WHO Group Research Articles

PHYSICIANS ATTITUDES TOWARD ANTICOAGULATION USE IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: The benefit of anticoagulant use in pulmonary arterial hypertension (PAH) patients remains unclear. Multiple studies have shown conflicting results regarding the utility of anticoagulation in PAH. Moreover, other points of controversies include selection of specific anticoagulant agent, intensity of anticoagulation, and patient selection based on PAH subtype. This study aims to evaluate the practice habits of physicians caring for patients with PAH in the United States of America (USA). METHODS: A seven-question web-based survey regarding anticoagulation management in patients with PAH in the USA was distributed by email to clinicians with experience treating patients with pulmonary hypertension and are registered members of the Pulmonary Hypertension Association (PHA). RESULTS: We received a total of 56 responses, predominantly from academic, non-profit institutions (82.14%, n=46); by PHA members serving as non-trainee physicians (98.21%, n=55). The majority of respondents (53.57%, n=31) rarely start anticoagulation in patients with WHO group 1 PAH. In idiopathic PAH (IPAH) subtype, providers mainly start in severe disease (22.82%, n=12) or for other coexisting indications (e.g., an indwelling catheter, underlying thrombogenic disorder, prior clots). Nearly all (86%, n=50) respondents rarely start anticoagulation in connective tissue disease related PAH (CTD-PAH). While the majority of respondents do not routinely use anticoagulation in general, those who do, use warfarin (46.3%, n=25) and target a lower range of INR (1.5–2). Few providers (18.18%, n=10) reported using direct oral anticoagulants. CONCLUSIONS: Despite the presence of limited evidence showing that the use of anticoagulation in patients with PAH may be associated with survival benefit—specifically in the idiopathic PAH subtype—the majority of clinicians who care for these patients believe that the risks outweigh the benefits unless there is a coexisting indication. Prospective and randomized studies are warranted for further evaluation. CLINICAL IMPLICATIONS: This study highlights the uncertainty among clinicians about the benefit of anticoagulation in patients with WHO group 1 PAH and the need for randomized trials. DISCLOSURES: No relevant relationships by Noura Alturaif, source=Web Response No relevant relationships by Jamie Kennedy, source=Web Response No relevant relationships by Sula Mazimba, source=Web Response Clinical Trial support relationship with Complexa, Inc Please note: $1001 - $5000 Added 04/02/2020 by Andrew Mihalek, source=Web Response, value=Grant/Research Support

PREVALENCE AND OUTCOMES OF INHALED, ORAL, AND PARENTERAL PROSTACYCLIN THERAPY IN PULMONARY HYPERTENSION CLINIC PATIENTS: A RETROSPECTIVE COHORT STUDY

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Prostacyclin therapy has become a standard of current management for patients with severe pulmonary arterial hypertension (PAH). CurrentlY therapy may be administered via inhaled, oral, and parenteral routes, however there use is often reserved for patients with severe disease. This study aimed to assess the prevalence and effect via hemodynamic evaluation and functional outcome measurements of inhaled, oral, and parenteral prostacyclin therapy among pulmonary hypertension clinic patients. METHODS: This was a retrospective cohort study of pulmonary hypertension (PH) clinic patients at Keck Medical Center. Patients were studied from time of initial clinic visit and most recent follow up. Data ranged from 2011 to 2020. Patient demographics, hemodynamics via right heart catheterization (RHC), transthoracic echocardiography findings (TTE), and functional capacity via six-minute walk testing (6MWT) were collected. Patients were then separated by presence of prostacyclin therapy and route of administration if present. RESULTS: Data was collected on 473 PH patients, 298 of which had complete therapy data and were included in the final analysis. WHO group 1 PAH patients comprised 72% (n = 214) of all patients. The composition of prostacyclin therapy was as follows 152 (51%) no prostacyclin therapy (NP), 29 (9.7%) inhaled prostacyclin therapy (IP), 25 (8.3%) oral prostacyclin therapy (OP), 85 (28.5%) parenteral prostacyclin therapy (PP), and 7 (2.3%) combination therapy. Percentage of patients in each group with PAH was as follows NP (58.6%), IP (75.9%), OP (80%), PP (90.6%), and combination (85.7%). RHC hemodynamics revealed a significant relationship between increasing pulmonary artery pressures and pulmonary vascular resistance (PVR) and therapy in order from NP to IP to OP to PP at initial and follow up visit. TTE findings showed a significant relationship between increasing right ventricular (RV) dilation, RV dysfunction, RVSP, presence of pericardial effusion, and prostacyclin therapy from NP to IP to OP to PP. 6MWT revealed the PP group had the furthest distance walked and had an increase between at follow up while the IP group had the shortest 6MWT distance and greatest reduction in average 6MWT distance at follow up. CONCLUSIONS: The cohort of patients between types of therapy differed significantly in baseline characteristics and outcomes on cardiopulmonary hemodynamics and functional status. The PP group compared to IP and OP were shown to have more severe pulmonary hypertension. Despite that, they had greater 6MWT distances and even improved values from initial to follow up testing. The increase in distance adds to the body of literature suggesting the benefit of parenteral prostacyclin long term in comparison to other modes of drug delivery. CLINICAL IMPLICATIONS: This study may contribute to identifying subsets of patients with pulmonary hypertension who would benefit from prostacyclin therapy. DISCLOSURES: No relevant relationships by Tiffany Chang, source=Web Response No relevant relationships by Lucas Cruz, source=Web Response No relevant relationships by Jared Geibig, source=Web Response No relevant relationships by Moses Koo, source=Web Response No relevant relationships by Ashil Panchal, source=Web Response Speaker/Speaker's Bureau relationship with Actelion, United therapeutic, and Bayer Please note: $20001 - $100000 Added 05/30/2020 by Bassam Yaghmour, source=Web Response, value=Honoraria

METASTATIC PULMONARY CALCIFICATION: A RARE CAUSE OF PULMONARY HYPERTENSION

SESSION TITLE: Fellows Pulmonary Vascular Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Metastatic calcification is seen at autopsy in 60-75% of CKD patients on hemodialysis (HD) due to increased calcium phosphate product (normal 40 mg2/dl2; MPC >70 mg2/dl2) (1,2). Metastatic pulmonary calcification associated with pulmonary hypertension (PH) is rare. We present a case of MPC associated combined postcapillary and precapillary PH (CpcPH). CASE PRESENTATION: A 58-year-old woman with SLE, CTD-ILD (FVC 64%, TLC 56 %), ESRD on HD since 2008 and diastolic heart failure was admitted to the hospital with worsening dyspnea, leg edema and orthopnea. Her calcium phosphate product was 61. CT chest showed diffuse ground glass opacity with mosaic perfusion, enlarged pulmonary artery (PA 4.3 cm) and chest wall calcifications. Echocardiogram showed grade 3 diastolic dysfunction, severely dilated left atrium and elevated right ventricular systolic pressure. Heart catheterization showed mean PA pressure 62 mm Hg, PA wedge pressure 29 mm Hg, transpulmonary gradient (TPG) 33, diastolic pulmonary gradient (DPG) 11, pulmonary vascular resistance 9 WU, LV end diastolic pressure 27 mm Hg, cardiac output 3.6, cardiac index 2.1. Given her severe PH, low CI and NYHA functional class IV, she was started on inhaled treprostinil with improvement in leg edema and orthopnea at 6-month follow up. DISCUSSION: Hyperphosphatemia in ESRD causes increased calcium phosphate product leading to calcium crystallization. Metastatic calcifications are usually seen in lamina propria of stomach, lung alveoli, renal tubules and interstitium(2). Acidosis between HD sessions causes leaching of calcium from bone, leading to deposition during post dialysis alkalosis. Uremia alters the configuration of tissue protein, rendering them more calcifiable. Three main CT patterns of MPC include centrilobular ground glass nodules, dense consolidation and small dense nodules(1). It is usually peripheral in distribution with upper lung zone dominance due to increased alkalinity (higher V/Q ratio causing low PaCO2) causing calcium salt deposition. Vascular calcification in chest and abdominal wall is a common finding as noted in our case. 30-50% of CKD and ESRD patients have PH. Vascular calcification can affect pulmonary arterial capacitance (low PAC in our case 0.81) and increase RV afterload. In this case, contributing factors to her PH are elevated LVEDP, ILD and ESRD (WHO group II, III and V). TPG >12 and DPG >7 suggested pulmonary vascular remodeling from shear stress and downstream pressure. This is an interesting case of MPC with associated PH. Initiation of the pulmonary vasodilator treprostinil reduced her PVR allowing for a better coupling of the RV-PA system. CONCLUSIONS: Treatment of MPC includes intensification of HD sessions and use of calcium and phosphate binders. In this case, inhaled pulmonary vasodilators for treatment of CpcPH after medical treatment optimization of other co-morbidities led to symptomatic improvement. Reference #1: Metastatic pulmonary calcification: HRCT findings in 23 cases, Radiol Bras.2017 Jul-Aug; 50(4): 231–236 Reference #2: Metastatic pulmonary calcification: State-of-the-art review focused on imaging findings, Respiratory Medicine Feb 2014 (108): 668-676 Reference #3: Pulmonary hypertension with extensive calcification in small pulmonary vessels and alveolar capillary wall in a chronic hemodialysis patient, Journal of Cardiology Cases 8 (Feb 2013) e13–e16 DISCLOSURES: No relevant relationships by Moises Cossio, source=Web Response No relevant relationships by Domingo Franco-Palacios, source=Web Response No relevant relationships by Kushagra Gupta, source=Web Response No relevant relationships by Shahzad Hussain, source=Web Response No relevant relationships by Venkateswara Kollipara, source=Web Response No relevant relationships by Toribiong Uchel, source=Web Response

Gas Exchange Score with VE/VCO2 and ETCO2 Reliably Predicts Pulmonary Vascular Disease in Suspected Pulmonary Hypertension

Introduction Non-invasive methods to identify phenotype of pulmonary hypertension (PH) remains a topic of interest. Cardiopulmonary exercise test (CPET) provides gas exchange (GX) parameters including end-tidal carbon dioxide (ETCO2) and ventilation of minute ventilation to carbon dioxide ventilation ratio (VE/VCO2). A direct correlation of these GX parameters with invasive hemodynamics can provide further insight into the ability of GX parameters to predict PH phenotype. Hypothesis Using a direct correlation of gas exchange parameters with invasive hemodynamics, we propose that in subjects with suspected PH, rest gas exchange parameters can reliably predict pulmonary vascular disease. Methods We reviewed clinical, echocardiographic and invasive CPET (iCPET) data for 41 patients. We then analyzed the data with receiver operator curve (ROC) to help estimate the area under the curve (AUC) of different gas exchange parameters to help define the hemodynamics of different PH groups and derive the most appropriate parameters to define PH. *p Results Among the overall cohort, mean age (± SD) was 63.9±11.35 years, and 20 subjects were female (49 %). The distribution of WHO groups of PH based on the final diagnosis among the overall cohort was: 8 patients WHO group I (19.5%), 21 patients WHO group II (51.2%), 3 patients WHO group III (7.3%), 1 patient WHO group IV (2.4%), and 8 patients had no evidence of rest or exercise PH (19.5%). For the purpose of analysis, we created three groups: 1) pulmonary vascular disease (PVD): combination of WHO group I, III and IV, 2) pulmonary venous hypertension (PVH): WHO group II, 3) Control: no PH group. On ROC analysis, rest and exercise ETCO2 and VE/VCO2 had equally high predictive ability to predict exercise PVR > 3 WU (rest ETCO2=0.806, exercise ETCO2=0.880, rest VE/VCO2=0.794, exercise VE/VCO2=0.820). Similar pattern of ETCO2 and VE/VCO2 was identified with prediction of rest PVR >3WU and WHO group I PAH. Based on the ROC analysis, we found that the ideal cutoffs (to predict rest PVR>3WU or exercise PVR>3WU or PVD group) were ≤30 mmHg for ETCO2 and ≥42 for VE/VECO2.Using these cutoffs, we created a scoring system of “rest-only” GX parameters (+1 for ETCO2 ≤30 and VE/VCO2 ≥42; and -1 for vice versa). Each patient would have a total score of -2, 0 or +2. The AUC for this rest-only scoring system to predict exercise PVR >3WU was 0.841. When applied to the whole cohort, score of -2 (n=14) included: 8 PVH and 5 with no PH, score of +2 (n=11) included 6 PVD (percentages shown in figure). Conclusions Among individuals with suspected PH, a composite gas exchange score with VE/VCO2 (≥42) and ETCO2 (≤30 mmHg) reliably predicts PVD.

Non-compliant Left Atrium Due to Scarring From Atrial Fibrillation Ablation Leads to Discordance of PAWP-LVEDP and Severe Post-Capillary Pulmonary Hypertension

Introduction Atrial fibrillation (AF) is one etiology of WHO group II post-capillary pulmonary hypertension (PH). Higher left atrial pressure, estimated as pulmonary artery wedge pressure (PAWP) out of proportion to left ventricular end-diastolic pressure (LVEDP), has been reported in AF. However, the impact of atrial scarring associated with AF ablation (ABL) on these pressure differences remains unclear. Hypothesis Extensive AF ABL leads to scarring of the left atrial wall, decreasing atrial compliance, which leads to elevated left atrial pressure in the presence of a lower LVEDP creating a PAWP-LVEDP gradient. Methods We selected all patients who were diagnosed with PH (n=4,945) between 2009 and 2019 at the University of Wisconsin-Madison who underwent simultaneous right and left heart catheterization and had an EP procedure (n=27), after excluding patients with significant mitral valve disease and amyloid. We then divided them into 3 groups: group 1 (AF-ABL) n=5, group 2 (AF) n=16, group 3 (no AF) n=6. Results The PAWP-LVEDP gradient among three groups was (AF-ABL vs AF vs No AF): +6.8±3.42 vs -0.2±4.4 vs -1.8±4.0 mm Hg (Figure). Among the overall cohort, we further analyzed the patients with PAWP-LVEDP gradient >2 (discordant) vs ≤2 (concordant). PAWP-LVEDP gradient between the discordant group (n=12) vs the concordant group (n=15) was +5.0±2.7 vs -2.7±3.6*. Among the discordant group, 5 had AF ABL and 6 had AF. Among the concordant group, 5 had no AF, 10 had AF and no patients had AF ABL. The characteristics between discordant (DIS) vs concordant (CON) groups were: Age 68.2 ± 10 vs 67.0 ± 19.3, BMI 33.6 ± 4.55 vs 30.8 ± 11.2, diabetes 33% vs 47%, hypertension 75% vs 67%, OSA 91% (11/12) vs 40% (6/15)*, systolic pulmonary artery pressure (PAP) 55±19 vs 41±11*, mean PAP 37±12 vs 29±8*, PAWP 20±6 vs 18±7*, LVEDP 15±6 vs 20±7*. All patients who underwent ablation had persistent type AF and had extensive ablation beyond PVI (4 of 5 with PVI). Among the 16 patients with AF (without ABL - 6 in DIS, 10 in CON groups), 8 had paroxysmal (3 in DIS, 5 in CON) and 8 had persistent AF (3 in DIS, 5 in CON). While age, BMI, HTN and DM were similar among DIS vs CON groups, the incidence of OSA was higher. However, given the patients with elevated PAWP-LVEDP gradient have worse PH, we suspect they were more likely to be tested for OSA (referral bias). Conclusion AF ablation is associated with an increased PAWP-LVEDP gradient likely from atrial scarring and non-compliance of the left atrium. Patients with elevated PAWP-LVEDP gradient have worse pulmonary hypertension and are more likely to be diagnosed with OSA.

The place of riociguat in the treatment of patients with pulmonary arterial hypertension associated with systemic connective tissue diseases

Pulmonary hypertension (PH) can develop in different systemic autoimmune rheumatic diseases (SARD), such as systemic scleroderma (SSD), systemic lupus erythematosus, rheumatoid arthritis, and mixed connective tissue disease In most cases, patients with SARD develop WHO group I PH (pulmonary arterial hypertension associated with systemic connective tissue diseases, PAH-SCTD). General prevalence of this pathology reaches 15 cases per million adults. Most cases of PAH-SCTD are induced by SSD. Survival of PAH-SCTD patients is generally lower than survival of patients with other forms of LAH. Treatment of any SARD, including in LAH, implies a complex approach using glucocorticoids, disease-modifying anti-rheumatic drugs (cyclophosphamide, methotrexate, azathioprine, and others), and genetically engineered biologics. Specific targeted therapy is indicated for most patients with PAH-SCTD. The representative of a new class (soluble guanylate cyclase (sGC) stimulators), riociguat, has been approved for the treatment of PAH. This drug has a unique double mechanism of action: (i) sGC sensibilization to endogenous nitric oxide (NO) by stabilizing the NO-sGC bond; and (ii) direct, NO-independent sGC stimulation. For patients with PAH-SCTD, riociguat is the major alternative to phosphodiesterase-5 inhibitors both as monotherapy and combination therapy.

Adaptation of the WHO group interpersonal therapy for people living with HIV/AIDS in Northwest Ethiopia: A qualitative study.

BackgroundPsychological treatments improve depressive symptoms in people living with HIV/AIDS (PLWHA). Adaptation of treatments should be based on explanatory models of depression and other elements within the given context.AimThis study aimed to examine explanatory models of depression and acceptable approaches for implementation of group IPT in Northwest Ethiopia.MethodsQualitative data were collected from April to May 2019 from case managers, adherence supporters and service users using focus group discussion and analysed thematically.ResultsPLWHA attributed depression to psychosocial problems, spiritual factors and biological factors. Depression had several impacts at individual and family level. Group-based interpersonal therapy (IPT) was acceptable if provided by trained peer counselors.ConclusionThe current study findings informed how to conduct feasibility and acceptability trials of group IPT in the HIV population in Ethiopia.

Impact of COVID-19 on global HCV elimination efforts

Background & AimsCoronavirus disease 2019 (COVID-19) has placed a significant strain on national healthcare systems at a critical moment in the context of hepatitis elimination. Mathematical models can be used to evaluate the possible impact of programmatic delays on hepatitis disease burden. The objective of this analysis was to evaluate the incremental change in HCV liver-related deaths and liver cancer, following a 3-month, 6-month, or 1-year hiatus in hepatitis elimination programs.MethodsPreviously developed models were adapted for 110 countries to include a status quo or ‘no delay’ scenario and a ‘1-year delay’ scenario assuming significant disruption in interventions (screening, diagnosis, and treatment) in the year 2020. Annual country-level model outcomes were extracted, and weighted averages were used to calculate regional (WHO and World Bank Income Group) and global estimates from 2020 to 2030. The incremental annual change in outcomes was calculated by subtracting the ‘no-delay’ estimates from the ‘1-year delay’ estimates.ResultsThe ‘1-year delay’ scenario resulted in 44,800 (95% uncertainty interval [UI]: 43,800–49,300) excess hepatocellular carcinoma cases and 72,300 (95% UI: 70,600–79,400) excess liver-related deaths, relative to the ‘no-delay’ scenario globally, from 2020 to 2030. Most missed treatments would be in lower-middle income countries, whereas most excess hepatocellular carcinoma and liver-related deaths would be among high-income countries.ConclusionsThe impact of COVID-19 extends beyond the direct morbidity and mortality associated with exposure and infection. To mitigate the impact on viral hepatitis programming and reduce excess mortality from delayed treatment, policy makers should prioritize hepatitis programs as soon as it becomes safe to do so.Lay SummaryCOVID-19 has resulted in many hepatitis elimination programs slowing or stopping altogether. A 1-year delay in hepatitis diagnosis and treatment could result in an additional 44,800 liver cancers and 72,300 deaths from HCV globally by 2030. Countries have committed to hepatitis elimination by 2030, so attention should shift back to hepatitis programming as soon as it becomes appropriate to do so.

Mortality in adults with multidrug-resistant tuberculosis and HIV by antiretroviral therapy and tuberculosis drug use: an individual patient data meta-analysis

HIV-infection is associated with increased mortality during multidrug-resistant tuberculosis treatment, but the extent to which the use of antiretroviral therapy (ART) and anti-tuberculosis medications modify this risk are unclear. Our objective was to evaluate how use of these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis. We did an individual patient data meta-analysis of adults 18 years or older with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between 1993 and 2016. Data included ART use and anti-tuberculosis medications grouped according to WHO effectiveness categories. The primary analysis compared HIV-positive with HIV-negative patients in terms of death during multidrug-resistant tuberculosis treatment, excluding those lost to follow up, and was stratified by ART use. Analyses used logistic regression after exact matching on country World Bank income classification and drug resistance and propensity-score matching on age, sex, geographic site, year of multidrug-resistant tuberculosis treatment initiation, previous tuberculosis treatment, directly observed therapy, and acid-fast-bacilli smear-positivity to obtain adjusted odds ratios (aORs) and 95% CIs. Secondary analyses were conducted among those with HIV-infection. We included 11 920 multidrug-resistant tuberculosis patients. 2997 (25%) were HIV-positive and on ART, 886 (7%) were HIV-positive and not on ART, and 1749 (15%) had extensively drug-resistant tuberculosis. By use of HIV-negative patients as reference, the aOR of death was 2·4 (95% CI 2·0-2·9) for all patients with HIV-infection, 1·8 (1·5-2·2) for HIV-positive patients on ART, and 4·2 (3·0-5·9) for HIV-positive patients with no or unknown ART. Among patients with HIV, use of at least one WHO Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death. Use of ART and more effective anti-tuberculosis drugs is associated with lower odds of death among HIV-positive patients with multidrug-resistant tuberculosis. Access to these therapies should be urgently pursued. American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Development of a novel nomogram incorporating platelet-to-lymphocyte ratio for the prediction of lymph node involvement in prostate carcinoma

ObjectiveThe available nomograms used to predict lymph node involvement (LNI) are not comprehensive. We sought to derive a novel nomogram incorporating the platelet to lymphocyte ratio (PLR) to predict LNI and compare its performance to validated preoperative risk nomograms in a cohort of men undergoing robotic-assisted radical prostatectomy at our institution. MethodsOur electronic health record was queried for patients who underwent robotic-assisted radical prostatectomy with bilateral pelvic lymphadenectomy between 2013 and 2019. A bootstrapped multivariate logistic regression model was constructed for the predictors of LNI while adjusting for other covariates. Then, we used the derived logistic regression formula to estimate each patient's risk (%) for LNI. Individualized risks were also calculated using the following verified nomograms: Briganti-2012, Cagiannos, Godoy, and Memorial Sloan Kettering Cancer Center. Subsequently, we plotted the risks for our nomogram and the 4 verified nomograms into receiver operating characteristics curves. We reported the area under the curve (AUC) for each of the 5 nomograms and the corresponding 95% confidence interval (CI). ResultsThe cohort included 173 patients, of which 13.9% demonstrated LNI. LNI was associated with higher preoperative prostate-specific antigen (PSA) ≥ 10 [odds ratio [OR] = 4.89; 95% confidence interval [CI] (1.42–16.83)], higher grade (WHO group ≥ 3)[19.21; (2.23–195.25)], and higher percentage of positive biopsy cores (≥60%) [3.38, (1.04–11.00)]. With every 30-unit increase in PLR the risk of LNI increased by 47%. The nomogram derived from our data had the highest AUC [(AUC 0.877; 95% CI (0.806–0.947)]. The Memorial Sloan Kettering Cancer Center and Briganti 2012 displayed almost congruent ability [0.836; 95% CI (0.758–0.915)] and [0.827; (0.752–0.902)] to identify patients with positive nodes in our cohort with perfect sensitivity and negative predictive value. ConclusionThe nomogram incorporating PLR demonstrated 94.7% sensitivity to predict LNI and avoided pelvic lymphadenectomy in half of the patients at a cut-off between 6.5% and 8.5%. A prospective study with a larger sample is needed to validate our findings.

Prospective evaluation of improving fluoroquinolone exposure using centralised therapeutic drug monitoring (TDM) in patients with tuberculosis (PERFECT): a study protocol of a prospective multicentre cohort study

IntroductionGlobal multidrug-resistant tuberculosis (MDR-TB) treatment success rates remain suboptimal. Highly active WHO group A drugs moxifloxacin and levofloxacin show intraindividual and interindividual pharmacokinetic variability which can cause low drug exposure....

Relationship between compliance and pulmonary vascular resistance in pulmonary arterial hypertension.

BackgroundPulmonary arterial compliance (PAC) was previously shown to be an important prognostic factor in pulmonary arterial hypertension (PAH), in addition to the conventional pulmonary vascular resistance (PVR). The product of PAC and PVR, the arterial time (RC) constant, expresses the logarithmic relationship between the hemodynamic parameters. The objective of the study was to test RC constant stability in PAH patients followed beyond 12 months after diagnosis, and to report possible RC variations in different etiologies.MethodsFourteen PAH patients followed between 2008 and 2019 were included. Type 1 PAH was defined as a mean pulmonary artery pressure (PAP) ≥25 mmHg at rest and PVR ≥3 Wood units (WU). All patients who fulfilled WHO group I PAH criteria and had undergone two right heart catheterizations at least 1 year apart were included. The recorded hemodynamic data for each patient were used to compute PVR and PAC.ResultsPAH etiologies included scleroderma (n=2), liver cirrhosis (n=1), hereditary hemorrhagic telangiectasia (HHT) (n=1), mixed connective tissue disease (MCTD) (n=3), and idiopathic (n=7). The RC constant remained stable for all 14 patients over a follow-up period of 3.9±2 years. Patients with MCTD displayed more favorable hemodynamics, evidenced by higher RC (12.54 vs. 10.01, P<0.01) and PAC values (2.59 vs. 1.62, P=0.02), when compared with non-MCTD PAH patients. For the entire cohort the mean PAP measured 51±14 mmHg at baseline, and 46±13 mmHg at follow-up, respectively.ConclusionsThe relationship between PAC and PVR remains stable in follow-up periods averaging 4 years, making compliance an important disease marker past the early stages. Patients with MCTD displayed more advantageous hemodynamic profiles when compared with patients with other PAH etiologies.

Understanding spending trends for tuberculosis

As the tuberculosis community strives to work towards tuberculosis elimination goals, financing and spending continue to be crucial issues.1 Tuberculosis usually affects the most poor and vulnerable populations and resources have always been few and strained.2 Year after year, reports from WHO, STOP TB, and other advocacy groups show that tuberculosis spending is inadequate to diagnose and treat existing cases, and recent meetings such as the 2018 UN high-level meeting on tuberculosis have elicited pledges to improve resources and finances available in the fight against tuberculosis.

Prognostic Significance of Echocardiographic Parameters in Predicting Early Decline in Patients with Pulmonary Arterial Hypertension

Echocardiography is routinely used for screening and longitudinal monitoring of patients with pulmonary arterial hypertension (PAH). While several echocardiographic parameters have been explored to predict outcomes in PAH, they may be discrepant with other clinical findings. We sought to determine if echocardiographic parameters can predict early decline in PAH. We identified patients from the Houston Methodist PAH Clinic with WHO Group 1 PAH with an "Event," defined by initiation of IV prostacyclins, referral for transplant, or death between January 2016 and September 2019. We reviewed their echocardiographic parameters six months prior to the Event when they were clinically stable. We also reviewed these parameters in Group 1 PAH patients who remained stable during the study period as controls. Differences between groups were determined by Fisher's exact tests for categorical variables and Wilcoxon rank-sum test for continuous variables. We included 41 patients: 12 with an Event (3 died, 3 were referred for transplant, 6 were started on IV prostacyclins) and 29 without an Event. Of the 41 patients, 34 were women and 7 were men. Of the 12 with an Event, 11 were women and one was a man. Of the 29 without an Event, 26 were women and 3 were men. The average age was 46 in the Event group and 52 in the control group, p=0.50. The echocardiogram in the Event group was obtained an average of 197 days prior to the Event. The WHO functional class (FC) and six minute walk distance (6MWD) (420m vs. 393m, p=0.46) did not differ significantly between groups. The B type natriuretic peptide was significantly higher in the Event group (142 pg/ml vs. 42 pg/ml, p=0.01). Right atrial (RA) volume index (54ml/m2 vs. 29ml/m2, p=0.01), end diastolic left ventricular eccentricity index (LVEI) (1.3 vs. 1.0, p=0.001), end systolic LVEI (1.5 vs. 1.1, p=0.001), estimated pulmonary artery systolic pressure (PASP) (74mmHg vs. 52mmHg, p=0.02) and right ventricular (RV) basal dimension (5.0cm vs. 4.3cm, p=0.049) were significantly higher in the Event group. Left ventricular stroke volume (LVSV) (51ml vs. 69ml, p=0.045) was significantly lower in the Event group. RA volume index, end diastolic/systolic LVEI, PASP, RV basal dimension and LVSV predict early decline in Group 1 PAH patients even when they are deemed clinically stable based on FC and 6MWD.

INSPIRE: Final Results from a Phase 3, Open-Label, Pivotal Study to Evaluate the Safety and Tolerability of LIQ861 in Pulmonary Arterial Hypertension

Significant advantages are associated with inhaled therapies for pulmonary arterial hypertension (PAH), including enhanced delivery of drug to the lungs at a lower overall dose, improved ventilation-perfusion matching, and decreased risk of systemic vasodilation and other systemic adverse effects. LIQ861 is an investigational, novel, dry-powder formulation of treprostinil (TRE) designed using PRINT® technology to enhance deep-lung drug deposition and enable delivery of TRE doses in 1 to 2 breaths per capsule 4 times per day while using a convenient dry-powder inhaler. The primary objective of the INSPIRE study is to evaluate the safety and tolerability of LIQ861 in PAH patients transitioning to LIQ861 from a stable dose of Tyvaso® (Transition Group) and those adding LIQ861 to therapy with ≤2 non-prostacyclin (PGI) oral agents (Add-on Group). Final results from INSPIRE will be presented. INSPIRE is a phase 3, open-label, multicenter study that enrolled WHO Group I PAH patients classified as New York Heart Association (NYHA) functional class (FC) II-IV. Patients in the Transition Group received an initial dose of LIQ861 that was believed to be comparable to their Tyvaso® dose, while those in the Add-on Group initiated LIQ861 at a dose of 25 mcg capsule strength QID. LIQ861 dose increases in both groups were titrated in 25 mcg capsule strength QID increments to tolerance and symptom relief. The primary endpoint is the incidence of treatment-emergent adverse events and serious adverse events at Month 2. Exploratory endpoints are changes from baseline through Month 2 in physician assessment of stability; six-minute walk distance; NYHA FC, N-terminal B-type natriuretic peptide levels; and patient-reported quality of life. An additional endpoint for the Transition Group is the proportion of patients maintaining a sustained transition through Month 2, with sustained transition defined as continued LIQ861 therapy after discontinuation of Tyvaso®, no interruptions in LIQ861 therapy for ≥7 days; and no treatment with any other PGI analog or PGI receptor agonist.

Evolutionary dynamics of influenza B strains detected from paediatric acute respiratory infections in central Vietnam

Influenza virus B belongs to the family Orthomyxoviridae with segmented negative-sense RNA genomes. Since 1970s, influenza B has diverged intoVictoria and Yamagata, which differs in antigenic and evolutionary characteristics. Yet, molecular-epidemiological information of influenza B from developing nations is limited. In central Vietnam, influenza A subtype-specific circulation pattern and clinical characteristics were previously described. However, molecular evolutionary characteristics of influenza B has not been discussed to date.We utilized the influenza B positives obtained from paediatric ARI surveillance during 2007–2013. Influenza B HA and NA genes were amplified, sequenced, and phylogenetic/molecular evolutionary analysis was performed using Maximum Likelihood and Bayesian MCMC. Phylodynamics analysis was performed with Bayesian Skyline Plot (BSP). Furthermore, we performed selection pressure analysis and estimated N-glycosylation sites. In the current study, overall positive rate for influenza B was 3.0%, and Victoria lineage immediately became predominant in post-A/H1N1pdm09 period. The noticeable shift in Victoria lineage WHO Group occurred. With respect to the evolutionary rate (substitutions/site/year), Victoria lineage HA gene was evolving faster than Yamagata lineage (2.43 × 10−3 vs 2.00 × 10−3). Furthermore, the evolutionary rate of Victoria Group 5 was greater than Group 1. BSP presented the rapid growth in Effective Population Size (EPS) of Victoria lineage occurred soon after the 1st A/H1N1pdm09 case was detected whereas the EPS of Yamagata lineage was stable for both genes. N-glycosylation pattern between lineages and among WHO Groups were slightly different, and HA gene had a total of 6 amino acid substitutions under positive section pressure (4 for Victoria and 2 for Yamagata).The current results highlight the importance of Victoria lineage in post-A/H1N1pdm09 period. Difference in evolutionary characteristics and phylodynamics may indicate lineage and WHO Group-specific evolutionary dynamics. It is necessary to further continue the molecular-epidemiological surveillance in local setting to gain a better understanding of local evolutionary characteristics of influenza B strains.

THE DIFFICULTIES IN THE DIAGNOSIS OF PULMONARY HYPERTENSION ASSOCIATED WITH CHRONIC LUNG DISEASE

Introduction: Chronic lung disease (WHO group 3) is the second leading cause of pulmonary hypertension (PH). In turn, the development of PH influences the course of lung disease, worsening the clinical symptoms and prognosis. The aim: To analyse the difficulties in the diagnosis of pulmonary hypertension due to chronic lung disease. Review and Discussion: According to recent literature, PH in the course of lung diseases develops as a result of both "parenchymal" and vascular pathology in patients with a genetic predisposition. Prolonged infection (especially viral) may be an additional promoting factor. Elevation of pulmonary arterial pressure (PAP) is usually moderate and correlates with severity of lung disease. In a small minority, PAP may reach that seen in WHO group 1 pulmonary arterial hypertension (PAH). Conclusions: Echocardiography and right heart catheterization are the principal tools for the diagnosis of PH in chronic lung diseases. Unfortunately, current medications for treating PAH have not shown benefit in controlled trials of group 3 PH, hence their routine use is not recommended. Patients with severe group 3 PH should be considered for referral to expert centres or entry into clinical trials.

The Labour Progression Study (LaPS): Duration of labour following Zhang's guideline and the WHO partograph – A cluster randomised trial

ObjectiveTo investigate labour duration in different phases of labour when adhering to Zhang's guideline for labour progression compared with the WHO partograph. DesignA secondary analysis of a cluster randomised controlled trial. SettingFourteen Norwegian birth care units, each with more than 500 deliveries per year constituted the clusters. ParticipantsA total of 7277 nulliparous women with singleton foetus in a cephalic presentation and spontaneous onset of labour at term were included. InterventionSeven clusters were randomised to the intervention group that adhered to Zhang's guideline (n = 3972) and seven to the control group that adhered to the WHO partograph (n = 3305) for labour progression. MeasurementsThe duration of labour from the first registration of cervical dilatation (≥ 4 cm) to the delivery of the baby and the duration of the first and second stages of labour; the time-to-event analysis was used to compare the duration of labour between the two groups after adjusting for baseline covariates. FindingsThe adjusted median duration of labour was 7.0 h in the Zhang group, compared with 6.2 h in the WHO group; the median difference was 0.84 h with 95% confidence interval [CI] (0.2–1.5). The adjusted median duration of the first stage was 5.6 h in the Zhang group compared with 4.9 h in the WHO group; the median difference was 0.66 h with 95% CI (0.1–1.2). The corresponding adjusted median duration of the second stage was 88 and 77 min; the median difference was 0.18 h with 95% CI (0.1–0.3). Key Conclusions: The women who adhered to Zhang's guideline had longer overall duration and duration of the first and second stages of labour than women who adhered to the WHO partograph. Implications for practice: Understanding the variations in the duration of labour is of great importance, and the results offer useful insights into the different labour progression guidelines, which can inform clinical practice.

Pulmonary Arterial Hypertension in Pregnancy: Outline of Multidisciplinary Care

Pulmonary Arterial Hypertension in pregnancy causes significant maternal and fetal morbidity. There is currently no consensus on recommendations for overall management in pregnancies complicated by pulmonary arterial hypertension. We recommend institutions help build a multidisciplinary team with knowledge about pulmonary arterial hypertension to coordinate care during pregnancy, at delivery and in the postpartum period. The purpose of this article is to highlight some of the challenges in caring for these women, review the literature and help guide care teams by outlining our management process for 5 pregnant patients with WHO Group 1 pulmonary arterial hypertension on epoprostenol.

P2535Pregnant patients with pulmonary hypertension-the case of a medical centre

Abstract Background Nowadays, Pulmonary Hypertension (PH) is one of the most pressing issues in cardiovascular disease. Subsequently, pregnant women have a high degree of risk of morbidity and mortality and this poses a big challenge. Studies show that very often PH occurs due to congenital heart disease and for this reason, it is recommended to avoid pregnancy or to terminate the pregnancy at an early stage. Women who choose to remain pregnant should be treated at specialized PH centers with the experience of managing PH during and after pregnancy. Purpose The main purpose of this study was to estimate the survival of pregnant pts with PH depending on the severity of PH and etiology. Methods 8336 women during delivery on admission were screened from the period spanning January 2014 to December 2016. Of this number, 4268 (51%) the medical records of pregnant women with cardiovascular disease were retrospectively reviewed to identify patients with coexisting PH and pregnancies. Data on 98 (1.18%) pts with PH were identified and included in the study. All patients' PH severity was measured by Doppler echocardiography. Pulmonary artery systolic pressure value of 35 to 50 mm Hg, 51 to 70 mm Hg, or greater than 71 mm Hg measured by echocardiography corresponded to the mild, moderate, or severe PH, respectively. Demographics, characteristics of PH and pregnancy, management and outcomes were as well analyzed. Results 54 cases (55%) were classified into WHO group 1, 40 cases (41%) in group 2 (reason –left heart disease), 4 cases (4%) in group 4 (reason - pulmonary thromboembolism), and none in group 3 or 5. The systolic pulmonary artery pressure was &lt;50 mmHg in 70,4% of patients, 51–70 mmHg in 18,4% and ≥70 mmHg in 11,2% The median age was 28 years. All deaths occurred in women with PH in WHO group 1, with moderate or severe PH severity, and with NYHA grade of III to IV. Pulmonary vascular-targeted medications were used in all pts with severe PH and in some cases with moderate PH 14 pts (14%), but none was administered to pts with mild PH. During pregnancy, 9 pts took monotherapy of the sildenafil but 1 pregnant patient took a combination of therapy with iloprost. After delivery, 14 pts took monotherapy and 9 took combination therapy. This notwithstanding, 3 pts who took the combination therapy (3%), died within 15 days after delivery (9,14,15 days, respectively). All of them died from uncontrolled PH and heart failure after delivery. Conclusion Our study shows that maternal mortality is associated with the severity of PH. Mortality in pregnant patients with pulmonary hypertension is still the most discussed problem in cardiology and obstetrics. It is necessary to diagnose this disease at an early stage, prevent pregnancy in pts with severe to moderate PH as much as possible, continue observation, adequately apply therapy in order to help curtail this problem.