Major challenges in clinical management of TB/HIV co-infected patients in Eastern Europe compared with Western Europe and Latin America.

INTRODUCTION Rates of both TB/HIV co-infection and multi-drug-resistant (MDR) TB are increasing in Eastern Europe (EE). Data on the clinical management of TB/HIV co-infected patients are scarce. Our aim was to study the clinical characteristics of TB/HIV patients in Europe and Latin America (LA) at TB diagnosis, identify factors associated with MDR-TB and assess the activity of initial TB treatment regimens given the results of drug-susceptibility tests (DST). MATERIAL AND METHODS We enrolled 1413 TB/HIV patients from 62 clinics in 19 countries in EE, Western Europe (WE), Southern Europe (SE) and LA from January 2011 to December 2013. Among patients who completed DST within the first month of TB therapy, we linked initial TB treatment regimens to the DST results and calculated the distribution of patients receiving 0, 1, 2, 3 and ≥4 active drugs in each region. Risk factors for MDR-TB were identified in logistic regression models. RESULTS Significant differences were observed between EE (n=844), WE (n=152), SE (n=164) and LA (n=253) for use of combination antiretroviral therapy (cART) at TB diagnosis (17%, 40%, 44% and 35%, p<0.0001), a definite TB diagnosis (culture and/or PCR positive for Mycobacterium tuberculosis; 47%, 71%, 72% and 40%, p<0.0001) and MDR-TB prevalence (34%, 3%, 3% and 11%, p <0.0001 among those with DST results). The history of injecting drug use [adjusted OR (aOR) = 2.03, (95% CI 1.00-4.09)], prior TB treatment (aOR = 3.42, 95% CI 1.88-6.22) and living in EE (aOR = 7.19, 95% CI 3.28-15.78) were associated with MDR-TB. For 569 patients with available DST, the initial TB treatment contained ≥3 active drugs in 64% of patients in EE compared with 90-94% of patients in other regions (Figure 1a). Had the patients received initial therapy with standard therapy [Rifampicin, Isoniazid, Pyrazinamide, Ethambutol (RHZE)], the corresponding proportions would have been 64% vs. 86-97%, respectively (Figure 1b). CONCLUSIONS In EE, TB/HIV patients had poorer exposure to cART, less often a definitive TB diagnosis and more often MDR-TB compared to other parts of Europe and LA. Initial TB therapy in EE was sub-optimal, with less than two-thirds of patients receiving at least three active drugs, and improved compliance with standard RHZE treatment does not seem to be the solution. Improved management of TB/HIV patients requires routine use of DST, initial TB therapy according to prevailing resistance patterns and more widespread use of cART.

Reproducibility and accuracy of linear measurements on dental models derived from cone-beam computed tomography compared with digital dental casts.

INTRODUCTION The aim of this study was to determine the reproducibility and accuracy of linear measurements on 2 types of dental models derived from cone-beam computed tomography (CBCT) scans: CBCT images, and Anatomodels (InVivoDental, San Jose, Calif); these were compared with digital models generated from dental impressions (Digimodels; Orthoproof, Nieuwegein, The Netherlands). The Digimodels were used as the reference standard. METHODS The 3 types of digital models were made from 10 subjects. Four examiners repeated 37 linear tooth and arch measurements 10 times. Paired t tests and the intraclass correlation coefficient were performed to determine the reproducibility and accuracy of the measurements. RESULTS The CBCT images showed significantly smaller intraclass correlation coefficient values and larger duplicate measurement errors compared with the corresponding values for Digimodels and Anatomodels. The average difference between measurements on CBCT images and Digimodels ranged from -0.4 to 1.65 mm, with limits of agreement values up to 1.3 mm for crown-width measurements. The average difference between Anatomodels and Digimodels ranged from -0.42 to 0.84 mm with limits of agreement values up to 1.65 mm. CONCLUSIONS Statistically significant differences between measurements on Digimodels and Anatomodels, and between Digimodels and CBCT images, were found. Although the mean differences might be clinically acceptable, the random errors were relatively large compared with corresponding measurements reported in the literature for both Anatomodels and CBCT images, and might be clinically important. Therefore, with the CBCT settings used in this study, measurements made directly on CBCT images and Anatomodels are not as accurate as measurements on Digimodels.

Orthodontic retention procedures in Switzerland.

OBJECTIVE To survey retention procedures used in orthodontic practices in Switzerland. MATERIAL AND METHODS A questionnaire previously developed by Renkema et al. (2009) was sent to 223 Swiss orthodontists. The questionnaire comprised six parts, mainly containing multiple-choice questions. Information as to background education of the individual orthodontist, retention in general, frequency of different types of removable or bonded retainers that were used, retention pro- tocol, and the type and size of the wire used for bonded retainers was assessed. RESULTS The overall response rate was 65 percent. Most orthodontists placed a bonded retainer in the upper and lower arch, except when the upper arch was expanded during treatment or when extractions were performed in the upper arch, in which case they placed a combination of fixed and removable retainers. Opinions varied with regard to how many hours the removable retainers should be worn and the duration of the retention phase. As far as bonded retainers were concerned, 87 percent of the orthodontists preferred life-long retention. Ninety-three percent of the orthodontists considered that the development of a guide- line on retention procedures would be useful. CONCLUSIONS The choice of retention procedures is mostly based on orthodontists personal preference. A further research into the long-term effectiveness of individual retention protocols is needed.

Late diagnosis of fucosidosis in a child with progressive fixed dystonia, bilateral pallidal lesions and red spots on the skin

Fucosidosis is a rare lysosomal storage disease. A 14-year-old girl is presented, with recurrent infections, progressive dystonic movement disorder and mental retardation with onset in early childhood. The clinical picture was also marked by mild morphologic features, but absent dysostosis multiplex and organomegaly. MRI images at 6.5 years of age were reminiscent of pallidal iron deposition ("eye-of-the-tiger" sign) seen in neurodegeneration with brain iron accumulation (NBIA) disorders. Progressively spreading angiokeratoma corporis diffusum led to the correct diagnosis. This case extends the scope of clinical and neuroradiological manifestations of fucosidosis.

Perception of critical situations involving football fans: dynamics of conflict escalation and de-escalation

Title: The perception of critical situations involving football fans – how conflicts escalate or de-escalate Authors: Brechbühl, A.1, Schumacher, A.1 & Seiler, R.1 1Institute of Sport Science, University of Bern, Switzerland Abstract: Introduction: Fan violence in the context of football matches is a prominent issue in today’s western societies and Switzerland presents no exception. A lot of research has been conducted on reasons for fan violence, mostly with fans of national teams. A prominent model is the Elaborated Social Identity Model (ESIM; Drury & Reicher, 2000): ESIM highlights the importance of interactions between the involved groups and their effect on the development of social identities. Another model is the aggravation mitigation model (AM model; Hylander & Guvå, 2010) which illustrates factors that can contribute towards an escalation or non-escalation of group violence, such as the “categorization” of the opponent group. Despite these models, research about the individual perceptions, and in particular, what factors distinguish between an escalation versus a non-escalation of a potentially violent situation in domestic football, is as yet scarce. This explorative study examines perceptions of critical situations in the domestic football fan context in Switzerland. Methods: An explorative qualitative design was employed to gather data about critical situations (CS) around football matches of two clubs of the Raiffeisen Super League. A CS is defined as a setting in or around the football stadium where violence between football fans and another group could occur. Eight CS were identified and analysed. Fifty-nine narrative interviews with individuals involved in a CS, e.g. fans, police officers or security personnel, were conducted. Interviews were analysed using interpretative phenomenological analysis (IPA). Results: The involved opposing groups expressed group-specific perceptions. Furthermore a strong tendency to negatively stereotype the opponent group was observed. Provocative symbols, such as balaclavas or riot-gear uniforms, were considered as highly relevant for the interpretation of the situation. Successful communication and sufficient distance between opponent groups supported the appeasement of a CS. These findings also underline the importance of knowledge about the local fan culture. This culture serves as basis for the perception of legitimacy, which was assessed to be essential for a de-escalation of a CS by fans. Discussion/Conclusion: This study improves the understanding of fan violence in the domestic football context in Switzerland. Based on the results it is suggested to deploy security or police forces without riot gear but with the goal of seeking dialogue with the fans to increase the likelihood of a peaceful ending in a CS. The findings also support the applicability of the ESIM (Drury & Reicher, 2000) and the AM model (Hylander & Guvå, 2010) in the context of domestic fan violence. Due to possible differences in the local fan cultures in Switzerland, research in this area should be continued. References: Drury, J., & Reicher, S. (2000). Collective action and psychological change: The emergence of new social identities. British Journal of Social Psychology, 39, 579-604. Hylander, I., & Guvå, G. (2010). Misunderstanding of out-group behaviour: Different interpretations of the same crowd events among police officers and demonstrators. Nordic Psychology, 62, 25-47.

STARTVerso1: A randomized trial of faldaprevir plus pegylated interferon/ribavirin for chronic HCV genotype-1 infection.

BACKGROUND & AIMS The efficacy and tolerability of faldaprevir, a potent hepatitis C virus (HCV) NS3/4A protease inhibitor, plus peginterferon and ribavirin was assessed in a double-blind, placebo-controlled phase 3 study of treatment-naïve patients with HCV genotype-1 infection. METHODS Patients were randomly assigned (1:2:2) to peginterferon/ribavirin plus: placebo (arm 1, n=132) for 24 weeks; faldaprevir (120 mg, once daily) for 12 or 24 weeks (arm 2, n=259); or faldaprevir (240 mg, once daily) for 12 weeks (arm 3, n=261). In arms 2 and 3, patients with early treatment success (HCV RNA <25 IU/mL at week 4 and undetectable at week 8) stopped all treatment at week 24. Other patients received peginterferon/ribavirin until week 48 unless they met futility criteria. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS SVR12 was achieved by 52%, 79%, and 80% of patients in arms 1, 2, and 3, respectively (estimated difference for arms 2 and 3 versus arm 1: 27%, 95% confidence interval 17%-36%; and 29%, 95% confidence interval, 19%-38%, respectively; P<.0001 for both). Early treatment success was achieved by 87% (arm 2) and 89% (arm 3) of patients, of whom 86% and 89% achieved SVR12. Adverse event rates were similar among groups; few adverse events led to discontinuation of all regimen components. CONCLUSIONS Faldaprevir plus peginterferon/ribavirin significantly increased SVR12, compared with peginterferon/ribavirin, in treatment-naïve patients with HCV genotype-1 infection. There do not seem to be any differences in responses of patients given once-daily 120 or 240 mg faldaprevir.

Body composition and all-cause mortality in subjects older than 65 y.

BACKGROUND A low or high body mass index (BMI) has been associated with increased mortality risk in older subjects without taking fat mass index (FMI) and fat-free mass index (FFMI) into account. This information is essential because FMI is modulated through different healthcare strategies than is FFMI. OBJECTIVE We aimed to determine the relation between body composition and mortality in older subjects. DESIGN We included all adults ≥65 y old who were living in Switzerland and had a body-composition measurement by bioelectrical impedance analysis at the Geneva University Hospitals between 1990 and 2011. FMI and FFMI were divided into sex-specific quartiles. Quartile 1 (i.e., the reference category) corresponded to the lowest FMI or FFMI quartile. Mortality data were retrieved from the hospital database, the Geneva death register, and the Swiss National Cohort until December 2012. Comorbidities were assessed by using the Cumulative Illness Rating Scale. RESULTS Of 3181 subjects included, 766 women and 1007 men died at a mean age of 82.8 and 78.5 y, respectively. Sex-specific Cox regression models, which were used to adjust for age, BMI, smoking, ambulatory or hospitalized state, and calendar time, showed that body composition did not predict mortality in women irrespective of whether comorbidities were taken into account. In men, risk of mortality was lower with FFMI in quartiles 3 and 4 [HR: 0.78 (95% CI: 0.62, 0.98) and 0.64 (95% CI: 0.49, 0.85), respectively] but was not affected by FMI. When comorbidities were adjusted for, FFMI in quartile 4 (>19.5 kg/m(2)) still predicted a lower risk of mortality (HR: 0.72; 95% CI: 0.54, 0.96). CONCLUSIONS Low FFMI is a stronger predictor of mortality than is BMI in older men but not older women. FMI had no impact on mortality. These results suggest potential benefits of preventive interventions with the aim of maintaining muscle mass in older men. This trial was registered at clinicaltrials.gov as NCT01472679.

Immune-Deficient Drosophila melanogaster: A Model for the Innate Immune Response to Human Fungal Pathogens

We explored the host-pathogen interactions of the human opportunistic fungus Candida albicans using Drosophila melanogaster. We established that a Drosophila strain devoid of functional Toll receptor is highly susceptible to the human pathogen C. albicans. Using this sensitive strain, we have been able to show that a set of specific C. albicans mutants of different virulence in mammalian infection models are also impaired in virulence in Drosophila and remarkably display the same rank order of virulence. This immunodeficient insect model also revealed virulence properties undetected in an immunocompetent murine model of infection. The genetic systems available in both host and pathogen will enable the identification of host-specific components and C. albicans genes involved in the host-fungal interplay.

The role of self-monitoring of blood glucose in patients treated with SGLT-2 inhibitors: a European expert recommendation.

The role for the novel treatment approach of sodium-glucose cotransporter-2 (SGLT-2) in type 2 diabetes is increasing. Structured self-monitoring of blood glucose (SMBG), based on a less intensive and a more intensive scheme, may contribute to an optimization of SGLT-2 inhibitor based treatment. The current expert recommendation suggests individualized approaches of SMBG, using simple and clinically applicable schemes. Potential benefits of SMBG in SGLT-2 inhibitor based treatment approaches are early assessment of treatment success or failure, timely modification of treatment, detection of hypoglycemic episodes, assessment of glucose excursions, and support of diabetes management and education. The length and frequency of SMBG should depend on the clinical setting and the quality of metabolic control.

Perceptions of critical situations involving football fans: the dynamics of conflict escalation or de-escalation

Fan violence in the context of football matches has drawn the attention of stakeholders and the media. This phenomenon has also attracted the scientific community’s attention, where research mostly focused on reasons for violence escalation. The Elaborated Social Identity Model (ESIM; Drury & Reicher, 2000) for example focuses on group-interactions and social identities, while the Aggravation Mitigation Model (AM model; Hylander & Guvå, 2010) concentrates on factors contributing to an escalation or a non-escalation of group-violence. However individual perceptions of the different persons involved in potential conflicts have not been sufficiently examined. Beside of that research in domestic football or involving ultrafans is scarce. Especially in Switzerland, there is a lack of research concerning the dynamics of the development or non-development of fan violence. This exploratory study included eight critical situations from the season 2012/2013 of the Swiss premier league to gather data about the perceptions of various persons involved (fans, police officers or security) and the dynamics contributing towards escalation or de-escalation. Fifty-nine narrative interviews were conducted and analysed with interpretative phenomenological analysis (Smith, Flowers, & Larkin, 2009). The individuals involved (fans, police and security personnel) showed groupspecific perceptions and a tendency to stereotype the opponent group. Provocative symbols (balaclavas or riot-gear uniforms) were important for the interpretation of the situation. No escalation occurred when successful communication and sufficient distance between the groups was established. Knowledge about the local fan culture is important, because it influences the perception of legitimacy on the side of the fans. This study improves the understanding of fan violence and is congruent with the ESIM and the AM model. It is suggested to deploy police dialogue teams without riot gear. Their task is to establish direct communication with the fans to facilitate a peaceful ending of a critical situation.

Identifying observable criteria defining a critical situation involving football fans: an expert focus group study

Critical situations (CSs) involving football fans is a well-researched phenomenon with most studies examining factors leading to an escalation of violence (e.g. Braun & Vliegenthart, 2008). However, research so far has fallen short of analysing CSs that do not escalate (e.g. Hylander & Guvå, 2010) as well as establishing observable criteria that constitute such CSs. Granström et al. (2009), for instance, put forward a definition of a CS describing such situations as characterised by a discrepancy between peace and war-making behaviours between police and demonstrators. Still, this definition remains vague and does not provide concrete, defining criteria that can be identified on site. The present study looks beyond fans’ violent acts per se and focuses on these situations with a potentially – but not necessarily - violent outcome. The aim of this preliminary study is to identify observable criteria defining such a CS involving football fans. This focus group comprised of five experts working with football fans in the German-speaking area of Switzerland who discussed observable characteristics of a CS. Inductive content analysis led to the identification of specific criteria such as, “arrest of a fan”, “insufficient distance (<30m) between fans and police” and “fans mask themselves”. These criteria were then assigned to four phases of a CS highlighting the dynamic aspect of this phenomenon: Antecedents, Causes, Reactions, Consequence. Specifically, Causes, Reactions and Consequences are observable on site, while Antecedents include relevant, background information directly influencing a CS. This study puts forward a working definition of a CS that can facilitate the assessment of actual situations in the football context as well as for further research on fan violence prevention and control. These results also highlight similarities with studies investigating fan violence in other European countries while acknowledging unique characteristics of the Swiss German fan culture.

Major Challenges in Clinical Management of TB/HIV Coinfected Patients in Eastern Europe Compared with Western Europe and Latin America.

OBJECTIVES Rates of TB/HIV coinfection and multi-drug resistant (MDR)-TB are increasing in Eastern Europe (EE). We aimed to study clinical characteristics, factors associated with MDR-TB and predicted activity of empiric anti-TB treatment at time of TB diagnosis among TB/HIV coinfected patients in EE, Western Europe (WE) and Latin America (LA). DESIGN AND METHODS Between January 1, 2011, and December 31, 2013, 1413 TB/HIV patients (62 clinics in 19 countries in EE, WE, Southern Europe (SE), and LA) were enrolled. RESULTS Significant differences were observed between EE (N = 844), WE (N = 152), SE (N = 164), and LA (N = 253) in the proportion of patients with a definite TB diagnosis (47%, 71%, 72% and 40%, p<0.0001), MDR-TB (40%, 5%, 3% and 15%, p<0.0001), and use of combination antiretroviral therapy (cART) (17%, 40%, 44% and 35%, p<0.0001). Injecting drug use (adjusted OR (aOR) = 2.03 (95% CI 1.00-4.09), prior anti-TB treatment (3.42 (1.88-6.22)), and living in EE (7.19 (3.28-15.78)) were associated with MDR-TB. Among 585 patients with drug susceptibility test (DST) results, the empiric (i.e. without knowledge of the DST results) anti-TB treatment included ≥3 active drugs in 66% of participants in EE compared with 90-96% in other regions (p<0.0001). CONCLUSIONS In EE, TB/HIV patients were less likely to receive a definite TB diagnosis, more likely to house MDR-TB and commonly received empiric anti-TB treatment with reduced activity. Improved management of TB/HIV patients in EE requires better access to TB diagnostics including DSTs, empiric anti-TB therapy directed at both susceptible and MDR-TB, and more widespread use of cART.