Illicit drug use and cerebral microbleeds in stroke and transient ischemic attack patients

Background: Cerebral microbleeds (CMB) signal cerebral small vessel disease and are associated with ischemic stroke (IS) incidence, recurrence, and complications. While illicit drug use (IDU) is associated with cerebral small vessel disease, the association between CMB and IDU is understudied. We sought to delineate differences in vascular risk factors between IDU and CMB and determine the effect of this relationship on outcomes in IS/transient ischemic attack (TIA) patients. Methods: We included 2001 consecutive IS and TIA patients (years 2009-2018) with a readable T2*gradient-echo MRI sequence. CMB rating followed standardized guidelines and CMB were grouped topographically into lobar, deep or infratentorial. IDU data (history and/or urine toxicology) was available for 1746 patients. The adverse composite outcome included pneumonia, urinary tract infection, deep venous thrombosis or death during hospitalization. Good functional outcome was defined as modified Rankin scale score < 3 and ambulatory on discharge. Univariate analysis was used to assess vascular risk factors and multivariable logistic regression was used to characterize the IDU/CMB relationship on outcomes. Results: We observed IDU in 13.8 % (n=241), and CMB in 32.9% (n=575, 53.8% lobar, 27.3% deep and 18.8% infratentorial). Patients with IDU and at least one CMB were older (53.6±10.5 vs. 56.9±11.5, p=0.04), had a lower BMI (28.1±5.9 vs. 26.6±4.4, p=0.04), and were more likely to have had a previous IS/TIA (25.1% vs. 41.9%, p=0.01). IDU trended higher for those with severe CMB (10+) compared with those without CMB and 1-9 CMB (25% [n=9] vs 14.3% [n=1171] and 12.1% [n=65] respectively; p=0.07) without individual drug deviations from this pattern. Adverse and good functional outcomes were observed in 177 and 905 total patients, respectively. No significant interaction was observed between IDU and CMB with either adverse or functional composite outcomes. Conclusion: IDU prevalence was high in our urban study population, and showed a borderline association with increasing CMB burden. Patients with CMB and IDU history were older and more likely to have had a previous IS/TIA. Further studies are required to clarify the clinical consequences related to the relationship between IDU and CMB.Author Disclosures: B. Petrie: None. H. Lau: None. F. Cajiga-Pena: None. S. Abbas: None. B. Finn: None. K. Dam: None. A. Cervantes-Arslanian: None. T.N. Nguyen: None. H. Aparicio: None. D. Greer: None. J.R. Romero: Speakers' Bureau; Modest; Received speaker honoraria from Ferrer Group

Implementation and resource needs for long-acting PrEP in low- and middle-income countries: a scoping review

INTRODUCTION: Several low- and middle-income countries (LMICs) are preparing to introduce long-acting pre-exposure prophylaxis (LAP). Amid multiple pre-exposure prophylaxis (PrEP) options and constrained funding, decision-makers could benefit from systematic implementation planning and aligned costs. We reviewed national costed implementation plans (CIPs) to describe relevant implementation inputs and activities (domains) for informing the costed rollout of LAP. We assessed how primary costing evidence aligned with those domains. METHODS: We conducted a rapid review of CIPs for oral PrEP and family planning (FP) to develop a consensus of implementation domains, and a scoping review across nine electronic databases for publications on PrEP costing in LMICs between January 2010 and June 2022. We extracted cost data and assessed alignment with the implementation domains and the Global Health Costing Consortium principles. RESULTS: We identified 15 implementation domains from four national PrEP plans and FP-CIP template; only six were in all sources. We included 66 full-text manuscripts, 10 reported LAP, 13 (20%) were primary cost studies-representing seven countries, and none of the 13 included LAP. The 13 primary cost studies included PrEP commodities (n = 12), human resources (n = 11), indirect costs (n = 11), other commodities (n = 10), demand creation (n = 9) and counselling (n = 9). Few studies costed integration into non-HIV services (n = 5), above site costs (n = 3), supply chains and logistics (n = 3) or policy and planning (n = 2), and none included the costs of target setting, health information system adaptations or implementation research. Cost units and outcomes were variable (e.g. average per person-year). DISCUSSION: LAP planning will require updating HIV prevention policies, technical assistance for logistical and clinical support, expanding beyond HIV platforms, setting PrEP achievement targets overall and disaggregated by method, extensive supply chain and logistics planning and support, as well as updating health information systems to monitor multiple PrEP methods with different visit schedules. The 15 implementation domains were variable in reviewed studies. PrEP primary cost and budget data are necessary for new product introduction and should match implementation plans with financing. CONCLUSIONS: As PrEP services expand to include LAP, decision-makers need a framework, tools and a process to support countries in planning the systematic rollout and costing for LAP

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome

Contains fulltext : 220851.pdf (Publisher’s version ) (Open Access)OBJECTIVES: Contradictory results have been reported regarding the association between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD). We assessed the cardiometabolic phenotype and prevalence of CVD in middle-aged women with PCOS, compared with age-matched controls from the general population, and estimated 10-year CVD risk and cardiovascular health score. DESIGN: A cross-sectional study. PARTICIPANTS: 200 women aged >45 with PCOS, and 200 age-matched controls. MEASUREMENTS: Anthropometrics, insulin, lipid levels, prevalence of metabolic syndrome and type II diabetes. Ten-year Framingham risk score and the cardiovascular health score were calculated, and carotid intima-media thickness (cIMT) was measured. RESULTS: Mean age was 50.5 years (SD = 5.5) in women with PCOS and 51.0 years (SD = 5.2) in controls. Increased waist circumference, body mass index and hypertension were more often observed in women with PCOS (P < .001). In women with PCOS, the prevalence of type II diabetes and metabolic syndrome was not significantly increased and lipid levels were not different from controls. cIMT was lower in women with PCOS (P < .001). Calculated cardiovascular health and 10-year CVD risk were similar in women with PCOS and controls. CONCLUSIONS: Middle-aged women with PCOS exhibit only a moderately unfavourable cardiometabolic profile compared to age-matched controls, even though they present with an increased BMI and waist circumference. Furthermore, we found no evidence for increased (10-year) CVD risk or more severe atherosclerosis compared with controls from the general population. Long-term follow-up of women with PCOS is necessary to provide a definitive answer concerning long-term risk for CVD

The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome

Objectives: Contradictory results have been reported regarding the association between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD). We assessed the cardiometabolic phenotype and prevalence of CVD in middle-aged women with PCOS, compared with age-matched controls from the general population, and estimated 10-year CVD risk and cardiovascular health score. Design: A cross-sectional study. Participants: 200 women aged >45 with PCOS, and 200 age-matched controls. Measurements: Anthropometrics, insulin, lipid levels, prevalence of metabolic syndrome and type II diabetes. Ten-year Framingham risk score and the cardiovascular health score were calculated, and carotid intima-media thickness (cIMT) was measured. Results: Mean age was 50.5 years (SD = 5.5) in women with PCOS and 51.0 years (SD = 5.2) in controls. Increased waist circumference, body mass index and hypertension were more often observed in women with PCOS (P <.001). In women with PCOS, the prevalence of type II diabetes and metabolic syndrome was not significantly increased and lipid levels were not different from controls. cIMT was lower in women with PCOS (P <.001). Calculated cardiovascular health and 10-year CVD risk were similar in women with PCOS and controls. Conclusions: Middle-aged women with PCOS exhibit only a moderately unfavourable cardiometabolic profile compared to age-matched controls, even though they present with an increased BMI and waist circumference. Furthermore, we found no evidence for increased (10-year) CVD risk or more severe atherosclerosis compared with controls from the general population. Long-term follow-up of women with PCOS is necessary to provide a definitive answer concerning lon

Women’s perspectives on caesarean section recovery, infection and the PREPS trial: a qualitative pilot study

Background In England, 27.8% of all pregnant women undergo caesarean sections (CS) to deliver their babies. Women undergoing CS are at risk of developing sepsis and post-natal infections, which not only contribute significantly to maternal mortality and morbidity, but also negatively impact upon post-natal recovery and wellbeing. This study explores patients’ priorities in relation to CS recovery, focusing on their knowledge and experiences of infection prevention. The study formed part of the PREPS (Vaginal Preparation at caesarean section to Reduce Endometritis and Prevent Sepsis – a feasibility study of chlorhexidine) Trial; patients’ views on the PREPS Trial were also sought. Methods Using qualitative methodology, two focus groups and six telephone interviews were carried out between September and October 2017 with a total of 21 women who had undergone a CS within the preceding six months. Focus groups and individual telephone interviews were audio-recorded and transcribed verbatim; a thematic analysis was conducted using NVivo 11. Results Women’s priorities around CS recovery centred on pain (or the lack thereof), mobility and the ability to resume everyday activities, including caregiving. Those undergoing a CS for the first time reported not feeling confident in their ability to identify signs of infection and sought visiting health professionals’ expertise and reassurance. Women were unable to recall whether they had received information regarding infection prevention and felt that they had not received sufficient advice. Some reported receiving general information regarding CS recovery, which ranged in quality. Prevention of womb infection is a major goal of the PREPS trial, however, the majority of women were not aware that womb (as opposed to wound) infection was a post CS risk. Conclusions Women undergoing a CS want more information on what constitutes a ‘normal’ post-operative recovery and specifically would welcome written information and infection prevention advice. This should be a key element of improving post-CS maternal experiences and potentially reducing sepsis and infection rates. CS stigma negatively impacts women’s recovery experiences and possibly information provision. The PREPS team incorporated findings regarding consent pathways for recruiting women into intrapartum research and developed two patient reported outcomes to collect in the main trial

The association of testosterone levels with overall sleep quality, sleep architecture, and sleep-disordered breathing. J Clin Endocrinol Metab

Context: Little is known about the association of low endogenous testosterone levels and abnormal sleep patterns in older men, although pharmacological doses of testosterone are associated with increased severity of sleep apnea and other sleep disturbances. Objective: The objective of the study was to examine the association between serum testosterone levels with objectively measured sleep characteristics. Design: This was a cohort study. Setting: Community-dwelling men aged 65 yr or older from six clinical centers in the United States participated in the study. Participants and Main Outcome Measures: A total of 1312 men had baseline total testosterone levels measured in 2000 -2002, followed 3.4 yr later by 72-h (minimum) actigraphy and one-night in-home polysomnography to assess sleep duration, sleep fragmentation, and sleep apnea. Analyses were performed by quartile of total testosterone and categorically defined low vs. higher total testosterone (Ͻ250 ng/dl vs. Ն250 ng/dl). Lifestyle and body size were covariates. Results: Total testosterone levels were unrelated to age or duration of sleep. Men with lower testosterone levels had lower sleep efficiency, with increased nocturnal awakenings and less time in slow-wave sleep as well as a higher apnea-hypopnea index and more sleep time with O 2 saturation levels below 90%. Low testosterone levels were associated with overweight, and all significant associations were attenuated or absent after adjusting for body mass index or waist circumference. In a post hoc analysis in men with higher body mass index (Ͼ27 kg/m2), testosterone was significantly associated with more periods awake after sleep onset and lower sleep efficiency. Conclusion: Low total testosterone levels are associated with less healthy sleep in older men. This association is largely explained by adiposity. Clinical trials are necessary to determine whether body weight acts directly or indirectly (via low testosterone) in the causal pathway for sleep-disordered breathing in older men. (J Clin Endocrinol Metab 93

The association of testosterone levels with overall sleep quality, sleep architecture, and sleep-disordered breathing. J Clin Endocrinol Metab

Context: Little is known about the association of low endogenous testosterone levels and abnormal sleep patterns in older men, although pharmacological doses of testosterone are associated with increased severity of sleep apnea and other sleep disturbances. Objective: The objective of the study was to examine the association between serum testosterone levels with objectively measured sleep characteristics. Design: This was a cohort study. Setting: Community-dwelling men aged 65 yr or older from six clinical centers in the United States participated in the study. Participants and Main Outcome Measures: A total of 1312 men had baseline total testosterone levels measured in 2000 -2002, followed 3.4 yr later by 72-h (minimum) actigraphy and one-night in-home polysomnography to assess sleep duration, sleep fragmentation, and sleep apnea. Analyses were performed by quartile of total testosterone and categorically defined low vs. higher total testosterone (Ͻ250 ng/dl vs. Ն250 ng/dl). Lifestyle and body size were covariates. Results: Total testosterone levels were unrelated to age or duration of sleep. Men with lower testosterone levels had lower sleep efficiency, with increased nocturnal awakenings and less time in slow-wave sleep as well as a higher apnea-hypopnea index and more sleep time with O 2 saturation levels below 90%. Low testosterone levels were associated with overweight, and all significant associations were attenuated or absent after adjusting for body mass index or waist circumference. In a post hoc analysis in men with higher body mass index (Ͼ27 kg/m2), testosterone was significantly associated with more periods awake after sleep onset and lower sleep efficiency. Conclusion: Low total testosterone levels are associated with less healthy sleep in older men. This association is largely explained by adiposity. Clinical trials are necessary to determine whether body weight acts directly or indirectly (via low testosterone) in the causal pathway for sleep-disordered breathing in older men. (J Clin Endocrinol Metab 93

Prototyping the GMT phasing camera with the Magellan AO system

The future diffraction-limited performance of the 25.4 meter Giant Magellan Telescope (GMT) will rely on the activeand adaptive wavefront sensing measurements made by the Acquisition, Guiding, and Wavefront Sensor (AGWS)currently being designed by SAO. One subsystem of the AGWS, the phasing camera, will be responsible for measuringthe piston phase difference between the seven GMT primary/secondary segment pairs to 50 nm accuracy with full skycoverage using natural guide stars that are 6-10 arcmin off-axis while the on-axis light is used for science operations.The phasing camera will use a dispersed fringe sensor to measure the phase difference in rectangular subaperturesspanning the gaps between adjacent mirror segments. The large gap between segments (&gt;295 mm, compared to 3 mmfor the Keck telescope) reduces the coherence of light across the subapertures, making this problem particularlychallenging. In support of the AGWS phasing camera technical goals, SAO has undertaken a series of prototypingefforts at the Magellan 6.5 meter Clay telescope to demonstrate the dispersed fringe sensor technology and validateatmospheric models. Our latest on-sky test, completed in December 2015, employs a dual-band (I and J) dispersedfringe sensor. This prototype uses an adaptive optics corrected beam from the Magellan AO adaptive secondary system.The system operates both on-axis and 6 arcmin off-axis from the natural guide star feeding the MagAO wavefrontsensor. This on-sky data will inform the development of the AGWS phasing camera design towards the GMT first light

On-sky demonstration of the GMT dispersed fringe phasing sensor prototype on the Magellan Telescope

The GMT is an aplanatic Gregorian telescope consisting of 7 primary and secondary mirror segments that must be phased to within a fraction of an imaging wavelength to allow the 25.4 meter telescope to reach its diffraction limit. When operating in Laser Tomographic Adaptive Optics (LTAO) mode, on-axis guide stars will not be available for segment phasing. In this mode, the GMT's Acquisition, Guiding, and Wavefront Sensing system (AGWS) will deploy four pickoff probes to acquire natural guide stars in a 6-10 arcmin annular FOV for guiding, active optics, and segment phasing. The phasing sensor will be able to measure piston phase differences between the seven primary/secondary pairs of up to 50 microns with an accuracy of 50 nm using a J-band dispersed fringe sensor. To test the dispersed fringe sensor design and validate the performance models, SAO has built and commissioned a prototype phasing sensor on the Magellan Clay 6.5 meter telescope. This prototype uses an aperture mask to overlay 6 GMT-sized segment gap patterns on the Magellan 6.5 meter primary mirror reimaged pupil. The six diffraction patterns created by these subaperture pairs are then imaged with a lenslet array and dispersed with a grism. An on-board phase shifter has the ability to simulate an arbitrary phase shift within subaperture pairs. The prototype operates both on-axis and 6 arcmin off-axis either with AO correction from the Magellan adaptive secondary MagAO system on or off in order to replicate as closely as possible the conditions expected at the GMT.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]