Effect on genital warts in Australian female and heterosexual male individuals after introduction of the national human papillomavirus gender-neutral vaccination programme: an analysis of national sentinel surveillance data from 2004–18

Background: In Australia, the government-funded human papillomavirus (HPV) vaccination programme was introduced in April, 2007, for girls and young women, and in February, 2013, for boys. As of Dec 31, 2018, all Australian-born female individuals younger than 38 years and male individuals younger than 21 years have been eligible for the free quadrivalent or nonavalent HPV vaccine. We aimed to examine the trends in genital wart diagnoses among Australian-born female and heterosexual male individuals who attended sexual health clinics throughout Australia before and after the introduction of the gender-neutral HPV vaccination programme in February, 2013. Methods: We did a serial cross-sectional analysis of genital wart diagnoses among Australian-born female and heterosexual male individuals attending a national surveillance network of 35 clinics between Jan 1, 2004, and Dec 31, 2018. We calculated prevalence ratios of genital warts, using log-binomial regression models, for the female-only vaccination period (July 1, 2007, to Feb 28, 2013), gender-neutral vaccination period (March 1, 2013, to Dec 31, 2018), and the whole vaccination period (July 1, 2007, to Dec 31, 2018) compared with the pre-vaccination period (Jan 1, 2004, to June 30, 2007). Findings: We included 121 038 men and 116 341 women in the analysis. Overall, we observed a 58% reduction (prevalence ratio 0·42, 95% CI 0·40–0·44) in genital wart diagnoses in female individuals and a 45% reduction (0·55, 0·53–0·57) in genital wart diagnoses in heterosexual male individuals after the introduction of the vaccination programme in 2007. The largest reduction in genital warts was observed in younger individuals, and there was a decreasing magnitude of reduction with increasing age (80%, 72%, 61%, 41%, and 16% reductions in female individuals aged 15–20 years, 21–25 years, 26–30 years, 31–35 years, and ≥36 years, respectively; 70%, 61%, 49%, 37%, and 29% reductions in male individuals aged 15–20 years, 21–25 years, 26–30 years, 31–35 years, and ≥36 years, respectively). Significant reductions observed in female individuals (0·32, 0·28–0·36) and male individuals (0·51, 0·43–0·61) aged 15–20 years in the female-only vaccination period were followed by a more substantial reduction in female individuals (0·07, 0·06–0·09) and male individuals (0·11, 0·08–0·15) aged 15–20 years in the gender-neutral vaccination period. Interpretation: The national gender-neutral HPV vaccination programme has led to substantial and ongoing reduction in genital warts among Australian female and heterosexual male individuals, with a marked reduction in young individuals who received the vaccine at school. Funding: Seqirus Australia and the Australian Government Department of Health

A bi-directional relationship between obesity and health-related quality of life : evidence from the longitudinal AusDiab study

Objective: To assess the prospective relationship between obesity and health-related quality of life, including a novel assessment of the impact of health-related quality of life on weight gain.Design and setting: Longitudinal, national, population-based Australian Diabetes, Obesity and Lifestyle (AusDiab) study, with surveys conducted in 1999/2000 and 2004/2005.Participants: A total of 5985 men and women aged 25 years at study entry.Main outcome measure(s): At both time points, height, weight and waist circumference were measured and self-report data on health-related quality of life from the SF-36 questionnaire were obtained. Cross-sectional and bi-directional, prospective associations between obesity categories and health-related quality of life were assessed.Results: Higher body mass index (BMI) at baseline was associated with deterioration in health-related quality of life over 5 years for seven of the eight health-related quality of life domains in women (all P0.01, with the exception of mental health, P&gt;0.05), and six out of eight in men (all P&lt;0.05, with the exception of role-emotional, P=0.055, and mental health, P&gt;0.05). Each of the quality-of-life domains related to mental health as well as the mental component summary were inversely associated with BMI change (all P&lt;0.0001 for women and P0.01 for men), with the exception of vitality, which was significant in women only (P=0.008). For the physical domains, change in BMI was inversely associated with baseline general health in women only (P=0.023).Conclusions: Obesity was associated with a deterioration in health-related quality of life (including both physical and mental health domains) in this cohort of Australian adults followed over 5 years. Health-related quality of life was also a predictor of weight gain over 5 years, indicating a bi-directional association between obesity and health-related quality of life. The identification of those with poor health-related quality of life may be important in assessing the risk of future weight gain, and a focus on health-related quality of life may be beneficial in weight management strategies.<br /

Statistical methods to correct for verification bias in diagnostic studies are inadequate when there are few false negatives: a simulation study

<p>Abstract</p> <p>Background</p> <p>A common feature of diagnostic research is that results for a diagnostic gold standard are available primarily for patients who are positive for the test under investigation. Data from such studies are subject to what has been termed "verification bias". We evaluated statistical methods for verification bias correction when there are few false negatives.</p> <p>Methods</p> <p>A simulation study was conducted of a screening study subject to verification bias. We compared estimates of the area-under-the-curve (AUC) corrected for verification bias varying both the rate and mechanism of verification.</p> <p>Results</p> <p>In a single simulated data set, varying false negatives from 0 to 4 led to verification bias corrected AUCs ranging from 0.550 to 0.852. Excess variation associated with low numbers of false negatives was confirmed in simulation studies and by analyses of published studies that incorporated verification bias correction. The 2.5^th– 97.5^thcentile range constituted as much as 60% of the possible range of AUCs for some simulations.</p> <p>Conclusion</p> <p>Screening programs are designed such that there are few false negatives. Standard statistical methods for verification bias correction are inadequate in this circumstance.</p

Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression

Factors associated with self-care activities among adults in the United Kingdom: a systematic review

Background: The Government has promoted self-care. Our aim was to review evidence about who uses self-tests and other self-care activities (over-the-counter medicine, private sector,complementary and alternative medicine (CAM), home blood pressure monitors). Methods: During April 2007, relevant bibliographic databases (Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Applied Social Sciences Index and Abstracts, PsycINFO,British Nursing Index, Allied and Complementary Medicine Database, Sociological Abstracts, International Bibliography of the Social Sciences, Arthritis and Complementary Medicine Database, Complementary and Alternative Medicine and Pain Database) were searched, and potentially relevant studies were reviewed against eligibility criteria. Studies were included if they were published during the last 15 years and identified factors, reasons or characteristics associated with a relevant activity among UK adults. Two independent reviewers used proformas to assess the quality of eligible studies. Results: 206 potentially relevant papers were identified, 157 were excluded, and 49 papers related to 46 studies were included: 37 studies were, or used data from questionnaire surveys, 36 had quality scores of five or more out of 10, and 27 were about CAM. Available evidence suggests that users of CAM and over-the-counter medicine are female, middle-aged, affluent and/or educated with some measure of poor health, and that people who use the private sector are affluent and/or educated. Conclusion: People who engage in these activities are likely to be affluent. Targeted promotion may, therefore, be needed to ensure that use is equitable. People who use some activities also appear to have poorer measures of health than non-users or people attending conventional services. It is, therefore, also important to ensure that self-care is not used as a second choice for people who have not had their needs met by conventional service

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD

Advances in Nondietary Management of Children with Atopic Dermatitis

This paper discusses recent advances in therapy of atopic dermatitis (AD), excluding those that include dietary management. Some of these therapies are anecdotal, experimental, or somewhat controversial. It is important to emphasize that physicians should not try what is new without first having given standard therapy a long and reasonable chance to succeed. This is important because AD does not last forever, and in many patients, mild disease heals spontaneously.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72467/1/j.1525-1470.1989.tb00820.x.pd

5-α reductase inhibitors and prostate cancer prevention: where do we turn now?

With the lifetime risk of being diagnosed with prostate cancer so great, an effective chemopreventive agent could have a profound impact on the lives of men. Despite decades of searching for such an agent, physicians still do not have an approved drug to offer their patients. In this article, we outline current strategies for preventing prostate cancer in general, with a focus on the 5-α-reductase inhibitors (5-ARIs) finasteride and dutasteride. We discuss the two landmark randomized, controlled trials of finasteride and dutasteride, highlighting the controversies stemming from the results, and address the issue of 5-ARI use, including reasons why providers may be hesitant to use these agents for chemoprevention. We further discuss the recent US Food and Drug Administration ruling against the proposed new indication for dutasteride and the change to the labeling of finasteride, both of which were intended to permit physicians to use the drugs for chemoprevention. Finally, we discuss future directions for 5-ARI research