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BMJ Global Health Jun 2024Clear guidelines to implement ancillary care (AC) in clinical trials conducted in resource-constrained settings are lacking. Here, we evaluate an AC policy developed for... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Clear guidelines to implement ancillary care (AC) in clinical trials conducted in resource-constrained settings are lacking. Here, we evaluate an AC policy developed for a vaccine trial in the Democratic Republic of the Congo and formulate policy recommendations.
METHODS
To evaluate the AC policy, we performed a longitudinal cohort study, nested in an open-label, single-centre, randomised Ebola vaccine trial conducted among healthcare personnel. Participants' demographic information, residence distance to the study site and details on the financial and/or medical support provided for any (serious) adverse events ((S)AE) were combined and analysed. To assess the feasibility of the AC policy, an expenditure analysis of the costs related to AC support outcomes was performed.
RESULTS
Enrolment in this evaluation study started on 29 November 2021. The study lasted 11 months and included 655 participants from the Ebola vaccine trial. In total, 393 participants used the AC policy, mostly for AE management (703 AE and 94 SAE) via medication provided by the study pharmacy (75.3%). Men had a 35.2% (95% CI 4.0% to 56.6%) lower likelihood of reporting AE compared with women. Likewise, this was 32.3% lower (95% CI 5.8% to 51.4%) for facility-based compared with community-based healthcare providers. The daily AE reporting was 78.8% lower during the passive vs the active trial stage, and 97.4% lower during unscheduled vs scheduled visits (p<0.001). Participants living further than 10 km from the trial site more frequently reported the travel distance as a reason for not using the policy (p<0.04). In practice, only 1.1% of the operational trial budget was used for AC policy support.
CONCLUSION
The trial design, study population and local health system impacted the use of the AC policy. Nonetheless, the AC policy implementation in this remote and resource-constrained setting was feasible, had negligible budgetary implications and contributed to participants' healthcare options and well-being.
Topics: Humans; Male; Female; Ebola Vaccines; Adult; Democratic Republic of the Congo; Longitudinal Studies; Hemorrhagic Fever, Ebola; Health Policy; Middle Aged; Health Personnel
PubMed: 38857947
DOI: 10.1136/bmjgh-2024-015259 -
Neurology Jul 2024Epigenetic age estimators indicating faster/slower biological aging vs chronological age independently associate with several age-related outcomes; however, longitudinal...
BACKGROUND AND OBJECTIVES
Epigenetic age estimators indicating faster/slower biological aging vs chronological age independently associate with several age-related outcomes; however, longitudinal associations with cognitive function are understudied. We examined associations of epigenetic age estimators with cognitive function measured annually.
METHODS
This longitudinal study consisted of older women enrolled in the Women's Health Initiative Memory Study with DNA methylation (DNAm) collected at baseline (1995-1998) from 3 ancillary studies and were followed up to 13 years. Global cognitive function was measured annually by Modified Mini-Mental State Examination (3MS; baseline-2007) and by modified Telephone Interview for Cognitive Status (TICS-m, 2008-2021). We calculated 5 epigenetic age estimators: extrinsic AgeAccel, intrinsic AgeAccel, AgeAccelPheno, AgeAccelGrim2, Dunedin Pace of Aging Calculated From the Epigenome (DunedinPACE), and AgeAccelGrim2 components (DNA-based plasma protein surrogates). We estimated longitudinal epigenetic age estimator-cognitive function associations using linear mixed-effects models containing age, education, race or ethnicity, and subsequently alcohol, smoking, body mass index, and comorbidities. We examined effect modification by ε4 carriage.
RESULTS
A total of 795 participants were enrolled. The mean baseline age was 70.8 ± 4 years (10.7% Black, 3.9% Hispanic or Latina, 85.4% White), A 1-SD (0.12) increment in DunedinPACE associated with faster annual declines in TICS-m scores in minimally adjusted (β = -0.118, 95% CI -0.202 to -0.034; = 0.0006) and fully adjusted (β = -0.123, 95% CI -0.211 to -0.036; = 0.006) models. AgeAccelPheno associated with faster annual declines in TICS-m with minimal adjustment (β = -0.091, 95% CI -0.176 to -0.006; = 0.035) but not with full adjustment. No other epigenetic age estimators associated with changes in 3MS or TICS-m. Higher values of DNAm-based surrogates of growth differentiation factor 15, beta-2 microglobulin, Cystatin C, tissue inhibitor metalloproteinase 1, and adrenomedullin associated with faster annual declines in 3MS and TICS-m. Higher DNAm log A1c associated with faster annual declines in TICS-m only. DunedinPACE associated with faster annual declines in 3MS among ε4 carriers but not among noncarriers (-interaction = 0.020).
DISCUSSION
Higher DunedinPACE associated with faster declines in TICS-m and 3MS scores among ε4 carriers. DunedinPACE may help identify older women at risk of future cognitive decline. Limitations include the ancillary studies that collected epigenetic data not designed to study epigenetics and cognitive function. We examined epigenetic age estimators with global cognitive function and not specific cognitive domains. Findings may not generalize to men and more diverse populations.
Topics: Humans; Female; Aged; Longitudinal Studies; Cognition; Aging; Epigenesis, Genetic; DNA Methylation; Women's Health; Aged, 80 and over; Middle Aged; Memory
PubMed: 38857479
DOI: 10.1212/WNL.0000000000209534 -
The Journal of Sexual Medicine Jun 2024Female cancer survivors often experience estrogen-deprivation symptoms, which may lead to decreases in sexual desire, vulvovaginal health (lubrication, dryness,...
BACKGROUND
Female cancer survivors often experience estrogen-deprivation symptoms, which may lead to decreases in sexual desire, vulvovaginal health (lubrication, dryness, discomfort), and sexual satisfaction. Interventions are needed to address these concerns.
AIM
The objective of this secondary analysis was to determine if women with higher (better) scores on the Female Sexual Function Index (FSFI) lubrication and pain subscales reported higher desire scores based on treatment with bupropion vs placebo.
METHODS
Participants were part of NRG Oncology's NRG-CC004 (NCT03180294), a randomized placebo-controlled clinical trial evaluating bupropion (150 vs 300 mg) to improve sexual desire in survivors of breast or gynecologic cancer. All participants with baseline data from the FSFI lubrication, pain, and desire subscales with 5- and/or 9-week data were analyzed. The FSFI subscale scores were correlated using Spearman correlation coefficients. Logistic regression was used to determine associations between FSFI desire and other FSFI subscales while accounting for treatment arm and other covariates.
OUTCOMES
The primary outcome of NRG Oncology's NRG-CC004 (NCT03180294) randomized phase II dose-finding trial was change from baseline to 9 weeks on the FSFI desire subscale score. Similar to the parent study, the primary outcome for this ancillary data study was the FSFI desire subscale score at 5 and 9 weeks.
RESULTS
Overall, 230 participants completed the FSFI at baseline and 189 at 9 weeks. The strongest correlations were between lubrication and pain at baseline (all participants, rho = 0.77; bupropion arms, rho = 0.82), week 5 (all participants, rho = 0.71; bupropion arms, rho = 0.68), and week 9 (all participants, rho = 0.75; bupropion arms, rho = 0.78), and the weakest correlations were between desire and pain. In patients in the treatment arms there were no interactions between lubrication or pain.The impact of various covariates on the FSFI score for desire at 9 weeks demonstrated that participants of non-White race (odds ratio [OR], 0.42; 95% CI, 0.21-0.81; P = .010), with a high lubrication score (OR, 0.36; 95% CI, 0.21-0.61; P = .0002), with a high pain score (less pain) (OR, 0.50; 95% CI, 0.29-0.87; P = .014), or with prior pelvic surgery (OR, 0.38; 95% CI, 0.23-0.63; P = .0002) had lower odds of having low desire.
CLINICAL IMPLICATIONS
Acute estrogen-deprivation symptoms should be addressed prior to sexual desire intervention.
STRENGTHS AND LIMITATIONS
This secondary analysis was not powered to examine all variables.
CONCLUSION
Lubrication and pain were predictors of low desire. Therefore, vulvovaginal atrophy and associated genitourinary symptoms of menopause such as vaginal dryness and dyspareunia should be addressed prior to or in parallel with interventions for sexual desire.
PubMed: 38856026
DOI: 10.1093/jsxmed/qdae061 -
Juntendo Iji Zasshi = Juntendo Medical... 2023Septal myectomy confers survival benefits on patients with hypertrophic cardiomyopathy. However, its role in the treatment of severe aortic stenosis (sAS) with left...
OBJECTIVES
Septal myectomy confers survival benefits on patients with hypertrophic cardiomyopathy. However, its role in the treatment of severe aortic stenosis (sAS) with left ventricular outflow tract obstruction (LVOTO) remains under investigation. Another challenging question in the era of transcatheter aortic valve replacement is who would benefit more from traditional surgical aortic valve replacement (SAVR) with myectomy. Therefore, this study aimed to investigate myectomy cases at our hospital in Japan.
METHODS
A total of 740 patients who underwent SAVR for sAS between 2012 and 2019 were identified. The demographics and baseline echocardiographic findings were retrospectively compared between patients who underwent concomitant myectomy and those who did not. The myectomy group was further assessed for factors predisposing to LVOTO, operative details, echocardiographic changes, and prognosis. The resected septa were histopathologically analyzed.
RESULTS
The myectomy group mostly comprised elderly females with a small hypercontractile heart. Myectomy with SAVR led to statistically significant improvements in concentric left ventricular hypertrophy and LVOTO parameters. Survival was comparable with that reported in previous reports, even in the elderly subset (≥ 75 years). The septa showed mild fibrosis.
CONCLUSIONS
Myectomy can be safely performed with SAVR for sAS with LVOTO, even in the elderly, and it effectively improves LVOTO. Special attention should be paid to elderly females with relatively more severe AS and a small yet extra-hypertrophic and extra-hypercontractile heart. Such patients warrant comprehensive assessment of LVOTO, and despite its invasiveness, SAVR may be potentially more beneficial by allowing direct observation of LVOTO and ancillary myectomy.
PubMed: 38855434
DOI: 10.14789/jmj.JMJ22-0036-OA -
Echocardiography (Mount Kisco, N.Y.) Jun 2024Aortic stenosis (AS) stands as the most common valvular heart disease in developed countries and is characterized by progressive narrowing of the aortic valve orifice... (Review)
Review
Aortic stenosis (AS) stands as the most common valvular heart disease in developed countries and is characterized by progressive narrowing of the aortic valve orifice resulting in elevated transvalvular flow resistance, left ventricular hypertrophy, and progressive increased risk of heart failure and sudden death. This narrative review explores clinical challenges and evolving perspectives in moderate AS, where discrepancies between aortic valve area and pressure gradient measurements may pose diagnostic and therapeutic quandaries. Transthoracic echocardiography is the first-line imaging modality for AS evaluation, yet cases of discordance may require the application of ancillary noninvasive diagnostic modalities. This review underscores the importance of accurate grading of AS severity, especially in low-gradient phenotypes, emphasizing the need for vigilant follow-up. Current clinical guidelines primarily recommend aortic valve replacement for severe AS, potentially overlooking latent risks in moderate disease stages. The noninvasive multimodality imaging approach-including echocardiography, cardiac magnetic resonance, computed tomography, and nuclear techniques-provides unique insights into adaptive and maladaptive cardiac remodeling in AS and offers a promising avenue to deliver precise indications and exact timing for intervention in moderate AS phenotypes and asymptomatic patients, potentially improving long-term outcomes. Nevertheless, what we may have gleaned from a large amount of observational data is still insufficient to build a robust framework for clinical decision-making in moderate AS. Future research will prioritize randomized clinical trials designed to weigh the benefits and risks of preemptive aortic valve replacement in the management of moderate AS, as directed by specific imaging and nonimaging biomarkers.
Topics: Humans; Aortic Valve Stenosis; Echocardiography; Aortic Valve; Severity of Illness Index
PubMed: 38853624
DOI: 10.1111/echo.15859 -
Contemporary Clinical Trials Jun 2024African Americans (AAs) face cardiovascular health (CVH) disparities linked to systemic racism. The 2020 police killing of Mr. George Floyd in Minneapolis, Minnesota,...
Rationale, design, and participant characteristics of the FAITH! Heart Health+ study: An exploration of the influence of the social determinants of health, stress, and structural racism on African American cardiovascular health.
BACKGROUND
African Americans (AAs) face cardiovascular health (CVH) disparities linked to systemic racism. The 2020 police killing of Mr. George Floyd in Minneapolis, Minnesota, alongside the COVID-19 pandemic, exacerbated adverse psychosocial factors affecting CVH outcomes among AAs. This manuscript describes the study protocol and participant characteristics in an ancillary study exploring the relationship between biopsychosocial factors and CVH among AAs.
METHODS
Using a community-based participatory approach, a mixed-methods ancillary study of 58 AA participants from an overarching randomized control trial (RCT) was conducted. Baseline RCT health assessments (November 2020) provided sociodemographic, medical, and clinical data. Subsequent health assessments (February-December 2022) measured sleep quality, psychosocial factors (e.g., high-effort coping), biomarkers (e.g., cortisol), and cardiovascular diagnostics (e.g., cardio-ankle vascular index). CVH was assessed using the American Heart Association Life's Simple 7 (LS7) (range 0 to 14, poor to ideal) and Life's Essential 8 (LE8) scores (range 0 to 100, low to high). Correlations between these scores will be examined. Focus group discussions via videoconferencing (March to April 2022) assessed psychosocial and structural barriers, along with the impact of COVID-19 and George Floyd's killing on daily life.
RESULTS
Participants were predominantly female (67%), with a mean age of 54.6 [11.9] years, high cardiometabolic risk (93% had overweight/obesity and 70% hypertension), and moderate LE8 scores (mean 57.4, SD 11.5).
CONCLUSION
This study will enhance understanding of the associations between biopsychosocial factors and CVH among AAs in Minnesota. Findings may inform risk estimation, patient care, and healthcare policies to address CVD disparities in marginalized populations.
PubMed: 38851481
DOI: 10.1016/j.cct.2024.107600 -
European Journal of Emergency Medicine... Jun 2024While the indication for noninvasive ventilation (NIV) in severely hypoxemic patients with acute heart failure (AHF) is often indicated and may improve clinical course,...
BACKGROUND
While the indication for noninvasive ventilation (NIV) in severely hypoxemic patients with acute heart failure (AHF) is often indicated and may improve clinical course, the benefit of early initiation before patient arrival to the emergency department (ED) remains unknown.
OBJECTIVE
This study aimed to assess the impact of early initiation of NIV during emergency medical service (EMS) transportation on outcomes in patients with AHF.
DESIGN
A secondary retrospective analysis of the EAHFE (Epidemiology of AHF in EDs) registry.
SETTING
Fifty-three Spanish EDs.
PARTICIPANTS
Patients with AHF transported by EMS physician-staffed ambulances who were treated with NIV at any time during of their emergency care were included and categorized into two groups based on the place of NIV initiation: prehospital (EMS group) or ED (ED group).
OUTCOME MEASURES
Primary outcome was the composite of in-hospital mortality and 30-day postdischarge death, readmission to hospital or return visit to the ED due to AHF. Secondary outcomes included 30-day all-cause mortality after the index event (ED admission) and the different component of the composite primary endpoint considered individually. Multivariate logistic regressions were employed for analysis.
RESULTS
Out of 2406 patients transported by EMS, 487 received NIV (EMS group: 31%; EMS group: 69%). Mean age was 79 years, 48% were women. The EMS group, characterized by younger age, more coronary artery disease, and less atrial fibrillation, received more prehospital treatments. The adjusted odds ratio (aOR) for composite endpoint was 0.66 (95% CI: 0.42-1.05). The aOR for secondary endpoints were 0.74 (95% CI: 0.38-1.45) for in-hospital mortality, 0.74 (95% CI: 0.40-1.37) for 30-day mortality, 0.70 (95% CI: 0.41-1.21) for 30-day postdischarge ED reconsultation, 0.80 (95% CI: 0.44-1.44) for 30-day postdischarge rehospitalization, and 0.72 (95% CI: 0.25-2.04) for 30-day postdischarge death.
CONCLUSION
In this ancillary analysis, prehospital initiation of NIV in patients with AHF was not associated with a significant reduction in short-term outcomes. The large confidence intervals, however, may preclude significant conclusion, and all point estimates consistently pointed toward a potential benefit from early NIV initiation.
PubMed: 38847652
DOI: 10.1097/MEJ.0000000000001141 -
Medical Research Archives Oct 2023Stress and stressful events are widely accepted risk factors for cardiometabolic diseases, including coronary heart disease and diabetes. As language plays a seminal...
Stress and stressful events are widely accepted risk factors for cardiometabolic diseases, including coronary heart disease and diabetes. As language plays a seminal role in development and regulation of emotions and appraisals of stressful situations, it may contribute to documented differences in the stress-cardiometabolic disease association across ethnic groups. We investigated associations between language preferences (Spanish vs English) and downstream health consequences of stress. Using data from the Sociocultural Ancillary Study of the Hispanic Community Health Study/Study of Latinos, we assessed the relationship between reported stress and risk factors (alcohol use, smoking, body mass index, depressive symptoms) and prevalence of self-reported (coronary heart disease, stroke, chronic obstructive pulmonary disease [COPD]) and clinically assessed chronic conditions (diabetes, hypertension) among 5154 Hispanic/Latino adults living in the US. Factor analysis was used to calculate a composite stress variable from participants' self-reported chronic stress, perceived stress, and adverse childhood experiences. Sampling weights and survey methodology were integrated in all analyses to account for this study's complex survey design. After controlling for sociodemographic factors (Hispanic/Latino background, study site, years in the US, social acculturation, education, income, age, sex), higher composite stress scores were associated with elevated risk factors and greater prevalence of coronary heart disease, diabetes, and COPD. Furthermore, the relationship between stress and COPD was significantly stronger among Hispanic/Latino adults who preferred to be interviewed in Spanish (compared to English). Stronger connections between stress and likelihood of drinking alcohol among English-preferring persons also emerged. These results are interpreted in light of the Hispanic health paradox and the role of cultural processes in the development of health risk factors and chronic conditions. Our findings can be integrated into relevant approaches to address health disparities within and across Hispanic/Latino populations in the US.
PubMed: 38846550
DOI: 10.18103/mra.v11i10.4625 -
Cureus May 2024Urinary bladder cancer (UBC) is amongst the most common urological malignancies.
BACKGROUND
Urinary bladder cancer (UBC) is amongst the most common urological malignancies.
AIM
To study different types of urinary bladder lesions in the north Indian population and to correlate various clinical and pathological findings.
MATERIALS AND METHODS
The present prospective study was conducted on 100 cases undergoing transurethral resection of bladder tumor (TURBT) and/or radical cystectomy over a period of 2.5 years followed by histopathological examination. Liquid-based cytology for malignant cells in urine was also performed. Immunohistochemistry was employed for tumor typing wherever needed.
RESULTS
A total of 100 cases were studied. Male to female ratio was 15.7:1 and most of the patients were in the sixth decade (40%). Painless hematuria was the commonest clinical presentation (60%) and smoking was the commonest risk factor (80%). The most common lesion was infiltrating urothelial carcinoma seen in 72 cases followed by papillary urothelial neoplasm of low malignant potential (PUNLMP) seen in eight cases. Grade and depth of invasion were assessed and correlated. Several variants of infiltrating urothelial carcinoma such as squamous differentiation, glandular differentiation, microcystic, clear cell, nested, and micropapillary were also identified. Clinical, cystoscopic and histopathological findings were correlated in all the cases.
CONCLUSION
Infiltrating urothelial carcinoma high grade was the most common bladder lesion identified and muscle invasion was more common with higher-grade lesions. A decade-younger age group was found to be more affected in the present series. Urine cytology for malignant cells is useful for early diagnosis of cancer. Immunohistochemistry is an important ancillary adjunct.
PubMed: 38846211
DOI: 10.7759/cureus.59792 -
Journal of Gynecology Obstetrics and... Jun 2024To evaluate whether the quality scores validated for second-trimester ultrasound scan can be used for third-trimester ultrasound scan.
OBJECTIVES
To evaluate whether the quality scores validated for second-trimester ultrasound scan can be used for third-trimester ultrasound scan.
METHODS
Prospective multicenter ancillary study using data from the RECRET study. Nulliparous women, with no reported history, with second- and third-trimester ultrasound examinations performed by the same ultrasonographer and using the same ultrasound machine were recruited. The global score and the individual score of each ultrasound image were compared between second- and third-trimester ultrasound scan. The sample size was calculated for a non-inferiority (one-sided) paired Student t test.
RESULTS
103 women with 1606 anonymized ultrasound images were included. The median term at second- and third-trimester ultrasound scan was 22.2 weeks gestation (22.0-22.7) and 31.6 weeks gestation (30.7-34.7), respectively. The mean global score of ultrasound images was comparable between the second- and the third-trimester ultrasound examination (32.37 ± 2.62 versus 31.80 ± 3.27, p = 0.13). Means scores for each biometric parameters i.e. head circumference, abdominal circumference, and femur diaphysis length were comparable. The scores for the four-chamber view (5.11 ± 0.91 versus 5.36 ± 0.75, p = 0.02) and the spine (4.18 ± 1.17 versus 5.22 ± 1.02, p < 0.001) were significantly lower in the third trimester compared to the second trimester. The score for the kidney image was significantly higher for third trimester images compared to second trimester images (4.73 ± 0.51 versus 4.32 ± 0.67, p < 0.001.
CONCLUSIONS
Biometrics parameters quality scores images previously validated for the second trimester ultrasound scan can be also used for the third trimester scan. However, anatomical quality scores images performances may vary between the second and the third trimester scan.
PubMed: 38844086
DOI: 10.1016/j.jogoh.2024.102805