Impact of two rounds of mass drug administration using diethylcarbamazine combined with albendazole on the prevalence of Brugia timori and of intestinal helminths on Alor Island, Indonesia

BACKGROUND: Annual mass drug administration (MDA) using diethylcarbamizine (DEC, 6 mg/kg) combined with albendazole (alb, 400 mg) is recommended by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). This strategy has been shown to be efficient in the of control bancroftian filariasis, but data on brugian filariasis as well as on the positive side effects on intestinal helminths are lacking. METHODS: The effect of one selective treatment and two rounds of MDA using DEC and alb on the prevalence and intensity of Brugia timori infection were studied on Alor island using a cross-sectional and a cohort approach. Before the campaign and ten months after each treatment cycle microfilariae (mf) were assessed by filtration of night blood. Before and ten months after MDA, stool samples were collected and the prevalence of intestinal helminths were determined. RESULTS: In all, the mf-rate dropped from 26.8% before any treatment to 3.8% following the second MDA. Almost all mf-positive, treated individuals showed very low mf densities. The crude prevalence of hookworm dropped from 25.3% to 5.9%. The reduction of prevalence of Ascaris lumbricoides (32.3% to 27.6%) and Trichuris trichiura (9.4% to 8.9%) was less pronounced. Within a cohort of 226 individuals, which was examined annually, the prevalence of A. lumbricoides dropped from 43.8% to 26.5% and of T. trichiura from 12.8% to 6.6%. The results indicate that this MDA approach reduces not only the mf prevalence of B. timori but also the prevalence of hookworm and to a lesser extent also of A. lumbricoides and T. trichiura. CONCLUSION: The MDA using DEC and alb as recommended by GPELF is extremely effective for areas with brugian filariasis. The beneficial effect of MDA on intestinal helminths may strengthen the national programme to eliminate lymphatic filariasis in Indonesia and may set resources free which are otherwise used for deworming campaigns of schoolchildren

The clinical course of idiopathic pulmonary fibrosis and its association to quality of life over time: longitudinal data from the INSIGHTS-IPF registry

Background: Quality of life (QoL) is profoundly impaired in patients with idiopathic pulmonary fibrosis (IPF). However, data is limited regarding the course of QoL. We therefore analysed longitudinal data from the German INSIGHTS-IPF registry. Methods: Clinical status and QoL were assessed at enrollment and subsequently at 6- to 12-months intervals. A range of different QoL questionnaires including the St. George’s Respiratory Questionnaire (SGRQ) were used. Results: Data from 424 patients were included; 76.9% male; mean age 68.7 ± 9.1 years, mean FVC% predicted 75.9 ± 19.4, mean DLCO% predicted 36.1 ± 15.9. QoL worsened significantly during follow-up with higher total SGRQ scores (increased by 1.47 per year; 95% CI: 1.17 to 1.76; p < 0.001) and higher UCSD-SOBQ scores and lower EQ-5D VAS and WHO-5 scores. An absolute decline in FVC% predicted of > 10% was associated with a significant deterioration in SGRQ (increasing by 9.08 units; 95% CI: 2.48 to 15.67; p = 0.007), while patients with stable or improved FVC had no significantly change in SGRQ. Patients with a > 10% decrease of DLCO % predicted also had a significant increase in SGRQ (+ 7.79 units; 95% CI: 0.85 to 14.73; p = 0.028), while SQRQ was almost stable in patients with stable or improved DLCO. Patients who died had a significant greater increase in SGRQ total scores (mean 11.8 ± 18.6) at their last follow-up visit prior to death compared to survivors (mean 4.2 ± 18.9; HR = 1.03; 95% CI: 1.01 to 1.04; p < 0.001). All QoL scores across the follow-up period were significantly worse in hospitalised patients compared to non-hospitalised patients, with the worst scores reported in those hospitalised for acute exacerbations. Conclusions: QoL assessments in the INSIGHTS-IPF registry demonstrate a close relationship between QoL and clinically meaningful changes in lung function, comorbidities, disease duration and clinical course of IPF, including hospitalisation and mortality

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Endoscopic lung volume reduction coil treatment in patients with very low FEV: an observational study

Background: Endoscopic lung volume reduction coil (LVRC) treatment is a therapeutic option for selected patients with advanced emphysema. The effects and the safety of endoscopic lung volume reduction in patients with very low forced expired volume in one second (FEV 1 ) remain to be determined. This study was conducted to assess the effects and the safety of LVRC treatment in patients with very low FEV 1 . Methods: The study was performed as a retrospective observational study in the Department of Respiratory Medicine at the University Medical Center Hamburg-Eppendorf on patients with very low FEV 1 , defined as an FEV 1 ⩽ 20% of predicted at baseline in whom LVRC treatment was performed between 1 April 2012 and 28 February 2017. Results: LVRC treatment was performed in 33 patients with very low FEV 1 . Of these, 45.5% were female and 54.5% were male. At baseline, mean FEV 1 was 0.46 ± 0.12 liters (15 ± 3% of predicted), mean forced vital capacity (FVC) was 1.61 ± 0.62 liters (42 ± 13% of predicted), mean residual volume (RV) was 6.03 ± 0.81 liters (275 ± 51% of predicted) and 6-minute walk distance was 229 ± 102 m. Bilateral LVRC treatment was completed in 21 of these patients (63.6%). Bilateral LVRC treatment led to significant improvements in functional parameters with an increase in mean FEV 1 from 0.44 ± 0.11 liters to 0.54 ± 0.12 liters ( p = 0.001), equivalent to a relative improvement of 24.5 ± 26.9%, an increase in mean FVC from 1.49 ± 0.54 liters to 1.84 ± 0.49 liters ( p = 0.001), a decrease in mean RV from 6.27 ± 0.83 liters to 5.83 ± 1.09 liters ( p = 0.004) and an improvement in 6-minute walk distance from 218 ± 91 m to 266 ± 96 m ( p = 0.01). There were no cases of respiratory failure requiring mechanical ventilation and no deaths. Conclusions: LVRC treatment was effective and safe in patients with very low FEV 1

Endoscopic lung volume reduction coil treatment in patients with chronic hypercapnic respiratory failure: an observational study

Background: Endoscopic lung volume reduction coil (LVRC) treatment is an option for selected patients with severe emphysema. In the advanced stages, emphysema leads to respiratory failure: hypoxemia and eventually chronic hypercapnic respiratory failure. It can be hypothesized that LVRC treatment, a procedure targeting hyperinflation and thereby reducing ventilatory workload, may be especially beneficial in patients with chronic hypercapnic respiratory failure. This study was conducted to gain first insights into the effects and the safety of LVRC treatment in patients with emphysema and chronic hypercapnic respiratory failure. Methods: A retrospective observational study conducted in the Department of Respiratory Medicine at the University Medical Center Hamburg-Eppendorf, Germany on all patients with chronic hypercapnic respiratory failure in whom bilateral LVRC treatment was performed between 1 April 2012 and 30 September 2015. Results: During the study period, bilateral LVRC treatment was performed in 10 patients with chronic hypercapnic respiratory failure. Compared with baseline, bilateral LVRC treatment led to a significant increase in mean forced expiratory volume in one second (FEV 1 ) from 0.5 ± 0.1 l to 0.6 ± 0.2 l ( p = 0.004), a decrease in residual volume (RV) from 6.1 ± 0.9 l to 5.6 ± 1.1 l ( p = 0.02) and a reduction in partial pressure of carbon dioxide in arterial blood (PaCO 2 ) from 53 ± 5 mmHg to 48 ± 4 mmHg ( p = 0.03). One case of hemoptysis requiring readmission to hospital was the only severe adverse event. Conclusions: LVRC treatment was safe and effective in patients with nonsevere chronic hypercapnic respiratory failure. It led not only to an improvement in lung function but also to a significant decrease in PaCO 2

Genetic evidence for a causative effect of airflow obstruction on left ventricular filling: a Mendelian randomisation study

Background!#!Observational studies on the general population have suggested that airflow obstruction associates with left ventricular (LV) filling. To limit the influence of environmental risk factors/exposures, we used a Mendelian randomisation (MR) approach based on common genetic variations and tested whether a causative relation between airflow obstruction and LV filling can be detected.!##!Methods!#!We used summary statistics from large genome-wide association studies (GWAS) on the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) measured by spirometry and the LV end-diastolic volume (LVEDV) as assessed by cardiac magnetic resonance imaging. The primary MR was based on an inverse variance weighted regression. Various complementary MR methods and subsets of the instrument variables were used to assess the plausibility of the findings.!##!Results!#!We obtained consistent evidence in our primary MR analysis and subsequent sensitivity analyses that reducing airflow obstruction leads to increased inflow to the LV (odds ratio [OR] from inverse variance weighted regression 1.05, 95% confidence interval [CI] 1.01-1.09, P = 0.0172). Sensitivity analyses indicated a certain extent of negative horizontal pleiotropy and the estimate from biased-corrected MR-Egger was adjusted upward (OR 1.2, 95% CI 1.09-1.31, P < 0.001). Prioritisation of single genetic variants revealed rs995758, rs2070600 and rs7733410 as major contributors to the MR result.!##!Conclusion!#!Our findings indicate a causal relationship between airflow obstruction and LV filling in the general population providing genetic context to observational associations. The results suggest that targeting (even subclinical) airflow obstruction can lead to direct cardiac improvements, demonstrated by an increase in LVEDV. Functional annotation of single genetic variants contributing most to the causal effect estimate could help to prioritise biological underpinnings