Persistence Rates Research Articles

Does the Easing of COVID-19 Restrictive Measures Improve Loneliness Conditions? Evidence from Japan

Given the substantial changes in health and safety protocols and economic activities over the past year, socioeconomic routines have returned to a state of normalcy. Therefore, it is important to conduct a longitudinal study to determine whether these recent changes have left a lasting imprint on loneliness, specifically among those who have experienced post-pandemic loneliness in previous years. We investigated the incidence of loneliness and the risk factors associated with it during the post-pandemic period using recent data. We utilized longitudinal data spanning from 2020 to 2023 and employed mean comparison tests and weighted probit regression models in this analysis. Our study reveals that loneliness continues to be a notable issue, with persistent, post-pandemic, and recent loneliness rates of 47.6%, 4.3%, and 2.2%, respectively. We also observed a slight reduction in both persistent and post-pandemic loneliness compared to the previous year. Younger people continued to experience higher persistent loneliness rates, with no significant age or sex differences in post-pandemic or recent loneliness. Various factors, such as demographics, socioeconomic status, and psychological factors, influence loneliness differently across sexes and age groups. The policy implications include ongoing monitoring, targeted interventions, and support for specific demographic and socioeconomic groups to address post-pandemic loneliness for the sustainable management of the loneliness issue in Japan.

Venous thromboembolism prophylaxis and multiple myeloma patients in real-life: Results of a large survey and clinical guidance recommendations from the IFM group

Venous thromboembolism (VTE) remains a critical issue in the management of patients with multiple myeloma (MM), particularly when immunomodulatory drugs (IMiDs) combined with dexamethasone therapy are being prescribed as first-line and relapse therapy. One possible explanation for the persistent high rates of VTE, is the use of inappropriate thromboprophylaxis strategies for patients starting antimyeloma treatment. To tackle the issue, the Intergroupe francophone du myélome (IFM) offered convenient guidance for VTE thromboprophylaxis in MM patients initiating systemic therapy. This guidance is mainly supported by the results of a large survey on the clinical habits regarding VTE of physicians who are substantially involved in daily care of MM patients. VTE prophylaxis should be considered for all patients treated with IMiDs in combination with dexamethasone, in the absence of significant comorbidities, such as renal failure or bleeding risk. Anticoagulant should be preferred to antiplatelet agents for thromboprophylaxis. Despite the absence of large randomized controlled trials comparing those attitudes/options, available data on direct oral anticoagulants, which are already used in daily management of MM patients, are consistent with their potential usefulness for VTE prophylaxis in such patients. However, in order to implement a personalized continuous improvement strategy, clinicians must to be organized to collect all the data regarding this management. In other situations, thromboprophylaxis should be evaluated by using risk models and after careful evaluation of the risk/benefit ratio.

Operationalizing Narrative Theory in the Reinstatement from Suspension Process

Abstract Students returning from suspension remain a focus for institutions that aim to improve retention and persistence rates and graduate all admitted students. Institutions need more precise mechanisms to identify students who will be academically successful upon return from suspension and to know what support those students will need. Previous research has not identified dependable objective criteria for administrators to use when making reinstatement decisions. Review of subjective criteria in this process is required. This study explored the impact of student narrative on reinstatement from suspension decisions through the narrative theory lens. Student participants and administrators in the reinstatement process were interviewed to understand their understanding of the importance of student narrative on reinstatement decisions and future student success.

Fertility Transition in China and its Causes

Abstract Demographic transition faced by modern economies, including China, are among the most important long-term socio-economic challenges. In 2022, China observed its population decline for the first time since the early 1960s. The low fertility rate was of critical importance. The unprecedented one-child policy is quite commonly indicated as the main reason for the low fertility rate. However, the departure from this restrictive policy and the actions introduced under the two-child policy implemented from 2016, and then the three-child policy from mid-2021, have not brought an improvement in fertility rates. The aim of the paper is to answer the following research questions: Should the decline and persistent low fertility rate in China be attributed solely or mainly to the unprecedented one-child policy, which was in force for over three decades? Fertility transition in China is the effect of several factors and depends largely on the studied period. In the 1970s and 1980s, the government’s family policy was a key determinant of the decline in fertility. However, contrary to the prevailing belief about the determining influence of the one-child policy, the first stage of the implementation of the birth control policy, the Wan, Xi, Shao program, had a greater impact. Since the 1990s, the low fertility rate has been mainly explained by the extraordinary socio-economic changes and rapidly increasing prosperity of the Chinese people. Since the beginning of the 21st century, cultural changes resulting mainly from the integration of the Chinese economy with the global system have been crucial. Cultural changes have affected reproductive behaviour, marriage patterns, marriage postponement, birth postponement, fertility, and family size in Chinese society, which is observed below-replacement fertility. China’s demographic future depends on the fertility trajectory. However, due to the size of the population, but also the position of the Chinese economy in the global economic system, Chinese demographic transition may also bring significant consequences for the global economy.

Factors associated with unknown primary status in head and neck squamous cell carcinoma

ObjectivesHead and neck cancer of unknown primary (CUP) poses significant therapeutic challenges. We compare CUP and oropharyngeal primary (OP) cases to identify factors associated with tumor detection. MethodsThe 2004–2019 National Cancer Database was queried to identify CUP and OP cases based on clinical and pathologic TNM staging. Clinical and demographic characteristics were compared by primary detection and HPV status with descriptive statistics. Multivariable logistic regression models to characterize OP detection were constructed. Among HPV-positive and negative patients, respectively, OP and CUP patients were matched by clinical nodal disease. Cox proportional-hazards models were constructed using matched cohorts to characterize survival. Results81,053 CUP and OP cases were identified; 64.3 % were HPV-positive. OP detection increased over time in HPV-positive and negative disease. HPV-positive status had higher odds of OP detection (odds ratio (OR) = 1.77, p < 0.001), while females (OR = 0.95, p = 0.008), and black (OR = 0.82, p < 0.001) and Asian (OR = 0.7, p < 0.001) patients had lower odds compared to males and whites, respectively. In HPV-positive and negative disease, OP patients had higher 2 and 5-year survival rates than CUP (p < 0.001). Primary detection status conferred lower death risk in HPV-positive (hazard ratio (HR) = 0.85, p < 0.001) and negative disease (HR = 0.87, p < 0.001) when controlling for age, sex, race, comorbidities, insurance, treatment facility, and income. ConclusionIn the largest cohort of CUP to date, we report a survival benefit in primary tumor detection regardless of HPV status. Groups with higher persistent CUP rates, including non-white, female, HPV-negative, and low income patients, may benefit from increased diagnostic workup to improve detection and treatment.

The Relationship Between Continued Fed Rate Hikes and the Risk of US Government Debt

The management of interest rates by central banks is a critical aspect of economic policy, and the Federal Reserve (the Fed) holds a central role in guiding the monetary course of the United States. Over the years, the Fed has utilized interest rate adjustments to achieve diverse objectives, from controlling inflation to promoting economic growth. However, the ongoing debate surrounding the Fed's persistent interest rate hikes centers on the potential risks that may arise in relation to the US government debt. This essay delves into the implications of these interest rate hikes on the risk associated with the US government's debt. By examining the impact of increased interest rates on the cost of borrowing, market dynamics, and the challenges of debt refinancing, we can gain insights into the potential ramifications on the fiscal health of the nation. In addition, we will explore counterarguments and potential mitigating measures put forth by policymakers to balance the objectives of economic stability and debt sustainability.

Analysis of persistence rate of cognitive enhancers in Alzheimer’s disease using the common data model

AbstractBackgroundAchEIs are used by first‐diagnosed Alzheimer’s dementia patients. The effect of drug has been proven in safety and efficacy but it is known that the drug cannot be taken continuously due to side effects of about 10% in existing studies. However, studies report higher drug discontinuation rates. Cognitive function improvers or ‘nootropics’ such as choline alfocerate are used together with AchEI. Therefore, purpose of this study was to analyze the usage patterns of cognitive enhancers in Alzheimer’s patients and to confirm retention rate using a common data model.MethodFrom 2010 to 2019, using the data of Alzheimer’s patients registered in the common data model server of Kangwon National University Hospital, we will investigate the prescription rate of cognitive function improving drugs (choline alfocerate) and drug analysis patterns such as ChEI and combination therapy. The analysis is conducted using the FeederNet‐based ATLAS WEB tool, and additional analysis is compared with the results obtained through the DBMS approach using SQL.ResultAs a result of the analysis of treatment trends and persistence for 10 years, among 2,658 newly diagnosed patients with Alzheimer’s disease, donepezil was prescribed the most with 1,518 patients (57.11%), choline alfocerate with 654 patients (24.6%), and memantine with 214 patients. (8.05%), rivastigmine in 74 (2.78%), and galantamine in 147 (5.53%) each. During observation, trend of increasing prescriptions was Donepezil (31.5% in 2010 to 68.7% in 2019), Nootropics (24.6% in 2010 to 34.2% in 2019), Memantine (3.7% in 2010 to 7.9% in 2019), and Rivastigmine(0.53% in 2010 to 3.32% in 2019), while galantamine decreased (12.2% in 2010 to 0.3% in 2019). Persistence was approximately 50% for donepezil and memantine and approximately 40% for rivastigmine, galantamine and choline alfocerate over 12 monthsConclusionComparing treatment trends of cognitive function improvers, donepezil, memantine, ribistigmine, and choline alfocerate showed a tendency to increase, whereas galantamine showed a tendency to decrease. Also, donepezil and memantine were associated with longer persistence than rivastigmine and galantamine and choline alfocerate. In particular, in case of Nootropics, a high rate of initial prescription is given to patients with dementia, but rate of continuous prescription is not high.

Endoscopic powered resection device for residual colonic lesions: the first multicenter, prospective, international clinical study

Background and AimsEndoscopic resection is standard treatment for adenomatous colorectal lesions. Depending on lesion morphology and resection technique, recurrence can occur. Scarred adenomas are challenging to resect and may require surgical management. This study evaluated safety and effectiveness of an endoscopic powered resection (EPR) system for scarred adenomatous colorectal lesions. MethodsSingle-arm, prospective, multicenter, study conducted from January 2018 to January 2021 at 12 sites. Patients with persistent flat or sessile colorectal lesions were enrolled. Primary endpoints were technical success (the ability of the device to resect the lesion(s) without use of other resection devices without device-related serious adverse events (SAE)) and safety (the occurrence of adverse events (AE) through 90 days). Secondary endpoints included endoscopic confirmation of resection completeness, occurrence of colon stenosis, disease persistence, and diagnostic value of resected specimens. ResultsSixty-five patients were in the intent-to-treat / safety analysis population. Primary analysis was performed on 45 per-protocol (PP) patients with 48 lesions. All PP-patients were solely treated by the EndoRotor device. Technical success was achieved in 44 (98%) patients. Three (5%) SAEs occurred: 2 delayed self-limited bleeds and 1 perforation. Non-serious AEs included 4 (6%) cases of mild intraprocedural bleeding. Completeness of resection and histopathological diagnosis of tissue specimens were achieved in all patients, 21 (46.7%) patients had disease persistence after the first treatment, and there was no colon stenosis. ConclusionsEPR is a safe and effective for benign, persistent, large (>20mm) scarred, colorectal adenomas and should be considered as an alternative treatment in lieu of surgery. Persistence rate of 46.7% show that more than one treatment are necessary for effective endoscopic treatment.

Real-World Evaluation of Treatment Patterns and Clinical Outcomes Among Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Asciminib in US Clinical Practice

Introduction: Tyrosine kinase inhibitors (TKIs) are the mainstay of treatment for CML-CP. Asciminib, a first-in-class inhibitor to Specifically Target the ABL Myristoyl Pocket (STAMP), was FDA-approved on 10/29/2021 for the treatment of adult patients with Philadelphia chromosome-positive (Ph+) CML-CP, previously treated with two or more TKIs or Ph+ CML-CP with the T315I mutation. This study described treatment patterns and real-world clinical outcomes of asciminib in the US. Methods: Data through 11/30/2022 from adult patients with Ph+ CML-CP who initiated asciminib were obtained from the Flatiron Health oncology electronic health record (EHR)-derived de-identified database. Patients who initiated asciminib after ≥2 previous TKIs, without a stem-cell transplant prior to asciminib, and without the T315I mutation, were included in the overall cohort. Time-to-treatment discontinuation and molecular response (MR; time-to-BCR::ABL1 ≤0.1% and time-to-BCR::ABL1 ≤1%, separately) were evaluated from asciminib initiation (index date) using Kaplan-Meier analyses overall, and by the number of TKIs used pre-index (2 previous TKIs, and ≥3 previous TKIs). Patients were required to have ≥1 MR test post-index to be included in the MR assessment; a sensitivity analysis was conducted excluding patients with BCR::ABL1 ≤0.1% or better (≤1% or better) for time-to-BCR::ABL1 ≤0.1% (time-to-BCR:ABL1 ≤1%), as evaluated in the ASCEMBL trial. Results: Overall,97 patients with Ph+ CML-CP initiated asciminib (median age: 63 years, 50.5% female, 64.9% White, 84.8% ECOG 0-1, 61.9% from community-based practices, median follow-up of 6 months post-index). Other malignancies (19.6%), chronic pulmonary disease (18.6%), renal disease (18.6%), and congestive heart failure (16.5%) were the most prevalent pre-index comorbidities. The distribution of last MR in the 3 months pre-index was: 24.7% BCR::ABL1 &amp;gt;10%, 18.6% BCR::ABL1 ≤10% and &amp;gt;1%, 12.4% BCR::ABL1 ≤1% and &amp;gt;0.1%, 12.4% BCR::ABL1 ≤0.1% and &amp;gt;0.01%, and 8.2% BCR::ABL1 ≤0.01% (23.7% not tested/documented). Forty-six patients (47.4%) initiated asciminib after 2 previous TKIs, 24 (24.7%) after 3 TKIs, and the remainder after ≥4 previous TKIs (27.8%). Most patients (78.4%) were prescribed 80 mg (40.2% once daily, 38.1% 40 mg twice a day) at treatment initiation. Use of TKIs prior to asciminib included dasatinib (85.6%), imatinib (63.9%), bosutinib (61.9%), nilotinib (53.6%), and ponatinib (15.5%). Treatment sequences among patients who initiated asciminib after 2 previous TKIs (n=46) are presented in Figure 1. Overall (n=97), persistence rates were 85.7% by 12-weeks (2 previous TKIs: 89.8%; ≥3 previous TKIs: 82.5%) and 78.1% by 24-weeks (2 previous TKIs: 81.8%; ≥3 previous TKIs: 75.3%) post-index. Among patients with ≥1 MR test post-index (n=70), 31.3% (2 previous TKIs: 43.3%; ≥3 previous TKIs: 21.6%) and 49.7% (2 previous TKIs: 71.5%; ≥3 previous TKIs: 33.4%) achieved or maintained BCR::ABL1 ≤0.1% by 12- and 24-weeks, respectively. In addition, 51.3% (2 previous TKIs: 68.7%; ≥3 previous TKIs: 37.2%) and 64.2% (2 previous TKIs: 79.7%; ≥3 previous TKIs: 51.4%) achieved or maintained BCR::ABL1 ≤1% by 12- and 24-weeks, respectively. For patients without BCR::ABL1 ≤0.1% prior to asciminib (n=52; Figure 2), 14.6% (2 previous TKIs: 20.6%; ≥3 previous TKIs: 10.4%) and 32.9% (2 previous TKIs: 56.7%; ≥3 previous TKIs: 17.9%) achieved BCR::ABL1 ≤0.1% by 12- and 24-weeks, respectively, with a median time of 30.7 weeks (2 previous TKIs: 23.0 weeks; ≥3 previous TKIs: 38.1 weeks). For patients without BCR::ABL1 ≤1% prior to asciminib (n=43), 35.6% (2 previous TKIs: 61.9%; ≥3 previous TKIs: 21.9%) and 46.3% (2 previous TKIs: 61.9%; ≥3 previous TKIs: 37.2%) achieved BCR::ABL1 ≤1% by 12- and 24-weeks, respectively, with a median time of 24.6 weeks (2 previous TKIs: 11.3 weeks; ≥3 previous TKIs: 26.9 weeks). Conclusion: This is the first real-world study describing treatment patterns and clinical outcomes among patients with Ph+ CML-CP treated with asciminib in the US. The findings of real-world treatment efficacy based on achieving BCR::ABL1 ≤0.1% were consistent with the ASCEMBL trial. Patients who initiated asciminib after 2 previous TKIs had higher persistence and treatment response rates than those initiated on asciminib after ≥3 previous TKIs. Further studies are warranted to continuously demonstrate the effectiveness of asciminib in a real-world setting.

Clinical and Radiographic Outcomes of Repair of Spondylolitic Spondylolisthesis Through Direct Pars Repair.

A retrospective chart review. The objective of this study is to investigate whether direct pars repair achieves bone healing and symptom relief in patients with spondylolitic spondylolisthesis. While most cases of spondylolysis can be managed nonoperatively, a small percentage of patients require surgical intervention. The outcome of direct pars repair through a standard pedicle-screw with wiring technique is controversial in patients with lumbar spondylolitic spondylolisthesis. Medical records of patients who had undergone an open surgical pars repair were retrospectively reviewed. Standard demographic and surgical parameters were collected. All patients underwent a primary repair of the pars with an autograft or bone morphogenetic protein and instrumentation using a pedicle-screw with spinous process wiring. At 6 to 12 months after the surgery, patient's pain symptoms, and postoperative computed tomography (CT) scans were independently reviewed to assess healing; which was graded as nonunion, partial union, or solid union. There were 68 patients identified (33 male and 35 female), with an average age of 18.6 years. The mean estimated blood loss was 139 ml, and the mean length of hospital stay was 3.7 days. CT evaluation revealed 35 (52%) solid unions, 21 (31%) partial unions, and 12 (18%) nonunions requiring revisions. Thirty-four (50%) patients had no postoperative pain, 24 (35%) had mild pain, and 10 (15%) had persistent pain. The majority of patients with nonunions on CT had mild or persistent pain. Patients with no or mild pain tended to be younger than those with persistent pain (17.5 vs. 24.6 yr, P =0.163). This study demonstrated a partial or complete union rate of 82% and a postoperative persistent pain rate of 15%. These figures are comparable to the previous study, and this pedicle-screw with wiring technique can be worth trying before interbody fusion for spondylolytic spondylolisthesis to preserve anatomical lumbar motion.

Real-World Switching Pattern, Persistence, and Associated Healthcare Resource Utilization of Bruton Tyrosine Kinase Inhibitors for the Treatment of Mantle Cell Lymphoma in the United States

Introduction: Mantle cell lymphoma (MCL) is an aggressive form of B-cell non-Hodgkin's lymphoma. While incurable, MCL can be controlled for a prolonged period of time, but typically becomes refractory or relapsed and requires additional treatment. Bruton tyrosine kinase inhibitors (BTKi) are approved for relapse/refractory MCL and recommended by the National Comprehensive Cancer Network (NCCN ®); However, it is unclear how BTKi are being utilized and switched in the real-world patient populations. This study aimed to examine treatment patterns, persistence, and associated healthcare resource utilization of BTKi use in patients with MCL in the US. Methods: A retrospective observational study was conducted using Symphony Integrated Dataverse (IDV ®), a comprehensive, longitudinal, open-claims database and integrated Electronic Medical Record (EMR) data. Patients aged ≥18 years with ≥1 diagnosis for MCL and initiated a BTKi between 1/1/20 and 12/31/22 were included in the study. Patients were required to be continuously enrolled for 365 days leading up to the index date and ≥90 days following the index date (date of BTKi initiation). The full patient history in the database was used to identify previous BTKi use and analyze switching patterns for each patient. Three mutually exclusive cohorts (ibrutinib, acalabrutinib, zanubrutinib) were developed based on first-initiated BTKi. Patients were followed until the end of the study period (3/31/23) or lost to follow-up. Treatment switching pattern, duration, persistence, time to discontinuation (TTD), and healthcare resource utilization (HCRU) were examined by each BTKi cohort. Treatment duration was defined as time from BTKi initiation to the end date of last BTKi prescription. TTD was defined as time from BTKi initiation to the end date of the BTKi prescription that had a gap of &amp;gt;60 days with a subsequent BTKi prescription. Treatment persistence was evaluated as the proportion of patients that were continually prescribed BTKi (≥80% proportion of days covered) across 30-day intervals. HCRU was measured by number of outpatient visits and inpatient services, per patient per month (PPPM), during the treatment regimen. Results: BTKi switching patterns were analyzed for the 1,674 patients that initiated any BTKi therapy during study period (acalabrutinib [n= 697]; ibrutinib [n=693]; zanubrutinib [n=284]). Switching rates were 23.8% for ibrutinib, 5.6% for acalabrutinib, and 2.8% for the zanubrutinib cohort. In the ibrutinib cohort, the majority of patients switched to acalabrutinib (72.7%). Of those who switched from acalabrutinib, more than half (59.9%) switched to zanubrutinib. Of those who switched in zanubrutinib cohort, they were equally switched to ibrutinib and acalabrutinib (Table 1). Mean outpatient visits PPPM were 1.39 for patients who initiated with ibrutinib then switched to zanubrutinib, and 1.49 for those who switched to acalabrutinib. Mean inpatient services PPPM were 0.39 for patients who switched from ibrutinib to zanubrutinib, and 0.59 for those who switched to acalabrutinib. The 3 BTKi cohorts were similar across sociodemographic characteristics. The zanubrutinib cohort had higher median TTD (days) (188.5) compared to ibrutinib (161.5) and acalabrutinib (179), as well as higher median treatment duration (200) compared to ibrutinib (171) and acalabrutinib (194). Among MCL patients continuously enrolled for ≥ 360 days, zanubrutinib patients consistently had higher persistence rates (p=0.0079. Figure 1). Persistence at 90-days was 66.9% for zanubrutinib compared to 56.3% for ibrutinib and 62.7% for acalabrutinib. After 360 days, zanubrutinib continued to have the highest persistence (16.9%) compared to ibrutinib (10.8%) or acalabrutinib (13.2%). Zanubrutinib had the least number of mean inpatient services PPPM (0.56) compared to ibrutinib (0.83) and acalabrutinib (0.71) and mean outpatient visits-zanubrutinib (1.53), ibrutinib (1.81), acalabrutinib (1.59). Conclusions: This real-world study suggested that US patients with MCL receiving zanubrutinib showed longer treatment persistence, treatment duration and TTD, as well as lower switching rates and HCRU compared to those receiving acalabrutinib and ibrutinib.

1535. Persistence With Human Immunodeficiency Virus Pre-exposure Prophylaxis in an Active-Duty Military Population

Abstract Background There is limited data on Human Immunodeficiency Virus Pre-exposure Prophylaxis (PrEP) use and persistence in the military. Despite universal access to care, there is concern that PrEP persistence may be lower in military populations due to frequent deployments, need for relocations, and perceived stigma. This study evaluated the persistence rates as well as reasons for PrEP discontinuation in a military cohort. Methods The Brooke Army Medical Center Infectious Diseases clinic provides PrEP to service members at Joint Base San Antonio. This study evaluated all active-duty service members who received PrEP between 2020-2022. All charts were examined to determine patient demographics and years on PrEP. If a patient stopped PrEP, they were contacted to determine etiology of discontinuation and invited to restart PrEP. Results In total, 112 service members received PrEP during the study period. The cohort was predominantly male (99%) with median age 30 [IQR: 26-34] and a median of 2 years [IQR: 0-3] receiving PrEP (Table 1). The most common indication was multiple sexual partners with less than 100% condom use (n=98, 88%). At the end of the study, most (n=88, 79%) patients were still receiving PrEP including 33 (37%) at other military or civilian facilities. Of the 24 service members who were no longer receiving PrEP, 18 (75%), were able to be contacted (Table 2). Two (1%) patients seroconverted while off PrEP with reasons for discontinuation being abstinence and difficulty making appointments. No patients contacted during this study were interested in restarting PrEP. Demographic Information of 112 Active-Duty Service Members Receiving PrEP at Brooke Army Medical Center 2020-2022 Reasons for PrEP Discontinuation at Brooke Army Medical Center 2020-2022 Conclusion This is the first study to evaluate PrEP persistence in an active-duty population. In this cohort with universal access to care, PrEP persistence rates and years receiving PrEP were greater than seen in other populations. While the most common reason for discontinuation was changes in sexual behavior, systemic factors still contributed to PrEP discontinuation. Future studies should elucidate the challenges to PrEP care in the military. Disclosures All Authors: No reported disclosures

Consecutive resections of double pituitary adenoma for resolution of Cushing disease: illustrative case.

Double pituitary adenomas are rare presentations of two distinct adenohypophyseal lesions seen in <1% of surgical cases. Increased rates of recurrence or persistence are reported in the resection of Cushing microadenomas and are attributed to the small tumor size and localization difficulties. The authors report a case of surgical treatment failure of Cushing disease because of the presence of a secondary pituitary adenoma. A 32-year-old woman with a history of prolactin excess and pituitary lesion presented with oligomenorrhea, weight gain, facial fullness, and hirsutism. Urinary and nighttime salivary cortisol elevation were elevated. Magnetic resonance imaging confirmed a 4-mm3 pituitary lesion. Inferior petrosal sinus sampling was diagnostic for Cushing disease. Primary endoscopic endonasal transsphenoidal resection was performed to remove what was determined to be a lactotroph-secreting tumor on immunohistochemistry with persistent hypercortisolism. Repeat resection yielded a corticotroph-secreting tumor and postoperative hypoadrenalism followed by long-term normalization of the hypothalamic-pituitary-adrenal axis. This case demonstrates the importance of multidisciplinary management and postoperative hormonal follow-up in patients with Cushing disease. Improved strategies for localization of the active tumor in double pituitary adenomas are essential for primary surgical success and resolution of endocrinopathies.

Transarterial Embolization of Simple Pulmonary Arteriovenous Malformations: Long-Term Outcomes of 0.018-Inch Coils versus Vascular Plugs

PurposeTo compare the safety, effectiveness, and persistence rates of 0.018-inch coils with those of Amplatzer vascular plugs (AVPs; Abbott Vascular, Abbott Park, Illinois) for the treatment of pulmonary arteriovenous malformations (PAVMs) in response to a growing concern that 0.018-inch coil embolization would increase the long-term persistence rate. Materials and MethodsThis is a retrospective, single-center study of a database (2002–2020) of 633 PAVM embolizations. Complex PAVMs and those not embolized with 0.018-inch coils or plugs were excluded. PAVM embolization material was classified into 4 groups: (a) 0.018-inch nonfibered coils (NFCs), (b) 0.018-inch fibered coils (FCs), (c) NFCs and FCs, or (d) plugs. Persistence was defined as flow through the PAVM on digital subtraction angiography (DSA) or as <30% diameter reduction of the aneurysmal sac on unenhanced computed tomography (CT). Kaplan–Meier analysis and Cox regression were used to assess PAVM’s persistence-free survival. ResultsA total of 312 PAVM embolizations with NFCs (43 PAVMs), FCs (127 PAVMs), NFCs and FCs (12 PAVMs), or plugs (130 PAVMs) in 109 patients (28% men; mean age = 49 years) were included. All PAVM embolizations were technically successful without any major adverse events. PAVM persistence-free survival rates at 10 years’ follow-up were 40.8% versus 44.7% in the NFC and FC groups (P = .22) and 47.3% versus 81.0% in the 0.018-inch coil (NFC or FC) and plug groups (P < .0001), respectively. There were 0.43 (79/182) and 0.08 (10/130) re-embolization procedures per PAVM in the 0.018-inch coil and plug groups, respectively (P < .001). ConclusionsPAVM embolization with 0.018-inch coils was safe, but persistence rate with PAVM embolization was significantly higher than that with plugs, with no significant differences between FCs and NFCs.

Persistence of Janus-kinase (JAK) inhibitors in rheumatoid arthritis: Australia wide study

BackgroundTo compare persistence of disease-modifying antirheumatic (DMARDs), with a focus on Janus kinase (JAK) inhibitors in Australian rheumatoid arthritis (RA) patients. MethodsA retrospective observational study was conducted among 4,521 RA patients (females n=3,181 [70.4%]), using data from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset, aged ≥18 years and initiating a DMARD between 2011 to 2021. Kaplan-Meier analysis was used to estimate persistence rates, defined as occurrence of 6 months gap after the end of a drug dispensing. ResultsTwelve-month persistence rates were 72% for upadacitinib, 61% for baricitinib, 58% for subcutaneous tumor necrosis factor-alpha inhibitors (TNFi), 55% for tocilizumab, 53% for tofacitinib, and 49% for abatacept. Median treatment persistence was not reached for upadacitinib (n=574) and baricitinib (n=553); and was 15.0 months for tofacitinib (95% CI 13.5–19.5), 20.5 months for TNFi (95% CI 19.0–22.4), 19.1 months for tocilizumab (95% CI 17.9–23.6), and 12.5 months for abatacept (95% CI 10.4–14.9). Persistence rates on first-line JAK inhibitors were 68% for upadacitinib and baricitinib and 55% for tofacitinib, and 49% for TNFi, 55% for abatacept, and 57% for tocilizumab; rates were sustained for upadacitinib, TNFi, and tocilizumab but dropped to 59% for baricitinib and 47% for abatacept in the second-line treatment. For each b/tsDMARD, persistence rates were higher when combined with methotrexate or other conventional synthetic DMARDs. The median oral glucocorticoid dose decreased from 4.3 mg/day (range:0–40) to 2.3 mg/day (range:0–22) over 2 years. Changes were significant for all RA DMARDs, tofacitinib and baricitinib combined (1–2 years post initiation only), TNFi, abatacept, and tocilizumab. ConclusionsIn a real-world setting, we showed highest persistence rates on upadacitinib, followed by baricitinib and then TNFi therapy and was improved by co-therapy. All agents appeared to be corticosteroid sparing.

Epidemiology and clinical significance of persistent bacteremia in severely burned patients

BackgroundThe utility of follow-up blood cultures (FUBC) for gram-negative bloodstream infections (BSIs) are controversial due to low rates of positivity. However, recent studies suggest higher rates of positivity in critically ill patients. The utility of FUBC in gram-negative BSI in patients with severe burn injuries is unknown. MethodsPatients ≥ 18 years old admitted to the US Army Institute of Surgical Research Burn Center for combat-related thermal burns from 1/2003–6/2014 with a monomicrobial BSI were included. FUBC were defined as repeat cultures 1–5 days from index BSI. Persistent BSI (pBSI) was defined as isolation of the same organism from initial and FUBC. The primary endpoint was all-cause in-hospital mortality in patients with gram-negative pBSI. ResultsOf 126 patients meeting inclusion criteria with BSI, 53 (42%) had pBSI. Compared to patients without persistence, patients with pBSI had more severe burns with median total body surface area (TBSA) burns of 47% ([IQR 34–63] vs. 35.3% [IQR 23.3–56.6], p = 0.02), increased mortality (38 vs. 11%, p = 0.001) compared to those with non-persistent BSI. On multivariate analysis, pBSI was associated with an odds ratio for mortality of 5.3 [95% CI 1.8–15.8, p = 0.003). Amongst gram-negative pathogens, persistence rates were high and associated with increased mortality (41% vs. 11%, p = 0.001) compared to patients without pBSI. ConclusionIn this cohort of military patients with combat-related severe burns, pBSI was more common than in other hospitalized populations and associated with increased mortality. Given this high frequency of persistence in patients with burn injuries and associated mortality, FUBC are an important diagnostic and prognostic study in this population.

Real-world effectiveness and persistence of secukinumab in the treatment of patients with psoriatic arthritis.

Psoriatic arthritis (PsA) is a complex and heterogeneous inflammatory disease. Secukinumab, a biologic disease-modifying antirheumatic drug (bDMARD), has extensive clinical evidence of efficacy and safety in the treatment of PsA but data in clinical practice are still limited. This study aims to provide real-world evidence on secukinumab use, effectiveness, and persistence in PsA. A retrospective, multicenter study was conducted on patients diagnosed with PsA and treated with secukinumab up to June 2021 at 12 centers in the Valencian Community (Spain). Data on DAS28-CRP, DAPSA, Tender and Swollen Joint Counts (TJC, SJC), enthesitis, dactylitis, skin and nail involvement, pain, patient and physician global assessment (ptGA, phGA) using 100-mm visual analog scale (VAS), and persistence for up to 24 months were collected. A total of 178 patients were included (49% men; mean [standard deviation, SD] age: 51.4 [10.5] years; 39% obese). Secukinumab was used as a first-, second-, or ≥ third-line bDMARD in 37, 21, and 42% of patients, respectively. The percentage of patients achieving at least low disease activity (DAS28-CRP ≤ 3.2) increased from 25% at baseline to 66% at month 6 (M6) and was maintained (75%) up to M24. Mean (SD) DAS28-CRP baseline values (3.9 [1.2]) decreased to 2.9 (1.1) (p < 0.001) at M6 and remained low through M24 (2.6 [1.1]) (p < 0.001). Secukinumab also improved peripheral arthritis increasing the percentage of patients with TJC = 0 (20% baseline; 57% M24) and SJC = 0 (37% baseline; 80% M24). Treatment reduced the percentage of patients with enthesitis (25% baseline; 6% M24), dactylitis (20% baseline; 4% M24), and skin (70% baseline; 17% M24), and nail (32% baseline; 2% M24) involvement. Additionally, we observed improvements in the mean pain VAS (-26.4 mm M24), ptGA (-26.2 mm M24), and phGA (-24.8 mm M24). Secukinumab showed an overall 24-month persistence rate of 67% (95% confidence interval [CI]: 60-74%). Patients receiving first-line secukinumab showed the highest 24-month persistence rate (83, 95% CI: 73-92; p = 0.024). Secukinumab showed long-term effectiveness across the six key PsA domains thus reducing disease activity and pain, which are major treatment goals. This was accompanied by high persistence rates, especially in bDMARD naive patients.

Ustekinumab as induction and maintenance therapy for ulcerative colitis – national extended follow-up and a review of the literature

ABSTRACT Introduction Ustekinumab use in ulcerative colitis had shown low adverse event and high persistence rates to 3 years via the UNIFI long-term extension study. Outcomes beyond 3 years have not been previously described. We describe the safety signals of the entire UNIFI Australian population beyond 3 years. Methods This retrospective multicenter observational cohort study recruited from all Australian UNIFI centers. The primary outcome was safety via adverse events. Secondary outcomes included the clinical relapse rate on ustekinumab, and the need to switch from ustekinumab to an alternate agent. Results There were 14 patients [11 male, mean age 47 (±14) years], with a median diagnosis of 10.8 (±4.5) years prior to UNIFI enrollment. Median follow-up was 298 weeks (5.7 years) (Interquartile range (IQR): 220–311 weeks). Within the long-term extension, there were three serious adverse events and one minor event. 42.9% (6/14) patients had clinical relapses, of which clinical remission was recaptured in 83.3% (5/6). 85.7% (12/14) persisted on ustekinumab in the long-term, with 7.1% (1/14) electively ceasing ustekinumab and 7.1% (1/14) changed from ustekinumab due to clinical relapse. Conclusion For moderate-to-severe UC in Australia, ustekinumab maintained efficacy beyond 3 years with a high persistence rate and no new safety signals. Trial Registration The trial is registered at ANZCTR (identifier: ACTRN12622001332718).

Real-World Effectiveness and Safety of SDZ ETN, an Etanercept Biosimilar, in Patients with Rheumatic Diseases: Final Results from Multi-Country COMPACT Study.

COMPACT, a non-interventional study, evaluated the persistence, effectiveness, safety and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA), axial-spondyloarthritis (axSpA) or psoriatic arthritis (PsA) treated with SDZETN (etanercept [ETN] biosimilar) in Europe and Canada. Patients (aged ≥ 18years) who have been treated with SDZETN were categorised on the basis of prior treatment status (groupsA-D): patients in clinical remission or with low disease activity under treatment with reference ETN or biosimilar ETN and switched to SDZETN; patients who received non-ETN targeted therapies and switched to SDZETN; biologic-naïve patients who started SDZETN after conventional therapy failure; or disease-modifying anti-rheumatic drug (DMARD)-naïve patients with RA considered suitable for treatment initiation with a biologic and started on treatment with SDZETN. The primary endpoint was drug persistence, defined as time from study enrolment until discontinuation of SDZETN treatment. Of the 1466 patients recruited, 844 (57.6%) had RA, 334 (22.8%) had axSpA and 288 (19.6%) had PsA. Patients had an ongoing SDZETN treatment at the time of enrolment for an observed average of 138days (range 1-841); 22.7% of patients discontinued SDZETN through 12months of study observation. Overall, all the patients receiving SDZETN showed good treatment persistence at 12months with discontinuation rates of 15.2%, 25.7% and 27.8% in groupsA, B and C, respectively. Across all patient groups, no major differences were observed in the disease activity and PRO scores between baseline and month12. Injection-site reactions were low across the treatment groups. These results support the effectiveness and safety of SDZETN treatment in patients with RA, axSpA or PsA in real-life conditions. The treatment persistence rates observed were consistent with previously published reports of patients treated with reference or other biosimilar ETN. No new safety signals were identified.

Chemical Peeling Therapy Using Phenol for the Cervico-Vaginal Intraepithelial Neoplasia.

Objective: This study aimed to validate the use of liquid phenol-based chemical peeling therapy for cervical and vaginal intraepithelial neoplasia (CIN and VaIN, respectively), with the goal of circumventing obstetric complications associated with surgical treatment and to determine the factors associated with treatment resistance. Methods: A total of 483 eligible women diagnosed with CIN, VaIN, or both, participated in this study. Participants underwent phenol-based chemical peeling therapy every 4 weeks until disease clearance. Disease clearance was determined by negative Pap tests for four consecutive weeks or by colposcopy. HPV genotyping was conducted at the onset of the study and after disease clearance in select cases. Our preliminary analysis compared the recurrence and persistence rates between 294 individuals who received phenol-based chemical peeling therapy and 189 untreated patients. Results: At 2 years following diagnosis, persistent disease was observed in 18%, 60%, and 88% of untreated patients with CIN1-3, respectively, and <2% of patients with CIN who received phenol-based chemical peeling therapy. Among 483 participants, 10 immune-suppressed patients required multiple treatments to achieve disease clearance, and 7 were diagnosed with cervical cancer. Of the 466 participants, except those with cancer or immune suppression, the number of treatment sessions until CIN/VaIN clearance ranged from 2 to 42 (average: 9.2 sessions). In total, 43 participants (9.2%) underwent surgical treatment. Six patients (1.3%) experienced recurrence of CIN2 or worse, suggesting that treatment failed in 46 patients (9.9%). No obstetrical complications were noted among the 98 pregnancies following this therapy. Factors associated with resistance to this therapy include immune suppression, ages 35-39 years, higher-grade lesions, and multiple HPV-type infections. Conclusions: Phenol-based therapy is safe and effective for CINs and VaINs. Women aged < 35 years and with persistent CIN1 or CIN2 with a single HPV-type infection are suitable candidates for phenol-based chemical peeling therapy. However, this therapy requires multiple lengthy sessions.