Essentials of forensic post-mortem MR imaging in adults

Post-mortem MR (PMMR) imaging is a powerful diagnostic tool with a wide scope in forensic radiology. In the past 20 years, PMMR has been used as both an adjunct and an alternative to autopsy. The role of PMMR in forensic death investigations largely depends on the rules and habits of local jurisdictions, availability of experts, financial resources, and individual case circumstances. PMMR images are affected by post-mortem changes, including position-dependent sedimentation, variable body temperature and decomposition. Investigators must be familiar with the appearance of normal findings on PMMR to distinguish them from disease or injury. Coronal whole-body images provide a comprehensive overview. Notably, short tau inversion–recovery (STIR) images enable investigators to screen for pathological fluid accumulation, to which we refer as “forensic sentinel sign”. If scan time is short, subsequent PMMR imaging may be focussed on regions with a positive forensic sentinel sign. PMMR offers excellent anatomical detail and is especially useful to visualize pathologies of the brain, heart, subcutaneous fat tissue and abdominal organs. PMMR may also be used to document skeletal injury. Cardiovascular imaging is a core area of PMMR imaging and growing evidence indicates that PMMR is able to detect ischaemic injury at an earlier stage than traditional autopsy and routine histology. The aim of this review is to present an overview of normal findings on forensic PMMR, provide general advice on the application of PMMR and summarise the current literature on PMMR imaging of the head and neck, cardiovascular system, abdomen and musculoskeletal system.

Feeling present in arousing virtual reality worlds: prefrontal brain regions differentially orchestrate presence experience in adults and children

Virtual reality (VR) is a powerful tool for simulating aspects of the real world. The success of VR is thought to depend on its ability to evoke a sense of "being there", that is, the feeling of "Presence". In view of the rapid progress in the development of increasingly more sophisticated virtual environments (VE), the importance of understanding the neural underpinnings of presence is growing. To date however, the neural correlates of this phenomenon have received very scant attention. An fMRI-based study with 52 adults and 25 children was therefore conducted using a highly immersive VE. The experience of presence in adult subjects was found to be modulated by two major strategies involving two homologous prefrontal brain structures. Whereas the right DLPFC controlled the sense of presence by down-regulating the activation in the egocentric dorsal visual processing stream, the left DLPFC up-regulated widespread areas of the medial prefrontal cortex known to be involved in self-reflective and stimulus-independent thoughts. In contrast, there was no evidence of these two strategies in children. In fact, anatomical analyses showed that these two prefrontal areas have not yet reached full maturity in children. Taken together, this study presents the first findings that show activation of a highly specific neural network orchestrating the experience of presence in adult subjects, and that the absence of activity in this neural network might contribute to the generally increased susceptibility of children for the experience of presence in VEs.

Virtual reality and the role of the prefrontal cortex in adults and children

In this review, the neural underpinnings of the experience of presence are outlined. Firstly, it is shown that presence is associated with activation of a distributed network, which includes the dorsal and ventral visual stream, the parietal cortex, the premotor cortex, mesial temporal areas, the brainstem and the thalamus. Secondly, the dorsolateral prefrontal cortex (DLPFC) is identified as a key node of the network as it modulates the activity of the network and the associated experience of presence. Thirdly, children lack the strong modulatory influence of the DLPFC on the network due to their unmatured frontal cortex. Fourthly, it is shown that presence-related measures are influenced by manipulating the activation in the DLPFC using transcranial direct current stimulation (tDCS) while participants are exposed to the virtual roller coaster ride. Finally, the findings are discussed in the context of current models explaining the experience of presence, the rubber hand illusion, and out-of-body experiences.

Effect of different breathing AIDS on ventilation distribution in adults with cystic fibrosis.

BACKGROUND AND OBJECTIVES We investigated the effect of different breathing aids on ventilation distribution in healthy adults and subjects with cystic fibrosis (CF). METHODS In 11 healthy adults and 9 adults with CF electrical impedance tomography measurements were performed during spontaneous breathing, continuous positive airway pressure (CPAP) and positive expiratory pressure (PEP) therapy randomly applied in upright and lateral position. Spatial and temporal ventilation distribution was assessed. RESULTS The proportion of ventilation directed to the dependent lung significantly increased in lateral position compared to upright in healthy and CF. This effect was enhanced with CPAP but neutralised with PEP, whereas the effect of PEP was larger in the healthy group. Temporal ventilation distribution showed exactly the opposite with homogenisation during CPAP and increased inhomogeneity with PEP. CONCLUSIONS PEP shows distinct differences to CPAP with respect to its impact on ventilation distribution in healthy adults and CF subjects EIT might be used to individualise respiratory physiotherapy.

Clinical and haematological predictors of antibiotic prescribing for acute cough in adults in Swiss practices - an observational study.

BackgroundAcute cough is a common problem in general practice and is often caused by a self-limiting, viral infection. Nonetheless, antibiotics are often prescribed in this situation, which may lead to unnecessary side effects and, even worse, the development of antibiotic resistant microorganisms worldwide. This study assessed the role of point-of-care C-reactive protein (CRP) testing and other predictors of antibiotic prescription in patients who present with acute cough in general practice.MethodsPatient characteristics, symptoms, signs, and laboratory and X-ray findings from 348 patients presenting to 39 general practitioners with acute cough, as well as the GPs themselves, were recorded by fourth-year medical students during their three-week clerkships in general practice. Patient and clinician characteristics of those prescribed and not-prescribed antibiotics were compared using a mixed-effects model.ResultsOf 315 patients included in the study, 22% were prescribed antibiotics. The two groups of patients, those prescribed antibiotics and those treated symptomatically, differed significantly in age, demand for antibiotics, days of cough, rhinitis, lung auscultation, haemoglobin level, white blood cell count, CRP level and the GP¿s license to self-dispense antibiotics. After regression analysis, only the CRP level, the white blood cell count and the duration of the symptoms were statistically significant predictors of antibiotic prescription.ConclusionsThe antibiotic prescription rate of 22% in adult patients with acute cough in the Swiss primary care setting is low compared to other countries. GPs appear to use point-of-care CRP testing in addition to the duration of clinical symptoms to help them decide whether or not to prescribe antibiotics.

Hepatic and intramyocellular glycogen stores in adults with type 1 diabetes and healthy controls.

Glycogen levels in liver and skeletal muscle assessed non-invasively using magnetic resonance spectroscopy after a 48-h pre-study period including a standardized diet and withdrawal from exercise did not differ between individuals with well-controlled Type 1 DM and matched healthy controls.

Low statin use in adults hospitalized with acute coronary syndrome.

OBJECTIVE To assess recommended and actual use of statins in primary prevention of cardiovascular disease (CVD) based on clinical prediction scores in adults who develop their first acute coronary syndrome (ACS). METHOD Cross-sectional study of 3172 adults without previous CVD hospitalized with ACS at 4 university centers in Switzerland. The number of participants eligible for statins before hospitalization was estimated based on the European Society of Cardiology (ESC) guidelines and compared to the observed number of participants on statins at hospital entry. RESULTS Overall, 1171 (37%) participants were classified as high-risk (10-year risk of cardiovascular mortality ≥5% or diabetes); 1025 (32%) as intermediate risk (10-year risk <5% but ≥1%); and 976 (31%) as low risk (10-year risk <1%). Before hospitalization, 516 (16%) were on statins; among high-risk participants, only 236 of 1171 (20%) were on statins. If ESC primary prevention guidelines had been fully implemented, an additional 845 high-risk adults (27% of the whole sample) would have been eligible for statins before hospitalization. CONCLUSION Although statins are recommended for primary prevention in high-risk adults, only one-fifth of them are on statins when hospitalized for a first ACS.

Clinical Use of Quantitative Computed Tomography–Based Finite Element Analysis of the Hip and Spine in the Management of Osteoporosis in Adults: the 2015 ISCD Official Positions—Part II

The International Society for Clinical Densitometry (ISCD) has developed new official positions for the clinical use of quantitative computed tomography (QCT)-based finite element analysis of the spine and hip. The ISCD task force for QCT reviewed the evidence for clinical applications and presented a report with recommendations at the 2015 ISCD Position Development Conference. Here we discuss the agreed upon ISCD official positions with supporting medical evidence, rationale, controversy, and suggestions for further study. Parts I and III address the clinical use of QCT of the hip, and the clinical feasibility of existing techniques for opportunistic screening of osteoporosis using CT scans obtained for other diagnosis such as colonography was addressed.

Clinical Use of Quantitative Computed Tomography–Based Advanced Techniques in the Management of Osteoporosis in Adults: the 2015 ISCD Official Positions—Part III

The International Society for Clinical Densitometry (ISCD) has developed new official positions for the clinical use of computed tomography (CT) scans acquired without a calibration phantom, for example, CT scans obtained for other diagnosis such as colonography. This also addresses techniques suggested for opportunistic screening of osteoporosis. The ISCD task force for quantitative CT reviewed the evidence for clinical applications of these new techniques and presented a report with recommendations at the 2015 ISCD Position Development Conference. Here we discuss the agreed upon ISCD official positions with supporting medical evidence, rationale, controversy, and suggestions for further study. Advanced techniques summarized as statistical parameter mapping methods were also reviewed. Their future use is promising but the clinical application is premature. The clinical use of QCT of the hip is addressed in part I and of finite element analysis of the hip and spine in part II.

Clinical Use of Quantitative Computed Tomography (QCT) of the Hip in the Management of Osteoporosis in Adults: the 2015 ISCD Official Positions—Part I

The International Society for Clinical Densitometry (ISCD) has developed new official positions for the clinical use of quantitative computed tomography of the hip. The ISCD task force for quantitative computed tomography reviewed the evidence for clinical applications and presented a report with recommendations at the 2015 ISCD Position Development Conference. Here, we discuss the agreed on ISCD official positions with supporting medical evidence, rationale, controversy, and suggestions for further study. Parts II and III address the advanced techniques of finite element analysis applied to computed tomography scans and the clinical feasibility of existing techniques for opportunistic screening of osteoporosis using computed tomography scans obtained for other diagnosis such as colonography was addressed.

Symptoms Have Modest Accuracy in Detecting Endoscopic and Histologic Remission in Adults With Eosinophilic Esophagitis.

BACKGROUND & AIMS It is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission. METHODS Between April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score <20 (range, 0-100); histologic remission was defined as a peak count of <20 eosinophils/mm(2) in a high-power field (corresponds to approximately <5 eosinophils/median high-power field); and endoscopic remission as absence of white exudates, moderate or severe rings, strictures, or combination of furrows and edema. We used receiver operating characteristic analysis to determine the best symptom score cutoff values for detection of remission. RESULTS Of the study subjects, 111 were in clinical remission (41.3%), 79 were in endoscopic remission (29.7%), and 75 were in histologic remission (27.9%). When the symptom score was used as a continuous variable, patients in endoscopic, histologic, and combined (endoscopic and histologic remission) remission were detected with area under the curve values of 0.67, 0.60, and 0.67, respectively. A symptom score of 20 identified patients in endoscopic remission with 65.1% accuracy and histologic remission with 62.1% accuracy; a symptom score of 15 identified patients with both types of remission with 67.7% accuracy. CONCLUSIONS In patients with EoE, endoscopic or histologic remission can be identified with only modest accuracy based on symptoms alone. At any given time, physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adults with EoE. ClinicalTrials.gov, Number: NCT00939263.

Canakinumab in adults with steroid-refractory pyoderma gangrenosum

BACKGROUND Pyoderma gangrenosum (PG) is a rare, neutrophilic, ulcerative skin disease that is difficult to treat, especially when unresponsive to steroids. OBJECTIVES To determine whether canakinumab is an effective and safe treatment in PG. METHODS Five adult patients with clinically and histologically confirmed steroid-refractory PG were enrolled in this prospective open-label study. They received canakinumab 150 mg subcutaneously at week 0 with an optional 150 mg at week 2 in case of an inadequate response [Physician's Global Assessment (PGA) ≥ 2], and an optional 150-300 mg at week 8 depending on PGA. The primary clinical end point was clinical improvement (PGA at least -1 from baseline) and/or complete remission (PGA 0 or 1) at week 16. Real-time quantitative polymerase chain reaction was performed on skin samples to quantify cytokine mRNA levels. RESULTS Interleukin (IL)-1β and its known target genes IL6, CXCL8 and IL36A were significantly increased in lesional skin of PG. Under canakinumab therapy, four of five patients showed a decrease in target-lesion size, PGA and Dermatology Life Quality Index (DLQI), and three of five achieved complete remission. The mean diameter of target lesions decreased from 4·32 ± 2·6 cm at visit 1 to 0·78 ± 1·3 cm at visit 7 (P = 0·03). Mean DLQI decreased from 15 ± 5 at visit 1 to 8 ± 4 by visit 7 (P = 0·01). Adverse effects were reported in two patients: fatigue in one and worsening of disease at a nontarget lesion in the other. CONCLUSIONS Our data indicate that IL-1β plays a key pathogenic role in PG and canakinumab may represent a therapeutic option for steroid-refractory PG.

The need for second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030: a mathematical modelling study.

BACKGROUND The number of patients in need of second-line antiretroviral drugs is increasing in sub-Saharan Africa. We aimed to project the need of second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030. METHODS We developed a simulation model for HIV and applied it to each sub-Saharan African country. We used the WHO country intelligence database to estimate the number of adult patients receiving antiretroviral therapy from 2005 to 2014. We fitted the number of adult patients receiving antiretroviral therapy to observed estimates, and predicted first-line and second-line needs between 2015 and 2030. We present results for sub-Saharan Africa, and eight selected countries. We present 18 scenarios, combining the availability of viral load monitoring, speed of antiretroviral scale-up, and rates of retention and switching to second-line. HIV transmission was not included. FINDINGS Depending on the scenario, 8·7-25·6 million people are expected to receive antiretroviral therapy in 2020, of whom 0·5-3·0 million will be receiving second-line antiretroviral therapy. The proportion of patients on treatment receiving second-line therapy was highest (15·6%) in the scenario with perfect retention and immediate switching, no further scale-up, and universal routine viral load monitoring. In 2030, the estimated range of patients receiving antiretroviral therapy will remain constant, but the number of patients receiving second-line antiretroviral therapy will increase to 0·8-4·6 million (6·6-19·6%). The need for second-line antiretroviral therapy was two to three times higher if routine viral load monitoring was implemented throughout the region, compared with a scenario of no further viral load monitoring scale-up. For each monitoring strategy, the future proportion of patients receiving second-line antiretroviral therapy differed only minimally between countries. INTERPRETATION Donors and countries in sub-Saharan Africa should prepare for a substantial increase in the need for second-line drugs during the next few years as access to viral load monitoring improves. An urgent need exists to decrease the costs of second-line drugs. FUNDING World Health Organization, Swiss National Science Foundation, National Institutes of Health.

Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis.

BACKGROUND Panic disorder is characterised by the presence of recurrent unexpected panic attacks, discrete periods of fear or anxiety that have a rapid onset and include symptoms such as racing heart, chest pain, sweating and shaking. Panic disorder is common in the general population, with a lifetime prevalence of 1% to 4%. A previous Cochrane meta-analysis suggested that psychological therapy (either alone or combined with pharmacotherapy) can be chosen as a first-line treatment for panic disorder with or without agoraphobia. However, it is not yet clear whether certain psychological therapies can be considered superior to others. In order to answer this question, in this review we performed a network meta-analysis (NMA), in which we compared eight different forms of psychological therapy and three forms of a control condition. OBJECTIVES To assess the comparative efficacy and acceptability of different psychological therapies and different control conditions for panic disorder, with or without agoraphobia, in adults. SEARCH METHODS We conducted the main searches in the CCDANCTR electronic databases (studies and references registers), all years to 16 March 2015. We conducted complementary searches in PubMed and trials registries. Supplementary searches included reference lists of included studies, citation indexes, personal communication to the authors of all included studies and grey literature searches in OpenSIGLE. We applied no restrictions on date, language or publication status. SELECTION CRITERIA We included all relevant randomised controlled trials (RCTs) focusing on adults with a formal diagnosis of panic disorder with or without agoraphobia. We considered the following psychological therapies: psychoeducation (PE), supportive psychotherapy (SP), physiological therapies (PT), behaviour therapy (BT), cognitive therapy (CT), cognitive behaviour therapy (CBT), third-wave CBT (3W) and psychodynamic therapies (PD). We included both individual and group formats. Therapies had to be administered face-to-face. The comparator interventions considered for this review were: no treatment (NT), wait list (WL) and attention/psychological placebo (APP). For this review we considered four short-term (ST) outcomes (ST-remission, ST-response, ST-dropouts, ST-improvement on a continuous scale) and one long-term (LT) outcome (LT-remission/response). DATA COLLECTION AND ANALYSIS As a first step, we conducted a systematic search of all relevant papers according to the inclusion criteria. For each outcome, we then constructed a treatment network in order to clarify the extent to which each type of therapy and each comparison had been investigated in the available literature. Then, for each available comparison, we conducted a random-effects meta-analysis. Subsequently, we performed a network meta-analysis in order to synthesise the available direct evidence with indirect evidence, and to obtain an overall effect size estimate for each possible pair of therapies in the network. Finally, we calculated a probabilistic ranking of the different psychological therapies and control conditions for each outcome. MAIN RESULTS We identified 1432 references; after screening, we included 60 studies in the final qualitative analyses. Among these, 54 (including 3021 patients) were also included in the quantitative analyses. With respect to the analyses for the first of our primary outcomes, (short-term remission), the most studied of the included psychological therapies was CBT (32 studies), followed by BT (12 studies), PT (10 studies), CT (three studies), SP (three studies) and PD (two studies).The quality of the evidence for the entire network was found to be low for all outcomes. The quality of the evidence for CBT vs NT, CBT vs SP and CBT vs PD was low to very low, depending on the outcome. The majority of the included studies were at unclear risk of bias with regard to the randomisation process. We found almost half of the included studies to be at high risk of attrition bias and detection bias. We also found selective outcome reporting bias to be present and we strongly suspected publication bias. Finally, we found almost half of the included studies to be at high risk of researcher allegiance bias.Overall the networks appeared to be well connected, but were generally underpowered to detect any important disagreement between direct and indirect evidence. The results showed the superiority of psychological therapies over the WL condition, although this finding was amplified by evident small study effects (SSE). The NMAs for ST-remission, ST-response and ST-improvement on a continuous scale showed well-replicated evidence in favour of CBT, as well as some sparse but relevant evidence in favour of PD and SP, over other therapies. In terms of ST-dropouts, PD and 3W showed better tolerability over other psychological therapies in the short term. In the long term, CBT and PD showed the highest level of remission/response, suggesting that the effects of these two treatments may be more stable with respect to other psychological therapies. However, all the mentioned differences among active treatments must be interpreted while taking into account that in most cases the effect sizes were small and/or results were imprecise. AUTHORS' CONCLUSIONS There is no high-quality, unequivocal evidence to support one psychological therapy over the others for the treatment of panic disorder with or without agoraphobia in adults. However, the results show that CBT - the most extensively studied among the included psychological therapies - was often superior to other therapies, although the effect size was small and the level of precision was often insufficient or clinically irrelevant. In the only two studies available that explored PD, this treatment showed promising results, although further research is needed in order to better explore the relative efficacy of PD with respect to CBT. Furthermore, PD appeared to be the best tolerated (in terms of ST-dropouts) among psychological treatments. Unexpectedly, we found some evidence in support of the possible viability of non-specific supportive psychotherapy for the treatment of panic disorder; however, the results concerning SP should be interpreted cautiously because of the sparsity of evidence regarding this treatment and, as in the case of PD, further research is needed to explore this issue. Behaviour therapy did not appear to be a valid alternative to CBT as a first-line treatment for patients with panic disorder with or without agoraphobia.