Individual inflammatory marker abnormalities or inflammatory marker scores to identify primary care patients with unexpected weight loss for cancer investigation?

BACKGROUND: Combinations of inflammatory markers are used as prognostic scores in cancer patients with cachexia. We investigated whether they could also be used to prioritise patients attending primary care with unexpected weight loss for cancer investigation. METHODS: We used English primary care electronic health records data linked to cancer registry data from 12,024 patients with coded unexpected weight loss. For each individual inflammatory marker and score we estimated the sensitivity, specificity, likelihood ratios, positive predictive value (PPV) and the area under the curve along with 95% confidence intervals for a cancer diagnosis within six months. RESULTS: The risk of cancer associated with two abnormal inflammatory markers combined in a score was higher than the risk associated with individual inflammatory marker abnormalities. However, the risk of cancer in weight loss associated with individual abnormalities, notably a raised C-reactive protein, was sufficient to trigger further investigation for cancer under current NICE guidelines. CONCLUSIONS: If scores including pairs of inflammatory marker abnormalities were to be used, in preference to individual abnormalities, fewer people would be investigated to diagnose one cancer with fewer false positives, but fewer people with cancer would be diagnosed overall.

UMBRELLA protocol: systematic reviews of multivariable biomarker prognostic models developed to predict clinical outcomes in patients with heart failure.

BACKGROUND: Heart failure (HF) is a chronic and common condition with a rising prevalence, especially in the elderly. Morbidity and mortality rates in people with HF are similar to those with common forms of cancer. Clinical guidelines highlight the need for more detailed prognostic information to optimise treatment and care planning for people with HF. Besides proven prognostic biomarkers and numerous newly developed prognostic models for HF clinical outcomes, no risk stratification models have been adequately established. Through a number of linked systematic reviews, we aim to assess the quality of the existing models with biomarkers in HF and summarise the evidence they present. METHODS: We will search MEDLINE, EMBASE, Web of Science Core Collection, and the prognostic studies database maintained by the Cochrane Prognosis Methods Group combining sensitive published search filters, with no language restriction, from 1990 onwards. Independent pairs of reviewers will screen and extract data. Eligible studies will be those developing, validating, or updating any prognostic model with biomarkers for clinical outcomes in adults with any type of HF. Data will be extracted using a piloted form that combines published good practice guidelines for critical appraisal, data extraction, and risk of bias assessment of prediction modelling studies. Missing information on predictive performance measures will be sought by contacting authors or estimated from available information when possible. If sufficient high quality and homogeneous data are available, we will meta-analyse the predictive performance of identified models. Sources of between-study heterogeneity will be explored through meta-regression using pre-defined study-level covariates. Results will be reported narratively if study quality is deemed to be low or if the between-study heterogeneity is high. Sensitivity analyses for risk of bias impact will be performed. DISCUSSION: This project aims to appraise and summarise the methodological conduct and predictive performance of existing clinically homogeneous HF prognostic models in separate systematic reviews.Registration: PROSPERO registration number CRD42019086990.

Self-monitoring of Blood Pressure in Patients With Hypertension-Related Multi-morbidity: Systematic Review and Individual Patient Data Meta-analysis.

BACKGROUND: Studies have shown that self-monitoring of blood pressure (BP) is effective when combined with co-interventions, but its efficacy varies in the presence of some co-morbidities. This study examined whether self-monitoring can reduce clinic BP in patients with hypertension-related co-morbidity. METHODS: A systematic review was conducted of articles published in Medline, Embase, and the Cochrane Library up to January 2018. Randomized controlled trials of self-monitoring of BP were selected and individual patient data (IPD) were requested. Contributing studies were prospectively categorized by whether they examined a low/high-intensity co-intervention. Change in BP and likelihood of uncontrolled BP at 12 months were examined according to number and type of hypertension-related co-morbidity in a one-stage IPD meta-analysis. RESULTS: A total of 22 trials were eligible, 16 of which were able to provide IPD for the primary outcome, including 6,522 (89%) participants with follow-up data. Self-monitoring was associated with reduced clinic systolic BP compared to usual care at 12-month follow-up, regardless of the number of hypertension-related co-morbidities (-3.12 mm Hg, [95% confidence intervals -4.78, -1.46 mm Hg]; P value for interaction with number of morbidities = 0.260). Intense interventions were more effective than low-intensity interventions in patients with obesity (P < 0.001 for all outcomes), and possibly stroke (P < 0.004 for BP control outcome only), but this effect was not observed in patients with coronary heart disease, diabetes, or chronic kidney disease. CONCLUSIONS: Self-monitoring lowers BP regardless of the number of hypertension-related co-morbidities, but may only be effective in conditions such obesity or stroke when combined with high-intensity co-interventions.

Determinants and extent of weight recording in UK primary care: an analysis of 5 million adults' electronic health records from 2000 to 2017.

BACKGROUND: Excess weight and unexpected weight loss are associated with multiple disease states and increased morbidity and mortality, but weight measurement is not routine in many primary care settings. The aim of this study was to characterise who has had their weight recorded in UK primary care, how frequently, by whom and in relation to which clinical events, symptoms and diagnoses. METHODS: A longitudinal analysis of UK primary care electronic health records (EHR) data from 2000 to 2017. Descriptive statistics were used to summarise weight recording in terms of patient sociodemographic characteristics, health professional encounters, clinical events, symptoms and diagnoses. Negative binomial regression was used to model the likelihood of having a weight record each year, and Cox regression to the likelihood of repeated weight recording. RESULTS: A total of 14,049,871 weight records were identified in the EHR of 4,918,746 patients during the study period, representing 26,998,591 person-years of observation. Around a third of patients had a weight record each year. Forty-nine percent of weight records were repeated within a year with an average time to a repeat weight record of 1.92 years. Weight records were most often taken by nursing staff (38-42%) and GPs (37-39%) as part of a routine clinical care, such as chronic disease reviews (16%), medication reviews (6-8%) and health checks (6-7%), or were associated with consultations for contraception (5-8%), respiratory disease (5%) and obesity (1%). Patient characteristics independently associated with an increased likelihood of weight recording were as follows: female sex, younger and older adults, non-drinkers, ex-smokers, low or high BMI, being more deprived, diagnosed with a greater number of comorbidities and consulting more frequently. The effect of policy-level incentives to record weight did not appear to be sustained after they were removed. CONCLUSION: Weight recording is not a routine activity in UK primary care. It is recorded for around a third of patients each year and is repeated on average every 2 years for these patients. It is more common in females with higher BMI and in those with comorbidity. Incentive payments and their removal appear to be associated with increases and decreases in weight recording.

Weight loss as a predictor of cancer and serious disease in primary care: an ISAC-approved CPRD protocol for a retrospective cohort study using routinely collected primary care data from the UK.

BACKGROUND: Unexpected weight loss is a symptom of serious disease in primary care, for example between 1 in 200 and 1 in 30 patients with unexpected weight loss go on to develop cancer. However, it remains unclear how and when general practitioners (GPs) should investigate unexpected weight loss. Without clarification, GPs may wait too long before referring (choosing to watch and wait and potentially missing a diagnosis) or not long enough (overburdening hospital services and exposing patients to the risks of investigation). The overall aim of this study is to provide the evidence necessary to allow GPs to more effectively manage patients with unexpected weight loss. METHODS: A retrospective cohort analysis of UK Clinical Practice Research Datalink (CPRD) data to: (1) describe how often in UK primary care the symptom of reported weight loss is coded, when weight is measured, and how GPs respond to a patient attending with unexpected weight loss; (2) identify the predictive value of recorded weight loss for cancer and serious disease in primary care, using cumulative incidence plots to compare outcomes between subgroups and Cox regression to explore and adjust for covariates. Preliminary work in CPRD estimates that weight loss as a symptom is recorded for approximately 148,000 eligible patients > 18 years and is distributed evenly across decades of age, providing adequate statistical power and precision in relation to cancer overall and common cancers individually. Further stratification by cancer stage will be attempted but may not be possible as not all practices within CPRD are eligible for cancer registry linkage, and staging information is often incomplete. The feasibility of using multiple imputation to address missing covariate values will be explored. DISCUSSION: This will be the largest reported retrospective cohort of primary care patients with weight measurements and unexpected weight loss codes used to understand the association between weight measurement, unexpected weight loss, and serious disease including cancer. Our findings will directly inform international guidelines for the management of unexpected weight loss in primary care populations.

Current and potential providers of blood pressure self-screening: a mixed methods study in Oxfordshire.

OBJECTIVES: To (1) establish the extent of opportunities for members of the public to check their own blood pressure (BP) outside of healthcare consultations (BP self-screening), (2) investigate the reasons for and against hosting such a service and (3) ascertain how BP self-screening data are used in primary care. DESIGN: A mixed methods, cross-sectional study. SETTING: Primary care and community locations in Oxfordshire, UK. PARTICIPANTS: 325 sites were surveyed to identify where and in what form BP self-screening services were available. 23 semistructured interviews were then completed with current and potential hosts of BP self-screening services. RESULTS: 18/82 (22%) general practices offered BP self-screening and 68/110 (62%) pharmacies offered professional-led BP screening. There was no evidence of permanent BP self-screening activities in other community settings.Healthcare professionals, managers, community workers and leaders were interviewed. Those in primary care generally felt that practice-based BP self-screening was a beneficial activity that increased the attainment of performance targets although there was variation in its perceived usefulness for patient care. The pharmacists interviewed provided BP checking as a service to the community but were unable to develop self-screening services without a clear business plan. Among potential hosts, barriers to providing a BP self-screening service included a perceived lack of healthcare commissioner and public demand, and a weak-if any-link to their core objectives as an organisation. CONCLUSIONS: BP self-screening currently occurs in a minority of general practices. Any future development of community BP self-screening programmes will require (1) public promotion and (2) careful consideration of how best to support-and reward-the community hosts who currently perceive little if any benefit.

From breathless to failure: symptom onset and diagnostic meaning in patients with heart failure-a qualitative study.

OBJECTIVES: To explore 2 key points in the heart failure diagnostic pathway-symptom onset and diagnostic meaning-from the patient perspective. DESIGN: Qualitative interview study. SETTING: Participants were recruited from a secondary care clinic in central England following referral from primary care. PARTICIPANTS: Over age 55 years with a recent (<1 year) diagnosis of heart failure confirmed by a cardiologist following initial presentation to primary care. METHODS: Semistructured interviews were carried out with 16 participants (11 men and 5 women, median age 78.5 years) in their own homes. Data were audio-recorded and transcribed. Participants were asked to describe their diagnostic journey from when they first noticed something wrong up to and including the point of diagnosis. Data were analysed using the framework method. RESULTS: Participants initially normalised symptoms and only sought medical help when daily activities were affected. Failure to realise that anything was wrong led to a delay in help-seeking. Participants' understanding of the term 'heart failure' was variable and 1 participant did not know he had the condition. The term itself caused great anxiety initially but participants learnt to cope with and accept their diagnosis over time. CONCLUSIONS: Greater public awareness of symptoms and adequate explanation of 'heart failure' as a diagnostic label, or reconsideration of its use, are potential areas of service improvement.

An internet-delivered handwashing intervention to modify influenza-like illness and respiratory infection transmission (PRIMIT): a primary care randomised trial.

BACKGROUND: Handwashing to prevent transmission of respiratory tract infections (RTIs) has been widely advocated, especially during the H1N1 pandemic. However, the role of handwashing is debated, and no good randomised evidence exists among adults in non-deprived settings. We aimed to assess whether an internet-delivered intervention to modify handwashing would reduce the number of RTIs among adults and their household members. METHODS: We recruited individuals sharing a household by mailed invitation through general practices in England. After consent, participants were randomised online by an automated computer-generated random number programme to receive either no access or access to a bespoke automated web-based intervention that maximised handwashing intention, monitored handwashing behaviour, provided tailored feedback, reinforced helpful attitudes and norms, and addressed negative beliefs. We enrolled participants into an additional cohort (randomised to receive intervention or no intervention) to assess whether the baseline questionnaire on handwashing would affect handwashing behaviour. Participants were not masked to intervention allocation, but statistical analysis commands were constructed masked to group. The primary outcome was number of episodes of RTIs in index participants in a modified intention-to-treat population of randomly assigned participants who completed follow-up at 16 weeks. This trial is registered with the ISRCTN registry, number ISRCTN75058295. FINDINGS: Across three winters between Jan 17, 2011, and March 31, 2013, we enrolled 20,066 participants and randomly assigned them to receive intervention (n=10,040) or no intervention (n=10,026). 16,908 (84%) participants were followed up with the 16 week questionnaire (8241 index participants in intervention group and 8667 in control group). After 16 weeks, 4242 individuals (51%) in the intervention group reported one or more episodes of RTI compared with 5135 (59%) in the control group (multivariate risk ratio 0·86, 95% CI 0·83-0·89; p<0·0001). The intervention reduced transmission of RTIs (reported within 1 week of another household member) both to and from the index person. We noted a slight increase in minor self-reported skin irritation (231 [4%] of 5429 in intervention group vs 79 [1%] of 6087 in control group) and no reported serious adverse events. INTERPRETATION: In non-pandemic years, an effective internet intervention designed to increase handwashing could have an important effect in reduction of infection transmission. In view of the heightened concern during a pandemic and the likely role of the internet in access to advice, the intervention also has potential for effective implementation during a pandemic. FUNDING: Medical Research Council.

Performance and persistence of a blood pressure self-management intervention: telemonitoring and self-management in hypertension (TASMINH2) trial.

This study aimed to evaluate, in detail, the implementation of the self-management intervention used in the TASMINH2 trial. The intervention, comprising self-monitoring for the first week of each month and an individualised treatment self-titration schedule, was developed from a previous trial of self-management. Two hundred and sixty-three patients with poorly controlled but treated hypertension were randomised to receive this intervention and underwent training over two or three sessions. Participants were followed up for 12 months during which time process data were collected regarding the persistence and fidelity of actual behaviour compared with intervention recommendations. Two hundred and forty-one (92%) patients completed training of whom 188 (72%) self-managed their BP and completed at least 90% of expected self-monitoring measurements for the full year of the study. Overall, 268/483 (55%) of recommended medication changes were implemented. Only 25 (13%) patients had controlled BP throughout the year and so were not recommended any medication changes. Adherence to the protocol reduced over time as the number of potential changes increased. Of those self-managing throughout, 131 (70%) made at least one medication change, with 77 (41%) implementing all their recommended changes. In conclusion, self-management of hypertension was possible in practice with most participants making at least one medication change. Although adherence to the intervention reduced over time, implementation of treatment recommendations appeared better than equivalent trials using physician titration. Future self-management interventions should aim to better support patients' decision making, perhaps through enhanced use of technology.

The potential role of NT-proBNP in screening for and predicting prognosis in heart failure: a survival analysis.

OBJECTIVE: To determine the potential role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in screening for and predicting prognosis in heart failure by examining diagnosis and survival of patients with a raised NT-proBNP at screening. DESIGN: Survival analysis. SETTING: Prospective substudy of the Echocardiographic Heart of England Screening study (ECHOES) to investigate 10-year survival in participants with an NT-proBNP level at baseline. PARTICIPANTS: 594 participants took part in the substudy. Records of all participants in the ECHOES cohort were flagged during the screening phase which ended on 25 February 1999. All deaths until 25 February 2009 were coded. OUTCOME MEASURES: Logistic regression was used to examine whether NT-proBNP is useful in predicting heart failure at screening after adjustment for age, sex and cohort. Kaplan-Meier curves and log rank tests were used to compare survival times of participants according to NT-proBNP level. Cox regression was carried out to assess the prognostic effect of NT-proBNP after allowing for significant covariates and receiver operator curves were used to determine test reliability. RESULTS: The risk of heart failure increased almost 18-fold when NT-proBNP was 150 pg/mL or above (adjusted OR=17.7, 95% CI 4.9 to 63.5). 10-year survival in the general population cohort was 61% (95% CI 48% to 71%) for those with NT-proBNP ≥150 pg/mL and 89% (95% CI 84% to 92%) for those below the cut-off at the time of the initial study. After adjustment for age, sex and risk factors for heart failure, NT-proBNP level ≥150 pg/mL was associated with a 58% increase in the risk of death within 10 years (adjusted HR=1.58, 95% CI 1.09 to 2.30). CONCLUSIONS: Raised NT-proBNP levels, when screening the general population, are predictive of a diagnosis of heart failure (at a lower threshold than guidelines for diagnosing symptomatic patients) and also predicted reduced survival at 10 years.

Is screening for AF worthwhile? Stroke risk in a screened population from the SAFE study.

INTRODUCTION: Atrial fibrillation (AF) is an important independent risk factor for stroke and oral anticoagulation therapy provides a highly effective treatment to reduce this risk. Active screening strategies improve detection of AF in comparison with routine care; however, whether screen-detected patients have stroke risk profiles favouring anticoagulation is unclear. Using data derived from the screening for AF in the elderly (SAFE) study, the aim of this article was to determine if patients with AF detected via active screening have stroke risk profiles that warrant prophylactic anticoagulation. METHODS: Secondary analysis of data derived from 25 general practices within which cohorts of 200 patients were randomly allocated to opportunistic [pulse and electrocardiogram (ECG)] or systematic screening (postal invitation for ECG). Stroke risk assessment was undertaken using baseline data extracted from medical records and CHADS2 criteria. CHADS2 scores were compared between the screening groups. RESULTS: One hundred and forty-nine new cases of AF were detected, 75 via opportunistic screening and 74 via systematic screening. CHADS2 scores were ≥1 in 83% [95% confidence interval (CI) 72.6-89.6] of patients detected via opportunistic screening and 78% (95% CI 67.7-86.2) detected via systematic screening. There were no significant differences in stroke risk profiles of patients detected via opportunistic and systematic screenings. CONCLUSION: Stroke risk profiles of patients detected via opportunistic and systematic screenings were similar. Data derived from the SAFE study suggest that active screening for AF in patients aged ≥65 years in primary care is a useful screening programme with 78-83% of patients identified eligible for anticoagulation treatment according to the CHADS2 criteria.

Self-monitoring in hypertension: a web-based survey of primary care physicians.

Although self-monitoring of blood pressure is common among people with hypertension, little is known about how general practitioners (GPs) use such readings. This survey aimed to ascertain current views and practice on self-monitoring of UK primary care physicians. An internet-based survey of UK GPs was undertaken using a provider of internet services to UK doctors. The hyperlink to the survey was opened by 928 doctors, and 625 (67%) GPs completed the questionnaire. Of them, 557 (90%) reported having patients who self-monitor, 191 (34%) had a monitor that they lend to patients, 171 (31%) provided training in self-monitoring for their patients and 52 (9%) offered training to other GPs. Three hundred and sixty-seven GPs (66%) recommended at least two readings per day, and 416 (75%) recommended at least 4 days of monitoring at a time. One hundred and eighty (32%) adjusted self-monitored readings to take account of lower pressures in out-of-office settings, and 10/5 mm Hg was the most common adjustment factor used. Self-monitoring of blood pressure was widespread among the patients of responding GPs. Although the majority used appropriate schedules of measurement, some GPs suggested much more frequent home measurements than usual. Further, interpretation of home blood pressure was suboptimal, with only a minority recognising that values for diagnosis and on-treatment target are lower than those for clinic measurement. Subsequent national guidance may improve this situation but will require adequate implementation.

PRImary care Streptococcal Management (PRISM) study: identifying clinical variables associated with Lancefield group A ß-haemolytic streptococci and Lancefield non-Group A streptococcal throat infections from two cohorts of patients presenting with an acute sore throat.

OBJECTIVE: To assess the association between features of acute sore throat and the growth of streptococci from culturing a throat swab. DESIGN: Diagnostic cohort. SETTING: UK general practices. PARTICIPANTS: Patients aged 5 or over presenting with an acute sore throat. Patients were recruited for a second cohort (cohort 2, n=517) consecutively after the first (cohort 1, n=606) from similar practices. MAIN OUTCOME: Predictors of the presence of Lancefield A/C/G streptococci. RESULTS: The clinical score developed from cohort 1 had poor discrimination in cohort 2 (bootstrapped estimate of area under the receiver operator characteristic (ROC) curve (0.65), due to the poor validity of the individual items in the second data set. Variables significant in multivariate analysis in both cohorts were rapid attendance (prior duration 3 days or less; multivariate adjusted OR 1.92 cohort, 1.67 cohort 2); fever in the last 24 h (1.69, 2.40); and doctor assessment of severity (severely inflamed pharynx/tonsils (2.28, 2.29)). The absence of coryza or cough and purulent tonsils were significant in univariate analysis in both cohorts and in multivariate analysis in one cohort. A five-item score based on Fever, Purulence, Attend rapidly (3 days or less), severely Inflamed tonsils and No cough or coryza (FeverPAIN) had moderate predictive value (bootstrapped area under the ROC curve 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection (38% in cohort 1, 36% in cohort 2 scored ≤1, associated with a streptococcal percentage of 13% and 18%, respectively). A Centor score of ≤1 identified 23% and 26% of participants with streptococcal percentages of 10% and 28%, respectively. CONCLUSIONS: Items widely used to help identify streptococcal sore throat may not be the most consistent. A modified clinical scoring system (FeverPAIN) which requires further validation may be clinically helpful in identifying individuals who are unlikely to have major pathogenic streptococci.

Impact of age and gender on blood pressure and low-density lipoprotein cholesterol reduction: results of a pooled analysis.

OBJECTIVES: To compare the simultaneous reduction of blood pressure (BP) to below 150 mmHg and low-density lipoprotein cholesterol (LDL-C) after treatment with single-pill amlodipine/atorvastatin (SPAA) among younger (<65 years), older (≥65 years) and elderly (≥75 years) men and women with hypertension and dyslipidemia. METHODS: Data from five, 14-20-week, open-label, multi-national studies (GEMINI US, GEMINI-Australia, Asia, Latin-America, Africa/Middle-East [AALA], JEWEL 1, JEWEL 2, and the Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points [CAPABLE]) were pooled. In these studies, SPAA (5/10 to 10/80 mg/mg) was electively titrated to achieve study-specific targets. Reductions in BP and LDL-C, and changes in renal and liver function tests, fasting glucose and adverse event (AE) rates were compared across the three age groups. RESULTS: A total of 3613 patients (65%) were <65 years, 1946 (35%) were ≥65 years and 441 (8%) were ≥75 years. Baseline mean systolic BP tended to increase with age and diastolic BP and LDL-C decreased, p<0.001. Final mean SPAA dose was similar (7.2/23.9, 7.1/24.3, 7.1/24.0 mg/mg). Final mean BP in the younger/older/elderly groups was 128.1/79.9, 131.3/75.0, 132.8/73.4 mmHg (adjusted BP reductions -20.2/-10.4, -18.6/-12.7, -17.7/-13.2 mmHg, p<0.001). Final mean LDL-C was 91, 87, 87 mg/dl (2.4, 2.3, 2.3 mmol/l) p<0.001; adjusted %LDL-C reductions -27.1, -26.8, -26.4, p<0.001. Estimated glomerular filtration rate increased in the younger group but decreased in the older and elderly groups (p=0.005). Small increases in liver function tests and fasting glucose were observed. Discontinuations due to AEs tended to increase with age but were low in all groups (6.2%, 7.9%, 8.8%, p=0.045). Study limitations include post hoc analysis and short duration of follow-up. CONCLUSIONS: Simultaneous reduction of BP to below 150 mmHg and LDL-C using SPAA is both effective and well-tolerated among younger and older men and women, including those aged≥75 years. Clinicians may be reassured by the low proportion of AEs that led to discontinuation in all groups suggesting that older patients were not disadvantaged by this treatment.

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

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

Treatment pathways for patients with atrial fibrillation.

BACKGROUND: Although there has been growing concordance over what constitutes best practice in recent guidelines for treatment of atrial fibrillation (AF), notably regarding anticoagulant use, it remains unclear whether patients are being treated accordingly. AIMS: The aims of this study were to explore the pattern of treatment pathways - i.e. how patients are treated over time - for patients with AF, and to test the hypothesis that comparative to patients in lower stroke-risk categories (as measured by CHADS(2) score), patients with higher CHADS(2) scores are less likely to discontinue anticoagulant therapy or, if not started on anticoagulant treatment, more likely to be transferred to anticoagulant therapy, in keeping with guideline recommendations. SETTING: A total of 67,857 patients with a diagnosis of AF in practices registered with the General Practice Research Database. METHODS: A series of possible treatment pathways were identified, and for each initial treatment, we estimated the probability of treatment change and the average time that a patient newly diagnosed with AF spent on a particular treatment, projected across 5 years and stratified by CHADS(2) score. RESULTS: There was no relationship between CHADS(2) score and maintenance or discontinuation of particular approaches to antithrombotic treatment. While those beginning on antiplatelet therapy were more likely to change treatment than those on anticoagulants (approximately 60% vs. 50% within the first year), as much as one-third of treatment time of all those starting on a therapeutic approach involving anticoagulants featured no use of anticoagulants (either as monotherapy or in combination) over the 5-year period, and whether treatment was discontinued or maintained did not vary by CHADS(2) score. No difference was found in treatment pathways controlling for post-2002 diagnoses as against the whole sample. CONCLUSIONS: Although there is more evidence of treatment maintenance than treatment change, especially in the first year after diagnosis, the amount of therapeutic change remains noteworthy and appears higher than in some previous studies. Prescription patterns for AF therapy suggest that too few high-risk patients are receiving best practice treatment, and particularly of concern is that some of these patients are being transferred away from best practice treatment over time.

Performance of stroke risk scores in older people with atrial fibrillation not taking warfarin: comparative cohort study from BAFTA trial.

OBJECTIVE: To compare the predictive power of the main existing and recently proposed schemes for stratification of risk of stroke in older patients with atrial fibrillation. DESIGN: Comparative cohort study of eight risk stratification scores. SETTING: Trial of thromboprophylaxis in stroke, the Birmingham Atrial Fibrillation in the Aged (BAFTA) trial. PARTICIPANTS: 665 patients aged 75 or over with atrial fibrillation based in the community who were randomised to the BAFTA trial and were not taking warfarin throughout or for part of the study period. MAIN OUTCOME MEASURES: Events rates of stroke and thromboembolism. RESULTS: 54 (8%) patients had an ischaemic stroke, four (0.6%) had a systemic embolism, and 13 (2%) had a transient ischaemic attack. The distribution of patients classified into the three risk categories (low, moderate, high) was similar across three of the risk stratification scores (revised CHADS(2), NICE, ACC/AHA/ESC), with most patients categorised as high risk (65-69%, n = 460-457) and the remaining classified as moderate risk. The original CHADS(2) (Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke) score identified the lowest number as high risk (27%, n = 180). The incremental risk scores of CHADS(2), Rietbrock modified CHADS(2), and CHA(2)DS(2)-VASc (CHA(2)DS(2)-Vascular disease, Age 65-74 years, Sex) failed to show an increase in risk at the upper range of scores. The predictive accuracy was similar across the tested schemes with C statistic ranging from 0.55 (original CHADS(2)) to 0.62 (Rietbrock modified CHADS(2)), with all except the original CHADS(2) predicting better than chance. Bootstrapped paired comparisons provided no evidence of significant differences between the discriminatory ability of the schemes. CONCLUSIONS: Based on this single trial population, current risk stratification schemes in older people with atrial fibrillation have only limited ability to predict the risk of stroke. Given the systematic undertreatment of older people with anticoagulation, and the relative safety of warfarin versus aspirin in those aged over 70, there could be a pragmatic rationale for classifying all patients over 75 as "high risk" until better tools are available.

Relative effectiveness of clinic and home blood pressure monitoring compared with ambulatory blood pressure monitoring in diagnosis of hypertension: systematic review.

OBJECTIVE: To determine the relative accuracy of clinic measurements and home blood pressure monitoring compared with ambulatory blood pressure monitoring as a reference standard for the diagnosis of hypertension. DESIGN: Systematic review with meta-analysis with hierarchical summary receiver operating characteristic models. Methodological quality was appraised, including evidence of validation of blood pressure measurement equipment. DATA SOURCES: Medline (from 1966), Embase (from 1980), Cochrane Database of Systematic Reviews, DARE, Medion, ARIF, and TRIP up to May 2010. Eligibility criteria for selecting studies Eligible studies examined diagnosis of hypertension in adults of all ages using home and/or clinic blood pressure measurement compared with those made using ambulatory monitoring that clearly defined thresholds to diagnose hypertension. RESULTS: The 20 eligible studies used various thresholds for the diagnosis of hypertension, and only seven studies (clinic) and three studies (home) could be directly compared with ambulatory monitoring. Compared with ambulatory monitoring thresholds of 135/85 mm Hg, clinic measurements over 140/90 mm Hg had mean sensitivity and specificity of 74.6% (95% confidence interval 60.7% to 84.8%) and 74.6% (47.9% to 90.4%), respectively, whereas home measurements over 135/85 mm Hg had mean sensitivity and specificity of 85.7% (78.0% to 91.0%) and 62.4% (48.0% to 75.0%). CONCLUSIONS: Neither clinic nor home measurement had sufficient sensitivity or specificity to be recommended as a single diagnostic test. If ambulatory monitoring is taken as the reference standard, then treatment decisions based on clinic or home blood pressure alone might result in substantial overdiagnosis. Ambulatory monitoring before the start of lifelong drug treatment might lead to more appropriate targeting of treatment, particularly around the diagnostic threshold.