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Evaluation of Provider Screening Practices for Fracture Risk Assessment among Patients with HIV Disease
Get PDFPeople living with HIV are known to have greater risk of low bone mineral density than HIV-negative peers. The reasons for this disparity are multifactorial. To address this increased risk, the Infectious Diseases Society of America (IDSA) released fracture risk screening recommendations in 2015, which differ significantly from recommendations that apply to the general population. A study was conducted at the University of Connecticut to assess for provider awareness and adherence to these recommendations. Electronic surveys were sent to providers, and patients were also surveyed for risk factors and prevalence of low bone mineral density. The results of the provider survey showed low rates of awareness of the IDSA screening recommendations. A substantial proportion of patients surveyed met criteria for low BMD screening but did not have dual-energy X-ray absorptiometry (DXA) ordered by their provider. As an intervention, providers were sent information via e-mail regarding current screening recommendations, as well as notifications if their patient met criteria for DXA screening. A twelve-month follow-up survey showed increased provider knowledge of screening recommendations and improved screening practices. Additionally, the results of a logistic regression analysis of patient factors showed that increasing age and male sex were positively associated with fragility fracture risk. Increased duration of antiretroviral therapy use was associated with a lower likelihood of fragility fracture.
1. Introduction
The risk of low bone mineral density (BMD) and its associated complications including fracture are significantly higher in people living with HIV (PLWH) compared to the uninfected population [1, 2]. The mechanisms leading to this disparity are multifactorial; some are likely related to viral factors, others to antiretroviral therapy (ART) [3, 4]. Secondary osteoporosis risk factors (i.e., malnutrition, coinfection with hepatitis C, substance abuse including tobacco, and alcohol dependence) also have a higher prevalence in the HIV positive population [5, 6]. HIV-infected men frequently develop low serum testosterone levels with aging, further predisposing to bone loss [2, 7]. Furthermore, several studies have found that more than 90 percent of PLWH have 25-hydroxy vitamin D deficiency [8].
To address the increased risk of low BMD in HIV patients, the Infectious Diseases Society of America (IDSA) released fracture risk screening recommendations in 2015 [1]. These significantly differ from screening practices recommended for the general population [9] but are consistent with more recent recommendations from the European AIDS Clinical Society [10]. Specifically, all HIV patients older than 40 years old should be screened for fracture risk using the Fracture Risk Assessment Tool (FRAX) [1]. Dual-energy X-ray absorptiometry (DXA) should also be used in addition to FRAX scores in men aged ≥50 years, postmenopausal women, patients with a history of fragility fracture, patients receiving chronic glucocorticoid treatment, and patients at high risk of falls [1]. Additionally, current guidelines suggest inclusion of HIV infection as a cause of secondary osteoporosis in the FRAX questionnaire [10].
Provider adherence rates to the IDSA screening recommendations are unknown, but there are likely many PLWH who meet criteria for screening and are missed. Primary care providers (PCPs) are less likely to be aware of HIV specific guidelines and may trust instead that this will be addressed by their patient’s Infectious Disease (ID) provider. Simultaneously, ID providers might assume that, as with the general population, screening would be performed by the PCP. ID providers may also be less comfortable testing and treating any underlying bone disease that they may uncover. Bone health screening in patients with HIV, therefore, represents an area of care in danger of falling between the cracks of primary and specialty care for PLWH.
The goal of this study was to evaluate provider knowledge and adherence to recent recommendations from international societies and to evaluate the efficacy of an intervention designed to improve provider knowledge and adherence at an academic medical center. In addition, we evaluated our cohort of patients to independently assess the prevalence of risk factors associated with fragility fracture in PLWH
Development of models for cervical cancer screening: construction in a cross-sectional population and validation in two screening cohorts in China
Get PDFCurrent methods for cervical cancer screening result in an increased number of referrals and unnecessary diagnostic procedures. This study aimed to develop and evaluate a more accurate model for cervical cancer screening.
Methods
Multiple predictors including age, cytology, high-risk human papillomavirus (hrHPV) DNA/mRNA, E6 oncoprotein, HPV genotyping, and p16/Ki-67 were used for model construction in a cross-sectional population including women with normal cervix (N = 1085), cervical intraepithelial neoplasia (CIN, N = 279), and cervical cancer (N = 551) to predict CIN2+ or CIN3+. A base model using age, cytology, and hrHPV was calculated, and extended versions with additional biomarkers were considered. External validations in two screening cohorts with 3-year follow-up were further conducted (NCohort-I = 3179, NCohort-II = 3082).
Results
The base model increased the area under the curve (AUC, 0.91, 95% confidence interval [CI] = 0.88–0.93) and reduced colposcopy referral rates (42.76%, 95% CI = 38.67–46.92) compared to hrHPV and cytology co-testing in the cross-sectional population (AUC 0.80, 95% CI = 0.79–0.82, referrals rates 61.62, 95% CI = 59.4–63.8) to predict CIN2+. The AUC further improved when HPV genotyping and/or E6 oncoprotein were included in the base model. External validation in two screening cohorts further demonstrated that our models had better clinical performances than routine screening methods, yielded AUCs of 0.92 (95% CI = 0.91–0.93) and 0.94 (95% CI = 0.91–0.97) to predict CIN2+ and referrals rates of 17.55% (95% CI = 16.24–18.92) and 7.40% (95% CI = 6.50–8.38) in screening cohort I and II, respectively. Similar results were observed for CIN3+ prediction.
Conclusions
Compared to routine screening methods, our model using current cervical screening indicators can improve the clinical performance and reduce referral rates
The association between mechanical ventilator compatible bed occupancy and mortality risk in intensive care patients with COVID-19: a national retrospective cohort study
Get PDFThe literature paints a complex picture of the association between mortality risk and ICU strain.
In this study, we sought to determine if there is an association between mortality risk in intensive care units (ICU) and occupancy of beds compatible with mechanical ventilation, as a proxy for strain.
Methods
A national retrospective observational cohort study of 89 English hospital trusts (i.e. groups of hospitals functioning as single operational units). Seven thousand one hundred thirty-three adults admitted to an ICU in England between 2 April and 1 December, 2020 (inclusive), with presumed or confirmed COVID-19, for whom data was submitted to the national surveillance programme and met study inclusion criteria. A Bayesian hierarchical approach was used to model the association between hospital trust level (mechanical ventilation compatible), bed occupancy, and in-hospital all-cause mortality. Results were adjusted for unit characteristics (pre-pandemic size), individual patient-level demographic characteristics (age, sex, ethnicity, deprivation index, time-to-ICU admission), and recorded chronic comorbidities (obesity, diabetes, respiratory disease, liver disease, heart disease, hypertension, immunosuppression, neurological disease, renal disease).
Results
One hundred thirty-five thousand six hundred patient days were observed, with a mortality rate of 19.4 per 1000 patient days. Adjusting for patient-level factors, mortality was higher for admissions during periods of high occupancy (> 85% occupancy versus the baseline of 45 to 85%) [OR 1.23 (95% posterior credible interval (PCI): 1.08 to 1.39)]. In contrast, mortality was decreased for admissions during periods of low occupancy (< 45% relative to the baseline) [OR 0.83 (95% PCI 0.75 to 0.94)].
Conclusion
Increasing occupancy of beds compatible with mechanical ventilation, a proxy for operational strain, is associated with a higher mortality risk for individuals admitted to ICU. Further research is required to establish if this is a causal relationship or whether it reflects strain on other operational factors such as staff. If causal, the result highlights the importance of strategies to keep ICU occupancy low to mitigate the impact of this type of resource saturation
Genome-wide association study followed by trans-ancestry meta-analysis identify 17 new risk loci for schizophrenia
Get PDFOver 200 schizophrenia risk loci have been identified by genome-wide association studies (GWASs). However, the majority of risk loci were identified in populations of European ancestry (EUR), potentially missing important biological insights. It is important to perform 5 GWASs in non-European populations.
Methods
To identify novel schizophrenia risk loci, we conducted a GWAS in Han Chinese population (3493 cases and 4709 controls). We then performed a large-scale meta-analysis (a total of 143,438 subjects) through combining our results with previous GWASs conducted in EAS and EUR. In addition, we also carried out comprehensive post-GWAS analysis, including heritability partitioning, enrichment of schizophrenia associations in tissues and cell types, trancscriptome-wide association study (TWAS), expression quantitative trait loci (eQTL) and differential expression analysis.
Results
We identified two new schizophrenia risk loci, including associations in SHISA9 (rs7192086, P = 4.92 × 10-08) and PES1 (rs57016637, P = 2.33 × 10−11) in Han Chinese population. A fixed-effect meta-analysis (a total of 143,438 subjects) with summary statistics from EAS and EUR identifies 15 novel genome-wide significant risk loci. Heritability partitioning with linkage disequilibrium score regression (LDSC) reveals a significant enrichment of schizophrenia heritability in conserved genomic regions, promoters, and enhancers. Tissue and cell-type enrichment analyses show that schizophrenia associations are significantly enriched in human brain tissues and several types of neurons, including cerebellum neurons, telencephalon inhibitory, and excitatory neurons. Polygenic risk score profiling reveals that GWAS summary statistics from trans-ancestry meta-analysis (EAS + EUR) improves prediction performance in predicting the case/control status of our sample. Finally, transcriptome-wide association study (TWAS) identifies risk genes whose cis-regulated expression change may have a role in schizophrenia.
Conclusions
Our study identifies 17 novel schizophrenia risk loci and highlights the importance and necessity of conducting genetic study in different populations. These findings not only provide new insights into genetic etiology of schizophrenia, but also facilitate to delineate the pathophysiology of schizophrenia and develop new therapeutic targets
How to Treat Proximal and Middle One-Third Humeral Shaft Fractures: The Role of Helical Plates
Get PDFComplex proximal third diaphyseal humeral fractures are uncommon patterns of injury mainly caused by high energy trauma. The anatomical shape of the humerus, the presence of the deltoid tuberosity and the close proximity of the radial nerve into the radial groove represent challenge elements to deal with. Historically, straight plates were manually twisted; subsequently, helical plates created for other anatomical sites (as distal tibia) were used in humeral fractures. In both these experiences surgeons observed several disadvantages. More recently, dedicated helical plates have been created. In this study, we expose our surgical technique for using helical humeral plates (A.L.P.S.® Proximal Humeral Plating System, Zimmer Biomet), with its advantages and operative recommendation. From 2019 to 2021, nine patients who were admitted to our institution for humeral fractures involving the proximal third diaphysis have been treated with humeral helical plates. At one and six months after surgery, standard antero-posterior and lateral radiographs were obtained, and at last follow-up (fourteen months on average) clinical evaluation was performed through range of motion assessment, Constant score and DASH score questionnaires. At six months, all fractures have healed. At last follow-up (fourteen months on average, 6–22) the average range of motion were flexion 135° (90–180°); abduction 124° (85–180°); external rotation 52° (20–80°), internal rotation at L3 (between scapulae-trochanter). Average Constant Shoulder Score was 70 (33–96), average Dash score was 21 (range 1,7–63). Three patients experienced temporary radial nerve palsy from injury, with subsequently improvement at EMG analysis within eight months from surgery. In our opinion this strategy avoids the deltoid tuberosity and reduces the risk of radial nerve injury, increasing the possibility of a rapid functional recovery after surgery
Ectopic Laryngeal Ossification after Bone Morphogenetic Protein-2
Get PDFWe report two cases of ectopic bone formation in the head and neck following treatment with recombinant human bone morphogenetic protein-2 (rhBMP-2). Surgical pathologic data, laryngoscopy imaging, CT imaging, and patient medical history were obtained. First, we report osseous metaplasia in the vocal fold in a 67-year-old male following mandibular dental implants with rhBMP-2; second, a case of severe bony overgrowth of the larynx and fusion to the anterior cervical spine (ACS) in a 73-year-old male following multiple anterior cervical discectomies and fusions with rhBMP-2. Ectopic bone formation following rhBMP-2 has been previously reported. Adverse events like local swelling and edema leading to dysphagia and even airway obstruction after cervical spine application of rhBMP-2 have also been widely reported. Due to the uncommon nature of abnormal bony growth in soft tissue areas of the head and neck and the previously documented adverse effects of rhBMP-2 use, especially in the cervical spine, we consider the two unusual case presentations of ectopic bony formation highly likely to be linked with rhBMP-2. We urge awareness of the adverse effects caused by rhBMP-2, and urge caution in dosin
[18F]-FDG PET/CT of the Pulmonary Benign Metastasizing Leiomyoma in a Breast Cancer Patient: A Case Report
Get PDF18F-fluorodeoxyglucose ([18F]-FDG) positron emission tomography/computed tomography (PET/CT) is a useful functional image technique to evaluate the disease extent in many cancers, as well as differentiate benign disease from malignant metastasis. We report the case of a 49-year-old woman with breast cancer and suspected lung metastasis by conventional images. After FDG-PET/CT demonstrating faint, or even no FDG uptake in bilateral pulmonary nodules, accompanied with obvious uterine fibroids, benign metastasizing leiomyoma (BML) of the lung was included in a differential diagnosis and finally confirmed by surgical pathology. FDG PET/CT showed its value in the diagnosis of BML in the breast cancer patient who was misleading as lung metastasis during outpatient follow-u
Humoral immune responses during SARS-CoV-2 mRNA vaccine administration in seropositive and seronegative individuals
Get PDFThe global pandemic of coronavirus disease 2019 (COVID-19) is caused by infection with the SARS-CoV-2 virus. Currently, there are three approved vaccines against SARS-CoV-2 in the USA, including two based on messenger RNA (mRNA) technology that has demonstrated high vaccine efficacy. We sought to characterize humoral immune responses, at high resolution, during immunization with the BNT162b2 (Pfizer-BioNTech) vaccine in individuals with or without prior history of natural SARS-CoV-2 infection.
Methods
We determined antibody responses after each dose of the BNT162b2 SARS-CoV-2 vaccine in individuals who had no prior history of SARS-CoV-2 infection (seronegative) and individuals that had previous viral infection 30–60 days prior to first vaccination (seropositive). To do this, we used both an antibody isotype-specific multiplexed bead-based binding assays targeting multiple SARS-CoV-2 viral protein antigens and an assay that identified potential SARS-CoV-2 neutralizing antibody levels. Moreover, we mapped antibody epitope specificity after immunization using SARS-CoV-2 spike protein peptide arrays.
Results
Antibody levels were significantly higher after a single dose in seropositive individuals compared to seronegative individuals and were comparable to levels observed in seronegative individuals after two doses. While IgG was boosted by vaccination for both seronegative and seropositive individuals, only seronegative individuals had increased IgA or IgM antibody titers after primary immunization. We identified immunodominant peptides targeted on both SARS-CoV-2 spike S1 and S2 subunits after vaccination.
Conclusion
These findings demonstrated the antibody responses to SARS-CoV-2 immunization in seropositive and seronegative individuals and provide support for the concept of using prior infection history as a guide for the consideration of future vaccination regimens. Moreover, we identified key epitopes on the SARS-CoV-2 spike protein that are targeted by antibodies after vaccination that could guide future vaccine and immune correlate development
A core outcome set for studies evaluating interventions to prevent and/or treat delirium for adults requiring an acute care hospital admission: an international key stakeholder informed consensus study
Get PDFTrials of interventions to prevent or treat delirium in adults in an acute hospital setting report heterogeneous outcomes. Our objective was to develop international consensus among key stakeholders for a core outcome set (COS) for future trials of interventions to prevent and/or treat delirium in adults with an acute care hospital admission and not admitted to an intensive care unit.
Methods
A rigorous COS development process was used including a systematic review, qualitative interviews, modified Delphi consensus process, and in-person consensus using nominal group technique (registration http://www.comet- initiative.org/studies/details/796).
Participants in qualitative interviews were delirium survivors or family members. Participants in consensus methods comprised international representatives from three stakeholder groups: researchers, clinicians, and delirium survivors and family members.
Results
Item generation identified 8 delirium-specific outcomes and 71 other outcomes from 183 studies, and 30 outcomes from 18 qualitative interviews, including 2 that were not extracted from the systematic review. De-duplication of outcomes and formal consensus processes involving 110 experts including researchers (N = 32), clinicians (N = 63), and delirium survivors and family members (N = 15) resulted in a COS comprising 6 outcomes: delirium occurrence and reoccurrence, delirium severity, delirium duration, cognition, emotional distress, and health-related quality of life. Study limitations included exclusion of non-English studies and stakeholders and small representation of delirium survivors/family at the in-person consensus meeting
Gestational diabetes mellitus is associated with the neonatal gut microbiota and metabolome
Get PDFGestational diabetes mellitus (GDM) is a metabolic disease that occurs in pregnant women and increases the risk for the development of diabetes. The relationship between GDM and meconium microbiota and metabolome remains incompletely understood.
Methods
Four hundred eighteen mothers (147 women with GDM and 271 normal pregnant women) and their neonates from the GDM Mother and Child Study were included in this study. Meconium microbiota were profiled by 16S rRNA gene sequencing. Meconium and maternal serum metabolome were examined by UPLC-QE.
Results
Microbial communities in meconium were significantly altered in neonates from the GDM mothers. A reduction in alpha diversity was observed in neonates of GDM mothers. At the phylum level, the abundance of Firmicutes and Proteobacteria changed significantly in neonates of GDM mothers. Metabolomic analysis of meconium showed that metabolic pathways including taurine and hypotaurine metabolism, pyrimidine metabolism, beta-alanine metabolism, and bile acid biosynthesis were altered in GDM subjects. Several changed metabolites varying by the similar trend across the maternal serum and neonatal meconium were observed.
Conclusion
Altogether, these findings suggest that GDM could alter the serum metabolome and is associated with the neonatal meconium microbiota and metabolome, highlighting the importance of maternal factors on early-life metabolism