Elevated serum beta-2-microglobulin — A prognostic marker for development of AIDS among patients with persistent generalized lymphadenopathy

Summary For evaluation of its prognostic value, the level of serum -2-microglobulin was determined in early serum samples from 88 patients with persistent generalized lymphadenopathy in a prospective longitudinal study. Patients with serum -2-microglobulin >2.6 mg/l were found to have a significantly higher risk of developing AIDS earlier when compared to patients with a lower level (p<0.001).

---

Erhöhte -2-Mikroglobulin-Serumspiegel — prognostischer Marker für den Übergang in AIDS bei Patienten mit persistierender, generalisierter Lymphadenopathie

Zusammenfassung In einer prospektiven longitudinalen Studie wurden in frühen Serumproben von 88 Patienten mit persistierender generalisierter Lymphadenopathie Messungen des -2-Mikroglobulin-Spiegels vorgenommen, um dessen Wert als prognostischer Faktor zu bestimmen. Das Risiko für den Übergang in AIDS erwies sich bei Patienten mit -2-Mikroglobulin-Spiegeln von >2,6 mg/l als signifikant höher als bei Patienten mit niedrigeren Spiegeln (p<0,001).

     

Identifying Goals of Care Conversations in the Electronic Health Record Using Natural Language Processing and Machine Learning

ContextGoals-of-care discussions are an important quality metric in palliative care. However, goals-of-care discussions are often documented as free text in diverse locations. It is difficult to identify these discussions in the electronic health record (EHR) efficiently.ObjectivesTo develop, train, and test an automated approach to identifying goals-of-care discussions in the EHR, using natural language processing (NLP) and machine learning (ML).MethodsFrom the electronic health records of an academic health system, we collected a purposive sample of 3183 EHR notes (1435 inpatient notes and 1748 outpatient notes) from 1426 patients with serious illness over 2008–2016, and manually reviewed each note for documentation of goals-of-care discussions. Separately, we developed a program to identify notes containing documentation of goals-of-care discussions using NLP and supervised ML. We estimated the performance characteristics of the NLP/ML program across 100 pairs of randomly partitioned training and test sets. We repeated these methods for inpatient-only and outpatient-only subsets.ResultsOf 3183 notes, 689 contained documentation of goals-of-care discussions. The mean sensitivity of the NLP/ML program was 82.3% (SD 3.2%), and the mean specificity was 97.4% (SD 0.7%). NLP/ML results had a median positive likelihood ratio of 32.2 (IQR 27.5–39.2) and a median negative likelihood ratio of 0.18 (IQR 0.16–0.20). Performance was better in inpatient-only samples than outpatient-only samples.ConclusionUsing NLP and ML techniques, we developed a novel approach to identifying goals-of-care discussions in the EHR. NLP and ML represent a potential approach toward measuring goals-of-care discussions as a research outcome and quality metric.     

Depressive symptoms and serum lipid levels in young adult women

Accumulating data suggest that depression is associated with risk factors for cardiovascular disease, but few studies have investigated potential behavioral mediators of such associations, particularly among women. In this study of healthy young adult women (n = 225), we examined associations among depressive symptoms, health behaviors, and serum lipid levels. Depressive symptoms were assessed with the 20-item Center for Epidemiologic Studies-Depression scale, and a fasting blood sample was obtained for serum lipid levels, including total cholesterol, high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C). Diet was measured using 24-h recalls, and other health behaviors (physical activity, smoking) were assessed via self-report questionnaire. Results indicated a modest negative association between depressive symptoms and LDL-C levels. Higher levels of depressive symptoms were also associated with lower total and insoluble dietary fiber intake, both of which were associated with HDL-C and LDL-C. Mediational analyses indicated a significant indirect effect of depressive symptoms on LDL-C via total and insoluble dietary fiber in unadjusted analyses, but not in adjusted analyses. The present findings suggest that depressive symptoms are inversely associated with serum LDL-C levels in young adult women, but that these associations are not likely mediated by adverse lifestyle behaviors.     

Investigation of the Relationship Between Prostate Cancer and MSMB and NCOA4 Genetic Variants and Protein Expression

Two genome‐wide association studies (GWAS) identified the β‐microseminoprotein (MSMB) promoter SNP, rs10993994:C>T, as significantly associated with prostate cancer (PC) risk. Follow‐up studies demonstrate that the variant allele directly affects expression of the MSMB‐encoded protein, PSP94, and also suggest that it affects mRNA expression levels of an adjacent gene, NCOA4, which is involved in androgen receptor transactivation. In a population‐based study of 1,323 cases and 1,268 age‐matched controls, we found the NCOA4 SNP, rs7350420:T>C, was associated with a 15% reduction in PC risk, but the association was not significant after adjustment for the rs10993994:C>T genotype. Tumor tissue microarrays of 519 radical prostatectomy patients were used to measure PSP94 and NCOA4 protein expression. Taken together, these data confirm that the rs10993994:C>T variant allele is associated with decreased PSP94 expression, and the association is stronger in tumor compared to normal prostate tissue. No association was observed between rs10993994:C>T and NCOA4 expression, and only moderate associations were seen between two NCOA4 SNPs, rs10761618:T>C and rs7085433:G>A, and NCOA4 protein expression. These data indicate that the increase in PC risk associated with rs10993994:C>T is likely mediated by the variant's effect on PSP94 expression; however, this effect does not extend to NCOA4 in the data presented here.     

Clarifying values: an updated review

Background

Consensus guidelines have recommended that decision aids include a process for helping patients clarify their values. We sought to examine the theoretical and empirical evidence related to the use of values clarification methods in patient decision aids.

Methods

Building on the International Patient Decision Aid Standards (IPDAS) Collaboration’s 2005 review of values clarification methods in decision aids, we convened a multi-disciplinary expert group to examine key definitions, decision-making process theories, and empirical evidence about the effects of values clarification methods in decision aids. To summarize the current state of theory and evidence about the role of values clarification methods in decision aids, we undertook a process of evidence review and summary.

Results

Values clarification methods (VCMs) are best defined as methods to help patients think about the desirability of options or attributes of options within a specific decision context, in order to identify which option he/she prefers. Several decision making process theories were identified that can inform the design of values clarification methods, but no single “best” practice for how such methods should be constructed was determined. Our evidence review found that existing VCMs were used for a variety of different decisions, rarely referenced underlying theory for their design, but generally were well described in regard to their development process. Listing the pros and cons of a decision was the most common method used. The 13 trials that compared decision support with or without VCMs reached mixed results: some found that VCMs improved some decision-making processes, while others found no effect.

Conclusions

Values clarification methods may improve decision-making processes and potentially more distal outcomes. However, the small number of evaluations of VCMs and, where evaluations exist, the heterogeneity in outcome measures makes it difficult to determine their overall effectiveness or the specific characteristics that increase effectiveness.

     

Medication-related osteonecrosis of the jaw: A literature review

BackgroundAntiresorptive agents such as bisphosphonates and denosumab, as well as angiogenesis inhibitors, may induce medication-related osteonecrosis of the jaw (MRONJ). However, the exact mechanisms of MRONJ are unclear and definitive treatment strategies have not yet been developed. Moreover, the aging population requiring antiresorptive agents and angiogenesis inhibitors has been increasing worldwide. Therefore, the aim of this literature review was to introduce the latest information on MRONJ. The epidemiology, triggering factors, risk factors, drug holiday, pathoetiology and treatment strategies for each drug-induced ONJ were investigated by conducting a PubMed search.HighlightThe prevalence and incidence of ONJ were very low. Some mechanisms of ONJ have been identified, although they were not definitive. Novel treatment strategies have been proposed in basic and clinical research. Several factors, including age and the administration duration of bisphosphonates, are risks for the development of bisphosphonate-related ONJ (BRONJ). Dental implant therapy and peri-implantitis could become risk factors of BRONJ, regardless of the onset timing of bisphosphonates. No reliable information about ONJ induced by denosumab and angiogenesis inhibitors was found.ConclusionCaution should be taken when dental treatment including implant therapy is performed in patients receiving bisphosphonates, denosumab, and angiogenesis inhibitors. There is limited scientific evidence regarding the relationship between MRONJ and older age. Further ONJ-related research on the aging population is required to manage the treatment of such diseases in older people in the future.     

The influence of sex on cardiovascular outcomes associated with diabetes among older black and white adults

AimsIt is unknown whether sex differences in the association of diabetes with cardiovascular outcomes vary by race. We examined sex differences in the associations of diabetes with incident congestive heart failure (CHF) and coronary heart disease (CHD) between older black and white adults.MethodsWe analyzed data from the Cardiovascular Health Study (CHS), a prospective cohort study of community-dwelling individuals aged ≥ 65 from four US counties. We included 4817 participants (476 black women, 279 black men, 2447 white women and 1625 white men). We estimated event rates and multivariate-adjusted hazard ratios for incident CHF, CHD, and all-cause mortality by Cox regression and competing risk analyses.ResultsOver a median follow-up of 12.5 years, diabetes was more strongly associated with CHF among black women (HR, 2.42 [95% CI, 1.70–3.40]) than black men (1.39 [0.83–2.34]); this finding did not reach statistical significance (P for interaction = 0.08). Female sex conferred a higher risk for a composite outcome of CHF and CHD among black participants (2.44 [1.82–3.26]) vs. (1.44 [0.97–2.12]), P for interaction = 0.03). There were no significant sex differences in the HRs associated with diabetes for CHF among whites, or for CHD or all-cause mortality among blacks or whites. The three-way interaction between sex, race, and diabetes on risk of cardiovascular outcomes was not significant (P = 0.07).ConclusionsOverall, sex did not modify the cardiovascular risk associated with diabetes among older black or white adults. However, our results suggest that a possible sex interaction among older blacks merits further study.