Perturbations in mitochondrial metabolism associated with defective cardiolipin biosynthesis: An in-organello real-time NMR study.

Mitochondria are central to cellular metabolism; hence, their dysfunction contributes to a wide array of human diseases. Cardiolipin, the signature phospholipid of the mitochondrion, affects proper cristae morphology, bioenergetic functions, and metabolic reactions carried out in mitochondrial membranes. To match tissue-specific metabolic demands, cardiolipin typically undergoes an acyl tail remodeling process with the final step carried out by the phospholipid-lysophospholipid transacylase tafazzin. Mutations in tafazzin are the primary cause of Barth syndrome. Here, we investigated how defects in cardiolipin biosynthesis and remodeling impacts metabolic flux through the TCA cycle and associated yeast pathways. Nuclear magnetic resonance was used to monitor in real-time the metabolic fate of 13C3-pyruvate in isolated mitochondria from three isogenic yeast strains. We compared mitochondria from a wild-type strain to mitochondria from a Δtaz1 strain that lacks tafazzin and contains lower amounts of unremodeled cardiolipin, and mitochondria from a Δcrd1 strain that lacks cardiolipin synthase and cannot synthesize cardiolipin. We found that the 13C-label from the pyruvate substrate was distributed through twelve metabolites. Several of the metabolites were specific to yeast pathways including branched chain amino acids and fusel alcohol synthesis. While most metabolites showed similar kinetics amongst the different strains, mevalonate concentrations were significantly increased in Δtaz1 mitochondria. Additionally, the kinetic profiles of α-ketoglutarate, as well as NAD+ and NADH measured in separate experiments, displayed significantly lower concentrations for Δtaz1 and Δcrd1 mitochondria at most time points. Taken together, the results show how cardiolipin remodeling influences pyruvate metabolism, tricarboxylic acid cycle flux, and the levels of mitochondrial nucleotides.

Ultra-Early Diffuse Lung Disease in an Infant with Pathogenic Variant in Telomerase Reverse Transcriptase (TERT) Gene.

The pathogenic variants in the telomerase reverse transcriptase (TERT) gene have been identified in adults with idiopathic pulmonary fibrosis, while their connection to childhood diffuse lung disease has not yet been described. Within this study, we present a case of a five-month-old, previously healthy infant, with early-onset respiratory failure. The clinical suspicion of diffuse lung disease triggered by cytomegalovirus (CMV) pneumonitis was based on clinical and radiological presentation. Multiorgan involvement was not confirmed. Considering the possible connection between CMV pneumonitis and early-onset respiratory failure, clinical exome sequencing was performed and a novel variant, classified as likely pathogenic in the TERT gene (c.280A>T, p.Lys94Ter) was detected. After segregation analysis yielded negative results, the de novo status of the variant was confirmed. Respiratory support, antiviral and anti-inflammatory therapy offered modest benefits, nevertheless, eighteen months after the initial presentation of disease, an unfavourable outcome occurred. In conclusion, severe viral pneumonia has the potential to induce extremely rare early-onset diffuse lung disease accompanied by chronic respiratory insufficiency. This is linked to pathogenic variants in the TERT gene. Our comprehensive presentation of the patient contributes to valuable insights into the intricate interplay of genetic factors, clinical presentations, and therapeutic outcomes in cases of early-onset respiratory failure.

Venous thromboembolism prophylaxis prescribing patterns for patients with orthopedic trauma: a clinical vignette survey.

Background: A recent clinical trial suggested aspirin is a viable alternative to enoxaparin for venous thromboembolism (VTE) prophylaxis in patients after orthopedic trauma. The initial impact of these findings on VTE prophylaxis prescribing is unknown. The study aimed to evaluate stated VTE prophylaxis prescribing patterns among clinicians who treat patients after orthopedic trauma. Methods: For this clinical vignette survey, we recruited surgeons and advanced practice providers who prescribed VTE prophylaxis to patients with orthopedic trauma across 40 states. Clinicians were shown seven clinical vignettes describing hypothetical patients with orthopedic trauma based on their fracture type, treatment, VTE risk factors, additional injuries and health insurance status. We assessed the stated VTE prophylaxis medications prescribed in-hospital and at discharge, patient factors associated with changes in medication prescribing preferences and practice variation by specialty and provider training. Results: Among the 287 respondents, the median age was 43 years (IQR, 38-50), and 154 (weighted average, 63%) were men. For in-hospital VTE prophylaxis, enoxaparin was prescribed in 83% of the presented scenarios, and aspirin was prescribed in 13% (p<0.001). At discharge, aspirin was prescribed more frequently than enoxaparin (50% vs 41%, p<0.001). Healthcare providers with an aspirin discharge preference were 12% more likely to switch to enoxaparin if the patient had additional VTE risk factors, such as obesity (95% CI 4% to 19%, p=0.005). Conclusions: Despite new clinical evidence, in-hospital VTE prophylaxis prescribing practices for patients with orthopedic trauma remain consistent with those reported a decade ago. However, compared with historical data, clinicians have significantly increased their preference for aspirin for thromboprophylaxis at discharge-unless the patient has additional thromboembolic risk factors. Level of evidence: 5-expert opinion.

Risk factors for infection in severe open tibial shaft fractures.

OBJECTIVE: To evaluate risk factors for infection in severe open tibial shaft fractures. METHODS: A secondary analysis of a multicenter prospective study investigated internal versus external fixation of severe open tibia fractures at 20 US Level I trauma centers. Adult patients, aged <65 years, with a Gustilo-Anderson Type IIIB or severe IIIA metaphyseal or diaphyseal tibia fracture were included. All fractures underwent definitive fixation with either a modern ring external fixator, intramedullary device, and/or plate. Fourteen variables previously identified as risk factors for infection were included in the analysis. Deep surgical site infection was defined as an infection treated with surgical debridement within 1 year of index surgery. RESULTS: The study cohort included 430 patients. Deep surgical site infection requiring reoperation occurred in 108 (25 %) patients. The final model identified four risk factors for infection: age >40 years (OR, 2.00; 95 % CI, 1.3-3.1), Gustilo-Anderson Type IIIB (OR, 1.80; 95 % CI, 1.1-3.0), embedded wound contamination (OR, 1.69; 95 % CI, 1.1-2.7), and wound length (OR, 1.02/cm; 95 % CI, 1.0-1.05). The model performed poorly at distinguishing infected from uninfected patients (Area Under the Curve=0.57; 95 % CI, 0.51-0.63). CONCLUSIONS: Surgeons can now counsel patients with these risk factors that they are at a markedly higher risk of infection. The identification of these risk factors may direct future research aimed at mitigating the risk of deep surgical site infection in this patient population.

Development and evaluation of the Capability, Opportunity, and Motivation to deliver Physical Activity in School Scale (COM-PASS).

BACKGROUND: Teachers are recognized as 'key agents' for the delivery of physical activity programs and policies in schools. The aim of our study was to develop and evaluate a tool to assess teachers' capability, opportunity, and motivation to deliver school-based physical activity interventions. METHODS: The development and evaluation of the Capability, Opportunity, and Motivation to deliver Physical Activity in School Scale (COM-PASS) involved three phases. In Phase 1, we invited academic experts to participate in a Delphi study to rate, provide recommendations, and achieve consensus on questionnaire items that were based on the Capability, Opportunity, and Motivation Behavior (COM-B) model. Each item was ranked on the degree to which it matched the content of the COM-B model, using a 5-point scale ranging from '1 = Poor match' to '5 = Excellent match'. In Phase 2, we interviewed primary and secondary school teachers using a 'think-aloud' approach to assess their understanding of the items. In Phase 3, teachers (n = 196) completed the COM-PASS to assess structural validity using confirmatory factor analysis (CFA). RESULTS: Thirty-eight academic experts from 14 countries completed three rounds of the Delphi study. In the first round, items had an average rating score of 4.04, in the second round 4.51, and in the third (final) round 4.78. The final tool included 14 items, which related to the six constructs of the COM-B model: physical capability, psychological capability, physical opportunity, social opportunity, reflective motivation, and automatic motivation. In Phase 2, ten teachers shared their interpretation of COM-PASS via a 20-min interview, which resulted in minor changes. In Phase 3, CFA of the 3-factor model (i.e., capability, opportunity, and motivation) revealed an adequate fit to the data (χ2 = 122.6, p < .001, CFI = .945, TLI = .924, RMSEA = .066). The internal consistencies of the three subscale scores were acceptable (i.e., capability: α = .75, opportunity: α = .75, motivation: α = .81). CONCLUSION: COM-PASS is a valid and reliable tool for assessing teachers' capability, opportunity, and motivation to deliver physical activity interventions in schools. Further studies examining additional psychometric properties of the COM-PASS are warranted.

External Validation of a Predictive Score for Fracture-Related Infections in Orthopedic Trauma Surgery.

BACKGROUND: The purpose of this study was to externally validate a predictive score for fracture-related infections, establishing generalizability for absolute and relative risk of infection in the setting of orthopedic fracture surgery. MATERIALS AND METHODS: This was a retrospective, case-control study performed at a level I academic trauma center that included 147 patients with fracture-related infection in the study group and 300 control patients. We analyzed the same 8 independent predictors of fracture-related infection cited by a previous study. We then used the area under the receiver operating characteristics curve (AUC) to compare the derivation and validation cohorts. The validation and derivation cohorts were then compared by grouping patients into 4 strata of Wise score groups. This allowed for comparison of AUC and risk of fracture-related infection in our institution with those in the previously studied institution. RESULTS: The resulting data yielded an AUC (0.74) nearly identical to that of the previously studied institution. It was also found that the relative risk of infection correlated with the Wise score in the same way the initial model did with the absolute risks being similar. CONCLUSION: The previous predictive model was externally validated and shown to be generalizable to a different patient population. The relative risk of a fracture-related infection can be determined using this scoring model preoperatively with the goal of aiding in patient counseling and surgical decision-making, giving a quantitative value to patient risk factors. [Orthopedics. 2024;47(5):e268-e272.].

Is the Orthopaedic Trauma Association-Open Fracture Classification (OTA-OFC) Better than the Gustilo-Anderson Classification at Predicting Fracture-Related Infections in the Tibia?

OBJECTIVES: To investigate and compare the predictive ability of the Orthopaedic Trauma Association Open Fracture Classification (OTA-OFC) and the Gustilo-Anderson classification systems for fracture-related infections (FRI) in patients with open tibia fractures. METHODS: Design: Retrospective cohort study. SETTING: Academic trauma center. PATIENT SELECTION CRITERIA: Patients aged 16 years or older with an operatively treated open tibia fracture (OTA-OTA 41, 42, and 43) between 2010 and 2021. OUTCOME MEASURES AND COMPARISONS: The primary outcome was FRI. The OTA-OFC and the Gustilo-Anderson classifications were compared in their ability to predict FRI. RESULTS: 890 patients (mean age, 43 years [range, 17 to 96]; 75% male) with 912 open tibia fractures were included. 142 (16%) had an infection. The OTA-OFC was not significantly better at predicting FRI than the Gustilo-Anderson classification (area under the curve, 0.66 vs. 0.66; P = 0.89). The Gustilo-Anderson classification was a stronger predictor of FRI than any single OTA-OFC domain, explaining 72% of FRI variance. Only the addition of the OTA-OFC wound contamination domain to Gustilo-Anderson significantly increased the variance explained (72% vs. 84%, P = 0.04). Embedded contamination increased the risk of FRI by approximately 10% as the risk of FRI with embedded contamination was 16% for Type I or IIs, 26% for Type IIIAs, 45% for Type IIIBs, and 46% for Type IIICs. CONCLUSIONS: The more complex OTA-OFC system was not better than the Gustilo-Anderson classification system in predicting FRIs in patients with open tibia fractures. Adding embedded wound contamination to the Gustilo-Anderson classification system significantly improved its prognostic ability. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Cyclin A/B RxL Macrocyclic Inhibitors to Treat Cancers with High E2F Activity.

Cancer cell proliferation requires precise control of E2F1 activity; excess activity promotes apoptosis. Here, we developed cell-permeable and bioavailable macrocycles that selectively kill small cell lung cancer (SCLC) cells with inherent high E2F1 activity by blocking RxL-mediated interactions of cyclin A and cyclin B with select substrates. Genome-wide CRISPR/Cas9 knockout and random mutagenesis screens found that cyclin A/B RxL macrocyclic inhibitors (cyclin A/Bi) induced apoptosis paradoxically by cyclin B- and Cdk2-dependent spindle assembly checkpoint activation (SAC). Mechanistically, cyclin A/Bi hyperactivate E2F1 and cyclin B by blocking their RxL-interactions with cyclin A and Myt1, respectively, ultimately leading to SAC activation and mitotic cell death. Base editor screens identified cyclin B variants that confer cyclin A/Bi resistance including several variants that disrupted cyclin B:Cdk interactions. Unexpectedly but consistent with our base editor and knockout screens, cyclin A/Bi induced the formation of neo-morphic Cdk2-cyclin B complexes that promote SAC activation and apoptosis. Finally, orally-bioavailable cyclin A/Bi robustly inhibited tumor growth in chemotherapy-resistant patient-derived xenograft models of SCLC. This work uncovers gain-of-function mechanisms by which cyclin A/Bi induce apoptosis in cancers with high E2F activity, and suggests cyclin A/Bi as a therapeutic strategy for SCLC and other cancers driven by high E2F activity.

Perturbations in mitochondrial metabolism associated with defective cardiolipin biosynthesis: An in-organello real-time NMR study.

Mitochondria are central to cellular metabolism; hence, their dysfunction contributes to a wide array of human diseases including cancer, cardiopathy, neurodegeneration, and heritable pathologies such as Barth syndrome. Cardiolipin, the signature phospholipid of the mitochondrion promotes proper cristae morphology, bioenergetic functions, and directly affects metabolic reactions carried out in mitochondrial membranes. To match tissue-specific metabolic demands, cardiolipin typically undergoes an acyl tail remodeling process with the final step carried out by the phospholipid-lysophospholipid transacylase tafazzin. Mutations in the tafazzin gene are the primary cause of Barth syndrome. Here, we investigated how defects in cardiolipin biosynthesis and remodeling impact metabolic flux through the tricarboxylic acid cycle and associated pathways in yeast. Nuclear magnetic resonance was used to monitor in real-time the metabolic fate of 13C3-pyruvate in isolated mitochondria from three isogenic yeast strains. We compared mitochondria from a wild-type strain to mitochondria from a Δtaz1 strain that lacks tafazzin and contains lower amounts of unremodeled cardiolipin, and mitochondria from a Δcrd1 strain that lacks cardiolipin synthase and cannot synthesize cardiolipin. We found that the 13C-label from the pyruvate substrate was distributed through about twelve metabolites. Several of the identified metabolites were specific to yeast pathways, including branched chain amino acids and fusel alcohol synthesis. Most metabolites showed similar kinetics amongst the different strains but mevalonate and α-ketoglutarate, as well as the NAD+/NADH couple measured in separate nuclear magnetic resonance experiments, showed pronounced differences. Taken together, the results show that cardiolipin remodeling influences pyruvate metabolism, tricarboxylic acid cycle flux, and the levels of mitochondrial nucleotides.

Functional diversity among cardiolipin binding sites on the mitochondrial ADP/ATP carrier.

Lipid-protein interactions play a multitude of essential roles in membrane homeostasis. Mitochondrial membranes have a unique lipid-protein environment that ensures bioenergetic efficiency. Cardiolipin (CL), the signature mitochondrial lipid, plays multiple roles in promoting oxidative phosphorylation (OXPHOS). In the inner mitochondrial membrane, the ADP/ATP carrier (AAC in yeast; adenine nucleotide translocator, ANT in mammals) exchanges ADP and ATP, enabling OXPHOS. AAC/ANT contains three tightly bound CLs, and these interactions are evolutionarily conserved. Here, we investigated the role of these buried CLs in AAC/ANT using a combination of biochemical approaches, native mass spectrometry, and molecular dynamics simulations. We introduced negatively charged mutations into each CL-binding site of yeast Aac2 and established experimentally that the mutations disrupted the CL interactions. While all mutations destabilized Aac2 tertiary structure, transport activity was impaired in a binding site-specific manner. Additionally, we determined that a disease-associated missense mutation in one CL-binding site in human ANT1 compromised its structure and transport activity, resulting in OXPHOS defects. Our findings highlight the conserved significance of CL in AAC/ANT structure and function, directly tied to specific lipid-protein interactions.

What outcomes do patients value after orthopaedic trauma: A best-worst scaling choice experiment.

INTRODUCTION: Patient-centered treatment and research should focus on the outcomes that matter to patients. The primary aim of this study was to determine the outcome preferences of patients after musculoskeletal trauma. The secondary aim was to identify discrepancies between outcome preferences of surgeons and patients. METHODS: A Best-worst scaling choice experiment survey was administered to patients with operative lower extremity injuries and orthopaedic surgeons who take trauma call. Participants completed 13 choice sets of 3 randomly-ordered outcomes, including: a full recovery (back to normal) without any problems; a problem that requires additional surgery or hospital stay versus medication or treatment in clinic/emergency department; minimal to moderate versus severe pain for 6 weeks; need for crutches/walker versus wheelchair for 6-12 weeks; being unable to work for 6-12 weeks; requiring 2-4 weeks in a facility; a perfect versus poor or worst-possible EuroQol 5 Dimension (EQ-5D) score at 1 year; and death. Within each set, participants ranked their "most-preferred" to "least-preferred" outcomes. Responses were aggregated to calculate the relative importance, or marginal utility, of each outcome stratified by respondent type. RESULTS: Fifty-five patients and 65 surgeons participated. The most preferred outcome for patients and surgeons was a full recovery (back to normal) without any problems, followed by minimal to moderate pain for 6 weeks and a perfect EQ-5D score. The least preferred outcomes were death and the worst EQ-5D score, which had similar marginal utility, followed by a poor EQ-5D score and a problem that needs another surgery or stay at a hospital, which also had similar marginal utility. Surgeons, in comparison to patients, assigned a higher marginal utility to perfect EQ-5D scores at one year (3.55 vs. 2.03; p < 0.0001) and a 2-4 week stay in a facility (0.52 vs. -0.21; p = 0.001), and a lower marginal utility to severe pain for 6 weeks (-0.58 vs. -0.08; p = 0.04) and a poor EQ-5D score (-1.88 vs. -1.03; p = 0.02). CONCLUSIONS: A full recovery (back to normal) without any problems was the most-preferred outcome for both patients and surgeons. Patient-centered care and research should focus on both patients' return to baseline and the avoidance of complications. LEVEL OF EVIDENCE: N/A.

Biomolecular condensates of Chlorocatechol 1,2-Dioxygenase as prototypes of enzymatic microreactors for the degradation of polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) are molecules with two or more fused aromatic rings that occur naturally in the environment due to incomplete combustion of organic substances. However, the increased demand for fossil fuels in recent years has increased anthropogenic activity, contributing to the environmental concentration of PAHs. The enzyme chlorocatechol 1,2-dioxygenase from Pseudomonas putida (Pp 1,2-CCD) is responsible for the breakdown of the aromatic ring of catechol, making it a potential player in bioremediation strategies. Pp 1,2-CCD can tolerate a broader range of substrates, including halogenated compounds, than other dioxygenases. Here, we report the construction of a chimera protein able to form biomolecular condensates with potential application in bioremediation. The chimera protein was built by conjugating Pp 1,2-CCD to low complex domains (LCDs) derived from the DEAD-box protein Dhh1. We showed that the chimera could undergo liquid-liquid phase separation (LLPS), forming a protein-rich liquid droplet under different conditions (variable protein and PEG8000 concentrations and pH values), in which the protein maintained its structure and main biophysical properties. The condensates were active against 4-chlorocatechol, showing that the chimera droplets preserved the enzymatic activity of the native protein. Therefore, it constitutes a prototype of a microreactor with potential use in bioremediation.

Venous thromboembolism testing practices after orthopaedic trauma: prophylaxis regimen does not influence testing patterns.

Objectives: To determine venous thromboembolism (VTE) testing patterns in an orthopaedic trauma population and to evaluate for differences in VTE surveillance by prophylaxis regimen through a secondary analysis of the ADAPT trial. Design: Prospective randomized trial. Setting: Level I trauma center. Patients: Three hundred twenty-nine adult (18 years and older) trauma patients presenting with an operative extremity fracture proximal to the metatarsals/carpals or any pelvic or acetabular fracture requiring VTE prophylaxis. Intervention: VTE imaging studies recorded within 90 days post injury. Main Outcome Measurements: Percentage of patients tested for VTE were compared between treatment groups using Fisher's exact test. Subsequently, multivariable regression was used to determine patient factors significantly associated with risk of receiving a VTE imaging study. Results: Sixty-seven patients (20.4%) had VTE tests ordered during the study period. Twenty (29.9%) of these 67 patients with ordered VTE imaging tests had a positive finding. No difference in proportion of patients tested for VTE by prophylaxis regimen (18.8% on aspirin vs. 22.0% on LMWH, P = 0.50) was observed. Factors associated with increased likelihood of VTE testing included White race (adjusted odds ratio [aOR]: 2.61, 95% CI: 1.26-5.42), increased Injury Severity Score (aOR for every 1-point increase: 1.10, 95% CI: 1.05-1.15), and lower socioeconomic status based on the Area Deprivation Index (aOR for every 10-point increase: 1.14, 95% CI: 1.00-1.30). Conclusions: VTE surveillance did not significantly differ by prophylaxis regimen. Patient demographic factors including race, injury severity, and socioeconomic status were associated with differences in VTE surveillance. Level of Evidence: Level I, Therapeutic.

Healthcare personnel opinions regarding the feasibility of a risk-tailored approach to contact precautions for methicillin-resistant Staphylococcus aureus in the acute care setting.

"All or none" approaches to the use of contact precautions for methicillin-resistant Staphylococcus aureus (MRSA) both fail to recognize that transmission risk varies. This qualitative study assessed healthcare personnel perspectives regarding the feasibility of a risk-tailored approach to use contact precautions for MRSA more strategically in the acute care setting.

Factors that Promote and Protect Against Financial Toxicity after Orthopaedic Trauma: A Qualitative Study.

INTRODUCTION: Financial toxicity is highly prevalent in patients after an orthopaedic injury. However, little is known regarding the conditions that promote and protect against this financial distress. Our objective was to understand the factors that cause and protect against financial toxicity after a lower extremity fracture. METHODS: A qualitative study was conducted using semi-structured interviews with 20 patients 3 months after surgical treatment of a lower extremity fracture. The interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis to identify themes and subthemes. Data saturation occurred after 15 interviews. The percentage of patients who described the identified themes are reported. RESULTS: A total of 20 patients (median age, 44 years [IQR, 38 to 58]; 60% male) participated in the study. The most common injury was a distal tibia fracture (n = 8; 40%). Eleven themes that promoted financial distress were identified, the most common being work effects (n = 14; 70%) and emotional health (n = 12; 60%). Over half (n = 11; 55%) of participants described financial toxicity arising from an inability to access social welfare programs. Seven themes that protected against financial distress were also identified, including insurance (n = 17; 85%) and support from friends and family (n = 17; 85%). Over half (n = 13; 65%) of the participants discussed the support they received from their healthcare team, which encompassed expectation setting and connections to financial aid and other services. Employment protection and workplace flexibility were additional protective themes. CONCLUSION: This qualitative study of orthopaedic trauma patients found work and emotional health-related factors to be primary drivers of financial toxicity after injury. Insurance and support from friends and family were the most frequently reported protective factors. Many participants described the pivotal role of the healthcare team in establishing recovery expectations and facilitating access to social welfare programs.

The reported impact of non-communicable disease investment cases in 13 countries.

Non-communicable diseases (NCDs) are a leading health and development challenge worldwide. Since 2015, WHO and the United Nations Development Programme have provided support to governments to develop national NCD investment cases to describe the socioeconomic dimensions of NCDs. To assess the impact of the investment cases, semistructured interviews and a structured process for gathering written feedback were conducted between July and October 2022 with key informants in 13 countries who had developed a national NCD investment case between 2015 and 2020. Investment cases describe: (1) the social and economic costs of NCDs, including their distribution and projections over time; (2) priority areas for scaled up action; (3) the cost and returns from investing in WHO-recommended measures to prevent and manage NCDs; and (4) the political dimensions of NCD responses. While no country had implemented all the recommendations set out in their investment case reports, actions and policy changes attributable to the investment cases were identified, across (1) governance; (2) financing; and (3) health service access and delivery. The pathways of these changes included: (1) stronger collaboration across government ministries and partners; (2) advocacy for NCD prevention and control; (3) grounding efforts in nationally owned data and evidence; (4) developing mutually embraced 'language' across health and finance; and (5) elevating the priority accorded to NCDs, by framing action as an investment rather than a cost. The assessment also identified barriers to progress on the investment case implementation, including the influence of some private sector entities on sectors other than health, the impact of the COVID-19 pandemic, and changes in senior political and technical government officials. The results suggest that national NCD investment cases can significantly contribute to catalysing the prevention and control of NCDs through strengthening governance, financing, and health service access and delivery.

Fix or Replace? Patient Preferences for the Treatment of Geriatric Lower Extremity Fractures: A Discrete Choice Experiment.

Introduction: When considering treatment options for geriatric patients with lower extremity fractures, little is known about which outcomes are prioritized by patients. This study aimed to determine the patient preferences for outcomes after a geriatric lower extremity fracture. Materials and Methods: We administered a discrete choice experiment survey to 150 patients who were at least 60 years of age and treated for a lower extremity fracture at a Level I trauma center. The discrete choice experiment presented study participants with 8 sets of hypothetical outcome comparisons, including joint preservation (yes or no), risk of reoperation at 6 months and 24 months, postoperative weightbearing status, disposition, and function as measured by return to baseline walking distance. We estimated the relative importance of these potential outcomes using multinomial logit modeling. Results: The strongest patient preference was for maintained function after treatment (59%, P < .001), followed by reoperation within 6 months (12%, P < .001). Although patients generally favored joint preservation, patients were willing to change their preference in favor of joint replacement if it increased function (walking distance) by 13% (SE, 66%). Reducing the short-term reoperation risk (12%, P < .001) was more important to patients than reducing long-term reoperation risk (4%, P = .33). Disposition and weightbearing status were lesser priorities to patients (9%, P < .001 and 7%, P < .001, respectively). Discussion: After a lower extremity fracture, geriatric patients prioritized maintained walking function. Avoiding short-term reoperation was more important than avoiding long-term reoperation. Joint preservation through fracture fixation was the preferred treatment of geriatric patients unless arthroplasty or arthrodesis provides a meaningful functional benefit. Hospital disposition and postoperative weightbearing status were less important to patients than the other included outcomes. Conclusions: Geriatric patients strongly prioritize function over other outcomes after a lower extremity fracture.

Effect of Aspirin Versus Low-Molecular-Weight Heparin Thromboprophylaxis on Medication Satisfaction and Out-of-Pocket Costs: A Secondary Analysis of a Randomized Clinical Trial.

BACKGROUND: Current guidelines recommend low-molecular-weight heparin for thromboprophylaxis after orthopaedic trauma. However, recent evidence suggests that aspirin is similar in efficacy and safety. To understand patients' experiences with these medications, we compared patients' satisfaction and out-of-pocket costs after thromboprophylaxis with aspirin versus low-molecular-weight heparin. METHODS: This study was a secondary analysis of the PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT) trial, conducted at 21 trauma centers in the U.S. and Canada. We included adult patients with an operatively treated extremity fracture or a pelvic or acetabular fracture. Patients were randomly assigned to receive 30 mg of low-molecular-weight heparin (enoxaparin) twice daily or 81 mg of aspirin twice daily for thromboprophylaxis. The duration of the thromboprophylaxis, including post-discharge prescription, was based on hospital protocols. The study outcomes included patient satisfaction with and out-of-pocket costs for their thromboprophylactic medication measured on ordinal scales. RESULTS: The trial enrolled 12,211 patients (mean age and standard deviation [SD], 45 ± 18 years; 62% male), 9725 of whom completed the question regarding their satisfaction with the medication and 6723 of whom reported their out-of-pocket costs. The odds of greater satisfaction were 2.6 times higher for patients assigned to aspirin than those assigned to low-molecular-weight heparin (odds ratio [OR]: 2.59; 95% confidence interval [CI]: 2.39 to 2.80; p < 0.001). Overall, the odds of incurring any out-of-pocket costs for thromboprophylaxis medication were 51% higher for patients assigned to aspirin compared with low-molecular-weight heparin (OR: 1.51; 95% CI: 1.37 to 1.66; p < 0.001). However, patients assigned to aspirin had substantially lower odds of out-of-pocket costs of at least $25 (OR: 0.15; 95% CI: 0.12 to 0.18; p < 0.001). CONCLUSIONS: Use of aspirin substantially improved patients' satisfaction with their medication after orthopaedic trauma. While aspirin use increased the odds of incurring any out-of-pocket costs, it protected against costs of ≥$25, potentially improving health equity for thromboprophylaxis. LEVEL OF EVIDENCE: Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.

Community perceptions, acceptability, and the durability of house screening interventions against exposure to malaria vectors in Nyimba district, Zambia.

BACKGROUND: House screening remains conspicuously absent in national malaria programs despite its recognition by the World Health Organization as a supplementary malaria vector-control intervention. This may be attributed, in part, to the knowledge gap in screen durability or longevity in local climatic conditions and community acceptance under specific cultural practices and socio-economic contexts. The objectives of this study were to assess the durability of window and door wire mesh screens a year after full house screening and to assess the acceptability of the house screening intervention to the participants involved. METHODS: This study was conducted in Nyimba district, Zambia and used both quantitative and qualitative methods of data collection and analysis. Both direct observation and questionnaires were employed to assess the durability of the screens and the main reasons for damage. Findings on damage were summarized as percentages. Focus group discussions were used to assess people's knowledge, perceptions, and acceptability of the closing eaves and house screening intervention. Deductive coding and inductive coding were used to analyse the qualitative data. RESULTS: A total of 321 out of 400 (80.3%) household owners of screened houses were interviewed. Many window screens (90.3%) were intact. In sharp contrast, most door screens were torn (n = 150; 46.7%) or entirely removed (n = 55; 17.1%). Most doors (n = 114; 76%) had their wire mesh damaged or removed on the bottom half. Goats (25.4%), rust (17.6%) and children (17.1%) were cited most as the cause of damage to door screens. The focus group discussion elicited positive experiences from the participants following the closing of eaves and screening of their windows and doors, ranging from sleeping peacefully due to reduced mosquito biting and/or nuisance and having fewer insects in the house. Participants linked house screening to reduced malaria in their households and community. CONCLUSION: This study demonstrated that in rural south-east Zambia, closing eaves and screening windows and doors was widely accepted. Participants perceived that house screening reduced human-vector contact, reduced the malaria burden and nuisance biting from other potentially disease carrying insects. However, screened doors are prone to damage, mainly by children, domestic animals, rust, and termites.