Recruitment and Retention of Older People in Clinical Research: A Systematic Literature Review

OBJECTIVE: To identify barriers and solutions for the recruitment and retention of older (aged ≥65 years) people in clinical trials. DESIGN: Systematic literature review. METHODS: Three databases (Medline, Embase, and CENTRAL) were searched for articles reporting on barriers or solutions regarding the recruitment or retention of older people. Only original research articles were included. RESULTS: Fifty eligible articles were identified. Exclusion criteria were the most common cause of poor recruitment of older adults (mainly age and comorbidities). Patients' families or physicians often advised against participation (22% of included studies). Lack of interest (18%) and problems with transportation (18%) were also commonly cited as challenges. Fourteen trials (28%) reported that monitoring and adapting their recruitment methods helped, along with a flexible research team (26%) and provision of transportation (24%). Retention was impaired by death (12%), illness (8%), and loss of interest (6%). Methods with a positive effect on retention included financial incentives and regular information about the progress of the study (12%), a low staff turnover (12%), flexibility in appointment making (10%), and expression of appreciation by the staff through letters, gifts, and cards to the participants (10%). CONCLUSION: We identified several barriers and have listed potential solutions that may improve recruitment and lead to fewer dropouts in trials involving older populations. Implementation of our findings may help mitigate the manifold challenges that come with running a trial with older people

Functional characterization of orbicularis oculi and extraocular muscles

The orbicularis oculi are the sphincter muscles of the eyelids and are involved in modulating facial expression. They differ from both limb and extraocular muscles (EOMs) in their histology and biochemistry. Weakness of the orbicularis oculi muscles is a feature of neuromuscular disorders affecting the neuromuscular junction, and weakness of facial muscles and ptosis have also been described in patients with mutations in the ryanodine receptor gene. Here, we investigate human orbicularis oculi muscles and find that they are functionally more similar to quadriceps than to EOMs in terms of excitation-contraction coupling components. In particular, they do not express the cardiac isoform of the dihydropyridine receptor, which we find to be highly expressed in EOMs where it is likely responsible for the large depolarization-induced calcium influx. We further show that human orbicularis oculi and EOMs express high levels of utrophin and low levels of dystrophin, whereas quadriceps express dystrophin and low levels of utrophin. The results of this study highlight the notion that myotubes obtained by explanting satellite cells from different muscles are not functionally identical and retain the physiological characteristics of their muscle of origin. Furthermore, our results indicate that sparing of facial and EOMs in patients with Duchenne muscular dystrophy is the result of the higher levels of utrophin expression

Analysis of hip joint loading during walking with different shoe types using instrumented total hip prostheses

Hip joint loads need careful consideration during postoperative physiotherapy after joint replacement. One factor influencing joint loads is the choice of footwear, but it remains unclear which footwear is favorable. The objective of the present study was to investigate the influence of footwear on hip joint loads in vivo. Instrumented hip endoprostheses were used for in vivo load measurements. The parameters resultant contact force (F-res), bending moment (M-bend) and torsional moment (M-tors) were evaluated during treadmill walking at 4 km/h with different shoe types. In general, footwear tended to increase hip joint loading, with the barefoot shoe having the least influence. F-res and M-bend were significantly increased during heel strike for all shoe types in comparison to barefoot walking, with everyday shoe (34.6%; p=0.028 and 47%; p=0.028, respectively) and men's shoe (33.2%; p=0.043 and 41.1%; p=0.043, respectively) resulting in the highest changes. M-tors at AbsMax was increased by all shoes except for the barefoot shoe, with the highest changes for men's shoe (+17.6%, p=0.043) and the shoe with stiffened sole (+17.5%, p=0.08). Shoes, especially those with stiff soles or elaborate cuishing and guiding elements, increase hip joint loads during walking. The influence on peak loads is higher for M-tors than for F-res and M-bend. For patients in which a reduction of hip joints loads is desired, e.g. during physiotherapy after recent surgery or to alleviate symptoms of osteoarthritis, low profile shoes with a flexible sole may be preferred over shoes with a stiff sole or elaborate cushioning elements

Maxima over random time intervals for heavy-tailed compound renewal and Lévy processes

We derive subexponential tail asymptotics for the distribution of the maximum of a compound renewal process with linear component and of a Lévy process, both with negative drift, over random time horizon τ that does not depend on the future increments of the process. Our asymptotic results are uniform over the whole class of such random times. Particular examples are given by stopping times and by τ independent of the processes. We link our results with random walk theory

Gerber-Shiu theory for discrete risk processes in a regime switching environment

In this paper we develop the Gerber-Shiu theory for the classic and dual discrete risk processes in a Markovian (regime switching) environment. In particular, by expressing the Gerber-Shiu function in terms of potential measures of an upward (downward) skip-free discrete-time and discrete-space Markov Additive Process (MAP), we derive closed form expressions for the Gerber-Shiu function in terms of the so-called (discrete) Wv and Zv scale matrices, which were introduced in [27]. We show that the discrete scale matrices allow for a unified approach for identifying the Gerber-Shiu function as well as the value function of the associated constant dividend barrier problems

Sodium adsorption using activated alumina for application in the dairy industry

Basic activated alumina with negatively charged surface is considered as a potential adsorbent for a targeted molecule with positive polarity. Adsorption of sodium by basic activated alumina was investigated as a method for desalting dairy waste streams, in which sodium ion concentration averaged 600 mg/L. Sodium equilibrium and kinetic adsorption were investigated using basic activated alumina with synthetic brines. The results of equilibrium adsorption show that uptake of sodium by activated alumina is significantly higher when the pH is greater than 8 and increases as the pH of the brines increases until pH reaches around 10. The results of kinetic adsorption show that 90 hours were needed to reach equilibrium for sodium adsorption. Binding and diffusion processes are suggested to have taken place within the activated alumina.<br /

Two refreshing views of Fluctuation Theorems through Kinematics Elements and Exponential Martingale

In the context of Markov evolution, we present two original approaches to obtain Generalized Fluctuation-Dissipation Theorems (GFDT), by using the language of stochastic derivatives and by using a family of exponential martingales functionals. We show that GFDT are perturbative versions of relations verified by these exponential martingales. Along the way, we prove GFDT and Fluctuation Relations (FR) for general Markov processes, beyond the usual proof for diffusion and pure jump processes. Finally, we relate the FR to a family of backward and forward exponential martingales.Comment: 41 pages, 7 figures; version2: 45 pages, 7 figures, minor revisions, new results in Section

Retinal cells derived from patients with DRAM2-dependent CORD21 dystrophy exhibit key lysosomal enzyme deficiency and lysosomal content accumulation

\ua9 2024 The Author(s)Biallelic mutations in DRAM2 lead to an autosomal recessive cone-rod dystrophy known as CORD21, which typically presents between the third and sixth decades of life. Although DRAM2 localizes to the lysosomes of photoreceptor and retinal pigment epithelium (RPE) cells, its specific role in retinal degeneration has not been fully elucidated. In this study, we generated and characterized retinal organoids (ROs) and RPE cells from induced pluripotent stem cells (iPSCs) derived from two CORD21 patients. Our investigation revealed that CORD21-ROs and RPE cells exhibit abnormalities in lipid metabolism, defects in autophagic flux, accumulation of aberrant lysosomal content, and reduced lysosomal enzyme activity. We identified potential interactions of DRAM2 with vesicular trafficking proteins, suggesting its involvement in this cellular process. These findings collectively suggest that DRAM2 plays a crucial role in maintaining the integrity of photoreceptors and RPE cells by regulating lysosomal function, autophagy, and potentially vesicular trafficking

Modelling direct and indirect water requirements of construction

Water consumed directly by the construction industry is known to be of little importance. However, water consumed in the manufacture of goods and services required by construction may be significant in the context of a building\u27s life cycle water requirements and the national water budget. This paper evaluates the significance of water embodied in the construction of individual buildings. To do this, an input-output-based hybrid embodied water analysis was undertaken on 17 Australian non-residential case studies. It was found that there is a considerable amount of water embodied in construction. The highest value was 20.1 kilolitres (kL)/m2 gross floor area (GFA), representing many times the enclosed volume of the building, and many years worth of operational water. The water required by the main construction process is minimal. However, the water embodied in building materials is considerable. These findings suggest that the selection of elements and materials has a great impact on a building\u27s embodied water. This research allows the construction industry to evaluate design and construction in broad environmental terms to select options that might be cost neutral or possibly cost positive while retaining their environmental integrity. The research suggests policies focused on operational water consumption alone are inadequate. <br /