Does Exposure to Stressors Predict Changes in Physiological Dysregulation?

Background

The allostatic load framework implies that cumulative exposure to stressors results in multi-system physiological dysregulation.

Purpose

The purpose of this study was to investigate the effect of stress burden on subsequent changes (2000–2006) in physiological dysregulation.

Methods

Data came from a population-based cohort study in Taiwan (n?=?521, aged 54+ in 2000, re-examined in 2006). Measures of stressful events and chronic strain were based on questions asked in 1996, 1999, and 2000. A measure of trauma was based on exposure to the 1999 earthquake. Dysregulation was based on 17 biomarkers (e.g., metabolic, inflammatory, neuroendocrine).

Results

There were some small effects among men: chronic strain was associated with subsequent increases in dysregulation (standardized β?=?0.08, 95 % CI?=?0.01 to 0.20), particularly inflammation; life events were also associated with increased inflammation (β?=?0.10, CI?=?0.01 to 0.26). There were no significant effects in women.

Conclusions

We found weak evidence that stress burden is associated with changes in dysregulation.     

Setting Up a Successful Vagus Nerve Stimulation Service for Patients With Difficult-to-Treat Depression

BackgroundA substantial number of patients with major depressive disorder (MDD) do not sufficiently remit after the first lines of antidepressant treatments, making them vulnerable to poor clinical outcomes. Patients who have not had adequate resolution of their depressive symptoms after four antidepressant treatments and/or have been experiencing their current episode of MDD for two years or more (with insufficient responses to adequate antidepressant treatments) should be evaluated for antidepressant vagus nerve stimulation (VNS Therapy). Adjunctive VNS Therapy is a promising long-term treatment option for patients with difficult-to-treat depression (DTD), offering significantly improved remission rates in comparison with usual treatments. However, VNS Therapy requires specialized treatment centers to support patients.Materials and MethodsIn this narrative review, we aim to outline the necessary steps for setting up an antidepressant VNS Therapy service in an efficient manner.ResultsEstablishing a VNS Therapy service requires several high-level considerations: initiation of a collaborative multidisciplinary team of health care professionals; developing a surgical pathway for implantation; consideration of reimbursement and health care coverage; setting up a specialist clinic to identify optimal candidates for VNS Therapy; educating patients and their families about VNS Therapy; and training health care providers on patient-specific VNS Therapy treatment and long-term treatment management.ConclusionsAntidepressant VNS Therapy is a promising treatment option for the long-term treatment of patients with DTD. We have successfully initiated four VNS Therapy service centers for DTD in the United States, Austria, and Germany. Based on our experiences and lessons learned, herein, we have provided advice to psychiatric centers planning to set up a VNS Therapy service for their patients with DTD.     

Comparison of renal function detriments after local tumor ablation or partial nephrectomy for renal cell carcinoma

Purpose

Local tumor ablation (LTA) and partial nephrectomy (PN) represent treatment alternatives for patients diagnosed with small renal mass and both may result in renal function detriments. The aim of the study was to compare renal function detriments after LTA or PN.

Methods

A Surveillance epidemiology and End Results-Medicare-linked retrospective cohort of 2850 T1 kidney cancer patients who underwent LTA or PN was abstracted. Short-term outcomes consisted of 30-day acute kidney injury (AKI) and 30-day dialysis rates. Long-term outcomes consisted of episodes of AKI, mild and moderate–severe chronic kidney disease (CKD), end-stage renal disease, hemodialysis and anemia in CKD. Analyses consisted of propensity score matching, logistic and Cox regression.

Results

After propensity score matching, 1122 patients remained. The 30-day incidence of AKI was 4.6 % after LTA and 9.4 % after PN. In multivariable analyses (MVAs), LTA was associated with a lower AKI rate (OR 0.42; p = 0.001). The 30-day incidence of any dialysis was <2 % after either LTA or PN. In MVA, LTA was not associated with a lower rate of any dialysis (OR 0.43; p = 0.2). At long-term assessment, both the unadjusted and adjusted rates of all six examined end points were not different between LTA and PN (all p > 0.5).

Conclusions

LTA offers short-term protective effect from AKI. The short-term rates of any dialysis treatment are similar after either LTA or PN. At long-term assessment, LTA and PN renal function detriment rates are not different. Concern for long-term functional outcomes should not be a barrier for PN.

     

Exploring the broader health and well-being outcomes of mining communities in low- and middle-income countries: A systematic review

Health and well-being outcomes in communities living in proximity to mining activity may be influenced by a broad spectrum of factors including population growth, economic instability or land degradation. This review aims to synthesise broader outcomes associated with mining activity and in doing so, further explore possible determinants in communities of low- and middle-income countries. Four databases were systematically searched and articles were included if the study targeted adults residing in proximity to mining activity, and measured individual or community-level health or well-being outcomes. Narrative synthesis was conducted. Twelve articles were included. Mining was perceived to influence health behaviours, employment conditions, livelihoods and socio-political factors, which were linked to poorer health outcomes. Family relationships, mental health and community cohesion were negatively associated with mining activity. High-risk health behaviours, population growth and changes in vector ecology from environmental modification were associated with increased infectious disease prevalence. This review presents the broader health and well-being outcomes and their determinants, and strengthens the evidence to improve measurement and management of the public health implications of mining. This will support the mining sector to make sustainable investments, and support governments to maximise community development and minimise negative impacts.     

Applying Kane’s validity framework to a simulation based assessment of clinical competence

Assessment of clinical competence is complex and inference based. Trustworthy and defensible assessment processes must have favourable evidence of validity, particularly where decisions are considered high stakes. We aimed to organize, collect and interpret validity evidence for a high stakes simulation based assessment strategy for certifying paramedics, using Kane’s validity framework, which some report as challenging to implement. We describe our experience using the framework, identifying challenges, decisions points, interpretations and lessons learned. We considered data related to four inferences (scoring, generalization, extrapolation, implications) occurring during assessment and treated validity as a series of assumptions we must evaluate, resulting in several hypotheses and proposed analyses. We then interpreted our findings across the four inferences, judging if the evidence supported or refuted our proposed uses of the assessment data. Data evaluating “Scoring” included: (a) desirable tool characteristics, with acceptable inter-item correlations (b) strong item-total correlations (c) low error variance for items and raters, and (d) strong inter-rater reliability. Data evaluating “Generalizability” included: (a) a robust sampling strategy capturing the majority of relevant medical directives, skills and national competencies, and good overall and inter-station reliability. Data evaluating “Extrapolation” included: low correlations between assessment scores by dimension and clinical errors in practice. Data evaluating “Implications” included low error rates in practice. Interpreting our findings according to Kane’s framework, we suggest the evidence for scoring, generalization and implications supports use of our simulation-based paramedic assessment strategy as a certifying exam; however, the extrapolation evidence was weak, suggesting exam scores did not predict clinical error rates. Our analysis represents a worked example others can follow when using Kane’s validity framework to evaluate, and iteratively develop and refine assessment strategies.     

Comparative Effectiveness of Robot-assisted Versus Open Radical Prostatectomy Cancer Control

Background

Robot-assisted radical prostatectomy (RARP) remains controversial, and no improvement in cancer control outcomes has been demonstrated over open radical prostatectomy (ORP).

Objective

To examine population-based, comparative effectiveness of RARP versus ORP pertaining surgical margin status and use of additional cancer therapy.

Design, setting, and participants

This was a retrospective observational study of 5556 RARP and 7878 ORP cases from 2004 to 2009 from Surveillance Epidemiology and End Results–Medicare linked data.

Intervention

RARP versus ORP.

Outcome measurements and statistical analysis

Propensity-based analyses were performed to minimize treatment selection biases. Generalized linear regression models were computed for comparison of RP surgical margin status and use of additional cancer therapy (radiation therapy [RT] or androgen deprivation therapy [ADT]) by surgical approach.

Results and limitations

In the propensity-adjusted analysis, RARP was associated with fewer positive surgical margins (13.6% vs 18.3%; odds ratio [OR]: 0.70; 95% confidence interval [CI], 0.66–0.75), largely because of fewer RARP positive margins for intermediate-risk (15.0% vs 21.0%; OR: 0.66; 95% CI, 0.59–0.75) and high-risk (15.1% vs 20.6%; OR: 0.70; 95% CI, 0.63–0.77) disease. In addition, RARP was associated with less use of additional cancer therapy within 6 mo (4.5% vs 6.2%; OR: 0.75; 95% CI, 0.69–0.81), 12 mo (OR: 0.73; 95% CI, 0.62–0.86), and 24 mo (OR: 0.67; 95% CI, 0.57–0.78) of surgery. Limitations include the retrospective nature of the study and the absence of prostate-specific antigen levels to determine biochemical recurrence.

Conclusions

RARP is associated with improved surgical margin status relative to ORP for intermediate- and high-risk disease and less use of postprostatectomy ADT and RT. This has important implications for quality of life, health care delivery, and costs.

Patient summary

Robot-assisted radical prostatectomy (RP) versus open RP is associated with fewer positive margins and better early cancer control because of less use of additional androgen deprivation and radiation therapy within 2 yr of surgery.     

Predicting Survival of Patients with Node-positive Prostate Cancer Following Multimodal Treatment

Background

According to the TNM staging system, patients with prostate cancer (PCa) with lymph node invasion (LNI) are considered a single-risk group. However, not all LNI patients share the same cancer control outcomes.

Objective

To develop and internally validate novel nomograms predicting cancer-specific mortality (CSM)–free rate in pN1 patients.

Design, setting, and participants

We evaluated 1107 patients with pN1 PCa treated with radical prostatectomy, pelvic lymph node dissection, and adjuvant therapy at two tertiary care centers between 1988 and 2010.

Outcome measurements and statistical analysis

Univariable and multivariable Cox regression models tested the relationship between CSM and patient clinical and pathologic characteristics, which consisted of prostate-specific antigen (PSA) value, pathologic Gleason score, pathologic tumor stage, status of surgical margins, number of positive lymph nodes, and status of adjuvant therapy. A Cox regression coefficient-based nomogram was developed and internally validated.

Results and limitations

All 1107 patients received adjuvant hormonal therapy (aHT). Additionally, 35% of patients received adjuvant radiotherapy (aRT). The 10-yr CSM-free rate was 84% in the entire cohort and 87% in patients treated with aRT plus aHT versus 82% in patients treated with aHT alone (p = 0.08). At multivariable analyses, PSA value, pathologic Gleason score, pathologic tumor stage, surgical margin status, number of positive lymph nodes, and aRT status were statistically significant predictors of CSM (all p ≤ 0.04). Based on these predictors, nomograms were developed to predict the 10-yr CSM-free rate in the overall patient population and in men with biochemical recurrence. These models showed high discrimination accuracy (79.5–83.3%) and favorable calibration characteristics. These results are limited by their retrospective nature.

Conclusions

Some patients with pN1 PCa have favorable CSM-free rates at 10 yr. We developed and internally validated the first nomograms that allow an accurate prediction of the CSM-free rate in these patients at an individual level.     

Mental health outcomes in elderly men with prostate cancer

ObjectiveTo examine the burden of mental health issues (MHI), namely anxiety, depressive disorders, and suicide, in a population-based cohort of older men with localized prostate cancer and to evaluate associations with primary treatment modality.Patients and methodsA total of 50,856 men, who were 65 years of age or older with clinically localized prostate cancer diagnosed between 1992 and 2005 and without a diagnosis of mental illness at baseline, were abstracted from the Surveillance, Epidemiology, and End Results–Medicare database. The primary outcome of interest was the development of MHI (anxiety, major depressive disorder, depressive disorder not elsewhere classified, neurotic depression, adjustment disorder with depressed mood, and suicide) after the diagnosis of prostate cancer.ResultsA total of 10,389 men (20.4%) developed MHI during the study period. Independent risk factors for MHI included age≥75 years (hazard ratio [HR] = 1.29); higher comorbidity (Charlson comorbidity index≥3, HR = 1.63); rural hospital location (HR = 1.14); being single, divorced, or widowed (HR = 1.12); later year of diagnosis (HR = 1.05); and urinary incontinence (HR = 1.47). Black race (HR = 0.79), very high-income status (HR = 0.87), and definitive treatment (radical prostatectomy [RP], HR = 0.79; radiotherapy [RT], HR= 0.85, all P<0.001) predicted a lower risk of MHI. The rates of MHI at 10 years were 29.7%, 29.0%, and 22.6% in men undergoing watchful waiting (WW), RT, and RP, respectively.ConclusionOlder men with localized prostate cancer had a significant burden of MHI. Men treated with RP or RT were at a lower risk of developing MHI, compared with those undergoing WW, with median time to development of MHI being significantly greater in those undergoing RP compared with those undergoing RT or WW.