Information about migraine disability influences physicians' perceptions of illness severity and treatment needs.

OBJECTIVE: To assess physician-patient communication about headache-related disability and to evaluate the influence of information about disability on physicians' perceptions of illness severity and the treatment needs of migraineurs. BACKGROUND: Evidence suggests that migraine is suboptimally treated in clinical practice, partly due to poor communication between physicians and their patients. METHODS: One hundred five neurologists and primary care physicians with an interest in headache participated in two interactive surveys, one in North America (n=42) and one in Europe (n=63). Each survey focused on the evaluation of four videotaped migraine cases. The first case was evaluated twice, initially after a typical symptom history that centered on diagnosis and then following a fuller history of migraine disability. Additional questions assessed the extent of the collection of migraine disability information in clinical practice. RESULTS: Physicians reported that they recorded symptoms relating to diagnosis (eg, pain location/intensity, associated symptoms) rather than information on headache-related disability. Only about one third of patients volunteered disability information. When made available to them, physicians rated information on disability as one of the most important factors in assessing treatment needs. In particular, when physicians knew the patient's disability history: (1) the proportion of physicians who rated the patient's illness as "severe" increased by 128% in North America, 27% in Europe; (2) the proportion of physicians who recommended immediate treatment increased by 63% in North America, 37% in Europe; and (3) the proportion of patients recommended for a follow-up visit increased by 15% in North America, 18% in Europe. CONCLUSIONS: Physicians and patients often fail to discuss headache-related disability during consultation. This information has a powerful influence on physicians' perceptions of illness severity, treatment choice, and the need for follow-up. Tools to improve communication about headache-related disability, such as the Migraine Disability Assessment questionnaire, may favorably improve migraine management.

Migraine-related disability: impact and implications for sufferers' lives and clinical issues.

Migraine is a common, debilitating disorder that imposes a large personal burden on sufferers and high economic costs on society. Sufferers have a significant level of migraine-related disability in all aspects of their daily lives, including employment, household work, and non-work activities. Despite this burden of illness, physicians often do not diagnose or treat the illness effectively. Physicians consider that specific treatment is necessary when disability information is known but, until recently, no criteria have been available for assessment of migraine severity. Two studies indicate that information on disability is an important criterion in assessing migraine severity and influences physicians in their judgments of illness severity and treatment needs. However, physicians and patients often do not seek or share migraine-associated disability, which may contribute to suboptimal management. Efforts to improve knowledge of headache-related disability in the consultation have the potential to improve migraine management. An assessment tool that could reliably quantify headache-related disability has the potential for grading migraine severity and improving care.

Symptoms, signs, and prescribing for acute lower respiratory tract illness.

BACKGROUND: Most patients who consult with acute lower respiratory symptoms receive antibiotics, usually without evidence of significant infection. The physical signs at presentation of acute lower respiratory tract illness and the rate at which symptoms resolve and normal activities recover is not well documented. AIM: To examine in patients with lower respiratory tract infection (LRTi), their physical signs at presentation, their relationship to antibiotic prescribing, and symptom resolution and resumption of normal activities. DESIGN OF STUDY: Analysis of data collected prospectively during presentation of acute LRTi in primary care and from patient symptom diary cards. SETTING: Forty GPs who were members of an informal Community Respiratory Infection Interest Group recruited 391 patients to the study. METHOD: Information was collected on pulse, oral temperature, respiratory rate, abnormalities on auscultation, and details of any antibiotic prescription. Patients completed symptom diary cards for the following 10 days. RESULTS: Of the 391 patients who consulted 71% received antibiotics. A minority had abnormal physical signs: 17% had a pulse greater than 90 bpm, 15% a respiratory rate greater than 20 breaths per minute, 4% had a temperature greater than 38 degrees C, and 25% had an abnormality on auscultation. Antibiotic prescribing was more common in the presence of abnormal chest signs (odds ratio = 8.71, 95% confidence interval = 3.69-20.61) or discoloured sputum (OR = 2.67, 95% CI = 1.57-4.56). Ten days after consultation, 58% of patients were still coughing and 29% had not returned to normal activities. CONCLUSION: Abnormal physical signs at presentation do not explain the high rates of antibiotic prescribing nor do they predict persisting cough and functional impairment at 10 days. Reconsultation for the same symptoms within a month is common and is strongly related to persisting cough, but not abnormalities at presentation.

Conflicts of interest between the prescriber, the regulator and the profit maker.

The traditional, highly valued, clinical freedom of doctors is under threat with the development of evidence-based protocols. Contact with the pharmaceutical industry provides doctors with education and resource but at what cost? Government has failed to match the industry in this arena. Conflicts of interest arise when the balance between the information provided by these two bodies is uneven. Authorities' desire for impartial prescribing is not matched by their willingness to support the training and working practices which would deliver it.

Retinoids and ovarian cancer.

Each year, an estimated 26,000 women in the United States are diagnosed with ovarian cancer. During any given year, approximately 14,500 women die from this disease. Ovarian cancer is the seventh most common cancer in women worldwide, after breast, cervix, colon/rectum, stomach, corpus uteri, and lung cancers. In the U.S., ovarian cancer is the second most common gynecologic cancer, and is the fourth leading cause of solid tumor cancer deaths among women. Currently, postoperative chemotherapy of ovarian cancer is still suboptimal. Drug resistance is a common problem resulting in only 20 approximately 30% overall 5-year survival rates. Clearly, continued development of alternative therapeutic strategies is essential for the management of this fatal disease. A number of recent studies have suggested that retinoids may play a potential role as an ovarian cancer chemotherapeutic agent. Retinoids, the natural and synthetic derivatives of vitamin A, have been shown to inhibit the growth of human ovarian cancer cells both in vivo and in culture. This review will initially summarize what is known about the pathological and molecular characteristics of ovarian carcinoma. It will then describe retinoid metabolism and the role of the cellular and nuclear retinoid binding proteins in mediating retinoid action. Following this general review of retinoids and their function, data supporting the role of retinoic acid as a suppresser of ovarian carcinoma cell growth will be presented. Particular attention will be paid to studies suggesting that members of the RB family of proteins and RB2/p130, in particular, are the molecular targets responsible for retinoid mediated inhibition of ovarian carcinoma cell growth. This review will then conclude with a brief discussion of two synthetic retinoids, 4 HPR R(fenretinide) and AHPN/CD437, which have been shown to induce apoptosis in ovarian tumor cells. It will be clear from the studies summarized in this review that retinoids represent a potentially powerful alternative to present chemotherapeutic approaches to the treatment of late stage ovarian cancer.

Induction of apoptosis in ovarian carcinoma cells by AHPN/CD437 is mediated by retinoic acid receptors.

Retinoids have great promise in the area of cancer therapy and chemoprevention. These natural and synthetic derivatives of vitamin A have been shown to play an important role in regulating cell differentiation and proliferation. While all-trans-retinoic acid (ATRA) has been demonstrated to inhibit the growth of several ovarian tumor cell lines, other ovarian carcinoma cell lines have been found to be resistant to retinoid dependent growth suppression. Interestingly, a novel synthetic retinoid, CD437 or AHPN, has been demonstrated to inhibit the growth of both ATRA-sensitive (CA-OV3) and ATRA-resistant (SK-OV3) ovarian tumor cell lines as well as to induce apoptosis. The overall goal of this research was to understand the mechanism by which AHPN/CD437 induces apoptosis in ovarian tumor cell lines. Since a number of studies have demonstrated the importance of nuclear receptors (RARs and RXRs) in mediating cellular responses to retinoids, we wished to determine the role of RARs in mediating the AHPN/CD437 response. We modulated RAR level and function by overexpressing either wild type RAR-gamma or a pan dominant negative mutant of all RAR subtypes called RAR-beta (R269Q), or through the use of an RAR-gamma antagonist, MM11253. We found that inhibition of RAR function reduced but did not eliminate induction of apoptosis in both CA-OV3 and SK-OV3 cells by AHPN/CD437. Likewise, overexpression of wild type RAR-gamma was found to increase apoptosis after treatment with AHPN/CD437. Our results suggest that in ovarian carcinomas, AHPN/CD437 induced apoptosis is mediated at least in part via an RAR pathway.

Characterisation of sulphonylurea and ATP-regulated K+ channels in rat pancreatic A-cells.

We have monitored whole-cell and single channel ATP-sensitive K+ (KATP) currents in isolated rat glucagon-secreting pancreatic A-cells. Tolbutamide produced a concentration-dependent decrease in the whole-cell KATP conductance (Ki = 6 microM) and initiated action potential firing. The K+ channel opener diazoxide, but not cromakalim or pinacidil, inhibited electrical activity and increased the whole-cell K+ conductance fourfold. ATP applied to the intracellular face of the membrane inhibited KATP channel activity with a Ki of 17 microM, an effect that could be counteracted by Mg-ADP and Mg-GDP. GTP and UTP did not affect KATP channel activity. Phosphatidylinositol 4,5-bisphosphate activated KATP channels inhibited by ATP after a delay of 90 s. In situ hybridisation demonstrated the expression of the mRNA encoding KATP channel subunits Kir6.2 and SUR1 but not Kir6.1 and SUR2. We conclude that rat pancreatic A-cells express KATP channels with the nucleotide-, sulphonylurea- and K+ channel-opener sensitivities expected for a channel formed by Kir6.2 and SUR1 subunits.

How do general practitioners respond to reports of abnormal chest X-rays?

General practitioners (GPs) in the UK have long had direct access to hospital radiological services, which in theory shortens investigation time and improves the quality of service. Chest X-rays (CXRs) account for a substantial proportion of requests, and we investigated what happened when an abnormality was detected. In one year, 204 GPs in the Nottingham area requested CXRs in 605 patients. 362 were reported normal, 165 abnormal but hospital follow-up not indicated and 71 abnormal with radiological follow-up or hospital referral indicated (mass lesion suspicious of tumours 27, infective shadowing 35, other 9). 64 of the 71 were seen in hospital within three months, and in those with suspected cancer the median time to follow-up was 20 days. These results show that GPs do act on the results of abnormal CXRs, but only 37% of those with a mass suspicious of cancer were seen in hospital within two weeks as recommended by the British Thoracic Society. Time might be saved if GPs agreed to direct referral from the radiology department to respiratory physicians.

Postmarketing surveillance study of a non-chlorofluorocarbon inhaler according to the safety assessment of marketed medicines guidelines.

OBJECTIVE: To evaluate the safety of a non-chlorofluorocarbon metered dose salbutamol inhaler. DESIGN: This was a postmarketing surveillance study, conducted under formal guidelines for company sponsored safety assessment of marketed medicines (SAMM). A non-randomised, non-interventional, observational design compared patients prescribed metered doses of salbutamol delivered by inhalers using either hydrofluoroalkane or chlorofluorocarbon as the propellant. Follow up was three months. SETTING: 646 general practices throughout the United Kingdom. SUBJECTS: 6614 patients with obstructive airways disease (1667 patient years of exposure). MAIN OUTCOME MEASURES: Proportions of patients who were: admitted to hospital for respiratory diseases, reported adverse side effects, or withdrew because of adverse affects. RESULTS: There were no significant differences between the hydrofluoroalkane (HFA 134a) and chlorofluorocarbon inhaler groups in relation to the proportions of patients admitted to hospital for respiratory diseases (odds ratio 0.75; 95% confidence interval 0.51 to 1.08) or the proportions who reported adverse events (1.01; 0.88 to 1.17). However, more patients using the hydrofluoroalkane inhaler than the chlorofluorocarbon inhaler withdrew because of adverse events (3.8% and 0.9% respectively). CONCLUSION: The hydrofluoroalkane inhaler was as safe as the chlorofluorocarbon inhaler when judged by hospital admissions and adverse affects. The study design successfully fulfilled the recommendations of the guidelines. Differences between postmarketing surveillance studies and randomised clinical trials in assessing safety were identified. These may lead to difficulties in the design of postmarketing surveillance studies.

Pattern of immediate type hypersensitivity reactions in the Eastern Province, Saudi Arabia.

BACKGROUND: In the period between July, 1992, and July, 1994, 1,159 patients in our Allergy Clinic tested positive to one or more inhalants. The nationalities of the population tested included 806 Saudi Arabs and 241 Western expatriates (mainly North Americans). The others were of various different nationalities. OBJECTIVES: Our objective was to determine the pattern of immediate type hypersensitivity reactions among the atopic population in the Eastern Province of the Kingdom of Saudi Arabia. METHODS: A standard prick skin test was applied and the reaction was considered positive if there was a 3-mm wheal associated with 10 mm of erythema, greater than the negative control. RESULTS: The ten most common reactions in the Saudi Arab patients were as follows: Chenopodium album 53%, Kochia 51%, mesquite 46%, cottonwood 38%, alfalfa 36%, dust mite-farinae 36%, cockroach 35%, house dust 31%, Bermuda grass 29%, and acacia 29%. For North American expatriates living in the area, the ten most common reactions were: dust mite-farinae 43%, house dust 41%, Alternaria 36%, grass mix 34%, Bermuda grass 33%, mesquite 32%, cat 31%, Kochia 28%, alfalfa 24%, and Chenopodium album 24%. CONCLUSIONS: Hypersensitivity to pollens, house dust, dust mite and cockroach was common. Mold and cat allergies were only common among Western expatriates.

The influence of antibiotics and other factors on reconsultation for acute lower respiratory tract illness in primary care.

BACKGROUND: Antibiotics are prescribed to the majority of patients consulting their general practitioner (GP) for lower respiratory tract illness (LRTi). A common reason for prescription is the belief that antibiotics reduce re-attendance; a motive supported by the high reconsultation rates for this largely self-limiting illness. Information about reconsultation following treatment of LRTi, and the factors that influence it, is scarce. AIM: To explore factors associated with reconsultation after initial management of LRTi. METHOD: Analysis of data collected prospectively during presentation of acute LRTi in primary care. RESULTS: Seventy-six per cent of 518 patients were prescribed antibiotics, and 30% reconsulted for similar symptoms within the next 28 days (29% of those who were given antibiotics and 33% of those who were not). Forty-one per cent of patients who had seen their GP 15 or more times in the previous two years reconsulted, compared with 13% of those who had made fewer than five visits. Reconsultation was more common in patients with a history of underlying disease (38.6% versus 24.3%) and in patients who reported dyspnoea (41.5% versus 24.3%). CONCLUSION: Reconsultation is common in acute LRTi and is associated with a heightened consulting habit prior to the index consultation, the presence of previous ill health, and dyspnoea. It appears not to be influenced by prescribing antibiotics.

Reducing reconsultations for acute lower respiratory tract illness with an information leaflet: a randomized controlled study of patients in primary care.

BACKGROUND: General practitioners (GPs) prescribe antibiotics to three-quarters of patients who consult with a lower respiratory tract illness (LRTi). In spite of this management, around a quarter of patients reconsult for the same symptoms within a month. AIM: To investigate the impact of providing a simple leaflet regarding the natural history of lower respiratory tract symptoms on reconsultation rates for previously well adults presenting to their GP with an LRTi. METHOD: Seventy-six GPs studied 1014 previously well adults presenting with an illness defined as an LRTi. Management was left to the GP's discretion. Half of the patients were randomly allocated to receive an information leaflet at the end of the consultation, blinded from the GP. The endpoint was reconsultation for the same symptoms within one month. RESULTS: Follow-up data was available for 1006 adults, of whom 182 (18%) reconsulted. Fewer patients who received the leaflet (75/505; 14.9%) returned to the surgery compared with those who did not (107/501; 21.4%; P = 0.007). The same benefit was found for the 723 (72%) adults treated initially with antibiotics; 16% (60/369) in the leaflet group returned compared with 23% (81/354) in the no leaflet group (P = 0.02). CONCLUSION: Informing previously well patients about the natural history of LRTi symptoms is an effective strategy for reducing reconsultations, benefiting the patient and the GP; it is likely to reduce antibiotic prescriptions and future patient consultation habits.