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High dose antipsychotic therapy (HDAT) is defined as “a total daily dose of a single antipsychotic which exceeds the upper limit stated in the SPC or BNF or a total daily dose of two or more antipsychotics exceeding the SPC or BNF maximum using the percentage method. Previous audits have looked at HDAT on both a national level (the Prescribing Observatory for Mental Health) and within Mersey Care NHS Foundation Trust. This audit aimed to identify the proportion of patients subject to HDAT and review combination antipsychotic strategies and consideration of Clozapine in patients subject to HDAT.
In August 2021, data were collected from the eight inpatient wards in Mersey Care NHS Foundation Trust. This involved using the Electronic Prescription and Administration system to identify those prescribed antipsychotics. Following this, the patient's electronic record was scrutinised for documentation of the rationale for HDAT, combination antipsychotics and consideration of Clozapine.
129 inpatients were identified as being prescribed antipsychotic medication. 21 (16.3%) patients were prescribed combination antipsychotic therapy, with four of these patients (3.1%) being prescribed HDAT. For these four HDAT patients, there was no recorded documentation of discussion of the option of Clozapine. The most common antipsychotic combination was Paliperidone depot with oral Risperidone. 38 out of 129 (29.5%) patients had been considered for Clozapine. Reasons for Clozapine being refused included the patient declining, concerns about non-concordance with oral medication, patients having had a neutropenia on an FBC, the patient being reluctant to have regular blood tests and a patient's comorbidities.
When comparing the proportion of patients subject to HDAT (3.1%) to the previous Trust audit in December 2020 (9.1%), there is a recurrent theme that antipsychotic prescribing practice in Mersey Care is safe, with minimal HDAT. Of note, the figure is significantly lower than the proportion of HDAT patients identified in the 2012 national study (28%). In this audit, none of the patients on HDAT had documented consideration of Clozapine. Three of the four patients were soon to be no longer subject to HDAT which may explain this result. Compared to the Trust's HDAT audit in 2020, the percentage of patients on combination antipsychotic therapy has stayed largely the same - 16.3% compared to 17.4%. The Trust needs to strive to continue minimal HDAT prescriptions and ensure that, in those patients subject to HDAT, there is consideration of and documentation of Clozapine being considered.
Cities and municipalities know they need to regulate the rideshare industry but have only recently taken steps to do so. Beyond obvious safety concerns, regulators need to tread carefully when trying to balance public concerns related to transit and mobility with private enterprise and independent contractor status.
At the same time, drivers constitute only one piece of the ride hailing puzzle. Drivers are not a monolith, as much as they may seem, and have competing priorities among themselves. From driver protests to organized driver groups like the Independent Drivers Guild, Rideshare Drivers United and Gig Workers Rising, drivers are coming together and demanding changes – but not all of these changes are supported by all drivers.
In terms of fundamental regulation for the ride hail industry, there are two main issues: insurance and wages. In these cases, regulators can have a real impact, and there is ample opportunity for regulators to get in early and set the tone. This chapter will delineate the path of ride hail regulation, how regulators can fix erroneous regulations and how to prevent future errors.
Members of online bipolar disorder forums often report experiences of mood-stabilisation on the ketogenic diet, which has traditionally been used in the treatment of epilepsy. We examined the nature and extent of such reports.
To investigate associations between a ketogenic diet and mood stabilisation among individuals with bipolar disorder.
We undertook an observational analytic study of free-text comments in online forums about mood effects of dietary interventions (ketogenic, omega-3 enriched or vegetarian) classified by a priori categories of change in mood stabilisation in 274 people with bipolar disorder.
There were 141 (85.5%) free-text comments on ketogenic diets that reported a positive impact on mood stabilisation. Reports of significant mood stabilisation or remission of symptoms over a period were substantially higher for a ketogenic diet than for other diets (93/165, 56.4%, 95% CI 48.4–64.1) v. 14/94, 14.9%, 95% CI 8.4–23.7), odds ratio 7.4, 95% CI 3.8–14.1, P < 0.0001), many with detailed reports of the improvements experienced and several lasting for extended periods (months to years). Other reported associations included fewer episodes of depression (in 41.2%, 95% CI 30.6–52.4 of individuals); improved clarity of thought and speech (28.2%, 95% CI 19.0–39.0); increased energy (25.9, 95% CI 17.0–36.5); and weight loss (25.9%, 95% CI 17.0–36.5).
Despite the inherent limitations of the observational data based on self-reports posted online, the association strength and reports of sustained benefit support a hypothesis of a ketogenic diet being associated with beneficial effects on mood stabilisation. Caution should be exercised in interpreting this data until a controlled trial can be carried out to examine this hypothesis. These preliminary observations are generally consistent with a mitochondrial dysfunction component to bipolar disorder aetiology with ketones bypassing a block between glycolysis and the tricarboxylic acid cycle.
Impetigo is common in remote Indigenous children of northern Australia, with the primary driver in this context being Streptococcus pyogenes [or group A Streptococcus (GAS)]. To reduce the high burden of impetigo, the transmission dynamics of GAS must be more clearly elucidated. We performed whole genome sequencing on 31 GAS isolates collected in a single community from children in 11 households with ⩾2 GAS-infected children. We aimed to determine whether transmission was occurring principally within households or across the community. The 31 isolates were represented by nine multilocus sequence types and isolates within each sequence type differed from one another by only 0–3 single nucleotide polymorphisms. There was evidence of extensive transmission both within households and across the community. Our findings suggest that strategies to reduce the burden of impetigo in this setting will need to extend beyond individual households, and incorporate multi-faceted, community-wide approaches.
The UK was one of few European countries to document a substantial wave of pandemic (H1N1) 2009 influenza in summer 2009. The First Few Hundred (FF100) project ran from April–June 2009 gathering information on early laboratory-confirmed cases across the UK. In total, 392 confirmed cases were followed up. Children were predominantly affected (median age 15 years, IQR 10–27). Symptoms were mild and similar to seasonal influenza, with the exception of diarrhoea, which was reported by 27%. Eleven per cent of all cases had an underlying medical condition, similar to the general population. The majority (92%) were treated with antiviral drugs with 12% reporting adverse effects, mainly nausea and other gastrointestinal complaints. Duration of illness was significantly shorter when antivirals were given within 48 h of onset (median 5 vs. 9 days, P=0·01). No patients died, although 14 were hospitalized, of whom three required mechanical ventilation. The FF100 identified key clinical and epidemiological characteristics of infection with this novel virus in near real-time.
The current rate of advances in genetic technology and statistical methods makes it difficult to discuss study design in mapping complex disease traits in a way that will have value beyond a relatively short time horizon. This chapter considers how knowledge about the nature of complex diseases and traits can inform study design and confines itself to genomic (rather than proteomic or metabonomic) approaches.
Genetic influences on complex traits can be considered in terms of susceptibility to disease (clinical and pre-clinical), susceptibility to differences in natural history of disease (severity, complications and prognosis), susceptibility to different therapeutic responses (efficacy and adverse effects) or in terms of the genetic determinants of normal phenotypic variation in health.
The choices between approaches depend not only on the context of the study, but also on the relative costs of ascertaining families, measuring phenotypes and genotyping. The costs of genotyping have been falling rapidly over the last decade and the trend is for genotyping to be done in a few automated high-throughput centres to maximize efficiency. In contrast, more stringent ethical and data protection legislation requirements have tended to increase unit recruitment costs, since ascertainment and recruitment procedures become more demanding and remain very labor intensive. It is likely therefore that the requirements for very large sample sizes and for large collaborative studies will increasingly involve research groups from countries of intermediate development which can assure high fidelity phenotyping, but at much lower cost than is possible in most industrialized nations.
Activity patterns of domesticated animals have largely focussed on hours of daylight and relatively few studies include detailed observations of night time activity. This has the potential to overlook behaviours of significance to the assessment of welfare. For example, stereotypic activities in laboratory mice are largely confined to dark periods, and consequently are not commonly reported by daytime laboratory workers. Use of low light video cameras coupled with infra-red or low intensity lighting now makes observation over entire light-dark cycle practical, whilst minimising disturbance to the sampled population. This paper describes the activity patterns of stabled horses over 24 hour periods. These observations can then be used as baseline for investigating the effects of changes to the stable environment on horses’ behaviour and welfare.
The contribution of air conduction auditory brainstem response (AC-ABR) testing in the paediatric population is widely accepted in clinical audiology. However, this does not allow for differentiation between conductive and sensorineural hearing loss. The purpose ofthis paper is to review the role of bone conduction auditory brainstem responses (BC-ABR). It is argued that despite such technical difficulties as a narrow dynamic range, masking dilemmas, stimulus artifact and low frequency underestimation of hearing loss, considerable evidence exists to suggest that BC-ABR testing provides an important contribution in the accurate assessmentof hearing loss in infants. Modification of the BC-ABR protocol is discussed and the technical difficulties that may arise are addressed, permitting BC-ABR to be used as a tool in the differential diagnosis between conductive and sensorineural hearing. Two relevant case studies are presented to highlight the growing importance of appropriate management in early identification of hearing loss. It can be concluded that BC-ABR should be adopted as a routine clinical diagnostic tool.
A large project, such as construction of a major highway or development of a large mine, will have a significant impact on the economy. The spending in the construction and operating phases will generate income and employment, and public sector decision-makers often take these effects into account in deciding whether or not to undertake the project. An economic impact analysis is a different procedure from a cost-benefit analysis in that it attempts to predict, but not evaluate, the effects of a project. Since the data assembled in the course of a cost-benefit analysis are often used as inputs to an economic impact analysis the two types of analyses tend to become related in the minds of decision-makers and may be undertaken by the same group of analysts.
In this Chapter we survey briefly three approaches to economic impact analysis: the income multiplier approach; the inter-industry model; and the computable general equilibrium model. Use of the latter two approaches involves a degree of technical expertise and would generally not be undertaken by the non-specialist. In discussing economic impacts we emphasize that these are not the same as the costs or benefits measured by a cost-benefit analysis. However there may be costs and benefits associated with the project's economic impact and the decision-maker may wish to take these into account.
The decision whether or not to take the multiplier or flow-on effects into account in the evaluation should be based on an assessment of the extent to which similar such effects would or would not occur in the absence of the project in question.
This Chapter deals with the methods and techniques used by economists to place monetary values on non-marketed goods and services, or, more specifically, those project inputs or outputs which affect the level of economic (material) welfare but which do not have market prices. While the discussion will focus mainly on environmental goods in order to illustrate the issues involved, the Chapter concludes with a brief discussion of various methods of valuing human life.
In previous Chapters we discussed how benefit-cost analysis involves the identification and valuation of a project's costs and benefits. Our analysis has so far been confined to those inputs and outputs that are exchanged through markets and where, in consequence, market prices exist. We recognized in Chapter 5 that the market does not always provide the appropriate measure of value and that shadow-prices sometimes have to be generated in order to better reflect project benefits or opportunity costs. This discussion was essentially about adjusting existing market prices where these were believed to be distorted, due perhaps to government intervention or to imperfections in the structure and functioning of markets. The present Chapter deals with another type of market failure – where there is no market for the input or output in question, and, therefore, no market price at which to value the cost or benefit.
As a starting point it is reasonable to ask why there is no private market for the commodity in question. Markets exist in order to trade ownership of goods and services – hamburgers and machine tools, haircuts and labour services. For economic agents to exchange ownership of a good or service there must exist a reasonably well-defined set of property rights that specify what is being traded.
As noted in Chapter 1, social benefit-cost analysis takes a wide, “social” perspective in the context of investment appraisal – it measures and compares the costs and benefits experienced by all members of “society”. In contrast, when a project is being evaluated by a private or public enterprise from a purely commercial or “private” perspective, account is taken only of the benefits and costs of the project that accrue to the enterprise itself and that affect its profitability. The project may have wider implications – environmental and employment effects, for example – but if these do not affect the enterprise's commercial profitability, they are omitted from the private analysis.
It is to be expected that the private enterprise would already have undertaken a private investment analysis of the project and will be basing its investment decision on the results of that analysis. However these results may not be available to the public sector decision-maker, and the social benefit-cost analysis, using discounted cash flow techniques very similar to those used in private benefit-cost analysis, and incorporating a private analysis, may be important in helping the public decision-maker decide what incentives are required in the form of tax concessions, for example, to induce the firm to undertake the project. For this reason the appraisal of a proposed project from a purely private viewpoint is often an integral part of a social benefit-cost analysis undertaken by the project analyst. This Chapter focuses on the methodology of private benefit-cost analysis, using discounted cash flow (DCF) analysis.
International Mining Corporation (IMC) Copper Mining Project
The Government of Indonesia is considering a proposed joint venture with a foreign investor, International Mining Corporation (IMC), to develop a new copper mine in the mountainous and remote Eastern Province (EP) where recent geological surveys have revealed significant copper deposits. Under the proposal, Eastern Province Mining Limited (EPML), in which the Government of Indonesia (GOI) will hold 30% of the shares, will mine and mill the copper ore on site. The concentrate will then be transported (in slurry form) by pipeline to a dedicated port facility at the mouth of the Eastern Province River, from where it will be shipped to Japan for refining and sale on the world market. Although the main product is copper, the concentrate will also contain some quantities of gold and silver that will also be extracted from the concentrate at the refining stage and sold on the world market.
Eastern Province is a low-income region with a population of 5 million and a per capita income of around US$300 per annum, considered the least developed part of the country. The local population living in the area rely mainly on subsistence agriculture and fishing for their livelihoods. At present there is very little economic or social infrastructure in the area, which means that apart from on-site investment in the mine, mill and tailings dam, EPML will need to make substantial off-site investments in infrastructure and logistics, such as transport equipment, the construction of roads, bridges, wharfs, an airstrip, storage facilities, housing, power generation and supply, as well as the establishment of a school, hospital, shops, recreational facilities and other amenities for the locally engaged and expatriate employees and families.
If benefit-cost analysis is to assist in the decision-making process the analysis must be conducted in advance of the project being undertaken. This means that the value of none of the variables involved in the analysis can be observed, but rather has to be predicted. Risk and uncertainty are always associated with predictions about the future and should be taken into account in the benefit-cost analysis. Since risk and uncertainty impose costs on decisionmakers, these costs need to be assessed and measures taken to reduce them if possible. One way of reducing risk and uncertainty is to acquire additional information mdash; what a benefit-cost analysis does mdash; and the value of information is briefly discussed in Chapter 10. The present Chapter discusses the related concepts of risk and uncertainty.
Risk and Uncertainty
In the preceding Chapters, exercises and case studies we have assumed that all costs and benefits to be included in a cash flow are known with certainty. While this assumption might be acceptable in the context of project evaluation where the analyst is undertaking an ex post assessment of what has already occurred, it is clearly an unrealistic assumption to make where the purpose of the analysis is to undertake an appraisal of proposed projects where one has to forecast future cost and benefit flows. The future is uncertain: we do not know with certainty what the future values of a project's costs and benefits will be.