A New Validated Approach for Identifying Childhood Immunizations in Electronic Health Records in the United Kingdom.

BACKGROUND: Routinely collected electronic health records (EHR) offer a valuable opportunity to carry out research on immunization uptake, effectiveness, and safety, using large and representative samples of the population. In contrast to other drugs, vaccines do not require electronic prescription in many settings, which may lead to ambiguous coding of vaccination status and timing. METHODOLOGY: We propose a comprehensive algorithm to identifying childhood immunizations in routinely collected EHR. In order to deal with ambiguous coding, over-recording, and backdating in EHR, we suggest an approach combining a wide range of medical codes in combination to identify vaccination events and using appropriate wash-out periods and quality checks. We illustrate this approach on a cohort of children born between 2006 and 2014 followed up to the age of five in the Clinical Practice Research Datalink (CPRD) Aurum, a UK primary care dataset of EHR, and validate the results against national estimates of vaccine coverage by NHS Digital and Public Health England. RESULTS: Our algorithm reproduced estimates of vaccination coverage, which are comparable to official national estimates and allows to approximate the age at vaccination. Electronic prescription data only do not cover vaccination events sufficiently. CONCLUSION: Our new proposed method could be used to provide a more accurate estimation of vaccination coverage and timing of vaccination for researchers and policymakers using EHR. As with all observational research using real-world data, it is important that researchers understand the context of the used dataset used and the clinical practice of recording.

Risk of fractures in half a million survivors of 20 cancers: a population-based matched cohort study using linked English electronic health records.

BACKGROUND: A history of multiple myeloma, prostate cancer, and breast cancer has been associated with adverse bone health, but associations across a broader range of cancers are unclear. We aimed to compare the risk of any bone fracture and major osteoporotic fractures in survivors of a wide range of cancers versus cancer-free individuals. METHODS: In this population-based matched cohort study, we used electronic health records from the UK Clinical Practice Research Datalink linked to hospital data. We included adults (aged ≥18 years) eligible for linkage, and we restricted the study start to Jan 2, 1998, onwards and applied administrative censoring on Jan 31, 2020. The cancer survivor group included survivors of the 20 most common cancers. Each individual with cancer was matched (age, sex, and general practice) to up to five controls (1:5) who were cancer-free. The primary outcomes were any bone fracture and any major osteoporotic fracture (pelvic, hip, wrist, spine, or proximal humeral fractures) occurring more than 1 year after index date (ie, the diagnosis date of the matched individual with cancer). We used Cox regression models, adjusted for shared risk factors, to estimate associations between cancer survivorship and bone fractures. FINDINGS: 578 160 adults with cancer diagnosed in 1998-2020 were matched to 3 226 404 cancer-free individuals. Crude incidence rates of fractures in cancer survivors ranged between 8·39 cases (95% CI 7·45-9·46) per 1000 person-years for thyroid cancer and 21·62 cases (20·18-23·18) per 1000 person-years for multiple myeloma. Compared with cancer-free individuals, the risk of any bone fracture was increased in 15 of 20 cancers, and of major osteoporotic fractures in 17 of 20 cancers. Effect sizes varied: adjusted hazard ratios (HRs) were largest for multiple myeloma (1·94, 95% CI 1·77-2·13) and prostate cancer (1·43, 1·39-1·47); HRs in the range 1·20-1·50 were seen for stomach, liver, pancreas, lung, breast, kidney, and CNS cancers; smaller associations (HR <1·20) were observed for malignant melanoma, non-Hodgkin lymphoma, leukaemia, and oesophageal, colorectal, and cervical cancers. Increased risks of major osteoporotic fracture were noted most substantially in multiple myeloma (2·25, 1·96-2·58) and CNS (2·12, 1·56-2·87), liver (1·62, 1·01-2·61), prostate (1·60, 1·53-1·67), and lung cancers (1·60, 1·44-1·77). Effect sizes tended to reduce over time since diagnosis but remained elevated for more than 5 years in several cancers, such as multiple myeloma and stomach, lung, breast, prostate, and CNS cancers. INTERPRETATION: Survivors of most types of cancer were at increased risk of bone fracture for several years after cancer, with variation by cancer type. These findings can help to inform mitigation and prevention strategies. FUNDING: Wellcome Trust.

The risk of acute kidney injury in colorectal cancer survivors: an english population-based matched cohort study.

BACKGROUND: Colorectal cancer survival has improved in recent decades but there are concerns that survivors may develop kidney problems due to adverse effects of cancer treatment or complications of the cancer itself. We quantified the risk of acute kidney injury (AKI) in colorectal cancer survivors compared to people with no prior cancer. METHODS: Retrospective matched cohort study using electronic health record primary care data from the Clinical Practice Research Datalink GOLD linked to hospital data in England (HES-APC). Individuals with colorectal cancer between 1997-2018 were individually matched on age, sex, and GP practice to people with no prior cancer. We used Cox models to estimate hazard ratios for an incident hospital diagnosis of AKI in colorectal cancer survivors compared to individuals without cancer, overall and stratified by time since diagnosis adjusted for other individual-level factors (adj-HR). RESULTS: Twenty thousand three hundred forty colorectal cancer survivors were matched to 100,058 cancer-free individuals. Colorectal cancer survivors were at increased risk of developing AKI compared to people without cancer (adj-HR = 2.16; 95%CI 2.05-2.27). The HR was highest in the year after diagnosis (adj-HR 7.47, 6.66-8.37), and attenuated over time, but there was still increased AKI risk > 5 years after diagnosis (adj-HR = 1.26, 1.17-1.37). The association between colorectal cancer and AKI was greater for younger people, men, and those with pre-existing chronic kidney disease. CONCLUSIONS: Colorectal cancer survivors were at increased risk of AKI for several years after cancer diagnosis, suggesting a need to prioritise monitoring, prevention, and management of kidney problems in this group of cancer survivors.

Ethnic differences in the indirect effects of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: a population-based, observational cohort study using the OpenSAFELY platform.

Background: The COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England. Methods: In this population-based, observational cohort study we used primary care electronic health record data with linkage to hospital episode statistics data and mortality data within OpenSAFELY, a data analytics platform created, with approval of NHS England, to address urgent COVID-19 research questions. We included adults aged 18 years and over registered with a TPP practice between March 1, 2018, and April 30, 2022. We excluded those with missing age, sex, geographic region, or Index of Multiple Deprivation. We grouped ethnicity (exposure), into five categories: White, Asian, Black, Other, and Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (blood pressure and Hba1c measurements, chronic obstructive pulmonary disease and asthma annual reviews) before and after March 23, 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to diabetes, cardiovascular disease, respiratory disease, and mental health before and after March 23, 2020. Findings: Of 33,510,937 registered with a GP as of 1st January 2020, 19,064,019 were adults, alive and registered for at least 3 months, 3,010,751 met the exclusion criteria and 1,122,912 were missing ethnicity. This resulted in 14,930,356 adults with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to the White ethnic group (Pre-pandemic hazard ratio (HR): 0.50, 95% confidence interval (CI) 0.41, 0.60, Pandemic HR: 0.75, 95% CI: 0.65, 0.87). There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in those of White ethnicity (heart failure risk difference: 5.4). Relatively, ethnic differences narrowed for heart failure admission in those of Asian (Pre-pandemic HR 1.56, 95% CI 1.49, 1.64, Pandemic HR 1.24, 95% CI 1.19, 1.29) and Black ethnicity (Pre-pandemic HR 1.41, 95% CI: 1.30, 1.53, Pandemic HR: 1.16, 95% CI 1.09, 1.25) compared with White ethnicity. For other outcomes the pandemic had minimal impact on ethnic differences. Interpretation: Our study suggests that ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes. Funding: LSHTM COVID-19 Response Grant (DONAT15912).

Severe Mental Illness Among Adults with Atopic Eczema or Psoriasis: Population-Based Matched Cohort Studies within UK Primary Care.

Background: Existing research exploring associations between atopic eczema (AE) or psoriasis, and severe mental illness (SMI - ie, schizophrenia, bipolar disorder, other psychoses) is limited, with longitudinal evidence particularly scarce. Therefore, temporal directions of associations are unclear. We aimed to investigate associations between AE or psoriasis and incident SMI among adults. Methods: We conducted matched cohort studies using primary care electronic health records (January 1997 to January 2020) from the UK Clinical Practice Research Datalink GOLD. We identified two cohorts: 1) adults (≥18 years) with and without AE and 2) adults with and without psoriasis. We matched (on age, sex, general practice) adults with AE or psoriasis with up to five adults without. We used Cox regression, stratified by matched set, to estimate hazard ratios (HRs) comparing incident SMI among adults with and without AE or psoriasis. Results: We identified 1,023,232 adults with AE and 4,908,059 without, and 363,210 with psoriasis and 1,801,875 without. After adjusting for matching variables (age, sex, general practice) and potential confounders (deprivation, calendar period) both AE and psoriasis were associated with at least a 17% increased hazard of SMI (AE: HR=1.17,95% CI=1.12-1.22; psoriasis: HR=1.26,95% CI=1.18-1.35). After additionally adjusting for potential mediators (comorbidity burden, harmful alcohol use, smoking status, body mass index, and, in AE only, sleep problems and high-dose glucocorticoids), associations with SMI did not persist for AE (HR=0.98,95% CI=0.93-1.04), and were attenuated for psoriasis (HR=1.14,95% CI=1.05-1.23). Conclusion: Our findings suggest adults with AE or psoriasis are at increased risk of SMI compared to matched comparators. After adjusting for potential mediators, associations with SMI did not persist for AE, and were attenuated for psoriasis, suggesting that the increased risk may be explained by mediating factors (eg, sleep problems). Our research highlights the importance of monitoring mental health in adults with AE or psoriasis.

Exploring the impact of mental health conditions on vaccine uptake in high-income countries: a systematic review.

BACKGROUND: Vaccination is an essential public health intervention to reduce morbidity and mortality from infectious diseases. Despite being at higher at risk of infectious diseases, health inequalities towards vaccine uptake in people with mental health issues have not been systematically appraised. METHODS: We searched 7 databases from 1994 to 26/03/2021. We included all studies with a relative measure of effect comparing a group with a mental health issue to a control group. All studies covering any mental health issue were eligible with no constraints to study population, vaccine type or region, provided in a high-income country for comparability of health care systems. The study outcomes were synthesised by study population, mental health issue and type of vaccine. RESULTS: From 4,069 titles, 23 eligible studies from 12 different countries were identified, focusing on adults (n = 13) or children (n = 4) with mental health issues, siblings of children with mental health issues (n = 2), and mothers with mental health issue and vaccine uptake in their children (n = 6). Most studies focused on depression (n = 12), autism, anxiety, or alcoholism (n = 4 respectively). Many studies were at high risk of selection bias. DISCUSSION: Mental health issues were associated with considerably lower vaccine uptake in some contexts such as substance use disorder, but findings were heterogeneous overall and by age, mental health issue or types of vaccine. Only individuals with mental health issues and physical comorbidities had consistently higher uptake in comparison to other adults. Mental health should be considered as a health inequality for vaccine uptake but more context specific research is needed focusing more on specific mental health issues and subgroups of the population to understand who misses vaccination and why.

Recording of patients' mental health and quality of life-related outcomes in primary care: a cross-sectional study in the UK.

OBJECTIVE: To compare patient-reported anxiety, depression and quality-of-life (QoL) outcomes, with data registered in patients' primary care electronic health record (EHR). DESIGN: Cross-sectional study. SETTING: Primary care in the UK. PARTICIPANTS: A convenience sample of 608 women registered in the Clinical Practice Research Datalink GOLD primary care database (data from a previous study on 356 breast cancer survivors (8.1 years postdiagnosis) and 252 women with no prior cancer). OUTCOME MEASURES: Patient-reported data on anxiety, depression and QoL, collected through postal questionnaires, and compared with coded information in EHR up to 2 years prior. RESULTS: Abnormal anxiety symptoms were reported by 118 of 599 women who answered the relevant questions (21%); 59/118 (50%) had general practitioner (GP)-recorded anxiolytic/antidepressant use, and 2 (1.6%) had anxiety coded in the EHR. 26/601 women (11%) reported depression symptoms, of whom 17 (65.4%) had GP-recorded antidepressant use and none had depression coded. 65 of 123 women reporting distress on the pain QoL domain (52.8%) had a corresponding record in the EHR <3 months before and 92 (74.8%) <24 months before. No patients reporting fatigue (n=157), sexual health problems (156), social avoidance (82) or cognitive problems (93) had corresponding codes in the EHR. There were no meaningful differences in the concordance results between breast cancer survivors and women with no history of cancer. CONCLUSION: Many patients reporting mental health and QoL problems had no record of this in coded primary care data. This finding suggests that coded data does not fully reflect the burden of disease. Further research is needed to understand whether or not GPs are aware of patient distress in cases where codes have not been recorded.

Respiratory diseases in survivors of adult cancer compared with the general population: a systematic review protocol.

INTRODUCTION: There is concern that survivors of adult cancers may be at increased risk of respiratory infections and of exacerbations of pre-existing respiratory conditions. Considering the high prevalence of respiratory disease in the general population, increased respiratory disease risk in survivors of adult cancers could translate into an important impact on morbidity and mortality. The aim of this systematic review is to summarise and assess the quality of all studies comparing respiratory outcomes between adult cancer survivors and individuals with no history of cancer. METHODS AND ANALYSIS: This systematic literature review will be conducted using Medline, EMBASE and Cochrane. We will include cohort or case-control studies that provide a comparative estimate of the risk of a respiratory disease of interest in survivors of adult cancer against a comparator cohort of cancer-free individuals. No geographic, time or language restrictions will be applied. We will assess the risk of bias using the Scottish Intercollegiate Guidelines Network methodology checklists. Results will be summarised by type of respiratory outcome, cancer type and cancer survivorship definition. If sufficient numbers of homogeneous studies are found, summary measures of association will be calculated using random effects meta-analysis models. ETHICS AND DISSEMINATION: Ethical approval is not applicable to our study. The results will be used to identify evidence gaps and priorities for future research to understand respiratory morbidity in survivors of adult cancers and identify possible mitigation strategies. Results from this review will be disseminated to clinical audiences and submitted to a peer-reviewed journal when completed. TRIAL REGISTRATION NUMBER: This study has been registered on PROSPERO (registration number: CRD42022311557).

Factors associated with excess all-cause mortality in the first wave of the COVID-19 pandemic in the UK: A time series analysis using the Clinical Practice Research Datalink.

BACKGROUND: Excess mortality captures the total effect of the Coronavirus Disease 2019 (COVID-19) pandemic on mortality and is not affected by misspecification of cause of death. We aimed to describe how health and demographic factors were associated with excess mortality during, compared to before, the pandemic. METHODS AND FINDINGS: We analysed a time series dataset including 9,635,613 adults (≥40 years old) registered at United Kingdom general practices contributing to the Clinical Practice Research Datalink. We extracted weekly numbers of deaths and numbers at risk between March 2015 and July 2020, stratified by individual-level factors. Excess mortality during Wave 1 of the UK pandemic (5 March to 27 May 2020) compared to the prepandemic period was estimated using seasonally adjusted negative binomial regression models. Relative rates (RRs) of death for a range of factors were estimated before and during Wave 1 by including interaction terms. We found that all-cause mortality increased by 43% (95% CI 40% to 47%) during Wave 1 compared with prepandemic. Changes to the RR of death associated with most sociodemographic and clinical characteristics were small during Wave 1 compared with prepandemic. However, the mortality RR associated with dementia markedly increased (RR for dementia versus no dementia prepandemic: 3.5, 95% CI 3.4 to 3.5; RR during Wave 1: 5.1, 4.9 to 5.3); a similar pattern was seen for learning disabilities (RR prepandemic: 3.6, 3.4 to 3.5; during Wave 1: 4.8, 4.4 to 5.3), for black or South Asian ethnicity compared to white, and for London compared to other regions. Relative risks for morbidities were stable in multiple sensitivity analyses. However, a limitation of the study is that we cannot assume that the risks observed during Wave 1 would apply to other waves due to changes in population behaviour, virus transmission, and risk perception. CONCLUSIONS: The first wave of the UK COVID-19 pandemic appeared to amplify baseline mortality risk to approximately the same relative degree for most population subgroups. However, disproportionate increases in mortality were seen for those with dementia, learning disabilities, non-white ethnicity, or living in London.

Indirect acute effects of the COVID-19 pandemic on physical and mental health in the UK: a population-based study.

BACKGROUND: There are concerns that the response to the COVID-19 pandemic in the UK might have worsened physical and mental health, and reduced use of health services. However, the scale of the problem is unquantified, impeding development of effective mitigations. We aimed to ascertain what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic. METHODS: Using de-identified electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (covering 13% of the UK population), between 2017 and 2020, we calculated weekly primary care contacts for selected acute physical and mental health conditions: anxiety, depression, self-harm (fatal and non-fatal), severe mental illness, eating disorder, obsessive-compulsive disorder, acute alcohol-related events, asthma exacerbation, chronic obstructive pulmonary disease exacerbation, acute cardiovascular events (cerebrovascular accident, heart failure, myocardial infarction, transient ischaemic attacks, unstable angina, and venous thromboembolism), and diabetic emergency. Primary care contacts included remote and face-to-face consultations, diagnoses from hospital discharge letters, and secondary care referrals, and conditions were identified through primary care records for diagnoses, symptoms, and prescribing. Our overall study population included individuals aged 11 years or older who had at least 1 year of registration with practices contributing to CPRD Aurum in the specified period, but denominator populations varied depending on the condition being analysed. We used an interrupted time-series analysis to formally quantify changes in conditions after the introduction of population-wide restrictions (defined as March 29, 2020) compared with the period before their introduction (defined as Jan 1, 2017 to March 7, 2020), with data excluded for an adjustment-to-restrictions period (March 8-28). FINDINGS: The overall population included 9 863 903 individuals on Jan 1, 2017, and increased to 10 226 939 by Jan 1, 2020. Primary care contacts for almost all conditions dropped considerably after the introduction of population-wide restrictions. The largest reductions were observed for contacts for diabetic emergencies (odds ratio 0·35 [95% CI 0·25-0·50]), depression (0·53 [0·52-0·53]), and self-harm (0·56 [0·54-0·58]). In the interrupted time-series analysis, with the exception of acute alcohol-related events (0·98 [0·89-1·10]), there was evidence of a reduction in contacts for all conditions (anxiety 0·67 [0·66-0·67], eating disorders 0·62 [0·59-0·66], obsessive-compulsive disorder [0·69 [0·64-0·74]], self-harm 0·56 [0·54-0·58], severe mental illness 0·80 [0·78-0·83], stroke 0·59 [0·56-0·62], transient ischaemic attack 0·63 [0·58-0·67], heart failure 0·62 [0·60-0·64], myocardial infarction 0·72 [0·68-0·77], unstable angina 0·72 [0·60-0·87], venous thromboembolism 0·94 [0·90-0·99], and asthma exacerbation 0·88 [0·86-0·90]). By July, 2020, except for unstable angina and acute alcohol-related events, contacts for all conditions had not recovered to pre-lockdown levels. INTERPRETATION: There were substantial reductions in primary care contacts for acute physical and mental conditions following the introduction of restrictions, with limited recovery by July, 2020. Further research is needed to ascertain whether these reductions reflect changes in disease frequency or missed opportunities for care. Maintaining health-care access should be a key priority in future public health planning, including further restrictions. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people with the conditions as well as health-care provision. FUNDING: Wellcome Trust Senior Fellowship, Health Data Research UK.

Associations between breast cancer survivorship and adverse mental health outcomes: A matched population-based cohort study in the United Kingdom.

BACKGROUND: Breast cancer is the most common cancer diagnosed in women globally, and 5-year net survival probabilities in high-income countries are generally >80%. A cancer diagnosis and treatment are often traumatic events, and many women struggle to cope during this period. Less is known, however, about the long-term mental health impact of the disease, despite many women living several years beyond their breast cancer and mental health being a major source of disability in modern societies. The objective of this study was to quantify the risk of several adverse mental health-related outcomes in women with a history of breast cancer followed in primary care in the United Kingdom National Health Service, compared to similar women who never had cancer. METHODS AND FINDINGS: We conducted a matched cohort study using data routinely collected in primary care across the UK to quantify associations between breast cancer history and depression, anxiety, and other mental health-related outcomes. All women with incident breast cancer in the Clinical Practice Research Datalink (CPRD) GOLD primary care database between 1988 and 2018 (N = 57,571, mean = 62 ± 14 years) were matched 1:4 to women with no prior cancer (N = 230,067) based on age, primary care practice, and eligibility of the data for linkage to hospital data sources. Cox models were used to estimate associations between breast cancer survivorship and each mental health-related outcome, further adjusting for diabetes, body mass index (BMI), and smoking and drinking status at baseline. Breast cancer survivorship was positively associated with anxiety (adjusted hazard ratio (HR) = 1.33; 95% confidence interval (CI): 1.29-1.36; p < 0.001), depression (1.35; 1.32-1.38; p < 0.001), sexual dysfunction (1.27; 1.17-1.38; p < 0.001), and sleep disorder (1.68; 1.63-1.73; p < 0.001), but not with cognitive dysfunction (1.00; 0.97-1.04; p = 0.88). Positive associations were also found for fatigue (HR = 1.28; 1.25-1.31; p < 0.001), pain (1.22; 1.20-1.24; p < 0.001), receipt of opioid analgesics (1.86; 1.83-1.90; p < 0.001), and fatal and nonfatal self-harm (1.15; 0.97-1.36; p = 0.11), but CI was wide, and the relationship was not statistically significant for the latter. HRs for anxiety and depression decreased over time (p-interaction <0.001), but increased risks persisted for 2 and 4 years, respectively, after cancer diagnosis. Increased levels of pain and sleep disorder persisted for 10 years. Younger age was associated with larger HRs for depression, cognitive dysfunction, pain, opioid analgesics use, and sleep disorders (p-interaction <0.001 in each case). Limitations of the study include the potential for residual confounding by lifestyle factors and detection bias due to cancer survivors having greater healthcare contact. CONCLUSIONS: In this study, we observed that compared to women with no prior cancer, breast cancer survivors had higher risk of anxiety, depression, sleep problems, sexual dysfunction, fatigue, receipt of opioid analgesics, and pain. Relative risks estimates tended to decrease over time, but anxiety and depression were significantly increased for 2 and 4 years after breast cancer diagnosis, respectively, while associations for fatigue, pain, and sleep disorders were elevated for at least 5-10 years after diagnosis. Early diagnosis and increased awareness among patients, healthcare professionals, and policy makers are likely to be important to mitigate the impacts of these raised risks.

Quality of life and mental health in breast cancer survivors compared with non-cancer controls: a study of patient-reported outcomes in the United Kingdom.

PURPOSE: There is limited high-quality evidence on quality of life, anxiety, and depressive symptoms in breast cancer survivors and women with no history of cancer. We aimed to address this by comparing patient-reported outcomes between breast cancer survivors and women with no history of breast cancer. METHODS: Breast cancer survivors and women with no prior cancer were selected from the UK Clinical Practice Research Datalink GOLD primary care database, which includes population-based primary care electronic health record data. Breast cancer survivors and controls were frequency matched by age and primary care practice. Outcomes were assessed with validated instruments via postal questionnaire. Linear and logistic regression models were fitted to estimate adjusted associations between breast cancer survivorship and outcomes. RESULTS: A total of 356 breast cancer survivors (8.1 years post diagnosis) and 252 women with no prior cancer participated in the study. Compared with non-cancer controls, breast cancer survivors had poorer QoL in the domains of cognitive problems (adjusted ß (aß) = 1.4, p = 0.01), sexual function (aß = 1.7, p = 0.02) and fatigue (aß = 1.3, p = 0.01), but no difference in negative feelings, positive feelings, pain, or social avoidance. Breast cancer survivors had higher odds of borderline-probable anxiety (score ≥ 8) (adjusted OR = 1.47, 95%CI:1.15-1.87), but no differences in depression. Advanced stage at diagnosis and chemotherapy treatment were associated with poorer QoL. CONCLUSIONS: Compared with women with no history of cancer, breast cancer survivors report more problems with cognition, sexual function, fatigue, and anxiety, particularly where their cancer was advanced and/or treated with chemotherapy. IMPLICATIONS FOR CANCER SURVIVORS: Breast cancer survivors with more advanced disease and/or treated with chemotherapy should be closely monitored and, when possible, offered evidence-based intervention for fatigue, cognitive dysfunction, and sexual problems.

Controlled drinking-non-abstinent versus abstinent treatment goals in alcohol use disorder: a systematic review, meta-analysis and meta-regression.

BACKGROUND AND AIMS: The proportion of untreated patients with alcohol use disorder (AUD) exceeds that of any other mental health disorder, and treatment alternatives are needed. A widely discussed strategy is to depart from the abstinence paradigm as part of controlled drinking approaches. This first systematic review with meta-analysis aims to assess the efficacy of non-abstinent treatment strategies compared with abstinence-based strategies. METHODS: CENTRAL, PubMed, PsycINFO and Embase databases were searched until February 2019 for controlled (randomized and non-randomized) clinical trials (RCTs and non-RCTs) among adult AUD populations, including an intervention group aiming at controlled drinking and a control group aiming for abstinence. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane Collaboration guidelines, literature search, data collection and risk of bias assessment were carried out independently by two reviewers [International Prospective Register of Systematic Reviews (PROSPERO), registration no. CRD42019128716]. The primary outcome was the proportion of participants consuming alcohol at or below the recommended threshold. Secondary outcomes were social functioning, drinking reductions, abstinence rates and dropouts. Using random-effects models, RCTs and non-RCTs were analyzed separately. Sensitivity and subgroup analyses accounted for methodological rigor, inclusion of goal-specific treatment, length of follow-up and AUD severity. RESULTS: Twenty-two studies (including five RCTs) with 4204 patients were selected. There was no statistically significant difference between both treatment paradigms in RCTs [odds ratio (OR) = 1.32, 95% confidence interval (CI) = 0.51-3.39]. Non-randomized studies of free goal choice favored abstinence-orientation (OR = 0.60, 95% CI = 0.40-0.90), unless goal-specific treatment was provided (OR = 0.79, 95% CI = 0.40-1.56), or in studies of low risk of bias (OR = 0.73, 95% CI = 0.49-1.09) or with long follow-up (OR = 1.49, 95% CI = 0.78-2.85). Effect sizes were not clearly dependent upon AUD severity. Abstinence- and controlled drinking interventions did not clearly differ in their effect on social functioning and drinking reductions. CONCLUSIONS: Available evidence does not support abstinence as the only approach in the treatment of alcohol use disorder. Controlled drinking, particularly if supported by specific psychotherapy, appears to be a viable option where an abstinence-oriented approach is not applicable.

Prevalence of COVID-19-related risk factors and risk of severe influenza outcomes in cancer survivors: A matched cohort study using linked English electronic health records data.

BACKGROUND: People with active cancer are recognised as at risk of COVID-19 complications, but it is unclear whether the much larger population of cancer survivors is at elevated risk. We aimed to address this by comparing cancer survivors and cancer-free controls for (i) prevalence of comorbidities considered risk factors for COVID-19; and (ii) risk of severe influenza, as a marker of susceptibility to severe outcomes from epidemic respiratory viruses. METHODS: We included survivors (≥1 year) of the 20 most common cancers, and age, sex and general practice-matched cancer-free controls, derived from English primary care data linked to cancer registrations, hospital admissions and death registrations. Comorbidity prevalences were calculated 1 and 5 years from cancer diagnosis. Risk of hospitalisation or death due to influenza was compared using Cox models adjusted for baseline demographics and comorbidities. FINDINGS: 108,215 cancer survivors and 523,541 cancer-free controls were included. Cancer survivors had more diabetes, asthma, other respiratory, cardiac, neurological, renal, and liver diseases, and less obesity, compared with controls, but there was variation by cancer site. There were 205 influenza hospitalisations/deaths, with cancer survivors at higher risk than controls (adjusted HR 2.78, 95% CI 2.04-3.80). Haematological cancer survivors had large elevated risks persisting for >10 years (HR overall 15.17, 7.84-29.35; HR >10 years from cancer diagnosis 10.06, 2.47-40.93). Survivors of other cancers had evidence of raised risk up to 5 years from cancer diagnosis only (HR >5 years 2.22, 1.31-3.74). INTERPRETATION: Risks of severe COVID-19 outcomes are likely to be elevated in cancer survivors. This should be taken into account in policies targeted at clinical risk groups, and vaccination for both influenza, and, when available, COVID-19, should be encouraged in cancer survivors.

Identification of mental health and quality of life outcomes in primary care databases in the UK: a systematic review.

OBJECTIVES: To summarise the definitions and combinations of codes used to identify outcomes of anxiety, depression, fatigue, cognitive dysfunction (including mild cognitive dysfunction and dementia), sexual dysfunction, pain, sleep disorders, and fatal and non-fatal self-harm in studies using electronic health records from primary care databases in the UK. DESIGN: Systematic review. DATA SOURCES: Medline, Embase and lists of publications of the main primary care databases in the UK. ELIGIBILITY CRITERIA: Included data from a UK primary care database and studied outcome(s) of interest. DATA EXTRACTION AND SYNTHESIS: We abstracted information on the outcomes definition and codelists. When necessary, authors were contacted to request codelists. RESULTS: 120 studies were eligible. Codelists were available for 17/42 studies of depression; 21/41 studies of fatal and non-fatal self-harm; 17/27 studies of dementia/cognitive dysfunction; 5/12 studies of anxiety; 4/8 studies of pain; 3/6 studies of fatigue and sexual dysfunction; 1/2 studies of sleep disorders. Depression was most often defined using codes for diagnoses (37/42 studies) and/or antidepressants prescriptions (21/42 studies); six studies reported including symptoms in their definition. Anxiety was defined with codes for diagnoses (12/12 studies); four studies also reported including symptoms. Fatal self-harm was ascertained in primary care data linked to the Office for National Statistics mortality database in nine studies. Most studies of cognitive dysfunction included Alzheimer's disease, and vascular and frontotemporal dementia. Fatigue definitions varied little, including chronic fatigue syndrome, neurasthenia and postviral fatigue syndrome. All studies of sexual dysfunction focused on male conditions, principally erectile dysfunction. Sleep disorders included insomnia and hypersomnia. There was substantial variability in the codelists; validation was carried out i21/120 studies. CONCLUSIONS: There is a need for standardised definitions and validated list of codes to assess mental health and quality of life outcomes in primary care databases in the UK.

Associations Between Breast Cancer Survivorship and Adverse Mental Health Outcomes: A Systematic Review.

Background: We aimed to systematically review the evidence on adverse mental health outcomes in breast cancer survivors (≥1 year) compared with women with no history of cancer. Methods: Studies were identified by searching MEDLINE, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature, and the Social Sciences Citation Index, and through backward citation tracking. Two researchers selected the studies, extracted data, and assessed the risk of bias. Results: Sixty studies were included. Of 38 studies of depression, 33 observed more depression in breast cancer survivors; this was statistically significant in 19 studies overall, including six of seven where depression was ascertained clinically, three of four studies of antidepressants, and 13 of 31 that quantified depressive symptoms. Of 21 studies of anxiety, 17 observed more anxiety in breast cancer survivors, statistically significant in 11 studies overall, including two of four with clinical/prescription-based outcomes, and in eight of 17 of anxiety symptoms. Breast cancer survivors also had statistically significantly increased symptoms/frequency of neurocognitive dysfunction (18 of 24 studies), sexual dysfunctions (5 of 6 studies), sleep disturbance (5 of 5 studies), stress-related disorders/PTSD (2 of 3 studies), suicide (2 of 2 studies), somatisation (2 of 2 studies), and bipolar and obsessive-compulsive disorders (1 of 1 study each). Studies were heterogeneous in terms of participants' characteristics, time since diagnosis, ascertainment of outcomes, and measures reported. Approximately one-half of the studies were at high risk of selection bias and confounding by socio-economic status. Conclusions: There is compelling evidence of an increased risk of anxiety, depression and suicide, and neurocognitive and sexual dysfunctions in breast cancer survivors compared with women with no prior cancer. This information can be used to support evidence-based prevention and management strategies. Further population-based and longitudinal research would help to better characterize these associations.

Manual lymphatic drainage and quality of life in patients with lymphoedema and mixed oedema: a systematic review of randomised controlled trials.

PURPOSE: To assess the impact of manual lymphatic drainage (MLD) on the health-related quality of life (HRQoL) of adults with lymphoedema or mixed oedema, through a systematic review of randomised controlled trials (RCTs). METHODS: MEDLINE, EMBASE, PsycINFO, CENTRAL, the Cochrane Database of Systematic Reviews and ClinicalTrials.gov were searched to identify RCTs evaluating HRQoL after a MLD intervention compared to non-MLD interventions (PROSPERO 2016:CRD42016042255). We extracted the effect of the interventions on the HRQoL (primary outcome) as well as data on volume and functional changes, and adverse events when available (secondary outcomes). RESULTS: Eight studies were eligible. The studies were heterogeneous in the aetiology of oedema, schemes of MLD applied, additional treatments offered with MLD, length of follow-up, instruments used to assess HRQoL and interventions offered to the control group. Five studies included patients with breast cancer-related arm lymphoedema; one study reported increased HRQoL among patients randomised to the MLD group. The two RCTs that involved patients with leg mixed oedema due to chronic venous insufficiency did not find between-group differences in the overall HRQoL. One trial included patients with hand oedema from systemic sclerosis and showed higher HRQoL in the group that received MLD. No studies reported reductions in HRQoL, or severe adverse events after MLD. The small numbers of patients analysed in all studies may have resulted in lack of power to detect between-group differences in HRQoL. CONCLUSIONS: The effect of MLD on the HRQoL of patients with chronic oedema is unclear.

Population-based cancer survival in the United States: Data, quality control, and statistical methods.

BACKGROUND: Robust comparisons of population-based cancer survival estimates require tight adherence to the study protocol, standardized quality control, appropriate life tables of background mortality, and centralized analysis. The CONCORD program established worldwide surveillance of population-based cancer survival in 2015, analyzing individual data on 26 million patients (including 10 million US patients) diagnosed between 1995 and 2009 with 1 of 10 common malignancies. METHODS: In this Cancer supplement, we analyzed data from 37 state cancer registries that participated in the second cycle of the CONCORD program (CONCORD-2), covering approximately 80% of the US population. Data quality checks were performed in 3 consecutive phases: protocol adherence, exclusions, and editorial checks. One-, 3-, and 5-year age-standardized net survival was estimated using the Pohar Perme estimator and state- and race-specific life tables of all-cause mortality for each year. The cohort approach was adopted for patients diagnosed between 2001 and 2003, and the complete approach for patients diagnosed between 2004 and 2009. RESULTS: Articles in this supplement report population coverage, data quality indicators, and age-standardized 5-year net survival by state, race, and stage at diagnosis. Examples of tables, bar charts, and funnel plots are provided in this article. CONCLUSIONS: Population-based cancer survival is a key measure of the overall effectiveness of services in providing equitable health care. The high quality of US cancer registry data, 80% population coverage, and use of an unbiased net survival estimator ensure that the survival trends reported in this supplement are robustly comparable by race and state. The results can be used by policymakers to identify and address inequities in cancer survival in each state and for the United States nationally. Cancer 2017;123:4982-93. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Liver cancer survival in the United States by race and stage (2001-2009): Findings from the CONCORD-2 study.

BACKGROUND: Worldwide, liver cancer is a leading cause of death for both men and women. The number of Americans who are diagnosed with and die of liver cancer has been rising slowly each year. Using data from the CONCORD-2 study, this study examined population-based survival by state, race, and stage at diagnosis. METHODS: Data from 37 statewide registries, which covered 81% of the US population, for patients diagnosed during 2001-2009 were analyzed. Survival up to 5 years was adjusted for background mortality (net survival) with state- and race-specific life tables, and it was age-standardized with the International Cancer Survival Standard weights. RESULTS: Liver cancer was diagnosed overall more often at the localized stage, with blacks being more often diagnosed at distant and regional stages than whites. 5-year net survival was 12.2% in 2001-2003 and 14.8% in 2004-2009. Whites had higher survival than blacks in both calendar periods (11.7% vs 9.1% and 14.3% vs 11.4%, respectively). During 2004-2009, 5-year survival was 25.7% for localized-stage disease, 9.5% for regional-stage disease, and 3.5% for distant-stage disease. CONCLUSIONS: Some progress has occurred in survival for patients with liver cancer, but 5-year survival remains low, even for those diagnosed at the localized stage. Efforts directed at controlling well-established risk factors such as hepatitis B may have the greatest impact on reducing the burden of liver cancer in the United States. Cancer 2017;123:5059-78. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.