An evaluation of semen characteristics in men 45 years of age or older after daily dosing with tadalafil 20mg: results of a multicenter, randomized, double-blind, placebo-controlled, 9-month study

OBJECTIVES: Assess the effects on spermatogenesis of daily tadalafil 20mg over three spermatogenesis cycles in men >or= 45 yr. METHODS: In this double-blind, placebo-controlled, noninferiority study, healthy men (or with mild erectile dysfunction) were randomized to receive tadalafil 20mg (n=125) or placebo (n=128) for 9 mo followed by a 6-mo, treatment-free period. Semen and serum samples were provided at baseline and every 10-12 wk. The primary outcome was the proportion of subjects with >or= 50% reduction in sperm concentration at end point. Secondary outcomes included sperm concentration, number per ejaculate, motility and morphology; serum concentrations of testosterone, luteinizing and follicle-stimulating hormones; and tolerability. RESULTS: Of 253 men enrolled, 191 (75%) completed treatment phase: 2 of 96 (2.1%, placebo) and 12 of 95 (12.6%, tadalafil) subjects had >or= 50% reduction in sperm concentration. Tadalafil was noninferior to placebo because the upper 95% confidence interval for the difference in proportions of tadalafil and placebo subjects with a >or= 50% reduction in sperm concentration was 17.5%, significantly less than the prespecified noninferiority margin of 20% (p=0.015). Ninety-four percent (179 of 191) of men completed the 6-mo, treatment-free period: Baseline sperm concentration levels were restored in 8 of 12 (tadalafil) and 1 of 2 (placebo) men. There were no significant differences between groups in secondary end points. Common treatment-emergent adverse events were headache, back pain, dyspepsia, gastroesophageal reflux disease, and myalgia. Twelve (9.6%) tadalafil and seven (5.5%) placebo subjects discontinued because of adverse events. CONCLUSIONS: This study demonstrated no deleterious effects of 9 mo of daily tadalafil 20mg on spermatogenesis or hormones related to testicular function in men >or= 45 yr.     

Treatment of Painful Osteoporotic Vertebral Fractures with Percutaneous Vertebroplasty or Kyphoplasty

Vertebral fracture is the most common complication of osteoporosis. It results in significant mortality and morbidity, including prolonged and intractable pain in a minority of patients. Vertebroplasty and kyphoplasty, procedures that involve percutaneous injection of bone cement into a collapsed vertebra, have recently been introduced for treatment of osteoporotic patients who have prolonged pain (several weeks or longer) following vertebral fracture. To determine the details of the procedures and to gather information on their safety and efficacy, we performed a MEDLINE search using the terms “vertebroplasty” and “kyphoplasty.” We reviewed reports of these procedures in patients with osteoporosis. We supplemented the articles found with other papers known to the authors and with presentations at national meetings. Randomized trials of vertebroplasty and kyphoplasty have not been reported. Case reports suggest that these procedures are associated with pain relief in 67% to 100% of cases. Short-term complications, mainly the result of extravasation of cement, include increased pain and damage from heat or pressure to the spinal cord or nerve roots. Proper patient selection and good technique should minimize complications, but rarely, decompressive surgery is needed. Long-term benefits have not yet been shown, but potentially include prevention of recurrent pain at the treated level(s) with both procedures, and, with kyphoplasty, reversal of height loss and spinal deformity, an improved level of function, and avoidance of chronic pain and restriction of internal organs. Possible long-term complications, again not fully evaluated, include local acceleration of bone resorption caused by the treatment itself or by foreign-body reaction at the cement–bone interface, and increased risk of fracture in treated or adjacent vertebrae through changes in mechanical forces. Controlled trials are needed to determine both short-term and long-term safety and efficacy of vertebroplasty and kyphoplasty. Both procedures may be useful for osteoporotic patients who have prolonged pain following acute vertebral fracture. Until there is conclusive evidence for efficacy and long-term safety, these procedures should be done only in carefully selected patients, only by experienced operators with appropriate high-quality imaging equipment, and ideally at centers that are participating in controlled trials. Received: 26 January 2001 / Accepted: 21 February 2001     

Why patients sign out against medical advice (AMA): factors motivating patients to sign out AMA

A retrospective review of the against medical advice (AMA) discharges revealed that the majority of the patients left AMA for personal reasons, i.e., sickness or death in the family; reconciliation with spouse, girl friend, or family members; financial problems; and legal issues such as a court date. Strategies to reduce AMA discharges and increase patient retention in treatment are suggested.     

Selection and gene flow on a diminishing cline of melanic peppered moths

Historical datasets documenting changes to gene frequency clines are extremely rare but provide a powerful means of assessing the strength and relative roles of natural selection and gene flow. In 19th century Britain, blackening of the environment by the coal-fired manufacturing industry gave rise to a steep cline in the frequency of the black (carbonaria) morph of the peppered moth (Biston betularia) across northwest England and north Wales. The carbonaria morph has declined across the region following 1960s legislation to improve air quality, but the cline had not been comprehensively described since the early 1970s. We have quantified changes to the cline as of 2002, equivalent to an interval of 30 generations, and find that a cline still exists but that it is much shallower and shifted eastward. Joint estimation of the dominant fitness cost of carbonaria and dispersal parameters consistent with the observed cline change indicate that selection against carbonaria is very strong across the landscape (s approximately 0.2), and that dispersal is much greater than previously assumed. The high dispersal estimate is further supported by the weak pattern of genetic isolation by distance at microsatellite loci, and it implies that in addition to adult dispersal, wind-dispersed first instar larvae also contribute to lifetime dispersal. The historical perspective afforded by this study of cline reversal provides new insight into the factors contributing to gene frequency change in this species, and it serves to illustrate that, even under conditions of high dispersal and strong reverse selection acting against it, complete erosion of an established cline requires many generations.     

Measuring the news and its impact on democracy

Since the 2016 US presidential election, the deliberate spread of misinformation online, and on social media in particular, has generated extraordinary concern, in large part because of its potential effects on public opinion, political polarization, and ultimately democratic decision making. Recently, however, a handful of papers have argued that both the prevalence and consumption of “fake news” per se is extremely low compared with other types of news and news-relevant content. Although neither prevalence nor consumption is a direct measure of influence, this work suggests that proper understanding of misinformation and its effects requires a much broader view of the problem, encompassing biased and misleading—but not necessarily factually incorrect—information that is routinely produced or amplified by mainstream news organizations. In this paper, we propose an ambitious collective research agenda to measure the origins, nature, and prevalence of misinformation, broadly construed, as well as its impact on democracy. We also sketch out some illustrative examples of completed, ongoing, or planned research projects that contribute to this agenda.     

Pragmatic language interpretation after closed head injury: Relationship to executive functioning

Introduction: Closed head injury is associated with impairment in a range of executive skills, and with everyday difficulties in social interactions. Comprehension of pragmatic language plays an important role in social interactions. The present study was designed to examine performance on a task involving pragmatic judgement in people who had suffered closed head injury (CHI), and the relationship between this and any impairments in executive skills. Methods: Participants with CHI were compared to a matched healthy control group on a pragmatic inference task consisting of a series of brief vignettes. Participants made judgements about alternative responses in relation to social appropriateness/skill, and carried out several nonsocial executive tasks thought to play a role in pragmatic judgement. Results: The CHI group was poorer than the control group on the pragmatic measure, showing less discrimination than the control group between direct, literal interpretations and correct, indirect interpretations. They also performed more poorly on the nonsocial executive measures. Regression analysis showed an association between pragmatic performance and one of the executive tasks, a measure of inhibition. Conclusions: More work is needed to explore further the nature of any relationship between pragmatic judgement and executive skills.