Self-reported non-adherence to antiretroviral therapy repeatedly assessed by two questions predicts treatment failure in virologically suppressed patients

BACKGROUND: The aim of this study was to explore the predictive value of longitudinal self-reported adherence data on viral rebound. METHODS: Individuals in the Swiss HIV Cohort Study on combined antiretroviral therapy (cART) with RNA <50 copies/ml over the previous 3 months and who were interviewed about adherence at least once prior to 1 March 2007 were eligible. Adherence was defined in terms of missed doses of cART (0, 1, 2 or >2) in the previous 28 days. Viral rebound was defined as RNA >500 copies/ml. Cox regression models with time-independent and -dependent covariates were used to evaluate time to viral rebound. RESULTS: A total of 2,664 individuals and 15,530 visits were included. Across all visits, missing doses were reported as follows: 1 dose 14.7%, 2 doses 5.1%, >2 doses 3.8% taking <95% of doses 4.5% and missing > or =2 consecutive doses 3.2%. In total, 308 (11.6%) patients experienced viral rebound. After controlling for confounding variables, self-reported non-adherence remained significantly associated with the rate of occurrence of viral rebound (compared with zero missed doses: 1 dose, hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.72-1.48; 2 doses, HR 2.17, 95% CI 1.46-3.25; >2 doses, HR 3.66, 95% CI 2.50-5.34). Several variables significantly associated with an increased risk of viral rebound irrespective of adherence were identified: being on a protease inhibitor or triple nucleoside regimen (compared with a non-nucleoside reverse transcriptase inhibitor), >5 previous cART regimens, seeing a less-experienced physician, taking co-medication, and a shorter time virally suppressed. CONCLUSIONS: A simple self-report adherence questionnaire repeatedly administered provides a sensitive measure of non-adherence that predicts viral rebound.

Culture, risk factors and mortality: can Switzerland add missing pieces to the European puzzle?

BACKGROUND: The aim was to compare cause-specific mortality, self-rated health (SRH) and risk factors in the French and German part of Switzerland and to discuss to what extent variations between these regions reflect differences between France and Germany. METHODS: Data were used from the general population of German and French Switzerland with 2.8 million individuals aged 45-74 years, contributing 176 782 deaths between 1990 and 2000. Adjusted mortality risks were calculated from the Swiss National Cohort, a longitudinal census-based record linkage study. Results were contrasted with cross-sectional analyses of SRH and risk factors (Swiss Health Survey 1992/3) and with cross-sectional national and international mortality rates for 1980, 1990 and 2000. RESULTS: Despite similar all-cause mortality, there were substantial differences in cause-specific mortality between Swiss regions. Deaths from circulatory disease were more common in German Switzerland, while causes related to alcohol consumption were more prevalent in French Switzerland. Many but not all of the mortality differences between the two regions could be explained by variations in risk factors. Similar patterns were found between Germany and France. CONCLUSION: Characteristic mortality and behavioural differentials between the German- and the French-speaking parts of Switzerland could also be found between Germany and France. However, some of the international variations in mortality were not in line with the Swiss regional comparison nor with differences in risk factors. These could relate to peculiarities in assignment of cause of death. With its cultural diversity, Switzerland offers the opportunity to examine cultural determinants of mortality without bias due to different statistical systems or national health policies.

Human and feline invasive cervical resorptions: the missing link?--Presentation of four cases

This report describes 4 patients presenting with multiple teeth affected by invasive cervical resorption (ICR). The cases came to our attention between 2006 and 2008; previously, no cases of multiple ICR (mICR) had been reported in Switzerland. Characteristics common to all 4 cases included progression of disease over time, similar clinical and radiographic appearance of lesions, and obscure etiology. The histologically assessed teeth showed a similar pattern of tooth destruction, with resorptive lesions being confined to the cervical region. Howship's lacunae and multinucleated, tartrate-resistant acid phosphatase-positive odontoclasts were detected. None of the teeth presented with internal resorption. The positive pulp sensitivity corresponded to the histologic findings, indicating that the pulp tissue resisted degradation even in advanced stages of resorptive lesions. Although mICR is rare in humans, a similar disease known as feline odontoclastic resorptive lesions (FORL) is common in domestic, captive, and wild cats. The etiology of FORL, like that of mICR, remains largely unknown. Because FORL has been associated with feline viruses, we asked our mICR patients whether they had had contact with cats, and interestingly, all patients reported having had direct (2 cases) or indirect (2 cases) contact. In addition, blood samples were taken from all patients for neutralization testing of feline herpes virus type 1 (FeHV-1). Indeed, the sera obtained were able to neutralize (2 cases) or partly inhibit (2 cases) replication of FeHV-1, indicating transmission of feline viruses to humans. Future studies on mICR (and FORL) should evaluate the possible role of a (feline) virus as an etiologic (co-)factor in this disease.

State of the science on controversial topics: missing maxillary lateral incisors - a report of the Angle Society of Europe 2012 meeting

BACKGROUND The optimal long-term management of the congenitally missing maxillary lateral incisor continues to cause controversy within the specialty. The Angle Society of Europe meeting 2012 dedicated a day to address some of the current controversies relating to the management of these missing lateral incisors. FINDINGS The format of the day consisted of morning presentations and afternoon breakout sessions to discuss a variety of questions related to the management of missing lateral incisors. CONCLUSIONS The consensus viewpoint from this day was that the care of patients with congenitally missing lateral incisors is best achieved through a multi-disciplinary approach. The current evidence base is weak, and further well-designed, prospective trials are needed.

Role of Epithelial-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma: Is Tumor Budding the Missing Link?

Pancreatic ductal adenocarcinoma (PDAC) ranks as the fourth commonest cause of cancer death while its incidence is increasing worldwide. For all stages, survival at 5 years is<5%. The lethal nature of pancreatic cancer is attributed to its high metastatic potential to the lymphatic system and distant organs. Lack of effective therapeutic options contributes to the high mortality rates of PDAC. Recent evidence suggests that epithelial-mesenchymal transition (EMT) plays an important role to the disease progression and development of drug resistance in PDAC. Tumor budding is thought to reflect the process of EMT which allows neoplastic epithelial cells to acquire a mesenchymal phenotype thus increasing their capacity for migration and invasion and help them become resistant to apoptotic signals. In a recent study by our own group the presence and prognostic significance of tumor budding in PDAC were investigated and an association between high-grade budding and aggressive clinicopathological features of the tumors as well as worse outcome of the patients was found. The identification of EMT phenotypic targets may help identifying new molecules so that future therapeutic strategies directed specifically against them could potentially have an impact on drug resistance and invasiveness and hence improve the prognosis of PDAC patients. The aim of this short review is to present an insight on the morphological and molecular aspects of EMT and on the factors that are involved in the induction of EMT in PDAC.

Principal-Agent Theory and the World Trade Organization: Complex Agency and ‘Missing Delegation’

This paper analyses the World Trade Organization within a principal-agent framework. The concept of complex agency is introduced to focus on the variety of actors that comprise an international organization. Special attention is paid to the relationship between contracting parties’ representatives and the Secretariat. In the empirical part, the paper analyses the role of the Secretariat in assisting negotiations and presents evidence of declining influence. It is shown how principal-agent theory can contribute to addressing this ‘puzzle of missing delegation’. The paper concludes with a cautionary note as to the ‘location’ of international organizations’ emerging pathologies and calls for additional research to address the relationship between material and social sources to explain behaviour of the key actors within the complex agency.

The missing link between clinical states and biomarkers in mental disorders

Current diagnostic definitions of psychiatric disorders based on collections of symptoms encompass very heterogeneous populations and are thus likely to yield spurious results when exploring biological correlates of mental disturbances. It has been suggested that large studies of biomarkers across diagnostic entities may yield improved clinical information. Such a view is based on the concept of assessment as a collection of symptoms devoid of any clinical judgment and interpretation. Yet, important advances have been made in recent years in clinimetrics, the science of clinical judgment. The current clinical taxonomy in psychiatry, which emphasizes reliability at the cost of clinical validity, does not include effects of comorbid conditions, timing of phenomena, rate of progression of an illness, responses to previous treatments, and other clinical distinctions that demarcate major prognostic and therapeutic differences among patients who otherwise seem to be deceptively similar since they share the same psychiatric diagnosis. Clinimetrics may provide the missing link between clinical states and biomarkers in psychiatry, building pathophysiological bridges from clinical manifestations to their neurobiological counterparts.

Search for supersymmetry in events with photons, bottom quarks, and missing transverse momentum in proton-proton collisions at a centre-of-mass energy of 7 TeV with the ATLAS detector

A search has been performed for the experimental signature of an isolated photon with high transverse momentum, at least one jet identified as originating from a bottom quark, and high missing transverse momentum. Such a final state may originate from supersymmetric models with gauge-mediated supersymmetry breaking in events in which one of a pair of higgsino-like neutralinos decays into a photon and a gravitino while the other decays into a Higgs boson and a gravitino. The search is performed using the full dataset of 7 TeV proton-proton collisions recorded with the ATLAS detector at the LHC in 2011, corresponding to an integrated luminosity of 4.7 fb(-1). A total of 7 candidate events are observed while 7.5 +/- 2.2 events are expected from the Standard Model background. The results of the search are interpreted in the context of general gauge mediation to exclude certain regions of a benchmark plane for higgsino-like neutralino production.

Search for dark matter candidates and large extra dimensions in events with a photon and missing transverse momentum in pp collision data at sqrts=7 TeV w the ATLAS detector

Results of a search for new phenomena in events with an energetic photon and large missing transverse momentum in proton-proton collisions at root s = 7 TeV are reported. Data collected by the ATLAS experiment at the LHC corresponding to an integrated luminosity of 4.6 fb(-1) are used. Good agreement is observed between the data and the standard model predictions. The results are translated into exclusion limits on models with large extra spatial dimensions and on pair production of weakly interacting dark matter candidates.

Search for direct slepton and gaugino production in final states with two leptons and missing transverse momentum with the ATLAS detector in pp collisions at sqrts=7 TeV

A search for the electroweak pair production of charged sleptons and weak gauginos decaying into final states with two leptons is performed using 4.7 fb(-1) of proton-proton collision data at root s = 7 TeV recorded with the ATLAS experiment at the Large Hadron Collider. No significant excesses are observed with respect to the prediction from Standard Model processes. In the scenario of direct slepton production, if the sleptons decay directly into the lightest neutralino, left-handed slepton masses between 85 and 195 GeV are excluded at 95% confidence level for a 20 GeV neutralino. Chargino masses between 110 and 340 GeV are excluded in the scenario of direct production of wino-like chargino pairs decaying into the lightest neutralino via an intermediate on-shell charged slepton for a 10 GeV neutralino. The results are also interpreted in the framework of the phenomenological minimal supersymmetric Standard Model.