-
Expert Opinion on Drug Safety Oct 2016To explore the usefulness of number needed to treat to be harmed (NNTH), in benefit-risk assessments, by studying the agreement between NNTH values and withdrawals of... (Meta-Analysis)
Meta-Analysis
Testing the usefulness of the number needed to treat to be harmed (NNTH) in benefit-risk evaluations: case study with medicines withdrawn from the European market due to safety reasons.
OBJECTIVE
To explore the usefulness of number needed to treat to be harmed (NNTH), in benefit-risk assessments, by studying the agreement between NNTH values and withdrawals of medicines from European market due to safety reasons.
METHODS
Medicines with data from longitudinal studies were included. Studies were identified from European Medicines Agency's Reports. Meta-analyses were performed to pool odds ratios (OR) with 95% confidence-intervals (CI). Published control event rates were applied to ORs to calculate NNTHs (95%CI) for selected adverse events.
RESULTS
NNTH (95%CI) decreased from pre- to post-marketing for the eight medicines included: peripheral neuropathy (∞ vs. 12[non-significant; NS] with almitrine; heart valve disease with benfluorex (∞ vs. NNTH ranging from 7[4-13] to 7[5-9]); myopathy (-4096[NS] vs. 797[421-1690]), new-onset diabetes (113[NS] vs. 390[425-778]), bleeding (∞ vs. 517[317-1153]), and infection (∞ vs. 253[164-463]) with niacin-laropiprant; psychiatric disorders (12[7-34] vs. 9[5-24]) with rimonabant; myocardial infarction (MI) [-1305 vs. 270[89-4362]) with rofecoxib; MI (-510 vs. NNTH ranging from 152[55-4003] to 568[344-1350]) with rosiglitazone; cardiovascular events (∞ vs. 245[129-1318]) with sibutramine; and liver injury (∞ vs. 5957[NS]) with ximelagatran.
CONCLUSION
NNTH have potential of use as a supportive tool in benefit-risk re-evaluations of medicines and may help regulators to making decisions on drug safety.
Topics: Adverse Drug Reaction Reporting Systems; Drug-Related Side Effects and Adverse Reactions; Europe; Humans; Numbers Needed To Treat; Product Surveillance, Postmarketing; Risk Assessment; Safety-Based Drug Withdrawals
PubMed: 27467204
DOI: 10.1080/14740338.2016.1217989 -
Journal of Cardiothoracic and Vascular... Aug 2014Almitrine enhances hypoxic pulmonary vasoconstriction (HPV) and can improve hypoxemia related to one-lung ventilation (OLV). Studies using almitrine have been conducted... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Almitrine enhances hypoxic pulmonary vasoconstriction (HPV) and can improve hypoxemia related to one-lung ventilation (OLV). Studies using almitrine have been conducted without inhaled anesthetics because they could inhibit HPV, counteracting the effect of almitrine. This hypothesis, however, has not been confirmed. This study's aim was to evaluate whether almitrine could improve oxygenation when administered during OLV with sevoflurane anesthesia.
DESIGN
A prospective, randomized, double-blind, placebo-controlled trial.
SETTING
A tertiary care, university teaching hospital.
PARTICIPANTS
Thirty adult patients undergoing open-chest thoracic surgery.
INTERVENTIONS
Patients were assigned randomly to receive almitrine or placebo during OLV. Respiratory and hemodynamic variables were recorded continuously. Anesthesia was maintained with sevoflurane and remifentanil. Intraoperative techniques and medical teams were the same all over the study.
MEASUREMENTS AND MAIN RESULTS
Respiratory and hemodynamic variables were measured during two-lung ventilation and during open-chest OLV. Two-way repeated-measures analysis of variance was used to compare the effects of almitrine and placebo. During OLV, PaO2 and shunt fraction worsened in all patients without significant differences between groups. At 30-minutes of OLV, PaO2 was 184±67 mmHg in the almitrine group and 145±56 mmHg in the placebo group, while shunt fraction were 31%±6% and 36%±13%, respectively. Mean pulmonary artery pressure was higher in the almitrine group (31±5 v 24±5 mmHg, p<0.001).
CONCLUSIONS
During anesthesia with sevoflurane for open-chest OLV, almitrine failed to improve oxygenation and increased pulmonary artery pressure. The combination of sevoflurane and almitrine should, therefore, be avoided.
Topics: Adolescent; Adult; Aged; Almitrine; Anesthesia, General; Anesthetics, Inhalation; Blood Gas Analysis; Double-Blind Method; Female; Hemodynamics; Humans; Hypoxia; Lung; Male; Methyl Ethers; Middle Aged; Monitoring, Intraoperative; One-Lung Ventilation; Oxygen Consumption; Prospective Studies; Respiratory System Agents; Sevoflurane; Thoracic Surgical Procedures; Young Adult
PubMed: 24016684
DOI: 10.1053/j.jvca.2013.03.019