Summary descriptive statistics for cases and controls.

<p>Summary descriptive statistics for cases and controls.</p

Sensitivity Analyses: excluding bisphosphonates used to treat bone metastases; excluding prescriptions for bisphosphonates commenced 6 months or less before diagnosis of all UGI cancer; excluding cases where the READ code for UGI cancer diagnosis was uncertain.

<p>Sensitivity Analyses: excluding bisphosphonates used to treat bone metastases; excluding prescriptions for bisphosphonates commenced 6 months or less before diagnosis of all UGI cancer; excluding cases where the READ code for UGI cancer diagnosis was uncertain.</p

Bisphosphonates and Risk of Upper Gastrointestinal Cancer — A Case Control Study Using the General Practice Research Database (GPRD)

<div><h3>Background</h3><p>Concerns have been raised as to the safety of bisphosphonates; in particular a possible link between bisphosphonate use and upper gastrointestinal (GI) cancer. Two published studies using different study populations but drawn from earlier versions of the same national UK database, reached differing conclusions: one finding no evidence for an increase in the risk of gastric or oesophageal cancer in bisphosphonate users and one finding a small but significantly increased risk of oesophageal cancer linked to duration of bisphosphonate use.</p> <h3>Methodology/ Principal Findings</h3><p>Design-A case control study comparing bisphosphonate prescribing in cases of upper GI cancer from 1995 to 2007 using UK primary care electronic health records (GPRD).</p> <p>Main Outcome Measure-Relative Risk (approximated to Odds Ratio for rare events) for oesophageal and gastric cancer development in bisphosphonate users compared to non–users. The odds of being a case of oesophageal cancer, adjusted for smoking status, were significantly increased in women who had had one or more bisphosphonate prescriptions, odds ratio 1·54 (95% CI 1·27–1·88) compared to non-users. There was no significant effect on gastric cancer in women, odds ratio adjusted for smoking status, 1.06 (95% CI 0.83–1.37) and also no apparent risk in men for either oesophageal or gastric cancer, odds ratio adjusted for smoking status 0.78 (95%CI 0.56–1.09) and 0.87 (95% CI 0.55–1.36) respectively.</p> <h3>Conclusions/ Significance</h3><p>Our results support a small but significant increased risk of oesophageal cancer in women prescribed bisphosphonates and is based on the largest number of exposed cases to date in the UK.</p> </div

Effect of alendronate on oesophageal cancer for men and women (mean number of observations 19,991.

<p>Effect of alendronate on oesophageal cancer for men and women (mean number of observations 19,991.</p

'Praelectiones Publicae ... Illustrissimi Parentis Mei'

<p>Risk of bisphosphonates on oesophageal and gastric cancer in men.</p

Hazard of carpal tunnel syndrome associated with the intake of bisphosphonates.

<p>Hazard of carpal tunnel syndrome associated with the intake of bisphosphonates.</p

Baseline characteristics.

<p>Distribution according to prognostic factors.</p

The human embryo does not elicit a secretory response in undifferentiated endometrium.

<p>Undifferentiated primary ESCs were co-cultured with embryos or not (control cultures, Con). Over the 72-hour co-culture period, 15 embryos arrested (Arr) whereas 6 continued to develop normally (Dev). Co-culture with either an arrested or developing embryo had no impact on the secreted levels of the indicated factors (<i>P</i>>0.05). The concentrations of IL-5, -12, -15, -17, -18, and eotaxin in culture supernatants of undifferentiated ESCs were below the level of detection.</p

Developmentally impaired human embryos inhibit the secretion of selective implantation modulators by decidualizing ESCs.

<p>Primary ESCs were first decidualized for 5 days and then co-cultured with human embryos or not (control cultures, Con). Over the 72-hour co-culture period, 30 embryos arrested (Arr) whereas 11 continued to develop normally (Dev). Analysis of the culture supernatants revealed that the presence of an arresting embryo inhibited the secretion of the indicated factors. The letters above the box plots indicate significant differences between groups. <i>P</i><0.01 for all comparisons except for IL-6 and IL-17 (<i>P</i><0.05).</p

Secreted decidual cytokines not regulated upon embryo co-culture.

<p>Primary ESCs were first decidualized for 5 days and then co-cultured with human embryos or not (control cultures, Con). Over the 72-hour co-culture period, 30 embryos arrested (Arr) whereas 11 continued to develop normally (Dev). Analysis of the culture supernatants revealed that the presence of an arresting or developing human embryo had no significant impact on the secretion of the indicated factors (<i>P</i>>0.05).</p