Liver Fibrosis, Fat, and Iron Evaluation with MRI and Fibrosis and Fat Evaluation with US: A Practical Guide for Radiologists.

Quantitative imaging biomarkers of liver disease measured by using MRI and US are emerging as important clinical tools in the management of patients with chronic liver disease (CLD). Because of their high accuracy and noninvasive nature, in many cases, these techniques have replaced liver biopsy for the diagnosis, quantitative staging, and treatment monitoring of patients with CLD. The most commonly evaluated imaging biomarkers are surrogates for liver fibrosis, fat, and iron. MR elastography is now routinely performed to evaluate for liver fibrosis and typically combined with MRI-based liver fat and iron quantification to exclude or grade hepatic steatosis and iron overload, respectively. US elastography is also widely performed to evaluate for liver fibrosis and has the advantage of lower equipment cost and greater availability compared with those of MRI. Emerging US fat quantification methods can be performed along with US elastography. The author group, consisting of members of the Society of Abdominal Radiology (SAR) Liver Fibrosis Disease-Focused Panel (DFP), the SAR Hepatic Iron Overload DFP, and the European Society of Radiology, review the basics of liver fibrosis, fat, and iron quantification with MRI and liver fibrosis and fat quantification with US. The authors cover technical requirements, typical case display, quality control and proper measurement technique and case interpretation guidelines, pitfalls, and confounding factors. The authors aim to provide a practical guide for radiologists interpreting these examinations. © RSNA, 2023 See the invited commentary by Ronot in this issue. Quiz questions for this article are available in the supplemental material.

Complementary gene regulation by NRF1 and NRF2 protects against hepatic cholesterol overload.

Hepatic cholesterol overload promotes steatohepatitis. Insufficient understanding of liver stress defense impedes therapy development. Here, we elucidate the role of stress defense transcription factors, nuclear factor erythroid 2 related factor-1 (NRF1) and -2 (NRF2), in counteracting cholesterol-linked liver stress. Using a diet that increases liver cholesterol storage, expression profiles and phenotypes of liver from mice with hepatocyte deficiency of NRF1, NRF2, or both are compared with controls, and chromatin immunoprecipitation sequencing is undertaken to identify target genes. Results show NRF1 and NRF2 co-regulate genes that eliminate cholesterol and mitigate inflammation and oxidative damage. Combined deficiency, but not deficiency of either alone, results in severe steatohepatitis, hepatic cholesterol overload and crystallization, altered bile acid metabolism, and decreased biliary cholesterol. Moreover, therapeutic effects of NRF2-activating drug bardoxolone require NRF1 and are supplemented by NRF1 overexpression. Thus, we discover complementary gene programming by NRF1 and NRF2 that counteract cholesterol-associated fatty liver disease progression.

Pulmonary MRA During Pregnancy: Early Experience With Ferumoxytol.

BACKGROUND: Ferumoxytol, an intravenous iron supplement, is commonly used to treat anemia in pregnancy. Ferumoxytol-enhanced magnetic resonance angiography (Fe-MRA) is a viable off-label alternative to gadolinium-enhanced MRA for assessment of pulmonary embolism (PE) in pregnancy. PURPOSE: To describe our clinical experience with Fe-MRA in pregnant women with suspected PE. STUDY TYPE: Retrospective, observational, cohort. POPULATION: A total of 98 Fe-MRA exams (consecutive sample) performed in 94 pregnant women. FIELD STRENGTH/SEQUENCE: A 1.5 T and 3.0 T, 3D T1-weighted MRA. ASSESSMENT: After IRB approval including a waiver of informed consent, electronic health records were reviewed retrospectively for all Fe-MRA exams performed at our institution in pregnant between January, 2017 and March, 2022. The Fe-MRA protocol included 3D-MRA for assessment of pulmonary arteries, and T1-weighted imaging for ancillary findings. Fe-MRA exam duration was measured from image time stamps. Fe-MRA exams were reviewed by three cardiovascular imagers using a 4-point Likert scale for image quality and confidence for PE diagnosis (score 4 = best, 1 = worst), and tabulation of ancillary findings. STATISTICAL TESTS: Continuous data are presented as mean ± standard deviation. The overall image quality and confidence score is given as the mean of three readers. RESULTS: The 98 Fe-MRA exams were performed in 94 pregnant women (age 30 ± 6, range 19-48 years, gestational week 23 ± 10, range 3-38 weeks), with four undergoing two Fe-MRA exams during their pregnancy. Median Fe-MRA exam durration was 8 minutes (interquantile range 6 minutes). Overall image quality score was 3.3 ± 0.9. Confidence score for diagnosing PE was 3.5 ± 0.8. One subject was positive for PE (1/94, 1%); 42 of the 94 (45%) subjects Fe-MRA had ancillary findings including hydronephrosis or pneumonia. CONCLUSION: Ferumoxytol enhanced MRA is a radiation- and gadolinium-free alternative for diagnosis of PE during pregancy. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 5.

Multicenter Reproducibility of Liver Iron Quantification with 1.5-T and 3.0-T MRI.

Background MRI is a standard of care tool to measure liver iron concentration (LIC). Compared with regulatory-approved R2 MRI, R2* MRI has superior speed and is available in most MRI scanners; however, the cross-vendor reproducibility of R2*-based LIC estimation remains unknown. Purpose To evaluate the reproducibility of LIC via single-breath-hold R2* MRI at both 1.5 T and 3.0 T with use of a multicenter, multivendor study. Materials and Methods Four academic medical centers using MRI scanners from three different vendors (three 1.5-T scanners, one 2.89-T scanner, and two 3.0-T scanners) participated in this prospective cross-sectional study. Participants with known or suspected liver iron overload were recruited to undergo multiecho gradient-echo MRI for R2* mapping at 1.5 T and 3.0 T (2.89 T or 3.0 T) on the same day. R2* maps were reconstructed from the multiecho images and analyzed at a single center. Reference LIC measurements were obtained with a commercial R2 MRI method performed using standardized 1.5-T spin-echo imaging. R2*-versus-LIC calibrations were generated across centers and field strengths using linear regression and compared using F tests. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic performance of R2* MRI in the detection of clinically relevant LIC thresholds. Results A total of 207 participants (mean age, 38 years ± 20 [SD]; 117 male participants) were evaluated between March 2015 and September 2019. A linear relationship was confirmed between R2* and LIC. All calibrations within the same field strength were highly reproducible, showing no evidence of statistically significant center-specific differences (P > .43 across all comparisons). Calibrations for 1.5 T and 3.0 T were generated, as follows: for 1.5 T, LIC (in milligrams per gram [dry weight]) = -0.16 + 2.603 × 10-2 R2* (in seconds-1); for 2.89 T, LIC (in milligrams per gram) = -0.03 + 1.400 × 10-2 R2* (in seconds-1); for 3.0 T, LIC (in milligrams per gram) = -0.03 + 1.349 × 10-2 R2* (in seconds-1). Liver R2* had high diagnostic performance in the detection of clinically relevant LIC thresholds (area under the ROC curve, >0.98). Conclusion R2* MRI enabled accurate and reproducible quantification of liver iron overload over clinically relevant ranges of liver iron concentration (LIC). The data generated in this study provide the necessary calibrations for broad clinical dissemination of R2*-based LIC quantification. ClinicalTrials.gov registration no.: NCT02025543 © RSNA, 2022 Online supplemental material is available for this article.

Assessment of nationally recommended antibiotics for treatment of UTI in U.S.-Mexico border emergency departments.

BACKGROUND: Urinary tract infections (UTIs) seen in the emergency department are commonly treated as an outpatient with oral antibiotics. Given that antibiotics are available for over-the-counter purchase in Mexico, there is speculation that potential misuse and overuse of antibiotics in United States-Mexico border areas could lead to antibiotic resistance patterns that would render some empiric treatments for UTIs less effective. The purpose of this study was to examine the effectiveness of Infectious Disease Society of America (IDSA) guideline-recommended antibiotics for treatment of outpatient UTI diagnosed in the emergency department. Data were collected from a county hospital on the U.S.-Mexico border with a metropolitan area of over 2 million people. Secondary analysis included frequency of urine culture isolated, resistance rates of urine pathogens, and prescriber habits. METHODS: This study was a retrospective chart review of adult patients diagnosed and treated for UTI from August 1, 2019, to February 29, 2020. Culture results of included patients were analyzed against in vitro-tested antibiotics. Bacterial isolate frequency, resistance rates, and prescribing habits were collected. RESULTS: A total of 985 patient charts were reviewed, of which 520 patients met inclusion criteria for analysis of prescribing habits. Of these, 329 positive bacterial culture growths were included in the analysis of antibiotic resistance rates. Oral antibiotics with comparatively lower resistance rates were amoxicillin/clavulanate, cefdinir, cefuroxime, and nitrofurantoin. Oral antibiotics with notably high resistance rates included trimethoprim-sulfamethoxazole (TMP-SMX), tetracycline, ciprofloxacin, levofloxacin, and cephalexin. Nitrofurantoin was prescribed most frequently for outpatient treatment of UTI/cystitis (41.6%) while cephalexin was the most commonly prescribed antibiotic for outpatient treatment of pyelonephritis (50%). CONCLUSION: Our findings suggest that, while part of standard IDSA guidelines, fluoroquinolones and TMP-SMX are not ideal empiric antibiotics for treatment of outpatient UTI in the U.S.-Mexico border region studied due to high resistance rates. Although not listed as first line agents per current IDSA recommendations, 2nd and 3rd generation cephalosporins, and amoxicillin/clavulanate would be acceptable options given resistance patterns demonstrated in accordance with IDSA allowance for tailoring selection to local resistance. Nitrofurantoin appears to be consistent with recommendations and demonstrates a favorable resistance profile for treatment of outpatient UTI within this region.

Efficacy and Safety of High-dose Cholecalciferol in Patients With Inflammatory Bowel Disease Receiving Infliximab.

OBJECTIVE: Vitamin D deficiency is prevalent in patients with inflammatory bowel disease (IBD). The goal of this study was to assess the efficacy and safety of high-dose, interval cholecalciferol administration in patients with IBD receiving infliximab. METHODS: This prospective, longitudinal, open-label study enrolled pediatric and young adult patients with IBD and vitamin D deficiency. Subjects received 50,000 IU every 4 to 5 weeks (n = 11) or 100,000 IU every 6 to 8 weeks (n = 32) of oral cholecalciferol for 1 year. Dosing was directly observed and administered in conjunction with infliximab infusions. The primary endpoint was vitamin D sufficiency, defined as a 25-hydroxy-vitamin D (25-OHD) level ≥30 ng/mL. RESULTS: Forty-three participants constituted the primary analysis population. 25-OHD levels reached steady-state after the third dose, and mean increases in 25-OHD levels were 8 vs. 4.5 ng/mL in the 100,000 IU vs. 50,000 IU treatment groups, respectively. Only 43.8% of patients receiving 100,000 IU and 18.2% of patients receiving 50,000 IU achieved sufficiency. There was no difference in the 25-OHD level responsiveness in patients with Crohn disease versus those with ulcerative colitis (P = 0.72). There was no correlation between 25-OHD levels and clinical disease activity in patients with Crohn disease (P = 0.85) or ulcerative colitis (P = 0.24). CONCLUSIONS: Supplementation with cholecalciferol was well-tolerated and direct observation is a promising paradigm for ensuring compliance with therapy. Patients with IBD, however, appear to require high doses of cholecalciferol, with less than half of patients (37% overall) achieving vitamin D sufficiency. Additional studies are necessary to determine the optimal treatment regimens.

How should we judge edible oils and fats? An umbrella review of the health effects of nutrient and bioactive components found in edible oils and fats.

Dietary guidelines for many Western countries base their edible oil and fat recommendations solely on saturated fatty acid content. This study aims to demonstrate which nutritional and bioactive components make up commonly consumed edible oils and fats; and explore the health effects and strength of evidence for key nutritional and bioactive components of edible oils. An umbrella review was conducted in several stages. Food composition databases of Australia and the United States of America, and studies were examined to profile nutrient and bioactive content of edible oils and fats. PUBMED and Cochrane databases were searched for umbrella reviews, systematic literature reviews of randomized controlled trials or cohort studies, individual randomized controlled trials, and individual cohort studies to examine the effect of the nutrient or bioactive on high-burden chronic diseases (cardiovascular disease, type 2 diabetes mellitus, obesity, cancer, mental illness, cognitive impairment). Substantial systematic literature review evidence was identified for fatty acid categories, tocopherols, biophenols, and phytosterols. Insufficient evidence was identified for squalene. The evidence supports high mono- and polyunsaturated fatty acid compositions, total biophenol content, phytosterols, and possibly high α-tocopherol content as having beneficial effects on high-burden health comes. Future dietary guidelines should use a more sophisticated approach to judge edible oils beyond saturated fatty acid content.

Design Factors for Food Supplementation and Nutrition Education Interventions That Limit Conclusions about Effectiveness for Wasting Prevention: A Scoping Review of Peer-Reviewed Literature.

We conducted a scoping review to characterize the evidence base for the effectiveness of food supplementation (FS), nutrition education (NE), or FS/NE interventions to prevent wasting among children aged 6 to 59 mo. We aimed to identify gaps in peer-reviewed literature and to develop recommendations for strengthening study designs. We identified 56 unique studies (FS = 21, NE = 19, FS/NE = 16) for which we assessed intervention design factors, implementation context, evaluation methods, and wasting impact. Compared with studies focused on stunting, fewer wasting-focused studies reported weight-for-height z score (WHZ). Midupper arm circumference (MUAC) was more commonly reported in wasting-focused studies (71.4%) than those focused on stunting (36.8%) or wasting and stunting (30.4%). FS studies measured anthropometry (mean, 95% CI) more frequently at every 11.3 (7.8, 14.8) wk than NE interventions at 36.3 (8.8, 62.1) wk (P = 0.036), but not FS/NE interventions at 25.8 (5.6, 49.1) wk (P = 0.138). NE interventions tended to be of longer duration than FS or FS/NE interventions. Only 6 studies followed and measured children after the intervention period ended. Across all studies, 45% reported a significant effect on wasting; these included FS, NE, and FS/NE interventions. The lack of comparability across studies limits conclusions about the effectiveness of specific types of interventions. To build a more unified evidence base for wasting prevention we recommend that future studies 1) report on a consistent set of metrics, including MUAC; 2) attempt to measure change in wasting incidence using more frequent measures; 3) measure wasting prevalence among the general population; 4) follow children postintervention to assess relapse; 5) measure food insecurity and diet quality; and 6) use harmonized protocols across multiple settings. Such efforts to improve study comparability will strengthen the evidence base, may help unite divergent professional communities, and ultimately accelerate progress toward eliminating child undernutrition.

The effect of mindfulness and job demands on motivation and performance trajectories across the workweek: An entrainment theory perspective.

Employee performance is commonly investigated as a static, one-time snapshot of prior employee behaviors. For the studies that do acknowledge that performance fluctuates over time, the timeframe decision is disconnected from theoretical underpinnings. To make this connection clearer, we draw on entrainment theory and investigate trajectories in motivation and performance across the 5-day workweek. We hypothesize that both motivational control (i.e., staying on course and sustaining effort in pursuit of goals through the redirection of attention) and performance have a declining trajectory across the workweek. Drawing on self-determination theory, we also hypothesize that trait-based mindfulness (i.e., nonjudgmental present moment attention and awareness) negatively relates to the downward trajectory in performance across the workweek via its effect on the trajectory of motivational control. Finally, we take a trait activation theory perspective, hypothesizing that mindfulness is relevant as an indirect influence on performance trajectories through motivational control trajectories only when job demands are high. We test our model using 151 full-time employees in a medical device company. We collected data from participants twice daily across the 5-day workweek. We then use these daily scores to create between-person (e.g., person-centric) trajectories to investigate the proposed relationships. The hypotheses are generally supported. There is a downward trajectory of both motivational control and performance across the workweek. Furthermore, job demands conditionally moderate the indirect effect of mindfulness on performance trajectories through motivational control trajectories. Theoretical and practical implications specific to dynamic motivation and performance, entrainment, and mindfulness literature are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Compound SBI-0090799 Inhibits Zika Virus Infection by Blocking De Novo Formation of the Membranous Replication Compartment.

Zika virus (ZIKV) is a mosquito-borne pathogen classified by the World Health Organization (WHO) as a public health emergency of international concern in 2016, and it is still identified as a priority disease. Although most infected individuals are asymptomatic or show mild symptoms, a risk of neurologic complications is associated with infection in adults. Additionally, infection during pregnancy is directly linked to microcephaly and other congenital malformations. Since there are no currently available vaccines or approved therapeutics for this virus, there is a critical unmet need in developing treatments to prevent future ZIKV outbreaks. Toward this end, we performed a large-scale cell-based high-content screen of 51,520 chemical compounds to identify potential antiviral drug candidates. The compound (2E)-N-benzyl-3-(4-butoxyphenyl)prop-2-enamide (SBI-0090799) was found to inhibit replication of multiple ZIKV strains and in different cell systems. SBI-0090799 did not affect viral entry or RNA translation but suppressed RNA replication by preventing the formation of the membranous replication compartment. Selection of drug-resistant viruses identified single-amino-acid substitutions in the N-terminal region of nonstructural protein NS4A, arguing this is the likely drug target. These resistance mutations rescued viral RNA replication and restored the formation of the membranous replication compartment. This mechanism of action is similar to clinically approved NS5A inhibitors for hepatitis C virus (HCV). Taken together, SBI-0090799 represents a promising lead candidate for the development of an antiviral treatment against ZIKV infection for the mitigation of severe complications and potential resurgent outbreaks of the virus. IMPORTANCE This study describes the elucidation of (2E)-N-benzyl-3-(4-butoxyphenyl)prop-2-enamide (SBI-0090799) as a selective and potent inhibitor of Zika virus (ZIKV) replication using a high-throughput screening approach. Mapping and resistance studies, supported by electron microscopy observations, indicate that the small molecule is functioning through inhibition of NS4A-mediated formation of ZIKV replication compartments in the endoplasmic reticulum (ER). Intriguingly, this defines a novel nonenzymatic target and chemical matter for the development of a new class of ZIKV antivirals. Moreover, chemical modulation affecting this nonstructural protein mirrors the identification and development of hepatitis C virus (HCV) NS5A inhibitor daclatasvir and its derivatives, similarly interfering with the formation of the viral replication compartment and also targeting a protein with no enzymatic activity, which have been part of a curative strategy for HCV.

'An Apple a Day'?: Psychiatrists, Psychologists and Psychotherapists Report Poor Literacy for Nutritional Medicine: International Survey Spanning 52 Countries.

Nutritional interventions have beneficial effects on certain psychiatric disorder symptomatology and common physical health comorbidities. However, studies evaluating nutritional literacy in mental health professionals (MHP) are scarce. This study aimed to assess the across 52 countries. Surveys were distributed via colleagues and professional societies. Data were collected regarding self-reported general nutrition knowledge, nutrition education, learning opportunities, and the tendency to recommend food supplements or prescribe specific diets in clinical practice. In total, 1056 subjects participated in the study: 354 psychiatrists, 511 psychologists, 44 psychotherapists, and 147 MHPs in-training. All participants believed the diet quality of individuals with mental disorders was poorer compared to the general population (p < 0.001). The majority of the psychiatrists (74.2%) and psychologists (66.3%) reported having no training in nutrition. Nevertheless, many of them used nutrition approaches, with 58.6% recommending supplements and 43.8% recommending specific diet strategies to their patients. Only 0.8% of participants rated their education regarding nutrition as 'very good.' Almost all (92.9%) stated they would like to expand their knowledge regarding 'Nutritional Psychiatry.' There is an urgent need to integrate nutrition education into MHP training, ideally in collaboration with nutrition experts to achieve best practice care.

"Fully recharged" evenings? The effect of evening cyber leisure on next-day vitality and performance through sleep quantity and quality, bedtime procrastination, and psychological detachment, and the moderating role of mindfulness.

Aligning with the recovery perspective, we propose a dual-path model to illustrate the effects of employees' evening cyber leisure on next-day work outcomes, namely, psychological vitality and performance. We argue that evening cyber leisure has contradicting effects on next-day performance and vitality through its effects on bedtime procrastination and psychological detachment, and in turn, sleep quantity and sleep quality. We also propose that trait mindfulness acts as an important boundary condition of the indirect effects of evening cyber leisure. We used an experience sampling methodology to collect 3 surveys per day for 10 days from 155 R&D employees of a biotech company. Our findings suggest that cyber leisure has a negative indirect effect on sleep quantity and sleep quality via bedtime procrastination, and a positive indirect effect on sleep quantity and sleep quality via evening psychological detachment. Additionally, sleep quantity was positively associated with performance, and sleep quality was positively associated with psychological vitality. Lastly, as trait mindfulness increased, the negative impact of cyber leisure on bedtime procrastination was mitigated, and the positive impact of cyber leisure on psychological detachment was enhanced. Theoretical and practical implications specific to the use of cyber devices for workplace recovery are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Randomized, controlled trial to assess the safety and efficacy of odanacatib in the treatment of men with osteoporosis.

Odanacatib (ODN) was investigated as an osteoporosis treatment in 292 men. Compared with placebo, odanacatib improved bone mineral density and led to sustained bone resorption decreases while producing relatively little bone formation reduction that leveled off with time. However, increased risk of stroke in another study stopped further odanacatib development. INTRODUCTION: ODN, a selective oral cathepsin K inhibitor, was in development for osteoporosis treatment. This phase 3, double-blind, randomized, placebo-controlled, 24-month study investigated ODN safety and efficacy in men with osteoporosis. METHODS: Men with idiopathic osteoporosis or osteoporosis due to hypogonadism and a lumbar spine or hip (total hip [TH], femoral neck [FN], or trochanter) bone mineral density (BMD) T-score of ≤ - 2.5 to ≥ - 4.0 without prior vertebral fracture or ≤ - 1.5 to ≥ - 4.0 with one prior vertebral fracture were randomized (1:1) to once-weekly ODN 50 mg or placebo. All received 5600 IU vitamin D3 weekly and calcium supplementation as needed (≥ 1200 mg daily). The primary efficacy outcome was changed from baseline in lumbar spine BMD versus placebo. RESULTS: Overall, 292 men, mean age 68.8 years, were randomly assigned to ODN or placebo. Versus placebo, ODN increased BMD from baseline at the lumbar spine, TH, FN, and trochanter by 5.6%, 2.0%, 1.7%, and 2.1%, respectively (all p < 0.01), and decreased uNTx/Cr (68%, p < 0.001), sCTx (77%, p < 0.001), sP1NP (16%, p = 0.001), and sBSAP (8%, p = 0.019). The between-group bone formation marker decrease peaked at 3 months, then returned toward baseline. The safety profile, including cardiovascular events, was similar between groups. CONCLUSION: Though a promising osteoporosis therapy for men, ODN development was discontinued due to increased risk of stroke in the LOFT phase 3 trial. TRIAL REGISTRATION: Clinicaltrials.gov NCT01120600 (registered May 11, 2010).

Muscle-Liver Trafficking of BCAA-Derived Nitrogen Underlies Obesity-Related Glycine Depletion.

Glycine levels are inversely associated with branched-chain amino acids (BCAAs) and cardiometabolic disease phenotypes, but biochemical mechanisms that explain these relationships remain uncharted. Metabolites and genes related to BCAA metabolism and nitrogen handling were strongly associated with glycine in correlation analyses. Stable isotope labeling in Zucker fatty rats (ZFRs) shows that glycine acts as a carbon donor for the pyruvate-alanine cycle in a BCAA-regulated manner. Inhibition of the BCAA transaminase (BCAT) enzymes depletes plasma pools of alanine and raises glycine levels. In high-fat-fed ZFRs, dietary glycine supplementation raises urinary acyl-glycine content and lowers circulating triglycerides but also results in accumulation of long-chain acyl-coenzyme As (acyl-CoAs), lower 5' adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in muscle, and no improvement in glucose tolerance. Collectively, these studies frame a mechanism for explaining obesity-related glycine depletion and also provide insight into the impact of glycine supplementation on systemic glucose, lipid, and amino acid metabolism.

The Cost-Effectiveness of Platelet-Rich Plasma Compared With Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis.

PURPOSE: To examine the cost-effectiveness of a series (total of 3 injections) of intra-articular platelet-rich plasma (PRP) injections in comparison to that of hyaluronic acid (HA) viscosupplementation for the treatment of symptomatic knee osteoarthritis. METHODS: Outcome data regarding the use of PRP or HA injections for the treatment of symptomatic knee osteoarthritis were determined from the highest-quality data (Level I) available in the literature until 2015. Health utility values were then derived from these high-quality data. Costs were determined by examining typical charges for patients undergoing a series of either PRP or HA injections for the treatment of this condition at a large private orthopaedic practice. These health utility values and costs were used to create an expected-value decision analysis model. RESULTS: The results of the model revealed that the cost per quality-adjusted life-year (QALY) of a series of PRP injections was $8,635.23/QALY and that of a series of HA injections was $5,331.75/QALY. A series of PRP injections was associated with a higher initial cost than a series of HA injections (difference, $1,433.67); however, PRP was also more effective (higher utility value) than HA by 0.11 QALYs (0.69 vs 0.58, P = .0062) at 1 year. The incremental cost-effectiveness ratio of the use of PRP injections as opposed to HA was $12,628.15/QALY. CONCLUSIONS: Although a series of either PRP ($8,635.23/QALY) or HA ($5,331.75/QALY) injections for the treatment of symptomatic knee osteoarthritis would be considered cost-effective (cost per QALY < $50,000), PRP injections were not more cost-effective than HA injections. However, PRP was significantly more effective at 1 year, and being associated with an incremental cost-effectiveness ratio of $12,628.15/QALY when compared with HA, a series of PRP injections should be considered a reasonable and acceptable alternative to HA injections for the treatment of symptomatic knee osteoarthritis. LEVEL OF EVIDENCE: Level II, economic and decision analysis of Level I studies.

How do nutrition professionals working in low-income countries perceive and prioritize actions to prevent wasting? A mixed-methods study.

Despite a shared commitment to achieving global nutrition targets, development and emergency-humanitarian actors tend to prioritize different nutrition outcomes and actions. New approaches are needed to bridge the divide between these communities and to strengthen the overall evidence base for prevention of wasting. To better understand how these different groups perceive and prioritize actions for wasting prevention, key informant interviews (n = 21) were conducted, and an online survey was fielded among nutrition professionals working in low-income countries (n = 107). Additionally, nutrition policy and strategy documents for select global and country institutions (n = 12) were analysed to identify interventions and approaches for addressing different forms of undernutrition. The findings of this study suggest that at both global and country levels, development actors tend to prioritize stunting prevention, and emergency-humanitarian actors tend to prioritize treatment of acute malnutrition. It was less common for wasting prevention to be mentioned as an explicit priority. Many interventions were perceived by respondents to influence both stunting and wasting despite limited published evidence of effectiveness on wasting for water, sanitation and hygiene, growth monitoring and promotion, breastfeeding promotion and micronutrient supplementation. To help unify the nutrition community around prevention of wasting, the discourse about priority interventions should shift from 'stunting versus wasting' and 'prevention versus treatment' to a life-course framing around child survival, growth and development. Respondents identified a need for more programme and research funding that prioritizes both wasting and stunting as outcomes. They also suggest leveraging existing national coordination bodies that bring development and emergency-humanitarian partners together.