Practice-Based Research Priorities for Palliative Care: Results From a Research-to-Practice Consensus Workshop

We employed the research-to-practice consensus workshop (RTP; workshops held in New York City and Tompkins County, New York, in 2013) model to merge researcher and practitioner views of translational research priorities in palliative care. In the RTP approach, a diverse group of frontline providers generates a research agenda for palliative care in collaboration with researchers. We have presented the major workshop recommendations and contrasted the practice-based research priorities with those of previous consensus efforts. We uncovered notable differences and found that the RTP model can produce unique insights into research priorities. Integrating practitioner-identified needs into research priorities for palliative care can contribute to addressing palliative care more effectively as a public health issue.Over the past 2 decades, palliative care has become established as a promising approach for addressing the needs of individuals with life-threatening illnesses from a holistic, interdisciplinary perspective. For this project, we defined palliative care as an approach that improves the quality of life of patients and families facing the problems encountered in life-threatening illness by preventing and relieving suffering. Core components of palliative care include providing relief from pain and other distressing symptoms, affirming dying as a normal process, integrating psychological and spiritual aspects of care, enhancing the quality of life of patients, and offering support systems to patients and their families to help them live as fully as possible until death occurs.Research suggests that palliative care results in positive patient outcomes, greater patient and family satisfaction, and significant cost savings.1,2 The American Public Health Association, the World Health Organization, and the Institute of Medicine3–6 have identified the development of a robust palliative care delivery system as a key public health issue because of the documented ability of palliative care to deliver effective and efficient patient- and symptom-focused care to a growing population in need.In its 2013 report the American Public Health Association specifically detailed the public health implications of palliative care, acknowledged the growing burden of advanced chronic illness and disease in older adults, and recommended key steps to address the problem. This policy statement called for federal, state, and local efforts to promote effective symptom management in populations with serious illness or at the end of life. Other recommended initiatives included the development of a palliative care workforce, educational programs to improve uptake and use of palliative and hospice care, and research funding to support the expansion of palliative care initiatives. Achieving these goals will require moving beyond traditional medical practices to include both policies and initiatives at the public health level.Despite the potential of palliative care to address the mental and physical health needs of individuals with advanced illness, significant knowledge gaps impede its reach and effectiveness. Reports from scientific bodies and consensus workshops have highlighted weaknesses in the literature and called for more research on palliative care and improved research methods.7–10 Thus, although both interest in and demand for palliative care are increasing, reviews of the knowledge base continue to lament the lack of research on many key issues.11,12Especially urgent is a research agenda that fits most closely with the needs of providers who deliver palliative care. The systematic engagement of community practitioners in a consensus process can lead to particularly useful and actionable recommendations for research,13–15 which are greatly needed at this stage in the development of the field. Therefore, to shed new light on research priorities in palliative care, we used a structured, participatory method designed to solicit practitioner input on research priorities: the research-to-practice consensus workshop (RTP) model.16We employed the RTP approach to identify knowledge gaps and types of studies that should be conducted to improve providers’ ability to deliver palliative care most effectively. This model harnesses practice wisdom by engaging clinicians, agency staff, and other practitioners with researchers in a process of articulating and refining research questions and research priorities that honors scientific expertise and practice wisdom.     

Therapy-induced preleukaemia in patients treated for Hodgkin''s lymphoma: clinical and therapeutic relevance of sequential chromosome banding studies

Between January 1978 and December 1982 successful sequential chromosome analyses were carried out on bone marrow cells of five patients previously treated for Hodgkin's lymphoma (HL) presenting unexplained cytopenia or pancytopenia during follow-up. All patients had concurrent morphological examination of bone marrow specimens showing signs of dysplasia and/or hypoplasia, without leukaemic infiltrate. Six other patients treated for HL who had normal haematological parameters served as controls. All the patients with unexplained cytopenias had clonal chromosome abnormalities; monosomy for chromosome No. 5 was the most frequent. No abnormalities were detected in the control group. Two patients have evolved to resistant leukaemia, one died of sepsis before leukaemic conversion while severely neutropenic, and two are in full marrow and cytogenetic recovery after aggressive anti-leukaemic treatment in the pre-leukaemic phase. Our data suggest that cytogenetic studies may be of crucial value in detecting therapy-induced preleukaemia (t-PL) at an early stage of its evolution and in planning appropriate therapy before the establishment of overt leukaemia.     

Prenatal treatment of congenital adrenal hyperplasia.

Prenatal diagnosis of congenital adrenal hyperplasia (CAH) is accurate and prenatal therapy is effective in significantly reducing or even eliminating virilization of females affected by CAH, sparing these children the consequences of genital surgery, sex missassignment and gender confusion. However, both the physical and psychological development of these children and the possibility of long-range adverse effects in the mothers need to be evaluated further. Prospective multicentre studies covering several decades are being designed.     

Age-related response of plasma testosterone, delta 4-androstenedione, and cortisol to adrenocorticotropin in infants, children, and adults.

The response of plasma testosterone (T), delta 4-androstenedione, and cortisol (F) to the administration of synthetic Zn beta 1-24 ACTH (0.5 mg/m2 im every 12 h for 3 days) was ascertained in 20 infants, 35 prepubertal children, 4 early pubertal boys, and 15 adults. At all ages and in both sexes, a significant rise in delta 4-androstenedione and F was observed (P less than 0.00001), whereas the response of T showed a sex difference: T levels increased in females (P less than 0.001) at all ages in response to ACTH, while they decreased (P less than 0.01) in males at periods of active testicular secretion (early infancy, puberty, and adulthood). In prepubertal boys, in the absence of significant Leydig cell activity, T levels increased after ACTH, as they did in girls. The post-ACTH values of T, expressed as percent-ages of the control levels, were significantly lower (P less than 0.01) in infants (3.17 +/- 16.7%) than in pubertal boys (59.5 +/- 14.6%) or adult men (57.9 +/- 7.7%). F levels were significantly higher after ACTH stimulation at 1-4 months of age (253 +/- 129 micrograms/dl) than at any later age studied (64 +/- 17 micrograms/dl). It would seem, therefore, that the suppressive effect of ACTh on testicular secretion might be glucocorticoid mediated and its magnitude might be related to circulating levels of F.     

Benign lymphoid hyperplasia manifesting as a cecal mass: Report of a case

Summary We have presented an unusual case of benign lymphoid hyperplasia, which manifested as a cecal deformity in a 15-year-old boy. The clinical manifestation may have been related to partial occlusion of the appendiceal orifice. In future cases of benign lymphoid hyperplasia, colonoscopy may be diagnostic, and if it is used for continuing observation, may avert unnecessary surgical procedures in children and young adults.     

Esophageal epithelial response to gastroesophageal reflux

Exposure of the distal esophageal mucosa to acid gastric juice was quantitated by 24-hr pH monitoring in 100 individuals and was correlated with morphologic data derived from esophageal biopsies. The degree of acid exposure to the distal esophagus correlated directly with increases in both relative and absolute length of the subepithelial papillae and to relative basal zone hyperplasia. Both papillary length and basal zone hyperplasia decreased after antireflux surgery had reduced acid exposure to normal. Reflux in the recumbent position resulted in prolonged exposure of the mucosa to acid because of poor acid clearing from the esophagus. This caused longer papillae than did upright reflux, where there were more frequent reflux episodes, but with rapid acid clearance. The presence of a hiatal hernia was associated with longer papilae, lower DES pressure, increased reflux frequency, and prolonged recumbent acid clearance. Twenty-four hour pH monitoring correlated better with papillary length than did symptoms or other clinical measures of gastroesophageal reflux.     

Platelet alpha-granule and plasma membrane share two new components: CD9 and PECAM-1

CD9 (p24) and PECAM1 (CD31) antigens are well-defined components of the platelet plasma membrane. Both are integral glycoproteins (GPs) implicated in the adhesive and aggregative properties of human platelets. In the present report, we have investigated their subcellular localization using immunoelectron microscopy. The monospecificity of the two polyclonal antibodies used was confirmed by immunoblotting. On normal resting platelets, immunolabeling for CD9 and PECAM1 was found lining the plasma membrane and the luminal face of the open canalicular system. Some labeling was also consistently found on the alpha-granule limiting membrane. This was confirmed by double labeling experiments in which fibrinogen and von Willebrand factor (vWF) were used as alpha-granule markers. CD9 and PECAM-1 were found lining the membrane of the same granules that contained fibrinogen and vWF in their matrix. CD9 and PECAM-1 thus appear to have an intracellular distribution identical to GPIIb-IIIa, a major aggregation platelet receptor. To rule out a cross-reactivity of the two polyclonal antibodies with GPIIb/IIIa, we studied PECAM1 and CD9 expression on the platelets from a patient with type I Glanzmann's thrombasthenia whose platelets are devoid of GPIIb/IIIa. The same pattern of labeling was observed for both antigens as for normal platelets. Normal platelets were further observed after stimulation by agonists that either fail to induce (ADP) or induce granule secretion (thrombin). After treatment with ADP, platelets changed shape and centralized their granules; the plasma membrane immunolabeling remained unchanged; and gold particles were still found decorating the periphery of the centralized alpha- granules. After thrombin treatment, alpha-granules fused with the platelet membrane and secretion occurred. A significant increase of labeling was then observed on the platelet surface. From these results we conclude that the alpha-granule membrane contains two additional receptors in common with the plasma membrane. This suggests that alpha- granule membrane receptors may originate from a dual mechanism: direct targeting from the Golgi complex in megakaryocytes (for alpha-granule- specific receptors such as P-selectin) or by endocytosis from the plasma membrane (for proteins distributed in the two compartments).