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Over the last decade, commercialization of insects for food and feed has been exponentially increasing. Insect protein is emerging as a sustainable livestock feed and human food alternative due to its low land and carbon footprint. The principles of insect industry are deeply embedded in the core values of sustainability and circular economy. Black soldier fly (BSF) is the crown jewel of insect industry and is one of the most commercially farmed insects. However, this steadfast growth is accompanied by generation of insect based biowaste such as dead flies and pupae exuviae. This will be a major waste fraction from this industry. This study discusses the valorization potential of this waste into chitin (which finds application in cosmetics, bioplastics, and pesticides, among other industries), biogas, fertilizer, and biochar. There is need to conduct more explorative research on value proposition of insect based biowaste to ensure that this industry can comply fully with circular economy and sustainability principles., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Debasree Purkayastha reports financial support was provided by European Commission. Debasree Purkayastha reports a relationship with Nord University - Steinkjer that includes: employment and funding grants. Prabhat Khanal reports a relationship with Nord University - Steinkjer that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The combination of CFTR modulators ivacaftor, tezacaftor and elexacaftor (Trikafta®, Kaftrio®) significantly improve outcomes, including survival in a broad range of cystic fibrosis patients. These drugs have complicated metabolic profiles that make the potential for drug interactions an important consideration for prescribers, care providers and patients. Prolonged survival also increases risk of age-related disease and their associated pharmacotherapy, further increasing the risk of drug interactions and the need for increased vigilance amongst care providers. We systematically searched the literature for studies identifying and evaluating pharmacokinetic and pharmacodynamic drug interactions involving the components of Trikafta®/Kaftrio®. We also searched electronic databases of drugs for possible drug interactions based on metabolic profiles. We identified 86 potential drug interactions of which 13 were supported by 14 studies. There is a significant need for research to describe the likelihood, magnitude and clinical impact of the drug interactions proposed here., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest or competing interests to declare., (Copyright © 2023. Published by Elsevier B.V.)

Background: In the Mammary Oncology Assessment of LEE011's (Ribociclib's) Efficacy and Safety (MONALEESA-2) study, combination treatment with the selective inhibitor of cyclin-dependent kinases 4/6 ribociclib with letrozole significantly improved progression-free survival (PFS) versus letrozole alone in postmenopausal women with hormone receptor-positive HR + /HER2 - advanced breast cancer (ABC). Herein we present results from the subset of US patients enrolled in MONALEESA-2., Patients and Methods: Postmenopausal women with HR + /HER2 - ABC without previous treatment for advanced disease were randomized (1:1) to ribociclib 600 mg/d (3 weeks on/1 week off) with letrozole 2.5 mg/d (continuous) or placebo with letrozole. The primary end point was locally assessed PFS., Results: Overall, 213 US patients were enrolled in MONALEESA-2 (ribociclib, n = 100; placebo, n = 113). Baseline characteristics were similar between treatment groups and consistent with the global population. With a median follow-up of 27 months, 38 (38%) and 29 (26%) patients in the ribociclib and placebo groups, respectively, had continued to receive treatment. Median PFS was 27.6 months with ribociclib and 15.0 months with placebo (hazard ratio, 0.53). The most common all-cause adverse events were neutropenia (ribociclib, 72.0% [n = 72]; placebo, 4.6% [n = 5]), nausea (ribociclib, 69.0% [n = 69]; placebo, 44.0% [n = 48]), and fatigue (ribociclib, 60.0% [n = 60]; placebo, 50.5% [n = 55]). Two patients (ribociclib, 2.0%; placebo, 0%) experienced febrile neutropenia., Conclusion: In the US subset of MONALEESA-2, ribociclib with letrozole showed superior efficacy versus letrozole alone. These findings are consistent with the global population and support first-line use of ribociclib with letrozole in patients with HR + /HER2 - ABC., (Copyright © 2019. Published by Elsevier Inc.)

Background: The clinical effects of roflumilast, a selective phosphodiesterase-4 inhibitor, are well established, but little is known about the anti-inflammatory mechanisms underlying the drug's efficacy. The aim of the ROflumilast Biopsy European Research Trial (ROBERT) was to assess the anti-inflammatory effects of roflumilast on bronchial mucosal inflammation in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) and chronic bronchitis., Methods: ROBERT was a randomised, double-blind, placebo-controlled trial done at 18 sites in five countries. Eligible patients were aged 40-80 years, had COPD, and had had a chronic productive cough for 3 months in each of the two previous years. Patients also had to have a post-bronchodilator predicted FEV 1 30-80% and a post-bronchodilator FEV 1 /forced vital capacity ratio of 70% or less. Patients entered a 6-week run-in period before being randomly assigned (1:1) via a computerised central randomisation system to roflumilast 500 μg once daily or placebo for 16 weeks, in addition to bronchodilator therapy (inhaled corticosteroids were not permitted). Randomisation was stratified by concomitant use of long-acting β agonist. Both participants and investigators were masked to group assignment. Roflumilast and placebo were supplied as identical yellow, triangular tablets. Airway inflammation was assessed by quantification of inflammatory cells in bronchial biopsy samples and induced sputum samples. The primary endpoint was the change in the number of CD8 inflammatory cells in bronchial biopsy submucosa from randomisation to week 16 in the intention-to-treat population. Changes in cell counts of additional inflammatory markers, including eosinophils, were assessed as secondary endpoints. This trial is registered with ClinicalTrials.gov, number NCT01509677, and is closed to new participants, with follow-up completed., Findings: Between Jan 4, 2012, and Feb 11, 2016, 158 patients were randomly assigned: 79 to the roflumilast group, and 79 to the placebo group. At week 16, the change in the number of CD8 cells in the bronchial submucosa did not differ significantly between the roflumilast and placebo groups (treatment ratio 1·03 [95% CI 0·82-1·30]; p=0·79). However, compared with placebo, roflumilast was associated with a significant reduction in eosinophils in bronchial biopsy samples at week 16 (treatment ratio 0·53 [95% CI 0·34-0·82]; p=0·0046). Significant reductions in both absolute (p=0·0042) and differential (p=0·0086) eosinophil cell counts in induced sputum were also noted with roflumilast compared with placebo, but peripheral blood eosinophil counts were not significantly affected. We noted no other significant effects of roflumilast on bronchial mucosal inflammatory cells. The most common (ie, occurring in >5% patients) moderate adverse events were worsening of COPD (three [4%] patients in the roflumilast group vs seven [9%] in the placebo group), cough (six [8%] vs four [5%]), diarrhoea (four [5%] vs three [4%]), and nasopharyngitis (three [4%] vs five [6%]). Severe adverse events included worsening of COPD, which occurred in four (5%) patients in the roflumilast group and two (3%) in the placebo group. No deaths occurred during the study. Serious adverse events occurred in eight (10%) patients in the roflumilast group and five (6%) in the placebo group., Interpretation: 16 weeks of treatment with roflumilast did not affect the number of CD8 cells in bronchial submucosa compared with placebo. However, we noted significant reductions in eosinophil cell counts in bronchial biopsy samples and induced sputum, generating the hypothesis that the effect of roflumilast in COPD could be mediated by an effect on lung eosinophils., Funding: Takeda and AstraZeneca., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Patients in complete cytogenetic response (CCyR) with detectable BCR-ABL1 after ≥2 years on imatinib were randomized to nilotinib (400 mg twice daily, n = 104) or continued imatinib (n = 103) in the Evaluating Nilotinib Efficacy and Safety in clinical Trials-Complete Molecular Response (ENESTcmr) trial. By 1 and 2 years, confirmed undetectable BCR-ABL1 was achieved by 12.5% vs 5.8% (P = .108) and 22.1% vs 8.7% of patients in the nilotinib and imatinib arms, respectively (P = .0087). Among patients without molecular response 4.5 (BCR-ABL1(IS) ≤0.0032%; MR(4.5)) and those without major molecular response at study start, MR(4.5) by 2 years was achieved by 42.9% vs 20.8% and 29.2% vs 3.6% of patients in the nilotinib and imatinib arms, respectively. No patient in the nilotinib arm lost CCyR, vs 3 in the imatinib arm. Adverse events were more common in the nilotinib arm, as expected with the introduction of a new drug vs remaining on a well-tolerated drug. The safety profile of nilotinib was consistent with other reported studies. In summary, switching to nilotinib enabled more patients with chronic myeloid leukemia in chronic phase (CML-CP) to sustain lower levels of disease burden vs remaining on imatinib. This trial was registered at www.clinicaltrials.gov as #NCT00760877., (© 2014 by The American Society of Hematology.)

Introduction: Carotid endarterectomy (CEA) should be performed within two weeks of symptoms for patients with carotid stenosis >50%. Whether these standards are being achieved and causes of delay between symptoms and CEA were investigated., Design: An analysis of prospectively collected multi-centre data., Materials: Consecutive data for patients undergoing CEA between January-2006 and September-2010 were collected. Asymptomatic patients and those with no details on the timing of cerebral symptoms were excluded., Methods: 'Delay' from symptom to CEA was defined as more than two weeks and 'prolonged-delay' more than eight weeks. Univariable and multivariable analyses were used to identify factors associated with these delays., Results: Of 2147 patients with symptoms of cerebral ischaemia, 1522(70.9%) experienced 'delay' and 920(42.9%) experienced 'prolonged delay'. Patients with ischaemic heart disease were more likely to experience 'delay' (OR = 1.56; 95% CI 1.11-2.19, p = 0.011), whereas patients with stroke (OR = 0.77; 95%CI 0.63-0.94, p = 0.011) and those treated at hospitals with a stroke-prevention clinic (OR = 0.57; 95%CI 0.46-0.71, p < 0.001) were less likely to experience 'delay'. Patients treated after the publication of National Institute for Health and Clinical Excellence (NICE) guidelines were less likely to experience 'prolonged delay' (OR = 0.77; 95%CI 0.65-0.91, p = 0.003) but not 'delay'., Conclusion: Few patients achieved CEA within two weeks of symptoms. Introducing stroke-prevention clinics with one-stop carotid imaging appears important., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Previously, we reported the efficacy of aliskiren/amlodipine in US minority adults with stage 2 hypertension, with additional blood pressure (BP) lowering from the addition of hydrochlorothiazide (HCTZ). A subgroup analysis in patients with hypertension and comorbidities of diabetes, cardiometabolic syndrome, or obesity, and in black participants is reported. This 8-week, multicenter, double-blind study included 412 self-identified minority patients with mean sitting systolic BP (msSBP) ≥160 mm Hg and <200 mm Hg). Patients were randomized to receive either combination aliskiren/amlodipine 150/5 mg or amlodipine 5 mg. Doses were forced-titrated to a maximum of aliskiren/amlodipine/HCTZ 300/10/25 mg or aliskiren/amlodipine 300/10 mg, respectively. There were 256 black (62%), 118 diabetic (29%), 284 cardiometabolic syndrome (69%), and 249 obese (60%) randomized patients. Baseline msSBP was ~167 mm Hg across all subgroups. Least-square mean reductions in msSBP, the primary efficacy outcome, from baseline to week 8 across all subgroups, ranged from 35 to 37 mm Hg with aliskiren/amlodipine/HCTZ and 28 to 30 mm Hg with aliskiren/amlodipine (P < .01 for all between-treatment comparisons). Both regimens were well tolerated. Among high-risk patients, such as diabetics or those with cardiometabolic syndrome, combination aliskiren/amlodipine is effective in lowering BP; the addition of HCTZ provided incremental BP-lowering efficacy while maintaining tolerability. However, because our subgroups were not mutually exclusive, the generalization of our findings to the population seen in clinical practice is limited., (Copyright © 2012 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Home blood pressure (BP) monitoring may enhance assessment of BP control. In this 16-week study, men and women 70 years or older with systolic BP between 150 and 200 mm Hg were randomized to receive valsartan/hydrochlorothiazide (V/HCTZ) 160/12.5 mg (n = 128), HCTZ 12.5 mg (n = 128), or V 160 mg (n = 128) for 4 weeks. Participants whose BP was 140/90 mm Hg or higher at weeks 4, 8, or 12 were uptitrated to a maximum of V/HCTZ 320/25 mg. Participants were evaluated by home BP monitoring using an automated device weekly before taking daily study medication (n = 301). Baseline BP ± SD for clinic (165.5 ± 11.8/85.1 ± 9.5 mm Hg) was approximately 3/1 mm Hg greater than home readings (162.5 ± 15.8/84.3 ± 10.2 mm Hg). Reductions in BP ± SEM at week 4 were similar for clinic (12.6 ± 1.0/4.7 ± 0.5 mm Hg) and home (10.9 ± 1.1/3.8 ± 0.5 mm Hg) readings (P = .25/P = .23; clinic versus home); differences between V/HCTZ and HCTZ or V were also similar for both home and clinic readings and results by either technique correlated significantly (P < .0001). Home BP measurements confirm that treatment initiated with V/HCTZ versus monotherapy resulted in greater antihypertensive efficacy. Home BP monitoring, if done with proper technique, provides a reliable indicator of BP control in elderly patients and may help guide drug dosing and titration., (Copyright © 2012 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

The extent to which the combination of a renin inhibitor with an angiotensin receptor blocker (ARB) lowers clinic and ambulatory blood pressure (BP) versus an ARB alone in stage 2 hypertension is not well known. Hence, we performed an 8-week, randomized, double-blind study in 451 patients with stage 2 hypertension to compare the efficacy of the combination of aliskiren/valsartan 300/320 mg versus valsartan 320 mg. The primary endpoint was change in seated systolic BP from baseline to week 8 analyzed on the intent-to-treat (ITT) population using the last-observation-carried-forward (LOCF) approach; patients completing the entire treatment period (per-protocol completers) were similarly analyzed. For the predefined primary analysis, systolic BP reductions for aliskiren/valsartan (n = 230) and valsartan (n = 217) were -22.1 and -20.5 mm Hg, respectively (P = .295). In per-protocol completers, aliskiren/valsartan (n = 201) lowered BP significantly greater than valsartan (n = 196); -23.7 mm Hg versus -20.3 mm Hg, respectively (P = .028). Although limited by a small sample size (n = 76) using ambulatory BP monitoring, aliskiren/valsartan lowered the 24-hour BP significantly more than valsartan alone (-14.6/-9.0 mm Hg versus -5.9/-4.2 mm Hg; P < .01). Safety and tolerability were similar for the two treatment groups. These data demonstrate the importance of multiple modalities to assess BP changes in clinical trials of antihypertensive therapies, particularly in stage 2 hypertension., (Copyright © 2012 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Objectives: Renal failure following abdominal aortic aneurysm (AAA) repair is a common and significant complication. The objective of this study was to identify risk factors for renal failure following open elective AAA repair., Design: A retrospective analysis of prospectively collected multi-centre data., Materials: Consecutive data on patients undergoing open elective AAA repair were collected between January 2000 and December 2010. Patients with pre-operative serum creatinine >200 μmol/L were excluded., Methods: Renal failure was reported by clinicians and included all patients requiring post-operative renal-replacement therapy. Univariate and multivariate analyses were used to identify renal failure risk factors. A simplified clinical risk score was developed., Results: Post-operative renal failure occurred in 140 (6.0%) of 2347 patients and was associated with age >75 (OR = 1.58, 95%CI 1.11-2.26), symptomatic AAA (OR = 1.77, 95%CI 1.24-2.52), supra/juxta renal AAA (OR = 2.17, 95%CI 1.32-3.57) pre-operative serum creatinine >150 (OR = 2.75, 95%CI 1.69-4.50), treated hypertension (OR = 1.87, 95%CI 1.28-2.74), and respiratory disease (OR = 2.08, 95%CI 1.45-2.97). Patients with post-operative renal failure had significantly higher 30-day mortality (35.0% vs. 4.3%, p < 0.001)., Conclusions: Renal failure following open elective AAA repair was associated with an increased risk of mortality. Risk factors for post-operative renal failure were identified and a simple clinical risk score developed to facilitate focussed care strategies for high-risk patients., (Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

The renin-angiotensin system (RAS) is a common link between hypertension and comorbidities of obesity and metabolic syndrome (MetS). We evaluated the antihypertensive efficacy and safety of the combination direct renin inhibitor, aliskiren, with amlodipine versus amlodipine alone in self-identified African Americans with stage 2 hypertension in a subgroup of patients with obesity or MetS participating in the Aliskiren Amlodipine Combination in African AmEricans with Stage 2 HypertenSion (AACESS) trial. Subjects, newly diagnosed and treatment naive or taking three or fewer antihypertensive drugs with a mean sitting systolic blood pressure (msSBP) of 160-199 mm Hg were randomized to receive aliskiren/amlodipine 150/5 mg or amlodipine 5 mg for 1 week; force-titrated to aliskiren/amlodipine 300/10 mg or amlodipine 10 mg, for an additional 7 weeks. Overall, 292 obese (body mass index ≥30 kg/m(2)) and 197 MetS subjects had baseline msSBP ranging from 167.0 to 167.5 mm Hg. Least-square mean reductions from baseline to 8 weeks in msSBP, the primary efficacy variable, were significantly higher with aliskiren/amlodipine than with amlodipine in both obese (-33.7 mm Hg vs. -27.9 mm Hg; P < .001) and MetS subjects (-36.4 mm Hg vs. -28.5 mm Hg; P < .001). Both treatments were well tolerated. Aliskiren/amlodipine 300/10 mg is more effective than amlodipine 10 mg in African Americans with stage 2 hypertension and obesity or MetS., (Copyright © 2011 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Combination therapy may reduce racial/ethnic differences in response to antihypertensives. In this post-hoc analysis, we evaluated treatment response by race/ethnicity among hypertensive adults enrolled in a 12-week, double-blind study in which patients previously uncontrolled (mean sitting systolic blood pressure [MSSBP] ≥150 and <200 mm Hg) on angiotensin receptor blocker (ARB) monotherapy (other than valsartan) for 28 days or more (n = 728) were randomized to amlodipine/valsartan 10/320 mg (intensive) or 5/160 mg (moderate). Treatment-naïve patients (in previous 28 days) or those who failed on a non-ARB first underwent a 28-day run-in period with olmesartan 20 mg or 40 mg, respectively. Hydrochlorothiazide (HCTZ) 12.5 mg was added to both arms at week 4; optional up-titration to 25 mg at week 8 (if MSSBP >140 mm Hg). Intensive treatment provided greater BP lowering versus moderate treatment throughout the study, regardless of race/ethnicity (474 white, 198 African American, 165 Hispanic individuals). Least-square mean reductions from baseline to week 4 in MSSBP (primary outcome) ranged from 20.4 to 23.5 mm Hg (intensive) versus 17.5 to 19.0 mm Hg (moderate), across racial/ethnic subgroups. Both regimens were well tolerated. Amlodipine/valsartan/HCTZ combination therapy was efficacious across racial/ethnic subgroups. Maximal efficacy was obtained with intensive treatment., (Copyright © 2011. Published by Elsevier Inc.)

Minority patients with hypertension generally require combination therapy to reach blood pressure (BP) goals. We examined the BP-lowering efficacy and safety of combination aliskiren/amlodipine therapy in self-identified minority patients in the United States with stage 2 hypertension and the impact of adding hydrochlorothiazide (HCTZ) to this combination. In this 8-week double-blind study, 412 patients were randomized to receive aliskiren/amlodipine (150/5 mg) or amlodipine (5 mg) with forced titration up to aliskiren/amlodipine/HCTZ (300/10/25 mg) or aliskiren/amlodipine (300/10 mg), respectively. Overall, mean age was 55.2 years, mean body mass index was 32 kg/m(2), 62.3% were black, 28.2% were Hispanic/Latino, and 69.1% had metabolic syndrome. Mean sitting systolic blood pressure (MSSBP), the primary efficacy outcome, was reduced from 167.1 mm Hg at baseline to 130.7 mm Hg at week 8 with aliskiren/amlodipine/HCTZ and from 167.4 mm Hg to 137.9 mm Hg with aliskiren/amlodipine (P < .0001 between groups). At week 8, BP goal (<140/90 mm Hg) was achieved in 72.6% and 53.2% of patients in the two treatment groups, respectively (P < .0001). Adverse events were experienced by 34.2% and 40.2%, respectively. Combination aliskiren/amlodipine therapy was effective in treating these high-risk patients but inclusion of HCTZ provided greater antihypertensive efficacy. Both treatments were similarly well tolerated., (Copyright © 2011 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Clinical practice guidelines recommend blockers of the renin-angiotensin system alone or in combination with other agents to reduce blood pressure and albuminuria in patients with type 2 diabetes. Dihydropyridine calcium channel blockers, however, may lower blood pressure but not albuminuria in these patients. Here we tested the hypothesis that combining an ACE inhibitor with either a thiazide diuretic or a calcium channel blocker will cause similar reductions in blood pressure and albuminuria in hypertensive type 2 diabetics. We conducted a double blind randomized controlled trial on 332 hypertensive, albuminuric type 2 diabetic patients treated with benazepril with either amlodipine or hydrochlorothiazide for 1 year. The trial employed a non-inferiority design. Both combinations significantly reduced the urinary albumin to creatinine ratio and sitting blood pressure of the entire cohort. The percentage of patients progressing to overt proteinuria was similar for both groups. When we examined patients who had only microalbuminuria and hypertension we found that a larger percentage of the diuretic and ACE inhibitor normalized their albuminuria. We conclude that initial treatment using benzaepril with a diuretic resulted in a greater reduction in albuminuria compared to the group of ACE inhibitor and calcium channel blocker. In contrast, blood pressure reduction, particularly the diastolic component, favored the combination with amilodipine. The dissociation between reductions in blood pressure and albuminuria may be related to factors other than blood pressure.

Background: Diastolic dysfunction might represent an important pathophysiological intermediate between hypertension and heart failure. Our aim was to determine whether inhibitors of the renin-angiotensin-aldosterone system, which can reduce ventricular hypertrophy and myocardial fibrosis, can improve diastolic function to a greater extent than can other antihypertensive agents., Methods: Patients with hypertension and evidence of diastolic dysfunction were randomly assigned to receive either the angiotensin receptor blocker valsartan (titrated to 320 mg once daily) or matched placebo. Patients in both groups also received concomitant antihypertensive agents that did not inhibit the renin-angiotensin system to reach targets of under 135 mm Hg systolic blood pressure and under 80 mm Hg diastolic blood pressure. The primary endpoint was change in diastolic relaxation velocity between baseline and 38 weeks as determined by tissue doppler imaging. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00170924., Findings: 186 patients were randomly assigned to receive valsartan; 198 were randomly assigned to receive placebo. 43 patients were lost to follow-up or discontinued the assigned intervention. Over 38 weeks, there was a 12.8 (SD 17.2)/7.1 (9.9) mm Hg reduction in blood pressure in the valsartan group and a 9.7 (17.0)/5.5 (10.2) mm Hg reduction in the placebo group. The difference in blood pressure reduction between the two groups was not significant. Diastolic relaxation velocity increased by 0.60 (SD 1.4) cm/s from baseline in the valsartan group (p<0.0001) and 0.44 (1.4) cm/s from baseline in the placebo group (p<0.0001) by week 38. However, there was no significant difference in the change in diastolic relaxation velocity between the groups (p=0.29)., Interpretation: Lowering blood pressure improves diastolic function irrespective of the type of antihypertensive agent used.