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

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

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

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

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

Changes in the pharmacological management of rheumatoid arthritis over two decades

Objectives To assess whether modern management of RA has reduced the prescription of oral corticosteroids and NSAIDs and to evaluate use of pharmacological prophylaxis strategies. Methods Using the Clinical Practice Research Datalink, we explored long-term (≥3/12 months; ≥6/12 in sub-analyses) DMARD, corticosteroid and NSAID prescribing (annually, in the year post-diagnosis and across the patient’s life course to 15 years post-diagnosis), annual proportion with co-prescribing for prophylaxis of associated bone (corticosteroids, women only) and gastrointestinal (NSAIDs) comorbidity. Results Reported incidence of RA was 5.98 (0.37) per 10 000 person-years and prevalence was 0.91% (0.014) in 2017. In 71 411 RA patients, long-term DMARD prescribing initially rose post-diagnosis from 41.6% in 1998 to 67.9% in 2009. Corticosteroid prescribing changed little, overall [22.2% in 1998, 19.1% in 2016; incident risk ratio (IRR) 0.92, 95% CI: 0.82, 1.03] and across the life course from the first to fifteenth year (22.2% to 16.9%). NSAID prescribing declined from 57.7% in 1998, and significantly so from 2008, to 27.1% in 2016 (IRR 0.50, 95% CI: 0.44, 0.56). This continued across the life course (41.2% to 28.4%). Bone prophylaxis increased to 68.1% in 2008 before declining to 56.4% in 2017; gastrointestinal prophylaxis increased from 11.5% in 1998 to 62.6% in 2017. Sub-analyses showed consistent patterns. Conclusion Despite modern treatment strategies, corticosteroid prescribing in RA patients remains substantial and persists beyond 6 months once initiated. Rheumatologists need to determine causes and develop strategies to reduce corticosteroid use to minimize adverse event occurrence

Clinically recorded heart rate and incidence of 12 coronary, cardiac, cerebrovascular and peripheral arterial diseases in 233,970 men and women: A linked electronic health record study

Background: In healthy population cohorts, resting heart rate above 90 bpm is associated with mortality from coronary heart disease, but it is not clear whether associations are present at lower heart rates or whether these associations differ between women. Methods: The CALIBER resource of linked electronic health records from primary care, hospitalisations, myocardial infarction registry and cause-specific mortality in the UK was used to assess associations between resting heart rate and 12 fatal and non-fatal coronary, cardiac, cerebral and peripheral vascular cardiovascular diseases and death using Cox proportional hazard models. Results: Among 233,970 patients, 29,690 fatal and non-fatal events occurred. Fully adjusted models showed that resting heart rate was not associated in men or women with cerebrovascular events. In men a resting heart rate of 70–79 bpm (29.1% of all men) versus less than 60 bpm was associated with an increased risk of heart failure (hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.26–2.16), unheralded coronary death (HR 1.65, 95% CI 1.13–2.41), total cardiovascular events (HR 1.22, 95% CI 1.15–1.28) and all-cause mortality (HR 1.39, 95% CI 1.22–1.58). Women with a higher resting heart rate level of 80–89 bpm versus 60 bpm had a higher risk of total cardiovascular disease events (HR 1.17, 95% CI 1.07–1.24) and all-cause mortality (HR 1.21, 95% CI 1.07–1.35) compared to a resting heart rate less than 60 bpm. The risk was also present at higher heart rates (>90 bpm) for heart failure and sudden cardiac death. Conclusions: A resting heart rate that clinicians currently consider as ‘normal’ in the general population is specifically associated with the incidence of certain major cardiovascular diseases and death, with the risk starting at lower resting heart rate levels in men compared to women. Further research is required to evaluate whether interventions to lower resting heart rate are warranted to prevent disease. The study is registered at: clinicaltrials.gov (ID: NCT01947361)

Good immune restitution but unsatisfactory viral suppression in children on ART in a remote Western Kenya area

Mexico AIDS Conference 200