Diabetes mellitus (DM) is a risk factor for active tuberculosis (TB) but little is known about the effect of DM on culture conversion among patients with multidrug-resistant (MDR)-TB. The primary aim was to estimate the association between DM and rate of TB sputum culture conversion. A secondary objective was to estimate the association between DM and the risk of poor treatment outcomes among patients with MDR-TB.A cohort of all adult patients starting MDR-TB treatment in the country of Georgia between 2009–2011 was followed during second-line TB therapy. Cox proportional models were used to estimate the adjusted hazard rate of sputum culture conversion. Log-binomial regression models were used to estimate the cumulative risk of poor TB treatment outcome.Among 1,366 patients with sputum culture conversion information, 966 (70.7%) had culture conversion and the median time to conversion was 68 days (interquartile range 50–120). The rate of conversion was similar among patients with MDR-TB and DM  compared to patients with MDR-TB only. The rate of culture conversion was significantly less in patients that currently smoked , had low body mass index , second-line resistance , lung cavities  and with disseminated TB . The cumulative risk of poor treatment outcome was also similar among TB patients with and without DM .In adjusted analyses, DM did not impact culture conversion rates in a clinically meaningful way but smoking did. In the past 5 years, the relationship between type 2 diabetes mellitus (DM) and tuberculosis (TB) has emerged as a global public health priority. Global increases in multidrug-resistant (MDR)-TB (defined as TB strains resistant to at least isoniazid and rifampin) have brought additional challenges to TB control efforts. In 2013 the World Health Organization (WHO) reported that 3.6% of new cases and 20.2% of previously treated cases had MDR-TB, for estimated 450,000 new MDR-TB cases globally. Little is known about the relationship between DM and MDR-TB. Several studies have reported a high prevalence of DM among patients with MDR-TB, Mycobacterium tuberculosis that is resistant to at least isoniazid (INH) and rifampicin (RIF). Second-line treatment at NCTBLD during the study period included initial empirical treatment that consisted of the following medications: capreomycin or kanamycin, levofloxacin, prothionamide, cycloserine, PAS and pyrazinamide. After final drug susceptibility test (DST) results became available, treatment regimens were individualized based on the results. When possible, regimens were designed to include at least four drugs to which the patient’s M. tuberculosis isolate was susceptible. All treatment regimens included a fluoroquinolone and an injectable agent for at least six months.A cohort of all adult (aged ≥18 years) patients with pulmonary MDR-TB starting second-line therapy between January 1, 2009 and December 30, 2011 in the country of Georgia was followed at the National Center for TB and Lung Disease (NCTBLD) in Tbilisi. Baseline data was collected on all patients who were then followed until a treatment outcome was achieved, or until January 2013, which ever occurred first. In Georgia, confirmation of pulmonary MDR-TB is defined by a positive sputum culture for time to culture conversion, was defined as time (in days) from MDR-TB treatment initiation until the first of two consecutive negative sputum cultures ≥30 days apart. Date of culture conversion was abstracted from patients’ medical records. Treatment outcomes were abstracted from the MDR-TB treatment registry and were based on WHO designated definitions. 21,22 The study’s secondary outcome, poor treatment outcome, was defined by combining the WHO outcome definitions of failed, defaulted, died, or transferred.The primary study outcome, 2) from patient height and weight at the time of treatment initiation. Hepatitis co-infection status was classified as positive if the patient had documented positive serology for hepatitis A, B, or C viruses. Patients were screened for HIV co-infection by rapid test, positive tests were confirmed with Western Blot. The primary study exposure of interest was diagnosed DM. Status of DM was assessed by physician diagnosis as recorded in the medical record. The secondary exposure of interest, current smoking status, was also assessed by physicians and recorded in patients’ medical records. Additional patient characteristics collected in the study included demographic and socio-behavioral information, concomitant infectious diseases, and TB clinical features. Body mass index (BMI) was calculated  in Tbilisi, which has received annual external quality assessment from Antwerp WHO Supranational TB Reference Laboratory since 2005. All data were entered into an electronic database and analyzed using SAS 9.3 . Bivariate associations were analyzed using χ2 tests for categorical variables, the Student’s t-test for normally distributed continuous variables (means), and the Kruskal-Wallis test for non-normally distributed continuous variables (medians). A two-sided p-value <0.05 was considered statistically significant for all analyses. Cox proportional hazards models were used to estimate hazard rate ratios (HR) and 95% confidence intervals (CI) for time to culture conversion. Patients were censored if at the time of treatment completion  they did not have a prior documented sputum conversion. Proportional hazard assumptions were assessed graphically (log-negative-log curves), with goodness-of-fit  and using time-dependent models. This study and was reviewed and approved by the Institutional Review Board of Emory University, Atlanta, USA. For the purposes of the study, all data were de-identified prior to access and analyses were performed anonymously by the researchers.During the study period, 1,884 patients with laboratory confirmed pulmonary MDR-TB began second-line anti-TB therapy through the NCTBLD. Among these, 98.3%  were adults and included in the study. Culture conversion and censorship follow-up information was available for 73.8%  of patients and 76.7%  had a WHO defined treatment outcome . As of JOf patients included in the study , most were male (81.2%), current smoking was common (47.7%), and the median age was 35.1 years . DiabeteAmong patients with MDR-TB included in the study, 70.7%  converted sputum cultures from positive to negative during second-line therapy . The medOverall 50.6%  of patients had a treatment outcome defined as cured or completed . After aThis cohort study of adult pulmonary MDR-TB patients from the country of Georgia found that after adjusting for important confounding factors, the rate of sputum culture conversion and the risk of poor treatment outcome was similar in MDR-TB patients with and without DM. Importantly, in multivariable analyses we did find factors significantly associated with lower conversion rates, including current smoking, cavitary disease, and disseminated TB. We also found low BMI (<18.5) and any second-line drug resistance were significantly associated with both lower culture conversion rates and greater risk of poor treatment outcome. Compared to patients with MDR-TB who culture converted, failure to convert sputum culture to negative was strongly associated with poor treatment outcome and increased the risk of death by nearly eight-fold.unadjusted rate  of sputum culture conversion among patients with DM. Few other studies have examined the effect of DM status on time until sputum culture conversion or risk of poor TB treatment outcome among patients with MDR-TB. Consistent with our adjusted HR estimate , a 2012 study of MDR-TB patients from five countries also reported a lower but not significant Existing evidence strongly suggests that smoking is risk factor for developing active TB This study was subject to limitations. First, DM status was not systematically measured for all patients at the time of second-line TB treatment initiation, which may have resulted in misclassification or an underestimation of the prevalence of dysglycemia among those with MDR-TB. However, patients with MDR-TB previously diagnosed with DM or who were taking drugs for glycemic control likely had DM status documented in their medical records and consequently the specificity of our measured DM status was likely high. We do not have reason to believe that misclassification of DM status was differential with respect to sputum culture conversion, and therefore our estimated effect of the exposure (DM) on the outcome (culture conversion) would plausibly be expected to be biased toward the null. Few other studies have examined the effect of DM on time to sputum culture conversion in drug-susceptible TB cohorts, and to our knowledge we present the first analysis of the adjusted effect of DM on culture conversion among TB patients with confirmed MDR. In addition, our study was able to control for multiple confounding factors not accounted for in previous studies of culture conversion and poor treatment outcome in patients with MDR-TB.Although previous studies suggest DM may increase the time to sputum culture conversion and risk of treatment failure among drug susceptible TB patients, our results did not detect a clinically meaningful difference in culture conversion rates or risk of poor treatment outcome in patients with MDR-TB from the country of Georgia. We did identify important predictive factors for both lower culture conversion rates and poor treatment outcomes including current smoking, low BMI, second-line drug resistance, cavitary disease, disseminated TB, and AFB smear grade.


Memory impairment is commonly noted in stroke survivors, and can lead to delay of functional recovery. Exercise has been proved to improve memory in adult healthy subjects. Such beneficial effects are often suggested to relate to hippocampal synaptic plasticity, which is important for memory processing. Previous evidence showed that in normal rats, low intensity exercise can improve synaptic plasticity better than high intensity exercise. However, the effects of exercise intensities on hippocampal synaptic plasticity and spatial memory after brain ischemia remain unclear. In this study, we investigated such effects in brain ischemic rats. The middle cerebral artery occlusion (MCAO) procedure was used to induce brain ischemia. After the MCAO procedure, rats were randomly assigned to sedentary (Sed), low-intensity exercise (Low-Ex), or high-intensity exercise (High-Ex) group. Treadmill training began from the second day post MCAO procedure, 30 min/day for 14 consecutive days for the exercise groups. The Low-Ex group was trained at the speed of 8 m/min, while the High-Ex group at the speed of 20 m/min. The spatial memory, hippocampal brain-derived neurotrophic factor (BDNF), synapsin-I, postsynaptic density protein 95 (PSD-95), and dendritic structures were examined to document the effects. Serum corticosterone level was also quantified as stress marker. Our results showed the Low-Ex group, but not the High-Ex group, demonstrated better spatial memory performance than the Sed group. Dendritic complexity and the levels of BDNF and PSD-95 increased significantly only in the Low-Ex group as compared with the Sed group in bilateral hippocampus. Notably, increased level of corticosterone was found in the High-Ex group, implicating higher stress response. In conclusion, after brain ischemia, low intensity exercise may result in better synaptic plasticity and spatial memory performance than high intensity exercise; therefore, the intensity is suggested to be considered during exercise training. Memory deficits are frequently noted after stroke, and are often related to impaired hippocampal function In this study, we thus investigated the effects of exercise intensity on spatial memory performance and hippocampal synaptic plasticity, by demonstrating the expressions of hippocampal BDNF, Synapsin-I, PSD-95, and dendritic structures in brain ischemic rats.Adult (8 week-old) Sprague-Dawley (SD) male rats were used. The rats were housed in pairs in a temperature-controlled (22±1°C) vivarium on a 12-hr light:dark cycle (lights on at 0700 hr) with free access to food and water. The Institutional Animal Care and Use Committee of the National Yang-Ming University approved all the experimental protocols.Right middle cerebral artery occlusion (MCAO) was induced using standard microsurgical techniques as described previously Forty-eight rats were subjected to this study. Before MCAO procedure, all rats experienced a 3-day familiarization of a motor-driven treadmill training  at the speed of 5 m/min, 5 min/day. After resting for 2 days, the MCAO procedure was performed, and the rats were randomly assigned to one of the three groups: sedentary (Sed), low-intensity exercise (Low-Ex) and high-intensity exercise (High-Ex) groups. Treadmill training was started at 24 hours post MCAO, 30 min per day, for a total of 14 consecutive days for the exercise groups. Rats in the Low-Ex group were trained on the treadmill at the speed of 8 m/min while rats in the High-Ex group at the speed of 20 m/min. Rats in the Sed group remained relatively inactive during the 14 days period.The Morris water maze test composes the acquisition phase and retention phase. In the acquisition phase, all rats in the three groups were trained on the MWM for 4 days (from day 10 to day 13 of the study period) with 3 training trials per day. In each trial, rats swam freely in the pool until they located the hidden platform, and those could not locate the platform within 90 s were gently guided to the platform. Escape latency (time needed to find the platform) was recorded during the trials. After completing the last treadmill training in the exercise groups or the comparable day of the Sed group (day 14), test for retention phase was executed, which the platform was removed from the pool. The rats were allowed to swim for 60 s during the retention test, and their behaviors were recorded. Two parameters were analyzed for comparisons during the retention phase: the duration of staying and the frequency of crossing the quadrant which the platform was previously located Western blotting was used to identify the levels of BDNF, synapsin-I and PSD-95 protein expressions. All rats were sacrificed after the last trial of MWM test. Hippocampal samples were dissected out on ice, homogenized in the lysis buffer , and centrifuged at 12500 rpm at 4°C for 30 min. For electrophoresis, equal amount of protein (10 µg) in each sample was separated in the 8% (for synapsin and PSD-95) or 12% (for BDNF) SDS-polyacrylamide gels, and then transferred onto the PVDF membranes. After blocking with the 3% BSA at room temperature for 1 hour and washed with 0.01% TBST buffer, the membranes were incubated with the anti-BDNF , anti-synapsin-I , anti-PSD-95  or anti-β-actin  antibodies at 4°C overnight. After washing with 0.01% TBST three times and incubated with the secondary antibodies at room temperature for 1 hour, the resulting signals were visualized with the enhanced chemiluminescence reagent . Optical densitometry was performed on each band using ImageJ software . Protein content loaded was normalized by β-actin signal.Serum corticosterone levels were detected using the corticosterone ELISA kit . Under deep anesthesia, blood samples were obtained by cardiac puncture. After centrifugation, serum samples were collected and diluted 10 times with the assay buffer provided by the kit. Competition ELISA procedures were conducted following the manufacturer's instructions and the sensitivity of the kit was approximately 27 pg/mL.We used golgi stain to identify the dendritic structure in rat hippocampus. After the last trial of MWM test, rats were anesthetized and sacrificed through transcardiac perfusion with ice-cold saline. The brain was immediately removed and placed in the mixture of mercuric chloride, potassium dichromate and potassium chromate solution provided by the FD Rapid Golgi Stain Kit . Golgi stain procedures were following the manufacturer's instructions. The brain sections were cut with a cryostat, affixed to slides, dehydrated, cleared with Xylene, and coverslipped in Permount® .http://www.biology.ucsd.edu/labs/ghosh/software/index.html) for ImageJ software . As shown in To acquire images for analyzing the dendritic complexity, we scanned the hippocampal tissue using a 40X objective on an Olympus BX61 microscope. For dendritic complexity measurement, we used Sholl analysis nd or 3rd dendritic terminal branches. Dendritic spine density was performed as number of spine/10 µm To acquire images for analyzing the spine density, we scanned the hippocampal dendritic segments using a 100X oil-immersion objective on an Olympus BX61 microscope. For quantification of the spine density, we sampled 8 neurons from each hippocampal DG, CA1 and CA3 regions. For each neuron, spine density was measured from eight 10 µm segments located on the distinct 2The One-way ANOVA was used to compare the protein levels, dendritic spine density and data from the retention phase of MWM test among groups. The Two-way repeated measures ANOVA was used to compare the dendritic complexity and escape latency in the acquisition phase of MWM test among groups. The Tukey test was used as the post-hoc comparisons, and the significant level was set at p<0.05.Results of hippocampal protein levels by western blotting are presented as percentage to the contralesional side of the Sed group . We founTwo-way repeated ANOVA revealed a significant group*ring interaction in the DG of both hemispheres (p<.01). Post hoc test showed that rats in the Low-Ex group demonstrated an increase in the numbers of dendrite-ring intersection between 70 µm and 120 µm from the cell body as compared with the other two groups . In the Rats in the Low-Ex group demonstrated more dendritic spines per 10 µm segment in the hippocampal DG and CA1 region of both hemispheres when compared with the Sed group P<.05; . MoreoveThe main findings of this study are that low-intensity, but not high-intensity, can improve spatial memory performance after brain ischemia. Such memory improvement is indicative of the structural and functional hippocampal plastic changes in bilateral hemispheres, including hippocampal BDNF, PSD-95 and dendritic complexity. In addition, high-intensity exercise does not exert such positive effects were probably due to the induced stress response.The beneficial effects of low-intensity exercise have also been noted in other study. Shimida et al. found that after 4 weeks of low-intensity (8 m/min) treadmill training, the performance in object recognition task is significantly better than high-intensity (22 m/min) treadmill training in MCAO rats, and this improvement paralleled with the increase of neurons in the hippocampal DG Dendritic morphological changes were observed after physical and environmental experiences in other studies. For instance, environmental enrichment can enhance the hippocampal dendritic structural plasticity, including higher dendritic spine density and thicker PSD region, and thus contribute to spatial memory performance In addition to structural plasticity induced by low intensity exercise, the functional aspects of synapse may also be enhanced as supported indirectly by the increase of BDNF levels. It is known that the existence of BDNF not only enhances synaptic response to tetanus stimulation and facilitates transient long-term potentiation (LTP), but also regulates actin motor complex to maintain LTP expression For synaptic protein concentrations, we observed a similar trend as in the dendritic structure; that is, only low-intensity exercise enhanced the expressions of hippocampal BDNF and PSD-95 in bilateral hemispheres, and synapsin-I in the contralesional hemisphere. The levels of PSD-95 and synapsin-I are possibly regulated by the BDNF, since there are several studies reporting the dominant role of BDNF in the hippocampal synaptic plasticity. Inhibition of BDNF-TrkB signalings blocked the exercise-induced BDNF, synapsin-I and CREB expressions, and abolished the improvement of spatial memory Previous study showed that low intensity exercise resulted in more positive effects on improving synaptic plasticity than high intensity exercise in normal rats. Previously, we demonstrated high-intensity treadmill training for 2 weeks resulted in better motor performance and decreased in infarct volume than low-intensity training in brain ischemic rats There are some limitations of this study should be noted. First, we only examined the levels of BDNF, synapsin-I and PSD-95 in whole hippocampal tissues, therefore, we cannot elucidate these changes with dendritic modifications in specific hippocampal subregions. Second, we only measured the corticosterone levels in serum, but not the hippocampus; therefore, the dendritic structural changes in DG, CA1 and CA3 influenced by corticosterone are only supported indirectly.Our study showed that after brain ischemia, low intensity exercise resulted in better effects on hippocampal synaptic plasticity and spatial memory, whereas high intensity exercise did not exert such beneficial effects possibly due to the stress induced by high intensity exercise.


Multiwalled boron nitride nanotubes (BNNTs) have very attractive mechanical and thermal properties, e.g., elasticity, tensile strength, and high resistance to oxidation, and may be considered as ideal reinforcing agents in lightweight metal matrix composites. Herein, for the first time, Al-BNNT ribbons with various BNNT contents (up to 3 wt.%) were fabricated via melt spinning in an argon atmosphere. BNNTs were randomly dispersed within a microcrystalline Al matrix under ribbon casting and led to more than doubling of room-temperature ultimate tensile strength of the composites compared to pure Al ribbons produced at the similar conditions. These dstrength ; the othe matrix . Also, iBoron nitride nanotubes (BNNTs) are another type of nanotubes with a very similar crystal structure to that of CNTs in which alternating B and N atoms substitute for C atoms in a honeycomb lattice. They exhibit many exciting properties, particularly valuable for structural and composite applications. First of all, BNNTs are chemically and thermally much more robust compared to CNTs. Under heating in air, they withstand temperatures in excess of 900°C without any traces of structural degradation or chemical modification . Also, din situ tensile and bending tests on individual Al-BNNT composite structures in a high-resolution transmission electron microscope equipped with a piezo-driven manipulator [For more than a decade, our group has been working on such tubes and various composites made of them. Successfully fabricated polymer or ceramic-BNNT composites had indeed been reported -11. Alsoipulator . As an oThus, the next logic-driven step would be a try to design and to realize such lightweight BNNT-containing composites with meaningful dimensions  in which BNNTs are somehow distributed in a real crystalline Al matrix. As the initial step toward this goal, here, we report the first-time utilization of a melt-spinning technique to prepare BNNT-loaded lightweight Al composite ribbons.Multiwalled BNNTs were synthesized at a high yield  through the so-called boron oxide-assisted CVD (BOCVD) method, as was reported in our previous publications ,10,12-14After subsequent high-temperature purification in argon atmosphere, the nanotubes were dispersed in ethanol. The Al-BNNT composites were cast using a melt-spinning technique in argon atmosphere. Figure −1. The fabricated melt-spun ribbons were approximately 50 μm in thickness and 4 to 5 mm in width. The length of the ribbons varied and was dependent on the stability of casting. As a rule, the fragments up to 1 m long could be obtained.To disperse BNNTs well within an Al powder, the tubes were kept in ethanol during their mixing with the powder . It was a very important step as some tube clustering may occur under powder mixing and further formed Al-BNNT pellets cannot be electrically conductive . This would prevent their further melting under induction heating. The Al powder and dispersed BNNTs were mixed by a mechanical mixer; approximately 0.5 g of the mixed material was put in a die and pressed at a pressure of approximately 20 MPa at room temperature, and numerous starting Al-BNNT pellets were fabricated. Al-BNNT composite ribbons were prepared using melt spinning  in an argon atmosphere. About 2 to 2.5 g of the prepared Al-BNNT pellets were used for a single experimental run. They were pre-placed in a quartz tube, which had a nozzle diameter of 1 mm, melted by the induction currents, and melt-spun on a rotating water-cooled copper drum at a wheel rotation speed of 24 m sKα1 radiation. The morphologies and micro- and atomic structures of the composite ribbons were studied by scanning electron microscopy  and high-resolution transmission electron microscopy  instruments, JEOL Ltd., Akishima, Tokyo, Japan). TEM samples were prepared by using focused ion beam (FIB) polishing. Energy dispersive X-ray spectrometry under SEM and TEM investigations  at accelerating voltages of 10 kV (SEM) and 300 kV (TEM), respectively, were employed to identify the composite chemistry and to spatially map the constituting species. Tensile tests were carried out at room temperature on a ‘Shimadzu’ testing machine  at a deformation rate of 1.67 × 10−4 s−1.The phase compositions and crystal structures of the prepared composites were analyzed by X-ray diffraction  using Cu Representative room-temperature stress–strain curves of pure melt-spun Al ribbons and those with various BNNT loading fractions are shown in Figure The maximum measured strengths of ribbons are 60 MPa (Al), 75 MPa (Al-BNNT 0.5 wt.%), 115 MPa (Al-BNNT 1.0 wt.%), and 145 MPa (Al-BNNT 3.0 wt.%). The curves for Al and Al-BNNT 0.5 wt.% ribbons look nearly similar, meaning that at such low BNNT loading fractions, the tensile properties still cannot be modified. However, with increasing BNNT content, the tensile strength and the slope of the curves (and thus the Young’s modulus) dramatically change. For example, the ultimate tensile strength and the Young’s modulus more than doubled in the sample with 3 wt.% BNNTs.It would be interesting to compare the obtained tensile strength data with the previously reported results for Al-CNT composites. For example, Kuzumaki et al.  measuredFigure The BNNT network is clearly seen at the edge of the Al matrix. Many nanotubes protrude out of the polished Al phase, creating a sort of internal microframe. The inset to this figure displays an optical image of the same ribbon after polishing and chemical etching of its surface. Most of the Al grains after melt spinning are very fine, around only 2 to 3 μm in size. Figure The ribbon casting rate can hardly be controlled using the present experimental setup. It is determined by the specific melting conditions inside the inductor of the melt-spinning equipment, which sometimes may vary. Perfect texturing/orientation of BNNTs within the melt-spun ribbons is difficult to achieve, and the tubes are mostly randomly oriented within the ribbons, having only a sort of quasi-alignment along the casting direction. Viscosity of the melt can be controlled by its overheating; this may result in better nanotube orientation under casting, but the overheating can lead to the negative phenomenon of BNNTs floating to the upper molten zone and inhomogeneous tube distribution in the ribbons after casting.Figure The atomically resolved TEM image in Figure The above-presented microscopic analysis revealed several important features of the nanotube-containing melt-spun material and its deformation process: (1) the multiwalled BNNTs are randomly distributed in the melt-spun ribbons; (2) no other phases except pure Al and well-preserved BNNTs are present in them; (3) BNNT cohesion strength with the metal is high enough and allows them not to be pulled out from the metal during tension; (4) the nanotubes, at least partially, carry the tensile load, as evidenced by their microscopic images for which the tube axes are somehow aligned along the deformation axis  with various multiwalled BNNT contents (0.5 to 3.0 wt.%) by melt spinning. Scanning and transmission electron microscopy, X-ray diffraction, and energy dispersive X-ray analysis confirmed the decent integration of the two phases into a dense and compact composite. No other phases, like Al borides or nitrides, form in the resultant melt-spun composites. The BNNTs are randomly oriented within the Al matrix and partially participate in carrying the tensile load, as evidenced by their presence and breakage at the composite fracture surfaces. The ultimate tensile strength of the composite ribbons with 3 wt.% of BNNT at room temperature was more than doubled (145 MPa) compared to non-loaded pure Al ribbons (60 MPa).The authors declare that they have no competing interests.YM made the composite ribbon samples and performed microscopic characterizations and tensile tests under the supervision of DG. AP took part in the SEM analysis of the fracture surfaces. YM, AP, and DG wrote the final manuscript. DMT, CZ, YB, KF, and DVS took part in the discussion of the results and read and approved the final manuscript. All authors read and approved the final manuscript.


Approximately 80% of patients with the first-episode schizophrenia reach symptomatic remission after antipsychotic therapy. However, within two years most of them relapse, mainly due to low levels of insight into the illness and nonadherence to their oral medication. Therefore, although the formal data available is limited, many experts recommend prescribing long-acting injectable second-generation antipsychotics  in the early stages of schizophrenia, particularly in patients who have benefited from the original oral molecule in the past and agree to receive long-term injectable treatment. Early application of long-acting injectable second-generation antipsychotics can significantly reduce the risk of relapse in the future and thus improve not only the social and working potential of patients with schizophrenia but also their quality of life. First-generation long-acting injectable (depot) antipsychotics AP1G) emerged in clinical practice in the 1960s. For the treatment of schizophrenia, their use resulted in a significant decrease in the number of patients relapses, including length and frequency of hospitalizations G emerged. This trTherapy for the first episode of schizophrenia has certain specific features. Patients respond to low doses of antipsychotics relatively well; yet they are more sensitive to the adverse effects, particularly extrapyramidal ones , 13. PatSchizophrenia is a chronic mental disease characterized among other things by a high degree of nonadherence to prescribed medication . It has Since available studies differ in methodology and primary observation goals , it is dDepot AP1Gs, let alone LAI AP2G, are rarely prescribed for patients with first-episode schizophrenia, although their levels of non-adherence and hence the risk of subsequent relapse are in reality very high , 30. Impnot using LAI antipsychotics in patients with first-episode schizophrenia. German psychiatrists stated that they find it difficult to present the benefits of a long-term injectable antipsychotic therapy to patients who do not have any personal experience with schizophrenia relapse, as they are still at the very beginning of their illness. Poor availability of LAI AP2G was identified as another reason, particularly when AP2G are strongly preferred over AP1G, especially in patients with first-episode schizophrenia. The last reason was mainly personal reservations of the psychiatrists associated associated with difficult control of adverse effects of depot antipsychotics, negative impact on patient-psychiatrist relationship, or higher amount of psychiatrist's time needed to manage depot medication administration [Heres et al.  used a qstration . The surstration , 32. Thistration , 34, 35.stration . AlternaRecent studies show that long-term injectable AP2G therapy is effective and also acceptable for first-episode patients, which is in opposition to the above-mentioned “conservative” attitudes , 37. Unfn = 15), patients treated with LAI risperidone showed more significant reduction of total PANSS score (by 16.1), as compared with oral AP2G (by 5.0) [As far as LAI AP2G products are concerned, researchers have clinical experience with LAI risperidone, olanzapine pamoate, and paliperidone palmitate. Although many studies in schizophrenia with these products have been performed, relatively limited data on their use specifically in first-episode patients is available. Only LAI risperidone has been specifically studied for the use in early stage of schizophrenia see  in addit(by 5.0) . Weiden (by 5.0)  publishe(by 5.0) . Ninetee(by 5.0) . Bartzok(by 5.0)  examined(by 5.0) .LAI AP2G have been used in clinical practice for several years. Nowadays, LAI AP2G are reserved mainly for patients with long-term course of schizophrenia who show low adherence to oral medication. The studies performed especially with LAI risperidone in patients with first episode or early stage of schizophrenia clearly indicated that this form of therapy could be effective and well tolerated also in this subgroup of patients with schizophrenia. Thanks to the familiar mother molecule  data concerning efficacy and tolerability of LAI risperidone in first-episode schizophrenia, patients could be applicable for paliperidone palmitate as well. Combined benefits of AP2G characteristics with an assured route of administration raise a question whether LAI AP2G should be recommended also in first-episode patients , 47. InsApproximately 80% of patients with a first episode of schizophrenia reach symptomatic remission after antipsychotic therapy. However, within two years most of them relapse mainly due to low insight into the illness and non-adherence to oral medication. Therefore, although the formal data available are limited many experts recommend prescribing long-acting second-generation antipsychotics  in the early stages of schizophrenia, particularly in patients who benefited from the original oral molecule in the past and agree to receive long-term injection treatment. Early application of long-acting injectable second-generation antipsychotics can significantly reduce the risk of relapses in future and thus improve not only social and working potential of patients with schizophrenia but also their quality of life.


Late gadolinium enhancement (LGE) occurs at the right ventricular (RV) insertion point (RVIP) in patients with pulmonary hypertension (PH) and has been shown to correlate with cardiovascular magnetic resonance (CMR) derived RV indices. However, the prognostic role of RVIP-LGE and other CMR-derived parameters of RV function are not well established. Our aim was to evaluate the predictive value of contrast-enhanced CMR in patients with PH.RV size, ejection fraction (RVEF), and the presence of RVIP-LGE were determined in 58 patients with PH referred for CMR. All patients underwent right heart catheterization, exercise testing, and N-terminal pro-brain natriuretic peptide (NT-proBNP) evaluation; results of which were included in the final analysis if performed within 4 months of the CMR study. Patients were followed for the primary endpoint of time to clinical worsening .Overall, 40/58 (69%) of patients had RVIP-LGE. Patients with RVIP- LGE had larger right ventricular volume index, lower RVEF, and higher mean pulmonary artery pressure (mPAP), all p < 0.05. During the follow-up period of 10.2 ± 6.3 months, 19 patients reached the primary endpoint. In a univariate analysis, RVIP-LGE was a predictor for adverse outcomes (p = 0.026). In a multivariate analysis, CMR-derived RVEF was an independent predictor of clinical worsening (p = 0.036) along with well-established prognostic parameters such as exercise capacity (p = 0.010) and mPAP (p = 0.001).The presence of RVIP-LGE in patients with PH is a marker for more advanced disease and poor prognosis. In addition, this study reveals for the first time that CMR-derived RVEF is an independent non-invasive imaging predictor of adverse outcomes in this patient population. Significant advances in our understanding of the pathophysiology of pulmonary hypertension (PH) have led to several therapies that have improved quality of life and decreased mortality. Indeed, in this decade, 1-year survival rate is 85% versus 68% in the 1980s . ClinicaDue to its relatively high intra- and inter-observer reproducibility, many have advocated the use of cardiovascular magnetic resonance (CMR) over echocardiography as a non-invasive way to predict outcomes and assess the effects of medical therapy on RV function over time -6. RecenWhile previous publications focused on the existence of RVIP-LGE in patients with PH and its association with multiple indices of RV failure, our study sought to investigate the potential role of RVIP-LGE and other CMR-derived parameters of RV function as non-invasive predictors of death, decompensated RV heart failure, initiation of prostacyclin or lung transplantation. Specifically, we hypothesized that: 1) the presence of RVIP-LGE significantly correlates with both the hemodynamic parameters of PH and associated RV findings, and 2) RV function, including RVIP-LGE, can be used to predict time to clinical worsening in patients with PH.2. All patients underwent right heart catheterization, exercise testing and measurement of N-terminal pro brain natriuretic peptide (NT-proBNP), but the results of these tests were included in the final analysis only if they were performed within 4 months of their CMR evaluation. Each patient underwent a thorough clinical evaluation by one of two physicians with expertise in PH (MG and SR), in which World Health Organization (WHO) functional status [1 and Table 2We evaluated 62 consecutive patients with PH referred for CMR as part of their clinical assessment between January 2009 and July 2010. Patients were excluded if they had an implantable cardioverter defibrillator or pacemaker, were claustrophobic, other contra-indication to CMR, or had a GFR of less than 30 ml/min/1.73 ml status  was assel status . PatientMedical records were reviewed for the primary endpoint of time to clinical worsening. Time to clinical worsening includes 1) all cause mortality 2) hospitalization due to clinically decompensated right ventricular heart failure requiring IV therapy 3) initiation of prostacyclin or 4) lung transplantation. All deaths were confirmed by the social security death index. Whenever possible, the causes for hospitalization and death were recorded. The study was approved by the Institutional Review Board. While patients were prospectively tracked from the time of their CMR study to the primary end point or completion of study, hemodynamic data, functional analysis and NT-proBNP were retrospectively obtained in order to include a reasonably comprehensive, clinically relevant dataset in as many patients with PH as possible.CMR images were acquired on a 1.5-T scanner . Retrospectively gated cine images were obtained using the steady-state free precession (SSFP) sequence . Standard long-axis views were obtained, including four-chamber, two-chamber, and three-chamber images. In addition, one series of short axis slices that included both right and left ventricles from base to apex were acquired and a series of axial cines were acquired in order to determine atrial volumes. LGE images of the short and long axis views were obtained 10 minutes after infusion of gadolinium-diethylene triamine-pentaacetic acid (Gd-DTPA 0.2 mmol/kg) using T1-weighted gradient echo pulse sequence with a phase sensitive inversion recovery reconstruction . An inversion time between 250 and 300 ms generally achieved successful nulling of the myocardium. During image acquisition, suspected partial volume and other artifacts seen on the LGE images were accounted for by either directly comparing the LGE image with an SSFP cine image taken at the same slice position or by swapping phase-encoding and frequency-encoding directions. If the existence of LGE was still in doubt, a second imaging plane was prescribed directly through the area of interest for further clarification.Images were analyzed using commercial software . Short axis slices were used to calculate left and right ventricular end-diastolic (first cine phase of the R wave triggered acquisition) and end-systolic  volumes, masses, and ejection fractions by the Simpson method of disks . Left anAlthough all patients had a right heart catheterization to initially diagnose PH, a subgroup of them underwent right heart catheterization (using a Swan-Ganz catheter) within 4 months their CMR study. Hemodynamics and mixed venous oxygen saturation were obtained. Cardiac output and index were calculated using the thermodilution technique. Pulmonary vascular resistance and right ventricular stroke work were recorded by standard formula.Although a majority had an NT-proBNP drawn at some point during their PH evaluation, NT-proBNP was measured in a subgroup of patients using a commercially available assay  within 4 months of their CMR study.A subgroup of patients underwent exercise treadmill testing performed using the Naughton-Balke protocol , whereint-test  to compare the means of normally distributed continuous variables in those patients with and without RVIP-LGE. The Mann-Whitney U test was used to compare the means for non-normally distributed variables. Categorical variables were compared using Fisher Exact or Chi-Square test. P values < 0.05 were considered statistically significant. In 26 randomly selected patients, interobserver reproducibility between the primary reader and an additional investigator was assessed by means of percent agreement and Cohen's kappa (κ) statistic. Cox proportional hazard analysis was performed to assess univariate and multivariate predictors of clinical worsening. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Multivariable analysis was performed using six variables that were the most statistically significant in the univariate analysis and satisfied the linearity and proportional hazard assumptions for linear regression. These variables include left ventricular end-diastolic volume index, RVEF, mean pulmonary artery pressure (mPAP), METs, NT-proBNP, and RVIP-LGE. The discriminatory capacity of the independent predictors of outcome was investigated using non-parametric estimates of the area under the receiver operating characteristic (ROC) curves. Survival curves for RVIP-LGE and each of the multivariate predictors of outcome were constructed with the Kaplan-Meier method and were compared by means of the log-rank test. The threshold values for each multivariate predictor of outcome were selected based on highest specificity and sensitivity as generated by the previously mentioned ROC curves. All statistical analyses were performed using Prism  or Stata . MIX 2.0 software was used to prepare the forest plot graphs [Categorical variables were expressed as percentages and continuous variables as mean ± standard deviation. We used an independent sample (unpaired) Student t graphs .Of the 62 patients, RVIP-LGE was indeterminate in 3 patients due to technical issues resulting in poor signal to noise ratio and excessive motion artifact in 1 patient. These 4 patients were not included in the final analysis. A total of 35 patients underwent right heart catheterization, 43 patients underwent NT-proBNP evaluation, and 42 patients underwent exercise stress testing within 4 months of their CMR study. During the mean follow-up period of 10.2 ± 6.3 months, 19/58 (33%) patients reached the primary endpoint of time to clinical worsening: 6 patients died, 11 were hospitalized for decompensated right ventricular heart failure, and 2 patients were hospitalized for initiation of prostacyclin analog. Of the patients who reached the primary endpoint, RVIP-LGE was present in 18/19 (95%). The patient without RVIP-LGE had sarcoidosis and was hospitalized for PH exacerbation.Overall, RVIP-LGE was present in 40/58 (69%) of patients Figure . In compThere was good interobserver agreement in identifying the existence of RVIP-LGE between the primary reader and an additional investigator .The HR, CI, and statistical significance for all invasive and non-invasive variables are reported in Figure Kaplan-Meier survival curves generated for RVIP-LGE and the three independent predictors of time to clinical worsening are shown in Figure In this study, we found that in patients with PH, not only is RVIP-LGE associated with RV dilation and hypertrophy, reduced RVEF, and more extensive hemodynamic abnormalities, but its presence is also a univariate predictor of time to clinical worsening. Although a few previous publications have discussed the existence and extent of RVIP-LGE in patients with PH and its inverse correlation with RV function, we have demonstrated in this study that it is also a non-invasive marker of adverse outcomes. In a multivariate analysis, although RVIP-LGE is no longer statistically significant, we show that CMR-derived RVEF is an independent predictor of time to clinical worsening along with known important clinical parameters of PH such as mPAP and METs.In 2005, Blyth et al. reported that 23/25 92%) of their patients with PH had RVIP-LGE and that the extent of LGE was highly correlated with RV volume, RV mass, mPAP, and inversely correlated with RVEF . A secon2% of theThe prevalence of RVIP-LGE in PH patients is not clearly defined; in fact, some previous publications have reported it as a nearly universal finding . In our Since the presence of RVIP-LGE is highly associated with reduced RV function, we followed all patients for an average of 10 months and found that patients with RVIP-LGE were ten times more likely to reach the primary endpoint of clinical worsening than those patients without RVIP-LGE. While significantly predictive in a univariate analysis, the presence of RVIP-LGE was not an independent predictor of poor outcomes in a multivariable analysis likely due to its strong association with other variables included in the model. However, the data suggest that it is a strong marker for detecting more severe disease manifested by higher mPAP and lower RVEF and functions as a simple, binary, reproducible, and visible reflection of these independent predictors of clinical worsening. Furthermore, the absence of RVIP-LGE predicted 100% survival in 14 months whereas only half of the patients with evidence of RVIP-LGE were alive or free from hospitalization or prostacyclin initiation in the same time frame.In our patient cohort, RVEF was the only independent prognostic variable obtained from the CMR examination. We also confirm previous reports  that mPAIn the only other publication studying the prognostic significance of CMR variables in patients with PH, van Wolferen et al. performed CMR, right heart catheterization, and the six minute walk test at baseline and 1-year later in patients with idiopathic pulmonary arterial hypertension . They foThe cause of RVIP-LGE in patients with PH remains to be fully elucidated. Myocardial infarction is highly unlikely, given the atypical pattern and focal distribution of RVIP-LGE. Although several studies have shown reversible ischemia in the right ventricle, particularly in PH patients with elevated pulmonary pressures, none have shown fixed perfusion defects in the RVIP . MyocardOne important limitation of our study is that only a subset of patients underwent right heart catheterization, NT-proBNP testing and/or functional testing within 4 months of their CMR exam. However, we felt it important to include these data (despite the above limitation) in our analysis because PH is a rare disorder with limited opportunities for study and that it would be important to define the prognostic value of CMR within the context of other clinically relevant variables. Another important limitation of our study is that we were unable to reliably quantify the amount RVIP-LGE due to partial volume effect, preventing us from accurately defining the borders of hyperenhancement in every patient. We believe, however, that there is significant clinical utility in being able to easily visualize the presence of RVIP-LGE and using it as a marker for detecting more severe disease and worse outcomes.Contrast-enhanced CMR may be a useful tool in the management of patients with PH. RVIP-LGE is a readily visible, non-invasive marker associated with more advanced PH, as reflected by its association with larger RV volumes and greater RV mass, reduced RVEF, and higher mPAP. Patients with RVIP-LGE are significantly more likely to worsen clinically than those without this marker. Additionally, CMR-derived RVEF is an independent predictor of adverse outcomes in patients with PH and its ability to risk stratify PH patients is similar to that of mPAP and METs. As new medications for PH are developed and patients with this disease are treated earlier in their disease course, contrast-enhanced CMR could potentially help in risk stratification so that appropriate therapy can be given in a timely manner.SLA: NIH-RO1-HL071115 and 1RC1HL099462-01, the American Heart Association, and the Roche Foundation for Anemia ResearchMGM: Actelion, Gilead, Lilly/Icos, Pfizer, Novartis, and United Therapeutics have provided funding to the University of Chicago to support conduct of clinical trials. MGM has served as a consultant/participant on data safety monitoring board/steering committee for clinical trials for Actelion, Gilead, Medtronic, and Pfizer. MGM does not do any promotional speaking. MGM has a patent filed entitled, "Compositions and Methods for Treating Pulmonary Hypertension" for the use of sorafenib in pulmonary hypertension. WO/2007/087575BHF was involved in acquiring and interpreting the data. He was primarily responsible for drafting the manuscript. MGM, SR, and SLA conceived of the idea for the project and helped critically revise the manuscript for intellectual content. SC and EBJ acquired and interpreted the data. ARP and RML helped conceive of the idea for the project, analyze the data, and critically revise the manuscript for intellectual content. VM helped analyze the data and helped in drafting the manuscript. All authors gave final approval of this version to be published.


Previous studies have reported an excess burden of cancer and mortality in populations with chronic hepatitis B (HBV) or C (HCV), but there are limited data comparing hospitalization rates. In this study, we compared hospitalization rates for all causes and viral liver disease in people notified with HBV or HCV in New South Wales (NSW), Australia.HBV and HCV notifications were linked to their hospital (July 2000-June 2006), HIV and death records. Standardized hospitalization ratios (SHRs) were calculated using rates for the NSW population. Random effects Poisson regression was used to examine temporal trends.P < 0.001).The SHR for all causes and non alcoholic liver disease was two-fold higher in the HCV cohort compared with the HBV cohort (SHRs 1.4 (95%CI: 1.4-1.4) v 0.6 (95%CI: 0.6-0.6) and 14.0 (95%CI: 12.7-15.4) v 5.4 (95%CI: 4.5-6.4), respectively), whilst the opposite was seen for primary liver cancer (SHRs 16.2 (95%CI: 13.8-19.1) v 29.1 (95%CI: 24.7-34.2)). HIV co-infection doubled the SHR except for primary liver cancer in the HCV/HIV cohort. In HBV and HCV mono-infected cohorts, all cause hospitalization rates declined and primary liver cancer rates increased, whilst rates for non alcoholic liver disease increased by 9% in the HCV cohort but decreased by 14% in the HBV cohort (Hospital-related morbidity overall and for non alcoholic liver disease was considerably higher for HCV than HBV. Improved treatment of advanced HBV-related liver disease may explain why HBV liver-related morbidity declined. In contrast, HCV liver-related morbidity increased and improved treatments, especially for advanced liver disease, and higher levels of treatment uptake are required to reverse this trend. Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is associated with increased morbidity and mortality. Several data linkage studies have reported an excess burden of hepatocellular carcinoma (HCC) and mortality, particularly from advanced liver disease -5. They There have been considerable advances in antiviral therapy for HBV and HCV since the mid-1990s. A population-based study examining trends in hospitalization rates, especially for liver-related admissions, may suggest an effect of improved therapy on disease burden. In particular, we hypothesize that trends in hospitalization rates for advanced HBV and HCV-related liver disease may be diverging, given that HBV therapy can be utilized in liver failure -10 and hThe study cohorts comprised all people notified with acute or chronic HCV or HBV infection in NSW (population 7 million), as recorded on the NSW Notifiable Diseases Database (NDD)  between Hospital admissions for each cohort were obtained from the Admitted Patient Data Collection , a data The Registry of Births Deaths and Marriages  is a regData linkage was carried out by the Centre for Health Record Linkage (CHeReL) . The NDDFor the study cohorts, we examined the distribution of hospitalizations around the time of diagnosis and determined that excluding admissions before or beginning within 14 days of the HCV or HBV diagnosis (or earliest of the two diagnosis dates if co-infected) was sufficient to reduce the bias towards higher rates of admission around the time of diagnosis, as previously noted   until the end of the study period or death (whichever came first). The time at risk included the time spent in hospital as the patient was still at risk of a new episode of care with a different principal diagnosis. Standardized hospitalization ratios (SHRs) were calculated by comparing numbers of admissions with those expected using hospitalization rates for the NSW population by 5 year age group, sex and calendar year. To account for the correlation between hospitalizations for the same person, 95% confidence intervals (CIs) for SHRs were calculated using the method by Stukel et al , and a rEthics approval for the use of these confidential health data was granted by the University of NSW and the NSW Population and Health Services Research Ethics Committee.There were 129 472 individuals notified with HBV, HCV or both infections eligible for the study. Of 86 501 HCV cases, 3.7% were also notified with HBV, 0.8% with HIV and 0.04% with both HBV and HIV. Of 46 188 HBV cases, 6.9% were also notified with HCV, 0.6% with HIV and 0.08% with both HCV and HIV. Compared with HBV mono-infected cases, HCV mono-infected cases were more likely to be male, have at least one hospitalization and die during the study period . Hospitalization rates for the HCV/HIV and HBV/HCV cohorts showed no change over time, whilst rates for the HBV/HIV cohort declined by 15% between 2000-2003 and 2004-2006, although this decline was not statistically significant.Between 2000 and 2006, hospitalization rates for all causes declined significantly for HBV and HCV mono-infection cohorts Table , with thP = 0.002 and P < 0.001, respectively).The highest hospitalization rates and SHRs for non alcoholic liver disease were in the co-infected cohorts Table . CompareFor both the HBV and HCV mono-infection cohorts, hospitalization rates for non alcoholic liver disease increased with age and the highest rates and SHRs were in the 60+ age group Figure . Rates aHospitalization rates for non alcoholic liver disease demonstrated contrasting trends over time for the HBV and HCV mono-infected cohorts, with a significant increase in the HCV cohort and a significant decrease in the HBV cohort Table . SimilarP < 0.001 for both). This was in contrast to the comparison for non alcoholic liver disease.The highest hospitalization rate and SHR for primary liver cancer was in the HIV/HBV co-infection cohort. However, due to the small sample size the SHR was not significantly different to that for other cohorts Table . In the For both HBV and HCV mono-infection cohorts, hospitalization rates for primary liver cancer increased with age and the highest rates were in the 60+ age group Figure . Rates aP = 0.028).Rates of hospitalization for primary liver cancer increased significantly between 2000 and 2006 for both the HBV and HCV mono-infection cohort Table . HoweverOur study revealed contrasting hospital-related morbidity among individuals diagnosed with HBV and HCV infection, and that hospitalization rates were consistently higher in all co-infected cohorts, particularly those with HIV. The all cause and non alcoholic liver disease hospitalization rates and SHRs were two-fold higher in the HCV mono-infection cohort compared with the HBV mono-infection cohort, with all cause rates for HBV mono-infection even lower than in the NSW population. In contrast, the HBV mono-infected cohort had a hospitalization rate and SHR for primary liver cancer close to two-fold higher than that for the HCV mono-infected cohort. Perhaps the most notable contrast, however, is that between 2000 and 2006 rates for non alcoholic liver disease increased significantly in the HCV mono-infected cohort but decreased significantly in the HBV mono-infected cohort. Trends that were further accentuated in the HIV co-infection cohorts and are suggestive of an impact of improved treatment for advanced HBV-related liver disease -10,12,14Contrasting all cause hospital-related morbidity between the HCV and HBV infected cohorts may relate to differing epidemiological patterns and health care utilization. In Australia, it is estimated that over 80% of HCV cases are in Australian-born injecting drug users, infected in their young adult years, with a smaller proportion among immigrants . In contRates of hospitalization for non alcoholic liver disease and primary liver cancer increased markedly with age in both the HBV and HCV infected cohorts, consistent with previous studies. In a systematic review, hepatic fibrosis progression was found to be non linear and significantly affected by duration of HCV infection . In addiAs expected, co-infection with HIV increased the burden of morbidity for both the HCV and HBV cohorts. Compared with the mono-infected cohorts, there was at least a two-fold increase in SHRs for all three admission types examined, except for primary liver cancer in the HCV/HIV cohort. HIV co-infection has been shown to be associated with an increased HBV and HCV viral load, a higher rate of fibrosis progression and increased risk of cirrhosis -35. In aThe burden of non alcoholic liver disease was expected have increased during 2000-2006. This is because the disease cohorts are aging, as well as continuing to expand, albeit at a slower rate than in previous decades ,38. HoweThere are several factors that may help to explain why HBV treatment has impacted on liver-related morbidity at a population level. First, therapy for HBV improved during the study period. Although lamivudine (available since 1998) can be successfully used to treat advanced HBV-related liver disease , the avaThe greater decline in non alcoholic liver disease hospitalizations for the HIV/HBV cohort compared with the HBV mono-infected cohort adds to the evidence for an impact of HBV therapy at a population level. Tenofovir was approved for HIV treatment in Australia in 2002, prior to approval of adefovir (2004), entecavir (2006) or tenofovir (2008) for HBV mono-infection. Tenofovir provides high and sustained levels of HBV DNA suppression in HIV/HBV and HBV populations, with no described resistance ,40, and The contrasting trends in non alcoholic liver disease morbidity are consistent with trends for liver transplantation and mortality data. U.S. liver transplant waiting list data showed a 27% decline in HBV-related end stage liver disease registrations between 1999 and 2006 . SimilarRates of hospitalization for both HBV- and HCV-related primary liver cancer increased during 2000-2006, consistent with the increasing number of liver cancer diagnoses in Australia ,44. A fuThe major strength of our study is that it is a large population-based linkage study including HIV co-infection status. By linkage of the cohorts to their hospital records we were also able to account for the correlation between hospitalizations for the same patient in our analyses of changes over time. The temporal trends presented here may therefore differ from the crude rate changes reported in other studies that were unable to account for within patient clustering or increases in the HCV and HBV infected population -50.Population-based studies have some methodological limitations. In particular, caution needs to be exercised when comparing the different cohorts as some of the differences may be due to unmeasured confounding factors. Differences in the overall burden and trends over time may be due to variations in health care utilization rather than differences in actual morbidity. Second, while the aim of our study was to examine morbidity in cases of chronic HBV and HCV infection, more than 65% of HBV records and 77% of HCV records did not specify whether a case was acute or chronic and only 2% and 1% of cases, respectively, were recorded as newly acquired. For this reason all records were included, which would lead to an underestimate chronic HBV and HCV-related morbidity as some of the notified cases may have cleared their infection. However, it is estimated that 74% HCV infections are chronic  and mostOur population-based study indicates that hospital-related morbidity overall and for non alcoholic liver disease is considerably higher in notified cases with HCV than in those with chronic HBV and that the gap in morbidity associated with these conditions is widening. The decline in HBV-related liver disease may, at least in part, be due to improved treatment of advanced HBV-related liver disease and the greater reduction in morbidity from non alcoholic liver disease in the HBV/HIV infected cohort supports this assertion. For the HCV infected cohort, liver-related morbidity is increasing and improved treatments, especially for advanced liver disease, and higher levels of treatment uptake are required to reverse this trend.The authors declare that they have no competing interests.The study was designed by HG and GD. Data extraction was undertaken by HG. The analysis was conducted by HG with assistance from ML and JA. The manuscript was drafted by HG with modifications by GD and ML. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/11/52/prepub


The risk assessment of falls is important, but still unsatisfactory and time-consuming. Our objective was to assess quantitative ultrasound (QUS) in the risk assessment of falls. Our study was designed as epidemiological cross-sectional study occurring from March 2009 to February 2010 by community survey at a medical center. The participants were collected from systemic sample of 1,200 community-dwelling people  40 years old and over in Yunlin County, Mid-Taiwan. Structural questionnaires including socioeconomic status, living status, smoking and drinking habits, exercise and medical history were completed. Quantitative ultrasound (QUS) at the non-dominant distal radial area (QUS-R) and the left calcaneal area (QUS-C) were measured. The overall prevalence of falls was 19.8%. In men, the independently associated factors for falls were age , fracture history , osteoarthritis history  and speed of sound  by QUS-R. In women, the independently associated factors for falls were current drinking  and broadband ultrasound attenuation  by QUS-C. The cutoffs at -2.5< T-score<-1 derived using QUS-R  in men or T-score ≦-2.5 derived using QUS-C  in women showed an independent association with falls. The lowest T-score derived using either QUS-R or QUS-C was also revealed as an independent factor for falls in both men  and women . Conclusions: Quantitative ultrasounds, measured either at the radial or calcaneal area, are convenient tools by which to assess the risk of falls in middle-aged and elderly people. It is well known that about 10–40% of community-dwelling people aged 65 year-old or older may have had one episode of falling in one year The more risk factors of falls elderly people have, the higher is the prevalence rate of falls Bone strength is constituted by both bone density and bone quality In meta-analysis, the long-term risk of hip fractures in 50 year-old males with previous Colles’ fractures was found to be 8%, which is higher than has been found for those with previous spinal fractures (6%) or with global fractures (3%) As the QUS is a popular tool for both professional and general population, it would have substantial impact to the public health strategy if the QUS can be used for risk assessment of falls, especially in an aging society. The aims of this study were (1) to assess the interrelationships between falls and bone parameters derived using either radial or calcaneal QUS in men and women across a middle-aged and elderly community-dwelling population, and (2) to disclose whether different sites for QUS measurement may play different roles according to gender in risk assessment for falls.In Taiwan, the elderly population has reached more than 11.0%. Yunlin County, with an elderly population of 15.4%, has been rated as the county with the second highest elderly population in Taiwan After fasting overnight, the anthropometry of the subjects, including the body height and body weight, was measured using DETECTO™. The body mass index (BMI) was calculated accordingly. Subjects were required to complete a structural questionnaire that included disclosure of exercise habits and other lifestyle habits , living and socioeconomic status, past medical conditions, drug history and fracture history. These questionnaires had been validated in previous studies We defined subjects to have a habit of moderate exercise if the frequency of exercise was more than 3 times per week, current smoking if participants still smoked 1 pack (20 cigarettes) at least per month for more than 6 months and current drinking if participants still drank 1 time per week for more than 6 months Each subject completed the QUS measurement in less than 5 minutes. Their bone parameters, including broadband ultrasound attenuation  using left calcaneal quantitative ultrasound , speed of sound  using non-dominant radial quantitative ultrasound  and T-scores derived from calcaneal or radial QUS were obtained. In this study, the correlation coefficients between QUS-C or QUS-R and bone mineral density as derived from dual energy X-ray absorptiometry  were 0.510–0.588 and 0.241–0.310, respectively. The QUS-derived T-scores using Asian references were used for the classification as normal (T-score ≧−1.0), low bone mass (osteopenia) (−1.0< T-score<−2.5) and osteoporosis (T-score ≦ −2.5) according to the definition available from the World Health Organization t test. Logistic regression models were used to evaluate the independent associations of risk factors for falls by gender. The BUA and SOS of the QUS, either in regard to continuous or categorical T-scores, were used for risk assessment of falls in different logistic regression models. Statistical significance was defined as p<0.05 for two-tailed analysis.Data were collected and analyzed using the Statistical Package of Social Science for Windows software Version 16 . All the continuous variables, such as age, body mass index, total smoking amount, SOS derived using radial QUS and BUA derived using calcaneal QUS were expressed as means (SD). The categorical variables including socioeconomic status, living alone, drinking, moderate exercise, past history of HTN, DM, arrhythmia, OA, psychiatric drug use and fractures were all expressed as percentages. Subjects were divided into either a faller group or a non-faller group. The comparisons between fallers and non-fallers in regard to categorical variables were analyzed using Chi-square test, and continuous variables were analyzed using independent In To disclose whether different sites of QUS measurement may play a different role by gender in risk assessment of falls, different parameters for radial and calcaneal QUS were used in the logistic regression model for both genders. In the regression model using radial QUS, the SOS  or a categorical variable  was an independently negative risk factor for falls in males only. Age, fracture history and osteoarthritis history were the remaining independent risk factors in males, as were the age and current alcohol drinking factors in females . In the Because discordant T-scores between calcaneal and radial QUS were not uncommon, the lowest T-score derived from either calcaneal or radial QUS was used as the predictor for the further analysis in the logistic regression model for falls. With the exception of the independent factors of age, current alcohol drinking, fracture history and osteoarthritis history, the osteopenic group (−1.0< T-score<−2.5) showed a significantly higher risk of falls  as compared to the normal group (T-score ≧−1.0) in males, and the osteoporotic group (T-score ≦−2.5) showed a significantly higher risk of falls  as compared to the normal group (T-score ≧−1.0) in females .Consistent with previous reports in Taiwan Considering the conventional risk factors of falls Physical performance, including gait speed and stability, has been assessed as indicators of frailty Based on bone architecture and the pathophysiology of bone fragility in both women and men, cortical bone loss to be more predominant in middle-aged men and loss of connectivity of trabecular bone has been shown to be predominant in adult women There are several limitations in this study that should be of concern. Those who are frail or non-ambulatory may have a higher risk of falls during daily activities Calcaneal QUS in women and radial QUS in men can be an effective screening tool for risk assessment of falls in community dwelling middle-aged and elderly people.


Affective tactile stimulation plays a key role in the maturation of neural circuits, but the development of brain mechanisms processing touch is poorly understood. We therefore used functional magnetic resonance imaging (fMRI) to study brain responses to soft brush stroking of both glabrous  and hairy (forearm) skin in healthy children (5–13 years), adolescents (14–17 years), and adults (25–35 years). Adult-defined regions-of-interests in the primary somatosensory cortex (SI), secondary somatosensory cortex (SII), insular cortex and right posterior superior temporal sulcus (pSTS) were significantly and similarly activated in all age groups. Whole-brain analyses revealed that responses in the ipsilateral SII were positively correlated with age in both genders, and that responses in bilateral regions near the pSTS correlated significantly and strongly with age in females but not in males. These results suggest that brain mechanisms associated with both sensory-discriminative and affective-motivational aspects of touch are largely established in school-aged children, and that there is a general continuing maturation of SII and a female-specific increase in pSTS sensitivity with age. Our work establishes a groundwork for future comparative studies of tactile processing in developmental disorders characterized by disrupted social perception such as autism. Each participant or their parent or guardian provided written consent according to a protocol approved by the Yale School of Medicine Human Investigations Committee.CT-targeted touch) and to the palm of the hand . In each participant, 8 cm of the arm and 4 cm of the palm were marked to control for the length of stimulated skin, and two trained experimenters administered the stimuli.The tactile stimuli consisted of manual strokes with a 7-cm wide watercolor brush applied with slow strokes at a CT optimal velocity (8 cm/s)  was applied to the right palm or forearm according to a block design Figure . Each blTR = 1230 ms; TE = 1.73 ms; FOV = 256 mm; image matrix 2562; voxel size = 1 × 1 × 1 mm). Whole-brain functional images were obtained using a single-shot, gradient-recalled echo planar pulse sequence .fMRI brain scans were acquired on a Siemens 3T Tim Trio scanner . Anatomical images were collected using a T1-weighted MPRAGE sequence . Functional data preprocessing included slice time correction (using sinc interpolation), three-dimensional rigid-body motion correction using trilinear-sinc interpolation, spatial smoothing with a FWHM 4-mm Gaussian kernel, linear trend removal, and temporal high-pass filtering . Functional images were co-registered to within-session anatomical images and normalized to Talairach space. In each participant, estimated motion plots and cine loops were inspected for head motion greater than 2 mm of translation in any direction or two degrees of rotation about any axis. Also, no participant had rotation or translation exceeding 1 mm between two consecutive volumes or 2 mm integrated over four consecutive volumes. A general linear model (GLM) analysis was performed in each participant. Regressors were defined as boxcar functions convolved with a double-gamma hemodynamic response function (HRF). Six motion predictors were included as predictors of no-interest.p < 0.01 and corrected for multiple comparisons with a cluster level threshold estimated through the Brain Voyager QX cluster-level statistical threshold estimator plug-in  was assessed. A cluster-corrected threshold was set at α < 0.05 for each contrast. Given the higher power of the larger group, the adult maps were thresholded at a higher threshold of p < 0.001 before cluster level correction. The cluster-level threshold was not applied in the displayed images for visualization purposes.Whole-brain random-effects group-level GLM analyses were conducted in each group  for the contrasts Arm touch > Rest and Palm touch > Rest. All group-level analyses were restricted to voxels within the Montreal Neurological Institute (MNI) template brain normalized to Talairach space. In children and adolescents, the results were assessed at p < 0.001, cluster level correction for multiple comparisons), and defined all significant clusters located to the left SI and bilateral SII as ROIs. We then examined brain regions associated with the CT-targeted, affective-motivational dimension of touch, including the contralateral (left) insular cortex , and significant voxel clusters located in the left insula, the right pSTS and the prefrontal cortex were identified. In each of the ROIs defined in the adult group, we extracted individual voxel-average brain responses  in all groups. We then performed a post-hoc Three-Way  analysis of variance (ANOVA) to examine differences between the groups, and a correlation analysis to assess correlations between β values and age. We also tested for gender differences in each ROI. Since the sex ratios were unbalanced in children  and adolescents , we combined these participants into one group (children/adolescents) in this analysis.To examine the extent to which brain responses in children and adolescents were adult-like, we performed a region-of-interest (ROI) analysis. Here, we first examined the network of sensory-discriminative brain regions, associated with stimulation of Aβ afferents, with focus on contralateral (left) SI and bilateral SII .In order to identify age-related changes in brain processing of touch, we conducted a whole-brain, voxel-wise correlation analysis assessing linear correlations between individual brain responses and age. Here, we also examined gender-specific developmental effects by repeating the analysis in females and males, separately. In order to match males and females in terms of power and age, we excluded the youngest male (5 years old) and two randomly selected adults. This resulted in 19 subjects of each gender, with no significant differences in age , including the left  SI, bilateral SII, left insular cortex, several prefrontal cortex areas and a cluster of voxels extending into the pSTS   Figure , Table 1p < 0.001, k = 12). Highly significant clusters were found with peak coordinates in the SII  and left SI  or any of the other adult ROIs . There were no significant differences between females and males in adults or children/adolescents .All adult somatosensory ROIs were significantly activated in children and adolescents . Significant clusters were found with peak coordinates in the pSTS/MTG, left insular cortex and several prefrontal regions with focus on the frontal gyrus (FG)  Table .post-hoc ANOVA showed that there was no significant effect of age group on the brain responses to Arm touch in either of the ROIs, including the prefrontal regions .The adult pSTS/MTG and left insula ROIs were robustly activated in children and adolescents Table , and thep < 0.01, k = 12) in the right  parietal operculum of SII, likely in the cytoarchitectonic region OP1 . Activity in these regions did not correlate with age in males, on the whole-brain level (Table ps > 0.1). Moreover, the female correlation coefficients were significantly larger than the male coefficients . The Arm only analysis did not reveal any additional regions.The gender-specific analysis revealed strong positive correlations between brain responses in females and age in bilateral pSTS/MTG, the right precuneus and right cerebellum  SII was robustly activated in all age groups, with significant activity on the whole-brain level in all contrasts. Although not comparably robust, children and adolescents significantly activated adult SI and ipsilateral SII ROIs and there were no significant differences between the age groups in these regions. This finding suggests that the sensory-discriminative, somatosensory network is recruited in an adult-like fashion in children. However, we did find an age-dependent linear decrease in a region located to the ipislateral SII area and a non-significant trend toward a positive increase in SI responses with age. Interestingly, Brodoehl et al.  recentlyThe prefrontal cortex was activated to some degree in adolescents, and not in children, suggesting a potential developmental effect in these regions. 10-month old, but not younger, toddlers activate the prefrontal cortex more in response to stimulation by soft velvet than to a wooden stimulus , but the ROI overlapped extensively with Ig2 and the centroid  was located in this subregion. It is therefore likely that the activations in children and adolescents in this ROI correspond to previously demonstrated Ig2 responses to CT-targeted stimuli in patients (Olausson et al., We found that children, adolescents and, adults alike robustly activate the posterior insular cortex in response to CT-targeted touch, with similar magnitudes, and no gender differences were identified. Selective CT stimulation in patients lacking Aβ fibers activates the posterior, granular insular cortex (Olausson et al., All age groups robustly activated a region extending into the right pSTS in response to soft brushing of the arm, and there was a female-specific correlation between age and brain responses in the bilateral pSTS. The pSTS is a key hub in the network of social cognition regions, and is associated with functions such as social attention (Nummenmaa and Calder, The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Women undergoing radical cystectomy (RC) and urinary diversion for bladder cancer experience substantial limitations in health-related quality of life (HRQOL). However, the level of discomfort caused by different urinary diversion has been never evaluated in long term survivors. The aim of this multicenter study is to evaluate differences in HRQOL among recurrence-free women undergoing cutaneous ureterostomy (CUS), Bricker's ileal conduit (BK-IC) and Orthotopic neobladder VIP (ONB-VIP) in disease-free females treated with radical cystectomy (RC), with long-term follow up .All consecutively treated female patients from two urological institutions who underwent RC and urinary diversion from January 2000 to December 2008, with no evidence of tumor recurrence at a minimum follow up of 36 months, were included. Patients received the European Organisation for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder cancer-specific instruments (QLQ-BLM30) and the Functional Assessment of Cancer Therapy for Bladder Cancer (FACT-BL). Clinical data and questionnaire results were analyzed in order to evaluate the HRQOL differences among diversion groups.We identified 37 females , including 12 status-post CUS, 16 who underwent BK-IC, and 9 who underwent ONB-VIP. Most were healthy . Women undergoing CUS endorsed worse FACT-BL scores compared with BK-IC and ONB-VIP patients, worse HRQOL regarding physical and emotional well-being , and a trend toward worse EORTC QLQ-C30 scores for appetite loss and fatigue (p=0.05 for both).In our study long-term disease-free females treated with CUS endorsed worse HRQOL compared with women who underwent BK-IC or ONB-VIP, mostly due to worse physical and emotional perception of their body image. Bladder cancer (BC) ranks ninth in worldwide cancer incidence. It is the 7th most common cancer in men and the 17th most common cancer in women with more than 330,000 new cases each year and more than 130,000 deaths per year .In contemporary series, patients may achieve excellent long-term functional and oncologic outcomes when treated at high-volume institutions by experienced surgeons. Beyond the primary aim of disease control, removal of the bladder requires reconstruction of a lower urinary tract. Surgeons can reconstruct complex urinary diversions that also safeguard patients’ health-related quality of life (HRQOL) , but thiSeveral studies have attempted to evaluate HRQOL following RC and focused on the effects of various types of lower urinary tract reconstruction ,7. HobisThe aim of this study is to evaluate differences in HRQOL between different forms of urinary diversion in a consecutive series of female who had RC for muscle-invasive bladder cancer. We concentrated on long term (3years or more) recurrence-free females in order to assess HRQOL in a cohort that would not be biased by bladder cancer treatments.In order to evaluate the differences in terms of HRQOL among women treated with CUS, or BK-IC or ONB-VIP after RC for clinically localized bladder cancer, all consecutively female patients treated in two urological institutions from January 2000 to December 2008 without any evidence of tumor recurrence after at least 36 months from surgery were considered for this study. We enrolled disease-free patients in order to exclude bother related to adjuvant and salvage therapies and avert the social/emotional implication of disease progression. Another reason to enroll patients after at least 36 months after surgery was to avoid the biases of peri-operative care (more complex urinary diversions require more intensive nursing care in the postoperative recovery period).All patients were retrospectively assessed with the following self-administered questionnaires (they had help to filling the questionnaire in if it was needed): the European Organization for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder cancer-specific surveys (QLQ-BLM30) and the Functional Assessment of Cancer Therapy for Bladder Cancer (FACT-BL). For analysis, patients were stratified according to urinary diversion type.Subsequently the responses were entered into a database. Data from the questionnaires were analyzed in order to test differences among the groups. Informed consent was obtained from all patients. The study was conducted in accordance with the principles of research involving human subjects as expressed in the Declaration of Helsinki and with Good Clinical Practice.Included patients were at least 18 years of age, who underwent RC and urinary diversion for clinically localized bladder cancer in accordance with EAU criteria . Only diPatients were followed according to the surveillance schedules suggested in EAU guidelines . RC withWe classified perioperative complications according to the Clavien–Dindo classification . For risWe used the general and bladder cancer-specific HRQOL questionnaires EORTC QLQ-C30 , EORTC QWe used the Italian version of the EORTC QLQ-C30. In brief, the EORTC QLQ-C30 is a 30-item questionnaire composed of multi-item scales and single items that reflect the multidimensionality of the quality-of-life construct . It incoWe used the validated Italian version of QLQ-BLM30 from EORTC to assess bladder cancer-specific HRQOL . All queThe FACT-BL similarly evaluated patients’ bladder cancer-specific HRQOL. We used the validated Italian version of FACT-BL . FACT-BLAs null hypothesis we assumed that there was no difference among the urinary diversion groups in terms of HRQOL. Continuous, normally distributed variables were reported as the mean value with standard deviation (SD). Summary scores and responses to individual items are presented using descriptive statistics.All data were stratified according to urinary diversion with univariate ANOVA analyses  and with unpaired sample T tests. Statistical significance was achieved if p was <0.05. All reported p-values were two-sides. All data were recorded, collected and analyzed by using Statistical Package for the Social Sciences 16.0 for Microsoft .We enrolled 41 female patients who had RC for muscle invasive bladder cancer without any evidence of tumor recurrence after at least 36 months from surgery. 4 patients were excluded: 1 had serious inflammatory bowel disease and 3 had previous lower tract genitourinary surgery. Overall, a total of 37 females patients were included in the study. Mean age at surgery was 67.3 ± 8.7 years; mean age at follow-up was 73.1 ± 8.7 years. Clinical and pathological characteristic of the patients at surgery, stratified by urinary diversion type, are described in Table Twelve women were treated with CUS, 16 with BK-IC and 9 with ONB-VIP. Comorbidity counts were 0 in 24 patients, 1-2 in 4 patients, and 3 in 9 patients. All groups were similar according to clinical, pathological and peri-operative characteristics at the time of RC. All patients were disease-free at most recent follow-up .All included patients completed all the questionnaires. More remarkable subscores of all questionnaires are reported in Table In the last two decades, there has been a growing recognition of the importance of HRQOL among patients undergoing invasive surgical procedures. Therefore, some patients achieve durable cancer-free outcomes. It becomes necessary to safeguard the patients’ HRQOL related to their bladder cancer and its treatment .In our trial we investigated with validated instruments the overall quality of life of a very selected population of patients. In particular, we demonstrated that women undergoing CUS experience a loss of appetite and a worsening of fatigue in daily activities, inducing a worsening of both the physical and emotional well being.In our paper some aspects are interesting: the study was conducted on long term disease free survivors after RC for clinically localized bladder cancer. This specific population allows us to avoid biases related to the initial postoperative worse HRQOL and/or the fear for tumor recurrence after RC . MoreoveA further strength of this paper is the use of more than one specific validated questionnaire. In the majority of scales and items no differences were found between treatment groups in several clinical trials, such as in our study: therefore, the use of several questionnaires allow us to define the minimal variances across different treatment groups.EORTC QLQ-C30), the effects of the urostomy (EORTC QLQ -BLM30) and patients well-being (FACT-BL).The quality of life in patients undergoing cystectomy should take into account many aspects that must be evaluated in order to have data that comes as close as possible to the real situation of the patients themselves. No questionnaire, even if validated, disease specific and well-built, will take into account all the aspects necessary to have a complete evaluation. For this reason we decided to use different and validated questionnaires to evaluate more aspects as possible like: functional, symptoms, global health aspects  and the decline of “physical well being” and “emotional well being” (FACT-BL) could be investigated only by using different questionnaires.Moreover, the multiplicity of aspects investigated allows us to evaluate possible differences between what is expected based on surgical and anatomical data in literature and the real quality of life of the patient. For example during cystectomy the neurovascular bundle could be damaged  causing The present study has several limitations that should be considered when interpreting our results: in particular, this is a retrospective, cross-sectional, non randomized study in a limited number of patients. It caused a lack of information about baseline pre-treatment HRQOL evaluation, even if all data have been collected and assumed by the case history. However, the possibility of baseline differences in terms of HRQOL among the groups cannot be ignored. Some items, not specific for urological patients, such as mood disturbance or cognitive status were not included in our evaluation. Because this was not a randomized clinical trial, certain biases may have been introduced into analysis that were not properly controlled for and may have impacted the outcome, including the policies regarding urological operations in two different urologic centers involved in this study. In particular, as reported in the “2nd International Consultation on Bladder Cancer recommendations on the reconstructive options after radical cystectomy”, there are no evidences to recommend one form of diversion over another one, in females . ConsequFinally, as suggested by Studer, there is a lack of specific items regarding the management of the stoma . We needIn conclusion, based on data from a cross-sectional, non randomized study in a limited number of cases, females treated with cutaneous ureterostomy seem to be affected by a worse HRQOL when compared with those treated with Bricker or Paduan Ileal Neobladder, for the deterioration of both the physical and emotional perception of their body image.Moreover, there is no an exclusive questionnaire that should be used as gold standard to measure HRQOL in female after cystectomy: therefore, several validated questionnaires, investigating different items, scales and scores, have to be used to measure all the aspects of quality of life after RC in female, in future studies.Further randomized prospective studies, based on the data of our pilot study, are needed to address this important outcome.RC: Radical cystectomy; HRQOL: Healt-related quality of life; CUS: Cutaneousureterostomy; BK-IC: Bricker-Ileal conduit; VIP-ONB: Paduan Ileal Neobladder- Orthotopic neoblader; FACT: Functional assessment cancer therapy; EORTC QLQ-BLM 30: European Organisation for Research and Treatment of Cancer Quality of life Questionnaire bladder muscle invasive; EORTC-QLQ-C30: Treatment of Cancer Quality of life Questionnaire Cancer.The author(s) declare that they have no competing interests.MG conception, design. OS, CD’E, LM, CG, ML and VV acquisition of data. OS and TC analysis of data. OS and JLG interpretation of data. AS and SS drafting the manuscript. GC, AM and MC revising the manuscript. JLG critically for important intellectual content. All authors read and approved the final manuscript.Box plot showing differences in physical well being average score across urinary diversions. .Click here for fileBox plot showing differences in emotional well being average score across urinary diversions. .Click here for file