Global acute malnutrition is associated with geography, season and malaria incidence in the conflict-affected regions of Ouham and Ouham Pendé prefectures, Central African Republic.

BACKGROUND: Ongoing conflict between multiple armed groups, including pastoralist herders in the Central African Republic (CAR) causes frequent population displacements, food insecurity and scarcity of healthcare services. The inaccessibility and insecurity of many areas of CAR limit data collection and assessments from national nutritional surveys. Community health workers (CHWs) trained by an international non-governmental organisation, The MENTOR Initiative, deliver basic healthcare to children under 5 years old living in hard-to-reach and conflict-affected areas in eight subprefectures of north-west CAR. Their nutritional status and its associations with geography, malaria, season and conflict are unknown. METHODS: CHW monthly records (October 2015-August 2021), Armed Conflict Location and Event Data project conflict data and The World Bank Group meteorological data for eight subprefectures of north-west CAR were analysed. Associations between counts of global acute malnutrition (GAM) assessed by mid-upper arm circumference and malaria, season and conflict were investigated using negative binomial regression. RESULTS: Of the 457,325 consultations with children aged 6-59 months, 6.2% and 0.4% were classified as moderately or severely malnourished, respectively. The negative binomial model demonstrated differences in counts of GAM by subprefecture. Counts of GAM were positively associated with the case rate of severe malaria (IRR = 1.045; 95% CI: 1.04-1.06) and the rainy season (July-September) (IRR = 1.10; 95% CI: 1.03-1.17). Conflict events coded as Battles in ACLED were associated with lower counts of GAM (IRR = 0.78; 95% CI: 0.62-0.97). CONCLUSIONS: This analysis shows geographical differences in levels of malnutrition in north-west CAR and demonstrates clear associations between malnutrition, season and malaria. It provides evidence that levels of GAM may be underestimated in north-west CAR in areas experiencing conflict. These findings highlight the need for targeted nutritional support to reach children most at risk of malnutrition. CHWs are a proven effective means of delivering essential primary healthcare services in hard-to-reach, conflict-affected areas.

Call for caution regarding the efficacy of large-scale afforestation and its hydrological effects.

Large-scale afforestation programmes are generally presented as effective ways of increasing the terrestrial carbon sink while preserving water availability and biodiversity. Yet, a meta-analysis of both numerical and observational studies suggests that further research is needed to support this view. The use of inappropriate concepts (e.g., the biotic pump theory), the poor simulation of key processes (e.g., tree mortality, water use efficiency), and the limited model ability to capture recent observed trends (e.g., increasing water vapour deficit, terrestrial carbon uptake) should all draw our attention to the limitations of available theories and Earth System Models. Observations, either based on remote sensing or on early afforestation initiatives, also suggest potential trade-offs between terrestrial carbon uptake and water availability. There is thus a need to better monitor and physically understand the observed fluctuations of the terrestrial water and carbon cycles to promote suitable nature-based mitigation pathways depending on pre-existing vegetation, scale, as well as baseline and future climates.

Correction to: Amanita Mushroom Toxin Poisoning in Los Angeles County.

[This corrects the article DOI: 10.14309/crj.0000000000001246.].

Significantly wetter or drier future conditions for one to two thirds of the world's population.

Future projections of precipitation are uncertain, hampering effective climate adaptation strategies globally. Our understanding of changes across multiple climate model simulations under a warmer climate is limited by this lack of coherence across models. Here, we address this challenge introducing an approach that detects agreement in drier and wetter conditions by evaluating continuous 120-year time-series with trends, across 146 Global Climate Model (GCM) runs and two elevated greenhouse gas (GHG) emissions scenarios. We show the hotspots of future drier and wetter conditions, including regions already experiencing water scarcity or excess. These patterns are projected to impact a significant portion of the global population, with approximately 3 billion people (38% of the world's current population) affected under an intermediate emissions scenario and 5 billion people (66% of the world population) under a high emissions scenario by the century's end (or 35-61% using projections of future population). We undertake a country- and state-level analysis quantifying the population exposed to significant changes in precipitation regimes, offering a robust framework for assessing multiple climate projections.

Amanita Mushroom Toxin Poisoning in Los Angeles County.

Mushroom (amatoxin) poisoning from ingestion is a rare but life-threatening medical emergency characterized by gastrointestinal symptoms before progression to multisystem organ failure in severe cases. Many therapies of amatoxin intoxication have been described, including supportive care, medical therapies, detoxification strategies, and liver transplant. The evidence supporting these therapies remains limited due to the rarity of amatoxin poisoning and challenge of a timely diagnosis. We report a case of amatoxin poisoning in Los Angeles causing severe liver injury without acute liver failure treated successfully using medical therapies, gallbladder drainage, and plasma exchange.

Early Outcomes of Interwoven Nitinol Wire Stent Placement versus Endarterectomy for the Treatment of Atherosclerotic Disease of the Common Femoral Artery.

PURPOSE: To compare the clinical outcomes of common femoral artery (CFA) atherosclerotic disease treated with either surgical endarterectomy or an interwoven nitinol wire stent system. MATERIALS AND METHODS: A retrospective review was conducted of all patients with chronic, de novo atherosclerotic CFA disease treated with surgical endarterectomy (CFAE) or stent placement between July 2019 and March 2022. Outcome measures assessed up to 12 months after procedure included clinical improvement, primary restenosis, target vessel revascularization (TVR), major adverse limb events (MALEs), and all-cause mortality. RESULTS: Thirty-nine stents were deployed in 33 patients, and 56 CFAEs were performed in 55 patients. No differences were noted in the rate of primary patency (95.5% vs 94.4%, P = .618), TVR (2.9% vs 1.8%, P = .777), MALE (5.1% vs 5.4%, P = .949), and all-cause mortality (14.1% vs 3.6%, P = .076) between the stent and CFAE groups up to 12 months after procedure. There was greater improvement in median clinical severity in the stent group than in the CFAE group (Rutherford score change of 3.0 vs 1.5, P = .013). The median length of stay was less for the stent group (3 vs 7 days, P = .002), and there was a lower likelihood of severe or disabling adverse events in the stent group (0 vs 9 cases, P = .010). CONCLUSIONS: Patients treated with an interwoven nitinol wire stent had patency rates comparable to those treated with CFAE while having a lower incidence of severe adverse events and a shorter length of hospital stay than those who underwent CFAE.

Confirmation of the presence of Anopheles stephensi among internally displaced people's camps and host communities in Aden city, Yemen.

BACKGROUND: Declines in global malaria cases and deaths since the millennium are currently challenged by multiple factors including funding limitations, limits of, and resistance to vector control tools, and also recent spread of the invasive vector species, Anopheles stephensi-especially into novel urban settings where malaria rates are typically low. Coupled with general increases in urbanization and escalations in the number of conflicts creating rapid and unplanned population displacement into temporary shelter camps within host urban areas, particularly in the Middle East and sub-Saharan Africa, increased urban malaria is a major threat to control and elimination. METHODS: Entomological monitoring surveys (targeting Aedes aegypti) of water containers across urban areas hosting internally displaced people (IDP) communities in Aden city, Yemen, were performed by The MENTOR Initiative, a non-governmental organisation. As part of these surveys in 2021 23 larvae collected and raised to adults were morphologically identified as An. stephensi. Twelve of the samples were sent to Liverpool School of Tropical Medicine for independent morphological assessment and genetic analysis by sequencing the ribosomal ITS2 region and the mitochondrial COI gene. RESULTS: All twelve samples were confirmed morphologically and by sequence comparison of the single ITS2 and COI haplotype detected to the NCBI BLAST database as An. stephensi. Phylogenetic analysis with comparable COI sequences indicated close relationship to haplotypes found in Djibouti and Ethiopia. CONCLUSION: The study results confirm the presence of An. stephensi in Yemen. Confirmation of the species in multiple urban communities hosting thousands of IDPs living in temporary shelters with widescale dependency on open water containers is of particular concern due to the vulnerability of the population and abundance of favourable breeding sites for the vector. Proactive monitoring and targeted integrated vector management are required to limit impacts in this area of typically low malaria transmission, and to prevent further the spread of An. stephensi within the region.

Durable wall lining for malaria control in Liberia: results of a cluster randomized trial.

BACKGROUND: Malaria control in Liberia depends upon universal coverage with pyrethroid-impregnated long-lasting insecticidal nets (LLINs). Despite regular mass distribution, LLIN coverage and usage is patchy. Pyrethroid resistance in malaria vectors may further reduce LLIN efficacy. Durable Wall Lining (DWL), a novel material treated with two non-pyrethroid class insecticides, was designed to be installed onto the surface of inner walls, and cover openings and ceiling surfaces of rural houses. OBJECTIVES: AIM: To determine the malaria control efficacy of DWL. PRIMARY OBJECTIVE: To determine if DWL has an additional protective effect in an area of pyrethroid resistance. SECONDARY OBJECTIVES: To compare surface bio-availability of insecticides and entomological effectiveness over the study duration. DESIGN: A cluster randomized trial. PARTICIPANTS: Children aged 2-59 months. CONTROL ARM: 50 houses per 20 clusters, all of which received LLIN within the previous 12 months. ACTIVE ARM: 50 houses per 20 experimental clusters, all of which received LLINs with the previous 12 months, and had internal walls and ceilings lined with DWL. RANDOMISATION: Cluster villages were randomly allocated to control or active arms, and paired on 4 covariates. MAIN OUTCOME MEASURES: PRIMARY MEASURE: Prevalence of infection with P. falciparum in children aged 2 to 59 months. SECONDARY MEASURE: Surface bioavailability and entomological effectiveness of DWL active ingredients. RESULTS: Plasmodium falciparum prevalence in active clusters after 12 months was 34.6% compared to 40.1% in control clusters (p = 0.052). The effect varied with elevation and was significant (RR = 1.3, p = 0.022) in 14 pairs of upland villages. It was not significant (RR = 1.3, p = 0.344) in 6 pairs of coastal villages. Pooled risk ratio (RR) was calculated in SAS (Cary, NC, USA) using the Cochran-Mantel-Haenszel (CMH) test for upland and coastal cluster pairs. DWL efficacy was sustained at almost 100% for 12 months. CONCLUSIONS: Findings indicate that DWL is a scalable and effective malaria control intervention in stable transmission areas with pyrethroid-resistant vectors, where LLIN usage is difficult to achieve, and where local housing designs include large gable and eve openings. Trial registration ClinicalTrials.gov identifier: NCT02448745 (19 May 2015): https://clinicaltrials.gov/ct2/show/NCT02448745.

What sounds like Aedes, acts like Aedes, but is not Aedes? Lessons from dengue virus control for the management of invasive Anopheles.

Aedes mosquitoes are responsible for transmission of dengue, chikungunya, Zika, and yellow fever viruses. Aedes mosquitoes are the pathfinders of invasive urban-living mosquitoes, and have spread into 129 countries over the past five decades. In the past 10 years Anopheles stephensi has been identified within densely populated cities in Yemen and across the Horn of Africa and as far west as Nigeria. A stephensi's aggressive spread is closely linked to increases in population movement due to migration, conflict, and climate change; rapid unplanned urbanisation; and resulting poor water quality, sanitation, waste container removal, and hygiene systems. As a highly invasive vector that is adept at transmitting malarial pathogens (eg, Plasmodium vivax and Plasmodium falciparum), A stephensi's spread holds huge implications for increasing malaria morbidity and mortality. Both vectors (ie, Aedes species and A stephensi) thrive in the same urban environments, and urgent action is needed to seize the opportunity to integrate disease control resources and generate innovative vector-control tools for urban populations, to protect the many millions at risk.

Accuracy and Reliability of Peripheral Artery Calcium Scoring Systems Using an Intravascular Ultrasound Reference Standard.

BACKGROUND: Peripheral artery calcium scoring systems are commonly used in clinical trials to categorize calcium severity but there are little data on their accuracy and reliability. The purpose of this study was to investigate the accuracy and reliability of these systems. METHODS: Angiographic, computed tomography angiography, and intravascular ultrasound (IVUS) imaging were obtained from 47 consecutive cases sourced from a prospectively collected database of patients undergoing femoropopliteal artery endovascular intervention. Two independent blinded readers graded calcium severity using the Peripheral Arterial Calcium Scoring System, Peripheral Academic Research Consortium, and Fanelli calcium scoring systems. IVUS maximum arc of calcium and calcium length were compared between severity grades for each scoring system. The diagnostic accuracy of each scoring system for identifying severe calcium was calculated using the reference standard of an IVUS maximum calcium arc ≥ 180°. Agreement testing was performed between scoring systems and between and within observers for each system. RESULTS: IVUS identified calcium in 85% (42/47) of cases, compared to 68% (32/47) of cases with angiography. There were no differences in IVUS calcium parameters between grades of calcium for any of the scoring systems. Severe calcium was detected by IVUS in 30 cases, in 23 cases by Peripheral Arterial Calcium Scoring System (sensitivity: 73%, specificity: 33%, positive predictive value [PPV]: 83%, negative predictive value [NPV]: 22%), in 12 cases by Peripheral Academic Research Consortium (sensitivity: 42%, specificity: 83%, PPV: 92%, NPV: 25%), and in 10 cases by Fanelli (sensitivity: 39%, specificity: 100%, PPV: 100%, NPV: 27%). Agreement between scoring systems was weak to moderate (range: k = 0.55-0.74). Interobserver agreement was weak (k = 0.41-0.54) and intraobserver agreement was highly variable ranging from k = 0.41 to k = 0.92. CONCLUSIONS: The poor diagnostic accuracy and weak-to-moderate reliability of calcium scoring systems raise doubts about the use of current calcium scoring systems for use in clinical trials.

Worsening drought of Nile basin under shift in atmospheric circulation, stronger ENSO and Indian Ocean dipole.

Until now, driving mechanisms behind recurring droughts and hydroclimate variations that controls the Nile River Basin (NRB) remains poorly understood. Our results show significant hydroclimatic changes that contributed to recent increasing aridity of NRB since the 1970s. Besides climate warming, the influence of stronger ENSO and Indian Ocean dipole (IOD) in NRB has increased after 1980s, which have significantly contributed to NRB's drought severity at inter-annual to inter-decadal timescales. Our results demonstrate that warming, El Niño and IOD have played a crucial role on NRB's inter-decadal hydroclimate variability, but IOD has played a more important role in modulating NRB's hydroclimate at higher timescales than El Niño. Results also indicate that the impacts of positive phases of ENSO and IOD events are larger than the negative phases in the NRB hydroclimate. Further, the southward (westward) shift in stream functions and meridional (zonal) winds caused an enhancement in the blocking pattern, with strong anticyclonic waves of dry air that keeps moving into NRB, has resulted in drier NRB, given stream function, geopotential height and U-wind anomalies associated with El Niño shows that changes in regional atmospheric circulations during more persistent and stronger El Niño has resulted in drier NRB. After 1970s, El Niño, IOD, and drought indices shows significant anti-phase relationships, which again demonstrates that more frequent and severe El Niño and IOD in recent years has led to more severe droughts in NRB. Our results also demonstrate that IOD and and the western pole of the Indian Ocean Dipole (WIO) are better predictors of the Nile flow than El Niño, where its flow has decreased by 13.7 (upstream) and by 114.1 m3/s/decade (downstream) after 1964. In summary, under the combined impact of warming and stronger IOD and El Niño, future droughts of the NRB will worsen.

Outcomes Following Percutaneous Cholecystostomy Tube Placement for Acalculous Versus Calculous Cholecystitis.

BACKGROUND: Acute acalculous cholecystitis (AAC) is often diagnosed in critically ill patients. Percutaneous cholecystostomy tube (PCT) placement facilitates less invasive gallbladder decompression in patients who are poor surgical candidates. Specific guidelines for optimal management of AAC patients following PCT placement remain to be defined. We hypothesize that AAC patients are at lower risk of recurrent cholecystitis than acute calculous cholecystitis (ACC) patients and do not require cholecystectomy after PCT placement. METHODS: A retrospective review of patients who underwent PCT placement for AAC or ACC between 6/1/2007 and 5/31/2019 was performed. Primary outcome was recurrent cholecystitis and interval cholecystectomy for patients surviving 30 days after PCT placement. Secondary outcome was 30 day mortality. A cox regression model calculated the adjusted hazard ratio (AHR) for the outcomes. RESULTS: Eighty-four AAC and 85 ACC patients underwent PCT placement. Compared to ACC patients, more AAC patients were male (72.6 vs. 48.2%; p < 0.01), younger (median age 62 vs. 73 years; p < 0.01), and required intensive care (69.0 vs. 52.9%; p = 0.04), with lower median Charlson Comorbidity Index (4.0 vs. 6.0; p < 0.01). 30 day mortality was higher among AAC patients than ACC patients (45.2 vs. 21.2%; p < 0.01). 2/24 (8.3%) AAC patients and 5/31 (16.1%) ACC patients developed recurrent cholecystitis at a median 208.0 days (IQR:64.0-417.0) after PCT placement and 115.0 days (IQR:7.0-403.0) following PCT removal. Cox regression analysis demonstrated that AAC patients had lower likelihood of interval cholecystectomy compared to ACC patients (AHR 2.35; 95% CI:1.11,4.96). CONCLUSION: Recurrent cholecystitis is rare in patients surviving 30 days following PCT placement. When compared with ACC patients, fewer AAC patients require cholecystectomy.

The Impact of Intravascular Ultrasound on Femoropopliteal Artery Endovascular Interventions: A Randomized Controlled Trial.

OBJECTIVES: The aim of this study was to investigate whether the addition of intravascular ultrasound (IVUS) guidance during femoropopliteal artery interventions reduced the rate of binary restenosis within 12 months compared with angiographic guidance alone. BACKGROUND: IVUS is more accurate than angiography for assessment of vessel size and disease severity. Low-level studies suggest that the use of IVUS in femoropopliteal endovascular interventions improves outcomes, but currently, no level 1 evidence exists. METHODS: This was a prospective single-center trial of 150 patients undergoing femoropopliteal endovascular intervention, randomized (1:1) to guidance by angiography or angiography and IVUS. The primary outcome measure was freedom from binary restenosis, on duplex ultrasound, within 12 months. Secondary outcomes included clinically driven target lesion revascularization, disagreements in imaging findings between modalities, and changes in treatment caused by IVUS. RESULTS: Freedom from binary restenosis at 12 months was significantly higher in the IVUS group (72.4% vs 55.4%; P = 0.008). There was no significant difference between groups for clinically directed target lesion revascularization (84.2% and 82.4%; P = 0.776). Mean vessel diameter was significantly larger with IVUS (5.60 mm vs 5.10 mm; P < 0.001). A change in treatment occurred caused by IVUS in 79% of cases. Binary restenosis was lower in the IVUS group for cases treated with drug-coated balloons (9.1% vs 37.5%; P = 0.001). CONCLUSIONS: The use of IVUS resulted in a significant reduction in the rate of restenosis after endovascular intervention. This is the first randomized controlled trial to demonstrate that IVUS improves outcomes in femoropopliteal interventions. This benefit may primarily relate to cases treated with drug-coated balloons. (Does the use of intravascular ultrasound improve outcomes of endovascular interventional procedures for peripheral vascular disease of the superficial femoral artery or popliteal artery?; ACTRN12614000006640).

Biomechanical and clinical outcomes in response to inpatient multidisciplinary hip and groin rehabilitation in UK military personnel.

INTRODUCTION: Hip and groin related pain is a common complaint among the military population across UK Defence Rehabilitation and addressing associated biomechanical dysfunction is a key treatment goal. Personnel are exposed to complex occupational loads, therefore assessing movement during demanding tasks may expose biomechanical deficits. Observing biomechanical and clinical outcomes in response to treatment is therefore an important consideration. The aims were to examine clinical and biomechanical outcomes prior to (T1) and 12 weeks post (T2) inpatient rehabilitation and explore the influence of pathological subgroup. METHODS: Prospective cohort study as part of a clinical service evaluation of 25 patients undergoing treatment for hip and groin related pain. Three-dimensional motion capture (3DM) during a single-leg squat, hip strength and patient-reported outcome measures were collected at T1 and T2. RESULTS: Increased abductor and external rotator strength with reductions in contralateral pelvic drop (1.9°; p=0.041) at T2 on the injured side. Pain reduced by 9.6 mm (p=0.017) but no differences were found for Non-Arthritic Hip Score (NAHS). No statistically significant differences were found between pathological subgroups. Kinematic profiles display variation between diagnostic subgroups and response to treatment. CONCLUSION: Strength and pain improved with treatment in this service evaluation although biomechanical adaptation and NAHS remain inconclusive. Small and uneven sample size prevents a firm conclusion regarding the effect of pathological subgroupings, however, the data can be considered hypothesis generating for future, larger studies to integrate 3DM for monitoring response to rehabilitation in pathological subgroups to support clinical decision making.

Percutaneous Cholecystostomy Tube for Acute Cholecystitis: Quantifying Outcomes and Prognosis.

BACKGROUND: Percutaneous cholecystostomy tubes (PCT) are utilized in the management of acute cholecystitis in patients deemed unsuitable for surgery. However, the drive for these decisions and the outcomes remain understudied. We sought to characterize the practices and utilization of PCT and evaluate associated outcomes at an urban medical center. METHODS: Patients undergoing PCT placement over a 12-y study period ending May 2019 were reviewed. Demographics, clinical presentation, labs, imaging studies, and outcomes were abstracted. The primary and secondary outcomes were 30-d mortality and interval cholecystectomy, respectively. RESULTS: Two hundred and four patients met inclusion criteria: 59.3% were male with a median age of 67.5 y and a National Surgical Quality Improvement Program (NSQIP) risk of serious complication of 8.0%. Overall, 57.8% of patients were located in an intensive care unit setting. The majority (80.9%) had an ultrasound and 48.5% had a hepatobiliary iminodiacetic acid scan. The overall 30-d mortality was 31.9%: 41.5% for intensive care unit and 18.6% for ward patients (P < 0.01). Of patients surviving beyond 30 d (n = 139), the PCT was removed from 106 (76.3%), and a cholecystectomy was performed in 55 (39.6%) at a median interval of 58.0 d. A forward logistic regression identified total bilirubin (Adjusted Odds Ratio: 1.12, adjusted P < 0.01) and NSQIP risk of serious complication (Adjusted Odds Ratio: 1.16, adjusted P < 0.01) as the only predictors for 30-d mortality. CONCLUSIONS: Patients selected for PCT placement have a high mortality risk. Despite subsequent removal of the PCT, the majority of surviving patients did not undergo an interval cholecystectomy. Total bilirubin and NSQIP risk of serious complication are useful adjuncts in predicting 30-d mortality in these patients.

Comparison of Angiographic Dissection Classification Systems in the Femoropopliteal Arteries Using IVUS Validation and Reliability Testing.

PURPOSE: Objective assessment of dissection severity is difficult. Recognition of this has led to the creation of classification systems. This study investigated the performance of the National Heart Lung and Blood Institute (NHLBI) and Kobayashi systems at differentiating severity of femoropopliteal dissection using intravascular ultrasound (IVUS) as the reference standard. Comparison between the 2 systems and the inter- and intra-observer reliability were also investigated. MATERIALS AND METHODS: Angiographic and IVUS imaging was assessed in 51 cases sourced from a RCT investigating the use of IVUS in femoropopliteal disease. A total of 2 readers independently scored the angiography images according to NHLBI and Kobayashi dissection classification systems and a consensus score was obtained for each system in each case. The NHLBI classification was condensed into 3 grades of dissection to allow comparison between systems. Dissection length, dissection arc, minimum lumen area, and lumen area stenosis were obtained from the IVUS imaging. IVUS parameters were compared between grades of severity for both systems. Agreement in grading between the systems was assessed and IVUS parameters for each level of dissection severity were compared between systems. Inter and intra-observer agreement tested for each system. RESULTS: Dissection was present on IVUS in 92.2% (47/51) of cases and angiography identified 78.7% (37/47) of these. No difference was present in any IVUS parameters between mild and severe dissections with either classification system. No difference in IVUS findings was present for the same grades of dissection between systems. The 2 systems agreed on severity grade in 47 of 51 cases. The inter-observer agreement was for NHLBI was k=0.549 and k=0.627 for Kobayashi. Intra-observer agreement for NHLBI was k=0.633 and k=0.633 and for Kobayashi was k=0.657 and k=0.297. CONCLUSION: The lack of difference in IVUS parameters between mild and severe dissection for the NHLBI and Kobayashi systems raises doubts about their ability to effectively differentiate dissection severity. Weak to moderate reliability suggests that variability in interpreting dissection may be higher than acceptable. IVUS imaging is more sensitive for detecting dissection than angiography and research is required to establish the value of adding IVUS to dissection classification systems.

The Role of ICS/LABA Fixed-Dose Combinations in the Treatment of Asthma and COPD: Bioequivalence of a Generic Fluticasone Propionate-Salmeterol Device.

Both asthma and chronic obstructive pulmonary disease (COPD) are inflammatory chronic respiratory conditions with high rates of morbidity and mortality worldwide. The objectives of this review are to briefly describe the pathophysiology and epidemiology of asthma and COPD, discuss guideline recommendations for uncontrolled disease, and review a new generic option for the treatment of asthma and COPD. Although mild forms of these diseases may be controlled with as-needed pharmacotherapy, uncontrolled or persistent asthma and moderate or severe COPD uncontrolled by bronchodilators with elevated eosinophilia or frequent exacerbations may require intervention with combination therapy with inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs), according to international guidelines. Fixed-dose combinations of ICS/LABA are commonly prescribed for both conditions, with fluticasone propionate (FP) and salmeterol forming a cornerstone of many treatment plans. An oral inhalation powder containing the combination of FP and salmeterol has been available as Advair Diskus® in the United States for almost 20 years, and the first and only substitutable generic version of this product has recently been approved for use: Wixela™ Inhub™. Bioequivalence of Wixela Inhub and Advair Diskus has been established. Furthermore, the Inhub inhaler was shown to be robust and easy to use, suggesting that Wixela Inhub may provide an alternative option to Advair Diskus for patients with asthma or COPD requiring intervention with an ICS/LABA.

Correction: The nuclear hypoxia-regulated NLUCAT1 long non-coding RNA contributes to an aggressive phenotype in lung adenocarcinoma through regulation of oxidative stress.

Lung cancer is the leading cause of cancer death worldwide, with poor prognosis and a high rate of recurrence despite early surgical removal. Hypoxic regions within tumors represent sources of aggressiveness and resistance to therapy. Although long non-coding RNAs (lncRNAs) are increasingly recognized as major gene expression regulators, their regulation and function following hypoxic stress are still largely unexplored. Combining profiling studies on early-stage lung adenocarcinoma (LUAD) biopsies and on A549 LUAD cell lines cultured in normoxic or hypoxic conditions, we identified a subset of lncRNAs that are both correlated with the hypoxic status of tumors and regulated by hypoxia in vitro. We focused on a new transcript, Nuclear LUCAT1 (NLUCAT1), which is strongly upregulated by hypoxia in vitro and correlated with hypoxic markers and poor prognosis in LUADs. Full molecular characterization showed that NLUCAT1 is a large nuclear transcript composed of six exons and mainly regulated by NF-κB and NRF2 transcription factors. CRISPR-Cas9-mediated invalidation of NLUCAT1 revealed a decrease in proliferative and invasive properties, an increase in oxidative stress and a higher sensitivity to cisplatin-induced apoptosis. Transcriptome analysis of NLUCAT1-deficient cells showed repressed genes within the antioxidant and/or cisplatin-response networks. We demonstrated that the concomitant knockdown of four of these genes products, GPX2, GLRX, ALDH3A1, and PDK4, significantly increased ROS-dependent caspase activation, thus partially mimicking the consequences of NLUCAT1 inactivation in LUAD cells. Overall, we demonstrate that NLUCAT1 contributes to an aggressive phenotype in early-stage hypoxic tumors, suggesting it may represent a new potential therapeutic target in LUADs.