General practice vs surgical-based follow-up for patients with colon cancer: randomised controlled trial

This trial examined the optimal setting for follow-up of patients after treatment for colon cancer by either general practitioners or surgeons. In all, 203 consenting patients who had undergone potentially curative treatment for colon cancer were randomised to follow-up by general practitioners or surgeons. Follow-up guidance recommended three monthly clinical review and annual faecal occult blood tests (FOBT) and were identical in both study arms. Primary outcome measures (measured at baseline, 12 and 24 months were (1) quality of life, SF-12; physical and mental component scores, (2) anxiety and depression: Hospital Anxiety and Depression Scale and (3) patient satisfaction: Patient Visit-Specific Questionnaire. Secondary outcomes (at 24 months) were: investigations, number and timing of recurrences and deaths. In all, 170 patients were available for follow-up at 12 months and 157 at 24 months. At 12 and 24 months there were no differences in scores for quality of life (physical component score, P=0.88 at 12 months; P=0.28 at 24 months: mental component score, P=0.51, P=0.47; adjusted), anxiety (P=0.72; P=0.11) depression (P=0.28; P=0.80) or patient satisfaction (P=0.06, 24 months). General practitioners ordered more FOBTs than surgeons (rate ratio 2.4, 95% CI 1.4–4.4), whereas more colonoscopies (rate ratio 0.7, 95% CI 0.5–1.0), and ultrasounds (rate ratio 0.5, 95% CI 0.3–1.0) were undertaken in the surgeon-led group. Results suggest similar recurrence, time to detection and death rates in each group. Colon cancer patients with follow-up led by surgeons or general practitioners experience similar outcomes, although patterns of investigation vary

The interpretation of low mood and worry by high users of secondary care with medically unexplained symptoms

DA - 20111021 IS - 1471-2296 (Electronic) IS - 1471-2296 (Linking) LA - eng PT - Journal Article SB - IMPeer reviewedPublisher PD

Protocol for a nested case-control study design for omics investigations in the Environmental Determinants of Islet Autoimmunity cohort

Background: The Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy-birth cohort investigates the developmental origins of type 1 diabetes (T1D), with recruitment between 2013 and 2019. ENDIA is the first study in the world with comprehensive data and biospecimen collection during pregnancy, at birth and through childhood from at-risk children who have a first-degree relative with T1D. Environmental exposures are thought to drive the progression to clinical T1D, with pancreatic islet autoimmunity (IA) developing in genetically susceptible individuals. The exposures and key molecular mechanisms driving this progression are unknown. Persistent IA is the primary outcome of ENDIA; defined as a positive antibody for at least one of IAA, GAD, ZnT8 or IA2 on two consecutive occasions and signifies high risk of clinical T1D.Method: A nested case-control (NCC) study design with 54 cases and 161 matched controls aims to investigate associations between persistent IA and longitudinal omics exposures in ENDIA. The NCC study will analyse samples obtained from ENDIA children who have either developed persistent IA or progressed to clinical T1D (cases) and matched control children at risk of developing persistent IA. Control children were matched on sex and age, with all four autoantibodies absent within a defined window of the case's onset date. Cases seroconverted at a median of 1.37 years (IQR 0.95, 2.56). Longitudinal omics data generated from approximately 16,000 samples of different biospecimen types, will enable evaluation of changes from pregnancy through childhood.Conclusions: This paper describes the ENDIA NCC study, omics platform design considerations and planned univariate and multivariate analyses for its longitudinal data. Methodologies for multivariate omics analysis with longitudinal data are discovery-focused and data driven. There is currently no single multivariate method tailored specifically for the longitudinal omics data that the ENDIA NCC study will generate and therefore omics analysis results will require either cross validation or independent validation.KEY MESSAGESThe ENDIA nested case-control study will utilize longitudinal omics data on approximately 16,000 samples from 190 unique children at risk of type 1 diabetes (T1D), including 54 who have developed islet autoimmunity (IA), followed during pregnancy, at birth and during early childhood, enabling the developmental origins of T1D to be explored.Helena Oakey ... Lynne C. Giles ... Rebecca L. Thomson ... Pat Ashwood ... Emma J. Knight ... Simon C. Barry ... Kelly McGorm ... Jennifer J. Couper ... Megan A. S. Penno ... the ENDIA Study Group ... et al

A surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetes.

OnlinePublAims/Introduction: Autoantibodies to pancreatic islet antigens identify young children at high risk of type 1 diabetes. On a background of genetic susceptibility, islet autoimmunity is thought to be driven by environmental factors, of which enteric viruses are prime candidates. We sought evidence for enteric pathology in children genetically atrisk for type 1 diabetes followed from birth who had developed islet autoantibodies (“seroconverted”), by measuring mucosa-associated cytokines in their sera. Materials and Methods: Sera were collected 3 monthly from birth from children with a first-degree type 1 diabetes relative, in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. Children who seroconverted were matched for sex, age, and sample availability with seronegative children. Luminex xMap technology was used to measure serum cytokines. Results: Of eight children who seroconverted, for whom serum samples were available at least 6 months before and after seroconversion, the serum concentrations of mucosaassociated cytokines IL-21, IL-22, IL-25, and IL-10, the Th17-related cytokines IL-17F and IL23, as well as IL-33, IFN-c, and IL-4, peaked from a low baseline in seven around the time of seroconversion and in one preceding seroconversion. These changes were not detected in eight sex- and age-matched seronegative controls, or in a separate cohort of 11 unmatched seronegative children. Conclusions: In a cohort of children at risk for type 1 diabetes followed from birth, a transient, systemic increase in mucosa-associated cytokines around the time of seroconversion lends support to the view that mucosal infection, e.g., by an enteric virus, may drive the development of islet autoimmunity.Leonard C Harrison, Esther Bandala-Sanchez, Helena Oakey, Peter G Colman, Kelly Watson, Ki Wook Kim, Roy Wu, Emma E Hamilton-Williams, Natalie L Stone, Aveni Haynes, Rebecca L Thomson, Peter J Vuillermin, Georgia Soldatos, William D Rawlinson, Kelly J McGorm, Grant Morahan, Simon C Barry, Richard O Sinnott, John M Wentworth, Jennifer J Couper, Megan AS Penno, on behalf of the ENDIA Study Grou

“Medically unexplained” symptoms and symptom disorders in primary care: prognosis-based recognition and classification

Background: Many patients consult their GP because they experience bodily symptoms. In a substantial proportion of cases, the clinical picture does not meet the existing diagnostic criteria for diseases or disorders. This may be because symptoms are recent and evolving or because symptoms are persistent but, either by their character or the negative results of clinical investigation cannot be attributed to disease: so-called “medically unexplained symptoms” (MUS). MUS are inconsistently recognised, diagnosed and managed in primary care. The specialist classification systems for MUS pose several problems in a primary care setting. The systems generally require great certainty about presence or absence of physical disease, they tend to be mind-body dualistic, and they view symptoms from a narrow specialty determined perspective. We need a new classification of MUS in primary care; a classification that better supports clinical decision-making, creates clearer communication and provides scientific underpinning of research to ensure effective interventions. Discussion: We propose a classification of symptoms that places greater emphasis on prognostic factors. Prognosis-based classification aims to categorise the patient’s risk of ongoing symptoms, complications, increased healthcare use or disability because of the symptoms. Current evidence suggests several factors which may be used: symptom characteristics such as: number, multi-system pattern, frequency, severity. Other factors are: concurrent mental disorders, psychological features and demographic data. We discuss how these characteristics may be used to classify symptoms into three groups: self-limiting symptoms, recurrent and persistent symptoms, and symptom disorders. The middle group is especially relevant in primary care; as these patients generally have reduced quality of life but often go unrecognised and are at risk of iatrogenic harm. The presented characteristics do not contain immediately obvious cut-points, and the assessment of prognosis depends on a combination of several factors. Conclusion: Three criteria (multiple symptoms, multiple systems, multiple times) may support the classification into good, intermediate and poor prognosis when dealing with symptoms in primary care. The proposed new classification specifically targets the patient population in primary care and may provide a rational framework for decision-making in clinical practice and for epidemiologic and clinical research of symptoms

Depression and anxiety in patients repeatedly referred to secondary care with medically unexplained symptoms: a case-control study.

BACKGROUND: One third of referrals from primary to secondary care are for medically unexplained symptoms (MUS). We aimed to determine the association of depression and anxiety disorders with high use of specialist services by patients with MUS. We did this by comparing their prevalence in patients who had been repeatedly referred with symptoms for which they had received repeated specialist diagnoses of MUS with that in two control groups. We also determined the adequacy of treatment received. METHOD: A case-control study in five general practices in Edinburgh, UK. Data collection was by case note review and questionnaire. Cases were 193 adults with three or more referrals over 5 years, at least two of which resulted in a diagnosis of MUS. Controls were: (a) patients referred only once over 5 years (n=152); (b) patients with three or more referrals for symptoms always diagnosed as medically explained (n=162). RESULTS: In total, 93 (48%) of the cases met our criteria for current depression, anxiety or panic disorders. This compared with 38 (25%) and 52 (35.2%) of the control groups; odds ratios (95% confidence intervals) of 2.6 (1.6-4.1) and 1.6 (1.01-2.4), respectively. Almost half (44%) of the cases with current depression or anxiety had not received recent minimum effective therapy. CONCLUSIONS: Depression, anxiety and panic disorders are common in patients repeatedly referred to hospital with MUS. Improving the recognition and treatment of these disorders in these patients has the potential to provide better, more appropriate and more cost-effective medical care

Healthcare costs incurred by patients repeatedly referred to secondary medical care with medically unexplained symptoms: a cost of illness study.

BACKGROUND: Some patients are repeatedly referred from primary to secondary care with medically unexplained symptoms (MUS). We aimed to estimate the healthcare costs incurred by such referrals and to compare them with those incurred by other referred patients from the same defined primary care sample. METHODS: Using a referral database and case note review, all adult patients aged less than 65 years, who had been referred to specialist medical services from one of five UK National Health Service primary care practices in a five-year period, were identified. They were placed in one of three groups: (i) repeatedly referred with MUS (N=276); (ii) infrequently referred (IRS, N=221), (iii) repeatedly referred with medically explained symptoms (N=230). Secondary care activities for each group (inpatient days, outpatient appointments, emergency department attendances and investigations) were identified from primary care records. The associated costs were allocated using summary data and the costs for each group compared. RESULTS: Patients who had been repeatedly referred with MUS had higher mean inpatient, outpatient and emergency department costs than those infrequently referred (£3,539, 95% CI 1458 to 5621, £778 CI 705 to 852 and £99, CI 74 to 123 respectively. The mean overall costs were similar to those of patients who had been repeatedly referred with medically explained symptoms. CONCLUSIONS: The repeated referral of patients with MUS to secondary medical care incurs substantial healthcare costs. An alternative form of management that reduces such referrals offers potential cost savings

Patients repeatedly referred to secondary care with symptoms unexplained by organic disease: prevalence, characteristics and referral pattern.

BACKGROUND: Patients with medically unexplained symptoms (MUS) are commonly referred to specialist clinics. Repeated referrals suggest unmet patient need and inefficient use of resources. OBJECTIVES: How often does this happen, who are the patients and how are they referred? METHODS: The design of the study is a case-control survey. The setting of the study is five general practices in Scotland, UK. The cases were 193 adults with three or more referrals over 5 years, at least two of which resulted in a diagnosis of MUS. The controls were (i) patients referred only once over 5 years and (ii) patients with three or more referrals with symptoms always diagnosed as medically explained. The measures of the study are SF-12 physical and mental component summaries; symptom count; and number of referrals, number of different GPs who had referred and number of specialist follow-up appointments. RESULTS: A total of 1.1% [95% confidence interval (CI) 1.0-1.2%] of patients had repeated (median 3, range 2-6) referrals with MUS. Compared to infrequently referred controls, they were older and more likely to be female, living alone and unemployed. Compared to controls with medically explained symptoms, their health status was comparable or worse: odds ratio for SF-12 physical component summary<40, 1.2 (95% CI 0.72-2.0); SF-12 mental component summary<40, 1.8 (95% CI 1.1-3.0); reporting eight or more physical symptoms, 2.2 (95% CI 1.2-3.8). They were referred by more GPs and received less specialist follow-up. CONCLUSIONS: A small proportion of primary care patients are repeatedly referred to specialist clinics where they receive multiple diagnoses of MUS. The needs of these patients and how they are managed merits greater attention

Is co-morbid depression adequately treated in patients repeatedly referred to specialist medical services with symptoms of a medical condition?

OBJECTIVE: Patients with a medical condition and co-morbid depression have more symptoms and use more medical services. We aimed to determine the prevalence of depression and the adequacy of its treatment in patients who had been repeatedly referred from primary to specialist medical care for the assessment of a medical condition. METHODS: All patients who had at least three referrals to medical and surgical specialists for an assessment of symptoms attributed to a medical condition, over a five year period from five primary care practices in Edinburgh, UK were identified using a referral database and review of records. Participants were sent a questionnaire which included the PHQ-9 depression scale and additional questions about depression during the preceding 5years. Details of treatment for depression were obtained from primary care records. RESULTS: Questionnaires were sent to 230 patients and returned by 162 (70.4%). Forty-one (25.3%) had a PHQ-9 score of 10 or more and hence probable current depressive disorder. An additional 36 (22.2%) reported depression in the previous 5years. Only eight (19.5%) of those reporting current depression and 20 (26%) of the 77 patients reporting previous depression had received minimally adequate treatment for it. CONCLUSION: Whilst we know that patients with medical conditions are often depressed and that such co-morbid depression is often undertreated, we have found that it is undertreated even in patients repeatedly referred to medical specialists. Better assessment and management of depression in such patients could both improve patients' quality of life and reduce the cost of care