Implementation and external validation of the Cambridge Multimorbidity Score in the UK Biobank cohort.

BACKGROUND: Patients with multiple conditions present a growing challenge for healthcare provision. Measures of multimorbidity may support clinical management, healthcare resource allocation and accounting for the health of participants in purpose-designed cohorts. The recently developed Cambridge Multimorbidity scores (CMS) have the potential to achieve these aims using primary care records, however, they have not yet been validated outside of their development cohort. METHODS: The CMS, developed in the Clinical Research Practice Dataset (CPRD), were validated in UK Biobank participants whose data is not available in CPRD (the cohort used for CMS development) with available primary care records (n = 111,898). This required mapping of the 37 pre-existing conditions used in the CMS to the coding frameworks used by UK Biobank data providers. We used calibration plots and measures of discrimination to validate the CMS for two of the three outcomes used in the development study (death and primary care consultation rate) and explored variation by age and sex. We also examined the predictive ability of the CMS for the outcome of cancer diagnosis. The results were compared to an unweighted count score of the 37 pre-existing conditions. RESULTS: For all three outcomes considered, the CMS were poorly calibrated in UK Biobank. We observed a similar discriminative ability for the outcome of primary care consultation rate to that reported in the development study (C-index: 0.67 (95%CI:0.66-0.68) for both, 5-year follow-up); however, we report lower discrimination for the outcome of death than the development study (0.69 (0.68-0.70) and 0.89 (0.88-0.90) respectively). Discrimination for cancer diagnosis was adequate (0.64 (0.63-0.65)). The CMS performs favourably to the unweighted count score for death, but not for the outcomes of primary care consultation rate or cancer diagnosis. CONCLUSIONS: In the UK Biobank, CMS discriminates reasonably for the outcomes of death, primary care consultation rate and cancer diagnosis and may be a valuable resource for clinicians, public health professionals and data scientists. However, recalibration will be required to make accurate predictions when cohort composition and risk levels differ substantially from the development cohort. The generated resources (including codelists for the conditions and code for CMS implementation in UK Biobank) are available online.

Universal screening for early detection of chronic autoimmune, metabolic and cardiovascular diseases in the general population using capillary blood (UNISCREEN): low-risk interventional, single-centre, pilot study protocol.

INTRODUCTION: Chronic autoimmune (type 1 diabetes and coeliac disease) and metabolic/cardiovascular (type 2 diabetes, dyslipidaemia, hypertension) diseases are highly prevalent across all age ranges representing a major public health burden. Universal screening for prediction/early identification of these conditions is a potential tool for reducing their impact on the general population. The aim of this study is to assess whether universal screening using capillary blood sampling is feasible at a population-based level. METHODS AND ANALYSIS: This is a low-risk interventional, single-centre, pilot study for a population-based screening programme denominated UNISCREEN. Participants are volunteers aged 1-100 who reside in the town of Cantalupo (Milan, Italy) undergoing: (1) interview collecting demographics, anthropometrics and medical history; (2) capillary blood collection for measurement of type 1 diabetes and coeliac disease-specific autoantibodies and immediate measurement of glucose, glycated haemoglobin and lipid panel by point-of-care devices; (3) venous blood sampling to confirm autoantibody-positivity; (4) blood pressure measurement; (5) fulfilment of a feasibility and acceptability questionnaire. The outcomes are the assessment of feasibility and acceptability of capillary blood screening, the prevalence of presymptomatic type 1 diabetes and undiagnosed coeliac disease, distribution of glucose categories, lipid panel and estimate of cardiovascular risk in the study population. With approximately 3000 inhabitants, the screened population is expected to encompass at least half of its size, approaching nearly 1500 individuals. ETHICS AND DISSEMINATION: This protocol and the informed consent forms have been reviewed and approved by the San Raffaele Hospital Ethics Committee (approval number: 131/INT/2022). Written informed consent is obtained from all study participants or their parents if aged <18. Results will be published in scientific journals and presented at meetings. CONCLUSIONS: If proven feasible and acceptable, this universal screening model would pave the way for larger-scale programmes, providing an opportunity for the implementation of innovative public health programmes in the general population. TRIAL REGISTRATION NUMBER: NCT05841719.

COVID-19 Immunity in the Cohort of IRCCS San Raffaele Hospital Employees after BNT162b2 Vaccination: A Retrospective Observational Study.

Introduction: The COVID-19 pandemic represents the most severe health and socioeconomic crisis of our century. It began with the first reports in China, in the Wuhan region in December 2019, and quickly spread worldwide, causing a new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Among the population most at risk of infection and developing severe forms of the disease are the elderly and healthcare workers, who are more exposed to infected individuals. On December 11, 2020, the Food and Drug Administration approved the emergency use of the BNT162b2 vaccine, the first mRNA vaccine in history. Since then, the total number of vaccine doses administered has exceeded 12 billion. Italy was the first European country to be affected by the pandemic, recording the highest number of total COVID-19 cases (25,695,311) and, after the first 70 days, had the highest crude mortality rate (141.0 per 100,000). In this study, we analyze the rate of SARS-CoV-2 infection among healthcare workers at the San Raffaele Scientific Institute in Milan before and after receiving the BNT162b2 vaccine. Study design: Retrospective observational cohort study. Methods: The study analyzed the immunization status of 858 employees of the San Raffaele Scientific Institute in Milan, including doctors, healthcare workers, and administrative staff. The analysis is based on previous studies on the same cohort and is integrated with extrapolation and additional analysis of data from the Preventive Medicine Service's Biobank dataset of the same hospital to estimate the infection rate, duration of the disease, and antibody levels recorded in the personnel before and after receiving the double BNT162b2 vaccination. Results: The analysis confirms the positive impact achieved by the introduction of mRNA vaccination in reducing the SARSCoV- 2 infection rate and increasing antibody levels in healthcare workers. Although the BNT162b2 vaccination may not provide complete protection against SARS-CoV-2, it appears to be able to reduce the number of infections, particularly the more severe and symptomatic forms often detected in individuals with various risk factors and comorbidities, making them more vulnerable. Healthcare workers, who have extensive contact with patients and record the greatest decrease in the infection rates, represent the population that receives the most benefit from vaccination. Conclusions: The evidence suggests that vaccinations are essential in protecting high-risk groups, such as healthcare workers, from SARS-CoV-2 infection. Providing adequate vaccination coverage to healthcare workers limits the spread of infections and decreases the severity of disease manifestations, while also reducing their duration.

Variations in avoidable hospital admissions and emergency visits by primary care characteristics: an ecological study in Italy.

Background: Primary healthcare plays a central role in providing preventive care, managing chronic conditions and reducing inappropriate emergency presentations. The study aimed at providing population-level evidence on the correlation between the characteristics of primary healthcare across Italian regions and health outcomes included in the National Programs Outcomes of the National Agency for Regional Healthcare Services. Study Design: Ecological study. Methods: We analysed healthcare data from the National Agency for Regional Healthcare Services, the public lists of primary care doctors and the National Federation of Surgeons and Dentists and the National Institutes of Statistics referring to the 20 Italian regions. Pearson's correlation and Spearman's correlation were used to assess the relationships between primary healthcare characteristics and health outcomes. Results: Overall, across all Italian regions each general practitioner had on average 1447 patients and was 57.5 years old. The study found positive correlations between the number of patients per general practitioner and non-urgent Emergency Department visits among adult patients (Pearson's r = 0.58, p = 0.008), the number of residents aged 65+ per general practitioner and the rate of chronic obstructive pulmonary disease admissions (Pearson's r = 0.49, p = 0.029), and the age of general practitioners and lower-extremity amputations in diabetes patients (Pearson's r = 0.56, p = 0.011). A negative correlation was observed between the age of general practitioners and urinary tract infection admissions (Pearson's r = -0.76; p < 0.001). A non-linear negative correlation was found between the age of general practitioners and chronic obstructive pulmonary disease admissions (Spearman's ρ = -0.46, p = 0.041). Conclusions: The findings emphasise the importance of guaranteeing sufficient numbers of primary healthcare physicians to meet patients' needs, and for limiting avoidable hospitalisations and emergency presentations. General practitioners' age might also influence the provision of care, but more research is needed on possible mechanisms.

Primary care doctors retirements in the context of an ageing population in Italy.

Background: Ongoing shortages in primary care doctors/primary care paediatricians and increasing healthcare needs due to ageing of the population represent a great challenge for healthcare providers, managers, and policymakers. To support planning of primary healthcare resource allocation we analyzed the geographic distribution of primary care doctors/primary care paediatricians across Italian regions, accounting for area-specific number and age of the population. Additionally, we estimated the number of primary care doctors/primary care paediatricians expected to retire over the next 25 years, with a focus on the next five years. Study design: Ecological study. Methods: We gathered the list of Italian general practitioners and primary care paediatricians and combined them with the data from the National Federation of Medical Doctors, Surgeons and Dentists. Using data from the National Institutes of Statistics, we calculated the average number of patients per doctor for each region using the number of residents above and under 14 years of age for general practitioners and primary care paediatricians respectively. We also calculated the number of residents over-65 and over-75 years of age per general practitioner, as elderly patients typically have higher healthcare needs. Results: On average the number of patients per general practitioner was 1,447 (SD: 190), while for paediatricians it was 1,139 (SD: 241), with six regions above the threshold of 1,500 patients per general practitioner and only one region under the threshold of 880 patients per paediatrician. We estimated that on average 2,228 general practitioners and 444 paediatricians are going to retire each year for the next five years, reaching more than 70% among the current workforce for some southern regions. The number of elderly patients per general practitioner varies substantially between regions, with two regions having >15% more patients aged over 65 years compared to the expected number. Conclusions: The study highlighted that some regions do not currently have the required primary care workforce, and the expected retirements and the ageing of the population will exacerbate the pressure on the already over-stretched healthcare services. A response from healthcare administrations and policymakers is urgently required to allow equitable access to quality primary care across the country.

Impact of the Covid pandemic on timely cancer diagnosis across European healthcare settings: a scoping review.

Introduction: The COVID-19 pandemic presented unprecedented challenges to European healthcare systems. The study aimed to review the available evidence on the impact of the pandemic on the timely diagnosis of cancer across European countries. The primary objective was to examine changes in diagnostic pathways and stage at diagnosis during the pandemic, compared to the pre-pandemic period, across European countries, taking healthcare system characteristics and COVID-19 policies into account. Methods: We conducted a review of the impact of the pandemic on cancer diagnosis in Europe, analyzing primary studies from 2018 to 2023 using both quantitative and qualitative methods through searches in PubMed and Scopus databases. Study quality was assessed using the Mixed Methods Appraisal Tool. The main explanatory factors analyzed were grouped into two categories: Covid-policies (government responses, using the Oxford COVID-19 Government Response Tracker and its stringency index as key metrics) and healthcare characteristics (healthcare system models, expenditure and resources, including hospital beds and the ratio of medical doctors). Study design: Scoping review. Results: Overall, 127 papers were screened, 80 retrieved for full-text evaluation and 50 articles were included in the review. The studies encompassed a total of 509,753 patients from 17 European countries. The pandemic period was characterised by worse process and outcome measures for all examined cancers, except for lung cancer, compared to the pre-pandemic period. Group-ing countries based on government actions and policy responses (stringency index) did not show any differences in timely cancer diagnosis. Countries with lower healthcare expenditure (per capita expenditure <2,000 euros) or lower investments in prevention reported more cancer diagnostic delays during the pandemic. Countries with >20% of General Practitioners over the total number of physicians and with more hospital beds per population experienced fewer diagnostic delays during the pandemic. Conclusions: Overall, the review suggests that diagnostic pathways and cancer stage at diagnosis during the COVID-19 pandemic varied across Europe, with countries' healthcare expenditure, investments in prevention, the proportion of General Practitioners and the number of hospital beds per population possibly playing a role. This analysis can inform healthcare policies aimed at addressing post-pandemic challenges and formulating resilience plans for future emergencies.

Phenotypes and rates of cancer-relevant symptoms and tests in the year before cancer diagnosis in UK Biobank and CPRD Gold.

Early diagnosis of cancer relies on accurate assessment of cancer risk in patients presenting with symptoms, when screening is not appropriate. But recorded symptoms in cancer patients pre-diagnosis may vary between different sources of electronic health records (EHRs), either genuinely or due to differential completeness of symptom recording. To assess possible differences, we analysed primary care EHRs in the year pre-diagnosis of cancer in UK Biobank and Clinical Practice Research Datalink (CPRD) populations linked to cancer registry data. We developed harmonised phenotypes in Read v2 and CTV3 coding systems for 21 symptoms and eight blood tests relevant to cancer diagnosis. Among 22,601 CPRD and 11,594 UK Biobank cancer patients, 54% and 36%, respectively, had at least one consultation for possible cancer symptoms recorded in the year before their diagnosis. Adjusted comparisons between datasets were made using multivariable Poisson models, comparing rates of symptoms/tests in CPRD against expected rates if cancer site-age-sex-deprivation associations were the same as in UK Biobank. UK Biobank cancer patients compared with those in CPRD had lower rates of consultation for possible cancer symptoms [RR: 0.61 (0.59-0.63)], and lower rates for any primary care consultation [RR: 0.86 (95%CI 0.85-0.87)]. Differences were larger for 'non-alarm' symptoms [RR: 0.54 (0.52-0.56)], and smaller for 'alarm' symptoms [RR: 0.80 (0.76-0.84)] and blood tests [RR: 0.93 (0.90-0.95)]. In the CPRD cohort, approximately representative of the UK population, half of cancer patients had recorded symptoms in the year before diagnosis. The frequency of non-specific presenting symptoms recorded in the year pre-diagnosis of cancer was substantially lower among UK Biobank participants. The degree to which results based on highly selected biobank cohorts are generalisable needs to be examined in disease-specific contexts.

A taxonomy of early diagnosis research to guide study design and funding prioritisation.

Researchers and research funders aiming to improve diagnosis seek to identify if, when, where, and how earlier diagnosis is possible. This has led to the propagation of research studies using a wide range of methodologies and data sources to explore diagnostic processes. Many such studies use electronic health record data and focus on cancer diagnosis. Based on this literature, we propose a taxonomy to guide the design and support the synthesis of early diagnosis research, focusing on five key questions: Do healthcare use patterns suggest earlier diagnosis could be possible? How does the diagnostic process begin? How do patients progress from presentation to diagnosis? How long does the diagnostic process take? Could anything have been done differently to reach the correct diagnosis sooner? We define families of diagnostic research study designs addressing each of these questions and appraise their unique or complementary contributions and limitations. We identify three further questions on relationships between the families and their relevance for examining patient group inequalities, supported with examples from the cancer literature. Although exemplified through cancer as a disease model, we recognise the framework is also applicable to non-neoplastic disease. The proposed framework can guide future study design and research funding prioritisation.

Innovative COVID-19 diagnostics and testing strategies in Italy, Denmark, UK, Israel and Sweden: a comparative analysis including tests, incidence and mortality.

Detecting SARS-CoV-2 remains a critical component in the global effort to control COVID-19, particularly with the emergence of variants. Since the outbreak, diagnostic techniques have evolved to meet different contexts and needs. Methods: In this study, we analyzed the use of these techniques in five countries (i.e. Italy, Denmark, the United Kingdom, Sweden, and Israel) based on their specific national testing and contact tracing strategies. We also examined the number of tests performed per week, the positivity rate of tests, and the mortality rate in these populations during the same time periods. These countries were chosen based on the directives of the consortium involved in the CORONADX project.

Delays in cancer diagnosis: challenges and opportunities in Europe.

BACKGROUND AND AIM: Early cancer diagnosis is a public health priority, but large proportions of patients are diagnosed with advanced disease or as an emergency, even in countries with universal healthcare coverage. The study aimed at examining factors contributing to diagnostic delays and inequalities in cancer care, discussing challenges and opportunities for improving the diagnosis of cancer. METHODS: We performed a critical review of the literature examining factors contributing to delays and inequalities in cancer diagnosis, published between 2019-2023, in Europe with a specific focus on Italy. RESULTS: Disparities in screening, cancer diagnosis and treatment have been reported in many European countries, with poorer outcomes for some population sub-groups. For example, some Northern regions in Italy have six-times higher screening participation versus Southern regions. In 2019 36% of the Italian population aged 50-74 reported colorectal cancer screening, higher than the EU average (33%), but lower than in countries like Denmark (>60%). In Italy, the EU country with the largest percentage of people aged 65+, incident cancers are expected to rise by 19.6% over two decades. Older age is also associated with multimorbidity, with physical and mental health morbidities possibly affecting cancer diagnostic pathways. For example, colon cancer patients with pre-existing mental health conditions were 28% less likely to have a prompt colonoscopy when presenting with red-flag symptoms, according to recent UK research. Covid-19 has exacerbated pre-existing inequalities, with reductions in scheduled surgery and oncological treatments, especially affecting women, older and less educated individuals. CONCLUSIONS: For ensuring appropriate care, it is crucial to better understand how different factors, including physical and mental health morbidities, impact cancer diagnosis. The "NextGenerationEU" program and the "National Recovery and Resilience Plan" (PNNR in Italy) following the Covid-19 pandemic offer opportunities for reducing inequalities, improving cancer care and chronic disease management for ageing populations.

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.

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.

Underlying cancer risk among patients with fatigue and other vague symptoms: a population-based cohort study in primary care.

BACKGROUND: Presenting to primary care with fatigue is associated with slightly increased cancer risk, although it is unknown how this varies in the presence of other 'vague' symptoms. AIM: To quantify cancer risk in patients with fatigue who present with other 'vague' symptoms in the absence of 'alarm' symptoms for cancer. DESIGN AND SETTING: Cohort study of patients presenting in UK primary care with new-onset fatigue during 2007-2015, using Clinical Practice Research Datalink data linked to national cancer registration data. METHOD: Patients presenting with fatigue without co-occurring alarm symptoms or anaemia were identified, who were further characterised as having co-occurrence of 19 other 'vague' potential cancer symptoms. Sex- and age-specific 9-month cancer risk for each fatigue-vague symptom cohort were calculated. RESULTS: Of 285 382 patients presenting with new-onset fatigue, 84% (n = 239 846) did not have co-occurring alarm symptoms or anaemia. Of these, 38% (n = 90 828) presented with ≥1 of 19 vague symptoms for cancer. Cancer risk exceeded 3% in older males with fatigue combined with any of the vague symptoms studied. The age at which risk exceeded 3% was 59 years for fatigue-weight loss, 65 years for fatigue-abdominal pain, 67 years for fatigue-constipation, and 67 years for fatigue-other upper gastrointestinal symptoms. For females, risk exceeded 3% only in older patients with fatigue-weight loss (from 65 years), fatigue-abdominal pain (from 79 years), or fatigue-abdominal bloating (from 80 years). CONCLUSION: In the absence of alarm symptoms or anaemia, fatigue combined with specific vague presenting symptoms, alongside patient age and sex, can guide clinical decisions about referral for suspected cancer.

The Effect of Older Age and Frailty on the Time to Diagnosis of Cancer: A Connected Bradford Electronic Health Records Study.

Over 60% of cancer diagnoses in the UK are in patients aged 65 and over. Cancer diagnosis and treatment in older adults is complicated by the presence of frailty, which is associated with lower survival rates and poorer quality of life. This population-based cohort study used a longitudinal database to calculate the time between presentation to primary care with a symptom suspicious of cancer and a confirmed cancer diagnosis for 7460 patients in the Bradford District. Individual frailty scores were calculated using the electronic frailty index (eFI) and categorised by severity. The median time from symptomatic presentation to cancer diagnosis for all patients was 48 days (IQR 21-142). 23% of the cohort had some degree of frailty. After adjustment for potential confounders, mild frailty added 7 days (95% CI 3-11), moderate frailty 23 days (95% CI 4-42) and severe frailty 11 days (95% CI -27-48) to the median time to diagnosis compared to not frail patients. Our findings support use of the eFI in primary care to identify and address patient, healthcare and system factors that may contribute to diagnostic delay. We recommend further research to explore patient and clinician factors when investigating cancer in frail patients.

Steroid prescribing in primary care increases prior to Hodgkin lymphoma diagnosis: A UK nationwide case-control study.

BACKGROUND: Steroid use is associated with increased risk of Hodgkin lymphoma (HL). However, allergic symptoms commonly treated with steroids are also presenting features of HL in some patients, thereby introducing protopathic bias in estimates of aetiological associations. It is therefore important to examine steroid prescribing patterns pre-diagnosis to understand timing of associations and when healthcare use increases before cancer diagnosis to inform future epidemiological study design. METHODS: We analysed steroid prescribing in 1232 HL patients and 7392 matched controls using primary care electronic health records (Clinical Practice Research Datalink (CPRD), 1987-2016). Using Poisson regression, we calculated monthly steroid prescribing rates for the 24-months preceding HL diagnosis, identifying the inflection point when they start to increase from baseline in cases, comparing rates with synchronous controls, and stratifying by route-of-administration and allergic disease status. RESULTS: 46 % of HL patients had a steroid prescription in the 24-months preceding diagnosis compared to 26 % of controls (OR 2.55, 95 %CI 2.25-2.89, p < 0.001). Odds of underlying HL were greatest in patients receiving multiple steroid prescriptions, oral steroids and in patients with a new allergic disease diagnosis. Among HL patients, steroid prescribing rates increased progressively from 7-months pre-diagnosis, doubling from 52 to 111 prescriptions/1000 patients/month. CONCLUSION: Steroid prescribing increases during periods leading up to HL diagnosis, suggesting steroid-treated symptoms may be early presenting features of HL. A diagnostic window of appreciable length exists for potential earlier HL diagnosis in some patients; this 7-month 'lag-period' pre-diagnosis should be excluded in studies examining aetiological associations between steroids and HL.

Mental Health Morbidities and Time to Cancer Diagnosis Among Adults With Colon Cancer in England.

Importance: Mental health morbidity (MHM) in patients presenting with possible cancer symptoms may be associated with prediagnostic care and time to cancer diagnosis. Objective: To compare the length of intervals to cancer diagnosis by preexisting MHM status in patients who presented with symptoms of as-yet-undiagnosed colon cancer and evaluate their risk of emergency cancer diagnosis. Design, Setting, and Participants: This cohort study was conducted using linked primary care data obtained from the population-based Clinical Practice Research Datalink, which includes primary care practices in England, linked to cancer registry and hospital data. Included participants were 3766 patients diagnosed with colon cancer between 2011 and 2015 presenting with cancer-relevant symptoms up to 24 months before their diagnosis. Data analysis was performed in January 2021 to April 2022. Exposures: Mental health conditions recorded in primary care before cancer diagnosis, including anxiety, depression, schizophrenia, bipolar disorder, alcohol addiction, anorexia, and bulimia. Main Outcomes and Measures: Fast-track (also termed 2-week wait) specialist referral for investigations, time to colonoscopy and cancer diagnosis, and risk of emergency cancer diagnosis. Results: Among 3766 patients with colon cancer (median [IQR] age, 75 [65-82] years; 1911 [50.7%] women ), 623 patients [16.5%] had preexisting MHM recorded in primary care the year before cancer diagnosis, including 562 patients (14.9%) with preexisting anxiety or depression (accounting for 90.2% of patients with preexisting MHM) and 61 patients (1.6%) with other MHM; 3143 patients (83.5%) did not have MHM. Patients with MHM had records of red-flag symptoms or signs (ie, rectal bleeding, change in bowel habit, or anemia) in the 24 months before cancer diagnosis in a smaller proportion compared with patients without MHM (308 patients [49.4%] vs 1807 patients [57.5%]; P < .001). Even when red-flag symptoms were recorded, patients with MHM had lower odds of fast-track specialist referral (adjusted odds ratio [OR] = 0.72; 95% CI, 0.55-0.94; P = .01). Among 2115 patients with red-flag symptoms or signs, 308 patients with MHM experienced a more than 2-fold longer median (IQR) time to cancer diagnosis (326 [75-552] days vs 133 [47-422] days) and higher odds of emergency diagnosis (90 patients [29.2%] vs 327 patients [18.1%]; adjusted OR = 1.63; 95% CI, 1.23-2.24; P < .001) compared with 1807 patients without MHM. Conclusions and Relevance: This study found that patients with MHM experienced large and prognostically consequential disparities in diagnostic care before a colon cancer diagnosis. These findings suggest that appropriate pathways and follow-up strategies after symptomatic presentation are needed for earlier cancer diagnoses and improved health outcomes in this large patient group.

Factors influencing symptom appraisal and help-seeking of older adults with possible cancer: a mixed-methods systematic review.

BACKGROUND: The cancer burden falls predominantly on older (≥65 years) adults. Prompt presentation to primary care with cancer symptoms could result in earlier diagnosis. However, patient symptom appraisal and help-seeking decisions involving cancer symptoms are complex and may be further complicated in older adults. AIM: To explore the effect of older age on patients' appraisal of possible cancer symptoms and their decision to seek help for these symptoms. DESIGN AND SETTING: Mixed-methods systematic review. METHOD: MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Library, Web of Science Core Collection, ASSIA, the ISRCTN registry, and the National Institute for Health and Care Excellence were searched for studies on symptom appraisal and help-seeking decisions for cancer symptoms by adults aged ≥65 years. Studies were analysed using thematic synthesis and according to the Synthesis Without Meta-Analysis guidelines. RESULTS: Eighty studies were included with a total of 32 995 participants. Studies suggested a possible association between increasing age and prolonged symptom appraisal interval. Reduced knowledge of cancer symptoms and differences in symptom interpretation may contribute to this prolonged interval. In contrast, in the current study a possible association was found between increasing age and prompt help-seeking. Themes affecting help-seeking in older adults included the influence of family and carers, competing priorities, fear, embarrassment, fatalism, comorbidities, a desire to avoid doctors, a perceived need to not waste doctors' time, and patient self-management of symptoms. CONCLUSION: This review suggests that increasing age is associated with delayed cancer symptom appraisal. When symptoms are recognised as potentially serious, increasing age was associated with prompt help-seeking although other factors could prolong this. Policymakers, charities, and GPs should aim to ensure older adults are able to recognise potential symptoms of cancer and seek help promptly.

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.

How does safety netting for lung cancer symptoms help patients to reconsult appropriately? A qualitative study.

BACKGROUND: Safety netting in primary care is considered an important intervention for managing diagnostic uncertainty. This is the first study to examine how patients understand and interpret safety netting advice around low-risk potential lung cancer symptoms, and how this affects reconsultation behaviours. METHODS: Qualitative interview study in UK primary care. Pre-covid-19, five patients were interviewed in person within 2-3 weeks of a primary care consultation for potential lung cancer symptom(s), and again 2-5 months later. The general practitioner (GP) they last saw was interviewed face-to-face once. During the covid-19 pandemic, an additional 15 patients were interviewed only once via telephone, and their GPs were not interviewed or contacted in any way. Audio-recorded interviews were transcribed verbatim and analysed using inductive thematic analysis. RESULTS: The findings from our thematic analysis suggest that patients prefer active safety netting, as part of thorough and logical diagnostic uncertainty management. Passive or ambiguous safety netting may be perceived as dismissive and cause delayed reconsultation. GP safety netting strategies are not always understood, potentially causing patient worry and dissatisfaction. Telephone consultations and the diagnostic overshadowing of COVID-19 on respiratory symptoms impacted GPs' safety netting strategies and patients' appetite for active follow up measures. CONCLUSIONS: Safety netting guidelines do not yet offer solutions that have been proven to promote symptom vigilance and timely reconsultation for low-risk lung cancer symptoms. This may have been affected by primary care practices during the COVID-19 pandemic. Patients prefer active or pre-planned safety netting coupled with thorough consultation techniques and a comprehensible diagnostic strategy, and may respond adversely to passive safety netting advice.