CRISPR-Cas9 In Vivo Gene Editing of KLKB1 for Hereditary Angioedema.

BACKGROUND: Hereditary angioedema is a rare genetic disease that leads to severe and unpredictable swelling attacks. NTLA-2002 is an in vivo gene-editing therapy based on clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9. NTLA-2002 targets the gene encoding kallikrein B1 (KLKB1), with the goal of lifelong control of angioedema attacks after a single dose. METHODS: In this phase 1 dose-escalation portion of a combined phase 1-2 trial of NTLA-2002 in adults with hereditary angioedema, we administered NTLA-2002 at a single dose of 25 mg, 50 mg, or 75 mg. The primary end points were the safety and side-effect profile of NTLA-2002 therapy. Secondary and exploratory end points included pharmacokinetics, pharmacodynamics, and clinical efficacy determined on the basis of investigator-confirmed angioedema attacks. RESULTS: Three patients received 25 mg of NTLA-2002, four received 50 mg, and three received 75 mg. At all dose levels, the most common adverse events were infusion-related reactions and fatigue. No dose-limiting toxic effects, serious adverse events, grade 3 or higher adverse events, or clinically important laboratory findings were observed after the administration of NTLA-2002. Dose-dependent reductions in the total plasma kallikrein protein level were observed between baseline and the latest assessment, with a mean percentage change of -67% in the 25-mg group, -84% in the 50-mg group, and -95% in the 75-mg group. The mean percentage change in the number of angioedema attacks per month between baseline and weeks 1 through 16 (primary observation period) was -91% in the 25-mg group, -97% in the 50-mg group, and -80% in the 75-mg group. Among all the patients, the mean percentage change in the number of angioedema attacks per month from baseline through the latest assessment was -95%. CONCLUSIONS: In this small study, a single dose of NTLA-2002 led to robust, dose-dependent, and durable reductions in total plasma kallikrein levels, and no severe adverse events were observed. In exploratory analyses, reductions in the number of angioedema attacks per month were observed at all dose levels. (Funded by Intellia Therapeutics; ClinicalTrials.gov number, NCT05120830.).

Use of Magnetic Resonance Imaging for Visualization of Oral Dosage Forms in the Human Stomach: A Scoping Review.

Oral dosage forms are the most widely and frequently used formulations to deliver active pharmaceutical ingredients (APIs), due to their ease of administration and noninvasiveness. Knowledge of intragastric release rates and gastric mixing is crucial for predicting the API release profile, especially for immediate release formulations. However, knowledge of the intragastric fate of oral dosage forms in vivo to date is limited, particularly for dosage forms administered when the stomach is in the fed state. An improved understanding of gastric food processing, dosage form location, disintegration times, and food effects is essential for greater understanding for effective API formulation design. In vitro standard and controlled modeling has played a significant role in predicting the behavior of dosage forms in vivo. However, discrepancies are reported between in vitro and in vivo disintegration times, with these discrepancies being greatest in the fed state. Studying the fate of a dosage form in vivo is a challenging process, usually requiring the use of invasive methods, such as intubation. Noninvasive, whole body imaging techniques can however provide unique insights into this process. A scoping review was performed systematically to identify and critically appraise published studies using MRI to visualize oral solid dosage forms in vivo in healthy human subjects. The review identifies that so far, an all-purpose robust contrast agent or dosage form type has not been established for dosage form visualization and disintegration studies in the gastrointestinal system. Opportunities have been identified for future studies, with particular focus on characterizing dosage form disintegration for development after the consumption food, as exemplified by the standard Food and Drug Administration (FDA) high fat meal.

Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults.

More than half of adults with epilepsy undergoing resective epilepsy surgery achieve long-term seizure freedom and might consider withdrawing antiseizure medications. We aimed to identify predictors of seizure recurrence after starting postoperative antiseizure medication withdrawal and develop and validate predictive models. We performed an international multicentre observational cohort study in nine tertiary epilepsy referral centres. We included 850 adults who started antiseizure medication withdrawal following resective epilepsy surgery and were free of seizures other than focal non-motor aware seizures before starting antiseizure medication withdrawal. We developed a model predicting recurrent seizures, other than focal non-motor aware seizures, using Cox proportional hazards regression in a derivation cohort (n = 231). Independent predictors of seizure recurrence, other than focal non-motor aware seizures, following the start of antiseizure medication withdrawal were focal non-motor aware seizures after surgery and before withdrawal [adjusted hazard ratio (aHR) 5.5, 95% confidence interval (CI) 2.7-11.1], history of focal to bilateral tonic-clonic seizures before surgery (aHR 1.6, 95% CI 0.9-2.8), time from surgery to the start of antiseizure medication withdrawal (aHR 0.9, 95% CI 0.8-0.9) and number of antiseizure medications at time of surgery (aHR 1.2, 95% CI 0.9-1.6). Model discrimination showed a concordance statistic of 0.67 (95% CI 0.63-0.71) in the external validation cohorts (n = 500). A secondary model predicting recurrence of any seizures (including focal non-motor aware seizures) was developed and validated in a subgroup that did not have focal non-motor aware seizures before withdrawal (n = 639), showing a concordance statistic of 0.68 (95% CI 0.64-0.72). Calibration plots indicated high agreement of predicted and observed outcomes for both models. We show that simple algorithms, available as graphical nomograms and online tools (predictepilepsy.github.io), can provide probabilities of seizure outcomes after starting postoperative antiseizure medication withdrawal. These multicentre-validated models may assist clinicians when discussing antiseizure medication withdrawal after surgery with their patients.

Surgical management of spiral oblique fractures of the fifth metatarsal leads to faster return to play in athletes: A systematic review.

PURPOSE: The purpose of this systematic review was to evaluate outcomes following both operative and nonoperative management of spiral oblique fractures of the fifth metatarsal. METHODS: During November 2023, the PubMed, Embase and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following operative and nonoperative management of dancer's fractures. Data regarding subjective clinical outcomes, radiological outcomes, complications and failure rates were extracted and analysed. RESULTS: Ten studies were included in this review. In total, 125 patients underwent operative treatment for dancer's fractures and 365 patients underwent nonoperative treatment for dancer's fractures. The weighted mean follow-up in the operative cohort was 15.3 ± 32.7 months and the weighted mean follow-up in the nonoperative cohort was 30.6 ± 24.3 months. The overall union rate in the operative cohort was 99.2% and the overall union rate in the nonoperative cohort was 98.6%. The weighted mean time to return to sport was 15.4 ± 6.7 and 22.4 ± 4.4 weeks in the operative cohort and nonoperative cohort, respectively. The complication rate in the operative cohort and nonoperative cohort was 12.0% and 15.1%, respectively. CONCLUSION: This current systematic review demonstrated comparable radiographic outcomes together with low failure rate and low complication rate following both operative and nonoperative management of dancer's fracture at short-term follow-up. However, faster return to sport rates was observed in the operative cohort, suggesting that surgical management of displaced spiral oblique fractures of the fifth metatarsal should be the mainstay treatment option. However, the under-reporting of data, marked heterogeneity between studies and paucity of comparative studies limits the generation of any robust conclusions; thus, further high-quality comparative studies are warranted. LEVEL OF EVIDENCE: Level IV.

From technical to understandable: Artificial Intelligence Large Language Models improve the readability of knee radiology reports.

PURPOSE: The purpose of this study was to evaluate the effectiveness of an Artificial Intelligence-Large Language Model (AI-LLM) at improving the readability of knee radiology reports. METHODS: Reports of 100 knee X-rays, 100 knee computed tomography (CT) scans and 100 knee magnetic resonance imaging (MRI) scans were retrieved. The following prompt command was inserted into the AI-LLM: 'Explain this radiology report to a patient in layman's terms in the second person:[Report Text]'. The Flesch-Kincaid reading level (FKRL) score, Flesch reading ease (FRE) score and report length were calculated for the original radiology report and the AI-LLM generated report. Any 'hallucination' or inaccurate text produced by the AI-LLM-generated report was documented. RESULTS: Statistically significant improvements in mean FKRL scores in the AI-LLM generated X-ray report (12.7 ± 1.0-7.2 ± 0.6), CT report (13.4 ± 1.0-7.5 ± 0.5) and MRI report (13.5 ± 0.9-7.5 ± 0.6) were observed. Statistically significant improvements in mean FRE scores in the AI-LLM generated X-ray report (39.5 ± 7.5-76.8 ± 5.1), CT report (27.3 ± 5.9-73.1 ± 5.6) and MRI report (26.8 ± 6.4-73.4 ± 5.0) were observed. Superior FKRL scores and FRE scores were observed in the AI-LLM-generated X-ray report compared to the AI-LLM-generated CT report and MRI report, p < 0.001. The hallucination rates in the AI-LLM generated X-ray report, CT report and MRI report were 2%, 5% and 5%, respectively. CONCLUSIONS: This study highlights the promising use of AI-LLMs as an innovative, patient-centred strategy to improve the readability of knee radiology reports. The clinical relevance of this study is that an AI-LLM-generated knee radiology report may enhance patients' understanding of their imaging reports, potentially reducing the responder burden placed on the ordering physicians. However, due to the 'hallucinations' produced by the AI-LLM-generated report, the ordering physician must always engage in a collaborative discussion with the patient regarding both reports and the corresponding images. LEVEL OF EVIDENCE: Level IV.

Particulated juvenile cartilage allograft for the treatment of osteochondral lesions of the talus is associated with a high complication rate and a high failure rate at short-term follow-up: A systematic review.

PURPOSE: The purpose of this systematic review was to evaluate the clinical and radiological outcomes together with the complication rates and failure rates at short-term follow-up following particulated juvenile cartilage allograft (PJCA) for the management of osteochondral lesions of the talus (OLT). METHODS: During October 2023, the PubMed, Embase and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following PJCA for the management of OLTs. Data regarding study characteristics, patient demographics, lesion characteristics, subjective clinical outcomes, radiological outcomes, complications and failures were extracted and analysed. RESULTS: Twelve studies were included. In total, 241 patients underwent PJCA for the treatment of OLT at a weighted mean follow-up of 29.0 ± 24.9 months. The weighted mean lesion size was 138.3 ± 59.6 mm2 . Prior surgical intervention was recorded in seven studies, the most common of which was microfracture (65.9%). The weighted mean American Orthopaedic Foot and Ankle Society score improved from a preoperative score of 58.5 ± 3.2 to a postoperative score of 83.9 ± 5.3. The weighted mean postoperative magnetic resonance observation of cartilage repair tissue (MOCART) score was 48.2 ± 3.3. The complication rate was 25.2%, the most common of which was allograft hypertrophy (13.2%). Thirty failures (12.4%) were observed at a weighted mean time of 9.8 ± 9.6 months following the index procedure. CONCLUSION: This systematic review demonstrated a moderate improvement in subjective clinical outcomes following PJCA for the treatment of OLT at short term follow-up. However, postoperative MOCART scores were reported as poor. In addition, a high complication rate (25.2%) and a high failure rate (12.4%) at short-term follow-up was observed, calling into question the efficacy of PJCA for the treatment of large OLTs. In light of the available evidence, PJCA for the treatment of large OLTs cannot be currently recommended. LEVEL OF EVIDENCE: Level IV.

Similar outcomes following scarf-Akin osteotomy compared to scarf-alone osteotomy for the treatment of hallux valgus: A systematic review and meta-analysis.

BACKGROUND: The purpose of this systematic review and meta-analysis was to compare the clinical and radiographic outcomes between patients undergoing scarf osteotomy and scarf-Akin osteotomy for the management of hallux valgus deformity. METHODS: A systematic review of the MEDLINE, EMBASE and Cochrane Library databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies reporting clinical data following scarf osteotomy and scarf-Akin osteotomy for the treatment of hallux valgus were included and assessed. The level and quality of evidence of the included studies were also evaluated. RESULTS: Four studies were included. In total, 388 patients (408 toes) underwent scarf osteotomy alone and 287 patients (295 toes) underwent scarf-Akin osteotomy for the treatment of hallux valgus deformity. There was no difference in postoperative American orthopedic foot and ankle society scores (p = 0.7828), visual analog scale scores (p = 0.4558), hallux valgus angle (p = 0.5116), intermetatarsal angle (p = 0.4830), proximal to distal phalangeal articular angle (p = 0.2411) between the scarf alone cohort and the scarf-Akin cohort. Similarly, there was no difference in complication rates (p = 0.6881) nor secondary surgical procedure rates (p = 0.3678) between the 2 cohorts. Finally, there was a higher recurrence rate in the scarf-alone cohort (11.4%) compared to the scarf-Akin cohort (5.7%), but this was not statistically significant (p = 0.4414). CONCLUSION: This systematic review demonstrates lower recurrence rates following scarf-Akin osteotomy compared to scarf osteotomy alone for the treatment of hallux valgus deformity. No difference in complication rates were noted between the 2 cohorts. Our review demonstrates that both the scarf osteotomy and the scarf-Akin osteotomy may be effective and safe procedures, however, the scarf-Akin osteotomy may provide more long-term benefit in the setting of moderate to severe hallux valgus.

From jargon to clarity: Improving the readability of foot and ankle radiology reports with an artificial intelligence large language model.

BACKGROUND: The purpose of this study was to evaluate the efficacy of an Artificial Intelligence Large Language Model (AI-LLM) at improving the readability foot and ankle orthopedic radiology reports. METHODS: The radiology reports from 100 foot or ankle X-Rays, 100 computed tomography (CT) scans and 100 magnetic resonance imaging (MRI) scans were randomly sampled from the institution's database. The following prompt command was inserted into the AI-LLM: "Explain this radiology report to a patient in layman's terms in the second person: [Report Text]". The mean report length, Flesch reading ease score (FRES) and Flesch-Kincaid reading level (FKRL) were evaluated for both the original radiology report and the AI-LLM generated report. The accuracy of the information contained within the AI-LLM report was assessed via a 5-point Likert scale. Additionally, any "hallucinations" generated by the AI-LLM report were recorded. RESULTS: There was a statistically significant improvement in mean FRES scores in the AI-LLM generated X-Ray report (33.8 ± 6.8 to 72.7 ± 5.4), CT report (27.8 ± 4.6 to 67.5 ± 4.9) and MRI report (20.3 ± 7.2 to 66.9 ± 3.9), all p < 0.001. There was also a statistically significant improvement in mean FKRL scores in the AI-LLM generated X-Ray report (12.2 ± 1.1 to 8.5 ± 0.4), CT report (15.4 ± 2.0 to 8.4 ± 0.6) and MRI report (14.1 ± 1.6 to 8.5 ± 0.5), all p < 0.001. Superior FRES scores were observed in the AI-LLM generated X-Ray report compared to the AI-LLM generated CT report and MRI report, p < 0.001. The mean Likert score for the AI-LLM generated X-Ray report, CT report and MRI report was 4.0 ± 0.3, 3.9 ± 0.4, and 3.9 ± 0.4, respectively. The rate of hallucinations in the AI-LLM generated X-Ray report, CT report and MRI report was 4%, 7% and 6%, respectively. CONCLUSION: AI-LLM was an efficacious tool for improving the readability of foot and ankle radiological reports across multiple imaging modalities. Superior FRES scores together with superior Likert scores were observed in the X-Ray AI-LLM reports compared to the CT and MRI AI-LLM reports. This study demonstrates the potential use of AI-LLMs as a new patient-centric approach for enhancing patient understanding of their foot and ankle radiology reports. Jel Classifications: IV.

The significance of heterotopic ossification following total ankle arthroplasty: a systematic review and meta-analysis.

PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate the prevalence and clinical significance of heterotopic ossification (HO) following total ankle replacement (TAR). METHODS: During August 2023, the PubMed, Embase and Cochrane library databases were systematically reviewed to identify clinical studies reporting HO following TAR. Data regarding surgical characteristics, pathological characteristics, subjective clinical outcomes, ankle range of motion, radiographic outcomes, reoperation rates were extracted and analysed. RESULTS: Twenty-seven studies with 2639 patients (2695 ankles) at a weighed mean follow-up time of 52.8 ± 26.9 months were included. The pooled prevalence rate was 44.6% (0.25; 0.66). The implant with the highest rate of HO was the INBONE I (100%) and BOX (100%) implants. The most common modified Brooker staging was grade 1 (132 patients, 27.0%). Random effects models of standardized mean differences found no difference in American orthopedic foot and ankle society (AOFAS) scores, visual analog scale scores (VAS) and ankle range of motion (ROM) between patients with HO and patients without HO. Random effects models of correlation coefficients found no correlation between AOFAS, VAS and ROM and the presence of HO. The surgical intervention rate for symptomatic HO was 4.2%. CONCLUSION: This systematic review and meta-analysis found that HO is a common finding following TAR that is not associated with inferior clinical outcomes. Surgical intervention was required only for moderate-to-severe, symptomatic HO following TAR. This study is limited by the marked heterogeneity and low level and quality of evidence of the included studies. Further higher quality studies are warranted to determine the precise prevalence and impact of HO on outcomes following TAR.

Polyvinyl alcohol hydrogel implant for the treatment of hallux rigidus is associated with a high complication rate and moderate failure rate at short-term follow-up: a systematic review.

PURPOSE: Moderate-to-severe hallux rigidus is a debilitating pathology that is optimally treated with surgical intervention. Arthrodesis produces reliable clinical outcomes but is limited by restriction in 1st metatarsophalangeal joint range of motion. The advent of polyvinyl alcohol hydrogel (PVA) implants have produced early promise based on initial trials, but more recent studies have called into question the efficacy of this procedure. The purpose of this systematic review was to evaluate the clinical and radiological outcomes following the use of PVA for hallux rigidus. METHODS: The MEDLINE, EMBASE and Cochrane library databases were systematically reviewed using the preferred reporting items for systematic reviews and meta-analyses guidelines. 18 studies were included. RESULTS: In total, 1349 patients (1367 feet) underwent PVA at a weighted mean follow-up of 24.1 ± 11.1 months. There were 168 patients (169 feet) included in the cheilectomy cohort and 322 patients (322 feet) included in the arthrodesis cohort. All 3 cohorts produced comparable improvements in subjective clinical outcomes. Postoperative imaging findings in the PVA cohort included joint space narrowing, peri-implant fluid, peri-implant edema and erosion of the proximal phalanx. The complication rate in the PVA cohort, cheilectomy cohort and arthrodesis cohort was 27.9%, 11.8% and 24.1%, respectively. The failure rates in the PVA cohort, cheilectomy cohort and arthrodesis cohort was 14.8%, 0.3% and 9.0%, respectively. CONCLUSION: This systematic review demonstrated that PVA produced a high complication rate (27.9%) together with concerning postoperative imaging findings at short-term follow-up. In addition, a moderate failure rate (14.8%) and secondary surgical procedure rate (9.5%) was noted for the PVA cohort. The findings of this review calls into question the efficacy and safety of PVA for the treatment of hallux rigidus. LEVEL OF EVIDENCE: IV.

In-Office Needle Arthroscopy for the Foot and Ankle.

In-office needle arthroscopy (IONA) has been a readily available tool dating back to the 1990s, primarily for diagnostic purposes. This technique was not fully accepted and implemented because of significant limitations with the image quality and lack of instrumentation available to simultaneously treat the identified pathologies. However, recent advancements in IONA technology have made it possible to perform arthroscopic procedures under local anesthesia in the office setting, which once required a full operating suite. IONA has revolutionized how we treat foot and ankle pathologies in our practice. IONA allows the patient to be an active participant in the procedure and provides an interactive experience. IONA can be used to treat a range of foot and ankle pathologies, including anterior ankle impingement, posterior ankle impingement, osteochondral lesions of the ankle joint, hallux rigidus, lateral ankle ligament repair, and tendoscopic treatment of Achilles, peroneal, and posterior tibial tendon disorders. Excellent outcomes with regard to subjective clinical outcomes, return to play times, and complications have been reported following IONA for these pathologies.

Supramalleolar osteotomy for the treatment of ankle osteoarthritis leads to favourable outcomes and low complication rates at mid-term follow-up: a systematic review.

PURPOSE: The purpose of this systematic review was to evaluate both the clinical and radiographic outcomes following supramalleolar osteotomy (SMO) in patients with ankle osteoarthritis, and to analyse the level of evidence (LOE) and quality of evidence (QOE) of the included studies. METHODS: A systematic review of the MEDLINE, EMBASE, and Cochrane Library databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies reporting clinical data following SMO for the treatment of ankle osteoarthritis were included and assessed. The level and quality of evidence of the included studies were also evaluated. RESULTS: Twenty-four studies with 1160 patients (1182 ankles) were included. Overall, 78.8% patients presented with post-traumatic ankle osteoarthritis. The weighted mean AOFAS score improved from 52.6 ± 9.7 (range 33.8-78.4) preoperatively to 78.1 ± 5.7 postoperatively at weighted mean follow-up of 50.4 ± 18.6 months (range 24.5-99.0). The most frequently utilised radiographic parameter was the tibial anterior surface angle, which improved from a preoperative weighted mean of 86.3° ± 5.6° (range 76.0°-102.0°) to a postoperative weighted mean of 89.9° ± 3.7° (range 84.9°-99.6°). The complication rate was 5.1% with non-union as the most commonly reported complication (1.6%). Secondary procedures were carried out in 28.2% of patients, the most common of which was implant and hardware removal (17.6%). The failure rate was 6.8%. Two studies were LOE II, 3 studies were LOE III, and 19 studies were LOE IV. The mean Modified Coleman Methodology Score was 59.3 ± 6.6 and the mean MINORS criteria score of all the included studies was 9.5 ± 3.7. CONCLUSION: This systematic review demonstrates good clinical and radiological outcomes, together with a low failure rate at mid-term follow-up following supramalleolar osteotomy in patients with ankle osteoarthritis. However, a moderate reoperation rate (28.2%) was reported. A low failure rate (6.8%) was reported, which must be interpreted in light of the shortcomings of the design of the included studies and a relatively short follow-up period. In addition, there is a low level and quality of evidence in the current literature with inconsistent reporting of data which underscores the need for further higher quality research to be conducted. Our review highlights that SMO may be an effective and safe procedure in the setting of early-to-intermediate-stage ankle osteoarthritis. LEVEL OF EVIDENCE: IV.

Increased incidence of acute achilles tendon ruptures in the peri-pandemic COVID era with parallels to the 2021-22 NFL season.

PURPOSE: Acute Achilles tendon ruptures (AATRs) are a common sporting injury, whether for recreational athletes or elite athletes. Prior research has shown returning to physical activity after extended periods of inactivity leads to increased rates of musculoskeletal injuries. The purpose of this study was to investigate rates of acute Achilles' tendon ruptures at a single academic institute in the peri-COVID era, with corollary to the recent NFL season. METHODS: A retrospective search was conducted using current procedural terminology to identify the total number of Achilles acute primary repair surgeries performed from years 2017 to 2021. Non-operatively managed AATRs were identified from the same electronic medical record using ICD-10 codes. NFL data were obtained from publicly available sites according to previously validated studies. RESULTS: A total of 588 patients who sustained AATRs and underwent primary surgical repair were identified, primarily men (75.7%, n = 445), with an average age of 43.22 ± 14.4 years. The number and corresponding incidence of AATR repairs per year was: 2017: n = 124 (21.1%), 2018: n = 110 (18.7%), 2019: n = 130 (22.1%), 2020: n = 86 (14.6%), 2021: n = 138 (23.5%), indicating a 7.5% decrease in rate of AATRs from 2019 to 2020, followed by an 8.9% increase in incidence from 2020 to 2021. Within the NFL, the number of AATRs resulting in an injured reserve stint increased every regular season from 2019 to 2020: n = 11 (21.2%), to 2020-2021: n = 17 (32.7%), to this past 2021-2022 season: n = 24 (46.2%). CONCLUSION: AATR surgeries seem to have increased in 2021 following a 2020 COVID pandemic-induced quarantine for recreational athletes at a single academic institution and for professional athletes in the NFL, although these results are of questionable clinical significance. This provides prognostic information when counseling patients and athletes on return to activity or sport. LEVEL OF EVIDENCE: Level IV.

A qualitative analysis of Ethiopian and Eritrean Americans' initiation and continuation of hookah smoking.

Hookah smoking is emerging as a popular social practice and health behavior risk among Ethiopian and Eritrean Americans. This qualitative study was the second phase of a sequential exploratory mixed methods study and examined factors that enable the initiation and facilitate the continuation of hookah smoking among Ethiopian and Eritrean Americans. Semi-structured interviews were conducted with twenty-five Ethiopian and Eritrean American hookah smokers residing in the Washington, DC Metropolitan Area of the United States. Interview questions were guided by the Theory of Planned Behavior and addressed: (1) initiation of hookah smoking, (2) past and current patterns of hookah smoking, and (3) behavioral, control and normative beliefs toward hookah smoking. Several themes were identified under the core constructs of 'factors influencing hookah smoking initiation' and 'factors influencing hookah smoking continuation' such as curiosity, lack of health knowledge, socio-cultural acceptance, accessibility, flavor, physical dependence, physiological effects and social connections. Based on these findings, it is recommended that future prevention activities (e.g. health messages) be embedded into a comprehensive tobacco prevention approach to address individual misperceptions of harm and addiction, community social norms and environmental access around hookah smoking, which contribute to both initiation and continuation in the Ethiopian and Eritrean American populations.

Traditional Chinese medicine Jia Wei Gui Pi Tang improves behavioural and psychological symptoms of dementia and favourable positive emotions in patients.

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are challenging to manage, leading to caregiver burden and often to subsequent transfer of patients to a nursing home or psychiatric hospital for treatment. Eliciting favourable positive emotions should be an important goal in the treatment of negative emotions associated with BPSD. To date, no data have indicated that antipsychotic medications can improve positive emotions. BPSD are known to be associated with anxiety in patients with dementia. The traditional Chinese medicine Jia Wei Gui Pi Tang is officially indicated and approved for anxiety treatment in Japan. METHODS: Here, we performed a multicentre, randomised, observer-blind control study of the effect of Jia Wei Gui Pi Tang on BPSD in Alzheimer's disease (AD) patients. Patients with AD or AD with cerebral vascular disease were randomly divided into the Jia Wei Gui Pi Tang treatment group and the control group that received no traditional Chinese medicine. BPSD were scored using the Neuropsychiatric Inventory Nursing Home Version (NPI-NH) and by favourable positive emotions using the Delightful Emotional Index (DEI). RESULTS: A total of 63 participants (18 male and 45 female; mean age: 83.3 ± 6.0 years) were included in the study. Changes in NPI-NH scores differed significantly between the two groups (one-way analysis of variance, P < 0.001). Within the treatment group, there was a significant improvement in the NPI-NH score from 29.8 ± 17.3 at baseline to 13.2 ± 9.4 at the endpoint (paired t-test, P < 0.001), whereas there was no statistically significant change in the control group. Changes in DEI scores differed significantly between the two groups. Within the treatment group, there was a significant improvement in the DEI score from 24.3 ± 23.0 at baseline to 32.5 ± 21.2 at the endpoint (paired t-test, P = 0.001), whereas there was no statistically significant change in the control group. CONCLUSION: The traditional Chinese medicine Jia Wei Gui Pi Tang significantly improved both BPSD and positive emotions.

A 3-Decade, Single-Center Experience of Liver Transplantation for Cholangiocarcinoma: Impact of Era, Tumor Size, Location, and Neoadjuvant Therapy.

Liver transplantation (LT) for cholangiocarcinoma (CCA) remains limited to a small number of centers. Although the role of neoadjuvant therapy (NAT) has been explored over time, an in-depth analysis of NAT strategies remains limited. Furthermore, controversy exists regarding acceptable tumor size during patient selection for LT. This study explores the impact of era, tumor size, and NAT strategy on LT outcomes for CCA. We conducted a retrospective review of 53 patients with CCA treated with LT from 1985 to 2019; 19 hilar CCA (hCCA) and 30 intrahepatic CCA (iCCA) were included. The relative contributions of varying NAT (neoadjuvant chemotherapy [NAC], neoadjuvant local therapy [NALT], and combined NAC and NALT [NACLT]) as well as the implication of tumor size and era were analyzed. The primary endpoint was overall survival (OS). Compared with the old era (1985-2007), 5-year OS in patients who underwent LT in the recent era (2008-2019) showed a superior trend. The 5-year OS from initial treatment in patients receiving NACLT for hCCA and iCCA were 88% and 100% versus 9% and 41% in patients without it, respectively (P = 0.01 for hCCA; P = 0.02 for iCCA), whereas NAC or NALT alone did not show significant differences in OS versus no NAT (P > 0.05). Although 33 patients had large-size tumors (hCCA ≥ 30 mm, n = 12, or iCCA ≥ 50 mm, n = 21), tumor size had no impact on survival outcomes. Outcomes of LT for CCA seem to have improved over time. Multimodal NAT is associated with improved survival in LT for both iCCA and hCCA regardless of tumor size.

Visual Attention to Health Warning Labels on Waterpipe Venue Menus in Immersive Virtual Reality.

INTRODUCTION: This study examined how health warning labels (HWL) on a waterpipe venue menu captured and held the attention of consumers and influenced waterpipe tobacco smoking (WTS) attitudes, beliefs, and behaviors. AIMS AND METHODS: A randomized experiment (N = 96) of young adult waterpipe smokers was conducted in an immersive virtual reality laboratory. Participants viewed one of two virtual reality scenarios, a menu with an HWL and nicotine concentration or menu without an HWL and nicotine concentration. Eye-tracking metrics were collected, and participants completed posttest questionnaires on demographics, tobacco use history, and WTS attitudes, beliefs, and behaviors. T-tests were used to assess group differences, and a mediation analysis conducted to examine the relationship between the HWL and intention to quit WTS. RESULTS: Participants in the HWL group demonstrated greater visual attention to the warning and nicotine areas and less visual attention to the flavor and ingredients areas of the menu compared to the control group. The HWL group demonstrated greater negative attitudes toward WTS (p = .002), greater perceived risk of decreased lung function (p = .026), and greater intention to quit WTS (p = 0.003). The mediation model indicated the relationship between the HWL on a menu and intention to quit WTS was mediated by an increase in negative attitudes toward WTS. CONCLUSIONS: The HWLs on a menu captured and held the attention of consumers and increased negative attitudes, perceptions of health risk, and intention to quit WTS indicating potential benefit of including a warning label or nicotine concentration on menus to correct misperceptions of WTS. IMPLICATIONS: The study contributes to the broader literature on communicating the harms and risks of WTS. The findings suggest that HWL and nicotine concentration on waterpipe venue menus attract attention from consumers in environments comparable to the real world and the strategy warrants further exploration as a targeted policy intervention to educate the public and reduce the health burden of WTS.

'We're not gonna have a big quit if loose ones are around': urban, African American smokers' beliefs concerning single cigarette use reduction.

Single cigarette use (i.e. loosies, loose ones, singles) poses risks for smoking continuation among urban, African American smokers. There is, however, limited research to inform health education interventions addressing this behavior. We conducted 25 in-depth interviews with urban, African American users (ages 20-58 years) from Baltimore, MD and the District of Columbia in June and July 2018 to assess their beliefs about reducing single cigarette use. Interviews were guided by the Health Belief Model and its constructs of perceived benefits, perceived barriers, perceived susceptibility, perceived severity and self-efficacy. We analyzed qualitative data using framework analysis. Perceived benefits of reducing single cigarette use involved the avoidance of health risks, including concerns about buying fake cigarettes and exposure to unknown personal hygiene practices from sellers. Perceived barriers were the convenience of buying singles due to their availability, accessibility and low cost. Participants shared they were willing to use cognitive behavioral strategies to reduce their purchasing and use of singles. This study provides insights on potential intervention targets related to beliefs towards reducing single cigarette use. These findings can inform enforcement policies and health education interventions targeting single cigarette use among urban, African American smokers who use singles.

Lung cancer screening decisional needs among African American smokers of lower socioeconomic status.

OBJECTIVES: Adherence to most evidence-based cancer screenings is lower among African Americans due to system- and individual-level factors that contribute to persistent disparities. Given the recommendation for low-dose computed tomography (LDCT) screening among individuals at high risk for lung cancer, we sought to describe aspects of decision-making for LDCT among African Americans and to examine associations between select components of decision-making and screening-related intentions. DESIGN: African Americans (N = 119) with a long-term smoking history, aged 55-80 years, and without lung cancer were recruited to participate in a cross-sectional survey. We measured knowledge, awareness, decisional conflict, preferences, and values related to lung cancer screening. RESULTS: The majority of the study population was of lower socioeconomic status (67.2% had an annual income of ≤$20,000) and long-term current (79%) smokers. Participants had a median 20 pack-years smoking history. Most participants (65.8%) had not heard of LDCT and the total lung cancer screening knowledge score was M = 7.1/15.0 (SD = 1.8). Participants with higher scores on the importance of the pros and cons of screening expressed greater likelihood of talking with a doctor, family, and friends about screening (p's < .10). CONCLUSIONS: Findings have implications for addressing the decisional needs of lower socioeconomic African American current and former smokers to promote informed decision-making for LDCT.

Ex vivo biomechanical comparison of four Center of Rotation Angulation Based Leveling Osteotomy fixation methods.

OBJECTIVE: To compare the strength of four constructs used to secure an osteotomy in a Center of Rotation Angulation (CORA)-Based Leveling Osteotomy (CBLO) in an ex vivo model. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Thirty-two canine tibiae from 17 skeletally mature cadavers weighing between 18 and 33.2 kg. METHODS: Thirty-two paired tibiae with patella and patellar tendon were collected. Each tibia was randomly allocated to a construct group: plate and pin (Plate), plate with countersink compression screw (HCS), plate with tension band (TB), or plate with HCS and TB (HCSTB). Samples were loaded by distraction until failure. The stiffness, yield load, and ultimate load were compared between each fixation method. RESULTS: No difference in stiffness of the constructs was detected between groups (p = .6937). Yield load for the HCSTB group (1211.06 N) was greater than the TB group (1016.41 N), the HCS group (907.20 N), and the Plate group (787.73 N) (p = .0069). The ultimate load for the HCSTB group (1387.82 N) was greater than the TB group (1076.36 N), HCS group (926.62 N), and the Plate group (774.35 N) (p = .0004). CONCLUSIONS: CBLO fixation augmented with a TB and HCS provided a stronger construct that withstood a greater yield load and ultimate load than either augmentation strategy alone. CLINICAL SIGNIFICANCE: Augmenting a CBLO fixation with a TB and a HCS can provide increased construct strength.