Clare Bankhead

Anticoagulation Control and Prediction of Adverse Events in Patients With Atrial Fibrillation A Systematic Review

Background—To date, there has been no systematic examination of the relationship between international normalized ratio (INR) control measurements and the prediction of adverse events in patients with atrial fibrillation on oral anticoagulation. Methods and Results—We searched MEDLINE, EMBASE, and Cochrane through January 2008 for studies of atrial fibrillation patients receiving vitamin-K antagonists that reported INR control measures (percentage of time in therapeutic range [TTR] and percentage of INRs in range) and major hemorrhage and thromboembolic events. In total, 47 studies were included from 38 published articles. TTR ranged from 29% to 75%; percentage of INRs ranged from 34% to 84%. From studies reporting both measures, TTR significantly correlated with percentage of INRs in range (P<0.001). Randomized controlled trials had better INR control than retrospective studies (64.9% versus 56.4%; P=0.01). TTR negatively correlated with major hemorrhage (r=−0.59; P=0.002) and thromboembolic rates (r=−0.59; P=0.01). This effect was significant in retrospective studies (major hemorrhage, r=−0.78; P=0.006 and thromboembolic rate, r=−0.88; P=0.03) but not in randomized controlled trials (major hemorrhage, r=0.18; P=0.33 and thromboembolic rate, r=−0.61; P=0.07). For retrospective studies, a 6.9% improvement in the TTR significantly reduced major hemorrhage by 1 event per 100 patient-years of treatment (95% CI, 0.29 to 1.71 events). Conclusions—In atrial fibrillation patients receiving orally administered anticoagulation treatment, TTR and percentage of INRs in range effectively predict INR control. Data from retrospective studies support the use of TTR to accurately predict reductions in adverse events.

Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data

BACKGROUND Uptake of self-testing and self-management of oral anticoagulation [corrected] has remained inconsistent, despite good evidence of their effectiveness. To clarify the value of self-monitoring of oral anticoagulation, we did a meta-analysis of individual patient data addressing several important gaps in the evidence, including an estimate of the effect on time to death, first major haemorrhage, and thromboembolism. METHODS We searched Ovid versions of Embase (1980-2009) and Medline (1966-2009), limiting searches to randomised trials with a maximally sensitive strategy. We approached all authors of included trials and requested individual patient data: primary outcomes were time to death, first major haemorrhage, and first thromboembolic event. We did prespecified subgroup analyses according to age, type of control-group care (anticoagulation-clinic care vs primary care), self-testing alone versus self-management, and sex. We analysed patients with mechanical heart valves or atrial fibrillation separately. We used a random-effect model method to calculate pooled hazard ratios and did tests for interaction and heterogeneity, and calculated a time-specific number needed to treat. FINDINGS Of 1357 abstracts, we included 11 trials with data for 6417 participants and 12,800 person-years of follow-up. We reported a significant reduction in thromboembolic events in the self-monitoring group (hazard ratio 0·51; 95% CI 0·31-0·85) but not for major haemorrhagic events (0·88, 0·74-1·06) or death (0·82, 0·62-1·09). Participants younger than 55 years showed a striking reduction in thrombotic events (hazard ratio 0·33, 95% CI 0·17-0·66), as did participants with mechanical heart valve (0·52, 0·35-0·77). Analysis of major outcomes in the very elderly (age ≥85 years, n=99) showed no significant adverse effects of the intervention for all outcomes. INTERPRETATION Our analysis showed that self-monitoring and self-management of oral coagulation is a safe option for suitable patients of all ages. Patients should also be offered the option to self-manage their disease with suitable health-care support as back-up. FUNDING UK National Institute for Health Research (NIHR) Technology Assessment Programme, UK NIHR National School for Primary Care Research.

Anticoagulation Control and Prediction of Adverse Events in Patients With Atrial FibrillationCLINICAL PERSPECTIVE

Background—To date, there has been no systematic examination of the relationship between international normalized ratio (INR) control measurements and the prediction of adverse events in patients with atrial fibrillation on oral anticoagulation. Methods and Results—We searched MEDLINE, EMBASE, and Cochrane through January 2008 for studies of atrial fibrillation patients receiving vitamin-K antagonists that reported INR control measures (percentage of time in therapeutic range [TTR] and percentage of INRs in range) and major hemorrhage and thromboembolic events. In total, 47 studies were included from 38 published articles. TTR ranged from 29% to 75%; percentage of INRs ranged from 34% to 84%. From studies reporting both measures, TTR significantly correlated with percentage of INRs in range (P<0.001). Randomized controlled trials had better INR control than retrospective studies (64.9% versus 56.4%; P=0.01). TTR negatively correlated with major hemorrhage (r=−0.59; P=0.002) and thromboembolic rates (r=−0.59; P=0.01). This effect was significant in retrospective studies (major hemorrhage, r=−0.78; P=0.006 and thromboembolic rate, r=−0.88; P=0.03) but not in randomized controlled trials (major hemorrhage, r=0.18; P=0.33 and thromboembolic rate, r=−0.61; P=0.07). For retrospective studies, a 6.9% improvement in the TTR significantly reduced major hemorrhage by 1 event per 100 patient-years of treatment (95% CI, 0.29 to 1.71 events). Conclusions—In atrial fibrillation patients receiving orally administered anticoagulation treatment, TTR and percentage of INRs in range effectively predict INR control. Data from retrospective studies support the use of TTR to accurately predict reductions in adverse events.

Clinical workload in UK primary care: a retrospective analysis of 100 million consultations in England, 2007–14

Summary Background Primary care is the main source of health care in many health systems, including the UK National Health Service (NHS), but few objective data exist for the volume and nature of primary care activity. With rising concerns that NHS primary care workload has increased substantially, we aimed to assess the direct clinical workload of general practitioners (GPs) and practice nurses in primary care in the UK. Methods We did a retrospective analysis of GP and nurse consultations of non-temporary patients registered at 398 English general practices between April, 2007, and March, 2014. We used data from electronic health records routinely entered in the Clinical Practice Research Datalink, and linked CPRD data to national datasets. Trends in age-standardised and sex-standardised consultation rates were modelled with joinpoint regression analysis. Findings The dataset comprised 101 818 352 consultations and 20 626 297 person-years of observation. The crude annual consultation rate per person increased by 10·51%, from 4·67 in 2007–08, to 5·16 in 2013–14. Consultation rates were highest in infants (age 0–4 years) and elderly people (≥85 years), and were higher for female patients than for male patients of all ages. The greatest increases in age-standardised and sex-standardised rates were in GPs, with a rise of 12·36% per 10 000 person-years, compared with 0·9% for practice nurses. GP telephone consultation rates doubled, compared with a 5·20% rise in surgery consultations, which accounted for 90% of all consultations. The mean duration of GP surgery consultations increased by 6·7%, from 8·65 min (95% CI 8·64–8·65) to 9·22 min (9·22–9·23), and overall workload increased by 16%. Interpretation Our findings show a substantial increase in practice consultation rates, average consultation duration, and total patient-facing clinical workload in English general practice. These results suggest that English primary care as currently delivered could be reaching saturation point. Notably, our data only explore direct clinical workload and not indirect activities and professional duties, which have probably also increased. This and additional research questions, including the outcomes of workload changes on other sectors of health care, need urgent answers for primary care provision internationally. Funding Department of Health Policy Research Programme.

Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials.

Aims/hypothesisObservational studies suggest that metformin may reduce cancer risk by approximately one-third. We examined cancer outcomes and all-cause mortality in published randomised controlled trials (RCTs).MethodsRCTs comparing metformin with active glucose-lowering therapy or placebo/usual care, with minimum 500 participants and 1-year follow-up, were identified by systematic review. Data on cancer incidence and all-cause mortality were obtained from publications or by contacting investigators. For two trials, cancer incidence data were not available; cancer mortality was used as a surrogate. Summary RRs, 95% CIs and I2statistics for heterogeneity were calculated by fixed effects meta-analysis.ResultsOf 4,039 abstracts identified, 94 publications described 14 eligible studies. RRs for cancer were available from 11 RCTs with 398 cancers during 51,681 person-years. RRs for all-cause mortality were available from 13 RCTs with 552 deaths during 66,447 person-years. Summary RRs for cancer outcomes in people randomised to metformin compared with any comparator were 1.02 (95% CI 0.82, 1.26) across all trials, 0.98 (95% CI 0.77, 1.23) in a subgroup analysis of active-comparator trials and 1.36 (95% CI 0.74, 2.49) in a subgroup analysis of placebo/usual care comparator trials. The summary RR for all-cause mortality was 0.94 (95% CI 0.79, 1.12) across all trials.Conclusions/interpretationMeta-analysis of currently available RCT data does not support the hypothesis that metformin lowers cancer risk by one-third. Eligible trials also showed no significant effect of metformin on all-cause mortality. However, limitations include heterogeneous comparator types, absent cancer data from two trials, and short follow-up, especially for mortality.

Symptoms associated with diagnosis of ovarian cancer: a systematic review

The overall five-year survival from ovarian cancer is currently poor at around 30%, with the majority of cancers being diagnosed at an advanced stage. The late stage at presentation has been blamed upon the insidious nature of the disease and the vagueness of the symptoms of ovarian cancer, which may be interpreted by patients as being normal changes in the body such as the effects of childbearing, menopause and ageing. In addition, many of the reported symptoms are not specific to ovarian cancer and may mimic conditions such as irritable bowel syndrome. The difficulties in recognising the likely symptoms of ovarian cancer are reflected in the often convoluted pathways that patients follow before being correctly diagnosed. Frequent symptoms recorded at presentation include pain and abdominal swelling, dyspepsia, vomiting, altered bowel habit and urinary symptoms of frequency or retention. These non-specific symptoms (as noted in the medical records) have been shown to be predictive of decreased survival. As the consequences of diagnosis at a late stage are catastrophic, the symptoms associated with the presence of ovarian cancer, and their subtleties, need to be better understood in order to facilitate appropriate and timely health-seeking behaviours and referral. Some research has been conducted in this field but has often been retrospective, limited and subject to recording and recall biases. In this study, the research to date has been identified and summarised.

Synthesising quantitative and qualitative research in evidence-based patient information

Background: Systematic reviews have, in the past, focused on quantitative studies and clinical effectiveness, while excluding qualitative evidence. Qualitative research can inform evidence-based practice independently of other research methodologies but methods for the synthesis of such data are currently evolving. Synthesising quantitative and qualitative research in a single review is an important methodological challenge. Aims: This paper describes the review methods developed and the difficulties encountered during the process of updating a systematic review of evidence to inform guidelines for the content of patient information related to cervical screening. Methods: Systematic searches of 12 electronic databases (January 1996 to July 2004) were conducted. Studies that evaluated the content of information provided to women about cervical screening or that addressed women’s information needs were assessed for inclusion. A data extraction form and quality assessment criteria were developed from published resources. A non-quantitative synthesis was conducted and a tabular evidence profile for each important outcome (eg “explain what the test involves”) was prepared. The overall quality of evidence for each outcome was then assessed using an approach published by the GRADE working group, which was adapted to suit the review questions and modified to include qualitative research evidence. Quantitative and qualitative studies were considered separately for every outcome. Results: 32 papers were included in the systematic review following data extraction and assessment of methodological quality. The review questions were best answered by evidence from a range of data sources. The inclusion of qualitative research, which was often highly relevant and specific to many components of the screening information materials, enabled the production of a set of recommendations that will directly affect policy within the NHS Cervical Screening Programme. Conclusions: A practical example is provided of how quantitative and qualitative data sources might successfully be brought together and considered in one review.

Symptoms and other factors associated with time to diagnosis and stage of lung cancer: a prospective cohort study

Background:This prospective cohort study aimed to identify symptom and patient factors that influence time to lung cancer diagnosis and stage at diagnosis.Methods:Data relating to symptoms were collected from patients upon referral with symptoms suspicious of lung cancer in two English regions; we also examined primary care and hospital records for diagnostic routes and diagnoses. Descriptive and regression analyses were used to investigate associations between symptoms and patient factors with diagnostic intervals and stage.Results:Among 963 participants, 15.9% were diagnosed with primary lung cancer, 5.9% with other thoracic malignancies and 78.2% with non-malignant conditions. Only half the cohort had an isolated first symptom (475, 49.3%); synchronous first symptoms were common. Haemoptysis, reported by 21.6% of cases, was the only initial symptom associated with cancer. Diagnostic intervals were shorter for cancer than non-cancer diagnoses (91 vs 124 days, P=0.037) and for late-stage than early-stage cancer (106 vs 168 days, P=0.02). Chest/shoulder pain was the only first symptom with a shorter diagnostic interval for cancer compared with non-cancer diagnoses (P=0.003).Conclusions:Haemoptysis is the strongest symptom predictor of lung cancer but occurs in only a fifth of patients. Programmes for expediting earlier diagnosis need to focus on multiple symptoms and their evolution.

What Is the Psychological Impact of Mammographic Screening on Younger Women With a Family History of Breast Cancer? Findings From a Prospective Cohort Study by the PIMMS Management Group

PURPOSE Studies are underway to establish the clinical effectiveness of annual mammographic screening in women younger than 50 years with a family history of breast cancer. This study investigated both the positive and negative psychological effects of screening on these women. PATIENTS AND METHODS Women who received an immediate all-clear result after mammography (n = 1,174) and women who were recalled for additional tests before receiving an all-clear result (false positive; n = 112) completed questionnaires: 1 month before mammography, and 1 and 6 months after receiving final results. The questionnaires included measures of cancer worry, psychological consequences, and perceived benefits of breast screening. RESULTS Women who received an immediate all-clear result experienced a decrease in cancer worry and negative psychological consequences immediately after the result, whereas women who were recalled for additional tests did not. By 6 months this cancer-specific distress had reduced significantly in both groups. Changes in levels of distress were significantly different between the two groups, but in absolute terms the differences were not large. Recalled women reported significantly greater positive psychological consequences of screening immediately after the result, and were also more positive about the benefits of screening compared with women who received an immediate all-clear result. CONCLUSION For women receiving an immediate all-clear result, participating in annual mammographic screening is psychologically beneficial. Furthermore, women who are recalled for additional tests do not appear to be harmed by screening: these womens positive views about mammography suggest that they view any distress caused by recall as an acceptable part of screening.

Information and cervical screening: a qualitative study of women's awareness, understanding and information needs about HPV

Objectives: To explore womens attitudes towards the information about human papilloma virus (HPV) provided during cervical screening and to describe womens HPV information needs. Setting: Women with a range of screening results (normal, inadequate, borderline and abnormal) were identified by three screening centres in England. Two consecutive samples of women attending for colposcopy for the first time following screening were also approached. Methods: Seven focus groups were conducted between May 2005 and April 2006 with 38 women who had recently been for cervical screening or had attended a colposcopy appointment. Results: Most women had no prior awareness of HPV. Many women queried the importance of being informed about HPV as no preventive advice or treatment is available. The HPV information included in the UK national screening programme abnormal result leaflet left women with more questions than answers (a list of unanswered questions is included with the results). Further information was requested about HPV detection, infection and transmission as well as the natural history and progression of cervical cancer. No consensus was reached regarding the best time to provide HPV information. Conclusions: Clear communication of the complicated issues surrounding HPV infection and the natural history of cervical cancer is a considerable educational challenge for screening providers. As awareness of HPV becomes more widespread and HPV testing is explored as a triage during cervical screening, women are likely to require more information about the virus and the implications of infection. Consideration should be given to the production of a separate national screening programme HPV leaflet.