Selection for transcatheter versus surgical aortic valve replacement and mid-term survival: results of the AUTHEARTVISIT study.

OBJECTIVES: Limited data are available from randomized trials comparing outcomes between transcatheter aortic valve replacement (TAVR) and surgery in patients with different risks and with follow-up of at least 4 years or longer. In this large, population-based cohort study, long-term mortality and morbidity were investigated in patients undergoing aortic valve replacement (AVR) for severe aortic stenosis using a surgically implanted bioprosthesis (sB-AVR) or TAVR. METHODS: Individual data from the Austrian Insurance Funds from 2010 through 2020 were analysed. The primary outcome was all-cause mortality, assessed in the overall and propensity score-matched populations. Secondary outcomes included reoperation and cardiovascular events. RESULTS: From January 2010 through December 2020, a total of 18 882 patients underwent sB-AVR (n = 11 749; 62.2%) or TAVR (n = 7133; 37.8%); median follow-up was 5.8 (95% CI 5.7-5.9) years (maximum 12.3 years). The risk of all-cause mortality was higher with TAVR compared with sB-AVR: hazard ratio (HR) 1.552, 95% confidence interval (CI) 1.469-1.640, p < 0.001; propensity score-matched HR 1.510, 1.403-1.625, p < 0.001. Estimated median survival was 8.8 years (95% CI 8.6-9.1) with sB-AVR versus 5 years (4.9-5.2) with TAVR. Estimated 5-year survival probability was 0.664 (0.664-0.686) with sB-AVR versus 0.409 (0.378-0.444) with TAVR overall, and 0.690 (0.674-0.707) and 0.560 (0.540-0.582), respectively, with propensity score matching. Separate subgroup analyses for patients aged 65-75 years and >75 years indicated a significant survival benefit in patients selected for sB-AVR in both groups. Other predictors of mortality were age, sex, previous heart failure, diabetes, and chronic kidney disease. CONCLUSIONS: In this retrospective national population-based study, selection for TAVR was significantly associated with higher all-cause mortality compared with sB-AVR in patients ≥65 years with severe, symptomatic aortic stenosis in the >2-year follow-up.

Multimodal and conventional resistance training interventions improve muscle function in older adults: Findings from the Training IMCT study.

Age-associated remodeling processes affect the intramuscular connective tissue (IMCT) network, which may significantly impair muscle function. Thus, we aimed to test whether including exercises shown to efficiently target the IMCT to a conventional resistance exercise intervention (CONV) would result in greater functional gains as compared to CONV alone. Fifty-three men and women (66.2 ± 3.3 years) were assigned to either CONV (n = 15), multimodal training (MULTI; n = 17) or a control (CTRL; n = 21) group. All subjects were tested at baseline, and those assigned to CONV or MULTI underwent a 16-week training intervention. The CONV group followed a progressive resistance training program, in which the number of weekly training sessions gradually increased from 1 to 3. In the MULTI group, one of these sessions was replaced with plyometric training, followed by self-myofascial release. Testing included maximal strength and power, imaging-based muscle volume, architecture, and functional performance. The intervention effects were analyzed using two- or three-way repeated measures ANOVA models (α = 0.05). Briefly, the maximal knee extension isometric contraction, one-repetition maximum, and isokinetic peak torque increased in all groups (p < 0.05), albeit to a lesser extent in CTRL. On the other hand, quadriceps femoris muscle volume (p = 0.019) and vastus lateralis pennation angle (p < 0.001) increased only in the MULTI group. Handgrip strength did not change in response to the intervention (p = 0.312), whereas Sit-to-Stand performance improved in all groups after the first 8-wks, but only in MULTI and CONV after 16-wks (all p < 0.001). In conclusion, we found that a resistance training intervention in which one weekly training session is replaced by plyometric training is feasible and as effective as a program consisting solely of conventional strength training sessions for inducing gains in muscle strength and function in older adults. Muscle size and architecture improved only in the MULTI group. German Clinical Trials: DRKS00015750.

Community Investments and Diet-Related Outcomes: A Longitudinal Study of Residents of Two Urban Neighborhoods.

INTRODUCTION: Investments in historically oppressed neighborhoods through food retail, housing, and commercial development are hypothesized to improve residents' health, nutrition, and perceptions of their neighborhood as a place to live. Although place-based development (e.g., housing, retail, business assistance) is happening in many communities, there is little evidence of the long-term correlates of multiple investments such as health and nutrition among residents. METHODS: A quasi-experimental longitudinal study was conducted using a cohort of randomly sampled households in two low-income, predominantly African American neighborhoods in Pittsburgh, PA, with surveys assessing residents' food insecurity, perception of their neighborhood as a place to live, perception of access to healthy foods, and dietary outcomes in 2011 and seven years later (2018), with an interim assessment in 2014. Analyses conducted in 2022 compared changes among residents of one neighborhood which had 2.6 times the investments over a 7-year period with changes among residents of a socio-demographically similar neighborhood that received fewer investments. RESULTS: It was found that residents in the neighborhood receiving substantial investments demonstrated statistically significant improvements in neighborhood satisfaction (12.6% improvement compared with a 2.2% decrease) and perceived access to healthy food (52% improvement compared with 18.2% improvement), and marginally significant change in food security (14% compared with 4.8% improvement) compared with residents in the neighborhood receiving fewer investments. CONCLUSIONS: Multiple place-based investments in neighborhoods can potentially induce positive change for residents in health and nutrition outcomes.

Revisiting aortic valve prosthesis choice in patients younger than 50 years: 10 years results of the AUTHEARTVISIT study.

OBJECTIVES: This population-based cohort study investigated mid-term outcome after surgical aortic valve replacement with a bioprosthetic or mechanical valve prosthesis in patients aged <50 years in a European social welfare state. METHODS: We analysed patient data from the main social insurance carriers in Austria (2010-2020). Subsequent patient-level record linkage with national health data provided patient characteristics and clinical outcome. Survival, reoperation, myocardial infarction, heart failure, embolic stroke or intracerebral haemorrhage, bleeding other than intracerebral haemorrhage and major adverse cardiac events were evaluated as outcomes. RESULTS: A total of 991 patients were analysed. Regarding demographics, no major differences between groups were observed. Multivariable Cox regression revealed no significant difference in overall survival (P = 0.352) with a median follow-up time of 6.2 years. Reoperation-free survival was decreased (hazard ratio = 1.560 [95% CI: 1.076-2.262], P = 0.019) and the risk for reoperation was increased (hazard ratio = 2.770 [95% CI: 1.402-5.472], P = 0.003) in patients who received bioprostheses. Estimated probability of death after reoperation was 0.23 (CL: 0.08-0.35) after 2 years and 0.34 (CL: 0.06-0.53) after 10 years over both groups. Regarding further outcomes, no significant differences between the two groups were observed. CONCLUSIONS: In patients below 50 years of age receiving aortic valve replacement, implantation of bioprostheses when compared to mechanical heart valve prostheses was associated with a significantly higher rate of reoperations and reduced reoperation-free survival. Nevertheless, we could not observe a difference in overall survival. However, long-term follow-up has to evaluate that a significantly lower rate of reoperations may translate in consistently improved long-term survival.

Prevalence and long-term implications of preoperative anemia in patients undergoing elective general surgery: a retrospective cohort study at a university hospital.

OBJECTIVE: The aim of this retrospective study was to assess the prevalence of anaemia in a cohort of patients undergoing elective general surgery at a university hospital. Furthermore, the authors investigated the influence of anaemia on short-term and long-term postoperative outcome. BACKGROUND: Awareness of the negative impact of preoperative anaemia on perioperative morbidity and mortality is rising. Anaemia is a potentially modifiable factor, and its therapy might improve patient outcome in elective surgery. Nevertheless, patients with preoperative anaemia frequently undergo elective surgery without receiving adequate preoperative treatment. METHODS: In this single-centre cohort study, the authors analyzed 6908 adult patients who underwent elective general surgery. Patients undergoing day-clinic surgery were excluded. In all patients, preoperative haemoglobin concentration and haematocrit was available. RESULTS: Of all patients analyzed, 32.9% were anaemic (21.0% mild, 11.8% moderate, 1.1% severe). Median time to last follow-up was 5.2 years. During the whole study period, 27.1% of patients died (1.2% died during the hospital stay); median time to death was 1.3 years. Patients with preoperative anaemia had significantly higher mortality rates ( P <0.001) and a higher probability of postoperative complications ( P <0.001). Likewise, receiving blood transfusions was associated with a higher risk of death ( P <0.001). CONCLUSION: This retrospective single-centre analysis confirmed that preoperative anaemia is common, and is a significant risk factor for unfavourable postoperative outcome. As anaemia is a modifiable risk factor, the implementation of a patient blood management concept is crucial to reduce detrimental postoperative events associated with anaemia.

Exploring differences in perceptions of gentrification, neighborhood satisfaction, social cohesion, and health among residents of two predominantly African American Pittsburgh neighborhoods (n = 60).

BACKGROUND: Gentrification often leads to changes in the social and physical environment of neighborhoods, which social capital theory has found are connected to aspects of resident health and wellbeing. A growing body of literature has explored the impact of gentrification on health and wellbeing of residents. The goal of this study is to qualitatively explore the ways in which gentrification may have impacted perceptions of neighborhood satisfaction, social cohesion, and health of neighborhood residents (n = 60) from two predominantly Black neighborhoods in Pittsburgh, Pennsylvania, one of which experienced Black gentrification during the study's time period. This analysis is unique in its ability to capture experiences of residents who remained in their neighborhood throughout the course of the study, as well as those who moved away from their neighborhood. METHODS: Participants were randomly selected from a larger cohort enrolled in a quasi-experimental study and categorized by whether they lived in a census tract that gentrified, whether they owned or rented their home, and whether they moved from the neighborhood or remained in the same place of residence between 2011 and 2018. Phone interviews lasting approximately 30 min were conducted with participants and were audio recorded and transcribed verbatim. Participants were provided a $40 gift card for their time. Interview data were analyzed using a directed content approach, and Cohen's Kappa was obtained (k = 0.924) to signal good inter-rater reliability. RESULTS: Results showed renters in gentrified census tracts overwhelmingly viewed gentrification trends as a negative change compared to homeowners. Overall, participants from gentrified census tracts reported being relatively satisfied with their neighborhood, though some suggested there were fewer resources in the neighborhood over time; felt their social cohesion had deteriorated over time; and more commonly reflected negative health changes over time. CONCLUSIONS: These findings suggest that while gentrification can bring much needed improvements to neighborhoods, it can also bring other disruptive changes that affect the health and wellbeing of existing residents.

Pretty in pink? Complementary strategies for analysing pink biofilms on historical buildings.

Salt-weathering is a deterioration mechanism affecting building materials that results from repetitive cycles of salt crystallisation-dissolution in the porous mineral network under changing environmental conditions, causing damage to surfaces. However, an additional biodeterioration phenomenon frequently associated with salt efflorescence is the appearance of coloured biofilms, comprising halotolerant/halophilic microorganisms, containing carotenoid pigments that cause pinkish patinas. In this work, two Austrian historical salt-weathered buildings showing pink biofilms, the St. Virgil's Chapel and the Charterhouse Mauerbach, were investigated. Substrate chemistry (salt concentration/composition) was analysed by ion chromatography and X-ray diffraction to correlate these parameters with the associated microorganisms. Microbiomes were analysed by sequencing full-length 16S rRNA amplicons using Nanopore technology. Data demonstrates that microbiomes are not only influenced by salt concentration, but also by its chemical composition. The chapel showed a high overall halite (NaCl) concentration, but the factor influencing the microbiome was the presence/absence of K+. The K+ areas showed a dominance of Aliifodinibius and Salinisphaera species, capable of tolerating high salt concentrations through the "salt-in" strategy by transporting K+ into cells. Conversely, areas without K+ showed a community shift towards Halomonas species, which favour the synthesis of compatible solutes for salt tolerance. In the charterhouse, the main salts were sulphates. In areas with low concentrations, Rubrobacter species dominated, while in areas with high concentrations, Haloechinothrix species did. Among archaea, Haloccoccus species were dominant in all samples, except at high sulphate concentrations, where Halalkalicoccus prevailed. Finally, the biological pigments visible in both buildings were analysed by Raman spectroscopy, showing the same spectra in all areas investigated, regardless of the building and the microbiomes, demonstrating the presence of carotenoids in the pink biofilms. Comprehensive information on the factors affecting the microbiome associated with salt-weathered buildings should provide the basis for selecting the most appropriate desalination treatment to remove both salt efflorescence and associated biofilms.

Customizing amino acid metabolism of Pichia pastoris for recombinant protein production.

Amino acids are the building blocks of proteins. In this respect, a reciprocal effect of recombinant protein production on amino acid biosynthesis as well as the impact of the availability of free amino acids on protein production can be anticipated. In this study, the impact of engineering the amino acid metabolism on the production of recombinant proteins was investigated in the yeast Pichia pastoris (syn Komagataella phaffii). Based on comprehensive systems-level analyses of the metabolomes and transcriptomes of different P. pastoris strains secreting antibody fragments, cell engineering targets were selected. Our working hypothesis that increasing intracellular amino acid levels could help unburden cellular metabolism and improve recombinant protein production was examined by constitutive overexpression of genes related to amino acid metabolism. In addition to 12 genes involved in specific amino acid biosynthetic pathways, the transcription factor GCN4 responsible for regulation of amino acid biosynthetic genes was overexpressed. The production of the used model protein, a secreted carboxylesterase (CES) from Sphingopyxis macrogoltabida, was increased by overexpression of pathway genes for alanine and for aromatic amino acids, and most pronounced, when overexpressing the regulator GCN4. The analysis of intracellular amino acid levels of selected clones indicated a direct linkage of improved recombinant protein production to the increased availability of intracellular amino acids. Finally, fed batch cultures showed that overexpression of GCN4 increased CES titers 2.6-fold, while the positive effect of other amino acid synthesis genes could not be transferred from screening to bioreactor cultures.

Capillary carbon dioxide tension increases in hospital staff wearing filtering facepiece masks: a prospective crossover study.

Background: The COVID-19 pandemic has changed worldwide hygiene practices. In particular, the use of filtering face piece (FFP) masks markedly increased. Concerns have been raised regarding possible negative respiratory effects of wearing FFP masks. The aim of this study was to investigate gas exchange and subjective breathing effort in hospital personnel wearing FFP2 or FFP3 masks. Methods: In this prospective, single-centre, crossover study, 200 hospital workers were assigned to alternately wear FFP2 or FFP3 masks for 1 h during routine activities. Capillary blood gas analysis was performed to evaluate gas exchange while wearing the FFP masks. The primary end-point was the change in capillary partial pressure of carbon dioxide (PcCO2). In addition, capillary partial pressure of oxygen (PcO2), respiratory rate and subjective breathing effort were assessed at the end of each hour. Changes between time points and study groups were estimated using univariate and multivariate models. Results: PcCO2 increased from 36.8±3.5 to 37.2±3.3 mmHg (p=0.047) and 37.4±3.2 mmHg (p=0.003) in individuals wearing FFP2 or FFP3 masks, respectively. Age (p=0.021) and male sex (p<0.001) were significantly associated with increased PcCO2. Similarly, the PcO2 increased from 70.7±8.4 to 73.4±8.8 mmHg (p<0.001) and 72.8±8.5 mmHg (p=0.004) in individuals wearing FFP2 or FFP3 masks, respectively. Respiratory rate and subjective breathing effort increased significantly while wearing FFP2 and FFP3 masks (p<0.001 for all analyses). The order of wearing FFP2 or FFP3 masks did not significantly affect the results. Conclusions: An hour of wearing FFP2 or FFP3 masks increased PcCO2 values, respiratory rate and subjective breathing effort in healthcare personnel performing routine activities.

PerIoperative iNflammatory reSponse assessment In hiGH-risk patienTs undergoing non-cardiac surgery (INSIGHT): study protocol of a prospective non-interventional observational study.

INTRODUCTION: Increased inflammatory processes after non-cardiac surgery are very common. The association between postoperative inflammation and the occurrence of cardiovascular complications after non-cardiac surgery are still not entirely clear. Therefore, we will evaluate the association between postoperative inflammation and the occurrence of major cardiovascular complications in patients at-risk for cardiovascular complications undergoing non-cardiac surgery. We will further evaluate the association of postoperative inflammation and days-at-home within 30 days after surgery (DAH30), the incidence of acute kidney injury, postoperative N-terminal probrain natriuretic peptide (NT-proBNP) concentrations and neurocognitive decline. METHODS AND ANALYSIS: In this multicentre study, we will include 1400 patients at-risk for cardiovascular complications undergoing non-cardiac surgery. Our primary aim is to evaluate the association of postoperative maximum C-reactive protein concentration and the occurrence of a composite of five major cardiovascular complications (myocardial infarction, myocardial injury after non-cardiac surgery, new onset of atrial fibrillation, stroke and death) within 30 days after surgery using a Mann-Whitney-U test as well as a logistic regression model. As our secondary aim, we will evaluate the association of a composite of three inflammatory biomarkers (interleukin 6, procalcitonin and copeptin) on the occurrence of our composite of five cardiovascular complications within 30 days and 1 year after surgery, acute kidney injury, DAH30 and NT-proBNP concentrations using linear or logistic regression models. We will measure inflammatory biomarkers before surgery, and on the first, second, third and fifth postoperative day. We will check medical records and conduct a telephone survey 30 days and 1 year after surgery. We evaluate neurocognitive function, using a Montreal Cognitive Assessment, before and 1 year after surgery. ETHICS AND DISSEMINATION: This study was approved by the ethics committees at the Medical University of Vienna (2458/2020) and at the Medical University of Graz (33-274 ex 20/21). TRIAL REGISTRATION NUMBER: NCT04753307.

Hemodynamic effects of intraoperative 30% versus 80% oxygen concentrations: an exploratory analysis.

Background: Supplemental oxygen leads to an increase in peripheral vascular resistance which finally increases systemic blood pressure in healthy subjects and patients with coronary artery disease, heart failure, undergoing heart surgery, and with sepsis. However, it is unknown whether this effect can also be observed in anesthetized patients having surgery. Thus, we evaluated in this exploratory analysis of a randomized controlled trial the effect of 80% versus 30% oxygen on intraoperative blood pressure and heart rate. Methods: We present data from a previous study including 258 patients, who were randomized to a perioperative inspiratory FiO2 of 0.8 (128 patients) versus 0.3 (130 patients) for major abdominal surgery. Continuous arterial blood pressure values were recorded every three seconds and were exported from the electronic anesthesia record system. We calculated time-weighted average (TWA) and Average Real Variability (ARV) of mean arterial blood pressure and of heart rate. Results: There was no significant difference in TWA of mean arterial pressure between the 80% (80 mmHg [76, 85]) and 30% (81 mmHg [77, 86]) oxygen group (effect estimate -0.16 mmHg, CI -1.83 to 1.51; p = 0.85). There was also no significant difference in TWA of heart rate between the 80 and 30% oxygen group (median TWA of heart rate in the 80% oxygen group: 65 beats.min-1 [58, 72], and in the 30% oxygen group: 64 beats.min-1 [58; 70]; effect estimate: 0.12 beats.min-1, CI -2.55 to 2.8, p = 0.94). Also for ARV values, no significant differences between groups could be detected. Conclusion: In contrast to previous results, we did not observe a significant increase in blood pressure or a significant decrease in heart rate in patients, who received 80% oxygen as compared to patients, who received 30% oxygen during surgery and for the first two postoperative hours. Thus, hemodynamic effects of supplemental oxygen might play a negligible role in anesthetized patients. Clinical Trail Registration: https://clinicaltrials.gov/ct2/show/NCT03366857?term=vienna&cond=oxygen&draw=2&rank=1.

Optical Coherence Tomography Angiography Characteristics of Polypoidal Lesions in Caucasians.

Purpose: The aim of the study is to analyze the swept source-optical coherence tomography angiography (SS-OCTA) characteristics of polypoidal lesions in Caucasian patients. Methods: In this retrospective observational case series, 43 polypoidal lesions in 32 eyes of 32 patients were diagnosed using indocyanine green angiography (ICGA) and compared to SS-OCTA at a tertiary medical retina center (Clinic Landstraße, Vienna Healthcare Group, Austria) between June 2017 and March 2020. Vascularity was identified by color-coded B-scan SS-OCTA while morphology was described as revealed by en face SS-OCTA after alignment with ICGA-confirmed findings. Results: In total, SS-OCTA detected all polypoidal lesions, as identified by ICGA. On B-scan SS-OCTA, circumscribed flow was detected in 33 (76.7%) polypoidal lesions and diffuse flow in 10 (23.3%) lesions. On en face SS-OCTA, polypoidal lesions appeared morphologically as 19 tangled vessel balls (44.2%), 6 tangled vessel balls next to dilated vessels (13.9%), 8 vascular dilatations (18.6%), and 8 ill-defined vascular networks (18.6%), leaving 2 lesions (4.6%) undetected. Circumscribed flow was significantly associated with tangled vessel balls (p = 0.005). Conclusion: This study highlights the importance of a multimodal imaging approach, including SS-OCTA, for the evaluation of polypoidal lesions. Our findings suggest a morphological heterogeneity of vascular patterns in Caucasian patients with polypoidal lesions, as pictured by SS-OCTA.

Meeting actual benchmarks for short- and long-term outcomes after cytoreductive surgery for peritoneal surface malignancy at a newly established academic treatment center.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is a curative treatment for selected patients with peritoneal surface malignancy. Reaching actual outcomes benchmarks is challenging given the complex nature of peritoneal surface malignancy surgery. The aim of this study was to assess how the benchmarks for morbidity and oncologic outcome can be reached at a newly established program for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. METHODS: Building on existing institutional experience in complex abdominal surgery and interdisciplinary ovarian cancer treatment, a peritoneal surface malignancy center for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy was established at the Medical University of Vienna using a structured mentoring process. This is a retrospective analysis of the first 100 consecutive patients. Morbidity and mortality were assessed using the Clavien-Dindo classification, and oncologic outcomes using overall survival. RESULTS: Major morbidity and mortality were 26% and 3%, and median overall survival was 49.0 months. In patients with colorectal peritoneal metastases, the median overall survival was 35.1 months (all colorectal peritoneal metastases patients) and 48.8 months in the subgroup with Peritoneal Surface Disease Severity Score ≤3. No median overall survival could be calculated in patients with low-grade appendiceal mucinous neoplasms, appendiceal adenocarcinoma, or peritoneal mesothelioma due to >50% of patients being alive at the end of follow-up. CONCLUSION: We show that the current morbidity and oncological outcomes benchmarks can be reached within the first 100 cases of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at a newly established peritoneal surface malignancy center. Previous institutional experience in complex abdominal surgery and a structured mentoring process are key factors in achieving this goal.

Effect of Supplemental Oxygen on von Willebrand Factor Activity and Ristocetin Cofactor Activity in Patients at Risk for Cardiovascular Complications Undergoing Moderate-to High-Risk Major Noncardiac Surgery-A Secondary Analysis of a Randomized Trial.

Increased von Willebrand Factor (vWF) activity mediates platelet adhesion and might be a contributor to the development of thrombotic complications after surgery. Although in vitro studies have shown that hyperoxia induces endovascular damage, the effect of perioperative supplemental oxygen as a possible trigger for increased vWF activity has not been investigated yet. We tested our primary hypothesis that the perioperative administration of 80% oxygen concentration increases postoperative vWF activity as compared to 30% oxygen concentration in patients at risk of cardiovascular complications undergoing major noncardiac surgery. A total of 260 patients were randomly assigned to receive 80% versus 30% oxygen throughout surgery and for two hours postoperatively. We assessed vWF activity and Ristocetin cofactor activity in all patients shortly before the induction of anesthesia, within two hours after surgery and on the first and third postoperative day. Patient characteristics were similar in both groups. We found no significant difference in vWF activity in the overall perioperative time course between both randomization groups. We observed significantly increased vWF activity in the overall study population throughout the postoperative time course. Perioperative supplemental oxygen showed no significant effect on postoperative vWF and Ristocetin cofactor activity in cardiac risk patients undergoing major noncardiac surgery. In conclusion, we found no significant influence of supplemental oxygen in patients undergoing major non-cardiac surgery on postoperative vWF activity and Ristocetin cofactor activity.

Limited role of children in transmission of SARS-CoV-2 virus in households-Immunological analysis of 26 familial clusters.

BACKGROUND: The impact of children on the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains uncertain. This study provides an insight into distinct patterns of SARS-CoV-2 household transmission in case of pediatric and adult index cases as well as age-dependent susceptibility to SARS-CoV-2 infection. METHODS: Immune analysis, medical interviewing, and contact tracing of 26 families with confirmed SARS-CoV-2 infection cases have been conducted. Blood samples were analyzed serologically with the use of a SARS-CoV-2-specific IgG assay and virus neutralization test (VNT). Uni- and multivariable linear regression and mixed effect logistic regression models were used to describe potential risk factors for higher contagiousness and susceptibility to SARS-CoV-2 infection. RESULTS: SARS-CoV-2 infection could be confirmed in 67 of 124 family members. Fourteen children and 11 adults could be defined as index cases in their households. Forty of 82 exposed family members were defined as secondarily infected. The mean secondary attack rate in households was 0.48 and was significantly higher in households with adult than with pediatric index cases (0.85 vs 0.19; p < 0.0001). The age (grouped into child and adult) of index case, severity of disease, and occurrence of lower respiratory symptoms in index cases were significantly associated with secondary transmission rates in households. Children seem to be equally susceptible to acquire a SARS-CoV-2 infection as adults, but they suffer milder courses of the disease or remain asymptomatic. CONCLUSION: SARS-CoV-2 transmission from infected children to other household members occurred rarely in the first wave of the pandemic, despite close physical contact and the lack of hygienic measures.

A qualitative exploration of health-related present bias among HIV-positive adults in Uganda.

Decision-making errors such as present bias (PB) can have important consequences for health behaviors, but have been largely studied in the financial domain. We conducted a mixed-method study on PB in the context of ART adherence among clinic-enrolled adults in Uganda (n = 39). Specifically, we quantified PB by asking about preferences between medication available sooner to minimize headaches versus available later to cure headaches. We describe demographic similarities among PB participants and qualitatively explored how participants reflected on their PB (or absence thereof) in the context of health. Participants reporting PB were predominantly male, single/unmarried, older, had higher levels of education and income and more advanced HIV progression. Three common reasons for more present-biased choices provided were: (1) wanting to avoid pain, (2) wanting to return to work, and (3) fear of one's health worsening if s/he did not address their illness immediately. While PB in the financial domain often suggests that poorer individuals are more likely to prefer immediate rewards over their wealthier counterparts, our results suggest poor health is potentially a driving factor of PB. Further research is needed to build on these finding and inform how programs can frame key messages regarding ART adherence to patients displaying PB.Trial registration: ClinicalTrials.gov identifier: NCT03494777.

OPTICAL COHERENCE TOMOGRAPHY AND OCT ANGIOGRAPHY CHARACTERISTICS OF INDOCYANINE GREEN ANGIOGRAPHIC PLAQUES IN NONEXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To describe characteristics of indocyanine green (ICG) angiographic plaques in the nonexudative fellow eye of White patients with unilateral treatment-naïve exudative neovascular age-related macular degeneration through optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: In this retrospective cross-sectional study, nonexudative eyes with ICG angiographic plaques were analyzed by OCT B-scans for the sensitivity of a double-layer sign, a pigment epithelium detachment, outer retinal atrophy, hyperreflective dots, and subretinal hyperreflective material (SRHM). The ICG angiographic plaque was matched with a macular neovascularization in OCTA en face scans and color-coded B scans. RESULTS: In total, 35 ICG angiographic plaques in 33 of 291 (11%) nonexudative eyes were diagnosed. OCT revealed 27 double-layer sign (78%), eight pigment epithelium detachment (23%), 8 outer retinal atrophy (23%), eight hyperreflective dots (23%), and one subretinal hyperreflective material (3%). OCTA confirmed a macular neovascularization in 28 plaques (80%): 7 (20%) in en face scans, 3 (9%) in color-coded B scans, and 18 (51%) in both. The area size in OCTA was significantly smaller than that of ICG angiography ( P = 0.002). CONCLUSION: The diagnosis of an ICG angiographic plaque in nonexudative fellow eyes of Whites with unilateral treatment-naïve exudative neovascular age-related macular degeneration was highly suggestive of a typical macular neovascularization type 1 as characterized by OCT and OCTA.

Availability and Accessibility of Mental Health Services in New York City.

Mental health services are critical components of public health infrastructure that provide essential supports to people living with psychiatric disorders. In a typical year, about 20 percent of people will have a psychiatric disorder, and about 5 percent will experience serious psychological distress, indicating a potentially serious mental illness. Nationally, the use of mental health services is low, and the use of care is not equitably distributed. In the United States as a whole and in New York City (NYC), non-Hispanic white individuals are more likely to use mental health services than non-Hispanic black individuals or Hispanic individuals. The challenges of ensuring the availability of mental health services for all groups in NYC are particularly acute, given the size of the population and its diversity in income, culture, ethnicity, and language. Adding to these underlying challenges, the coronavirus disease 2019 (COVID-19) pandemic has disrupted established patterns of care. To advance policy strategy for addressing gaps in the mental health services system, RAND researchers investigate the availability and accessibility of mental health services in NYC. The RAND team used two complementary approaches to address these issues. First, the team conducted interviews with a broad group of professionals and patients in the mental health system to identify barriers to care and potential strategies for improving access and availability. Second, the team investigated geographic variations in the availability of mental health services by compiling and mapping data on the locations and service characteristics of mental health treatment facilities in NYC.

Impact of adaptive filtering on power and false discovery rate in RNA-seq experiments.

BACKGROUND: In RNA-sequencing studies a large number of hypothesis tests are performed to compare the differential expression of genes between several conditions. Filtering has been proposed to remove candidate genes with a low expression level which may not be relevant and have little or no chance of showing a difference between conditions. This step may reduce the multiple testing burden and increase power. RESULTS: We show in a simulation study that filtering can lead to some increase in power for RNA-sequencing data, too aggressive filtering, however, can lead to a decline. No uniformly optimal filter in terms of power exists. Depending on the scenario different filters may be optimal. We propose an adaptive filtering strategy which selects one of several filters to maximise the number of rejections. No additional adjustment for multiplicity has to be included, but a rule has to be considered if the number of rejections is too small. CONCLUSIONS: For a large range of simulation scenarios, the adaptive filter maximises the power while the simulated False Discovery Rate is bounded by the pre-defined significance level. Using the adaptive filter, it is not necessary to pre-specify a single individual filtering method optimised for a specific scenario.

A Comprehensive Evaluation of the Performance of Prediction Algorithms on Clinically Relevant Missense Variants.

The rapid integration of genomic technologies in clinical diagnostics has resulted in the detection of a multitude of missense variants whose clinical significance is often unknown. As a result, a plethora of computational tools have been developed to facilitate variant interpretation. However, choosing an appropriate software from such a broad range of tools can be challenging; therefore, systematic benchmarking with high-quality, independent datasets is critical. Using three independent benchmarking datasets compiled from the ClinVar database, we evaluated the performance of ten widely used prediction algorithms with missense variants from 21 clinically relevant genes, including BRCA1 and BRCA2. A fourth dataset consisting of 1053 missense variants was also used to investigate the impact of type 1 circularity on their performance. The performance of the prediction algorithms varied widely across datasets. Based on Matthews Correlation Coefficient and Area Under the Curve, SNPs&GO and PMut consistently displayed an overall above-average performance across the datasets. Most of the tools demonstrated greater sensitivity and negative predictive values at the expense of lower specificity and positive predictive values. We also demonstrated that type 1 circularity significantly impacts the performance of these tools and, if not accounted for, may confound the selection of the best performing algorithms.