Logistical Reasons Research Articles

Middle-grade led Expedited Gall bladder lists: Is it safe and feasible?

Gallstone-related acute admissions account for a significant percentage of acute general surgery admissions. Providing a dedicated expedited gall bladder list service to deal with these cases appears to be not only clinically effective but also cost-effective. There are various logistical reasons why hospitals are unable to provide such dedicated lists, inadequate surgical staff being one of them. We initiated a middle-grade-led expedited gall bladder list with indirect consultant oversight at our hospital as a consultant-led list was not feasible. This study evaluates the safety and efficacy of this service post-implementation. A retrospective analysis was conducted on prospectively collected data from February 2022 to September 2023. Patients were triaged using a dedicated questionnaire and operated on within 2-8 weeks of admission. The outcomes measured included complications, readmissions and the need for consultant opinion and assistance. Amongst 101 patients, the mean age was 50.59 ± 15.25 years, with a majority being female and having an American Society of Anaesthesiologists grade of 2. Consultant assistance was required in 14 cases, with 9 requiring active participation. Complications were comparable to national averages, with four cases of bile leaks and one small bowel injury. Six readmissions were recorded for various postoperative issues. The middle-grade led expedited gall bladder service demonstrated a safe and effective alternative to consultant-led lists, offering a pragmatic approach to addressing surgical demands within the constraints of staff and facility limitations.

Maintenance Intramuscular Ketamine-Assisted Psychotherapy, a Retrospective Chart Review of Efficacy, Adverse Events, and Dropouts from a Community Practice

ABSTRACT The use of ketamine and ketamine-assisted psychotherapy (KAP) for treatment of depression has grown dramatically, though much of these data are short term. The clinical profile of maintenance treatment remains poorly characterized. We assessed maintenance KAP for efficacy, tolerability, and reasons for dropout. This observational study retrospectively analyzed electronic health records from an addiction psychiatry practice offering intramuscular ketamine with contemporaneous psychotherapy for the treatment of depression. All patients receiving treatment between January 2016 and September 2022 were included, yielding 1,114 sessions from 70 patients. The response was quantified via the clinical global impression-severity scale. Side effects and reasons for dropout were extracted from charts. Comorbidities include an anxiety disorder (79%) or substance use disorder (49%). The induction yielded 82% response, maintained above 80% after six months (sessions q21 days, 1.13 mg/kg mean dose). Many (38%) remained in treatment for at least one year. Nausea management accounted for nearly all as-needed medication use. Antihypertensives were seldom utilized. Chronic side effects were notable for one case of ketamine use disorder, resulting in residential treatment. Dropouts cited logistical reasons half the time and side effects only 9.7% of the time. KAP yielded robust improvements in mood, anxiety, and substance use. Maintenance sessions effectively extended benefit and were largely well tolerated.

Systematic vitamin K antagonist reversal with prothrombin complex concentrate in patients with mild traumatic brain injury: randomized controlled trial.

Traumatic brain injury (TBI) in patients on vitamin K antagonists (VKAs) is linked to a high rate of intracranial hemorrhage (ICH). Rapid reversal can reduce ICH progression and mortality, but its effectiveness depends on the time between bleeding onset and coagulation normalization. The PREVACT study aimed to assess the efficacy and safety of prompt systematic reversal of anticoagulation in patients presenting to emergency departments (EDs) for recent mild-TBI while receiving a VKA. A randomized, open-label, blinded-endpoint clinical trial was conducted in 21 French EDs. Patients receiving a VKA, having experienced a TBI within the last 6 h, and presenting a Glasgow Coma Score ≥13 were included. Patients were randomized to systematic immediate VKA reversal with 25 IU/kg of four-factor prothrombin complex concentrate (4f-PCC) before any investigation (intervention group) or standard-of-care signifying reversal only if the initial cranial computed tomography (CT) scan indicated ICH (control group). The primary outcome was the rate of ICH detected on a cranial CT scan 24 h post-inclusion. The study was prematurely stopped for logistic reasons after the randomization of 202 patients (101 and 101 in the intervention and control groups, respectively, mean age 90; 51.8% female). On the 24-h cranial CT scan, 6 of 98 patients (6.1%) in the intervention group manifested ICH vs. 12 of 99 patients (12.1%) in the control group [odds ratio: 0.47 (95% confidence interval: 0.14-1.44); P = 0.215]. In patients with recent mild-TBI receiving a VKA, systematic prompt reversal with 4f-PCC did not statistically significantly reduce ICH rate at 24 h. However, the study was prematurely stopped and does not exclude a clinically relevant benefit of the strategy tested. Clinicaltrials.gov (NCT01961804).

Dopamine Cell-Based Replacement Therapies.

Parkinson's disease (PD) is a common disorder that has, as part of its core pathology, the loss of the nigral dopaminergic nerve cells that project to the striatum. Replacing this loss with dopaminergic drugs has been the mainstay of therapy in PD for more than 50 years and while offering significant clinical benefit, especially in early-stage disease, leads to side effects over time. A conceptually more effective way to treat this aspect of the PD pathology would be to replace the missing dopaminergic system with grafts of new dopamine cells. This approach has been investigated for nearly 40 years using a variety of different dopamine cell sources. To date, a proof-of-principle has been shown using human fetal dopamine cells in patients with PD, but the more widespread adoption of this approach has been hampered by logistical reasons around tissue supply, the ethics of the cell source, and, most importantly, by the inconsistent results shown across trials, which in some cases have reported worrying side effects. Reasons for all this have been discussed extensively in the literature and one solution may lie in the development of new human stem cell-derived dopamine cells, which are now just entering first in human clinical trials.

Barriers to Voice Therapy: A Report From Beginners, Performers, and Teachers of Carnatic Music

AimThe study aimed to understand awareness, perceptions, and barriers to voice therapy among beginners, performers, and teachers of Carnatic music. MethodBarriers from the literature were obtained, and the guide for the semistructured interview was developed. Twelve Carnatic singers (four each identified as beginners, performers, and teachers) were contacted and interviewed on an online platform. The interviews were audio recorded and transcribed verbatim. The transcriptions were loaded and coded in the Qualitative Data Analysis Miner Lite software. The codes were grouped according to beginners, performers, and teachers. The codes were analyzed using a deductive-inductive approach, and thematic analysis was performed to report the findings. Results and DiscussionOverall, three themes emerged during thematic analysis. Beginners were familiar with the signs and symptoms of voice problems related to singing. The performers and teachers were able to identify causes related to posture and lifestyle that impacted singing. The need for seeking help differed with expertise and personal experience. Beginners believed in home remedies as their first choice and considered them sufficient to resolve voice problems. Performers and teachers believed in modifying singing techniques as a remedy to voice problems and considered medical intervention only as a second option. Mixed perceptions about the outcomes of voice therapy and the anticipation of quick results from voice therapy/therapists were major deterrents to seeking professional voice care. Beginners’ views on perceptions of medical intervention for voice problems were strongly influenced by their singing teachers. Beginners also expressed limited access to voice therapy due to several logistical reasons and financial constraints as barriers to attending therapy. Performers and teachers sought medical help as a final resort since the presence of voice problems affected their livelihoods and careers. ConclusionThis qualitative study highlights socioculturally relevant information deeply rooted in the belief systems of Carnatic musicians. These opinions from beginners, performers, and teachers are important to be addressed during counseling and awareness sessions to support vocal health in this sophisticated but vulnerable professional voice group.

The influence of prolonged antibiotic treatment before lead extraction procedures on the outcomes of device reimplantation in cardiac implantable electronic device infections

Abstract Background Cardiac implantable electronic devices (CIED) related infections have a considerable clinical and economic burden in the cohort of CIED-implanted patients and require a complex and thoughtful approach of the "heart team". Complete CIED removal is recommended for all patients with confirmed CIED infection, but the optimal duration of antibiotic therapy (AT) before lead extraction (LE) and its impact on the time of reimplantation are still debatable [1-2]. This study was aimed to evaluate the impact of prolonged AT before LE on the outcomes of device reimplantation. Methods Consecutive cases of LE due to CIED infection at our centre from 2013 to 2022 were reviewed. Our approach assumed the duration of AT for a minimum of 2 weeks for patients with pocket infection (PI), and at least 4 weeks for endocarditis with the exception of non-response to the AT. The target time for reimplantation was 2-3 days after LE with the exception of uncontrolled infection, positive blood culture, logistical reasons or reevaluation of pacing indications during follow-up. Results From a total of 256 LE, 202 (in 198 patients) were due to CIED infection (pacemaker-67,8%, CRT-19,8%, ICD-12,4%). In 62,4% of the cases there was only PI, in 24,7% only endocarditis and in 12,9% it was concomitant. Systemic infection was found in 43,1% of the cases. The mean dwell time of the leads was 92.2±5.0 months (n=201, median 84, IQR 29.0-132.0). In cases of PI, the mean time of AT before LE was 21,7±1,0 days (n=124, median 21, IQR 14.0-28.0), whereas it was 31,6±1,7 days (n=76, median 28, IQR 21.0-42.0) in cases of endocarditis (p<0.05). The duration of AT after LE was 17.7±0.8 days (n=121, median 14, IQR 14.0-21.0) in cases of PI and 22.7±1.4 days (n=76, median 21, IQR 14.0-28.0) in cases of endocarditis (p<0.05). Procedural success was achieved in 98,5% and the procedural failure rate was 1,5%. Major complication rate was 2,5% and minor complication rate was 8,9%. There was no intraprocedural death. Device reimplantation after LE was performed in 68,8% (139) of all patients. The majority of reimplantations (57,6%) occurred within 7 days after LE (figure 1). The mean reimplantation time was 43.6±12.1 days (n=135, median 6, IQR 4.0-15.0), without statistically significant difference in time to reimplantation between PI and endocarditis (p=0.78). 9 patients were reimplanted with epicardial ventricular lead and 1 with leadless pacemaker. Total reinfection rate was 2% (4), all the cases were due to contralateral PI with reimplantation after LE in 11, 12, 38 and 596 days, respectively. One of the patients was also diagnosed with an allergy to silicone, nickel and palladium. Mortality rate during the first 30 days was 5%. Uneventful 12-month follow-up was achieved by 80,2%. Conclusions Appropriate prolonged AT before LE led to feasibility of early device reimplantation with a low rate of reinfection.Time to preimplantation

A retrospective study on real world, 2-stent left main bifurcation PCI using DK crush technique with IVUS guidance - a single center experience

Abstract Objectives The aim of this study is to investigate clinical outcome of the IVUS guided 2-stent bifurcation strategy using DK crush technique performed in a complex Left Main (LM) bifurcation lesions defined according to DEFINITION study in our local setting. We seek to assess the composite endpoint of target vessel failure (TVF) at 9-12 months. Methods All patients underwent IVUS guided 2-stent Bifurcation PCI with DK crush technique for complex LM bifurcation lesions defined by the DEFINITION criteria performed in a heart institute from 1.1.2019 to 31.7.2023 were included..Patient baseline characteristics, post-procedural and 12-months follow-up outcomes including cardiac death,myocardial infarction (MI),rate of target vessel failure (TVF),rate of stent thrombosis (ST) and major adverse coronary event (MACE) were analysed.Exclusion criteria are patients age <18 years and previous stenting in the target vessel Results A total of 50 patients were included in this analysis. Mean age was 64.3±9.1 years with predominant males (n= 38, 76%).Majority were hypertensive (n=37, 74%) and diabetes mellitus accounted for 32 (64%) cases.Patients with pre-existing coronary artery disease were 39 (78%) cases. 40% presented with history of recent myocardial infarction (MI), 12% had new onset angina and 6% had heart failure. Pre-existing chronic renal failure (18%) and history of CVA (2%). Among chronic renal failure cases, 50% had eGFR <50 during index procedure.Additionally, previous PCI was performed in 22 cases (44%) and 2 previous CABG cases included (4%).Majority of the cases were performed as staged elective procedure ( n=45, 90%) and others were indicated for ACS ( n=5, 10%). Radial approach was predominantly preferred with 25 cases (50%), where additional 5 cases (10%) were converted to femoral approach due to severe radial spasm. Among these 50 cases, 1 case required additional PCI to CTO LAD and mid LCX, while 7 cases (14%) had calcified lesions requiring scoring / cutting balloons and atherectomy device utilization for adequate lesion preparation prior to bifurcation stenting.All 50 patients received combination of both aspirin and a P2Y12 inhibitors for 12 months. Follow up done at at 30-day, 60-days and 1 year after the index procedure.Clinical follow-up were available in 46 (92%) patients only.4 cases were lost to follow up due to logistic reasons. At 1 year follow-up, cardiac death occurred in 5 (10.9%) patients, out of which 3 (6.5%) cases were cardiac related and 2 (4.4%) are non-cardiac. Major adverse cardiac events (MACE) and target vessel failure (TVF) occurred in total 4 (8.7%) cases, where 3 (6.5%) cases resulted in cardiac death and 1 (2.2%) case had MI and clinically driven target lesion revascularization. Conclusion Our experience demonstrates that IVUS guided, upfront 2-stent Bifurcation PCI using DK crush technique for complex bifurcation lesions is effective and safe with a low MACE and TLR rate at 1 year follow-up.

Cohen vs Pfannenstiel cesarean skin incision for body mass index ≥35 kg/m2: a randomized controlled trial

Background: Maternal obesity is recognized as a significant risk factor for adverse pregnancy outcomes, including increased cesarean delivery rates and heightened surgical complications. It is unclear if the Cohen or Pfannenstiel skin incisions at cesarean delivery are associated with different outcomes. Objective: To evaluate the impact of either Cohen or Pfannenstiel cesarean skin incision type on maternal morbidity. Study Design: Pregnant individuals with a BMI of ≥35 kg/m2, carrying either singleton or multiple gestations, were consented prenatally and in labor. Eligible participants who underwent a cesarean delivery between 24 and 41 weeks of gestation were randomized to either Pfannenstiel or Cohen skin incisions at Thomas Jefferson University Hospital from October 2016 to March 2020. The study aimed to recruit 284 participants based on a sample size calculation assuming a 50% reduction in wound complications with Cohen versus Pfannenstiel incisions (80% power, α=0.05), but recruitment was terminated early after 72 participants were randomized. The primary outcome was a composite maternal morbidity within six weeks, which consisted of the following: wound infection, hematoma, seroma, separation of skin ≥1 cm, readmission for wound complications, endometritis, and postpartum hemorrhage. Statistical analyses included bivariate tests, t-tests, and non-parametric analyses. Results: Of 331 pregnant individuals consented prenatally and in labor, 72 eventually underwent cesarean delivery and were randomized, 34 to Cohen and 38 to Pfannenstiel skin incisions. The mean BMI was >42 kg/m2, about two thirds of the patients had a pannus, 56% were Black, 47% had diabetes, and 56% hypertensive disorders. The primary outcome of composite maternal morbidity occurred in 47.1% in the Cohen and 36.8% in the Pfannenstiel groups (RR 1.24, 95% CI 0.71-2.08), and was also similar regardless of the presence of a pannus, or by degree of obesity. Surgical site infection, hematoma, seroma, wound separation/dehiscence, endometritis, and postpartum hemorrhage were each similar between Cohen and Pfannenstiel participants. Neonatal outcomes were also similar between the Cohen and Pfannenstiel groups, except that the Cohen group was found to have statistically significant lower Apgar score at 5 minutes and higher need for respiratory support compared to the Pfannenstiel group, possibly related to the trend for a longer time from skin incision to delivery. Physicians were found to be significantly less satisfied with the Cohen compared to the Pfannenstiel incision. Conclusion: In pregnant patients with BMI of ≥35 kg/m2, obstetrical providers can chose from either a Cohen or an Pfannenstiel skin incision, as they are associated in general with similar outcomes, except for lower Apgar scores and lower physician satisfaction associated with the Cohen incision. The findings of this study are limited by its early cessation for logistical reasons, leading to an underpowered analysis. It is crucial to acknowledge that these results must be interpreted cautiously due to the reduced sample size and the circumstances surrounding the study's termination. These data can inform future trial design and implementation as well as fuel individual patient level meta-analyses on this topic.

Real-world experience with long-term albumin in patients with cirrhosis and ascites

Background and AimsLong-term albumin (LTA) is currently standard of care for patients with decompensated cirrhosis in many Italian hepatological centres. This real-life study aimed to describe patient, logistical and treatment-related characteristics in daily clinical practice and to identify predictors of response. MethodsMulticentre, retrospective, observational study in patients with cirrhosis and ascites receiving LTA between 01/2016 and 02/2022 and followed until death, TIPS, transplantation or 02/2023. Results312 patients, the majority with alcohol-related cirrhosis, were included. At baseline, median Child-Pugh was 8, MELD 15, and MELD-Na 18. Ascites was grade 2 in 55% of patients, grade 3 in 35% and refractory in 27%, while 47% had paracentesis in the previous 6 months. Median LTA was 10 months with a median dose of 40 g/week.Ascites resolved to grade 0-1 in 34% of patients within the first 3 months and 56% at the end of treatment. Predictors of ascites resolution were age (p=0.007), baseline grade of ascites (p=0.007), no paracentesis in the previous 6 months (p=0.001), etiological treatment in the past 12 months or during LTA (p=0.005), weekly albumin dose (p=0.014) and serum albumin concentration of 40 g/L after one month of treatment (p=0.017). Of the 83 patients with refractory ascites at inclusion, 26% had grade 0/1 ascites at the last observation. No severe albumin-related side-effects were reported and only 1% discontinued due to logistic reasons. ConclusionsLTA is feasible as an outpatient treatment for the management of ascites. In the current study, more than half of patients receiving LTA on top of diuretics resolved their ascites, including some with refractory ascites. Predictors of response to LTA provide useful information for tailoring treatment. IMPACT AND IMPLICATIONSThe ANSWER randomized clinical trial has shown that long-term albumin treatment (LTA) is an effective approach for the management of patients with cirrhosis and ascites. This observational study provides novel information on target patients, modalities and length of treatment, predictors of ascites resolution, stopping criteria, and clinical trajectories of patients on treatment.LTA is a feasible option in the daily clinical practice for the management of ascites when given on top of diuretics. Rather than an alternative therapy, LTA should be integrated with the other treatments options already available for patients with difficult-to-treat ascites. The predictive factors of response identified in the present study can help physicians to individualize LTA and optimize the decision-making process.

Virtual dental autopsy: undertaking forensic dental identification remotely using an intra-oral video camera.

The aim of this study was to evaluate whether a forensic odontologist working remotely could accurately undertake forensic dental identifications using videos produced by non-dental forensic staff operating an intra-oral video camera (IOVC). The study's aims were to assess the accuracy and time taken to perform remote forensic dental identifications in this manner. Eight cadavers from the Centre for Anatomy and Human Identification (CAHID), University of Dundee, UK, were examined by a forensic odontologist via a traditional dental examination. Their dental condition was recorded to serve as ante-mortem records for this study. Videos of each dentition were produced using an IOVC operated by a medical student. Post-mortem records were produced for each dentition from the videos by a remote second forensic odontologist who was not present at the traditional dental examination. The ante-mortem and post-mortem records were then compared, and identification was classified as positively established, possible or excluded. Established identifications were positively made in all eight cases although there were some non-critical inconsistencies between ante-mortem and post-mortem records. Before the second opinion, 85.6% of the teeth per study subject were charted consistently. After the second opinion, the percentage of consistency increased to 97.2%. Each video on average was about 4.13 minutes in duration and the average time taken to interpret and chart the post-mortem dental examination at the first attempt was 11.63 minutes. The time taken to chart from the videos was greater than is typical of a traditional dental examination. This pilot study supports the feasibility of undertaking remote dental identification. This novel "tele-dental virtopsy" approach could be a viable alternative to a traditional post-mortem dental examination, in situations where access to forensic dental services is difficult or limited due to geographical, logistical, safety, and/or political reasons.

Coverage of cervical cancer prevention interventions among people in Australia who inject drugs

BackgroundThe human papillomavirus (HPV) vaccine and regular (i.e., every five years) cervical screening are essential to prevent cervical cancer. Australia has high overall coverage of both interventions but little is known about coverage among people who inject drugs. and known barriers to preventive care among this population may extend to cervical cancer control measures. MethodsData were obtained from the 2023 Illicit Drug Reporting System interviews, in which people who regularly inject drugs participated. The sample was restricted to people with a cervix, with participants aged 25–74 years eligible for the National Cervical Screening Program and participants born after 1980 eligible for HPV vaccination. Age-standardised prevalence ratios were used to compare coverage among this sample to the Australian general population; other results were summarised descriptively. FindingsAmong participants eligible for screening (n = 243), most (96.7 %) reported lifetime uptake, while 70.2 % had been screened during the past five years, which was similar to the general population (prevalence ratio [PR]: 1.14, 95 % confidence interval [CI]: 0.96–1.31). Among those never or overdue for screening (n = 57), one third (31.7 %) were aware that self-sampling is available and barriers to screening varied, with similar numbers reporting personal (e.g., ‘I didn't know I needed to’), logistical (e.g., ‘I don't have time’), and test-related reasons (e.g., ‘the test is uncomfortable/painful’). Among participants eligible for HPV vaccination (n = 99), coverage was 27.2 %, 38 % lower than the general population (PR: 0.62, 95 % CI: 0.39–0.86). ConclusionsCervical screening coverage among this sample of people who inject drugs was similar to the Australian population. Health promotion messaging that focuses on the availability of self-sampling and the importance of regular screening may improve coverage among those overdue for screening. HPV vaccination was lower than the general population, warranting targeted efforts to offer the vaccine to eligible people who inject drugs.

Readiness and Barriers Toward Voice Therapy Among Indian Classical Singers and Western Singers – A Scoping Review

ABSTRACT This scoping review explored the literature on different barriers and readiness toward voice therapy among singers. For the search, key terms were formulated, and six databases (Medline, PubMed, Scopus, SpringerLink, Web of Science, and Google Scholar) were used. After title and abstract-level screening, 12 full-length articles that identified barriers were reviewed and compiled using the PRISMA flow chart. However, no research related to readiness for voice therapy among singers was identified. The barriers were categorized into two broad categories (internal and external) and eight subcategories. Twenty-five barriers were categorized into nine sub-themes, such as awareness, knowledge of voice therapy, mental status of the singer, referral, financial reasons, perceptions of voice therapy by music teachers, perceptions of voice therapy by singers, logistic reasons, and accessibility. From the 12 full-length articles, informations such as target population, study design, objectives, and methods used to elicit the barriers were analyzed, and lacunae in the method used to obtain barriers were identified. These findings would be beneficial in developing tools to assess the barriers and readiness for voice therapy among singers and can be applied to improve compliance and concordance with voice interventions.

Odynophagia and Retrosternal Pain Are Common in Eosinophilic Esophagitis and Associated with an Increased Overall Symptom Severity

Background and AimsDysphagia is the hallmark symptom in eosinophilic esophagitis (EoE). However, data are limited regarding the overall prevalence and potential implications of atypical symptoms like odynophagia and retrosternal pain.MethodsPatients enrolled into the Swiss EoE cohort study (SEECS) were analyzed regarding the presence of odynophagia and retrosternal pain. Demographics, other EoE-related symptoms, histologic and endoscopic activity were compared between EoE-patients with vs. without odynophagia and/or retrosternal pain.Results474 patients (75.2% male) were analyzed. In their individual course of disease 110 (23.2%) patients stated to have ever experienced odynophagia and 64 (13.5%) retrosternal pain independent of food intake, 24 (5%) patients complained about both symptoms. Patients with odynophagia consistently scored higher in symptom severity (p < 0.001), EREFS score (median 3.0 vs. 2.0, p = 0.006), histologic activity and a lower quality of life (p = 0.001) compared to patients without odynophagia. Sex, age at diagnosis, EoE-specific treatment, complications such as candida or viral esophagitis and disease duration were similar in patients with vs. without odynophagia. Also patients with retrosternal pain scored higher in symptom severity (2.0 vs. 1.0, p = 0.001 and 2.0 vs. 1.0, p < 0.001 in physician and patient questionnaire assessment, respectively). However, there was neither a difference in endoscopic/histologic disease activity nor in quality of life according to presence or absence of retrosternal pain. Due to logistic reasons, a stratification regarding the presence of concomitant dysphagia was not possible.ConclusionOdynophagia and swallowing-independent retrosternal pain are common symptoms in patients with EoE, associate with an overall higher EoE-related symptom severity and for the case of odynophagia lower quality of life. However, the influence of concomitant dysphagia and its severity remains unclear and needs to be included in future analyses.

Arthroplasty at Very High Altitude with Restricted Resources: Our Experience and Review of Literature.

Patients living in high altitudes are often deprived of total knee arthroplasty (TKA) due to logistic reasons, economic, and social challenges in performing surgical procedures for management of knee pain. Surgical procedures in high-altitude dwellers have associated risk of deep venous thrombosis/pulmonary embolism (DVT/PE). In patients undergoing these procedures at lower altitudes, return to high altitudes can cause high-altitude pulmonary edema (HAPE). We share our experience of performing TKA in high-altitude dwellers by setting up a surgical camp at 11,000 feet. A retrospective assessment of patients undergoing total knee arthroplasty at a camp set up at 11,000 feet between 2014 and 2020 was undertaken. Follow-up data of patients which included clinical assessment by the Knee Society Score (KSS) and complications like DVT, infection, residual deformity, etc. were included in the study. Radiographic evaluation to look for evidence of implant loosening was also inculcated. 132 patients (202 knee joints in 50 male and 82 female patients) underwent TKA during annual camps. The average follow-up of patients was 60months. Mean pre-operative KSS was 38, which was increased to 83 at 1-year follow-up post-surgery. There was no evidence of DVT or superficial or deep infection in any patient in the post-operative period. With this study, we want to highlight that total knee arthroplasty can be safely performed at high altitudes and remote areas with limited health facilities. We believe it is a safer and more convenient prospect for the residents of high-altitude regions. III.

Participant adherence in a lung cancer screening (LCS) program in a non-smoking population.

10556 Background: LCS guidelines in smoking populations includes an annual low-dose CT Chest (LDCT) scan. Historically, real-world adherence to repeat imaging following the baseline LDCT has been low at 22% (Silvestri et al. Chest 2023). Various reasons for non-adherence have been cited and can be amplified in populations where English is not the primary language, low health literacy, or logistical reasons that interfere with scheduling. We are conducting the Female Asian Nonsmoker Screening Study (FANSS), which is a pilot study for Asian women with no smoking history to provide LDCTs to this population. We describe the strategies utilized to address potential barriers to adherence and report the participant (pt) adherence observed to date for this population. Methods: FANSS is an IRB-approved trial that provides LDCTs annually for 3 years and has an interim follow-up phone call every 6 months. All aspects of the study other than the LDCT could be conducted virtually pending pt preference. All pt interactions were conducted in the pt’s requested language. LDCTs were interpreted according to Lung-RADS. Review of the LDCT results were available in-person or virtually by a nurse practitioner or the principal investigator. The timeline for the 2nd and 3rd LDCT after the baseline scan was determined as follows: pts with negative findings were recommended for a repeat LDCT in 1 year; pts with suspicious findings were reviewed at the NYU Multidisciplinary Nodule Board and recommended for a repeated LDCT in a 3 or 6 month interval. A bilingual (English and Chinese speaking) research coordinator and medical secretaries reached out to pts at their preferred contact (email, phone, or text) for scheduling the follow-up LDCT. Up to three attempts to reach pts to schedule their follow-up LDCT were made. Results: From 3/5/21 to 1/27/24, 634 subjects completed their baseline LDCTs. Language interpretation services were utilized in 30% of pts. As of 1/27/24, 215 pts were due for their 2nd LDCT: 195 (91%) completed (186) or scheduled (9) the LDCT, 5 pts withdrew their consent, and 15 did not complete the scan. The main reasons for not completing the scans were: living outside New York City, other health concerns, and lost to follow-up. As of 1/27/24, 95 pts were due for their 3rd LDCT: 87 (92%) completed (82) and scheduled (5) the LDCT, and 8 did not complete the scan due to being lost to follow-up. Conclusions: The FANSS population is a unique pt cohort comprised of all Asian women who do not qualify for current LCS guidelines. Interventions to address potential adherence issues were implemented. In our research-based setting, virtual conduct of most of the study procedures allowed pt flexibility. Pt outreach to ensure follow-up by contacting through various methods also ensured adherence of &gt;90%. These interventions can be considered for use in other LCS programs to improve adherence to LCS follow-up.

Outcomes with perioperative durvalumab (D) in pts with resectable NSCLC and baseline N2 lymph node involvement (N2 R-NSCLC): An exploratory subgroup analysis of AEGEAN.

8011 Background: In the phase 3 AEGEAN study (NCT03800134), perioperative D + neoadj chemotherapy (CT) vs neoadj CT alone significantly improved the primary EPs of event-free survival (EFS) and pathological complete response (pCR; absence of residual viable tumor [RVT] in resection specimen, incl. primary tumor and sampled lymph nodes) with manageable safety in pts with R-NSCLC (modified ITT [mITT] population). Here, we report exploratory analyses of pts in AEGEAN with baseline N2 nodal status. Methods: Pts with Tx-naïve R-NSCLC (stage II–IIIB[N2]; AJCC 8th ed) were randomized (1:1) to 4 cycles of platinum-based CT plus D 1500 mg IV or placebo (PBO) Q3W before surgery (Sx), followed by D or PBO (Q4W, 12 cycles) after Sx. The mITT population excluded pts with known EGFR/ ALK alterations. Efficacy was assessed in an mITT subpopulation with baseline N2 nodal status (per investigator). Safety was assessed in all N2 R-NSCLC pts who had ≥1 Tx dose. Results: Of 740 pts in the mITT population, 366 (49.5%) had baseline N2 nodal status (D, n = 181; PBO, n = 185). In the N2 subgroup, 83.4% in the D arm and 84.9% in the PBO arm completed 4 cycles of platinum-doublet CT; 77.9% and 77.8%, respectively, had Sx; and 73.5% and 71.9% completed Sx. In the N2 subgroup, similar to the overall mITT population, EFS was prolonged in the D vs PBO arm (HR, 0.63 [95% CI: 0.43–0.90]); rates of pCR (16.6% vs 4.9%; difference, 11.7% [95% CI: 5.6–18.4]) and major pathological response (MPR, ≤10% RVT in primary tumor; 32.6% vs 15.1%; difference, 17.5% [95% CI: 8.8–26.0]) were higher in the D vs PBO arm. While EFS benefit in the D vs PBO arm was similar among pts with single- (HR, 0.61 [95% CI: 0.39–0.94]) or multi-station N2 (HR, 0.69 [95% CI: 0.33–1.38]), pCR benefit was less pronounced in multi-station pts (difference in pCR rate, 13.9% [95% CI: 6.6–21.7] for single-station N2 vs 3.8% [95% CI: –9.2–18.8] for multi-station N2). Among pts in the N2 subgroup who had Sx, similar proportions in the D and PBO arms had open (47.5% vs 50.0%) and minimally invasive procedures (50.4% vs 46.5%); 9.2% vs 11.1% had pneumonectomy (9.2% vs 9.6% in the overall mITT population). Of pts in the N2 subgroup who completed Sx, the proportion with R0 resection in the D vs PBO arm (94.7% vs 91.7%) was similar to that in the overall mITT population. Sx was delayed in a similar proportion who had Sx in the D vs PBO arm (19.9% vs 23.6%, respectively), most commonly for logistical reasons (e.g., scheduling issues). Among 394 pts who received Tx (N2 safety analysis subset; D, n = 200; PBO, n = 194), max grade 3/4 any-cause AEs occurred in 38.5% vs 41.8% in the D and PBO arm, respectively, similar to rates in the overall safety analysis set. Conclusions: With clinically meaningful improvement in efficacy, no adverse impact on Sx outcomes and a manageable safety profile, the addition of perioperative D to neoadj CT remains a potential new Tx option for pts with N2 R-NSCLC. Clinical trial information: NCT03800134 .

Analysing vaccine efficacy evaluated in phase 3 clinical trials carried out during outbreaks

In this paper we examine several definitions of vaccine efficacy (VE) that we found in the literature, for diseases that express themselves in outbreaks, that is, when the force of infection grows in time, reaches a maximum and then vanishes. The fact that the disease occurs in outbreaks results in several problems that we analyse. We propose a mathematical model that allows the calculation of VE for several scenarios. Vaccine trials usually needs a large number of volunteers that must be enrolled. Ideally, all volunteers should be enrolled in approximately the same time, but this is generally impossible for logistic reasons and they are enrolled in a fashion that can be replaced by a continuous density function (for example, a Gaussian function). The outbreak can also be replaced by a continuous density function, and the use of these density functions simplifies the calculations. Assuming, for example Gaussian functions, one of the problems one can immediately notice is that the peak of the two curves do not occur at the same time. The model allows us to conclude: First, the calculated vaccine efficacy decreases when the force of infection increases; Second, the calculated vaccine efficacy decreases when the gap between the peak in the force of infection and the peak in the enrollment rate increases; Third, different trial protocols can be simulated with this model; different vaccine efficacy definitions can be calculated and in our simulations, all result are approximately the same. The final, and perhaps most important conclusion of our model, is that vaccine efficacy calculated during outbreaks must be carefully examined and the best way we can suggest to overcome this problem is to stratify the enrolled volunteer's in a cohort-by-cohort basis and do the survival analysis for each cohort, or apply the Cox proportional hazards model for each cohort.

Transplanting Livers in Young Children - Looking Back at 100 Cases.

Despite advances in medical therapy, liver replacement continues to be the only definitive mode of therapy for children with end-stage liver disease (ESLD). However, its acceptance in India has been discouraging more due to financial and logistic reasons than the availability of expertise. This report outlines our journey and highlights issues pertinent to circumstances in an emerging economy like India. The aim is to review a single center's 100 case experience with liver transplantation (LT). A prospective analysis of all children who underwent LT since 2005 at our institute was done. The data were collated from a maintained structured database. Hundred children underwent LT. Sixty-four were boys. Age ranged from 5 to 144 months, with a median of 17 months. The mean weight of the cohort was 7.5 kg (ranging from 3.7 to 31.5 kg), with 60% of our children weighing between 5 and 10 kg. Biliary atresia is the most common indication (57%); others include metabolic disorders, progressive familial intrahepatic cholestasis, and hepatoblastoma. Two patients were for acute liver failure. Ninety-one children underwent live donor LT (mothers being the majority of the donors). None of the donors had any major postoperative complications. Major intraoperative complications include sepsis (39%), vascular complications (17%), biliary leak (11%), and intestinal complications (11%). Early postoperative deaths occurred in 18% of patients with sepsis being most common cause. The mean follow-up was 8.5 years and the overall survival is 70%. The mean survival is time (months) = 176.1. All surviving patients were followed up and had achieved good catch up growth by 3rd and 5th years posttransplant. The long-term sequalae include recurrent intercurrent infections, graft rejection (9%), posttransplant lymphoproliferative disease (5%), and portal vein stenosis (5%). Our experience demonstrates the feasibility of LT in children with ESLD in India. With longer-living grafts, patients often struggle with other issues such as compliance with follow-up, financial issues, recurrent infections, and neurological problems. Close monitoring with regular follow-up of patients helps in early recognition and treatment of late-onset complications, thus helping the overall long-term outcomes.

Advantages of high cell concentration prior to cryopreservation of initial leukapheresis in CAR-T cell therapy.

Chimeric antigen receptor (CAR) T-cell therapy is increasingly used in patients affected by B-cell lymphoma and acute lymphoblastic leukemia. For logistical reasons, initial apheresis products may be cryopreserved for shipment to manufacturing centers. Due to the characteristics of these patients, cells are often collected in large volumes, meaning more bags must be cryopreserved. This requires increased storage, time and monetary costs. In this context, we aimed to evaluate a high cell concentration cryopreservation protocol by centrifugation to standardize the initial CAR-T manufacturing procedure. Sixty-eight processes of leukapheresis of 57 patients affected by refractory/relapsed B cell lymphoma and 9 patients affected by acute lymphoblastic leukemia who were eligible for anti-CD19 CAR-T cell treatment performed between June 2019 and October 2022 were analyzed. Whole blood count, percentage and number of T cells were assessed on the apheresis final product. The apheresis product, which was alternatively stored overnight at 4°C, was centrifuged, adjusting the volume to approximately 40 mL. The product was immediately cryopreserved to achieve a final cell concentration of 50-200×106 cells/ml for cryopreservation. Leukapheresis volume was reduced by almost fivefold (median: 185 to 40 mL), resulting in a higher product concentration in one bag. In addition, the number of non-target cells (monocytes, platelets and erythrocytes) was also reduced during the development of CAR-T cell therapy, thereby maintaining T lymphocyte levels and providing a purer starting material. The advantages of the protocol include reducing economic costs, saving storage space, simplifying the manufacturing process, and facilitating shipping logistics. In conclusion, we present a validated, simple, and cost-effective cell enrichment processing protocol that provides high-quality cryopreserved products as starting material for the CAR-T cell manufacturing process.

Pulmonary rehabilitation in Iranian outpatients with mustard gas lung disease: a randomised controlled trial

ObjectivePeople with mustard gas lung disease experience cough, sputum, breathlessness and exercise limitation. We hypothesised that pulmonary rehabilitation (PR) would be beneficial in this condition.DesignAn assessor-blind, two-armed, parallel-design randomised controlled...