Quantitative estimation of rare adverse events which follow a biological progression: a new model applied to chronic NSAID use
Humans; Cohort Studies; Death; Disease Progression; Risk Assessment; Non-U.S. Gov't; Research Support; Models; Statistical; Anti-Inflammatory Agents; Databases; Factual; Digestive System; Endoscopy; Gastrointestinal Hemorrhage/chemically induced/mortality; Non-Steroidal/adverse effects; Peptic Ulcer Perforation/chemically induced/mortality
Randomised controlled trials (RCTs) alone are unlikely to provide reliable estimates of the incidence of rare events because of their limited size. Cohort, case control, and other observational studies have large numbers but are vulnerable to various kinds of bias. Wanting to estimate the risk of death from bleeding or perforated gastroduodenal ulcers with chronic usage of non-steroidal anti-inflammatory drugs (NSAIDs) with greater precision, we developed a model to quantify the frequency of rare adverse events which follow a biological progression. The model combined data from both RCTs and observational studies. We searched systematically for any report of chronic (>/=2 months) use of NSAIDs which gave information on gastroduodenal ulcer, bleed or perforation, death due to these complications, or progression from one level of harm to the next. Fifteen RCTs (19364 patients exposed to NSAIDs for 2-60 months), three cohort studies (215076 patients redeeming a NSAID prescription over a 3-12 month period), six case-control studies (2957 cases) and 20 case series (7406), and case reports (4447) were analysed. In RCTs the incidence of bleeding or perforation in 6822 patients exposed to NSAIDs was 0.69%; two deaths occurred. Of 11040 patients with bleeding or perforation with or without NSAID exposure across all reports, 6-16% (average 12%) died; the risk was lowest in RCTs and highest in case reports. Death from bleeding or perforation in all controls not exposed to NSAIDs occurred in 18 out of 849489 (0.002%). From these numbers we calculated the number-needed-to-treat for one patient to die due to gastroduodenal complications with chronic (>/=2 months) NSAIDs as 1/((0.69x inverted question mark6-16%, average 12% inverted question mark)-0.002%))=909-2500 (average 1220). On average 1 in 1200 patients taking NSAIDs for at least 2 months will die from gastroduodenal complications who would not have died had they not taken NSAIDs. This extrapolates to about 2000 deaths each year in the UK.
2000
Tramer MR; Moore RA; Reynolds DJ; McQuay HJ
Pain
2000
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1016/s0304-3959(99)00267-5" target="_blank" rel="noreferrer">10.1016/s0304-3959(99)00267-5</a>
Brain and gut neuropeptides in peripheral blood mononuclear cells
Humans; Male; Adult; Aged; Middle Aged; Brain; Animals; Rats; 80 and over; Sprague-Dawley; Aging/metabolism; beta-Endorphin/blood/pharmacology; Chemotaxis/drug effects; Cholecystokinin/blood/pharmacology; Digestive System; Headache/blood; Lymphocytes/metabolism; Neuropeptides/blood; Schizophrenia/blood; Vasoactive Intestinal Peptide/blood/pharmacology
Neuropeptides, initially thought to be common features of gut and brain, are only synthesized in immune cells and modulate immune functions. The presence and possible functions of these peptides in immune cells in both physiological or pathological conditions have been investigated in our laboratory in the last years. Some of the data obtained are reviewed here, and future developments of the field are indicated.
1993
Panerai AE; Sacerdote P
Journal Of Physiology, Paris
1993
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1016/0928-4257(93)90034-q" target="_blank" rel="noreferrer">10.1016/0928-4257(93)90034-q</a>
Gastroesophageal reflux
Child; Humans; Prognosis; adolescent; Preschool; infant; Nervous System Diseases/complications; Nutritional Failure; Diagnosis; Differential; Digestive System; Pediatrics/methods; Proton Pumps/antagonists & inhibitors; Enzyme Inhibitors/therapeutic use; Diagnostic Techniques; Gastroesophageal Reflux/complications/diagnosis/physiopathology/therapy; Histamine H2 Antagonists/therapeutic use; Medical History Taking/methods; Respiratory Tract Diseases/etiology/prevention & control; Vomiting/diagnosis/etiology
2007
Michail S
Pediatrics In Review / American Academy Of Pediatrics
2007
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1542/pir.28-3-101" target="_blank" rel="noreferrer">10.1542/pir.28-3-101</a>