawn from three groups: professional participants; people with experience of drug use; and affected family members. Findings focus on perceived harm reduction impacts of DCS delivery in Scotland, with participants highlighting the potential for drug checking to impact a number of key groups including: individual service users; harm reduction services and staff; drug market monitoring structures and networks; and wider groups of people who use and sell drugs, in shaping their interactions with the drug market. Whilst continued evaluation of individual health behaviour outcomes is crucial to building the evidence base for DCS, the findings highlight the importance of extending evaluation beyond these outcomes. This would include evaluation of processes such as: information sharing across a range of parties; engagement with harm reduction and treatment services; knowledge building; and increased drug literacy. These broader dynamics may be particularly important for evaluations of community-based DCS serving individuals at higher-risk, given the complex relationship between information provision and health behaviour change which may be mediated by mental and physical health, stigma, criminalisation and the risk environment. This paper is of international relevance and adds to existing literature on the potential impact of DCS on individuals, organisations, and public health structures

A Randomized Trial to Assess Anti-HIV Activity in Female Genital Tract Secretions and Soluble Mucosal Immunity Following Application of 1% Tenofovir Gel

Preclinical and early phase clinical microbicide studies have not consistently predicted the outcome of efficacy trials. To address this gap, candidate biomarkers of microbicide pharmacodynamics and safety were evaluated in a double-blind, placebo-controlled trial of tenofovir gel, the first microbicide to demonstrate significant protection against HIV acquisition.30 women were randomized to apply a single daily dose of tenofovir or placebo gel for 14 consecutive days. Anti-HIV activity was measured in cervicovaginal lavage (CVL) on Days 0, 3, 7, 14 and 21 by luciferase assay as a surrogate marker of pharmacodynamics. Endogenous activity against E. coli and HSV-2 and concentrations of immune mediators were quantified in CVL as candidate biomarkers of safety. Tenofovir levels were measured in CVL and blood.A significant increase in anti-HIV activity was detected in CVL from women who applied tenofovir gel compared to their endogenous anti-HIV activity in genital tract secretions on Day 0 and compared to activity in CVL from women in the placebo group. The activity correlated significantly with CVL concentration of tenofovir (r = 0.6, p<0.001) and fit a sigmoid E(max) pharmacodynamic model. Anti-HIV activity in CVL from women who applied tenofovir persisted when virus was introduced in semen, whereas endogenous anti-HIV activity decreased. Tenofovir did not trigger an inflammatory response or induce sustained loss in endogenous antimicrobial activity or immune mediators.Tenofovir gel had no deleterious impact on soluble mucosal immunity. The increased anti-HIV activity in CVL, which persisted in the presence of semen and correlated with tenofovir concentration, is consistent with the efficacy observed in a recent clinical trial. These results promote quantified CVL anti-HIV activity as a surrogate of tissue pharmacodynamics and as a potential biomarker of adherence to product. This simple, feasible and inexpensive bioassay may promote the development of models more predictive of microbicide efficacy.ClinicalTrials.gov NCT00594373

'It's not going to be a one size fits all': a qualitative exploration of the potential utility of three drug checking service models in Scotland

Background Scotland currently has the highest rates of drug-related deaths in Europe, so drug checking services are being explored due to their potential role in reducing these deaths and related harms. Drug checking services allow individuals to submit presumed psychoactive drug samples for analysis, and then receive individualised feedback and counselling. This paper explores participants' views on the advantages and challenges of three hypothetical service models, to inform future service delivery in Scotland. Methods Semi-structured interviews were conducted with 43 people: 27 professional stakeholders, 11 people with experience of drug use, and five family members across three cities. Vignettes were used to provide short descriptions of three hypothetical service models during the interviews. Interviews were audio-recorded, transcribed and analysed using thematic analysis. Results Participants identified advantages and challenges for each of the three potential service models. The third sector (not-for-profit) model was favoured overall by participants, and the NHS substance use treatment service was the least popular. Participants also noted that multiple drug checking sites within one city, along with outreach models would be advantageous, to meet the diverse needs of different groups of people who use drugs. Conclusions Drug checking services need to be tailored to local context and needs, with a range of service models being possible, in order to meet the needs of a heterogeneous group of people who use drugs. Addressing issues around stigma, accessibility, and concerns about the potential impact of accessing drug checking on access to and outcomes of drug treatment, are essential for successful service delivery

Discovery of the inhibitory effect of a phosphatidylinositol derivative on P-glycoprotein by virtual screening followed by <i>in vitro</i> cellular studies

P-glycoprotein is capable of effluxing a broad range of cytosolic and membrane penetrating xenobiotic substrates, thus leading to multi-drug resistance and posing a threat for the therapeutic treatment of several diseases, including cancer and central nervous disorders. Herein, a virtual screening campaign followed by experimental validation in Caco-2, MDKCII, and MDKCII mdr1 transfected cell lines has been conducted for the identification of novel phospholipids with P-gp transportation inhibitory activity. Phosphatidylinositol-(1,2-dioctanoyl)-sodium salt (8∶0 PI) was found to significantly inhibit transmembrane P-gp transportation in vitro in a reproducible-, cell line-, and substrate-independent manner. Further tests are needed to determine whether this and other phosphatidylinositols could be co-administered with oral drugs to successfully increase their bioavailability. Moreover, as phosphatidylinositols and phosphoinositides are present in the human diet and are known to play an important role in signal transduction and cell motility, our finding could be of substantial interest for nutrition science as well

Analysis of RNA splicing defects in PITX2 mutants supports a gene dosage model of Axenfeld-Rieger syndrome

BACKGROUND: Axenfeld-Rieger syndrome (ARS) is associated with mutations in the PITX2 gene that encodes a homeobox transcription factor. Several intronic PITX2 mutations have been reported in Axenfeld-Rieger patients but their effects on gene expression have not been tested. METHODS: We present two new families with recurrent PITX2 intronic mutations and use PITX2c minigenes and transfected cells to address the hypothesis that intronic mutations effect RNA splicing. Three PITX2 mutations have been analyzed: a G>T mutation within the AG 3' splice site (ss) junction associated with exon 4 (IVS4-1G>T), a G>C mutation at position +5 of the 5' (ss) of exon 4 (IVS4+5G>C), and a previously reported A>G substitution at position -11 of 3'ss of exon 5 (IVS5-11A>G). RESULTS: Mutation IVS4+5G>C showed 71% retention of the intron between exons 4 and 5, and poorly expressed protein. Wild-type protein levels were proportionally expressed from correctly spliced mRNA. The G>T mutation within the exon 4 AG 3'ss junction shifted splicing exclusively to a new AG and resulted in a severely truncated, poorly expressed protein. Finally, the A>G substitution at position -11 of the 3'ss of exon 5 shifted splicing exclusively to a newly created upstream AG and resulted in generation of a protein with a truncated homeodomain. CONCLUSION: This is the first direct evidence to support aberrant RNA splicing as the mechanism underlying the disorder in some patients and suggests that the magnitude of the splicing defect may contribute to the variability of ARS phenotypes, in support of a gene dosage model of Axenfeld-Rieger syndrome

Rasch scaling procedures for informing development of a valid Fetal Surveillance Education Program multiple-choice assessment

<p>Abstract</p> <p>Background</p> <p>It is widely recognised that deficiencies in fetal surveillance practice continue to contribute significantly to the burden of adverse outcomes. This has prompted the development of evidence-based clinical practice guidelines by the Royal Australian and New Zealand College of Obstetricians and Gynaecologists and an associated Fetal Surveillance Education Program to deliver the associated learning. This article describes initial steps in the validation of a corresponding multiple-choice assessment of the relevant educational outcomes through a combination of item response modelling and expert judgement.</p> <p>Methods</p> <p>The Rasch item response model was employed for item and test analysis and to empirically derive the substantive interpretation of the assessment variable. This interpretation was then compared to the hierarchy of competencies specified a priori by a team of eight subject-matter experts. Classical Test Theory analyses were also conducted.</p> <p>Results</p> <p>A high level of agreement between the hypothesised and derived variable provided evidence of construct validity. Item and test indices from Rasch analysis and Classical Test Theory analysis suggested that the current test form was of moderate quality. However, the analyses made clear the required steps for establishing a valid assessment of sufficient psychometric quality. These steps included: increasing the number of items from 40 to 50 in the first instance, reviewing ineffective items, targeting new items to specific content and difficulty gaps, and formalising the assessment blueprint in light of empirical information relating item structure to item difficulty.</p> <p>Conclusion</p> <p>The application of the Rasch model for criterion-referenced assessment validation with an expert stakeholder group is herein described. Recommendations for subsequent item and test construction are also outlined in this article.</p

Prognostic factors in left-sided endocarditis: results from the andalusian multicenter cohort

<p>Abstract</p> <p>Background</p> <p>Despite medical advances, mortality in infective endocarditis (IE) is still very high. Previous studies on prognosis in IE have observed conflicting results. The aim of this study was to identify predictors of in-hospital mortality in a large multicenter cohort of left-sided IE.</p> <p>Methods</p> <p>An observational multicenter study was conducted from January 1984 to December 2006 in seven hospitals in Andalusia, Spain. Seven hundred and five left-side IE patients were included. The main outcome measure was in-hospital mortality. Several prognostic factors were analysed by univariate tests and then by multilogistic regression model.</p> <p>Results</p> <p>The overall mortality was 29.5% (25.5% from 1984 to 1995 and 31.9% from 1996 to 2006; Odds Ratio 1.25; 95% Confidence Interval: 0.97-1.60; p = 0.07). In univariate analysis, age, comorbidity, especially chronic liver disease, prosthetic valve, virulent microorganism such as <it>Staphylococcus aureus</it>, <it>Streptococcus agalactiae </it>and fungi, and complications (septic shock, severe heart failure, renal insufficiency, neurologic manifestations and perivalvular extension) were related with higher mortality. Independent factors for mortality in multivariate analysis were: Charlson comorbidity score (OR: 1.2; 95% CI: 1.1-1.3), prosthetic endocarditis (OR: 1.9; CI: 1.2-3.1), <it>Staphylococcus aureus </it>aetiology (OR: 2.1; CI: 1.3-3.5), severe heart failure (OR: 5.4; CI: 3.3-8.8), neurologic manifestations (OR: 1.9; CI: 1.2-2.9), septic shock (OR: 4.2; CI: 2.3-7.7), perivalvular extension (OR: 2.4; CI: 1.3-4.5) and acute renal failure (OR: 1.69; CI: 1.0-2.6). Conversely, <it>Streptococcus viridans </it>group etiology (OR: 0.4; CI: 0.2-0.7) and surgical treatment (OR: 0.5; CI: 0.3-0.8) were protective factors.</p> <p>Conclusions</p> <p>Several characteristics of left-sided endocarditis enable selection of a patient group at higher risk of mortality. This group may benefit from more specialised attention in referral centers and should help to identify those patients who might benefit from more aggressive diagnostic and/or therapeutic procedures.</p