Medication Blood Levels Research Articles

Mood disorders and suicide: pilot study on postmortem toxicologic evidence and adherence to psychiatric therapy by determining blood levels of medications.

Suicide is one of the leading causes of death today, and among all mental illness, mood disorders account for one of the main risk factors. It is well known and proven that suicides are very common among people undergoing treatment and prescribed psychiatric medication. So far, however, there have only been a few studies dealing with this particular phenomenon. For this reason, autopsy patients who died by suicide, suffered from a mood disorder, and were known to be taking psychiatric medication at the time of death were selected for this study. The blood and urine samples taken during the autopsy underwent toxicological analysis and the results were compared with the prescribed therapy. A total of 22 people were included in the study: 12 presenting with depression and 10 with bipolar disorder. The toxicological analysis revealed that only 6 cases (27%) showed a qualitative match with the prescribed medication. In 5 cases (22.7%) the medication was only partially complied with and in 11 cases (50%) it was not complied with at all. Furthermore, even when medication was present, the value was often below the therapeutic range. Overall, more than 70% of the test subjects adhered to their medication only partially or not at all. Since treatment adherence is considered as a key factor in reducing the risk of suicide, this inevitably raises relevant clinical and forensic questions. Against this background, prospective monitoring of post-mortem medication levels in suicidal individuals and synergistic collaboration between clinicians and forensic pathologists could help to evaluate the effectiveness of specific medical interventions, highlight existing critical problems and develop new approaches to suicide prevention.

The prevalence of off-label use and supratherapeutic blood levels of outpatient psychotropic medication in suicidal adolescents.

Adolescents with mental disorders show an increased risk of suicidal phenomena. Vice versa, suicidality is a serious adverse event of psychotropic drug therapy in adolescents. There are only a few new psychotropic agents approved for this young age group. We evaluated the (pre-pandemic) prevalence of off-label use as well as detailed blood concentrations of outpatient psychotropic medication and sex differences in a clinical population of suicidal adolescents. The urine presence and serum levels of psychotropic substances of adolescents hospitalized due to their acute suicidality but without a known actual suicide attempt (i.e., no acute intoxication or serious self-injuries) were investigated routinely between 01.03.2017 and 31.01.2018. Urine (N = 205) and blood samples (N = 193) were taken at the beginning of closed inpatient admission, i.e., the results of the laboratory analysis reflect outpatient drug intake. The serum levels of psychopharmacological medication and OTC medication were measured. Our sample consists of 231 cases (boys: N = 54; girls: N = 177, ratio: 1:3.3), aged 12-17 years (average age: 15,4 years). The most prevalent psychiatric diagnoses were depressive episodes (54%) and adjustment disorders (25%), and girls were more often diagnosed with depressive disorders than boys (boy/girl ratio: 1:9.5, p < 0.0001). More than half of adolescents (56%) used at least one prescribed psychotropic drug at admission (24.8% ≥ two psychotropic drugs). Off-label use of second-generation antipsychotics was significantly more frequent than off-label use of antidepressants (85% vs. 31%, p < 0.01). Adolescents suffering from depressive disorders were significantly more often on-label treated than adolescents with neurotic or stress-related disorders (56% vs. 10%). Female cases with prescribed psychotropic drug use showed significantly more frequent supratherapeutic drug levels than male cases (5% vs. 27%, p < 0.05). Female adolescents may have an increased risk of supratherapeutic blood levels, especially when outpatient prescribed psychotropic drugs are off-label used. Measurement of blood levels of outpatient-prescribed psychotropic drugs could be used to enhance the safety and efficacy of the individual psychopharmacological treatment of adolescent suicidal patients. There is an urgent need for more real-world evidence on the effective treatment of adolescents with psychotropic drugs.

Therapeutic drug monitoring of lacosamide among children: is it helpful?

Objective: This study aimed to investigate the efficacy and tolerability of Lacosamide (LCM) in a pediatric population with epilepsy using LCM serum concentration and its correlation to the age of the participants and the dosage of the drug. Methods: Demographic and clinical data were collected from the medical records of children with epilepsy treated with LCM at Shamir Medical Center between February 2019 to September 2021, in whom medication blood levels were measured. Trough serum LCM concentration was measured in the biochemical laboratory using High-Performance Liquid Chromatography (HPLC) and correlated with the administered weight-based medication dosing and clinical report. Results: Forty-two children aged 10.43 ± 5.13years (range: 1-18) were included in the study. The average daily dose of LCM was 306.62 ± 133.20mg (range: 100-600). The average number of seizures per day was 3.53 ± 7.25 compared to 0.87 ± 1.40 before and after LCM treatment, respectively. The mean LCM serum concentration was 6.74 ± 3.27mg/L. No statistically significant association was found between LCM serum levels and the clinical response (p = 0.58), as well as the correlation between LCM dosage and the change in seizure rate (p = 0.30). Our study did not find a correlation between LCM serum concentration and LCM dosage and the gender of the participants: males (n = 17) females (n = 23) (p = 0.31 and p = 0.94, respectively). A positive trend was found between age and LCM serum concentrations (r = 0.26, p = 0.09). Conclusion: Based on the data that has been obtained from our study, it appears that therapeutic drug monitoring for LCM may not be necessary. Nonetheless, further research in this area is needed in the light of the relatively small sample size of the study.

Pharmacogenomic Profiling of Pediatric Patients on Psychotropic Medications in an Emergency Department.

The aim of the study was to evaluate the ability of a combinatorial pharmacogenomic test to predict medication blood levels and relative clinical improvements in a selected pediatric population. This study enrolled patients between ages 3 to 18 years who presented to a pediatric emergency department with acute psychiatric, behavioral, or mental health crisis and/or concerns, and had previously been prescribed psychotropic medications. Patients received combinatorial pharmacogenomic testing with medications categorized according to gene-drug interactions (GDIs); medications with a GDI were considered "incongruent," and medications without a GDI were considered "congruent." Blood levels for escitalopram, fluoxetine, aripiprazole, and clonidine were evaluated according to level of GDI. Relative clinical improvements in response to the prescribed psychotropic medications were measured using a parent-rated Clinical Global Impression of Improvement (CGI-I) assessment, where lower scores corresponded with greater improvement. Of the 100 patients enrolled, 73% reported taking ≥1 incongruent medication. There was no significant difference in CGI-I scores between patients prescribed congruent versus incongruent medications (3.37 vs 3.68, P = 0.343). Among patients who presented for depression or suicidal ideation, those prescribed congruent medications had significantly lower CGI-I scores compared with those taking incongruent medications ( P = 0.036 for depression, P = 0.018 for suicidal ideation). There was a significant association between medication GDI and blood levels for aripiprazole (n = 15, P = 0.01) and escitalopram (n = 10, P = 0.01). Our preliminary findings suggest that combinatorial pharmacogenomic testing can predict medication blood levels and relative outcomes based on medication congruency in children presenting to an emergency department with acute psychiatric/behavioral crises. Additional studies will be needed to confirm these findings.

Fetal Exposure to Antiseizure Medications.

According to this study: Cognitive outcomes at two years of age in the language domain of the Bayley Scales of Infant and Toddler Development, Third Edition, didn't differ between children of women with epilepsy and children of healthy women.In adjusted analyses, however, higher blood levels of antiseizure medication in the third trimester were associated with lower scores for the motor and general adaptive domains.

Remote intervention engagement and outcomes in the Clinical Trials in Organ Transplantation in Children consortium multisite trial

Remote interventions are increasingly used in transplant medicine but have rarely been rigorously evaluated. We investigated a remote intervention targeting immunosuppressant management in pediatric lung transplant recipients. Patients were recruited from a larger multisite trial if they had a Medication Level Variability Index (MLVI) ≥2.0, indicating worrisome tacrolimus level fluctuation. The manualized intervention included three weekly phone calls and regular follow-up calls. A comparison group included patients who met enrollment criteria after the subprotocol ended. Outcomes were defined before the intent-to-treat analysis. Feasibility was defined as ≥50% of participants completing the weekly calls. MLVI was compared pre- and 180days postenrollment and between intervention and comparison groups. Of 18 eligible patients, 15 enrolled. Seven additional patients served as the comparison. Seventy-five percent of participants completed ≥3 weekly calls; average time on protocol was 257.7days. Average intervention group MLVI was significantly lower (indicating improved blood level stability) at 180days postenrollment (2.9±1.29) compared with pre-enrollment (4.6±2.10), p=.02. At 180days, MLVI decreased by 1.6 points in the intervention group but increased by 0.6 in the comparison group (p=.054). Participants successfully engaged in a long-term remote intervention, and their medication blood levels stabilized. NCT02266888.

Impact of CytoSorb on kinetics of vancomycin and bivalirudin in critically ill patients.

CytoSorb is a promising tool to treat severe inflammatory status with multiple mechanisms in the acute care setting. Its effect on drugs is, however, poorly documented in vivo, although removal of small molecules might translate into decreased blood levels of life-saving medications. The aim of this study was to assess the impact of CytoSorb on vancomycin and bivalirudin clearance in a large population of critically ill patients. We performed a single-center analysis of CytoSorb treatments performed between January 2018 and March 2019 in critically ill patients admitted to our intensive care unit. A total of 109 CytoSorb treatments were performed in 89 patients. A decrease in lactate dehydrogenase (P=.007), troponin T (P=.022), and creatine phosphokinase (P=.013) was reported during treatment. Vancomycin dose required significant adjustments during treatment (P<.001), but no significant change was necessary after the first 3days. Similarly, the requirements of bivalirudin significantly changed over days (P<.001), but no dose adjustment was needed after the first 3days of treatment. No differences in terms of vancomycin and bivalirudin dose need was observed between patients on extracorporeal membrane oxygenation and those who were not (P=.6 and P=.6, respectively), between patients with and without continuous veno-venous hemofiltration (P=.9 and P=.9, respectively), and between CytoSorb responders or not (P=.4 and P=.7, respectively). CytoSorb is effective in mitigating the systemic inflammatory response and safe with respect to vancomycin and bivalirudin administration. These preliminary data further support the use of CytoSorb as adjunct therapy in critically ill patients.

Clinical validation of combinatorial pharmacogenomic testing and single-gene guidelines in predicting psychotropic medication blood levels and clinical outcomes in patients with depression

We evaluated the clinical validity of a combinatorial pharmacogenomic test and single-gene Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines against patient outcomes and medication blood levels to assess their ability to inform prescribing in major depressive disorder (MDD).This is a secondary analysis of the Genomics Used to Improve DEpression Decisions (GUIDED) randomized-controlled trial, which included patients with a diagnosis of MDD, and ≥1 prior medication failure. The ability to predict increased/decreased medication metabolism was validated against blood levels at screening (adjusted for age, sex, smoking status). The ability of predicted gene-drug interactions (pharmacogenomic test) or therapeutic recommendations (single-gene guidelines) to predict patient outcomes was validated against week 8 outcomes (17-item Hamilton Depression Rating Scale; symptom improvement, response, remission). Analyses were performed for patients taking any eligible medication (outcomes N=1,022, blood levels N=1,034) and the subset taking medications with single-gene guidelines (outcomes N=584, blood levels N=372). The combinatorial pharmacogenomic test was the only significant predictor of patient outcomes. Both the combinatorial pharmacogenomic test and single-gene guidelines were significant predictors of blood levels for all medications when evaluated separately; however, only the combinatorial pharmacogenomic test remained significant when both were included in the multivariate model. There were no substantial differences when all medications were evaluated or for the subset with single-gene guidelines. Overall, this evaluation of clinical validity demonstrates that the combinatorial pharmacogenomic test was a superior predictor of patient outcomes and medication blood levels when compared with guidelines based on individual genes.

Combinatorial Pharmacogenomic Algorithm is Predictive of Citalopram and Escitalopram Metabolism in Patients with Major Depressive Disorder

Pharmacogenomic tests used to guide clinical treatment for major depressive disorder (MDD) must be thoroughly validated. One important assessment of validity is the ability to predict medication blood levels, which reflect altered metabolism. Historically, the metabolic impact of individual genes has been evaluated; however, we now know that multiple genes are often involved in medication metabolism. Here, we evaluated the ability of individual pharmacokinetic genes (CYP2C19, CYP2D6, CYP3A4) and a combinatorial pharmacogenomic test (GeneSight Psychotropic®; weighted assessment of all three genes) to predict citalopram/escitalopram blood levels in patients with MDD. Patients from the Genomics Used to Improve DEpression Decisions (GUIDED) trial who were taking citalopram/escitalopram at screening and had available blood level data were included (N=191). In multivariate analysis of the individual genes and combinatorial pharmacogenomic test separately (adjusted for age, smoking status), the F statistic for the combinatorial pharmacogenomic test was 1.7 to 2.9-times higher than the individual genes, showing that it explained more variance in citalopram/escitalopram blood levels. In multivariate analysis of the individual genes and combinatorial pharmacogenomic test together, only the combinatorial pharmacogenomic test remained significant. Overall, this demonstrates that the combinatorial pharmacogenomic test was a superior predictor of citalopram/escitalopram blood levels compared to individual genes.

Interaction with St. John's wort due to exposure with blackcurrant aroma? How not to present a case report of an adverse event.

Background: Adverse events case reports are important for signal generation in pharmacovigilance. They require a thorough collation of the facts, otherwise they may lead to erroneous conclusions which may conceal other treatment-related causes of the observation. Methods: We describe a case report from the literature that arrives at an erroneous conclusion merely from taking insufficient care when collating and interpreting the facts: The authors of the case report confused blackcurrant (Ribes nigrum) with St. John's wort preparation (Hypericum perforatum) and erroneously assumed that the intake of a herbal preparation was responsible for a drop in serum levels of everolimus. Results: The clinical observations in this case report may actually reflect a potentially lethal situation emerging from the prescribed medication everolimus. St. John's wort preparations rich in hyperforin do in fact reproducibly lead to the decrease of blood levels of medications metabolized through cytochrome P450 subtype 3A4. However, a case report requires more care than just ascribing the blame to something seemingly well-known. Conclusion: The readers of this report might have profited more from the description of the risks of treating graft-versus-host disease with everolimus, and the action to be taken in case of potentially severe adverse reactions to everolimus.

Tobacco use disorder and treatment: new challenges and opportunities

Tobacco use remains a global problem, and options for consumers have increased with the development and marketing of e-cigarettes and other new nicotine and tobacco products, such as "heat-not-burn" tobacco and dissolvable tobacco. The increased access to these new products is juxtaposed with expanding public health and clinical intervention options, including mobile technologies and social media. The persistent high rate of tobacco-use disorders among those with psychiatric disorders has gathered increased global attention, including successful approaches to individual treatment and organizational-level interventions. Best outcomes occur when medications are integrated with behavioral therapies and community-based interventions. Addressing tobacco in mental health settings requires training and technical assistance to remove old cultural barriers that restricted interventions. There is still "low-hanging fruit" to be gained in educating on the proper use of nicotine replacement medications, how smoking cessation can change blood levels of specific medications and caffeine, and how to connect with quitlines and mobile technology options. Future innovations are likely to be related to pharmacogenomics and new technologies that are human-, home-, and community-facing.

Psychosocial predictors of medication adherence in pediatric heart and lung organ transplantation.

Few studies have identified the psychosocial characteristics of those children and their families associated with future non-adherence to immunosuppressive medications following a heart or lung transplant. UNOS data and medical records information were used to test the association between patient and family psychosocial characteristics and medication adherence. Medication adherence outcomes were obtained using the physician assessments in the UNOS data and measured through patient-level standard deviation scores of immunosuppressive medication blood levels. Complete data were collected on 105 pediatric heart and lung transplant recipients and their families. Multivariate, stepwise analyses were conducted with each adherence outcome. Physician reports of adherence were associated with age of the child at transplantation, parental education, two-parent families, significant psychosocial problems, and the pretransplant life support status of the child. The resulting model (χ2 =28.146, df=5, P<.001) explained approximately 39.5% of the variance in physician reports of adherence (Nagelkerke r2 =.395). Blood level standard deviation scores were predicted by age at transplant (F=5.624, P=.02, r2 =.05). Results point to the difficulties experienced by children and families when undergoing a heart or lung transplantation. Efforts to develop standardized and evidence-based pretransplant psychosocial assessments in pediatric populations are suggested, especially those surrounding familial risk factors.

Self-efficacy beliefs, locus of control, religiosity and non-adherence to immunosuppressive medications in kidney transplant patients.

Adherence to immunosuppressive medication is essential for favourable kidney transplant outcomes. The present study aims to investigate how self-efficacy beliefs, health locus of control and religiosity are associated with adherence to immunosuppressives in post kidney transplant recipients. This is a cross-sectional study with 88 recipients with more than 1 year after transplantation. Three methods were used to classify patients as adherent or non-adherent: Basel Assessment of Adherence Scale for Immunosuppressives - BAASIS, the collateral report and blood levels of immunosuppressive medications. Self-efficacy, health locus of control, and religiosity were evaluated applying General Perceived Self-Efficacy Scale, Multidimensional Health Locus of Control Scale and Duke University Religion Index, respectively. Non-adherence was modelled by uni- and multivariated analysis. Sixty-three percent of the patients were male, age 47.2 ± 12.9 years, and median post-transplant time 108.71 (49.0-266.0) months. We found 70.5% of patients were non-adherent through at least one method. Adherent patients presented higher self-efficacy scores (45.1 ± 4.9 vs 38.3 ± 8.6; P < 0.001) and higher intrinsic religiosity (14.0 ± 1.6 vs. 12.8 ± 2.5; P = 0.016) compared to the non-adherents. Organizational and non-organizational religiosity did not differ between these groups. By logistic regression, non-adherence was associated with lower self-efficacy (OR 0.81, IC 0.70-0.92, P = 0.002), chance locus of control (OR 1.23, IC 1.04-1.45, P = 0.016) and lower intrinsic religiosity (OR 0.56, IC 0.38-0.84, P = 0.006). Our study showed that self-efficacy, chance locus of control, and intrinsic religiosity were associated with non-adherence to immunosuppressives. A broader perception of the kidney transplant patient´s integrality can help health professionals to design strategies to promote adherence in this population.

Psychiatric clearance for patients started on interferon-alpha-based therapies.

Increasingly, psychiatrists are asked to provide “psychiatric clearance” for patients who are to be treated with a regimen that includes recombinant preparations of interferon-alpha (IFN-a), often in combination with other antiviral medications. The most common use for IFN-a is in the treatment of chronic hepatitis C, which affects about 2% of the general U.S. population and about 20% of people with severe mental illness (1). Each year, more people in the United States die from hepatitis C complications, such as severe cirrhosis and hepatocellular cancer, than from HIV. IFN-a is also used, in combination with other medications, to treat some cancers, such as metastatic melanoma. This recombinant inflammatory cytokine has been associated with adverse effects on mental health, worse quality of life, increased risk for suicide, and treatment discontinuation. Most patients develop some fatigue and loss of appetite during treatment, which can be severe but is usually tolerable. However, 10%–40% additionally develop a full depressive disorder syndrome that can include suicidal ideation, amotivation, social withdrawal, guilt, anhedonia, irritability, anxiety, and crying (2–8). Untreated depression is a major contributor to dosage reductions or treatment discontinuations and consequent risk for viral relapse (9–11). Additionally, many patients with hepatitis C already have preexisting mental health disorders (12) that often go unrecognized (13). Such disorders can adversely affect a person’s ability to tolerate a 24to 48-week course of antiviral IFN-a therapy. In addition to depression during IFN-a treatment, many patients (up to 25%) may develop anger and irritability (14–17), which can be independent of depression. These symptoms can occasionally be serious enough to result in road rage, spousal discord, and problems at work. Another common side effect of IFN-a is severe fatigue. Less commonly, mania, delirium, and psychosis can occur. Monitoring for these various psychiatric side effects, as well as distinguishing among these distinct conditions, is one role for the psychiatrist. Also, coadministered medications such as telaprevir and boceprevir (antiviral protease inhibitors) can inhibit cytochrome P450 (CYP) 3A4, resulting in increased blood levels of many psychiatric medications. A knowledge of psychopharmacology and potential medication interactions is thus also important. Finally, IFN-a treatment commonly has mild side effects such as nausea and malaise and occasionally is complicated by severe hematologic abnormalities. Both sustained adherence and psychosocial stability are necessary, even in patients who do not develop frank neuropsychiatric syndromes.

PP129: Sirolimus levels in blood vs. saliva in chronically treated patients – A rational basis for topical use

Purpose Sirolimus, currently used as an immunosuppressant, is a potent mammalian target of rapamycin blocker with antiproliferative activity. Its potential for the management of oral pathologies and cancer and has been suggested. Topical application in the oral cavity can enhance availability and efficacy of the drug. The objective of this study was to establish an analytical method for determining sirolimus levels in human saliva in those using sirolimus chronically as well as calculation of the blood vs. saliva ratio. Materials and methods Chemiluminescent microparticle immunoassay technology was used to determine blood and saliva levels of sirolimus in kidney transplant patients. All patients signed informed consent forms and an examination of the oral cavity was performed, clinical findings and oral symptoms, if any, were recorded along with the medical status of the patient. Blood and saliva samples were collected at the same time and analyzed. The study was approved by the institutional review board. Results An analytical method for determining sirolimus levels in human saliva was established. Four patients were enrolled in the study. In all patients medication blood levels were stable. None of the patients had pathological lesions in their oral cavities. A substantial variability was observed among samples. No linear correlation was found. The saliva levels were on average four times lower than blood levels. Conclusions The sensitive Chemiluminescent microparticle immunoassay method determined sirolimus levels both in saliva and blood in treated patients. Sirolimus saliva levels are significantly lower than blood levels.These results emphasize the need for delivery methods with better oral topical biological availability and reinforce the rationale for using sirolimus topically for the treatment of responsive oral pathologies.

Management of breakthrough pain due to cancer [Polish version: Bóle przebijające u pacjentów z chorobą nowotworową p. 502

Breakthrough pain is defined as the transient exacerbation of pain occurring in a patient with otherwise stable, persistent pain. It is estimated to affect over 50% of patients, particularly those with moderate to severe background pain. Breakthrough pain is one of the most difficult pain syndromes to treat. There are several types of breakthrough cancer pain: incidental type involves flares of pain associated with movement or activity; idiopathic type is transitory pain unrelated to a specific activity; and in end-of-dose failure pain occurs when blood levels of medications fall below an analgesic threshold at the end of a dosing interval. Persistent and breakthrough pain are distinct components of cancer pain and require separate management. Successful management of breakthrough pain may require a combination of pharmacological and non-pharmacological treatment strategies. Supplemental analgesia, known as rescue medication, is a common pharmacological treatment option. Breakthrough pain is treated with supplemental short-acting opioid use, as needed, e.g. short-acting morphine, intranasal fentanyl and buccal tablets of fentanyl.

The embryotoxicity of sera from patients with autoimmune diseases on post-implantation rat embryos in culture persists during remission and is not related to oxidative stress

We evaluated the embryolethality and embryotoxicity of sera from patients suffering from autoimmune diseases during remission on post-implantation rat embryos cultured on these sera and determined the association between the patients' clinical history, high blood levels of specific antibodies, medications, and oxidative stress parameters. One hundred and eighty, 10.5-day-old rat embryos were cultured in their yolk sacs in 33 sera of systemic lupus erythematosus (SLE)/antiphospholipid syndrome (APS) patients, and compared with 84 embryos cultured in rat sera and 88 embryos cultured in control human sera. The sera proved to be lethal and embryotoxic but not teratogenic resulting in smaller yolk sacs and embryos, lower protein level and lower developmental score. Significantly less embryos cultured in 'toxic' SLE/APS sera had peak 2 of low molecular weight antioxidants (LMWA) wave, implying a delayed maturation of the antioxidant defense. Lower peak 1 of LMWA correlated with a history of recurrent abortions. Embryonic levels of superoxide dismutase (SOD) and catalase (CAT) did not correlate with sera toxicity, patients' clinical history or specific antibodies. We conclude that SLE/APS patients' clinical remission did not prevent death or developmental delay accompanied by later appearance of peak 2 of LMWA in post-implantation rat embryo cultures. The normal levels of the antioxidant enzymes evaluated may indicate that sera toxicity is not related to oxidative stress.

The Progression of Electronic Health Records and Implications for Psychiatry

The Progression of Electronic Health Records and Implications for Psychiatry

Tobacco dependence, treatment and smoke-free policies: a survey of mental health professionals' knowledge and attitudes

Background Mental health inpatient units in England have to be smoke-free by law. Preliminary studies have indicated that staff may not have the necessary knowledge and resources to support the implementation of a smoke-free policy. Objective The objective of this study was to investigate staff knowledge and attitudes relating to smoking prevalence, dependence, treatment and the relationship between smoking and mental illness. Design This study used a questionnaire survey for all the clinical staff of 25 inpatient mental health units of a UK National Health Service mental health Trust. Results Four hundred fifty-nine (68%) staff returned the questionnaire. Less than half (42%) of the participants agreed that dealing with patients' smoking was their responsibility as a mental health professional, and only half (50%) asserted that they could make time to treat smoking in their working routine. All professional groups demonstrated a lack of knowledge about tobacco dependence, treatment and its relation with mental illness, with healthcare assistants being least knowledgeable overall. Nevertheless, 41% of doctors were unaware that smoking can decrease blood levels of antipsychotic medications, and 36% were unaware that stopping smoking could reduce the dose needed. Staff overestimated the prevalence of smoking in the general population, and over a third (36.4%) believed that nicotine was carcinogenic. Staff smoking prevalence was 26% (10% of doctors, 22% of other qualified staff and 37% of nonqualified staff), and smokers were more likely to have reservations about the importance of the smoke-free policy and the treatment of nicotine dependence among patients. Reported participation in training was associated with greater knowledge related to some items of the questionnaire. Conclusions Support for inpatient smokers by staff is likely to be severely compromised by low levels of knowledge and awareness of tobacco dependence. Further training and support for all staff groups are urgently required.

5% 5‐Fluorouracil Cream for Treatment of Verruca Vulgaris in Children

Warts are a common pediatric skin disease. Most treatments show only modest benefit, and some are poorly tolerated because of pain. 5-fluorouracil interferes with deoxyribonucleic acid and ribonucleic acid synthesis, and is used to treat genital warts in adults. Efficacy, safety, and tolerability of topical 5% 5-fluorouracil for treatment of common warts were examined in an open-label pilot study with pediatric patients. Thirty-nine children who have at least two hand warts applied 5% 5-fluorouracil cream (Efudex, Valeant Pharmaceuticals International) once or twice daily, under occlusion for 6 weeks. Assessment of treatment response and side effects was performed at baseline, treatment completion, and 3- and 6-month follow-ups. Hematology measures, liver function tests, and medication blood levels were reassessed at treatment completion. Eighty-eight percent of treated warts improved after 6 weeks of treatment, and 41% of subjects had complete resolution of at least one wart. Treatment response did not differ between once or twice daily applications. Tolerability and patient satisfaction were excellent. No subject had clinically significant blood levels of 5-fluorouracil. At 6 month follow-up, 87% of complete responders had no wart recurrence. Topical 5% 5-fluorouracil is a safe, effective, and well-tolerated treatment for warts in children.