The law that came in from the cold.

As winter draws on it is timely to look at ways in which nurses in the community may be faced with problems, expected and unexpected, when their patients are particularly affected by cold conditions and at the precautions which need to be taken to avoid or lessen adverse effects on their health. As in the case of heat-related risks to health, examined in an earlier article, so too in the case of cold those most at risk are elderly patients and those who are vulnerable due to a pre-existing condition affecting health even in a more clement climate. Cold weather attracts extra legal responsibilities which are examined in this article.

Legal responsibilities relating to isolation.

Isolation can cause harm in everyday life, even in the most benign conditions. Taking on responsibility for a patient in the community who is isolated can entail a responsibility to steer them on a course, which they might otherwise not have taken and which might redound to their benefit. In this article, John Finch, a freelance journalist specialising in clinical law and ethics, examines some of the legal responsibilities which are added by the effects of isolation to the already heavy burden carried by community nurses.

Legal issues related to heat.

Health problems related to climate change are with us to stay, some say for a good while. The effect of excessive heat on the human frame are manifold and they are encountered first in the home. During hot weather, community nurses are likely to be faced with an array of health issues not encountered in more temperate conditions. Those very health issues can also impact on legal issues. John Finch, a freelance journalist specialising in clinical law and ethics, examines how.

Supervision and restriction of patients at home.

There are laws laid down in mental health legislation, which permit the detention of patients in hospital under clinical supervision. But there is no legislative provision for patients who are cared for at home in association with district nurses. The law relating to the care of such patients comes from the ordinary common law relating to duties of care and their associated standards, to consent to treatment and to confidentiality and privacy of information. Much of established English law is to be found in court decisions relating to claimants who have been in hospital. The law relating to the supervision of patients who are being cared for at home requires separate examination. John Finch, a freelance journalist specialising in the law and ethics of healthcare, takes a look at some of the legal aspects of home care and treatment with a particular eye supervision and restrictions which need to be placed on liberty and movement which would not be required in the absence of vulnerability.

Advance planning in district nursing practice.

Most district nurses would willingly know precisely what the future has in store, as they would spend their professional time raking over past mistakes. Legal responsibilities require both, though each in a limited way. John Finch, a freelance journalist specialising in tax and ethics affecting clinical practice, examines how the building blocks of legal responsibility manifest themselves in advance planning in district nursing.

Patient decisions in a domiciliary setting.

Nurses working in the community frequently begin their professional relationship with a patient based on the reason for which their services were initially sought; but, as the relationship develops, community nurses can find that their strictly clinical expertise is not the only factor in the relationship which the patient seeks. This article looks at some aspects of the relationship between practitioner and patient which go beyond the strictly clinical and which attract further legal and ethical considerations. These further responsibilities may not have been examined in detail during training and can be learned only by experience.

The influence of facility and home pen design on the welfare of the laboratory-housed dog.

We have an ethical and scientific obligation to Refine all aspects of the life of the laboratory-housed dog. Across industry there are many differences amongst facilities, home pen design and husbandry, as well as differences in features of the dogs such as strain, sex and scientific protocols. Understanding how these influence welfare, and hence scientific output is therefore critical. A significant proportion of dogs' lives are spent in the home pen and as such, the design can have a considerable impact on welfare. Although best practice guidelines exist, there is a paucity of empirical evidence to support the recommended Refinements and uptake varies across industry. In this study, we examine the effect of modern and traditional home pen design, overall facility design, husbandry, history of regulated procedures, strain and sex on welfare-indicating behaviours and mechanical pressure threshold. Six groups of dogs from two facilities (total n=46) were observed in the home pen and tested for mechanical pressure threshold. Dogs which were housed in a purpose-built modern facility or in a modern design home pen showed the fewest behavioural indicators of negative welfare (such as alert or pacing behaviours) and more indicators of positive welfare (such as resting) compared to those in a traditional home pen design or traditional facility. Welfare indicating behaviours did not vary consistently with strain, but male dogs showed more negative welfare indicating behaviours and had greater variation in these behaviours than females. Our findings showed more positive welfare indicating behaviours in dogs with higher mechanical pressure thresholds. We conclude that factors relating to the design of home pens and implementation of Refinements at the facility level have a significant positive impact on the welfare of laboratory-housed dogs, with a potential concomitant impact on scientific endpoints.

A multi-site comparison of in vivo safety pharmacology studies conducted to support ICH S7A & B regulatory submissions.

INTRODUCTION: Parts A and B of the ICH S7 guidelines on safety pharmacology describe the in vivo studies that must be conducted prior to first time in man administration of any new pharmaceutical. ICH S7A requires a consideration of the sensitivity and reproducibility of the test systems used. This could encompass maintaining a dataset of historical pre-dose values, power analyses, as well as a demonstration of acceptable model sensitivity and robust pharmacological validation. During the process of outsourcing safety pharmacology studies to Charles River Laboratories, AstraZeneca set out to ensure that models were performed identically in each facility and saw this as an opportunity to review the inter-laboratory variability of these essential models. METHODS: The five in vivo studies outsourced were the conscious dog telemetry model for cardiovascular assessment, the rat whole body plethysmography model for respiratory assessment, the rat modified Irwin screen for central nervous system assessment, the rat charcoal meal study for gastrointestinal assessment and the rat metabolic cage study for assessment of renal function. Each study was validated with known reference compounds and data were compared across facilities. Statistical power was also calculated for each model. RESULTS: The results obtained indicated that each of the studies could be performed with comparable statistical power and could achieve a similar outcome, independent of facility. DISCUSSION: The consistency of results obtained from these models across multiple facilities was high thus providing confidence that the models can be run in different facilities and maintain compliance with ICH S7A and B.

The Florida Shock Anxiety Scale (FSAS) for patients with implantable cardioverter defibrillators: testing factor structure, reliability, and validity of a previously established measure.

BACKGROUND: The implantable cardioverter defibrillator (ICD) reduces mortality in patients at risk for life-threatening arrhythmias via high energy shock. The Florida Shock Anxiety Scale (FSAS) was developed to measure ICD patient shock-related anxiety. Initial psychometric evaluation revealed good reliability and validity. The purpose of this study was to examine the psychometrics of the FSAS in a large US sample of ICD patients. METHODS: Participants were recruited via e-mail and the survey was completed online. Ultimately, 443 ICD patients (359 male and 421 White) completed the 10-item FSAS. RESULTS: Means for FSAS were comparable to previously published data (M = 15.18, SD = 6.5). Interitem reliability was good (Cronbach's α= 0.89). The FSAS was negatively correlated with single-item measures of emotional well-being (r =-0.378, P < 0.01), sense of security (r =-0.365, P < 0.01), perceived general health (r =-0.185, P < 0.01), and quality of life (r =-0.216, P < .01), demonstrating discriminant validity. Convergent validity was supported through significant correlations with number of shocks (r = 0.464, P < 0.01) and reported disruptiveness of shock (r = 0.484, P < 0.01). Confirmatory factor analysis revealed that a single (second-order) factor model (χ(2) [34] = 75.34, P < 0.05, comparative fit index = 0.98, root mean-square error of approximation = 0.05) had the best fit. CONCLUSIONS: Shock anxiety as a construct can be measured in a reliable and valid method by the FSAS. These nationally representative data suggest that a single score for shock anxiety is an easy to use and appropriate method of assessment.

Toxicologic significance of histologic change in the larynx of the rat following inhalation exposure: a critical review.

The larynx is a site in the respiratory tract of animals that often shows a response to inhaled substances. In many cases, the most sensitive endpoint in repeated dose inhalation studies is squamous metaplasia (often of minimal severity) of the larynx. The U.S. Environmental Protection Agency has speculated that squamous metaplasia in the rodent larynx might be a pre-neoplastic lesion or a precursor to other serious effects and has proposed to use the effect of squamous metaplasia occurring in subchronic inhalation toxicology studies as a toxicologic endpoint for use in quantitative risk assessment [U.S. Environmental Protection Agency, 2006a. Reregistration Eligibility Decision for MGK-264, U.S. Environmental Protection Agency, 2006b, Reregistration Eligibility Decision for Piperonyl Butoxide, U.S. Environmental Protection Agency, 2006c. Reregistration Eligibility Decision for Pyrethrins]. To reach a conclusion as to its significance, we sought to establish the nature of this effect in the relevant context of rodent inhalation studies. A comprehensive review of the literature shows that laryngeal metaplasia can be produced by a wide range of chemically dissimilar substances, and even by "non-chemical" means such as irritation by aerosols and particles, and dehydration by alcohols or low humidity air. There is no published evidence that this effect is pre-neoplastic and it is clearly and repeatedly characterized as an adaptive response. Moreover, the well-differentiated character of laryngeal squamous metaplasia, the reversibility of incidence and severity of it during recovery periods, combined with no significant clinical observations and the lack of progression over time indicates that this response is adaptive and should not be considered to be indicative of significant human risk. We therefore conclude that squamous metaplasia of the rodent larynx is not a relevant toxicologic endpoint.

Longitudinal effects of hope on depression and anxiety: a latent variable analysis.

This study tested the prospective effects of hope on depression and anxiety using a longitudinal design. A sample of 522 college students completed self-report measures of hope, depression, and anxiety at three time points, with 1-month delays between administrations. Structural equation modeling was employed to test two cross-lagged panel models of the reciprocal effects of the Agency and Pathways components of hope on depression and anxiety. Results indicated statistically significant negative effects for the Agency component of hope on later depression but no unique effect of the Pathways component of hope on depression. Likewise, Agency showed a statistically significant negative effect on later anxiety, but again Pathways had no significant influence on anxiety. In both cases, neither depression nor anxiety demonstrated any longitudinal effects on either the Agency or Pathways components of hope. Implications of these findings are discussed, along with potential directions for future research.

A mode of action for induction of liver tumors by Pyrethrins in the rat.

High doses of Pyrethrins produce liver tumors in female rats. To elucidate the mode of action for tumor formation, the hepatic effects of Pyrethrins have been investigated. Male Sprague-Dawley CD rats were fed diets containing 0 (control) and 8000 ppm Pyrethrins and female rats' diets containing 0, 100, 3000 and 8000 ppm Pyrethrins for periods of 7, 14 and 42 days and 42 days followed by 42 days of reversal. As a positive control, rats were also fed diets containing 1200-1558 ppm sodium Phenobarbital (NaPB) for 7 and 14 days. The treatment of male rats with 8000 ppm Pyrethrins, female rats with 3000 and 8000 ppm Pyrethrins and both sexes with NaPB resulted in increased liver weights, which were associated with hepatocyte hypertrophy. Hepatocyte replicative DNA synthesis was also increased by treatment with Pyrethrins and NaPB. The treatment of male and female rats with Pyrethrins and NaPB produced significant increases in hepatic microsomal cytochrome P450 (CYP) content and a marked induction of CYP2B-dependent 7-pentoxyresorufin O-depentylase and testosterone 16beta-hydroxylase activities. Significant increases were also observed in CYP3A-dependent testosterone 6beta-hydroxylase activity. The hepatic effects of Pyrethrins were dose-dependent in female rats with 100 ppm being a no effect level and on cessation of treatment were reversible in both sexes. This study demonstrates that Pyrethrins are mitogenic CYP2B form inducers in rat liver. The mode of action for Pyrethrins-induced rat liver tumor formation appears to be similar to that of NaPB and some other non-genotoxic CYP2B inducers of hepatic xenobiotic metabolism.