Nevin Manimala

J Prev Alzheimers Dis. 2025 Oct 27:100391. doi: 10.1016/j.tjpad.2025.100391. Online ahead of print.

ABSTRACT

BACKGROUND: A new era of Alzheimer’s disease (AD) research is beginning with multiple approved anti-amyloid monoclonal antibodies (mABs). These drugs are currently not widely used, but may be soon, especially at clinical trial sites. Putative disease-modifying therapies (DMTs) may alter the progression rate, potentially reducing our ability to detect effects on top of mABs. Co-administration of amyloid-targeted agents may diminish benefit (antagonism, due to the overlapping mechanism of action); alternatively, complementary treatment mechanisms may increase benefit (synergy).

METHOD: We consider several clinical trial design scenarios: a 2-arm trial added-on to a mAB, a 2-arm combination compared to double placebo, and a 4-arm full factorial trial. We calculate the required sample sizes for the shortest practical study for secondary prevention (prevention of AD clinical diagnosis in biomarker positive individuals, 2-year study), early AD (18-months), and mild-to-moderate AD (1-year). We consider additivity, antagonism, and synergy.

RESULT: The expected interaction between investigational and mAB treatment can have a large effect on power and study design. Antagonistic treatment effects often require double the sample size of synergistic effects. The 4-arm scenario required ∼10-fold increase compared to a 2-arm combination study.

CONCLUSION: Studies evaluating investigational therapies as add-on to mABs are complex, and their cost will depend on the interaction between treatments. An inescapable fact in add-on trials is the slower progression of the control arm; and it is difficult to further slow already slow progression. Treatments that are likely to work better with amyloid removal will be easier to study due to their complementary MOA. Symptomatic treatments may require fewer additional subjects than disease-modifying treatments since they are less affected by the presence or absence of mABs.

PMID:41145342 | DOI:10.1016/j.tjpad.2025.100391

J Prev Alzheimers Dis. 2025 Oct 27:100392. doi: 10.1016/j.tjpad.2025.100392. Online ahead of print.

ABSTRACT

Statistical methods in clinical research tend to become entrenched. Innovations threaten the status quo. The “right way” becomes frozen in lore. This is so even when the “right way” is not best. “Statistical significance” and the associated requirement of “high power” is an example. This attitude is an impediment to efficient design. Willingness to address some design issues with moderate power enables building highly informative and highly efficient clinical trials. This article considers several types of clinical trials, including dose-finding, combinations, and factorial designs. Bayesian adaptive methods are used to show that trials can be made more efficient and more informative. Surprisingly, the approach is consistent with many attitudes of the widely regarded “Father of Modern Statistics,” R.A. Fisher. Fisher was anti-Bayesian in rejecting its subjective interpretations. But Fisher and Bayes come to the same conclusion in many applied matters. Fisher invented factorial design. Its principal attraction for him was enabling addressing two or more questions with a single experiment. He complained about attitudes that hindered progress: “No aphorism is more frequently repeated in connection with field trials [and clinical trials], than that we must ask Nature few questions, or, ideally, one question at a time… this view is wholly mistaken.” Fisher’s primary analysis required modeling and making assumptions. For example, his first analysis in a factorial setting assumed no interactions among the factors. He investigated possibilities of interactions but he did not see the need for doing so with high power.

PMID:41145340 | DOI:10.1016/j.tjpad.2025.100392

Cardiovasc Revasc Med. 2025 Oct 17:S1553-8389(25)00545-7. doi: 10.1016/j.carrev.2025.10.010. Online ahead of print.

ABSTRACT

BACKGROUND: Tricuspid regurgitation (TR) is a common valvular disorder linked to significant morbidity and mortality. Transcatheter tricuspid valve intervention (TTVI) has emerged as a novel therapeutic option for high-risk patients. However, randomized controlled trials (RCTs) evaluating its clinical efficacy remain limited in sample size, making it difficult to draw definitive conclusions.

METHODS: We conducted a systematic review of studies comparing outcomes between TTVI vs. optimal medical therapy (OMT) published between January 2000 to June 2025 in PubMed, Cochrane, and Embase. The primary outcomes were all-cause mortality and heart failure hospitalization (HFH). The secondary outcomes included cardiovascular death, TR severity, NYHA class improvement, and Kansas City Cardiomyopathy Questionnaire (KCCQ) score.

RESULTS: Three RCTs, including 1264 patients (TTVI: 696; OMT: 568), were analyzed. At one year, there was no significant difference in all-cause mortality (RR: 1.12; 95 % CI: 0.77-1.63; p = 0.55), HFH (RR: 0.83; 95 % CI: 0.64-1.07; p = 0.15) and cardiovascular death (RR: 1.11; 95 % CI: 0.7-1.77; p = 0.65) between groups. Patients in TTVI group significantly improved at least 1 class in NYHA functional classification (RR: 2.77; 95 % CI: 1.72-4.49; p < 0.0001), had greater changes in KCCQ scores (+15.23 points; 95 % CI: 12.03-18.44; p < 0.0001), and markedly reduced the incidence of ≥ severe TR at follow-up (RR: 0.09; 95 % CI: 0.03-0.27; p < 0.0001) compared to OMT.

CONCLUSIONS: Although TTVI has not demonstrated statistically significant reductions in all-cause mortality or HFH, it is associated with substantial improvements in functional class, quality of life, and TR severity, supporting its role in select high-risk patients.

PMID:41145332 | DOI:10.1016/j.carrev.2025.10.010

J Hepatol. 2026 Jan 30:S0168-8278(25)02478-X. doi: 10.1016/j.jhep.2025.08.039. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Given country-specific variance in legislation, limited information is available regarding outcomes of liver transplantation (LT) using medical assistance in dying (MAiD) donation after circulatory death (DCD type-V) grafts. We compared outcomes following LT using DCD type-V vs. conventional DCD type-III grafts.

METHODS: We reviewed all LTs using DCD-V and DCD-III donors performed across Canadian provinces between 2016 (MAiD legalization) and 2023. Primary outcomes were patient and graft survival at 1, 3, and 5 years. Secondary outcomes included early allograft dysfunction, length of stay, postoperative complications, and biliary complications.

RESULTS: Among 313 recipients, 56 (17.9%) received DCD-V and 257 (82.1%) DCD-III grafts. DCD-V donors were older (56 vs. 38 years, p <0.0001), and had similar warm ischemic time (20 vs. 23 min, p = 0.190). Patient survival for DCD-V was 89.3%, 85.7%, and 85.7% at 1, 3, and 5 years, with graft survival of 82.1%, 78.6%, and 78.6%, comparable to DCD-III. DCD-V was not associated with graft loss (odds ratio 1.64; 95% CI 0.66-4.08), which was confirmed by multivariable Cox regression analysis (hazard ratio 1.53; 95% CI 0.74-3.15). Early allograft dysfunction occurred more frequently with DCD-III (57.5% vs. 42.9%, p = 0.047), whereas length of stay was longer with DCD-V (21.5 vs. 15 days, p = 0.011). Overall complication rates were similar; biliary complications were more common in DCD-V, but this was not statistically significant (32.1% vs. 23.1%, p = 0.153).

CONCLUSIONS: Liver grafts from MAiD donors provide outcomes comparable to DCD-III and increased Canadian DCD activity by 21.8%. These findings support MAiD as a valuable additional source of liver grafts, though larger studies are needed to validate long-term safety and efficacy.

IMPACT AND IMPLICATIONS: Liver transplantation using grafts from donors following medical assistance in dying (MAiD) achieves satisfactory patient and graft survival, with complication rates comparable to those following conventional donation after circularly death. MAiD donation increased donation after circularly death liver transplant activity in Canada by 21.8% over 7 years. These findings support MAiD as a valuable additional source of grafts, while also honoring the wishes of patients who choose to donate their organs.

PMID:41145323 | DOI:10.1016/j.jhep.2025.08.039

J Adv Nurs. 2025 Oct 27. doi: 10.1111/jan.70312. Online ahead of print.

ABSTRACT

AIM: To report on women’s experiences of perimenopause and menopause.

DESIGN: A mixed-methods design using an online survey and interviews.

METHODS: Data were collected simultaneously between April and July 2022. Women over the age of 18 who self-identified as being in perimenopause or menopause were invited to complete an online survey. Women who completed the survey were also invited to participate in an interview to discuss their experiences in more detail. Quantitative data were analysed using descriptive statistics. Qualitative data were transcribed verbatim and thematically analysed.

RESULTS: Four hundred and eleven women completed the survey in its entirety. Twenty-five women who self-identified as being in perimenopause and menopause participated in one-on-one interviews. Both quantitative and qualitative data are presented under three themes: (1) The unexpected sequelae on daily life; (2) Experiencing stigma and shame; and (3) Feeling dismissed and devalued.

CONCLUSION: Gender inequality, silence and stigma negatively impact the health and well-being of women experiencing perimenopause and menopause. Encouraging conversations and challenging existing negative attitudes to perimenopause and menopause can reduce stigma, improve health literacy and enhance women’s experiences of this life transition.

IMPLICATIONS FOR THE PROFESSION AND OR PATIENT CARE: Further education for nurses and other health care professionals about perimenopause and menopause is required to better diagnose, treat and support women. Nurse-led models of care could provide timely access to menopause care. Workplaces could enhance the productivity and work satisfaction of women experiencing perimenopause and menopause by changing policy to ensure flexibility in the workplace and implementing measures to ensure their comfort.

SUMMARY STATEMENT: Women are largely unprepared for the impact perimenopause/menopause has on their everyday lives. The stigma and shame associated with perimenopause and menopause limits women’s access to support and contributes to negative outcomes for their health and well-being. Health professionals often have inadequate knowledge about perimenopause and menopause and can be dismissive of women experiencing this transition.

REPORTING METHOD: Reporting of the study was guided by The Good Reporting of a Mixed Methods Study (GRAMMS) checklist.

NO PATIENT OR PUBLIC CONTRIBUTION: This study did not include patient or public involvement in its design, conduct or reporting.

PMID:41145319 | DOI:10.1111/jan.70312

Yonsei Med J. 2025 Nov;66(11):797-805. doi: 10.3349/ymj.2024.0544.

ABSTRACT

PURPOSE: Recent concerns regarding the delivery of surgical services in South Korea emphasize the need for close monitoring of spatial access to surgical care in patients with acute appendicitis at the regional level.

MATERIALS AND METHODS: This study included emergency department (ED) visits with acute appendicitis and subsequent appendectomies from the National Emergency Department Information System database (2015-2021). Travel distances to the hospital were measured, and the proportion of patients admitted to regional hospitals was visualized on a geographic map. Factors related to complicated appendicitis were analyzed using logistic regression.

RESULTS: Among 207344 patients who visited the EDs, those from areas with low population density had higher proportions of patients aged ≥65 years (23.2%), Medical Aid recipients (4.8%), transfers from other hospitals (39.3%), and cases of complicated appendicitis (7.0%) compared to other regions. Additionally, patients in low-density regions had the highest proportion of traveling 50 km or more (27.7%), compared to those in mid-density (5.9%) and high-density (2.5%) regions. In the multivariate analysis, patients aged ≥65 years exhibited a stronger association with complicated appendicitis compared to other age groups.

CONCLUSION: The current results suggested that regions with low population density experienced low access to surgical care, revealing significant regional variation linked to population density. Given the rapidly aging population and the concentration of residents in urban areas in South Korea, urgent policy action is needed to ensure the adequate delivery of emergency general surgery services in low-density regions.

PMID:41145315 | DOI:10.3349/ymj.2024.0544

Yonsei Med J. 2025 Nov;66(11):790-796. doi: 10.3349/ymj.2024.0490.

ABSTRACT

PURPOSE: We aimed to investigate the association between the results of color vision tests and simulation tests for police tasks among participants with color vision deficiencies (CVDs) and those with normal vision, and to assess the agreement between the results of various color vision tests.

MATERIALS AND METHODS: Participants with CVDs and healthy controls were recruited. Participants in the CVD group were classified into three subgroups (mild weakness, severe weakness, and color blindness). All participants performed simulation tests (bloodstain identification, traffic light test, and analysis of dashboard camera recordings) and clinical color vision tests. We statistically analyzed the association between color vision tests and simulation tests and quantitatively assessed the agreement between various color vision tests.

RESULTS: We evaluated 25 participants with normal vision (92.0% male) and 21 with CVDs (95.2% male). Even in the mild CVD group, the scores for the traffic light test and dashboard camera recordings were lower than those of the control group (9.40±0.57 vs. 9.06±0.84, and 1.80±0.40 vs. 1.44±0.77, all p<0.05). However, no difference in the bloodstain identification test scores was observed between the control and CVD groups (p=0.190). Additionally, the association with anomaloscope results was strongest in the following order: Ishihara, Hardy-Rand-Rittler, Farnsworth-Munsell 100 hue, and Farnsworth D-15 tests.

CONCLUSION: This study demonstrated a correlation between the results of clinical color vision tests and police-related simulation tests. Particularly, the score for recognizing traffic signs or analyzing dashboard camera recordings was lower even in those with mild CVD than in those with normal vision.

PMID:41145314 | DOI:10.3349/ymj.2024.0490

Yonsei Med J. 2025 Nov;66(11):722-730. doi: 10.3349/ymj.2025.0058.

ABSTRACT

PURPOSE: Pneumocystis jirovecii pneumonia (PJP) is a life-threatening infection. The prevalence of PJP in patients without human immunodeficiency virus (HIV) (non-HIV-PJP) is increasing. Previous studies have separately evaluated the clinical characteristics of PJP patients with and without HIV infection. Therefore, this study aimed to comparatively analyze the clinical characteristics of PJP patients with and without HIV.

MATERIALS AND METHODS: We retrospectively reviewed patients with PJP who were admitted to a single tertiary center for 15 years. PJP patients were classified according to the presence or absence of HIV, and differences in their clinical characteristics and prognoses were analyzed. Forty-four HIV-PJP patients and 175 non-HIV-PJP patients were included.

RESULTS: Cough, dyspnea, typical computed tomography findings of PJP, and cytomegalovirus (CMV) pneumonitis co-infection were more common in the HIV-PJP group. The durations from symptom onset to PJ polymerase chain reaction (PCR) testing and to the start of treatment were longer in the HIV-PJP group; however, the time from the PJ PCR test to antibiotic administration was shorter in the HIV-PJP group. The 28-day survival rates were 68.6% and 88.6% in the non-HIV-PJP and HIV-PJP groups, respectively (p=0.011). The survival rate of patients with CMV pneumonitis co-infection in the non-HIV-PJP group was significantly lower.

CONCLUSION: The clinical characteristics of patients with HIV-PJP and non-HIV-PJP were statistically different. The initial clinical features appeared to be worse in the HIV-PJP group; however, the 28-day mortality rate was higher in the non-HIV-PJP group.

PMID:41145307 | DOI:10.3349/ymj.2025.0058

Am J Hosp Palliat Care. 2025 Oct 27:10499091251393485. doi: 10.1177/10499091251393485. Online ahead of print.

ABSTRACT

BackgroundEarly-onset Alzheimer’s disease is a rapidly progressing condition that severely disrupts quality of life. Early palliative care incorporation helps identify patients’ needs and facilitates family decision-making and advanced care planning for later stages.AimThe study aimed to assess palliative care needs, level of suffering, and most frequent symptoms in Early-onset Alzheimer’s patients.MethodsWe present a preliminary observational analysis as part of a larger, 18-month longitudinal study of patients with early-onset Alzheimer’s disease. Patients with the PSEN1-E280 A variant of Early-onset Alzheimer’s disease attending the Antioquia Neuroscience Group at the University of Antioquia in Medellín, Colombia, participated. Data were collected using NECPAL, Edmonton Symptom Assessment System Revised, Global Deterioration Scale/Functional Assessment Staging (GDS/FAST), Pain Assessment in Advanced Dementia (PAINAD), and a numeric rating scale. Regarding data analyses from visit 1 (V1), variables were described according to their nature. A Poisson regression was performed, and prevalence ratios, 95% confidence intervals, and P values were obtained. Statistical significance was defined with an alpha value of 5%.ResultsThirty-six patients participated in V1. Median age was 53. Most of them were women and lived in urban areas. The prevalence of palliative care needs was 22.22%. Poisson regression showed an association between clinician-perceived need for palliative care and dysphagia, pressure ulcers, asthenia, insomnia, functional decline, resource utilization, positive surprise question in NECPAL instrument, and scores of the PAINAD and GDS/FAST scales.ConclusionPatients with Early-onset Alzheimer’s have palliative care needs associated with symptoms related to disease progression, prognosis, resource utilization, and pain.

PMID:41144993 | DOI:10.1177/10499091251393485

Am J Hosp Palliat Care. 2025 Oct 27:10499091251388625. doi: 10.1177/10499091251388625. Online ahead of print.

ABSTRACT

Palliative Care Consultation (PCC) is an established intervention that prioritizes goals of care conversations and assists patients with complex medical decision-making. Evidence suggests that PCC can reduce the amount of non-goal concordant care patients receive such as fewer invasive procedures, less mechanical ventilation, and quicker transition to hospice and referral to appropriate resources, if that aligns with patient wishes. This results in decreased resource utilization, reduced anxiety for patients and their family members, and decreased moral distress for the health care team. Studies generally agree that benefits of PCC are greater the quicker the time to intervention, but results are mixed regarding hospital and intensive care unit (ICU) length of stay (LOS). LOS is a surrogate marker for goal-concordant care, and shorter LOS has been associated with decreased health care costs. This systematic literature review seeks to clarify the effects of early PCC versus standard PCC on length of stay. From an extensive search of CINAHL, EMBASE, Scopus, and PubMed, 17 articles met criteria to be reviewed. These articles include 2 randomized controlled trials (RCTs), 6 prospective cohort studies, and 9 retrospective cohort studies. Nine studies found statistically significant results linking early PCC with shorter length of stay. These results indicate that a change in practice could be considered given the multiple positive outcomes associated with early PCC. Further research is recommended with larger sample sizes across multiple institutions to improve generalizability of these initial findings, and to examine the different modalities of implementing early PCC into existing ICU workflows.

PMID:41144983 | DOI:10.1177/10499091251388625