Fracture liaison service-a multidisciplinary approach to osteoporosis management.

A fracture liaison service is a systems-level multidisciplinary approach designed to reduce subsequent fracture risk in patients who recently sustained fragility fractures. It is estimated that one in three women and one in five men over the age of 50 years old have osteoporosis. Nonetheless, only 9 to 20% of patients who sustain an initial fragility fracture eventually receive any osteoporosis treatment. With the aim of preventing subsequent fractures, a fracture liaison service (FLS) works through identifying patients presenting with fragility fractures to the hospital and providing them with easier access to osteoporosis care through referrals for bone health and fracture risk assessment and recommendation or initiation of osteoporosis treatment. Currently, there are four major types of FLS models ranging from services that only identify at-risk patients and inform and educate the patient but take no further part in communicating their findings to other stakeholders in patients' care, to services that identify, investigate, and initiate treatment at the other end of the spectrum. In this article, we review the benefits, challenges, and outcomes of FLS in the American healthcare system with further exploration of the roles each member of the multidisciplinary team can play in improving patients' bone health.

Trisomy 8 Defines a Distinct Subtype of Myeloproliferative Neoplasms Driven by the MYC-Alarmin Axis.

Despite advances in understanding the genetic abnormalities in myeloproliferative neoplasms (MPN) and the development of JAK2 inhibitors, there is an urgent need to devise new treatment strategies, particularly for patients with triple-negative (TN) myelofibrosis (MF) who lack mutations in the JAK2 kinase pathway and have very poor clinical outcomes. Here we report that MYC copy number gain and increased MYC expression frequently occur in TN-MF and that MYC-directed activation of S100A9, an alarmin protein that plays pivotal roles in inflammation and innate immunity, is necessary and sufficient to drive development and progression of MF. Notably, the MYC-S100A9 circuit provokes a complex network of inflammatory signaling that involves numerous hematopoietic cell types in the bone marrow microenvironment. Accordingly, genetic ablation of S100A9 or treatment with small molecules targeting the MYC-S100A9 pathway effectively ameliorates MF phenotypes, highlighting the MYC-alarmin axis as a novel therapeutic vulnerability for this subgroup of MPNs. Significance: This study establishes that MYC expression is increased in TN-MPNs via trisomy 8, that a MYC-S100A9 circuit manifest in these cases is sufficient to provoke myelofibrosis and inflammation in diverse hematopoietic cell types in the BM niche, and that the MYC-S100A9 circuit is targetable in TN-MPNs.

Dysphagia After Anterior Cervical Spine Surgery: Pathophysiology, Diagnosis, and Management.

Anterior cervical spine surgery (ACSS) is a surgical intervention widely used for a myriad of indications including degenerative, oncologic, inflammatory, traumatic, and congenital spinal conditions. A primary concern for surgeons performing ACSS is the postoperative development of oropharyngeal dysphagia. Current literature reports a wide incidence of this complication ranging from 1 to 79%. Dysphagia after ACSS is multifactorial, with common risk factors being prolonged duration of operation, revision surgeries, multilevel surgeries, and use of recombinant human bone morphogenetic protein-2. Many technical strategies have been developed to reduce the risk of postoperative dysphagia, including the development of low-profile implants and retropharyngeal local steroid application. In this article, we review the most recent literature regarding the epidemiology and pathophysiology, diagnostic criteria, risk factors, and management of dysphagia after ACSS.

Trends in Orthopaedic Surgery Workforce Diversity: Analyzing Changes Over Time.

INTRODUCTION: There are many reasons why orthopaedic surgeons move or change careers. We asked the questions: (1) What is the geographic distribution of orthopaedic surgeons with respect to age, sex, and race and ethnicity? (2) How has our workforce changed over time with regard to these factors? (3) Are there any patterns or trends detected regarding policy or regulatory events that coincide with these differences? METHODS: The American Academy of Orthopaedic Surgeons surveys over 30,000 members, collecting data on demographics, age, race sex, and practice statistics. We calculated geographic distributions and evaluated these differences over time-potential influences from malpractice suits or tort reform were investigated. RESULTS: Overall surgeon density increased over time. The largest negative changes were noted in District of Columbia, Wyoming, and North Dakota and positive changes in Colorado, South Dakota, and West Virginia. Age across all states increased (mean 1.7 years). Number of female surgeons increased in most states (4.6% to 5.7%). Number of African Americans increased from 1.6% to 1.8%, Hispanic/LatinX from 1.8% to 2.2%, Asian from 5.5% to 6.7%, and multiracial from 0.8% to 1.2%. No change was noted in the percentage of Native American surgeons. DISCUSSION: Surgeon density increased from 2012 to 2018; the cause for this change was not evident. Small increases in surgeon population, female surgeons, and in some underrepresented minorities were seen.

Nanonization and Deformable Behavior of Fattigated Peptide Drug in Mucoadhesive Buccal Films.

This study was tasked with the design of mucoadhesive buccal films (MBFs) containing a peptide drug, leuprolide (LEU), or its diverse nanoparticles (NPs), for enhanced membrane permeability via self-assembled nanonization and deformable behavior. An LEU-oleic acid conjugate (LOC) and its self-assembled NPs (LON) were developed. Additionally, a deformable variant of LON (d-LON) was originally developed by incorporating l-α-phosphatidylcholine into LON as an edge activator. The physicochemical properties of LON and d-LON, encompassing particle size, zeta potential, and deformability index (DI), were evaluated. MBFs containing LEU, LOC, and NPs (LON, d-LON) were prepared using the solvent casting method by varying the ratio of Eudragit RLPO and hydroxypropyl methylcellulose, with propylene glycol used as a plasticizer. The optimization of MBF formulations was based on their physicochemical properties, including in vitro residence time, dissolution, and permeability. The dissolution results demonstrated that the conjugation of oleic acid to LEU exhibited a more sustained LEU release pattern by cleaving the ester bond of the conjugate, as compared to the native LEU, with reduced variability. Moreover, the LOC and its self-assembled NPs (LON, d-LON), equivalent to 1 mg LEU doses in MBF, exhibited an amorphous state and demonstrated better permeability through the nanonization process than LEU alone, regardless of membrane types. The incorporation of lauroyl-L-carnitine into the films as a permeation enhancer synergistically augmented drug permeability. Most importantly, the d-LON-loaded buccal films showed the highest permeability, due to the deformability of NPs. Overall, MBF-containing peptide NPs and permeation enhancers have the potential to replace parenteral LEU administration by improving LEU druggability and patient compliance.

Association between non-medical cannabis legalization and alcohol sales: Quasi-experimental evidence from Canada.

BACKGROUND: There is increasing interest in understanding the impact of non-medical cannabis legalization on use of other substances, especially alcohol. Evidence on whether cannabis is a substitute or complement for alcohol is both mixed and limited. This study provides the first quasi-experimental evidence on the impact of Canada's legalization of non-medical cannabis on beer and spirits sales. METHODS: We used the interrupted time series design and monthly data on beer sales between January 2012 and February 2020 and spirits sales between January 2016 and February 2020 across Canada to investigate changes in beer and spirits sales following Canada's cannabis legalization in October 2018. We examined changes in total sales, nationally and in individual provinces, as well as changes in sales of bottled, canned and kegged beer. RESULTS: Canada-wide beer sales fell by 96 hectoliters per 100,000 population (p=0.011) immediately after non-medical cannabis legalization and by 4 hectoliters per 100,000 population (p>0.05) each month thereafter for an average monthly reduction of 136 hectoliters per 100,000 population (p<0.001) post-legalization. However, the legalization was associated with no change in spirits sales. Beer sales reduced in all provinces except the Atlantic provinces. By beer type, the legalization was associated with declines in sales of canned and kegged beer but there was no reduction in sales of bottled beer. CONCLUSIONS: Non-medical cannabis legalization was associated with a decline in beer sales in Canada, suggesting substitution of non-medical cannabis for beer. However, there was no change in spirits sales following the legalization.

Cost-Effectiveness of Lecanemab for Individuals With Early-Stage Alzheimer Disease.

BACKGROUND AND OBJECTIVES: Little is known regarding the cost-effectiveness of lecanemab (Leqembi), a monoclonal antibody approved by the US Food and Drug Administration in January 2023 for the treatment of mild cognitive impairment (MCI) or mild dementia due to Alzheimer disease (AD). This study aims to quantify the cost-effectiveness of lecanemab and how it varies based on the accuracy of AD testing and individuals' APOE ε4 status. METHODS: Seven alternative test-treat-target strategies defined by combinations of testing approaches (PET, CSF, or plasma assay), treatment choices (standard of care [SoC] alone or lecanemab in addition to SoC), and targeting strategies (targeting APOE ε4 noncarriers or heterozygous patients or not) were compared. A hybrid decision tree-Markov cohort model was constructed with 5 states: (1) MCI (Clinical Dementia Rating-Sum of Boxes [CDR-SB] 0-4.5); (2) mild dementia (CDR-SB 4.6-9.5); (3) moderate dementia (CDR-SB 9.6-16); (4) severe dementia (CDR-SB >16); and (5) death. Effectiveness was measured by quality-adjusted life years and costs from third-party and societal perspectives were estimated in 2022 US dollars over a lifetime horizon. RESULTS: Among the 7 test-treat-target strategies, SoC alone was the optimal strategy from a cost-effectiveness perspective. Neither targeted lecanemab treatment nor treatment unrestricted by APOE ε4 genotype was cost-effective vs SoC alone, regardless of the test used to diagnose patients with early-stage AD. However, CSF assay followed by targeted treatment would become cost-effective if lecanemab is priced below $5,100 per year. These results were robust to the accuracy of diagnostic testing and rates of lecanemab discontinuation and adverse events. DISCUSSION: Neither targeted lecanemab treatment nor treatment unrestricted by APOE ε4 genotype is cost-effective vs SoC alone for patients with MCI or mild dementia due to AD. Lecanemab would be cost-effective in some settings if priced below $5,100 per year.

Trends in the Main Residency Match From 2007 to 2020.

Background The United States Medical Licensing Exam (USMLE) Step 1 was recently changed from a numerically scored grading system to a pass/fail grading system. Until late 2024, there will be no formal studies about the impact that the grading change will have on the match process. To thoroughly assess the impact that this change will have on the overall match process, it is important to look at what the trends in applicants' objective measures have been in the years before the change. We aim to systematically evaluate the rates of change and mean trend of objective metrics found in residency applications in the main residency match.  Methods Objective medical student data of matched and unmatched applicants were queried from the National Matching Program's Charting Outcomes in the Match Reports for the 2007 to 2020 application cycles. Data were used to create linear regression analyses and statistical tests were performed to evaluate trends over time. Results For matched applicants, there were statistically significant positive trends for the mean number of contiguous ranks (m=0.33, p<0.01), having another non-doctoral graduate degree (m=0.67, p<0.01), membership to Alpha Omega Alpha (AOA) honor society (m=0.22, p<0.01), mean USMLE Step 1 score (m=1.01, p<0.01), mean USMLE Step 2 score (m=1.68, p<0.01), mean number of research experiences (m=0.12, p<0.01), and mean number of abstracts, presentations, and publications (m=0.34, p<0.01). Additionally, there was a statistically significant negative trend for the percentage who graduated from a top 40 National Institutes of Health-funded medical school (m=-0.41, p<0.01). For unmatched applicants, there were statistically significant positive trends for having another non-doctoral graduate degree (m=0.83, p<0.01), mean USMLE Step 1 score (m=1.26, p<0.01), mean USMLE Step 2 score (m=2.27, p<0.01), mean number of research experiences (m=0.13, p<0.01), and mean number of abstracts, presentations, and publications (m=0.33, p<0.01). Conclusion Our study shows that there have been statistically significant increases in almost all objective measures in the residency application. Recent changes to the abstracts, presentations, and publications on the Step 1 scoring system will force almost all residency programs to overhaul their application process and potentially increase reliance on Step 2, research, and other nonobjective factors. For students early in their medical education, emphasis on Step 2 and research will yield increased chances of matching into residency in the future.

British Columbia's Safer Opioid Supply Policy and Opioid Outcomes.

Importance: In March 2020, British Columbia, Canada, became the first jurisdiction globally to launch a large-scale provincewide safer supply policy. The policy allowed individuals with opioid use disorder at high risk of overdose or poisoning to receive pharmaceutical-grade opioids prescribed by a physician or nurse practitioner, but to date, opioid-related outcomes after policy implementation have not been explored. Objective: To investigate the association of British Columbia's Safer Opioid Supply policy with opioid prescribing and opioid-related health outcomes. Design, Setting, and Participants: This cohort study used quarterly province-level data from quarter 1 of 2016 (January 1, 2016) to quarter 1 of 2022 (March 31, 2022), from British Columbia, where the Safer Opioid Supply policy was implemented, and Manitoba and Saskatchewan, where the policy was not implemented (comparison provinces). Exposure: Safer Opioid Supply policy implemented in British Columbia in March 2020. Main Outcomes and Measures: The main outcomes were rates of prescriptions, claimants, and prescribers of opioids targeted by the Safer Opioid Supply policy (hydromorphone, morphine, oxycodone, and fentanyl); opioid-related poisoning hospitalizations; and deaths from apparent opioid toxicity. Difference-in-differences analysis was used to compare changes in outcomes before and after policy implementation in British Columbia with those in the comparison provinces. Results: The Safer Opioid Supply policy was associated with statistically significant increases in rates of opioid prescriptions (2619.6 per 100 000 population; 95% CI, 1322.1-3917.0 per 100 000 population; P < .001) and claimants (176.4 per 100 000 population; 95% CI, 33.5-319.4 per 100 000 population; P = .02). There was no significant change in prescribers (15.7 per 100 000 population; 95% CI, -0.2 to 31.6 per 100 000 population; P = .053). However, the opioid-related poisoning hospitalization rate increased by 3.2 per 100 000 population (95% CI, 0.9-5.6 per 100 000 population; P = .01) after policy implementation. There were no statistically significant changes in deaths from apparent opioid toxicity (1.6 per 100 000 population; 95% CI, -1.3 to 4.5 per 100 000 population; P = .26). Conclusions and Relevance: Two years after its launch, the Safer Opioid Supply policy in British Columbia was associated with higher rates of safer supply opioid prescribing but also with a significant increase in opioid-related poisoning hospitalizations. These findings will help inform ongoing debates about this policy not only in British Columbia but also in other jurisdictions that are contemplating it.

Recreational and Medical Cannabis Legalization and Opioid Prescriptions and Mortality.

Importance: While some have argued that cannabis legalization has helped to reduce opioid-related morbidity and mortality in the US, evidence has been mixed. Moreover, existing studies did not account for biases that could arise when policy effects vary over time or across states or when multiple policies are assessed at the same time, as in the case of recreational and medical cannabis legalization. Objective: To quantify changes in opioid prescriptions and opioid overdose deaths associated with recreational and medical cannabis legalization in the US. Design, Setting, and Participants: This quasiexperimental, generalized difference-in-differences analysis used annual state-level data between January 2006 and December 2020 to compare states that legalized recreational or medical cannabis vs those that did not. Intervention: Recreational and medical cannabis law implementation (proxied by recreational and medical cannabis dispensary openings) between 2006 and 2020 across US states. Main Outcomes and Measures: Opioid prescription rates per 100 persons and opioid overdose deaths per 100 000 population based on data from the US Centers for Disease Control and Prevention. Results: Between 2006 and 2020, 13 states legalized recreational cannabis and 23 states legalized medical cannabis. There was no statistically significant association of recreational or medical cannabis laws with opioid prescriptions or overall opioid overdose mortality across the 15-year study period, although the results also suggested a potential reduction in synthetic opioid deaths associated with recreational cannabis laws (4.9 fewer deaths per 100 000 population; 95% CI, -9.49 to -0.30; P = .04). Sensitivity analyses excluding state economic indicators, accounting for additional opioid laws and using alternative ways to code treatment dates yielded substantively similar results, suggesting the absence of statistically significant associations between cannabis laws and the outcomes of interest during the full study period. Conclusions and Relevance: The results of this study suggest that, after accounting for biases due to possible heterogeneous effects and simultaneous assessment of recreational and medical cannabis legalization, the implementation of recreational or medical cannabis laws was not associated with opioid prescriptions or opioid mortality, with the exception of a possible reduction in synthetic opioid deaths associated with recreational cannabis law implementation.

Changes in Medical Cannabis Use After Recreational Cannabis Legalization in Canada.

Background: As part of its recreational cannabis legalization in October 2018, Canada imposed an excise tax of 10% (or $1 a gram, whichever is higher) on both recreational and medical cannabis. There is little evidence to inform the ongoing debate on whether the legalization had adverse impacts on medical cannabis use. Methods: We used an interrupted time series design and data on medical cannabis shipments (i.e., mail-order deliveries of cannabis from a licensed producer to a patient authorized to obtain medical cannabis) in Canada between quarter 1 of 2014 and quarter 1 of 2020. We examined changes in medical cannabis shipments after Canada's recreational cannabis legalization both across Canada and for each province. As this study used publicly available, province-level aggregate data, ethics approval was not required. Results: Recreational cannabis legalization was associated with significant reductions in medical cannabis use in 7 out of 10 Canadian provinces. Compared with the counterfactual estimated from prelegalization trends, the reduction in quarter 1 of 2020 varied from 500 shipments per 100,000 population (95% CI=312-688 shipments per 100,000 population) or 32% (95% CI=22-43%) in Newfoundland and Labrador to 3,778 shipments per 100,000 population (95% CI=2,972-4,585 shipments per 100,000 population) or 74% (95% CI=68-79%) in Alberta. At the national level, the number of medical cannabis shipments decreased by 823 per 100,000 population (95% CI=725-921 shipments per 100,000 population) or 48% (95% CI=45-52%). Conclusions: Recreational cannabis legalization was associated with reductions in medical cannabis use. Our findings call for policy attention to address possible adverse impacts of recreational cannabis legalization on medical cannabis users.

Clinical effectiveness of reduction and fusion versus in situ fusion in the management of degenerative lumbar spondylolisthesis: a systematic review and meta-analysis.

PURPOSE: To compare the clinical effectiveness of reduction and fusion with in situ fusion in the management of patients with degenerative lumbar spondylolisthesis (DLS). METHODS: The systematic review was conducted following the PRISMA guidelines. Relevant studies were identified from PubMed, Embase, Scopus, Cochrane Library, ClinicalTrials.gov, and Google Scholar. The inclusion criteria were: (1) comparative studies of reduction and fusion versus in situ fusion for DLS patients, (2) outcomes reported as VAS/NRS, ODI, JOA score, operating time, blood loss, complication rate, fusion rate, or reoperation rate, (3) randomized controlled trials and observational studies published in English from the inception of the databases to January 2023. The exclusion criteria included: (1) reviews, case series, case reports, letters, and conference reports, (2) in vitro biomechanical studies and computational modeling studies, (3) no report on study outcomes. The risk of bias 2 (RoB2) tool and the Newcastle-Ottawa scale was conducted to assess the risk of bias of RCTs and observational studies, respectively. RESULTS: Five studies with a total of 704 patients were included (375 reduction and fusion, 329 in situ fusion). Operating time was significantly longer in the reduction and fusion group compared to in situ fusion group (weighted mean difference 7.20; 95% confidence interval 0.19, 14.21; P = 0.04). No additional significant intergroup differences were noted in terms of other outcomes analyzed. CONCLUSION: While the reduction and fusion group demonstrated a statistically longer operating time compared to the in situ fusion group, the clinical significance of this difference was minimal. The findings suggest no substantial superiority of lumbar fusion with reduction over without reduction for the management of DLS.

Roles of Fatty Acid Chain Length and Enzyme-Oriented Drug Controlled Release from pH-Triggering Self-Assembled Fatty Acid Conjugated Quetiapine Nanosuspensions.

Background: Quetiapine (QTP) is a first-line antipsychotic drug, but its therapeutic druggability and patient adherence were limited due to high oral dose strength, low bioavailability and physicochemical/biopharmaceutical issues. Purpose: To investigate the roles of fatty acid chain length and enzyme-oriented QTP controlled release from pH-triggering self-assembled fatty acid conjugated QTP nanosuspensions (NSPs). Methods: QTP was conjugated with different chain length fatty acids (C10-decanoic acid, C14-myristic acid, C18-stearic acid) to obtain QTP-fatty acid conjugates (QFCs: QD, QM, QS) by exploiting 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/4-dimethylaminopyridine (EDC/DMAP) conjugation chemistry. Then, the solubility, partitioning coefficient (log P), cell viability and cleavage kinetics of QFCs were evaluated. The pH-triggering self-assembled behaviors of QFCs to form QTP-fatty acid NSPs (QDN, QMN, QSN) by varying pH, QFC concentration and proton-to-QTP ratios were characterized. The morphological images, critical micelle concentration (CMC), physicochemical properties and enzyme-oriented QTP controlled release of NSPs were examined. Results: Three QFCs were synthesized with different chain length fatty acids from QTP after desalting fumarate from QTP fumarate. The pH, QFC concentration and proton-to-quetiapine molar ratio could influence physicochemical properties and nanonization behaviors of QFCs. All three QFCs showed no effect on the viability of myoblast cells. The pH-triggering self-assembly of amphiphilic QFCs to form nanoparticles (NPs) occurred as the amine moiety of QTP was readily ionized in a strongly acidic environment (pH 1.2). Interestingly, the longer the fatty acid chain length, the lower water solubility, the higher log P (lipophilicity) and the smaller NP particle size were observed. The conversion rate of QFCs to liberate QTP by esterase in human plasma and liver S9 fractions was also inversely proportional to the fatty acid carbon chain length. Interestingly, the freeze-dried QMN showed the esterase-oriented controlled release of QTP over one month, unlike the initial burst release of QDN or the slowly delayed release pattern of QSN. Conclusion: A new pH-triggering self-assembled nanonization platform was developed using different chain length fatty acid conjugated QTP in low pH environment. By varying fatty acid chain length, the enzyme-oriented QTP controlled release dosage form was challenged to enhance the therapeutic effectiveness of QTP.

Polyelectrolyte-based solid dispersions for enhanced dissolution and pH-Independent controlled release of sildenafil citrate.

The aim of this study was to design a novel matrix tablet with enhanced dissolution and pH-independent controlled release of sildenafil citrate (SIL), a drug with pH-dependent solubility, by using solid dispersions (SDs) and polyelectrostatic interactions. SIL-loaded SDs were prepared using various polymeric carriers such as poloxamer 188, poloxamer 407, Soluplus®, polyvinylpyrrolidone (PVP) K 12, and PVP K 17 by the solvent evaporation method. Among these polymers, Soluplus® was found to be the most effective in SDs for enhancing the drug dissolution over 6 h in pH 6.8 intestinal fluid. SIL was well dispersed in Soluplus®-based SDs in an amorphous form. When the Soluplus®-based SDs were added in the tablet containing positively charged chitosan and negatively charged Eudragit® L100, the drug release rate was further modulated in a controlled manner. The charge density of the tablet was higher at pH 6.8 than at pH 1.2 due to the polyelectrostatic interaction between chitosan and Eudragit® L100. This interaction could provide a pH-independent controlled release of SIL. Our study demonstrates that a combinatory approach of Soluplus®-based SDs and polyelectrostatic interactions can improve the dissolution and pH-independent release performance of SIL. This approach could be a promising pharmaceutical strategy to design a matrix tablet of poorly water-soluble drugs for the enhanced bioavailability.

Bayesian merging of numerical modeling and remote sensing for saltwater intrusion quantification in the Vietnamese Mekong Delta.

Saltwater intrusion has become one of the most concerning issues in the Vietnamese Mekong Delta (VMD) due to its increasing impacts on agriculture and food security of Vietnam. Reliable estimation of salinity plays a crucial role to mitigate the impacts of saltwater intrusion. This study developed a hybrid technique that merges satellite imagery with numerical simulations to improve the estimation of salinity in the VMD. The salinity derived from Landsat images and by numerical simulations was fused using the Bayesian inference technique. The results indicate that our technique significantly reduces the uncertainties and improves the accuracy of salinity estimates. The Nash-Sutcliffe coefficient is 0.74, which is much higher than that of numerical simulation (0.63) and Landsat estimation (0.6). The correlation coefficient between the ensemble and measured salinity is relatively high (0.88). The variance of the ensemble salinity errors (5.0 ppt2) is lower than that of Landsat estimation (10.4 ppt2) and numerical simulations (9.6 ppt2). The proposed approach shows a great potential to combine multiple data sources of a variable of interest to improve its accuracy and reliability wherever these data are available.

Cost-Effectiveness of Antiobesity Drugs for Adolescents With Severe Obesity.

Importance: Although the American Academy of Pediatrics has recommended treatment with antiobesity drugs for adolescents, the cost-effectiveness of antiobesity drugs for this population is still unknown. Objective: To quantify cost-effectiveness of different antiobesity drugs available for pediatric use. Design, Setting, and Participants: This economic evaluation used a Markov microsimulation model with health states defined by obesity levels. Effectiveness was measured by quality-adjusted life-years (QALYs) and costs were calculated from third-party payer perspective, estimated in 2023 US dollars over a 10-year horizon. Data were obtained from the published literature. Intervention: Antiobesity drugs orlistat, liraglutide, semaglutide, and phentermine-topiramate vs no treatment. Metformin hydrochloride and 2 types of bariatric surgical procedures (sleeve gastrectomy and gastric bypass) were considered in sensitivity analysis. Main Outcomes and Measures: Incremental cost-effectiveness ratio. Results: Among the 4 antiobesity drugs currently approved for pediatric use, phentermine-topiramate was the most cost-effective with an incremental cost-effectiveness ratio of $93 620 per QALY relative to no treatment in this simulated cohort of 10 000 adolescents aged 12 to 17 years (mode, 15 years) with severe obesity (62% female). While semaglutide offered more QALYs than phentermine-topiramate, its higher cost resulted in an incremental cost-effectiveness ratio ($1 079 480/QALY) that exceeded the commonly used willingness-to-pay threshold of $100 000 to $150 000/QALY. Orlistat and liraglutide cost more and were less effective than phentermine-topiramate and semaglutide, respectively. Sleeve gastrectomy and gastric bypass were more effective than phentermine-topiramate but were also more costly, rendering them not cost-effective compared with phentermine-topiramate at the willingness-to-pay threshold of $100 000 to $150 000/QALY. Conclusions and Relevance: In this economic evaluation of weight loss drugs for adolescents with severe obesity, we found phentermine-topiramate to be a cost-effective treatment at a willingness-to-pay threshold of $100 000 to $150 000/QALY. Further research is needed to determine long-term drug efficacy and how long adolescents continue treatment.

Historical Perspective on Lung Cancer Screening.

Lung cancer represents a large burden on society with a staggering incidence and mortality rate that has steadily increased until recently. The impetus to design an effective screening program for the deadliest cancer in the United States and worldwide began in 1950. It has taken more than 50 years of numerous clinical trials and continued persistence to arrive at the development of modern-day screening program. As the program continues to grow, it is important for clinicians to understand its evolution, track outcomes, and continually assess the impact and bias of screening on the medical, social, and economic systems.

Cellular Efficacy of Fattigated Nanoparticles and Real-Time ROS Occurrence Using Microfluidic Hepatocarcinoma Chip System: Effect of Anticancer Drug Solubility and Shear Stress.

The objective of this study was to evaluate the effectiveness of organ-on-chip system investigating simultaneous cellular efficacy and real-time reactive oxygen species (ROS) occurrence of anticancer drug-loaded nanoparticles (NPs) using hepatocarcinoma cells (HepG2) chip system under static and hepatomimicking shear stress conditions (5 dyne/cm2). Then, the role of hepatomimetic shear stress exposed to HepG2 and drug solubility were compared. The highly soluble doxorubicin (DOX) and poorly soluble paclitaxel (PTX) were chosen. Fattigated NPs (AONs) were formed via self-assembly of amphiphilic albumin (HSA)-oleic acid conjugate (AOC). Then, drug-loaded AONs (DOX-AON or PTX-AON) were exposed to a serum-free HepG2 medium at 37 °C and 5% carbon dioxide for 24 h using a real-time ROS sensor chip-based microfluidic system. The cellular efficacy and simultaneous ROS occurrence of free drugs and drug-loaded AONs were compared. The cellular efficacy of drug-loaded AONs varied in a dose-dependent manner and were consistently correlated with real-time of ROS occurrence. Drug-loaded AONs increased the intracellular fluorescence intensity and decreased the cellular efficacy compared to free drugs under dynamic conditions. The half-maximal inhibitory concentration (IC50) values of free DOX (13.4 µg/mL) and PTX (54.44 µg/mL) under static conditions decreased to 11.79 and 38.43 µg/mL, respectively, under dynamic conditions. Furthermore, DOX- and PTX-AONs showed highly decreased IC50 values of 5.613 and 21.86 µg/mL, respectively, as compared to free drugs under dynamic conditions. It was evident that cellular efficacy and real-time ROS occurrence were well-correlated and highly dependent on the drug-loaded nanostructure, drug solubility and physiological shear stress.

Impact of the COVID-19 Pandemic on the Severity and Early Postoperative Outcomes of Acute Appendicitis.

Background The coronavirus disease 2019 (COVID-19) pandemic caused changes in surgical practice. For acute appendicitis (AA), measures to control the pandemic might hinder patients from seeking medical care timely, resulting in increasing severity, postoperative complications, and mortality. This study aimed to investigate whether the COVID-19 pandemic had a negative impact on the severity and postoperative outcomes of patients with AA. Methodology We retrospectively reviewed medical records of AA patients treated operatively at Nhan Dan Gia Dinh Hospital hospital from June 1st to September 30th in three consecutive years: pre-pandemic (2019)/Group 1, minor waves (2020)/Group 2, and major wave (2021)/Group 3 (2021). Data were collected focusing on the duration of symptoms, severity of AA, time from admission to operation, postoperative complications, and mortality. Results There were 1,055 patients, including 452 patients in Group 1, 409 in Group 2, and 194 in Group 3. The overall number of patients decreased mainly in non-complicated AA. The percentages of hospital admission after 24 hours gradually increased (20.8%, 27.9%, and 43.8%, p < 0.05). The percentages of complicated AA in Group 2 and Group 3 were statistically higher than in Group 1 (39% and 55% vs. 31%, p < 0.05). Waiting time for operation increased to five hours during the major wave. Laparoscopic appendectomy was performed in 98-99% of AA patients during the pandemic, with an early postoperative complication rate of 5-9% and a mortality rate of 0.2-1%. Conclusions Although the percentages of hospital admission after 24 hours and complicated AA increased, laparoscopic appendectomy was still feasible and effective and should be maintained as the standard management for AA during the COVID-19 pandemic.