Moir\'e Fringes in Conductive Atomic Force Microscopy

Moir\'e physics plays an important role for the characterization of functional materials and the engineering of physical properties in general, ranging from strain-driven transport phenomena to superconductivity. Here, we report the observation of moir\'e fringes in conductive atomic force microscopy (cAFM) scans gained on the model ferroelectric Er(Mn,Ti)O$_3$. By performing a systematic study of the impact of key experimental parameters on the emergent moir\'e fringes, such as scan angle and pixel density, we demonstrate that the observed fringes arise due to a superposition of the applied raster scanning and sample-intrinsic properties, classifying the measured modulation in conductance as a scanning moir\'e effect. Our findings are important for the investigation of local transport phenomena in moir\'e engineered materials by cAFM, providing a general guideline for distinguishing extrinsic from intrinsic moir\'e effects. Furthermore, the experiments provide a possible pathway for enhancing the sensitivity, pushing the resolution limit of local transport measurements by probing conductance variations at the spatial resolution limit via more long-ranged moir\'e patterns

Impact of opioid rescue medication for breakthrough pain on the efficacy and tolerability of long-acting opioids in patients with chronic non-malignant pain

There is little evidence that short-acting opioids as rescue medication for breakthrough pain is an optimal long-term treatment strategy in chronic non-malignant pain. We compared clinical studies of long-acting opioids that allowed short-acting opioid rescue medication with those that did not, to determine the impact of opioid rescue medication use on the analgesic efficacy and tolerability of chronic opioid therapy in patients with chronic non-malignant pain. We searched MEDLINE (1950 to July 2006) and EMBASE (1974 to July 2006) using terms for chronic non-malignant pain and long-acting opioids. Independent review of the search results identified 48 studies that met the study selection criteria. The effect of opioid rescue medication on analgesic efficacy and the incidence of common opioid-related side-effects were analysed using meta-regression. After adjusting for potentially confounding variables (study design and type of opioid), the difference in analgesic efficacy between the 'rescue' and the 'no rescue' studies was not significant, with regression coefficients close to 0 and 95% confidence intervals that excluded an effect of more than 18 points on a 0-100 scale in each case. There was also no significant difference between the 'rescue' and the 'no rescue' studies for the incidence of nausea, constipation, or somnolence in both the unadjusted and the adjusted analyses. We found no evidence that rescue medication with short-acting opioids for breakthrough pain affects analgesic efficacy of long-acting opioids or the incidence of common opioid-related side-effects among chronic non-malignant pain patients

Impact of long-term use of opioids on quality of life in patients with chronic, non-malignant pain

Objective: The use of opioids in the management of non-malignant pain remains controversial. For many physicians, pain relief stemming from opioid use is not enough unless there is also a noticeable change in quality of life (QoL) and patient functioning. The impact of long-term opioid treatment on patients' QoL has been investigated in a limited number of trials, and these studies differ considerably with respect to their design and principal findings. This systematic review presents the results of these studies. Design and methods: MEDLINE (1966 to November/December 2004), EMBASE (1974 to November/December 2004), the Oxford Pain Relief Database (Bandolier; 1954-1994) and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant papers by combining search terms for function with terms for opioid analgesia, non-malignant and pain. Studies were eligible for inclusion if they met all of the pre-defined criteria specifying study design, population, intervention and outcome measures. Results: Eleven studies evaluated long-term treatment with opioids in patients with chronic, non-malignant pain and assessed QoL (N = 2877). Six studies were randomised trials and the remaining five were observational studies. In general, the former had higher Jadad rating scores for the quality of the paper than the latter. Of the four randomised studies in which baseline OoL was reported, three showed an improvement in OoL. Similarly, of the five observational studies, a significant improvement in OoL was reported in four. Conclusions: There is both moderate/high- and low-quality evidence suggesting that long-term treatment with opioids can lead to significant improvements in functional outcomes, including OoL, in patients with chronic, non-malignant pain. However, further methodologically rigorous investigations are required to confirm the long-term QoL benefit of opioid treatment in these patients, and to elucidate the effect of physical tolerance, withdrawal and addiction, which are all associated with long-term use of opioids, on patients' functional status

Treatment of Chronic Pain by Long-Acting Opioids and the Effects on Sleep

Chronic pain affects a substantial part of the population, and conveys a huge economic cost to society. Owing to its prevalence and adverse impact, it is of particular interest to clinicians, patients, and the pharmaceutical industry. Conversely, the effects of pain on sleep, sleep on pain, and opioid analgesics on sleep represent a large gap in our understanding, even though pain and sleep are closely linked, inter-related conditions. Chronic pain is often treated by opioid analgesics, which are often thought to promote restful sleep. Indeed it may be assumed that by relieving pain, sleep quality will improve concomitantly. In fact, the reality is much more complicated. The effects of opioids vary according to their formulation and duration of action, and have diverse effects on sleep processes. Despite the prevalence of this problem, there is a surprising paucity of data on the effects of opioids on sleep. This review attempts to summarize the links between pain and sleep, and to look at the studies with opioid analgesics, particularly those with extended-release formulations, that have investigated the effects of opioid analgesics on sleep. © 2010 Johnson and Johnson Pharmaceutical Services; Pain Practice © 2010 World Institute of Pain

Comparative effectiveness study of paliperidone palmitate 6-month with a real-world external comparator arm of paliperidone palmitate 1-month or 3-month in patients with schizophrenia

Background: The paliperidone palmitate 6-month (PP6M) long-acting injectable formulation is currently the longest dosing interval available for schizophrenia treatment. Objective: To compare treatment outcomes between a real-world external comparator arm (ECA; NeuroBlu database) and the PP6M open-label extension (OLE) clinical trial arm. Methods: The ECA comprised patients receiving PP 1-month (PP1M) or PP 3-month (PP3M) for ⩾12 months without a relapse. The PP6M OLE arm included patients with PP1M treatment prior to randomization who completed the 12-month double-blind PP6M study on either PP3M or PP6M relapse-free. Inverse probability treatment weighting (IPTW) was used to study time-to-relapse (primary outcome) and change in Clinical Global Impressions-Severity (CGI-S) score (secondary outcome). Results: At 24 months, 3.9% (7/178) of patients in the PP6M cohort experienced a relapse versus 15.6% (26/167) in the ECA. Time-to-relapse was longer in the PP6M cohort versus the ECA at 12-, 18-, and 24-months across the different weighting methods; median time-to-relapse was not reached in both cohorts. Hazard ratio (HR) for relapse was significantly lower for the PP6M cohort versus the ECA throughout the duration of the study [HR at 24 months: 0.18 (95% CI: 0.08–0.42), p  < 0.001]. At 24 months, change in CGI-S score for the PP6M cohort was 0.76 points lower than the ECA ( p  < 0.001). Results were similar in a sensitivity analysis using propensity score matching (PSM); IPTW resulted in larger sample sizes in balanced dataset than PSM. Conclusion: Consistent findings across weighting and matching methods suggest PP6M efficacy in reducing and delaying relapses and long-term symptom control compared to PP1M/PP3M in usual-care settings. Additional confounds, such as greater illness severity and more frequent comorbidities and comedications in the ECA, were not fully controlled by the applied statistical methods. Future real-world studies directly comparing PP6M with PP3M/PP1M and adjusting for these confounders are warranted