Enhancing Trial Delivery in Parkinson\u27s Disease: Qualitative Insights from PD STAT

\ua9 2022 - The authors. Published by IOS Press. Background: Recruitment and retention of participants in clinical trials for Parkinson\u27s disease (PD) is challenging. A qualitative study embedded in the PD STAT multi-centre randomised controlled trial of simvastatin for neuroprotection in PD explored the motivators, barriers and challenges of participants, care partners and research staff. Objective: To outline a set of considerations informing a patient-centred approach to trial recruitment, retention, and delivery. Method: We performed semi-structured interviews and focus groups with a subset of trial participants and their care partners. Quantitative and qualitative data were obtained through surveys circulated among the 235 participants across 23 UK sites at the beginning, middle and end of the 2-year trial. We also interviewed and surveyed research staff at trial closure. Results: Twenty-seven people with PD, 6 care partners and 9 researchers participated in interviews and focus groups. A total of 463 trial participant survey datasets were obtained across three timepoints, and 53 staff survey datasets at trial closure. Trial participants discussed the physical and psychological challenges they faced, especially in the context of OFF state assessments, relationships, and communication with research staff. Care partners shared their insights into OFF state challenges, and the value of being heard by research teams. Research staff echoed many concerns with suggestions on flexible, person-centred approaches to maximising convenience, comfort, and privacy. Conclusion: These considerations, in favour of person-centred research protocols informed by the variable needs of participants, care partners and staff, could be developed into a set of recommendations for future trials

Enhancing Trial Delivery in Parkinson’s Disease: Qualitative Insights from PD STAT

Background: Recruitment and retention of participants in clinical trials for Parkinson’s disease (PD) is challenging. A qualitative study embedded in the PD STAT multi-centre randomised controlled trial of simvastatin for neuroprotection in PD explored the motivators, barriers and challenges of participants, care partners and research staff. Objective: To outline a set of considerations informing a patient-centred approach to trial recruitment, retention, and delivery. Method: We performed semi-structured interviews and focus groups with a subset of trial participants and their care partners. Quantitative and qualitative data were obtained through surveys circulated among the 235 participants across 23 UK sites at the beginning, middle and end of the 2-year trial. We also interviewed and surveyed research staff at trial closure. Results: Twenty-seven people with PD, 6 care partners and 9 researchers participated in interviews and focus groups. A total of 463 trial participant survey datasets were obtained across three timepoints, and 53 staff survey datasets at trial closure. Trial participants discussed the physical and psychological challenges they faced, especially in the context of OFF state assessments, relationships, and communication with research staff. Care partners shared their insights into OFF state challenges, and the value of being heard by research teams. Research staff echoed many concerns with suggestions on flexible, person-centred approaches to maximising convenience, comfort, and privacy. Conclusion: These considerations, in favour of person-centred research protocols informed by the variable needs of participants, care partners and staff, could be developed into a set of recommendations for future trials.</jats:p

Allergic rhinitis and asthma: inflammation in a one-airway condition

BACKGROUND: Allergic rhinitis and asthma are conditions of airway inflammation that often coexist. DISCUSSION: In susceptible individuals, exposure of the nose and lungs to allergen elicits early phase and late phase responses. Contact with antigen by mast cells results in their degranulation, the release of selected mediators, and the subsequent recruitment of other inflammatory cell phenotypes. Additional proinflammatory mediators are released, including histamine, prostaglandins, cysteinyl leukotrienes, proteases, and a variety of cytokines, chemokines, and growth factors. Nasal biopsies in allergic rhinitis demonstrate accumulations of mast cells, eosinophils, and basophils in the epithelium and accumulations of eosinophils in the deeper subepithelium (that is, lamina propria). Examination of bronchial tissue, even in mild asthma, shows lymphocytic inflammation enriched by eosinophils. In severe asthma, the predominant pattern of inflammation changes, with increases in the numbers of neutrophils and, in many, an extension of the changes to involve smaller airways (that is, bronchioli). Structural alterations (that is, remodeling) of bronchi in mild asthma include epithelial fragility and thickening of its reticular basement membrane. With increasing severity of asthma there may be increases in airway smooth muscle mass, vascularity, interstitial collagen, and mucus-secreting glands. Remodeling in the nose is less extensive than that of the lower airways, but the epithelial reticular basement membrane may be slightly but significantly thickened. CONCLUSION: Inflammation is a key feature of both allergic rhinitis and asthma. There are therefore potential benefits for application of anti-inflammatory strategies that target both these anatomic sites

Locomotor Adaptation versus Perceptual Adaptation when Stepping Over an Obstacle with a Height Illusion

Background During locomotion, vision is used to perceive environmental obstacles that could potentially threaten stability; locomotor action is then modified to avoid these obstacles. Various factors such as lighting and texture can make these environmental obstacles appear larger or smaller than their actual size. It is unclear if gait is adapted based on the actual or perceived height of these environmental obstacles. The purposes of this study were to determine if visually guided action is scaled to visual perception, and to determine if task experience influenced how action is scaled to perception. Methodology/Principal Findings Participants judged the height of two obstacles before and after stepping over each of them 50 times. An illusion made obstacle one appear larger than obstacle two, even though they were identical in size. The influence of task experience was examined by comparing the perception-action relationship during the first five obstacle crossings (1–5) with the last five obstacle crossings (46–50). In the first set of trials, obstacle one was perceived to be 2.0 cm larger than obstacle two and subjects stepped 2.7 cm higher over obstacle one. After walking over the obstacle 50 times, the toe elevation was not different between obstacles, but obstacle one was still perceived as 2.4 cm larger. Conclusions/Significance There was evidence of locomotor adaptation, but no evidence of perceptual adaptation with experience. These findings add to research that demonstrates that while the motor system can be influenced by perception, it can also operate independent of perception

Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

Altered Rest-Activity Patterns Evolve via Circadian Independent Mechanisms in Cave Adapted Balitorid Loaches

Circadian rhythms and rest homeostasis are independent processes, each regulating important components of rest-activity patterns. Evolutionarily, the two are distinct from one another; total rest time is maintained unaffected even when circadian pacemaker cells are ablated. Throughout the animal kingdom, there exists a huge variation in rest-activity patterns, yet it is unclear how these behaviors have evolved. Here we show that four species of balitorid cavefish have greatly reduced rest times in comparison to rest times of their surface relatives. All four cave species retained biological rhythmicity, and in three of the four there is a pronounced 24-hour rhythm; in the fourth there is an altered rhythmicity of 38–40 hours. Thus, consistent changes in total rest have evolved in these species independent of circadian rhythmicity. Taken together, our data suggest that consistent reduction in total rest times were accomplished evolutionarily through alterations in rest homeostasis

Mothers' perceptions of child weight status and the subsequent weight gain of their children : a population based longitudinal study

BACKGROUND: There is a plethora of cross sectional work on maternal perceptions of child weight status showing that mothers typically do not classify their overweight child as being overweight according to commonly used clinical criteria. Awareness of overweight in their child is regarded as an important prerequisite for mothers to initiate appropriate action. The gap in the literature is determining whether, if mothers do classify their overweight child's weight status correctly, this is associated with a positive outcome for the child's body mass index (BMI) at a later stage. OBJECTIVE: To explore longitudinal perceptions of child weight status from mothers of a contemporary population-based birth cohort (Gateshead Millennium Study) and relationships of these perceptions with future child weight gain. METHODS: Data collected in the same cohort at 7, 12 and 15 years of age: mothers' responses to two items concerning their child's body size; child's and mother's BMI; pubertal maturation; demographic information. RESULTS: Mothers' perceptions of whether their child was overweight did not change markedly over time. Child BMI was the only significant predictor of mothers' classification of overweight status, and it was only at the extreme end of the overweight range and in the obese range that mothers reliably described their child as overweight. Even when mothers did appropriately classify their child as overweight at an earlier stage, this was not related to relatively lower child BMI a few years later. CONCLUSIONS: Mothers tend to classify their child as overweight in only more extreme cases. It is an important finding that no beneficial impact was shown on later child BMI in overweight children whose mothers classified their child's weight status as overweight at an earlier stage.International Journal of Obesity accepted article preview online, 25 January 2017. doi:10.1038/ijo.2017.20

Immediate breast reconstruction with a saline implant and AlloDerm, following removal of a Phyllodes tumor

<p>Abstract</p> <p>Background</p> <p>Phyllodes tumors are uncommon tumors of the breast that exhibit aggressive growth. While surgical management of the tumor has been reported, a single surgical approach with immediate breast reconstruction using AlloDerm has not been reported.</p> <p>Case presentation</p> <p>A 22-year-old woman presented with a 4 cm mass in the left breast upon initial examination. Although the initial needle biopsy report indicated a fibroadenoma, the final pathologic report revealed a 6.5 cm × 6.4 cm × 6.4 cm benign phyllodes tumor <it>ex vivo</it>. Treatment was a simple nipple-sparing mastectomy coupled with immediate breast reconstruction. After the mastectomy, a subpectoral pocket was created for a saline implant and AlloDerm was stitched to the pectoralis and serratus muscle in the lower-pole of the breast.</p> <p>Conclusions</p> <p>Saline implant with AlloDerm can be used for immediate breast reconstruction post-mastectomy for treatment of a phyllodes tumor.</p

Epidemiologic aspects of the malaria transmission cycle in an area of very low incidence in Brazil

BACKGROUND: Extra-Amazonian autochthonous Plasmodium vivax infections have been reported in mountainous regions surrounded by the Atlantic Forest in Espírito Santo state, Brazil. METHODS: Sixty-five patients and 1,777 residents were surveyed between April 2001 and March 2004. Laboratory methods included thin and thick smears, multiplex-PCR, immunofluorescent assay (IFA) against P. vivax and Plasmodium malariae crude blood-stage antigens and enzyme-linked immunosorbent assay (ELISA) for antibodies against the P. vivax-complex (P. vivax and variants) and P. malariae/Plasmodium brasilianum circumsporozoite-protein (CSP) antigens. RESULTS: Average patient age was 35.1 years. Most (78.5%) were males; 64.6% lived in rural areas; 35.4% were farmers; and 12.3% students. There was no relevant history of travel. Ninety-five per cent of the patients were experiencing their first episode of malaria. Laboratory data from 51 patients were consistent with P. vivax infection, which was determined by thin smear. Of these samples, 48 were assayed by multiplex-PCR. Forty-five were positive for P. vivax, confirming the parasitological results, while P. malariae was detected in one sample and two gave negative results. Fifty percent of the 50 patients tested had IgG antibodies against the P. vivax-complex or P. malariae CSP as determined by ELISA. The percentages of residents with IgM and IgG antibodies detected by IFA for P. malariae, P. vivax and Plasmodium falciparum who did not complain of malaria symptoms at the time blood was collected were 30.1% and 56.5%, 6.2% and 37.7%, and 13.5% and 13%, respectively. The same sera that reacted to P. vivax also reacted to P. malariae. The following numbers of samples were positive in multiplex-PCR: 23 for P. vivax; 15 for P. malariae; 9 for P. falciparum and only one for P. falciparum and P. malariae. All thin and thick smears were negative. ELISA against CSP antigens was positive in 25.4%, 6.3%, 10.7% and 15.1% of the samples tested for "classical" P. vivax (VK210), VK247, P. vivax-like and P. malariae, respectively. Anopheline captures in the transmission area revealed only zoophilic and exophilic species. CONCLUSION: The low incidence of malaria cases, the finding of asymptomatic inhabitants and the geographic separation of patients allied to serological and molecular results raise the possibility of the existence of a simian reservoir in these areas

Remodeling of extra-bronchial lung vasculature following allergic airway inflammation

<p>Abstract</p> <p>Background</p> <p>We previously observed that allergen-exposed mice exhibit remodeling of large bronchial-associated blood vessels. The aim of the study was to examine whether vascular remodeling occurs also in vessels where a spill-over effect of bronchial remodeling molecules is less likely.</p> <p>Methods</p> <p>We used an established mouse model of allergic airway inflammation, where an allergic airway inflammation is triggered by inhalations of OVA. Remodeling of bronchial un-associated vessels was determined histologically by staining for α-smooth muscle actin, procollagen I, Ki67 and von Willebrand-factor. Myofibroblasts were defined as and visualized by double staining for α-smooth muscle actin and procollagen I. For quantification the blood vessels were divided, based on length of basement membrane, into groups; small (≤250 μm) and mid-sized (250–500 μm).</p> <p>Results</p> <p>We discovered marked remodeling in solitary small and mid-sized blood vessels. Smooth muscle mass increased significantly as did the number of proliferating smooth muscle and endothelial cells. The changes were similar to those previously seen in large bronchial-associated vessels. Additionally, normally poorly muscularized blood vessels changed phenotype to a more muscularized type and the number of myofibroblasts around the small and mid-sized vessels increased following allergen challenge.</p> <p>Conclusion</p> <p>We demonstrate that allergic airway inflammation in mice is accompanied by remodeling of small and mid-sized pulmonary blood vessels some distance away (at least 150 μm) from the allergen-exposed bronchi. The present findings suggest the possibility that allergic airway inflammation may cause such vascular remodeling as previously associated with lung inflammatory conditions involving a risk for development of pulmonary hypertension.</p