Current Medical Research and Opinion最新文献

Introduction: Adult-type granulosa cell tumor of the testis is an extremely rare sex cord-stromal tumor. While most AGCTs are considered indolent with low metastatic potential, a small subset may exhibit aggressive behavior. Due to the rarity of this tumor, optimal management strategies and prognostic markers remain unclear. We present a rare case of adult-type granulosa cell tumor of the testis with pulmonary metastases and review the clinical features, treatments, and outcomes of previously reported metastatic cases.

Case report: A 33-year-old man presented with a four-month history of left testicular enlargement. Partial orchiectomy revealed AGCT with a low proliferative index (Ki-67 ∼ 10%) and a negative FOXL2 mutation. One month later, he developed a local recurrence with elevated Ki-67 (∼60%) and vascular invasion. PET/CT revealed multiple pulmonary metastases. The patient received four cycles of BEP chemotherapy and achieved a partial response. However, early disease progression followed. Second-line treatment with tislelizumab, nab-paclitaxel, carboplatin, and anlotinib led to temporary stabilization. Salvage chemotherapy with doxorubicin, ifosfamide, and dacarbazine failed, and the patient died two months later. A review of 11 additional metastatic AGCT cases showed that patients with resectable metastases had favorable outcomes, while those with distant metastases responded poorly to systemic therapy.

Conclusion: Although adult-type granulosa cell tumor of the testis is generally indolent, some cases may behave aggressively. Tumor size, vascular invasion, and proliferative index may correlate with metastatic potential. Patients who undergo complete resection of metastatic lesions tend to achieve better outcomes, whereas responses to systemic therapy are generally poor. Early identification of high-risk features and consideration of retroperitoneal lymph node dissection may improve prognosis in selected patients.

The placebo effect, often dismissed as statistical noise, is a real mind-body phenomenon caused by conditioning and expectation. We should distinguish between the placebo effect (the psychobiological process) and the placebo response (the outcome). This commentary argues that placebo effects are often underestimated in randomized controlled trials (RCTs) because trial outcomes are reported as averages of both responders and non-responders. Averaging can conceal meaningful effects, distort comparisons with active treatments, and generate inaccurate conclusions about treatment efficacy. To illustrate this, I use data from my research to show how averaging across participants diminishes the statistics-based placebo effect. Therefore, ignoring response heterogeneity can reduce accuracy and mask actual effects in responders. This issue extends beyond methodology. Underestimating placebo responses can lead to Type I errors in drug approvals, while in clinical practice, it can prevent practitioners from leveraging placebo mechanisms as part of holistic care. Ethical concerns also arise when the total placebo response approaches that of a drug, raising questions about exposing patients to unnecessary medication risks. Future trials should capture individual differences, such as expectancy assessments, prior-experience measures, stratified randomization, latent-class models, and biomarker research. Although these approaches pose challenges, they could incorporate heterogeneity into analysis and practice. In conclusion, embracing variability in placebo and treatment responses is more than a technical change; it is a shift toward greater validity, reliability, and personalized medicine. Moving beyond group averages and recognizing individual differences can help research produce more reliable evidence to guide treatment decisions.

Introduction: Patient engagement (PE) is increasingly recognized as an essential component of medicine development, yet there remains limited empirical evidence on its value from the patient perspective. Existing literature points to benefits such as empowerment, improved trial design, and greater acceptability, but challenges around communication, authenticity, and sustainability persist.

Objectives: This study explored the perceived value, challenges, and strategies for effective PE from the perspective of patients, carers, and patient advocates involved in medicines development.

Methods: A qualitative study was conducted using semi-structured interviews on Microsoft Teams. Participants were recruited via LinkedIn and academic networks if they had lived experience of a health condition, caregiving responsibilities, or advocacy roles and had engaged with the pharmaceutical industry. Twenty-two interviews were conducted online between 23 April and 26 November 2024, recorded, transcribed, and analyzed using reflexive thematic analysis.

Results: Six overarching themes and 23 sub-themes were identified covering participants' understanding, motivations, initiatives, value, challenges and strategies for being involved. Engagement was valued for enhancing clinical trial outcomes, personal empowerment, and community support. Challenges included structural barriers, tokenism, lack of feedback, and inconsistent practices across companies and patient organizations. Strategies to improve PE emphasized clear communication, simplification and formalization of processes, greater inclusivity, capacity building, and stronger alliances among advocacy groups. Participants also highlighted the need for fair compensation and balancing regulation with meaningful involvement.

Conclusions: Patients perceive PE as transformative when authentic, inclusive, and supported by transparent communication. Addressing structural inconsistencies, recognizing diverse patient identities, and prioritizing relational over transactional approaches are critical for embedding meaningful and sustainable PE in medicine development.

Objective: To describe long-term changes in proteinuria, treatment status, and clinical events among patients with lupus nephritis (LN) in Japan using a database containing electronic medical records and health insurance claims.

Methods: Patients aged 18-50 years with active LN (i.e. urine protein/creatinine ratio [UPCR] ≥ 0.5 g/gCr or a qualitative urine protein test result of ≥2+) were identified. Assessment variables included temporal changes in UPCR and glucocorticoid (GC) use/dose. The time to renal remission or flare was examined using the Kaplan-Meier analysis and Cox proportional hazards model. Clinical events were identified.

Results: Of 917 patients with active LN, the mean UPCR in 392 patients with UPCR ≥0.5 g/gCr was 2.7 ± 4.0 g/gCr at LN diagnosis, with a median 1.3 (first quartile, third quartile: 0.6, 3.1) g/gCr, followed by a gradual decline until ≥60 months. GC therapies were provided to up to 53.5% of patients within 2 weeks of LN diagnosis, and the proportion persisted thereafter. The median oral GC dose was 10.0-17.8 mg/day within 2 weeks, 17.0-18.9 mg/day until 2 months, and 11.0 (7.3, 16.9) mg/day at 6 months, followed by continuous use with a slight decline. Female sex and visiting more clinical departments were likely to be associated with renal remission, whereas older age was associated with non-remission. No baseline variables were predictive of flares.

Conclusion: Using urine laboratory test results, we presented invaluable data on long-term changes in UPCR, GC use, and clinical events. These reports may serve as a foundation for developing treatment strategies for these patients.

Objective: Colorectal cancer (CRC) screening rates fall short of national goals. This study aimed to understand eligible individuals' preferences regarding CRC screening modalities to improve screening adherence.

Methods: Two cohorts took a discrete choice experiment survey: adults aged 45-75 years at average risk for CRC, and physicians who recommend CRC screening. Five attributes (test type, test frequency, true positive rate, true negative rate, adenoma true positive rate) from four different CRC screening modalities (cell-free DNA blood test [cf-DNA-BT], colonoscopy, fecal immunochemical test [FIT], multi-target stool DNA [mt-sDNA] test) were assessed. Test-specific performance was derived from clinical data. Predicted choice probability (PrCP) of each modality was calculated from the results of a mixed logit model. Subgroup analyses were performed.

Results: Among 1249 adult respondents, mt-sDNA was the preferred modality (PrCP 39.4%) versus colonoscopy (24.8%), cf-DNA-BT (21.1%), and FIT (14.7%). In all subgroups, respondents preferred mt-sDNA. Respondents with previous non-invasive CRC screening experience (PrCP 53.5%) and with no prior CRC screening (42.1%) preferred mt-sDNA. PrCP for colonoscopy was lower for populations historically less likely to be adequately screened for CRC (such as 45-49-year-old respondents [PrCP 21.1%] and non-White respondents [23.1%]). PrCP among 400 physicians was highest for colonoscopy (PrCP 95.0%) versus mt-sDNA (4.3%), cf-DNA-BT (0.4%), and FIT (0.3%). No significant difference in preferences was found between primary care providers and gastroenterologists.

Conclusion: US adults eligible for CRC screening preferred mt-sDNA testing over other screening modalities, while physicians highly preferred colonoscopy. Offering CRC screening options that align with patient preferences may result in higher screening adherence.

Introduction: Primary bone lymphoma (PBL) is a rare extranodal subtype of diffuse large B-cell lymphoma (DLBCL) that poses significant diagnostic challenges due to nonspecific clinical and radiological features. Molecular profiling and ctDNA monitoring now offer promising approaches for precision treatment and disease surveillance in DLBCL.

Case report: A 54-year-old woman presented with persistent knee pain and multiple osteolytic lesions. After several nondiagnostic biopsies, open surgical biopsy confirmed germinal center B-cell-like DLBCL with high-risk molecular features (BCL2/MYC rearrangements, EZB subtype). The patient received molecularly guided therapy with Pola-R-CHP plus venetoclax, achieving complete metabolic remission. However, persistent MEF2B and TET2 mutations in ctDNA indicated MRD positivity, prompting consolidative CAR-T therapy (axicabtagene ciloleucel), after which she achieved sustained molecular remission with undetectable ctDNA.

Conclusion: This case highlights three key aspects in managing PBL: the critical role of surgical biopsy for definitive diagnosis, particularly with concealed lesions; the value of molecular profiling in guiding targeted therapy; and the utility of ctDNA monitoring for MRD detection and treatment guidance. An integrated approach incorporating these strategies may improve outcomes for this rare lymphoma subtype.

Objective: This study aimed to estimate the projected budget impact of introducing MP-AzeFlu, a fixed-dose nasal of a corticosteroid (fluticasone propionate) and an antihistamine (azelastine hydrochloride). The evaluation focused on the potential cost savings for patients and healthcare systems in Saudi Arabia and the United Arab Emirates (UAE).

Methods: A budget impact model was developed in Excel over a period of five years, as per the ISPOR guidelines. The analysis focused exclusively on direct medication costs sourced from the Saudi FDA and UAE Department of Health, excluding costs related to healthcare resource utilization or productivity. Drug prices were obtained from each Ministry of Health price list and inflated to 2024 values (no discounting). It was assumed that the population size would remain constant over five years.

Results: In Saudi Arabia, substituting dual therapy with MP-AzeFlu yielded marginal cost savings of SAR 3.9 million by year five (1.4% of the baseline expenditure of SAR 273.9 million). In the UAE, a similar switch resulted in cost savings of AED 0.55 million (1.4% of the baseline expenditure of AED 38.4 million). A scenario analysis comparing MP-AzeFlu to triple therapy showed even greater cost savings: SAR 10.5 million in the KSA (2.6% of the baseline expenditure of SAR 405.4 million) and AED 1.5 million in the UAE (2.7% of the baseline expenditure of AED 59.07 million).

Conclusion: The introduction of MP-AzeFlu in Saudi Arabia and the United Arab Emirates showed cost-neutral to cost-saving impacts, depending on whether it replaces dual or triple therapy regimens.

Objective: This qualitative interview study explored the preferences of people living with schizophrenia or bipolar I disorder (BP-I), caregivers, and prescribers regarding the features of long-acting injectable (LAI) antipsychotics, as well as factors influencing preferences for a hypothetical LAI administered once every 2 months.

Methods: Trained moderators conducted online video interviews with stable adult patients with schizophrenia or BP-I receiving a once-monthly LAI, caregivers, and prescribers in the United States and Canada. The interview transcripts were analyzed for themes.

Results: Twelve patients, five caregivers, and five prescribers were included in the schizophrenia and BP-I samples. For patients and caregivers, an ideal treatment was efficacious, administered less often than a once-monthly LAI, and had minimal or no side-effects. Important LAI features included staying on the same medication, choice of injection site, and dosing frequency. Patients and caregivers viewed a once-every-2-months LAI positively, due to fewer appointments and reduced injection impact, but noted concerns about its effectiveness and potential side-effects. When prescribing LAIs, prescribers considered patient- and treatment-related factors, access, and control. The potential for greater patient freedom and stability with a once-every-2-months LAI was noted, but a loss of dosing control was a concern. Several differences between schizophrenia and BP-I samples were identified, including the level of patient/caregiver involvement in treatment decisions and unique treatment goals.

Conclusions: People living with schizophrenia or BP-I, caregivers, and prescribers in the United States and Canada generally had favorable views of LAIs administered once every 2 months. Quantitative follow-up research that extends these findings is warranted.

Objective: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recommended as glucose-lowering therapies for people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). Real-world evidence is limited comparing cardiovascular (CV) outcomes between once-weekly (OW) GLP-1 RAs vs other non-insulin glucose lowering therapies (ONIGLTs) including SGLT2is. This study aimed to compare CV outcomes among Medicare Advantage (MA) beneficiaries with T2D and ASCVD initiating OW GLP-1 RAs or ONIGLTs.

Methods: This observational cohort study included MA beneficiaries with T2D and ASCVD within Optum's de-identified Clinformatics Data Mart Database (01/2007-03/2024). Propensity score matching was used to compare adults initiating OW GLP-1 RAs or ONIGLTs. Incidence rates and time to the first event of ischemic stroke (IS), myocardial infarction (MI), 2-, 3-, and 5-point major adverse cardiovascular event (MACE) during follow-up were assessed. Individual OW GLP-1 RAs were compared with SGLT2is.

Results: Post-matching, 41,835 adults were treated with OW GLP-1 RAs and 77,599 with ONIGLTs. Compared with ONIGLTs, OW GLP-1 RAs had 18% lower risk for IS, 14% lower for MI, 17% lower for 2-point MACE, 28% lower for 3-point MACE, and 27% lower for 5-point MACE. Compared with SGLT2is, OW GLP-1 RAs had 14% lower risk of 2-point MACE, 15% lower risk of 3-point MACE, and 14% lower risk of 5-point MACE. Semaglutide had lower risk of all CV outcomes vs SGLT2is.

Conclusion: Among MA beneficiaries with T2D and ASCVD, risk of CV outcomes was lower with OW GLP-1 RAs, particularly semaglutide, vs ONIGLTs including SGLT2is.

Objective: To assess incremental all-cause healthcare resource utilization (HCRU) and costs among people living with HIV (PLWH) with and without chronic kidney disease (CKD) in the United States.

Methods: A retrospective administrative claims analysis was conducted using Optum's de-identified Clinformatics^® Data Mart Database (Jan 2020-Dec 2022). Adult PLWH with ≥1 pharmacy claims for anchor antiretroviral (ART) agent in 2021 (index date: earliest anchor ART claim) were followed for 12 months or to the end of continuous enrollment and stratified based on the baseline presence of CKD (yes/no). Differences between CKD groups in per-person-per-month (PPPM) HCRU and costs (converted to 2023 USD) were estimated using multivariable generalized linear models adjusted for baseline characteristics.

Results: Of 22,402 PLWH identified, 3,753 (16.8%) had CKD. PLWH with versus without CKD were older (mean age 63.35 vs 53.02 years), a larger proportion were women (23.2% vs >18.0%) or Black (35.7% vs 29.0%), and they had higher mean Quan-Charlson Comorbidity Index scores (3.23 vs 0.92) and baseline total costs ($5,259 vs $3,644); all p<0.001. Compared to PLWH without CKD, PLWH with CKD had significantly higher unadjusted all-cause PPPM HCRU and costs (all p<0.001), and significantly greater all-cause adjusted PPPM HCRU, total costs, medical costs, and inpatient costs (all p<0.001), whereas adjusted pharmacy costs were significantly lower (p=0.025).

Conclusions: PLWH with CKD generally experience greater HCRU and cost burden than those without CKD. These increases may be mitigated by recognizing modifiable CKD risk factors and tailoring HIV care, which may also improve overall health of PLWH.