Vitamin D time profile based on the contribution of non-genetic and genetic factors in HIV-infected individuals of European ancestry.

BACKGROUND: Vitamin D deficiency is prevalent in HIV-infected individuals and vitamin D supplementation is proposed according to standard care. This study aimed at characterizing the kinetics of 25(OH)D in a cohort of HIV-infected individuals of European ancestry to better define the influence of genetic and non-genetic factors on 25(OH)D levels. These data were used for the optimization of vitamin D supplementation in order to reach therapeutic targets. METHODS: 1,397 25(OH)D plasma levels and relevant clinical information were collected in 664 participants during medical routine follow-up visits. They were genotyped for 7 SNPs in 4 genes known to be associated with 25(OH)D levels. 25(OH)D concentrations were analysed using a population pharmacokinetic approach. The percentage of individuals with 25(OH)D concentrations within the recommended range of 20-40 ng/ml during 12 months of follow-up and several dosage regimens were evaluated by simulation. RESULTS: A one-compartment model with linear absorption and elimination was used to describe 25(OH)D pharmacokinetics, while integrating endogenous baseline plasma concentrations. Covariate analyses confirmed the effect of seasonality, body mass index, smoking habits, the analytical method, darunavir/ritonavir and the genetic variant in GC (rs2282679) on 25(OH)D concentrations. 11% of the inter-individual variability in 25(OH)D levels was explained by seasonality and other non-genetic covariates, and 1% by genetics. The optimal supplementation for severe vitamin D deficient patients was 300,000 IU two times per year. CONCLUSIONS: This analysis allowed identifying factors associated with 25(OH)D plasma levels in HIV-infected individuals. Improvement of dosage regimen and timing of vitamin D supplementation is proposed based on those results.

Incidence and Risk Factors of Abdominal Complications After Lung Transplantation.

BACKGROUND: Due to the underlying diseases and the need for immunosuppression, patients after lung transplantation are particularly at risk for gastrointestinal (GI) complications that may negatively influence long-term outcome. The present study assessed the incidences and impact of GI complications after lung transplantation and aimed to identify risk factors. METHODS: Retrospective analysis of all 227 consecutively performed single- and double-lung transplantations at the University hospitals of Lausanne and Geneva was performed between January 1993 and December 2010. Logistic regressions were used to test the effect of potentially influencing variables on the binary outcomes overall, severe, and surgery-requiring complications, followed by a multiple logistic regression model. RESULTS: Final analysis included 205 patients for the purpose of the present study, and 22 patients were excluded due to re-transplantation, multiorgan transplantation, or incomplete datasets. GI complications were observed in 127 patients (62 %). Gastro-esophageal reflux disease was the most commonly observed complication (22.9 %), followed by inflammatory or infectious colitis (20.5 %) and gastroparesis (10.7 %). Major GI complications (Dindo/Clavien III-V) were observed in 83 (40.5 %) patients and were fatal in 4 patients (2.0 %). Multivariate analysis identified double-lung transplantation (p = 0.012) and early (1993-1998) transplantation period (p = 0.008) as independent risk factors for developing major GI complications. Forty-three (21 %) patients required surgery such as colectomy, cholecystectomy, and fundoplication in 6.8, 6.3, and 3.9 % of the patients, respectively. Multivariate analysis identified Charlson comorbidity index of ≥3 as an independent risk factor for developing GI complications requiring surgery (p = 0.015). CONCLUSION: GI complications after lung transplantation are common. Outcome was rather encouraging in the setting of our transplant center.

Impact of geographical and cultural factors on clinical trials in acute mania: lessons from a ziprasidone and haloperidol placebo-controlled study

Clinical trials today are conducted in multiple countries to enhance patient recruitment and improve efficiency of trials. However, the demographic and cultural diversity may contribute to variations in study outcomes. Here we conducted post-hoc analyses for a placebo-controlled study with ziprasidone and haloperidol for the treatment of acute mania to address the demographic, dosing, and outcome disparities in India, Russia and the USA. We compared the baseline characteristics, outcomes and discontinuations in patients and explored the relationship between the outcome measures across these countries. We found substantial differences in baseline characteristics of subjects, administered dosage and disease severity in India compared to the USA and Russia. Conversely, US subjects had a higher placebo response compared to subjects in Russia and India. These results are probably due to demographic differences in patient populations and psychiatric clinical practice across countries. While we offer initial ideas to address the disparities identified in this analysis, it is clear that further research to improve our understanding of geographical differences is essential to ensure globally applicable results for clinical trials in psychiatry.

Frequency of and Risk Factors for Depression among Participants in the Swiss HIV Cohort Study (SHCS).

OBJECTIVES: We studied the incidence and prevalence of, and co-factors for depression in the Swiss HIV Cohort Study. METHODS: Depression-specific items were introduced in 2010 and prospectively collected at semiannual cohort visits. Clinical, laboratory and behavioral co-factors of incident depression among participants free of depression at the first two visits in 2010 or thereafter were analyzed with Poisson regression. Cumulative prevalence of depression at the last visit was analyzed with logistic regression. RESULTS: Among 4,422 participants without a history of psychiatric disorders or depression at baseline, 360 developed depression during 9,348 person-years (PY) of follow-up, resulting in an incidence rate of 3.9 per 100 PY (95% confidence interval (CI) 3.5-4.3). Cumulative prevalence of depression during follow-up was recorded for 1,937/6,756 (28.7%) participants. Incidence and cumulative prevalence were higher in injection drug users (IDU) and women. Older age, preserved work ability and higher physical activity were associated with less depression episodes. Mortality (0.96 per 100 PY, 95% CI 0.83-1.11) based upon 193 deaths over 20,102 PY was higher among male IDU (2.34, 1.78-3.09), female IDU (2.33, 1.59-3.39) and white heterosexual men (1.32, 0.94-1.84) compared to white heterosexual women and homosexual men (0.53, 0.29-0.95; and 0.71, 0.55-0.92). Compared to participants free of depression, mortality was slightly elevated among participants with a history of depression (1.17, 0.94-1.45 vs. 0.86, 0.71-1.03, P = 0.033). Suicides (n = 18) did not differ between HIV transmission groups (P = 0.50), but were more frequent among participants with a prior diagnosis of depression (0.18 per 100 PY, 95%CI 0.10-0.31; vs. 0.04, 0.02-0.10; P = 0.003). CONCLUSIONS: Depression is a frequent co-morbidity among HIV-infected persons, and thus an important focus of care.

Perceptions of Alzheimer's Disease in the French Population : Evolutions between 2008 and 2013 and Associated Factors in 2013

Abstract: Background. The negative image surrounding AD has a substantial impact on caregiving and on those affected by the disease. Opinion surveys was created as part of the 2008-2012 Alzheimer Plan in France, which included two surveys in general population, at the beginning and at the end. Objective. To evaluate changes of the French population in perceptions, knowledge and beliefs since 5 years and to analyze dimensions with sociodemographics criteria and proximity with AD. Methods. After selection by quota sampling, 2013 French people aged 18 years and over were interviewed by phone in 2008 and 2509 in 2013. Chi-squared tests were carried out to measure the changes between two periods and multivariate logistics regressions were used to assess perceptions. Results. People who cited AD as one of the three most serious diseases increased in 2013 (33.6% versus 26.7% in 2008; p < 0.001). There was no significant change as regards the fear, the sense of being informed and the feeling of embarrassment. Opinions "there are treatments available to improve the wellbeing of patients" and "it is normal to suffer memory loss as you get older" decreased in 2013. Close family carers had a greater sense of the seriousness, a higher risk perception, a better sense of being informed and a greater ease in the presence of a person with AD. Conclusions. The results serve as indicators of the effects of the Alzheimer Plan on French society and testify to the rather weak impact of the Plan on public opinion.

Perceived Barriers to Physical Activity and Related Factors in Spanish University Students

Objective: The purpose of this study was to identify the influence of readiness of change for physical activity (PA), sociodemographic factors, lifestyle and physical activity status (PAS) on perceived barriers among Spanish university students. Participants: Seven hundred and seventy two (n = 772) men and women ages 17 - 39 at a north-west regional university in Spain participated in the study. Methods: The International Physical Activity Questionnaire, the States of Change for Physical Activity Behaviour Questionnaire and the Self-perceived Barriers for Physical Activity Questionnaire were used. Description, correlation and multiple regression analyses were completed. Results: Participants self-perceived low average-score barriers (2.6 ± 1.4 over 10.0). The 3-higher scores barriers corresponded to “too much work”; “lack of time for exercise” and “laziness”. Gender, PAS and self-perceived health were shown to be associated with perceived barriers. Conclusions: University institutions should consider those factors that predict barriers to PA to develop effective intervention programs.

A retrospective study of deep sternal wound infections: clinical and microbiological characteristics, treatment, and risk factors for complications.

Deep sternal wound infection (DSWI) is a feared complication following cardiac surgery. This study describes clinical, microbiological, and treatment outcomes of DSWI and determines risk factors for complications. Of 55 patients with DSWI, 66% were male and mean age was 68.2years. Initial sternotomy was for coronary artery bypass graft in 49% of patients. Sternal debridement at mean 25.4±18.3days showed monomicrobial (94%), mainly Gram-positive infection. Secondary sternal wound infection (SSWI) occurred in 31% of patients, was mostly polymicrobial (71%), and was predominantly due to Gram-negative bacilli. Risk factors for SSWI were at least 1 revision surgery (odds ratio [OR] 4.8 [95% confidence interval {CI} 1.0-22.4], P=0.047), sternal closure by muscle flap (OR 4.6 [1.3-16.8], P=0.02), delayed sternal closure (mean 27 versus 14days, P=0.03), and use of vacuum-assisted closure device (100% versus 58%, P=0.008). Hospital stay was significantly longer in patients with SSWI (69days versus 48days, P=0.04).

Sharp mandibular bone irregularities after lower third molar extraction: Incidence, clinical features and risk factors

Objectives: The purpose of this study was to determine the incidence and clinical symptoms associated with sharp mandibular bone irregularities (SMBI) after lower third molar extraction and to identify possible risk factors for this complication. Study Design: A mixed study design was used. A retrospective cohort study of 1432 lower third molar extractions was done to determine the incidence of SMBI and a retrospective case-control study was done to determine potential demographic and etiologic factors by comparing those patients with postoperative SMBI with controls. Results: Twelve SMBI were found (0.84%). Age was the most important risk factor for this complication. The operated side and the presence of an associated radiolucent image were also significantly related to the development of mandibular bone irregularities. The depth of impaction of the tooth might also be an important factor since erupted or nearly erupted third molars were more frequent in the SMBI group. Conclusions: SMBI are a rare postoperative complication after lower third molar removal. Older patients having left side lower third molars removed are more likely to develop this problem. The treatment should be the removal of the irregularity when the patient is symptomatic

The influence of genetic and environmental factors among MDMA users in cognitive performance

This study is aimed to clarify the association between MDMA cumulative use and cognitive dysfunction, and the potential role of candidate genetic polymorphisms in explaining individual differences in the cognitive effects of MDMA. Gene polymorphisms related to reduced serotonin function, poor competency of executive control and memory consolidation systems, and high enzymatic activity linked to bioactivation of MDMA to neurotoxic metabolites may contribute to explain variations in the cognitive impact of MDMA across regular users of this drug. Sixty ecstasy polydrug users, 110 cannabis users and 93 non-drug users were assessed using cognitive measures of Verbal Memory (California Verbal Learning Test, CVLT), Visual Memory (Rey-Osterrieth Complex Figure Test, ROCFT), Semantic Fluency, and Perceptual Attention (Symbol Digit Modalities Test, SDMT). Participants were also genotyped for polymorphisms within the 5HTT, 5HTR2A, COMT, CYP2D6, BDNF, and GRIN2B genes using polymerase chain reaction and TaqMan polymerase assays. Lifetime cumulative MDMA use was significantly associated with poorer performance on visuospatial memory and perceptual attention. Heavy MDMA users (>100 tablets lifetime use) interacted with candidate gene polymorphisms in explaining individual differences in cognitive performance between MDMA users and controls. MDMA users carrying COMT val/val and SERT s/s had poorer performance than paired controls on visuospatial attention and memory, and MDMA users with CYP2D6 ultra-rapid metabolizers performed worse than controls on semantic fluency. Both MDMA lifetime use and gene-related individual differences influence cognitive dysfunction in ecstasy users.

Early relationship between very preterm infant and mother: The role of infant, maternal and dyadic factors

Pienipainoisen keskosen ja äidin varhainen suhde: Lapsen, äidin ja dyadisten muuttujien vaikutus Tämän tutkimuksen tavoitteena oli tutkia keskosvauvan ja äidin varhaista suhdetta. Tutkimuksessa selvitettiin myös vauvan itkukäyttäytymisen, vauvan sylissä olon ja äidin masentuneisuuden yhteyttä äidin ja keskosvauvan varhaiseen suhteeseen. Tutkimusryhmät koostuivat 32:sta (tutkimus I-II) ja 38:sta (tutkimus III-IV) keskosena syntyneestä vauvasta (syntymäpaino < 1501 g tai GI < 32 viikkoa) sekä 46:sta täysiaikaisena syntyneestä terveestä verrokkivauvasta. Lapsen ja äidin vuorovaikutusta arvioitiin 6 ja 12 kuukauden iässä (korjattu ikä) PCERAmenetelmällä. Äidin mielikuvia lapsestaan tutkittiin WMCI-haastattelulla, kun lapsi oli 12 kuukautta. Baby Day Diary -menetelmää käytettiin vauvan itkukäyttäytymisen ja sylissä olon keston mittaamisessa vauvan ollessa 5 kuukautta. Äidin masentuneisuutta arvioitiin EDPS-lomakkeella, kun lapsi oli 6 kuukautta. Tulokset osoittivat, että turvallisten kiintymyssuhdemielikuvien määrä tai vuorovaikutuksen laatu eivät keskosvauvan äideillä eronneet täysiaikaisina syntyneiden vauvojen äitien vastaavista. Ryhmien välillä ei löytynyt eroja myöskään dyadisen vuorovaikutuksen laadussa. Keskosena syntyneet lapset olivat kuitenkin vetäytyvämpiä ja heillä oli laadullisesti heikommat keskittymisen ja leikin taidot vuorovaikutustilanteessa 12 kuukauden iässä täysiaikaisina syntyneisiin lapsiin nähden. Lisäksi äidin masentuneisuus ja lapsen pitkittynyt itkuisuus olivat negatiivisessa yhteydessä vuorovaikutuksen laatuun keskosvauvojen ryhmässä. Vauvan itkukertojen määrän, sylissä olon keston sekä äidin ja vauvan vuorovaikutuksen laadun välillä löytyi positiivinen yhteys ainoastaan keskosena syntyneiden lasten ryhmässä. Tulostemme perusteelle toteamme, että lapsen ennenaikainen syntymä itsessään ei näytä muodostavan riskiä äidin vuorovaikutuksen laadulle tai turvalliselle kiintymyssuhteelle. Yhdessä muiden riskitekijöiden kanssa keskosuus kuitenkin altistaa vauvat ja heidän äitinsä varhaisen vuorovaikutuksen ongelmille. Lisäksi tuloksemme viittaavat siihen, että vauvan itku ja siitä seuraava sylissä olo toimivat suojaavana mekanismina pienipainoisen keskosen ja äidin varhaisessa suhteessa.

Critical Success and Failure Factors of Knowledge Management Implementation in a Large Multinational Company

More and more companies are interested in implementing knowledge management. However, the majority of knowledge management initiatives will fail to have any significant impact. In this study, theories regarding knowledge management implementation and adoption are investigated further. The objective of this study is to deepen understanding regarding the critical factors that contribute to successful knowledge management adoption in large multinational companies. The study is formulated around the following four research questions: 1. What are the key success and failure factors in knowledge management implementation? 2. How can knowledge management adoption be improved at the individual, group and organizational levels of the company? 3. What are the critical factors that hinder knowledge management adoption in the case company? 4. How can the case company promote the adoption of knowledge management among company personnel? The methodology used in this study is a combination of a literature review and an explanatory, exploratory, qualitative single-case study. The literature review answers the first and second research questions. Based on the literature review, a framework is presented to illustrate the factors contributing to the success of knowledge management implementation. The framework also links together knowledge management implementation and adoption. The third research question is answered by revealing the relevant findings from 21 expert interviews and 2 online questionnaires with 42 respondents in total. By comparing and contrasting the results of the literature review with the findings of the empirical case study, the fourth research question is answered. The concrete outcomes of this study are a framework to elucidate the factors contributing to the success of knowledge management implementation, a case study highlighting the issues that hinder knowledge management adoption within the case company, and recommendations for the case company.