Within-person analysis of welfare transitions in a longitudinal panel survey reveals change in mental health service use.

Background: While international research shows that receipt of welfare benefits is associated with poor mental health, less is known about the relationship between welfare receipt and mental health service use. We investigate whether within-person change in welfare recipient status is associated with change in mental health service use. Methods: Analysis of two waves of data from an Australian national household survey. Random- and fixed-effect models considered the effect of change in welfare receipt status, and assessed whether change in mental health service use differed by type of welfare benefit or the direction of welfare transition. Results: Individuals were more likely to report greater mental health service use at times of welfare receipt. These associations were attenuated, but remained significant, after adjusting for mental health. Increased health service use was not tied to specific types of welfare benefits. The increase in mental health service use associated with a transition onto welfare benefits was much greater than the decline in service use associated with the transition off benefits. Conclusions: Within individuals, welfare receipt is associated with greater mental health service use. While this does reflect poorer mental health at the time of welfare receipt, other factors seem to facilitate health service use.

Application of an innovative design space optimization strategy to the development of liquid chromatographic methods to combat potentially counterfeit nonsteroidal anti-inflammatory drugs.

In the context of the battle against counterfeit medicines, an innovative methodology has been used to develop rapid and specific high performance liquid chromatographic methods to detect and determine 18 non-steroidal anti-inflammatory drugs, 5 pharmaceutical conservatives, paracetamol, chlorzoxazone, caffeine and salicylic acid. These molecules are commonly encountered alone or in combination on the market. Regrettably, a significant proportion of these consumed medicines are counterfeit or substandard, with a strong negative impact in countries of Central Africa. In this context, an innovative design space optimization strategy was successfully applied to the development of LC screening methods allowing the detection of substandard or counterfeit medicines. Using the results of a unique experimental design, the design spaces of 5 potentially relevant HPLC methods have been developed, and transferred to an ultra high performance liquid chromatographic system to evaluate the robustness of the predicted DS while providing rapid methods of analysis. Moreover, one of the methods has been fully validated using the accuracy profile as decision tool, and was then used for the quantitative determination of three active ingredients and one impurity in a common and widely used pharmaceutical formulation. The method was applied to 5 pharmaceuticals sold in the Democratic Republic of Congo. None of these pharmaceuticals was found compliant to the European Medicines Agency specifications.

A dynamical pattern recognition model of γ activity in auditory cortex.

This paper describes a dynamical process which serves both as a model of temporal pattern recognition in the brain and as a forward model of neuroimaging data. This process is considered at two separate levels of analysis: the algorithmic and implementation levels. At an algorithmic level, recognition is based on the use of Occurrence Time features. Using a speech digit database we show that for noisy recognition environments, these features rival standard cepstral coefficient features. At an implementation level, the model is defined using a Weakly Coupled Oscillator (WCO) framework and uses a transient synchronization mechanism to signal a recognition event. In a second set of experiments, we use the strength of the synchronization event to predict the high gamma (75-150 Hz) activity produced by the brain in response to word versus non-word stimuli. Quantitative model fits allow us to make inferences about parameters governing pattern recognition dynamics in the brain.

Audiogram of a stranded Blainville's beaked whale (Mesoplodon densirostris) measured using auditory evoked potentials.

Quantifying and understanding the impact of anthropogenic sound on marine mammals has been the focus of many researchers both in laboratory settings as well as in the field. This study presents the audiogram of a sub-adult Blainville's beaked whale that stranded in Hawaii. The hearing measurements were conducted using the non-invasive auditory brainstem response technique. A total of 11 sinusoidally amplitude modulated tones were tested ranging from 5.6 to 160 kHz. The audiogram data indicated that the region of best hearing was found between 40 and 50 kHz with thresholds below 50 dB. This frequency range partially overlaps with the frequency modulated upsweep that Blainville's beaked whales have been reported to use during echolocation. These results match the frequency range obtained from the hearing measurements of a Gervais' beaked whale previously tested using contact acoustic stimulation and emphasize the importance of obtaining rapid hearing measurements on live stranded animals to improve the understanding of poorly known species.

Lesion sites that predict the ability to gesture how an object is used.

We used a two stage procedure to predict which stroke patients would have chronic difficulties gesturing how to use an object when object recognition and hand movements were intact. First, we searched our PLORAS database by behavior and identified 5 patients who had chronic difficulty gesturing object use but no difficulty recognising objects, comprehending words or moving their hands. High definition lesion analyses showed that all 5 patients had damage to the white matter underlying the left ventral supramarginal gyrus, (A) close to the cortex, (B) deep towards the midline and (C) extending into the temporal lobe. In addition, 2 patients had damage to (D) the left posterior middle temporal cortex, and 3 patients had damage to (E) the left dorsal supramarginal gyrus and (F) the left premotor cortex. Second, we searched our database by lesion location for patients who had damage to any part of regions ABCDEF. The incidence of gesturing difficulties was higher in patients with damage to ABCD (7/9), ABCE (7/10) or ABCDE (10/13) than ABCF (7/13), ABC (8/16) or partial damage to ABCF (6/32). Thus behaviour was best predicted by the combination of regions that were damaged (a "network-lesion") rather than on the basis of each region alone or overall lesion size. Our results identify which parts of the temporal and parietal lobes impair the ability to gesture object use and which parts need to be intact to support it after damage. Our methods provide a framework for future studies aiming to predict the consequences of brain damage.

Changing meaning causes coupling changes within higher levels of the cortical hierarchy.

Processing of speech and nonspeech sounds occurs bilaterally within primary auditory cortex and surrounding regions of the superior temporal gyrus; however, the manner in which these regions interact during speech and nonspeech processing is not well understood. Here, we investigate the underlying neuronal architecture of the auditory system with magnetoencephalography and a mismatch paradigm. We used a spoken word as a repeating "standard" and periodically introduced 3 "oddball" stimuli that differed in the frequency spectrum of the word's vowel. The closest deviant was perceived as the same vowel as the standard, whereas the other 2 deviants were perceived as belonging to different vowel categories. The neuronal responses to these vowel stimuli were compared with responses elicited by perceptually matched tone stimuli under the same paradigm. For both speech and tones, deviant stimuli induced coupling changes within the same bilateral temporal lobe system. However, vowel oddball effects increased coupling within the left posterior superior temporal gyrus, whereas perceptually equivalent nonspeech oddball effects increased coupling within the right primary auditory cortex. Thus, we show a dissociation in neuronal interactions, occurring at both different hierarchal levels of the auditory system (superior temporal versus primary auditory cortex) and in different hemispheres (left versus right). This hierarchical specificity depends on whether auditory stimuli are embedded in a perceptual context (i.e., a word). Furthermore, our lateralization results suggest left hemisphere specificity for the processing of phonological stimuli, regardless of their elemental (i.e., spectrotemporal) characteristics.

Inter-subject variability in the use of two different neuronal networks for reading aloud familiar words.

Cognitive models of reading predict that high frequency regular words can be read in more than one way. We investigated this hypothesis using functional MRI and covariance analysis in 43 healthy skilled readers. Our results dissociated two sets of regions that were differentially engaged across subjects who were reading the same familiar words. Some subjects showed more activation in left inferior frontal and anterior occipito-temporal regions while other subjects showed more activation in right inferior parietal and left posterior occipito-temporal regions. To explore the behavioural correlates of these systems, we measured the difference between reading speed for irregularly spelled words relative to pseudowords outside the scanner in fifteen of our subjects and correlated this measure with fMRI activation for reading familiar words. The faster the lexical reading the greater the activation in left posterior occipito-temporal and right inferior parietal regions. Conversely, the slower the lexical reading the greater the activation in left anterior occipito-temporal and left ventral inferior frontal regions. Thus, the double dissociation in irregular and pseudoword reading behaviour predicted the double dissociation in neuronal activation for reading familiar words. We discuss the implications of these results which may be important for understanding how reading is learnt in childhood or re-learnt following brain damage in adulthood.

Statistical bases for defining level of assurance.

Assurance of a low risk that material produced in cell culture harbours adventitious agents is provided through carefully conducted clearance studies, as well as quality control testing. Clearance studies are a form of quality assurance, and are used to demonstrate the ability of the manufacturing process to minimize or neutralize unwanted contaminants. Quality control testing is confirmation of a low risk that manufactured lots are contaminated with an adventitious agent. Neither of these can guarantee, however, that product released to the customer will be completely free of contaminants. Clearance studies provide information on log reduction of a contaminant, but by their nature cannot demonstrate complete elimination. In quality control testing, the ability to support the claim that there is minimal risk of a lot containing an adventitious agent depends on the quantity of material being tested and on the sensitivity of the detection assay. Statistical methods can be used both to design clearance studies, as well as control tests, to achieve a desirable level of assurance that the contaminant is below a defined threshold in the product. Basic data analysis methods, such as confidence intervals, improve the quality of information, by showing the range of adventitious agent reduction or level.

RCGP Quality Team Development programme: an illuminative evaluation.

BACKGROUND: There is increasing interest in quality initiatives that are locally owned and delivered, team based, multiprofessional, and formative. The Royal College of General Practitioners' Quality Team Development (QTD) programme is one such initiative aimed at developing primary healthcare teams and their services. AIMS: To evaluate QTD from the perspective of participants and assessors. SETTING: UK primary health care. DESIGN AND METHOD: Twelve of 14 practices and all four primary care organisations (PCOs) approached agreed to participate. Thirty four semi-structured interviews were conducted with key stakeholders. The interviews were taped, transcribed, and analysed using the constant comparative method. RESULTS: The QTD programme appears to be highly valued by participating organisations. Practice based respondents perceived it as acceptable and feasible, and reported positive changes in teamwork and patient services. They valued its formative, participative, and multiprofessional nature, especially the peer review element. PCOs saw QTD as a method of delivering on prevailing national policies on clinical quality and modernization agendas as well as promoting interorganizational collaboration. The main concerns raised were the workload, particularly for assessors, and maintaining the quality of the assessments and the programme. CONCLUSION: This qualitative study suggests positive benefits for participants in the QTD programme. However, such practices are a self-selecting innovative minority. Further research is needed on more typical practices to identify barriers to their participation in QTD or other formative, team based quality improvement programmes.

Ethics of evidence based medicine in the primary care setting.

Evidence based medicine has had an increasing impact on primary care over the last few years. In the UK it has influenced the development of guidelines and quality standards for clinical practice and the allocation of resources for drug treatments and other interventions. It has informed the thinking around patient involvement in decision making with the concept of evidence based patient choice. There are, however, concerns among primary care clinicians that evidence based medicine is not always relevant to primary care and that undue emphasis placed on it can lead to conflict with a clinician's duty of care and respect for patient autonomy. In this paper we consider the impact of evidence based medicine on primary care, and the ethical implications of its increasing prominence for clinicians and managers in primary care.

In vitro versus in vivo concordance: a case study of the replacement of an animal potency test with an immunochemical assay.

Early in its development, the potency of Merck's recombinant hepatitis B vaccine, RECOMBIVAX HB, was monitored using an assay performed in mice. A specification was determined to be the lowest potency which induced acceptable response in clinical trials. As a post-licensing commitment, Merck was asked to replace its mouse potency assay with an in vitro procedure for product release in the US market. Early studies with a commercial enzyme immunoassay (EIA) yielded highly variable results. That assay, combined with a sample pretreatment step, proved more dependable and predictive of potency in the mouse assay. Based on measurements made on manufactured materials, combined with experiments contrived to yield a wide range of reactivity in the two assays, concordance was established between the EIA and the mouse potency assay. This concordance was used to calibrate a specification for the in vitro assay that is predictive of a satisfactory response in vivo. Data from clinical trials established a correspondence between human immunogenicity and these potency markers.

Cluster randomised controlled trial to compare three methods of promoting secondary prevention of coronary heart disease in primary care.

OBJECTIVE: To assess the effectiveness of three different methods of promoting secondary prevention of coronary heart disease in primary care. DESIGN: Pragmatic, unblinded, cluster randomised controlled trial. SETTING: Warwickshire. SUBJECTS: 21 general practices received intervention; outcome measured in 1906 patients aged 55-75 years with established coronary heart disease. INTERVENTIONS: Audit of notes with summary feedback to primary health care team (audit group); assistance with setting up a disease register and systematic recall of patients to general practitioner (GP recall group); assistance with setting up a disease register and systematic recall of patients to a nurse led clinic (nurse recall group). MAIN OUTCOME MEASURES: At 18 months' follow up: adequate assessment (defined) of 3 risk factors (blood pressure, cholesterol, and smoking status); prescribing of hypotensive agents, lipid lowering drugs, and antiplatelet drugs; blood pressure, serum cholesterol level, and plasma cotinine levels. RESULTS: Adequate assessment of all 3 risk factors was much more common in the nurse and GP recall groups (85%, 76%) than the audit group (52%). The advantage in the nurse recall compared with the audit group was 33% (95% confidence interval 19% to 46%); in the GP recall group compared with the audit group 23% (10% to 36%), and in the nurse recall group compared with the GP recall group 9% (-3% to 22%). However, these differences in assessment were not reflected in clinical outcomes. Mean blood pressure (148/80, 147/81, 148/81 mm Hg), total cholesterol (5.4, 5.5, 5.5 mmol/l), and cotinine levels (% probable smokers 17%, 16%, 19%) varied little between the nurse recall, GP recall, and audit groups respectively, as did prescribing of hypotensive and lipid lowering agents. Prescribing of antiplatelet drugs was higher in the nurse recall group (85%) than the GP recall or audit groups (80%, 74%). After adjustment for baseline levels, the advantage in the nurse recall group compared with the audit group was 10% (3% to 17%), in the nurse recall group compared with the GP recall group 8% (1% to 15%) and in the GP recall group compared with the audit group 2% (-6% to 10%). CONCLUSIONS: Setting up a register and recall system improved patient assessment at 18 months' follow up but was not consistently better than audit alone in improving treatment or risk factor levels. Understanding the reasons for this is the key next step in improving the quality of care of patients with coronary heart disease.

Dissolved air flotation in drinking water production.

Dissolved Air Flotation (DAF) has become increasingly important in the field of potable water treatment, as a preferred option for treating upland and stored lowland waters. This paper outlines the development of dissolved air flotation (DAF) in potable water treatment, the benefits and disadvantages and the recent advances that has taken the process technology from an art to a science.

Producing criteria for static mattress tender and purchase.

When selecting mattresses criteria such as health and safety plus clinical and cost-effectiveness should be considered. These can then form the basis of contract tender specifications.

An assessment of morbidity registers for coronary heart disease in primary care. ASSIST (ASSessment of Implementation STrategy) trial collaborative group.

BACKGROUND: Organised care delivered systematically to all patients with established coronary heart disease (CHD) can reduce their risk factors and improve their quality of life. Therefore, identifying all patients with established CHD in a general practice population is an important first step for delivering this effective healthcare. However, there is little information on how registers are compiled, the factors that predict inclusion on the register or the relationship between registration and level of care provided. AIM: To assess the completeness of morbidity registers for CHD in primary care, the factors that predict inclusion on the register, and the relationship between registration and level of care provided. METHOD: Observational study at baseline of 1979 patients aged 55 to 75 years with established CHD in 18 general practices recruited for a cluster randomised controlled trial. RESULTS: The proportion of CHD patients correctly identified on practice morbidity registers varied from 29.3% to 100%. Four factors were significantly and independently associated with being on a register: a relevant surgery contact since diagnosis (OR = 2.1, 95% CI = 1.6%-2.9%); a relevant repeat prescription since diagnosis (OR = 1.6, 95% CI = 1.1%-2.3%); a diagnosis of myocardial infarction (OR = 1.5, 95% CI = 1.2%-1.9%); and a revascularisation procedure (OR = 1.5, 95% CI = 1.1%-2.0%). Inclusion on a register was strongly associated with being adequately assessed (i.e. assessed for smoking status, blood pressure, and cholesterol) (OR = 1.8, 95% CI = 1.3%-2.3%) and with treatment with aspirin or a lipid-lowering agent (OR = 1.4 for each agent). CONCLUSION: A wide variation in registration levels between practices exists. There is evidence that practices using multiple methods of case detection achieve higher levels of registration. The association between registration and better care does not prove causality but an effective call-recall system is impossible without complete registration.

Understanding men's health and illness: a gender-relations approach to policy, research, and practice.

Men's health has emerged as an important public concern that may require new kinds of healthcare interventions and increased resources. Considerable uncertainty and confusion surround prevailing understandings of men's health, particularly those generated by media debate and public policy, and health research has often operated on oversimplified assumptions about men and masculinity. A more useful way of understanding men's health is to adopt a gender-relations approach. This means examining health concerns in the context of men's and women's interactions with each other, and their positions in the larger, multidimensional structure of gender relations. Such an approach raises the issue of differences among men, which is a key issue in recent research on masculinity and an important health issue. The gender-relations approach offers new ways of addressing practical issues of healthcare for men in college environments.

Validation of assays for use with combination vaccines.

A general methodology is presented for the validation of assays used for testing combination vaccines. The presentation is detailed and technical as our intention is to address challenges that we have encountered in the design and statistical analysis of assay validation studies. There are several noteworthy features which render the approach particularly useful in practice. It employs a statistical experimental design approach to the investigation of assay ruggedness with respect to manufacturing variability; it makes use of the assay variability results to determine the level of test-run replication necessary to achieve precision compatible with the product specifications; and, it provides a generic approach to assay validation. With combination vaccines, as with other pharmaceuticals, the analytical methods for release and stability must be validated early in the development programme Several things, though, distinguish this task with combination vaccines: (1) assays are typically pre-existing and often have been validated for use with an established sample matrix, e.g. a monovalent formulation; (2) sample matrices are complex and therefore more subject to manufacturing variability and more likely to cause assay interferences; and (3) the analytical workload is considerable due to the number of antigens. The methodology presented here was developed jointly by Merck Research Laboratories (West Point, PA) and Pasteur Mérieux Connaught, Inc. (Swiftwater, PA). Many of the issues discussed here have application outside of combination vaccines and are common features of all assay validations.