28,958 research outputs found

    Preliminary findings from need assessment.

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    Despite the policy recommendation and effectiveness of administering the hepatitis B birth-dose vaccine (HepB-BD) to newborns to prevent mother-to-child hepatitis B transmission, timely uptake remains an issue. Countries adopting the HepB-BD to their national immunization schedule report programmatic challenges to administering the vaccine within the recommended 24-hour window after delivery. Further, while the World Health Organization recommends streamlining three birth-dose vaccines (HepB-BD, BCG, and OPV0), scarce Sub-Saharan(SSA)-based literature reports on a streamlined and timely approach to birth-dose vaccines. As more SSA countries adopt the new birth-dose vaccine to their immunization schedules, a systematically developed implementation strategy—Vaccination of Newborns–Innovative Strategies to Hasten Birth-Dose vaccines’ delivery (VANISH-BD)—will facilitate the adoption and implementation of timely birth-dose vaccine uptake. In this paper, we describe the development of the implementation strategy using intervention mapping, an evidence-based and theory-driven approach. We report on the development of our intervention, beginning with the needs assessment based in Kinshasa Province, Democratic Republic of the Congo (DRC), informing step 1 of intervention mapping. The intervention is contextually relevant, locally produced, sustainable, and designed to improve timely birth-dose vaccine uptake in the DRC. We intend to inform future implementers about improving timely and streamlined birth-dose vaccine uptake and for VANISH-BD to be adapted for similar contexts.</div

    Table_5_Obesity modulates the cellular and molecular microenvironment in the peritoneal cavity: implication for ovarian cancer risk.docx

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    IntroductionAbdominal obesity increases the risk of developing ovarian cancer but the molecular mechanisms of how obesity supports ovarian cancer development remain unknown. Here we investigated the impact of obesity on the immune cell and gene expression profiles of distinct abdominal tissues, focusing on the peritoneal serous fluid (PSF) and the omental fat band (OFB) as critical determinants for the dissemination of ovarian metastases and early metastatic events within the peritoneal cavity.MethodsFemale C57BL/6 mice were fed a low-fat (LFD) or a high-fat diet (HFD) for 12 weeks until the body weights in the HFD group were significantly higher and the mice displayed an impaired glucose tolerance. Then the mice were injected with the murine ovarian cancer cells (MOSE-LTICv) while remaining on their diets. After 21 days, the mice were sacrificed, tumor burden was evaluated and tissues were harvested. The immune cell composition of abdominal tissues and changes in gene expression in the PSF and OFB were evaluated by flow cytometry and qPCR RT2-profiler PCR arrays and confirmed by qRT-PCR, respectively. Other peritoneal adipose tissues including parametrial and retroperitoneal white adipose tissues as well as blood were also investigated.ResultsWhile limited effects were observed in the other peritoneal adipose tissues, feeding mice the HFD led to distinct changes in the immune cell composition in the PSF and the OFB: a depletion of B cells but an increase in myeloid-derived suppressor cells (MDSC) and mono/granulocytes, generating pro-inflammatory environments with increased expression of cyto- and chemokines, and genes supporting adhesion, survival, and growth, as well as suppression of apoptosis. This was associated with a higher peritoneal tumor burden compared to mice fed a LFD. Changes in cellular and genetic profiles were often exacerbated by the HFD. There was a large overlap in genes that were modulated by both the HFD and the cancer cells, suggesting that this ‘genetic fingerprint’ is important for ovarian metastases to the OFB.DiscussionIn accordance with the ‘seed and soil’ theory, our studies show that obesity contributes to the generation of a pro-inflammatory peritoneal environment that supports the survival of disseminating ovarian cancer cells in the PSF and the OFB and enhances the early metastatic adhesion events in the OFB through an increase in extracellular matrix proteins and modulators such as fibronectin 1 and collagen I expression as well as in genes supporting growth and invasion such as Tenacin C. The identified genes could potentially be used as targets for prevention strategies to lower the ovarian cancer risk in women with obesity.</p

    Matrices of change.

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    Despite the policy recommendation and effectiveness of administering the hepatitis B birth-dose vaccine (HepB-BD) to newborns to prevent mother-to-child hepatitis B transmission, timely uptake remains an issue. Countries adopting the HepB-BD to their national immunization schedule report programmatic challenges to administering the vaccine within the recommended 24-hour window after delivery. Further, while the World Health Organization recommends streamlining three birth-dose vaccines (HepB-BD, BCG, and OPV0), scarce Sub-Saharan(SSA)-based literature reports on a streamlined and timely approach to birth-dose vaccines. As more SSA countries adopt the new birth-dose vaccine to their immunization schedules, a systematically developed implementation strategy—Vaccination of Newborns–Innovative Strategies to Hasten Birth-Dose vaccines’ delivery (VANISH-BD)—will facilitate the adoption and implementation of timely birth-dose vaccine uptake. In this paper, we describe the development of the implementation strategy using intervention mapping, an evidence-based and theory-driven approach. We report on the development of our intervention, beginning with the needs assessment based in Kinshasa Province, Democratic Republic of the Congo (DRC), informing step 1 of intervention mapping. The intervention is contextually relevant, locally produced, sustainable, and designed to improve timely birth-dose vaccine uptake in the DRC. We intend to inform future implementers about improving timely and streamlined birth-dose vaccine uptake and for VANISH-BD to be adapted for similar contexts.</div

    Assessment of Dofetilide or Sotalol Tolerability in the Elderly

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    Background: Dofetilide and sotalol are potassium channel antagonists that require inpatient QTc monitoring during initiation, due to increased risk of fatal arrhythmias. Elderly patients are especially subject to an increased risk of fatal arrhythmias due to polypharmacy, comorbidities, and physiologic cardiac changes with aging. This study will describe the tolerability and risk factors associated with the initiation of sotalol or dofetilide in patients ≄80 years of age. Methodology: This is a multicenter, retrospective, descriptive study of patients ≄80 years old who were initiated on either dofetilide or sotalol between May 8, 2018 and July 31, 2021 at institutions within the Mayo Clinic Health System. The percentage of patients who received nonpackage insert recommended doses was identified. Incidence of and reasons for dose reductions or discontinuations due to safety-related events or clinical concerns during the initial loading period were collected. Results: The final analysis included 104 patients. The majority of patients (75%) received nonstandard initial doses of dofetilide or sotalol based on baseline estimated creatinine clearance or QTc. Overall, 39% ( N  = 41) of patients experienced a dose reduction or discontinuation due to a safety-related event or concern. Patients who received nonstandard initial doses of dofetilide or sotalol had 4.7 times greater odds of experiencing a safety-related event requiring dose reduction or discontinuation. Conclusion: Following package insert dosing in elderly patients increases safety and tolerability relative to more aggressive dosing of dofetilide or sotalol

    Effectiveness of Hypertension Management Strategies in SPRINT‐Eligible US Adults: A Simulation Study

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    Background Despite reducing cardiovascular disease (CVD) events and death in SPRINT (Systolic Blood Pressure Intervention Trial), intensive systolic blood pressure goals have not been adopted in the United States. This study aimed to simulate the potential long‐term impact of 4 hypertension management strategies in SPRINT‐eligible US adults. Methods and Results The validated Blood Pressure Control–Cardiovascular Disease Policy Model, a discrete event simulation of hypertension care processes (ie, visit frequency, blood pressure [BP] measurement accuracy, medication intensification, and medication adherence) and CVD outcomes, was populated with 25 000 SPRINT‐eligible US adults. Four hypertension management strategies were simulated: (1) usual care targeting BP <140/90 mm Hg (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care), (2) intensive care per the SPRINT protocol targeting BP <120/90 mm Hg (SPRINT intensive), (3) usual care targeting guideline‐recommended BP <130/80 mm Hg (American College of Cardiology/American Heart Association usual care), and (4) team‐based care added to usual care and targeting BP <130/80 mm Hg. Relative to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, among the 18.1 million SPRINT‐eligible US adults, an estimated 138 100 total CVD events could be prevented per year with SPRINT intensive, 33 900 with American College of Cardiology/American Heart Association usual care, and 89 100 with team‐based care. Compared with the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, SPRINT intensive care was projected to increase treatment‐related serious adverse events by 77 600 per year, American College of Cardiology/American Heart Association usual care by 33 300, and team‐based care by 27 200. Conclusions As BP control has declined in recent years, health systems must prioritize hypertension management and invest in effective strategies. Adding team‐based care to usual care may be a pragmatic way to manage risk in this high‐CVD‐risk population

    Table_4_Obesity modulates the cellular and molecular microenvironment in the peritoneal cavity: implication for ovarian cancer risk.docx

    No full text
    IntroductionAbdominal obesity increases the risk of developing ovarian cancer but the molecular mechanisms of how obesity supports ovarian cancer development remain unknown. Here we investigated the impact of obesity on the immune cell and gene expression profiles of distinct abdominal tissues, focusing on the peritoneal serous fluid (PSF) and the omental fat band (OFB) as critical determinants for the dissemination of ovarian metastases and early metastatic events within the peritoneal cavity.MethodsFemale C57BL/6 mice were fed a low-fat (LFD) or a high-fat diet (HFD) for 12 weeks until the body weights in the HFD group were significantly higher and the mice displayed an impaired glucose tolerance. Then the mice were injected with the murine ovarian cancer cells (MOSE-LTICv) while remaining on their diets. After 21 days, the mice were sacrificed, tumor burden was evaluated and tissues were harvested. The immune cell composition of abdominal tissues and changes in gene expression in the PSF and OFB were evaluated by flow cytometry and qPCR RT2-profiler PCR arrays and confirmed by qRT-PCR, respectively. Other peritoneal adipose tissues including parametrial and retroperitoneal white adipose tissues as well as blood were also investigated.ResultsWhile limited effects were observed in the other peritoneal adipose tissues, feeding mice the HFD led to distinct changes in the immune cell composition in the PSF and the OFB: a depletion of B cells but an increase in myeloid-derived suppressor cells (MDSC) and mono/granulocytes, generating pro-inflammatory environments with increased expression of cyto- and chemokines, and genes supporting adhesion, survival, and growth, as well as suppression of apoptosis. This was associated with a higher peritoneal tumor burden compared to mice fed a LFD. Changes in cellular and genetic profiles were often exacerbated by the HFD. There was a large overlap in genes that were modulated by both the HFD and the cancer cells, suggesting that this ‘genetic fingerprint’ is important for ovarian metastases to the OFB.DiscussionIn accordance with the ‘seed and soil’ theory, our studies show that obesity contributes to the generation of a pro-inflammatory peritoneal environment that supports the survival of disseminating ovarian cancer cells in the PSF and the OFB and enhances the early metastatic adhesion events in the OFB through an increase in extracellular matrix proteins and modulators such as fibronectin 1 and collagen I expression as well as in genes supporting growth and invasion such as Tenacin C. The identified genes could potentially be used as targets for prevention strategies to lower the ovarian cancer risk in women with obesity.</p

    Screening for depression in children and adolescents in primary care or non-mental health settings: a systematic review update

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    Abstract Background The transition from childhood to adolescence is associated with an increase in rates of some psychiatric disorders, including major depressive disorder, a debilitating mood disorder. The aim of this systematic review is to update the evidence on the benefits and harms of screening for depression in primary care and non-mental health clinic settings among children and adolescents. Methods This review is an update of a previous systematic review, for which the last search was conducted in 2017. We searched Ovid MEDLINEÂź ALL, Embase Classic+Embase, PsycINFO, Cochrane Central Register of Controlled Trials, and CINAHL on November 4, 2019, and updated on February 19, 2021. If no randomized controlled trials were found, we planned to conduct an additional search for non-randomized trials with a comparator group. For non-randomized trials, we applied a non-randomized controlled trial filter and searched the same databases except for Cochrane Central Register of Controlled Trials from January 2015 to February 2021. We also conducted a targeted search of the gray literature for unpublished documents. Title and abstract, and full-text screening were completed independently by pairs of reviewers. Results In this review update, we were unable to find any randomized controlled studies that satisfied our eligibility criteria and evaluated the potential benefits and harms of screening for depression in children and adolescents. Additionally, a search for non-randomized trials yielded no studies that met the inclusion criteria. Conclusions The findings of this review indicate a lack of available evidence regarding the potential benefits and harms of screening for depression in children and adolescents. This absence of evidence emphasizes the necessity for well-conducted clinical trials to evaluate the effectiveness of depression screening among children and adolescents in primary care and non-mental health clinic settings. Systematic review registration PROSPERO CRD42020150373

    Exploring the complexities of pain phenotypes: OMERACT 2023 chronic pain working group workshop

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    Objective: To educate and discuss pain mechanisms (nociceptive, neuropathic, nociplastic) illuminating its possible impact when measuring different outcomes, which may modify, confound and potentially bias the outcome measures applied across various aspects of Rheumatic Musculoskeletal Diseases (RMDs) clinical trials. Methods: In the plenary presentations, PM lectured on different pain mechanisms and impact on disease activity assessment. Data from two data sets of RMDs patients, which assessed the prevalence and impact of nociplastic pain were presented and reviewed. Audience breakout group sessions and polling were conducted. Results: Mixed pain etiologies may differentially influence disease activity assessment and therapeutic decision-making. Polling demonstrated a consensus on the need to assess different types of pain as a phenotype, as it constitutes an important contextual factor (a variable that is not an outcome of the trial, but needs to be recognized [and measured] to understand the study results), and to standardize across RMDs. Conclusion: There is need for a standardized pain measure that can differentiate underlying pain mechanisms
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