Antibody responses after first and second Covid-19 vaccination in patients with chronic lymphocytic leukaemia.

B-cell chronic lymphocytic leukaemia (CLL) is associated with immunosuppression and patients are at increased clinical risk following SARS-CoV-2 infection. Covid-19 vaccines offer the potential for protection against severe infection but relatively little is known regarding the profile of the antibody response following first or second vaccination. We studied spike-specific antibody responses following first and/or second Covid-19 vaccination in 299 patients with CLL compared with healthy donors. 286 patients underwent extended interval (10-12 week) vaccination. 154 patients received the BNT162b2 mRNA vaccine and 145 patients received ChAdOx1. Blood samples were taken either by venepuncture or as dried blood spots on filter paper. Spike-specific antibody responses were detectable in 34% of patients with CLL after one vaccine (n = 267) compared to 94% in healthy donors with antibody titres 104-fold lower in the patient group. Antibody responses increased to 75% after second vaccine (n = 55), compared to 100% in healthy donors, although titres remained lower. Multivariate analysis showed that current treatment with BTK inhibitors or IgA deficiency were independently associated with failure to generate an antibody response after the second vaccine. This work supports the need for optimisation of vaccination strategy in patients with CLL including the potential utility of booster vaccines.

Primary care management of early stage chronic lymphocytic leukaemia is safe and effective.

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the commonest leukaemia in western society. Most patients are detected incidentally at an early stage and require 'watch and wait' follow-up. In the UK, management of Stage A0 CLL varies with some centres advising regular outpatient haematology follow-up, whereas others recommend management within primary care. The safety and effectiveness of these two management options are currently unknown. METHODS: An observational retrospective cohort study in outpatient Haematology clinics at Queen Elizabeth Hospital Birmingham (QEH) and Birmingham Heartlands Hospital (BHH) and primary care practices in West Midlands, UK. All patients diagnosed with stable stage A0 CLL since 2002 at BHH or QEH were identified. At BHH, patients were discharged to primary care follow-up, whilst QEH patients remained under haematology for follow-up. Evidence of disease progression, need for treatment and overall mortality was documented. RESULTS: Two hundred and forty-six Stage A0 CLL patients were identified. One hundred and five (43%) patients were discharged to primary care, whilst 141 (57%) patients were followed up in haematology outpatient clinics. No difference in mortality or need for treatment was found between the two groups. Of those discharged, 93 (66%) remained in primary care. CONCLUSION: The management of stable-stage A0 CLL within primary or secondary care leads to equivalent clinical outcomes. The prevalence of early-stage CLL is expected to increase with the ageing population and management within primary care should be considered as a potentially effective approach.

Patterns of self-management practices undertaken by cancer survivors: variations in demographic factors.

The study purpose was to examine self-management (SM) use among cancer survivors; and to explore variations in uptake of SM in survivorship and whether these differed in relation to age, income, gender, ethnicity, cancer type and treatment type. This is an important area for exploration as SM utilisation has the potential to impact on the health status, health behaviours and quality of life (QoL) of cancer survivors. A postal survey was conducted among 445 cancer survivors identified from a hospital in the West Midlands, UK. Demographic data were collected and respondents were asked to identify which practices across six SM categories - diet, exercise, complementary and alternative medicine (CAM), psychological therapies, support groups and spirituality/religion - they had used (if any). The findings indicate that the large majority (91%) had used some form of SM after their cancer treatment. Exercise (84%) and diet (56%) were the most popular SM interventions for cancer survivors and socio-demographic and cancer-related factors were associated with SM uptake. These findings can form the basis for designing and implementing appropriate SM interventions aimed at improving the health, well-being and QoL of cancer survivors.

Patient preferences for clinical follow-up after primary treatment for soft tissue sarcoma: a cross-sectional survey and discrete choice experiment.

BACKGROUND: Patients treated for soft tissue sarcoma (STS) require long-term follow-up to detect recurrent or metastatic disease, yet marked differences exist in clinical approaches to the length of follow-up, frequency of consultations and investigations undertaken at follow-up visits. There has been no published work assessing patient expectations or the acceptability of post-treatment follow-up strategies. This study aimed to assess the patient acceptability of different follow-up strategies following curative surgery for soft tissue sarcoma and to investigate the hypothetical levels of recurrence risk at which different follow-up regimes were acceptable. METHODS: Patients were recruited from the Royal Orthopaedic Hospital in Birmingham. The study used a cross-sectional survey incorporating a best-worst scaling discrete choice experiment to assess patient preferences regarding different aspects of follow-up. RESULTS: 132 patients participated (47% response). The nature of investigations undertaken during follow-up was the most important aspect of post-surgical care. Patients typically preferred appointments routinely consisting of clinical examination and chest X-ray, and for follow-up to remain in secondary care rather than general practice. CONCLUSION: Clear protocols for STS patient follow-up can improve consistency and equity of care. In determining the optimum follow-up plan for STS patients from the patient perspective, this study provides valuable information that should be considered alongside the clinical effectiveness of follow-up strategies to maximise patient outcomes and use NHS resources appropriately.

Evaluation of serum lysyl oxidase as a blood test for colorectal cancer.

AIMS: Lysyl oxidase (LOX) expression is elevated in colorectal cancer (CRC) tissue and associated with disease progression. A blood test may form a more acceptable diagnostic test for CRC although LOX has not previously been measured in the serum. We therefore sought to determine the clinical usefulness of a serum LOX test for CRC in a symptomatic population. METHODS: Adult patients referred to a hospital colorectal clinic with bowel symptoms completed a questionnaire and provided a blood sample for serum LOX measurement. Associations between presenting symptoms, serum LOX concentrations and outcomes of investigations were tested by univariate and multivariate analyses to determine if serum LOX was clinically useful in the prediction of CRC. LOX expression in CRC and adjacent colon biopsies was evaluated by ELISA and immunohistochemistry. RESULTS: Thirty-one cases of colorectal cancer and 16 high-risk polyps were identified from a total of 962 participants. There was no association between serum LOX concentration and the presence of CRC, high-risk polyps or cancers at any site. LOX expression was significantly increased in CRC tissue compared to adjacent colon. CONCLUSION: Despite overexpression of LOX in CRC tissue, elevated serum levels could not be demonstrated. Serum LOX measurement is therefore not a clinically useful test for CRC.

Assessing the value of matrix metalloproteinase 9 (MMP9) in improving the appropriateness of referrals for colorectal cancer.

BACKGROUND: A blood test may be an effective means of improving the appropriateness of referrals for symptomatic patients referred to specialist colorectal clinics. We evaluated the accuracy of a serum matrix metalloproteinase (MMP9) test in indicating colorectal cancer or its precursor conditions in a symptomatic population. METHODS: Patients aged over 18, referred urgently or routinely to secondary care following primary care presentation with colorectal symptoms completed a questionnaire and provided a blood sample for serum MMP9 estimation. Univariate analysis and logistic regression modelling investigated the association between presenting symptoms, MMP9 measurements and the diagnostic outcome of patient investigations, in order to derive the combination of factors which best predicted a high risk of malignancy. RESULTS: Data were analysed for 1002 patients. Forty-seven cases of neoplasia were identified. Age, male gender, absence of anal pain, diabetes, blood in stools, urgent referral, previous bowel polyps and previous bowel cancer were significantly associated with neoplasia. Matrix metalloproteinase 9 measurements were not found to be associated with significant colorectal pathology. CONCLUSION: This study, despite robust sampling protocols, showed no clear association between MMP9 and colorectal neoplasia. Matrix metalloproteinase 9 therefore appears to have little value as a tool to aid referral decisions in the symptomatic population.

Are women ready for the new cervical screening protocol in England? A systematic review and qualitative synthesis of views about human papillomavirus testing.

BACKGROUND: A new protocol for human papillomavirus (HPV) testing within the UK cervical screening programme commenced in April 2011, creating new patient experiences. This is the first review to synthesise a substantial body of international evidence of women's information needs, views and preferences regarding HPV testing. We aimed to inform the development of educational materials to promote informed choice, reduce anxiety and improve disease control. METHODS: We searched 12 bibliographic databases. Two reviewers independently screened papers and assessed study quality; disagreements were resolved by discussion. Results were extracted verbatim and authors' findings treated as primary data. Studies were synthesised collaboratively using framework methods. RESULTS: We synthesised findings from 17 studies. Women had overwhelmingly negative concerns; an HPV diagnosis was daunting, had associated problems of disclosure of a sexually transmitted infection (STI), impacted on relationships and provoked fear of stigmatisation. Nevertheless, many thought HPV testing could be a preferable alternative to repeat cytology. Knowledge was poor; women struggled to interpret limited information in the context of existing knowledge about STIs and cervical cancer. CONCLUSION: Women are likely to be poorly informed, have limited understanding and many unanswered questions. This could increase anxiety and reduce ability to make informed choices, presenting a substantial challenge for those who design and provide information.

Serum matrix metalloproteinase 9 and colorectal neoplasia: a community-based evaluation of a potential diagnostic test.

BACKGROUND: A blood test may be a more acceptable routine colorectal cancer (CRC) screening test than faecal occult blood test, flexible sigmoidoscopy or colonoscopy, and could be safer and cheaper. We evaluated the accuracy of a serum matrix metalloproteinase (MMP9) test for CRC in a non-presenting symptomatic population. METHODS: A cohort, aged 50-69 with lower gastrointestinal symptoms, was identified by community-based survey. Accuracy of serum MMP9 was assessed by comparison with colonoscopy. Logistic regression identified predictors of neoplasia and receiver operating characteristic curve analyses determined the cutoff to maximise the sensitivity. RESULTS: Data were available for 748 patients. Overall, 46 cases of neoplasia were identified. Univariate analysis demonstrated that demographic characteristics, behavioural factors, clinical symptoms and raised serum MMP9 concentration were all significantly associated with the presence of neoplasia. Our final logistic regression model had a sensitivity of 79% and specificity of 70%. CONCLUSION: We demonstrated a significant association between serum MMP9 concentration and the presence of neoplasia. Serum MMP9 levels are raised in those with cancer and high-risk adenomas, although MMP9 estimation is likely to have the greatest predictive utility when used as part of a panel of biomarkers. Further work is required to identify biomarkers that are sufficiently accurate for implementing into routine practice.

The effect of seeking consent on the representativeness of patient cohorts: iron-deficiency anaemia and colorectal cancer.

AIM: The study aimed to establish the level of selection bias that may occur should individual patient consent be sought, by comparing characteristics of consenters and nonconsenters to a request for access to medical records within a cohort of patients diagnosed with iron-deficiency anaemia (IDA). METHOD: A cohort study and cross-sectional survey was carried out of consent preferences that compared the sociodemographic characteristics of patients providing or not providing consent for access to their records, the consent rates by participant subgroup and the predictors of consent/nonconsent. RESULTS: Of 599 patients mailed requesting consent for access to their medical records, 425 (71.0%) responses were received. Of the valid responses, explicit consent was granted by 371 (62.7%) respondents, with 47 (7.9%) refusals. The characteristics of consenters and nonconsenters differed with regard to age, gender and deprivation quartile. Nonconsent was associated with younger age (40-60 years vs 60 + years; bivariate OR = 2.84; 95% CI = 2.01-4.02), female gender (OR = 1.62; 95% CI = 1.13-2.34) and being socioeconomically deprived (OR = 1.61; 95% CI = 1.15-2.26). CONCLUSION: The current research governance framework demonstrates a conflict between protecting the rights of the individual and the development of a sound research base to improve the delivery of healthcare services for society as a whole. If epidemiological research includes data only from individuals who have given consent for access to their records, the resulting selection bias may have consequences for the scientific validity and generalizability of research findings, and ultimately the quality of patient care.

Pandemic influenza A (H1N1) 2009 in a critical care and theatre setting: beliefs and attitudes towards staff vaccination.

West Midlands was particularly affected by the 2009 H1N1 influenza A (pH1N1) pandemic. Vaccination of frontline healthcare professionals (HCPs) aimed to prevent spread to vulnerable patients, minimise service disruption and protect staff. HCPs involved in upper airway management are particularly at risk of aerosol exposure. We assessed the attitudes of these HCPs towards pandemic influenza A (H1N1) 2009 vaccination uptake: primary reasons for acceptance, barriers to vaccination, and knowledge surrounding pH1N1 influenza. We performed a voluntary, anonymous questionnaire survey based in two West Midlands National Health Service Trusts, one month after introduction of the vaccine. In all, 187 useable responses were received (60.5% response rate); 43.8% (N=82) had/intended to receive vaccination. Concern over long term side-effects was the main deterrent (37.4%, N=70). Primary reasons for potentially accepting vaccination were: to protect themselves (36.9%, N=69), to protect family (35.3%, N=66), and to protect patients (10.2%, N=19). Of responders, 76.5% were unsure that the vaccines had undergone suitably rigorous clinical trials to ensure safety; 20.9% correctly identified reported vaccine efficacy. We conclude that pH1N1 vaccination uptake among high risk HCPs remained low, although twice that of peak seasonal influenza vaccination rates. HCPs' knowledge of vaccine efficacy is poor. Barriers to vaccination include concerns over safety profile given the short chronological time-span between the pandemic being declared and vaccine introduction. Side-effects, both acute and chronic, are a significant barrier to vaccination. Further reassurance/education surrounding vaccine safety/efficacy at the time of any future pandemic may improve uptake rates.

The use of herbal medicines by people with cancer: a cross-sectional survey.

BACKGROUND: A large proportion of cancer patients are estimated to use herbal medicines, but data to substantiate this are lacking. This study aimed to investigate the prevalence of herbal medicine use among cancer patients in the West Midlands, and determine the characteristics predicting herbal medicine use. METHODS: A cross-sectional survey of oncology patients (n=1498) being followed up at a hospital in Coventry was undertaken. Recipients were asked about herbal medicine use since their cancer diagnosis, and the association between sociodemographic and cancer-related characteristics and herbal medicine use was evaluated. RESULTS: A total of 1134 responses were received (75.7%). The prevalence of herbal medicine use was 19.7% (95% CI: 17.4-22.1; n=223). Users were more likely to be affluent, female, and aged under 50 years. Usage increased with time since cancer diagnosis (X(2) for trend=4.63; P=0.031). A validation data set, derived from a survey of oncology patients in Birmingham (n=541) with differing socioeconomic characteristics showed no significant difference in estimated prevalence (16.6%; 95% CI: 11.9-22.2). CONCLUSION: A substantial number of people with cancer are likely to be taking herbal medicines. Understanding the self-medication behaviours of these individuals is essential if health-care professionals are to support treatment adherence and avoid unwanted pharmacological interactions.

Iron deficiency anaemia and delayed diagnosis of colorectal cancer: a retrospective cohort study.

AIM: The extent to which different referral pathways following a primary care diagnosis of iron deficiency anaemia (IDA) are associated with delay in diagnosis of colorectal cancer (CRC) was determined. METHOD: Eligible patients aged 40 or more years, with IDA diagnosed in primary care, and a subsequent diagnosis of CRC, were studied retrospectively. Referral pathways were identified using the specialty of first recorded GP referral following IDA diagnosis. Differences in time to diagnosis of CRC were assessed by referral specialty. Differences in the proportion of cases referred before and after the re-issue of the NICE urgent referral guidelines for suspected lower gastrointestinal (GI) cancer were also assessed. RESULTS: Of 628,882 eligible patients, 3.1% (n = 19,349) were diagnosed with IDA during the study period; 3.0% (n = 578) were subsequently diagnosed with CRC. Two hundred and fifty-nine (44.8%) patients had no recorded referral or a referral unrelated to anaemia or the GI tract. Only 35% (n = 201) of patients were referred to a relevant specialty. Median time to CRC diagnosis ranged from 2.5 months (referral to a relevant surgical specialty) to 31.9 months (haematology). Time to diagnosis was longer in patients referred to a medical compared with a relevant surgical specialty (P = 0.024). There was no significant difference in time to CRC diagnosis before and after the NICE guidelines were re-issued in 2005. CONCLUSION: Significant differences exist between referral specialties in time to CRC diagnosis following a primary care diagnosis of IDA. Despite NICE referral recommendations, a significant proportion of patients are still not managed within recommended care pathways to CRC diagnosis.

How do the information needs of cancer patients differ at different stages of the cancer journey? A cross-sectional survey.

OBJECTIVES: Providing information to cancer patients can have significant benefits to their psychological wellbeing. The aim of this study was to investigate whether and how information needs may differ for patients at different stages of the cancer journey. DESIGN: Cross-sectional, self-completed survey using convenience sampling. SETTING: Oncology outpatients in Wolverhampton, West Midlands. PARTICIPANTS: Cancer patients aged 18 years and over. MAIN OUTCOME MEASURES: The survey used Likert scales to determine whether patients wished to know more about 35 items of information categorized under seven domains: cancer (diagnosis); prognosis; treatment; rehabilitation; psychological/spiritual; social/family; and body image/sexuality. Each domain was scored, with higher scores indicating a greater wish for information. RESULTS: There were 187 participants (50% response rate). Patients tended to want more information, particularly related to prognosis. Post-treatment patients continued to have information needs comparable to patients undergoing treatment or at the pre-treatment stage, except with reference to treatment-related information (p = <0.01), although as time from diagnosis increased, information needs reduced. Educational attainment, age, treatment status, gender and ethnicity were all significant predictors of scores in various domains. CONCLUSION: This study indicates that the time since diagnosis may interact with various demographic and disease-related factors in contributing to the information needs of cancer patients. The majority of cancer patients wish to know more about a wide range of factors, and such information seeking preferences are present regardless of an individual's stage following diagnosis.

Healthcare workers' perceptions of the duty to work during an influenza pandemic.

Healthcare workers (HCWs) are often assumed to have a duty to work, even if faced with personal risk. This is particularly so for professionals (doctors and nurses). However, the health service also depends on non-professionals, such as porters, cooks and cleaners. The duty to work is currently under scrutiny because of the ongoing challenge of responding to pandemic influenza, where an effective response depends on most uninfected HCWs continuing to work, despite personal risk. This paper reports findings of a survey of HCWs (n = 1032) conducted across three National Health Service trusts in the West Midlands, UK, to establish whether HCWs' likelihood of working during a pandemic is associated with views about the duty to work. The sense that HCWs felt that they had a duty to work despite personal risk emerged strongly regardless of professional status. Besides a strong sense that everyone should pull together, all kinds of HCWs recognised a duty to work even in difficult circumstances, which correlated strongly with their stated likelihood of working. This suggests that HCWs' decisions about whether or not they are prepared to work during a pandemic are closely linked to their sense of duty. However, respondents' sense of the duty to work may conflict with their sense of duty to family, as well as other factors such as a perceived lack of reciprocity from their employers. Interestingly, nearly 25% of doctors did not consider that they had a duty to work where doing so would pose risks to themselves or their families.

The use of herbal medicines by people with cancer in the UK: a systematic review of the literature.

BACKGROUND AND AIM: Little is known about the use of herbal medicines by people living with cancer in the UK. This systematic review aimed to estimate the prevalence of herbal medicine use by this group, the characteristics of users, factors motivating use, and attitudes towards herbal remedies. DESIGN AND METHODS: Fifteen electronic databases were searched. People who were research-active in the field were contacted and asked about further published or unpublished work. All studies identified as relevant to the purpose of the review were assessed. Searches were not restricted by publication type or date. RESULTS: Of 1288 unique references identified, 11 met the eligibility criteria. Studies were excluded where research had been conducted outside the UK; where information on herbal medicine use was not differentiated from that relating to complementary and alternative therapies more broadly, and where neither prevalence of use nor information on user characteristics was included. Prevalence estimates ranged from 3.1 to 24.9%. Most studies did not obtain information specifically on herbal medicines and only one examined the characteristics and motivations of users of herbal medicines as distinct from complementary and alternative therapies in general. CONCLUSION: The high degree of heterogeneity of methodology, sample selection and characteristics, and research design resulted in a wide range of estimates of prevalence. Well-designed research is needed to define the evidence base about the herbal medicines taken by people with cancer in the UK, the reasons for use, knowledge about possible effects and potential risks, and where people seek information.

Factors affecting attitudes toward colorectal cancer screening in the primary care population.

BACKGROUND: Colorectal cancer (CRC) is a major cause of death in the United Kingdom. Regular screening could significantly reduce CRC-related morbidity and mortality. However, screening programmes in the United Kingdom have to date seen uptake rates of less than 60%. Attitudes towards screening are the primary factors determining patient uptake. METHODS: A questionnaire was sent to people aged 50-69 years who were registered with general practices in the West Midlands. A total of 11 355 people (53%) completed the questionnaire. Multivariable logistic regression analyses were performed to identify those factors (gender, age, ethnicity, deprivation, number of symptoms, and their duration) that most strongly contributed to negative/positive attitudes in the primary care population. RESULTS: Fourteen percent of respondents had a negative attitude towards screening. Men, older people, and those with Indian ethnic backgrounds were more likely to have negative attitudes toward screening, whereas people with Black-Caribbean ethnic background, people with multiple symptoms and those reporting abdominal pain, bleeding, and tiredness were more likely to have a positive attitude. CONCLUSION: Culturally relevant screening strategies should aim to increase knowledge of the symptoms and signs related to bowel cancer among South Asian ethnic groups in the United Kingdom. It is also important to find ways to increase the acceptability of screening among asymptomatic patients.