Design and baseline data from the vanguard of the Comparison of Depression Interventions after Acute Coronary Syndrome (CODIACS) randomized controlled trial

This paper describes the rationale and design of the vanguard for the Comparison of Depression Interventions after Acute Coronary Syndrome (CODIACS), a multicenter, randomized, controlled trial of a patient preference‐based, stepped care protocol for persistent depressive symptoms after acute coronary syndrome (ACS). The overall aim of the vanguard phase was to determine whether the patient-preference, stepped care protocol, which is based on the intervention used in the recent Coronary Psychosocial Evaluation Studies (COPES) trial, was feasible in patients with recent ACS who were recruited from 5 geographically diverse sites. Innovative design features of this trial include randomization to either initial patient-preference of treatment or to a referred care arm in which the primary care provider decided upon care. Additionally, delivery of psychotherapy was accomplished by telephone, or webcam, depending upon patient preference. The vanguard phase provides estimates of eligibility and screening/enrollment ratios, patient acceptance of screening, and retention. In this report, we describe the innovative features and the baseline results of the vanguard phase of CODIACS. The data from this vanguard study will be used to finalize planning for a large, phase III clinical trial designed to evaluate the effect of treatment on depressive symptoms, coronary events, and death

Centralized, Stepped, Patient Preference–Based Treatment for Patients With Post–Acute Coronary Syndrome Depression

IMPORTANCE: Controversy remains about whether depression can be successfully managed after acute coronary syndrome (ACS) and the costs and benefits of doing so. OBJECTIVE: To determine the effects of providing post-ACS depression care on depressive symptoms and health care costs. DESIGN: Multicenter randomized controlled trial. SETTING: Patients were recruited from 2 private and 5 academic ambulatory centers across the United States. PARTICIPANTS: A total of 150 patients with elevated depressive symptoms (Beck Depression Inventory [BDI] score ≥10) 2 to 6 months after an ACS, recruited between March 18, 2010, and January 9, 2012. INTERVENTIONS: Patients were randomized to 6 months of centralized depression care (patient preference for problem-solving treatment given via telephone or the Internet, pharmacotherapy, both, or neither), stepped every 6 to 8 weeks (active treatment group; n = 73), or to locally determined depression care after physician notification about the patient's depressive symptoms (usual care group; n = 77). MAIN OUTCOME MEASURES: Change in depressive symptoms during 6 months and total health care costs. RESULTS: Depressive symptoms decreased significantly more in the active treatment group than in the usual care group (differential change between groups, -3.5 BDI points; 95% CI, -6.1 to -0.7; P = .01). Although mental health care estimated costs were higher for active treatment than for usual care, overall health care estimated costs were not significantly different (difference adjusting for confounding, -$325; 95$2639 to $1989; P = .78). CONCLUSIONS: For patients with post-ACS depression, active treatment had a substantial beneficial effect on depressive symptoms. This kind of depression care is feasible, effective, and may be cost-neutral within 6 months; therefore, it should be tested in a large phase 3 pragmatic trial. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01032018

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Strengthening subject recruitment and retention of the older Black population in Alzheimer’s Disease and related dementias studies through community outreach

Abstract Background Representation in dementia research is extremely important in creating effective prevention methods, interventions, and treatments across all populations (Lennon et. al 2022; Barnes 2022). One of the main goals set by the National Institute on Aging (NIA) for the years 2020‐2025, is to disseminate information to several outlets including older adult‐support organizations about research and interventions. The NYU Healthy Brain Aging and Sleep Center (HBASC) has successfully built relationships with community organizations in an effort to contribute to meeting the NIA’s goal using the PEACE method. We evaluated pre‐post subject retention rate, after instigation of PEACE. Method In 2019, HBASC began recruitment for a longitudinal study focusing on sleep and Alzheimer’s Disease (AD) in healthy older Blacks (ages 60‐75 years) in the New York Metropolitan Area using community outreach/education as a method of recruitment (i.e. partnering with senior recreation centers, local churches, etc.). Study team members implemented the PEACE method in their outreach efforts. Team members practiced Patience, when accommodating organizations’ needs and requests, Empathy, for the members of the communities they were working in, Appreciation, for the organizations’ aid in reaching the community, Cultural competence, when planning or participating in community events, and prioritized Educating the community, on AD and other related dementias before recruitment. Result Within the first year of recruitment, ∼77% vs. ∼23% of subjects were successfully recruited from the community favoring the PEACE method. When the PEACE method was successfully executed, the study team gained the trust of members of the community and retained ∼ 70% of subjects recruited from the community. Older Blacks trusted the HBASC study team because the PEACE method demonstrates dedication to the community. This in turn increases the likelihood of follow‐up response in longitudinal ADRD studies. Conclusion Collaborating directly with community organizations, is an efficient method not only of recruitment, but also retention of older Black subjects in ADRD studies. Collaborations with well‐known trusted community partners can establish a strong relationship between the Black community and research

Advancing Engagement and Enrollment of Older Black Americans in Alzheimer’s disease and Dementia‐Related Research

Abstract Background The under‐enrollment of racial and ethnic minorities in clinical trials limits the development of culturally tailored disease treatments and preventative strategies. For example, African Americans experience a greater risk of Alzheimer’s disease (AD), yet they remain woefully underrepresented in AD research. This limits understanding of how AD may operate differently in black populations, who have a higher burden of socio‐structural determinants of health. To improve older black American enrollment, The NYU Healthy Brain Aging and Sleep Center (HBASC) team developed a method tailored toward increasing minority enrollment in clinical trials by collaborating with community‐based organizations and minority populations to reexamine barriers to trial participation. Method HBASC conducted a single‐site (New York Metropolitan Area) longitudinal study examining sleep and AD in healthy black adults (aged 60‐75). From the study, barriers to trial enrollment were evaluated on a systemic and individual level. The degree to which each level directly or indirectly contributed to barriers to enrollment was further explored using a series of steps and practices seeking to engage underrepresented communities in research. In doing so, team members established and implemented a community‐focused method called FEED. Study personnel demonstrated the feed method by Finding groups, organizations, and trusted community members to collaborate with, Educating community members, Engaging community members through events and educational seminars, and Delivering resources to the community. Result Through collaborations with community leaders and organizations, the study team performed community outreach events, raising disease awareness, sustaining trustful relationships, and providing educational resources. The study team saw ∼50% increase in black participant enrollment through the FEED method. Increased engagement in medical research was accomplished when underrepresented communities were empowered with the tools and resources to make knowledgeable decisions. Conclusion Diverse populations of patients face complex and multifaceted barriers to enrollment in clinical trials. A FEED framework will help address these barriers at an individual and systemic level

Associations of Alzheimer’s disease Plasma Biomarkers' and slow wave sleep within Black and White Cognitively Normal Older‐Adults

Abstract Background We studied whether plasma levels of Aβ40, Aβ42, Aβ42/Aβ40, Tau, tau/Aβ42 and NfL are associated with slow wave sleep, and if this association varied within non‐Hispanic Whites and Blacks/African‐Americans. Method This was a cross‐sectional analysis of baseline data from 171 cognitively normal older‐adults, volunteering in active NYU studies on memory and sleep. Plasma Aβ40, Aβ42, Tau and NfL were measured using single molecule array (SIMOA). Non‐rapid eye movement sleep (NREM) slow wave sleep (SWS) duration was assessed from 2 nights of in‐lab NPSGs. Associations of NREM SWS duration and plasma AD biomarker levels were examined by applying adjusted generalized linear models and Pearson correlation analysis after data normalization. Analyses were adjusted for age, sex, BMI, race, and education. Result Of the 171 subjects (128 Whites and 43 Blacks), 112 (65.5%) were females, and mean (SD) age was 68.6 (6.6) years, BMI was 27.6 (6.1) kg/m**2, and education was 16.9 (2.1). There were no racial differences in age, sex, and BMI, SWS and AHI4%. In comparison to whites, blacks had significantly lower years of education (14.2 vs. 17.2, p <.01). Black/African‐American subjects had significantly lower plasma Aβ40 (248.3 vs. 262.5 pg/ml) and NfL levels (11.4 vs. 15.2 pg/ml). p<.05 for both. There were no significant racial differences in levels of plasma Aβ42, Aβ42/Aβ40, Tau, Tau/Aβ40 and Tau/Aβ42. NREM SWS duration was not associated with plasma Aβ42, Aβ40 or tau in the overall sample. However, in Whites, SWS negatively correlated with plasma Aβ42 (r = ‐0.28, p< = 0.05). In Black/African‐Americans, SWS positively correlated with plasma Aβ42 (r = 0.48, p = 0.05). In Whites, SWS negatively correlated with plasma Aβ40 (r = ‐0.087, p = 0.72), though not significant. In Black/African‐Americans, SWS positively correlated with plasma Aβ40 levels (r = 0.32, p = 0.04). In Whites, SWS negatively correlated with plasma Tau (r = ‐0.153, p = 0.27), though not significant. In Black/African‐Americans, SWS positively correlated with plasma Tau levels (r = 0.52, p = 0.04). NREM SWS was not associated with plasma tau/Aβ42, plasma tau/Aβ40 or plasma NfL in the overall sample and across racial‐subgroups. Conclusion Race‐specific relationships between NREM SWS and plasma Aβ42, Aβ40 & Tau might propose differences in SDOH mechanisms that may affect sleep and AD‐risk in older‐adults

Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques.

BACKGROUND:Zika virus (ZIKV; Flaviviridae, Flavivirus) was declared a public health emergency of international concern by the World Health Organization (WHO) in February 2016, because of the evidence linking infection with ZIKV to neurological complications, such as Guillain-Barre Syndrome in adults and congenital birth defects including microcephaly in the developing fetus. Because development of a ZIKV vaccine is a top research priority and because the genetic and antigenic variability of many RNA viruses limits the effectiveness of vaccines, assessing whether immunity elicited against one ZIKV strain is sufficient to confer broad protection against all ZIKV strains is critical. Recently, in vitro studies demonstrated that ZIKV likely circulates as a single serotype. Here, we demonstrate that immunity elicited by African lineage ZIKV protects rhesus macaques against subsequent infection with Asian lineage ZIKV. METHODOLOGY/PRINCIPAL FINDINGS:Using our recently developed rhesus macaque model of ZIKV infection, we report that the prototypical ZIKV strain MR766 productively infects macaques, and that immunity elicited by MR766 protects macaques against heterologous Asian ZIKV. Furthermore, using next generation deep sequencing, we found in vivo restoration of a putative N-linked glycosylation site upon replication in macaques that is absent in numerous MR766 strains that are widely being used by the research community. This reversion highlights the importance of carefully examining the sequence composition of all viral stocks as well as understanding how passage history may alter a virus from its original form. CONCLUSIONS/SIGNIFICANCE:An effective ZIKV vaccine is needed to prevent infection-associated fetal abnormalities. Macaques whose immune responses were primed by infection with East African ZIKV were completely protected from detectable viremia when subsequently rechallenged with heterologous Asian ZIKV. Therefore, these data suggest that immunogen selection is unlikely to adversely affect the breadth of vaccine protection, i.e., any Asian ZIKV immunogen that protects against homologous challenge will likely confer protection against all other Asian ZIKV strains

ZIKV-002 macaques challenged with ZIKV MR766 are protected from heterologous reinfection with ZIKV-FP.

<p><b>A.</b> Study timeline with dates of primary and secondary, heterologous ZIKV challenges. Samples were collected daily from 0 to 10 dpi, and then weekly thereafter until secondary challenge (denoted by ticks along the timeline). Challenge stocks were derived from the East African and French Polynesian virus strains detailed above the timeline. <b>B.</b> Plasma viral loads, shown as vRNA copies/mL for each of the macaques challenged with 1 x 10⁶ (solid green line), 1x 10⁵ (solid orange line), or 1 x 10⁴ (solid blue line) PFU/mL of ZIKV MR766 challenge stock from the date of primary challenge through 10 days post heterologous challenge with ZIKV-FP. For comparison of plasma viral loads between ZIKV strains, solid light grey lines depict the plasma viral load trajectories for animals that were challenged with the same dose of ZIKV-FP and then rechallenged with homologous ZIKV-FP [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005168#pntd.0005168.ref022" target="_blank">22</a>]. <b>C.</b> Oral swab and <b>D.</b> pan urine viral loads.</p

An N-linked glycosylation site in envelope is rapidly selected in vivo.

<p>Envelope sequences from the three animals were sequenced at three days post infection, and from two of the animals at day six post infection. A Muscle alignment of the translated sequences was generated in Geneious. Dots represent identity to the consensus sequence. Dashes represent deletions. Capital letters represent amino acids. Only regions of the E protein with sequence variants are depicted. <b>A.</b> E protein amino acid positions 136–178. The frequencies of the deletion and the restored deletion are shown below each of the stock sequences, with the indicated site boxed. Amino acid variant frequencies matching the variant sites in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005168#pntd.0005168.g001" target="_blank">Fig 1A</a> are shown. The gray ellipse above the sequence alignment represents the 150 loop of the E protein [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005168#pntd.0005168.ref020" target="_blank">20</a>]. <b>B.</b> E protein amino acid positions 271–313. <b>C.</b> E protein amino acid positions 361–450. There were two additional nonsynonymous variants at greater than 5% in animal 562876 at day three, and the frequency of the amino acid variants from the other animals and time points are shown below each sample.</p

East African ZIKV MR766 envelope sequences often contain an in-frame deletion of an N-linked glycosylation site and are heterologous with respect to Asian ZIKV.

<p>The amino acid sequences of the Envelope protein for six ZIKV MR766 Genbank sequences were aligned to the consensus amino acid sequences of the three ZIKV MR766 stock viruses (Chal Stck, CDC Stock, and WRCEVA stock) using a Muscle alignment in Geneious. Dots represent identity to the consensus sequence. Dashes represent deletions. Only sections of the E protein with variations are shown, all other parts of the E protein showed no variation. Capital letters represent amino acids. The frequencies of the deletion and the restored deletion are shown below each of the stock sequences. Genbank reference sequence AY632535 had two amino acids that were different from the other reference sequences. The frequency of reads with these amino acid variants as determined by deep sequencing are shown below each of the stock sequences. <b>A.</b> Envelope protein amino acid region 136–178. The gray ellipse above the sequences represent the 150 loop of the E protein [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005168#pntd.0005168.ref020" target="_blank">20</a>]. <b>B.</b> Envelope protein amino acid region 271–313.</p