Risk factors for fatal outcome in patients with opioid dependence treated with methadone in a family medicine setting in Croatia

Aim To determine the risk factors for fatal outcome in patients with opioid dependence treated with methadone at the primary care level. Methods A group of 287 patients with opioid dependence was monitored prospectively from 1995 to 2007. At the beginning of the study, we collected the data on patient baseline characteristics, treatment characteristics, and living environment. At the annual check-up, we collected the data on daily methadone dose, method of methadone therapy administration, and family physician’s assessment of the patient’s drug use status. Results Out of 287 patients, 8% died. Logistic regression analysis showed that the predictors of fatal outcome were continuation of drug use during previous therapeutic attempts (odds ratio [OR], 19.402; 95% confidence interval [CI], 1.659-226.873), maintenance therapy as the planned treatment modality (OR, 3.738; 95% CI, 1.045-13.370), living in an unstable relationship (OR, 9.275; 95% CI, 2.207- 38.984), and loss of continuity of care (OR, 12.643; 95% CI, 3.001-53.253). Conclusion The patients presenting these risk factors require special attention. It is important for family physicians to insist on compliance with the treatment protocol and intervene when they lose contact with the patient to prevent the fatal outcome

Fascicles and the interfascicular matrix show decreased fatigue life with ageing in energy storing tendons

Tendon is composed of rope-like fascicles bound together by interfascicular matrix (IFM). The IFM is critical for the function of energy storing tendons, facilitating sliding between fascicles to allow these tendons to cyclically stretch and recoil. This capacity is required to a lesser degree in positional tendons. We have previously demonstrated that both fascicles and IFM in energy storing tendons have superior fatigue resistance compared with positional tendons, but the effect of ageing on the fatigue properties of these different tendon subunits has not been determined. Energy storing tendons become more injury-prone with ageing, indicating reduced fatigue resistance, hence we tested the hypothesis that the decline in fatigue life with ageing in energy storing tendons would be more pronounced in the IFM than in fascicles. We further hypothesised that tendon subunit fatigue resistance would not alter with ageing in positional tendons. Fascicles and IFM from young and old energy storing and positional tendons were subjected to cyclic fatigue testing until failure, and mechanical properties were calculated. The results show that both IFM and fascicles from the SDFT exhibit a similar magnitude of reduced fatigue life with ageing. By contrast, the fatigue life of positional tendon subunits was unaffected by ageing. The age-related decline in fatigue life of tendon subunits in energy storing tendons is likely to contribute to the increased risk of injury in aged tendons. Full understanding of the mechanisms resulting in this reduced fatigue life will aid in the development of treatments and interventions to prevent age-related tendinopathy

World Measuring Living standards within cities

This report is divided into three main chapters. In this first chapter, we explore ‘the good, the bad, and the ugly’ of survey design for urban areas. The objective is to contribute to best practice and knowledge sharing on surveying urban areas through a frank discussion of successes and failures of the pilots, drawing particular attention to challenges associated with working in urban areas. The second chapter provides detailed information on the survey methodology. This section will act as a guide on the sampling strategy and weighting of the survey that is likely to be useful for analysts that work with data. The final chapter draws on descriptive statistics from the two pilot surveys to provide a first look at the kinds of insights that can be supported by this new survey instrument. Although this is only a preliminary analysis, the descriptive statistics provided in this chapter already demonstrate the advantages of looking at cities through a more focused lens. The chapter sheds new light on the challenges of access to basic services, informality, urban mobility, and housing in Dar es Salaam and Durban

Proteomic Analysis Reveals Age-related Changes in Tendon Matrix Composition, with Age- and Injury-specific Matrix Fragmentation

Energy storing tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT), are highly prone to injury, the incidence of which increases with aging. The cellular and molecular mechanisms that result in increased injury in aged tendons are not well established but are thought to result in altered matrix turnover. However, little attempt has been made to fully characterize the tendon proteome nor determine how the abundance of specific tendon proteins changes with aging and/or injury. The aim of this study was, therefore, to assess the protein profile of normal SDFTs from young and old horses using label-free relative quantification to identify differentially abundant proteins and peptide fragments between age groups. The protein profile of injured SDFTs from young and old horses was also assessed. The results demonstrate distinct proteomic profiles in young and old tendon, with alterations in the levels of proteins involved in matrix organization and regulation of cell tension. Furthermore, we identified several new peptide fragments (neopeptides) present in aged tendons, suggesting that there are age-specific cleavage patterns within the SDFT. Proteomic profile also differed between young and old injured tendon, with a greater number of neopeptides identified in young injured tendon. This study has increased the knowledge of molecular events associated with tendon aging and injury, suggesting that maintenance and repair of tendon tissue may be reduced in aged individuals and may help to explain why the risk of injury increases with aging

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Background: Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. Methods: The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. Findings: Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. Interpretation: In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. Funding: Novo Nordisk

Managing IT Services: Aligning Best Practice with a Quality Method

Managing information technology services is becoming an increasingly difficult task. To support the management of IT services, different standards and methodologies have been developed. ITIL (short for IT Infrastructure Library) is the most commonly used best practice approach to effective IT Service Management to date. ITIL focuses primarily on what to do in order to ensure value of IT services, but it does not explain how to achieve this effectively. This shortcoming can be overcome by complementing the framework with other quality approaches to service management. In this context several methodologies are mentioned including the use of Six Sigma (6s) methodology. The statistical nature of the Six Sigma methodology enables us to analyze the vast amount of data gathered from the field of IT. Only after these value-based metrics are obtained can the overall health of the IT service be determined and the necessary improvement measures made. The aim of this paper is to analyze in detail the two approaches. We will establish a common link between them, with it the opportunity to complement ITIL with the Six Sigma methodology, and consequently set foundations for introduction of necessary measurable changes

Zeno Cosini – (ne)zanesljivi pripovedovalec svojega življenja

The key issue when reading the novel Zeno’s Conscience (1923) by the Italian writer Italo Svevo (whose real name was Ettore Schmitz) (1861–1928) arises when we try to define its main hero and narrator, Zeno Cosini, and specifically the degree to which he is (un)reliable. Some key theoretical considerations that deal with the concept of (un)reliability will be addressed, and these tools then applied to Svevo\u27s novel. The research that has been done in the field of (un)reliability is of an interdisciplinary nature and belongs to postclassical narrative theory. However, since the issue of (un)reliability in general, and especially in the case of Zeno’s Conscience, is closely related to the concept of the narrator, the analysis will also take into account the findings of Gérard Genette (1930–2018) and his trichotomic concept of narrative reality, Mieke Bal (1946–) and her concept of focalization, and Uri Margolin (1942–) and his more recent classification of (un)reliability, which are all directly relevant to the study of the narrator’s (un)reliability. Svevo’s novel Zeno’s Conscience is marked by multi-layered (un)reliability. In the postclassical definition of (un)reliability, this quality can be found in all three phases when dealing with a narrative text: the semantic, pragmatic and psychological phases. In the case of Zeno, the narrator and main focalizer, the boundaries between his intentional deceptions and his unintentional self-delusions are neither easily definable nor is it straightforward to define the prototypical characteristics of such an (un)reliable narrator. This opens up many possibilities for questioning one\u27s own life and the workings of human consciousness as such.Osrednje vprašanje, s katerim se soočimo ob branju romana Zenova zavest (1923) italijanskega pisatelja Itala Sveva (s pravim imenom Ettore Schmitz) (1861–1928), je vprašanje (ne)zanesljivosti glavnega pripovedovalca Zena Cosinija. Predstavili bomo nekatera naratološka teoretska izhodišča, ki obravnavajo pojem (ne)zanesljivosti, kot tudi v ožjem smislu, ko to teorijo apliciramo na Svevov roman. Raziskave, ki so bile narejene na področju (ne)zanesljivosti in ki jih predstavljamo, so interdisciplinarne narave in spadajo v polje postklasične teorije pripovedi, čeprav je nastavke zanje postavila že klasična naratologija. Zato se z vprašanjem (ne)zanesljivosti pripovedovalca ukvarjamo tudi v navezavi na delo dveh klasičnih naratologov, in sicer Gérarda Genetta (1930–2018), znotraj katerega je relevanten trihotomični koncept pripovedne resničnosti, in Mieke Bal (1946–), ki posebno pozornost posveča fokalizaciji, ter Urija Margolina (1942–), ki se v svojih novejših študijah neposredno ukvarja s konceptom (ne)zanesljivosti. Svevov roman Zenova zavest zaznamuje večravninska nezanesljivost in fokalizacijska kompleksnost osrednjega pripovedovalca. V postklasičnem določanju (ne)zanesljivosti najdemo (ne)zanesljivost v vseh treh fazah: semantični, pragmatski in psihološki fazi. Pri Zenu pripovedovalcu meje med njegovim intencionalnim zavajanjem in neintencionalno zavedenostjo niso preprosto določljive kot tudi ne prototipske značilnosti nezanesljivega pripovedovalca, kar odraža zapletenost delovanja zavesti kot take in poskusov njenega predstavljanja