Inflammatory marker testing in primary care in the year before Hodgkin lymphoma diagnosis: a UK population-based case-control study in patients aged ≤50 years

BACKGROUND: Proinflammatory conditions are associated with increased risk of Hodgkin lymphoma, although the neoplastic process per se often induces an inflammatory response. AIM: To examine pre-diagnostic inflammatory marker test use to identify changes that may define a 'diagnostic window' for potential earlier diagnosis. DESIGN AND SETTING: This was a matched case-control study in UK primary care using Clinical Practice Research Datalink data (2002-2016). METHOD: Primary care inflammatory marker test use and related findings were analysed in 839 Hodgkin lymphoma patients and 5035 controls in the year pre-diagnosis. Poisson regression models were used to calculate monthly testing rates to examine changes over time in test use. Longitudinal trends in test results and the presence/absence of 'red-flag' symptoms were examined. RESULTS: In patients with Hodgkin lymphoma, 70.8% (594/839) had an inflammatory marker test in the year pre-diagnosis versus 16.2% (816/5035) of controls (odds ratio 13.7, 95% CI = 11.4 to 16.5, P<0.001). The rate of inflammatory marker testing and mean levels of certain inflammatory marker results increased progressively during the year pre-diagnosis in Hodgkin lymphoma patients while remaining stable in controls. Among patients with Hodgkin lymphoma with a pre-diagnostic test, two-thirds (69.5%, 413/594) had an abnormal result and, among these, 42.6% (176/413) had no other 'red-flag' presenting symptom/sign. CONCLUSION: Increases in inflammatory marker requests and abnormal results occur in many patients with Hodgkin lymphoma several months pre-diagnosis, suggesting this period should be excluded in aetiological studies examining inflammation in Hodgkin lymphoma development, and that a diagnostic time window of appreciable length exists in many patients with Hodgkin lymphoma, many of whom have no other red-flag features

Impact of a case-management intervention for reducing emergency attendance on primary care: randomised control trial

BACKGROUND: The impact on primary care workload of case-management interventions to reduce emergency department (ED) attendances is unknown. AIM: To examine the impact of a telephone-based case-management intervention targeting people with high ED attendance on primary care use. DESIGN AND SETTING: A single-site data extract from a larger randomised control trial, using the patient-level data from primary care electronic health records (2015–2020), was undertaken. METHOD: A total of 363 patients at high risk of ED usage were randomised to receive a 6-month case-management intervention (253 patients) or standard care (110 patients). Poisson regression models were used to calculate monthly rates of primary care use over time for the 2 years post-randomisation, comparing both arms. Usage was subclassified into face-to-face, telephone, letter, and community and secondary care referrals, stratified by patient demographics. RESULTS: No significant difference was found in the mean annual rate of primary care events between the intervention and control arms (P = 0.70). Secondary care referrals saw a 26% reduction in the mean annual referral rate (incident rate ratio [IRR] 0.74, 95% confidence interval [CI] = 0.64 to 0.86, P<0.001) and letters sent increased by 6% in the intervention arm compared with the control arm (IRR 1.06, 95% CI = 1.01 to 1.11, P = 0.01). In the case-managed arm, in patients aged ≥80 years there was a 33% increase in primary care usage (IRR 1.33, 95% CI = 1.28 to 1.40, P<0.001); with a corresponding 10% decrease in patients aged <80 years when compared with controls (IRR 0.90, 95% CI = 0.87 to 0.92, P<0.001). CONCLUSION: A targeted case-management intervention to reduce ED attendances did not increase overall primary care use. Redistribution of usage is seen among some patient groups, particularly older people, which may have important implications for primary healthcare planning

The Role of Type 2 Diabetes in Patient Symptom Attribution, Help-Seeking, and Attitudes to Investigations for Colorectal Cancer Symptoms: An Online Vignette Study

Objectives: Type 2 diabetes is associated with a higher risk of colorectal cancer (CRC) and advanced-stage cancer diagnosis. To help diagnose cancer earlier, this study aimed at examining whether diabetes might influence patient symptom attribution, help-seeking, and willingness to undergo investigations for possible CRC symptoms. Methods: A total of 1307 adults (340 with and 967 without diabetes) completed an online vignette survey. Participants were presented with vignettes describing new-onset red-flag CRC symptoms (rectal bleeding or a change in bowel habits), with or without additional symptoms of diabetic neuropathy. Following the vignettes, participants were asked questions on symptom attribution, intended help-seeking, and attitudes to investigations. Results: Diabetes was associated with greater than two-fold higher odds of attributing changes in bowel habits to medications (OR = 2.48; 95% Cl 1.32–4.66) and of prioritising diabetes-related symptoms over the change in bowel habits during medical encounters. Cancer was rarely mentioned as a possible explanation for the change in bowel habits, especially among diabetic participants (10% among diabetics versus 16% in nondiabetics; OR = 0.55; 95% CI 0.36–0.85). Among patients with diabetes, those not attending annual check-ups were less likely to seek help for red-flag cancer symptoms (OR = 0.23; 95% Cl 0.10–0.50). Conclusions: Awareness of possible cancer symptoms was low overall. Patients with diabetes could benefit from targeted awareness campaigns emphasising the importance of discussing new symptoms such as changes in bowel habits with their doctor. Specific attention is warranted for individuals not regularly attending healthcare despite their chronic morbidity

Pre-diagnostic prescribing patterns in dyspnoea patients with as-yet-undiagnosed lung cancer: A longitudinal study of linked primary care and cancer registry data

Introduction: Patients with as-yet undiagnosed lung cancer (LC) can present to primary care with non-specific symptoms such as dyspnoea, often in the context of pre-existing chronic obstructive pulmonary disease (COPD). Related medication prescriptions pre-diagnosis might represent opportunities for earlier diagnosis, but UK evidence is limited. Consequently, we explored prescribing patterns of relevant medications in patients who presented with dyspnoea in primary care and were subsequently diagnosed with LC. // Method: Linked primary care (Clinical Practice Research Datalink) and National Cancer Registry data were used to identify 5434 patients with incident LC within a year of a dyspnoea presentation in primary care between 2006 and 2016. Primary care prescriptions relevant to dyspnoea management were examined: antibiotics, inhaled medications, oral steroids, and opioid analgesics. Poisson regression models estimated monthly prescribing rates during the year pre-diagnosis. Variation by COPD status (52 % pre-existing, 36 % COPD-free, 12 % new-onset) was examined. Inflection points were identified indicating when prescribing rates changed from the background rate. // Results: 63 % of patients received 1 or more relevant prescriptions 1–12 months pre-diagnosis. Pre-existing COPD patients were most prescribed inhaled medications. COPD-free and new-onset COPD patients were most prescribed antibiotics. Most patients received 2 or more relevant prescriptions. Monthly prescribing rates of all medications increased towards time of diagnosis in all patient groups and were highest in pre-existing COPD patients. Increases in prescribing activity were observed earliest in pre-existing COPD patients 5 months pre-diagnosis for inhaled medications, antibiotics, and steroids. // Conclusion: Results indicate that a diagnostic window of appreciable length exists for potential earlier LC diagnosis in some patients. Lung cancer diagnosis may be delayed if early symptoms are misattributed to COPD or other benign conditions

Allergic disease, corticosteroid use, and risk of Hodgkin lymphoma: A United Kingdom nationwide case-control study.

BACKGROUND: Immunodeficiency syndromes (acquired/congenital/iatrogenic) are known to increase Hodgkin lymphoma (HL) risk, but the effects of allergic immune dysregulation and corticosteroids are poorly understood. OBJECTIVE: We sought to assess the risk of HL associated with allergic disease (asthma, eczema, and allergic rhinitis) and corticosteroid use. METHODS: We conducted a case-control study using the United Kingdom Clinical Practice Research Datalink (CPRD) linked to hospital data. Multivariable logistic regression investigated associations between allergic diseases and HL after adjusting for established risk factors. Potential confounding or effect modification by steroid treatment were examined. RESULTS: One thousand two hundred thirty-six patients with HL were matched to 7416 control subjects. Immunosuppression was associated with 6-fold greater odds of HL (adjusted odds ratio [aOR], 6.18; 95% CI, 3.04-12.57), with minimal change after adjusting for steroids. Any prior allergic disease or eczema alone was associated with 1.4-fold increased odds of HL (aOR, 1.41 [95% CI, 1.24-1.60] and 1.41 [95% CI, 1.20-1.65], respectively). These associations decreased but remained significant after adjustment for steroids (aOR, 1.25 [95% CI, 1.09-1.43] and 1.27 [95% CI, 1.08-1.49], respectively). There was no effect modification by steroid use. Previous steroid treatment was associated with 1.4-fold greater HL odds (aOR, 1.38; 95% CI, 1.20-1.59). CONCLUSIONS: In addition to established risk factors (immunosuppression and infectious mononucleosis), allergic disease and eczema are risk factors for HL. This association is only partially explained by steroids, which are associated with increased HL risk. These findings add to the growing evidence that immune system malfunction after allergic disease or immunosuppression is central to HL development

Guideline concordance for timely chest imaging after new presentations of dyspnoea or haemoptysis in primary care: a retrospective cohort study

BACKGROUND: Guidelines recommend urgent chest X-ray for newly presenting dyspnoea or haemoptysis but there is little evidence about their implementation. METHODS: We analysed linked primary care and hospital imaging data for patients aged 30+ years newly presenting with dyspnoea or haemoptysis in primary care during April 2012 to March 2017. We examined guideline-concordant management, defined as General Practitioner-ordered chest X-ray/CT carried out within 2 weeks of symptomatic presentation, and variation by sociodemographic characteristic and relevant medical history using logistic regression. Additionally, among patients diagnosed with cancer we described time to diagnosis, diagnostic route and stage at diagnosis by guideline-concordant status. RESULTS: In total, 22 560/162 161 (13.9%) patients with dyspnoea and 4022/8120 (49.5%) patients with haemoptysis received guideline-concordant imaging within the recommended 2-week period. Patients with recent chest imaging pre-presentation were much less likely to receive imaging (adjusted OR 0.16, 95% CI 0.14-0.18 for dyspnoea, and adjusted OR 0.09, 95% CI 0.06-0.11 for haemoptysis). History of chronic obstructive pulmonary disease/asthma was also associated with lower odds of guideline concordance (dyspnoea: OR 0.234, 95% CI 0.225-0.242 and haemoptysis: 0.88, 0.79-0.97). Guideline-concordant imaging was lower among dyspnoea presenters with prior heart failure; current or ex-smokers; and those in more socioeconomically disadvantaged groups.The likelihood of lung cancer diagnosis within 12 months was greater among the guideline-concordant imaging group (dyspnoea: 1.1% vs 0.6%; haemoptysis: 3.5% vs 2.7%). CONCLUSION: The likelihood of receiving urgent imaging concords with the risk of subsequent cancer diagnosis. Nevertheless, large proportions of dyspnoea and haemoptysis presenters do not receive prompt chest imaging despite being eligible, indicating opportunities for earlier lung cancer diagnosis

Socioeconomic deprivation and regional variation in Hodgkin's lymphoma incidence in the UK: a population-based cohort study of 10 million individuals.

OBJECTIVES: Hodgkin's lymphoma (HL) is the the most common cancer in teenagers and young adults. This nationwide study conducted over a 25-year period in the UK investigates variation in HL incidence by age, sex, region and deprivation to identify trends and high-risk populations for HL development. DESIGN: Population-based cohort study. SETTING: Clinical Practice Research Datalink (CPRD) electronic primary care records linked to Hospital Episode Statistics and Index of Multiple Deprivation data were used. PARTICIPANTS: Data on 10 million individuals in the UK from 1992 to 2016 were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: Poisson models were used to explore differences in HL incidence by age, sex, region and deprivation. Age-specific HL incidence rates by sex and directly age-standardised incidence rates by region and deprivation group were calculated. RESULTS: A total of 2402 new cases of HL were identified over 78 569 436 person-years. There was significant variation in HL incidence by deprivation group. Individuals living in the most affluent areas had HL incidence 60% higher than those living in the most deprived (incidence rate ratios (IRR) 1.60, 95% CI 1.40 to 1.83), with strong evidence of a marked linear trend towards increasing HL incidence with decreasing deprivation (p=<0.001). There was significant regional variation in HL incidence across the UK, which persisted after adjusting for age, sex and deprivation (IRR 0.80-1.42, p=<0.001). CONCLUSIONS: This study identified high-risk regions for HL development in the UK and observed a trend towards higher incidence of HL in individuals living in less deprived areas. Consistent with findings from other immune-mediated diseases, this study supports the hypothesis that an affluent childhood environment may predispose to development of immune-related neoplasms, potentially through fewer immune challenges interfering with immune maturation in early life. Understanding the mechanisms behind this immune dysfunction could inform prevention, detection and treatment of HL and other immune diseases

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with prognosis of estrogen receptor-negative breast cancer after chemotherapy

Introduction: Tumor lymphocyte infiltration is associated with clinical response to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify variants in immunosuppressive pathway genes associated with prognosis after adjuvant chemotherapy for ER-negative patients, we studied stage I-III invasive breast cancer patients of European ancestry, including 9,334 ER-positive (3,151 treated with chemotherapy) and 2,334 ER-negative patients (1,499 treated with chemotherapy). Methods: We pooled data from sixteen studies from the Breast Cancer Association Consortium (BCAC), and employed two independent studies for replications. Overall 3,610 single nucleotide polymorphisms (SNPs) in 133 genes were genotyped as part of the Collaborative Oncological Gene-environment Study, in which phenotype and clinical data were collected and harmonized. Multivariable Cox proportional hazard regression was used to assess genetic associations with overall survival (OS) and breast

2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy

Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204-A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10 â ̂'9). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities