Melanoma of unknown primary origin: A population-based study in the Netherlands

AimFew population-based studies have been published on melanoma of unknown primary origin (MUP). This study’s aim is to describe characteristics and survival of MUP patients in the Netherlands, based on nationwide data from the Netherlands Cancer Registry (NCR).MethodsPatient and tumour characteristics of MUP patients were retrieved from the NCR. Subgroups were made according to metastatic site: nodal or distant. Survival rates were calculated using the Kaplan–Meier method. To obtain a better insight in the composition and prognosis of the MUP group, the survival was compared to that of patients with melanoma of a known primary origin (MKP), tumour-node-metastasis (TNM) stage III and IV.ResultsOf all 33,181 melanoma patients diagnosed between 2003 and 2009, 2.6% (n = 857) were diagnosed with MUP. MUP patients with nodal metastases had a similar survival as MKP stage III with macroscopic nodal involvement. After stratification according to the number of involved lymph nodes, the survival of patients with nodal metastases with one involved lymph node was not significantly different between MUP and MKP. The survival of MUP patients with two or more involved lymph nodes was slightly worse than that of MKP stage III patients with macroscopic nodal involvement with two or more involved lymph nodes. MUP patients with distant metastases had a similar survival as MKP stage IV. After stratification according to number of metastatic sites and metastatic site category, the survival in MKP stage IV patients with (sub)cutaneous metastases was slightly worse than MUP distant patients with (sub)cutaneous metastases.ConclusionsThe results of this study imply that MUP patients form a heterogeneous group, and that MUP patients with nodal metastases could be classified as stage III melanoma with macroscopic nodal involvement, and MUP patients with distant metastases as stage IV melanoma.     

Chemical emissions from residential dryer vents during use of fragranced laundry products

Common laundry products, used in washing and drying machines, can contribute to outdoor emissions through dryer vents. However, the types and amounts of chemicals emitted are largely unknown. To investigate these emissions, we analyzed the volatile organic compounds (VOCs) both in the headspace of fragranced laundry products and in the air emitted from dryer vents during use of these products. In a controlled study of washing and drying laundry, we sampled emissions from two residential dryer vents during the use of no products, fragranced detergent, and fragranced detergent plus fragranced dryer sheet. Our analyses found more than 25 VOCs emitted from dryer vents, with the highest concentrations of acetaldehyde, acetone, and ethanol. Seven of these VOCs are classified as hazardous air pollutants (HAPs) and two as carcinogenic HAPs (acetaldehyde and benzene) with no safe exposure level, according to the US Environmental Protection Agency. As context for significance, the acetaldehyde emissions during use of one brand of laundry detergent would represent 3% of total acetaldehyde emissions from automobiles in the study area. Our study points to the need for additional research on this source of emissions and the potential impacts on human and environmental health.     

A subconvulsive dose of kainate selectively compromises astrocytic metabolism in the mouse brain in vivo

Despite the well-established use of kainate as a model for seizure activity and temporal lobe epilepsy, most studies have been performed at doses giving rise to general limbic seizures and have mainly focused on neuronal function. Little is known about the effect of lower doses of kainate on cerebral metabolism and particularly that associated with astrocytes. We investigated astrocytic and neuronal metabolism in the cerebral cortex of adult mice after treatment with saline (controls), a subconvulsive or a mildly convulsive dose of kainate. A combination of [1,2-¹³C]acetate and [1-¹³C]glucose was injected and subsequent nuclear magnetic resonance spectroscopy of cortical extracts was employed to distinctively map astrocytic and neuronal metabolism. The subconvulsive dose of kainate led to an instantaneous increase in the cortical lactate content, a subsequent reduction in the amount of [4,5-¹³C]glutamine and an increase in the calculated astrocytic TCA cycle activity. In contrast, the convulsive dose led to decrements in the cortical content and ¹³C labeling of glutamate, glutamine, GABA, and aspartate. Evidence is provided that astrocytic metabolism is affected by a subconvulsive dose of kainate, whereas a higher dose is required to affect neuronal metabolism. The cerebral glycogen content was dose-dependently reduced by kainate supporting a role for glycogen during seizure activity.     

Analysis of terrain effects on the interfacial force distribution at the hand and forearm during crutch gait

Forces transferred to the upper body during crutch use can lead to both short-term and long-term injuries, including joint pain, crutch palsy, and over-use injuries. While this force transmission has been studied in controlled laboratory settings, it is unclear how these forces are affected by irregular terrains commonly encountered during community ambulation. The purpose of this study was to determine the effects of walking speed and uneven terrain on the load magnitude, distribution, and rate of loading at the human-crutch contact surfaces. Our results show that the rates of loading were significantly increased with higher walking speeds and while negotiating certain irregular terrains, despite there being no apparent effect on the peak force transmission, suggesting load rate may be a more appropriate metric for assessing terrain effects on crutch gait. Furthermore, irrespective of the type of terrain and walking condition, the largest compressive forces were found to reside in the carpal-tunnel region of the hand, and may therefore be a primary contributor to carpal-tunnel injury.     

Psychoeducation for bipolar disorder: A discourse analysis

Psychoeducation has become a common intervention within mental health settings. It aims to increase people's ability to manage a life with a long‐term illness. For people with bipolar disorder, psychoeducation is one of a range of psychosocial interventions now considered part of contemporary mental health practice. It has taken on a ‘common sense’ status that results in little critique of psychoeducation practices. Using a published manual on psychoeducation and bipolar disorder as its data, Foucauldian discourse analysis was used in the present study for a critical perspective on psychoeducation in order to explore the taken‐for‐granted assumptions on which it is based. It identifies that the text produces three key subject positions for people with bipolar disorder. To practice self‐management, a person must: (i) accept and recognize the authority of psychiatry to know them; (ii) come to see that they can moderate themselves; and (iii) see themselves as able to undertake a reflexive process of self‐examination and change. These findings highlight the circular and discursive quality to the construct of insight that is central to how psychoeducation is practiced. Using Foucault's construct of pastoral power, it also draws attention to the asymmetrical nature of power relations between the clinician and the person with bipolar disorder. An effect of the use of medical discourse in psychoeducation is to limit its ability to work with ambivalence and contradiction. A critical approach to psychotherapy and education offers an alternate paradigm on which to basis psychoeducation practices.     

Effects of Tadalafil on Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia and on Erectile Dysfunction in Sexually Active Men with Both Conditions: Analyses of Pooled Data from Four Randomized,Placebo‐Controlled Tadalafil Clinical Studies

IntroductionErectile dysfunction (ED) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) are common in aging males and frequently occur together. Tadalafil has demonstrated efficacy in treating both conditions.AimThe study aims to evaluate the efficacy and safety of tadalafil 5 mg once daily vs. placebo over 12 weeks in treating both LUTS/BPH and ED in sexually active men. We also assessed relationships of baseline disease severity and prostate specific antigen (PSA) to outcomes.MethodsData were pooled from four multinational, randomized studies of men ≥45 years with LUTS/BPH, with analyses restricted to sexually active men with ED. Randomization (baseline) followed a 4‐week placebo run‐in; changes from baseline were assessed vs. placebo using analysis of covariance.Main Outcome MeasuresInternational Prostate Symptom Score (IPSS), IPSS subscores, Quality‐of‐Life Index (IPSS‐QoL), BPH Impact Index (BII), and International Index of Erectile Function‐Erectile Function (IIEF‐EF) Domain score were used in this study.ResultsTadalafil (N = 505) significantly improved total IPSS vs. placebo (N = 521); mean changes from baseline were ?6.0 and ?3.6, respectively (P < 0.001). Improvements in IIEF‐EF Domain score (tadalafil, 6.4; placebo, 1.4) were also significant vs. placebo, as were the IPSS storage and voiding subscores, IPSS‐QoL, and BII (all P < 0.001).No significant impact of baseline ED severity or PSA category on IPSS response was observed (interaction P values, 0.463 and 0.149, respectively). Similarly, improvement in IIEF‐EF Domain score was not significantly impacted by baseline LUTS/BPH severity or PSA category (interaction P values, 0.926 and 0.230, respectively). Improvements in IPSS and IIEF‐EF Domain score during treatment were weakly correlated (r = ?0.229). Treatment‐emergent adverse events were consistent with previous reports.ConclusionsTadalafil was efficacious and well tolerated in treating ED and LUTS/BPH in sexually active men with both conditions. Improvements in both conditions were significant regardless of baseline severity. Improvements in the total IPSS and the IIEF‐EF Domain score were weakly correlated. Porst H, Roehrborn CG, Secrest RJ, Esler A, and Viktrup L. Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia and on erectile dysfunction in sexually active men with both conditions: Analyses of pooled data from four randomized, placebo‐controlled tadalafil clinical studies. J Sex Med 2013;10:2044–2052.