Clozapine levels as a predictor for therapeutic response: A systematic review and meta-analysis.

OBJECTIVES: Clozapine levels may be a more useful predictor of therapeutic response than the dose, given the variability in clozapine metabolism between individuals. We therefore systematically reviewed and meta-analysed the impact of clozapine levels on response and/or relapse to provide guidance on optimal clozapine levels. METHODS: We systematically searched PubMed, PsycInfo and Embase for studies exploring clozapine levels and response and/or relapse. Our primary meta-analysis was rates of response above and below clozapine level thresholds of 350 ng/ml and 600 ng/ml. Secondary analyses were undertaken of mean clozapine levels, dose and concentration/dose (C/D) ratio and response and/or relapse. A meta-regression by study duration was conducted. RESULTS: Twenty studies met inclusion criteria. Clozapine levels above 350 ng/ml were associated with statistically significantly higher rates of response (OR 2.27 95% CI 1.40-3.67, p < 0.001), but not above 600 ng/ml (OR 1.40 95% CI 0.85-2.31, p = 0.19). Higher mean clozapine levels were associated with better rates of response (SMD 0.24, 95% CI 0.00-0.49, p = 0.05), and lower rates of relapse (SMD -0.72, 95% CI -1.26 to -0.19, p = 0.008). By contrast, neither clozapine dose nor C/D ratio was associated with differing rates of response. Similarly, study duration did not affect outcome. CONCLUSIONS: Our findings are in keeping with current guidelines that recommend targeting clozapine levels above 350 ng/ml before augmentation is considered. As some clozapine associated ADRs are dose dependent, levels above 600 ng/ml may have an unfavourable risk-benefit ratio.

Risk Factors for Surgical Site Infection in Minor Dermatological Surgery: A Systematic Review.

OBJECTIVE: To identify patient- and procedure-related risk factors for surgical site infection following minor dermatological surgery. DATA SOURCES: The MEDLINE, Cumulative Index of Nursing and Allied Health Literature, Informit, and Scopus databases were searched for relevant literature on patient populations receiving minor surgery, where risk factors for surgical site infection were explicitly stated. STUDY SELECTION: Studies involving major dermatological surgery were excluded. The preliminary search yielded 820 studies after removing duplicates; 210 abstracts were screened, and 42 full texts were assessed for eligibility. A total of 13 articles were included. Studies were appraised using the Newcastle-Ottawa Quality Assessment Scale. DATA EXTRACTION: An electronic data collection tool was constructed to extract information from the eligible studies, and this information was distributed to participating authors. DATA SYNTHESIS: Risk factors identified included age, sex, diabetes mellitus, chronic obstructive pulmonary disease, use of antihypertensive or corticosteroid medications, smoking, surgery on the lower or upper extremities, excision of nonmelanocytic skin cancers, large skin excisions, and complex surgical techniques. No more than two studies agreed on any given risk factor, and there were insufficient studies for meta-analysis. CONCLUSIONS: Re-excision of skin cancer, below-knee excisions, and intraoperative hemorrhagic complications were predictive for infection in more than one study. More high-quality studies are required to accurately identify risk factors so they can be reliably used in clinical guidelines.