SEM-microphotogrammetry, a new take on an old method for generating high-resolution 3D models from SEM images.

The method we present here uses a scanning electron microscope programmed via macros to automatically capture dozens of images at suitable angles to generate accurate, detailed three-dimensional (3D) surface models with micron-scale resolution. We demonstrate that it is possible to use these Scanning Electron Microscope (SEM) images in conjunction with commercially available software originally developed for photogrammetry reconstructions from Digital Single Lens Reflex (DSLR) cameras and to reconstruct 3D models of the specimen. These 3D models can then be exported as polygon meshes and eventually 3D printed. This technique offers the potential to obtain data suitable to reconstruct very tiny features (e.g. diatoms, butterfly scales and mineral fabrics) at nanometre resolution. Ultimately, we foresee this as being a useful tool for better understanding spatial relationships at very high resolution. However, our motivation is also to use it to produce 3D models to be used in public outreach events and exhibitions, especially for the blind or partially sighted.

Transient bone marrow oedema syndrome in an HIV-infected patient on highly active antiretroviral therapy.

Bone marrow oedema syndrome (BMES, also known as transient osteoporosis) is an uncommon, self-limiting condition characterized by disabling pain, reversible osteopaenia on X-rays and by bone marrow oedema pattern on magnetic resonance imaging (MRI). Here we describe the first reported case of BMES in an HIV-positive patient on highly active antiretroviral therapy.

Antipsychotics and cognitive decline in Alzheimer's disease: the LASER-Alzheimer's disease longitudinal study.

OBJECTIVE: To investigate in a longitudinal cohort of people with Alzheimer's disease whether taking antipsychotics is associated with more rapid cognitive deterioration. METHOD: From a sample of 224 people with Alzheimer's disease recruited as epidemiologically representative, those taking antipsychotic drugs for more than 6 months were compared with those who were not, in terms of change in three measures of cognition. The effects of potential mediators and confounders (demographic factors, neuropsychiatric symptoms, cognitive severity and cholinesterase inhibitors) were also examined. RESULTS: No significant difference was observed in cognitive decline between those taking antipsychotics (atypical or any) and others on any measure of cognition. The only predictor of more cognitive decline was greater baseline cognitive severity (B = 3.3, 95% confidence interval 0.6 to 6.1, t = 2.4, p<0.05). Although mortality was higher in those treated with antipsychotics, this reflected their greater age and severity of dementia. The results were the same when the whole cohort was included rather than the select group with potential to change who had been taking antipsychotics continuously. CONCLUSIONS: In this, the first cohort study investigating the effects of atypical antipsychotics on cognitive outcome in Alzheimer's disease, those taking antipsychotics were no more likely to decline cognitively over 6 months. Although clinicians should remain cautious when prescribing antipsychotic drugs to people with Alzheimer's disease, any increase in cognitive deterioration is not of the magnitude previously reported. There is a need for cohort studies that follow up patients from first prescription in clinical practice for a period of months rather than weeks to determine "real-life" risks and benefits.

Caregivers' experience of risk in dementia: the LASER-AD study.

The objective was to explore caregivers' experience of and concerns about the safety of care recipients (CRs) with Alzheimer's disease (AD) living at home. We interviewed family caregivers about their concerns regarding CR's safety, occurrence of risk over the last year and safety measures taken to manage risk. A total of 89 family caregiver/CR dyads participated. All had been recruited as part of a larger longitudinal study based in London and South East Region (LASER) of the UK. Caregivers spent a substantial proportion of the day supervising the CR (mean = 15.5 hours). Most caregivers (39; 81.2%) of the 48/89 CRs left alone worried about their safety. Sixty-one (68.5%) caregivers reported at least one incident in which the CR had been at risk within the past year. A majority (71; 79.8%) had taken measures to prevent risk behaviours. Greater impairment in activities of daily living and the caregiver not being the CR's spouse were associated with more measures being taken. Caregivers themselves provide supervision most of the time for the CR, and are worried when they are left alone. This is realistic as despite caregiver's attempts at managing their CR's risks, including direct supervision, dangerous incidents still frequently occur in people with AD.

Health inequalities across socio-economic groups: comparing geographic-area-based and individual-based indicators.

OBJECTIVES: To compare health inequality estimates obtained with different types of indicators of socio-economic status (SES), and study whether some of these are better predictors of health status, as indicated by observed disability data, than others. METHODS: Australian data were used to compare the use of the geographically based Socio-economic Index for Areas (SEIFA) in health inequality studies with two individual-based SES indicators able to account for family income and size. Inequalities in disability prevalences by SES were measured using age-standardized rate ratios. Logistic regression was used to determine which type of SES measure is a better predictor of the observed disability prevalences. RESULTS: Estimates of health inequalities obtained with the SEIFA were considerably lower than those obtained with the individual-based SES indicators. With the SEIFA, the proportion of disabled people amongst the most disadvantaged 20% of Australians was estimated to be 82% higher than amongst the most advantaged 20%, compared with over 150% with the individual-based SES measures. Also, the individual-based indicators were considerably better predictors of observed disability status than the SEIFA. CONCLUSION: An individual-level SES indicator, such as one based on family income, is a better predictor of people with a disability than a geographic-area-based index. Also, the main reason for the considerably lower inequality estimates obtained with the SEIFA is that, unlike the individual-based indicators, such location-based indices cannot account for the significant, often age-related variations in SES that exist amongst people living in a particular area.

Issues in data monitoring and interim analysis of trials.

OBJECTIVES: To address issues about data monitoring committees (DMCs) for randomised controlled trials (RCTs). DATA SOURCES: Electronic databases. Handsearching of selected books. Personal contacts with experts in the field. REVIEW METHODS: Systematic literature reviews of DMCs and small group processes in decision-making; sample surveys of: reports of RCTs, recently completed and ongoing RCTs and policies of major organisations involved in RCTs; case studies of four DMCs; and interviews with experienced DMC members. All focused on 23 prestated questions. RESULTS: Although still a minority, RCTs increasingly have DMCs. There is wide agreement that nearly all trials need some form of data monitoring. Central to the role of the DMC is monitoring accumulating evidence related to benefit and toxicity; variation in emphasis has been reflected in the plethora of names. DMCs for trials performed for regulatory purposes should be aware of any special requirements and regulatory consequences. Advantages were identified for both larger and smaller DMCs. There is general agreement that a DMC should be independent and multidisciplinary. Consumer and ethicist membership is controversial. The chair is recognised as being particularly influential, and likely to be most effective if he or she is experienced, understands both statistical and clinical issues, and is facilitating in style and impartial. There is no evidence available to judge suggested approaches to training. The review suggested that costs should be covered, but other rewards must be so minimal as to not affect decision-making. It is usual to have a minimum frequency of DMC meetings, with evidence that face-to-face meetings are preferable. It is common to have open sessions and a closed session. A report to a DMC should cover benefits and risks in a balanced way, summarised in an accessible style, avoiding excessive detail, and be as current as possible. Disadvantages of blinded analyses seem to outweigh advantages. Information about comparable studies should be included, although interaction with the DMCs of similar ongoing trials is controversial. A range of formal statistical approaches can be used, although this is only one of a number of considerations. DMCs usually reach decisions by consensus, but other approaches are sometimes used. The general, but not unanimous, view is that DMCs should be advisory rather than executive on the basis that it is the trial organisers who are ultimately responsible for the conduct of the trial. CONCLUSIONS: Some form of data monitoring should be considered for all RCTs, with reasons given where there is no DMC or when any member is not independent. An early DMC meeting is helpful, determining roles and responsibilities; planned operations can be agreed with investigators and sponsors/funders. A template for a DMC charter is suggested. Competing interests should be declared. DMC size (commonly three to eight people) is chosen to optimise performance. Members are usually independent and drawn from appropriate backgrounds, and some, particularly the chair, are experienced. A minimum frequency of meetings is usually agreed, with flexibility for more if needed. The DMC should understand and agree the statistical approach (and guidelines) chosen, with both the DMC statistician and analysis statistician competent to apply the method. A DMC's primary purpose is to ensure that continuing a trial according to its protocol is ethical, taking account of both individual and collective ethics. A broader remit in respect of wider ethical issues is controversial; arguably, these are primarily the responsibility of research ethics committees, trial steering committees and investigators. The DMC should know the range of recommendations or decisions open to it, in advance. A record should be kept describing the key issues discussed and the rationale for decisions taken. Errors are likely to be reduced if a DMC makes a thorough review of the evidence and has a clear understanding of how it should function, there is active participation by all members, differences are resolved through discussion and there is systematic consideration of the various decision options. DMCs should be encouraged to comment on draft final trial reports. These should include information about the data monitoring process and detail the DMC membership. It is recommended that groups responsible for data monitoring be given the standard name 'Data Monitoring Committee' (DMC). Areas for further research include: widening DMC membership beyond clinicians, trialists and statisticians; initiatives to train DMC members; methods of DMC decision-making; 'open' data monitoring; DMCs covering a portfolio of trials rather than single trials; DMC size and membership, incorporating issues of group dynamics; empirical study of the workings of DMCs and their decision-making, and which trials should or should not have a DMC.

A randomised controlled trial of a tailored multifaceted strategy to promote implementation of a clinical guideline on induced abortion care.

OBJECTIVE: To evaluate the effectiveness and efficiency of a tailored multifaceted strategy, delivered by a national clinical effectiveness programme, to implement a guideline on induced abortion. DESIGN: Cluster randomised controlled trial. SETTING AND PARTICIPANTS: All 26 hospital gynaecology units in Scotland providing induced abortion care. INTERVENTION: Following the identification of barriers to guideline implementation, intervention units received a package comprising audit and feedback, unit educational meetings, dissemination of structured case records and promotion of a patient information booklet. Control units received printed guideline summaries alone. MAIN OUTCOME MEASURES: Compliance with five key guideline recommendations (primary outcomes) and compliance with other recommendations, patient satisfaction and costs of the implementation strategy (secondary outcomes). RESULTS: No effect was observed for any key recommendation: appointment with a gynaecologist within five days of referral (odds ratio 0.89; 95% confidence interval 0.50 to 1.58); ascertainment of cervical cytology history (0.93; 0.36 to 2.40); antibiotic prophylaxis or screening for lower genital tract infection (1.70; 0.71 to 5.99); use of misoprostol as an alternative to gemeprost (1.00; 0.27 to 1.77); and offer of contraceptive supplies at discharge (1.11; 0.48 to 2.53). Median pre-intervention compliance was near optimal for antibiotic prophylaxis and misoprostol use. No intervention benefit was observed for any secondary outcome. The intervention costs an average of pound 2607 per gynaecology unit. CONCLUSIONS: The tailored multifaceted strategy was ineffective. This was possibly attributable to high pre-intervention compliance and the limited impact of the strategy on factors outside the perceived control of clinical staff.

Does pericapsular lignocaine reduce pain during transrectal ultrasonography-guided biopsy of the prostate?

OBJECTIVE: To evaluate whether injection with pericapsular lignocaine before transrectal ultrasonography (TRUS)-guided biopsy reduces the perceived pain of prostatic biopsy. PATIENTS AND METHODS: The study included 121 patients referred for TRUS-guided biopsy of the prostate; 27 underwent biopsy with no previous injection and 94 were randomized to pericapsular injection with either 1% lignocaine or a placebo (saline). Both patient and operator were unaware of the content of the injection. The injection was delivered under TRUS guidance to the apex of the prostate. Routine sextant biopsies were taken using an 18 G needle in a spring-loaded biopsy gun. A validated pain scale, the NRS11 (0, no pain, to 10, unbearable pain), was used to record the pain of each biopsy. RESULTS: No significant placebo effect was detected between the 'no injection' and the placebo-injection group, with mean (95% confidence interval) pain scores of 3.58 (2.77-4.39) and 4.01 (3.46-4.51), respectively, using the unpaired Student's t-test (P = 0.409). There was a statistically significant lower mean pain score in the lignocaine group, at 2.54 (2.00-3.10), than in the placebo-injection group (P < 0.001). CONCLUSION: Pericapsular injection with 1% lignocaine significantly reduces the perceived pain of TRUS-guided prostatic biopsy.

Educational strategies to promote evidence-based community pharmacy practice: a cluster randomized controlled trial (RCT).

BACKGROUND: Community pharmacists have increasing involvement in the self-management of minor illness as a result of the availability of a wider range of over-the-counter (OTC) medicines. We undertook a randomized controlled trial (RCT) to assess the effectiveness and efficiency of educational strategies to implement evidence-based guidelines for the sale of OTC anti-fungals in the community pharmacy setting. OBJECTIVE: The aim of the study was to compare the effectiveness and efficiency of two guideline dissemination strategies in community pharmacy settings. METHODS: A 2 x 2 factorial, cluster RCT was conducted with 60 community pharmacies in the Grampian region of Scotland. The interventions included dissemination of an evidence-based guideline for OTC management of vulvovaginal candidiasis (thrush) by postal dissemination (control), educational outreach visit or attendance at a continuing professional education session. Pre- and post-intervention simulated patient visits were made to participating pharmacies. The simulated patients completed assessment forms following each visit. The primary outcome was the appropriateness (based upon the guidelines) of sale or no sale of OTC anti-fungals. RESULTS: There were no significant differences in the proportion of appropriate outcomes following educational outreach [odds ratio (OR) = 1.1; 95% confidence interval (CI) 0.52 to 2.45] or continuing professional education (OR = 0.88; 95% CI 0.41 to 1.91). CONCLUSIONS: Neither strategy was effective in improving the appropriateness of OTC management of vulvovaginal candidiasis by community pharmacy staff. Further research is needed to identify barriers to guideline implementation and evidence-based practice in this setting.

Assessment of nutritional status in hospital in-patients.

BACKGROUND: The King's Fund and British Association of Parenteral and Enteral Nutrition recommend that all hospital patients should have height and weight recorded, to detect the need for nutritional support. Systematic review evidence also suggests that protein and energy supplementation of adults in hospital with a wide range of conditions improves outcome. AIM: To assess the recording of weight and height in hospitals. DESIGN: Survey (random sample). METHODS: As part of a survey on the provision of deep venous thrombosis prophylaxis, we collected information on height and weight recording from medical and nursing notes. We randomly selected five medical, five surgical, five orthopaedic, and five obstetrics and gynaecology directorates from across Scotland. Six hundred case notes were requested, and 88% were available for data extraction. Some 67% of hospital episodes provided information about weight, and 41% on both height and weight. General medicine directorates had the lowest recording of weight, and in medical and surgical directorates, both weight and height were rarely recorded in comparison with the other two directorates (p<0.001). DISCUSSION: Our survey suggests that recommendations to assess nutritional risk are not being followed, and that many patients at risk of malnutrition are not being detected or treated.

A systematic review of discharge coding accuracy.

BACKGROUND: The aim of the study was to review systematically the literature measuring the accuracy of routine UK hospital statistics that classify patients on discharge. METHODS: A systematic review was carried out of studies comparing routine discharge statistics about an episode of hospital care with the original medical record. Dual quality assessment and extraction was completed for included studies. Qualitative and descriptive analyses were undertaken. Additional comparisons of factors that could potentially introduce systematic variation in coding accuracy were also undertaken. RESULTS: Thirty studies were identified, of which 21 were included in the review. Twelve of these were conducted in England and Wales, and nine in Scotland. The majority assessed the accuracy of a single diagnosis, or selection of diagnoses in a limited range of hospital settings. The median coding accuracy rates were 91 per cent for diagnostic codes and 69.5 per cent for operation or procedure codes in studies in England or Wales; 82 per cent for diagnostic codes and 98 per cent for operation or procedure codes in Scottish studies. There were no significant differences in coding accuracy over time or in the type or rarity of the codes being assessed. Accuracy rates were higher for ICD7 codes (median 96.5 per cent) than for ICD8 (median 87 per cent) or ICD9 (median 77 per cent). CONCLUSIONS: Coding accuracy on average is high in the United Kingdom, especially for operations and procedures. However, policy-makers, planners and researchers need to recognize and account for the degree of inaccuracy in routine hospital information statistics. Further research is needed into methods of improving and maintaining coding accuracy.

MR imaging of the skin and nipple of the breast: differentiation between tumour recurrence and post-treatment change.

Contrast-enhanced MR imaging of the breast has been found to be valuable in the assessment of local recurrence of previously treated breast cancer. We looked specifically at the appearances of the skin and nipple of the treated breast in order to describe the appearances of post-treatment change and recurrence in this region. Thirty-nine women treated for breast cancer had MR imaging of one or both breasts reviewed retrospectively with particular attention to the nipple and skin. The skin and chest wall were assessed for patients with mastectomies. All available histology of the skin and/or nipple, obtained following MR imaging, was reviewed. In patients who did not undergo surgery following MR imaging, clinical follow-up was obtained. Six of 39 cases had nodular enhancing areas seen on MR imaging, which correlated with histology demonstrating tumour recurrence within the skin and/or nipple. Of the remaining 33 patients, changes of linear or diffuse enhancement were seen in the skin and/or nipple of 15 patients. These changes were shown to be benign post-treatment changes at surgery/biopsy in 4 cases or by clinical follow-up in the remainder. In this article we demonstrate differing patterns of contrast enhancement within the skin and nipple in recurrent breast carcinoma vs. post-treatment changes. This suggests that contrast-enhanced MR imaging of the breast may be a useful tool in differentiating tumour recurrence from post-treatment changes within the skin and nipple.

Dose reduction in evacuation proctography.

The goal of this study was to reduce the patient radiation dose from evacuation proctography. Ninety-eight consecutive adult patients referred for proctography to investigate difficult rectal evacuation were studied using a digital imaging system with either a standard digital program for barium examinations, a reduced dose digital program (both with and without additional copper filtration), or Video fluoroscopy. Dose-area products were recorded for each examination and the groups were compared. All four protocols produced technically acceptable examinations. The low-dose program with copper filtration (median dose 382 cGy cm2) and Video fluoroscopy (median dose 705 cGy cm2) were associated with significantly less dose than other groups (p < 0.0001). Patient dose during evacuation proctography can be reduced significantly without compromising the diagnostic quality of the examination. A digital program with added copper filtration conveyed the lowest dose.

Salient beliefs and intentions to prescribe antibiotics for patients with a sore throat.

OBJECTIVES: General practitioners (GPs) in the UK continue to prescribe antibiotics for patients with sore throats despite evidence that they are ineffective and can contribute to the growth of antibiotic resistance in the population. This study uses the theory of planned behaviour (TPB) to investigate the strength of intention to prescribe antibiotics, and to identify the salient beliefs associated with this intention. DESIGN: Cross-sectional study testing hypotheses derived from the TPB. METHOD: A 66-item postal questionnaire was distributed to a random sample of GPs in one NHS region (N = 185). The questionnaire included measures of intention to prescribe antibiotics, attitude, behavioural beliefs and evaluations, normative beliefs and evaluations, perceived behavioural control, control beliefs, and past prescribing. RESULTS: Two-thirds of the GPs returned complete questionnaires (N = 126, 68%). The majority intended to prescribe antibiotics for less than half of their patients with sore throats (N = 69, 55%). The variables specified in TPB predicted 48% of the variance in intention, with past behaviour adding a further 15%. Seven salient beliefs distinguished between doctors who intend to prescribe antibiotics and those who do not. CONCLUSIONS: Attitudes towards antibiotics and control beliefs are important predictors of intention to prescribe, as predicted by TPB. Interventions could target salient beliefs associated with motivation to prescribe.

Community pharmacists' views and beliefs about the treatment of symptoms suggestive of vaginal thrush in community pharmacies.

OBJECTIVE: To investigate the views and beliefs of community pharmacists about the benefits and disadvantages to the customer, pharmacy and pharmacist of treating women with symptoms suggestive of vaginal thrush. DESIGN: Semi-structured interviews. SETTING: Community pharmacists from within Grampian Primary Care NHS Trust. OUTCOME MEASURES: Pharmacists' views and beliefs analysed using content analysis. RESULTS: Of the 26 pharmacists contacted, 19 (73%) pharmacists from 16 pharmacies completed interviews. The pharmacists were generally positive towards the treatment of women with vaginal symptoms and perceived few disadvantages. Immediate access to treatment and rapid symptom relief were perceived to be the greatest advantages to the customer. The main problems were customer embarrassment, cost and the risk of masking a serious condition. Customer embarrassment was perceived to be influenced by lack of privacy and the gender of the member of staff involved in the consultation. Five pharmacists perceived vaginal thrush to be an infection that could be spread by sexual transmission. DISCUSSION: There is a need to make pharmacists aware of the current evidence regarding the treatment of vaginal thrush, particularly the sexual partners of women with acute, uncomplicated thrush do not require treatment with an antifungal. The main difficulties that community pharmacists reported with the treatment of this condition were obtaining an accurate history and this was influenced by customer embarrassment. The gender of pharmacy staff and lack of private consultation facilities were suggested as factors that are associated with customer embarrassment and hence, the ability to obtain an accurate history.

A recruitment strategy for cluster randomized trials in secondary care settings.

Trials of educational or organizational interventions to change clinical practice require cluster randomization, that is, randomization of units such as hospitals or clinical teams rather than individual patients. Cluster randomization is relatively novel in health care settings and raises new methodological challenges, in particular: are units willing to be randomized at an organizational level; and, what procedures should be followed to successfully enrol all of the clinicians in a unit rather than individual clinicians as in conventional multicentre trials. This is particularly problematic for trials of large units such as hospitals. The aim of this study was to develop and partially evaluate a strategy to recruit acute, secondary care NHS hospitals in the UK into cluster randomized trials. Literature search and interviews with senior staff in acute hospitals and relevant national organizations were used to develop a recruitment strategy. The strategy was evaluated by inviting 32 randomly selected clinical directorates to participate in a trial feasibility study. A seven step recruitment strategy was developed: (1) Identify stakeholders and gatekeepers; (2) Inform stakeholders and gatekeepers; (3) Approach gatekeepers; (4) Local negotiation; (5) Conduct the research; (6) Feedback to gatekeepers; (7) Feedback to stakeholders. Key problems were the possibility of multiple gatekeepers and identification of all possible stakeholders in varying organizational structures. The strategy was effective in two respects. First, 32 (100%) of the directorates approached agreed to participate. Second, baseline data collection was successfully achieved in all of the directorates. However, the strategy is costly in terms of time and resources. We conclude that NHS trusts are willing to participate in cluster randomized trials. This recruitment strategy is successful and could be widely adopted, but realistic time and financial cost estimates are required at the planning stage.

Biotransformation of chlorpromazine and methdilazine by Cunninghamella elegans.

When tested as a microbial model for mammalian drug metabolism, the filamentous fungus Cunninghamella elegans metabolized chlorpromazine and methdilazine within 72 h. The metabolites were extracted by chloroform, separated by high-performance liquid chromatography, and characterized by proton nuclear magnetic resonance, mass, and UV spectroscopic analyses. The major metabolites of chlorpromazine were chlorpromazine sulfoxide (36%), N-desmethylchlorpromazine (11%), N-desmethyl-7-hydroxychlorpromazine (6%), 7-hydroxychlorpromazine sulfoxide (36%), N-hydroxychlorpromazine (11%), 7-hydroxychlorpromazine sulfoxide (5%), and chlorpromazine N-oxide (2%), all of which have been found in animal studies. The major metabolites of methdilazine were 3-hydroxymethdilazine (3%). (18)O(2) labeling experiments indicated that the oxygen atoms in methdilazine sulfoxide, methdilazine N-oxide, and 3-hydroxymethdilazine were all derived from molecular oxygen. The production of methdilazine sulfoxide and 3-hydroxymethdilazine was inhibited by the cytochrome P-450 inhibitors metyrapone and proadifen. An enzyme activity for the sulfoxidation of methdilazine was found in microsomal preparations of C. elegans. These experiments suggest that the sulfoxidation and hydroxylation of methdilazine and chlorpromazine by C. elegans are catalyzed by cytochrome P-450.

The physiological basis of concussion: 50 years later.

In this brief narrative, the author compares what is known today about the physiological basis of concussion with the results of studies described 50 years ago in the Journal of Neurosurgery. The author was a member of the team that originally reported these findings in the first volume of the Journal of Neurosurgery.

Chloracne--study of an outbreak with new clinical observations.

A recent outbreak of chloracne in 17 workers is reported at a plant manufacturing dichloroaniline derivatives. Comedones developed 6-12 weeks after accidental exposure to the chloracnegenic contaminants and were present in every case. Cutaneous xerosis and a folliculitis, previously only rarely described as manifestations of chloracne, were noted in half the patients. The pathogenesis of these lesions is uncertain but may involve a disorder of keratinization.