OBJECTIVES: To evaluate the evidence for the effectiveness of clonidine, when given as a premedication, in reducing postoperative pain in children less than 18 years of age. We also sought evidence of any clinically significant side effects.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 12, 2012), Ovid MEDLINE (1966 to 21 December 2012) and Ovid EMBASE (1982 to 21 December 2012), as well as reference lists of other relevant articles and online trial registers.
SELECTION CRITERIA: We included all randomized (or quasi-randomized), controlled trials comparing clonidine premedication to placebo, a higher dose of clonidine, or another agent when used for surgical or other invasive procedures in children under the age of 18 years and where pain or a surrogate (principally the need for supplementary analgesia) was reported.
DATA COLLECTION AND ANALYSIS: Two authors independently performed the database search, decided on the inclusion eligibility of publications, ascertained study quality and extracted data. They then resolved any differences between their results by discussion. The data were entered into RevMan 5 for analyses and presentation. Sensitivity analyses were performed, as appropriate, to exclude studies with a high risk of bias.
MAIN RESULTS: We identified 11 trials investigating a total of 742 children in treatment arms relevant to our study question. Risks of bias in the studies were mainly low or unclear, but two studies had aspects of their methodology that had a high risk of bias. Overall, the quality of the evidence from pooled studies was low or had unclear risk of bias. Four trials compared clonidine with a placebo or no treatment, six trials compared clonidine with midazolam, and one trial compared clonidine with fentanyl. There was substantial methodological heterogeneity between trials; the dose and route of clonidine administration varied as did the patient populations, the types of surgery and the outcomes measured. It was therefore difficult to combine the outcomes of some trials for meta-analysis.When clonidine was compared to placebo, pooling studies of low or unclear risk of bias, the need for additional analgesia was reduced when clonidine premedication was given orally at 4 µg/kg (risk ratio (RR) 0.24, 95% confidence interval (CI) 0.11 to 0.51). Only one small trial (15 patients per arm) compared clonidine to midazolam for the same outcome; this also found a reduction in the need for additional postoperative analgesia (RR 0.25, 95% CI 0.09 to 0.71) when clonidine premedication was given orally at 2 or 4 µg/kg compared to oral midazolam at 0.5 mg/kg. A trial comparing oral clonidine at 4 µg/kg with intravenous fentanyl at 3 µg/kg found no statistically significant difference in the need for rescue analgesia (RR 0.89, 95% CI 0.56 to 1.42). When clonidine 4 µg/kg was compared to clonidine 2 µg/kg, there was a statistically significant difference in the number of patients requiring additional analgesia, in favour of the higher dose, as reported by a single, higher-quality trial (RR 0.38, 95% CI 0.23 to 0.65).The effect of clonidine on pain scores was hard to interpret due to differences in study methodology, the doses and route of drug administration, and the pain scale used. However, when given at a dose of 4 µg/kg, clonidine may have reduced analgesia requirements after surgery. There were no significant side effects of clonidine that were reported such as severe hypotension, bradycardia, or excessive sedation requiring intervention. However, several studies used atropine prophylactically with the aim of preventing such adverse effects.
AUTHORS' CONCLUSIONS: There were only 11 relevant trials studying 742 children having surgery where premedication with clonidine was compared to placebo or other drug treatment. Despite heterogeneity between trials, clonidine premedication in an adequate dosage (4 µg/kg) was likely to have a beneficial effect on postoperative pain in children. Side effects were minimal, but some of the studies used atropine prophylactically with the intention of preventing bradycardia and hypotension. Further research is required to determine under what conditions clonidine premedication is most effective in providing postoperative pain relief in children.
METHODS: We developed a quantitative tool - the Toolkit for Evaluating Alcohol policy Stringency and Enforcement (TEASE-16) - to assess the level of stringency and enforcement of 16 alcohol control policies. TEASE-16 was applied to policy data from nine study areas in the western Pacific: Australia, China excluding Hong Kong Special Administrative Region (SAR), Hong Kong SAR, Japan, Malaysia, New Zealand, the Philippines, Singapore and Viet Nam. Correlation and regression analyses were then used to examine the relationship between alcohol policy scores and income-adjusted levels of alcohol consumption per capita.
FINDINGS: Vast differences exist in how alcohol control policies are implemented in the western Pacific. Out of a possible 100 points, the nine study areas achieved TEASE-16 scores that ranged from 24.1 points for the Philippines to 67.5 points for Australia. Study areas with high policy scores - indicating relatively strong alcohol policy frameworks - had lower alcohol consumption per capita. Sensitivity analyses indicated scores and rankings for each study area remained relatively stable across different weighting schemes, indicating that TEASE-16 was robust.
CONCLUSION: TEASE-16 could be used by international and national regulatory bodies and policy-makers to guide the design, implementation, evaluation and refinement of effective policies to reduce alcohol consumption and related problems.
METHODOLOGY: Data for the study, consisting of 2553 older adults aged 60 years and older, were drawn from a nationwide household survey entitled "Determinants of Wellness among Older Malaysians: A Health Promotion Perspective" conducted in 2010.
RESULTS: Current smokers had lower rates of cognitive impairment compared to never smokers (17.4% vs 25.9%), while cognitive function in former or ex-smokers was almost similar to that of the never smokers. Findings from multiple logistic regression analysis showed that current smokers were 37% less likely to be cognitively impaired, compared to the never smokers (odds ratio [OR] = .63; 95% confidence interval [CI]: .46-.86) while controlling for potential confounders. No difference in cognitive function was observed between former smokers and never smokers (OR = .94; 95% CI: .71-1.25).
CONCLUSION: Although the findings indicated a negative association between cigarette smoking and cognitive impairment, we are unable to conclude whether this relationship is causal or affected by other unmeasured confounding factors, especially survival bias.