Development and assessment of the performance of a shared ventilatory system that uses clinically available components to individualize tidal volumes.

OBJECTIVES: To develop and assess a system for shared ventilation using clinically available components to individualize tidal volumes. DESIGN: Evaluation and in vitro validation study SETTING: Ventilator shortage during the SARS-CoV-2 pandemic. PARTICIPANTS: The team consisted of physicians, bioengineers, computer programmers, and medical technology professionals. METHODS: Using clinically available components, a system of ventilation consisting of two ventilatory limbs was assembled and connected to a ventilator. Monitors for each limb were developed using open-source software. Firstly, the effect of altering ventilator settings on tidal volumes delivered to each limb was determined. Secondly, the impact of altering the compliance and resistance of one limb on the tidal volumes delivered to both limbs was analysed. Experiments were repeated three times to determine system variability. RESULTS: The system permitted accurate and reproducible titration of tidal volumes to each limb over a range of ventilator settings and simulated lung conditions. Alteration of ventilator inspiratory pressures, of respiratory rates, and I:E ratio resulted in very similar tidal volumes delivered to each limb. Alteration of compliance and resistance in one limb resulted in reproducible alterations in tidal volume to that test lung, with little change to tidal volumes in the other lung. All tidal volumes delivered were reproducible. CONCLUSIONS: We demonstrate the reliability of a shared ventilation system assembled using commonly available clinical components that allows titration of individual tidal volumes. This system may be useful as a strategy of last resort for Covid-19, or other mass casualty situations, where the need for ventilators exceeds supply.

Secondary healthcare costs after mastectomy and immediate breast reconstruction for women with breast cancer in England: population-based cohort study.

BACKGROUND: Immediate breast reconstruction after mastectomy can improve the quality of life for women with breast cancer and rates are increasing. Long-term inpatient costs of care were estimated to understand the impact of different immediate breast reconstruction procedures on healthcare expenditure. METHODS: Hospital Episode Statistics Admitted Patient Care data were used to identify women undergoing unilateral mastectomy and immediate breast reconstruction in English National Health Service hospitals (1 April 2009 to 31 March 2015) and any subsequent procedures performed to revise, replace, or complete the breast reconstruction. Costs were assigned to Hospital Episode Statistics Admitted Patient Care data using the Healthcare Resource Group 2020/21 National Costs Grouper. Generalized linear models were used to estimate mean cumulative costs for five immediate breast reconstruction procedures over 3 and 8 years, adjusting for covariates (age/ethnicity/deprivation). RESULTS: A total of 16 890 women underwent mastectomy and immediate breast reconstruction: implant (5192; 30.7 per cent), expander (2826; 16.7 per cent), autologous latissimus dorsi flap (2372; 14.0 per cent), latissimus dorsi flap with expander/implant (3109; 18.4 per cent), and abdominal free-flap reconstruction (3391; 20.1 per cent). The mean (95 per cent c.i.) cumulative cost was lowest for latissimus dorsi flap with expander/implant reconstruction (€20 103 (€19 582 to €20 625)) over 3 years and highest for abdominal free-flap reconstruction (€27 560 (€27 037 to €28 083)). Over 8 years, expander (€29 140 (€27 659 to €30 621)) and latissimus dorsi flap with expander/implant (€29 312 (€27 622 to €31 003)) reconstructions were the least expensive, while abdominal free-flap reconstruction (€34 536 (€32 958 to €36 113)) remained the most expensive, despite having lower costs for revisions and secondary reconstructions. This was driven primarily by the cost of the index procedure (€5435 (expander reconstruction) to €15 106 (abdominal free-flap reconstruction)). CONCLUSION: Hospital Episode Statistics Admitted Patient Care Healthcare Resource Group data provided a comprehensive longitudinal cost assessment of secondary care. Although abdominal free-flap reconstruction was the most expensive option, higher costs of the index procedure need to be balanced against ongoing long-term costs of revisions/secondary reconstructions, which are higher after implant-based procedures.

Variations in policies for accessing elective musculoskeletal procedures in the English National Health Service: A documentary analysis.

OBJECTIVE: The overall aim of this study was to investigate how commissioning policies for accessing clinical procedures compare in the context of the English National Health Service. Our primary objective was to compare policy wording and categorise any variations identified. Our secondary objective was to explore how any points of variation relate to national guidance. METHODS: This study entailed documentary analysis of commissioning policies that stipulated criteria for accessing eight elective musculoskeletal procedures. For each procedure, we retrieved policies held by regions with higher and lower rates of clinical activity relative to the national average. Policies were subjected to content and thematic analysis, using constant comparison techniques. Matrices and descriptive reports were used to compare themes across policies for each procedure and derive categories of variation that arose across two or more procedures. National guidance relating to each procedure were identified and scrutinised, to explore whether these provided context for explaining the policy variations. RESULTS: Thirty-five policy documents held by 14 geographic regions were included in the analysis. Policies either focused on a single procedure/treatment or covered several procedures/treatments in an all-encompassing document. All policies stipulated criteria that needed to be fulfilled prior to accessing treatment, but there were inconsistences in the evidence cited. Policies varied in recurring ways, with respect to specification of non-surgical treatments and management, requirements around time spent using non-surgical approaches, diagnostic requirements, requirements around symptom severity and disease progression, and use of language, in the form of terms and phrases ('threshold modifiers') which could open up or restrict access to care. National guidance was identified for seven of the procedures, but this guidance did not specify criteria for accessing the procedures in question, making direct comparisons with regional policies difficult. CONCLUSIONS: This, to our knowledge, is the first study to identify recurring ways in which policies for accessing treatment can vary within a single-payer system with universal coverage. The findings raise questions around whether formulation of commissioning policies should receive more central support to promote greater consistency - especially where evidence is uncertain, variable or lacking.

Exploring trends in admissions and treatment for ankle fractures: a longitudinal cohort study of routinely collected hospital data in England.

BACKGROUND: Evidence on the most effective and cost-effective management of ankle fractures is sparse but evolving. A recent large RCT in older patients with unstable fractures found that management with close-contact-casting was functionally equivalent and more cost-effective than internal fixation. We describe temporal and geographic variation in ankle fracture management and estimate the potential savings if close-contact-casting was used more often in older patients. METHODS: Patients admitted to hospital in England between 2007/08 and 2016/17 with an ankle fracture were identified using routine hospital episode statistics. We tested whether the use of internal fixation, and the proportion of internal fixations using intramedullary implants, changed over time. We estimated the potential annual cost savings if patients aged 60+ years were treated with close-contact-casting rather than internal fixation, in line with emerging evidence. RESULTS: Over the 10-year period, there were 223,465 hospital admissions with a primary ankle fracture diagnosis. The incidence (per 100,000) of internal fixation was fairly consistent over time in younger (33.2 in 2007/08, 30.9 in 2016/17) and older (36.5 in 2007/08, 37.4 in 2016/17) patients. The proportion of internal fixations which used intramedullary implants increased in both age groups (17.0-19.5% < 60 years; 15.2-17.4% 60+ years). In 2016/17, the cost of inpatient hospital care for ankle fractures in England was over £63.1million. If 50% of older patients who had an internal fixation instead had close-contact-casting, we estimate that approximately £1.56million could have been saved. CONCLUSIONS: Despite emerging evidence that non-surgical and surgical management achieve equivalent functional outcomes in older patients, the rate of surgical fixation has remained relatively stable over the decade. The health service could achieve substantial savings if a higher proportion of older patients were treated with close-contact-casting, in line with recent evidence.

Varenicline versus nicotine replacement therapy for long-term smoking cessation: an observational study using the Clinical Practice Research Datalink.

BACKGROUND: Smoking is the leading avoidable cause of illness and premature mortality. The first-line treatments for smoking cessation are nicotine replacement therapy and varenicline. Meta-analyses of experimental studies have shown that participants allocated to the varenicline group were 1.57 times (95% confidence interval 1.29 to 1.91 times) as likely to be abstinent 6 months after treatment as those allocated to the nicotine replacement therapy group. However, there is limited evidence about the effectiveness of varenicline when prescribed in primary care. We investigated the effectiveness and rate of adverse events of these medicines in the general population. OBJECTIVE: To estimate the effect of prescribing varenicline on smoking cessation rates and health outcomes. DATA SOURCES: Clinical Practice Research Datalink. METHODS: We conducted an observational cohort study using electronic medical records from the Clinical Practice Research Datalink. We extracted data on all patients who were prescribed varenicline or nicotine replacement therapy after 1 September 2006 who were aged ≥ 18 years. We investigated the effects of varenicline on smoking cessation, all-cause mortality and cause-specific mortality and hospitalisation for: (1) chronic lung disease, (2) lung cancer, (3) coronary heart disease, (4) pneumonia, (5) cerebrovascular disease, (6) diabetes, and (7) external causes; primary care diagnosis of myocardial infarction, chronic obstructive pulmonary disease, depression, or prescription for anxiety; weight in kg; general practitioner and hospital attendance. Our primary outcome was smoking cessation 2 years after the first prescription. We investigated the baseline differences between patients prescribed varenicline and patients prescribed nicotine replacement therapy. We report results using multivariable-adjusted, propensity score and instrumental variable regression. Finally, we developed methods to assess the relative bias of the different statistical methods we used. RESULTS: People prescribed varenicline were healthier at baseline than those prescribed nicotine replacement therapy in almost all characteristics, which highlighted the potential for residual confounding. Our instrumental variable analysis results found little evidence that patients prescribed varenicline had lower mortality 2 years after their first prescription (risk difference 0.67, 95% confidence interval -0.11 to 1.46) than those prescribed nicotine replacement therapy. They had similar rates of all-cause hospitalisation, incident primary care diagnoses of myocardial infarction and chronic obstructive pulmonary disease. People prescribed varenicline subsequently attended primary care less frequently. Patients prescribed varenicline were more likely (odds ratio 1.46, 95% confidence interval 1.42 to 1.50) to be abstinent 6 months after treatment than those prescribed nicotine replacement therapy when estimated using multivariable-adjusted for baseline covariates. Patients from more deprived areas were less likely to be prescribed varenicline. However, varenicline had similar effectiveness for these groups. CONCLUSION: Patients prescribed varenicline in primary care were more likely to quit smoking than those prescribed nicotine replacement therapy, but there was little evidence that they had lower rates of mortality or morbidity in the 4 years following the first prescription. There was little evidence of heterogeneity in effectiveness across the population. FUTURE WORK: Future research should investigate the decline in prescribing of smoking cessation products; develop an optimal treatment algorithm for smoking cessation; use methods for using instruments with survival outcomes; and develop methods for comparing multivariable-adjusted and instrumental variable estimates. LIMITATIONS: Not all of our code lists were validated, body mass index and Index of Multiple Deprivation had missing values, our results may suffer from residual confounding, and we had no information on treatment adherence. TRIAL REGISTRATION: This trial is registered as NCT02681848. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 9. See the NIHR Journals Library website for further project information.

Smoking is the number one avoidable cause of ill health and death. Experiments suggest that more smokers will quit after being given the drug varenicline than with any other smoking cessation treatment. However, most of the experiments used to license varenicline had a relatively short follow-up (< 1 year) and did not necessarily recruit participants who were representative of smokers seen in a general practice in the UK, who tend to be older, are sicker and more likely to have neuropsychiatric illnesses. In this study, we investigated the outcomes of 287,079 patients prescribed varenicline or nicotine replacement therapy (e.g. nicotine patches and gum). We followed each patient for up to 4 years after they received their prescriptions and matched their data to information on deaths from the Office for National Statistics and hospital admissions. We investigated how often these patients subsequently attended their general practitioner, and how often they received a diagnosis of myocardial infarction, chronic obstructive pulmonary disease, depression or anxiety in primary care. We found that patients who were prescribed varenicline were much more likely to quit smoking up to 4 years after they received treatment and subsequently attended their general practitioner less frequently. These findings were robust across the three different analysis methods we used. We also found that patients prescribed varenicline were much less likely to be ill or to die than those prescribed nicotine replacement therapy. However, these results may be because the patients who were prescribed varenicline were much healthier before they received the prescription. Therefore, these differences in health are unlikely to be caused by taking varenicline or quitting smoking. In conclusion, varenicline helped patients quit smoking, but there was little causal evidence that prescribing patients varenicline causally reduced rates of mortality or morbidity compared with prescribing nicotine replacement therapy.

Longitudinal study of use and cost of subacromial decompression surgery: the need for effective evaluation of surgical procedures to prevent overtreatment and wasted resources.

OBJECTIVES: To illustrate the need for better evaluation of surgical procedures, we investigated the use and cost of subacromial decompression in England over the last decade compared with other countries and explored how this related to the conduct and outcomes of randomised, placebo-controlled clinical trials. DESIGN: Longitudinal observational study using Hospital Episode Statistics linked to Payment by Results tariffs in England, 2007/2008 to 2016/2017. SETTING: Hospital care in England; Finland; New York State, USA; Florida State, USA and Western Australia. PARTICIPANTS: Patients with subacromial shoulder pain. INTERVENTIONS: Subacromial decompression. MAIN OUTCOME MEASURES: National procedure rates, costs and variation between clinical commissioning groups in England. RESULTS: Without robust clinical evidence, the use of subacromial decompression in England increased by 91% from 15 112 procedures (30 per 100 000 population) in 2007/2008, to 28 802 procedures (52 per 100 000 population) in 2016/2017, costing over £125 million per year. Rates of use of subacromial decompression are even higher internationally: Finland (131 per 100 000 in 2011), Florida State (130 per 100 000 in 2007), Western Australia (115 per 100 000 in 2013) and New York State (102 per 100 000 in 2006). Two randomised placebo-controlled trials have recently (2018) shown the procedure to be no more effective than placebo or conservative approaches. Health systems appear unable to avoid the rapid widespread use of procedures of unknown effectiveness, and methods for ceasing ineffective treatments are under-developed. CONCLUSIONS: Without good evidence, nearly 30 000 subacromial decompression procedures have been commissioned each year in England, costing over £1 billion since 2007/2008. Even higher rates of procedures are carried out in countries with less regulated health systems. High quality randomised trials need to be initiated before widespread adoption of promising operative procedures to avoid overtreatment and wasted resources, and methods to prevent or desist the use of ineffective procedures need to be expedited.

Breaking bread: examining the impact of policy changes in access to state-funded provisions of gluten-free foods in England.

BACKGROUND: Coeliac disease affects approximately 1% of the population and is increasingly diagnosed in the United Kingdom. A nationwide consultation in England has recommend that state-funded provisions for gluten-free (GF) food should be restricted to bread and mixes but not banned, yet financial strain has prompted regions of England to begin partially or fully ceasing access to these provisions. The impact of these policy changes on different stakeholders remains unclear. METHODS: Prescription data were collected for general practice services across England (n = 7176) to explore changes in National Health Service (NHS) expenditure on GF foods over time (2012-2017). The effects of sex, age, deprivation and rurality on GF product expenditure were estimated using a multi-level gamma regression model. Spending rate within NHS regions that had introduced a 'complete ban' or a 'complete ban with age-related exceptions' was compared to spending in the same time periods amongst NHS regions which continued to fund prescriptions for GF products. RESULTS: Annual expenditure on GF products in 2012 (before bans were introduced in any area) was £25.1 million. Higher levels of GF product expenditure were found in general practices in areas with lower levels of deprivation, higher levels of rurality and higher proportions of patients aged under 18 and over 75. Expenditure on GF food within localities that introduced a 'complete ban' or a 'complete ban with age-related exceptions' were reduced by approximately 80% within the 3 months following policy changes. If all regions had introduced a 'complete ban' policy in 2014, the NHS in England would have made an annual cost-saving of £21.1 million (equivalent to 0.24% of the total primary care medicines expenditure), assuming no negative sequelae. CONCLUSIONS: The introduction of more restrictive GF prescribing policies has been associated with 'quick wins' for NHS regions under extreme financial pressure. However, these initial savings will be largely negated if GF product policies revert to recently published national recommendations. Better evidence of the long-term impact of restricting GF prescribing on patient health, expenses and use of NHS services is needed to inform policy.

A longitudinal study to assess the frequency and cost of antivascular endothelial therapy, and inequalities in access, in England between 2005 and 2015.

OBJECTIVES: High-cost antivascular endothelial growth factor (anti-VEGF) medicines for eye disorders challenge ophthalmologists and policymakers to provide fair access for patients while minimising costs. We describe the growth in the use and costs of these medicines and measure inequalities in access. DESIGN: Longitudinal study using Hospital Episode Statistics (2005/2006 to 2014/2015) and hospital prescribing cost reports (2008/2009 to 2015/2016). We used Poisson regression to estimate standardised rates and explore temporal and geographical variations. SETTING: National Health Service (NHS) care in England. POPULATION: Patients receiving anti-VEGF injections for age-related macular degeneration, diabetic macular oedema and other eye disorders. INTERVENTIONS: Higher-cost drugs (ranibizumab or aflibercept) recommended by the National Institute for Health and Care Excellence or lower-cost drug (bevacizumab) not licensed for eye disorders. MAIN OUTCOME MEASURES: National procedure rates and variation between and within clinical commissioning groups (CCGs). Cost of ranibizumab and aflibercept prescribing. RESULTS: Injection procedures increased by 215% between 2010/2011 and 2014/2015. In 2014/2015 there were 388 031 procedures (714 per 100 000). There is no evidence that the dramatic growth in rates is slowing down. Since 2010/2011 the estimated cost of ranibizumab and aflibercept increased by 247% to £447 million in 2015/2016, equivalent to the entire annual budget of a CCG. There are large inequalities in access; in 2014/2015 procedure rates in a 'high use' CCG were 9.08 times higher than in a 'low use' CCG. In the South-West of England there was twofold variation in injections per patient per year (range 2.9 to 5.9). CONCLUSIONS: The high and rising cost of anti-VEGF therapy affects the ability of the NHS to provide care for other patients. Current regulations encourage the increasing use of ranibizumab and aflibercept rather than bevacizumab, which evidence suggests is more cost-effective. NHS patients in England do not have equal access to the most cost-effective care.

Can commonly prescribed drugs be repurposed for the prevention or treatment of Alzheimer's and other neurodegenerative diseases? Protocol for an observational cohort study in the UK Clinical Practice Research Datalink.

INTRODUCTION: Current treatments for Alzheimer's and other neurodegenerative diseases have only limited effectiveness meaning that there is an urgent need for new medications that could influence disease incidence and progression. We will investigate the potential of a selection of commonly prescribed drugs, as a more efficient and cost-effective method of identifying new drugs for the prevention or treatment of Alzheimer's disease, non-Alzheimer's disease dementias, Parkinson's disease and amyotrophic lateral sclerosis. Our research will focus on drugs used for the treatment of hypertension, hypercholesterolaemia and type 2 diabetes, all of which have previously been identified as potentially cerebroprotective and have variable levels of preclinical evidence that suggest they may have beneficial effects for various aspects of dementia pathology. METHODS AND ANALYSIS: We will conduct a hypothesis testing observational cohort study using data from the Clinical Practice Research Datalink (CPRD). Our analysis will consider four statistical methods, which have different approaches for modelling confounding. These are multivariable adjusted Cox regression; propensity matched regression; instrumental variable analysis and marginal structural models. We will also use an intention-to-treat analysis, whereby we will define all exposures based on the first prescription observed in the database so that the target parameter is comparable to that estimated by a randomised controlled trial. ETHICS AND DISSEMINATION: This protocol has been approved by the CPRD's Independent Scientific Advisory Committee (ISAC). We will publish the results of the study as open-access peer-reviewed publications and disseminate findings through national and international conferences as are appropriate.

Interventions for preventing or treating malnutrition in problem drinkers who are homeless or vulnerably housed: protocol for a systematic review.

BACKGROUND: Problem alcohol drinking in homeless and vulnerably housed people can lead to malnutrition, which is associated with complications such as alcohol-related brain damage. Homeless alcohol drinkers are likely to have worse health outcomes and different nutritional needs compared with housed alcohol-drinking persons. It is not clear whether interventions to improve nutritional status in this population have been effective. The purpose of this review is to assess the effectiveness and cost-effectiveness of interventions for preventing or correcting micronutrient deficiencies and other forms of malnutrition and related comorbidities in this population. METHODS/DESIGN: A systematic search for studies of a nutrition-based intervention applied in the homeless or vulnerably housed population with problem drinking will be conducted. The following electronic databases will be systematically searched for relevant studies: MEDLINE, EMBASE, Web of Science, PsycINFO, CAB abstracts, CINAHL, Cochrane Public Health Group Register and Cochrane Drugs and Alcohol Group Register. Screening of identified abstracts for relevance and assessment of papers for inclusion will be done in duplicate. One reviewer will extract data from the studies and assess quality, and this will be checked by another reviewer. Discrepancies will be resolved by consensus. The primary outcomes are (mal)nutrition status or micronutrient deficiencies or change in (mal)nutrition status or micronutrient deficiencies, measures of liver damage and cognitive function. Secondary outcomes include comorbidities, quality of life and functional scales, resources used to deliver treatment, uptake/acceptability of the intervention and engagement with treatment services. Results will be analysed descriptively, and, if appropriate, meta-analyses will be performed. DISCUSSION: The results of this review should help to inform the development of effective interventions that can be implemented in the community to improve the health of homeless people who are problem drinkers. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015024247.

Primary care characteristics and stage of cancer at diagnosis using data from the national cancer registration service, quality outcomes framework and general practice information.

BACKGROUND: Survival from cancer is worse in England than in some European countries. To improve survival, strategies in England have focused on early presentation (reducing delay to improve stage at diagnosis), improving quality of care and ensuring equity throughout the patient pathway. We assessed whether primary care characteristics were associated with later stage cancer at diagnosis (stages 3/4 versus 1/2) for female breast, lung, colorectal and prostate cancer. METHODS: Data obtained from the National Cancer Registration Service, Quality Outcomes Framework, GP survey and GP workforce census, linked by practice code. Risk differences (RD) were calculated by primary care characteristics using a generalised linear model, accounting for patient clustering within practices. Models were adjusted for age, sex and an area-based deprivation measure. RESULTS: For female breast cancer, being with a practice with a higher two week wait (TWW) referral rate (RD -1.8% (95 % CI -0.5% to -3.2%) p = 0.003) and a higher TWW detection rate (RD -1.7% (95 % CI -0.3% to -3.0%) p = 0.003) was associated with a lower proportion diagnosed later. Being at a practice where people thought it less easy to book at appointment was associated with a higher percentage diagnosed later (RD 1.8% (95 % CI 0.2% to 3.4%) p = 0.03). For lung cancer, being at practices with higher TWW referral rates was associated with lower proportion advanced (RD-3.6% (95 % CI -1.8%, -5.5%) p < 0.001) whereas being at practices with more patients per GP was associated with higher proportion advanced (RD1.8% (95 % CI 0.2, 3.4) p = 0.01). A higher rate of gastrointestinal investigations was associated with a lower proportion of later stage colorectal cancers (RD -2.0% (95 % CI -0.6% to -3.6%) p = 0.01). No organisational characteristics were associated with prostate cancer stage. CONCLUSION: Easier access to primary care, faster referral and more investigation for gastrointestinal symptoms could reduce the proportion of people diagnosed later for female breast, lung and colorectal, but not prostate cancer. Differences between the four main cancers suggest different policies may be required for individual cancers to improve outcomes.

Feline panleukopenia. ABCD guidelines on prevention and management.

OVERVIEW: Feline panleukopenia virus (FPV) infects all felids as well as raccoons, mink and foxes. This pathogen may survive in the environment for several months and is highly resistant to some disinfectants. INFECTION: Transmission occurs via the faecal-oral route. Indirect contact is the most common route of infection, and FPV may be carried by fomites (shoes, clothing), which means indoor cats are also at risk. Intrauterine virus transmission and infection of neonates can occur. DISEASE SIGNS: Cats of all ages may be affected by FPV, but kittens are most susceptible. Mortality rates are high - over 90% in kittens. Signs of disease include diarrhoea, lymphopenia and neutropenia, followed by thrombocytopenia and anaemia, immunosuppression (transient in adult cats), cerebellar ataxia (in kittens only) and abortion. DIAGNOSIS: Feline panleukopenia virus antigen is detected in faeces using commercially available test kits. Specialised laboratories carry out PCR testing on whole blood or faeces. Serological tests are not recommended, as they do not distinguish between infection and vaccination. DISEASE MANAGEMENT: Supportive therapy and good nursing significantly decrease mortality rates. In cases of enteritis, parenteral administration of a broad-spectrum antibiotic is recommended. Disinfectants containing sodium hypochlorite (bleach), peracetic acid, formaldehyde or sodium hydroxide are effective. VACCINATION RECOMMENDATIONS: All cats - including indoor cats - should be vaccinated. Two injections, at 8-9 weeks of age and 3-4 weeks later, are recommended, and a first booster 1 year later. A third vaccination at 16-20 weeks of age is recommended for kittens from environments with a high infection pressure (cat shelters) or from queens with high vaccine-induced antibody levels (breeding catteries). Subsequent booster vaccinations should be administered at intervals of 3 years or more. Modified-live virus vaccines should not be used in pregnant queens or in kittens less than 4 weeks of age.

Bioreactivity of leachate from municipal solid waste landfills - assessment of toxicity.

With the UK producing 400 million tonnes of waste each year, the problem of waste disposal is recognised as one of the most serious environmental problems facing the nation. Of this, over 35 million tonnes is municipal waste, largely derived from households, but also includes some commercial and industrial waste. There are strong national and international concerns about the possible adverse health effects of living in the vicinity of municipal waste landfills. An understanding of the ranges of toxicity of landfill emissions is crucial to determine the degree of concern we should have about the potential effects they could have upon nearby populations and the surrounding environment. Leachates from three different types of landfills have been collected and screened for their potential to induce toxicity. Bioreactivity was measured by a plasmid DNA scission assay (PSA), and 2',7'-dichlorodihydrofluorescin fluorescence (DCFH). The results indicate that leachates cause damage to plasmid DNA in a dose-dependent manner and that toxicity varies between different types of landfills as well as within individual waste sites. Overall, the data implies that the complex chemistry involved in leachate formation has yet to be delineated in terms of the toxicological response.

Assessment of regional left ventricular function: accuracy and reproducibility of positioning standard short-axis sections in cardiac MR imaging.

The assessment of regional left ventricular (LV) function with cardiac magnetic resonance (MR) cine techniques requires a standardized section positioning. A simple selective short-axis method for selective positioning of three short-axis sections (basal, midcavity, apical) was tested for its accuracy, compared with accepted criteria, in 21 volunteers (mean age, 32 years +/- 11) and in 23 patients with myocardial infarction (mean age, 56 years +/- 12). Reproducibility of section positioning and of regional LV parameters was tested in the volunteers. Among the six accuracy criteria defined for standard sections, the selective short-axis approach had an average accuracy of 90.9% in volunteers and 87.7% in patients, compared with 92.1% and 90.6%, respectively, for a multisection approach covering the whole LV. There was very good reproducibility of the selected intersection gap (r = 0.89, P < .001) and of measured midcavity end-diastolic diameters in vertical (r = 0.83, P < .001) and horizontal (r = 0.85, P < .001) long-axis orientations. The proposed method produces standardized short-axis section positions that meet the recommendations for cardiac imaging. The study was approved by the local ethics committee, and all subjects gave written informed consent.

Assessment of ventricular function and mass by cardiac magnetic resonance imaging.

Cardiac magnetic resonance imaging is currently the technique of choice for precise measurements of ventricular volumes, function and left ventricular (LV) mass. The technique is 3D and hence independent of geometrical assumptions; this, along with its excellent definition of endocardial and epicardial borders, makes it highly accurate and reproducible. Cardiac magnetic resonance (CMR) is particularly useful in research, as it is highly sensitive to small changes in ejection fraction and mass, and only a small number of subjects are required for a study. The excellent reproducibility makes temporal follow-up of any individual patient in the clinical setting a realistic possibility. This review examines the merits of CMR and describes the techniques used.

Coronary artery disease: assessment with a comprehensive MR imaging protocol--initial results.

A comprehensive magnetic resonance (MR) imaging protocol for assessment of coronary artery disease (CAD) is presented. The protocol includes multiphase gradient-echo cine MR imaging for assessment of cardiac function, first-pass myocardial perfusion imaging at rest and during adenosine stress, MR imaging with delayed contrast enhancement for assessment of myocardial viability, and coronary MR angiography with a three-dimensional respiratory navigator-gated technique. In 10 patients, the protocol was completed in 61.5 minutes +/- 5.5 and yielded high image quality and diagnostic accuracy. This protocol may provide an integrated noninvasive screening tool for patients with CAD.