Taste assessment for paediatric drug Development: A comparison of bitterness taste aversion in children versus Naïve and expert young adult assessors

Medicines for children often taste bitter, presenting a significant challenge to treatment compliance. However, most studies on paediatric drug development rely on adult volunteers for sensory research, and the level of expertise required from these assessors is unclear. This study aimed to address this gap by investigating perceived bitterness aversion to taste strips impregnated with different concentrations of quinine hydrochloride in 439 school-aged children. Expert (n = 26) and naïve (n = 65) young adult assessors evaluated quinine solutions as well as taste strips, for methodological bridging purposes. All assessors differentiated the aversiveness of the taste strips in a dose dependent manner. Younger children aged 4–8 years had difficulty discriminating higher bitter concentrations, whereas pre-adolescents 9–11 years and naive adults showed better discrimination at the top of the scale. Naive assessors showed similar bitter perception as children. However, the results were slightly different between strips and solution in adults. These findings highlight the key role that adult panels can play in paediatric formulation development. Taste strips show promise as a safe and pragmatic tool for sensory pharmaceutical evaluations, though further studies are warranted to establish the relationship between age and hedonic taste perception using compounds with diverse physicochemical and sensory qualities

Testing a newly developed activity pacing framework for chronic pain/fatigue : a feasibility study

Objectives: To test the feasibility of using a new activity pacing framework to standardise healthcare professionals’ instructions of pacing, and explore whether measures of activity pacing/symptoms detected changes following treatment. Design: Single-arm, repeated measures study. Setting: One National Health Service (NHS) Pain Service in Northern England, UK. Participants: Adult patients with chronic pain/fatigue, including chronic low back pain, chronic widespread pain, fibromyalgia and chronic fatigue syndrome/myalgic encephalomyelitis. Interventions: Six-week rehabilitation programme, standardised using the activity pacing framework. Outcome measures: Feasibility was explored via patients’ recruitment/attrition rates, adherence and satisfaction, and healthcare professionals’ fidelity. Questionnaire data were collected from patients at the start and end of the programme (T1 and T2, respectively) and 3 months’ follow-up (T3). Questionnaires included measures of activity pacing, current/usual pain, physical/mental fatigue, depression, anxiety, self-efficacy, avoidance, physical/mental function and quality of life. Mean changes in activity pacing and symptoms between T1-T2, T2-T3 and T1-T3 were estimated. Results: Of the 139 eligible patients, 107 patients consented (recruitment rate=77%); 65 patients completed T2 (T1-T2 attrition rate=39%), and 52 patients completed T3 (T1-T3 attrition rate=51%). At T2, patients’ satisfaction ratings averaged 9/10, and 89% attended ≥5 rehabilitation programme sessions. Activity pacing and all symptoms improved between T1 and T2, with smaller improvements maintained at T3. Conclusion: The activity pacing framework was feasible to implement and patients’ ability to pace and manage their symptoms improved. Future work will employ a suitable comparison group and test the framework across wider settings to explore the effects of activity pacing in a randomised controlled trial. Trial registration number: NCT03497585

Stone clearance in lower pole nephrolithiasis after extra corporeal shock wave lithotripsy – the controversy continues

BACKGROUND: To determine factors influencing the clearance of fragments after extra-corporeal shock wave lithotripsy (ESWL) for lower pole calyceal (LPC) stones. METHODS: In the period between July 1998 and Oct 2001, 100 patients with isolated lower polar calyceal calculi ≤ 20 mm, in patients aged ≥ 14 years, were included in the study. Intravenous urograms (IVU) were reviewed to define the LPC anatomy (width of the infundibulum and pelvicalyceal angle). Study end points i.e. stone free status; number of shock waves used and number of sessions were correlated with variables like LPC anatomy, body mass index and stone size. RESULTS: At three months follow up the clearance for stone size ≤ 10 mm, 11–15 mm and 16–20 mm were 95, 96 and 90% respectively. Patients with acute LPC (<90°) and obtuse angle (>90°) had stone clearance of 94 and 100% respectively. For the infundibular width of < 4 mm, the stone clearance was 93% were as for > 4 mm, it was 100%. For body mass index (BMI) less than and > 30 kg/m(2), the stone clearance was 92 and 95% respectively. CONCLUSIONS: There is a trend towards more ESWL sessions and shock wave requirement in patients with acute pelvi-calyceal angle and narrow infundibulum but it is not statistically significant. Size (≤ 20 mm) and BMI has no relation with stone clearance. With modern lithotripter, stones up to 20 mm could primarily be treated by ESWL, irrespective of an un-favorable lower polar calyceal anatomy and body habitus

Housing Arrangement and Location Determine the Likelihood of Housing Loss Due to Wildfire

Surging wildfires across the globe are contributing to escalating residential losses and have major social, economic, and ecological consequences. The highest losses in the U.S. occur in southern California, where nearly 1000 homes per year have been destroyed by wildfires since 2000. Wildfire risk reduction efforts focus primarily on fuel reduction and, to a lesser degree, on house characteristics and homeowner responsibility. However, the extent to which land use planning could alleviate wildfire risk has been largely missing from the debate despite large numbers of homes being placed in the most hazardous parts of the landscape. Our goal was to examine how housing location and arrangement affects the likelihood that a home will be lost when a wildfire occurs. We developed an extensive geographic dataset of structure locations, including more than 5500 structures that were destroyed or damaged by wildfire since 2001, and identified the main contributors to property loss in two extensive, fire-prone regions in southern California. The arrangement and location of structures strongly affected their susceptibility to wildfire, with property loss most likely at low to intermediate structure densities and in areas with a history of frequent fire. Rates of structure loss were higher when structures were surrounded by wildland vegetation, but were generally higher in herbaceous fuel types than in higher fuel-volume woody types. Empirically based maps developed using housing pattern and location performed better in distinguishing hazardous from non-hazardous areas than maps based on fuel distribution. The strong importance of housing arrangement and location indicate that land use planning may be a critical tool for reducing fire risk, but it will require reliable delineations of the most hazardous locations

Early and long-term outcome of elective stenting of the infarct-related artery in patients with viability in the infarct-area: Rationale and design of the Viability-guided Angioplasty after acute Myocardial Infarction-trial (The VIAMI-trial)

BACKGROUND: Although percutaneous coronary intervention (PCI) is becoming the standard therapy in ST-segment elevation myocardial infarction (STEMI), to date most patients, even in developed countries, are reperfused with intravenous thrombolysis or do not receive a reperfusion therapy at all. In the post-lysis period these patients are at high risk for recurrent ischemic events. Early identification of these patients is mandatory as this subgroup could possibly benefit from an angioplasty of the infarct-related artery. Since viability seems to be related to ischemic adverse events, we initiated a clinical trial to investigate the benefits of PCI with stenting of the infarct-related artery in patients with viability detected early after acute myocardial infarction. METHODS: The VIAMI-study is designed as a prospective, multicenter, randomized, controlled clinical trial. Patients who are hospitalized with an acute myocardial infarction and who did not have primary or rescue PCI, undergo viability testing by low-dose dobutamine echocardiography (LDDE) within 3 days of admission. Consequently, patients with demonstrated viability are randomized to an invasive or conservative strategy. In the invasive strategy patients undergo coronary angiography with the intention to perform PCI with stenting of the infarct-related coronary artery and concomitant use of abciximab. In the conservative group an ischemia-guided approach is adopted (standard optimal care). The primary end point is the composite of death from any cause, reinfarction and unstable angina during a follow-up period of three years. CONCLUSION: The primary objective of the VIAMI-trial is to demonstrate that angioplasty of the infarct-related coronary artery with stenting and concomitant use of abciximab results in a clinically important risk reduction of future cardiac events in patients with viability in the infarct-area, detected early after myocardial infarction

Rapid short-duration hypothermia with cold saline and endovascular cooling before reperfusion reduces microvascular obstruction and myocardial infarct size

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to evaluate the combination of a rapid intravenous infusion of cold saline and endovascular hypothermia in a closed chest pig infarct model.</p> <p>Methods</p> <p>Pigs were randomized to pre-reperfusion hypothermia (n = 7), post-reperfusion hypothermia (n = 7) or normothermia (n = 5). A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min. Hypothermia was started after 25 min of ischemia or immediately after reperfusion by infusion of 1000 ml of 4°C saline and endovascular hypothermia. Area at risk was evaluated by in vivo SPECT. Infarct size was evaluated by ex vivo MRI.</p> <p>Results</p> <p>Pre-reperfusion hypothermia reduced infarct size/area at risk by 43% (46 ± 8%) compared to post-reperfusion hypothermia (80 ± 6%, p < 0.05) and by 39% compared to normothermia (75 ± 5%, p < 0.05). Pre-reperfusion hypothermia infarctions were patchier in appearance with scattered islands of viable myocardium. Pre-reperfusion hypothermia abolished (0%, p < 0.001), and post-reperfusion hypothermia significantly reduced microvascular obstruction (10.3 ± 5%; p < 0.05), compared to normothermia: (30.2 ± 5%).</p> <p>Conclusion</p> <p>Rapid hypothermia with cold saline and endovascular cooling before reperfusion reduces myocardial infarct size and microvascular obstruction. A novel finding is that hypothermia at the onset of reperfusion reduces microvascular obstruction without reducing myocardial infarct size. Intravenous administration of cold saline combined with endovascular hypothermia provides a method for a rapid induction of hypothermia suggesting a potential clinical application.</p

Influence of Psychological Factors on Pain and Disability in Anterior Knee Pain Patients

AKP patients express chronic pain but also disability. However, the correlation between pain and disability is not complete and linear. Some patients with a lot of pain show mild disability while others with much less pain also show great disability. The disability is profoundly influenced by other emotional and cognitive factors that are associated with the perception of pain. Therefore, the clinical efforts do not have to be focused only on treating the pain as a feeling but on identifying and modifying these factor

A core outcome set for evaluating self-management interventions in people with comorbid diabetes and severe mental illness : study protocol for a modified Delphi study and systematic review

BACKGROUND: People with diabetes and comorbid severe mental illness (SMI) form a growing population at risk of increased mortality and morbidity compared to those with diabetes or SMI alone. There is increasing interest in interventions that target diabetes in SMI in order to help to improve physical health and reduce the associated health inequalities. However, there is a lack of consensus about which outcomes are important for this comorbid population, with trials differing in their focus on physical and mental health. A core outcome set, which includes outcomes across both conditions that are relevant to patients and other key stakeholders, is needed. METHODS: This study protocol describes methods to develop a core outcome set for use in effectiveness trials of self-management interventions for adults with comorbid type-2 diabetes and SMI. We will use a modified Delphi method to identify, rank, and agree core outcomes. This will comprise a two-round online survey and multistakeholder workshops involving patients and carers, health and social care professionals, health care commissioners, and other experts (e.g. academic researchers and third sector organisations). We will also select appropriate measurement tools for each outcome in the proposed core set and identify gaps in measures, where these exist. DISCUSSION: The proposed core outcome set will provide clear guidance about what outcomes should be measured, as a minimum, in trials of interventions for people with coexisting type-2 diabetes and SMI, and improve future synthesis of trial evidence in this area. We will also explore the challenges of using online Delphi methods for this hard-to-reach population, and examine differences in opinion about which outcomes matter to diverse stakeholder groups. TRIAL REGISTRATION: COMET registration: http://www.comet-initiative.org/studies/details/911 . Registered on 1 July 2016

An Assessment of the Impact of Hafting on Paleoindian Point Variability

It has long been argued that the form of North American Paleoindian points was affected by hafting. According to this hypothesis, hafting constrained point bases such that they are less variable than point blades. The results of several studies have been claimed to be consistent with this hypothesis. However, there are reasons to be skeptical of these results. None of the studies employed statistical tests, and all of them focused on points recovered from kill and camp sites, which makes it difficult to be certain that the differences in variability are the result of hafting rather than a consequence of resharpening. Here, we report a study in which we tested the predictions of the hafting hypothesis by statistically comparing the variability of different parts of Clovis points. We controlled for the potentially confounding effects of resharpening by analyzing largely unused points from caches as well as points from kill and camp sites. The results of our analyses were not consistent with the predictions of the hypothesis. We found that several blade characters and point thickness were no more variable than the base characters. Our results indicate that the hafting hypothesis does not hold for Clovis points and indicate that there is a need to test its applicability in relation to post-Clovis Paleoindian points