Artificially raised creatinine concentrations due to analytical interference for samples contaminated with total parenteral nutrition fluid.

BACKGROUND: A sample received in the laboratory from a patient receiving total parenteral nutrition (TPN) indicated that the patient may have renal dysfunction, but the results were not considered to be reliable enough to report. Investigations using a reference method for measurement of creatinine confirmed positive interference in the creatinine assay and distribution of samples via an External Quality Assessment (EQA) Scheme showed that this positive interference was method dependent. METHODS: Residual TPN fluid (Nutriflex Lipid Special) left in the bag after the patient had completed the infusion was collected and added to a patient serum pool in increasing amounts and distributed to different laboratories for analysis of creatinine and glucose through an EQA Scheme. RESULTS: Positive interference in a number of different creatinine assays was identified as a result of a component in the TPN fluid. Positive interference from high concentrations of glucose has been demonstrated to be a cause for falsely high results in Jaffe creatinine assays. CONCLUSIONS: The concern would be that a sample contaminated with TPN fluid would have both abnormal electrolytes and creatinine concentrations and give the impression that the patient was in renal failure due to analytical interference in the creatinine assay and laboratory staff need to be aware of this problem.

How is the COVID-19 lockdown impacting the mental health of parents of school-age children in the UK? A cross-sectional online survey.

OBJECTIVE: Investigate the impact of the COVID-19 lockdown on feelings of loneliness and social isolation in parents of school-age children. DESIGN: Cross-sectional online survey of parents of primary and secondary school-age children. SETTING: Community setting. PARTICIPANTS: 1214 parents of school-age children in the UK. METHODS: An online survey explored the impact of lockdown on the mental health of parents with school-age children, and in particular about feelings of social isolation and loneliness. Associations between the UCLA Three-Item Loneliness Scale (UCLATILS), the Direct Measure of Loneliness (DMOL) and the characteristics of the study participants were assessed using ordinal logistic regression models. MAIN OUTCOME MEASURES: Self-reported measures of social isolation and loneliness using UCLATILS and DMOL. RESULTS: Half of respondents felt they lacked companionship, 45% had feelings of being left out, 58% felt isolated and 46% felt lonely during the first 100 days of lockdown. The factors that were associated with higher levels of loneliness on UCLATILS were female gender, parenting a child with special needs, lack of a dedicated space for distance learning, disruption of sleep patterns and low levels of physical activity during the lockdown. Factors associated with a higher DMOL were female gender, single parenting, parenting a child with special needs, unemployment, low physical activity, lack of a dedicated study space and disruption of sleep patterns during the lockdown. CONCLUSIONS: The COVID-19 lockdown has increased feelings of social isolation and loneliness among parents of school-age children. The sustained adoption of two modifiable health-seeking lifestyle behaviours (increased levels of physical activity and the maintenance of good sleep hygiene practices) wmay help reduce feelings of social isolation and loneliness during lockdown.

An IgG complexed form of vitamin B12 is a common cause of elevated serum concentrations.

OBJECTIVES: To report detailed investigations in a case of elevated serum B(12) due to the presence of an IgG-B(12) complex, to determine the prevalence of this phenomenon and to review the literature. DESIGN AND METHODS: 431 samples with elevated B(12) (median 1250 ng/L, range 901-114,480 ng/L) were treated with polyethylene glycol to precipitate immunoglobulin complexes. Samples with >50% of precipitable B(12) (PPB(12)) were further investigated by protein G adsorption, gel filtration chromatography and measurement of B(12) on different analytical platforms. RESULTS: Median PPB(12) was 22.6%, but in 35 samples (8.1%), median PPB(12) was more than 50%. Investigation of 27 of these samples with protein G-Sepharose confirmed the presence of an IgG-B(12) complex in 24, and in 15 cases, B(12) fell to within the reference range. After treatment of serum with reagents releasing B(12) from binding proteins, immunoreactivity co-eluted with free B(12). Immunoreactivity of the IgG-bound form of B(12) was confirmed using five B(12) assays in common use in the UK. CONCLUSIONS: At least 8% of samples with elevated vitamin B(12) contain an immunoglobulin complexed form of circulating B(12); this possibility should be considered in the interpretation of results.

UK cost-consequence analysis of aripiprazole in schizophrenia: diabetes and coronary heart disease risk projections (STAR study).

Patients with schizophrenia experience elevated rates of morbidity and mortality, largely due to an increased incidence of cardiovascular disease and diabetes. There is increasing concern that some atypical antipsychotic therapies are associated with adverse metabolic symptoms, such as weight gain, dyslipidaemia and glucose dysregulation. These metabolic symptoms may further increase the risk of coronary heart disease (CHD) and diabetes in this population and, subsequently, the cost of treating these patients' physical health. The STAR study showed that the metabolic side effects of aripiprazole treatment are less than that experienced by those receiving standard-of-care (SOC). In a follow-up study the projected risks for diabetes or CHD, calculated using the Stern and Framingham models, were lower in the aripiprazole treatment group. Assuming the risk of diabetes onset/CHD events remained linear over 10 years, these risks were used to estimate the difference in direct and indirect cost consequences of diabetes and CHD in schizophrenia patients treated with aripiprazole or SOC over a 10-year period. Diabetes costs were estimated from the UKPDS and UK T(2)ARDIS studies, respectively, and CHD costs were estimated using prevalence data from the Health Survey of England and the published literature. All costs were inflated to 2007 costs using the NHS pay and prices index. The number of avoided diabetes cases (23.4 cases per 1,000 treated patients) in patients treated with aripiprazole compared with SOC was associated with estimated total (direct and indirect) cost savings of 37,261,293 pounds over 10 years for the UK population. Similarly, the number of avoided CHD events (3.7 events per 1,000 treated patients) was associated with estimated total cost savings of 7,506,770 pounds over 10 years. Compared with SOC, aripiprazole treatment may provide reductions in the health and economic burden to schizophrenia patients and health care services in the UK as a result of its favourable metabolic profile.

Management of physical health in schizophrenia: a stepping stone to treatment success.

While patients with schizophrenia are known to have an increased risk of physical health co-morbidity including coronary heart disease, diabetes, hypertension, stroke and emphysema, their physical wellbeing often goes unnoticed by health care professionals. In many cases the patient's only contact with the health service is through the mental health team. However, many psychiatrists consider their primary function to be the provision of clinical care in terms of symptom control and are reluctant to switch medication despite the presence of physical health issues. Nevertheless outcomes in schizophrenia may be improved by expanding the remit of the clinician to include assessments of both physical and mental health. Simple measurements such as waist circumference, weight, height, blood pressure and blood sampling would provide the psychiatrist with useful information that could be used to optimize treatment and improve overall quality of life for patients with schizophrenia.

A prospective, multicentre, open-label study of aripiprazole in the management of patients with schizophrenia in psychiatric practice in Europe: Broad Effectiveness Trial with Aripiprazole in Europe (EU-BETA).

OBJECTIVE: To examine the effectiveness of aripiprazole in schizophrenia in a naturalistic setting in 14 European countries. METHODS: This multicentre, open-label study of aripiprazole evaluated outpatients with schizophrenia for whom a medication switch was clinically reasonable or antipsychotic initiation was required. Patients (n = 833) were randomized in a 4:1 ratio to aripiprazole (recommended starting dose 15 mg/day, permitted adjustment 10-30 mg/day) (n = 680) or another antipsychotic (safety control [SC] group) (n = 153) for 8 weeks. The control group received an antipsychotic different to their recent pre-study medication. The primary effectiveness measure was the Clinical Global Impression - Improvement (CGI - I) score of aripiprazole-treated patients at Week 8 (last observation carried forward [LOCF]). Patients' and caregivers' medication preference was assessed using the Preference of Medication (POM) questionnaire. The Investigator Assessment Questionnaire (IAQ) was used to record investigators' assessments of their patients' responses to the study antipsychotic. Adverse events (AEs) were recorded. RESULTS: At endpoint (Week 8, LOCF), the mean CGI - I score of 3.16 (95% confidence interval, [CI]: 3.04, 3.28) demonstrated the effectiveness of aripiprazole. At endpoint, 43% of aripiprazole-treated patients showed a response (CGI - I score = 1/2). Aripiprazole was rated as slightly or much better than previous antipsychotic at endpoint by 68% of patients and 65% of caregivers. The mean CGI - I score (Week 8, LOCF) for the SC group was 3.37 (95% CI: 3.14, 3.60). No major differences in the occurrence of AEs were noted between aripiprazole- and SC-treated patients. LIMITATIONS: As this is an open-label design, there may have been a bias. Secondly, the study was not powered to show differences between treatment groups and no statistical comparisons were planned. Thirdly, 8 weeks is too short to evaluate long-term effectiveness. CONCLUSIONS: Aripiprazole was effective, well tolerated and well accepted by patients and caregivers in this naturalistic study.

Practical prescribing with aripiprazole in schizophrenia: consensus recommendations of a UK multidisciplinary panel.

BACKGROUND: The atypical antipsychotic, aripiprazole, differs from other antipsychotics in its pharmacology and clinical outcomes. Aripiprazole's clinical outcomes include beneficial effects on mood, quality of life and cognition; favourable tolerability with low potential for sedation; and a favourable physical health profile, with low potential for weight change, sexual dysfunction or adverse metabolic effects. Such outcomes, particularly cognitive improvements, may allow for greater psychosocial intervention and improved social inclusion. In accordance with the UK NICE guidance on the use of antipsychotic treatment for schizophrenia (2002), aripiprazole may be an appropriate therapeutic option for patients with schizophrenia who are newly diagnosed, in acute relapse or experiencing tolerability problems, adverse metabolic effects or dissatisfaction with their current medication. SCOPE: A multidisciplinary panel was convened in the UK in October 2006 to discuss and provide practical guidance regarding the potential benefits and risks of prescribing aripiprazole. This report describes the consensus recommendations agreed during the meeting and includes practical guidance on the optimal approach to prescribing aripiprazole, which patients might benefit from aripiprazole and how best to approach initiation of and switching to treatment with aripiprazole. A PubMed/MEDLINE literature search was conducted to support these recommendations. FINDINGS: To support antipsychotic therapy, a therapeutic partnership should be established between the patient and a well-informed, multidisciplinary care team. Aripiprazole should be initiated at the minimal efficacious dose (10 mg/day) and titrated as required (usually to 15 mg/day) after a minimum of 2 weeks. The primary goal during aripiprazole initiation is to ensure the patient completes the first few days of treatment, with support from concomitant medications if required. Nausea, insomnia and agitation may occur in 10-20% of patients, but are manageable and typically resolve during the first 3-7 days of therapy. The dose of any prior antipsychotic should remain stable until the response to aripiprazole is satisfactory and then the previous antipsychotic should be tapered off slowly over several weeks or more. CONCLUSION: Patients are more likely to adhere to treatment with aripiprazole--and indeed any other antipsychotic--and derive long-term therapeutic benefits if they and a well-informed care team are involved in the treatment decision, establish a therapeutic partnership, are aware of the transient nature of any adverse events and understand what the potential long-term benefits are.

Predictors of discontinuation on clozapine: a population study.

OBJECTIVES: A quarter of people with schizophrenia may be classed as 'treatment-resistant'. Clozapine is an antipsychotic that holds significant potential benefit for this patient group and has recently been recommended by the National Institute for Clinical Excellence. Early discontinuation is common. This study explores the factors that predict such discontinuation. METHOD: This retrospective cohort design was carried out on two hundred and one people with treatment resistant schizophrenia who had commenced clozapine between 1990 and 1997 identified from the Clozaril Patient Monitoring Service (CPMS) in Northern Ireland. Clinical and socio-demographic data was collected for three years before and after commencement on clozapine. Kaplan Meier survival analyses were conducted to identify differences in discontinuation rates according to a range of variables. RESULTS: Forty-five per cent of patients had discontinued before three years. No difference in rates were found between men and women, nor whether side-effects were reported or not Patients who had commenced clozapine at an older age had significantly higher cessation rates. People who had started clozapine at age 50+ were four times more likely to stop taking clozapine within three years than people aged between 17-29 years. CONCLUSIONS: Differences in continuation rates may be due to a number of factors. Treatment resistance may increase with age, side-effects may worsen or patient willingness to tolerate such effects may reduce. Alternatively, clinicians may be more anxious about prescribing clozapine as levels of co-morbidity increase. Further research is required to identify precise reasons and develop interventions to reduce discontinuation rates among older patients.