Association of HIV and HCV Infection With Carotid Artery Plaque Echomorphology in the MACS/WIHS Combined Cohort Study.

BACKGROUND: HIV and hepatitis C virus (HCV) are associated with increased risk of carotid artery atherosclerotic plaque and stroke. We examined associations of HIV- and HCV-related factors with echomorphologic features of carotid artery plaque. METHODS: This cross-sectional study included participants from the MACS (Multicenter AIDS Cohort Study)/WIHS (Women's Interagency HIV Study) Combined Cohort Study who underwent high-resolution B-mode carotid artery ultrasound. Plaques were characterized from 6 areas of the right carotid artery. Poisson regression controlling for demographic and cardiometabolic risk factors determined adjusted prevalence ratios (aPRs) and 95% CIs for associations of HIV- and HCV-related factors with echomorphologic features. RESULTS: Of 2655 participants (65% women, median age 44 [interquartile range, 37-50] years), 1845 (70%) were living with HIV, 600 (23%) were living with HCV, and 425 (16%) had carotid plaque. There were 191 plaques identified in 129 (11%) women with HIV, 51 plaques in 32 (7%) women without HIV, 248 plaques in 171 (28%) men with HIV, and 139 plaques in 93 (29%) men without HIV. Adjusted analyses showed that people with HIV and current CD4+ count <200 cells/µL had a significantly higher prevalence of predominantly echolucent plaque (aPR, 1.86 [95% CI, 1.08-3.21]) than those without HIV. HCV infection alone (aPR, 1.86 [95% CI, 1.08-3.19]) and HIV-HCV coinfection (aPR, 1.75 [95% CI, 1.10-2.78]) were each associated with higher prevalence of predominantly echogenic plaque. HIV-HCV coinfection was also associated with higher prevalence of smooth surface plaque (aPR, 2.75 [95% CI, 1.03-7.32]) compared with people without HIV and HCV. CONCLUSIONS: HIV with poor immunologic control, as well as HCV infection, either alone or in the presence of HIV, were associated with different echomorphologic phenotypes of carotid artery plaque.

HIV, HIV-specific Factors and Myocardial Disease in Women.

BACKGROUND: People with HIV (PWH) have an increased risk of cardiovascular disease (CVD). Cardiac magnetic resonance (CMR) has documented higher myocardial fibrosis, inflammation and steatosis in PWH, but studies have mostly relied on healthy volunteers as comparators and focused on men. METHODS: We investigated the associations of HIV and HIV-specific factors with CMR phenotypes in female participants enrolled in the Women's Interagency HIV Study's New York and San Francisco sites. Primary phenotypes included myocardial native (n) T1 (fibro-inflammation), extracellular volume fraction (ECV, fibrosis) and triglyceride content (steatosis). Associations were evaluated with multivariable linear regression, and results pooled or meta-analyzed across centers. RESULTS: Among 261 women with HIV (WWH, total n = 362), 76.2% had undetectable viremia at CMR. For the 82.8% receiving continuous antiretroviral therapy (ART) in the preceding 5 years, adherence was 51.7%, and 71.3% failed to achieve persistent viral suppression (42.2% with peak viral load < 200 cp/mL). Overall, WWH showed higher nT1 than women without HIV (WWOH) after full adjustment. This higher nT1 was more pronounced in those with antecedent or current viremia or nadir CD4+ count < 200 cells/µL, the latter also associated with higher ECV. WWH and current CD4+ count < 200 cells/µL had less cardiomyocyte steatosis. Cumulative exposure to specific ART showed no associations. CONCLUSIONS: Compared with sociodemographically similar WWOH, WWH on ART exhibit higher myocardial fibro-inflammation, which is more prominent with unsuppressed viremia or CD4+ lymphopenia. These findings support the importance of improved ART adherence strategies, along with better understanding of latent infection, to mitigate cardiac end-organ damage in this population.

Prevalence of Sleep CALM nocturia factors in a male veteran population.

INTRODUCTION: Nocturia is a complex and multifactorial condition, associated with several genitourinary abnormalities as well as a host of conditions beyond the urinary tract, and thus often poses a significant diagnostic challenge in real-world practice. Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications, the so-called "Sleep C.A.L.M." factors, are five common causes of nocturia requiring judicious evaluation according to current consensus guidelines. This study aims to assess the prevalence of the Sleep C.A.L.M. factors in a nocturia clinical population. METHODS: Retrospective analysis of frequency-volume charts from men with ≥2 nocturnal voids as well as concurrent demographic, clinical, and medical history data to identify patients with each of the Sleep C.A.L.M. FACTORS: Comorbidities and medications were classified as a single group. RESULTS: A total of 213 subjects met the criteria for inclusion (median age 68.0 [63.5-75.5] years). The prevalence of 1) sleep disorders, 2) comorbidities and/or medication use, 3) actions (i.e., modifiable behaviors/lifestyle factors), and 4) lower urinary tract dysfunction was 31%, 31%, 19%, and 41%, respectively. Among included participants, 73% were found to have at least 1 Sleep C.A.L.M. factor, and 33% had multiple Sleep C.A.L.M. FACTORS: Results were similar upon stratification by age and nocturnal polyuria status. CONCLUSIONS: The Sleep C.A.L.M. factors are highly common among nocturia patients in the clinical urology setting. Although many of these factors are strongly associated with advanced age in community-based nocturia study samples, they appear common even among younger men in a nocturia patient population; the differential effect of age and individual Sleep C.A.L.M. factors on nocturia pathophysiology requires further investigation.

Nocturia and Blood Pressure Elevation in Adolescents.

Nocturia has been increasingly recognized as a manifestation of various non-urological conditions including hypertension. In adults, blood pressure (BP) elevation has been identified as a robust correlate of nocturia, but such a relationship has not been studied in pediatric populations where nocturia is often attributed to hormonal, sleep, physiological or psychological disorders. Accordingly, this study aimed to determine the relationship between nocturia and BP elevation in adolescents. We prospectively studied 100 patients, aged 10-18 years, recruited from pediatric clinics at our institution. Nocturia (defined as ≥ 1 voids on voiding diary analysis) was present in 45% of the study sample (range: 1-4 voids/night). 37% of subjects self-reported awakening to urinate, and 34% of subjects had BP elevation according to age-dependent thresholds from current Pediatrics guidelines. On multivariate analyses, BP elevation was strongly associated with nocturia determined by both voiding diary (OR 26.2, 95% CI: 6.5, 106.0) and self-report. Conversely, nocturia was associated with increased odds of elevated BP by diary (26.3, 95% CI: 6.5, 106.4) and self-report (OR 8.1, 95% CI: 3.2, 20.5). In conclusion, nocturia appears to be common and is strongly associated with BP elevation in adolescents. These findings suggest that eliciting a history of nocturia holds promise as a simple method of identifying adolescents at risk for hypertension.

Human Immunodeficiency Virus and Cardiac End-Organ Damage in Women: Findings From an Echocardiographic Study Across the United States.

BACKGROUND: People with human immunodeficiency virus (HIV) have been reported to have increased risk of clinical and subclinical cardiovascular disease. Existing studies have focused on men and often have been uncontrolled or lacked adequate HIV-negative comparators. METHODS: We performed echocardiography in the Women's Interagency HIV Study to investigate associations of HIV and HIV-specific factors with cardiac phenotypes, including left ventricular systolic dysfunction (LVSD), isolated LV diastolic dysfunction (LVDD), left atrial enlargement (LAE), LV hypertrophy (LVH), and increased tricuspid regurgitation velocity (TRV). RESULTS: Of 1654 participants (age 51 ± 9 years), 70% had HIV. Sixty-three (5.4%) women with HIV (WWH) had LVSD; 71 (6.5%) had isolated LVDD. Compared with women without HIV (WWOH), WWH had a near-significantly increased risk of LVSD (adjusted relative risk = 1.69; 95% confidence interval = 1.00 to 2.86; P = .051). No significant association was noted for HIV seropositivity with other phenotypes, but there was a risk gradient for decreasing CD4+ count among WWH that approached or reached significance for isolated LVDD, LAE, and LVH. WWH with CD4+ count <200 cells/mm3 had significantly higher prevalence of LAE, LVH, and high TRV than WWOH. There were no consistent associations for viral suppression or antiretroviral drug exposure. CONCLUSIONS: This study suggests that WWH have a higher risk of LVSD compared with sociodemographically similar WWOH, but their risk for isolated LVDD, LAE, LVH, and high TRV is increased only with reduced CD4+ count. Although these findings warrant replication, they support the importance of cardiovascular risk-factor and HIV-disease control for heart disease prevention in this population.

Psychosocial Syndemic Classes and Longitudinal Transition Patterns Among Sexual Minority men Living with or Without HIV in the Multicenter AIDS Cohort Study (MACS).

Mental health and substance use epidemics interact to create psychosocial syndemics, accelerating poor health outcomes. Using latent class and latent transition analyses, we identified psychosocial syndemic phenotypes and their longitudinal transition pathways among sexual minority men (SMM) in the Multicenter AIDS Cohort Study (MACS, n = 3,384, mean age 44, 29% non-Hispanic Black, 51% with HIV). Self-reported depressive symptoms and substance use indices (i.e., smoking, hazardous drinking, marijuana, stimulant, and popper use) at the index visit, 3-year and 6-year follow-up were used to model psychosocial syndemics. Four latent classes were identified: "poly-behavioral" (19.4%), "smoking and depression" (21.7%), "illicit drug use" (13.8%), and "no conditions" (45.1%). Across all classes, over 80% of SMM remained in that same class over the follow-ups. SMM who experienced certain psychosocial clusters (e.g., illicit drug use) were less likely to transition to a less complex class. These people could benefit from targeted public health intervention and greater access to treatment resources.

Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications ("Sleep C.A.L.M.") in the evaluation and management of nocturia: A simple approach to a complex diagnosis.

INTRODUCTION: Nocturia arises from a fundamental mismatch between nocturnal urine production, storage capacity, and sleep architecture, which may be driven by abnormalities of the genitourinary tract, but also by sleep disorders, medical diseases, patient actions/lifestyle factors, or medications. This article introduces a novel system for organizing the complex differential diagnosis for nocturia, as proposed by an international collective of practicing urologists, physician specialists, and sleep experts: "Sleep CALM"-Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications. METHODS: Narrative review of current evidence regarding the relevance of each "Sleep CALM" factor to nocturia pathogenesis, evaluation, and management. RESULTS: Nocturia and sleep disorders are highly intertwined and often bidirectional, such that nocturnal awakenings for reasons other than a sensation of bladder fullness should not be used as grounds for exclusion from nocturia treatment, but rather leveraged to broaden therapeutic options for nocturia. Nocturia is an important potential harbinger of several serious medical conditions beyond the genitourinary tract. Urologists should have a low threshold for primary care and medical specialty referral for medical optimization, which carries the potential to significantly improve nocturnal voiding frequency in addition to overall health status. Adverse patient actions/lifestyle factors, lower urinary tract dysfunction, and medication use commonly coexist with disordered sleep and comorbid medical conditions, and may be the primary mediators of nocturia severity and treatment response, or further exacerbate nocturia severity and complicate treatment. CONCLUSION: "Sleep CALM" provides a memorable and clinically relevant means by which to structure the initial patient history, physical exam, and clinical testing in accordance with current best-practice guidelines for nocturia. Although not intended as an all-encompassing diagnostic tool, the "Sleep CALM" schema may also be useful in guiding individualized ancillary testing, identifying the need for specialty referral and multidisciplinary care, and uncovering first-line treatment targets.

Home Blood Pressure Monitoring And Nocturia In Adults.

Although widely viewed as a urological condition, nocturia has been increasingly recognized to accompany various non-urological conditions such as hypertension and blood pressure (BP) elevation on office determination. Home BP monitoring (HBPM) has been shown superior to office-based readings and provides an opportunity to assess potential relationships between nocturia and novel indices derived from multiple BP recordings including BP load, BP variability, and arterial stiffness, which have prognostic significance. We retrospectively studied 103 home BP logs and nocturia frequencies provided by 61 stable cardiology patients ≥ 21 years without medication change. Nocturnal voids ranged from 0 to 5 voids per night, median: 1.5. Nocturia frequency was significantly correlated with home and office systolic BPs and with BP load, but not with diastolic BPs, BP variability or arterial stiffness. On Poisson regression analysis, the estimated prevalence ratio (PR) for home and office systolic BPs were 1.025 (CI: 1.01, 1.04; p < .001) and 1.01 (CI:1.00, 1.02; p = .019), indicating 2.5% and 1% increases in the risk of nocturia per mmHg increases in BP respectively. In conclusion, higher mean home and office systolic BPs are associated with self-reported nocturia frequency with stronger associations seen for home BP measurement. Nocturia frequency appears unrelated to mean home and office diastolic BPs. Nocturia may be related to BP load, (percentage of elevated BP values), but not to BP variability or arterial stiffness. Future prospective studies using HBPM are needed to confirm these findings and to contribute to the understanding of the elevated BP-nocturia link.

Combined protein and transcript single-cell RNA sequencing in human peripheral blood mononuclear cells.

BACKGROUND: Cryopreserved peripheral blood mononuclear cells (PBMCs) are frequently collected and provide disease- and treatment-relevant data in clinical studies. Here, we developed combined protein (40 antibodies) and transcript single-cell (sc)RNA sequencing (scRNA-seq) in PBMCs. RESULTS: Among 31 participants in the Women's Interagency HIV Study (WIHS), we sequenced 41,611 cells. Using Boolean gating followed by Seurat UMAPs (tool for visualizing high-dimensional data) and Louvain clustering, we identified 50 subsets among CD4+ T, CD8+ T, B, NK cells, and monocytes. This resolution was superior to flow cytometry, mass cytometry, or scRNA-seq without antibodies. Combined protein and transcript scRNA-seq allowed for the assessment of disease-related changes in transcriptomes and cell type proportions. As a proof-of-concept, we showed such differences between healthy and matched individuals living with HIV with and without cardiovascular disease. CONCLUSIONS: In conclusion, combined protein and transcript scRNA sequencing is a suitable and powerful method for clinical investigations using PBMCs.

Phenotyping the Association between Nocturia and Hypertension: A Systematic Review and Meta-Analysis.

PURPOSE: The association between nocturia and hypertension has been widely reported yet remains poorly characterized, precluding a more refined understanding of blood pressure as it relates to the clinical urology setting. We synthesized current evidence on the relationship between nocturia and hypertension as a function of nocturia severity, age, gender, race, body mass index and diuretic use. MATERIALS AND METHODS: We searched PubMed®, EMBASE® and Cochrane databases for studies published up to May 2020. Random effects meta-analyses were performed to identify pooled odds ratios for nocturia given the presence of hypertension. Meta-regression and subgroup analyses were performed to identify differences across study samples. RESULTS: Of 1,193 identified studies, 25 met the criteria for inclusion. The overall pooled OR for the association of nocturia with hypertension was 1.25 (95% CI 1.21-1.28, p <0.001). Pooled estimates were 1.20 (1.16-1.25, p <0.001) and 1.30 (1.25-1.36, p <0.001) using a 1-void and 2-void cutoff for nocturia, respectively (p <0.001 between cutoffs). The association was more robust in patient-based (1.74 [1.54-1.98], p <0.001) vs community-based (1.24 [1.24-1.29], p <0.001) study samples (p <0.001). The association was stronger in females compared to males (1.45 [1.32-1.58] vs 1.28 [1.22-1.35], p <0.001), and Black (1.56 [1.25-1.94]) and Asian (1.28 [1.23-1.33]) vs White subgroups (1.16 [1.08-1.24]; p <0.05 for both). No effect was observed for age or body mass index. Evidence on diuretics was limited. CONCLUSIONS: Hypertension is associated with a 1.2-fold to 1.3-fold higher risk of nocturia. This association is more robust at a higher nocturia cutoff, in patient-based study samples, among females and in Black and Asian patients, but unrelated to age or body mass index.

Characterization of microvascular disease in pediatric sickle cell disease using nailfold capillaroscopy.

Sickle cell disease (SCD) is a disorder with repetitive vaso-occlusive crises resulting in microvascular obstruction and tissue ischemia that may lead to multi-organ ischemia and dysfunction. Nailfold videocapillaroscopy (NFC) is an imaging technique utilized in clinical rheumatology to visualize capillaries located near the fingertip. To characterize NFC abnormalities in the setting of pediatric SCD, we performed NFC using a video capillaroscope on 8 digits in 44 stable SCD patients and 65 age matched healthy controls. Mean capillary number was lower (6.4 ± 1.3 vs 7.5 ± 1.8, p = 0.001) in the SCD group compared to controls. The percentage of dilated capillaries was similar (7.1 ± 8.3 vs. 5.9 ± 8.2, p = 0.4). The large majority of capillaries visualized in the SCD and control groups were normal capillary types per the EULAR definition, with a similar percentage of normal, nonspecific capillary morphologies and abnormal types. Regarding normal capillary sub-types, the SCD group and controls exhibited similar percentages of stereotype hairpin shapes, and tortuous or once or twice crossing type capillaries. On multivariate analyses, mean capillary number was independently associated with SCD after adjusting for age, body mass index, systolic blood pressure and gender. In conclusion, pediatric SCD is associated with lower capillary number but similar percentage of dilated capillaries and morphology on NFC. In our SCD cohort, capillary number was unrelated to our available markers of disease severity, including history of sickle crises, previous hospitalization for crises or Hemoglobin F levels.

Higher comorbidities and early death in hospitalized African-American patients with Covid-19.

BACKGROUND: African-Americans/Blacks have suffered higher morbidity and mortality from COVID-19 than all other racial groups. This study aims to identify the causes of this health disparity, determine prognostic indicators, and assess efficacy of treatment interventions. METHODS: We performed a retrospective cohort study of clinical features and laboratory data of COVID-19 patients admitted over a 52-day period at the height of the pandemic in the United States. This study was performed at an urban academic medical center in New York City, declared a COVID-only facility, serving a majority Black population. RESULTS: Of the 1103 consecutive patients who tested positive for COVID-19, 529 required hospitalization and were included in the study. 88% of patients were Black; and a majority (52%) were 61-80 years old with a mean body mass index in the "obese" range. 98% had one or more comorbidities. Hypertension was the most common (79%) pre-existing condition followed by diabetes mellitus (56%) and chronic kidney disease (17%). Patients with chronic kidney disease who received hemodialysis were found to have lower mortality, than those who did not receive it, suggesting benefit from hemodialysis Age > 60 years and coronary artery disease were independent predictors of mortality in multivariate analysis. Cox proportional hazards modeling for time to death demonstrated a significantly high ratio for COPD/Asthma, and favorable effects on outcomes for pre-admission ACE inhibitors and ARBs. CRP (180, 283 mg/L), LDH (551, 638 U/L), glucose (182, 163 mg/dL), procalcitonin (1.03, 1.68 ng/mL), and neutrophil:lymphocyte ratio (8.3:10.0) were predictive of mortality on admission and at 48-96 h. Of the 529 inpatients 48% died, and one third of them died within the first 3 days of admission. 159/529patients received invasive mechanical ventilation, of which 86% died and of the remaining 370 patients, 30% died. CONCLUSIONS: COVID-19 patients in our predominantly Black neighborhood had higher in-hospital mortality, likely due to higher prevalence of comorbidities. Early dialysis and pre-admission intake of ACE inhibitors/ARBs improved patient outcomes. Early escalation of care based on comorbidities and key laboratory indicators is critical for improving outcomes in African-American patients.

First voided volume: A novel approach to characterize nocturia.

AIMS: Nocturnal polyuria syndrome (NPS) denotes nocturnal polyuria (NP) in the absence of identifiable contributory factors. The trajectory of nocturnal urine production (NUP; typically expressed as ml/hour) may be useful in delineating between NP patients with versus without NPS, but changes in absolute urine volume, the directly measured substrate for behavioral and pharmacologic interventions targeting nocturnal urine production, have not been well characterized. This study compares the ratio of the first nocturnal voided volume (FNVV) to the nocturnal average voided volume (NAVV) in patients with versus without NPS. METHODS: Secondary analysis of 24-h voiding diaries from male patients greater than or equal to 18 years of age with two or more nocturnal voids and NP using two different criteria for NP: NUP greater than or equal to 90 ml/h and nocturnal polyuria index (NPi) greater than or equal to 0.33. Patients with diabetes insipidus and CPAP-adherent obstructive sleep apnea (OSA) were excluded. Patients were divided into 2 groups: secondary NP (OSA, congestive heart failure, and chronic kidney disease) and NPS (absence of edema, diuretic use, and the aforementioned comorbidities). FNVV was defined as the volume of urine accompanying the first nocturic episode. NAVV was defined as nocturnal urine volume/(number of nocturnal voids + 1). The nocturnal urine trajectory ratio (NUTR) was defined as FNVV/NAVV. RESULTS: At NUP greater than or equal to 90 ml/h, NUTR was significantly greater in patients with (n = 73) versus without (n = 28) NPS (1.10 [0.89-1.33] vs. 0.91 [0.55-1.15], p = .012). At NPi greater than or equal to 0.33, NUTR was likewise significantly greater in patients with (n = 92) versus without (n = 32) NPS (1.09 [0.90-1.33] vs. 0.91 [0.57-1.17], p = .010). CONCLUSIONS: The volume of urine produced in the early hours of sleep is central to identification of NPS in patients with nocturia.

Nocturia and electrocardiographic abnormalities among patients at an inner-city cardiology clinic.

AIMS: Nocturia has been increasingly recognized as a potential manifestation of cardiovascular disease. However, the relationship between nocturia and electrocardiographic (ECG) abnormalities has not been studied. This study aims to characterize the diagnostic utility of nocturia in identifying left ventricular hypertrophy (LVH), left atrial enlargement (LAE), and prolonged QTc on ECG. METHODS: Retrospective analysis of nocturnal voiding frequency and contemporaneous ECG data from consecutive patients evaluated at a university-based outpatient cardiology clinic. Three sets of three incremental binary multiple logistic regression models controlling for (1) age, (2) sex and race, and (3) body mass index, hypertension, diabetes mellitus, and diuretic utilization were performed to determine whether nocturia was predictive of LVH, LAE, and prolonged QTc. RESULTS: Included patients (n = 143, 77.6% nocturia) were predominantly African-American (89.5%), female (74.1%), and obese (61.5%), of whom 44.1%, 41.3%, and 27.3% had LVH, LAE, and prolonged QTc, respectively. Older age, African-American race, obesity, hypertension, diuretic use, LVH, and LAE were significantly associated with nocturia on univariate analysis. No significant differences were observed in the strength of associations between nocturia and LVH, LAE, or QTc prolongation based on age. Nocturia independently predicted LVH in Models I-III (odds ratios [ORs], 2.99-3.20; relative risks [RRs], 1.18 for all, p ≤ .046) and LAE in Models I-III (ORs, 4.24-4.72; RRs, 1.21 for all, p ≤ .015). No significant associations were observed between nocturia and prolonged QTc. CONCLUSIONS: Nocturia may be a risk marker for underlying structural cardiac abnormalities.

Nocturia is Associated with High Atherosclerotic Cardiovascular Disease Risk in Women: Results from the National Health and Nutrition Examination Survey.

Growing evidence has identified nocturia as a potential manifestation of several cardiovascular disease states. We aimed to determine whether a relationship exists between nocturia and global atherosclerotic cardiovascular disease (ASCVD) risk, defined by the American College of Cardiology/American Heart Association (ACC/AHA) ASCVD risk calculator, using a large nationally-representative study sample from the United States. We explored potential associations between nocturia and ASCVD risk in adults aged 40-79 years with no prior history of overt/known atherosclerotic disease from 7 consecutive cycles of the National Health and Nutrition Examination Survey. Subjects were classified by whether they met the ASCVD high-risk threshold following current ACC/AHA consensus guidelines (10-year major adverse cardiovascular event risk ≥ 20%). Logistic regression analyses were used to explore associations between nocturia (defined as ≥ 2 nocturnal voids) and ASCVD risk. The prevalence of nocturia and high ASCVD risk were 27.0% and 10.9%, respectively. Nocturia, older age, increased body mass index, and diuretic use were associated with high ASCVD risk on univariate logistic regression. After adjusting for age, body mass index, and diuretic use, nocturia remained associated with significantly greater odds of high ASCVD risk in females but not in males. Elicitation of nocturia on clinical history taking may serve to identify high cardiovascular risk in females. Future studies are needed to elucidate mechanisms underlying this association.

Foundational Statistical Principles in Medical Research: Sensitivity, Specificity, Positive Predictive Value, and Negative Predictive Value.

Sensitivity, which denotes the proportion of subjects correctly given a positive assignment out of all subjects who are actually positive for the outcome, indicates how well a test can classify subjects who truly have the outcome of interest. Specificity, which denotes the proportion of subjects correctly given a negative assignment out of all subjects who are actually negative for the outcome, indicates how well a test can classify subjects who truly do not have the outcome of interest. Positive predictive value reflects the proportion of subjects with a positive test result who truly have the outcome of interest. Negative predictive value reflects the proportion of subjects with a negative test result who truly do not have the outcome of interest. Sensitivity and specificity are inversely related, wherein one increases as the other decreases, but are generally considered stable for a given test, whereas positive and negative predictive values do inherently vary with pre-test probability (e.g., changes in population disease prevalence). This article will further detail the concepts of sensitivity, specificity, and predictive values using a recent real-world example from the medical literature.

Blinding in Clinical Trials: Seeing the Big Picture.

Blinding mitigates several sources of bias which, if left unchecked, can quantitively affect study outcomes. Blinding remains under-utilized, particularly in non-pharmaceutical clinical trials, but is often highly feasible through simple measures. Although blinding is generally viewed as an effective method by which to eliminate bias, blinding does also pose some inherent limitations, and it behooves clinicians and researchers to be aware of such caveats. This article will review general principles for blinding in clinical trials, including examples of useful blinding techniques for both pharmaceutical and non-pharmaceutical trials, while also highlighting the limitations and potential consequences of blinding. Appropriate reporting on blinding in trial protocols and manuscripts, as well as future directions for blinding research, will also be discussed.

Elevated Plasma Ceramides Are Associated With Antiretroviral Therapy Use and Progression of Carotid Artery Atherosclerosis in HIV Infection.

BACKGROUND: Ceramides have been implicated in the pathophysiology of HIV infection and cardiovascular disease. However, no study, to our knowledge, has evaluated circulating ceramide levels in association with subclinical cardiovascular disease risk among HIV-infected individuals. METHODS: Plasma levels of 4 ceramide species (C16:0, C22:0, C24:0, and C24:1) were measured among 398 women (73% HIV+) and 339 men (68% HIV+) without carotid artery plaques at baseline from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. We examined associations between baseline plasma ceramides and risk of carotid artery plaque formation, assessed by repeated B-mode carotid artery ultrasound imaging over a median 7-year follow-up. RESULTS: Plasma levels of C16:0, C22:0, and C24:1 ceramides were significantly higher in HIV-infected individuals compared with those without HIV infection (all P<0.001), and further analysis indicated that elevated ceramide levels were associated with antiretroviral therapy use, particularly protease inhibitor use, in HIV-infected individuals (all P<0.001). All 4 ceramides were highly correlated with each other ( r=0.70-0.94; all P<0.001) and significantly correlated with total-cholesterol ( r=0.42-0.58; all P<0.001) and low-density lipoprotein cholesterol ( r=0.24-0.42; all P<0.001) levels. Of note, C16:0 and C24:1 ceramides, rather than C22:0 and C24:0 ceramides, were more closely correlated with specific monocyte activation and inflammation markers (eg, r=0.30 between C16:0 ceramide and soluble CD14; P<0.001) and surface markers of CD4+ T-cell activation. A total of 112 participants developed carotid artery plaques over 7 years, and higher levels of C16:0 and C24:1 ceramides were significantly associated with increased risk of carotid artery plaques (relative risk [95% CI]=1.55 [1.29, 1.86] and 1.51 [1.26, 1.82] per standard deviation increment, respectively; both P<0.001), after adjusting for demographic and behavioral factors. After further adjustment for cardiovascular disease risk factors and immune activation markers, these associations were attenuated but remained significant. The results were consistent between men and women and between HIV-infected and HIV-uninfected participants. CONCLUSIONS: In 2 HIV cohorts, elevated plasma levels of C16:0 and C24:1 ceramides, correlating with immune activation and inflammation, were associated with antiretroviral therapy use and progression of carotid artery atherosclerosis.

Associations between nighttime and daytime maximum voided volumes: Relevance for nocturia?

AIM: The relationship between maximum voided volumes (MVV) during the night and day is poorly understood. Such measurements are important because they are often used to indicate functional bladder capacity (FBC), a relevant parameter for nocturia. This study examined the association of such nighttime and daytime measurements in men with nocturia. METHODS: We retrospectively analyzed 356 24-hour voiding diaries showing ≥2 nocturnal voids from 220 men at an outpatient urology clinic. We defined small FBC as MVV ≤ 200 mL. RESULTS: A total of 131 entries demonstrated a nocturnal MVV ≤ 200 mL, of which a majority (98 [74.8%]) also showed a 24-hour MVV ≤ 200 mL (ie, global small FBC), and 33 (25.2%) exceeded the 200 mL threshold during the day (ie, nocturnal-specific small FBC). Correspondingly, among voiding diaries without global small FBC (n = 258), most (225/258 [87.2%]) showed a nocturnal MVV > 200 mL. Data were similar when analyzing only the first complete voiding diary per case, when limiting analyses to those without benign prostatic obstruction, and when limiting analyses to cases with nocturnal polyuria. CONCLUSION: Nocturia may be attributable to nocturnal-specific small FBC or global small FBC. Although the etiology of nocturnal-specific small FBC remains unclear, it was present in a significant minority of patients with small FBC, thus necessitating more directed research. Conversely, diminished nocturnal MVV was nevertheless relatively uncommon in the absence of global small FBC, such that nocturnal-only voiding diaries may provide a rational alternative for follow-up evaluation in patients with nocturia due to global small bladder capacity.

Time of peak nocturnal diuresis rate between men with secondary nocturnal polyuria versus nocturnal polyuria syndrome.

AIM: Compare the circadian trajectory of diuresis between nocturnal polyuria (NP) patients with versus without identifiable contributory comorbidities. METHODS: Retrospective analysis of frequency-volume charts from male patients with clinically-significant nocturia (≥2 nocturnal voids) and NP (defined by nocturnal urine production [NUP] ≥90 mL/hour or nocturnal polyuria index [NPi] ≥0.33). Patients with NP and chronic kidney disease, congestive heart failure, and/or undertreated obstructive sleep apnea (OSA) were deemed to have secondary NP. Nocturnal polyuria syndrome (NPS) was defined as NP without edema, loop diuretic use, or the aforementioned conditions. Patients with diabetes insipidus or OSA with appropriate continuous positive airway pressure utilization were excluded. The timing and volumes of nocturnal voids were used to derive "early" and "late" nocturnal diuresis rates (mL/hour of urine produced before and after the first nocturnal awakening, respectively). The likelihood of an early peak nocturnal diuresis rate (ie, early >late nocturnal diuresis rate) was compared between patients with NPS versus secondary NP using both a crude and adjusted odds ratio. RESULTS: The likelihood of an early peak nocturnal diuresis rate in patients with NPS compared with secondary NP was 2.58 (1.05-6.31) at NUP ≥ 90 mL/hour and 1.96 (0.87-4.42) at NPi ≥ 0.33 on crude analysis, and 2.44 (0.96-6.24) and 1.93 (0.83-4.48) after adjustment, respectively. CONCLUSIONS: A peak early nocturnal diuresis rate was significantly more likely in patients with NPS at NUP ≥ 90 mL/hour, with similar odds ratios at NPi ≥ 0.33 and following adjustment. Delineating nocturic patients by NP subgroup may facilitate more individualized management. PATIENT SUMMARY: Many people have to wake up to urinate because they produce too much urine at night-a condition known as "nocturnal polyuria." Nocturnal polyuria might be caused by drinking too much fluid, other behavioral factors, or conditions that make your body hold on to too much fluid, like heart disease, kidney disease, and sleep apnea. In cases of nocturnal polyuria where no clear cause can be identified, it is thought that patients may suffer from a deficiency in nighttime vasopressin, a hormone that plays a key role in how much urine you produce. In this study, we compared the pattern of nighttime urine production in patients with different causes of nocturnal polyuria, which may lead to more personalized treatment options for patients with this condition.