Immuno-virological and toxicity outcomes of HIV-infected patients after 48 months of ART in Phnom Penh, Cambodia

Mexico AIDS Conference 200

Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records

Introduction: To evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM) patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design. Methods: Population based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997–2010), all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding. Results: Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67–43.72]), cardiac arrest or sudden cardiac death (6.33 [3.69–10.85]), heart failure (4.31, [3.30–5.62]), and atrial fibrillation (3.80 [3.04–4.75]). HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27–2.84]) and coronary revascularisation (2.32 [1.46–3.69]).The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding. Conclusions: Our study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases

Glucocorticoid dose-dependent risk of type 2 diabetes in six immune-mediated inflammatory diseases: a population-based cohort analysis

Introduction: In immune-mediated inflammatory diseases, there is a lack of -estimates of glucocorticoid dose–response diabetes risk that consider changes in prescribed dose over time and disease activity. Research design and methods: Population-based longitudinal analysis of electronic health records from the UK Clinical Practice Research Datalink, linked to hospital admissions and the mortality registry (1998–2017). We included 100 722 adult patients without diabetes history, diagnosed with giant cell arteritis or polymyalgia rheumatica (n=32 593), inflammatory bowel disease (n=29 272), rheumatoid arthritis (n=28 365), vasculitis (n=6082), or systemic lupus erythematosus (n=4410). We estimated risks and HRs of type 2 diabetes associated with time-variant daily and total cumulative prednisolone-equivalent glucocorticoid dose using Cox regression methods. Results: Average patient age was 58.6 years, 65 469 (65.0%) were women and 8858 (22.6%) had a body mass index (BMI) ≥30 kg/m2. Overall, 8137 (8.1%) people developed type 2 diabetes after a median follow-up of 4.9 years. At 1 year, the cumulative risk of diabetes increased from 0.9% during periods of non-use to 5.0% when the daily prednisolone-equivalent dose was ≥25.0 mg. We found strong dose-dependent associations for all immune-mediated diseases, BMI levels and underlying disease duration, even after controlling for periods of active systemic inflammation. Adjusted HR for a <5.0 mg daily dose versus non-use was 1.90, 95% CI 1.44 to 2.50; range 1.70 for rheumatoid arthritis to 2.93 for inflammatory bowel disease. Conclusions: We report dose-dependent risks of type 2 diabetes associated with glucocorticoid use for six common immune-mediated inflammatory diseases. These results underline the need for regular diabetic risk assessment and testing during glucocorticoid therapy in these patients

Variation in methods, results and reporting in electronic health record-based studies evaluating routine care in gout: A systematic review

Objective: To perform a systematic review examining the variation in methods, results, reporting and risk of bias in electronic health record (EHR)-based studies evaluating management of a common musculoskeletal disease, gout. Methods: Two reviewers systematically searched MEDLINE, Scopus, Web of Science, CINAHL, PubMed, EMBASE and Google Scholar for all EHR-based studies published by February 2019 investigating gout pharmacological treatment. Information was extracted on study design, eligibility criteria, definitions, medication usage, effectiveness and safety data, comprehensiveness of reporting (RECORD), and Cochrane risk of bias (registered PROSPERO CRD42017065195). Results: We screened 5,603 titles/abstracts, 613 full-texts and selected 75 studies including 1.9M gout patients. Gout diagnosis was defined in 26 ways across the studies, most commonly using a single diagnostic code (n = 31, 41.3%). 48.4% did not specify a disease-free period before ‘incident’ diagnosis. Medication use was suboptimal and varied with disease definition while results regarding effectiveness and safety were broadly similar across studies despite variability in inclusion criteria. Comprehensiveness of reporting was variable, ranging from 73% (55/75) appropriately discussing the limitations of EHR data use, to 5% (4/75) reporting on key data cleaning steps. Risk of bias was generally low. Conclusion: The wide variation in case definitions and medication-related analysis among EHR-based studies has implications for reported medication use. This is amplified by variable reporting comprehensiveness and the limited consideration of EHR-relevant biases (e.g. data adequacy) in study assessment tools. We recommend accounting for these biases and performing a sensitivity analysis on case definitions, and suggest changes to assessment tools to foster this

Timeliness of Clinic Attendance is a good predictor of Virological Response and Resistance to Antiretroviral drugs in HIV-infected patients

Ensuring long-term adherence to therapy is essential for the success of HIV treatment. As access to viral load monitoring and genotyping is poor in resource-limited settings, a simple tool to monitor adherence is needed. We assessed the relationship between an indicator based on timeliness of clinic attendance and virological response and HIV drug resistance

Lower Urinary Tract Infections: Management, Outcomes and Risk Factors for Antibiotic Re-prescription in Primary Care

Background: Urinary tract infections (UTIs) are major drivers of antibiotic prescribing in primary care. Inappropriate antibiotic prescribing for UTIs likely drives antibiotic resistance. We aimed to describe current investigation and antibiotic treatment to examine opportunities for improved antimicrobial stewardship. Methods: We identified a cohort of all patients with lower UTI diagnosis between 2011 and 2015 in the 390 primary care practices contributing data to ResearchOne in England. We examined investigation, antibiotic treatment and antibiotic re-prescription within 28 days according to guideline-defined patient groups. We assessed risk factors for re-prescription using mixed-effect logistic regression. Findings: In total, 494,675 UTIs were diagnosed in 300,354 patients. Median age was 54 years, and 83.3% were women. Same-day antibiotic was prescribed for 85.7% of UTIs; 56.8% were treated with trimethoprim, and urine sampling was undertaken in 25.0%. The antibiotic re-prescription rate was low (17,430, 4.1%) and increased slightly over time in men (from 5.2% in 2011 to 6.2% in 2015). Overall, 21.1% of pre-prescription were for the same antibiotic. The percentage of adults with recurrent UTIs ranged from 1.0% in 18–64 year-old men to 2.6% in women ≥65 years. The risk of antibiotic re-prescription increased with age, calendar year, recent antibiotic prescribing and treatment with antibiotic other than trimethoprim or nitrofurantoin. Interpretation: Most patients diagnosed with lower UTI in primary care receive same-day empirical antibiotics with little diversity in choice of agent. The antibiotic re-prescription rate is low. Microbiological investigation and re-prescription of the same antibiotic given for the initial episode happened in one quarter of UTIs. Funding: UK National Health Service Improvement

Changes in ankylosing spondylitis incidence, prevalence and time to diagnosis over two decades

Objectives To assess changes in ankylosing spondylitis (AS) incidence, prevalence and time to diagnosis, between 1998 and 2017. Methods Using UK GP data from the Clinical Practice Research Datalink, we identified patients diagnosed with AS between 1998 and 2017. We estimated the annual AS incidence, prevalence and length of time from first recorded symptom of back pain to rheumatology referral and diagnosis. Results We identified 12 333 patients with AS. The incidence declined from 0.72 (±0.14) per 10 000 patient-years in 1998 to 0.39 (±0.06) in 2007, with this decline significant only in men, then incidence rose to 0.57 (±0.11) in 2017. By contrast, prevalence increased between 1998 and 2017 (from 0.13%±0.006 to 0.18%±0.006), rising steeply among women (from 0.06%±0.05 to 0.10%±0.06) and patients aged ≥60 (from 0.14%±0.01 to 0.26%±0.01). The overall median time from first symptom to rheumatology referral was 4.87 years (IQR=1.42–10.23). The median time from first symptom to diagnosis rose between 1998 and 2017 (from 3.62 years (IQR=1.14–7.07) to 8.31 (IQR=3.77–15.89)) and was longer in women (6.71 (IQR=2.30–12.36)) than men (5.65 (IQR=1.66–11.20)). Conclusion AS incidence declined significantly between 1998 and 2007, with an increase between 2007 and 2017 that may be explained by an improvement in the recognition of AS or confidence in diagnosing AS over time, stemming from increased awareness of inflammatory back pain and the importance of early treatment. The rising AS prevalence may indicate improved patient survival. The persisting delay in rheumatology referral and diagnosis remains of concern, particularly in women

Heterogeneous associations between smoking and a wide range of initial presentations of cardiovascular disease in 1937360 people in England: lifetime risks and implications for risk prediction.

BACKGROUND: It is not known how smoking affects the initial presentation of a wide range of chronic and acute cardiovascular diseases (CVDs), nor the extent to which associations are heterogeneous. We estimated the lifetime cumulative incidence of 12 CVD presentations, and examined associations with smoking and smoking cessation. METHODS: Cohort study of 1.93 million people aged ≥30years, with no history of CVD, in 1997-2010. Individuals were drawn from linked electronic health records in England, covering primary care, hospitalizations, myocardial infarction (MI) registry and cause-specific mortality (the CALIBER programme). RESULTS: During 11.6 million person-years of follow-up, 114859 people had an initial non-fatal or fatal CVD presentation. By age 90 years, current vs never smokers' lifetime risks varied from 0.4% vs 0.2% for subarachnoid haemorrhage (SAH), to 8.9% vs 2.6% for peripheral arterial disease (PAD). Current smoking showed no association with cardiac arrest or sudden cardiac death [hazard ratio (HR)=1.04, 95% confidence interval (CI) 0.91-1.19).The strength of association differed markedly according to disease type: stable angina (HR=1.08, 95% CI 1.01-1.15),transient ischaemic attack (HR=1.41, 95% CI 1.28-1.55), unstable angina (HR=1.54, 95% CI 1.38-1.72), intracerebral haemorrhage (HR=1.61, 95% CI 1.37-1.89), heart failure (HR=1.62, 95% CI 1.47-1.79), ischaemic stroke (HR=1.90, 95% CI 1.72-2.10), MI (HR=2.32, 95% CI 2.20-2.45), SAH (HR= 2.70, 95% CI 2.27-3.21), PAD (HR=5.16, 95% CI 4.80-5.54) and abdominal aortic aneurysm (AAA) (HR=5.18, 95% CI 4.61-5.82). Population-attributable fractions were lower for women than men for unheralded coronary death, ischaemic stroke, PAD and AAA. Ten years after quitting smoking, the risks of PAD, AAA (in men) and unheralded coronary death remained increased (HR=1.36, 1.47 and 2.74, respectively). CONCLUSIONS: The heterogeneous associations of smoking with different CVD presentations suggests different underlying mechanisms and have important implications for research, clinical screening and risk prediction

Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring.

In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia

Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people.

BACKGROUND: The contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. We aimed to study associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease. METHODS: We used linked primary care, hospital admission, disease registry, and death certificate records from the CALIBER programme, which links data for people in England recorded in four electronic health data sources. We included people who were (or turned) 30 years or older between Jan 1, 1998, to March 25, 2010, who were free from cardiovascular disease at baseline. The primary endpoint was the first record of one of 12 cardiovascular presentations in any of the data sources. We compared cumulative incidence curves for the initial presentation of cardiovascular disease and used Cox models to estimate cause-specific hazard ratios (HRs). This study is registered at ClinicalTrials.gov (NCT01804439). FINDINGS: Our cohort consisted of 1 921 260 individuals, of whom 1 887 062 (98·2%) did not have diabetes and 34 198 (1·8%) had type 2 diabetes. We observed 113 638 first presentations of cardiovascular disease during a median follow-up of 5·5 years (IQR 2·1-10·1). Of people with type 2 diabetes, 6137 (17·9%) had a first cardiovascular presentation, the most common of which were peripheral arterial disease (reported in 992 [16·2%] of 6137 patients) and heart failure (866 [14·1%] of 6137 patients). Type 2 diabetes was positively associated with peripheral arterial disease (adjusted HR 2·98 [95% CI 2·76-3·22]), ischaemic stroke (1·72 [1·52-1·95]), stable angina (1·62 [1·49-1·77]), heart failure (1·56 [1·45-1·69]), and non-fatal myocardial infarction (1·54 [1·42-1·67]), but was inversely associated with abdominal aortic aneurysm (0·46 [0·35-0·59]) and subarachnoid haemorrhage (0·48 [0·26-0.89]), and not associated with arrhythmia or sudden cardiac death (0·95 [0·76-1·19]). INTERPRETATION: Heart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The differences between relative risks of different cardiovascular diseases in patients with type 2 diabetes have implications for clinical risk assessment and trial design. FUNDING: Wellcome Trust, National Institute for Health Research, and Medical Research Council