Statistical Inference in Large Antenna Arrays under Unknown Noise Pattern

In this article, a general information-plus-noise transmission model is assumed, the receiver end of which is composed of a large number of sensors and is unaware of the noise pattern. For this model, and under reasonable assumptions, a set of results is provided for the receiver to perform statistical eigen-inference on the information part. In particular, we introduce new methods for the detection, counting, and the power and subspace estimation of multiple sources composing the information part of the transmission. The theoretical performance of some of these techniques is also discussed. An exemplary application of these methods to array processing is then studied in greater detail, leading in particular to a novel MUSIC-like algorithm assuming unknown noise covariance.Comment: 25 pages, 5 figure

Estimation of Toeplitz Covariance Matrices in Large Dimensional Regime with Application to Source Detection

In this article, we derive concentration inequalities for the spectral norm of two classical sample estimators of large dimensional Toeplitz covariance matrices, demonstrating in particular their asymptotic almost sure consistence. The consistency is then extended to the case where the aggregated matrix of time samples is corrupted by a rank one (or more generally, low rank) matrix. As an application of the latter, the problem of source detection in the context of large dimensional sensor networks within a temporally correlated noise environment is studied. As opposed to standard procedures, this application is performed online, i.e. without the need to possess a learning set of pure noise samples.Comment: 20 pages, 3 figures, submitted to IEEE Transactions on Signal Processin

Risk of bleeding with direct oral anticoagulants versus warfarin: cohort studies using primary care datasets

Background: There is limited evidence on the safety of direct oral anticoagulants (DOACs) in real world settings.Aim: To investigate risks of bleeding and all-cause mortality in DOACs compared to warfarin.Method: Prospective cohorts of incident oral anticoagulant users between 2011 and 2016 derived from two UK databases (QResearch and CPRD) linked to hospital and mortality data, with no anticoagulant prescriptions in the year before entry, were selected. Overall, 132,231 warfarin, 7744 dabigatran, 37,863 rivaroxaban, and 18,223 apixaban users, were sub-grouped into those with atrial-fibrillation (AF) and without (non-AF), followed up until any major bleed leading to hospital admission or death. Analyses were adjusted for demographics, life style, comorbidities and prescribed medications.Results: Compared to warfarin, apixaban was associated with decreased risk of major bleeding (hazard ratio 0.62, 95% confidence interval [CI] = 0.54 to 0.73), intracranial (HR 0.48, 95% CI = 0.34 to 0.68) and gastro-intestinal (HR 0.67, 95% CI = 0.54 to 0.83). Dabigatran and rivaroxaban were associated with decreased risk of intracranial bleeding (HR 0.44, 95% CI = 0.27 to 0.71; HR 0.73, 95% CI = 0.59 to 0.90). Rivaroxaban was associated with increased risk of all-cause mortality (HR 1.34, 95% CI = 1.26 to 1.42), consistent for both sub-cohorts. A small increased all-cause mortality risk for apixaban (HR 1.14, 95% CI = 1.05 to 1.24) was statistically significant on the lower doses (HR 1.31, 95% CI = 1.19 to 1.45) but not on higher doses (HR 0.98, 95% CI = 0.87 to 1.10).Conclusion: Overall, apixaban was found to be the safest drug for any major bleed, particularly for patients with increased risk of intracranial or gastro-intestinal bleeding

Exposure to combined oral contraceptives and risk of venous thromboembolism: a protocol for nested case–control studies using the QResearch and the CPRD databases

INTRODUCTION: Many studies have found an increased risk of venous thromboembolism (VTE) associated with the use of combined hormonal contraceptives, but various methodologies have been used in the study design relating to definition of VTE event and the selection of appropriate cases for analysis. This study will focus on common oral hormonal contraceptives, including compositions with cyproterone because of their contraceptive effect and will perform a number of sensitivity analyses to compare findings with previous studies. METHODS AND ANALYSIS: 2 nested case–control studies will be based on the general population using records from UK general practices within the QResearch and Clinical Practice Research Datalink databases. Cases will be female patients aged 15–49 with primary VTE diagnosed between 2001 and 2013. Each case will be matched by age, year of birth and practice to five female controls, who are alive and registered with the practice at the time of diagnosis of the case (index date). Exposure to different hormonal contraceptives will be defined as at least one prescription for that contraceptive in the year before the index date. The effects of duration and the length of any gap since last use will also be investigated. Conditional logistic regression will be applied to calculate ORs adjusted for smoking, ethnicity, comorbidities and use of other medications. Possible indications for prescribing hormonal contraceptives, such as menstrual disorders, acne or hirsutism will be included in the analyses as confounding factors. A number of sensitivity analyses will be carried out. ETHICS AND DISSEMINATION: The initial protocol has been reviewed and approved by ISAC (Independent Scientific Advisory Committee) for Medicine and Healthcare Products Regulatory Agency Database Research. The project has also been reviewed by QResearch and meets the requirements of the Trent Research Ethics Committee. The results will be published in a peer-reviewed journal

Exposure to bisphosphonates and risk of cancer: a protocol for nested case–control studies using the QResearch primary care database

Introduction: Bisphosphonates are becoming a common treatment for osteoporosis particularly after discovery of the association between hormone replacement therapy and increased risk of breast cancer. As osteoporosis develops with age, treatment is a long-term intervention. Randomised control trials typically have limited follow-up times, which restricts investigation of the effects of the drugs on risk of primary cancers. A few observational studies have demonstrated a reduced risk of breast cancer and possibly of endometrial cancer in bisphosphonate users. Two epidemiological studies have studied the effect of the drugs on oesophageal cancer but did not reach any definite conclusions. So far, no effects on colorectal and stomach cancer have been shown. This study will investigate the association of bisphosphonates with risks of the 10 most common primary cancers. Methods and analysis: A series of nested caseecontrol studies will be based on the general population using records from 660 UK general practices within the QResearch Database. Cases will be patients with primary cancers diagnosed between 1996 and 2011. Each case will be matched by age, sex, practice and calendar year to five controls, who are alive and registered with the practice at the time of diagnosis of the case. Exposure to bisphosphonates will be defined as at least one prescription during the study period. For the most common cancers with substantial numbers of observations, the effect of the duration of the treatment and different types of bisphosphonates will be studied. Conditional logistic regression will be applied to produce ORs adjusted for smoking status, socioeconomic status, ethnicity, cancer-specific co-morbidities and use of other medications

Exposure to statins and risk of common cancers: a series of nested case-control studies

<p>1 Abstract</p> <p>Background</p> <p>Many studies and meta-analyses have investigated the effects of statins on cancer incidence but without showing consistent effects.</p> <p>Methods</p> <p>A series of nested case-control studies was conducted covering 574 UK general practices within the QResearch database. Cases were patients with primary cancers diagnosed between 1998 and 2008. The associations between statin use and risk of ten site-specific cancers were estimated with conditional logistic regression adjusted for co-morbidities, smoking status, socio-economic status, and use of non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2 inhibitors and aspirin.</p> <p>Results</p> <p>88125 cases and 362254 matched controls were analysed. The adjusted odds ratio for any statin use and cancer at any site were 1.01 (95%CI 0.99 to 1.04). For haematological malignancies there was a significant reduced risk associated with any statin use (odds ratio 0.78, 95%CI 0.71 to 0.86). Prolonged (more than 4 years) use of statins was associated with a significantly increased risk of colorectal cancer (odds ratio 1.23, 95%CI 1.10 to 1.38), bladder cancer (odds ratio 1.29, 95%CI 1.08 to 1.54) and lung cancer (odds ratio 1.18, 95%CI 1.05 to 1.34). There were no significant associations with any other cancers.</p> <p>Conclusion</p> <p>In this large population-based case-control study, prolonged use of statins was not associated with an increased risk of cancer at any of the most common sites except for colorectal cancer, bladder cancer and lung cancer, while there was a reduced risk of haematological malignancies.</p

Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care

Objective: To investigate the associations between direct oral anticoagulants (DOACs) and risks of bleeding, ischaemic stroke, venous thromboembolism, and all cause mortality compared with warfarin. Design: Prospective open cohort study. Setting: UK general practices contributing to QResearch or Clinical Practice Research Datalink. Participants: 132 231 warfarin, 7744 dabigatran, 37 863 rivaroxaban, and 18 223 apixaban users without anticoagulant prescriptions for 12 months before study entry, subgrouped into 103 270 patients with atrial fibrillation and 92 791 without atrial fibrillation between 2011 and 2016. Main outcome measures: Major bleeding leading to hospital admission or death. Specific sites of bleeding and all cause mortality were also studied. Results: In patients with atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (adjusted hazard ratio 0.66, 95% confidence interval 0.54 to 0.79) and intracranial bleeding (0.40, 0.25 to 0.64); dabigatran was associated with a decreased risk of intracranial bleeding (0.45, 0.26 to 0.77). An increased risk of all cause mortality was observed in patients taking rivaroxaban (1.19, 1.09 to 1.29) or on lower doses of apixaban (1.27, 1.12 to 1.45). In patients without atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (0.60, 0.46 to 0.79), any gastrointestinal bleeding (0.55, 0.37 to 0.83), and upper gastrointestinal bleeding (0.55, 0.36 to 0.83); rivaroxaban was associated with a decreased risk of intracranial bleeding (0.54, 0.35 to 0.82). Increased risk of all cause mortality was observed in patients taking rivaroxaban (1.51, 1.38 to 1.66) and those on lower doses of apixaban (1.34, 1.13 to 1.58). Conclusions: Overall, apixaban was found to be the safest drug, with reduced risks of major, intracranial, and gastrointestinal bleeding compared with warfarin. Rivaroxaban and low dose apixaban were, however, associated with increased risks of all cause mortality compared with warfarin

Discontinuation and restarting in patients on statin therapy: a cohort study using a primary care database

Objectives: To estimate rates of discontinuation and restarting of statins, and to identify patient characteristics associated with either discontinuation or restarting. Design: Prospective open cohort study. Setting: 664 general practices contributing to the Clinical Practice Research Datalink in the United Kingdom. Data extracted in October 2014. Participants: Incident statin users aged 25-84 years identified between January 2002 and September 2013. Patients with statin prescriptions divided into two groups: primary prevention and secondary prevention (those already diagnosed with cardiovascular disease). Patients with statin prescriptions in the 12 months before study entry were excluded. Main outcome measures: Discontinuation of statin treatment (first 90 day gap after the estimated end date of a statin prescription), and restarting statin treatment for those who discontinued (defined as any subsequent prescription between discontinuation and study end). Results: Of 431 023 patients prescribed statins as primary prevention with a median follow-up time of 137 weeks, 47% (n=204 622) discontinued treatment and 72% (n=147 305) of those who discontinued restarted. Of 139 314 patients prescribed statins as secondary prevention with median follow-up time of 182 weeks, 41% (n=57 791) discontinued treatment and 75% (43 211) of those who discontinued restarted. Younger patients (aged ≤50 years), older patients (≥75 years), women, and patients with chronic liver disease were more likely to discontinue statins and less likely to restart. However, patients in ethnic minority groups, current smokers, and patients with type 1 diabetes were more likely to discontinue treatment but then were more likely to restart, whereas patients with hypertension and type 2 diabetes were less likely to discontinue treatment and more likely to restart if they did discontinue. These results were mainly consistent in the primary prevention and secondary prevention groups. Conclusions: Although a large proportion of statin users discontinue, many of them restart. For many patient groups previously considered as “stoppers,” the problem of statin treatment “stopping” could be part of the wider issue of poor adherence. Identification of patient groups associated with completely stopping or stop-starting behaviour has positive implications for patients and doctors as well as suggesting areas for future research

Protocol to assess risk of venous thromboembolism associated with use of hormone replacement therapy in real world settings: two nested case-control studies in primary care

Hormone replacement therapy (HRT) is used to help women suffering from menopausal symptoms. Although effective, the therapy may have a rare but serious side effect – an increased risk of venous thromboembolism (VTE). Previous studies have not been powerful enough to investigate the risks associated with different types of HRT. The proposed nested case-control study aims to fill this gap. Women diagnosed with VTE between 1998 and 2017 will be matched to 5 controls by age, practice and calendar year. Exposure to each type of HRT will be defined as at least one prescription for that HRT in the year before the index date (date of diagnosis of VTE or equivalent date in matched controls). Conditional logistic regression will be used to assess the risks associated with the different types of oestrogen and progestogen. The effects of duration, length of any gap since last use and method of application will be analysed for the most common types of HRT