Individual inflammatory marker abnormalities or inflammatory marker scores to identify primary care patients with unexpected weight loss for cancer investigation?

BACKGROUND: Combinations of inflammatory markers are used as prognostic scores in cancer patients with cachexia. We investigated whether they could also be used to prioritise patients attending primary care with unexpected weight loss for cancer investigation. METHODS: We used English primary care electronic health records data linked to cancer registry data from 12,024 patients with coded unexpected weight loss. For each individual inflammatory marker and score we estimated the sensitivity, specificity, likelihood ratios, positive predictive value (PPV) and the area under the curve along with 95% confidence intervals for a cancer diagnosis within six months. RESULTS: The risk of cancer associated with two abnormal inflammatory markers combined in a score was higher than the risk associated with individual inflammatory marker abnormalities. However, the risk of cancer in weight loss associated with individual abnormalities, notably a raised C-reactive protein, was sufficient to trigger further investigation for cancer under current NICE guidelines. CONCLUSIONS: If scores including pairs of inflammatory marker abnormalities were to be used, in preference to individual abnormalities, fewer people would be investigated to diagnose one cancer with fewer false positives, but fewer people with cancer would be diagnosed overall.

Risk markers for both chronic fatigue and irritable bowel syndromes: a prospective case-control study in primary care.

BACKGROUND: Fatigue syndromes and irritable bowel syndrome (IBS) often occur together. Explanations include being different manifestations of the same condition and simply sharing some symptoms. METHOD: A matched case-control study in UK primary care, using data collected prospectively in the General Practice Research Database (GPRD). The main outcome measures were: health-care utilization, specific symptoms and diagnoses. Risk markers were divided into distant (from 3 years to 1 year before diagnosis) and recent (1 year before diagnosis). RESULTS: A total of 4388 patients with any fatigue syndrome were matched to two groups of patients: those attending for IBS and those attending for another reason. Infections were specific risk markers for both syndromes, with viral infections being a risk marker for a fatigue syndrome [odds ratios (ORs) 2.3-6.3], with a higher risk closer to onset, and gastroenteritis a risk for IBS (OR 1.47, compared to a fatigue syndrome). Chronic fatigue syndrome (CFS) shared more distant risk markers with IBS than other fatigue syndromes, particularly other symptom-based disorders (OR 3.8) and depressive disorders (OR 2.3), but depressive disorders were a greater risk for CFS than IBS (OR 2.4). Viral infections were more of a recent risk marker for CFS compared to IBS (OR 2.8), with gastroenteritis a greater risk for IBS (OR 2.4). CONCLUSIONS: Both fatigue and irritable bowel syndromes share predisposing risk markers, but triggering risk markers differ. Fatigue syndromes are heterogeneous, with CFS sharing predisposing risks with IBS, suggesting a common predisposing pathophysiology.

Risk and predictors of fatigue after infectious mononucleosis in a large primary-care cohort.

BACKGROUND: Fatigue has been found to complicate infectious mononucleosis (IM) when patients are directly asked about it. We do not know whether such fatigue is clinically significant, nor whether IM is a specific risk for fatigue (or whether it can follow other common infections). Various risk markers for post-infectious fatigue have been identified, but findings are inconsistent. AIM: To determine the risk of clinically reported fatigue (compared with depression) after IM (compared with both influenza and tonsillitis) in patients attending primary care, and to examine risk markers for post-IM fatigue. DESIGN: Comparison of matched primary-care cohorts. METHODS: We identified 1438 adult patients with a positive heterophil antibody test for IM from the UK General Practice Research Database. These patients were individually matched on age, sex and practice to two comparison groups; one with a clinical diagnosis of influenza and the other of tonsillitis. RESULTS: The odds ratios (ORs) (95%CI) for reported fatigue after IM vs. influenza and tonsillitis were 4.4 (2.9-6.9) and 6.6 (4.2-10.4), respectively. Risk markers for post-IM fatigue included female sex and premorbid mood disorder. By comparison, the ORs for depression after IM vs. influenza and tonsillitis were 1.6 (0.9-2.6) and 2.3 (1.4-3.9), respectively. DISCUSSION: IM is a specific and significant risk for clinically reported fatigue, which is both separate from, and more common than, depression. Female sex and premorbid mood disorder are risk markers for fatigue. These can be used both to target prevention strategies and to explore aetiological mechanisms.

Frequency of attendance in general practice and symptoms before development of chronic fatigue syndrome: a case-control study.

BACKGROUND: Chronic fatigue syndrome (CFS) research has concentrated on infective, immunological, and psychological causes. Illness behaviour has received less attention, with most research studying CFS patients after diagnosis. Our previous study on the records of an insurance company showed a highly significant increase in illness reporting before development of CFS. AIM: To investigate the number and type of general practitioner (GP) consultations by patients with CFS for 15 years before they develop their condition. DESIGN OF STUDY: Case-control study in 11 general practices in Devon. SETTING: Forty-nine patients with CFS (satisfying the Centers for Disease Control criteria), 49 age, sex, and general practice matched controls, and 37 patients with multiple sclerosis (MS) were identified from the general practices' computerised databases. METHOD: The number of general practice consultations and symptoms recorded in three five-year periods (quinquennia) were counted before development of the patients' condition. RESULTS: The median number of consultations was significantly higher for CFS patients than that of matched controls in each of the quinquennia: ratios for first quinquennium = 1.88, P = 0.01; second quinquennium = 1.70, P = 0.005; last quinquennium = 2.25, P < 0.001. More CFS patients than controls attended for 13 of the 18 symptoms studied. Significant increases were found for upper respiratory tract infection (P < 0.001), lethargy (P < 0.001), and vertigo (P = 0.02). Similar results were found for CFS patients when compared with MS. CONCLUSIONS: CFS patients consulted their GP more frequently in the 15 years before development of their condition, for a wide variety of complaints. Several possibilities may explain these findings. The results support the hypothesis that behavioural factors have a role in the aetiology of CFS.

Increased illness experience preceding chronic fatigue syndrome: a case control study.

BACKGROUND: Almost all published work on chronic fatigue syndrome (CFS) has involved retrospective surveys of cases, which may introduce recall bias. Only medical records collected before diagnosis of CFS can eliminate this. METHODS: Using data collected several years prior to the development of the illness, we performed a case control study, comparing the reported illness records of all people who subsequently made an insurance claim as a result of CFS, with those of future multiple sclerosis (MS) claimants, and those of non-claimant controls (NC). RESULTS: The study encompassed 133 CFS, 75 MS and 162 NC cases. CFS cases had recorded significantly more illnesses at time of proposal for insurance than the two control groups, and had significantly more claims between proposal and diagnosis of their disorder. Almost all disease categories were reported higher in future CFS sufferers, lethargy having the highest odds ratio after adjustment in a multivariate model. INTERPRETATION: The results of this paper on CFS patients who claim permanent health insurance do not support a specific viral or immunological explanation for CFS. We conclude that abnormal illness behaviour is of greater importance than previously recognised.

Angiographic evidence of absent ductus arteriosus in severe right ventricular outflow obstruction.

The angiocardiograms of 5 newborn infants with autopsy and/or surgically-proven congenital absence of the ductus arteriosus (ADA) and right ventricular outflow obstruction (Group A), and of 14 neonates with pulmonary atresia complex and patent ductus arteriosus (Group B) were reviewed. Aortic size was similar in both groups; however, the diameters of the right and left pulmonary arteries were much smaller in Group A than in Group B (right pulmonary artery: 2.6 vs 4.5 mm, P less than 0.005; left pulmonary artery: 2.5 vs 4.3 mm, P less than 0.005). Extensive bronchial collaterals were observed in Group A but not in Group B. Tricuspid aortic valve stenosis was present in 2 patients in Group A but in none in Group B. The diagnosis of ADA may be made in newborn infants with severe right ventricular outflow obstruction if the angiocardiograms reveal hypoplasia of the pulmonary arteries, extensive bronchial collaterals, and nonvisualization of the ductus arteriosus. Other suggestive features include aortic valve stenosis and/or right aortic arch with aberrant left subclavian artery.