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.

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.

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.

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.

The association between community-level socioeconomic status and cognitive function among Chinese middle-aged and older adults: a study based on the China Health and Retirement Longitudinal Study (CHARLS).

BACKGROUND: Although numerous studies focused on the relationship between area socioeconomic status (SES) and health, only a few of them investigated how community-level SES was linked to late-life cognitive function as well as the potential pathways underlying this association, and very few of them focused on the context of China. This study examined how community-level SES was linked to cognitive function and the potential pathways underlying this association among middle-aged and older adults in China. METHODS: Data was drawn from the waves 1-4 of China Health and Retirement Longitudinal Study. We measured cognitive function with the components of the Telephone Interview of Cognitive Status battery. Community-level SES was derived from a sum of z scores of the percentage of the illiterate and the per-capita net income status within communities. We adopted two-level hierarchical linear regression models to explore the associations between community-level SES and cognitive function. A multilevel mediation analysis with structural equation modeling was undertaken to disaggregate the direct and indirect pathways of the associations. RESULTS: Higher community-level SES was associated with better cognitive function (ß = 0.562, 95% CI = 0.390, 0.734), and this significant association was only present in rural participants, not in urban participants. Furthermore, we discovered the mediating effects of outdoor exercise facilities within communities (ß = 0.023, 95% CI = 0.000, 0.056) and individual-level SES (ß = 0.108, 95% CI = 0.057, 0.156) to explain the relationship between community SES and cognitive function. CONCLUSIONS: These findings highlight the importance of community environmental interventions in maintaining individuals' cognitive health in China, especially for older adults. Our results provided solid empirical evidence for reducing mental health inequalities in China, and suggested that developing an aging-friendly environment and properly distributing community resources are important to improve cognitive function of older adults.

Use of the Bedside-Placed Angel Catheter IVC Filter for Venous Thromboembolic Disease in Critically Ill Medical Patients.

Venous thromboembolic disease is a major problem among critically ill patients, with significant associated morbidity and mortality. Many critically ill patients have contraindications to systemic anticoagulation, and inferior vena cava (IVC) filters are an important alternative in preventing pulmonary emboli (PE) in this population. The Angel Catheter (Mermaid, Stenlose, Denmark) is a novel percutaneous and removable IVC filter attached to the end of a triple lumen central venous catheter which has been demonstrated to reduce PE in surgical and trauma patients. This case series describes 18 critically ill medical patients who had an Angel catheter placed either for diagnosed PE or due to high risk for PE; over half had at least submassive PE at the time of Angel catheter placement. None of the patients had a recurrence of PE during Angel catheter use, 29.4% had clot found in the filter via cavogram upon removal, and only one had a minor complication which had no clinical consequence. In 2 patients, the placement of the Angel Catheter resulted in the prevention of PE during catheter-directed thrombolysis of extensive deep vein thrombosis. This case series demonstrates that in a population of critically ill, elderly, and obese medical patients the bedside placement of the Angel IVC filter is feasible, safe, and may be effective for preventing PE.

Schizophrenia and education in Chinese metropolises: a population-based study.

OBJECTIVE: Schizophrenia is a public concern in metropolises. Increases in city size may strengthen the correlation between prevalence of schizophrenia and indices of socioeconomic status, such as education. This study used population-based data of adults to investigate the association between education and schizophrenia in Chinese metropolises and its differences between inner city areas and outer suburbs. METHODS: Data was obtained from the Second China National Sample Survey on Disability in 2006, and analysis was restricted to 189,143 participants aged 18 years or older in all counties (districts) of Beijing, Shanghai, and Tianjin. Schizophrenia diagnoses were ascertained according to the International Statistical Classification of Diseases, 10th Revision. Logistic regression models were fitted to examine the association between education and schizophrenia. RESULTS: An inverse U-shaped pattern between education and schizophrenia was found in inner city areas of Chinese metropolises. Compared with the primary school or below group, the odds ratios of junior high school group and senior high school or above group was 2.79 (95% CI 1.96, 3.96) and 1.45(95% CI 0.99, 2.13), respectively. In outer suburbs, junior high school (OR = 0.87, 95% CI 0.63, 1.19) and senior high school or above groups (0.58, 95% CI 0.38, 0.87) were less likely to develop schizophrenia than the primary school or below group. CONCLUSIONS: This study showed an association between education and schizophrenia in Chinese metropolises. In inner city areas, the association was an inverse U-shaped pattern between education and schizophrenia, whereas in suburban areas, the association was a negative linear pattern. Our findings can help identify high-risk populations of schizophrenia in Chinese metropolises. Programs for prevention and early intervention of schizophrenia will need to consider the socioeconomic disparities between inner city and outer suburban areas. Public policies can help improve mental health by developing social security for migrants in inner city areas and promoting regional equality.

A Highly Stretchable Polyacrylonitrile Elastomer with Nanoreservoirs of Lubricant Using Cyano-Silver Complexes.

Stretchable materials are indispensable for applications such as deformable devices, wearable electronics, and future robotics. However, designs for new elastomers with high stretchability have undergone only limited research. Here we have fabricated highly stretchable Ag+/polyacrylonitrile elastomer with nanoreservoirs of lubricant using cyano-silver complexes. The prepared products feature nanoconfinement structures of lubricant surrounded by polymer chains with coordination bond through chelates of cyano-silver, resulting in an enhanced stretchability of more than 600% from 2%. The elastomeric properties were investigated, and a mechanical response model was proposed, which explained the structural evolution including the polymer chain fluidity under external deformation. Also, the easy breakage and dynamic reformation of cyano-silver coordination complexes promises a strain recovery under various stretching conditions. This elastomer itself can directly work as sensors and open paths to alternative substrates for soft electronics development.

Phylogenetic Tools for Generalized HIV-1 Epidemics: Findings from the PANGEA-HIV Methods Comparison.

Viral phylogenetic methods contribute to understanding how HIV spreads in populations, and thereby help guide the design of prevention interventions. So far, most analyses have been applied to well-sampled concentrated HIV-1 epidemics in wealthy countries. To direct the use of phylogenetic tools to where the impact of HIV-1 is greatest, the Phylogenetics And Networks for Generalized HIV Epidemics in Africa (PANGEA-HIV) consortium generates full-genome viral sequences from across sub-Saharan Africa. Analyzing these data presents new challenges, since epidemics are principally driven by heterosexual transmission and a smaller fraction of cases is sampled. Here, we show that viral phylogenetic tools can be adapted and used to estimate epidemiological quantities of central importance to HIV-1 prevention in sub-Saharan Africa. We used a community-wide methods comparison exercise on simulated data, where participants were blinded to the true dynamics they were inferring. Two distinct simulations captured generalized HIV-1 epidemics, before and after a large community-level intervention that reduced infection levels. Five research groups participated. Structured coalescent modeling approaches were most successful: phylogenetic estimates of HIV-1 incidence, incidence reductions, and the proportion of transmissions from individuals in their first 3 months of infection correlated with the true values (Pearson correlation > 90%), with small bias. However, on some simulations, true values were markedly outside reported confidence or credibility intervals. The blinded comparison revealed current limits and strengths in using HIV phylogenetics in challenging settings, provided benchmarks for future methods' development, and supports using the latest generation of phylogenetic tools to advance HIV surveillance and prevention.

Characterization of Hepatitis C Virus (HCV) Envelope Diversification from Acute to Chronic Infection within a Sexually Transmitted HCV Cluster by Using Single-Molecule, Real-Time Sequencing.

In contrast to other available next-generation sequencing platforms, PacBio single-molecule, real-time (SMRT) sequencing has the advantage of generating long reads albeit with a relatively higher error rate in unprocessed data. Using this platform, we longitudinally sampled and sequenced the hepatitis C virus (HCV) envelope genome region (1,680 nucleotides [nt]) from individuals belonging to a cluster of sexually transmitted cases. All five subjects were coinfected with HIV-1 and a closely related strain of HCV genotype 4d. In total, 50 samples were analyzed by using SMRT sequencing. By using 7 passes of circular consensus sequencing, the error rate was reduced to 0.37%, and the median number of sequences was 612 per sample. A further reduction of insertions was achieved by alignment against a sample-specific reference sequence. However, in vitro recombination during PCR amplification could not be excluded. Phylogenetic analysis supported close relationships among HCV sequences from the four male subjects and subsequent transmission from one subject to his female partner. Transmission was characterized by a strong genetic bottleneck. Viral genetic diversity was low during acute infection and increased upon progression to chronicity but subsequently fluctuated during chronic infection, caused by the alternate detection of distinct coexisting lineages. SMRT sequencing combines long reads with sufficient depth for many phylogenetic analyses and can therefore provide insights into within-host HCV evolutionary dynamics without the need for haplotype reconstruction using statistical algorithms.IMPORTANCE Next-generation sequencing has revolutionized the study of genetically variable RNA virus populations, but for phylogenetic and evolutionary analyses, longer sequences than those generated by most available platforms, while minimizing the intrinsic error rate, are desired. Here, we demonstrate for the first time that PacBio SMRT sequencing technology can be used to generate full-length HCV envelope sequences at the single-molecule level, providing a data set with large sequencing depth for the characterization of intrahost viral dynamics. The selection of consensus reads derived from at least 7 full circular consensus sequencing rounds significantly reduced the intrinsic high error rate of this method. We used this method to genetically characterize a unique transmission cluster of sexually transmitted HCV infections, providing insight into the distinct evolutionary pathways in each patient over time and identifying the transmission-associated genetic bottleneck as well as fluctuations in viral genetic diversity over time, accompanied by dynamic shifts in viral subpopulations.

Extubation to high-flow nasal cannula in critically ill surgical patients.

BACKGROUND: High-flow nasal cannula (HFNC) is increasingly used to reduce reintubations in patients with respiratory failure. Benefits include providing positive end expiratory pressure, reducing anatomical dead space, and decreasing work of breathing. We sought to compare outcomes of critically ill surgical patients extubated to HFNC versus conventional therapy. METHODS: A retrospective review was conducted in the surgical intensive care unit of an academic center during August 2015 to February 2016. Data including demographics, ventilator days, oxygen therapy after extubation, reintubation rates, surgical intensive care unit and hospital length of stay, and mortality were collected. Self and palliative extubations were excluded. Characteristics and outcomes, with the primary outcome being reintubation, were compared between those extubated to HFNC versus cool mist/nasal cannula (CM/NC). RESULTS: Of the 184 patients analyzed, 46 were extubated to HFNC and 138 to CM/NC. Mean age and days on ventilation before extubation were 57.8 years and 4.3 days, respectively. Both cohorts were similar in age, sex, and had a similar prevalence of cardiopulmonary diagnoses at admission. Although prior to extubation HFNC had lengthier ventilation requirements (7.1 versus 3.4 days, P < 0.01) and ICU stays (7.8 versus 4.1 days, P < 0.01), the rate of reintubation was similar to CM/NC (6.5% versus 13.8%, P = 0.19). Multivariable analysis demonstrated HFNC to be associated with a lower risk of reintubation (adjusted odds ratio = 0.15, P = 0.02). Mortality rates were similar. CONCLUSIONS: Ventilated patients at risk for recurrent respiratory failure have reduced reintubation rates when extubated to HFNC. Patients with prolonged intubation or those with high-risk comorbidities may benefit from extubation to HFNC.

Theoretical and experimental assessment of degenerate primer tagging in ultra-deep applications of next-generation sequencing.

Primer IDs (pIDs) are random oligonucleotide tags used in next-generation sequencing to identify sequences that originate from the same template. These tags are produced by degenerate primers during the reverse transcription of RNA molecules into cDNA. The use of pIDs helps to track the number of RNA molecules carried through amplification and sequencing, and allows resolution of inconsistencies between reads sharing a pID. Three potential issues complicate the above applications. First, multiple cDNAs may share a pID by chance; we found that while preventing any cDNAs from sharing a pID may be unfeasible, it is still practical to limit the number of these collisions. Secondly, a pID must be observed in at least three sequences to allow error correction; as such, pIDs observed only one or two times must be rejected. If the sequencing product contains copies from a high number of RT templates but produces few reads, our findings indicate that rejecting such pIDs will discard a great deal of data. Thirdly, the use of pIDs could influence amplification and sequencing. We examined the effects of several intrinsic and extrinsic factors on sequencing reads at both the individual and ensemble level.

Characterization at Atomic Resolution of Carbon Nanotube/Resin Interface in Nanocomposites by Mapping sp 2-Bonding States Using Electron Energy-Loss Spectroscopy.

Functionalization is critical for improving mechanical properties of carbon nanotubes (CNTs)/polymer nanocomposites. A fundamental understanding of the role of the CNT/polymer interface and bonding structure is key to improving functionalization procedures for higher mechanical performance. In this study, we investigated the effects of chemical functionalization on the nanocomposite interface at atomic resolution to provide direct and quantifiable information of the interactions and interface formation between CNT surfaces and adjacent resin molecules. We observed and compared electronic structures and their changes at the interfaces of nonfunctionalized and functionalized CNT/polymer nanocomposite samples via scanning transmission electron microscopy and electron energy-loss spectroscopy (EELS) spectrum imaging techniques. The results show that the state of sp 2 bonding and its distribution at the CNT/resin interface can be clearly visualized through EELS mapping. We found that the functionalized CNT/polymer samples exhibited a lower fraction of sp 2 bonding and a lower π*/σ* ratio compared with the nonfunctionalized cases. A good correlation between near-edge fine structures and low-loss plasmon energies was observed.

Global origin and transmission of hepatitis C virus nonstructural protein 3 Q80K polymorphism.

Hepatitis C virus (HCV) has a naturally occurring polymorphism, Q80K, in the nonstructural protein 3 (NS3) gene encoding the viral protease, which has been associated with reduced susceptibility to the direct-acting antiviral inhibitor simeprevir. Q80K is observed predominantly in HCV genotype 1a and seldom in other HCV genotypes; moreover, it has a markedly high prevalence in the United States. Here, we reconstruct the evolutionary history of this polymorphism to investigate why it is so highly localized in prevalence and whether it is stably transmitted between hosts. We found that the majority (96%) of HCV infections carrying Q80K were descended from a single lineage in which a Q80K substitution occurred around the 1940s in the United States, which implies that this polymorphism is likely highly transmissible. Furthermore, we identified 2 other substitutions in NS3 that may interact with Q80K and contribute to its stability. Our results imply that the current distribution and prevalence of Q80K are unlikely to change significantly in the short term.

An evaluation of phylogenetic methods for reconstructing transmitted HIV variants using longitudinal clonal HIV sequence data.

UNLABELLED: A population of human immunodeficiency virus (HIV) within a host often descends from a single transmitted/founder virus. The high mutation rate of HIV, coupled with long delays between infection and diagnosis, make isolating and characterizing this strain a challenge. In theory, ancestral reconstruction could be used to recover this strain from sequences sampled in chronic infection; however, the accuracy of phylogenetic techniques in this context is unknown. To evaluate the accuracy of these methods, we applied ancestral reconstruction to a large panel of published longitudinal clonal and/or single-genome-amplification HIV sequence data sets with at least one intrapatient sequence set sampled within 6 months of infection or seroconversion (n = 19,486 sequences, median [interquartile range] = 49 [20 to 86] sequences/set). The consensus of the earliest sequences was used as the best possible estimate of the transmitted/founder. These sequences were compared to ancestral reconstructions from sequences sampled at later time points using both phylogenetic and phylogeny-naive methods. Overall, phylogenetic methods conferred a 16% improvement in reproducing the consensus of early sequences, compared to phylogeny-naive methods. This relative advantage increased with intrapatient sequence diversity (P < 10(-5)) and the time elapsed between the earliest and subsequent samples (P < 10(-5)). However, neither approach performed well for reconstructing ancestral indel variation, especially within indel-rich regions of the HIV genome. Although further improvements are needed, our results indicate that phylogenetic methods for ancestral reconstruction significantly outperform phylogeny-naive alternatives, and we identify experimental conditions and study designs that can enhance accuracy of transmitted/founder virus reconstruction. IMPORTANCE: When HIV is transmitted into a new host, most of the viruses fail to infect host cells. Consequently, an HIV infection tends to be descended from a single "founder" virus. A priority target for the vaccine research, these transmitted/founder viruses are difficult to isolate since newly infected individuals are often unaware of their status for months or years, by which time the virus population has evolved substantially. Here, we report on the potential use of evolutionary methods to reconstruct the genetic sequence of the transmitted/founder virus from its descendants at later stages of an infection. These methods can recover this ancestral sequence with an overall error rate of about 2.3%-about 15% more information than if we had ignored the evolutionary relationships among viruses. Although there is no substitute for sampling infections at earlier points in time, these methods can provide useful information about the genetic makeup of transmitted/founder HIV.

The role of stem cells and tissue engineering in orthopaedic sports medicine: current evidence and future directions.

The use of stem cell therapies for the treatment of orthopaedic injuries continues to advance. The purpose of this review was to provide an update of the current role and future directions of stem cell strategies in sports medicine. The application of cell-based treatments in the sports medicine arena has expanded in recent years. Promising preclinical results have led to translation of these novel therapies into the clinical setting. Early well-designed comparative clinical studies have also shown positive outcomes. Despite significant advances in this arena, there remains a need for additional high-powered and well-designed clinical trials to confirm the safety and efficacy of treatment.

Total knee arthroplasty in patients with skeletal dysplasia.

INTRODUCTION: Dwarfism is a challenge in arthroplasty. The anatomical features provide a lot of pitfalls. The aim of this study was to follow-up growth-restricted patients after endoprosthetic treatment. MATERIALS AND METHODS: 138 knee arthroplasties in patients with a height ≤150 cm between January 1, 2000 and May 5, 2013 at our institution were enrolled in this study. 124 cases were available for 1-year follow-up. Out of these, 43 cases were available for 5-year follow-up so far. 14 patients were lost to follow-up. RESULTS: IKS score increased from 35 ± 16 on admission to 67 ± 22 (p < 0.001) at 1-year follow-up and 65 ± 23 (p < 0.001) at 5-year follow-up. Function Score increased from 40 ± 29 on admission to 64 ± 21 (p < 0.001) at 1-year follow-up and 63 ± 23 (p < 0.001) at 5-year follow-up. Revision surgery was required in one case (0.8 %) after 1-year follow-up, and in an additional three cases (7 %) after 5-year follow-up. CONCLUSIONS: Knee arthroplasty can be performed in patients suffering from dwarfism with good clinical benefits. However, survival rates are worse compared to the general population.

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.

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.

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.