Preclinical Evidence for the Benefits of Penile Rehabilitation Therapy following Nerve-Sparing Radical Prostatectomy

Erectile dysfunction following radical prostatectomy remains a frequent problem despite the development of nerve-sparing techniques. This erectile dysfunction is believed to be neurogenic, enhanced by hypoxia-induced structural changes which result in additional veno-occlusive dysfunction. Recently, daily use of intracavernous vasoactive substances and oral use of PDE5-inhibitors have been clinically studied for treatment of postprostatectomy erectile dysfunction. Since these studies showed benefits of “penile rehabilitation therapy,” these effects have been studied in a preclinical setting. We reviewed experimental literature on erectile tissue preserving and neuroregenerative treatment strategies, and found that preservation of the erectile tissue by the use of intracavernous nitric oxide donors or vasoactive substances, oral PDE5-inhibitors, and hyperbaric oxygen therapy improved erectile function by antifibrotic effects and preservation of smooth muscle. Furthermore, neuroregenerative strategies using neuroimmunophilin ligands, neurotrophins, growth factors, and stem cell therapy show improved erectile function by preservation of NOS-containing nerve fibers

The Effect of Star Formation History on the Inferred Initial Stellar Mass Function

Peaks and lulls in the star formation rate (SFR) over the history of the Galaxy produce plateaux and declines in the present day mass function (PDMF) where the main-sequence lifetime overlaps the age and duration of the SFR variation. These PDMF features can be misinterpreted as the form of the intrinsic stellar initial mass function (IMF) if the star formation rate is assumed to be constant or slowly varying with time. This effect applies to all regions that have formed stars for longer than the age of the most massive stars, including OB associations, star complexes, and especially galactic field stars. Related problems may apply to embedded clusters. Evidence is summarized for temporal SFR variations from parsec scales to entire galaxies, all of which should contribute to inferred IMF distortions. We give examples of various star formation histories to demonstrate the types of false IMF structures that might be seen. These include short-duration bursts, stochastic histories with log-normal amplitude distributions, and oscillating histories with various periods and phases. The inferred IMF should appear steeper than the intrinsic IMF over mass ranges where the stellar lifetimes correspond to times of decreasing SFRs; shallow portions of the inferred IMF correspond to times of increasing SFRs. If field regions are populated by dispersed clusters and defined by their low current SFRs, then they should have steeper inferred IMFs than the clusters. The SFRs required to give the steep field IMFs in the LMC and SMC are determined. Structure observed in several determinations of the Milky Way field star IMF can be accounted for by a stochastic and bursty star formation history.Comment: accepted by ApJ for 1 Jan 2006, Vol 636, 12 pages + 6 figure

Changing current practice in urology: Improving guideline development and implementation through stakeholder engagement

Effective stakeholder integration for guideline development should improve outcomes and adherence to clinical practice guidelines

The active living gender's gap challenge: 2013-2017 Eurobarometers physical inactivity data show constant higher prevalence in women with no progress towards global reduction goals

BACKGROUND: The World Health Organization (WHO) considers physical inactivity (PIA) as a critical noncommunicable factor for disease and mortality, affecting more women than men. In 2013, the WHO set a 10% reduction of the PIA prevalence, with the goal to be reached by 2025. Changes in the 2013-2017 period of physical inactivity prevalence in the 28 European Union (EU) countries were evaluated to track the progress in achieving WHO 2025 target. METHODS: In 2013 and 2017 EU Special Eurobarometers, the physical activity levels reported by the International Physical Activity Questionnaire of 53,607 adults were analyzed. Data were considered as a whole sample and country-by-country. A χ2 test was used to analyze the physical inactivity prevalence (%) between countries, analyzing women and men together and separately. Additionally, PIA prevalence was analyzed between years (2013-2017) for the overall EU sample and within-country using a Z-Score for two population proportions. RESULTS: The PIA prevalence increased between 2013 and 2017 for the overall EU sample (p <  0.001), and for women (p = 0.04) and men (p < 0.001) separately. Data showed a higher PIA prevalence in women versus men during both years (p <  0.001). When separately considering changes in PIA by gender, only Belgium's women and Luxembourg's men showed a reduction in PIA prevalence. Increases in PIA prevalence over time were observed in women from Austria, Croatia, Germany, Lithuania, Malta, Portugal, Romania, and Slovakia and in men from Bulgaria, Croatia, Czechia, Germany, Italy, Lithuania, Portugal, Romania, Slovakia, and Spain. CONCLUSIONS: PIA prevalence showed an overall increase across the EU and for both women and men between 2013 and 2017, with higher rates of PIA reported for women versus men during both years. PIA prevalence was reduced in only Belgium's women and Luxembourg's men. Our data indicate a limited gender-sensible approach while tacking PIA prevalence with no progress reaching global voluntary reductions of PIA for 2025

Treatment of chronic low back pain in patients with spinal deformities using a sagittal re-alignment brace

<p>Abstract</p> <p>Background</p> <p>For adult scoliosis patients with chronic low back pain bracing is initially indicated before spinal surgery is considered. Until recently there has been a lack of research into the effect upon pain reductions in the mid and long-term. Promising results have been documented in short-term studies for the application of a sagittal re-alignment brace in patients with spinal deformities and along with pain; however mid-term and long-term results are not yet available. The purpose of this study is to investigate the mid-term effects of this brace with respect to pain control.</p> <p>Materials and methods</p> <p>67 patients (58 females and 9 males) with chronic low back pain (> 24 months) and the diagnosis of scoliosis or hyperkyphosis were treated with a sagittal re-alignment brace (physio-logic brace™) between January 2006 and July 2007. The indication for this kind of brace treatment was derived from a positive sagittal re-alignment test (SRT) and the exclusion of successful conservative treatment during the last 24 months. The aim of this type of conservative intervention was to avoid surgery for chronic low back pain.</p> <p>Results</p> <p>The average pain intensity was measured on the Roland and Morris VRS (5 steps) before treatment. This was 3.3 (t1), at the time of brace adjustment it was 2.7 (t2) and after at an average observation time of 18 months it was 2.0 (t3). The differences were highly significant in the Wilcoxon test.</p> <p>Discussion</p> <p>Short-term measurements showed that a significant pain reduction is possible in chronic postural low back pain using a sagittal re-alignment brace inducing lumbar re-lordosation. In a preliminary report at adjustment (t2), highly significant improvements of pain intensity have also been demonstrated. At 6 months of treatment however, no improvement was measured. The improvement of the mid-term effects (18 months) found in this study compared to the preliminary report may be due to the changed approach to compliance: whilst the bracing standard was not changed; the patients in this study were obligated to wear the brace for a minimum of 20 hrs per day for the first 6 months of treatment.</p> <p>Conclusion</p> <p>The effect of the sagittal re-alignment brace leads to promising short-term improvements in patients with chronic low back pain and spinal deformities. Contrary to unspecific orthoses, which after a short period without persistent pain reduction are omitted by the patients, the sagittal re-alignment brace (physio-logic™ brace) leads to an effective reduction of pain intensity in mid-term even in patients who have stopped brace treatment after the initial 6 months of treatment. In conservative treatment of chronic low back pain specific approaches such as the sagittal re-alignment brace are indicated prior to considering the surgical options.</p

Randomized Phase II trial assessing estramustine and vinblastine combination chemotherapy vs estramustine alone in patients with progressive hormone-escaped metastatic prostate cancer

Abstract Based on the results of combined data from three North American Phase II studies, a randomised Phase II study in the same patient population was performed, using combination chemotherapy with estramustine phosphate (EMP) and vinblastine (VBL) in hormone refractory prostate cancer patients. In all, 92 patients were randomised into a Phase II study of oral EMP (10 mg kg day continuously) or oral EMP in combination with intravenous VBL (4 mg m(2) week for 6 weeks, followed by 2 weeks rest). The end points were toxicity and PSA response in both groups, with the option to continue the trial as a Phase III study with time to progression and survival as end points, if sufficient responses were observed. Toxicity was unexpectedly high in both treatment arms and led to treatment withdrawal or refusal in 49% of all patients, predominantly already during the first treatment cycle. The mean treatment duration was 10 and 14 weeks, median time to PSA progression was 27.2 and 30.8 weeks, median survival time was 44 and 50.9 weeks, and PSA response rate was only 24.6 and 28.9% in the EMP/VBL and EMP arms, respectively. There was no correlation between PSA response and survival. While the PSA response in the patients tested was less than half that recorded in the North American studies, the toxicity of EMP monotherapy or in combination with VBL was much higher than expected. Further research on more effective and less toxic treatment strategies for hormone refractory prostate cancer is mandatory

Hypertension and Cardiovascular Morbidity Following Surgery for Kidney Cancer

BACKGROUND: Despite better renal function following nephron-sparing surgery (NSS) relative to radical nephrectomy (RN), there is no consensus with respect to the long-term sequelae associated with surgery. OBJECTIVE: To investigate the effect of surgery and the temporal pattern of two different cardiovascular event (CVe) categories after NSS versus RN. DESIGN, SETTING, AND PARTICIPANTS: We collected data of 898 patients with cT1-2 N0 M0 renal mass and no history of CVe treated with NSS versus RN. CVe categories were dichotomised in (1) de novo hypertension (HT) and (2) other major cardiovascular events (MCEs). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable competing regression analyses (MVAs) tested the adjusted effect of surgery type on each CVe category. RESULTS AND LIMITATIONS: Among patients treated with RN, 38% of HT events occurred immediately after surgery. Conversely, in NSS counterparts, the onset of HT was diluted over the years after surgery (10% of HT events in the first 6 mo). When an MCE was considered, an increasing long-term time-dependent prevalence of the outcome was observed in both groups, with no statistically significantly difference between NSS and RN. At MVA, RN was associated with a higher HT risk (hazard ratio [HR] 2.89; p=0.006) than but a similar MCE risk (HR 0.85; p=0.6) to NSS. CONCLUSIONS: Relative to RN, NSS showed an independent protective effect on HT but not on MCEs. In patients with no history of preoperative HT or MCEs, the onset of HT after RN is a very early event, due probably to the acute loss of renal parenchyma. This is not the case for the other cardiovascular morbidity, which develops in the long-term period, regardless of the type of surgery performed. PATIENT SUMMARY: In renal cancer patients without a medical history of cardiopathy, preserving healthy kidney tissue at surgery is associated with a decreased risk of developing postoperative hypertension

Application of the Occupational Sitting and Physical Activity Questionnaire (OSPAQ) to office based workers

Background The workplace is a setting where sedentary behaviour is highly prevalent. Accurately measuring physical activity and sedentary behaviour is crucial to assess the impact of behavioural change interventions. This study aimed to evaluate the reliability and criterion validity of the Occupational Sitting and Physical Activity Questionnaire (OSPAQ) and compare with data collected by accelerometers. Methods A test-retest study was undertaken on 99 participants using the OSPAQ. Data were then compared to accelerometer records of 41 participants. Reliability was assessed by paired t-test and intra-class correlations (ICC) via a two-way mixed model based on absolute agreement. Difference and agreement were measured by comparison of mean self-reported data with accelerometer data using the Pearson’s correlation coefficient and Bland-Altman plots. Results The ICCs for minutes spent sitting (0.66), standing (0.83) and walking (0.77) showed moderate to strong test-retest reliability. No significant differences were found between the repeated measurements taken seven days apart. Correlations with the accelerometer readings were moderate. The Bland-Altman plots showed moderate agreement for standing time and walking time but systematic variation for sedentary time. Conclusion The OSPAQ appears to have acceptable reliability and validity measurement properties for application in the office workplace setting

Urbanization and mortality in Britain, c. 1800-50.

In the long-running debate over standards of living during the industrial revolution, pessimists have identified deteriorating health conditions in towns as undermining the positive effects of rising real incomes on the 'biological standard of living'. This article reviews long-run historical relationships between urbanization and epidemiological trends in England, and then addresses the specific question: did mortality rise especially in rapidly growing industrial and manufacturing towns in the period c. 1830-50? Using comparative data for British, European, and American cities and selected rural populations, this study finds good evidence for widespread increases in mortality in the second quarter of the nineteenth century. However, this phenomenon was not confined to 'new' or industrial towns. Instead, mortality rose in the 1830s especially among young children (aged one to four years) in a wide range of populations and environments. This pattern of heightened mortality extended between c. 1830 and c. 1870, and coincided with a well-established rise and decline in scarlet fever virulence and mortality. The evidence presented here therefore supports claims that mortality worsened for young children in the middle decades of the nineteenth century, but also indicates that this phenomenon was more geographically ubiquitous, less severe, and less chronologically concentrated than previously argued.Leverhulme Trust (award RPG-2012-803) Wellcome Trust (award no. 103322