Socio-demographic disparities in HER2+ breast cancer trastuzumab receipt: An English population-based study.

BACKGROUND: Socio-demographic disparities in traditional breast cancer treatment receipt in non-publicly funded healthcare systems are well documented. This study investigated trastuzumab receipt by socio-demographic factors within a female, HER2+ breast cancer population in England's publicly funded National Health Service. METHODS: The English national population-based cancer registry and linked Systemic Anti-Cancer Therapy (SACT) database identified 36,985 women with HER2+ invasive breast cancer diagnosed 01/01/2012-31/12/2017. Multivariable logistic regression determined likelihood of trastuzumab receipt in (i) early and (ii) metastatic disease by deprivation category of area of residence and other socio-demographic characteristics. RESULTS: Early-stage trastuzumab receipt followed a socio-economic gradient. Women residing in the most deprived areas were 10% less likely to receive trastuzumab (multivariable OR 0.90, (95% CI) 0.83, 0.98) compared to women residing in the least deprived areas. In both early and metastatic disease, trastuzumab receipt was less likely in older women with more comorbidities, ER positive disease, and who were not discussed at a multidisciplinary team meeting. CONCLUSIONS: Despite provision of free at the point of delivery care in England, socio-demographic disparities in early-stage HER2+ trastuzumab receipt occur. Further research determining how inequities contribute to disparities in outcomes is warranted to ensure optimized trastuzumab use for all. IMPACT: Fair access to novel cancer treatments regardless of place of residence, socio-demographic characteristics, and/or cancer stage requires prioritization in future cancer improvement policies.

Cardiovascular and bone health outcomes in older people with subclinical hypothyroidism treated with levothyroxine: a systematic review and meta-analysis.

BACKGROUND: Thyroid dysfunction is common in older people, with females at higher risk. Evidence suggests that thyroid-stimulating hormone (TSH) levels naturally increase with age. However, as uniform serum TSH reference ranges are applied across the adult lifespan, subclinical hypothyroidism (SCH) diagnosis is more likely in older people, with some individuals also being commenced treatment with levothyroxine (LT4). It is unclear whether LT4 treatment in older people with SCH is associated with adverse cardiovascular or bone health outcomes. METHODS: A systematic review and meta-analysis were performed to synthesise previous studies evaluating cardiovascular and bone health outcomes in older people with SCH, comparing LT4 treatment with no treatment. PubMed, Embase, Cochrane Library, MEDLINE, and Web of Science databases were searched from inception until March 13, 2023, and studies that evaluated cardiovascular and bone health events in people with SCH over 50 years old were selected. RESULTS: Six articles that recruited 3853 participants were found, ranging from 185 to 1642 participants, with the proportion of females ranging from 45 to 80%. The paucity of data resulted in analysis for those aged over 65 years only. Additionally, a study with 12,212 participants aged 18 years and older was identified; however, only data relevant to patients aged 65 years and older were considered for inclusion in the systematic review. Of these 7 studies, 4 assessed cardiovascular outcomes, 1 assessed bone health outcomes, and 2 assessed both. A meta-analysis of cardiovascular outcomes revealed a pooled hazard ratio of 0.89 (95% CI 0.71-1.12), indicating no significant difference in cardiovascular risk between older individuals with SCH treated with LT4 compared to those without treatment. Due to overlapping sub-studies, meta-analysis for bone health outcomes was not possible. CONCLUSIONS: This systematic review and meta-analysis found no significant association between LT4 use and cardiovascular and bone health outcomes in SCH participants over 65 years. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022308006.

Knowledge and barriers of out of hospital cardiac arrest bystander intervention and public access automated external defibrillator use in the Northeast of England: a cross-sectional survey study.

Intervention by members of the public during an out of hospital cardiac arrest (OHAC) including resuscitation attempts and accessible automated external defibrillator (AED) has been shown to improve survival. This study aimed to investigate the OHCA and AED knowledge and confidence, and barriers to intervention, of the public of North East England, UK. This study used a face-to-face cross-sectional survey on a public high street in Newcastle, UK. Participants were asked unprompted to explain what they would do when faced with an OHCA collapse. Chi-Square analysis was used to test the association of the independent variables sex and first aid trained on the participants' responses. Of the 421 participants recruited to our study, 82.9% (n = 349) reported that they would know what to do during an OHCA collapse. The most frequent OHCA action mentioned was call 999 (64.1%, n = 270/421) and 58.2% (n = 245/421) of participants reported that they would commence CPR. However, only 14.3% (n = 60/421) of participants spontaneously mentioned that they would locate an AED, while only 4.5% (n = 19/421) recounted that they would apply the AED. Just over half of participants (50.8%, n = 214/421) were first aid trained, with statistically more females (57.3%, n = 126/220) than males (43.9%,  n = 87/198) being first aiders (p = 0.01 χ2 = 7.41). Most participants (80.3%, n = 338/421) knew what an AED was, and 34.7% (n = 326/421) reported that they knew how to use one, however, only 11.9% (n = 50/421) mentioned that they would actually shock a patient. Being first aid trained increased the likelihood of freely recounting actions for OHCA and AED intervention. The most common barrier to helping during an OHCA was lack of knowledge (29.9%, n = 126/421). Although most participants reported they would know what to do during an OHCA and had knowledge of an AED, low numbers of participants spontaneously mentioned specific OHCA and AED actions. Improving public knowledge would help improve the public's confidence of intervening during an OHCA and may improve OHCA survival.

Assessing the cardiovascular effects of levothyroxine use in an ageing United Kingdom population (ACEL-UK) protocol: a cohort and target trial emulation study.

BACKGROUND: Subclinical hypothyroidism is diagnosed when serum thyroid stimulating hormone levels are higher whilst free thyroxine levels remain within their respective reference ranges. These reference ranges are uniformly applied in all adults, despite serum thyroid stimulating hormone levels naturally increasing with age. Research has found that mildly elevated thyroid stimulating hormone levels may be associated with some benefits in ageing patients, including reduced mortality and better cardiorespiratory fitness. Levothyroxine is typically prescribed to patients with hypothyroidism, but no conclusive evidence exists on whether levothyroxine therapy is beneficial or detrimental in older subclinical hypothyroid patients. Despite this, prescriptions for levothyroxine are increasing year-on-year. This study aims to determine if receiving levothyroxine affects the cardiovascular and bone health outcomes of subclinical patients in primary care aged 50 years and over. METHODS: This project includes a retrospective cohort analysis and a target trial emulation study using electronic patient records collected between 2006 and 2021 and recorded in The Health Improvement Network database. The primary outcome of this study is to compare the cardiovascular outcomes of subclinical hypothyroid patients aged over 50 years treated with levothyroxine compared to those untreated. Secondary outcomes are bone health and all-cause mortality outcomes. Descriptive and inferential statistics will both be employed to analyse the data. Secondary analysis will explore confounding factors, including age, sex, smoking status, body mass index, co-morbidities, and levothyroxine dosage. DISCUSSION: There needs to be a greater understanding of the potential risks of the current treatment for older patients with subclinical hypothyroidism in a primary care setting. We will investigate the clinical importance of this issue and whether older subclinical hypothyroid patients have poorer outcomes when treated. Clarifying this concern may help address the healthcare resource implications of ageing patients being misclassified as having mild hypothyroidism, as these patients are more likely to repeat their blood tests. This could reduce prescription wastage and improve patient outcomes and quality of life in the ageing population. TRIAL REGISTRATION: Not applicable.

Quality in colonoscopy: time to ensure national standards are implemented?

Background: High-quality colonoscopy is crucial to ensure complete mucosal visualisation and to maximise detection of pathology. Previous audits showing variable quality have prompted national and international colonoscopy improvement programmes, including the development of quality assurance standards and key performance indicators (KPIs). The most widely used marker of mucosal visualisation is the adenoma detection rate (ADR), however, histological confirmation is required to calculate this. We explored the relationship between core colonoscopy KPIs. Methods: Data were collected from colonoscopists in eight hospitals in North East England over a 6-month period, as part of a quality improvement study. Procedural information was collected including number of colonoscopies, caecal intubation rate (CIR), ADR and polyp detection rate (PDR). Associations between KPIs and colonoscopy performance were analysed. Results: 9265 colonoscopies performed by 118 endoscopists were included. Mean ADR and PDR per endoscopist were 16.6% (range 0-36.3, SD 7.4) and 27.2% (range 0-57.5, SD 9.3), respectively. Mean number of colonoscopies conducted in 6 months was 78.5 (range 4-334, SD 61). Mean CIR was 91.2% (range 55.5-100, SD 6.6). Total number of colonoscopies and ADR>15% were significantly associated (p=0.04). Undertaking fewer colonoscopies and using hyoscine butylbromide less frequently was significantly associated with ADR<15%. CIR, endoscopist grade, % male patients, mean patient age and CIR were not significantly related to ADR<15%. In adjusted analyses, factors which affected ADR were PDR and mean patient age. Conclusion: Colonoscopists who perform fewer than the nationally stipulated minimum of 100 procedures per year had significantly lower ADRs. This study demonstrates that PDR can be used as a marker of ADR; providing age is also considered.

Socioeconomic Inequalities in Novel NSCLC Treatments During the Era of Tumor Biomarker-Guided Therapy: A Population-Based Cohort Study in a Publicly Funded Health Care System.

INTRODUCTION: Socioeconomic inequalities in the utilization of conventional NSCLC treatments are well documented. Nevertheless, it is not known whether these inequalities are also observed with novel anticancer therapies. This study evaluated associations between deprivation and utilization of novel anticancer therapies targeting tumor biology, the immune system, or both, within the English national publicly funded health care system. METHODS: A retrospective analysis of 90,785 patients diagnosed with having a histologically confirmed stage IV NSCLC from January 1, 2012, to December 31, 2017, sourced from the English national population-based cancer registry and linked Systemic Anti-Cancer Therapy database, was undertaken. Multivariable logistic regression evaluated the likelihood of novel anticancer therapy utilization by deprivation category of area of residence at diagnosis (measured by quintiles of the income domain of the index of multiple deprivation). RESULTS: Multivariable analyses revealed marked treatment inequalities by deprivation. Patients residing in the most deprived areas were more than half as likely to use any novel therapy (multivariable OR [mvOR] = 0.45, 95% confidence interval [CI]: 0.41-0.49) compared with patients residing in the most affluent areas. Deprivation associations with treatment utilization were slightly stronger with targeted treatments ([most versus least deprived] mvOR = 0.39, 95% CI: 0.35-0.43) than immune checkpoint inhibitors (mvOR = 0.58, 95% CI: 0.51-0.66). CONCLUSIONS: There are marked socioeconomic inequalities in NSCLC novel treatment utilization, even in the English National Health Service where treatment is free at the point of delivery. These findings have important implications for equitable delivery of drugs, which have transformed outcomes in metastatic lung cancer. Further work exploring the underlying causes is now needed.

Are there socio-economic inequalities in utilization of predictive biomarker tests and biological and precision therapies for cancer? A systematic review and meta-analysis.

BACKGROUND: Novel biological and precision therapies and their associated predictive biomarker tests offer opportunities for increased tumor response, reduced adverse effects, and improved survival. This systematic review determined if there are socio-economic inequalities in utilization of predictive biomarker tests and/or biological and precision cancer therapies. METHODS: MEDLINE, Embase, Scopus, CINAHL, Web of Science, PubMed, and PsycINFO were searched for peer-reviewed studies, published in English between January 1998 and December 2019. Observational studies reporting utilization data for predictive biomarker tests and/or cancer biological and precision therapies by a measure of socio-economic status (SES) were eligible. Data was extracted from eligible studies. A modified ISPOR checklist for retrospective database studies was used to assess study quality. Meta-analyses were undertaken using a random-effects model, with sub-group analyses by cancer site and drug class. Unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed for each study. Pooled utilization ORs for low versus high socio-economic groups were calculated for test and therapy receipt. RESULTS: Among 10,722 citations screened, 62 papers (58 studies; 8 test utilization studies, 37 therapy utilization studies, 3 studies on testing and therapy, 10 studies without denominator populations or which only reported mean socio-economic status) met the inclusion criteria. Studies reported on 7 cancers, 5 predictive biomarkers tests, and 11 biological and precision therapies. Thirty-eight studies (including 1,036,125 patients) were eligible for inclusion in meta-analyses. Low socio-economic status was associated with modestly lower predictive biomarker test utilization (OR 0.86, 95% CI 0.71-1.05; 10 studies) and significantly lower biological and precision therapy utilization (OR 0.83, 95% CI 0.75-0.91; 30 studies). Associations with therapy utilization were stronger in lung cancer (OR 0.71, 95% CI 0.51-1.00; 6 studies), than breast cancer (OR 0.93, 95% CI 0.78-1.10; 8 studies). The mean study quality score was 6.9/10. CONCLUSIONS: These novel results indicate that there are socio-economic inequalities in predictive biomarker tests and biological and precision therapy utilization. This requires further investigation to prevent differences in outcomes due to inequalities in treatment with biological and precision therapies.

Evaluation of the referral management systems (RMS) used by GP practices in Northumberland: a qualitative study.

OBJECTIVE: Exploring the views of stakeholders to the referral management systems (RMS) used by GP practices in Northumberland, UK to evaluate its perceived effectiveness. DESIGN: This was an in-depth qualitative semi-structured interview study. PARTICIPANTS AND SETTING: 32 participants (GPs, hospital consultants, referral support, hospital managers, Clinical Commissioning Group manager) in the North East of England, UK. METHOD: Interviews using a grounded theory approach and thematic analysis. RESULTS: The main benefit of RMS mentioned by participants was that it allowed for unnecessary referrals to be vetted by consultants, and helps ensure patients are sent to the correct clinic. Generally, the consultants in our study felt that RMS did not significantly help them reject referrals. Some GPs experienced that RMS undermined GP autonomy and did not help when they had exhausted their abilities to manage a patient in primary care, and it was suggested that in some cases RMS may delay rather than prevent a referral. The main perceived disadvantage of RMS was the additional workload for GPs and consultants, and RMS was felt to be a barrier to commutation between GPs and consultants. Frustration with the system design and lack of knowledge of its cost-effectiveness were articulated. CONCLUSION: Although RMS was reported to reduce some unnecessary referrals, the effect of referral delay and rejection is unknown. Although there were some positive attributes described, RMS was mostly received negatively by the stakeholders.

Austerity and families with disabled children: a European survey.

AIM: To describe the impact austerity measures have had on families with disabled children across Europe and on professionals providing services for them. METHOD: Cross-sectional surveys were disseminated via professional and family networks in 32 European countries for 3 months from December 2016. RESULTS: Families (n=731), of whom 45% met UNICEF criteria for severe poverty, and professionals (n=959) responded from 23 and 32 countries respectively. Respondents were grouped into those from countries with and without austerity. The direct and indirect impact of austerity cuts and worse working conditions were reported more often by professionals from countries with austerity, compared to those without. Most families reported services to be worse in quality than 3 years ago. Families with completely dependent disabled children said the needs of their disabled children are significantly less well met now, compared to 10 years ago. INTERPRETATION: A decline in quality of services for disabled children was reported by most family and many professional respondents across Europe, regardless of austerity. Where implemented, austerity measures were reported to have impacted significantly on families with disabled children. What this paper adds Stigma about disability remains a challenge in many countries across Europe. Most families and many health care professionals reported worsening quality of services than 3 years ago, regardless of austerity. Austerity cuts are reported to have impacted especially negatively on families with dependent disabled children.

Attitudes, perceptions, and behaviours associated with hospital admission avoidance: a qualitative study of high-risk patients in primary care.

BACKGROUND: There is little evidence documenting the attitudes, experiences, and behavioural factors of high-risk patients who are associated with avoiding hospital. AIM: To explore the health, healthcare management, and behavioural factors that contribute to enabling high-risk patients to avoid unplanned hospital admissions. DESIGN AND SETTING: This was an in-depth qualitative, primary care, interview study with patients who were registered on the Northumberland High Risk Patient Programme (NHRPP) in Northumberland, UK. METHOD: There were 30 participants in this study, of who 21 were high-risk patients and nine were carers, spouses, or relatives. A grounded-theory approach was used to explore themes that emerged from the semi-structured interviews. RESULTS: Participants described physical enablers that helped them to avoid hospital including medication, living aids, and resting; however, the benefit of these may be challenged by patient decision making. The strategies that patients used to cope with their health conditions included acceptance, positive reinterpretation, and growth. Participants felt that support networks of family and friends helped them to avoid hospital, although the strain on the spouse should be considered. The majority of patients described having trust and confidence in their healthcare providers, and continuity of care was important to patients. CONCLUSION: Reinforcing the importance of the physical enablers, as well as support networks to patients, carers, and healthcare providers, could help patients to avoid hospital. Highlighting the coping strategies that patients use may help patients to manage their health, while promoting continuity of care will also contribute to helping high-risk patients to avoid unplanned hospital admissions.

Attitudes and perceptions of health professionals towards management of hypothyroidism in general practice: a qualitative interview study.

OBJECTIVE: To explore the attitudes and perceptions of health professionals towards management of hypothyroidism that contributes to the suboptimal treatment of hypothyroidism in general practice. DESIGN: A qualitative interview study using semistructured interviews. PARTICIPANTS: Sixteen participants were interviewed between March and August 2016 comprising nine general practitioners (GPs), four pharmacists, two practice nurses and one nurse practitioner. SETTING: General practice and community pharmacies in the counties of Northumberland, Tyne and Wear, Stockton-on-Tees and North Cumbria, North of England, UK. METHOD: A grounded-theory approach was used to generate themes from interviews, which were underpinned by the theory of planned behaviour to give explanation to the data. RESULTS: Although health professionals felt that hypothyroidism was easy to manage, GPs and nurses generally revealed inadequate knowledge of medication interactions and levothyroxine pharmacokinetics. Pharmacists felt limited in the advice that they provide to patients due to lack of access to patient records. Most GPs and nurses followed local guidelines, and relied on blood tests over clinical symptoms to adjust levothyroxine dose. The information exchanged between professional and patient was usually restricted by time and often centred on symptoms rather than patient education. Health professionals felt that incorrect levothyroxine adherence was the main reason behind suboptimal treatment, although other factors such as comorbidity and concomitant medication were mentioned. Enablers perceived by health professionals to improve the management of hypothyroidism included continuity of care, blood test reminders, system alerts for interfering medications and prescription renewal, and accessible blood tests and levothyroxine prescriptions for patients. CONCLUSION: There is a significant health professional behavioural component to the management of hypothyroidism. Addressing the differences in patient and professional knowledge and perceptions could reduce the barriers to optimal treatment, while continuity of care and increased involvement of pharmacists and practice nurses would help to promote optimal thyroid replacement.

Clinical, behavioural and pharmacogenomic factors influencing the response to levothyroxine therapy in patients with primary hypothyroidism-protocol for a systematic review.

BACKGROUND: Suboptimal thyroid hormone therapy including under-replacement and over-replacement is common amongst patients with hypothyroidism. This is a significant health concern as affected patients are at risk of adverse cardiovascular or metabolic consequences. Despite a growing body of evidence on the effects of various factors on thyroid hormone replacement, a systematic appraisal of the evidence is lacking. This review aims to appraise and quantify the extent to which clinical, behavioural and pharmacogenomic factors affect levothyroxine therapy in patients with primary hypothyroidism. METHODS/DESIGN: The databases Web of Science, Cochrane Library, EMBASE and PubMed will be searched. Patients must be adults over the age of 18 years, suffering from primary hypothyroidism including overt and subclinical hypothyroidism and receiving levothyroxine treatment. Studies in children, pregnant women and patients with secondary or tertiary hypothyroidism will not be included. We will also exclude studies focused on forms of thyroid hormone replacement therapy other than levothyroxine. The primary outcome is to quantify the effect of clinical, behavioural and pharmacogenomic factors on thyroid stimulating hormone (TSH) levels. Secondary outcomes are the effect these factors have on thyroxine (T4) and triiodothyronine (T3) levels, mortality, morbidity, quality of life, treatment complications, adverse effects, physical and social functioning. Studies will be screened through reading the title, abstract and then full text. Two reviewers will independently extract the data and select articles, and a third reviewer will be consulted if there is any disagreement. We will undertake a meta-analysis of studies in which there is a defined intervention or exposure, patients are receiving levothyroxine for hypothyroidism, there is an appropriate control group of levothyroxine treated patients that are not exposed to the intervention, and the primary outcome is determined by serum TSH levels. Studies will comprise of randomised controlled trials as well as observational data. Eligible studies will be assessed for bias using the risk of bias tool available in the Cochrane handbook 2011, and the quality of evidence will be judged according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. A flow diagram describing the data search will be created according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis: The PRISMA statement. A narrative synthesis will be undertaken in the description of the data, and summary tables will be created of the results. DISCUSSION: This review will be the first systematic review of this nature. The evidence synthesised will be useful to general practitioners in their management of hypothyroidism. Findings will be disseminated at conferences and in professional and peer-reviewed journals. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015027211.

Patients' attitudes and perceptions towards treatment of hypothyroidism in general practice: an in-depth qualitative interview study.

BACKGROUND: Suboptimal thyroid hormone replacement is common in patients with hypothyroidism and the behavioural factors underlying this are poorly understood. AIM: To explore the attitudes and perceptions of patients to thyroid hormone replacement therapy. DESIGN & SETTING: An in-depth qualitative interview study with patients with hypothyroidism residing in Northumberland, and Tyne and Wear, UK. METHOD: Twenty-seven patients participated, of which 15 patients had thyroid stimulating hormone (TSH) levels within the reference range (0.4-4.0 mU/L) and 12 patients had TSH levels outside the reference range. A grounded theory approach was used to explore and develop emerging themes, which were mapped to the health belief model (HBM). RESULTS: Patients generally had a low understanding of their condition or of the consequences of suboptimal thyroid hormone replacement. Patients that had experienced hypothyroid symptoms at initial diagnosis had a better perception of disease susceptibility, and this was reflected in excellent adherence to levothyroxine in this group of patients. The main benefits of optimal thyroid replacement were improved wellbeing and performance. However, patients who remained unwell despite a normal serum TSH level felt that their normal result presented a barrier to further evaluation of their symptoms by their GP. CONCLUSION: Educating patients with hypothyroidism regarding the consequences of inadequate thyroid hormone replacement may reduce barriers and improve treatment outcomes. An over-reliance on TSH as a sole marker of wellbeing reduced opportunities for clinicians to address patient symptoms. Evaluating symptoms in combination with biochemical indices, may lead to better patient outcomes than relying on laboratory tests alone.