Multi-stakeholder consensus on a target product profile for an HIV cure

Developing a cure for HIV is a global priority. Target product profiles are a tool commonly used throughout the drug development process to align interested parties around a clear set of goals or requirements for a potential product. Three distinct therapeutic modalities (combination therapies, ex-vivo gene therapy, and in-vivo gene therapy) for a target product profile for an HIV cure were identified. Using a process of expert face-to-face consultation and an online Delphi consultation, we found a high degree of agreement regarding the criteria for the optimum target product profile. Although the minimum attributes for a cure were debated, the broad consensus was that an acceptable cure need not be as safe and effective as optimally delivered antiretroviral therapy. An intervention that successfully cured a reasonable fraction of adults would be sufficient to advance to the clinic. These target product profiles will require further discussion and ongoing revisions as the field matures

Reproductive life disorders in Italian celiac women. A case-control study

BACKGROUND: The aim of this study is to explore the association between celiac disease and menstrual cycle, gestation and puerperal disorders. METHODS: The association between celiac disease and menstrual cycle, gestation and puerperal disorders in a sample of 62 childbearing age women (15-49 age) was assessed within an age and town of residence matched case-control study conducted in 2008. Main outcome measures were the presence of one or more disorders in menstrual cycle and the presence of one or more complication during pregnancy. RESULTS: 62 celiac women (median age: 31.5, range: 17-49) and 186 healthy control (median age: 32.5, range: 15-49) were interviewed. A higher percentage of menstrual cycle disorders has been observed in celiac women. 19.4% frequency of amenorrhea was reported among celiac women versus 2.2% among healthy controls (OR = 33, 95% CI = 7.17-151.8;, p = 0.000). An association has been observed between celiac disease and oligomenorrhea, hypomenorrhea, dysmenorrhea and metrorrhagia (p < 0.05). The likelihood of having at least one complication during pregnancy has been estimated to be at least four times higher in celiac women than in healthy women (OR = 4.1, 95% CI = 2-8.6, p = 0.000). A significant correlation has emerged for celiac disease and threatened abortion, gestational hypertension, placenta abruption, severe anaemia, uterine hyperkinesia, intrauterine growth restriction (p < 0.001). A shorter gestation has on average been observed in celiac women together with a lower birth weight of celiac women babies (p < 0.001). CONCLUSIONS: The occurrence of a significant correlation between celiac disease and reproductive disorders could suggest to consider celiac disease diagnostic procedures (serological screening) in women affected by these disorders

Febrile seizures and mechanisms of epileptogenesis: insights from an animal model.

Temporal lobe epilepsy (TLE) is the most prevalent type of human epilepsy, yet the causes for its development, and the processes involved, are not known. Most individuals with TLE do not have a family history, suggesting that this limbic epilepsy is a consequence of acquired rather than genetic causes. Among suspected etiologies, febrile seizures have frequently been cited. This is due to the fact that retrospective analyses of adults with TLE have demonstrated a high prevalence (20--&gt;60%) of a history of prolonged febrile seizures during early childhood, suggesting an etiological role for these seizures in the development of TLE. Specifically, neuronal damage induced by febrile seizures has been suggested as a mechanism for the development of mesial temporal sclerosis, the pathological hallmark of TLE. However, the statistical correlation between febrile seizures and TLE does not necessarily indicate a causal relationship. For example, preexisting (genetic or acquired) 'causes' that result independently in febrile seizures and in TLE would also result in tight statistical correlation. For obvious reasons, complex febrile seizures cannot be induced in the human, and studies of their mechanisms and of their consequences on brain molecules and circuits are severely limited. Therefore, an animal model was designed to study these seizures. The model reproduces the fundamental key elements of the human condition: the age specificity, the physiological temperatures seen in fevers of children, the length of the seizures and their lack of immediate morbidity. Neuroanatomical, molecular and functional methods have been used in this model to determine the consequences of prolonged febrile seizures on the survival and integrity of neurons, and on hyperexcitability in the hippocampal-limbic network. Experimental prolonged febrile seizures did not lead to death of any of the seizure-vulnerable populations in hippocampus, and the rate of neurogenesis was also unchanged. Neuronal function was altered sufficiently to promote synaptic reorganization of granule cells, and transient and long-term alterations in the expression of specific genes were observed. The contribution of these consequences of febrile seizures to the epileptogenic process is discussed

Burden of acute otitis media in primary care pediatrics in Italy: A secondary data analysis from the Pedianet database

Background: The incidence of acute otitis media (AOM) vary from country to country. Geographical variations together with differences in study designs, reporting and settings play a role. We assessed the incidence of AOM in Italian children seen by primary care paediatricians (PCPs), and described the methods used to diagnose the disease.Methods: This secondary data analysis from the Pedianet database considered children aged 0 - 6 years between 01/2003 and 12/2007. The AOM episodes were identified and validated by means of patient diaries. Incidence rates/100 person-years (PY) were calculated for total AOM and for single or recurrent AOM.Results: The 92,373 children (52.1% males) were followed up for a total of 227,361 PY: 23,039 (24.9%) presented 38,241 episodes of AOM (94.6% single episodes and 5.4% recurrent episodes). The total incidence rate of AOM in the 5-year period was 16.8 episodes per 100 PY (95% CI: 16.7-16.9), including single AOM (15.9 episodes per 100 PY; 95% CI: 15.7-16.1) and recurrent AOM (0.9 episodes per 100 PY; 95% CI: 0.9-0.9). There was a slight and continuously negative trend decrease over time (annual percent change -4.6%; 95%CI: -5.3, -3.9%). The AOM incidence rate varied with age, peaking in children aged 3 to 4 years (22.2 episodes per 100 PY; 95% CI 21.8-22.7). The vast majority of the AOM episodes (36,842/38,241, 96.3%) were diagnosed using a static otoscope; a pneumatic otoscope was used in only 3.7%.Conclusions: Our data fill a gap in our knowledge of the incidence of AOM in Italy, and indicate that AOM represents a considerable burden for the Italian PCP system. Educational programmes concerning the diagnosis of AOM are needed, as are further studies to monitor the incidence in relation to the introduction of wider pneumococcal conjugate vaccines

Development and psychometric properties of a belief-based Physical Activity Questionnaire for Diabetic Patients (PAQ-DP)

<p>Abstract</p> <p>Background</p> <p>This study carried out to develop a scale for assessing diabetic patients' perceptions about physical activity and to test its psychometric properties (The Physical Activity Questionnaire for Diabetic Patients-PAQ-DP).</p> <p>Methods</p> <p>An item pool extracted from the Theory of Planned Behavior literature was generated. Then an expert panel evaluated the items by assessing content validity index and content validity ratio. Consequently exploratory factor analysis (EFA) was performed to indicate the scale constructs. In addition reliability analyses including internal consistency and test-retest analysis were carried out.</p> <p>Results</p> <p>In all a sample of 127 women with diabetes participated in the study. Twenty-two items were initially extracted from the literature. A six-factor solution (containing 19 items) emerged as a result of an exploratory factor analysis namely: instrumental attitude, subjective norm, perceived behavioral control, affective attitude, self-identity, and intention explaining 60.30% of the variance observed. Additional analyses indicated satisfactory results for internal consistency (Cronbach's alpha ranging from 0.54 to 0.8) and intraclass correlation coefficients (ranging from 0.40 to 0.92).</p> <p>Conclusions</p> <p>The Physical Activity Questionnaire for Diabetic Patients (PAQ-DP) is the first instrument that applies the Theory of Planned Behavior in its constructs. The findings indicated that the PAQ-DP is a reliable and valid measure for assessing physical activity perceptions and now is available and can be used in future studies.</p

Gender Nonconformity During Adolescence:Links with Stigma, Sexual Minority Status, and Psychosocial Outcomes

Both gender nonconformity and sexual minority status during adolescence are associated with elevated levels of victimization and harassment, experiences that have serious consequences for adolescent psychosocial outcomes. While gender nonconformity and sexual minority status reflect separate constructs, they are associated because (1) sexual minority youth report higher levels of gender nonconformity and (2) gender nonconformity is frequently used to attribute sexual minority status by others. Following from classic stigma theory, the current chapter focuses on the role of gender nonconformity in explaining variation in social exclusion and victimization among both sexual minority and sexual majority youth. Of particular interest is the potential for gender nonconformity to mediate or moderate the association between sexual minority status and individual mental health and wellbeing outcomes. Gender differences will also be discussed, focusing on differences between girls and boys in the links between sexual minority status, gender nonconformity, experiences of victimization, and negative psychosocial outcomes. Additionally, the emerging literature on conceptualizing gender nonconformity among trans and non-binary youth will be addressed. Finally, the current chapter will finish with a discussion of how and why gender nonconformity must be taken into consideration in the development of programs aimed at reducing homophobia among adolescent populations

User's perspectives of barriers and facilitators to implementing quality colonoscopy services in Canada: a study protocol

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) represents a serious and growing health problem in Canada. Colonoscopy is used for screening and diagnosis of symptomatic or high CRC risk individuals. Although a number of countries are now implementing quality colonoscopy services, knowledge synthesis of barriers and facilitators perceived by healthcare professionals and patients during implementation has not been carried out. In addition, the perspectives of various stakeholders towards the implementation of quality colonoscopy services and the need of an efficient organisation of such services have been reported in the literature but have not been synthesised yet. The present study aims to produce a comprehensive synthesis of actual knowledge on the barriers and facilitators perceived by all stakeholders to the implementation of quality colonoscopy services in Canada.</p> <p>Methods</p> <p>First, we will conduct a comprehensive review of the scientific literature and other published documentation on the barriers and facilitators to implementing quality colonoscopy services. Standardised literature searches and data extraction methods will be used. The quality of the studies and their relevance to informing decisions on colonoscopy services implementation will be assessed. For each group of users identified, barriers and facilitators will be categorised and compiled using narrative synthesis and meta-analytical techniques. The principle factors identified for each group of users will then be validated for its applicability to various Canadian contexts using the Delphi study method. Following this study, a set of strategies will be identified to inform decision makers involved in the implementation of quality colonoscopy services across Canadian jurisdictions.</p> <p>Discussion</p> <p>This study will be the first to systematically summarise the barriers and facilitators to implementation of quality colonoscopy services perceived by different groups and to consider the local contexts in order to ensure the applicability of this knowledge to the particular realities of various Canadian jurisdictions. Linkages with strategic partners and decision makers in the realisation of this project will favour the utilisation of its results to support strategies for implementing quality colonoscopy services and CRC screening programs in the Canadian health system.</p

Mathematical Modeling and Simulation of Ventricular Activation Sequences: Implications for Cardiac Resynchronization Therapy

Next to clinical and experimental research, mathematical modeling plays a crucial role in medicine. Biomedical research takes place on many different levels, from molecules to the whole organism. Due to the complexity of biological systems, the interactions between components are often difficult or impossible to understand without the help of mathematical models. Mathematical models of cardiac electrophysiology have made a tremendous progress since the first numerical ECG simulations in the 1960s. This paper briefly reviews the development of this field and discusses some example cases where models have helped us forward, emphasizing applications that are relevant for the study of heart failure and cardiac resynchronization therapy