Adverse events study

Costs of direct hospital care, essentially additional time in hospital, have recently been estimated from the Dutch adverse events study finding that about 3 % of all bed days and 1 % of the total health budget could be attributed to preventable adverse events. The real overall costs are probably a good deal higher, as this estimate does not include additional treatments and investigations or any of the associated societal costs discussed above. Remember also that these estimates are confined to the hospital sector we have no idea of the additional costs of adverse events in primary care or mental health. 

The power of the major adverse event studies is that they reveal the overall scale of harm to patients and also, to some extent, the nature and causes... 

In all the major adverse event studies for which it was possible to extract evidence regarding the elderly, there is incontrovertible evidence that elderly people experience... 

Baker, G.R., Norton, RG., Flintoff, V. etal. (2004) The Canadian adverse events study the incidence of adverse events among hospital patients in Canada. Canadian Medical Association Journal, 170(11), 1678-1686. 

Schioler, T., Lipczak, H., Pedersen, B.L. et al. (2001) Danish adverse event study. [Incidence of adverse events in hospitals. A retrospective study of medical records]. Ugeskr Laeger, 163(1), 1585-1586. 

Baker, G. R., Norton, P. G., et al.. The Canadian Adverse Events Study The Incidence of Adverse Events among Hospital Patients in Canada, Canadian Medical Association Journal, Vol. 170, No. 11,2004, pp. 1678-1685. 

Rafter N, Hickey A, Conroy RM et al (2016) The Irish National Adverse Events Study (INAES) the frequency and nature of adverse events in Irish hospitals - a retrospective record review study. BMJ Qual Saf. doi 10.1136/bmjqs-2015-004828 [Epub ahead of print]... 

Based on adverse event studies and reports, a number of specific risk reduction strategies for dialysis units have been recommended recently [ 17,23]. These include for example ... 

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

The following points are worthy of note in terms of the placement of data. In the case of studies with multiple objectives, reports should be placed in the section corresponding to their primary purpose. Reports of laboratory studies conducted with human materials to investigate pharmacokinetic effects should be placed in Section 5.3.2 of the clinical module, as opposed to the non-clinical module. A US submission requires that the individual case report forms of all trial subjects that died or were dropped from a study due to adverse events are included in Section 5.3.7. 

In general, for smokers with cardiac disease, the benefits of nicotine replacement therapy outweigh the potential risks. In a safety and efficacy study that included veterans with cardiac disease, smoking concurrently with the nicotine patch was not associated with an increase in adverse events (Joseph et al. 1996). Although bupropion SR is generally well tolerated by smokers, it has not been adequately studied in persons with cardiac disease, and definitive conclusions regarding its safety in this patient population cannot currently be made (Society for Research on Nicotine and Tobacco 2003). 

Expert opinion is a source, frequently elicited by survey, that is used to obtain information where no or few data are available. For example, in our experience with a multicountry evaluation of health care resource utilization in atrial fibrillation, very few country-specific published data were available on this subject. Thus the decision-analytic model was supplemented with data from a physician expert panel survey to determine initial management approach (rate control vs. cardioversion) first-, second-, and third-line agents doses and durations of therapy type and frequency of studies that would be performed to initiate and monitor therapy type and frequency of adverse events, by body system and the resources used to manage them place of treatment and adverse consequences of lack of atrial fibrillation control and cost of these consequences, for example, stroke, congestive heart failure. This method may also be used in testing the robustness of the analysis [30]. 

Reconfiguration of Data. Drug safety data from different sources are often pooled or combined in databases. Reasons for combining data vary. In the case of premarketing studies, data from different sites are routinely combined because one site may not be able to recruit enough patients for a study. Data from different studies are often combined to increase sample size and therefore statistical power for detecting an uncommon adverse event. 

Study and control groups. Investigators need to consider whether the adverse events that occur are due to abnormalities in the distribution, metabolism, and excretion of drugs as a result of underlying disease. These analyses could be systematically facilitated by having standardized ways of measuring blood (and in some cases, tissue) levels of drugs and their metabolites. 

Refer to Chapter 14 on gastroesophageal reflux disease for more information on the PPIs. The PPI omeprazole is superior to both ranitidine and misoprostol for preventing recurrence of NSAID-associated PUD. In one study, omeprazole 20 mg daily was compared to misoprostol 200 meg twice daily for NSAID-associated PUD prevention. At 6 months, the omeprazole-treated group had significantly fewer ulcers than those taking misoprostol. Furthermore, more patients discontinued ulcer prophylaxis in the misoprostol group due to adverse events.26... 

Study Treatment Outcome Adverse Events Comments... 

Studies in patients with dementia sementics have revealed a higher rate of cerebrovascular adverse events, some resulting in fatalities in the active treatment group. 

Sirolimus is currently the only FDA-approved ToR inhibitor. One of its derivatives, everolimus, is in phase III clinical trials and has been approved for use in some European countries.30 Sirolimus is a macrolide antibiotic that has no effect on cal-cineurin phosphatase.11,31,32 Sirolimus inhibits T cell activation and proliferation by binding to and inhibiting the activation of the mammalian ToR, which suppresses cellular response to IL-2 and other cytokines (i.e., IL-4 and IL-15J.11,31 Studies have shown that sirolimus may be used safely and effectively with either cyclosporine or tacrolimus as a replacement for either azathioprine or mycophenolate mofetil.33 However, when using both sirolimus and cyclosporine as part of a patient s immunosuppressant therapy, because of a drug interaction between the two resulting in a marked increase in sirolimus concentrations, it is recommended to separate the sirolimus and cyclosporine doses by at least 4 hours. Sirolimus also can be used as an alternative agent for patients who do not tolerate calcineurin inhibitors due to nephrotoxicity or other adverse events.34... 

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