Preventing Ovarian Cancer through early Excision of Tubes and late Ovarian Removal (PROTECTOR): protocol for a prospective non-randomised multi-center trial.

BACKGROUND: Risk-reducing salpingo-oophorectomy is the 'gold standard' for preventing tubo-ovarian cancer in women at increased risk. However, when performed in pre-menopausal women, it results in premature menopause and associated detrimental health consequences. This, together with acceptance of the central role of the fallopian tube in etiopathogenesis of high-grade serous carcinoma, by far the most common type of tubo-ovarian cancer, has led to risk-reducing early salpingectomy with delayed oophorectomy being proposed as a two-step surgical alternative for pre-menopausal women declining/delaying oophorectomy. PRIMARY OBJECTIVE: To evaluate the impact on sexual function of risk-reducing early salpingectomy, within a two-step, risk-reducing, early salpingectomy with delayed oophorectomy tubo-ovarian cancer prevention strategy in pre-menopausal women at increased risk of tubo-ovarian cancer. STUDY HYPOTHESIS: Risk-reducing early salpingectomy is non-inferior for sexual and endocrine function compared with controls; risk-reducing early salpingectomy is superior for sexual/endocrine function, non-inferior for quality-of-life, and equivalent in satisfaction to the standard risk-reducing salpingo-oophorectomy. TRIAL DESIGN: Multi-center, observational cohort trial with three arms: risk-reducing early salpingectomy with delayed oophorectomy; risk-reducing salpingo-oophorectomy; controls (no surgery). Consenting individuals undergo an ultrasound, serum CA125, and follicle-stimulating hormone measurements and provide information on medical history, family history, quality-of-life, sexual function, cancer worry, psychological well-being, and satisfaction/regret. Follow-up by questionnaire takes place annually for 3 years. Women receiving risk-reducing early salpingectomy can undergo delayed oophorectomy at a later date of their choosing, or definitely by the menopause. MAJOR INCLUSION/EXCLUSION CRITERIA: Inclusion criteria: pre-menopausal; aged >30 years; at increased risk of tubo-ovarian cancer (mutation carriers or on the basis of a strong family history); completed their family (for surgical arms). EXCLUSION CRITERIA: post-menopausal; previous bilateral salpingectomy or bilateral oophorectomy; pregnancy; previous tubal/ovarian/peritoneal malignancy; <12 months after cancer treatment; clinical suspicion of tubal/ovarian cancer at baseline. PRIMARY ENDPOINT: Sexual function measured by validated questionnaires. SAMPLE SIZE: 1000 (333 per arm). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: It is estimated recruitment will be completed by 2023 and results published by 2027. TRIAL REGISTRATION NUMBER: ISRCTN registry: 25 173 360 (https://doi.org/10.1186/ISRCTN25173360)

Shorter courses of parenteral antibiotic therapy do not appear to influence response rates for children with acute hematogenous osteomyelitis: a systematic review

BACKGROUND: Acute hematogenous osteomyelitis (AHO) occurs primarily in children and is believed to evolve from bacteremia followed by localization of infection to the metaphysis of bones. Currently, there is no consensus on the route and duration of antimicrobial therapy to treat AHO. METHODS: We conducted a systematic review of a short versus long course of treatment for AHO due primarily to Staphylococcus aureus in children aged 3 months to 16 years. We searched Medline, Embase and the Cochrane trials registry for controlled trials. Clinical cure rate at 6 months was the primary outcome variable, and groups receiving less than 7 days of intravenous therapy were compared with groups receiving one week or longer of intravenous antimicrobials. RESULTS: 12 eligible prospective studies, one of which was randomized, were identified. The overall cure rate at 6 months for the short course of intravenous therapy was 95.2% (95% CI = 90.4, 97.7) compared to 98.8% (95% CI = 93.6, 99.8) for the longer course of therapy. There was no significant difference in the duration of oral therapy between the two groups. CONCLUSIONS: Given the potential increased morbidity and cost associated with longer courses of intravenous therapy, this finding should be confirmed through a randomized controlled equivalence trial

Mapping autism risk loci using genetic linkage and chromosomal rearrangements.

International audienceAutism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs

Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

When public action undermines public health: A critical examination of antifluoridationist literature

Background: The addition of the chemical fluorine to the water supply, called water fluoridation, reduces dental caries by making teeth more resistant to demineralisation and more likely to remineralise when initially decayed. This process has been implemented in more than 30 countries around the world, is cost-effective and has been shown to be efficacious in preventing decay across a person's lifespan. However, attempts to expand this major public health achievement in line with Australia's National Oral Health Plan 2004–2013 are almost universally met with considerable resistance from opponents of water fluoridation, who engage in coordinated campaigns to portray water fluoridation as ineffective and highly dangerous. Discussion: Water fluoridation opponents employ multiple techniques to try and undermine the scientifically established effectiveness of water fluoridation. The materials they use are often based on Internet resources or published books that present a highly misleading picture of water fluoridation. These materials are used to sway public and political opinion to the detriment of public health. Despite an extensive body of literature, both studies and results within studies are often selectively reported, giving a biased portrayal of water fluoridation effectiveness. Positive findings are downplayed or trivialised and the population implications of these findings misinterpreted. Ecological comparisons are sometimes used to support spurious conclusions. Opponents of water fluoridation frequently repeat that water fluoridation is associated with adverse health effects and studies are selectively picked from the extensive literature to convey only claimed adverse findings related to water fluoridation. Techniques such as "the big lie" and innuendo are used to associate water fluoridation with health and environmental disasters, without factual support. Half-truths are presented, fallacious statements reiterated, and attempts are made to bamboozle the public with a large list of claims and quotes often with little scientific basis. Ultimately, attempts are made to discredit and slander scientists and various health organisations that support water fluoridation. Summary: Water fluoridation is an important public health initiative that has been found to be safe and effective. Nonetheless, the implementation of water fluoridation is still regularly interrupted by a relatively small group of individuals who use misinformation and rhetoric to induce doubts in the minds of the public and government officials. It is important that public health officials are aware of these tactics so that they can better counter their negative effectJason M Armfiel

AUDIT-C Alcohol Screening Results and Postoperative Inpatient Health Care Use.

BACKGROUND: Alcohol screening scores 5 on the Alcohol Use Disorders Identification Test–Consumption (AUDIT-C) up to a year before surgery have been associated with postoperative complications, but the association with postoperative health care use is unknown. This study evaluated whether AUDIT-C scores in the year before surgery were associated with postoperative hospital length of stay, total ICU days, return to the operating room, and hospital readmission. STUDY DESIGN: This cohort study included male Veterans Affairs patients who completed the AUDIT-C on mailed surveys (October 2003 through September 2006) and were hospitalized for nonemergent noncardiac major operations in the following year. Postoperative health care use was evaluated across 4 AUDIT-C risk groups (scores 0, 1 to 4, 5 to 8, and 9 to 12) using linear or logistic regression models adjusted for sociodemographics, smoking status, surgical category, relative value unit, and time from AUDIT-C to surgery. Patients with AUDIT-C scores indicating low-risk drinking (scores 1 to 4) were the referent group. RESULTS: Adjusted analyses revealed that among eligible surgical patients (n 5,171), those with the highest AUDIT-C scores (ie, 9 to 12) had longer postoperative hospital length of stay (5.8 [95% CI, 5.06.7] vs 5.0 [95% CI, 4.75.3] days), more ICU days (4.5 [95% CI, 3.25.8] vs 2.8 [95% CI, 2.63.1] days), and increased probability of return to the operating room (10% [95% CI, 613%] vs 5% [95% CI, 46%]) in the 30 days after surgery, but not increased hospital readmission within 30 days postdischarge, relative to the low-risk group. CONCLUSIONS: AUDIT-C screening results could be used to identify patients at risk for increased postoperative health care use who might benefit from preoperative alcohol interventions