Erectile dysfunction - an update of current practice and future strategies

Erectile dysfunction (ED) is defined as the inability to achieve and maintain a penile erection adequate for satisfactory sexual intercourse.1 Up to 150 million men worldwide suffer from ED and this figure is likely to double by the year 2025.2 A number of studies have attempted to characterise the true prevalence of ED. In a Danish study, Ventegodt reported that 5.4% of all patients had a decreased ability to achieve an erection.3 The prevalence was reported to be highest (18%) in those aged over 58 years. The Massachusetts Male Aging Study (MMAS)4 reported the results of a regional survey of 1709 men aged 40–69 years. In this study 52% reported some degree of ED, with 10% having complete ED. Moreover, the results suggest that the probability of complete ED at age 70 was threefold compared to that at age 40; the probability of moderate ED was two-fold

Socioeconomic indicators of health inequalities and female mortality: a nested cohort study within the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

Evidence is mounting that area-level socioeconomic indicators are important tools for predicting health outcomes. However, few studies have examined these alongside individual-level education. This nested cohort study within the control arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) assesses the association of mutually adjusted individual (education) and area-level (Index of Multiple Deprivation-IMD 2007) socioeconomic status indicators and all-cause female mortality

Type and Timing of Rehabilitation Following Acute and Subacute Spinal Cord Injury: A Systematic Review

Objectives: The objective of this study was to conduct a systematic review of the literature to address the following clinical questions: In adult patients with acute and subacute complete or incomplete traumatic SCI, (1) does the time interval between injury and commencing rehabilitation affect outcome?; (2) what is the comparative effectiveness of different rehabilitation strategies, including different intensities and durations of treatment?; (3) are there patient or injury characteristics that affect the efficacy of rehabilitation?; and (4) what is the cost-effectiveness of various rehabilitation strategies? Methods: A systematic search was conducted for literature published through March 31, 2015 that evaluated rehabilitation strategies in adults with acute or subacute traumatic SCI at any level. Studies were critically appraised individually and the overall strength of evidence was evaluated using methods proposed by the GRADE (Grades of Recommendation Assessment, Development and Evaluation) working group. Results: The search strategy yielded 384 articles, 19 of which met our inclusion criteria. Based on our results, there was no difference between body weight–supported treadmill training and conventional rehabilitation with respect to improvements in Functional Independence Measure (FIM) Locomotor score, Lower Extremity Motor Scores, the distance walked in 6 minutes or gait velocity over 15.2 m. Functional electrical therapy resulted in slightly better FIM Motor, FIM Self-Care, and Spinal Cord Independence Measure Self-Care subscores compared with conventional occupational therapy. Comparisons using the Toronto Rehabilitation Institute Hand Function Test demonstrated no differences between groups in 7 of 9 domains. There were no clinically important differences in Maximal Lean Test, Maximal Sidewards Reach Test, T-shirt Test, or the Canadian Occupational Performance Measure between unsupported sitting training and standard in-patient rehabilitation. Conclusion: The current evidence base for rehabilitation following acute and subacute spinal cord injury is limited. Methodological challenges have contributed to this and further research is still needed. © 2017, © The Author(s) 2017

Quality of life and other psychological factors in patients with tooth wear

Aim: To investigate the relationship between generic and condition-specific (CS) quality of life, general psychological wellbeing and personality in patients with tooth wear. / Materials and methods: Ethical approval was granted (REC:10/H0709/21). Patients aged 18-70 years with tooth wear completed the Oral Impact on Daily Performance (OIDP) quality of life questionnaire, the NEO-FFI Personality questionnaire and the General Health Questionnaire-12 (GHQ). Tooth wear was measured with the Basic Erosive Wear Examination (BEWE). / Results: In total, 102 subjects were recruited. Increased BEWE scores were correlated with older age and worse generic and CS-related quality of life. Increased neuroticism was correlated with increased: generic and CS OIDP scores; generic and CS eating scores; CS smiling scores; and CS carrying out major work scores. Increased GHQ scores were positively correlated with increased: generic and CS OIDP scores; generic and CS eating scores; CS speaking scores; generic and CS cleaning scores; generic relaxing scores; generic and CS smiling scores; and generic emotional state scores (p <0.05). Multivariable linear regression analyses showed that increased neuroticism and decreased GHQ both had an independent effect on generic and CS OIDP scores when adjusted for tooth wear severity (p <0.05). / Conclusion: Quality of life perception is complex and was not only affected by worsening levels of tooth wear

Metformin reduces airway glucose permeability and hyperglycaemia-induced Staphylococcus aureus load independently of effects on blood glucose

Background Diabetes is a risk factor for respiratory infection, and hyperglycaemia is associated with increased glucose in airway surface liquid and risk of Staphylococcus aureus infection. Objectives To investigate whether elevation of basolateral/blood glucose concentration promotes airway Staphylococcus aureus growth and whether pretreatment with the antidiabetic drug metformin affects this relationship. Methods Human airway epithelial cells grown at air–liquid interface (±18 h pre-treatment, 30 μM–1 mM metformin) were inoculated with 5×105 colony-forming units (CFU)/cm2 S aureus 8325-4 or JE2 or Pseudomonas aeruginosa PA01 on the apical surface and incubated for 7 h. Wild-type C57BL/6 or db/db (leptin receptor-deficient) mice, 6–10 weeks old, were treated with intraperitoneal phosphate-buffered saline or 40 mg/kg metformin for 2 days before intranasal inoculation with 1×107 CFU S aureus. Mice were culled 24 h after infection and bronchoalveolar lavage fluid collected. Results Apical S aureus growth increased with basolateral glucose concentration in an in vitro airway epithelia–bacteria co-culture model. S aureus reduced transepithelial electrical resistance (RT) and increased paracellular glucose flux. Metformin inhibited the glucose-induced growth of S aureus, increased RT and decreased glucose flux. Diabetic (db/db) mice infected with S aureus exhibited a higher bacterial load in their airways than control mice after 2 days and metformin treatment reversed this effect. Metformin did not decrease blood glucose but reduced paracellular flux across ex vivo murine tracheas. Conclusions Hyperglycaemia promotes respiratory S aureus infection, and metformin modifies glucose flux across the airway epithelium to limit hyperglycaemia-induced bacterial growth. Metformin might, therefore, be of additional benefit in the prevention and treatment of respiratory infection

Change-point of multiple biomarkers in women with ovarian cancer

To date several algorithms for longitudinal analysis of ovarian cancer biomarkers have been proposed in the literature. An issue of specific interest is to determine whether the baseline level of a biomarker changes significantly at some time instant (change-point) prior to the clinical diagnosis of cancer. Such change-points in the serum biomarker Cancer Antigen 125 (CA125) time series data have been used in ovarian cancer screening, resulting in earlier detection with a sensitivity of 85% in the most recent trial, the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS, number ISRCTN22488978; NCT00058032). Here we propose to apply a hierarchical Bayesian change-point model to jointly study the features of time series from multiple biomarkers. For this model we have analytically derived the conditional probability distribution of every unknown parameter, thus enabling the design of efficient Markov Chain Monte Carlo methods for their estimation. We have applied these methods to the estimation of change-points in time series data of multiple biomarkers, including CA125 and others, using data from a nested case-control study of women diagnosed with ovarian cancer in UKCTOCS. In this way we assess whether any of these additional biomarkers can play a role in change-point detection and, therefore, aid in the diagnosis of the disease in patients for whom the CA125 time series does not display a change-point. We have also investigated whether the change-points for different biomarkers occur at similar times for the same patient. The main conclusion of our study is that the combined analysis of a group of specific biomarkers may possibly improve the detection of change-points in time series data (compared to the analysis of CA125 alone) which, in turn, are relevant for the early diagnosis of ovarian cancer

Socioeconomic Status and Ovarian Cancer Stage at Diagnosis: A Study Nested Within UKCTOCS

BACKGROUND: Tubo-ovarian cancer (OC) continues to be the most lethal of all gynaecological cancers. Over half of women are diagnosed with late stage (III/IV) disease, which has a five-year survival rate of 11%. Socioeconomic status (SES) has been shown to have an impact on outcomes of several cancer types, including OC. This study aims to investigate any potential association between SES and stage at diagnosis of OC. METHODS: Women from the non-screening arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) with a confirmed diagnosis of OC prior to 01 January 2015 and an English index of multiple deprivation (IMD) score were eligible for the study. The association between IMD and OC stage (FIGO) was analysed using an ordinal logistic regression model adjusted for age at diagnosis and BMI. RESULTS: Four-hundred and fifty seven women were eligible for inclusion in the primary analysis. The odds of being diagnosed with the higher dichotomization of stage (I vs. II/III/IV; I/II vs. III/IV; I/II/III vs. IV) was 1.29 (p = 0.017; 95% CI: 1.048-1.592) per unit SD (standard deviation) increase in IMD. This translates to a 29% increase in odds of being diagnosed at the higher stage per each unit SD increase in IMD. CONCLUSION: Increased deprivation is consistently associated with a higher probability of being diagnosed with later stage OC

Lignin peroxidases, manganese peroxidases, and other ligninolytic enzymes produced by Phlebia radiata during solid-state fermentation of wheat-straw

The white rot fungus Phlebia radiata 79 (ATCC 64658) produces lignin peroxidase (LiP), manganese peroxidase (MnP), glyoxal oxidase (GLOX), and laccase in the commonly used glucose low-nitrogen liquid medium. However, the enzymes which this fungus utilizes for selective removal of lignin during degradation of different lignocellulosic substrates have not been studied before. Multiple forms of LiP, MnP, GLOX, and laccase were purified from P. radiata culture extracts obtained after solid-state fermentation of wheat straw. However, the patterns of extracellular lignin-modifying enzymes studied were different from those of the enzymes usually found in liquid cultures of P. radiata. Three LiP isoforms were purified. The major LiP isoform from solid-state cultivation was LiP2. LiP3, which has usually been described as the major isoenzyme in liquid cultures, was not expressed during straw fermentation. New MnP isoforms have been detected in addition to the previously reported MnPs. GLOX was secreted in rather high amounts simultaneously with LiP during the first 2 weeks of growth. GLOX purified from P. radiata showed multiple forms, with pIs ranging from 4.0 to 4.6 and with a molecular mass of ca. 68 kDa

Validity of self-reported hysterectomy: a prospective cohort study within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

To evaluate the validity of self-reported hysterectomy against the gold standard of uterine visualisation using pelvic ultrasound