Recruitment of a multi-site randomized controlled trial of aerobic exercise for older adults with amnestic mild cognitive impairment: The EXERT trial.

INTRODUCTION: Effective strategies to recruit older adults with mild cognitive impairment (MCI) into nonpharmacological intervention trials are lacking. METHODS: Recruitment for EXERT, a multisite randomized controlled 18-month trial examining the effects of aerobic exercise on cognitive trajectory in adults with amnestic MCI, involved a diverse portfolio of strategies to enroll 296 participants. RESULTS: Recruitment occurred September 2016 through March 2020 and was initially slow. After mass mailings of 490,323 age- and geo-targeted infographic postcards and brochures, recruitment rates increased substantially, peaking at 16 randomizations/month in early 2020. Mass mailings accounted for 52% of randomized participants, whereas 25% were recruited from memory clinic rosters, electronic health records, and national and local registries. Other sources included news broadcasts, public service announcements (PSA), local advertising, and community presentations. DISCUSSION: Age- and geo-targeted mass mailing of infographic materials was the most effective approach in recruiting older adults with amnestic MCI into an 18-month exercise trial.

Infection of male rats with Toxoplasma gondii induces effort-aversion in a T-maze decision-making task.

Rats chronically infected with protozoan Toxoplasma gondii exhibit greater delay aversion in an inter-temporal task. Moreover T. gondii infection also results in dendritic atrophy of basolateral amygdala neurons. Basolateral amygdala is reported to bias decision making towards greater effortful alternatives. In this context, we report that T. gondii increases effort aversion in infected male rats. This host-parasite association has been widely studied in the context of loss of innate fear in the infected males. It is suggested that reduced fear towards predators reflects a parasitic behavioral manipulation to enhance trophic transmission of T. gondii. Observations reported here extend this paradigm away from a monolithic change in fear and towards a multi-dimensional change in decision making.

Toxoplasma gondii infection and testosterone congruently increase tolerance of male rats for risk of reward forfeiture.

Decision making under risk involves balancing the potential of gaining rewards with the possibility of loss and/or punishment. Tolerance to risk varies between individuals. Understanding the biological basis of risk tolerance is pertinent because excessive tolerance contributes to adverse health and safety outcomes. Yet, not much is known about biological factors mediating inter-individual variability in this regard. We investigate if latent Toxoplasma gondii infection can cause risk tolerance. Using a rodent model of the balloon analogous risk task, we show that latent T. gondii infection leads to a greater tolerance of reward forfeiture. Furthermore, effects of the infection on risk can be recapitulated with testosterone supplementation alone, demonstrating that greater testosterone synthesis by the host post-infection is sufficient to change risk tolerance. T. gondii is a frequent parasite of humans and animals. Thus, the infection status can potentially explain some of the inter-individual variability in the risky decision making.

Infection of male rats with Toxoplasma gondii results in enhanced delay aversion and neural changes in the nucleus accumbens core.

Rats infected with the protozoan parasite Toxoplasma gondii exhibit reduced avoidance of predator odours. This behavioural change is likely to increase transmission of the parasite from rats to cats. Here, we show that infection with T. gondii increases the propensity of the infected rats to make more impulsive choices, manifested as delay aversion in an intertemporal choice task. Concomitantly, T. gondii infection causes reduction in dopamine content and neuronal spine density of the nucleus accumbens core, but not of the nucleus accumbens shell. These results are consistent with a role of the nucleus accumbens dopaminergic system in mediation of choice impulsivity and goal-directed behaviours. Our observations suggest that T. gondii infection in rats causes a syndromic shift in related behavioural constructs of innate aversion and making foraging decisions.

Rapid Access From Primary Care to a Multidisciplinary Clinic at Tertiary Care Improves Clinical Outcomes for Patients With Diabetic Foot Ulcers: Results From Diabetic Foot in Primary and Tertiary (DEFINITE) Care's Lower Extremity Amputation Prevention Program (LEAPP) Clinic.

Diabetic Foot in Primary and Tertiary (DEFINITE) Care is an inter-institutional, multidisciplinary team (MDT) program for patients with diabetic foot ulcers (DFU) within a healthcare cluster in Singapore. This is one of our subgroup analyses within DEFINITE Care, assessing clinical outcomes of lower extremity amputation prevention program (LEAPP), a multidisciplinary diabetic foot clinic, and non-LEAPP patients within the program. From June 2020 to June 2022, 2798 patients within the DEFINITE cohort completed a minimum of 12-month follow up. Of these patients, 20.6% were managed by LEAPP, whereas 79.4% were non-LEAPP patients. Patients in the LEAPP cohort were older with co-existing metabolic conditions and complications of diabetes. Using non-LEAPP cohort as the reference group and after adjusting for age, gender, ethnicity, comorbidities, and medications, there was a significantly lower risk of death (odds ratio [OR] 0.60, P = .001) and composite major lower extremity amputation (LEA) or death (OR 0.66, P = .002) among LEAPP patients at 1 year with longer mean days from enrollment to minor LEA, major LEA, and death. The adjusted 1-year healthcare utilization outcomes for LEAPP patients demonstrated an increase in inpatient admissions, primary care polyclinic visits, hospital specialist outpatient clinic (SOC) visits and elective day surgery procedures. Despite the increased in inpatients admissions, cumulative hospital length of stay in LEAPP patients were lower. This subgroup analysis has demonstrated that the MDT approach to caring for patients with DFU in tertiary centers not only improves mortality by 40%, but also delayed the incidence of minor LEA, major LEA, and death.

T2 Protect AD: Achieving a rapid recruitment timeline in a multisite clinical trial for individuals with mild to moderate Alzheimer's disease.

Introduction: The reporting of approaches facilitating the most efficient and timely recruitment of Alzheimer's disease (AD) patients into pharmacologic trials is fundamental to much-needed therapeutic progress. Methods: T2 Protect AD (T2), a phase 2 randomized placebo-controlled trial of troriluzole in mild to moderate AD, used multiple recruitment strategies. Results: T2 exceeded its recruitment target, enrolling 350 participants between July 2018 and December 2019 (randomization rate: 0.87 randomizations/site/month, or 3-fold greater than recent trials of mild to moderate AD). The vast majority (98%) of participants were enrolled during a 10-month window of intense promotion in news media, TV and radio advertisements, and social media. The distribution of primary recruitment sources included: existing patient lists at participating sites (72.3%), news media (12.3%), physician referral (6.0%), word of mouth (3.1%), and paid advertising (2.9%). Discussion: The rapid recruitment of participants with mild to moderate AD was achieved through a range of approaches with varying success.

Improving asthma care with Asthma-COPD Afterhours Respiratory Nurse at Emergency (A-CARE).

BACKGROUND: Emergency departments (ED) are important providers of asthma care, particularly after-hours. We identified gaps for quality improvement such as suboptimal adherence rates to three key recommendations from the Global Initiative for Asthma (GINA) guidelines for discharge management asthma guidelines. These were: the prescription of oral and inhaled corticosteroids (OCS and ICS) and issuance of outpatient follow-up for patients discharged from the ED. AIM: To achieve an adherence rate of 80% to GINA guidelines for ED discharge management by providing after-hours asthma counselling services. METHODS: We implemented Asthma-COPD Afterhours Respiratory Nurse at Emergency (A-CARE) according to the Plan-Do-Study-Act (PDSA) framework to provide after-hours asthma counselling and clinical decision support to ED physicians three nights a week. Data on adherence rates to the GINA guidelines were collected and analysed on a run chart. RESULTS: After 17 months' follow-up, a sustained improvement was observed in patients reviewed by A-CARE in the median adherence rates to OCS prescription (58% vs 86%), ICS initiation (27% vs 67%) and issuance of follow-up (69% vs 92%), respectively. The overall impact was, however, limited by a suboptimal referral rate to A-CARE (16%) in a clinical audit of all ED patients with asthma. Nonetheless, in this audit, attendance rates for patients referred to our respiratory department for follow-up were higher in those receiving asthma counselling compared with those who did not (41.7% vs 15.9%, p=0.0388). CONCLUSION: Sustained improvements in the adherence rates to guidelines were achieved for patients reviewed by A-CARE but were limited in overall impact due to suboptimal referral rate. We plan to improve the quality of asthma care by implementing further PDSA cycles to increase the referral rates to A-CARE.

Determination of pyridostigmine bromide and its metabolites in biological samples.

Pyridostigmine bromide (PB) is a quartenary ammonium compound that inhibits the hydrolysis of acetylcholine by competitive reversible binding to acetylcholinesterase. PB is used for the symptomatic treatment of myasthenia gravis and has been applied as a prophylaxis against nerve agents. Many studies on PB have involved the reliance on techniques that extract and quantify PB in biological samples. This article presents an overview of the currently applied methodologies for the determination of PB and its metabolites in various biological samples. Articles published from January 1975 to the July 2005 were taken into consideration for the discussion of the metabolism and analytical method of PB. HPLC and GC methods have been used and discussed in most of the references cited in this review. Other methods such as RIA and CE that have been recently reported are also mentioned in this article. Basic information about the type of sample used for analysis, sample preparation, chromatographic column, mobile phase, detection mode and validation data are summarized in a table.