Impact of a pharmacist-led thiopurine monitoring service in outpatients with inflammatory bowel disease.

BACKGROUND: Thiopurines are effective therapies for inflammatory bowel disease (IBD); however, treatment comes with safety concerns and adverse effects. Knowledge of the impact of pharmacists performing thiopurine monitoring is limited. AIMS: To determine the impact of a pharmacist-led monitoring service in patients with IBD commencing thiopurine therapy managed in the ambulatory care setting. METHODS: Patients commencing thiopurine therapy for IBD pre- and post-introduction of a pharmacist-led monitoring intervention were assessed. Pre-intervention patients received standard of care, while the post-intervention cohort was managed by the pharmacist. Data were acquired via retrospective audit of hospital medical records. The primary end-point was the proportion of patients with documented review for thiopurine adverse effects within the initial 3 weeks. Secondary end-points included achievement of therapeutic drug levels, persistence with thiopurine therapy, IBD-related episodes of care and number of outpatient medical reviews. RESULTS: Pre- and post-intervention cohorts comprised of 37 and 33 patients respectively. Pharmacist intervention increased the proportion of patients with documented monitoring within 3 weeks from 8.1% to 84.8% (P < 0.01). No difference in thiopurine dose optimisation was seen (27% vs 27.3%). Persistence with thiopurine therapy increased from 65.7% to 87.9% (P < 0.03) at 6 months. IBD-related emergency department presentations were not significantly decreased (8.1% vs 3%; P = 0.62). No significant change was observed in hospital admissions (16.2% vs 12.1%; P = 0.74) or outpatient medical reviews. CONCLUSIONS: Pharmacist monitoring of thiopurine therapy initiation in IBD outpatients improves adverse effect monitoring and increases medication persistence.

Epidemiology of Escherichia coli bacteraemia in England: results of an enhanced sentinel surveillance programme.

BACKGROUND: Escherichia coli causes more than one-third of the bacteraemia cases in England each year, and the incidence of these infections is increasing. AIM: To determine the underlying risk factors associated with E. coli bacteraemia. METHODS: A three-month enhanced sentinel surveillance study involving 35 National Health Service hospitals was undertaken in the winter of 2012/13 to collect risk factor information and further details on the underlying source of infection to augment data already collected by the English national surveillance programme. Antimicrobial susceptibility results for E. coli isolated from blood and urine were also collected. FINDINGS: A total of 1731 cases of E. coli bacteraemia were included. The urogenital tract was the most frequently reported source of infection (51.2% of cases) with previous treatment for a urinary tract infection being the largest independent effect associated with this infection source. Half of all patients had previous healthcare exposure in the month prior to the bacteraemia with antimicrobial therapy and urinary catheterization being reported in one-third and one-fifth of these patients, respectively. Previous healthcare exposure was associated with a higher proportion of antibiotic non-susceptibility in the blood culture isolates (P=0.001). CONCLUSION: Analysis of risk factors suggests the potential benefit of community- and hospital-related interventions, especially the better use of urinary catheters and improved antibiotic management of urinary tract infections. As part of the latter strategy, antibiotic resistance profiles need to be closely monitored to ensure that treatment guidelines are up to date to limit inappropriate empiric therapy.

A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1.

Genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of childhood acute lymphoblastic leukemia (ALL). To identify new susceptibility loci for the largest subtype of ALL, B-cell precursor ALL (BCP-ALL), we conducted a meta-analysis of two GWASs with imputation using 1000 Genomes and UK10K Project data as reference (totaling 1658 cases and 7224 controls). After genotyping an additional 2525 cases and 3575 controls, we identify new susceptibility loci for BCP-ALL mapping to 10q26.13 (rs35837782, LHPP, P=1.38 × 10-11) and 12q23.1 (rs4762284, ELK3, P=8.41 × 10-9). We also provide confirmatory evidence for the existence of independent risk loci at 9p21.3, but show that the association marked by rs77728904 can be accounted for by linkage disequilibrium with the rare high-impact CDKN2A p.Ala148Thr variant rs3731249. Our data provide further insights into genetic susceptibility to ALL and its biology.

Impact of national policies on the microbial aetiology of surgical site infections in acute NHS hospitals in England: analysis of trends between 2000 and 2013 using multi-centre prospective cohort data.

Our study aimed to evaluate changes in the epidemiology of pathogens causing surgical site infections (SSIs) in England between 2000 and 2013 in the context of intensified national interventions to reduce healthcare-associated infections introduced since 2006. National prospective surveillance data on target surgical procedures were used for this study. Data on causative organism were available for 72% of inpatient-detected SSIs meeting the standard case definitions for superficial, deep and organ-space infections (9767/13 531) which were analysed for trends. A multivariable logistic linear mixed model with hospital random effects was fitted to evaluate trends by pathogen. Staphylococcus aureus was the predominant cause of SSI between 2000 (41%) and 2009 (24%), decreasing from 2006 onwards reaching 16% in 2013. Data for 2005-2013 showed that the odds of SSI caused by S. aureus decreased significantly by 14% per year [adjusted odds ratio (aOR) 0·86, 95% confidence interval (CI) 0·83-0·89] driven by significant decreases in methicillin-resistant S. aureus (MRSA) (aOR 0·71, 95% CI 0·68-0·75). However a small significant increase in methicillin-sensitive S. aureus was identified (aOR 1·06, 95% CI 1·02-1·10). Enterobacteriaceae were stable during 2000-2007 (12% of cases overall), increasing from 2008 (18%) onwards, being present in 25% of cases in 2013; the model supported these increasing trends during 2007-2013 (aOR 1·12, 95% CI 1·07-1·18). The decreasing trends in S. aureus SSIs from 2006 and the increases in Enterobacteriaceae SSIs from 2008 may be related to intensified national efforts targeted at reducing MRSA bacteraemia combined with changes in antibiotic use aimed at controlling C. difficile infections.

Impact of obesity on the risk of wound infection following surgery: results from a nationwide prospective multicentre cohort study in England.

We sought to assess the impact of body mass index on the risk of surgical site infection in a prospective cohort study of 206 National Health Service (NHS) hospitals in England between 2007 and 2011. Body mass index was available for 159,720 of 350,089 operations among patients undergoing abdominal hysterectomy, coronary artery bypass graft, hip replacement, knee replacement, or large-bowel surgery. Among these patients, the risk of surgical site infection ranged from 0.65% for knee replacement to 11.04% for large-bowel surgery. Overall, 127,512 (79.8%) patients were overweight or obese (body mass index of ≥25 kg/m(2)). Obesity was associated with a 1.1-fold to 4.4-fold increase in the adjusted odds of developing surgical site infection as compared with normal weight, depending on the type of surgery. The population-attributable fraction (PAF) for body mass index was greatest in overweight (body mass index of 25.0-29.9 kg/m(2)) patients undergoing coronary artery bypass graft, accounting for 15% of their overall risk of surgical site infection (PAF 0.15; 95% CI 0.09-0.22). Being overweight or obese substantially increased the likelihood of patients developing surgical site infection. Given the increasingly high proportion of the surgical population who are overweight, this is likely to place a considerable additional burden on the NHS. Strategies for mitigating this excess risk need to be found.

Determining the genome-wide kinship coefficient seems unhelpful in distinguishing consanguineous couples with a high versus low risk for adverse reproductive outcome.

BACKGROUND: Offspring of consanguineous couples are at increased risk of congenital disorders. The risk increases as parents are more closely related. Individuals that have the same degree of relatedness according to their pedigree, show variable genomic kinship coefficients. To investigate whether we can differentiate between couples with high- and low risk for offspring with congenital disorders, we have compared the genomic kinship coefficient of consanguineous parents with a child affected with an autosomal recessive disorder with that of consanguineous parents with only healthy children, corrected for the degree of pedigree relatedness. METHODS: 151 consanguineous couples (73 cases and 78 controls) from 10 different ethnic backgrounds were genotyped on the Affymetrix platform and passed quality control checks. After pruning SNPs in linkage disequilibrium, 57,358 SNPs remained. Kinship coefficients were calculated using three different toolsets: PLINK, King and IBDelphi, yielding five different estimates (IBDelphi, PLINK (all), PLINK (by population), King robust (all) and King homo (by population)). We performed a one-sided Mann Whitney test to investigate whether the median relative difference regarding observed and expected kinship coefficients is bigger for cases than for controls. Furthermore, we fitted a mixed effects linear model to correct for a possible population effect. RESULTS: Although the estimated degrees of genomic relatedness with the different toolsets show substantial variability, correlation measures between the different estimators demonstrated moderate to strong correlations. Controls have higher point estimates for genomic kinship coefficients. The one-sided Mann Whitney test did not show any evidence for a higher median relative difference for cases compared to controls. Neither did the regression analysis exhibit a positive association between case-control status and genomic kinship coefficient. CONCLUSIONS: In this case-control setting, in which we compared consanguineous couples corrected for degree of pedigree relatedness, a higher degree of genomic relatedness was not significantly associated with a higher likelihood of having an affected child. Further translational research should focus on which parts of the genome and which pathogenic mutations couples are sharing. Looking at relatedness coefficients by determining genome-wide SNPs does not seem to be an effective measure for prospective risk assessment in consanguineous parents.

Thirty day all-cause mortality in patients with Escherichia coli bacteraemia in England.

Escherichia coli is the commonest cause of bacteraemia in England, with an incidence of 50.7 cases per 100 000 population in 2011. We undertook a large national study to estimate and identify risk factors for 30-day all-cause mortality in E. coli bacteraemia patients. Records for patients with E. coli bacteraemia reported to the English national mandatory surveillance system between 1 July 2011 and 30 June 2012 were linked to death registrations to determine 30-day all-cause mortality. A multivariable regression model was used to identify factors associated with 30-day all-cause mortality. There were 5220 deaths in 28 616 E. coli bacteraemia patients, a mortality rate of 18.2% (95% CI 17.8-18.7%). Three-quarters of deaths occurred within 14 days of specimen collection. Factors independently associated with increased mortality were: age < 1 year or > 44 years; an underlying respiratory or unknown infection focus; ciprofloxacin non-susceptibility; hospital-onset infection or not being admitted; and bacteraemia occurring in the winter. Female gender and a urogenital focus were associated with a reduction in mortality. This is the first national study of mortality among E. coli bacteraemia patients in England. Interventions to reduce mortality need to be multifaceted and include both primary and secondary healthcare providers. Greater awareness of the risk factors for and symptoms of E. coli bacteraemia may prompt earlier diagnosis and treatment. Changes in antimicrobial resistance patterns need to be monitored for their potential impact on infection and mortality.

Acceptability of prenatal testing and termination of pregnancy in Pakistan.

This study aimed to assess acceptability of prenatal testing (PNT) and termination of pregnancy (TOP) for a range of conditions in Pakistani parents with and without a child with a genetic condition. A structured questionnaire assessing acceptability of PNT and TOP for 30 conditions was completed by 400 Pakistani participants: 200 parents with a child with a genetic condition (100 fathers and 100 mothers) and 200 parents without an affected child (100 fathers and 100 mothers). There was a high level of interest in PNT, where over 80 % of parents in all four study groups would want PNT for the majority of the conditions. There was comparatively less interest in TOP for the same conditions (ranging from 5 to 70 % of parents, with mothers of an affected child being most interested). Parents were most likely to be interested in TOP for conditions at the serious end of the continuum. More than half of the participants in each group would consider TOP for anencephaly and quadriplegia. The interest in PNT and TOP for a range of conditions suggests that rapidly developing PNT technologies are likely to be acceptable in Pakistan, a low-middle income level and Muslim country. The comparatively lower level of interest in TOP for the same conditions highlights ethical dilemmas that such technologies are likely to raise.

Diagnosis of fetal submicroscopic chromosomal abnormalities in failed array CGH samples: copy number by sequencing as an alternative to microarrays for invasive fetal testing.

OBJECTIVES: Array comparative genomic hybridization (CGH) has become the technology of choice for high-resolution prenatal whole genome analysis. Limitations of microarrays are mainly related to the analog nature of the analysis, and poor-quality DNA can result in failed quality metrics with these platforms. We examined a cohort of abnormal fetuses with failed array CGH results using a next-generation sequencing algorithm, CNV-Seq. We assessed the ability of the platform to handle suboptimal prenatal samples and generate interpretable molecular karyotypes. METHODS: Nine samples obtained from abnormal fetuses and one from a normal control fetus were sequenced using an Illumina GAIIx. A segmentation algorithm for sequencing data was used to determine regional copy number data on the sequencing datasets. RESULTS: Phred quality scores were satisfactory for analysis of all samples. CNV-Seq identified both large- and small-scale abnormalities in the cohort, and normal results were obtained for fetuses for which microarray data were previously uninterpretable. No variants of uncertain significance were detected. Analysis of the digital sequencing datasets offered some advantages over array CGH output. CONCLUSIONS: Using next-generation sequencing for the detection of genomic copy number variants may be advantageous for poor-quality, invasively-acquired prenatal samples. CNV-Seq could become a potential alternative to array CGH in this setting.

Vancomycin MIC as a predictor of outcome in MRSA bacteraemia in the UK context.

UNLABELLED: Received 29 November 2012; returned 20 February 2013; revised 16 May 2013; accepted 18 May 2013 OBJECTIVES: Raised vancomycin MICs have been associated with poor outcomes for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in the USA and mainland Europe. We investigated if this also applies in the UK, where EMRSA-15 (clonal complex 22) dominates. METHODS: Isolates from UK patients receiving vancomycin therapy for MRSA bacteraemia in 2008-10 were collected, along with clinical details. Outcomes (i.e. patient survival or bacteraemia resolution) were reported 28 days after vancomycin therapy ended. The relationship between clinical outcome and MIC--as determined by CLSI and BSAC agar dilution methods--was assessed. RESULTS: Among 228 MRSA bacteraemias, 82% were caused by EMRSA-15; 65% of the patients were male and the median age was 70.5 years. MICs correlated between methods, but CLSI agar dilution testing gave a mode at 1 mg/L with only 12% of results either side, whereas the BSAC method gave a mode straddling 0.7-1 mg/L with <4% outliers. Twenty-three percent of patients died, with MRSA contributory in half; another 17% had unresolved bacteraemia at 28 days. Neither death nor unresolved bacteraemia was significantly associated with higher vancomycin MICs by either method. Rifampicin co-therapy had no quantifiable effect on outcome. The patient's age was the only significant correlate of patient outcome (P < 0.01); the underlying medical condition of the patient was important for the resolution of bacteraemia (P < 0.01), though not for overall mortality. CONCLUSIONS: Subtle vancomycin MIC differences did not correlate with worse outcomes for vancomycin monotherapy or for vancomycin/rifampicin co-therapy in MRSA bacteraemia. Regardless of the exact MIC-outcome relationship, detecting such small MIC differences seems unlikely to be reliable in routine laboratories.

Inter-hospital comparison of rates of surgical site infection following caesarean section delivery: evaluation of a multicentre surveillance study.

BACKGROUND: Short postoperative stays following caesarean section delivery make it difficult to assess accurately the risk of surgical site infection (SSI). Methods of case-finding that minimize variation are required to support effective surveillance systems, especially where used for benchmarking. AIM: To evaluate the efficacy of case-finding methods for SSI following caesarean delivery and their utility in establishing benchmark rates of SSI. METHODS: Hospitals conducted surveillance over one or two 13-week periods. Patients were reviewed during their inpatient stay, post partum by community midwives and via patient questionnaire at 30 days post delivery. To estimate the reliability of case-finding methods, case-note reviews were undertaken in a random sample of four hospitals. FINDINGS: A total of 404 SSIs were detected in 4107 caesarean deliveries from 14 hospitals. The median time to SSI was 10 days, 66% were detected in-hospital or by community midwives, and an additional 34% were patient-reported. The rate of SSI was 9.8% but the proportion of patients followed up varied significantly between centres. The estimated sensitivity and specificity of case-finding was 91.4% [95% confidence interval (CI): 53.4-98.4] and 98.6% (95% CI: 98.4-98.8), the positive predictive value 91.0% (95% CI: 82.4-96.1) and negative predictive value 98.6% (95% CI: 93.9-99.5). CONCLUSIONS: Combined case ascertainment methods are a feasible way to achieve active post-discharge surveillance and had high negative and positive predictive values. Additional SSIs can be detected by patient questionnaires but rates of SSI were strongly influenced by variation in intensity of both healthcare worker- and patient-based case-finding. This factor must be taken into account when comparing or benchmarking rates of SSI.

Risk factors for surgical site infection following caesarean section in England: results from a multicentre cohort study.

OBJECTIVE: To assess the frequency and risk factors for surgical site infection following caesarean section. DESIGN: Prospective multicentre cohort study. SETTING: Fourteen NHS hospitals in England, April to September 2009. POPULATION: Women who underwent caesarean section at participating hospitals during designated study periods. METHODS: Infections that met standard case definitions were identified through active follow up by healthcare staff during the hospital stay, on return to hospital, during midwife home visits and through self-completed patient questionnaires. MAIN OUTCOME MEASURE: Surgical site infection within 30 days of operation. RESULTS: Altogether, 9.6% (394/4107) of women in the study developed a postsurgical infection following caesarean section with 0.6% (23/4107) readmitted for treatment of the infection. Being overweight (body mass index [BMI] 25-30 kg/m(2) odds ratio [OR] 1.6, 95% confidence interval [95% CI] 1.2-2.2) or obese (BMI 30-35 kg/m(2) OR 2.4, 95% CI 1.7-3.4; BMI > 35 kg/m(2) OR 3.7, 95% CI 2.6-5.2) were major independent risk factors for infection (compared with BMI 18.5-25 kg/m(2)). There was a suggestion that younger women, and operations performed by associate specialist and staff grade surgeons had a greater odds of developing surgical site infection with OR 1.9, 95% CI 1.1-3.4 (<20 years versus 25-30 years), and OR 1.6, 95% CI 1.0-2.4 (versus consultants), respectively. CONCLUSIONS: This study identified high rates of postsurgical infection following caesarean section. Given the number of women delivering by caesarean section in the UK, substantial costs will be incurred as a result of these infections. Prevention of these infections should be a clinical and public health priority.

Attitudes towards prenatal testing and termination of pregnancy in British Pakistani parents and relatives of children with recessive conditions in the UK.

OBJECTIVE: To compare British Pakistani parents' and their relatives' attitudes to prenatal testing (PND) and termination of pregnancy (TOP) for a range of conditions. METHOD: A total of 222 British Pakistani participants: 117 parents of children with a child with a genetic condition (52 fathers and 65 mothers) and 103 of their relatives (51 males and 52 females) completed a structured questionnaire about their attitudes toward PND and TOP for 30 different conditions. RESULTS: Parents were more accepting of PND (P < 0.001) and TOP (P < 0.001) than their relatives for most of the conditions. Male relatives were consistently least interested in PND and TOP, except for conditions at the serious end of the continuum, where over 90% would opt for PND for quadriplegia and anencephaly, and over 60% would opt for TOP for these conditions. CONCLUSION: The lower level of interest in PND and TOP in relatives, particularly men, may be due to lack of information disseminated by parents about their child's recessive inheritance and its implications for relatives, resulting in poor understanding of genetic risk. These findings highlight the need for the provision of proactive genetic counselling to raise awareness of genetic risk and facilitate informed reproductive decision-making in at-risk relatives.

Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance?

BACKGROUND: Abiraterone and docetaxel are both approved treatments for men with metastatic castration-resistant prostate cancer (mCRPC). Abiraterone pre-docetaxel is currently undergoing evaluation in a phase III study. In vitro studies indicate that taxanes may act by disrupting androgen receptor signalling. We hypothesised that prior abiraterone exposure would adversely impact docetaxel efficacy. PATIENTS AND METHODS: We retrospectively evaluated activity of docetaxel in mCRPC patients previously treated with abiraterone, using Prostate Cancer Working Group and radiological criteria. RESULTS: Of the 54 patients treated with abiraterone, 35 subsequently received docetaxel. Docetaxel resulted in a prostate-specific antigen (PSA) decline of ≥50% in nine patients [26%, 95% confidence interval (CI) 13% to 43%], with a median time to PSA progression of 4.6 months (95% CI 4.2% to 5.9%). PSA declines ≥30% were achieved by 13 patients (37%, 95% CI 22% to 55%). The median overall survival was 12.5 months (95% CI 10.6-19.4). All patients who failed to achieve a PSA fall on abiraterone and were deemed abiraterone-refractory were also docetaxel-refractory (N = 8). In the 24 patients with radiologically evaluable disease, partial responses were reported in four patients (11%), none of whom were abiraterone-refractory. CONCLUSION: The activity of docetaxel post-abiraterone appears lower than anticipated and no responses to docetaxel were observed in abiraterone-refractory patients.

Common genetic variation contributes significantly to the risk of childhood B-cell precursor acute lymphoblastic leukemia.

Recent genome-wide association studies (GWAS) have provided the first unambiguous evidence that common genetic variation influences the risk of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), identifying risk single-nucleotide polymorphisms (SNPs) localizing to 7p12.2, 9p21.3, 10q21.2 and 14q11.2. The testing of SNPs individually for an association in GWA studies necessitates the imposition of a very stringent P-value to address the issue of multiple testing. While this reduces false positives, real associations may be missed and therefore any estimate of the total heritability will be negatively biased. Using GWAS data on 823 BCP-ALL cases by considering all typed SNPs simultaneously, we have calculated that 24% of the total variation in BCP-ALL risk is accounted for common genetic variation (95% confidence interval 6-42%). Our findings provide support for a polygenic basis for susceptibility to BCP-ALL and have wider implications for future searches for novel disease-causing risk variants.

Trends in sources of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia: data from the national mandatory surveillance of MRSA bacteraemia in England, 2006-2009.

The national mandatory surveillance system for reporting meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia in England has captured data on the source of reported bacteraemias since 2006. This study analysed episodes of MRSA bacteraemia (N=4404) where a probable source of infection was reported between 2006 and 2009. In 2009, this information was available for one-third of reported episodes of MRSA bacteraemia. Of these, 20% were attributed to intravascular devices and 28% were attributed to skin and soft tissue infection. Sixty-four percent of the patients were male, and urinary tract infection was a significantly more common source of MRSA bacteraemia in males compared with females (12% vs 3%). Detection of bacteraemia within two days of hospital admission does not reliably discriminate between community- and hospital-associated MRSA bacteraemia as community cases are frequently associated with an invasive procedure/device. Between 2006 and 2009, there was a significant decline in the proportion of episodes of MRSA bacteraemia associated with central vascular catheters [incidence rate ratio (IRR) 0.42, 95% confidence interval (CI) 0.29-0.61; P<0.001], peripheral vascular catheters (IRR 0.69, 95% CI 0.48-0.99; P=0.042) and surgical site infection (IRR 0.42, 95% CI 0.25-0.72; P=0.001), and a significant increase in the proportion of episodes of MRSA bacteraemia associated with skin and soft tissue infection (IRR 1.33, 95% CI 1.05-1.69; P=0.017) and attributed to contamination of the specimen (IRR 1.96, 95% CI 1.25-3.06; P=0.003). Since data were not available for all cases, the generalizability of these trends depends on the assumption that records with source data reflect a reasonably random sample of cases in each year. These changes have occurred in the context of a general decline in the rate of MRSA bacteraemia in England since 2006.

Metabolic and endocrine adverse effects of second-generation antipsychotics in children and adolescents: A systematic review of randomized, placebo controlled trials and guidelines for clinical practice.

Second-generation antipsychotics (SGA) are being used more often than ever before in children and adolescents with psychotic and a wide range of non-psychotic disorders. Several SGA have received regulatory approval for some paediatric indications in various countries, but off-label use is still frequent. The aim of this paper was to perform a systematic review and critically evaluate the literature on cardiometabolic and endocrine side-effects of SGA in children and adolescents through a Medline/Pubmed/Google Scholar search of randomized, placebo controlled trials of antipsychotics in children and adolescents (<18 years old) until February 2010. In total, 31 randomized, controlled studies including 3595 paediatric patients were identified. A review of these data confirmed that SGA are associated with relevant cardiometabolic and endocrine side-effects, and that children and adolescents have a high liability to experience antipsychotic induced hyperprolactinaemia, weight gain and associated metabolic disturbances. Only weight change data were sufficiently reported to conduct a formal meta-analysis. In 24 trials of 3048 paediatric patients with varying ages and diagnoses, ziprasidone was associated with the lowest weight gain (-0.04kg, 95% confidence interval [CI]: -0.38 to +0.30), followed by aripiprazole (0.79kg, 95% CI: 0.54 to 1.04], quetiapine (1.43kg, 95% CI: 1.17 to 1.69) and risperidone (1.76kg, 95% CI: 1.27 to 2.25) were intermediate, and olanzapine was associated with weight gain the most (3.45kg, 95% CI: 2.93 to 3.97). Significant weight gain appeared to be more prevalent in patients with autistic disorder who were also younger and likely less exposed to antipsychotics previously. These data clearly suggest that close screening and monitoring of metabolic side effects is warranted and that the least cardiometabolically problematic agents should be used first whenever possible. A good collaboration between child- and adolescent psychiatrists, general practitioners and paediatricians is essential to maximize overall outcomes and to reduce the likelihood of premature cardiovascular morbidity and mortality.

Screening for anorexia nervosa via measurement of serum leptin levels.

Due to their sub-normally low fat mass, leptin levels in patients with acute anorexia nervosa (AN) are well below reference levels for age and sex-matched controls. This hypoleptinemia entails endocrinological and behavioral characteristics observed in AN patients during starvation. We aimed to study the appropriateness of hypoleptinemia as a diagnostic marker for AN by assessing sensitivity, specificity and likelihood ratios for different referral serum leptin levels for predicting anorexia nervosa and healthy leanness. For prediction, we additionally generated a score based on a multivariate logistic model including body mass index (BMI; kg/m²) and leptin level. For this purpose, we measured leptin levels in 74 female patients with acute AN upon admission for inpatient or outpatient treatment. Adolescent and adult patients were recruited according to DSM-IV criteria from two multi-center studies. Additionally, leptin levels were measured in 65 female healthy, lean students. Mean serum leptin level was significantly decreased in patients with AN compared to underweight controls (0.87 ± 0.90 vs. 6.43 ± 3.55 µg/L, p < 0.001). Leptin predicted AN independently of BMI; we confirmed a cutoff value in the range of 2 µg/L as having both high specificity and sensitivity. Hypoleptinemia represents a state marker of acute AN and is useful for a laboratory-based diagnostic screening.