To investigate the extent of objective 'non-beneficial treatments (NBTs)' (too much) anytime in the last 6 months of life in routine hospital care.
English language publications in Medline, EMBASE, ...PubMed, Cochrane library, and the grey literature (January 1995-April 2015).
All study types assessing objective dimensions of non-beneficial medical or surgical diagnostic, therapeutic or non-palliative procedures administered to older adults at the end of life (EOL).
A 13-item quality score estimated independently by two authors.
Evidence from 38 studies indicates that on average 33-38% of patients near the EOL received NBTs. Mean prevalence of resuscitation attempts for advanced stage patients was 28% (range 11-90%). Mean death in intensive care unit (ICU) was 42% (range 11-90%); and mean death rate in a hospital ward was 44.5% (range 29-60%). Mean prevalence of active measures including dialysis, radiotherapy, transfusions and life support treatment to terminal patient was 7-77% (mean 30%). Non-beneficial administration of antibiotics, cardiovascular, digestive and endocrine treatments to dying patients occurred in 11-75% (mean 38%). Non-beneficial tests were performed on 33-50% of patients with do-not-resuscitate orders. From meta-analyses, the pooled prevalence of non-beneficial ICU admission was 10% (95% CI 0-33%); for chemotherapy in the last six weeks of life was 33% (95% CI 24-41%).
This review has confirmed widespread use of NBTs at the EOL in acute hospitals. While a certain level of NBT is inevitable, its extent, variation and justification need further scrutiny.
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BFBNIB, NMLJ, NUK, PNG, UL, UM, UPUK
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is ...mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been uncertain whether the observed amnesia in the early stages of AD is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early AD, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are used, revealing a retrieval, rather than a storage impairment. Before amyloid plaque deposition, the amnesia in these mice is age-dependent, which correlates with a progressive reduction in spine density of hippocampal dentate gyrus engram cells. We show that optogenetic induction of long-term potentiation at perforant path synapses of dentate gyrus engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of dentate gyrus engram cells containing restored spine density prevents the rescue of long-term memory. Thus, selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in the early stages of AD.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
PURPOSE OF REVIEWThe COVID-19 pandemic has had unprecedented global effects, yet the rapid emergence of telehealth across the globe has allowed healthcare professionals to connect virtually with ...patients and families while following safe social distancing guidelines. Telehealth has been used relatively well in patients from remote regions with limited access to subspecialty healthcare providers. This article discusses novel ways of using telehealth during the current pandemic and measures that would need to be taken to sustain telehealth and teleconsultations.
RECENT FINDINGSTelehealth has expanded to outpatient pediatric cardiology clinics across the globe during the pandemic. Technological advancements in video conferencing and the abundance of readily available wearable devices have allowed cardiologists to establish a preliminary diagnosis and set forth a treatment plan. Additional support by insurance providers and relaxation of mandatory regulations by the government have allowed telehealth to succeed during the pandemic. Although many subdisciplines within pediatric cardiology can be easily adapted into a sustainable telehealth model, some unique patient interactions, such as fetal cardiology, exercise physiology, and echocardiograms cannot be done remotely. The field of telehealth medicine with HIPAA-compliant programs and both insurance and government support should remain in our armamentarium of available resources for all patients and families.
SUMMARYAlthough not unique to pediatric cardiology, telehealth has emerged as an avenue to perform an initial evaluation and even establish a care pathway for patients. It is well recognized that telehealth visits will not supplant all patient--physician interactions but is a very acceptable first step in the majority of cases and can often steer the patient to subsequently undergo more selective and streamlined care.
To provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer.
The Society of Gynecologic ...Oncology and the American Society of Clinical Oncology convened an Expert Panel and conducted a systematic review of the literature.
Four phase III clinical trials form the primary evidence base for the recommendations. The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer, neoadjuvant chemotherapy and interval cytoreduction are noninferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality.
All women with suspected stage IIIC or IV invasive epithelial ovarian cancer should be evaluated by a gynecologic oncologist prior to initiation of therapy. The primary clinical evaluation should include a CT of the abdomen and pelvis, and chest imaging (CT preferred). Women with a high perioperative risk profile or a low likelihood of achieving cytoreduction to < 1 cm of residual disease (ideally to no visible disease) should receive neoadjuvant chemotherapy. Women who are fit for primary cytoreductive surgery, and with potentially resectable disease, may receive either neoadjuvant chemotherapy or primary cytoreductive surgery. However, primary cytoreductive surgery is preferred if there is a high likelihood of achieving cytoreduction to < 1 cm (ideally to no visible disease) with acceptable morbidity. Before neoadjuvant chemotherapy is delivered, all patients should have confirmation of an invasive ovarian, fallopian tube, or peritoneal cancer. Additional information is available at www.asco.org/NACT-ovarian-guideline and www.asco.org/guidelineswiki.
PURPOSE OF REVIEWPremature ventricular beats (PVCs) are frequently identified in healthy children with structurally normal hearts and generally have a benign clinical course often disappearing ...spontaneously. However, a small percentage of children may develop a cardiomyopathy. The purpose of this review is to understand which children may be at risk of development of left ventricular (LV) dysfunction with idiopathic PVCs.
RECENT FINDINGSThere is increasing evidence that a ventricular ectopic burden more than 24% in adults may lead to LV dysfunction. Most of the pediatric studies to date are retrospective, small case series from single institutions and have conflicting results regarding a direct correlation of the PVC burden to LV dysfunction. Development of a cardiomyopathy from frequent PVCs in children is likely multifactorial relating to the burden itself, presence of higher levels of ectopy (couplets and runs of ventricular tachycardia) as well as the duration of ventricular ectopy. Understanding the duration of ectopy is often unknown as patients are asymptomatic and the irregular heart beat was identified at a well-child examination.
SUMMARYAsymptomatic children with normal ventricular function and a low ectopy burden can be followed without any intervention and generally reassured. Children with an ectopy burden more than 30% are at some risk of developing LV dysfunction and should be more closely followed with noninvasive imaging. Development of symptoms attributed to the ectopy or signs of increasing LV dimensions or LV dysfunction should be treated with medication or catheter ablation.
Purpose of review
The purpose of this review is to explore the historical and serendipitous events that led to the creation of modern-day pacemakers. In addition, this review will explore how ...contemporary conduction site-specific pacing has overcome some of the deleterious effects from historical chronic right ventricular apical pacing.
Recent findings
Recently, there have been tremendous advances in not just the lead design but the tools required to promote more physiologic pacing. Although cardiac resynchronization pacing has been around for nearly 2 decades, this review also introduces and discusses the early results of His-bundle pacing and left bundle branch pacing and some of the potential applicability of this technology for our children.
Summary
Pacemakers have evolved significantly in the last 30 years through collaborative partnerships between physicians and engineers. The future of cardiac pacing is bright compared to the field of electrotherapy 50 years ago. Future iterations of pacemakers must consider unusual anatomy and growing children. Pediatric patients contribute to a small percentage of the overall device volume, but the majority of these patients will have a pacemaker for life. We need to be proactive and consider what are the best short and long-term solutions for this cohort.
Abstract Purpose To provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer. Methods The ...Society of Gynecologic Oncology and the American Society of Clinical Oncology convened an Expert Panel and conducted a systematic review of the literature. Results Four phase III clinical trials form the primary evidence base for the recommendations. The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer, neoadjuvant chemotherapy and interval cytoreduction are non-inferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality. Recommendations All women with suspected stage IIIC or IV invasive epithelial ovarian cancer should be evaluated by a gynecologic oncologist prior to initiation of therapy. The primary clinical evaluation should include a CT of the abdomen and pelvis, and chest imaging (CT preferred). Women with a high perioperative risk profile or a low likelihood of achieving cytoreduction to < 1 cm of residual disease (ideally to no visible disease) should receive neoadjuvant chemotherapy. Women who are fit for primary cytoreductive surgery, and with potentially resectable disease, may receive either neoadjuvant chemotherapy or primary cytoreductive surgery. However, primary cytoreductive surgery is preferred if there is a high likelihood of achieving cytoreduction to < 1 cm (ideally to no visible disease) with acceptable morbidity. Before neoadjuvant chemotherapy is delivered, all patients should have confirmation of an invasive ovarian, fallopian tube, or peritoneal cancer. Additional information is available at www.asco.org/NACT-ovarian-guideline and www.asco.org/guidelineswiki.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Summary
Bypassing agents are presently the standard of care for the treatment of bleeding episodes in patients with hemophilia and high‐titer inhibitors and are also used for bleed prevention. Only ...two bypassing agents are available to patients, and these products trace their lineage to the 1970s (activated prothrombin complex concentrates) and the 1980s (recombinant factor VIIa). Given the limited repertoire of available products, clinicians have relied on experience, empirical observation, registry data and individualized care to improve clinical outcomes on a case‐by‐case basis. Research over the past two decades has culminated in a greatly improved understanding of human coagulation; resulting from this, new products have been developed that offer treatment options and mechanisms of actions that differ from current bypassing agents. The most advanced in clinical development is emicizumab, a bispecific antibody that mimics the function of FVIIIa in the intrinsic Xase complex and is indicated for once‐weekly or every‐other‐week prophylactic dosing in inhibitor patients. Other non‐traditional products in clinical development include fitusiran and antibodies directed against tissue factor pathway inhibitor. As non‐factor‐based therapies become more widely utilized over time, the use of bypassing agents may be expected to decrease; however, bypassing agents will remain essential for the foreseeable future. As such, clinical development of bypassing agents continues, with some products (e.g. eptacog beta) under regulatory review. In this review we examine the optimal use of bypassing agents and their mechanism of action. We also discuss newer products and how these might theoretically be administered in conjunction with traditional bypassing agents.
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FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background:
Platelet-rich plasma (PRP) and bone marrow concentrate (BMC) are orthobiologic therapies with numerous growth factors and other bioactive molecules. Before the clinical utility of PRP and ...BMC is optimized as a combined therapy or monotherapy, an improved understanding of the components and respective concentrations is necessary.
Purpose:
To prospectively measure and compare anabolic, anti-inflammatory, and proinflammatory growth factors, cytokines, and chemokines in bone marrow aspirate (BMA), BMC, whole blood, leukocyte-poor PRP (LP-PRP), and leukocyte-rich PRP (LR-PRP) from samples collected and processed concurrently on the same day from patients presenting for elective knee surgery.
Study Design:
Cross-sectional study; Level of evidence, 3.
Methods:
Patients presenting for elective knee surgery were prospectively enrolled over a 3-week period. Whole blood from peripheral venous draw and BMA from the posterior iliac crest were immediately processed via centrifugation and manual extraction methods to prepare LR-PRP, LP-PRP, and BMC samples, respectively. BMA, BMC, whole blood, LR-PRP, and LP-PRP samples were immediately assayed and analyzed to measure protein concentrations.
Results:
BMC had a significantly higher interleukin 1 receptor antagonist (IL-1Ra) concentration than all other preparations (all P < .0009). LR-PRP also had a significantly higher IL-1Ra concentration than LP-PRP (P = .0006). There were no significant differences in IL-1Ra concentration based on age, sex, body mass index, or chronicity of injury in all preparations. LR-PRP had significantly higher concentrations of platelet-derived growth factor AA (PDGF-AA) and PDGF-AB/BB than all other preparations (all P < .0006). LR-PRP also had significantly higher concentrations of matrix metalloproteinase 1 (MMP-1) and soluble CD40 ligand than all other preparations (all P < .004). LP-PRP had significantly higher concentrations of MMPs, namely MMP-2, MMP-3, and MMP-12, than all other preparations (all P < .007).
Conclusion:
BMC is a clinically relevant source of anti-inflammatory biologic therapy that may be more effective in treating osteoarthritis and for use as an intra-articular biologic source for augmented healing in the postsurgical inflammatory and healing phases, owing to its significantly higher concentration of IL-1Ra as compared with LR-PRP and LP-PRP. Additionally, LR-PRP had a significantly higher concentration of IL-1Ra than LP-PRP. In cases where increased vascularity and healing are desired for pathological or injured tissues, including muscle and tendon, LR-PRP may be optimal given its higher overall concentrations of PDGF, TGF-β, EGF, VEGF, and soluble CD40 ligand.
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FSPLJ, NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
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