Nerve blocks in palliative care.

Although between 85% and 90% of patients with advanced cancer can have their pain well controlled with the use of analgesic drugs and adjuvants, there are some patients who will benefit from an interventional procedure. This includes a variety of nerve blocks and also some neurosurgical procedures. Approximately 8-10% of patients may benefit from a peripheral nerve block and around 2% from a central neuraxial block. The most common indication is because opioid dose escalation is limited by signs of opioid toxicity but some patients will benefit from one component of their pain being relieved by a simple peripheral block. Most patients about to undergo these procedures are already taking high doses of opiods and obtaining valid consent may pose problems. The use of peripheral nerve blocks, epidural and intrathecal infusions, and plexus blocks is discussed.

Bilateral hand oedema related to acupuncture.

We report the case of bilateral hand swelling following acupuncture therapy for chronic low back pain. Despite thorough history, examination and laboratory testing no systemic cause for the swelling could be elicited. This case highlights the incomplete knowledge of acupuncture mechanisms and that limited acupuncture therapy can have significant adverse effects.

A retrospective cohort study of post mastectomy pain syndrome.

Post mastectomy pain syndrome is a condition which can occur following breast surgery and has until recently been regarded as uncommon. Recent reports have suggested that it may affect 20% or more of women following mastectomy. The symptoms are distressing and may be difficult to treat however treatment for neuropathic pain can be successful. This paper reports a retrospective cohort of consecutive mastectomy cases over a six year period in one region of whom 511 survivors were traced and eligible for survey. A total of 408 completed a questionnaire survey which revealed that 175 (43%) had ever suffered from postmastectomy pain syndrome and 119 (29%) reported current symptoms although the majority were decreasing in intensity. A striking finding was the very high cumulative prevalence in younger women (65%) decreasing to 26% in the over 70 year group. The details of the onset, frequency and intensity of symptoms are described along with their natural history. The age effect on the frequency of the syndrome influences the marital status, employment status, housing, and educational status of those who report typical symptoms. Body weight and height are also associated with the frequency of post mastectomy pain syndrome. Relationship between the frequency of post mastectomy pain syndrome and radiotherapy, chemotherapy and the use of tamoxifen are difficult to unravel because of the combinations of pre and post operative treatments received confounded by age. The implications of a much higher frequency of post mastectomy pain are discussed with regard to management and counselling. The high frequency of the syndrome in the younger women is important and possible explanations are explored.

Relationship between the chronic pain grade and measures of physical, social and psychological well-being.

Chronic pain is an important cause of suffering, disability and loss of productivity within the community. Chronic pain can also be viewed as a multidimensional phenomenon, and may be associated with increased suffering of a social and psychological nature, as well as physical suffering. In this paper, the severity of the chronic pain gradings (CPG) is defined in terms of physical, social and psychological well-being, as measured by the SF36 and Glasgow Pain Questionnaire. Although previous work has shown the chronic pain grade to be a valid measure of chronic pain severity, little is known of the relationship between this and other health measures. A random sample of 5036 individuals, representative of the general population, stratified for age and sex, was drawn. A further sample of 4175 patients was drawn from a list of patients enrolled for repeat prescriptions for analgesic medication. A questionnaire survey was carried out, and response rates of 82 and 87% were achieved, respectively. The comparisons described confirm the widespread impact of chronic pain on all aspects of health, supporting the multidimensional view. These findings are important in addressing the management of chronic pain patients, and in particular, the social and psychological well-being of a patient needs to be addressed in parallel with the physical well-being in order to successfully reduce the suffering associated with chronic pain.

The course of chronic pain in the community: results of a 4-year follow-up study.

Little is known about the course of chronic pain in the community. Such information is needed for the prevention and management of chronic pain. We undertook a 4-year follow-up study of 2184 individuals living in Grampian, UK to describe patterns and predictors of change in chronic pain over time. In October 2000, participants completed a postal questionnaire including case definition questions, the chronic pain grade questionnaire, the SF-36 and socio-demographic questions. Information from this questionnaire was compared to information collected from a similar questionnaire in 1996. A response rate of 83% was achieved for the follow-up study. The overall prevalence of chronic pain (pain or discomfort present either all the time or on and off for 3 months or longer) increased from 45.5% at baseline to 53.8% at follow-up. Seventy-nine percent of those with chronic pain at baseline still had it at follow-up. The average annual incidence was 8.3% and the average annual recovery rate was 5.4%. Individuals in the study samples who are in lowest quartile of SF-36 domains--physical functioning, social functioning and bodily pain at baseline--were more likely to develop chronic pain at follow-up, and respondents who were retired were less likely to develop chronic pain. Individuals in the study samples in the lowest quartile of SF-36 domains, bodily pain and general health at baseline, were less likely to recover from their chronic pain, as were those aged 45-74 compared with those aged 25-34. We concluded that chronic pain is a common, persistent problem in the community with relatively high incidence and low recovery rates. The lack of association between onset or recovery from chronic pain and most traditional socio-demographic factors, highlights the need to broaden the range of factors included in studies of chronic pain aetiology.

The Chronic Pain Grade questionnaire: validation and reliability in postal research.

The Chronic Pain Grade questionnaire has been proposed as an interview-administered, multi-dimensional measure of chronic pain severity in selected populations with chronic pain in the United States of America. It has not previously been tested in the United Kingdom, in self-completion form or in an unselected general population. We undertook a postal survey to assess its reliability, validity and acceptability in these circumstances, using a general practice population in Scotland, with a practice population of 11202 patients. A random sample of 400 patients aged over 18 was drawn, stratified for age, gender and receipt or non-receipt of regular prescriptions for pain-relieving medication. The dimensions and sub-scales of the Chronic Pain Grade were compared with the SF-36 general health questionnaire and questions relating to duration of any pain and attempts to seek treatment for this. The methodological approach proposed by Streiner and Norman (1989) was used to assess validity and reliability. A response rate of 76% was achieved. Cronbach's alpha was > 0.9 and item-total correlations were all high, indicating good internal consistency and reliability. Validity was confirmed by psychometric testing, including confirmatory factor analysis. Good correlations with comparable dimensions of the SF-36 general health questionnaire confirmed convergent validity. Construct validity was confirmed by testing scores against duration of pain and treatment sought for pain. We concluded that the Chronic Pain Grade questionnaire is a useful, reliable and valid measure of severity of chronic pain. It translates well into UK English and is acceptable in general population postal research.

The prevalence of chronic chest and leg pain following cardiac surgery: a historical cohort study.

Chronic pain after surgery is recognised as an important post-operative complication; recent studies have shown up to 30% of patients reporting persistent pain following mastectomy and inguinal hernia repair. No large-scale studies have investigated the epidemiology of chronic pain at two operative sites following coronary artery bypass grafting (CABG). This paper reports the follow-up of a cohort of 1348 patients who underwent cardiac surgery between 1996 and 2000 at one cardiothoracic unit in northeast Scotland. Chronic pain was defined as pain in the location of surgery, different from that suffered pre-operatively, arising post-operatively and persisting beyond 3 months. The survey questionnaire consisted of the short-form-36 (SF-36), Rose angina questionnaire, McGill pain questionnaire and the University of California and San Francisco (UCSF) pain service questionnaire. Of the 1080 responders, 130 reported chronic chest pain, 100 chronic post-saphenectomy pain and 194 reported pain at both surgical sites. The cumulative prevalence of post-cardiac surgery pain was 39.3% (CI(95) 36.4-42.2%) and mean time of 28 months since surgery (SD 15.3 months). Patients who reported pain at both sites had lower quality of life scores across all eight health domains compared to patients with pain at one site only and those who were pain-free. Prevalence of chronic pain decreased with age, from 55% in those aged under 60 years to 34% in patients over 70 years. Patients with pre-operative angina and those who were overweight or obese (BMI>/=25) at the time of surgery were more likely to report chronic pain. Chronic pain following median sternotomy and saphenous vein harvesting is more common than hitherto reported and that patients undergoing CABG should be warned of this possibility.

Conjunctival allergen challenge. A clinical approach to studying allergic conjunctivitis.

To evaluate antiallergic agents, we conducted five allergen challenge studies of increasing refinement. The final study design that evolved included two baseline visits, when skin test-positive subjects were administered a bilateral ocular allergen challenge. At the first visit, the threshold dose of reactivity was determined by increasing allergen doses at 10-minute intervals. At the second baseline visit, 3 days later, the responsive subjects were challenged with the final, highest dose used on visit 1 to assure that the allergic reaction was reproducible and not a cumulative effect of multiple allergen doses. The responsive subjects then returned 3 days later for the drug efficacy evaluation. After a slit-lamp examination, subjects were pretreated with the test drug in one eye and the placebo in the fellow eye in a randomized, double-masked fashion. After 10 minutes, subjects were challenged bilaterally with the allergen dose identified on the previous visits. Postchallenge evaluations of hyperemia, itching, chemosis, eyelid swelling, and tearing were performed at 3, 10, and 20 minutes. Subjects were rechallenged 4 hours after drug administration to assess duration of action. Slit-lamp examinations were again performed at the same intervals as after the initial challenge. A total of 396 subjects were given a baseline allergen challenge; 83.6% responded with a moderate (2+) ocular allergic reaction. Of the 266 given a second baseline challenge, 87.2% responded positively again, suggesting that ocular challenge was highly correlated with skin reactivity and reproducible with a second challenge. No statistically significant difference in redness and itching was found when both eyes were challenged with the same dose of allergen.(ABSTRACT TRUNCATED AT 250 WORDS)

The Level of Expressed Need--a measure of help-seeking behaviour for chronic pain in the community.

Chronic pain is a common and disabling condition, with a high impact on health and the health services in the community. The extent of help-seeking behaviour and factors that influence this are complex, but poorly understood. A simple, valid measure of help-seeking behaviour would be useful for community-based research, with a view to developing and evaluating interventions. The aims of the study were to test a hierarchical scale designed to measure help-seeking behaviour in chronic pain in postal surveys of the community, and to explore factors associated with responses. As part of a community survey of chronic pain, we developed the Level of Expressed Need (LEN) scale, based on questions about the use of treatment and professional advice for chronic pain. We compared this scale with two measures of chronic pain severity--the Chronic Pain Grade (CPG), and the Glasgow Pain Questionnaire (GPQ)--and analyzed associations with the SF36 general health questionnaire and demographic variables. Of 3605 respondents (corrected response rate 82%), 1817 reported chronic pain. Of these, 17% were at the mildest and 28% at the severest LEN. There were strong correlations with both the CPG (r=0.48) and the GPQ (r=0.55). There were, however, many important disparities in responses to these measures. Several other factors were independently associated with a high LEN in chronic pain: female gender, lower educational level, and physical, mental, pain and general health dimensions of the SF36 questionnaire. The LEN is a useful tool for measuring the help-seeking response to chronic pain in the general population. The findings confirm that this response is influenced by clinical and demographic factors in addition to the severity of the pain. Further development work will strengthen the instrument to explore these.

Pregnancy and the risk of hemorrhage from cerebral arteriovenous malformations.

We conducted a retrospective analysis of 451 women with an arteriovenous malformation (AVM) of the brain to determine whether pregnancy is a risk factor for cerebral hemorrhages. A total of 540 pregnancies occurred among our patient population, resulting in 438 live births and 102 abortions. There were 17 pregnancies complicated by a cerebral hemorrhage. The hemorrhage rate during pregnancy for women with an unruptured AVM was 0.035 +/- 0.005 per person-year. The hemorrhage rate for nonpregnant women of childbearing age with an unruptured AVM was 0.031 +/- 0.002 per person-year. Pregnancy did not increase significantly the rate of first cerebral hemorrhage from an AVM (P = 0.35). We found that women with an AVM face a 3.5% risk of hemorrhage during pregnancy. Pregnancy is not a risk factor for hemorrhage in women without a previous hemorrhage. This conclusion assumes no selection bias exists in our study population; a bias would be introduced if the risk of fatal outcome after a hemorrhage were greater in pregnant women than in nonpregnant women.

Ampicillin resistant Haemophilus parainfluenzae endocarditis.

A case of Haemophilus parainfluenzae bacterial endocarditis is described. This is the first reported case of endocarditis caused by ampicillin resistant H parainfluenzae. Resistance was not mediated by a beta lactamase. Ampicillin therapy had not controlled the infection, but a four-week course of chloramphenicol was curative. Several general therapeutic points are discussed.

Number of animals for sequential testing.

US regulatory agencies have used six animals in eye irritation tests. Analyses of eye irritation tests on pesticides (n = 48), consumer products and cosmetics (n = 53), Marzulli and Ruggles database (n = 139), and cleaning products and ingredients (n = 30) have greatly extended previous investigations of the merit of reducing animal sample size in the eye test. Given the existing scoring system for positive animal responses (corneal opacity > or = 1, iritis > or = 1, conjunctival redness > or = 2 and conjunctival chemosis > or = 2), the accuracy of the classification systems currently used by these agencies was determined. The US Consumer Product Safety Commission, US Food and Drug Administration, and US Occupational Safety and Health Administration use a classification system by which a substance is designated as an irritant when at least four of six animals give a positive response. This decision rule leads to a very high accuracy of at least 99% with essentially no false positive and false negative judgments. In contrast, the system used by the US Environmental Protection Agency pesticide program, in which only one or more of six treated animals result in an irritant decision, has an accuracy of only 50-80% with very high false positive rates. Analyses indicated that test sample size could be reduced to three and still preserve very good accuracy, whereas two-animal and one-animal tests did not give satisfactory responses. A two-stage test, in which two animals are tested and evaluated in the first stage before the need for testing one more animal in the second stage is determined, also demonstrated good operating characteristics. Both the one-stage/three-animal test and the two-stage test deserve consideration.

Scoring for eye irritation tests.

Scoring of the rabbit eye test and the resulting evaluation and classification should provide useful information about the likelihood that a test material may cause injury on contact with the human eye. When an animal test is necessary, a rabbit eye test based on the following characteristics is proposed for deriving the maximum information from the fewest animals. The ocular effects of interest should include corneal opacity, iritis and conjunctival redness. Animals should be scored for each ocular effect at 24, 48 and 72 hr after the test substance is administered. If an animal is negative at all three scoring times, it can be removed from the test at 72 hr. If it shows a positive effect at a scoring time but the lesion clears at 72 hr, it can be removed at 72 hr. If it shows a positive effect that does not clear at 72 hr, it should be scored again on day 7 when the test ends. However, if an animal shows severe effects at one or more scoring times, it can be removed from the test at 72 hr. An animal is positive if any one of the following criteria is observed at 24, 48 or 72 hr: corneal opacity of 1 or above, iritis of 1 or above, or conjunctival redness of 2 or above. Severe ocular effects (noted at 24, 48 or 72 hr) that may endanger sight deserve special recognition for the classification of chemicals and include corneal opacity of 3 or above, or iritis of 2. This proposal is consistent with the opinions of the majority of respondents who attended the Workshop on Updating Eye Irritation Test Methods, Proposals for Regulatory Consensus. The most notable exception was the suggestion by respondents to add conjunctival chemosis as one of the scoring parameters.

An eye irritation test protocol and an evaluation and classification system.

An in vivo test protocol and an evaluation and classification system for the determination of eye irritation potential of chemicals and mixtures (substances) is proposed. The protocol uses two or three rabbits and reduces distress in test animals. The test substances are classified as non-irritant, irritant or severe irritant to meet regulatory needs. They may be classified on the basis of past experience with similar compounds or mixtures. Screens such as structure-activity relationships, pH extremes, validated and accepted in vitro tests, severe dermal irritation (primary dermal irritation index > or = 5) or severe dermal toxicity (lethality at < 200 mg/kg body weight) should be used to classify irritant or severe irritant materials when one or more of the screens can provide convincing evidence. For suspected severe irritant materials, the proposed in vivo test permits the use of one rabbit and instillation of 0.01 ml (0.01 g) of the test material into the cornea. Materials that are not classified irritant or severe irritant by screens or severe irritant by one rabbit test are tested in two or three rabbits; 0.1 ml (0.1 g) is instilled into the conjunctival sac. The responses (corneal opacity, iritis and conjunctival redness) are scored according to the modified Draize scoring system at 24, 48 and 72 hr and 7 days post-instillation. A rabbit is considered positive when corneal opacity of 1 or above, iritis of 1 or above or conjunctival redness of 2 or above is present at 24, 48 or 72 hr post-instillation. The material is classified as a severe irritant when the rabbit in the one-animal test or two or more rabbits in the standard test have responses of corneal opacity of 3 or above and iritis of 2 at 24, 48 or 72 hr, or positive responses on day 7 after instillation. The material is classified as an eye irritant when two or more rabbits are positive but the responses are not severe and they clear 7 days after instillation. The material is classified as a non-irritant when no more than one rabbit is positive. The opinions expressed in this article are those of the authors and do not necessarily reflect the views of US Federal agencies.

Criteria for in vitro alternatives for the eye irritation test.

A proposal encompassing considerations and criteria for the development of in vitro alternatives to the eye irritation test has been developed and is presented here. Two factors need to be considered initially in developing an alternative test. The first is to determine whether the alternative assay is to be used as a screen or as a replacement for the eye irritation test. Less stringent acceptance criteria are required for an assay used as a screen than for that used as a replacement test. A screen is a preliminary test for the assessment of eye irritation. It is used for making preliminary decisions or establishing the direction for further testing. Screens answer fewer and less complex questions than a replacement test would, since the results from screens are usually confirmed by more definitive testing. A replacement test, however, must provide the same answers as in vivo methods for the assessment of eye irritation and must provide data for making a definitive toxicological assessment of eye irritation. The second factor to be considered is knowledge of the in vivo assay intended to be replaced. This knowledge should include the procedural aspects of the test and the regulatory information it provides. The following may be considered as criteria for in vitro tests used as screens or as replacements for the eye irritation test in rabbits: rationale (there should be a clear statement regarding the rationale for the use of a particular test in relation to the availability of other tests); relevance (the in vitro endpoint should have biological or physiological relevance to the effect to be detected in vivo); and validational (intralaboratory as well as interlaboratory validation must be conducted).

Use of ophthalmic topical anaesthetics.

Pretreatment of the eyes of rabbits with a topical anaesthetic can be viewed as a refinement of the test for eye irritation. It reduces pain at the time of test-material administration, decreases animal distress and permits easier application of the test agent to the eye. In some cases, however, use of an anaesthetic either alone or in combination with the test substance may alter ocular responses or provide little benefit. Although anaesthetic pretreatment may result in decreased pain at the time of test-compound administration, it does not affect possible pain after the effects of the anaesthetic have dissipated. Some anaesthetics are themselves irritating to eyes. In addition, anaesthetics reduce blinking and tearing, thereby maintaining the test-material concentration at the surface of the eye longer. Corneal permeability may also be increased with pretreatment use of an anaesthetic, and may bring the test agent into contact with more structures of the eye. Some anaesthetics delay healing after ocular injury. All of these varied effects may result in increased irritation to the eye. Overall, pretreatment with anaesthetics has usually resulted in a tendency for slightly higher irritation scores; eye irritancy classification is usually unaffected.

Screening procedures for eye irritation.

Screens aid in identifying some severe irritants or corrosives and eliminating them from consideration for in vivo eye irritation testing. Products may be evaluated for ocular irritation potential in a stepwise progression as follows: (1) products at pH extremes of 2 or below or of 11.5 or above may be considered to be ocular irritants; (2) based on chemical structure-activity considerations, some products may be judged to have ocular irritation potential; (3) validated and accepted in vitro systems may possibly be used as a screen in the future; (4) when a test material demonstrates severe acute dermal toxicity (lethality at < or = 200 mg/kg body weight), further testing for either dermal or ocular irritation may not need to be undertaken; (5) if a substance shows a primary dermal irritation index of 5 or above, it may be considered to be an ocular irritant; (6) materials that are not removed from consideration based on these proposed screens may then be considered for testing for ocular irritation in rabbits under accepted procedures. In a survey given to participants in the workshop, a high percentage believed that screens should be used. However, opinions on the use of the individual screens varied between the different interested groups attending, with the possible future use of in vitro screens for specific product lines having the highest percentage of agreement (57-100%).

The use of low-volume dosing in the eye irritation test.

The Draize rabbit eye test was developed to provide a method for assessing the irritation potential of materials that might come in contact with human eyes. The method involves the instillation of 0.1 ml of a test liquid (100 mg solid) into the conjunctival sac of an animal's eye. A refinement of the Draize test is the low-volume eye test in which 0.01 ml of a substance is placed directly on the cornea of the eye. Studies indicate that the low-volume method provides a better correlation to human eye irritation experience for some substances. The Interagency Regulatory Alternatives Group (IRAG) proposes that the low-volume eye test can be used to substantiate the irritancy of suspect severe ocular irritants that have not been eliminated by various pre-eye test 'screens'. A substance testing positive by the low-volume method can be classified as an irritant; one that tests negative will require further testing by the use of the 0.1-ml volume procedure. For all other definitive testing, the Draize test (0.1 ml) should be used. Results from a questionnaire distributed at the IRAG workshop showed that many workshop participants thought that the low-volume test should be used as an eye irritation screening procedure.