Modelling the cost-effectiveness of pharmacotherapy compared with cognitive-behavioural therapy and combination therapy for the treatment of moderate to severe depression in the UK.

BACKGROUND: The National Institute of Health and Care Excellence (NICE) in England and Wales recommends the combination of pharmacotherapy and psychotherapy for the treatment of moderate to severe depression. However, the cost-effectiveness analysis on which these recommendations are based has not included psychotherapy as monotherapy as a potential option. For this reason, we aimed to update, augment and refine the existing economic evaluation. METHOD: We constructed a decision analytic model with a 27-month time horizon. We compared pharmacotherapy with cognitive-behavioural therapy (CBT) and combination treatment for moderate to severe depression in secondary care from a healthcare service perspective. We reviewed the literature to identify relevant evidence and, where possible, synthesized evidence from clinical trials in a meta-analysis to inform model parameters. RESULTS: The model suggested that CBT as monotherapy was most likely to be the most cost-effective treatment option above a threshold of £ 22,000 per quality-adjusted life year (QALY). It dominated combination treatment and had an incremental cost-effectiveness ratio of £ 20,039 per QALY compared with pharmacotherapy. There was significant decision uncertainty in the probabilistic and deterministic sensitivity analyses. CONCLUSIONS: Contrary to previous NICE guidance, the results indicated that even for those patients for whom pharmacotherapy is acceptable, CBT as monotherapy may be a cost-effective treatment option. However, this conclusion was based on a limited evidence base, particularly for combination treatment. In addition, this evidence cannot easily be transferred to a primary care setting.

Anxious and non-anxious forms of major depression: familial, personality and symptom characteristics.

BACKGROUND: Earlier clinical studies have suggested consistent differences between anxious and non-anxious depression. The aim of this study was to compare parental pathology, personality and symptom characteristics in three groups of probands from the general population: depression with and without generalized anxiety disorder (GAD) and with other anxiety disorders. Because patients without GAD may have experienced anxious symptoms for up to 5 months, we also considered GAD with a duration of only 1 month to produce a group of depressions largely unaffected by anxiety. METHOD: Depressive and anxiety disorders were assessed in a 10-year prospective longitudinal community and family study using the DSM-IV/M-CIDI. Regression analyses were used to reveal associations between these variables and with personality using two durations of GAD: 6 months (GAD-6) and 1 month (GAD-1). RESULTS: Non-anxious depressives had fewer and less severe depressive symptoms, and higher odds for parents with depression alone, whereas those with anxious depression were associated with higher harm avoidance and had parents with a wider range of disorders, including mania. CONCLUSIONS: Anxious depression is a more severe form of depression than the non-anxious form; this is true even when the symptoms required for an anxiety diagnosis are ignored. Patients with non-anxious depression are different from those with anxious depression in terms of illness severity, family pathology and personality. The association between major depression and bipolar disorder is seen only in anxious forms of depression. Improved knowledge on different forms of depression may provide clues to their differential aetiology, and guide research into the types of treatment that are best suited to each form.

Proposed new diagnoses of anxious depression and bodily stress syndrome in ICD-11-PHC: an international focus group study.

BACKGROUND: The World Health Organization is revising the primary care classification of mental and behavioural disorders for the International Classification of Diseases (ICD-11-Primary Health Care (PHC)) aiming to reduce the disease burden associated with mental disorders among member countries. OBJECTIVE: To explore the opinions of primary care professionals on proposed new diagnostic entities in draft ICD-11-PHC, namely anxious depression and bodily stress syndrome (BSS). METHODS: Qualitative study with focus groups of primary health-care workers, using standard interview schedule after draft ICD-11-PHC criteria for each proposed entity was introduced to the participants. RESULTS: Nine focus groups with 4-15 participants each were held at seven locations: Austria, Brazil, Hong Kong, New Zealand, Pakistan, Tanzania and United Kingdom. There was overwhelming support for the inclusion of anxious depression, which was considered to be very common in primary care settings. However, there were concerns about the 2-week duration of symptoms being too short to make a reliable diagnosis. BSS was considered to be a better term than medically unexplained symptoms but there were disagreements about the diagnostic criteria in the number of symptoms required. CONCLUSION: Anxious depression is well received by primary care professionals, but BSS requires further modification. International field trials will be held to further test these new diagnoses in draft ICD-11-PHC.

Insecure attachment and frequent attendance in primary care: a longitudinal cohort study of medically unexplained symptom presentations in ten UK general practices.

BACKGROUND: In primary care frequent attenders with medically unexplained symptoms (MUS) pose a clinical and health resource challenge. We sought to understand these presentations in terms of the doctor-patient relationship, specifically to test the hypothesis that such patients have insecure emotional attachment. METHOD: We undertook a cohort follow-up study of 410 patients with MUS. Baseline questionnaires assessed adult attachment style, psychological distress, beliefs about the symptom, non-specific somatic symptoms, and physical function. A telephone interview following consultation assessed health worry, general practitioner (GP) management and satisfaction with consultation. The main outcome was annual GP consultation rate. RESULTS: Of consecutive attenders, 18% had an MUS. This group had a high mean consultation frequency of 5.24 [95% confidence interval (CI) 4.79-5.69] over the follow-up year. The prevalence of insecure attachment was 28 (95% CI 23-33) %. A significant association was found between insecure attachment style and frequent attendance, even after adjustment for sociodemographic characteristics, presence of chronic physical illness and baseline physical function [odds ratio (OR) 1.96 (95% CI 1.05-3.67)]. The association was particularly strong in those patients who believed that there was a physical cause for their initial MUS [OR 9.52 (95% CI 2.67-33.93)]. A possible model for the relationship between attachment style and frequent attendance is presented. CONCLUSIONS: Patients with MUS who attend frequently have insecure adult attachment styles, and their high consultation rate may therefore be conceptualized as pathological care-seeking behaviour linked to their insecure attachment. Understanding frequent attendance as pathological help seeking driven by difficulties in relating to caregiving figures may help doctors to manage their frequently attending patients in a different way.

The structure of depression, anxiety and somatic symptoms in primary care.

BACKGROUND: Observed co-morbidity among the mood and anxiety disorders has led to the development of increasingly sophisticated dimensional models to represent the common and unique features of these disorders. Patients often present to primary care settings with a complex mixture of anxiety, depression and somatic symptoms. However, relatively little is known about how somatic symptoms fit into existing dimensional models. METHOD: We examined the structure of 91 anxiety, depression and somatic symptoms in a sample of 5433 primary care patients drawn from 14 countries. One-, two- and three-factor lower-order models were considered; higher-order and hierarchical variants were studied for the best-fitting lower-order model. RESULTS: A hierarchical, bifactor model with all symptoms loading simultaneously on a general factor, along with one of three specific anxiety, depression and somatic factors, was the best-fitting model. The general factor accounted for the bulk of symptom variance and was associated with psychosocial dysfunction. Specific depression and somatic symptom factors accounted for meaningful incremental variance in diagnosis and dysfunction, whereas anxiety variance was associated primarily with the general factor. CONCLUSIONS: The results (a) are consistent with previous studies showing the presence and importance of a broad internalizing or distress factor linking diverse emotional disorders, and (b) extend the bounds of internalizing to include somatic complaints with non-physical etiologies.

Where should bipolar disorder appear in the meta-structure?

BACKGROUND: The extant major psychiatric classifications, DSM-IV and ICD-10, are purportedly atheoretical and largely descriptive. Although this achieves good reliability, the validity of a medical diagnosis is greatly enhanced by an understanding of both risk factors and clinical history. In an effort to group mental disorders on the basis of risk factors and clinical manifestations, five clusters have been proposed. The purpose of this paper is to consider the position of bipolar disorder (BPD), which could be either with the psychoses, or with emotional disorders, or in a separate cluster. METHOD: We reviewed the literature on BPD, unipolar depression (UPD) and schizophrenia in relation to 11 validating criteria proposed by the DSM-V Task Force Study Group, and then summarized similarities and differences between BPD and schizophrenia on the one hand, and UPD on the other. RESULTS: There are differences, often substantial and never trivial, for 10 of the 11 validators between BPD and UPD. There are also important differences between BPD and schizophrenia. CONCLUSION: BPD has previously been classified together with UPD, but this is the least justifiable place for it. If it is to be recruited to a 'psychotic cluster', there are several important respects in which it differs from schizophrenia, so the cluster would have a division within it. The alternative would be to allow it to be in an intermediate position in a cluster of its own.

Emotional disorders: cluster 4 of the proposed meta-structure for DSM-V and ICD-11.

BACKGROUND: The extant major psychiatric classifications DSM-IV, and ICD-10, are atheoretical and largely descriptive. Although this achieves good reliability, the validity of a medical diagnosis would be greatly enhanced by an understanding of risk factors and clinical manifestations. In an effort to group mental disorders on the basis of aetiology, five clusters have been proposed. This paper considers the validity of the fourth cluster, emotional disorders, within that proposal. METHOD: We reviewed the literature in relation to 11 validating criteria proposed by a Study Group of the DSM-V Task Force, as applied to the cluster of emotional disorders. RESULTS: An emotional cluster of disorders identified using the 11 validators is feasible. Negative affectivity is the defining feature of the emotional cluster. Although there are differences between disorders in the remaining validating criteria, there are similarities that support the feasibility of an emotional cluster. Strong intra-cluster co-morbidity may reflect the action of common risk factors and also shared higher-order symptom dimensions in these emotional disorders. CONCLUSION: Emotional disorders meet many of the salient criteria proposed by the Study Group of the DSM-V Task Force to suggest a classification cluster.

Exploring the feasibility of a meta-structure for DSM-V and ICD-11: could it improve utility and validity?

BACKGROUND: The organization of mental disorders into 16 DSM-IV and 10 ICD-10 chapters is complex and based on clinical presentation. We explored the feasibility of a more parsimonious meta-structure based on both risk factors and clinical factors. METHOD: Most DSM-IV disorders were allocated to one of five clusters as a starting premise. Teams of experts then reviewed the literature to determine within-cluster similarities on 11 predetermined validating criteria. Disorders were included and excluded as determined by the available data. These data are intended to inform the grouping of disorders in the DSM-V and ICD-11 processes. RESULTS: The final clusters were neurocognitive (identified principally by neural substrate abnormalities), neurodevelopmental (identified principally by early and continuing cognitive deficits), psychosis (identified principally by clinical features and biomarkers for information processing deficits), emotional (identified principally by the temperamental antecedent of negative emotionality), and externalizing (identified principally by the temperamental antecedent of disinhibition). CONCLUSIONS: Large groups of disorders were found to share risk factors and also clinical picture. There could be advantages for clinical practice, public administration and research from the adoption of such an organizing principle.

The impact of language skills on mental health in teenagers with hearing impairments.

OBJECTIVE: The aim of this study was to examine the relationship of language competence level and mental distress in teenagers with hearing impairments. METHOD: 43 pupils were given a battery of linguistic tests and the Strengths and Difficulties Questionnaire (SDQ), which was also completed by 40 parents. Comparisons were made between the group of 33 children in mainstream education and 10 who were in a segregated school for the deaf. RESULTS: The children had impaired language skills relative to published norms, especially marked in segregated schools. Parents rated children as having more distress than published norms. Those with superior level of spoken language had fewer peer relationship problems in mainstream education, but significantly more in segregated schools. The reverse was almost significant for those proficient in signed language. CONCLUSION: Peer relationship problems are associated with the language competence levels in the way that children at school communicate with one another.

Somatization in cross-cultural perspective: a World Health Organization study in primary care.

OBJECTIVE: The purpose of this study was to examine the phenomenon of somatization in different cultures by determining its frequency and correlates in primary care settings in 14 countries. METHOD: Consecutive primary care patients (N = 25,916) were screened with the 12-item General Health questionnaire, and a stratified sample (N = 5,438) was interviewed with the Composite International Diagnostic Interview. Interviewed patients were also assessed for physical disease burden, self-rated overall health, physician-rated physical health status, number of disability days, and interviewer-rated occupational role functioning. The authors determined center-specific associations with the use of logistic regression analyses in which confounding variables were controlled. RESULTS: ICD-10 defined somatization disorder was relatively uncommon in most primary care settings. A less restrictively defined form was more common. Symptom rates were much higher in South American sites. There was a modest association with low education. Otherwise, frequency of unexplained somatic symptoms did not clearly vary according to geography or level of economic development. Somatizing patients were at elevated risk for self-reported disease burden, negative perception of their health, and comorbid depression and generalized anxiety disorder. Somatization was also commonly associated with disability. Cultures did not differ markedly in the pattern of these associated features. CONCLUSION: Somatization is a common problem in primary care across cultures and is associated with significant problems and disability.

Guided bone growth in sheep: a model for tissue-engineered bone flaps.

The emerging field of tissue engineering is yielding a variety of new strategies for bone replacement. In vivo assessment of candidate bone substitutes to demonstrate biocompatibility, degradability, and the ability to produce meaningful quantities of bone is essential prior to clinical use. We present results of a large animal model using formed plastic chambers implanted adjacent to the rib periosteum in sheep to fabricate vascularized bone flaps of different shapes. Chambers packed with morcellized corticocancellous bone graft, representing the most favorable natural circumstances for bone formation, were compared to empty chambers, representing the least favorable. Implants containing bone chips yielded formed blocks of vascularized bone after 6 weeks with evidence of remodeling after 13 weeks. Histomorphometric analysis demonstrated that there was full bone penetration into shallow (5 mm) chambers and 8.8 mm (+/-0.6) penetration into deep (10 mm) implants after 6 weeks. Molded bone segments failed to grow in empty chambers. This model presents a quantifiable range of bone forming potential to which different bone substitutes may be compared for usefulness in creating tissue engineered bone flaps for reconstructive surgery.

A model complex of a possible intermediate in the mechanism of action of peptide deformylase: first example of an (N2S)zinc(II)-formate complex.

The synthesis and crystallographic characterization of a new (N2S)zinc-alkyl complex and (N2S)zinc-formate complex is described; the bonding mode of the formate complex has implications for the mechanism of action of the enzyme peptide deformylase.

Psycho-social stress and puerperal depression.

This study assessed the role of psycho-social stress in the development of psychiatric disorder during pregnancy and after childbirth. The samples were a consecutive series of women admitted to a psychiatric Mother and Baby Unit with a depressive illness and a random sample of women who had recently given birth. Whereas prepartum-onset disturbances were found to be overwhelmingly stress-related, women with a postpartum onset of depression were considerably less likely to have experienced a recent stress event or difficulty before onset. The relative lack of psycho-social antecedents among women who became ill within 2-3 weeks of giving birth strengthens the argument that puerperal depression may have a distinct, possibly biological aetiology.

The effects of physical illness on psychiatric disorder.

Somatic symptoms of both organic and non-organic causes are associated with an increase in psychiatric morbidity irrespective of setting; patients with chronic medical conditions are approximately twice as likely to report psychiatric disorder as controls. This increase cannot be entirely explained in terms of help-seeking behaviour, recognition rates by treating doctors or treatment outcome. The detection and treatment of coincident psychiatric disorder in this group of patients needs further clarification.

Somatic presentations of psychiatric illness in primary care setting.

We have tried to describe somatisation, not as a disease, but as a common and important human mechanism involving both doctor and patient. It is the single most common reason why psychiatric illness goes undetected in general medical settings, and it often occurs in conjunction with physical disease processes. The association with dysphoric affect has been recognised at least since George Cheyne 250 years ago, and the reason for this is that both anxiety and depression serve to amplify pains. However, it seems likely that somatisation can occur in the absence of dysphoria. Once it has been established, it is easy to see how it continues: it secures advantages from spouse, family and employers; and it tends to be encouraged by doctors--who differentially reward somatic symptoms. But why does it occur in the first place? We have argued that it seems to have three functions: First, it allows people who are unsympathetic to psychological illness, or who live in cultures where mental illness is stigmatised, to nonetheless occupy the sick-role while psychologically unwell. Second, it is blame-avoiding: instead of being responsible for the mayhem, one is cast in the role of the suffering victim. Finally, by reducing blame, it appears to save patients from being as depressed as they might otherwise have been.

Somatic presentation of DSM III psychiatric disorders in primary care.

This paper describes a study assessing the correlates and possible determinants of 'somatisation' by patients consulting their family doctor with a new illness. Operational criteria of 'somatisation' are given and the relationship between DSM III psychiatric disorders and physical illness are described. The epidemiological findings that are presented illustrate that 'somatisation' is a common phenomenon and accounts for a substantial proportion of 'hidden psychiatric morbidity' in primary care.

Detection and treatment of psychiatric illness in a general medical ward: a modified cost-benefit analysis.

This article describes a prospective, randomized, controlled trial of screening and treatment for psychiatric disorder in medical in-patients. The study has assessed whether increased recognition of psychiatric disorder among medical in-patients improves clinical outcome and reduces the costs of care, and whether routine involvement of a psychiatrist in the assessment and care of medical in-patients with probable psychiatric disorder is superior to the efforts of the physicians alone. A total of 218 medical in-patients who scored over the screening threshold for psychiatric disorder on the General Health Questionnaire were randomly allocated to one of two intervention groups or a control group. Six months later their mental health, subjective health status, quality of life, and costs of care was reassessed. Mental health and quality of life at 6 months were similar in the two intervention groups and the control group. Patients whose physicians were told the results of the screening test had lower costs for subsequent admissions, but this was probably due to differences between the groups in terms of employment status. Treatments recommended by psychiatrists broke down when patients were discharged home, leading to inadequate treatment of psychiatric disorders. We have not been able to show that routine screening for psychiatric disorder produces any benefit, either in better outcome for patients or reduced costs for the NHS. Further research should: consider examining a more homogeneous group in terms of costs of care; screen only for disorders likely to respond to a specific treatment; and ensure that treatment recommendations are carried out.

Oncologic and reconstructive considerations in nonmelanotic skin and lip cancers.

The conceptual approach to the reconstruction of skin and lip cancer defects is no different than the reconstruction of other tumors in other locations. To plan and execute the reconstructive effort properly requires a careful assessment of the anticipated extirpative defect, the consideration of additional postoperative therapy, if any, and the restoration of function and aesthetic form. Similar to other malignancies, a working knowledge of tumor behavior is an integral ingredient of a successful reconstructive plan.

Link between the ability to detect and manage emotional disorders: a study of general practitioner trainees.

Independent ratings were made of videotaped consultations involving six general practice vocational trainees, of whom three were poor identifiers and three were able identifiers of emotional illness. Taped consultations were selected so that each trainee was rated interviewing five patients with low general health questionnaire scores, and five patients with high scores. It was found that able identifiers of emotional illness were more likely than poor identifiers to offer patients information, advice and treatment relevant to their illness, and that they did so in a manner likely to maximize patient satisfaction and cooperation. This was true for both distressed and non-distressed patients. It is argued that both the ability to identify emotional disturbances and the ability to manage emotional illness are characteristics of a generally superior interview style. This may reflect a common variable: the possession of good communication skills.

Effects of a community mental health service on the practice and attitudes of general practitioners.

Recent years have seen closer links developing between general practitioners and mental health specialists. A study was undertaken in Manchester to determine the effects of a new community mental health service on the practice and attitudes of general practitioners. Ten doctors had access to the community based psychiatric team over a three year period while another 10 doctors continued to use hospital services. Those with access to the team were significantly more satisfied with the specialist support services, and were more likely to give high priority to community psychiatric nurses and psychiatric social workers working as part of a primary health care team than those without access to the service. Those with access were more willing than those without access to share with psychiatrists the care of patients with chronic neurotic disorders. The community mental health team was considered particularly helpful in reducing the burden posed by patients with neurotic and psychosocial problems, but this resulted in the general practitioners doing less counselling themselves. The study did not find that the new service had an effect on the general practitioners' ability to detect or manage psychiatric illness.