Mini-Mental State Examination (MMSE) for the detection of dementia in clinically unevaluated people aged 65 and over in community and primary care populations.

BACKGROUND: The Mini Mental State Examination (MMSE) is a cognitive test that is commonly used as part of the evaluation for possible dementia. OBJECTIVES: To determine the diagnostic accuracy of the Mini-Mental State Examination (MMSE) at various cut points for dementia in people aged 65 years and over in community and primary care settings who had not undergone prior testing for dementia. SEARCH METHODS: We searched the specialised register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), LILACS (BIREME), ALOIS, BIOSIS previews (Thomson Reuters Web of Science), and Web of Science Core Collection, including the Science Citation Index and the Conference Proceedings Citation Index (Thomson Reuters Web of Science). We also searched specialised sources of diagnostic test accuracy studies and reviews: MEDION (Universities of Maastricht and Leuven, www.mediondatabase.nl), DARE (Database of Abstracts of Reviews of Effects, via the Cochrane Library), HTA Database (Health Technology Assessment Database, via the Cochrane Library), and ARIF (University of Birmingham, UK, www.arif.bham.ac.uk). We attempted to locate possibly relevant but unpublished data by contacting researchers in this field. We first performed the searches in November 2012 and then fully updated them in May 2014. We did not apply any language or date restrictions to the electronic searches, and we did not use any methodological filters as a method to restrict the search overall. SELECTION CRITERIA: We included studies that compared the 11-item (maximum score 30) MMSE test (at any cut point) in people who had not undergone prior testing versus a commonly accepted clinical reference standard for all-cause dementia and subtypes (Alzheimer disease dementia, Lewy body dementia, vascular dementia, frontotemporal dementia). Clinical diagnosis included all-cause (unspecified) dementia, as defined by any version of the Diagnostic and Statistical Manual of Mental Disorders (DSM); International Classification of Diseases (ICD) and the Clinical Dementia Rating. DATA COLLECTION AND ANALYSIS: At least three authors screened all citations.Two authors handled data extraction and quality assessment. We performed meta-analysis using the hierarchical summary receiver-operator curves (HSROC) method and the bivariate method. MAIN RESULTS: We retrieved 24,310 citations after removal of duplicates. We reviewed the full text of 317 full-text articles and finally included 70 records, referring to 48 studies, in our synthesis. We were able to perform meta-analysis on 28 studies in the community setting (44 articles) and on 6 studies in primary care (8 articles), but we could not extract usable 2 x 2 data for the remaining 14 community studies, which we did not include in the meta-analysis. All of the studies in the community were in asymptomatic people, whereas two of the six studies in primary care were conducted in people who had symptoms of possible dementia. We judged two studies to be at high risk of bias in the patient selection domain, three studies to be at high risk of bias in the index test domain and nine studies to be at high risk of bias regarding flow and timing. We assessed most studies as being applicable to the review question though we had concerns about selection of participants in six studies and target condition in one study.The accuracy of the MMSE for diagnosing dementia was reported at 18 cut points in the community (MMSE score 10, 14-30 inclusive) and 10 cut points in primary care (MMSE score 17-26 inclusive). The total number of participants in studies included in the meta-analyses ranged from 37 to 2727, median 314 (interquartile range (IQR) 160 to 647). In the community, the pooled accuracy at a cut point of 24 (15 studies) was sensitivity 0.85 (95% confidence interval (CI) 0.74 to 0.92), specificity 0.90 (95% CI 0.82 to 0.95); at a cut point of 25 (10 studies), sensitivity 0.87 (95% CI 0.78 to 0.93), specificity 0.82 (95% CI 0.65 to 0.92); and in seven studies that adjusted accuracy estimates for level of education, sensitivity 0.97 (95% CI 0.83 to 1.00), specificity 0.70 (95% CI 0.50 to 0.85). There was insufficient data to evaluate the accuracy of the MMSE for diagnosing dementia subtypes.We could not estimate summary diagnostic accuracy in primary care due to insufficient data. AUTHORS' CONCLUSIONS: The MMSE contributes to a diagnosis of dementia in low prevalence settings, but should not be used in isolation to confirm or exclude disease. We recommend that future work evaluates the diagnostic accuracy of tests in the context of the diagnostic pathway experienced by the patient and that investigators report how undergoing the MMSE changes patient-relevant outcomes.

Pricing of monoclonal antibody therapies: higher if used for cancer?

OBJECTIVES: The rising prices of specialty drugs have prompted a debate about how medications are priced. With the average price of cancer drugs doubling in the last decade, the unsustainability of drug prices is especially concerning in oncology and hematology. The objective of this study was to compare the prices of monoclonal antibodies (mAbs) approved in the last 20 years by the FDA across disease states. STUDY DESIGN: We identified all indications approved by the FDA for mAbs from 1997 to 2016 and calculated the annual price of 1-year treatment for each mAb-indication combination as the product of the US average wholesale price per milligram and the recommended dose. METHODS: We compared the annual price of treatment with each mAb across disease states using generalized linear models with gamma distribution and log link, controlling for route of administration, chemical structure, source, and time since FDA approval. RESULTS: The average annual price of a mAb was $96,731, exceeding $100,000 for 34 mAb-indication combinations. Oncology and hematology mAbs represented 40% of the mAb-indication combinations approved, yet they accounted for more than 85% of those priced $100,000 or higher. After adjusting for factors that can affect production costs, the annual price of oncology or hematology mAbs was $149,622 higher than those used in cardiovascular or metabolic disorders; $98,981 higher than in immunology; $128,856 higher than in infectious diseases or allergy; and $106,830 higher than in ophthalmology (all P <.001). CONCLUSIONS: The annual price of mAb therapies is about $100,000 higher in oncology and hematology than in other disease states.

Neuropsychiatric sequelae in an efavirenz treated patient with hepatitis B.

We report the case of a 34-year-old man of African origin, positive for both HIV and hepatitis B virus, who developed symptoms of mania and psychosis while being treated with efavirenz (a non-nucleoside reverse transcriptase inhibitor used in HIV therapy) that required inpatient psychiatric admission and treatment with antipsychotic medication. Our case illustrates multiple predisposing and precipitating factors occurring simultaneously that have been previously implicated individually in the development of neuropsychiatric complications with efavirenz (and other HIV treatments in general). We suggest that patient's commenced on antiretroviral medication should have a screening process for pre-existing mental and medical health problems as well as psychosocial risk factors that might put a patient at risk. In addition with advances in pharmacogenomics we advocate future cytochrome P450 gene variant testing coupled with routine efavirenz plasma concentration monitoring to help ensure maximum treatment benefit and minimal risk of side effects.

Anesthesia and electroconvulsive therapy: a retrospective study comparing etomidate and propofol.

BACKGROUND: The choice of anesthetic can influence the efficacy of electroconvulsive therapy (ECT). In the UK, propofol is a popular induction agent for ECT, but is associated with higher stimulus charge, shorter seizures, and known to affect seizure threshold. Etomidate is an alternative induction agent but there are concerns over its adverse events and safety. OBJECTIVES: We examined the differences between propofol and etomidate in the real life situation of an ECT clinic by assessing their effect on (i) length of course of ECT (ie, number of treatments required to remission), (ii) adverse effects of each induction agent, (iii) the number of 'missed seizures,' and (iv) stimulus dose (charge in mC), which relates to seizure threshold. METHOD: Using a retrospective naturalistic study design, 94 patients were identified over a 36-month period in our ECT clinic, of which, 65 met the inclusion criteria. Of these, 36 had received etomidate and 29 had received propofol as induction agents throughout their course of ECT. RESULTS: Patients who received propofol had a significantly longer course of ECT, higher seizure thresholds, and increased amounts of electrical charge (mC) over their course. There were no significant differences in adverse events with either of the induction agents. CONCLUSIONS: When used for acute courses of ECT, propofol and etomidate are equally well tolerated as induction agents. Patients who received propofol had longer acute courses of ECT and, consequently, longer and costlier inpatient stays. Etomidate could be a better alternative induction agent in ECT.

Folie a deux in bipolar affective disorder: a case report.

BACKGROUND: The syndrome of folie a deux is uncommon and often described in the context of schizophrenia. We report a case of induced delusional disorder associated with bipolar affective disorder (BAD). CASE REPORT: We present a case of monozygotic twins in their late 60s with an unusually close relation with one another and relative isolation from other people. Both twins have been diagnosed as suffering from BAD and relapsed into mania with psychotic symptoms. During their hospital stay they exhibited features consistent with folie a deux. Separation caused disappearance of the phenomenon whilst the affective disorder persisted. CONCLUSION: This case highlights the unusual and rare phenomenon of folie a deux occurring in the context of BAD. It also suggests current difficulty in defining folie a deux as an entity according to current diagnostic criteria.