BACKGROUNDTransthyretin amyloidosis, also called ATTR amyloidosis, is a life-threatening disease characterized by progressive accumulation of misfolded transthyretin (TTR) protein in tissues, predominantly the nerves and heart. NTLA-2001 is an in vivo gene-editing therapeutic agent that is designed to treat ATTR amyloidosis by reducing the concentration of TTR in serum. It is based on the clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease (CRISPR-Cas9) system and comprises a lipid nanoparticle encapsulating messenger RNA for Cas9 protein and a single guide RNA targeting TTR. METHODSAfter conducting preclinical in vitro and in vivo studies, we evaluated the safety and pharmacodynamic effects of single escalating doses of NTLA-2001 in six patients with hereditary ATTR amyloidosis with polyneuropathy, three in each of the two initial dose groups (0.1 mg per kilogram and 0.3 mg per kilogram), within an ongoing phase 1 clinical study. RESULTSPreclinical studies showed durable knockout of TTR after a single dose. Serial assessments of safety during the first 28 days after infusion in patients revealed few adverse events, and those that did occur were mild in grade. Dose-dependent pharmacodynamic effects were observed. At day 28, the mean reduction from baseline in serum TTR protein concentration was 52% (range, 47 to 56) in the group that received a dose of 0.1 mg per kilogram and was 87% (range, 80 to 96) in the group that received a dose of 0.3 mg per kilogram. CONCLUSIONSIn a small group of patients with hereditary ATTR amyloidosis with polyneuropathy, administration of NTLA-2001 was associated with only mild adverse events and led to decreases in serum TTR protein concentrations through targeted knockout of TTR. (Funded by Intellia Therapeutics and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT04601051.

It is generally agreed in the nursing literature that the maintenance of patient dignity is an important element of nursing care that is highly valued by patients. Despite this, dignity is seldom defined and there are few guidelines that nurses may use in their practice to safeguard individual patients' dignity. This phenomenological study aimed to uncover patients' and nurses' perceptions of dignity, formulate a definition of dignity based on the experience of patients and nurses, and identify nursing practices that maintain or compromise patient dignity. The study found that the characteristics nurses associated with dignity were many and varied. Important elements in the meaning the nurses ascribed to the notion of patient dignity were the elements of respect, privacy, control, advocacy and time. The themes which emerged from the patient interviews were similar to those which emerged from the interviews with nurses. The characteristics that patients attributed to dignity and its maintenance included respect, privacy, control, choice, humour and matter-of-factness.

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This study was designed to identify the feelings and experiences of critical care nurses who have been involved in nursing brain dead patients prior to organ donation. The purpose of the study was to generate knowledge which informs the discipline of nursing. A number of themes relating to nurses' experiences of caring for brain dead organ donor patients were uncovered in this interpretative study. Overall, caring for patients who are diagnosed as brain dead is a challenging experience for nurses and they are intensely involved in a search for meaning in each event. The interpretative analysis in this study has revealed a range of meanings articulated by the nurses involved. However, the primary focus of care--as identified by the participating nurses--was the donor family.

Therapeutic interpersonal relationships are the primary component of all health care interactions that facilitate the development of positive clinician–patient experiences. Therapeutic interpersonal relationships have the capacity to transform and enrich the patients’ experiences. Consequently, with an increasing necessity to focus on patient-centered care, it is imperative for health care professionals to therapeutically engage with patients to improve health-related outcomes. Studies were identified through an electronic search, using the PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO databases of peer-reviewed research, limited to the English language with search terms developed to reflect therapeutic interpersonal relationships between health care professionals and patients in the acute care setting. This study found that therapeutic listening, responding to patient emotions and unmet needs, and patient centeredness were key characteristics of strategies for improving therapeutic interpersonal relationships.