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Abstract Background The development of novel antischistosomal drugs is crucial, as currently no vaccine and only a single drug is available for the treatment of schistosomiasis. Fast and accurate in vitro assays are urgently needed to identify new drug candidates and research efforts should include Schistosoma haematobium. The aim of the present study was to develop a S. haematobium drug sensitivity assay based on newly transformed schistosomula (NTS). Methods We first undertook comparative studies on the cercarial emergence rhythms of the intermediate host snails Biomphalaria glabrata (S. mansoni) and Bulinus truncatus (S. haematobium). Two transformation methods as well as three purification methods were studied on S. haematobium cercariae in order to produce a large number of viable and clean NTS. Known antischistosomal drugs were tested in the established NTS assay in vitro. Drug effects were evaluated either microscopically or fluorometrically, using a resazurin based viability marker. Microscopically obtained IC50 values were compared with results obtained for S. mansoni. Results A circadian rhythm existed in both snail species. Infected B. truncatus snails shed less cercariae than B. glabrata during the testing period. The highest transformation rate (69%) of S. haematobium cercariae into NTS was obtained with the vortex transformation (mechanical input) and the highest purification factor was observed using Percoll®. The fluorimetric readout based on resazurin was very precise in detecting dead or/and severely damaged schistosomula. Conclusions With the use of viability markers such as resazurin, drug screening assays using S. haematobium NTS can be efficiently performed. However, drugs acting on the morphology and motility of S. haematobium NTS, such as metrifonate are missed. Drug sensitivity assays with NTS of both species, S. haematobium and S. mansoni, showed very similar results using known antischistosomal drugs. The S. mansoni NTS assay might be more suitable as primary screen in drug discovery efforts, which ultimately aim for a broad-spectrum antischistosomal drug as a larger number of S. mansoni NTS can be generated.

Background: Remote delivery may improve access to pulmonary rehabilitation (PR). Existing studies are largely limited to individuals with COPD, and the interventions have lacked codesign elements to reflect the needs and experiences of people with chronic respiratory disease, their carers/families and healthcare professionals. The aim of this study was, using experience-based codesign (EBCD), to collaborate with people with interstitial lung disease (ILD), their carers/families and healthcare professionals, to codesign a remote PR programme ready for testing in a future study., Methods: EBCD comprises interviews, stakeholder workshops and codesign meetings. One-to-one videorecorded interviews with purposively selected people with ILD with experience of PR, their carers/families and healthcare professionals, were edited into a 20 min film. The film was shown at three audiorecorded stakeholder feedback events to identify key themes and touchpoints, and short-list key programme components. The programme was finalised at two further codesign workshops., Results: Ten people with ILD, four carers/families and seven healthcare professionals were interviewed. Participants in the codesign workshops included service-user group: n=14 and healthcare professional group: n=11; joint event: n=21. Final refinements were made with small codesign teams, one comprising three people with ILD and one carer/family member, one with five healthcare professionals. The final codesigned model is a group based, supervised programme delivered by videoconference. Key elements of programme specific to ILD include recommendations to ensure participant safety in the context of desaturation risk, dedicated time for peer support and adaption of the education programme for ILD needs, including signposting to palliative care., Conclusion: In this EBCD project, a remote PR programme for people with ILD was codesigned by service-users, their carers/families and multidisciplinary healthcare professionals. Future research should explore the feasibility and acceptability of this intervention., Competing Interests: Competing interests: NS, JG-N, KAI and JH report no competing interests. LJB was funded by an ESRC Post-doctoral fellowship ES/X005259/1 and was supported by the NIHR Applied Research Collaboration South London (NIHR ARC South London) at King’s College Hospital NHS Foundation Trust. CMN reports funding from the Royal Brompton and Harefield Charity, National Institute for Health Research for Patient Benefit and Brunel University London BRIEF award. WD-CM reports grants from National Institute for Health Research, grants from British Lung Foundation, outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: The adherence to and clinical efficacy of pulmonary rehabilitation in idiopathic pulmonary fibrosis (IPF), particularly in comparison with COPD, remains uncertain. The objectives of this real-world study were to compare the responses of patients with IPF with a matched group of patients with COPD undergoing the same supervised, outpatient pulmonary rehabilitation program and to determine whether pulmonary rehabilitation is associated with survival in IPF., Research Question: Do people with IPF improve to the same extent with pulmonary rehabilitation as a matched group of individuals with COPD, and are noncompletion of or nonresponse to pulmonary rehabilitation, or both, associated with 1-year all-cause mortality in IPF?, Study Design and Methods: Using propensity score matching, 163 patients with IPF were matched 1:1 with a control group of 163 patients with COPD referred for pulmonary rehabilitation. We compared between-group pulmonary rehabilitation completion rates and response. Survival status in the IPF cohort was recorded over 1 year after pulmonary rehabilitation discharge. Cox proportional hazards regression explored the association between pulmonary rehabilitation status and all-cause mortality., Results: Similar pulmonary rehabilitation completion rates (IPF, 69%; COPD, 63%; P = .24) and improvements in exercise response were observed in both groups with no significant mean between-group differences in incremental shuttle walk test (ISWT) change (mean, 2 m [95% CI, -18 to 22 m]). Pulmonary rehabilitation noncompletion (hazard ratio [HR], 5.62 [95% CI, 2.24-14.08]) and nonresponse (HR, 3.91 [95% CI, 1.54-9.93]) were associated independently with increased 1-year all-cause mortality in IPF., Interpretation: This real-word study demonstrated that patients with IPF have similar completion rates and magnitude of response to pulmonary rehabilitation compared with a matched group of patients with COPD. In IPF, noncompletion of and nonresponse to pulmonary rehabilitation were associated with increased all-cause mortality. These data reinforce the benefits of pulmonary rehabilitation in patients with IPF., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: We previously demonstrated low levels of digital literacy amongst pulmonary rehabilitation service-users prior to the COVID-19 pandemic. We aimed to identify whether the pandemic accelerated digital literacy in this population, resulting in greater acceptance of remote web-based pulmonary rehabilitation programme models., Methods: We surveyed digital access and behaviours and pulmonary rehabilitation delivery preferences of service-users referred to pulmonary rehabilitation in 2021 (cohort 2021) and propensity score-matched them to a cohort who completed the survey in 2020 (cohort 2020)., Results: There were indicators that digital access and confidence were better amongst the Cohort 2021 but no difference was seen in the proportion of patients choosing remote web-based pulmonary rehabilitation as an acceptable method of receiving pulmonary rehabilitation., Conclusion: In an unselected cohort of service-users, remote web-based pulmonary rehabilitation was considered acceptable in only a minority of patients which has implications on healthcare commissioning and delivery of pulmonary rehabilitation.

Background: The COPD Assessment Test (CAT) is a recently introduced instrument to assess health-related quality of life in COPD. We aimed to evaluate the longitudinal change in CAT following Pulmonary Rehabilitation (PR), and test the relationship between CAT and CRQ-Self Report (SR) over time. We hypothesised that the CAT would show similar responsiveness to PR as the CRQ-SR both in the short and medium-term., Methods: 118 COPD patients completed an eight-week outpatient multidisciplinary PR programme. CAT, CRQ-SR and the incremental shuttle walk (ISW) were measured prior to starting PR (T1), completion of PR (T2) and 6 months after completion of PR (T3)., Results: There was a significant improvement in CAT, CRQ-SR and ISW immediately following PR (p < 0.001). Although there was decline between T2 and T3, CAT, CRQ-SR and ISW remained significantly better at T3 compared with T1 (ANOVA p < 0.001). Both between T1-T2 and between T2-T3, change in CAT correlated significantly with change in CRQ (both r = -0.44 and p < 0.001). The slope of the relationship between CAT change and CRQ-SR change at T1-T2 and T2-T3 was not significantly different (ANCOVA: intercept p = 0.79, interaction effect p = 0.95)., Conclusions: In COPD, the CAT score is immediately responsive to PR and remains improved at 6 months. There is no significant difference in the short and medium term changes in the CAT and CRQ-SR following PR. We propose that for most clinical indications for assessing health-related quality of life in COPD, the CAT is a robust and practical alternative to longer-established instruments such as the CRQ-SR.

Quantification of daily physical activity is of clinical interest in chronic obstructive pulmonary disease (COPD). Objective measures using activity monitors may take several days to obtain reliable results. The aim of our study was to evaluate the Stanford Seven-Day Physical Activity Recall questionnaire (PAR) against the SenseWear armband (SWA) and compare its validity with three other physical activity questionnaires. 43 COPD patients wore the SWA for 7 days. Patients completed the PAR, Baecke, Physical Activity Scale for the Elderly (PASE) and Zutphen questionnaires. Spearman rank correlation, intraclass correlation coefficients (ICC) and receiver-operating characteristics (ROC) curves were used to assess the relationship between the questionnaires and SWA. Assessed by PAR, time spent at ≥3.0 metabolic equivalents (METs) correlated significantly (r=0.54, p<0.001) with equivalent measures from SWA, with an ICC of 0.40. No relationship was seen between the other questionnaires and the SWA. The PAR predicted active patients (≥30 min at ≥3.0 METs or a physical activity level (PAL) ≥1.55) and very inactive patients (PAL <1.40) with an area under ROC curve of 0.83, 0.77 and 0.70, respectively. While the PAR did not measure physical activity sufficiently accurately to make individual recommendations, it was able to identify COPD patients at extremes of the physical activity spectrum, potentially reducing the number of patients requiring direct measurement.

This randomized, double-blind, controlled clinical trial assessed lipid responses in mildly hyper-triglyceridemic men and women to consumption of docosahexaenoic acid (DHA)-enriched eggs or ordinary chicken eggs. The study included 153 subjects aged 21-80 years, with serum triglyceride concentrations between 140 and 450 mg/dL, inclusive, and serum total cholesterol concentrations < 300 mg/dL. Subjects were randomly assigned to receive either DHA-enriched (147 mg DHA/egg) or ordinary eggs (20 mg DHA/egg), added to their usual diets for six weeks (10 eggs/week). Both treatments significantly lowered triglycerides and increased high-density lipoprotein (HDL) cholesterol levels from baseline; however, these changes were not significantly different between treatments. Low-density lipoprotein (LDL) cholesterol concentrations increased significantly in subjects who consumed DHA-enriched eggs (p = 0.047 vs. control). This increase was significantly higher than that observed with ordinary eggs. However, there was no significant increase in cholesterol carried by small, dense LDL particles, as determined by nuclear magnetic resonance analysis. Results of exploratory analyses suggest favorable effects of the DHA-enriched eggs over ordinary eggs on triglyceride and HDL cholesterol levels in subjects with body mass index > or = 30 kg/m2; the DHA treatment produced a larger reduction in serum triglyceride concentration vs. ordinary eggs (-12.3 vs. 2.1%; p = 0.027), and there was a greater increase for HDL cholesterol in the DHA-enriched vs. ordinary egg group (5.0 vs. 1.1%; p = 0.040).

Background: Diacylglycerol is a natural component of edible oils that has metabolic characteristics that are distinct from those of triacylglycerol., Objective: We assessed the efficacy of an oil containing mainly 1,3-diacylglycerol in reducing body weight and fat mass when incorporated into a reduced-energy diet., Design: The study was a randomized, double-blind, parallel intervention trial that was conducted at an outpatient clinical research center. The subjects (n = 131) were overweight or obese men (waist circumference > or = 90 cm) and women (waist circumference > or = 87 cm). Food products (muffins, crackers, soup, cookies, and granola bars) containing diacylglycerol or triacylglycerol oil and having the same fatty acid composition were incorporated into a reduced-energy diet (2100-3350-kJ/d deficit) for 24 wk. Percentages of change in body weight, fat mass, and intraabdominal fat area were assessed., Results: In an intention-to-treat analysis, body weight and fat mass decreased significantly more in the diacylglycerol group than in the triacylglycerol group (P = 0.025 and 0.037, respectively). By the end of the trial, mean body weight had decreased 3.6% and 2.5% in the diacylglycerol and triacylglycerol groups, respectively. Fat mass decreased 8.3% and 5.6% in the diacylglycerol and triacylglycerol groups, respectively., Conclusion: Foods containing diacylglycerol oil promoted weight loss and body fat reduction and may be useful as an adjunct to diet therapy in the management of obesity.

Increased rates of coronary heart disease (CHD) occur with advancing age in both sexes, although CHD rates in women lag behind those of men by about 10 years. There is a sharp increase in CHD rate among women after approximately 50 years of age. The reasons for this are not completely understood and are undoubtedly multifactorial. Cross-sectional data from large-scale population studies suggest that around the time of the menopause, low-density lipoprotein (LDL)-cholesterol levels increase by approximately 15 to 25%. Because this increase is larger than that observed in men over the same age span and closely approximates that observed in women after oophorectomy, it is likely that reduced circulating estrogen levels associated with menopause play a role in the adverse changes in both blood lipid levels and CHD incidence. There is clear evidence that treating hypercholesterolemia reduces cardiovascular risk in women, as well as in men. In the US National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines, diet and other lifestyle changes are recommended as first-line therapy. If the treatment goals cannot be achieved through non-pharmacological measures, drug therapy should be added. Of the available lipid-lowering agents, HMG CoA reductase inhibitors (statins) are the clear choice to decrease LDL-cholesterol levels. However the favourable effects of statins on high-density lipoprotein (HDL)-cholesterol and triglyceride levels are more modest, and statins are not known to decrease lipoprotein (a) [Lp(a)] levels. Estrogen or hormone replacement therapy (ERT/HRT) and nicotinic acid improve LDL- and HDL-cholesterol levels and also decrease Lp(a) levels. However, ERT/HRT is no longer recommended as first-line therapy for decreasing CHD risk. Nicotinic acid is particularly useful for decreasing triglyceride levels (as are fibrates) and raising HDL-cholesterol levels. Bile-acid sequestrants reduce LDL-cholesterol and slightly increase HDL-cholesterol levels. Both bile acid sequestrants and ERT/HRT tend to raise triglyceride levels, therefore they should be used cautiously in women with hypertriglyceridaemia. Treatment should be individualised for each patient. It is important to evaluate the primary form of dyslipidaemia, other CHD risk factors, comorbidities, and the extent of lipid improvement needed in order to reach treatment goals. The effects of each type of therapy and potential adverse effects should also be considered.

Objective/design: The safety and tolerability of three levels of plant sterol-esters administered in reduced-fat spread and salad dressing vs. control products were evaluated in this randomized, double-blind, four-arm parallel study., Methods: Eighty-four free-living men and women consumed reduced-fat spread and salad dressing providing 0.0 g/day (n = 21), 3.0 g/day (n = 21), 6.0 g/day (n = 19) or 9.0 g/day (n = 23) of phytosterols as esters for an eight-week treatment period., Results: Side effects did not differ among the groups during the study, and there were no study product-related serious adverse events. There were no changes in clinical laboratory values in response to phytosterol intake. Blood concentrations of all fat-soluble vitamins remained within normal reference ranges, and there were no differences in serum vitamin responses among the four groups. Alpha- and trans-beta-carotene levels were reduced in the 9.0 g/day group vs. control (p < 0.05), but all carotenoid values remained within normal ranges throughout the study. All groups receiving phytosterols had significant increases in serum campesterol vs. control (p < 0.001), but beta-sitosterol responses did not differ from control. Total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol responses did not differ significantly among the groups. The total:HDL cholesterol response in the 9.0 g/day group was significantly different from the control group response (-9.6% vs. 2.6%, p < 0.05). A median increase of 7.8% in serum triglycerides was observed in the control group, which differed significantly from the response in the 3.0 g/day arm (-13.3%, p < 0.05)., Discussion: The results of this study indicate that phytosterol esters are well tolerated and show no evidence of adverse effects at a daily intake of up to 9.0 g of phytosterols for eight weeks.

Background: Plant sterol esters reduce cholesterol absorption and lower circulating blood cholesterol concentrations when incorporated into the habitual diet., Objective: This randomized, double-blind, 3-group parallel, controlled study evaluated the influence of esterified plant sterols on serum lipid concentrations in adults with mild-to-moderate primary hypercholesterolemia., Design: Subjects incorporated a conventional 50%-fat spread into a National Cholesterol Education Program Step I diet for a 4-wk lead-in period, followed by a 5-wk intervention period of the diet plus either a control reduced-fat spread (40% fat; n = 92) or a reduced-fat spread enriched with plant sterol esters to achieve intakes of 1.1 g/d (n = 92; low-sterol group) or 2.2 g/d (n = 40; high-sterol group)., Results: Subjects in the low- and high-sterol groups who consumed > or = 80% of the scheduled servings (per-protocol analyses) had total cholesterol values that were 5.2% and 6.6% lower, LDL-cholesterol values that were 7.6% and 8.1% lower, apolipoprotein B values that were 6.2% and 8.4% lower, and ratios of total to HDL cholesterol that were 5.9% and 8.1% lower, respectively, than values for the control group (P < 0.001 for all). Additionally, triacylglycerol concentrations decreased by 10.4% in the high-sterol group. Serum concentrations of fat-soluble vitamins and carotenoids were generally within reference ranges at baseline and postintervention. Serum plant sterol concentrations increased from baseline (0.48% of total sterol by wt) to 0.64% and 0.71% by wt for the low- and high-sterol groups, respectively (P < 0.05 compared with control)., Conclusion: A reduced-fat spread containing plant sterol esters incorporated into a low-fat diet is a beneficial adjunct in the dietary management of hypercholesterolemia.

Hydroxypropylmethylcellulose (HPMC) is a food gum that shares certain characteristics, such as high viscosity, with soluble fibers. In this trial, the safety and cholesterol-lowering efficacy of HPMC consumed with and between meals was evaluated in free-living male volunteers with mild-to-moderate hypercholesterolemia. After a 14-d baseline period, men (n = 51) with LDL cholesterol between 3.36 and 4.91 mmol/L and triglycerides <3.95 mmol/L were randomly assigned to consume 5.0 g/d HPMC in 240 mL of orange drink, taken either with or between meals, for a 2-wk treatment period. In the Between Meals group, total cholesterol was reduced by 8.0% vs. baseline in wk 1 of treatment (P < 0.05) and 5.1% in wk 2 (P < 0.01). LDL cholesterol concentrations fell by 12.0 and 7.7% (P < 0.01). In the With Meals group, reductions were 9.5 and 8.3% for total cholesterol, and 12.5 and 12.8% for LDL cholesterol (wk 1 and 2, respectively, P < 0.01). In both groups, HDL cholesterol decreased by approximately 5% during wk 1 of treatment (P < 0.01), but the wk 2 concentrations were not significantly different from baseline. There were no significant differences between groups in lipid responses, although there was a trend for a smaller LDL cholesterol-lowering effect during wk 2 of treatment in the Between Meals group (P < 0.06). Gastrointestinal-related adverse experiences (mostly mild) were twice as common among participants who ingested HPMC with meals (P < 0.05). These results suggest that HPMC has a lipid-lowering effect, which may be more consistent when taken with meals.