Stimulant Reduction Intervention using Dosed Exercise (STRIDE) - CTN 0037: Study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>There is a need for novel approaches to the treatment of stimulant abuse and dependence. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse, with direct effects on decreased use and craving. In addition, exercise has the potential to improve other health domains that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight gain, quality of life, and anhedonia, since it has been shown to improve many of these domains in a number of other clinical disorders. Furthermore, neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes. The current manuscript presents the rationale, design considerations, and study design of the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE) study.</p> <p>Methods/Design</p> <p>STRIDE is a multisite randomized clinical trial that compares exercise to health education as potential treatments for stimulant abuse or dependence. This study will evaluate individuals diagnosed with stimulant abuse or dependence who are receiving treatment in a residential setting. Three hundred and thirty eligible and interested participants who provide informed consent will be randomized to one of two treatment arms: Vigorous Intensity High Dose Exercise Augmentation (DEI) or Health Education Intervention Augmentation (HEI). Both groups will receive TAU (i.e., usual care). The treatment arms are structured such that the quantity of visits is similar to allow for equivalent contact between groups. In both arms, participants will begin with supervised sessions 3 times per week during the 12-week acute phase of the study. Supervised sessions will be conducted as one-on-one (i.e., individual) sessions, although other participants may be exercising at the same time. Following the 12-week acute phase, participants will begin a 6-month continuation phase during which time they will attend one weekly supervised DEI or HEI session.</p> <p>Clinical Trials Registry</p> <p>ClinicalTrials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01141608">NCT01141608</a></p> <p><url>http://clinicaltrials.gov/ct2/show/NCT01141608?term=Stimulant+Reduction+Intervention+using+Dosed+Exercise&rank=1</url></p

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Insecticide resistance of Miami-Dade Culex quinquefasciatus populations and initial field efficacy of a new resistance-breaking adulticide formulation.

Sporadic outbreaks of human cases of West Nile virus (WNV), primarily vectored by Culex quinquefasciatus Say in suburban and urban areas, have been reported since introduction of the virus into Florida in 2001. Miami-Dade County, Florida is part of one of the largest metropolitan areas in the United States, supports Cx. quinquefasciatus year-round, and recently experienced over 60 human cases of WNV during one outbreak. To facilitate more effective integrated vector management and public health protection, we used the Centers for Disease Control and Prevention (CDC) bottle bioassay method to evaluate the susceptibility of adult Cx. quinquefasciatus collected from 29 locations throughout Miami-Dade County to pyrethroid and organophosphate adulticide active ingredients (AIs) used by Miami-Dade County Mosquito Control. We also determined the frequency of the 1014 knockdown resistance (kdr) mutation for Cx. quinquefasciatus from a subset of 17 locations. We detected resistance to two pyrethroid AIs in all tested locations (permethrin: 27 locations, deltamethrin: 28 locations). The 1014F allele was widely distributed throughout all 17 locations sampled; however, 29.4% of these locations lacked 1014F homozygotes even though phenotypic pyrethroid resistance was present. Organophosphate resistance was more variable; 20.7% of the locations tested were susceptible to malathion, and 33.3% of the populations were susceptible to naled. We subsequently conducted a field trial of ReMoa Tri, a recently approved multiple AI adulticide formulation labelled for resistant mosquitoes, against a mixed location field population of Miami-Dade Cx. quinquefasciatus. Average 24-hr mortality was 65.1 ± 7.2% and 48-hr mortality increased to 85.3 ± 9.1%, indicating good control of these resistant Cx. quinquefasciatus. This current study shows that insecticide resistance is common in local Cx. quinquefasciatus but effective options are available to maintain control during active disease transmission in Miami-Dade County

Mosquito Control Priorities in Florida—Survey Results from Florida Mosquito Control Districts

Florida lies within a subtropical region where the climate allows diverse mosquito species including invasive species to thrive year-round. As of 2021, there are currently 66 state-approved Florida Mosquito Control Districts, which are major stakeholders for Florida public universities engaged in mosquito research. Florida is one of the few states with extensive organized mosquito control programs. The Florida State Government and Florida Mosquito Control Districts have long histories of collaboration with research institutions. During fall 2020, we carried out a survey to collect baseline data on the current control priorities from Florida Mosquito Control Districts relating to (1) priority control species, (2) common adult and larval control methods, and (3) major research questions to address that will improve their control and surveillance programs. The survey data showed that a total of 17 distinct mosquito species were considered to be priority control targets, with many of these species being understudied. The most common control approaches included truck-mounted ultra-low-volume adulticiding and biopesticide-based larviciding. The districts held interest in diverse research questions, with many prioritizing studies on basic science questions to help develop evidence-based control strategies. Our data highlight the fact that mosquito control approaches and priorities differ greatly between districts and provide an important point of comparison for other regions investing in mosquito control, particularly those with similar ecological settings, and great diversity of potential mosquito vectors, such as in Florida. Our findings highlight a need for greater alignment of research priorities between mosquito control and mosquito research. In particular, we note a need to prioritize filling knowledge gaps relating to understudied mosquito species that have been implicated in arbovirus transmission

Fig 1 -

Percent mortality of Miami-Dade County Cx. quinquefasciatus populations at diagnostic times in CDC bottle bioassays against permethrin (A) and deltamethrin (B). Mortality percentages are colored according to outcome based on the CDC scale. Red type indicates resistance, green type indicates susceptibility, and black type indicates developing resistance according to the CDC scale [38].</p

Weather during ReMoa Tri ground ULV field trial.

Sporadic outbreaks of human cases of West Nile virus (WNV), primarily vectored by Culex quinquefasciatus Say in suburban and urban areas, have been reported since introduction of the virus into Florida in 2001. Miami-Dade County, Florida is part of one of the largest metropolitan areas in the United States, supports Cx. quinquefasciatus year-round, and recently experienced over 60 human cases of WNV during one outbreak. To facilitate more effective integrated vector management and public health protection, we used the Centers for Disease Control and Prevention (CDC) bottle bioassay method to evaluate the susceptibility of adult Cx. quinquefasciatus collected from 29 locations throughout Miami-Dade County to pyrethroid and organophosphate adulticide active ingredients (AIs) used by Miami-Dade County Mosquito Control. We also determined the frequency of the 1014 knockdown resistance (kdr) mutation for Cx. quinquefasciatus from a subset of 17 locations. We detected resistance to two pyrethroid AIs in all tested locations (permethrin: 27 locations, deltamethrin: 28 locations). The 1014F allele was widely distributed throughout all 17 locations sampled; however, 29.4% of these locations lacked 1014F homozygotes even though phenotypic pyrethroid resistance was present. Organophosphate resistance was more variable; 20.7% of the locations tested were susceptible to malathion, and 33.3% of the populations were susceptible to naled. We subsequently conducted a field trial of ReMoa Tri, a recently approved multiple AI adulticide formulation labelled for resistant mosquitoes, against a mixed location field population of Miami-Dade Cx. quinquefasciatus. Average 24-hr mortality was 65.1 ± 7.2% and 48-hr mortality increased to 85.3 ± 9.1%, indicating good control of these resistant Cx. quinquefasciatus. This current study shows that insecticide resistance is common in local Cx. quinquefasciatus but effective options are available to maintain control during active disease transmission in Miami-Dade County.</div

Genotype and Allele Percentages for the leucine to phenylalanine 1014 mutation in Miami-Dade county <i>Cx</i>. <i>quinquefasciatus</i> populations.

Genotype and Allele Percentages for the leucine to phenylalanine 1014 mutation in Miami-Dade county Cx. quinquefasciatus populations.</p

Droplet parameters from ReMoa Tri ground ULV field trial.

Droplet parameters from ReMoa Tri ground ULV field trial.</p

Miami-Dade County <i>Cx</i>. <i>quinquefasciatus</i> mortality at diagnostic times and 120 minutes of exposure in CDC bottle bioassays against multiple active ingredients.

Miami-Dade County Cx. quinquefasciatus mortality at diagnostic times and 120 minutes of exposure in CDC bottle bioassays against multiple active ingredients.</p