Nevin Manimala

Clin Rheumatol. 2025 Aug 6. doi: 10.1007/s10067-025-07596-5. Online ahead of print.

ABSTRACT

BACKGROUND: There are no effective pharmacological treatments for calcium pyrophosphate deposition (CPPD) disease. We aim to identify potential therapeutic targets for CPPD disease by integrating various publicly available datasets.

METHODS: We integrated data from druggable genomes, cis-expression quantitative trait loci (cis-eQTL)/cis-protein quantitative trait loci (cis-pQTL) in human blood and skeletal muscle tissues, and genome-wide association study (GWAS) summary statistics related to CPPD disease. This integration aimed to investigate potential causal relationships between drug target genes and CPPD disease using Mendelian randomization (MR) method. To validate these causal links, we performed sensitivity analyses and Bayesian colocalization. Furthermore, we applied phenome-wide Mendelian randomization (Phe-MR) approach to assess potential side effects or alternative therapeutic indications for the identified drug targets. Finally, we explored actionable drugs for these target genes using existing databases.

RESULTS: MR analysis identified four druggable genes-ULK3, CSK, PPIE, and NFKB1-that may have potential causal associations with CPPD disease in human blood or skeletal muscle tissue. These genes were further confirmed by Bayesian colocalization (PPH4 > 80%). The upregulation of ULK3 (blood eQTL, beta: 0.62, 95% CI: 1.129-3.091, P = 0.015; muscle eQTL, beta: 0.93, 95% CI: 1.055-6.146, P = 0.037; blood pQTL, beta: 2.51, 95% CI: 1.199-126.169, P = 0.034), CSK (blood eQTL, beta: 0.69, 95% CI: 1.094-3.650, P = 0.024; muscle eQTL, beta: 0.98, 95% CI: 1.058-6.707, P = 0.037; blood pQTL, beta: 3.41, 95% CI: 1.509-606.864, P = 0.025), and PPIE (blood eQTL, beta: 0.52, 95% CI: 1.218-2.321, P = 0.001; muscle eQTL, beta: 0.85, 95% CI: 1.384-3.962, P = 0.001; blood pQTL, beta: 1.06, 95% CI: 1.094-7.565, P = 0.032) in blood and skeletal muscle tissues was positively associated with the risk of CPPD disease. Conversely, NFKB1 showed an inverse relationship with CPPD disease risk (blood eQTL, beta: – 0.99, 95% CI: 0.147-0.935, P = 0.035; muscle eQTL, beta: – 1.95, 95% CI: 0.046-0.437, P = 0.001; blood pQTL, beta: – 3.17, 95% CI: 0.002-0.762, P = 0.032). The Phe-MR analysis indicated that the four potential therapeutic targets for CPPD disease had no significant adverse effects.

CONCLUSIONS: Our research indicated that ULK3, CSK, PPIE, and NFKB1 may be promising targets for CPPD disease. Key Points • ULK3, CSK, PPIE, and NFKB1 may be drug target genes in CPPD disease.

PMID:40768106 | DOI:10.1007/s10067-025-07596-5

Support Care Cancer. 2025 Aug 6;33(9):758. doi: 10.1007/s00520-025-09813-y.

ABSTRACT

PURPOSE: Although digital health technologies (DHTs) are promising to improve health outcomes in older adults with cancer, the low adoption and limited use remain significant gaps in their effective digital health care. Little is known about their concerns about adopting and using DHTs in routine life, particularly in the continued use phase. This study aims to explore factors affecting the initial adoption and continued use of DHTs among older adults with cancer.

METHODS: A secondary analysis of qualitative data was conducted based on interviews with 21 older adults (≥ 65 years) with breast, prostate, lung, or colorectal cancer. The transcripts of interview recordings were analyzed using a thematic analysis.

RESULTS: Three major themes and several subthemes were identified as potential factors affecting the (1) initial adoption, (2) continued use, and (3) limited use of DHTs. Digitalized healthcare systems and access to technology influenced the initial adoption of DHTs. Perceived ease of use, perceived usefulness, expected timely care from providers, and increased sense of control emerged as leading factors to the continued use. The limited use of DHTs was influenced by a lack of knowledge and skills, a lack of direct interaction with providers, and concerns about digital communication quality.

CONCLUSIONS: Ensuring digital access and providing technology-based solutions that meet diverse patient needs is crucial to promoting the adoption and use of DHTs among older adults with cancer. Healthcare providers should address older adults’ low digital literacy and uncertainty to ensure the quality of cancer care provided through DHTs.

PMID:40768101 | DOI:10.1007/s00520-025-09813-y

Pediatr Radiol. 2025 Aug 6. doi: 10.1007/s00247-025-06293-4. Online ahead of print.

ABSTRACT

BACKGROUND: Our institution decided to implement an awake MRI scanning quality improvement project using audiovisual distraction (AVD) technology.

OBJECTIVE: To reduce the utilization of minimal/moderate sedation by at least 20% in children 4 to 18 years, while maintaining comparable diagnostic quality and adhering to allotted exam times, through the implementation of an awake MRI program.

MATERIALS AND METHODS: This project was conducted at a pediatric sedation clinic between October 2021 and January 2024. We included patients 4 to 18 years of age, scheduled for an MRI at the pediatric hospital, and eligible for either minimal/moderate sedation or AVD. The outcome measure was the percentage of patients referred to our sedation clinic who completed an MRI with AVD and without sedation, analyzed on a statistical process control (SPC) P-Chart. Process measures were the number of children eligible for AVD per month, analyzed on an SPC C-Chart. Balance measures were the number of studies that exceeded allotted exam time or were non-diagnostic.

RESULTS: Of 734 MRI referrals aged 4 to 18 years, 320 patients met inclusion criteria. Two hundred twenty-eight (71.3%) received minimal/moderate sedation (mean age [SD] 9.7 years [± 3.0]) and 92 (28.8%) underwent AVD (mean age 10.0 years [± 2.7]). The average monthly decrease in minimal/moderate sedation use was 28.8 percentage points. The average number of children considered eligible for AVD increased by special cause variation from 3.8 to 7 patients per month. All 92 MRI referrals triaged to AVD completed their MRI successfully without sedation; all studies were diagnostic, and 96% of studies were within the allotted exam time.

CONCLUSION: We implemented an awake MRI program with AVD that decreased monthly sedation needs by 28.8 percentage points while maintaining a high rate of diagnostic studies and no MRI delays.

PMID:40768097 | DOI:10.1007/s00247-025-06293-4

Cancer Control. 2025 Jan-Dec;32:10732748251362950. doi: 10.1177/10732748251362950. Epub 2025 Aug 6.

ABSTRACT

IntroductionHealth and psychosocial outcomes are often interdependent for people with cancer and their informal caregivers. However, few studies have examined interdependence among U.S. Black patients and their caregivers. In this prospective study, we analyzed whether Black women with breast cancer and their caregivers demonstrated interdependence in depressive symptoms and other outcomes over time.MethodsPatient and caregiver data were collected via telephone surveys at three timepoints (baseline, two months, four months). Actor-Partner Interdependence Models (random-intercept cross-panel models in Mplus) were used to analyze depressive symptoms (Center for Epidemiology Studies Depression scale; CES-D), physical and mental health quality of life, perceived social support, and health behaviors. We hypothesized patients and caregivers would demonstrate interdependence for these outcomes both cross-sectionally and over time.ResultsWe enrolled 210 participants. All patients and 93% of caregivers identified as Black/African American; 70% of caregivers identified as female. Two-thirds (66%) of dyads did not live together. Mean baseline CES-D score was 15.0 (SD = 10.9) for patients and 11.9 (SD = 9.0) for caregivers. We did not find prospective interdependence for any outcomes. Dyad members were moderately correlated in overall levels (intercepts) of physical health quality of life (r = .25), mental health quality of life (r = .28), social support (r = .37), and health behavior scores (r = .33).ConclusionThis study is one of the first longitudinal, dyadic examinations of outcomes for Black breast cancer patients and their informal caregivers. Although our hypothesis of prospective interdependence was not supported, we observed moderate correlations of overall levels of several measures. These results suggest that patients with lower social support, poor health behaviors, and worse quality of life may also have caregivers who could benefit from intervention.

PMID:40767116 | DOI:10.1177/10732748251362950

J Adv Nurs. 2025 Aug 6. doi: 10.1111/jan.70128. Online ahead of print.

ABSTRACT

AIM: To describe the experiences of Finnish registered nurses aged 45 and over working during menopause.

DESIGN: Multiple methods study.

METHODS: The data were collected from Finnish registered nurses aged 45 and over, using two different methods. Quantitative data (n = 3487), collected in January 2023, were analysed using descriptive statistical methods. Qualitative data were collected during the summer of 2023 through individual interviews (n = 23). The participants were recruited from a survey, where registered nurses (n = 3487) who responded to the survey indicated their willingness to participate in the interview study (n = 718). Participants for the interviews were selected through random sampling, and interviews were conducted until saturation was reached. The quantitative data were analysed with descriptive statistics, and qualitative data were analysed using inductive content analysis. The results of quantitative and qualitative data were combined in the discussion section.

RESULTS: Limited attention has been given to understanding the menopause and its consequences on the nursing workforce. Menopause remains a taboo topic, with a perceived divide between genders and generations, even within the healthcare sector. However, peer support from female colleagues of a similar age was considered invaluable. During menopause, nurses did not receive sufficient support from their managers or occupational health services, despite experiencing various challenges. Fatigue, for instance, was reported by 76% of nurses aged 45 and over. Nevertheless, nurses continued working despite their symptoms, as taking sick leave was perceived as difficult.

CONCLUSION: The consequences of menopause on nursing work are not yet sufficiently recognised within workplaces, or by the leadership and occupational health services. Support for nurses working during menopause seems to be insufficient. Open and informed discussions are needed across various levels of society to increase understanding of the problems of working during menopause.

IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The research findings can be used to develop improved occupational health and nursing management practices to support the well-being of menopausal nurses in the workplace.

IMPACT: Currently, there is insufficient knowledge about working as a registered nurse during menopause. However, research findings are enhancing our understanding of the impact of menopause on nursing work and the corresponding needs during this period.

REPORTING METHOD: The Standards for Reporting Qualitative Research (SRQR).

PMID:40767100 | DOI:10.1111/jan.70128

Tijdschr Gerontol Geriatr. 2024 Jun 5;55(2):16-32. doi: 10.54195/tgg18688.

ABSTRACT

INTRODUCTION: This study aimed to determine the association between the physical, social, and cognitive characteristics of acutely admitted older individuals and their discharge destination.

METHOD: Retrospective study including consecutive individuals aged 65 or older who were acutely admitted to an academic hospital. From these, patients who had been living independently and were clinically judged to have an increased risk of falling or physical limitations upon admission were selected. In addition to sociodemographic and medical characteristics, the following measurements of physical and cognitive functioning were conducted at admission or shortly thereafter: the Katz-ADL, handgrip strength, Timed-Up-and-Go test, 4-Meter-Walk Test, and the Six-item Cognitive Impairment Test (6-CIT). Univariate analysis and multivariable logistic regression analysis were used to compare the characteristics of patients discharged home or not.

RESULTS: Among the 49 patients who were included (mean age 81 (standard deviation ± 7,8) years, 24 (49% ) female), 20 (41%) were not discharged home. In the univariate comparisons, patients not discharged home were statistically significantly older, less often admitted for infection, and had worse scores on all measures of physical and cognitive functioning. In the multivariate analysis adjusted for age, only a worse Katz-ADL score was associated with not being discharged home.

CONCLUSION: In older, independently living vulnerable patients who were acutely admitted to a hospital physical functioning as measured by the Katz-ADL at admission was most strongly associated with the discharge destination.

PMID:40767078 | DOI:10.54195/tgg18688

Tijdschr Gerontol Geriatr. 2024 Jun 5;55(2):2-15. doi: 10.54195/tgg18488.

ABSTRACT

Older adults are more at risk for side effects from medications. Mainly anticholinergic side effects can lead to central and peripheral side effects on somatic and cognitive levels. In this study, we determined the anticholinergic load of the medication regimens of residents of a residential care centre using two validated measurement scales. We also examined to which extent the class(es) of medications influence this anticholinergic load. Finally, we analysed the association of a high anticholinergic load with incidents (urinary tract infections, falls, delirium).In this pilot study, we see a high degree of polymedication and use of psychotropic drugs with an anticholinergic effect. On average, we established a score of 1.67 on the ACB and a score of 0.87 on the DBI. The anticholinergic load in the ACB is mainly determined by antipsychotics (β = 0,647, p ‹ 0.001), in the DBI an influence of all medications with total anticholinergic and sedative load (F = 6.764, p ‹ 0.001). A risk score on the DBI has a statistically significant correlation with experiencing a urinary tract infection (F = 5.877, p = 0.018). This influence remains significant after adjusting for covariates.The anticholinergic load of medication regimens in residents is high. An increased anticholinergic load is also associated with urinary tract infection. Reducing the anticholinergic load within residential care centres therefore represents an important challenge for the future.

PMID:40767077 | DOI:10.54195/tgg18488

Tijdschr Gerontol Geriatr. 2025 Jun 10;56(2):6-27. doi: 10.54195/tgg21665.

ABSTRACT

BACKGROUND: The benefit-harm balance of antihypertensive treatment in older adults with advanced dementia is unclear. This study assesses whether discontinuing antihypertensive treatment reduces neuropsychiatric symptoms (NPS) and maintains quality of life (QoL) in nursing home residents with dementia.

METHODS: This outcome-blinded RCT (trial registration: NL7365) randomised Dutch long-term care residents with moderate-to-severe dementia and systolic blood pressure (SBP) ≤160mmHg during antihypertensive treatment (planned sample size n=492) to either antihypertensive treatment discontinuation (n=101) or usual care (n=104). Outcomes were NPS (Neuropsychiatric Inventory-Nursing Home [NPI-NH]) and QoL (Qualidem) at 16 weeks.

RESULTS: 205 participants (median age 86 years [IQR 80-90]; 79.5% female; median SBP 134mmHg [IQR 123-146]) were included. Randomisation ceased prematurely 29 months after start randomisation because of safety concerns, combined with lacking benefits. No significant differences were found between groups for NPI-NH (mean difference 1.6 [95%CI -2.3 to 5.6]) or Qualidem (mean difference -2.5 [95%CI -6.0 to 1.0]). Serious adverse events, such as cardiovascular events or death, occurred in 36% (discontinuation) and 24% (usual care) of the participants (adjusted hazard ratio 1.65 [95%CI 0.98 to 2.79], at a median of 135 (IQR 66-209) days in the discontinuation and 103 (IQR 54-171) days in the usual care group).

CONCLUSION: Because of lacking benefits and an observed increase in adverse events, proactive discontinuation of antihypertensive treatment is not recommended in older adults with dementia.

PMID:40767075 | DOI:10.54195/tgg21665

J Evid Based Integr Med. 2025 Jan-Dec;30:2515690X251363709. doi: 10.1177/2515690X251363709. Epub 2025 Aug 6.

ABSTRACT

Objectivethis meta-analysis evaluates the effects of mind-body exercise (MBE) on cognitive function in older adults with or without mild cognitive impairment (MCI). We examined the impact of different MBE, including yoga, tai chi, qigong, and meditation, on six cognitive domains: attention, executive function, working memory, verbal memory, processing speed, and visual-spatial construction.MethodsWe searched eight electronic databases from inception till August 2024. The literature search, study selection, data extraction, methodological quality assessment and statistical analyses were performed.ResultsA total of 45 studies, comprising 4602 participants, were included. Results indicated that MBE had a moderate positive effect on visual-spatial construction (Hedges’ g = 0.46) and small effects on other domains such as verbal memory (Hedge’s g = 0.24), processing speed (Hedge’s g = 0.26), working memory (Hedges’ g = 0.15) and executive function (Hedges’ g = 0.10). However, there was no improvement in attention (Hedge’s g = 0.08, 95% CI = -0.07 to 0.23). The meta-regression analysis further revealed that participants with MCI experienced greater improvements in visual-spatial construction and executive function than healthy participants. Additionally, significant differences were observed among intervention types, with yoga and tai chi showing stronger effects on visual-spatial construction and verbal memory than meditation.ConclusionsThese findings suggest MBE is an effective intervention for improving cognitive function, especially in MCI populations and with certain types of interventions. Utilization of validated modules for MBE intervention and inclusion of long-term follow-up assessments to establish conclusive findings were also suggested.

PMID:40767037 | DOI:10.1177/2515690X251363709

Med Care. 2025 Jul 1;63(7):507-513. doi: 10.1097/MLR.0000000000002159. Epub 2025 May 6.

ABSTRACT

BACKGROUND: Historically, US Veterans have reported higher chronic disease burden than non-Veterans. However, whether Veteran and Veterans Affairs (VA) coverage status continue to be associated with chronic disease burden or how these associations vary by age, especially among younger Veterans, is unknown.

OBJECTIVE: To examine the number of chronic conditions among male Veterans with and without VA coverage, and male non-Veterans, overall and by age group.

DESIGN AND PARTICIPANTS: Using 2018 National Health Interview Survey data, our sample included 2301 male Veterans and 9243 male non-Veterans.

MAIN MEASURES: The primary outcome was a number of chronic conditions, measured as a count (range 0-15) and categorically (0, 1, 2, 3+). We created a 3-category main independent variable (Veteran with VA coverage, Veteran without VA coverage, non-Veteran). Generalized linear regression models were used to estimate relationships between Veteran and VA coverage status and count of chronic conditions, overall and by age group (18-44, 45-64, 65+), adjusting for sociodemographic characteristics.

KEY RESULTS: Veterans with VA coverage, Veterans without VA coverage, and non-Veterans had an age-standardized mean of 1.44, 1.16, and 1.09 chronic conditions, respectively. In adjusted analyses, Veterans with VA coverage had 0.36 (95% CI: 0.25-0.46) more conditions and Veterans without VA coverage had 0.12 (95% CI: 0.04-0.21) more conditions compared with non-Veterans. In age-stratified analyses, Veterans with VA coverage aged 18-44 had 0.22 (95% CI: 0.06-0.38) more conditions; 45-64, 0.71 (95% CI: 0.41-0.99) more conditions; and 65+, 0.38 (95% CI: 0.18-0.57) more conditions compared with similar-aged non-Veterans.

CONCLUSIONS: Veterans with VA coverage had the greatest number of chronic conditions, including when stratified by age group.

PMID:40766989 | DOI:10.1097/MLR.0000000000002159