Vonoprazan is Efficacious for Treatment of Heartburn in Non-erosive Reflux Disease: A Randomized Trial.

BACKGROUND & AIMS: Potassium-competitive acid blockers have documented efficacy for erosive esophagitis. We performed a randomized trial in United States subjects diagnosed with non-erosive reflux disease of vonoprazan vs placebo for 4 weeks, followed by a 20-week active-treatment extension. METHODS: Adult subjects with heartburn ≥4 days/week during screening without erosive esophagitis on endoscopy were randomized to placebo, vonoprazan 10 mg, or vonoprazan 20 mg. After 4 weeks, subjects on placebo were re-randomized to vonoprazan 10 mg or 20 mg, and those already on vonoprazan continued at the same dose for 20 weeks. Electronic diaries were completed twice daily. The primary endpoint was percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days). RESULTS: Among 772 randomized subjects, the percentage of 24-hour heartburn-free days was 27.7% for placebo vs 44.8% for vonoprazan 10 mg (least squares mean difference, 17.1%; P < .0001) and 44.4% for vonoprazan 20 mg (least squares mean difference, 16.7%; P < .0001). Differences in percentage of subjects with a 24-hour heartburn-free day for vonoprazan 10 mg vs placebo and vonoprazan 20 mg vs placebo were 8.3% and 11.6% on day 1 and 18.1% and 23.2% on day 2. The mean/median percentages of 24-hour heartburn-free days over the extension period were similar across the 4 study arms: 61%-63%/76%-79%. CONCLUSIONS: Vonoprazan reduced heartburn symptoms in subjects diagnosed with non-erosive reflux disease, with the benefit appearing to begin as early as the first day of therapy. Treatment effect persisted after the initial 4-week placebo-controlled period throughout the 20-week extension period. The 2 vonoprazan doses (10 mg and 20 mg) were similar in efficacy. (ClinicalTrials.gov: NCT05195528).

A kV-MV approach to CBCT metal artifact reduction using multi-layer MV-CBCT.

Objective. To demonstrate that complete cone beam CT (CBCT) scans from both MV-energy and kV-energy LINAC sources can reduce metal artifacts in radiotherapy guidance, while maintaining standard-of-care x-ray doses levels.Approach. MV-CBCT and kV-CBCT scans are acquired at half normal dose. The impact of lowered dose on MV-CBCT data quality is mitigated by the use of a 4-layer MV-imager prototype and reduced LINAC energy settings (2.5 MV) to improve photon capture. Additionally, the MV-CBCT is used to determine the 3D position and pose of metal implants, which in turn is used to guide model-based poly-energetic correction and interleaving of the kV-CBCT and MV-CBCT data. Certain edge-preserving regularization steps incorporated into the model-based correction algorithm further reduce MV data noise.Main results. The method was tested in digital phantoms and a real pelvis phantom with large 2.5″ spherical inserts, emulating hip replacements of different materials. The proposed method demonstrated an appealing compromise between the high contrast of kV-CBCT and low artifact content of MV-CBCT. Contrast-to-noise improved 3-fold compared to MV-CBCT with a clinical 1-layer architecture at matched dose (37 mGy) and edge blur levels. Visual delineation of the bladder and prostate improved noteably over kV- or MV-CBCT alone.Significance. The proposed method demonstrates that a full MV-CBCT scan can be combined with kV-CBCT to reduce metal artifacts without resorting to complicated beam collimation strategies to limit the MV-CBCT dose contribution. Additionally, significant improvements in CNR can be achieved as compared to metal artifact reduction through current clinical MV-CBCT practices.

Randomised clinical trial: Efficacy and safety of on-demand vonoprazan versus placebo for non-erosive reflux disease.

BACKGROUND: Non-erosive reflux disease (NERD) symptoms are often episodic, making on-demand treatment an attractive treatment approach. AIMS: We compared the efficacy and safety of on-demand vonoprazan versus placebo in patients with NERD. METHODS: Patients with NERD, defined as heartburn for ≥6 months and for ≥4/7 consecutive days with normal endoscopy, received once-daily vonoprazan 20 mg during a 4-week run-in period. Patients without heartburn during the last 7 days and with ≥80% study drug and diary compliance were randomised 1:1:1:1 to vonoprazan 10, 20, 40 mg or placebo on-demand for 6 weeks. The primary endpoint was the percentage of evaluable heartburn episodes completely relieved within 3 h of on-demand dosing and sustained for 24 h. RESULTS: Of 458 patients in the run-in period, 207 entered the on-demand period. In the vonoprazan 10 mg group, 56.0% (201/359) of evaluable heartburn episodes met the criteria for complete and sustained relief; 60.6% (198/327) in the 20 mg group; and 70.0% (226/323) in the 40 mg group, compared with 27.3% (101/370) in the placebo group (p < 0.0001 versus placebo for each vonoprazan group). By 1 h post-dose, vonoprazan was associated with complete relief of significantly more heartburn episodes compared with placebo. No serious treatment-emergent adverse events were reported. CONCLUSION: On-demand vonoprazan may be a potential alternative to continued daily acid suppression therapy for the relief of episodic heartburn in patients with NERD. CLINICALTRIALS: gov: NCT04799158.

The redistributive power of cash transfers vs VAT exemptions: A multi-country study.

Like high-income countries, low- and middle-income countries (LMICs) offer reduced rates and exemptions on particular goods and services in their value-added tax (VAT) systems. These policies are often motivated by distributional concerns and target items thought to take up a larger share of the budgets of poorer households. This paper explores the effectiveness of such policies in six LMICs. We estimate their impact on tax revenues, inequality and poverty, and compare these effects to existing cash transfer schemes and a hypothetical Universal Transfer (UT) funded by broadening the VAT base. To do so, we use tax-benefit microsimulation models incorporating input-output tables, allowing us to estimate the impact of exemptions on consumer prices due to VAT embedded in supply chains. We show that although preferential VAT rates reduce poverty, they are not well targeted towards poor households overall. Existing cash transfer schemes are better targeted but generally have limited coverage. A UT funded by a broader VAT base would create large net gains for the poorest households, reducing inequality and most measures of extreme poverty in each of the countries studied. Our results suggest that the widespread practice of providing special VAT treatment to certain goods and services is an expensive way of reaching poor households. In principle, expanding the VAT base and social protection schemes in tandem has the potential to both raise tax revenues and reduce poverty. Such reforms therefore warrant consideration for LMICs as they pursue Domestic Revenue Mobilisation and broader development objectives.

Abbreviated on-treatment CBCT using roughness penalized mono-energization of kV-MV data and a multi-layer MV imager.

Simultaneous acquisition of cone beam CT (CBCT) projections using both the kV and MV imagers of an image guided radiotherapy system reduces set-up scan times-a benefit to lung cancer radiation oncology patients-but increases noise in the 3D reconstruction. In this article, we present a kV-MV scan time reduction technique that uses two noise-reducing measures to achieve superior performance. The first is a high-DQE multi-layer MV imager prototype. The second is a beam hardening correction algorithm which combines poly-energetic modeling with edge-preserving, regularized smoothing of the projections. Performance was tested in real acquisitions of the Catphan 604 and a thorax phantom. Percent noise was quantified from voxel values in a soft tissue volume of interest (VOI) while edge blur was quantified from a VOI straddling a boundary between air and soft material. Comparisons in noise/resolution performance trade-off were made between our proposed approach, a dose-equivalent kV-only scan, and a kV-MV reconstruction technique previously published by Yinet al(2005Med. Phys.329). The proposed technique demonstrated lower noise as a function of spatial resolution than the baseline kV-MV method, notably a 50% noise reduction at typical edge blur levels. Our proposed method also exhibited fainter non-uniformity artifacts and in some cases superior contrast. Overall, we find that the combination of a multi-layer MV imager, acquiring at a LINAC source energy of 2.5 MV, and a denoised beam hardening correction algorithm enables noise, resolution, and dose performance comparable to standard kV-imager only set-up CBCT, but with nearly half the gantry rotation time.

The heterogeneous impact of a successful tobacco control campaign: a case study of Mauritius.

BACKGROUND: Mauritius has one of the highest smoking prevalences in Africa, contributing to its high burden of non-communicable diseases. Mauritius implemented a series of tobacco control measures from 2009 to 2012, including tobacco tax increases. There is evidence that these policies reduced tobacco consumption, but it is not clear what impact they had across different socioeconomic groups. METHOD: The impact of tobacco control measures on different income groups was analysed by contrasting household tobacco expenditures reported in 2006-2007 and 2012 household expenditure surveys. We employed the seemingly unrelated regression model to assess the impact of tobacco use on other household expenditures and calculated Gini coefficients to assess tobacco expenditure inequality. RESULTS: From 2006 to 2012, excise taxes and retail cigarette prices increased by 40.6% and 15.3% in real terms, respectively. These increases were accompanied by numerous non-price tobacco control measures. The share of tobacco-consuming households declined from 35.7% to 29.3%, with the largest relative drop among low-income households. The Gini coefficient of household tobacco expenditures increased by 10.4% due to decreased spending by low-income households. Low-income households demonstrated the largest fall in their tobacco budget shares, and the impact of tobacco consumption on poverty decreased by 26.2%. Households that continued purchasing tobacco reduced their expenditures on transportation, communication, health, and education. CONCLUSIONS: These results suggest that tobacco control policies, including sizeable tax increases, were progressive in their impact. We conclude that tobacco use increases poverty and inequality, but stronger tobacco control policies can mitigate the impact of tobacco use on impoverishment.

IP-10 is a potential biomarker of cystic fibrosis acute pulmonary exacerbations.

BACKGROUND: Cystic fibrosis (CF) is characterized by acute pulmonary exacerbations (APE). The CF nasal airway exhibits a similar ion transport defect as the lung, and colonization, infection, and inflammation within the nasal passages are common among CF patients. Nasal lavage fluid (NLF) is a minimally invasive means to collect upper airway samples. METHODS: We collected NLF at the onset and resolution of CF APE and compared a 27-plex cytokine profile to stable CF outpatients and normal controls. We also tested IP-10 levels in the bronchoalveolar lavage fluid (BALF) of CF patients. Well-differentiated murine sinonasal monolayers were exposed to bacterial stimulus, and IP-10 levels were measured to test epithelial secretion. RESULTS: Subjects hospitalized for APE had elevated IP-10 (2582 pg/mL [95% CL of mean: 818,8165], N=13) which significantly decreased (647 pg/mL [357,1174], P<0.05, N =13) following antimicrobial therapy. Stable CF outpatients exhibited intermediately elevated levels (680 pg/mL [281,1644], N=13) that were less than CF inpatients upon admission (P=0.056) but not significantly different than normal controls (342 pg/mL [110,1061]; P=0.3, N=10). IP-10 was significantly increased in CF BALF (2673 pg/mL [1306,5458], N=10) compared to healthy post-lung transplant patients (8.4 pg/mL [0.03,2172], N=5, P<0.001). IP-10 levels from well-differentiated CF murine nasal epithelial monolayers exposed to Pseudomonas PAO-1 bacteria-free prep or LPS (100 nM) apically for 24 hours were significantly elevated (1159 ± 147, P<0.001 for PAO-1; 1373 ± 191, P<0.001 for LPS vs. 305 ± 68 for vehicle controls). Human sino-nasal epithelial cells derived from CF patients had a similar response to LPS (34% increase, P<0.05, N=6). CONCLUSIONS: IP-10 is elevated in the nasal lavage of CF patients with APE and responds to antimicrobial therapy. IP-10 is induced by airway epithelia following stimulation with bacterial pathogens in a murine model. Additional research regarding IP-10 as a potential biomarker is warranted.

Baseline ecological risk assessment of the Calcasieu Estuary, Louisiana: Part 1. Overview and problem formulation.

A remedial investigation/feasibility study (RI/FS) of the Calcasieu Estuary cooperative site was initiated in 1998. This site, which is located in the southwestern portion of Louisiana in the vicinity of Lake Charles, includes the portion of the estuary from the saltwater barrier on the Calcasieu River to Moss Lake. As part of the RI/FS, a baseline ecological risk assessment (BERA) was conducted to assess the risks to aquatic organisms and aquatic-dependent wildlife exposed to environmental contaminants. The purpose of the BERA was to determine if adverse effects on ecological receptors are occurring in the estuary; to evaluate the nature, severity, and areal extent of any such effects; and to identify the substances that are causing or substantially contributing to effects on ecological receptors. This article describes the environmental setting and site history, identifies the chemicals of potential concern, presents the exposure scenarios and conceptual model for the site, and summarizes the assessment and measurement endpoints that were used in the investigation. Two additional articles in this series describe the results of an evaluation of effects-based sediment-quality guidelines as well as an assessment of risks to benthic invertebrates associated with exposure to contaminated sediment.