Residual Disease Burden Among European Patients With Inflammatory Bowel Disease: A Real-World Survey.

BACKGROUND: Understanding disease burden is imperative for improving inflammatory bowel disease (IBD) management. This real-world survey investigated residual disease burden and treatment satisfaction among European patients with moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD). METHODS: The Adelphi Real World IBD Disease Specific Programme was a multinational, cross-sectional survey with retrospective collection of patient- and physician-reported data on disease burden and management. Between October 2020 and March 2021, participating gastroenterologists recruited their next 7 (UC) and 8 (CD) eligible patients and reported demographics and clinical characteristics. Patients completed symptom, health-related quality of life (HRQoL), and treatment satisfaction questionnaires. Data were adjusted for confounding variables and compared between patients in remission (clinical remission, endoscopic remission, or both) and not in remission. RESULTS: Overall, 1040 patients (UC, n = 502; CD, n = 538) were included. Although most patients were in remission (UC, 66.1%; CD, 69.5%), most still reported symptoms (UC, 63.7%; CD, 74.1%), including flatulence, fatigue/tiredness, and abdominal pain/distension. In UC, there were no significant differences in the likelihood of experiencing 7 of 23 symptoms between patients in remission and not in remission. In CD, there was no significant difference in 19 of 23 symptoms between patients in remission and not in remission. Several symptoms were significantly associated with reduced HRQoL. HRQoL was significantly better among patients in remission than not in remission. CONCLUSIONS: Patients with IBD, both in remission and not in remission, experience residual symptoms that impair HRQoL. Comprehensive endpoints, incorporating HRQoL and patients' perspectives, and improved treatments are needed to address residual disease and patients' needs.

This real-world study investigated the residual burden of inflammatory bowel disease on European patients. We found that patients­including those in remission­experience significant symptomatic burden and impaired quality of life, highlighting gaps in current therapeutics and patients' unmet needs.

Nanohardness and Young's Modulus of Pb1-xCdxTe Crystals Grown by the SSVG and MBE Methods.

The nanohardness and Young's modulus of Pb1-xCdxTe single crystals prepared by the self-selecting vapor growth (SSVG) method and thick, MBE-grown layers with a total Cd content of up to 7% metal atoms were studied using the nanoindentation technique; the nanohardness and Young's modulus were calculated by the Oliver and Pharr method. Significant hardening of SSVG crystals with increasing number of Cd atoms replacing Pb atoms in the formed solid solution was observed, and low anisotropy of the nanohardness and Young's modulus were found. The CdTe solubility limit in the solid solution grown using an MBE equal to 2.1% was demonstrated; even for the significantly higher total Cd concentration in the layer, the possible presence of precipitates was not detected. Significant differences were found for both the energy of elastic crystal deformation and Young's modulus determined for samples grown using the two methods. An increase in nanohardness with an increase in the number of Cd atoms outside the cation sublattice was shown. The different ratios of hardening mechanisms acting simultaneously in the analyzed crystals in various ranges of Cd concentrations were demonstrated and discussed. The observed effects were attributed to the much higher concentration of point defects in MBE-grown layers than in SSVG crystals, in particular, the interstitial Cd-Te vacancy complexes effectively hampering nucleation and propagation of dislocations in the former case.

Initial Optimization of the Growth Conditions of GaAs Homo-Epitaxial Layers after Cleaning and Restarting the Molecular Beam Epitaxy Reactor.

The molecular beam epitaxy (MBE) technique is renowned as the most suitable for the growth of high-quality crystalline materials and nanostructures such as GaAs. However, once established, optimal growth parameters required for repeatability of top-quality structures may be easily lost as MBE is highly sensitive to any changes in the system. Especially, routine servicing procedures, which include any activity which requires unsealing of the growth chamber, are devastating for developed growth parameters and force the necessity of recalibration. In this work, we present the process of growth parameter pre-optimization for obtaining homoepitaxial GaAs layers after servicing and restarting the MBE system. Namely, we present how each step of reestablishing optimal growth condition influences various characteristics of obtained GaAs layers. Those include in situ, structural, and spectral measurement techniques. An additional aspect was to compare the optimal conditions for the growth of homoepitaxial GaAs layers from two growth campaigns in which the main difference is the addition of an ion pump and increasing the temperature gradient on the Ga cell.

Strain-Balanced InAs/AlSb Type-II Superlattice Structures Growth on GaSb Substrate by Molecular Beam Epitaxy.

We demonstrate strain-balanced InAs/AlSb type-II superlattices (T2SL) grown on GaSb substrates employing two kinds of interfaces (IFs): AlAs-like IF and InSb-like IF. The structures are obtained by molecular beam epitaxy (MBE) for effective strain management, simplified growth scheme, improved material crystalline quality, and improved surface quality. The minimal strain T2SL versus GaSb substrate can be achieved by a special shutters sequence during MBE growth that leads to the formation of both interfaces. The obtained minimal mismatches of the lattice constants is smaller than that reported in the literature. The in-plane compressive strain of 60-period InAs/AlSb T2SL 7ML/6ML and 6ML/5ML was completely balanced by the applied IFs, which is confirmed by the HRXRD measurements. The results of the Raman spectroscopy (measured along the direction of growth) and surface analyses (AFM and Nomarski microscopy) of the investigated structures are also presented. Such InAs/AlSb T2SL can be used as material for a detector in the MIR range and, e.g., as a bottom n-contact layer as a relaxation region for a tuned interband cascade infrared photodetector.

Tocilizumab as a first-line biologic treatment in rheumatoid arthritis patients - the impact of concomitant methotrexate treatment and Rheumatic Disease Comorbidity Index on the clinical response - results from the multicenter observational ACT-POL study.

Objectives: According to the EULAR recommendations, remission or low disease activity (LDA) in rheumatoid arthritis should be achieved by a maximum of 6 months (M6) of treatment. Data on the use of tocilizumab (TCZ) as first-line biologic treatment in rheumatoid arthritis (RA) in routine clinical practice in Poland are lacking. Material and methods: This multicenter, non-interventional, prospective, observational study recruited adults, presenting with moderate-to-severe RA, showing an inadequate response or intolerance to disease-modifying antirheumatic drugs, where TCZ was the first-line biologic treatment. The effectiveness of TCZ was assessed by the proportion of patients achieving remission and low disease activity following 6 months of treatment with intravenous TCZ. The impact of comorbidities on treatment outcomes was measured using the Rheumatic Disease Comorbidity Index (RDCI). Results: Total remission rates at months 3 and 6 were 6% and 31%, respectively. Low disease activity was reported in 10% and 92% of the patients at 3 and 6 months, respectively. The response was comparable between TCZ as monotherapy and in combination with methotrexate. Mean DAS28 decreased from 6.61 at baseline to 4.27 at the scheduled time of the assessment (3 and 6 months). The Rheumatic Disease Comorbidity Index was not correlated with the number of patients achieving LDA at M3 and M6 or remission rates at M6. Remission rates correlated with RDCI at M3. A total of 114 adverse events were reported in 61 patients, among which five were considered as serious. Conclusions: The study confirms the effectiveness and safety of TCZ in real-world settings as a first-line biologic treatment in patients with moderate-to-severe RA. Importantly, comorbidities do not affect the results of 6-month treatment with TCZ, that is, the optimal time to achieve at least LDA. Our results may improve the effects of RA therapy in Poland, especially in patients with comorbidities and those who, for various reasons, cannot receive optimal treatment with methotrexate.

Management of rheumatoid arthritis in Poland - where daily practice might not always meet evidence-based guidelines.

INTRODUCTION: International recommendations are intended to help rheumatologists in the effective management of rheumatoid arthritis (RA) through an evidence-based approach. This research aimed to evaluate management patterns and associated difficulties encountered by rheumatologists in daily practice. MATERIAL AND METHODS: Interviewers recruited 101 Polish rheumatologists in a random quota-based, nationwide sample of outpatient clinics. Quantitative data were input online using a computer-assisted web interview tool. RESULTS: Disease-modifying antirheumatic drugs (DMARDs) are not initiated at the time of diagnosis in 15% of RA patients, most often due to difficulties in patient-provider communication. The RA activity is assessed every 4 to 6 months by 30% of rheumatologists, and 64% of patients are reported to never achieve remission. Composite indices are the most reliable indicators of remission only for 38% of responders. Despite inadequate disease control with ≥ 2 treatment schedules with synthetic DMARDs, 34% of these patients are not considered for biological DMARDs (bDMARDs). Contraindications and reimbursement barriers are the most frequently stated reasons. Therapy with glucocorticoid (GC) lasting over 3 months is reported by 70% of rheumatologists. International recommendations are stated as the most common basis for treatment decisions. CONCLUSIONS: Awareness of recommendations is not sufficient to ensure their application in clinical practice. Inadequate management of RA is quite prevalent, with a substantial contribution of non-medical factors. Daily practice mainly deviates from guidelines regarding frequency and mode of monitoring measures, time to DMARD initiation, and duration of GC treatment. Education programs and policy changes may significantly narrow the gap between evidence and practice.

Modification of fentanyl analgesia by antidepressants.

Clinical practice often requires simultaneous administration of antidepressants with opioids (oncology, rheumatology). Coadministration may either attenuate or potentiate opioid analgesia. The purpose of this paper was to verify how the analgesic action of fentanyl (0.05 mg/kg) is affected by single administration as well as 4- or 21-day premedication with antidepressants characterized by various mechanisms of action. The effects of amitriptyline 3 mg/kg, moclobemide 5 mg/kg, fluoxetine 5 mg/kg and reboxetine 0.08 mg/kg were investigated. Experiments were conducted on normotensive Wistar Kyoto rats. The pain threshold was measured using an analgesimeter. It was concluded that the single administration of an antidepressant increases the analgesic action of fentanyl. Four-day premedication with fluoxetine and reboxetine significantly attenuated the antinociceptive action of fentanyl, whereas 21-day premedication with all antidepressants investigated (fluoxetine, amitriptyline, moclobemide, reboxetine) markedly decreased it. The potential clinical importance of this observation is discussed.