Bow-tie diagrams for risk management in anaesthesia.

Bow-tie analysis is a risk analysis and management tool that has been readily adopted into routine practice in many high reliability industries such as engineering, aviation and emergency services. However, it has received little exposure so far in healthcare. Nevertheless, its simplicity, versatility, and pictorial display may have benefits for the analysis of a range of healthcare risks, including complex and multiple risks and their interactions. Bow-tie diagrams are a combination of a fault tree and an event tree, which when combined take the shape of a bow tie. Central to bow-tie methodology is the concept of an undesired or 'Top Event', which occurs if a hazard progresses past all prevention controls. Top Events may also occasionally occur idiosyncratically. Irrespective of the cause of a Top Event, mitigation and recovery controls may influence the outcome. Hence the relationship of hazard to outcome can be viewed in one diagram along with possible causal sequences or accident trajectories. Potential uses for bow-tie diagrams in anaesthesia risk management include improved understanding of anaesthesia hazards and risks, pre-emptive identification of absent or inadequate hazard controls, investigation of clinical incidents, teaching anaesthesia risk management, and demonstrating risk management strategies to third parties when required.

Major depression and depressive symptoms in Australian Gulf War veterans 20 years after the Gulf War.

BACKGROUND: Risk of major depression (depression) was elevated in Australia's Gulf War veterans in a 2000-2002 (baseline) study. A follow up study has measured the Gulf War-related risk factors for depression, also the current prevalence and severity of depression, use of anti-depressant medication, and persistence, remittance or incidence of depression since baseline in Gulf War veterans and a military comparison group. METHODS: Participants completed the Composite International Diagnostic Interview v.2.1, the 9-item Patient Health Questionnaire and the Military Service Experience Questionnaire, and consented to Repatriation Pharmaceutical Benefits Scheme (RPBS) and PBS linkage. RESULTS: Prevalence of depression (9.7% Gulf War veterans and 7.7% comparison group; adj RR=1.2, 95% CI 0.8-1.7), and pattern of persistence, remittance and incidence of depression since baseline, were similar in the two groups, however veterans reported slightly more severe symptoms (adj median difference 1, 95% CI 0.26-1.74) and were more likely to have been dispensed anti-depressant medication (adj RR=1.56, 95% CI 1.05-2.32). Depression amongst veterans was associated with self-reported Gulf War-related stressors in a dose-response relationship (adj RR 1.06, 95% CI 1.02-1.09). LIMITATIONS: Lower participation rates at follow up resulted in reduced statistical power compared with baseline, Gulf War related stressor data collected at baseline was at risk of recall bias, and RPBS and PBS databases do not capture all dispensed Nervous System medications. CONCLUSIONS: More than 20 years after the Gulf War, veterans are experiencing slightly more severe depressive symptoms than a military comparison group, and depression continues to be associated with Gulf War-related stressors.

Postnatal demoralisation among women admitted to a hospital mother-baby unit: validation of a psychometric measure.

Demoralisation is a psychological state characterised by experiences of distress and sadness, helplessness, subjective incompetence and hopelessness, in the context of a stressful situation. Experiences of demoralisation may be particularly relevant to women who have recently given birth, who can feel incompetent, isolated and helpless. The psychometric properties of the Demoralisation Scale among women in the postnatal period participating in a clinical program were examined. Women admitted with their infants to a hospital mother-baby unit in Australia for five nights were recruited consecutively (N = 209) and assessed at admission and discharge. The Demoralisation Scale was perceived as relevant and exhibited high reliability, acceptable construct validity and good sensitivity to change. The mean demoralisation score was high (M = 30.9, SD = 15.5) and associated with negative experiences of motherhood and functional impairment, independent of depression and anxiety symptoms. Mean demoralisation decreased significantly after program completion (M = 18.4, SD = 12.4). More participants showed a significant improvement in demoralisation (57.5 %) than in depression (34.8 %) and anxiety (9.8 %) symptoms. Demoralisation can provide a useful framework for understanding and measuring the experiences of women participating in postnatal clinical programs and in directing treatment towards helping women to acquire the necessary caregiving skills and increasing parental efficacy. The Demoralisation Scale is a useful clinical tool for assessing intervention effects.

Targeted induction of apoptosis via TRAIL and cryoablation: a novel strategy for the treatment of prostate cancer.

Adjuvant therapies contribute to the successful treatment of cancer. Our previous reports have shown that combining cryoablation with cytotoxic agents enhances cell death. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic agent that preferentially induces apoptosis in a variety of human cancer cells. Human prostate cancer cells (PC-3) are resistant to many cytodestructive agents, including cryoablation and TRAIL. Here, we evaluated the effects of TRAIL combined with cryoablation on PC-3 and normal prostate (RWPE-1) cell death. Exposure of PC-3 cells to freezing (-10 degrees C) or TRAIL (500 ng/ml) results in minimal cell death, whereas a complete loss of viability is observed with the simultaneous combination. The synergistic effect was found to be due to a marked increase in apoptosis. Western blot analysis revealed a significant level of caspase-8 and -3 cleavage between 12 and 24 h post-exposure. Caspase activation assays provided similar results and also indicated a role for caspase-9. Inhibitors to caspase-8 and -9 along with a pan-caspase inhibitor were incorporated to determine which pathway was necessary for the combined efficacy. Inhibition of caspase-8 significantly blocked the combination-induced cell death compared to cells that did not receive the inhibitor (63% compared to 10% viable). The addition of the caspase-9 inhibitor resulted in only a minimal protection. Importantly, the combination was not effective when applied to normal prostate cells. The results describe a novel therapeutic model for the treatment of prostate cancer and provide support for future in vivo studies.

The contribution of spirituality and spiritual coping to anxiety and depression in women with a recent diagnosis of gynecological cancer.

The objective of this study was to determine whether, after accounting for illness and demographic variables, spiritual involvement and beliefs and positive and negative spiritual coping could account for any of the variation in anxiety and depression among women within 1 year's diagnosis of gynecological cancer (GC). One hundred patients from outpatient GC clinics at two Melbourne-based hospitals completed a brief structured interview and self-report measures of anxiety, depression, spirituality, and spiritual coping. Using two sequential regression analyses, we found that younger women with more advanced disease, who used more negative spiritual coping, had a greater tendency towards depression and that the use of negative spiritual coping was associated with greater anxiety scores. Although not statistically significant, patients with lower levels of generalized spirituality also tended to be more depressed. The site of disease and phase of treatment were not predictive of either anxiety or depression. We conclude that spirituality and spiritual coping are important to women with GC and that health professionals in the area should consider these issues.

Caregivers' use of, and attitudes towards, written asthma action plans in North-West Melbourne.

We investigated the attitudes of caregivers towards written asthma action plans (WAAPs). A small number of caregivers participating in a larger randomised controlled trial (RCT) participated in qualitative interviews. 'Ownership and use of WAAPs' and 'Schools and WAAPs' were the main themes to emerge. The new school year is an opportunity to review and update WAAPs.

Recent progress in understanding the mechanism of P-glycoprotein-mediated drug efflux.

P-glycoprotein (P-gp) is an ATP-dependent drug pump that can transport a broad range of hydrophobic compounds out of the cell. The protein is clinically important because of its contribution to the phenomenon of multidrug resistance during AIDS/HIV and cancer chemotherapy. P-gp is a member of the ATP-binding cassette (ABC) family of proteins. It is a single polypeptide that contains two repeats joined by a linker region. Each repeat has a transmembrane domain consisting of six transmembrane segments followed by a hydrophilic domain containing the nucleotide-binding domain. In this mini-review, we discuss recent progress in determining the structure and mechanism of human P-glycoprotein.

Rapid screening for depression--validation of the Brief Case-Find for Depression (BCD) in medical oncology and palliative care patients.

Depression in oncology patients is under-recognised and associated with poor outcomes. Screening can increase case recognition. The Brief Case-Find for Depression (BCD) is a four-question, interviewer-administered instrument that has been previously validated in a general medical setting. The primary aim of this study was to validate the BCD in a medical oncology/palliative care setting, primarily by comparing its association with physical illness measures and with the Primary Care Evaluation of Mental Disorders (PRIME-MD), the Beck Depression Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS). Eligible adult oncology patients gave informed consent and completed the above measures and a pain scale. Agreement between the BCD and other instruments was assessed. Construct validity was determined by comparing depressed/nondepressed patients with respect to performance status, symptoms, pain score and functional impairment. A total of 100 patients had a median age of 58 (range 21-90) and ECOG performance status (PS) 2 (0-4). In all, 60% had metastatic disease. The therapeutic goal was curative/adjuvant in 39% and palliative in 61%. Prevalence of depression according to the various measures was: BCD 34%, PRIME-MD 12%, BDI 19% and HADS 14%. In total, 45% of patients responded positively to a single-item screening question. The BCD showed fair agreement with the PRIME-MD (kappa=0.21), moderate agreement with the BDI (kappa=0.43) and fair agreement with the HADS (kappa=0.27). Against the PRIME-MD diagnosis of depression, the BCD had greater sensitivity, but lesser specificity and overall agreement, compared with the BDI and depression scale of the HADS. Patients with probable depression (according to BCD) had inferior PS (P=0.0064), increased pain (P=0.045) and greater impairment of functioning (PRIME-MD: P=0.0003). There was no association with gender, age, disease status or therapeutic goal. Depression is common in oncology patients. The BCD is a quick, easy-to-administer screen for depression, which has reasonable psychometric properties in this population.

Chemo-cryo combination therapy: an adjunctive model for the treatment of prostate cancer.

Despite continuing research and the development of alternate therapeutic options, prostate cancer remains problematic. Chemotherapy has played a minor role as a treatment option due to its lack of efficacy. Whereas cryotherapy has received renewed attention as a treatment modality, it too fails to offer an absolute curative option. Previously, we reported on the utilization of a therapeutic model, which, in combination, increases cell death in a canine renal cell model. Based upon that study, we investigated a combination therapy model as an alternative for the treatment modality for prostate cancer. We hypothesized that the combination of chemotherapy and cryosurgery would result in enhanced cell death, thereby presenting a more effective treatment of prostate cancer. A human prostate cancer cell (PC-3) model was exposed to 5-fluorouracil (5-FU) for 2 and 4 days (prefreeze), freezing (-5 to -100 degrees C), or a combination of the two treatments, and each was assessed for effectiveness over a 2-week posttreatment period. Additionally, investigation into the mechanisms of cell death initiated by the respective therapies was performed through DNA cleavage analysis. For chemotherapy, cultures exposed to 5-FU (2-4 days) yielded a 15-25% loss in cell survival. For cryotherapy, cultures exposed to a temperature window of -5 to -20 degrees C yielded an initial 5-70% loss of viability but cells propagated over time. Cultures exposed to temperatures of -25 to -80 degrees C yielded a 90-99% (+/-4.5%) initial loss in viability with repopulation observed by 12 days postthaw. Cells frozen to -100 degrees C yielded 100% (+/-0.3%) loss of viability and exhibited no signs of propagation. For chemo-cryo therapy, combination treatment at milder temperatures (-5 to -25 degrees C) resulted in an enhanced loss of cell viability compared to that for either treatment alone. Combination treatment at lower temperatures (-40 to -80 degrees C) resulted in a complete loss of cell viability. DNA fragmentation analysis at 48 h posttreatment revealed that dead (detached) cells treated with 5-FU died primarily through apoptosis, whereas dead cells from freezing (-15 degrees C) alone died primarily through freeze-rupture and necrosis. Detached cell analysis from combination treatment at -15 degrees C revealed the presence of apoptotic, necrotic, and freeze-rupture cell death. Scanning electron micrographs of cells exposed to freezing contributing to cell death. These data demonstrate that the combination of 5-FU at sublethal doses and freezing temperatures improves human prostate cancer cell death efficacy. Further, we suggest that chemo-cryo therapy offers a potential alternative treatment for the control and eradication of prostate cancer.

Determining the dimensions of the drug-binding domain of human P-glycoprotein using thiol cross-linking compounds as molecular rulers.

The human multidrug resistance P-glycoprotein (P-gp) interacts with a broad range of compounds with diverse structures and sizes. There is considerable evidence indicating that residues in transmembrane segments 4-6 and 10-12 form the drug-binding site. We attempted to measure the size of the drug-binding site by using thiol-specific methanethiosulfonate (MTS) cross-linkers containing spacer arms of 2 to 17 atoms. The majority of these cross-linkers were also substrates of P-gp, because they stimulated ATPase activity (2.5- to 10.1-fold). 36 P-gp mutants with pairs of cysteine residues introduced into transmembrane segments 4-6 and 10-12 were analyzed after reaction with 0.2 mm MTS cross-linker at 4 degrees C. The cross-linked product migrated with lower mobility than native P-gp in SDS gels. 13 P-gp mutants were cross-linked by MTS cross-linkers with spacer arms of 9-25 A. Vinblastine and cyclosporin A inhibited cross-linking. The emerging picture from these results and other studies is that the drug-binding domain is large enough to accommodate compounds of different sizes and that the drug-binding domain is "funnel" shaped, narrow at the cytoplasmic side, at least 9-25 A in the middle, and wider still at the extracellular surface.

Cross-linking of human multidrug resistance P-glycoprotein by the substrate, tris-(2-maleimidoethyl)amine, is altered by ATP hydrolysis. Evidence for rotation of a transmembrane helix.

We identified a thiol-reactive substrate, Tris-(2-maleimidoethyl)amine (TMEA), to explore the contribution of the TM segments 6 and 12 of the human multidrug resistance P-glycoprotein (P-gp) during transport. TMEA is a trifunctional maleimide and stimulated the ATPase activity of Cys-less P-gp about 7-fold. Cysteine-scanning mutagenesis of TM12 showed that the activity of mutant V982C was inhibited by TMEA. P-gp mutants containing V982C (TM12) and another cysteine in TM6 were constructed and tested for cross-linking with TMEA. A cross-linked product was observed in SDS-polyacrylamide gel electrophoresis for mutant L339C(TM6)/V982C(TM12). Cross-linking by TMEA also inhibited the ATPase activity of the mutant protein. Substrates such as cyclosporin A, vinblastine, colchicine, or verapamil inhibited cross-linking by TMEA. In the presence of ATP at 37 degrees C, cross-linking of mutant L339C/V982C was decreased. In contrast, there was enhanced cross-linking of mutant F343C(TM6)/V982C(TM12) in the presence of ATP. These results show that cross-linking must be within the drug-binding domain, that residues L339C(TM6)/V982C(TM12) must be at least 10 A apart, and that ATP hydrolysis promotes rotation of one or both TM helices.

Demoralization syndrome--a relevant psychiatric diagnosis for palliative care.

Hopelessness, loss of meaning, and existential distress are proposed as the core features of the diagnostic category of demoralization syndrome. This syndrome can be differentiated from depression and is recognizable in palliative care settings. It is associated with chronic medical illness, disability, bodily disfigurement, fear of loss of dignity, social isolation, and--where there is a subjective sense of incompetence--feelings of greater dependency on others or the perception of being a burden. Because of the sense of impotence or helplessness, those with the syndrome predictably progress to a desire to die or to commit suicide. A treatment approach is described which has the potential to alleviate the distress caused by this syndrome. Overall, demoralization syndrome has satisfactory face, descriptive, predictive, construct, and divergent validity, suggesting its utility as a diagnostic category in palliative care.

Defining the drug-binding site in the human multidrug resistance P-glycoprotein using a methanethiosulfonate analog of verapamil, MTS-verapamil.

Defining the residues involved in the binding of a substrate provides insight into how the human multidrug resistance P-glycoprotein (P-gp) can transport a wide range of structurally diverse compounds out of the cell. Because verapamil is the most potent stimulator of P-gp ATPase activity, we synthesized a thiol-reactive analog of verapamil (MTS-verapamil) and used it with cysteine-scanning mutagenesis to identify the reactive residues within the drug-binding domain of P-gp. MTS-verapamil stimulated the ATPase activity of Cys-less P-gp and had a K(m) value (25 microM) that was similar to that of verapamil. 252 P-gp mutants containing a single cysteine within the predicted transmembrane (TM) segments were expressed in HEK 293 cells and purified by nickel-chelate chromatography and assayed for inhibition by MTS-verapamil. The activities of 15 mutants, Y118C (TM2), V125C (TM2), S222C (TM4), L339C (TM6), A342C (TM6), A729C (TM7), A841C (TM9), N842C (TM9), I868C (TM10), A871C (TM10), F942C (TM11), T945C (TM11), V982C (TM12), G984C (TM12), and A985C (TM12), were inhibited by MTS-verapamil. Four mutants, S222C (TM4), L339C (TM6), A342C (TM6), and G984C (TM12), were significantly protected from inhibition by MTS-verapamil by pretreatment with verapamil. Less protection was observed in mutants I868C (TM10), F942C (TM11) and T945C (TM11). These results indicate that residues in TMs 4, 6, 10, 11, and 12 must contribute to the binding of verapamil.

Consultation-liaison psychiatrists' management of somatoform disorders.

The authors studied interventions recommended by consultation-liaison (C-L) psychiatrists when they diagnosed somatoform disorder prospectively in a cohort of 4,401 consecutive inpatients referred to the C-L psychiatry service of a general teaching hospital, using standardized MICRO-CARES methodology. A DSM-III-R somatoform disorder was diagnosed in 2.9%, somatoform pain disorder in 1.4%, conversion disorder in 0.7%, hypochondriasis or somatization disorder undifferentiated/not otherwise specified in 0.6%, and somatization disorder in 0.2%. In 3.4%, somatoform disorder was considered a differential diagnosis. Psychiatric comorbidity included mood disorder (39%), personality disorder (37%), and psychoactive substance use disorder (19%). Recommendations were made about antidepressants in 40% of the patients, anxiolytics in 18%, sedatives in 18%, and antipsychotics in 10%. Psychiatrists recommended the following: more laboratory tests for 14%; additional medical/surgical consultations for 11%; an increase in the vigor of medical treatment for 13%; and psychological treatment for 76%; also they stressed an earlier discharge of 16%. Psychiatrists were more likely to request a prolongation of inpatient stay for patients with comorbid somatoform, mood, anxiety, and personality disorder. Differences in characteristics and treatment of the subgroups tended to be consistent with their constructs and comorbid psychiatric diagnoses.

Dimensions of psychopathology in the medically ill. A latent trait analysis.

The authors examined the latent structure of psychiatric symptoms occurring in patients with medical illness. Symptom data were collected from 312 hospitalized medically ill patients using the Monash Interview for Liaison Psychiatry and subjected to latent trait analysis. A model with 5 dimensions provided an acceptable fit to the data. Dimensions were characterized as demoralization, anhedonia, autonomic anxiety, somatic symptoms, and grief. The demoralization dimension was similar to the concept of demoralization described by Frank and to the "giving up-given up complex" described by Engel. The concepts of demoralization, grief, and anhedonia may be useful in increasing understanding of the minor depressions in people with medical illness and in increasing the specificity of psychological and pharmacological treatments for these disorders.

Identification of residues within the drug-binding domain of the human multidrug resistance P-glycoprotein by cysteine-scanning mutagenesis and reaction with dibromobimane.

P-glycoprotein (P-gp) can transport a wide variety of cytotoxic compounds that have diverse structures. Therefore, the drug-binding domain of the human multidrug resistance P-gp likely consists of residues from multiple transmembrane (TM) segments. In this study, we completed cysteine-scanning mutagenesis of all the predicted TM segments of P-gp (TMs 1-5 and 7-10) and tested for inhibition by a thiol-reactive substrate (dibromobimane) to identify residues within the drug-binding domain. The activities of 189 mutants were analyzed. Verapamil-stimulated ATPase activities of seven mutants (Y118C and V125C (TM2), S222C (TM4), I306C (TM5), S766C (TM9), and I868C and G872C (TM10)) were inhibited by more than 50% by dibromobimane. The activities of mutants S222C (TM4), I306C (TM5), I868C (TM10), and G872C (TM10), but not that of mutants Y118C (TM2), V125C (TM2), and S776C (TM9), were protected from inhibition by dibromobimane by pretreatment with verapamil, vinblastine, or colchicine. These results and those from previous studies (Loo, T. W. and Clarke, D. M. (1997) J. Biol. Chem. 272, 31945-31948; Loo, T. W. and Clarke, D. M. (1999) J. Biol. Chem. 274, 35388-35392) indicate that the drug-binding domain of P-gp consists of residues in TMs 4, 5, 6, 10, 11, and 12.

Blockage of drug resistance in vitro by disulfiram, a drug used to treat alcoholism.

BACKGROUND: P-glycoprotein (P-gp) pumps a wide range of cytotoxic drugs out of cells. Inhibiting maturation of P-gp would be a novel method for circumventing P-gp-mediated multidrug resistance, which complicates cancer chemotherapy and treatment of patients infected with human immunodeficiency virus. We examined the effect of disulfiram (Antabuse(TM)) on the maturation and activity of P-gp. METHODS: Embryonic kidney cells were transfected with a complementary DNA for the P-pg gene, and the effects of disulfiram on the sensitivity of the transfected cells to cytotoxic agents were determined. Enzyme assays were used to determine the effects of disulfiram on the verapamil-stimulated adenosine triphosphatase (ATPase) activity of P-gp. Disulfiram modifies cysteine residues, and mutant forms of P-gp that lack individual cysteines were used to determine whether particular cysteine residues mediate disulfiram's effects on P-gp activity. Maturation of recombinant P-gp was followed on immunoblots. RESULTS: Disulfiram increased the sensitivity of P-gp-transfected cells to vinblastine and colchicine and inhibited P-gp's verapamil-stimulated ATPase activity. Half-maximal inhibition of ATPase activity occurred at 13.5 microM disulfiram. Disulfiram (at 100 microM) inhibited a P-gp mutant by 43% (95% confidence interval [CI] = 37%-48%) when cysteine was present at position 431 only and by 72% (95% CI = 66%-77%) when cysteine was present at position 1074 only. Treatment of P-gp-transfected cells with 50 nM disulfiram blocked maturation of recombinant P-gp. CONCLUSIONS: Disulfiram can potentially reduce P-gp-mediated drug resistance by inhibiting P-gp activity (possibly via cysteine modification) and/or by blocking its maturation. These results suggest that disulfiram has the potential to increase the efficacy of drug therapies for cancer and acquired immunodeficiency syndrome.

Drug-stimulated ATPase activity of human P-glycoprotein is blocked by disulfide cross-linking between the nucleotide-binding sites.

P-glycoprotein (P-gp) is an ATP-dependent drug pump that contains two nucleotide-binding domains (NBDs). Disulfide cross-linking analysis was done to determine if the two NBDs are close to each other. Residues within or close to the Walker A (GNSGCGKS in NDB1 and GSSGCGKS in NBD2) sequences for nucleotide binding were replaced with cysteine, and the mutant P-gps were subjected to oxidative cross-linking. Cross-linking was detected in two mutants, G427C(NBD1)/Cys-1074(NBD2) and L439C(NBD1)/Cys-1074(NBD2), because the cross-linked proteins migrated slower in SDS gels. Mutants G427C(NBD1)/Cys-1074(NBD2) and L439C(NBD1)/Cys-1074(NBD2) retained 10% and 82%, respectively, of the drug-stimulated ATPase activity relative to that of Cys-less P-gp. The cross-linking properties of the more active mutant L439C(NBD1)/Cys-1074(NBD2) were then studied. Cross-linking was reversed by addition of dithiothreitol and could be prevented by pretreatment of the mutant with N-ethylmaleimide. Cross-linking was also inhibited by MgATP, but not by the verapamil. Oxidative cross-linking of mutant L439C(NBD1)/Cys-1074(NBD2) resulted in almost complete inhibition of drug-stimulated ATPase activity. More than 60% of the drug-stimulated ATPase activity, however, was recovered after treatment with dithiothreitol. The results indicate that the two predicted nucleotide-binding sites are close to each other and that cross-linking inhibits ATP hydrolysis.

Somatisation. What is it?

BACKGROUND: Patients with a strong somatic conviction despite an absence of objective measures of physical disease are vexing and frustrating for doctors. OBJECTIVE: This paper describes the phenomenon of somatisation and the common forms of presentation. DISCUSSION: Somatisation--the expression of distress in somatic form--is perhaps the commonest of the psychiatric phenomena seen in general practice. It is usually accompanied by degrees of depression and anxiety. General practitioners have a special opportunity for recognition and early intervention in order to prevent the development of chronic somatizing states.

Management of somatoform disorders.

BACKGROUND: Physical illness, where there is no apparent disease, is a problem for doctors and the health system. Such an illness is also a cause of distress and anguish for patients and families. General practitioners are inevitably involved. OBJECTIVE: This paper describes the technique of re-attribution used to reduce patients' somatic focus, and presents principles for the management of chronic somatizers. DISCUSSION: General practitioners have a critical role to play with somatizing patients. For those patients presenting occasionally, or for the first time, with somatoform symptoms, GPs have the opportunity, through education, reassurance and re-attribution, to prevent reinforcement of the somatic perception and to reduce illness behaviour. In the care of patients with chronic somatizing disorders, GPs have an equally important role as case managers and carers, in order to prevent unnecessary medical interventions and to help maximise patient functioning.