Years In Patients Research Articles

DOP018 Etrasimod for the treatment of Ulcerative Colitis: Up to 4 years of safety data from the global clinical programme

Abstract Background Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). The long-term safety, tolerability and efficacy of etrasimod are being evaluated in an ongoing open-label extension (OLE) study.1 We report an updated cumulative safety analysis from the etrasimod UC clinical programme with a maximum of 4 years of exposure. Methods Patients who received etrasimod in completed phase 2 (OASIS; OASIS OLE), phase 3 (ELEVATE UC 52; ELEVATE UC 12) and ongoing ELEVATE UC OLE (data cutoff 30 Aug 2023) and ES101002 OLE (data snapshot 30 Aug 2022) studies were included. Treatment-emergent adverse event (TEAE) frequency and exposure-adjusted incidence rates (IRs) per 1 patient-year (PY) were analysed. Results A total of 1196 patients received ≥1 dose of etrasimod 1 mg or 2 mg once daily with a mean (standard deviation) exposure of 70.66 (54.36) weeks, and 1619.5 PYs of total exposure. Demographics and baseline characteristics are reported in Table 1. Most TEAEs were nonserious and rarely led to discontinuation. The IRs of TEAEs of interest were generally low (Table 2). Serious infections and herpes zoster infections were infrequently reported (all IR ≤0.02). Three patients experienced four nonserious events of macular oedema (0.3%, IR <0.01), including one event leading to discontinuation that resolved. One patient experienced two nonserious events of cystoid macular oedema (<0.1%; IR <0.01) that resolved. Malignancies were uncommon and included five patients with serious events (0.4%), two patients with squamous cell carcinomas and one with basal cell carcinoma. Eleven patients (0.9%) had alanine aminotransferase (ALT) levels >3 times the upper limit of normal (ULN) at two consecutive post-baseline visits. Notably, no patients exhibited >3× ULN in either ALT or aspartate aminotransferase and >2× ULN in total bilirubin (laboratory criteria for Hy’s law). TEAEs leading to death were reported in three patients (all deemed unrelated to treatment). No serious adverse events of hypertension or bradycardia were reported. No events of second-degree Mobitz type 2 atrioventricular (AV) block or third-degree AV block occurred. Conclusion Etrasimod remains well tolerated in patients with moderately to severely active UC, with a favourable safety profile that has not changed with longer-term treatment exposure for up to 4 years.

Sutureless Bioprostheses for Aortic Valve Replacement: An Updated Systematic Review with Long-Term Results.

Background: In recent years, in case of aortic valve replacement (AVR), a significant increase in the use of bioprostheses has been observed. The Perceval sutureless bioprosthesis has proven to be safe and reliable in the short and mid-term, with limited but promising long-term results. An updated systematic review with the long-term results of patients who underwent a sutureless bioprosthesis implantation with a Perceval biological valve is herewith presented. Methods: Studies published between 2015 and 2024, including the long-term outcomes-with clinical as well as echocardiographic information for up to five years-of patients who underwent a Perceval implantation for AVR were selected from the published literature. The Cochrane GRADE system was used to assess the study quality, and the risk of bias in non-randomized studies (ROBINS-I) tool was used to evaluate studies. Results: Ten studies were selected with an overall number of 5221 patients. The long-term survival ranged from 64.8 to 87.9%, freedom from structural valve degeneration (SVD) from 96.1 to 100%, freedom from significant paravalvular leak from 98.5 to 100%, freedom from prosthetic endocarditis from 90.7 to 99%, and freedom from reintervention from 94 to 100%. The long-term mortality ranged from 6.5 to 27.4%. SVD was observed in 0-4.8% patients. Significant paravalvular leak was observed in 0-3.4% patients, and infective endocarditis was observed in 0-3.4%. A bioprosthesis-related reintervention at long-term follow-up was required for 0-4.3% of patients, and 1.7-7.1% of patients required a late new pacemaker implantation. The transprosthetic mean pressure gradient ranged from 9 to 14.7 mmHg, peak pressure gradient ranged from 17.8 to 26.5 mmHg, and EOA ranged from 1.5 to 1.7 cm2. Conclusions: This systematic review shows that there is still a paucity of data about sutureless bioprostheses. Nevertheless, the clinical results from prospective studies or retrospective series are encouraging. Medium- and long-term results seem to support the increasing use of this type of prosthesis.

Comparison of EsophyX2.0 and MUSE systems for transoral incisionless fundoplication: Technical aspects and outcomes up to 3 years.

We compared the efficacy and safety of transoral incisionless fundoplication (TIF) with the EsophyX2.0 and MUSE systems for treatment of gastroesophageal reflux disease (GERD). TIF outcomes from prospective protocols (Esophy2.0X: 2007-2012; MUSE: 2015-2019) were retrospectively compared regarding technical success, moderate/severe adverse events, morpho-functional findings up to 1 year, and clinical outcomes up to 3 years. Inclusion criteria were: (i) at least 6-month symptomatic GERD, full/partial response to proton pump inhibitors (PPI), esophagitis, and nonerosive reflux disease/hypersensitive esophagus (both protocols); (ii) hiatal hernia <3 cm (Esophy2.0X) and ≤2.5 cm (MUSE); and (iii) Barrett's esophagus <3 cm (MUSE). In the 50 EsophyX2.0 and 46 MUSE procedures, technical success and adverse event rates were similar, but MUSE-related adverse events (4.4%) were life-threatening. At 12 months, hiatal hernia recurred more frequently after EsophyX2.0 (P = 0.008). At 6 months, significantly fewer total and acid refluxes were reported after both TIF, but not more significantly at 1 year. Symptoms improved after both TIF up to 1 year (P < 0.0001), but to a greater extent in MUSE patients up to 3 years (P < 0.0001 vs. P < 0.01 for EsophyX2.0). The rates of 3-year off-PPI therapy patients were 73.5% in the MUSE and 53.3% in the EsophyX2.0 series (P = 0.069). Although no conclusion could be drawn from this limited study, the MUSE technique seemed more effective in the long term in patients with hiatal hernia; however, there were more severe adverse events than with EsophyX2.0.

IL6 and WNK2 polymorphisms and prognosis in patients with intracerebral hemorrhage receiving edaravone

ObjectiveEdaravone is utilized in intra-cerebral hemorrhage (ICH) patients for years, while personalized variances were observed in clinic. To explore the precision medicine strategy for Edaravone, this study investigated the association between genetic polymorphisms and Edaravone efficacy in ICH patients. MethodsWe genotyped 7 SNPs in 4 potential genes, including COL4A2, TNF, WNK2 and IL6, from the peripheral blood of 217 ICH patients with or without Edaravone utilizations. PLINK and SPSS were utilized for association tests, Student's t tests, Mann-Whitney U tests and Chi-square tests. ResultsRs1800796 (C>G) in IL6 (OR: 0.41, 95 % CI: 0.18-0.94, p-value = 0.03) and rs16936752 (G>T) in WNK2 (OR: 0.28, 95 % CI: 0.09-0.88, p-value = 0.02) were found to be significantly associated with Edaravone efficacy. The association of rs1800796 and rs16936752 were found to be different in patients with or without smoking habit, alcohol drinking habit, hypertension history and hyperlipemia history were found to be different. Both of these two SNPs were found to be associated with the concentration of high-density lipoprotein cholesterol (HDL) in ICH patients. ConclusionsThe IL6 rs1800796 and the WNK2 rs16936752 could be useful biomarkers for prognosis prediction during Edaravone treatment. These SNPs should be considered in the personalized medicine strategy for Edaravone in the future.

Exploring the association between phytopharmaceutical use and antibiotic prescriptions in upper respiratory infections: results from a German cohort study evaluating the impact of naturopathy qualifications of general practitioners using routine data.

Antibiotic resistance is a significant global health threat, exacerbated by inappropriate prescribing practices, particularly for upper respiratory infections that are predominantly viral. Complementary and Integrative Medicine (CIM), including the use of phytopharmaceuticals, offers a potential strategy to reduce antibiotic prescriptions. This study aimed to describe the impact of General Practitioners' (GPs) naturopathy (NP) qualifications and phytopharmaceutical prescriptions on the rate of antibiotic prescribing for upper respiratory infections (RTI). We conducted a retrospective cohort study using routine data from the CONTinuous morbidity registration Epidemiologic NeTwork (CONTENT), which includes over 200,000 patients across four federal states in Germany. The study included data from n = 36 GPs who recorded at least one ICD-10 diagnosis of RTI. Antibiotic and phytopharmaceutical prescriptions were identified and analyzed through mixed-effects logistic regression models to explore the influence of GPs' naturopathy qualifications and phytopharmaceutical use on antibiotic prescribing patterns. The study included 40,344 patients managed by 36 GPs. Prescriptions of phytopharmaceuticals significantly reduced the likelihood of antibiotic use (OR 0.48, 95% CI 0.45-0.52). Additionally, holding a naturopathy qualification was associated with lower rates of antibiotic prescriptions (OR 0.73, 95% CI 0.69-0.78). The interaction between naturopathy qualification and phytopharmaceutical prescriptions also showed a significant effect (OR 1.43, 95% CI 1.27-1.62). Patient's year of birth influenced prescribing patterns indicating a reduction of antibiotic prescriptions for younger patients, while patients' gender did not reveal a significant effect. Prescriptions of phytopharmaceuticals were significantly associated with a decrease antibiotic prescriptions among GPs, especially when combined with naturopathy qualifications. Training in naturopathic approaches could enhance antibiotic stewardship efforts in primary care settings, suggesting that broader integration of CIM elements into medical training could be beneficial in mitigating antibiotic resistance.

Prognostic factors associated with worse outcomes in patients with GBS: A systematic review.

Guillain-Barré syndrome (GBS) is an autoimmune polyradiculoneuropathy with diverse clinical subtypes, characterized by rapidly evolving motor weakness, sensory disturbances and areflexia. The global prevalence of GBS has been steadily increasing, with regional disparities. Mortality rates vary but remain elevated in patients requiring mechanical ventilation. This systematic review aimed to evaluate the predictive risk factors for the severity of the disease and poor shortand long-term outcomes of GBS. The literature search was conducted using the PubMed database by 2 independently working researchers. After a screening process of studies published before November 2023, a total of 109 articles were selected. Original articles, systematic and narrative reviews, meta-analyses, and editorials were selected based on their clinical relevance. The exclusion criteria included patients under 18 years of age, pregnant women and articles in languages other than English and Polish. Long-lasting GBS complications included pain, fatigue and persistent neurological deficits, affecting patients for years after recovery. Identifying the appropriate therapeutic methods, risk factors and prognoses of GBS at an early stage is crucial. Various risk factors for death and poor functional outcomes were found, regarding patient characteristics, the clinical course of GBS, laboratory and neurographic results, as well as treatment methods.

Analysis of Risk Factors for Death from Melanoma and Genitourinary Diseases in Male Patients with Cutaneous Melanoma: A Cohort Propensity Score Matching Study.

To analyze the influencing factors of male cutaneous melanoma (CM) patients dying from genitourinary diseases (GUD). We searched the surveillance, epidemiology, and end results (SEER) database and extracted data on male CM patients according to the inclusion and exclusion criteria, including male patients whose cause of death was CM (cohort A) or GUD (cohort B). Comparisons between the two cohorts were performed before and after propensity score matching (PSM). An interaction analysis between age and year of diagnosis was also conducted. Cox regression analysis were performed to find the risk factors for death from GUD. Seven thousand seventy-eight CM patients were included, including 6415 (90.6%) in cohort A and 663 (9.4%) in cohort B. Compared with cohort A, cohort B patients were older (median age 74 ys. vs 65 ys.) and were more under the localized stage and had longer survival time no matter before or after PSM (all p<0.001). The stage was an inhibitory factor for cohort B (p <0.001). After PSM, only age and year of diagnosis were found to be cohort B's promoting factors (p<0.001). The interaction analysis showed that older patients diagnosed in later years (2009-2020) had a higher risk of dying from GUD compared to those diagnosed earlier (p<0.05). Patients with a later year of diagnosis (2009-2020) had a lower median survival time than patients with an earlier year of diagnosis (2000-2008) (p<0.001). When the patient's year of diagnosis was earlier (2000-2008), older patients (>75 ys.) had a higher risk of dying from GUD than younger patients (≤75 ys.) (p<0.001). We first reported a significant interaction between age and year of diagnosis in male CM patients dying from GUD, highlighting the increased risk in older patients diagnosed more recently. We may pay attention to the possibility of dying from genitourinary diseases for CM patients.

Lower Risk of Postoperative Complications and Rotator Cuff Retear Associated With Semaglutide Use in Patients with Type II Diabetes Mellitus Undergoing Arthroscopic Rotator Cuff Repair

PurposeTo investigate the potential impact of preoperative semaglutide use (active agent in Ozempic® and Wegovy®) on ninety-day postoperative outcomes and two-year rotator cuff retear following arthroscopic rotator cuff repair (ARCR) for type II diabetes mellitus (T2DM) patients. MethodsT2DM patients undergoing primary ARCR were identified from the PearlDiver database using administrative billing codes. Exclusion criteria included: patients <18 years old, prior RCR, concurrent non-rotator cuff related arthroscopic shoulder procedures, any traumatic, neoplastic, or infectious diagnoses within 90-days before surgery, and <90-days follow-up.T2DM patients using semaglutide within one-year of ARCR ([+]semaglutide) were matched 1:4 with T2DM patients who did not ([-]semaglutide) by age, sex, Elixhauser Comorbidity Index (ECI), diabetes complications, obesity, tobacco, insulin, and metformin use.Occurrence of any, severe, and minor adverse events (AAE, SAEs, MAEs, respectively) within 90-days were compared by multivariable logistic regression. Two-year retear was assessed by Kaplan-Meier survival analysis and compared by log-rank test. ResultsThere were 1,094 ARCR (+)semaglutide and 4,110 ARCR (-)semaglutide patients meeting inclusion criteria after matching. The incidence of AAE for the ARCR (-)semaglutide vs. ARCR (+)semaglutide patients was 27.4% vs. 11.0%, SAE was 10.5% vs. 3.5%, and MAE was 22.0% vs. 8.5%, respectively (p<0.001 for all). ARCR (-)semaglutide patients had a higher odds ratio (OR) of AAE (3.65, p<0.001) and SAEs (3.62, p<0.001), including surgical-site infection (2.22, p=0.049), venous thromboembolism (3.10, p<0.001), sepsis (3.87, p<0.001), and cardiac events (3.96, p<0.001). Also, greater odds of MAEs (3.59, p<0.001), including urinary tract infection (3.27), pneumonia (3.88), acute kidney injury (3.91), and ED visits (2.51) (p<0.001 for all). Additionally, (-)semaglutide patients revealed higher 2-year retear vs (+)semaglutide patients (18.3% vs 12.5%, respectively) (p<0.001). ConclusionPreoperative semaglutide use for T2DM patients undergoing ARCR was associated with decreased odds of minor and serious 90-day adverse events, and lower 2-year rotator cuff retear. Level of EvidenceLevel III, retrospective comparative study

Long-term persistence of carrier-bound fibrin sealant (TachoSil®) following abdominal surgery: a decade-long follow-up study.

This study analyzed the long-term effects of carrier-bound fibrin sealant (CBFS) following abdominal surgery by tracking patients for years post-application. From 2006 to 2022, patients who underwent this procedure were contacted via telephone. Those who died due to underlying diseases, natural causes, or refused the check-up were excluded from the study. After 11years of follow-up, CBFS was observed in different forms on computed tomography scans in four patients. Our findings indicate that CBFS can persist for years after the procedure. While we cannot confirm any secondary effects, it appears that CBFS sponges are not resorbed within 12weeks and can remain for many years post-implantation.

Parichay Patient Support Program: Useful Tool for Improving Compliance in Kidney Transplant Recipients

IntroductionMedication non-adherence (MNA) in organ transplant recipients is associated with increased risk of rejection, allograft loss, patients’ death and higher healthcare costs. Various approaches have been used to reduce MNA. A patient support program (PSP) can be an invaluable tool in improving patient outcomes. Hence, the aim was to analyze available data of PSP for kidney transplant recipients. Material and MethodsA total of 3352 patients were prospectively enrolled in Parichay PSP between Jan 2021 - April 2023 from all over the country. Baseline demographic details were recorded. A monthly call was made thereafter. Data was analyzed for demographic details, compliance rate, drop-outs and tacrolimus levels (whenever available). This study was supported by Biocon Biologics. ResultsParichay program had enrolled a total of 1371, 1620 and 361 kidney transplant patients in years 2021, 2022 and 2023 (Jan-April) respectively from different parts of India (N-25%, E-35%, S-26%, W-14%). Patients who had received Tacrolimus (Tacrograf®) (n=2626) revealed that 2158 (82%) patients were male with the mean age of 42 years. Majority (61%) of patients were in age group of 28-48 years. Patient compliance rate of >90% was maintained for over 13 months (n = 1920, April 2022 - April 2023). Of the 3352 patients, 250 (7.4%) dropped out of the study. Thus, use of PSP ensured a compliance of 92.6% in our study. ConclusionsThis analysis demonstrates that participation in the PSP can be a useful tool to monitor compliance and tacrolimus therapeutic drug monitoring in kidney transplant recipients.

The First Observational Study of Acute Medical Unit in Qatar.

Background Acute medical unit (AMU) is a dedicated facility to treat patients with acute medical conditions requiring a short hospital stay (< 72 hours) with the support of a multidisciplinary team led by a medical consultant. We aim to present a study of the AMU model of care from Qatar to provide insight into its effects on patient care and management. Methods Retrospective data from AMU facility at Hamad General Hospital (HGH), Doha, Qatar, was collected from January 2019 to December 2020 from the electronic patient record. The data were analyzed for demographic characteristics of the patients, length of stay (LOS), readmission rate, and postdischarge follow-up. The effectiveness of the AMU system was studied closely from this data. An extensive literature search was also performed for comparative results analysis in other AMU facilities outside Qatar. Results Total admissions under the AMU facility were 8,371 from january2019 to December 2020. The 28 days readmission rate was 10.25 and 9.9% in 2019 and 2020, respectively. The average LOS was approximately 3.2 days. Around 88.7% of the patients were discharged home, 7.8% were admitted to medical wards due to longer stays, and 0.5% left against medical advice. Most of the patients admitted under AMU were 18 to 60 years old. The top primary diagnoses of admissions were minor stroke, transient ischemic attack, chest infection, urinary tract infections, and gastrointestinal and liver diseases. The most common comorbidities were hypertension, diabetes, acute kidney injury, and chronic kidney disease. A total of 2,858 patients were booked for a follow-up visit in the postdischarge clinic on discharge from the AMU for the year 2019 and 2020. The analysis of these followed up patients showed 73% of patients were discharged from clinic after first visit while the readmission from clinic was on only 1% (28 patients for year 2019 and 2020). Conclusion Attentive patient care under AMU with a designated multidisciplinary medical team led by an internal medicine consultant is the cornerstone for the success of the AMU unit. This unit has proven very helpful for the smooth disposition of patients from the emergency department with reduced LOS, readmission rate, and overall mortality.

Resurgence of Kawasaki Disease Following Relaxation of Coronavirus Disease 2019 Pandemic Restrictions in Japan

ObjectivesTo compare the number and incidence of Kawasaki disease (KD) patients in years 2 through 4 of the coronavirus disease 2019 (COVID-19) pandemic, and determine the impact of 3 years of implementation infection control measures and their subsequent relaxation on the epidemiology of KD in Japan. Study designWe conducted a population-based, cohort study including consecutive KD patients in Kobe City between 2021 and 2023. We compared the incidence of KD cases, in relation to timing of infection control measures, as well as infectious disease cases based on a regional surveillance system. Data from a previous 2016 through 2020 study were used for comparison. ResultsA total of 566 children with KD were identified during the study period. During the infection control period in 2021 to 2022, the incidence of KD remained low compared with the pre-pandemic level (281.3 and 327.5/100,000 children aged 0-4 years in 2021to 2022 and 2016 through 2019, respectively), but a recovery trend began in the 0-1-year age group. During the relaxation period in 2023, the incidence of KD increased across a wide age range, reaching the highest recorded in Japan (426.7/100,000 children aged 0-4 years), and the median age of onset increased to age 30 months. The resurgence of KD coincided with the patterns for multiple infectious diseases in 2023. The seasonality of KD observed before the pandemic was altered. ConclusionsKD resurged in 2023 after relaxation of the prolonged COVID-19 pandemic restrictions in Japan. This phenomenon coincided with the rise of multiple infectious diseases, and supports the pathogenesis of KD being triggered by infectious agents.

Time to Dementia Diagnosis Among Veterans with Comorbid Insomnia and Depressive Episodes.

Older adults with heart failure are at elevated risk of Alzheimer's disease and related dementias (AD/ADRD). Research suggests that insomnia and depressive episodes contribute somewhat dissociable impacts on risk for AD/ADRD in this patient population, although the temporal ordering of effects is unknown. This study examined time to dementia diagnosis among patients with comorbid insomnia and/or depressive episodes in an epidemiological sample. Secondary data analyses were conducted using a cohort study of 203,819 Veterans with a primary admission diagnosis of heart failure in 129 VA Medical Centers. Patients with diagnoses of both insomnia and depressive episodes had the shortest time to a dementia diagnosis at both 1-year (Hazard ratio = 1.43, 95% CI [1.36, 1.51]) and 3-year follow-up time points (Hazard ratio = 1.40, 95% CI [1.34, 1.47]) versus patients with one or neither comorbidity. Individuals with both comorbidities had the shortest time to dementia onset. Screening for these comorbidities may help to identify patients at elevated risk of dementia who could benefit from enhanced monitoring or early intervention strategies for more rapid detection and management of dementia symptoms.

Examining autocorrection of concurrent cervical malalignment following thoracolumbar deformity surgery.

The aim of the study was to assess preoperative radiographic parameters predictive of cervical deformity (CD) autocorrection in patients undergoing thoracolumbar deformity (ASD) surgery. This was a retrospective cohort study. Inclusion criteria were operative ASD patients with complete baseline (BL) and 2-year radiographic data. Patients with cervical fusion during index surgery, revision involving cervical fusion, and those who developed proximal junctional kyphosis by 2-year postoperative were excluded from the study. If patients met CD criteria at BL but not at 6 weeks or 2 years postoperatively, they were considered autocorrected (AC). Descriptive and univariate analysis, binominal logistic regression, and multivariable backward stepwise regression. Two hundred and twenty ASD patients were included. 51.4% of patients had preoperative CD. By 6-week postoperative, 32.7% achieved AC. At 2 years, 24.8% of preoperative CD patients obtained AC. 2-year AC patients had lower BL sacral slope, lumbar lordosis (LL), T1 slope, cervical lordosis (CL), and C2-T3, and T2-T12 kyphosis (all P < 0.05). Patients with BL-unmatched Roussouly types are corrected postoperatively and are more likely to experience autocorrection at 1 year (45.2% vs. 19.0%; P = 0.042) and at 2 years (31% vs. 4.8%; P = 0.018). Multivariable analysis revealed that patients with BL-mismatched Roussouly types were corrected postoperatively and showed a significant increase in likelihood of AC at 1 year (odds ratio [OR]: 18.72; P = 0.029) and 2 years (OR: 8.5; P = 0.047). Similarly, BL LL (OR: 0.772; P = 0.003) and CL (OR: 0.829; P = 0.005) exhibited significant predictive value for autocorrection at 1 year and 2 years (OR: 0.927; P = 0.004 | OR: 0.942; P = 0.039; respectively). Autocorrection is more likely in patients with postoperatively corrected Roussouly types, those with lower BL cervical, and LL. Given these findings, it may not be necessary to routinely extend reconstruction into the cervical spine for ASD patients with similar characteristics to those in this study.

Deep learning detection of diabetic retinopathy in Scotland’s diabetic eye screening programme

Background/AimsSupport vector machine-based automated grading (known as iGradingM) has been shown to be safe, cost-effective and robust in the diabetic retinopathy (DR) screening (DES) programme in Scotland. It triages screening...

Budget impact analysis of the novel PD-1 inhibitor toripalimab versus pembrolizumab in recurrent or metastatic nasopharyngeal carcinoma

Aim To estimate the budget impact of adding a toripalimab regimen as a treatment option to the existing pembrolizumab regimen, both including gemcitabine and cisplatin, in untreated recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) using the published wholesale acquisition cost (WAC) and average sales price (ASP). Methods Budget impact analysis comparing a treatment mix “without” versus “with” the toripalimab regimen in the US eligible annual incident R/M NPC population, a 3-year time horizon, toripalimab/pembrolizumab market splits of 60/40 (Y1) and 80/20 (Y2/3), and medication adjustments for discontinuation or progression. Cost inputs included drugs, administration, and adverse event (AE) management. The models were replicated for a hypothetical 1-million-member health plan in which costs per-member-per-month (PMPM) and per-member-per-year (PMPY) were estimated. One-way (OWSA) and probabilistic sensitivity analyses (PSA) as well as scenario analyses were performed. Results In the “without” scenario, the 3-year WAC-based costs for the pembrolizumab regimen total $1,449,695,333 ($1,305,632,448 for treatment and $144,062,885 for managing AEs). In the “with” scenario, total 3-year costs for pembrolizumab decline to $380,012,135 with toripalimab adding $885,505,900 ($779,206,567 for treatment and $106,299,333 for AE management). Annual net savings range from $46,526,152 in 2024 to $71,194,214 in 2026, for 3-year savings of $184,177,298. Associated net savings in a 1-million-member health plan are $543,068 over 3 years with savings of $0.045 PMPM and $0.543 PMPY. The ASP-based model shows similar patterns with 3-year net savings of $174,235,983 in the US incident population and savings of $0.043 PMPM and $0.514 PMPY in a 1-million-member health plan. The PSA support base case findings; OWSA and scenario analyses reveal how parameter variability impacts results. Conclusion Savings between $174 million and $184 million can be achieved from treating 60% of R/M NPC patients in year 1 and 80% in years 2 and 3 with the toripalimab regimen over a similar pembrolizumab regimen.

The Efficacy of Metformin as a Therapeutic Agent in the Treatment of Acne Vulgaris: A Systematic Review.

A large portion of the world's population is affected by acne vulgaris (AV), with many of these individuals being adolescents. The underlying mechanism of AV is hyperkeratinization and Cutibacterium acnes infection of the pilosebaceous follicle secondary to excessive stimulation of sebaceous glands by androgens. Metformin is a biguanide medication primarily used in efforts to lower patients' sugar levels in the management of type 2 diabetes. It has been proven to reduce levels of circulating androgens in patients with insulin resistance, indicating its potential for treating AV. A search strategy was developed and performed using the databases Ovid Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Controlled Register of Trials (CENTRAL), and Web of Science. The keywords "metformin" and "acne" were searched, along with related Medical Subject Headings (MeSH) and other subject headings. Studies that met the inclusion criteria were controlled trials, published after 2010, and in the English language. Participants with and without comorbidities such as polycystic ovary syndrome (PCOS) were considered. Two independent reviewers screened studies based on predefined criteria and extracted data from each study, which were quantitatively combined. A total of 15 studies were included in this systematic review. Across the 15 studies, there were 1,046 participants, with 13 studies looking exclusively at women with PCOS. Of the remaining two studies, one examined males with altered metabolic profiles, while the other included men and women with moderate AV. Notable risks of bias included studies that did not exclusively state the blindness of the study. Of the studies that were examined, 13 showed that metformin reduces AV, with seven studies showing statistical significance. Acne vulgaris is an inflammatory condition that has plagued patients for years due to the limited treatment options available. The hyperglycemic medication metformin, used in the management of type 2 diabetes, is being explored as a novel therapeutic that can possibly be repurposed for the treatment of AV. The use of metformin in AV is hypothesized to disrupt the proposed linkage between insulin resistance and AV proliferation. This proposed research could offer physicians a new option for the treatment of AV as well as render an alternative AV treatment for patients.

Trends in survival after heart transplantation based on Social Vulnerability Index in the United States

IntroductionThe association of social vulnerability (SV) and cardiac transplant survival remains poorly defined, particularly related to long-term outcomes. The purpose of this study was to define the impact of SV on survival among heart transplant recipients with at least 1-year of survival post-transplant. MethodsHeart transplant recipients were identified using the United Network for Organ Sharing database between 6/1/06-12/31/20. The Center for Disease Control’s Social Vulnerability Index (SVI) database was used to stratify patients based on SVI into three groups: Low: <25; Average: 26-74; High: 75+. The groups were analyzed with comparative statistics, and unadjusted survival was assessed using Kaplan-Meier methods. To determine the independent association between SVI and survival, a multivariable Cox proportional hazard model was created. ResultsThere were 27,740 recipients identified. High SVI patients more commonly identified as Black individuals and had a higher incidence of diabetes, pre-transplant intensive care unit admission and need for concomitant kidney transplant (p<0.05 for all). Additionally, High SVI patients had the longest length of stay post-transplant (21.4 days) (p<0.05). High and Average SVI patients had inferior 3-year, 5-year, and 10-year survival versus Low SVI patients (p<0.05). After adjustment, Average (hazard ratio [HR]:1.12) and High (HR:1.16) SVI were independently associated with an increased risk of mortality on multivariable analysis (both p<0.001). ConclusionHigh or average SVI is independently associated with increased mortality following heart transplantation in patients with 1-year conditional survival. These findings demonstrate that disparities persist among heart transplant recipients during long-term follow up.

Immune evasion by dormant disseminated cancer cells: A Fermi paradox?

Rare disseminated tumor cells (DTCs) can persist after treatment in patients for years, and the immune system does not eliminate them. Goddard etal. propose that immune evasion by rare dormant DTCs is due to an improbability of contact imposed by large distances separating effector Tcells and DTCs.

Small Fenestra Stapedotomy in Comparison to Large Fenestra Stapedectomy in Improving Hearing Loss Caused by Otosclerosis: A Retrospective Study

Background: A retrospective study done on all otosclerotic patients who underwent stapes surgery between January 2019 and June 2022 in the department of otorhinolaryngology in a tertiary care hospital in North India. Material and Methods: Fifty four patients were enrolled in the study. The inclusion criteria of the study included patients in the age group of 18–55 years with conductive hearing loss and an intact tympanic membrane and an air–bone gap (ABG) of more than 30 dB. Diagnosis of otosclerosis is based on clinical history of progressive hearing loss and audiometric evaluation. Pure Tone Average shows typical conductive hearing loss pattern. Aim and Objective: Preoperative and 6 months postoperative audiological evaluation was conducted to understand the difference in hearing. The same surgical technique was used in all the cases, except that the dimension of the foot plate removed was different. Results: The mean age of patients in years who underwent stapes surgery was 31.6 ± 6.4 years. Out of the 54 patients, 24 (44.44%) were male and 30 (55.56%) were female. The number of patients who underwent large fenestra stapedectomy was 30 (55.56%) and who underwent small fenestra stapedotomy was 24 (44.44%). There was a significant improvement in the hearing parameters (PTA and ABG) in both the groups after surgery, but there was no significant difference between the small fenestra and large fenestra groups in terms of improvement in PTA and ABG. Conclusion: In conclusion, both small fenestra stapedotomy and large fenestra stapedectomy are safe and effective procedures for improving conductive hearing loss in otosclerosis patients.