Corticosteroids Use and Incidence of Severe Infections in People Living with HIV Compared to a Matched Population.

BACKGROUND: People living with HIV (PLWH) have been shown to have an increased risk of autoimmune diseases. Corticosteroids are the cornerstone of autoimmune diseases treatment, but their use is associated with an increased risk of infections. It is unclear how HIV status affects the risk of infection associated with corticosteroids use. METHODS: We conducted a retrospective cohort study from 1991 to 2011, using a medico-administrative database from Quebec. Medical billing codes were used to identify PLWH, and we matched them on age, sex, and index date with up to 4 HIV-negative controls. The exposure of interest was the use of corticosteroids, defined as a systemic corticosteroid dispensation lasting at least 20 days. The outcome of interest was hospitalization for severe infection. Crude and adjusted incidence rates ratios of infection were obtained using a random effect Poisson model, and results were stratified by HIV status. RESULTS: In total, 4798 PLWH were matched to 17 644 HIV-negative controls, among which 1083 (22.6%) PLWH and 1854 (10.5%) HIV-negative controls received at least one course of corticosteroid. The mean duration of corticosteroids use was 4 ± 4.4 months in PLWH and 1.6 ± 5.5 months in HIV-negative controls. The incidence rate ratio (IRR) for infections associated with corticosteroids use was 2.49[1.71-3.60] in PLWH and 1.32[0.71-2.47] in HIV-negative controls (P value for interaction 0.18). The most frequent infections were pulmonary infections (50.4%), followed by urinary tract infections (26%) and opportunistic infections (10.5%). CONCLUSION: Although our interaction term did not reach significance, the increased risk of infection associated with corticosteroids use was more pronounced in PLWH. However, further research with contemporary data is warranted to confirm if the risk associated with corticosteroids use remains high in PLWH with well-controlled HIV infection.

Prevalence and Risk Factors of QTc Prolongation in Prostate Cancer Patients Undergoing Brachytherapy.

QTc prolongation is linked to Torsade de Pointes, sudden cardiac death, and overall cardiovascular mortality. 754 prostate cancer patients undergoing brachytherapy were analyzed, prolonged QTc was defined as ≥450ms. A prolonged QTc was more frequent (10.1 vs. 5.1%, p = 0.040) in patients with high-risk cancer than in low to intermediate risk patients. The absolute QTc-time was correlated with age (r = 0.125), neutrophil count (r = 0.130) and negatively correlated with the testosterone level (r=-0.205). Treating physicians should be aware of this and monitor the QTc during ADT to possibly decrease cardiac morbidity/mortality in these patients who are more likely to require ADT.

Renal Cell Carcinoma With Cardiac Metastases.

The median survival of metastatic renal cell carcinoma (mRCC) is 5 months with a 1-year survival rate of 29%. Cardiac metastasis from RCC is a rare finding and there is scarce data available on treatment options. Recently, the combination of nivolumab and ipilimumab has been approved as a first-line treatment for advanced RCC in patients with a poor prognosis. Here we present a case of a 45-year-old male who presented to the emergency room with cough, dyspnea, and fever. Chest X-ray showed hilar lymphadenopathy and diffuse reticulonodular opacities, whereas a thoracic computed tomography (CT) scan revealed carcinomatosis lymphangitis, pleural carcinosis and multiple heterogenous zones on the cardiac wall. A transthoracic echocardiogram and a cardiac magnetic resonance imaging (MRI) revealed cardiac metastases. Subsequent imaging showed abundant distal metastases whereas a renal biopsy confirmed clear cell RCC making it a high-grade stage IV metastatic RCC. The patient was treated with the combination of nivolumab and ipilimumab. The unique feature about this case is that we have found a rare case of cardiac metastases that persists after a 3-month follow-up. Previously, there was only one case report of a patient with RCC and cardiac metastases who showed persistent response to nivolumab after 12 months. The key points from this case report are that a high index of suspicion is required for diagnosing cardiac metastases given that the signs and symptoms of metastatic cardiac involvement can be non-specific. Spread has been described as directly through the renal vein and vena cava or indirectly via the lymphatic system, which confers a worse prognosis. Furthermore, cardiac metastases can be mistaken for thrombi, endocarditis, or primary tumors, therefore echocardiograms can be limiting. Supplemental imaging with cardiac MRI or positron emission tomography/CT (PET/CT) is often needed for further characterization.

Incidence of autoimmune diseases in people living with HIV compared to a matched population: a cohort study.

The objective of this paper is to estimate incidence and relative risk of autoimmune conditions in patients living with HIV compared to an HIV-negative matched population. We conducted a retrospective study in the medico-administrative database of the province of Québec, Canada. All HIV-positive patients treated with antiretrovirals were matched to up to 4 HIV-negative controls for age, sex, and period of follow-up. The following autoimmune conditions were identified using medical billing codes: vasculitis, hematological (immune thrombocytopenic purpura and immune hemolytic anemia), ankylosing spondylitis, psoriasis and psoriatic arthritis, inflammatory bowel disease and associated arthritis, connectivitis, and systemic lupus erythematosus. Incidence rates and adjusted hazard ratios (aHR) were obtained using survival models. A total of 4245 HIV-positive patients were matched to 16493 HIV-negative patients. Autoimmune diseases were diagnosed in 407 (9.6%) HIV-positive and 508 (3%) HIV-negative patients. The aHR for autoimmune diseases associated to HIV was 2.40 95% CI [2.10-2.75]. The strongest associations were seen for hematological disorders (aHR 8.34 95% CI [6.13-11.36]), followed by ankylosing spondylitis (1.82 95% CI [1.03-3.21]), inflammatory bowel disease and associated arthritis (1.80 95% CI [1.37-2.35]), psoriasis and associated arthritis (1.69 95% CI [1.23-2.33]), and rheumatoid arthritis (1.51 95% CI [1.08-2.11]).We found no association between HIV and the incidence of vasculitis, connectivitis, and systemic lupus erythematosus, but the number of cases for these diseases were few. Autoimmune diseases are more frequent among people living with HIV than age and sex-matched population-based controls. Key Points • Strength: The major strength of this study is its large sample size of 4200 people treated as HIV infection, matched to 16000 HIV negative for sex and age. • Novelty: We found that people living with HIV were more than twice as likely to suffer from auto-immune diseases than their matched counterparts.

HIV-Infected Patient Diagnosed With Osteomedullary and Hepatic Syphilis on Positron Emission Tomography: A Case Report.

A human immunodeficiency virus (HIV)-positive man presented with a recent history of weight loss and B symptoms. Positron emission tomography (PET) scan revealed multiple hypercaptation foci, including diffuse osteomedullary lesions and a dominant liver nodule. Syphilis screening was positive, with a rapid plasma reagin (RPR) titer of 1:1,024. Following antibiotic therapy, repeat PET scan demonstrated complete resolution of hypermetabolic lesions, arguing toward an infectious etiology. Cases of disseminated syphilis characterized on nuclear imaging typically demonstrate radiological evidence of target tissue inflammation. PET scan could however also represent a sensitive modality for evaluation of early subclinical secondary syphilis.

Use of modified intention-to-treat analysis in studies of direct oral anticoagulants and risk of selection bias: a systematic review.

BACKGROUND: Following their evaluation in randomised controlled trials (RCTs), direct oral anticoagulants (DOACs) have replaced warfarin for stroke prevention in atrial fibrillation (AF), and treatment and prevention of venous thromboembolism (VTE). To avoid selection bias, it is recommended that RCTs use an intention-to-treat (ITT) analysis strategy. OBJECTIVE: The objective of this study was to systematically review and compare reported analytical strategies, the proportion of randomised patients included in analyses and the reasons for participant exclusions. STUDY SELECTION: A systematic search of PubMed, EMBASE and the Cochrane library for phase III trials of DOACs was conducted. Titles and abstracts were screened for relevance by two independent reviewers. Patient population, intervention studied, number of patients included in randomisation and analysis, reasons for exclusions from analysis and trial conclusions were extracted from each article. FINDINGS: Twenty-nine studies were included, five were about stroke prevention in AF, 10 about VTE treatment and 14 about thromboprophylaxis. Trials of AF and VTE treatment had low proportions of postrandomisation exclusions (around 1%). In contrast, surgical and medical thromboprophylaxis trials excluded almost 30% of participants postrandomisation. This was in spite of authors' claims of using an ITT or modified ITT approach. Higher exclusion proportions in these trials were associated with non-clinically defined primary outcomes and incomplete outcome assessments. CONCLUSIONS: Clinicians should be aware that the level of evidence in favour of DOAC use for thromboprophylaxis is weak due to high rates of postrandomisation exclusions and risks of selection bias.

Impact of diabetes and metformin use on prostate cancer outcome of patients treated with radiation therapy: results from a large institutional database.

INTRODUCTION: Conflicting data exists on the influence of metformin on prostate cancer. We investigated the importance of metformin in patients treated with radiotherapy or brachytherapy. MATERIALS AND METHODS: All patients from a large institutionalized database, treated for primary localized prostate cancer with either brachytherapy or external-beam radiotherapy ± androgen deprivation therapy were identified. Groups were compared by Kaplan-Meier analyses and Cox regression models. Multivariate analysis was adjusted for CAPRA-Score, type of treatment and age. RESULTS: A total of 2441 patients with complete data was identified. Among the 382 patients (16% of total) were diabetic. Two-hundred and eighty-one of the 382 diabetics (74%) were treated with metformin and 101 were treated with other anti-diabetic medication. Median follow up was 48 months (interquartile range [IQR] 24-84). Two-hundred eighteen patients (9%) died and 150 (6%) experienced biochemical recurrence (BCR). On unadjusted univariate analysis for BCR-free survival, metformin users showed a 50% reduction in BCR compared to non-metformin users. The results remained significant on multivariate analysis comparing diabetic metformin users to non-metformin users (diabetics and non-diabetics combined) (hazard ratio [HR] 0.5-0.6, p = 0.03-0.04) but lost its significance when adjusting for cancer aggressiveness. On multivariate analysis, diabetics had worse overall survival (OS) than non-diabetics (HR 1.5, 95% confidence interval [CI] 1.08-2.06, p = 0.01), but diabetics on metformin fared better than diabetics not taking metformin (HR 0.5, 95% CI 0.26-0.86, p = 0.01). CONCLUSION: Metformin use in this analysis appears to be associated with better BCR and OS. Larger datasets and prospective trials are warranted to validate these results.

Diagnostic precision of mentally estimated home blood pressure means.

CONTEXT: Paper home blood pressure (HBP) charts are commonly brought to physicians at office visits. The precision and accuracy of mental calculations of blood pressure (BP) means are not known. METHODS: A total of 109 hypertensive patients were instructed to measure and record their HBP for 1 week and to bring their paper charts to their office visit. Study section 1: HBP means were calculated electronically and compared to corresponding in-office BP estimates made by physicians. Study section 2: 100 randomly ordered HBP charts were re-examined repetitively by 11 evaluators. Each evaluator estimated BP means four times in 5, 15, 30, and 60 s (random order) allocated for the task. BP means and diagnostic performance (determination of therapeutic systolic and diastolic BP goals attained or not) were compared between physician estimates and electronically calculated results. RESULTS: Overall, electronically and mentally calculated BP means were not different. Individual analysis showed that 83% of in-office physician estimates were within a 5-mmHg systolic BP range. There was diagnostic disagreement in 15% of cases. Performance improved consistently when the time allocated for BP estimation was increased from 5 to 15 s and from 15 to 30 s, but not when it exceeded 30 s. CONCLUSION: Mentally calculating HBP means from paper charts can cause a number of diagnostic errors. Chart evaluation exceeding 30 s does not significantly improve accuracy. BP-measuring devices with modern analytical capacities could be useful to physicians.

Preoperative antihypertensive medication intake and acute kidney injury after major vascular surgery.

OBJECTIVE: Postoperative acute kidney injury (AKI) is frequent after major vascular surgery and is associated with significant morbidity and mortality. It remains unclear whether the administration of combined oral antihypertensive medications on the day of surgery can increase the risk of postoperative AKI. METHODS: We performed a retrospective cohort study of hypertensive patients undergoing elective major vascular surgery to determine the association between the number of antihypertensive medications continued on the morning of surgery and AKI at 48 hours postoperatively. RESULTS: A total of 406 patients who had undergone suprainguinal vascular surgery were included, and 10.3% suffered postoperative AKI. In multivariable analysis, the number of antihypertensive medications taken on the morning of surgery was independently associated with AKI (P = .026). Compared with patients who took no medication, taking one medication (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 0.68-3.75) and taking two or more medications (aOR, 2.70; 95% CI, 1.13-6.44) were associated with a 1.6-fold and 2.7-fold increased risk of postoperative AKI, respectively. Other predictors of AKI were suprarenal surgery (aOR, 3.37; 95% CI, 1.53-7.44), age (aOR, 2.29 per 10 years; 95% CI, 1.40-3.74), length of surgery (aOR, 1.40 per 1 hour; 95% CI, 1.10-1.76), hemoglobin drop (aOR, 1.37 per 10 g/L; 95% CI, 1.10-1.74), and history of coronary artery disease (aOR, 2.33; 95% CI, 1.08-5.00). CONCLUSIONS: In patients undergoing major vascular surgery who are treated with chronic antihypertensive therapy, the administration of antihypertensive drugs on the morning of surgery is independently associated with an increased risk of postoperative AKI. Further prospective studies are needed to confirm this finding.

Comparison of Different Automated Office Blood Pressure Measurement Devices: Evidence of Nonequivalence and Clinical Implications.

BACKGROUND: Automated office blood pressure (AOBP) measuring devices are increasingly recommended as preferred blood pressure (BP) diagnostic tools, but it is unclear how they compare and how clinical environments impact their performance. METHODS: This prospective randomized factorial parallel 4-group study compared BP estimates by BpTRU (VSM MedTech, Vancouver, BC, Canada) and Omron HEM 907 (Omron Healthcare, Kyoto, Japan) devices in closed vs open areas. Patients diagnosed with hypertension were recruited during office visits. After baseline open-room AOBP measurement with the BpTRU, patients had a second BP measurement with either the BpTRU or HEM 907 in either open or closed areas. Absolute BP levels and differences between the first and second measurements were compared. Diagnostic performance was also assessed. RESULTS: Two hundred fifty-eight patients were studied. Their mean age was 66.2 ± 12.0 years, and 62% were men. The mean of first AOBP estimates was 127.4/73.3 mm Hg. Analyses of subsequent measurements revealed no influence of open or closed areas on BP means and diagnostic performance. Conversely, the Omron HEM 907 exceeded BpTRU systolic BP measurements by 4.6 mm Hg (< 0.01) in closed areas and by 3.9 mm Hg (< 0.01) in open areas. The discrepancy between devices was amplified at lower BP levels. CONCLUSIONS: Although different areas did not influence BP estimates, the Omron HEM 907 significantly exceeded BpTRU measurements on average and especially at lower BP levels. These differences should be considered when interchanging devices and could have clinical decision impacts in a population of patients treated for hypertension. Our results support the constant use of only 1 device type in a given clinic.

The Gap Between Manual and Automated Office Blood Pressure Measurements Results at a Hypertension Clinic.

BACKGROUND: Blood pressure (BP) readings taken in clinics are often higher than BP readings taken in a research setting. Recent guidelines and clinical trials have highlighted the necessity of using automated office blood pressure (AOBP) devices and standardizing measurement procedures. The goal of the present study was to compare AOBP vs manual BP measurement in both research and clinical environments in which operators and devices were the same and measurement procedures were standardized and optimal. METHODS: Clinical manual BP and AOBP measurement estimates were gathered from a retrospective cohort of patients followed in a hypertension clinic. Research AOBP and manual BP measurement data were obtained from past research studies. Descriptive statistics and agreement analyses with Cohen kappa coefficients were developed. The AOBP/manual BP measurement gap between clinical and research follow-up was compared using an unpaired t test. RESULTS: Two hundred eighty-eight patients were included in the clinical cohort, and 195 patients contributed to research-grade BP data. All patients had hypertension. AOBP averages were lower than manual measurement averages in both clinical (-3.6 ± 14.9 mm Hg / -3.0 ± 8.8 mm Hg) and research (-2.7 ± 10.0 / -2.4 ± 6.3 mm Hg) environments. The gap between measurement methods did not differ between research and clinical data. Cohen kappa coefficient was lower in the clinical context because of greater variability and more time between BP measurements (5.5 ± 2.9 months). CONCLUSIONS: Manual BP readings were slightly higher than AOBP estimates. The difference was not influenced by the real-world context of clinical practice. Office nonautomated BP measurements may still be valuable if measurement procedures are well standardized and performed by trained nurses.

Ketoacidosis in a Non-Diabetic Adult With Chronic EtOH Consumption.

Although much more rare than its diabetic counterpart, ketoacidosis secondary to alcohol withdrawal in the context of fasting has its own complex pathophysiology and can easily mimic the acute insulin deficiency presentation. We present here a rare case of a non-diabetic alcoholic patient who presented in ketoacidosis after a period of reduced intake.

Quantification of the External Validity of Randomized Controlled Trials Supporting Clinical Care Guidelines: The Case of Thromboprophylaxis.

BACKGROUND: Clinical guidelines are based on the results of several randomized controlled trials. However, due to the stringent exclusion criteria of these trials, their external validity may be low. We aimed to evaluate the external validity of the randomized controlled trials cited in the American College of Chest Physicians guidelines for the use of pharmacological thromboprophylaxis in hospitalized medical patients. METHODS: We conducted a cross-sectional, chart-review study of a random sample of patients admitted between July 1, 2013 and June 30, 2014 to the Internal Medicine ward of a large Canadian teaching university hospital. We identified the proportion of our population presenting exclusion criteria used in the randomized controlled trials cited in support of clinical care guidelines on thromboprophylaxis in the medical setting. RESULTS: Nine trials were identified for a total of 28,793 included patients following 23 distinct exclusion criteria. We included 429 patients. Median age was 65 years (interquartile ratio 51-77 years), and 236 (55%) were males. Of those not already anticoagulated at admission (n = 351), between 26% and 67% (weighted average, 51%) of our population presented at least one exclusion criterion, making them ineligible to be enrolled in randomized controlled trials. When restricting our population to patients with an indication for thromboprophylaxis based on a Padua risk score at admission ≥4, 21% to 76% (weighted average 55%) were ineligible to be enrolled in individual trials. CONCLUSIONS: Our cross-sectional study illustrates that the external validity of randomized controlled trials cited in the guidelines was low in our population, and lower when applying the risk-stratification tool recommended by guidelines. This can bias the clinicians toward treating patients that were not represented in the supporting evidence.

Unreliability of home blood pressure measurement and the effect of a patient-oriented intervention.

BACKGROUND: Home blood pressure (BP) measurement (HBPM) is recommended for the diagnosis and follow-up of high BP. It is unclear how this aspect of BP monitoring has evolved over the years and whether interventions could influence patient adherence to HBPM guidelines. METHODS: After a questionnaire-based cross-sectional study performed in 2010, a passive, multimodal intervention, focused on improving adherence to HBPM guidelines, was implemented. A second study was conducted in 2014 to measure its effect. RESULTS: In 2010 and 2014, 1010 and 1005 patients, respectively, completed the questionnaire. In 2010 and 2014, 82% and 84% of patients, respectively, self-measured their BP. Reporting of HBPM and adherence to recommended procedures was suboptimal. Only 34.0% of patients in 2010 and 31.7% in 2014 brought > 80% of their measurements to their doctor. Only 49.6% in 2010 and 52.9% in 2014 prepared > 80% of the time for HBPM. Only 48.1% in 2010 and 52.1% in 2014 rested for 5 minutes > 80% of the time before HBPM. Only 15% of patients in 2010 and 18% in 2014 were defined as sufficiently compliant with all HBPM procedures. Paired analysis of a subset of 535 patients who participated in the 2010 and 2014 studies showed no clinically significant differences in reliability between the 2 surveys. CONCLUSIONS: Adherence to HBPM guidelines was suboptimal in 2010 and still is in 2014 despite a passive, multimodal intervention. Active training in HBPM procedures should be studied. Greater automation could improve HBPM reliability.

Recurrent arterial and venous thromboemboli as initial presentation of acute promyelocytic leukemia.

We report a case of a 52-year-old Caucasian woman diagnosed with a synchronic arterial and venous thrombosis as an initial presentation of an acute promyelocytic leukemia (APL). After the diagnosis, the patient was treated with all trans-retinoic acid and arsenic chemotherapy concomitant to systemic anticoagulation. This treatment regimen led to a complete remission and absence of relapse of the thrombosis or APL during the follow-up. To our knowledge, this presentation is the second case in the literature. We use this opportunity to emphasize the importance of performing a complete medical evaluation in cases of unusual thromboembolic events.

Extracorporeal membrane oxygenation in diffuse alveolar hemorrhage secondary to systemic lupus erythematosus.

Diffuse alveolar hemorrhage (DAH) is a rare and potentially deadly complication of systemic lupus erythematosus (SLE). We report two adult cases where extracorporeal membrane oxygenation (ECMO) was used as rescue therapy for severe respiratory failure in this setting. We discuss the risk related to coagulation disturbance and the need for the circuit anticoagulation in this particular setting. We also briefly discuss the clinical problem of lack of knowledge on the bioavailability of the immunosuppressive treatment with the use of ECMO. We think that ECMO should be used as rescue therapy in patients with DAH caused by SLE, but strategies for anticoagulation require further precision.