T-Cell Responses to COVID-19 Vaccines and Breakthrough Infection in People Living with HIV Receiving Antiretroviral Therapy.

People living with HIV (PLWH) can exhibit impaired immune responses to vaccines. Accumulating evidence indicates that PLWH, particularly those receiving antiretroviral therapy, mount strong antibody responses to COVID-19 vaccines, but fewer studies have examined cellular immune responses to the vaccinations. Here, we used an activation-induced marker (AIM) assay to quantify SARS-CoV-2 spike-specific CD4+ and CD8+ T cells generated by two and three doses of COVID-19 vaccines in 50 PLWH receiving antiretroviral therapy, compared to 87 control participants without HIV. In a subset of PLWH, T-cell responses were also assessed after post-vaccine breakthrough infections and/or receipt of a fourth vaccine dose. All participants remained SARS-CoV-2 infection-naive until at least one month after their third vaccine dose. SARS-CoV-2 infection was determined by seroconversion to a Nucleocapsid (N) antigen, which occurred in 21 PLWH and 38 control participants after the third vaccine dose. Multivariable regression analyses were used to investigate the relationships between sociodemographic, health- and vaccine-related variables, vaccine-induced T-cell responses, and breakthrough infection risk. We observed that a third vaccine dose boosted spike-specific CD4+ and CD8+ T-cell frequencies significantly above those measured after the second dose (all p < 0.0001). Median T-cell frequencies did not differ between PLWH and controls after the second dose (p > 0.1), but CD8+ T-cell responses were modestly lower in PLWH after the third dose (p = 0.02), an observation that remained significant after adjusting for sociodemographic, health- and vaccine-related variables (p = 0.045). In PLWH who experienced a breakthrough infection, median T-cell frequencies increased even higher than those observed after three vaccine doses (p < 0.03), and CD8+ T-cell responses in this group remained higher even after a fourth vaccine dose (p = 0.03). In multivariable analyses, the only factor associated with an increased breakthrough infection risk was younger age, which is consistent with the rapid increase in SARS-CoV-2 seropositivity that was seen among younger adults in Canada after the initial appearance of the Omicron variant. These results indicate that PLWH receiving antiretroviral therapy mount strong T-cell responses to COVID-19 vaccines that can be enhanced by booster doses or breakthrough infection.

Sensory impairment, loneliness, and the discordance between subjective and objective cognitive function among older adults: A multi-cohort study.

OBJECTIVES: This study aimed to examine the association between sensory impairment and the discordance between subjective/objective cognitive function among older adults and test the mediating effect of loneliness. METHODS: We used data from four cohort studies conducted in 16 countries (N = 19,119). Sensory impairment and subjective cognitive impairment were self-reported. Objective cognitive impairment was measured in three dimensions. Generalized estimating equations were conducted to examine the association between sensory impairment and discordance in subjective/objective cognitive function. Cross-lagged panel model and a bootstrap method with 2,000 samples were employed to verify the mediating effect. RESULTS: Sensory impairment was related to an increased risk of subjective cognitive impairment (OR = 4.70, 95 % CI 4.33-5.10), objective impairment (OR = 1.51, 95 %CI 1.31-1.74), as well as the discordance in subjective/objective cognitive function (OR = 1.35, 95 %CI 1.06-1.71 for older adults with normal subjective cognitive function). In contrast, sensory impairment was associated with a decreased risk of discordant subjective/objective cognitive function among those with subjective cognitive impairment (OR = 0.79, 95 %CI 0.66-0.94). Moreover, loneliness mediated the association between sensory impairment and subjective cognitive impairment (standardized indirect effect = 0.002, 95 %CI 0.001-0.004), objective cognitive impairment (standardized indirect effect = 0.005, 95 %CI 0.003-0.007) as well as the discordance in subjective/objective cognitive function (standardized indirect effect = 0.001, 95 %CI 0.001-0.003 for older adults with normal subjective cognitive function). CONCLUSIONS: Significant association between sensory impairment and discordance in subjective/objective cognitive function and the mediating role of loneliness were revealed, varying by subjective cognitive function. Early screening on sensory impairment and targeted interventions on loneliness should be considered in future policies on cognitive impairment.

Outcome of pregnancy oral glucose tolerance test and preterm birth.

BACKGROUND: Gestational diabetes is associated with adverse outcomes such as preterm birth (<37 weeks). However, there is no international consensus on screening criteria or diagnostic levels for gestational diabetes, and it is unknown whether body mass index (BMI) or obesity modifies the relation between glucose level and preterm birth. METHODS: We studied a pregnancy cohort restricted to two Danish regions from the linked Danish Medical Birth Register to study associations between glucose measurements from the 2-hour post-load 75-gram oral glucose tolerance test (one-step approach) and preterm birth from 2004-2018. In Denmark, gestational diabetes screening is a targeted strategy for mothers with identified risk factors. We used Poisson regression to estimate rate ratios (RR) of preterm birth with z-standardized glucose measurements. We assessed effect measure modification by stratifying analyses and testing for heterogeneity. RESULTS: Among 11,337 pregnancies (6.2% delivered preterm), we observed an adjusted preterm birth RR of 1.2 (95% CI: 1.1-1.3) for a 1 standard deviation glucose increase of 1.4 mmol/L from the mean 6.7 mmol/L. There was evidence for effect measure modification by obesity, e.g., adjusted RR for non-obese (BMI <30): 1.2 (95%CI: 1.1-1.3) vs. obese (BMI ≥30): 1.3 (95%CI: 1.2-1.5), P=0.05 for heterogeneity. CONCLUSIONS: Among mothers screened for gestational diabetes, increased glucose levels, even those below the diagnostic level for gestational diabetes in Denmark, were associated with increased preterm birth risk. Obesity (BMI ≥30) may be an effect measure modifier, not just a confounder, of the relation between blood glucose and preterm birth risk.

Estimating the joint association of adverse childhood experiences and asthma with subsequent depressive symptoms: a marginal structural modelling approach.

BACKGROUND: The relationship between adverse childhood experiences (ACEs) and depression risk has been well documented. However, it remains unclear whether stress-related chronic conditions associated with ACEs, such as asthma, increase the long-term mental health burden of ACEs. OBJECTIVE: To investigate the joint association of ACEs and asthma with subsequent depressive symptoms among US adults. METHODS: This study used data from the Behavioural Risk Factor Surveillance System 2010, including 21 544 participants over 18 years old from four states where participants were questioned about ACEs. We used logistic regression models to calculate the adjusted OR (aOR) for elevated depressive symptoms evaluated by Patient Health Questionnaire-8 according to ACEs and asthma, along with marginal structural models (MSM) to consider ACE-related confounders between asthma and depression. We evaluated the additive interaction between ACEs and asthma on depressive symptoms with the relative excess risk due to interaction (RERI). FINDINGS: Of the 21 544 participants (mean age: 56, women: 59.5%), 52.3% reported ≥1 ACEs, 14.9% reported a history of asthma and 4.0% had depressive symptoms. ACEs and asthma were independently associated with elevated depressive symptoms (aORs (95% CI) were 2.85 (2.30 to 3.55) and 2.24 (1.50 to 3.27), respectively). Furthermore, our MSM revealed an additive interaction between ACEs and asthma for depressive symptoms (RERI (95% CI)=+1.63 (0.54 to 2.71)). CONCLUSIONS: These findings suggest that asthma amplifies the risk of depressive symptoms associated with ACEs. CLINICAL IMPLICATIONS: Prevention and treatment of asthma, along with establishing preventive environments and services against ACEs, are effective in mitigating the potential burden of ACEs on mental health.

Dynamics of T-cell Responses Following COVID-19 mRNA Vaccination and Breakthrough Infection in Older Adults.

Introduction: While older adults generally mount weaker antibody responses to a primary COVID-19 vaccine series, T-cell responses remain less well characterized in this population. We compared SARS-CoV-2 spike-specific T-cell responses after 2- and 3-dose COVID-19 mRNA vaccination and subsequent breakthrough infection in older and younger adults. Methods: We quantified CD4+ and CD8+ T-cells reactive to overlapping peptides spanning the ancestral SARS-CoV-2 spike protein in 40 older adults (median age 79) and 50 younger health care workers (median age 39), all COVID-19 naive, using an activation-induced marker assay. T-cell responses were further assessed in 24 participants, including 8 older adults, who subsequently experienced their first SARS-CoV-2 breakthrough infection. Results: A third COVID-19 mRNA vaccine dose significantly boosted spike-specific CD4+ and CD8+ T-cell frequencies to above 2-dose levels in older and younger adults. T-cell frequencies did not significantly differ between older and younger adults after either dose. Multivariable analyses adjusting for sociodemographic, health, and vaccine-related variables confirmed that older age was not associated with impaired cellular responses. Instead, the strongest predictors of CD4+ and CD8+ T-cell frequencies post-third-dose were their corresponding post-second-dose frequencies. Breakthrough infection significantly increased both CD4+ and CD8+ T-cell frequencies, to comparable levels in older and younger adults. Exploratory analyses revealed an association between HLA-A*02:03 and higher post-vaccination CD8+ T-cell frequencies, which may be attributable to numerous strong-binding HLA-A*02:03-specific CD8+ T-cell epitopes in the spike protein. Conclusion: Older adults mount robust T-cell responses to 2- and 3-dose COVID-19 mRNA vaccination, which are further boosted following breakthrough infection.

Guideline Compliance and Indications for Inferior Vena Cava Filter Placement at a Quaternary Care Medical Center.

PURPOSE: This study investigated physician compliance with indications for inferior vena cava (IVC) filter placement according to the 2012 American College of Chest Physicians (ACCP) and the 2011 Society of Interventional Radiology (SIR) guidelines. MATERIALS AND METHODS: A retrospective medical record review of 231 retrievable IVC filters placed between August 15, 2016, and December 28, 2017, at a large urban academic medical center. Guideline compliance to the 2012 ACCP and the 2011 SIR guidelines, and indications for IVC filter placements were assessed through an adjudication protocol. Filter retrieval and complication rates were also examined. RESULTS: Compliance to guidelines was low (60.2% for ACCP; 74.0% for SIR), especially for non-intensive care unit (ICU) patients (ICU 74.6% vs non-ICU 54.8%, p=0.007 for ACCP; ICU 82.5% vs non-ICU 70.8%, p=0.092 for SIR). After adjudication, 8.2% (19/231) of filters were considered non-indicated but reasonable, 17.7% (41/231) non-indicated and unreasonable, and 13.9% (32/231) SIR-indicated but not ACCP-indicated. The most common indication was venous thromboembolism with contraindication to anticoagulation. The most common reasons for non-compliance were distal deep venous thrombosis with contraindication to anticoagulation (19/60, 31.6%) and clot burden (19/60, 31.6%). One-year filter retrieval and 90-day complication rates were 32.0% (74/231) and 6.1% (14/231), respectively. CONCLUSION: Compliance to established guidelines was low. Reasons for non-compliance included limitations or discrepancies in guidelines, as well as non-evidence-based filter placements. CLINICAL IMPACT: Despite increasing utilization of inferior vena cava (IVC) filters, guideline compliance for IVC filter placement among providers is unclear. The results of this study indicate that physician compliance to established guidelines is poor, especially in non-intensive-care-unit patients. Noncompliance stems from non-evidence-based filter placement as well as differences and limitations in guidelines. Avoiding non-indicated IVC filter placement and consolidation of guidelines may significantly improve guideline compliance. The critical insights gained from this study can help promote judicious use of IVC filters and highlight the role of venous thromboembolism experts in navigating complex cases and nuances of guidelines.

Economic insecurity exposure and cognitive function in late life.

OBJECTIVES: This study took the State-owned Enterprises (SOE) reform from 1996 to 2002 in China as a natural experiment to explore the consequences of economic insecurity exposure during early-adulthood and mid-adulthood on cognitive function in later life. METHODS: Data were obtained from the China Health and Retirement Longitudinal Survey (CHARLS), 2014 and 2015. CHARLS is a nationally representative survey covering 28 provinces in China. A total of 4536 urban dwellers born earlier than 1971 (aged 25 years old and above at the start of the SOE reform in 1996) were included in our analyses. Using province-year-level economic loss from the layoffs, we examined the impact of economic insecurity exposure on the cognitive function score by using a difference-in-differences model with 1996-2002 as the cut-off. RESULTS: Individuals exposed to economic insecurity have significantly decreased cognitive function, in which a 1% point increase in expected economic loss would decrease the cognitive function score by 0.09 (95% CI: -0.17 to -0.01). Given that the average intensity of expected economic loss was 11.59% and the mean score of cognitive function was 21.26, exposure to the SOE reforms led to an average decrease in the cognitive function score by at least 4.91%. CONCLUSIONS: Providing cognitive health surveillance and psychological counselling may be important for preventing cognitive decline among those experiencing economic insecurity.

Associations between county-level public health expenditures and community health planning activities with COVID-19 incidence and mortality.

The COVID-19 pandemic has revealed consequences of past defunding of the U.S. public health system, but the extent to which public health infrastructure is associated with COVID-19 burden is unknown. We aimed to determine whether previous county-level public health expenditures and community health planning activities are associated with COVID-19 cases and deaths. We examined 3050 of 3143 U.S. counties and county equivalents from March 1, 2020 to February 28, 2022. Multivariable-adjusted linear regression and generalized additive models were used to estimate associations between county-level public health expenditures and completion of community health planning activities by a county health department with outcomes of county-level COVID-19 cases and deaths per 100,000 population. After adjusting for county-level covariates, counties in the highest tertile of public health expenditures per capita had on average 542 fewer COVID-19 cases per 100,000 population (95% CI, -1004 to -81) and 21 fewer deaths per 100,000 population (95% CI, -32 to -10) than counties in the lowest tertile. For analyses of community health planning activities, adjusted estimates of association remained negative for COVID-19 deaths, but confidence intervals included negative and positive values. In conclusion, higher levels of local public health expenditures and community health planning activities were associated with fewer county-level COVID-19 deaths, and to a lesser extent, cases. Future public health funding should be aligned with evidence for the value of county health departments programs and explore further which types of spending are most cost effective.

Consequences of China's special send-down movement on infectious disease control in rural areas: a natural experiment.

Background: China's send-down movement in the 1960s and 1970s, as a natural experiment, provides a unique opportunity to investigate the relationship between peers' dissemination of health literacy, community health workers, and infectious disease control in areas with weak health systems and inadequate human resources. To address the lack of studies on the health effects of the send-down movement, this study examined the associations between prenatal exposure to the send-down movement and infectious diseases in China. Methods: We analyzed 188,253 adults born in 1956-1977 with rural hukou who participated in the Second National Sample Survey on Disability in 2006 across 734 counties of China. Difference-in-difference models were used to detect the effect of the send-down movement on infectious diseases. Infectious diseases were ascertained by using the combination of self- or family members' reports and on-site medical diagnosis of disabilities attributed to infectious disease by experienced specialists. The density of the relocated urban sent-down youth or "sent-down youths" (SDYs) in each county defined the intensity variable of the send-down movement. Results: Individuals in SDY-receiving areas with increased intensity of prenatal exposure to the send-down movement had a decreased probability of infectious diseases (ß = -0.0362, 95% CI: 0.0591, -0.0133) after controlling for a set of regional and cohort characteristics. This association was stronger in counties with more prevalent infectious diseases prior to the send-down movement (ß = -0.0466, 95% CI: 0.0884, -0.0048) than in those with less prevalence (ß = -0.0265, 95% CI: 0.0429, -0.010). No substantial differences were found across sex-specific groups or by strictness of send-down movement implementation. On average, prenatal exposure to the send-down movement corresponded to a decrease in the probability of infectious diseases in rural areas by 19.70%. Conclusions: For areas with weak health systems, strengthening community health workers and promoting health literacy may be two key points to address the burden of infectious diseases. Increasing education and primary health care through peer-to-peer dissemination may contribute to the reduction of infectious disease prevalence.

Cardiometabolic multimorbidity, lifestyle behaviours, and cognitive function: a multicohort study.

BACKGROUND: Little is known about the effect of lifestyle factors on cognitive decline related to cardiometabolic multimorbidity. We aimed to examine the association between cardiometabolic multimorbidity and cognitive decline, and the role of lifestyle factors in this association. METHODS: We did a pooled multi-cohort study using pooled data from four cohort studies (the Health and Retirement Study; the English Longitudinal Study of Ageing; the Survey of Health, Ageing and Retirement in Europe; and the China Health and Retirement Longitudinal Study) across 14 countries. Eligible participants were age 50 years and older, and those who were missing information on exposure and outcomes, or who had been diagnosed with dementia or Parkinson's disease, were excluded. Cardiometabolic multimorbidity was defined as the co-occurrence of two or three cardiometabolic diseases, including diabetes, heart disease, and stroke. The primary outcome of cognitive function was measured in three domains, on the basis of the mean and SD of the corresponding tests: memory, numeracy, and orientation, in all participants with available data. A global cognitive score was created by summing the individual scores. FINDINGS: The final sample consisted of 160 147 individuals across all four studies (73 846 [46·1%] men and 86 301 [53·9%] women) and participants had a mean age of 67·49 years (SD 10·43). An increasing number of cardiometabolic diseases was dose-dependently associated with the decline in cognitive function score (one disease, ß=-0·15 [95% CI -0·17 to -0·13]; two diseases, ß=-0·37 [-0·40 to -0·34]; three diseases, ß=-0·57 [-0·64 to -0·50]), with comorbid diabetes and stroke (ß=-0·23 [-0·29 to -0·17]) contributing most strongly to cardiometabolic disease-associated cognitive decline. Cognitive decline associated with cardiometabolic disease was accelerated with physical inactivity (one cardiometablic disease, p=0·020; two cardiometablic diseases, p=0·42; and three cardiometablic diseases, p=0·24), excessive alcohol use (one cardiometablic disease, p=0·016; two cardiometablic diseases, p=0·65; and three cardiometablic diseases, p=0·50), and the higher number of unhealthy lifestyle factors (one cardiometablic disease, p=0·79; two cardiometablic diseases, p=0·0050; and three cardiometablic diseases, p=0·888). INTERPRETATION: These findings indicated a targeted approach for simultaneously developing preventative interventions on lifestyles and integrated treatment for cardiometabolic comorbidities to delay cognitive decline in older people. FUNDING: Major Project of the National Social Science Fund of China, National Natural Science Foundation of China, China Medical Board, and Young Elite Scientists Sponsorship Program by CAST.

Associations between pregnancy glucose measurements and risk of preterm birth: a retrospective cohort study of commercially insured women in the United States from 2003 to 2021.

PURPOSE: To investigate associations between glucose measurements during pregnancy and risk of preterm birth (PTB). METHODS: Retrospective cohort study of commercially insured women with singleton live births in the United States from 2003 to 2021 using longitudinal medical claims, socioeconomic data, and eight glucose results from different fasting and post-load tests performed between 24 and 28 weeks of gestation for gestational diabetes screening. Risk ratios of PTB (<37 weeks) were estimated via Poisson regression for z-standardized glucose measures. Non-linear relationships for continuous glucose measures were examined via generalized additive models. RESULTS: Elevations in all eight glucose measures were associated with increased risk (adjusted risk ratio point estimates: 1.05-1.19) of PTB for 196,377 women with non-fasting 50-g glucose challenge test (one glucose result), 31,522 women with complete 100-g, 3-hour fasting oral glucose tolerance test (OGTT) results (four glucose results), and 10,978 women with complete 75-g, 2-hour fasting OGTT results (three glucose results). Associations were consistent after adjusting for and stratifying by sociodemographic and clinical factors. Substantial non-linear relationships (U-, J-, and S-shaped) were observed between several glucose measurements and PTB. CONCLUSIONS: Elevations in various glucose measures were linearly and non-linearly associated with increased PTB risk, even before diagnostic thresholds for gestational diabetes.

SARS-CoV-2 live virus neutralization after four COVID-19 vaccine doses in people with HIV receiving suppressive antiretroviral therapy.

OBJECTIVE: Limited data exist regarding the immune benefits of fourth COVID-19 vaccine doses in people with HIV (PWH) receiving antiretroviral therapy (ART), particularly now that most have experienced a SARS-CoV-2 infection. We quantified wild-type, Omicron-BA.5 and Omicron-BQ.1-specific neutralization up to 1 month post-fourth COVID-19 vaccine dose in 63 (19 SARS-CoV-2-naive and 44 SARS-CoV-2-experienced) PWH. DESIGN: A longitudinal observational cohort. METHODS: Quantification of wild-type-, Omicron-BA.5, and Omicron-BQ.1-specific neutralization using live virus assays. RESULTS: Participants received monovalent (44%) and bivalent (56%) mRNA fourth doses. In COVID-19-naive PWH, fourth doses enhanced wild-type and Omicron-BA.5-specific neutralization modestly above three-dose levels ( P  = 0.1). In COVID-19-experienced PWH, fourth doses enhanced wild-type specific neutralization modestly ( P  = 0.1) and BA.5-specific neutralization substantially ( P  = 0.002). Consistent with humoral benefits of 'hybrid' immunity, COVID-19-experienced PWH exhibited the highest neutralization post-fourth dose, wherein those with Omicron-era infections displayed higher wild-type specific ( P  = 0.04) but similar BA.5 and BQ.1-specific neutralization than those with pre-Omicron-era infections. Nevertheless, BA.5-specific neutralization was significantly below wild-type in everyone regardless of COVID-19 experience, with BQ.1-specific neutralization lower still (both P  < 0.0001). In multivariable analyses, fourth dose valency did not affect neutralization magnitude. Rather, an mRNA-1273 fourth dose (versus a BNT162b2 one) was the strongest correlate of wild-type specific neutralization, while prior COVID-19, regardless of pandemic era, was the strongest correlate of BA.5 and BQ.1-specific neutralization post-fourth dose. CONCLUSION: Fourth COVID-19 vaccine doses, irrespective of valency, benefit PWH regardless of prior SARS-CoV-2 infection. Results support recommendations that all adults receive a fourth COVID-19 vaccine dose within 6 months of their third dose (or their most recent SARS-CoV-2 infection).

Comparison of 24-Month Clinical Outcomes after Prostatic Artery Embolization in Prostate Glands Larger versus Smaller than 80 mL: A Systematic Review.

PURPOSE: This review was undertaken to compare the clinical outcomes of prostatic artery embolization (PAE) in patients with >80 versus <80 mL prostatic volume (PV) at the 24-month follow-up to determine whether PV predicted the effectiveness or durability of PAE. MATERIALS AND METHODS: The PubMed/MEDLINE database was searched for articles published between 2010 and 2022 using the search term "(prostat∗ artery embolization) AND (long term OR follow-up OR 24-month)." Articles were included if they discussed PAE for benign prostatic hyperplasia (BPH) and reported a minimum follow-up of 24 months. Articles with <10 patients were excluded. A subgroup analysis was performed to evaluate for any difference in clinical outcomes at the 24-month post-PAE follow-up between studies with a mean PV of >80 mL and those with a mean PV of <80 mL. RESULTS: A total of 14 studies with 2,260 patients were included, all of which demonstrated significant reduction in symptoms at the 24-month follow-up after PAE. Four studies were included as part of the >80-mL PV subgroup (n = 467), and 10 studies were included as part of the <80-mL PV subgroup (n = 1,793). There was a statistically significant difference between the mean preprocedural PV (128.5 vs 64.0 mL; P = .015). At the 24-month follow-up, there were no significant differences between groups across any of the compared parameters. The collective incidence of major adverse events reported in the studies within this review was <1%. CONCLUSIONS: PAE is both safe and durable for patients suffering from BPH and can be effective across a wide range of baseline PVs.

Characteristics and treatment patterns of autism spectrum disorder in China, 2020.

This study aimed to investigate the characteristics of children diagnosed with ASD in China and to estimate ASD treatment patterns in 2020. This study used data from the 2020 Survey on Family Circumstance and Demand Support and Resources among Autistic Children in China. The study sample included 4,557 children diagnosed with ASD aged 2-16 years old. Data were collected through questionnaires completed by parents. Of the 4,557 children with ASD, there was a male-to-female ratio of 5.75:1, and the average age when ASD risk symptoms were first reported was 27.97(SD=10.83) months. Higher proportions of families with highly educated parents (college and above; around 58%) and advanced parental age at childbirth (≥35 years; over 50%) were found among autistic children. Additionally, about 41.05% of autistic children had an immediate family member diagnosed with mental/intellectual disorders. In terms of the treatment patterns for autistic children, 84.82% had received behavioral and developmental treatments and 77.74% had received therapy-based treatments, whereas 3% children had not received any treatment. Higher odds of non-treatment were found among children who were male (OR=1.69, 95% CI: 1.01,3.03) and had ASD diagnosed later on (OR= 1.02, 95% CI:1.01,1.03), as compared to their counterparts. Future studies will need to explore the etiology of the disparities of ASD, and policy efforts are critically needed to understand and address the barriers for children with ASD to receive appropriate treatments.

Impact of SARS-CoV-2 lockdown on expansion of HIV transmission clusters among key populations: A retrospective phylogenetic analysis.

Background: Public health measures designed to reduce SARS-CoV-2 transmission led to reduced access to care and prevention services for people living with or at risk of acquiring HIV, particularly during the initial introduction of extensive restrictions. This reduction in access may have contributed to increases in HIV transmission not outweighed by decreases in transmission occurring as a result of reduced contact rates promoted by the same public health measures. Methods: We synthesize available province-wide HIV data in British Columbia, Canada, together with public mobility data to phylogenetically investigate the early impacts of SARS-CoV-2 on HIV transmission. Cluster growth, coalescent branching events and lineage-level diversification rates were assessed in "pre-lockdown" (January 22-March 21, 2020), "lockdown" (March 22-May 20, 2020) and "post-lockdown" (May 21-July 19, 2020) to facilitate comparison of transmission trends across key populations. Findings: Results reveal increased HIV transmission in a limited number of clusters in association with reduced access to health services during the initial introduction of SARS-CoV-2-related restrictions. In particular, clusters associated with people who inject drugs (PWID) show rapid growth, extensive branching events in phylogenetic trees during and following the lockdown period, and elevated median change in individuals' viral diversification rates during lockdown compared to clusters associated with men who have sex with men (MSM), consistent with increased transmission rates between PWID. Interpretation: Increased vigilance and innovative targeted solutions are critical to offset potential negative impacts of SARS-CoV-2 or future pandemic-related restrictions on HIV epidemic dynamics. Funding: Funding sources include Genome Canada and Genome BC, the Public Health Agency of Canada, the BC Centre for Excellence in HIV/AIDS, and the Canadian Institutes of Health Research Coronavirus Rapid Response Programme. Student funding includes a NSERC CREATE scholarship and a Canadian Institutes of Health Research graduate fellowship.

Phylogenetic prioritization of HIV-1 transmission clusters with viral lineage-level diversification rates.

Background and objectives: Public health officials faced with a large number of transmission clusters require a rapid, scalable and unbiased way to prioritize distribution of limited resources to maximize benefits. We hypothesize that transmission cluster prioritization based on phylogenetically derived lineage-level diversification rates will perform as well as or better than commonly used growth-based prioritization measures, without need for historical data or subjective interpretation. Methodology: 9822 HIV pol sequences collected during routine drug resistance genotyping were used alongside simulated sequence data to infer sets of phylogenetic transmission clusters via patristic distance threshold. Prioritized clusters inferred from empirical data were compared to those prioritized by the current public health protocols. Prioritization of simulated clusters was evaluated based on correlation of a given prioritization measure with future cluster growth, as well as the number of direct downstream transmissions from cluster members. Results: Empirical data suggest diversification rate-based measures perform comparably to growth-based measures in recreating public heath prioritization choices. However, unbiased simulated data reveals phylogenetic diversification rate-based measures perform better in predicting future cluster growth relative to growth-based measures, particularly long-term growth. Diversification rate-based measures also display advantages over growth-based measures in highlighting groups with greater future transmission events compared to random groups of the same size. Furthermore, diversification rate measures were notably more robust to effects of decreased sampling proportion. Conclusions and implications: Our findings indicate diversification rate-based measures frequently outperform growth-based measures in predicting future cluster growth and offer several additional advantages beneficial to optimizing the public health prioritization process.

Azithromycin-Induced Liver Injury in an Asthma Exacerbation Patient With Autoimmune Features.

Drug-induced liver injury (DILI) is one of the leading causes of acute liver failure in the United States. Antimicrobials are the most common class of drugs implicated in this pathology. Although azithromycin has been documented as a relatively safe drug, one of its rare and potentially fatal side effects is DILI. Diagnosing DILI is difficult because it is a diagnosis of exclusion. Autoimmune hepatitis (AIH) may present similarly to DILI, and a liver biopsy may be needed to differentiate between the two conditions. We present a case of azithromycin-induced liver injury in an asthma exacerbation patient with features of AIH.

Systemic Lupus Erythematosus vs. Mixed Connective Tissue Disease Disguised As Scabies.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves numerous body systems and may initially present as a malar or discoid rash. When there are features of other autoimmune disorders present, such as scleroderma or polymyositis, the term mixed connective tissue disorder (MCTD) may be used. The current literature illustrates that the diagnostic criteria for MCTD are unclear. Additionally, the literature presents cases of scabies mimicking the presentation of various autoimmune disorders with cutaneous manifestations. We introduce a case of a young African American female who developed a pruritic rash on her face, abdomen, hands, and scalp. An initial diagnosis of scabies was made, however, failed to improve after a course of permethrin 5% topical cream. Subsequently, she was hospitalized, and diagnosed with pancytopenia, cardiomyopathy, microscopic hematuria and trace proteinuria. Systemic lupus erythematosus/scleroderma overlap syndrome was later confirmed by serologic testing. The patient was started on corticosteroids, with resultant improvement in her symptoms and laboratory findings.

The association between community-level socioeconomic status and depressive symptoms among middle-aged and older adults in China.

BACKGROUND: There was little evidence concerning the association of community socioeconomic status (SES) and the cross-level interaction between community- and individual-level SES with depressive symptoms in China. This study aimed to investigate the association of community-level SES with depressive symptoms among Chinese middle-aged and older people and to examine whether individual-level SES moderates this relationship. METHODS: Using data from the China Health and Retirement Longitudinal 2011-2018 Study, the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10) short form was used to measure depressive symptoms in 35,546 Chinese individuals aged 45 years and older. Community SES was calculated as a sum of z scores of the average years of schooling and household income per capita, which were derived by aggregating the individual measures to the community level. Two-level hierarchical linear regression was used. RESULTS: Community SES was negatively related to CES-D-10 scores (coef=-0.438). A 1-SD increase in individual SES was associated with lower CES-D-10 scores (coef=-0.490). The cross-level interaction on individual- and community-level SES was significantly associated with depressive symptoms, indicating that with the increase of individual-level SES, the effect of community-level SES on depression decreases. Stratified analyses observed robust associations of community SES with CES-D scores between urban and rural residents. CONCLUSIONS: This study showed that individuals who live in lower-SES communities had more severe depressive symptoms, particularly individuals with low SES. Additional attention should be given to the community socioeconomic context of middle-aged and older adults with lower SES, which may be helpful to reduce SES inequalities in depressive symptoms in China.