Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

Chronic fatigue syndromes: real illnesses that people can recover from.

The 'Oslo Chronic Fatigue Consortium' consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.

Psychiatric comorbidity and risk of premature mortality and suicide among those with chronic respiratory diseases, cardiovascular diseases, and diabetes in Sweden: A nationwide matched cohort study of over 1 million patients and their unaffected siblings.

BACKGROUND: Persons with noncommunicable diseases have elevated rates of premature mortality. The contribution of psychiatric comorbidity to this is uncertain. We aimed to determine the risks of premature mortality and suicide in people with common noncommunicable diseases, with and without psychiatric disorder comorbidity. METHODS AND FINDINGS: We used nationwide registries to study all individuals born in Sweden between 1932 and 1995 with inpatient and outpatient diagnoses of chronic respiratory diseases (n = 249,825), cardiovascular diseases (n = 568,818), and diabetes (n = 255,579) for risks of premature mortality (≤age 65 years) and suicide until 31 December 2013. Patients diagnosed with either chronic respiratory diseases, cardiovascular diseases, or diabetes were compared with age and sex-matched population controls (n = 10,345,758) and unaffected biological full siblings (n = 1,119,543). Comorbidity with any psychiatric disorder, and by major psychiatric categories, was examined using diagnoses from patient registers. Associations were quantified using stratified Cox regression models that accounted for time at risk, measured sociodemographic factors, and unmeasured familial confounders via sibling comparisons. Within 5 years of diagnosis, at least 7% (range 7.4% to 10.8%; P < 0.001) of patients with respiratory diseases, cardiovascular diseases, or diabetes (median age at diagnosis: 48 to 54 years) had died from any cause, and 0.3% (0.3% to 0.3%; P < 0.001) had died from suicide, 25% to 32% of people with these medical conditions had co-occurring lifetime diagnoses of any psychiatric disorder, most of which antedated the medical diagnosis. Comorbid psychiatric disorders were associated with higher all-cause mortality (15.4% to 21.1%) when compared to those without such conditions (5.5% to 9.1%). Suicide mortality was also elevated (1.2% to 1.6% in comorbid patients versus 0.1% to 0.1% without comorbidity). When we compared relative risks with siblings without noncommunicable diseases and psychiatric disorders, the comorbidity with any psychiatric disorder was associated with substantially increased mortality rates (adjusted HR range: aHRCR = 7.2 [95% CI: 6.8 to 7.7; P < 0.001] to aHRCV = 8.9 [95% CI: 8.5 to 9.4; P < 0.001]). Notably, comorbid substance use disorders were associated with a higher mortality rate (aHR range: aHRCR = 8.3 [95% CI: 7.6 to 9.1; P < 0.001] to aHRCV = 9.9 [95% CI: 9.3 to 10.6; P < 0.001]) than depression (aHR range: aHRCR = 5.3 [95% CI: 4.7 to 5.9; P < 0.001] to aHRCV = 7.4 [95% CI: 7.0 to 7.9; P < 0.001]), but risks of suicide were similar for these 2 psychiatric comorbidities. One limitation is that we relied on secondary care data to assess psychiatric comorbidities, which may have led to missing some patients with less severe comorbidities. Residual genetic confounding is another limitation, given that biological full siblings share an average of half of their cosegregating genes. However, the reported associations remained large even after adjustment for shared and unmeasured familial confounders. CONCLUSIONS: In this longitudinal study of over 1 million patients with chronic health diseases, we observed increased risks of all-cause and suicide mortality in individuals with psychiatric comorbidities. Improving assessment, treatment, and follow-up of people with comorbid psychiatric disorders may reduce the risk of mortality in people with chronic noncommunicable diseases.

Evidence-Based Care for People with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

Chronic fatigue syndrome (CFS), sometimes referred to as myalgic encephalomyelitis (ME) and often as CFS/ME, is an illness characterized by disabling fatigue and other symptoms, typically worsened by activity. The main evidence-based treatments are rehabilitative in nature and include specific types of cognitive behavior therapy (CBT) and graded exercise therapy (GET). In this article, we briefly review the evidence for their safety and effectiveness and propose that much of the controversy about them arises from misunderstandings about their nature and delivery. In particular, we emphasize that successful rehabilitation from CFS/ME does not indicate that the illness is not real. We recommend that rehabilitative treatment always be preceded by a thorough clinical assessment and delivered by appropriately trained therapists working in close collaboration with the patient. We conclude that properly applied rehabilitative treatments offer the best hope of safely improving fatigue and function for patients with CFS/ME. However, we also recognize the need for more research into the treatment of this neglected condition, especially for those most severely disabled by it.

The impact of the COVID-19 pandemic on radiotherapy services in England, UK: a population-based study.

BACKGROUND: The indirect impact of the COVID-19 pandemic on cancer outcomes is of increasing concern. However, the extent to which key treatment modalities have been affected is unclear. We aimed to assess the impact of the pandemic on radiotherapy activity in England. METHODS: In this population-based study, data relating to all radiotherapy delivered for cancer in the English NHS, between Feb 4, 2019, and June 28, 2020, were extracted from the National Radiotherapy Dataset. Changes in mean weekly radiotherapy courses, attendances (reflecting fractions), and fractionation patterns following the start of the UK lockdown were compared with corresponding months in 2019 overall, for specific diagnoses, and across age groups. The significance of changes in radiotherapy activity during lockdown was examined using interrupted time-series (ITS) analysis. FINDINGS: In 2020, mean weekly radiotherapy courses fell by 19·9% in April, 6·2% in May, and 11·6% in June compared with corresponding months in 2019. A relatively greater fall was observed for attendances (29·1% in April, 31·4% in May, and 31·5% in June). These changes were significant on ITS analysis (p<0·0001). A greater reduction in treatment courses between 2019 and 2020 was seen for patients aged 70 years or older compared with those aged younger than 70 years (34·4% vs 7·3% in April). By diagnosis, the largest reduction from 2019 to 2020 in treatment courses was for prostate cancer (77·0% in April) and non-melanoma skin cancer (72·4% in April). Conversely, radiotherapy courses in April, 2020, compared with April, 2019, increased by 41·2% in oesophageal cancer, 64·2% in bladder cancer, and 36·3% in rectal cancer. Increased use of ultra-hypofractionated (26 Gy in five fractions) breast radiotherapy as a percentage of all courses (0·2% in April, 2019, to 60·6% in April, 2020; ITS p<0·0001) contributed to the substantial reduction in attendances. INTERPRETATION: Radiotherapy activity fell significantly, but use of hypofractionated regimens rapidly increased in the English NHS during the first peak of the COVID-19 pandemic. An increase in treatments for some cancers suggests that radiotherapy compensated for reduced surgical activity. These data will assist health-care providers in understanding the indirect consequences of the pandemic and the role of radiotherapy services in minimising these consequences. FUNDING: None.

Major Depression and Survival in People With Cancer.

OBJECTIVE: The question of whether depression is associated with worse survival in people with cancer remains unanswered because of methodological criticism of the published research on the topic. We aimed to study the association in a large methodologically robust study. METHODS: We analyzed data on 20,582 patients with breast, colorectal, gynecological, lung, and prostate cancers who had attended cancer outpatient clinics in Scotland, United Kingdom. Patients had completed two-stage screening for major depression as part of their cancer care. These data on depression status were linked to demographic, cancer, and subsequent mortality data from national databases. We estimated the association of major depression with survival for each cancer using Cox regression. We adjusted for potential confounders and interactions between potentially time-varying confounders and the interval between cancer diagnosis and depression screening, and used multiple imputation for missing depression and confounder data. We pooled the cancer-specific results using fixed-effects meta-analysis. RESULTS: Major depression was associated with worse survival for all cancers, with similar adjusted hazard ratios (HRs): breast cancer (HR = 1.42, 95% confidence interval [CI] = 1.15-1.75), colorectal cancer (HR = 1.47, 95% CI = 1.11-1.94), gynecological cancer (HR = 1.36, 95% CI = 1.08-1.71), lung cancer (HR = 1.39, 95% CI = 1.24-1.56), and prostate cancer (HR = 1.76, 95% CI = 1.08-2.85). The pooled HR was 1.41 (95% CI = 1.29-1.54, p < .001, I2 = 0%). These findings were not materially different when we only considered the deaths (90%) that were attributed to cancer. CONCLUSIONS: Major depression is associated with worse survival in patients with common cancers. The mechanisms of this association and the clinical implications require further study.

Dynamic tracking of microvascular hemoglobin content for continuous perfusion monitoring in the intensive care unit: pilot feasibility study.

PURPOSE: There is a need for bedside methods to monitor oxygen delivery in the microcirculation. Near-infrared spectroscopy commonly measures tissue oxygen saturation, but does not reflect the time-dependent variability of microvascular hemoglobin content (MHC) that attempts to match oxygen supply with demand. The objective of this study is to determine the feasibility of MHC monitoring in critically ill patients using high-resolution near-infrared spectroscopy to assess perfusion in the peripheral microcirculation. METHODS: Prospective observational cohort of 36 patients admitted within 48 h at a tertiary intensive care unit. Perfusion was measured on the quadriceps, biceps, and/or deltoid, using the temporal change in optical density at the isosbestic wavelength of hemoglobin (798 nm). Continuous wavelet transform was applied to the hemoglobin signal to delineate frequency ranges corresponding to physiological oscillations in the cardiovascular system. RESULTS: 31/36 patients had adequate signal quality for analysis, most commonly affected by motion artifacts. MHC signal demonstrates inter-subject heterogeneity in the cohort, indicated by different patterns of variability and frequency composition. Signal characteristics were concordant between muscle groups in the same patient, and correlated with systemic hemoglobin levels and oxygen saturation. Signal power was lower for patients receiving vasopressors, but not correlated with mean arterial pressure. Mechanical ventilation directly impacts MHC in peripheral tissue. CONCLUSION: MHC can be measured continuously in the ICU with high-resolution near-infrared spectroscopy, and reflects the dynamic variability of hemoglobin distribution in the microcirculation. Results suggest this novel hemodynamic metric should be further evaluated for diagnosing microvascular dysfunction and monitoring peripheral perfusion.

Predisposing Risk Factors for Functional Limb Weakness: A Case-Control Study.

OBJECTIVE: Functional limb weakness is a common symptom of functional neurological disorder. Few controlled studies have examined possible predisposing factors to determine their specificity for this symptom. METHODS: In this prospective case-control study, patients with functional limb weakness (<2 years duration, N=107) were compared with a control group (comprising patients with weakness attributable to neurological disease, N=46, and healthy individuals, N=39). A structured clinical interview and questionnaires assessed potential predisposing factors, including family structure and childhood abuse and neglect (Childhood Trauma Questionnaire [CTQ]), personality traits (NEO Five-Factor Inventory), medical and surgical comorbidity, and exposure to a symptom model. RESULTS: The patients with functional limb weakness and the control subjects were similar in gender and age. Self-reported childhood sexual abuse (15% versus 5%, p<0.01), and physical abuse (18% versus 7%, p<0.01; CTQ "moderate or above") were more common in the functional limb weakness group, although the absolute frequency was lower than anticipated. In the functional limb weakness group, there were modest differences in two personality traits, compared with the control group: higher neuroticism (p=0.02) and lower openness (p=0.01). Medical comorbidity, including appendectomy (33% versus 5%), irritable bowel syndrome (36% versus 18%), and chronic back pain (40% versus 16%), was more frequent in the functional limb weakness group. There were no differences in birth order or exposure to a symptom model. CONCLUSIONS: Medical and surgical comorbidity and adverse childhood experience are risk factors, but not essential, for the development of functional limb weakness. However, evidence for personality traits or exposure to a symptom model is less robust.

Chronic fatigue syndrome and an illness-focused approach to care: controversy, morality and paradox.

Contemporary medicine distinguishes between illness and disease. Illness refers to a person's subjective experience of symptoms; disease refers to objective bodily pathology. For many illnesses, medicine has made great progress in finding and treating associated disease. However, not all illnesses are successfully relieved by treating the disease. In some such cases, the patient's suffering can only be reduced by treatment that is focused on the illness itself. Chronic disabling fatigue is a common symptom of illness, for which disease-focused treatment is often not effective, but for which illness-focused treatments (psychological or behavioural) often are. In this article, we explore a controversy surrounding illness-focused treatments for fatigue. We do this by contrasting their acceptance by people whose fatigue is associated with a disease (using the example of cancer-related fatigue) with their controversial rejection by some people whose fatigue is not associated with an established disease (chronic fatigue syndrome or CFS, sometimes called ME (myalgic encephalomyelitis)). In order to understand this difference in acceptability we consider the differing moral connotations of illness and disease and then go on to examine the limitations of the concepts of illness and disease themselves. We conclude that a general acceptance of illness-focused treatments by all who might benefit from them will require a major long-term change in thinking about illness, but that improvements to the care of individual patients can be made today.

The prevalence of depression in general hospital inpatients: a systematic review and meta-analysis of interview-based studies.

BACKGROUND: Comorbid depression in the medically ill is clinically important. Admission to a general hospital offers an opportunity to identify and initiate treatment for depression. However, we first need to know how common depression is in general hospital inpatients. We aimed to address this question by systematically reviewing the relevant literature. METHODS: We reviewed published prevalence studies in any language which had used diagnostic interviews of general hospital inpatients and met basic methodological quality criteria. We focussed on interview-based studies in order to estimate the proportion of patients with a diagnosis of depressive illness. RESULTS: Of 158 relevant articles, 65 (41%) describing 60 separate studies met our inclusion criteria. The 31 studies that focussed on general medical and surgical inpatients reported prevalence estimates ranging from 5% to 34%. There was substantial, highly statistically significant, heterogeneity between studies which was not materially explained by the covariates we were able to consider. The average of the reported prevalences was 12% (95% CI 10-15), with a 95% prediction interval of 4-32%. The remaining 29 studies, of a variety of specific clinical populations, are described. CONCLUSIONS: The available evidence suggests a likely prevalence high enough to make it worthwhile screening hospital inpatients for depression and initiating treatment where appropriate. Further, higher quality, research is needed to clarify the prevalence of depression in specific settings and to further explore the reasons for the observed heterogeneity in estimates.

Screening Medical Patients for Depression: Lessons From a National Program in Cancer Clinics.

BACKGROUND: Screening has been recommended to improve the identification of depression in medical patients. There is, therefore, a need for useful practical information on how to successfully implement large-scale depression screening in medical clinics. OBJECTIVE: To describe the practical lessons learned from our experience of implementing a large-scale depression screening program in cancer clinics throughout Scotland, UK. METHOD: Reflective review based on the experience of the screening team and records of the iterative development of the program. FINDINGS: Systematic screening for depression in patients with medical illnesses can be delivered in clinics as long as the program is well designed. Design issues include ensuring the engagement of staff and patients, implementing efficient 2-stage screening processes and effectively managing workflow and quality assurance. DISCUSSION: Screening has the potential to offer a solution to the well-documented problem of missed depression and other psychiatric diagnoses, thereby improving patient care if closely linked to treatment provision.

The Effect of Sepsis on the Erythrocyte.

Sepsis induces a wide range of effects on the red blood cell (RBC). Some of the effects including altered metabolism and decreased 2,3-bisphosphoglycerate are preventable with appropriate treatment, whereas others, including decreased erythrocyte deformability and redistribution of membrane phospholipids, appear to be permanent, and factors in RBC clearance. Here, we review the effects of sepsis on the erythrocyte, including changes in RBC volume, metabolism and hemoglobin's affinity for oxygen, morphology, RBC deformability (an early indicator of sepsis), antioxidant status, intracellular Ca2+ homeostasis, membrane proteins, membrane phospholipid redistribution, clearance and RBC O2-dependent adenosine triphosphate efflux (an RBC hypoxia signaling mechanism involved in microvascular autoregulation). We also consider the causes of these effects by host mediated oxidant stress and bacterial virulence factors. Additionally, we consider the altered erythrocyte microenvironment due to sepsis induced microvascular dysregulation and speculate on the possible effects of RBC autoxidation. In future, a better understanding of the mechanisms involved in sepsis induced erythrocyte pathophysiology and clearance may guide improved sepsis treatments. Evidence that small molecule antioxidants protect the erythrocyte from loss of deformability, and more importantly improve septic patient outcome suggest further research in this area is warranted. While not generally considered a critical factor in sepsis, erythrocytes (and especially a smaller subpopulation) appear to be highly susceptible to sepsis induced injury, provide an early warning signal of sepsis and are a factor in the microvascular dysfunction that has been associated with organ dysfunction.

Exploratory longitudinal cohort study of associations of fatigue after stroke.

BACKGROUND AND PURPOSE: The pathogenesis of poststroke fatigue is unclear. In this prospective study, we explored whether reduced physical activity might contribute to poststroke fatigue or be a consequence of it. METHODS: Patients with a recent acute stroke were assessed at 1, 6, and 12 months with, Fatigue Assessment Scale (FAS), a fatigue case definition, Hospital Anxiety and Depression Score, sleepiness, quality of life, and accelerometry (ActivPAL). Bivariate analyses determined associations between fatigue and step count at each time point. Multiple linear regression tested whether 1-month step count independently predicted 6- and 12-month FAS. RESULTS: A total of 136 participants (mean age, 72 years; 64% men) attended ≥1 assessment. ActivPAL data were available for 84 (64%), 69 (66%), and 58 (64%) participants at 1, 6, and 12 months, respectively. At 6 and 12 months, a positive fatigue case definition was associated with lower daily step counts (P=0.014 and 0.013, respectively). At 1, 6, and 12 months, higher FAS (more fatigue) was associated with lower step count (P<0.001, 0.01, and 0.007), higher depression (P<0.001), anxiety scores (P<0.001) and sleepiness (P<0.001), and poorer quality of life (P<0.001). Lower daily step count (P<0.002 and 0.006) and greater anxiety (P<0.001 for both) at 1 month independently predicted higher FAS at 6 and 12 months. CONCLUSIONS: Lower step counts at 1 month independently predicted greater FAS for ≤12 months. Physical activity might be a therapeutic target for poststroke fatigue.

Integrated collaborative care for comorbid major depression in patients with cancer (SMaRT Oncology-2): a multicentre randomised controlled effectiveness trial.

BACKGROUND: Medical conditions are often complicated by major depression, with consequent additional impairment of quality of life. We aimed to compare the effectiveness of an integrated treatment programme for major depression in patients with cancer (depression care for people with cancer) with usual care. METHODS: SMaRT Oncology-2 is a parallel-group, multicentre, randomised controlled effectiveness trial. We enrolled outpatients with major depression from three cancer centres and their associated clinics in Scotland, UK. Participants were randomly assigned in a 1:1 ratio to the depression care for people with cancer intervention or usual care, with stratification (by trial centre) and minimisation (by age, primary cancer, and sex) with allocation concealment. Depression care for people with cancer is a manualised, multicomponent collaborative care treatment that is delivered systematically by a team of cancer nurses and psychiatrists in collaboration with primary care physicians. Usual care is provided by primary care physicians. Outcome data were collected up until 48 weeks. The primary outcome was treatment response (≥50% reduction in Symptom Checklist Depression Scale [SCL-20] score, range 0-4) at 24 weeks. Trial statisticians and data collection staff were masked to treatment allocation, but participants could not be masked to the allocations. Analyses were by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN40568538. FINDINGS: 500 participants were enrolled between May 12, 2008, and May 13, 2011; 253 were randomly allocated to depression care for people with cancer and 247 to usual care. 143 (62%) of 231 participants in the depression care for people with cancer group and 40 (17%) of 231 in the usual care group responded to treatment: absolute difference 45% (95% CI 37-53), adjusted odds ratio 8·5 (95% CI 5·5-13·4), p<0·0001. Compared with patients in the usual care group, participants allocated to the depression care for people with cancer programme also had less depression, anxiety, pain, and fatigue; and better functioning, health, quality of life, and perceived quality of depression care at all timepoints (all p<0·05). During the study, 34 cancer-related deaths occurred (19 in the depression care for people with cancer group, 15 in the usual care group), one patient in the depression care for people with cancer group was admitted to a psychiatric ward, and one patient in this group attempted suicide. None of these events were judged to be related to the trial treatments or procedures. INTERPRETATION: Our findings suggest that depression care for people with cancer is an effective treatment for major depression in patients with cancer. It offers a model for the treatment of depression comorbid with other medical conditions. FUNDING: Cancer Research UK and Chief Scientist Office of the Scottish Government.

Impact of Incremental Perfusion Loss on Oxygen Transport in a Capillary Network Mathematical Model.

OBJECTIVES: To quantify how incremental capillary PL, such as that seen in experimental models of sepsis, affects tissue oxygenation using a computation model of oxygen transport. METHODS: A computational model was applied to capillary networks with dimensions 84 × 168 × 342 (NI) and 70 × 157 × 268 (NII) µm, reconstructed in vivo from rat skeletal muscle. FCD loss was applied incrementally up to ~40% and combined with high tissue oxygen consumption to simulate severe sepsis. RESULTS: A loss of ~40% FCD loss decreased median tissue PO2 to 22.9 and 20.1 mmHg in NI and NII compared to 28.1 and 27.5 mmHg under resting conditions. Increasing RBC SR to baseline levels returned tissue PO2 to within 5% of baseline. HC combined with a 40% FCD loss, resulted in tissue anoxia in both network volumes and median tissue PO2 of 11.5 and 8.9 mmHg in NI and NII respectively; median tissue PO2 was recovered to baseline levels by increasing total SR 3-4 fold. CONCLUSIONS: These results suggest a substantial increase in total SR is required in order to compensate for impaired oxygen delivery as a result of loss of capillary perfusion and increased oxygen consumption during sepsis.

The science of clinical practice: disease diagnosis or patient prognosis? Evidence about "what is likely to happen" should shape clinical practice.

BACKGROUND: Diagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful. DISCUSSION: Disease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous 'yes' or 'no' is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient's future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome. SUMMARY: Patient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care.

Somatic symptom count scores do not identify patients with symptoms unexplained by disease: a prospective cohort study of neurology outpatients.

OBJECTIVE: Somatic symptoms unexplained by disease are common in all medical settings. The process of identifying such patients requires a clinical assessment often supported by clinical tests. Such assessments are time-consuming and expensive. Consequently the observation that such patients tend to report a greater number of symptom has led to the use of self-rated somatic symptom counts as a simpler and cheaper diagnostic aid and proxy measure for epidemiological surveys. However, despite their increasing popularity there is little evidence to support their validity. METHODS: We tested the score on a commonly used self-rated symptom questionnaire- the Patient Health Questionnaire (PHQ 15) (plus enhanced iterations including an additional 10 items on specific neurological symptoms and an additional 5 items on mental state) for diagnostic sensitivity and specificity against a medical assessment (with 18 months follow-up) in a prospective cohort study of 3781 newly attending patients at neurology clinics in Scotland, UK. RESULTS: We found 1144/3781 new outpatients had symptoms that were unexplained by disease. The patients with symptoms unexplained by disease reported higher symptoms count scores (PHQ 15: 5.6 (95% CI 5.4 to 5.8) vs 4.2 (4.1 to 4.4) p<0.0001). However, the PHQ15 performed little better than chance in its ability to identify patients with symptoms unexplained by disease. The findings with the enhanced scales were similar. CONCLUSIONS: Self-rated symptom count scores should not be used to identify patients with symptoms unexplained by disease.