Vitamin D supplementation and adverse skeletal and non-skeletal outcomes in individuals at increased cardiovascular risk: Results from the International Polycap Study (TIPS)-3 randomized controlled trial.

BACKGROUND AND AIMS: Vitamin D has mostly been tested in Western populations. We examined the effect of high dose vitamin D in a population drawn predominantly from outside of Western countries. METHODS AND RESULTS: This randomized trial tested vitamin D 60,000 IU monthly in 5670 participants without vascular disease but at increased CV risk. The primary outcome was fracture. The secondary outcome was the composite of CV death, myocardial infarction stroke, cancer, fracture or fall. Death was a pre-specified outcome. Mean age was 63.9 years, and 3005 (53.0%) were female. 3034 (53.5%) participants resided in South Asia, 1904 (33.6%) in South East Asia, 480 (8.5%) in South America, and 252 (4.4%) in other regions. Mean follow-up was 4.6 years. A fracture occurred in 20 participants (0.2 per 100 person years) assigned to vitamin D, and 19 (0.1 per 100 person years) assigned to placebo (HR 1.06, 95% CI 0.57-1.99, p-value = 0.86). The secondary outcome occurred in 222 participants (1.8 per 100 person years) assigned to vitamin D, and 198 (1.6 per 100 person years) assigned to placebo (HR 1.13, 95% CI 0.93-1.37, p = 0.22). 172 (1.3 per 100 person years) participants assigned to vitamin D died, compared with 135 (1.0 per 100 person years) assigned to placebo (HR 1.29, 95% CI 1.03-1.61, p = 0.03). CONCLUSION: In a population predominantly from South Asia, South East Asia and South America, high-dose vitamin D did not reduce adverse skeletal or non-skeletal outcomes. Higher mortality was observed in the vitamin D group. REGISTRATION NUMBER: NCT01646437.

Nocturnal polyuria in women: results from the EpiNP study.

INTRODUCTION AND HYPOTHESIS: Data from a large US population-based, cross-sectional, epidemiological study (the EpiNP Study) were used to assess the symptoms and bother experienced by women with nocturnal polyuria (NP). METHODS: Consenting participants recruited from an online panel completed the baseline EpiNP survey online (Lower Urinary Tract Symptoms Tool and urological comorbidities). All reporting ≥2 voids/night and a random sample of 100 respondents, each reporting 0 or 1 void/night were asked to complete a 3-day web-based bladder diary recording time, volume, and urgency rating of each void. NP was calculated by the proportion of urine production that occurred during nocturnal hours using a Nocturnal Polyuria Index (NPI33) threshold of >0.33 or nocturnal urine production of >90 ml/h (NUP90). The frequency of participants reporting LUTS and bother was determined by age and NP: idiopathic NP, NP associated with overactive bladder (NPOAB), NP associated with comorbidities (NPCom), and no NP (did not meet NP criteria). RESULTS: A total of 5,290 women completed the baseline survey. Mean age (range) was 54.9 (30-95) years; 1,841 (34.8%) reported ≥2 nocturnal voids. The prevalence of LUTS increased across the lifespan; however, bother associated with each LUTS decreased with increasing age. The percentage of women rating bother by nocturia episodes ≥2 "> somewhat" ranged from 40.3% to 68.3%, with bother ratings highest in the NPOAB and No NP groups. CONCLUSIONS: NP is prevalent in women with considerable bother and is often associated with other urinary symptoms. Multifactorial causes and potential treatments of NP should be considered, particularly at a later age.

Description and validation of an improved method to feed solitary bees (Osmia spp.) known amounts of pesticides.

Pesticide exposure is an important driver of bee declines. Laboratory toxicity tests provide baseline information on the potential effects of pesticides on bees, but current risk assessment schemes rely on one species, the highly social honey bee, Apis mellifera, and there is uncertainty regarding the extent to which this species is a suitable surrogate for other pollinators. For this reason, Osmia cornuta and Osmia bicornis have been proposed as model solitary bee species in the EU risk assessment scheme. The use of solitary bees in risk assessment requires the development of new methodologies adjusted to the biology of these species. For example, oral dosing methods used with honey bees cannot be readily applied to solitary bees due to differences in feeding behaviour and social interactions. In this study, we describe the "petal method", a laboratory feeding method, and validate its use in acute and chronic exposure oral tests with Osmia spp. We conducted five experiments in which we compared the performance of several artificial flowers combining visual and olfactory cues against the petal method, or in which variations of the petal method were confronted. We then use the results of these experiments to optimize the feeding arenas and propose standardized methods for both acute and chronic exposure tests. The petal method provides high levels of feeding success, thus reducing the number of bees needed. It works with a wide variety of petal species and with both female and male Osmia spp., thus ensuring reproducibility across studies. To validate the use of the petal method in ecotoxicology tests, we assess the toxicity of a standard reference insecticide, dimethoate, in O. cornuta adults and determine LD50 values for this species. The petal method should facilitate the inclusion of solitary bees in risk assessment schemes therefore increasing the protection coverage of pesticide regulation.

Differences in the Prevalence of Nocturnal Polyuria in the U.S. by Definition: Results from the Epidemiology of Nocturnal Polyuria Study.

PURPOSE: Prevalence data on nocturnal polyuria (NP), nocturia caused by overproduction of urine during sleep, is primarily limited to men and varies by NP definition. This U.S.-representative epidemiological study of men and women ≥30 years old assessed the prevalence of NP. MATERIALS AND METHODS: Consenting participants completed the baseline EpiNP (Epidemiology of Nocturnal Polyuria) survey (eg Lower Urinary Tract Symptoms Tool, comorbidities). All reporting ≥2 voids/night and a target of 100 random respondents reporting 0 or 1 void/night were asked to complete 3-day bladder diaries. NP was defined as nocturnal polyuria index (NPI) >0.33 (NPI33) and nocturnal urine production >90 ml/hour (NUP90). Extrapolated prevalence was stratified by sex and subgroups: idiopathic (without underlying causes), associated with overactive bladder (NPOAB), bladder outlet obstruction (NPBOO; men) and comorbidities. Voided volumes and timing, including first uninterrupted sleep period, were assessed by subgroup. RESULTS: A total of 10,190 individuals completed the baseline survey; mean age (range) was 54.4 (30-95). A total of 3,938 individuals were invited to complete the diary; 1,763 (49.3%) completed 3-day bladder diaries. Urine production (maximum nighttime volume, total volume, nocturnal urine production, nocturia index) was higher in both men and women with idiopathic NP and comorbidities. The median number of nighttime voids was greatest for NPBOO in men and NPOAB in women. Bother associated with nighttime voiding differed by NP subgroup but was highest in NPBOO for men (NPI33: 69.6%; NUP90: 71.1%) and NPOAB for women (NPI33: 67.5%; NUP90: 66.0%). CONCLUSIONS: This population-based NP prevalence study including men and women characterizes NP subgroups and provides insights into nocturia treatment by emphasizing factors influencing urine production versus factors influencing bladder capacity.

Additional surgical procedures and perioperative morbidity in post-chemotherapy retroperitoneal lymph node dissection for metastatic testicular cancer in two intermediate volume hospitals.

PURPOSE: To evaluate the perioperative morbidity of PC-RPLND in two intermediate volume centers and to identify predictors of high morbidity. METHODS: Retrospective analysis of 124 patients treated with open PC-RPLND at two tertiary referral centers between 2001 and 2018. Perioperative morbidity was determined by analyzing additional surgical procedures, intra-operative blood loss, and postoperative complications. RESULTS: An additional procedure was necessary for 33 patients (26.6%). The risk was higher in patients with IGCCCG intermediate/poor prognosis (OR 3.56; 95% CI 1.33-9.52) and residual tumor size > 5 cm (OR 3.53; 95% CI 1.39-8.93). Blood loss was higher in patients with IGCCCG intermediate/poor prognosis (ß = 0.177; p = 0.029), large residual tumor (ß = 0.570; p < 0.001), an additional intervention (ß = 0.342; p < 0.001) and teratoma on retroperitoneal histology (ß = - 0.19; p = 0.014). Thirty-one patients had a postoperative complication Clavien-Dindo Grade ≥ 2 (25.0%). Complication risk was highest in patients undergoing an additional intervention (OR 3.46; 95% CI 1.03-11.60; p = 0.044). CONCLUSIONS: The rate of additional interventions in our series is comparable to what has been reported in high-volume centers. IGCCCG intermediate/poor prognosis patients with high-volume disease and patients undergoing an additional surgical procedure can be classified as high-risk patients.

Clinical outcome of robot-assisted residual mass resection in metastatic nonseminomatous germ cell tumor.

PURPOSE: To evaluate the outcome of robot-assisted residual mass resection (RA-RMR) in nonseminomatous germ cell tumor (NSGCT) patients with residual tumor following chemotherapy. PATIENTS AND METHODS: Retrospective medical chart analysis of all patients with NSGCT undergoing RA-RMR at two tertiary referral centers between January 2007 and April 2019. Patients were considered for RA-RMR in case of a residual tumor between 10 and 50 mm at cross-sectional computed tomography (CT) imaging located ventrally or laterally from the aorta or vena cava, with normalized tumor markers following completion of chemotherapy, and no history of retroperitoneal surgery. RESULTS: A total of 45 patients were included in the analysis. The Royal Marsden stage before chemotherapy was IIA in 13 (28.9%), IIB in 16 (35.6%), IIC in 3 (6.7%) and IV in 13 patients (28.9%). The median residual tumor size was 1.9 cm (interquartile range [IQR] 1.4-2.8; range 1.0-5.0). Five procedures (11.1%) were converted to an open procedure due to a vascular injury (n = 2), technical difficulty (n = 2) or tumor debris leakage (n = 1). A postoperative adverse event occurred in two patients (4.4%). Histopathology showed teratoma, necrosis and viable cancer in 29 (64.4%), 14 (31.1%), and two patients (4.4%), respectively. After a median follow-up of 41 months (IQR 22-70), one patient (2.2%) relapsed in the retroperitoneum. The one- and 2-year recurrence-free survival rate was 98%. CONCLUSION: RA-RMR is an appropriate treatment option in selected patients, potentially providing excellent cure rates with minimal morbidity. Long-term outcome data are needed to further support this strategy and determine inclusion and exclusion criteria.

Differences in treatment choices between prostate cancer patients using a decision aid and patients receiving care as usual: results from a randomized controlled trial.

OBJECTIVE: To determine whether or not decision aid (DA) use influences treatment decisions in patients with low and intermediate risk prostate cancer (PC). PATIENTS AND METHODS: In a cluster randomized controlled trial, patients were randomized to either DA use (DA group) or no DA use (control group). Between 2014 and 2016, newly diagnosed patients with low or intermediate risk PC were recruited in 18 hospitals in the Netherlands. DA users had access to a web-based DA that provided general PC information, PC-treatment information, and values clarification exercises to elicit personal preferences towards the treatment options. Control group patients received care as usual. Differences in treatment choice were analysed using multilevel logistic regressions. Differences in eligible treatment options between groups were compared using Pearson Chi-square tests. RESULTS: Informed consent was given by 382 patients (DA group N = 273, control group N = 109). Questionnaire response rate was 88% (N = 336). Active surveillance (AS) was an option for 38%, radical prostatectomy (RP) for 98%, external beam radiotherapy (EBRT) for 88%, and brachytherapy (BT) for 79% of patients. DA users received AS significantly more often than control group. Patients (29 vs 16%, p = 0.01), whereas the latter more often chose BT (29 vs 18%, p < 0.01). No differences were found between groups regarding RP and EBRT. DA users who were not eligible for AS, received surgery more often compared to the control group (53 vs 35%, p = 0.01). Patient and disease characteristics were evenly distributed between groups. CONCLUSION: DA-using PC patients chose the AS treatment option more often than non-DA-using patients did.

Emergency medical services evaluations for chest pain during first COVID-19 lockdown in Hollands-Midden, the Netherlands.

OBJECTIVE: To assess whether the COVID-19 lockdown in 2020 had negative indirect health effects, as people seem to have been reluctant to seek medical care. METHODS: All emergency medical services (EMS) transports for chest pain or out-of-hospital cardiac arrest (OHCA) in the Dutch region Hollands-Midden (population served > 800,000) were evaluated during the initial 6 weeks of the COVID-19 lockdown and during the same time period in 2019. The primary endpoint was the number of evaluated chest pain patients in both cohorts. In addition, the number of EMS evaluations of ST-elevation myocardial infarction (STEMI) and OHCA were assessed. RESULTS: During the COVID-19 lockdown period, the EMS evaluated 927 chest pain patients (49% male, age 62 ± 17 years) compared with 1041 patients (51% male, 63 ± 17 years) in the same period in 2019, which corresponded with a significant relative risk (RR) reduction of 0.88 (95% confidence interval (CI) 0.81-0.96). Similarly, there was a significant reduction in the number of STEMI patients (RR 0.52, 95% CI 0.32-0.85), the incidence of OHCA remained unchanged (RR 1.23, 95% CI 0.83-1.83). CONCLUSION: During the first COVID-19 lockdown, there was a significant reduction in the number of patients with chest pain or STEMI evaluated by the EMS, while the incidence of OHCA remained similar. Although the reason for the decrease in chest pain and STEMI consultations is not entirely clear, more attention should be paid to the importance of contacting the EMS in case of suspected cardiac symptoms in possible future lockdowns.

Systematic review and meta-analysis of the associations between body mass index, prostate cancer, advanced prostate cancer, and prostate-specific antigen.

PURPOSE: The relationship between body mass index (BMI) and prostate cancer remains unclear. However, there is an inverse association between BMI and prostate-specific antigen (PSA), used for prostate cancer screening. We conducted this review to estimate the associations between BMI and (1) prostate cancer, (2) advanced prostate cancer, and (3) PSA. METHODS: We searched PubMed and Embase for studies until 02 October 2017 and obtained individual participant data from four studies. In total, 78 studies were identified for the association between BMI and prostate cancer, 21 for BMI and advanced prostate cancer, and 35 for BMI and PSA. We performed random-effects meta-analysis of linear associations of log-PSA and prostate cancer with BMI and, to examine potential non-linearity, of associations between categories of BMI and each outcome. RESULTS: In the meta-analyses with continuous BMI, a 5 kg/m2 increase in BMI was associated with a percentage change in PSA of - 5.88% (95% CI - 6.87 to - 4.87). Using BMI categories, compared to normal weight men the PSA levels of overweight men were 3.43% lower (95% CI - 5.57 to - 1.23), and obese men were 12.9% lower (95% CI - 15.2 to - 10.7). Prostate cancer and advanced prostate cancer analyses showed little or no evidence associations. CONCLUSION: There is little or no evidence of an association between BMI and risk of prostate cancer or advanced prostate cancer, and strong evidence of an inverse and non-linear association between BMI and PSA. The association between BMI and prostate cancer is likely biased if missed diagnoses are not considered.

Progression of Alzheimer's disease and effect of scFv-h3D6 immunotherapy in the 3xTg-AD mouse model: An in vivo longitudinal study using Magnetic Resonance Imaging and Spectroscopy.

Alzheimer's disease (AD) is an incurable disease that affects most of the 47 million people estimated as living with dementia worldwide. The main histopathological hallmarks of AD are extracellular ß-amyloid (Aß) plaques and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein. In recent years, Aß-immunotherapy has been revealed as a potential tool in AD treatment. One strategy consists of using single-chain variable fragments (scFvs), which avoids the fragment crystallizable (Fc) effects that are supposed to trigger a microglial response, leading to microhemorrhages and vasogenic edemas, as evidenced in clinical trials with bapineuzumab. The scFv-h3D6 generated by our research group derives from this monoclonal antibody, which targets the N-terminal of the Aß peptide and recognizes monomers, oligomers and fibrils. In this study, 3xTg-AD mice were intraperitoneally and monthly treated with 100 µg of scFv-h3D6 (a dose of ~3.3 mg/kg) or PBS, from 5 to 12 months of age (-mo), the age at which the mice were sacrificed and samples collected for histological and biochemical analyses. During treatments, four monitoring sessions using magnetic resonance imaging and spectroscopy (MRI/MRS) were performed at 5, 7, 9, and 12 months of age. MRI/MRS techniques are widely used in both human and mouse research, allowing to draw an in vivo picture of concrete aspects of the pathology in a non-invasive manner and allowing to monitor its development across time. Compared with the genetic background, 3xTg-AD mice presented a smaller volume in almost all cerebral regions and ages examined, an increase in both the intra and extracellular Aß1-42 at 12-mo, and an inflammation process at this age, in both the hippocampus (IL-6 and mIns) and cortex (IL-6). In addition, treatment with scFv-h3D6 partially recovered the values in brain volume, and Aß, IL-6, and mIns concentrations, among others, encouraging further studies with this antibody fragment.

Lymphovascular invasion and presence of embryonal carcinoma as risk factors for occult metastatic disease in clinical stage I nonseminomatous germ cell tumour: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the literature on the prognostic value of lymphovascular invasion (LVI) and embryonal carcinoma (EC) for occult metastatic disease in clinical stage I nonseminomatous germ cell tumour (CS I NSGCT). MATERIALS AND METHODS: The PubMed, Embase (OVID) and SCOPUS databases were searched up to March 2019. Studies reporting on the association between LVI and/or EC and occult metastatic disease were considered for inclusion. The quality and risk of bias were evaluated by the Quality in Prognosis Studies tool. RESULTS: We screened 5287 abstracts and 207 full-text articles. We included 35 studies in the narrative synthesis and 24 studies in a meta-analysis. LVI showed the strongest effect. Pooled rates of occult metastasis were 47.5% and 16.9% for LVI-positive and LVI-negative patients, respectively (odds ratio [OR] 4.33, 95% confidence interval [CI] 3.55-5.30; P < 0.001). Pooled rates of occult metastasis were 33.2% for EC presence and 16.2% for EC absence (OR 2.49, 95% CI 1.64-3.77; P < 0.001). Pooled rates of occult metastasis were 40.0% for EC >50% and 20.0% for EC <50% (OR 2.62, 95% CI 1.93-3.56; P < 0.001). CONCLUSIONS: LVI is the strongest risk factor for relapse. The prognostic value of EC is high, but there is no common agreement on how to define this risk factor. Both EC presence and EC >50% have similar ORs for occult metastasis. This shows that the assessment of EC presence is sufficient for the classification of EC.

Sentinel node biopsy in clinical stage I testicular cancer enables early detection of occult metastatic disease.

OBJECTIVES: To report the long-term results of the sentinel node (SN) approach in patients with clinical stage I testicular tumours in our facility. PATIENTS AND METHODS: We conducted an analysis of 27 consecutive patients suspected of clinical stage I testicular germ cell tumour (TGCT) and treated with an SN procedure at our tertiary referral centre. SNs were identified using lymphoscintigraphy with or without single-photo-emission computed tomography with CT (SPECT/CT). Patients underwent laparoscopic retroperitoneal SN excision with inguinal orchiectomy. Patients with a tumour-positive SN underwent adjuvant treatment. Follow-up was conducted according to then-current guidelines. RESULTS: In two patients, no SNs were visualized on scintigraphy. In the remaining 25 patients, a median (range) of 3 (1-4) SNs per patient were removed. Two patients showed no malignancy on histopathological examination of the testis. Of the 23 patients diagnosed with TGCT (16 seminomas, seven non-seminomas), three (13.0%) had occult metastatic disease. All 23 patients were without evidence of disease at a median (range) follow-up of 63.9 (29.0-143.4) months. CONCLUSION: The SN procedure allows early identification of patients with occult metastatic disease in clinical stage I TGCT, enabling early treatment.

Striae reconstructed, a full thickness skin model that recapitulates the pathology behind stretch marks.

OBJECTIVE: Stretch marks are disfiguring skin lesions that often cause problems of self-esteem, but little effort has been put to studying this pathology. We therefore analysed cell cultures of dermal fibroblasts isolated from a striae albae, to thereafter reconstruct a full thickness skin model. METHODS: Human Dermal Fibroblasts (HDF) were isolated from a striae distensae (SD) lesion and from the adjacent non-lesioned skin. The dermis of two full thickness skin models was reconstructed with either striae- or normal-HDF, while the epidermis was in both reconstructed with Normal Human Epidermal Keratinocytes. RESULTS: Main observations and pertinent data: Gene expression analysis of cell cultures revealed a generalized decomposition of the Extra Cellular Matrix (ECM), since collagens type I and III, lysyl oxidase (LOX), biglycan, lumican and fibronectin were downregulated, while MMP3 was increased together with a decrease of its natural inhibitors (TIMP1, TIMP2 and PAI-1). These findings were statistically corroborated for key ECM elements at the protein level (COL1, MMP1 and TGFB1). Interestingly, striae albae fibroblasts retained a pro-inflammatory phenotype, as suggested by increased gene expression of CXCL8, HAS1 and TNFA. We next reconstructed a full thickness skin model (Striae Reconstructed) with dermal fibroblasts from striae albae. Gene expression analysis showed that the Striae Reconstructed elicited not only ECM decomposition, but also skin ageing, as indicated by the upregulation of P16, PTGS2 and SOD2. Discussion points: Although the epidermis was constructed with normal human epidermal keratinocytes, the Striae Reconstructed presented epidermal atrophy and a dramatic increase of ß1-integrin at the epidermal-dermal junction providing, for the first time to our knowledge, a rationale showing that the key cell player behind stretch marks are dermal fibroblasts rather than epidermal keratinocytes. CONCLUSION: New knowledge: Taken together, our findings shed new light into the aetiology of stretch marks and indicate that the Striae Reconstructed, a new model for in vitro testing and drug screening, may open new avenues for the treatment of stretch marks.

OBJECTIFS: Les vergetures sont des lésions cutanées défigurantes qui posent souvent des problèmes d'estime de soi, mais peu d'efforts ont été consacrés dans l'étude de cette pathologie. Nous avons donc analysé des cultures cellulaires de fibroblastes dermiques isolés d'un stria alba, afin de reconstruire ensuite un modèle de peau avec une pleine épaisseur. METHODES: Des fibroblastes dermiques humains (FDH) ont été isolés d'une lésion de Stria distensae (SD) et d'une peau adjacente sans lésion. Le derme de deux modèles de peau de pleine épaisseur a été reconstruit avec du HDF striae- ou normal, tandis que l'épiderme était reconstruit avec des kératinocytes humains normaux. RESULTATS: Principales observations et données pertinentes: L'analyse de l'expression génique de cultures cellulaires a révélé une décomposition généralisée de la matrice extra-cellulaire (MEC) car les collagènes de types I et III, la lysyl oxydase, le biglycane, le lumican et la fibronectine étaient régulés négativement, tandis que la MMP3 augmentait ses inhibiteurs naturels diminuaient (TIMP1, TIMP2 et PAI-1). Ces résultats ont été corroborés statistiquement pour les éléments clés de la MEC au niveau de la protéine (COL1, MMP1 et TGFB1). Il est intéressant de noter que les fibroblastes de Striae albae ont conservé un phénotype proinflammatoire, comme le suggère l'augmentation de l'expression des gènes de CXCL8, HAS1 et TNFA. Nous avons ensuite reconstruit un modèle de peau de pleine épaisseur (Stria Reconstructed) avec des fibroblastes dermiques de Striae albae. L'analyse de l'expression génique a montré que la reconstruction de Striae induisait non seulement la décomposition de la MEC, mais également le vieillissement de la peau, comme l'indique la régulation à la hausse de P16, PTGS2 et SOD2. Points de discussion : Bien que l'épiderme ait été construit avec des kératinocytes humains normaux, les stries reconstruites présentaient une atrophie épidermique et une augmentation spectaculaire du taux de ß1-intégrine au niveau de la jonction épidermo-dermique, fournissant pour la première fois une explication rationnelle qui démontre que les cellules principales impliquées dans la pathologie de la Striae sont les fibroblastes et non les kératinocytes. CONCLUSION: Nouvelles connaissances: Ensemble, nos résultats donnent une nouvelle lumière sur l'étiologie des vergetures et indiquent que le Striae Reconstructed, un nouveau modèle de test in vitro et de dépistage du médicament, pourrait être une avancée pour le traitement des vergetures.

Shared Decision Making in Prostate Cancer Care-Encouraging Every Patient to be Actively Involved in Decision Making or Ensuring the Patient Preferred Level of Involvement?

PURPOSE: The aims of this study were to 1) describe preferred and experienced roles in treatment decision making among patients with localized prostate cancer, 2) identify how often the roles experienced by patients matched their preferred roles and 3) determine whether active involvement in decision making regardless of role preferences or concordance between preferred and experienced roles would be the strongest predictor of more favorable patient reported outcomes. MATERIALS AND METHODS: In this prospective, multicenter, observational study we obtained serial questionnaire data from 454 patients with newly diagnosed, localized prostate cancer (cT1-cT2, or Gleason 7 or less and prostate specific antigen 20 ng/ml or less). Questionnaires were completed prior to treatment and at the 3, 6 and 12-month posttreatment followups. Clinical data were obtained from the patient medical records. Active involvement and role concordance were operationalized using the CPS (Control Preferences Scale). ANOVA and effect sizes (small and medium Cohen d = 0.2 and 0.5, respectively) were used to compare patient knowledge of prostate cancer, decision conflict, decision regret and overall health related quality of life. RESULTS: Of the patients 393 (87%) reported having been actively involved in treatment decision making. However, 78 patients (17%) indicated having had less or more involvement than preferred. Active involvement was significantly associated with more prostate cancer knowledge (d = 0.30), less decision conflict (d = 0.52) and less decision regret (d = 0.34). Role concordance was also but less strongly associated with less decision conflict (d = 0.41). CONCLUSIONS: Our findings support a policy of encouraging all patients with localized prostate cancer regardless of their stated role preferences to be actively involved in the treatment decision.

The association of self-reported diabetes with impaired social functioning in low-, middle- and high-income countries: findings from the World Health Survey.

AIM: Epidemiological studies from high-income countries show that diabetes is associated with impaired social functioning. As healthcare systems in middle- and low-income countries offer fewer resources to curtail the potential social impact of diabetes, we performed a comparative study on the diabetes-social impairment link in low-, middle- and high-income countries. METHODS: We use data from the cross-sectional World Health Survey (n = 235 428 from 10 low-income, 29 middle-income and 9 high-income countries). Diabetes was defined by self-reports of a diagnosis. Impaired social functioning was considered present if participants reported severe or extreme difficulties with personal relationships or participation in the community. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) in the overall sample and by income regions. ORs were corrected for demographics and health-related lifestyles, and then additionally adjusted for impairments that may explain any observed association (i.e. impaired vision, mood, cognition and mobility). RESULTS: In the overall sample, we confirmed an association between self-reported diabetes and impaired social functioning (OR = 1.47, 95% CI = 1.18-1.83). The strength of that relationship increased with decreasing country income (e.g. OR in low-income countries = 2.23, 95% CI = 1.14-4.37). Associations were substantially attenuated by further correction for impairments, in particular mood problems, in the overall sample (OR = 0.92, 95% CI = 0.72-1.16) and all income regions. CONCLUSIONS: Self-reported diabetes is associated with impaired social functioning in high- and middle-income countries, and this relationship is even stronger in low-income countries. Associations are largely explained by physical and mental impairments, which may be due to diabetes.

Proximal hypospadias treated with a transverse preputial island tube: long-term functional, sexual, and cosmetic outcomes.

OBJECTIVE: To study long-term urinary and sexual function, and cosmetic outcomes in adult patients who underwent single-stage transverse preputial island tube (TPIT) for proximal hypospadias repair in childhood. Long-term data on outcomes of patients with proximal hypospadias with severe coexisting curvature and insufficient urethral plate are scarce, but are necessary to decide which repair technique is most beneficial. PATIENTS, SUBJECTS AND METHODS: Patients with proximal hypospadias operated with TPIT (TPIT Group) were compared to patients with distal hypospadias repair (Distal Group) and to a control group of male medical students (Control Group). Participants completed the International Prostate Symptom Score, the International Index of Erectile Function (IIEF-15), additional non-validated questions, and performed uroflowmetry. Cosmesis was assessed in the patients with hypospadias using the Pediatric Penile Perception Score (PPPS); stretched penile length was also measured. RESULTS: Of the 121 eligible patients with hypospadias, 54 with either TPIT or distal hypospadias repairs participated. The TPIT Group comprised 12 patients (median age of 20.0 years) and the Distal Group comprised 42 patients (median age of 19.6 years). The complication rates were similar, at 8 of the 12 patients in the TPIT Group vs 26/42 (62%) in the Distal Group (P = 0.76). Urinary outcomes were similar in the TPIT, Distal, and the Control (comprised of 148 medical students with a median age of 21.0 years) groups. The TPIT Group had a lower maximum urinary flow rate compared to the Control Group, at 24.1 vs 28.6 mL/s (P < 0.05). IIEF-15 scores were similar in the TPIT, Distal and Control groups, except for 'Orgasmic Function' (7.5 vs 10.0 vs 10.0, respectively; P < 0.01). Although the TPIT Group had a smaller penile length compared to the Distal Group (10.1 vs 12.9 cm, P < 0.01), PPPS outcomes were similar. CONCLUSION: In these TPIT patients, long-term urinary, sexual and cosmetic outcomes were similar to those in patients with distal hypospadias repairs and controls.

The accuracy of patients' perceptions of the risks associated with localised prostate cancer treatments.

OBJECTIVES: To assess the accuracy of patients' perceptions of the risks associated with localised prostate cancer treatments (radical prostatectomy [RP], radiotherapy [RT], and active surveillance [AS]), and to identify correlates of misperceptions. PATIENTS AND METHODS: We used baseline data (questionnaires completed after treatment information was provided but before treatment) of 426 patients with newly diagnosed localised prostate cancer who participated (87% response rate) in a prospective, longitudinal, multicentre study. Patients' pretreatment perceptions of differences in adverse outcomes of treatments were compared to those based on the literature. We used univariate and multivariate linear regression to identify correlates of misperceptions. RESULTS: About two-thirds (68%, n = 211) of the patients did not understand that the risk of disease recurrence is comparable between RP and RT. More than half of the patients did not comprehend that RP patients are at greater risk of urinary incontinence (65%, n = 202) and erectile dysfunction (61%, n = 190), and less at risk of bowel problems (53%, n = 211) compared to RT patients. Many patients overestimated the risk of requiring definitive treatment following AS (45%, n = 157) and did not understand that mortality rates following AS, RP, and RT are comparable (80%, n = 333). Consulting a radiotherapist or a clinical nurse specialist was positively associated with, and emotional distress was negatively associated with, better understanding of the risks (P < 0.05), although effect sizes were small. CONCLUSION: Prior to choosing treatment, most patients with prostate cancer poorly understood the differences in treatment risks. Greater efforts should be made to better understand why these misperceptions occur and, most importantly, how they can be corrected.

Airway management changes associated with rising radiologic incidence of external laryngotracheal injury.

BACKGROUND: Traumatic laryngeal injuries are uncommon life-threatening injuries that require prompt, rational management of a potentially precarious airway. It is unclear whether the current incidence of laryngotracheal injury is due to enhanced injury detection or increased occurrence. The objective of this study was to evaluate the relations between diagnostic imaging with both initial airway management and surgical treatment in patients with external laryngotracheal injuries (ELTIs) in Alberta. METHODS: In this large-scale population-based analysis, we used regional health databases containing inpatient admissions, emergency department visits and trauma service activations employing International Classification of Diseases diagnostic codes to identify all ELTIs diagnosed from Apr. 1, 1995, to Dec. 31, 2011, in adults (age ≥ 16 yr). We evaluated health records and diagnostic imaging for injury features, airway management, operative interventions and hospital length of stay (LOS). RESULTS: Eighty-nine patients met the inclusion criteria. The incidence of ELTIs increased over time, paralleling a rise in detection during the period incorporating greater computed tomography (CT) use (p = 0.002). Endotracheal tube intubation was performed in 8/30 cases (27%) in the pre-CT era, compared to 38/59 cases (64%) in the post-CT era (p = 0.001); the use of surgical intervention remained consistent. The largest contributors to increased endotracheal tube placements were the emergency department and emergency medical services. No change in survival was detected, but mean LOS among patients admitted for minor, isolated ELTIs increased by 2.3 (95% confidence interval 0.14-4.8) days (p = 0.06), mostly for patients admitted under critical care for mechanical ventilation. CONCLUSION: Management of ELTIs shifted from predominantly conservative airway monitoring to endotracheal tube intubation over the study period in spite of no clinically significant change in injury severity or operative intervention frequency. The location of endotracheal tube placement suggests less comfort with ELTI among first-responder and emergency personnel.

CONTEXTE: Les lésions traumatiques du larynx sont des blessures rares qui peuvent être mortelles et nécessitent une prise en charge rapide et efficiente, en raison de l'état potentiellement précaire des voies respiratoires. On ignore si l'incidence actuelle des lésions laryngo-trachéales est attribuable à une amélioration de la détection ou à une augmentation de la fréquence réelle. Cette étude avait pour but d'évaluer le lien entre l'imagerie diagnostique, et la prise en charge initiale des voies respiratoires ainsi que le traitement chirurgical chez des patients ayant subi des lésions laryngo-trachéales externes (LLTE) en Alberta. MÉTHODES: Dans le cadre de cette analyse de grande envergure basée sur une population, nous avons interrogé des bases de données régionales sur les hospitalisations, les consultations aux services d'urgence et la prestation de services de traumatologie. Nous nous sommes servis des codes diagnostiques de la Classification statistique internationale des maladies pour repérer tous les cas de LLTE diagnostiqués entre le 1er avril 1995 et le 31 décembre 2011 chez des adultes (16 ans et plus). Nous avons examiné les dossiers de santé et les résultats d'imagerie diagnostique pour en extraire des données sur les caractéristiques des lésions, la prise en charge des voies respiratoires, les interventions chirurgicales et la durée de séjour à l'hôpital. RÉSULTATS: Au total, 89 patients répondaient aux critères d'inclusion. L'incidence des LLTE a augmenté au fil du temps; en parallèle, l'utilisation répandue de la tomographie par ordinateur a entraîné une augmentation de la détection de ces lésions (p = 0,002). Une intubation trachéale a été réalisée chez 8/30 patients (27 %) pendant la période prétomographie, et chez 38/59 patients (64 %) pendant la période post-tomographie (p = 0,001); le recours à la chirurgie est demeuré constant. L'augmentation du nombre d'intubations est principalement attribuable aux interventions effectuées par le personnel ambulancier et par les services d'urgence. Aucun changement du taux de survie n'a été enregistré; toutefois, la durée de séjour moyenne des patients hospitalisés en raison de LLTE mineures et isolées a augmenté de 2,3 jours (intervalle de confiance à 95 % : 0,14-4,8; p = 0,06), surtout pour les patients admis aux soins intensifs pour recevoir une ventilation mécanique. CONCLUSION: Durant la période à l'étude, la prise en charge des LLTE est passée d'un suivi essentiellement conservateur des voies respiratoires à la prépondérance de l'intubation trachéale, bien qu'aucun changement significatif n'ait été observé quant à la gravité des lésions ou à la fréquence des interventions chirurgicales. Le contexte où ont lieu les intubations laisse croire que le personnel ambulanciers et les premiers intervenants sont moins à l'aise de prendre en charge les LLTE.

Effect of viral suppression on hepatic venous pressure gradient in hepatitis C with cirrhosis and portal hypertension.

Portal hypertension is a predictor of liver-related clinical events and mortality in patients with hepatitis C and cirrhosis. The effect of interferon-free hepatitis C treatment on portal pressure is unknown. Fifty patients with Child-Pugh-Turcotte (CPT) A and B cirrhosis and portal hypertension (hepatic venous pressure gradient [HVPG] >6 mm Hg) were randomized to receive 48 weeks of open-label sofosbuvir plus ribavirin at Day 1 or after a 24-week observation period. The primary endpoint was sustained virologic response 12 weeks after therapy (SVR12) in patients who received ≥1 dose of treatment. Secondary endpoints included changes in HVPG, laboratory parameters, and MELD and CPT scores. A subset of patients was followed 48 weeks posttreatment to determine late changes in HVPG. SVR12 occurred in 72% of patients (33/46). In the 37 patients with paired HVPG measurements at baseline and the end of treatment, mean HVPG decreased by -1.0 (SD 3.97) mm Hg. Nine patients (24%) had ≥20% decreases in HVPG during treatment. Among 39 patients with pretreatment HVPG ≥12 mm Hg, 27 (69%) achieved SVR12. Four of the 33 (12%) patients with baseline HVPG ≥12 mm Hg had HVPG <12 mm Hg at the end of treatment. Of nine patients with pretreatment HVPG ≥12 mm Hg who achieved SVR12 and completed 48 weeks of follow-up, eight (89%) had a ≥20% reduction in HVPG, and three reduced their pressure to <12 mm Hg. Patients with chronic HCV and compensated or decompensated cirrhosis who achieve SVR can have clinically meaningful reductions in HVPG at long-term follow-up. (EudraCT 2012-002457-29).