High Attrition Research Articles

The relationship between salivary Fibroblast Growth Factor-2 and cortisol reactivity and psychological outcomes prior to and during the COVID-19 pandemic.

Fibroblast growth factor-2 (FGF2) is a biomarker that is associated with depression, anxiety and stress in rodents. In humans, we have previously demonstrated that salivary FGF2 increased following stress in a similar pattern to cortisol, and FGF2 (but not cortisol) reactivity predicted repetitive negative thinking, a transdiagnostic risk factor for mental illness. The current study assessed the relationship between FGF2, cortisol, and mental health before and during the COVID-19 pandemic. We employed a longitudinal correlational design using a convenience sample. We assessed whether FGF2 and cortisol reactivity following the Trier Social Stress Task (TSST) were associated with DASS-21 depression, anxiety and stress, measured at the time of the TSST in 2019-20 (n=87; time 1), and then again in May 2020 during the first wave of COVID-19 in Sydney (n=34 of the original sample; time 2). FGF2 reactivity (but not absolute FGF2 levels) at time 1 predicted depression, anxiety, and stress across timepoints. Cortisol reactivity at time 1 was associated with stress over timepoints, and absolute cortisol levels were associated with depression across timepoints. The sample was comprised of mostly healthy participants from a student population, and there was high attrition between timepoints. The outcomes need to be replicated in larger, more diverse, samples. FGF2 and cortisol may be uniquely predictive of mental health outcomes in healthy samples, potentially allowing for early identification of at-risk individuals.

Agility and the transition from uncertainty to recovery: the Indian IT industry and COVID-19

This paper reports a study of how the Indian IT industry navigated the COVID-19 pandemic. Agility emerged as the crucial determining factor aiding the industry’s successful survival. IT organisations’ agility, facilitated by the state’s response to the pandemic and by both their anticipation of the lockdown and their technological capabilities, helped them overcome the crisis. The slowdown forced firms to downsize, reduce bench strength, freeze wages and intensify work, while deferring client payments. When the economy recovered, high attrition, termed ‘The Great Resignation’, forced employers to increase wages. Employers were unable to compel employees to return to the office, despite facing issues relating to organisational culture, data security and moonlighting. Remote working helped employees maintain work–life balance and save on cost of living, forcing employers to provide a hybrid option.

A narrative review of teen mothers’ long-term outcomes: what birth cohort studies tell us

Studies examining the relationship between young maternal age and maternal outcomes are often cross-sectional or short term. We review birth cohort studies that investigate life course outcomes of teen mothers past age 25. Strengths of birth cohort studies include a focus on a complete cohort, rather than a sample, and prospective data collection beginning before or at birth. Limitations are high cost, attrition and unmeasured background factors. Some 20 studies from six countries met study criteria. This narrative review describes how teenage mothers fare as adults, identifies factors that modify outcomes and examines whether outcomes reflect specific time periods or cohorts. Childhood disadvantage was a greater marker of teen mothering in more recent cohorts, even in countries with strong social welfare programmes. The effects of young maternal age on all outcomes diminished when strong controls adjusted for selectivity into teen mothering.

Self-guided digital acceptance and commitment therapy for fibromyalgia management: results of a randomized, active-controlled, phase II pilot clinical trial

Although empirically validated for fibromyalgia (FM), cognitive and behavioral therapies, including Acceptance and Commitment Therapy (ACT), are inaccessible to many patients. A self-guided, smartphone-based ACT program would significantly improve accessibility. The SMART-FM study assessed the feasibility of conducting a predominantly virtual clinical trial in an FM population in addition to evaluating preliminary evidence for the safety and efficacy of a digital ACT program for FM (FM-ACT). Sixty-seven patients with FM were randomized to 12 weeks of FM-ACT (n = 39) or digital symptom tracking (FM-ST; n = 28). The study population was 98.5% female, with an average age of 53 years and an average baseline FM symptom severity score of 8 out of 11. Endpoints included the Fibromyalgia Impact Questionnaire-Revised (FIQ-R) and the Patient Global Impression of Change (PGIC). The between-arm effect size for the change from baseline to Week 12 in FIQ-R total scores was d = 0.44 (least-squares mean difference, − 5.7; SE, 3.16; 95% CI, − 11.9 to 0.6; P = .074). At Week 12, 73.0% of FM-ACT participants reported improvement on the PGIC versus 22.2% of FM-ST participants (P < .001). FM-ACT demonstrated improved outcomes compared to FM-ST, with high engagement and low attrition in both arms. Retrospectively registered at ClinicalTrials.gov (NCT05005351) on August 13, 2021.

A Review of Staff Attrition in the Hotel Industry – An Indian Perspective

The hospitality industry has a bad name for a high staff attrition rate and the human resource department or the hotel authorities have the daunting task of having control over that issue. Due to the high turnover of employees, hotels suffer on account of the extra cost of new recruitment, training, and also reputation loss of the company. This review article examined the root causes of attrition in the hotel industry in India. Several issues related to employee turnover intentions were examined through the eyes of all employees and employers of luxury hotels. Interviews and questionnaires were used to gather information related to organizational culture, satisfaction level of staff, work environment, growth opportunity, average salary, work environment, work-life balance, training facilities, supervision, job security, and job embeddedness. Unfortunately, most of the hotels were found to be ineffective in their policy-making to retain competent employees. Low salaries, long and hard work were identified among the most crucial factors affecting attrition. The study recommended certain key strategies to curb the high attrition rate.

Retaining U.S. stem women faculty during the COVID-19 pandemic: the important role of family-supportive supervisor behaviors to lower work-to-life conflict

PurposeThe COVID-19 pandemic may negatively impact the careers of U.S. women faculty in computer science (CS) – a field with few women and high attrition rates among women – due to difficulties balancing increased work and family demands (author citation). Thus, it is important to understand whether supervisors may help to decrease this work-to-life conflict and increase the odds of retaining women faculty. This study examined whether family-supportive supervisor behaviors (FSSB) were associated with better retention-related job outcomes (e.g., lower turnover intentions) among women faculty in CS, and whether this association was mediated by lower work-to-life conflict.Design/methodology/approachA total of 379 CS faculty across the U.S. (54% women, 52% with children at home) were surveyed during the COVID-19 pandemic (Fall 2020-Spring 2021).FindingsCompared to men, women CS faculty reported significantly higher work-to-life conflict, and that higher work-to-life conflict predicted poorer retention-related work outcomes for all faculty. However, for women only, FSSB predicted lower levels of work-to-life conflict, and in turn, better retention-related work outcomes.Practical implicationsResults suggest that emotionally-supportive supervisor behaviors may lower work-to-life conflict during the pandemic, which has important implications for retention-related work outcomes among women faculty in CS.Originality/valueResearch has yet to disentangle how managers can help to retain women CS faculty in light of the increasing and changing work and home demands due to the pandemic. The present study focused on whether FSSB – particularly emotional support – may benefit women CS faculty.

Illustrating Productive and Unproductive Cognitive Interactions in an Online Intermediate Algebra Course

Universities have drawn on an assortment of strategies to address the learning challenges and high attrition rates of developmental mathematics students. One of those strategies has been utilizing computer adaptive instruction (CAI) mathematics software. Reports about the efficacy of CAI vary from glowing to unfavorable. This article presents an instrumental case study, meaning that the purpose is to examine and describe a single case in depth to explain observed phenomena and illustrate a theory [Baxter and Jack 2008. Qualitative case study methodology: Study design and Implementation for novice researchers. The Qualitative Report. 14(4): 544–559]. The phenomena described in this article is productive and unproductive student interactions with a CAI environment. The vignettes in this article illustrate how students, even the same student, can have both productive and unproductive interactions with a CAI system. The vignettes are followed by recommendations for curriculum, instruction, assessment, and further research. Although these recommendations are gathered from observations of student interactions with CAI software in an asynchronous online Intermediate Algebra course, the observations have implications for different modes of instruction (e.g., synchronous online, flipped, hybrid, or face-to-face) that utilize online homework systems.

Effectiveness of the SAFE eHealth Intervention for Women Experiencing Intimate Partner Violence and Abuse: Randomized Controlled Trial, Quantitative Process Evaluation, and Open Feasibility Study.

Intimate partner violence and abuse (IPVA) is a pervasive societal issue that impacts many women globally. Web-based help options are becoming increasingly available and have the ability to eliminate certain barriers in help seeking for IPVA, especially in improving accessibility. This study focused on the quantitative evaluation of the SAFE eHealth intervention for women IPVA survivors. A total of 198 women who experienced IPVA participated in a randomized controlled trial and quantitative process evaluation. Participants were largely recruited on the internet and signed up through self-referral. They were allocated (blinded for the participants) to (1) the intervention group (N=99) with access to a complete version of a help website containing 4 modules on IPVA, support options, mental health, and social support, and with interactive components such as a chat, or (2) the limited-intervention control group (N=99). Data were gathered about self-efficacy, depression, anxiety, and multiple feasibility aspects. The primary outcome was self-efficacy at 6 months. The process evaluation focused on themes, such as ease of use and feeling helped. In an open feasibility study (OFS; N=170), we assessed demand, implementation, and practicality. All data for this study were collected through web-based self-report questionnaires and automatically registered web-based data such as page visits and amount of logins. We found no significant difference over time between groups for self-efficacy, depression, anxiety, fear of partner, awareness, and perceived support. However, both study arms showed significantly decreased scores for anxiety and fear of partner. Most participants in both groups were satisfied, but the intervention group showed significantly higher scores for suitability and feeling helped. However, we encountered high attrition for the follow-up surveys. Furthermore, the intervention was positively evaluated on multiple feasibility aspects. The average amount of logins did not significantly differ between the study arms, but participants in the intervention arm did spend significantly more time on the website. An increase in registrations during the OFS (N=170) was identified: the mean amount of registrations per month was 13.2 during the randomized controlled trial and 56.7 during the OFS. Our findings did not show a significant difference in outcomes between the extensive SAFE intervention and the limited-intervention control group. It is, however, difficult to quantify the real contribution of the interactive components, as the control group also had access to a limited version of the intervention for ethical reasons. Both groups were satisfied with the intervention they received, with the intervention study arm significantly more so than the control study arm. Integrated and multilayered approaches are needed to aptly quantify the impact of web-based IPVA interventions for survivors. Netherlands Trial Register NL7108 NTR7313; https://trialsearch.who.int/Trial2.aspx?TrialID=NTR7313.

The non-stranger rapist-oriented interview for complainants: Eliciting high-quality accounts

Non-stranger rape (NSR) cases are often not prosecuted because of the poor quality of the accounts obtained from complainants. However, a growing body of research suggests that such high attrition rates are likely to improve when the quality of these accounts is increased by skilled interviewing. To assist police interviewers in eliciting high-quality accounts, the development of a guide for the interviewing of NSR complainants has recently been recommended. The present study aims to make the first step in developing such a guide. A multidisciplinary literature search was conducted. The newly developed Non-Stranger Rapist-Oriented Interview (NSROI) is specifically designed to promote complainants’ disclosure of evidentially relevant information in the form of a clear, chronological and concise narrative (i.e., a high-quality account). The guide is divided into the ‘preparatory’, ‘rape’ and ‘rape aftermath’ phase. The three themes and questions of the first phase focus on revealing the context in which the alleged rape occurred. The five themes and questions of the second phase concentrate on the day of sexual penetration. The third phase’s ninth theme and questions focus on the psychological impact of the events on the complainant. The guide includes the following themes: (i) vulnerabilities, (ii) relationship history, (iii) indications of planning and premeditation, (iv) method to gain control, (v) method to keep control, (vi) offered resistance, (vii) sexual acts performed, sequence and degree of penetration, (viii) perpetrator’s behaviour after the performed sexual acts and (ix) victim’s post-event psychological injury. The potential, implications and limitations of the NSROI are discussed.

A Study on Employee Attrition Rate in Coir Industry

Employee attrition, the rate at which employees voluntarily leave an organization, poses significant challenges to the Coir industry, a sector involved in the production and processing of natural fiber extracted from coconut husks. High attrition rates can adversely impact productivity, disrupt operations, increase costs, and hinder organizational growth. Therefore, it is crucial to understand the factors contributing to attrition and develop effective strategies to mitigate its negative effects. The study utilizes a mixed-methods approach, incorporating both quantitative and qualitative research methodologies. The quantitative phase involves collecting attrition data from multiple Coir industry companies over a specified period. The data includes employee turnover rates, demographics, job roles, tenure, and reasons for departure. Statistical analysis techniques such as regression analysis and correlation tests will be employed to determine the relationship between attrition and various factors, including job satisfaction, compensation, career development opportunities, work-life balance, and organizational culture.

Dentofacial effects of miniscrew-anchored maxillary protraction on prepubertal children with maxillary deficiency: a randomized controlled trial

BackgroundThe introduction of bone-anchored maxillary protraction eliminated the side effects of facemask in the early treatment of patients with maxillary retrusion. This study aimed to evaluate the effects of miniscrew-anchored maxillary protraction (MAMP) and compare them with the growth changes in an untreated control group in growing patients with Class III malocclusion.MethodsForty growing patients with Class III malocclusion and retrognathic maxilla were randomly allocated into two groups: treated and control groups. In the treated group, patients were treated with full-time intermaxillary Class III elastics (C3E) anchored by a hybrid hyrax (HH) in the maxilla and a bone-supported bar in the mandible. Protraction was stopped after obtaining a positive overjet. Cephalometric radiographs were acquired before and after the treatment. Data were statistically analyzed on an intention-to-treat basis. Intergroup comparisons were also made using analysis of covariance with the readings at T0 as a covariate.ResultsForty patients agreed to participate, and 30 of them completed the study (treated group, n = 17; control group, n = 13). The average treatment duration was 11.9 months. MAMP resulted in a significant maxillary advancement (A-VR, 4.34 mm) with significant control over the mandibular growth. No significant increase in the mandibular plane angle was found in the treated group compared with the control group. The upper and lower incisors showed significant protrusion in the treated group.ConclusionsWithin the limitations of this study and high attrition rate, the MAMP protocol can effectively increase maxillary forward growth with good control over the growth of the mandible antero-posteriorly and vertically.

Effectively utilizing publicly available databases for cancer target evaluation.

The majority of compounds designed against cancer drug targets do not progress to become approved drugs, mainly due to lack of efficacy and/or unmanageable toxicity. Robust target evaluation is therefore required before progressing through the drug discovery process to reduce the high attrition rate. There are a wealth of publicly available databases that can be mined to generate data as part of a target evaluation. It can, however, be challenging to learn what databases are available,how and when they should be used, and to understand the associated limitations. Here, we have compiled and present key, freely accessible and easy-to-use databases that house informative datasets from in vitro, in vivo and clinical studies. We also highlight comprehensive target review databases that aim to bring together information from multiple sources into one-stop portals. In the post-genomics era, a key objective is to exploit the extensive cell, animal and patient characterization datasets in order to deliver precision medicine on a patient-specific basis. Effective utilization of the highlighted databases will go some way towards supporting the cancer research community achieve these aims.

Quinolone analogues of benzothiazinone: Synthesis, antitubercular structure-activity relationship and ADME profiling

Mycobacterium tuberculosis (Mtb) has an impermeable cell wall which gives it an inherent ability to resist many antibiotics. DprE1, an essential enzyme in Mtb cell wall synthesis, has been validated as a target for several TB drug candidates. The most potent and developmentally advanced DprE1 inhibitor, PBTZ169, is still undergoing clinical development. With high attrition rate, there is need to populate the development pipeline. Using a scaffold hopping strategy, we imprinted the benzenoid ring of PBTZ169 onto a quinolone nucleus. Twenty-two compounds were synthesised and screened for activity against Mtb, with six compounds exhibiting sub micromolar activity of MIC90 <0.244 μM. Compound 25 further demonstrated sub-micromolar activity when evaluated against wild-type and fluoroquinolone-resistant Mtb strains. This compound maintained its sub-micromolar activity against a DprE1 P116S mutant strain but showed a significant reduction in activity when tested against the DprE1 C387S mutant.

Circumstances, policing, and attrition of multiple compared to single perpetrator rape cases within the South African criminal justice system

BackgroundResearch into the circumstances of rape, and criminal justice system responses, is pivotal to informing prevention and improving the likelihood of justice for victims. In this paper, we explore the differences in the circumstances of multiple-perpetrator rapes (MPRs) and single-perpetrator rapes (SPRs), their case management, and attrition, and describe areas for improvemensuplt around rape response within the South African criminal justice system.MethodsThe sample comprised 3952 rape cases reported to the South African Police Services (SAPS) in 2012, selected through a multi-stage random sampling of 172 police stations from a total of 1164 police stations in the nine provinces, followed by the random selection of cases from each station’s case list. Data were abstracted from police dockets, medico-legal examination forms, charge sheets, and trial transcripts. MPRs were defined as cases in which more than one perpetrator had sexual contact with the victim during a single incident, i.e., sexually assaulted or raped. Descriptive statistics and Chi-square tests for associations were used to compare MPRs and SPRs in circumstances of the rape, case management, and attrition.ResultsSeventeen percent of cases were MPRs. MPRs were comparably more violent crimes with a higher frequency of aggressive tactics employed by perpetrators, for example, abductions, firearms use, and threats to kill. Overall, cases were often poorly handled by police, and there were deviations from standard policing and investigation procedures; we found more evidence of this with MPRs compared to SPRs. MPR cases were most likely to have been closed by police due to undetected perpetrators in combination with other victim reasons. The weaker investigations of MPRs were associated with higher attrition rates compared to SPRs, firstly at the police investigation and subsequent stages.ConclusionsThe findings confirm differences in case management, patterns of attrition and trajectories of MPRs compared to SPRs. In an overall context of high rape case attrition and impunity for perpetrators, MPR victims are even less likely to see justice served than SPR victims. There needs to be much more effective supervision of rape case investigations by SAPS, particularly in MPR cases. Continual investigator training strengthened supervision and better resourcing are necessary to improve MPRs detection and convictions in adherence to the Directives for rape policing.

Role and capacity needs of community based surveillance volunteers in the integrated management of skin neglected tropical diseases (skin NTDs): a qualitative study from central Ghana

BackgroundCommunity Based Surveillance Volunteers (CBSVs) have been instrumental in the management of Neglected Tropical Diseases (NTDs) but a concern that their services in scale up programmes may be affected due to high attrition rates has been widely acknowledged. We explored the roles and capacity needs of existing CBSVs to inform for a successful integrated NTD management programme in Ghana and similar contexts.MethodsWe conducted qualitative interviews with 50 CBSVs, 21 Community Nurses, 4 Disease control officers, 7 skin NTD researchers, 2 skin NTD patients and a Director of District Health Services in Central Ghana. Interviews were digitally recorded, transcribed and coded prior to translation and thematic analysis.ResultsThe roles of CBSVs in NTD management were shown to have an impact on disease identification, surveillance, health seeking behaviours and status of CBSVs. Lack of motivation, inadequate structures for engagement of CBSVs within the health system and delayed management of reported cases were identified as gaps that hinder effective delivery of CBSV roles. Provision of incentives as recognition for the unpaid services rendered by CBSVs was seen as a major factor to reduce the rate of CBSV attrition in this scale up programme. Other factors included the formulation of policies by government to guide CBSV engagement, regular training of CBSV in NTD management as well as provision of resources and logistics.ConclusionMeasures including continuous training, institution of rewards and incentivization are important for ensuring the sustainability of CBSVs in the provision of skin NTD services in Ghana.

Canadian (CAN) real-world outcomes for relapsed/recurrent (R/R) metastatic triple-negative breast cancer (mTNBC) in the first-line or later (1L+) setting by early or late recurrence status.

e18798 Background: Little epidemiological data characterizing the mTNBC population in Canada exist, limiting the understanding of treatment patterns, attrition rates, and unmet need for CAN patients (pts) with R/R mTNBC. This study examined real-world outcomes and palliative treatment patterns for CAN pts with 1L+ R/R mTNBC, stratified by early vs late recurrence. Methods: This retrospective study used real-world, population-based data from the Oncology Outcomes database in Alberta to identify pts diagnosed with early stage (I to III) TNBC between 2010-2019 who progressed to mTNBC. Algorithms reliably identified recurrent pts as those who received 2+ cycles of systemic therapy &gt; 240 days from the initiation of adjuvant treatment or surgery. Clinical outcomes from 1L+ treatment of mTNBC, including time to next treatment (TTNT) or death and overall survival (OS), were ascertained. Diagnosis, demographics, treatment patterns, and attrition rates were stratified by treatment-free interval (TFI), early (8-12 mo TFI) or late ( &gt; 12 mo TFI). Results: Data from 181 CAN pts with R/R mTNBC (recurred early, n = 59; recurred late, n = 122) were analyzed. Baseline characteristics were generally comparable between groups. Pts who recurred late were on average older at recurrence (59 y vs 55 y, P= 0.03) and less likely to be stage III (21% vs 51%, P&lt; 0.001) at initial diagnosis. The median time to recurrence was 17 mo. The most common 1L therapies were capecitabine monotherapy (35%), other chemotherapy combinations (16%), and taxane monotherapy (12%), with a median duration of therapy (DOT) of 4.9 mo, 3.5 mo, and 4.5 mo, respectively. Rates of attrition between lines of therapy (LOT) were relatively high, with 96 pts (53%) initiating 2L therapy (among the 85 pts who did not start 2L treatment, 63 had died). Median DOT was 3.6 mo for 1L, 3.0 mo for 2L, and 3.0 mo for 3L. Stratifying by early or late recurrence did not show differences in TTNT (4 mo vs 4 mo; HR, 0.94; 95% CI, 0.64-1.38; P= 0.75) or OS (10 mo vs 11 mo; HR, 0.96; 95% CI, 0.64-1.44; P= 0.84). Exploratory analyses showed improved OS (23 mo vs 10 mo; HR, 0.60; 95% CI, 0.40-0.92; P= 0.02) in pts with TFI ≥24 mo (n = 61) but not in pts with TFI 12-24 mo (11 vs 10 mo; HR: 0.96; 95% CI: 0.64-1.44; P= 0.84) vs pts with TFI of 8-12 mo. Conclusions: This retrospective study showed higher than expected rates of early recurrence and high attrition between LOT in a CAN breast cancer population that progressed to mTNBC. The short DOT across lines was similar and consistent with CAN practice. OS for 1L+ R/R mTNBC were similar for individuals who recurred between 8-12 vs 12-24 mo. These findings confirmed the poor prognosis of pts with R/R mTNBC and the need for improved therapies especially in 1L, where the most common treatments, including capecitabine, may not deliver the most meaningful impact.

Biobehavioral Influences of Stress and Inflammation on Mucositis in Adolescents and Young Adults with Cancer: Results from a Pilot Study.

Purpose: Chemotherapy-induced mucositis is a prevalent and burdensome toxicity among adolescent and young adults (AYAs) with cancer and impedes the delivery of optimal therapy. Its development is not well understood, but baseline stress and inflammation may be contributory factors. This pilot study evaluates stress and inflammation as risk factors for mucositis, identifies effect size estimates, and evaluates the feasibility of a prospective study to investigate mucositis development. Methods: Thirty AYAs receiving chemotherapy with substantial risk of mucositis completed baseline stress measures, and serum was collected for inflammatory biomarker analysis. Regression and mediation analyses determined the relationship between stress/inflammation and mucositis. Results: Stress appears to be a significant risk factor for incidence of mucositis (odds ratio 1.13, p = 0.125) and predicts total mucositis score (β = 0.281, p = 0.023) as well as peak incidence (β = 0.052, p = 0.018). Baseline levels of interleukin (IL)-1a and epidermal growth factor (EGF) predicted mucositis development, and EGF and IL-8 may mediate the relationship between stress and mucositis. Findings suggest that stress-induced inflammation exacerbates symptom development. Conclusion: Results from this pilot study inform mucositis symptom models, suggesting that psychosocial and physiologic factors are involved in development. Importantly, this pilot study provides initial effect size estimates, including magnitude and direction of relationships, that are essential to informing larger, more robustly powered studies. High enrollment, low attrition, and minimal missing data in this study suggest this model is feasible for research in this population. Importantly, this work is a first step in identifying new risk factors for mucositis and targets for nurse-led interventions to prevent toxicity development.

Reliability, validity, and feasibility of a smartphone‐based cognitive assessment for preclinical Alzheimer disease

AbstractBackgroundSmartphone‐based ecological momentary assessments (EMA) have the potential to capture subtle changes in cognition associated with preclinical Alzheimer disease (AD) in older adults. The Ambulatory Research in Cognition (ARC) smartphone application is based on EMA principles and administers brief tests of associative memory, processing speed, and working memory ∼4 times per day over 7 consecutive days. Participants perform these 7‐day cycles every ∼6 months, longitudinally. ARC was designed to be performed unsupervised, on participants’ personal devices, and in their everyday environments in order to increase accessibility, testing, and reliability.MethodWe evaluated the reliability, validity, and feasibility of ARC in a large, well‐characterized sample of cognitively normal older adults (ages 65‐97) and individuals with very mild dementia (ages 61‐88). Participants completed at least one 7‐day cycle of ARC testing along with conventional cognitive assessments. Most participants also had cerebrospinal fluid, amyloid and tau PET, and structural MRI data available. The reliability, validity, and feasibility of ARC as an unsupervised, high‐frequency cognitive assessment tool using participants’ personal smartphones was tested by examining (1) between‐subjects and test‐retest reliability, (2) correlations with age, conventional cognitive measures, and AD‐related biomarkers, and (3) adherence and attrition rates of older adults with varying technology familiarity.ResultFirst, ARC tasks demonstrated good reliability such that between‐person reliability across the 7‐day cycle and test‐retest reliabilities at 6‐month and 1‐year follow‐ups all exceeded intraclass correlations of 0.85. Second, ARC demonstrated construct validity as evidenced by correlations with conventional cognitive measures. Third, ARC measures correlated with AD biomarker burden at baseline to a similar degree as conventional cognitive measures. Finally, high adherence rates and low attrition rates indicated that ARC was feasible and, to some extent, enjoyable, for older adult participants.ConclusionUltimately, these results suggest that ARC is a reliable and valid measure of cognition in older adults at risk for AD and is a feasible tool for assessing subtle cognitive changes associated with the earliest stages of AD.

Phase 1/2a clinical trial in ALS with ropinirole, a drug candidate identified by iPSC drug discovery

iPSC-based drug discovery led to a phase 1/2a trial of ropinirole in ALS. 20 participants with sporadic ALS received ropinirole or placebo for 24weeks in the double-blind period to evaluate safety, tolerability, and therapeutic effects. Adverse events were similar in both groups. During the double-blind period, muscle strength and daily activity were maintained, but a decline in the ALSFRS-R, which assesses the functional status of ALS patients, was not different from that in the placebo group. However, in the open-label extension period, the ropinirole group showed significant suppression of ALSFRS-R decline and an additional 27.9weeks of disease-progression-free survival. iPSC-derived motor neurons from participants showed dopamine D2 receptor expression and a potential involvement of the SREBP2-cholesterol pathway in therapeutic effects. Lipid peroxide represents a clinical surrogate marker to assess disease progression and drug efficacy. Limitations include small sample sizes and high attrition rates in the open-label extension period, requiring further validation.

A meta-analysis of post-exercise outcomes in people with amyotrophic lateral sclerosis.

To systematically evaluate post-exercise outcomes related to function and quality of life in people with ALS. PRISMA guidelines were used for identifying and extracting articles. Levels of evidence and quality of articles were judged based on The Oxford Centre for Evidence-based Medicine Levels of Evidence and the QualSyst. Outcomes were analyzed with Comprehensive Meta-Analysis V2 software, random effects models, and Hedge's G. Effects were examined at 0-4months, up to 6months, and>6months. Pre-specified sensitivity analyses were performed for 1) controlled trials vs. all studies and 2) ALSFRS-R bulbar, respiratory, and motor subscales. Heterogeneity of pooled outcomes was computed with the I2 statistic. 16 studies and seven functional outcomes met inclusion for the meta-analysis. Of the outcomes explored, the ALSFRS-R demonstrated a favorable summary effect size and had acceptable heterogeneity and dispersion. While FIM scores demonstrated a favorable summary effect size, heterogeneity limited interpretations. Other outcomes did not demonstrate a favorable summary effect size and/or could not be reported due to few studies reporting outcomes. This study provides inconclusive guidance regarding exercise regimens to maintain function and quality of life in people with ALS due to study limitations (e.g., small sample size, high attrition rate, heterogeneity in methods and participants, etc.). Future research is warranted to determine optimal treatment regimens and dosage parameters in this patient population.