Historical Cohort Research Articles

Implementing oral antibiotics for bone and joint infections: Lessons learned and opportunities for improvement

Abstract Background Although intravenous antibiotics have historically been the standard of care for bone and joint infections, clinical trial data has highlighted the safety and efficacy of oral antibiotics. Despite this, intravenous antibiotics are still commonly used and evaluations of institutional guidelines advancing oral antibiotic use are limited. Methods In April 2023, we implemented a new institutional guideline to preferentially treat patients with bone and joint infections with oral antibiotics. The post-guideline cohort was compared with a historical pre-guideline cohort via retrospective chart review. The primary outcome was the proportion of patients discharged exclusively on oral antibiotics. Secondary outcomes included 90-day treatment failure, length of stay, and adverse effects. Results One hundred and eighty-six patients (53 pre-guideline and 133 post-guideline) were included in the analysis. Patients in the post-guideline cohort were more likely to be discharged exclusively on oral antibiotics (25% vs. 70%, p<0.01), with no difference in 90-day treatment failure (8% vs. 9%, p=0.75). Patients in the post-guideline cohort had a shorter length of stay than pre-guideline (median days: 8 vs. 7, p=0.04) and trended towards fewer PICC-related adverse events (6% vs. 1% p=0.07). Conclusion An institutional guideline was effective in increasing the proportion of patients with bone and joint infections discharged on oral antibiotics. We observed similar clinical outcomes after implementing the guidelines while reducing length of hospital stay.

The Association Between Elevated Thyroid-Stimulating Hormone Levels and Prolonged Length of Stay Among Adult Diabetic Patients Hospitalized in Internal Medicine Departments: A Large Historical Cohort Study

Background/Objectives: Type 2 diabetes mellitus (DM2) and hypothyroidism are two of the most common endocrine disorders in clinical practice. Hospital length of stay (LOS) is a quality metric of the health systems. We evaluated the association between elevated thyroid-stimulating hormone (TSH) levels and prolonged LOS among all adult patients (age ≥ 18 years) with DM admitted to our Internal Medicine departments between 2014 and 2022. Methods: Data on patient characteristics, LOS, and in-hospital mortality were collected. A TSH level > 4.7 μIU/mL was considered as being elevated. A LOS > 75th percentile and in-hospital mortality were defined as being prolonged. Univariate and multivariable analyses were applied, and propensity score matching controlled for differences between patients with normal and those with elevated TSH levels. Results: Of the 19,066 study participants (median age 75.6 years, IQR 75.9–83.3), 1524 (7.9%) had elevated TSH levels, and prolonged LOS was significantly more common among them (before matching: 38.6% vs. 29.1%, p < 0.001; after matching: 38.7% vs. 32.6%, p = 0.001). After adjustment for potential confounders, elevated TSH levels were also associated with prolonged LOS (OR = 1.22, 95% CI 1.07–1.39, p = 0.002). Conclusions: Elevated TSH levels in diabetic patients hospitalized in Internal Medicine departments are associated with prolonged LOS, emphasizing the importance of identifying hypothyroidism among them.

Monovalent XBB.1.5 COVID-19 vaccine effectiveness against hospitalisations and deaths during the omicron BA.2.86/JN.1 period among older adults in seven European countries: a VEBIS-EHR network study

ABSTRACT Background We aimed to estimate XBB.1.5 vaccine effectiveness (VE) against COVID-19-related hospitalizations and deaths during BA.2.86/JN.1 predominance, among EU/EEA individuals with ≥ 65-years. Research design and methods We linked electronic health records to create historical cohorts in Belgium, Denmark, Italy, Navarre (Spain), Norway, Portugal and Sweden. We included individuals aged ≥ 65-years eligible for the autumnal 2023 COVID-19 vaccine. Follow-up started when ≥ 80% of country-specific sequenced viruses were BA.2.86/JN.1 (4/dec/23 to 08/jan/24) and ended 25 February 2024. At study site level, we estimated the vaccine confounder-adjusted hazard ratio (aHR) of COVID-19 hospitalizations and deaths between individuals with ≥14 days after vaccination versus unvaccinated in autumn 2023, overall, by time since vaccination and age groups. VE was estimated as (1-pooled aHR)x100 with a random-effects model. Results XBB.1.5 VE against COVID-19 hospitalizations was 50% (95%CI: 45 to 55) and 41% (95%CI: 35 to 46) in 65-79-year-olds and in ≥ 80-year-olds respectively. VE against COVID19-related-death was 58% (95%CI: 42 to 69) and 48% (95%CI: 38 to 57), respectively, in both age groups. VE estimates against each outcome declined in all age groups over time. Conclusion Monovalent XBB.1.5 vaccine had a moderate protective effect against severe and fatal COVID-19 likely caused by BA.2.86/JN.1 during the 2023/2024 winter, among persons aged ≥ 65.

Accuracy of adult height predictions in patients with axial leg deviations using the Modified and the Abbreviated Modified Fels Knee System.

The accurate estimation of residual growth is crucial for the appropriate timing of growth-guiding surgery in patients with axial leg deviations. Skeletal age methods such as the Modified and the Abbreviated Modified Fels Knee System were developed on historical patient cohorts and the applicability to the modern pediatric population with axial leg deviation has not yet been evaluated. Are both final adult height prediction methods (the Modified Fels Knee System (FKS) and the Abbreviated Modified Fels Knee System (aFKS)) accurate to determine SA and the final adult height on long leg radiographs in patients with axial leg deviations?Which multiplier table shows highest association between predicted and true final adult body height?Do FKS- and aFKS- skeletal age determination methods improve final adult body height prediction accuracy compared to the simple use of chronological age? A single center, retrospective study of 31 patients who underwent temporary hemiepiphysiodesis due to axial leg deviations in the frontal plane between 2018 and 2020 was conducted. Skeletal age at the time of surgery was determined on an anterior-posterior long leg X-ray using FKS and aFKS. Adult height predictions were calculated using three different multiplier tables (Paley et al., Sanders-Greulich and Pyle (SGP), Sanders-Peak Height Velocity (PHV)). The accuracy of adult height prediction was determined by comparing the mean differences and mean absolute differences between predicted and true adult height. All adult height predictions overestimated the true adult height. The final height prediction using aFKS and the SGP multiplier showed the lowest overestimation (mean 3.2 cm, SD 5.5 cm). The PHV multiplier table showed the highest correlation between predicted and true adult height (FHPRE_FKS_PHV: r = 0.913, p < 0.001 and FHPRE_aFKS_PHV: r = 0.862, p < 0.001). The simple use of chronological age at the time of surgical intervention (CASI) with the Paley multiplier table showed the highest median delta absolute values and lowest correlations with true adult height (median 7.4 cm, 25%-75% percentile: 3.5-10.0 cm, r = 0.838, p < 0.001). Nevertheless, no significant differences in delta absolute values between various adult height predictions methods could be shown. Overall, the results of the present retrospective cohort study show that there was no significant improvement in final height prediction accuracy when using the FKS or the aFKS method compared to the simple use of chronological age. One reason could be that patients with varus/valgus malalignment have specific growth characteristics that are not accounted for in multiplier tables or the FKS and aFKS method. Since there is no significant difference in prediction accuracy between the methods, the choice of method may depend on other factors, such as clinical preference or availability of resources. However, due to the small sample size, the study cannot definitively rule out potential differences between the prediction methods, and larger studies are required to validate these findings.

Sonographic and Disease Activity Findings Related With Medication Change in JIA: A Historical Cohort Study.

Musculoskeletal ultrasound (MSUS) is increasingly used to evaluate pediatric inflammatory arthritis. This study aimed to explore the relationship between MSUS findings with medication modifications in patients with juvenile idiopathic arthritis (JIA) and clinical disease activity measurements (clinical Juvenile Arthritis Disease Activity Score [cJADAS-10], active joint count [AJC], patient/parent global assessment [PPGA], and physician global assessment [PGA]). Data from patients with JIA who underwent a 12-joint (bilateral second and third metacarpophalangeal, wrist, elbow, knee, and ankle) MSUS examination during a 57-month period were collected. Patients were categorized into 2 groups: a medication change group and a control group (patients without medication change). A pediatric-specific MSUS scoring system was used to assess MSUS findings. The association between clinical and MSUS findings was examined for the study groups. A total of 38 patients, 23 in the medication change group and 15 in the control group were included. The medication change group had higher AJC, PGA, and cJADAS-10. These patients also had a statistically significant presence of abnormal knee MSUS findings. For other joints, the frequency of abnormal MSUS findings was slightly higher in patients with a medication change, but the difference was not statistically significant. No strong correlation was observed between MSUS findings and clinical disease activity measurements. Abnormal MSUS findings were not observed to be higher in patients with a change in medication except for the involvement of the knee joint. Further longitudinal studies are needed to understand the role of MSUS in the medical decision-making process in JIA.

New Diagnoses of Juvenile Idiopathic Arthritis Early in the COVID-19 Pandemic

Background/Objective Little is known about the rates of rheumatic disease diagnosis among children during the COVID-19 pandemic. We examined the impact of the pandemic on the diagnosis of juvenile idiopathic arthritis (JIA) in the United States. Methods We performed a historical cohort study using US commercial insurance data (2016–2021) to identify children aged &lt;18 years without prior JIA diagnosis or treatment in the prior ≥12 months. New JIA diagnoses were identified using a combination of ICD-10-CM diagnosis codes, location, and timing of medical services. Crude rates with 95% confidence intervals (CIs) of JIA diagnosis per 100,000 enrolled children per quarter were estimated and stratified by age group, sex, region, JIA type, and uveitis. The incidence rate ratio (95% CI) for JIA diagnosis was estimated using Poisson regression, adjusted for various demographic variables. Results From 2018–2021, 643 children were diagnosed with JIA. Crude new JIA diagnoses per 100,000 children per quarter dropped from 2.62 (95% CI, 2.39–2.87) prepandemic to 1.94 (95% CI, 1.66–2.25) during the pandemic. Declines in JIA diagnosis were more apparent in the US Northeast and West regions and among children aged 6–11 years. After adjustment for covariates, JIA diagnoses fell by 30% during the pandemic compared with the prior 3 years (IRR, 0.70; 95% CI, 0.59–0.83). Conclusions Compared with the prepandemic period, JIA was diagnosed 30% less often during the early pandemic among commercially insured children in the United States. More research is needed to understand the underlying reasons for these changes in JIA diagnosis and more recent trends.

Abstract 4136584: The Association of De Novo Niacin Use with Long-Term Mortality

Introduction: Niacin is a non-statin lipid-lowering therapy that has been shown to lower triglycerides and improve other risk factors for cardiovascular diseases. However, previous studies have reported inconsistent effects of niacin on mortality, and its effect on long-term prognosis has not been well studied. Goals: The aim of this study is to examine the association of niacin therapy with long-term all-cause mortality. Methods: In a nationwide historical cohort of 1,139,630 US Veterans with normal baseline kidney function, we examined the association of de novo niacin prescription from 2004 to 2006 with all-cause mortality during a 14-year follow-up. Associations were examined in Cox proportional hazard models adjusted for demographics, major comorbidities, and laboratory measurements. Prescription time-distribution matching was used to control for survival bias. Results: We identified 133,450 new users of niacin. Overall, patients had a mean (standard deviation) age of 60 (13) years, with 6% female, 78% White, 16% Black, and 6% Hispanic. Niacin users were more likely to be male, White, current, or former smokers and had higher frequencies of comorbidities. Niacin use (vs. non-use) was associated with a lower risk of death (Hazard ratio: 0.89, 95% confidential interval: 0.88-0.90) in the fully adjusted model (Model 4, Figure). Conclusion: In a large national cohort of US Veterans, niacin use was associated with a lower risk of death. Further studies are needed to corroborate the potential benefits of niacin on survival.

Abstract 4124293: Exercise Capacity in Patients with Fontan Physiology

Introduction/Background: In the absence of a sub-pulmonary ventricle in the Fontan circulation, augmentation of pulmonary blood flow and filling of the systemic ventricle during exercise are limited. Cardiopulmonary exercise testing (CPET) is a reliable method for evaluation of aerobic capacity, gas exchange, and other physiologic parameters used for risk stratification in this population. Despite the ubiquitous use of CPET, reference ranges for patients with Fontan physiology are limited. The purpose of this study is to describe exercise characteristics and their relationship with different characteristics of Fontan physiology, imaging, and hemodynamics. Methods/Approach: In this retrospective cohort study, CPET results were reviewed for adult Fontan patients at the University of Washington between May 2021 and February 2024. Demographics, comorbidities, medications, type of Fontan conduit, imaging characteristics, hemodynamics, and exercise characteristics were included. Results were compared to a large previously published cohort of Fontan patients. Univariate linear regression was used to identify associations between demographics, cardiac anatomy, and exercise parameters. A p-value of less than 0.05 was considered statistically significant. Results/Data: Baseline demographics were notable for an older patient population (31±7 years) with lower indexed peak VO 2 (20.5±5.6 mL/kg/min) and greater V E /VCO 2 slope (37±7) compared to the historic cohort. Indexed peak VO2 was associated with age, BMI, type of Fontan conduit, FEV1, FVC, resting oxygen saturation, peak systolic blood pressure, and peak heart rate. Indexed peak VO 2 was notably not significantly associated with sex, systemic ventricular morphology, ventricular systolic function, Fontan pressure, or the presence of conventional heart failure medical therapy. Conclusions: In the growing population of older patients with Fontan physiology, development of age-specific population normative data may increase the clinical utility of CPET. Further investigation of the relationship between imaging characteristics, hemodynamics, and exercise parameters is needed in the Fontan population.

INNV-17. SAME-DAY DISCHARGE AFTER LASER INTERSTITIAL THERMAL THERAPY: A PROSPECTIVE COHORT PILOT STUDY WITH A MATCHED CONTROL GROUP

Abstract BACKGROUND Laser interstitial thermal therapy (LITT) has emerged as a minimally invasive treatment modality for intracranial pathologies, offering precision and control over tissue damage. With implementation of enhanced recovery after surgery (ERAS) protocols within neurosurgery, identifying patients amenable for same-day discharge (SDD) is an important step towards streamlining perioperative care following LITT, and correspondingly, we aim to summarize our initial experience. METHODS We conducted a prospective study at the University of Miami Hospital of 7 patients who underwent LITT for intracranial pathologies and were discharged on the same day of ablation (post-ablation day 0, PAD0). We then performed a retrospective case-control study against a historic matched PAD1 cohort comparing categorical and continuous variables for statistical significance. RESULTS The mean age of the PAD0 cohort was 55 years with 71% males. Preoperative neurological status and comorbidities did not differ significantly between the PAD0 and PAD1 cohorts for KPS (median [IQR]: 80 [80-90] vs. 90 [80-90], p=0.40), mFI-5 (median [IQR]: 1 [1.5] vs. 0 [1], p=0.54), and mFI-11 (median [IQR]: 1 [1.5] vs. 1 [1], p=0.52). PAD0 outcomes demonstrated no immediate complications, neurosurgical readmissions, or significant neurological deficits within 6 months post-procedure and were non-significantly different than PAD1 patients. No PAD0 patient experienced intracranial hemorrhage or vasogenic edema following LITT that necessitated further intervention. CONCLUSIONS Our study demonstrates the safety and feasibility of same-day discharge following LITT for intracranial pathologies in the appropriately selected patient. Through meticulous patient selection and optimized perioperative protocols, expedited recovery without compromising patient outcomes was achieved. This approach holds potential for substantial cost savings and resource optimization within healthcare systems. Further research and quality improvement initiatives are warranted to refine patient selection criteria and maximize the benefits of same-day discharge in LITT practice.

A History of Cesarean Birth as a Risk Factor for Postpartum Hemorrhage Even After Successful Planned Vaginal Birth.

It is unclear if a history of cesarean birth (CB) is a risk factor for postpartum hemorrhage (PPH) even after a successful planned vaginal birth. A historical retrospective cohort study from all deliveries (42,456) between 2004 and 2019. Inclusion criteria were as follows: (i) women with only one previous CB; (ii) liveborn cephalic singleton pregnancy and term spontaneous labor; (iii) successful planned vaginal birth; (iv) no operative vaginal delivery; and (v) no history of PPH. Women who experienced intrapartum uterine rupture leading to CB were excluded. Those who experienced uterine rupture diagnosed after vaginal birth were not excluded. The labor after cesarean (LAC) group (109 women with previous CB and current vaginal birth) were compared with 2 control groups to consider the parity: control group 1 (1633 nulliparous women) and control group 2 (4197 parous women). The main outcome was the rate of PPH (> 500 mL). Multivariate analysis was performed to investigate whether previous CB was an independent risk factor for PPH. Bivariate analysis and causal framework was used to determine the relation between variables of clinical interest. The PPH rates in the LAC group, control group 1, and control group 2 were 12.8%, 5.3%, and 6.4%, respectively. Irrespective of the group control (1 or 2), a history of CB was associated with an increased risk of PPH: adjusted odds ratio (aOR) 2.38 [95% confidence interval (CI) 1.28-4.44] (adjusted with maternal age, overweight, hyperthermia, and use of oxytocin) and aOR 2.16 [95% CI 1.20-3.87] (adjusted with maternal age and overweight) for Groups 1 (parous) and 2 (nulliparous), respectively. A history of cesarean birthcould be a risk factor for PPH even after successful planned vaginal delivery.

DPYD genotype-guided dose personalisation for fluoropyrimidine-based chemotherapy prescribing in solid organ cancer patients in Australia: GeneScreen 5-FU study protocol

BackgroundFluoropyrimidine (FP) chemotherapies are commonly prescribed for upper and lower gastrointestinal, breast and head and neck malignancies. Over 16,000 people with cancer require FP chemotherapies per annum in Australia. Between 10 and 40% patients experience grade 3–4 (≥ G3) toxicities that require hospital-based management ± intensive care admission. Approximately 1% of patients die secondary to FP toxicities. Prospective screening for DPYD gene variants (encoding the key enzyme for FP catabolism) can identify patients at risk of ≥ G3 toxicity and allow for dose adjustment prior to first FP exposure. Evidence supports this as a cost-effective method of improving patient safety and reducing healthcare burden internationally; however, no Australian data confirms its feasibility on a large scale.MethodThis investigator-led, single-arm study will determine large scale feasibility of prospective DPYD genotyping, confirming patient safety and cost-effectiveness within the Australian health care system. 5000 patients aged 18 years and older with solid organ cancers requiring FP chemotherapy will be consented and genotyped prior to commencing treatment, and early toxicity (within 60 days) post-FP exposure will be determined. Toxicity data for DPYD variant carriers who have dose adjustments will be compared to the wild-type cohort and historical cohorts of carriers who did not undergo genotyping prior to FP exposure, and prospective variant carriers who do not undergo dose-adjustment. Prevalence of the four standard DPYD gene variants will be confirmed in an Australian population. Additionally, health economic analysis, implementation research via semi-structured interviews of patients and clinicians, and feasibility of UGT1A1 genotyping will be conducted.DiscussionThis study will determine the prevalence of DPYD gene variant status in Australia and its impact on FP-induced toxicity among Australians with cancer. Feasibility and cost-effectiveness for Australian health care system will be estimated to support national roll-out of prospective DPYD genotyping prior to FP administration. Additionally, feasibility will be confirmed with the intention of including UGT1A1 in future pharmacogenomic panels to aid chemotherapy prescribing.Trial registrationThis trial was registered with the Australian and New Zealand Cancer Trials Registry on 13th Dec 2023, ACTRN12623001301651.

Associations of Microvascular Risk Factors with Sporadic Vestibular Schwannoma Outcomes Following Stereotactic Radiosurgery.

Stereotactic radiosurgery (SRS) is increasingly used for small-to-medium-sized sporadic vestibular schwannoma (VS) and is associated with good tumor control and low-risk of adverse radiation-associated events. The exact mechanism of VS tumor control is unknown but may relate to microvascular hyalinization and resultant tumoral ischemia. This study examined associations of microvascular risk factors with outcomes following SRS. Historical cohort of patients who underwent SRS for sporadic VS from 2000 to 2022. Tertiary academic center. Associations of microvascular risk factors with tumor control and complications were evaluated using Cox proportional hazards regression. In total 749 patients were studied, 31% with a history of smoking, 38% obesity, 19% hypertension, 8% diabetes, 3% peripheral vascular disease, and 2% history of coronary bypass. Regarding tumor control, no factor was associated with salvage treatment following SRS (n = 42). Hypertension (hazard ratio [HR] 2.81; P = .02) and coronary bypass (HR 6.91; P = .002) were significantly associated with developing facial nerve paresis (n = 22). No significant associations with new facial spasms (n = 53) were identified. Lastly, 191 of 294 patients with serviceable hearing at SRS progressed to nonserviceable hearing at a median 2.0 years (interquartile range: 1.0-5.0). After multivariable adjustment for age and ipsilateral hearing status, the HR for the association of smoking history with time to nonserviceable hearing was 1.46 (95% confidence interval 1.04-2.04; P = .03). We demonstrate that hypertension and history of coronary bypass may be associated with development of facial nerve weakness, while smoking may be associated with accelerated hearing loss in patients undergoing SRS for sporadic VS. These data may help guide patient counseling and inform decision-making regarding treatment.

Treatment sequences and survival outcomes in advanced HR + HER2- breast cancer patients: a real-world cohort.

Palliative treatment options for HR + HER2- advanced breast cancer (ABC) patients have increased, but data is lacking about the optimal treatment sequence. We used real-world data from a comprehensive cancer center to describe applied treatment sequences and we determined treatment-related and survival outcomes. Patients aged 18 years and older with HR + HER2- ABC treated with systemic treatment were included in this historic cohort study. Sequential treatment schedules, time to treatment discontinuation, time to chemotherapy, and overall survival (OS) were determined, stratified by first-line treatment. 202 patients were included. They received a total of 650 treatment lines (median 3; range: 1-11). 91 (45%), 25 (12%), 24 (12%), 28 (14%), 22 (11%) and 12 (6%) patients started first-line treatment with non-steroidal aromatase inhibitors (NSAI), NSAI + cyclin dependent kinase 4/6-inhibitors (CDK4/6i), fulvestrant + CDK4/6i, tamoxifen, chemotherapy and other treatment, respectively. 10, 13, and 14 different treatment regimens were given in first, second and third-line, respectively. Of the patients who started first-line NSAI monotherapy (n = 91), 3 (3%) died before receiving second-line treatment. In this real-world cohort, we observed a wide variety of different treatment sequences applied in daily clinical practice, some of which were in discordance with the current guidelines. Fear that patients may never get around to treatment with CDK4/6i if a patient did not start with a CDK4/6i was not supported by our study results.

Rapid viral suppression using integrase inhibitors during acute HIV-1 infection.

Antiretroviral therapy (ART) is recommended for all individuals with HIV infection, including those with acute HIV-1 infection (AHI). While recommendations are similar to those for chronic infection, efficacy data regarding treatment of acute HIV is limited. This was a single arm, 96-week study of a once-daily integrase inhibitor (INSTI)-based regimen using elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) in AHI. Primary endpoint was proportion of participants with HIV-1 RNA <200 copies/mL and <50 copies/mL by treatment weeks 24 and 48, respectively. We also examined time to viral suppression and weight gain after treatment initiation. Outcomes and characteristics were compared with a historical AHI cohort using a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen with efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). Thirty-three participants with AHI were enrolled with 31 available for analyses. Most were African American (61%) and men who have sex with men (73%). Median age was 26 (IQR 22-42). Demographics were similar between the two AHI cohorts. By Week 24, 100% in the INSTI and 99% in the NNRTI cohort were <200 copies/mL; by Week 48, 100% in both cohorts were <50 copies/mL. Time to viral suppression was shorter in the INSTI cohort (median 54 versus 99 days). Mean weight change was similar with a 3.6 kg increase in the INSTI cohort and 2.4 kg in the NNRTI cohort at 96 weeks. INSTI-based ART during AHI resulted in rapid and sustained viral suppression. Over 96 weeks, weight increased in the INSTI-based cohort but was similar to weight increase in a historical NNRTI-based AHI cohort.

Revalidation of Proactive Gastrostomy Tube Placement Guidelines for Head and Neck Cancer Patients Receiving Helical Intensity-Modulated Radiotherapy

The Royal Brisbane and Women’s Hospital (RBWH) Swallowing and Nutrition Management Guidelines for Patients with Head and Neck Cancer were developed to enable evidence-based decision-making by the Head and Neck Multidisciplinary Team (H&amp;N MDT) regarding enteral nutrition support options. The purpose of this study was to revalidate these guidelines in a cohort of patients receiving helical intensity-modulated radiotherapy (H-IMRT) compared to a historical cohort who received primarily 3D-conformal radiotherapy. Eligible patients attending the RBWH H&amp;N MDT between 2013 and 2014 (n = 315) were assessed by the guidelines, with high-risk patients being recommended proactive gastrostomy tube placement. Data were collected on guideline adherence, gastrostomy tube insertions, the duration of enteral tube use and weight change. Sensitivity, specificity and positive predictive and negative predictive values were calculated and compared with the historical cohort. Overall guideline adherence was 84%, with 60% and 96% adherence to the high-risk and low-risk pathways, respectively. Seventy patients underwent proactive gastrostomy tube placement (n = 62 high-risk; n = 8 low-risk). Validation outcomes were sensitivity 73% (compared to 72%) and specificity 86% (compared to 96%). The guidelines yielded a high sensitivity and specificity, remaining valid in a cohort of patients treated with H-IMRT. Further studies are recommended to improve the sensitivity and understand the decrease in specificity in order to make ongoing guideline improvements.

Patient-reported outcome was close to the Danish background population 6 months after non-surgical treatment of Neer 2-part surgical neck fractures: a prospective cohort study in patients aged 60 or above.

Neer 2-part surgical neck fractures are the most common displaced proximal humerus fractures. We aimed to evaluate patient-reported outcome in a consecutive series of older people receiving nonoperative treatment. This is a single-center prospective cohort study. We included patients aged 60 or above referred to a Danish university hospital. The preregistered protocol followed the recommendations from randomized trials. Patients were followed at the outpatient clinic at 2, 6, and 24 weeks. After 24 weeks, they were evaluated with Oxford Shoulder Score (OSS, 0-48, 48 best) and EuroQoL 5 dimensions, 3 levels (EQ-5D-3L, -0.624 to 1, 1 best). Clinical failure was defined as conversion to surgery or OSS ≤ 24. Population norms were reported to interpret the cohort data, but no formal statistical comparisons between historical cohorts were planned. We used descriptive statistics to report rates and proportions. For 36 months, 268 patients (mean age 76, 79% female) with Neer 2-part surgical neck fractures received non-surgical treatment. After excluding patients with concomitant fractures, dementia, or death, complete follow-up was available for 167 patients. 8 patients (3.0%) had surgery. The mean OSS was 37.2 (SD 8.1), which equals 78% of maximum shoulder function. The norm for the population of the same age and gender was 82%. The mean EQ-5D-3L score was 0.79 (SD 0.16), while the norm for the same-age population was 0.82. 16 (10%) had an OSS score of 24 or below. Non-surgical treatment in older people with Neer 2-part surgical neck fractures resulted after 6 months in patient-reported shoulder function and quality of life close to that of the Danish background population.

Influence of Inflammatory State on the Need to Customize Parenteral Nutrition in Adolescents.

Parenteral nutrition (PN) can be standardized or customized according to a patient's individual needs, including clinical, metabolic, nutritional, and inflammatory conditions. The influence of inflammation on the indication of standard or customized PN for adolescents hospitalized in a quaternary hospital in the southeastern of Brazil was evaluated. A historical cohort study of 61 adolescents admitted to the hospital was conducted. Nutritional, clinical, and biochemical data from the first 7 days of PN use were analyzed. Elevated serum mineral and triglyceride levels, as well as renal or liver failure (grade III or IV), were considered unequivocal reasons for PN customization, while restoring energy-protein adequacy and low serum mineral levels were considered questionable reasons. Inflammatory status was analyzed during the study period. A total of 128 PN solutions were prescribed, comprising 55 standardized and 73 customized. Overall, 40/61 patients required customized PN. The main reason for customization was to restore energy-protein adequacy (n = 48), while 24.7% (n = 18) of individualizations were for unequivocal reasons. Restoring energy-protein adequacy in the first 48 h was shown to have contributed to high transthyretin, which reduced the need for additional customized PN (r = -0.544; p = 0.044). A positive correlation was found between the total number of PN readjustments and C-Reactive Protein levels (r = 0.509; p = 0.044). Conditions such as malnutrition or an inflammatory state in adolescents presenting metabolic changes are indications for the use of customized PN.

Real-world evidence for pembrolizumab in non-small cell lung cancer: a nationwide cohort study.

Based on favourable results from clinical trials, immune checkpoint inhibitors (ICI) have become the standard first line (1 L) systemic anticancer treatment (SACT) for advanced stage non-small cell lung cancer (NSCLC) without targetable mutations. We evaluate whether these results are generalizable to everyday clinical practice and compare overall survival (OS) of patients treated with ICI to a historical cohort of patients treated with chemotherapy and results from clinical trials. Our study comprised all advanced NSCLC patients initiating SACT in 2012-21 in Norway. Clinical characteristics and treatment information was retrieved from Norwegian Health Registries. Survival for all 8416 advanced NSCLC patients treated with SACT increased concurrently with the gradual implementation of ICIs. Median OS of patients treated with 1 L pembrolizumab after 2017 was better (mono-/combination therapy: 13.8/12.8 months) than for patients treated with chemotherapy before 2017 (8.0 months). Although median OS for patients treated with pembrolizumab was lower in clinical practice than clinical trials (Keynote-024/189: 26.3/22.0 months), the survival benefit relative to chemotherapy was similar. Our nationwide study demonstrated a survival benefit over conventional chemotherapy of a similar magnitude as observed in clinical trials and confirms the effectiveness of pembrolizumab in routine clinical practice.

Pan-Cancer Survival Impact of Immune Checkpoint Inhibitors in a National Healthcare System.

The cumulative, health system-wide survival benefit of immune checkpoint inhibitors (ICIs) is unclear, particularly among real-world patients with limited life expectancies and among subgroups poorly represented on clinical trials. We sought to determine the health system-wide survival impact of ICIs. We identified all patients receiving PD-1/PD-L1 or CTLA-4 inhibitors from 2010 to 2023 in the national Veterans Health Administration (VHA) system (ICI cohort) and all patients who received non-ICI systemic therapy in the years before ICI approval (historical control). ICI and historical control cohorts were matched on multiple cancer-related prognostic factors, comorbidities, and demographics. The effect of ICI on overall survival was quantified with Cox regression incorporating matching weights. Cumulative life-years gained system-wide were calculated from the difference in adjusted 5-year restricted mean survival times. There were 27,322 patients in the ICI cohort and 69,801 patients in the historical control cohort. Among ICI patients, the most common cancer types were NSCLC (46%) and melanoma (10%). ICI demonstrated a large OS benefit in most cancer types with heterogeneity across cancer types (NSCLC: adjusted HR [aHR] 0.56, 95% confidence interval [CI] 0.54-0.58, p < 0.001; urothelial: aHR 0.91, 95% CI 0.83-1.01, p = 0.066). The relative benefit of ICI was stable across patient age, comorbidity, and self-reported race subgroups. Across VHA, 15,859 life-years gained were attributable to ICI within 5-years of treatment, with NSCLC contributing the most life-years gained. We demonstrated substantial increase in survival due to ICIs across a national health system, including in patient subgroups poorly represented on clinical trials.

Efficacy and Safety of Avatrombopag in Combination with Standard Immunosuppressive Therapy for Severe Aplastic Anemia

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disease. The addition of eltrombopag to immunosuppressive therapy (IST) improves the response rate and response quality of SAAs, but its hepatotoxicity is concerning. Avatrombopag (AVA), another small-molecule thrombopoietin receptor agonist without hepatotoxicity, has unknown efficacy in SAA treatment. This retrospective study aimed to assess the efficacy and safety of AVA, a small-molecule thrombopoietin receptor agonist, when added to IST in SAA patients. A total of 42 patients treated with IST and AVA were compared to a historical cohort of 84 patients receiving IST alone, utilizing propensity score matching. The median age was 31.5 (6.0-67.0) years old in Group A and 26 (16.0-45.0) years old in Group B. At 3 months, Group A showed higher complete response (CR) and overall response (OR) rates than Group B (CR: 19.0% vs. 4.8%, P = 0.024; OR: 54.8% vs. 39.3%, P=0.145). Higher CR and OR rates were also found at 6 months in Group A than in Group B (CR 31.0% vs. 14.3%, P=0.145; OR 71.4% vs. 51.2%, P=0.048). In multivariate analysis of Group A, a shorter interval from disease onset to anti-thymocyte globulin (ATG) treatment (≤6 months) (P=0.005) predicted better responses rate at 6 months. Event free survival was also improved in Group A (60.7% vs. 49.6%). AVA was well-tolerated, with no hepatic injury observed during treatment, even in those with pre-existing hepatic impairment. The addition of AVA to IST improves both the response rate and response quality in SAA patients while ensuring safety.