Measuring outcomes in adult outpatient psychiatry

Despite growing pressure for accountability, mental health professionals continue to debate the value of routinely measuring treatment outcomes. This paper sought to move the outcomes measurement debate forward by reviewing some of the current limitations in outcomes methodology and by providing initial strategies to address them. Using these strategies, we evaluated outcomes for a large diagnostically diverse group of adult outpatients receiving treatment as usual (TAU) within an academic medical centre. Initial self-report and clinician-rated assessments were obtained from 5546 patients, and follow-up data were obtained from 1572 (28%) patients. Using the subset of patients with the follow-up data, we determined treatment effect sizes, rates of reliable improvement (and deterioration) and rates of clinically significant improvement for all patients and for specific diagnostic groups (depression, anxiety, substance abuse, mood disorders not otherwise specified, bipolar and psychotic conditions). TAU outcomes for depression and anxiety were also compared with benchmarks derived from the randomized controlled trial literature. Lastly, the impact of patient or sample characteristics on outcome was explored. Overall, these findings generally support the benefit of TAU over no treatment while also highlighting both the utility and limitations inherent in the current approaches to evaluating treatment outcomes. Suggestions for improving outcomes measurement are provided.     

A new species of Isospora (Apicomplexa: Eimeriidae) from the greenfinch Carduelis chloris (Passeriformes: Fringillidae)

A new species of isosporan (Apicomplexa: Eimeriidae) is reported from the greenfinch, Carduelis chloris (Passeriformes: Fringillidae), in England. Oocysts of Isospora daszaki n.sp. are spherical to subspherical, 18.8?×?20.3 (16.8-22.4?×?16.8-25.2)?μm, with a shape index (length/width) of 1.08 (1.07-1.1). Micropyle, polar granules and oocyst residuum are absent. Sporocysts are 9.4?×?14.8 (8.4-11.2?×?12.6-18.2)?μm, a shape index of 1.6, with Stieda and substieda bodies. Gamogony was seen in the ileum, and merozoites were present in blood lymphocytes.     

Arginine can be synthesized from enteral proline in healthy adult humans

There is considerable controversy recently in identifying dietary precursors for arginine synthesis. We have previously shown in human neonates and piglets that proline is the sole dietary precursor for arginine synthesis. It is unclear in adult humans whether proline is a dietary precursor for arginine. We performed a multi-tracer stable isotope study in adults using (15)N(2)-ureido arginine and (15)N proline to elucidate synthesis of citrulline and arginine and determine whether proline is a precursor for arginine. Primed, intermittent infusions of the labeled amino acids were given enterally to 5 healthy men consuming a standardized milkshake diet. Blood was sampled during plateau enrichment between 1.5 and 3 h. Plasma enrichment occurred for both tracers, giving enteral turnover estimates of 93 μmol · kg(-1) · h(-1) for arginine and 154 μmol · kg(-1) · h(-1) for proline. Appearance of the label from proline in arginine and the intermediaries, ornithine and citrulline, was measured in all participants. The rate of synthesis of arginine from proline was 3.7 μmol · kg(-1) · h(-1), which is estimated to be ~40% of newly synthesized arginine. In this first study in adult humans using an enteral proline tracer, we have demonstrated synthesis of arginine from this dietary amino acid. Therefore, as in newborns, proline must now be considered a dietary precursor for arginine in healthy adults.     

Current status of hybrid coronary revascularization

Hybrid coronary revascularization combines coronary artery bypass surgery with percutaneous coronary intervention techniques to treat coronary artery disease. The potential benefits of such a technique are to offer the patients the best available treatments for coronary artery disease while minimizing the risks of the surgery. Hybrid coronary revascularization has resulted in the establishment of new 'hybrid operating suites', which incorporate and integrate the capabilities of a cardiac surgery operating room with that of an interventional cardiology laboratory. Hybrid coronary revascularization has greatly augmented teamwork and cooperation between both fields and has demonstrated encouraging as well as good initial outcomes.     

Management of medullary thyroid cancer

Molecular genetics analyses have indicated that approximately 55% of medullary thyroid cancer (MTC) tumors bear activating mutations of the RET gene, including inherited and sporadic cases. Tumoral RET mutations, especially M918T, have a strong negative prognostic impact. RET is the most important target for recent systemic therapy trials of MTC, along with vascular endothelial growth factor receptors. This review discusses promising recent clinical trials data for multikinase inhibitors including motesanib, vandetanib, sunitinib, sorafenib, and cabozantinib/XL184. Across multiple studies reported to date, RET mutations, although prevalent in these subjects, have not proven so far to predict whether patients will respond to multikinase inhibitors. In addition to comparing available data for efficacy and toxicity of these agents, the review focuses on critical questions related to appropriate selection of MTC patients for systemic treatment, and how best to integrate these therapies with established modalities of surgery and radiation therapy.     

The extent and nature of need for mealtime support among adults with intellectual disabilities

Background For many adults with an intellectual disability (ID), mealtimes carry significant health risks. While research and allied clinical guidance has focused mainly on dysphagia, adults with a range of physical and behavioural difficulties require mealtime support to ensure safety and adequate nutrition. The extent of need for and nature of such support within the wider ID population has yet to be reported. Methods In this study, we have estimated the prevalence of need for mealtime support among people with ID in the UK, using a population of 2230 adults known to specialist ID services (in Cambridgeshire, UK, total population 586 900). In a sample (n = 69, aged 19 to 79 years, with mild to profound ID), we characterised the support provided, using a structured proforma to consult support workers and carers providing mealtime support, and health and social care records. Results Mealtime support was found to be required by a significant minority of people with ID for complex and varied reasons. Prevalence of need for such support was estimated at 15% of adults known to specialist ID services or 56 per 100 000 total population. Within a sample, support required was found to vary widely in nature (from texture modification or environmental adaptation to enteral feeding) and in overall level (from minimal to full support, dependent on functional skills). Needs had increased over time in almost half (n = 34, 49.3%). Reasons for support included difficulties getting food into the body (n = 56, 82.2%), risky eating and drinking behaviours (n = 31, 44.9%) and slow eating or food refusal (n = 30, 43.5%). These proportions translate into crude estimates of the prevalence of these difficulties within the known ID population of 11.9%, 6.6% and 6.4% respectively. Within the sample of those requiring mealtime support, need for support was reported to be contributed to by the presence of additional disability or illness (e.g. visual impairment, poor dentition and dementia; n = 45, 65.2%) and by psychological or behavioural issues (e.g. challenging behaviour, emotional disturbance; n = 36, 52.2%). Conclusions These findings not only highlight the need for a multidisciplinary approach to mealtime interventions (paying particular attention to psychological and environmental as well as physical issues), but also signal the daily difficulties faced by carers and paid support workers providing such support and illustrate their potentially crucial role in managing the serious health risks associated with eating and drinking difficulties in this population.     

Cholinergic dysregulation produced by selective inactivation of the dystonia-associated protein torsinA

DYT1 dystonia, a common and severe primary dystonia, is caused by a 3-bp deletion in TOR1A which encodes torsinA, a protein found in the endoplasmic reticulum. Several cellular functions are altered by the mutant protein, but at a systems level the link between these and the symptoms of the disease is unclear. The most effective known therapy for DYT1 dystonia is the use of anticholinergic drugs. Previous studies have revealed that in mice, transgenic expression of human mutant torsinA under a non-selective promoter leads to abnormal function of striatal cholinergic neurons. To investigate what pathological role torsinA plays in cholinergic neurons, we created a mouse model in which the Dyt1 gene, the mouse homolog of TOR1A, is selectively deleted in cholinergic neurons (ChKO animals). These animals do not have overt dystonia, but do have subtle motor abnormalities. There is no change in the number or size of striatal cholinergic cells or striatal acetylcholine content, uptake, synthesis, or release in ChKO mice. There are, however, striking functional abnormalities of striatal cholinergic cells, with paradoxical excitation in response to D2 receptor activation and loss of muscarinic M2/M4 receptor inhibitory function. These effects are specific for cholinergic interneurons, as recordings from nigral dopaminergic neurons revealed normal responses. Amphetamine stimulated dopamine release was also unaltered. These results demonstrate a cell-autonomous effect of Dyt1 deletion on striatal cholinergic function. Therapies directed at modifying the function of cholinergic neurons may prove useful in the treatment of the human disorder.     

Running wheel exercise ameliorates methamphetamine-induced damage to dopamine and serotonin terminals

Repeated administration of methamphetamine (mAMPH) to rodents in a single-day "binge" produces long-lasting damage to dopaminergic and serotonergic terminals. Because previous research has demonstrated that physical activity can ameliorate nigrostriatal injury, this study investigated whether voluntary exercise in rats can alter the monoaminergic damage resulting from a neurotoxic mAMPH binge. Adult male rats were allowed constant access to running wheels or kept in nonwheel cages for three weeks, then given a binge dosing regimen of mAMPH or saline. The rats were returned to their original environments for three additional weeks post-mAMPH. [(125) I]RTI-55 binding and autoradiography was used to quantify dopamine transporters (DAT), and radioimmunocytochemistry was used to quantify striatal tyrosine hydroxylase (TH). Binge mAMPH treatment significantly reduced striatal DAT and TH in a regionally specific pattern; with greatest effects in ventral caudate-putamen (CP) and relative sparing of the nucleus accumbens septi (NAc). The effects of mAMPH on striatal DAT and TH were ameliorated in the running, compared to the sedentary, animals. Also, mAMPH was found to reduce [(125) I]RTI-55 binding to serotonin transporters (SERT) in frontoparietal cortex, and this too was significantly attenuated by exercise. Additional correlational analyses showed that the post-mAMPH running of individual animals predicted the amelioration of striatal DAT and TH as well as frontoparietal SERT. Overall, voluntary exercise significantly diminished mAMPH-induced forebrain monoaminergic damage. The significant correlations between post-mAMPH exercise and markers of monoaminergic terminal integrity provide novel evidence that voluntary exercise may exert beneficial effects on behavior in recovering mAMPH addicts.