Real World Data in Adaptive Biomedical Innovation: A Framework for Generating Evidence Fit for Decision-Making.

Analyses of healthcare databases (claims, electronic health records [EHRs]) are useful supplements to clinical trials for generating evidence on the effectiveness, harm, use, and value of medical products in routine care. A constant stream of data from the routine operation of modern healthcare systems, which can be analyzed in rapid cycles, enables incremental evidence development to support accelerated and appropriate access to innovative medicines. Evidentiary needs by regulators, Health Technology Assessment, payers, clinicians, and patients after marketing authorization comprise (1) monitoring of medication performance in routine care, including the materialized effectiveness, harm, and value; (2) identifying new patient strata with added value or unacceptable harms; and (3) monitoring targeted utilization. Adaptive biomedical innovation (ABI) with rapid cycle database analytics is successfully enabled if evidence is meaningful, valid, expedited, and transparent. These principles will bring rigor and credibility to current efforts to increase research efficiency while upholding evidentiary standards required for effective decision-making in healthcare.

A 4-arm randomized controlled pilot trial of innovative solutions for jugular central venous access device securement in 221 cardiac surgical patients.

PURPOSE: To improve jugular central venous access device (CVAD) securement, prevent CVAD failure (composite: dislodgement, occlusion, breakage, local or bloodstream infection), and assess subsequent trial feasibility. MATERIALS AND METHODS: Study design was a 4-arm, parallel, randomized, controlled, nonblinded, pilot trial. Patients received CVAD securement with (i) suture+bordered polyurethane (suture + BPU; control), (ii) suture+absorbent dressing (suture + AD), (iii) sutureless securement device+simple polyurethane (SSD+SPU), or (iv) tissue adhesive+simple polyurethane (TA+SPU). Midtrial, due to safety, the TA+SPU intervention was replaced with a suture + TA+SPU group. RESULTS: A total of 221 patients were randomized with 2 postrandomization exclusions. Central venous access device failure was as follows: suture + BPU controls, 2 (4%) of 55 (0.52/1000 hours); suture + AD, 1 (2%) of 56 (0.26/1000 hours, P=.560); SSD+SPU, 4 (7%) of 55 (1.04/1000 hours, P=.417); TA+SPU, 4 (17%) of 23 (2.53/1000 hours, P=.049); and suture + TA+SPU, 0 (0%) of 30 (P=.263; intention-to-treat, log-rank tests). Central venous access device failure was predicted (P<.05) by baseline poor/fair skin integrity (hazard ratio, 9.8; 95% confidence interval, 1.2-79.9) or impaired mental state at CVAD removal (hazard ratio, 14.2; 95% confidence interval, 3.0-68.4). CONCLUSIONS: Jugular CVAD securement is challenging in postcardiac surgical patients who are coagulopathic and mobilized early. TA+SPU was ineffective for CVAD securement and is not recommended. Suture + TA+SPU appeared promising, with zero CVAD failure observed. Future trials should resolve uncertainty about the comparative effect of suture + TA+SPU, suture + AD, and SSD+SPU vs suture + BPU.

Nursing team leader handover in the intensive care unit contains diverse and inconsistent content: An observational study.

BACKGROUND: Despite a proliferation of evidence and the development of standardised tools to improve communication at handover, evidence to guide the handover of critical patient information between nursing team leaders in the intensive care unit is limited. OBJECTIVE: The study aim was to determine the content of information handed over during intensive care nursing team leader shift-to-shift handover. DESIGN: A prospective observational study. SETTING: A 21-bed medical/surgical adult intensive care unit specialising in cardiothoracic surgery at a tertiary referral hospital in Queensland, Australia. PARTICIPANTS: Senior nurses (Grade 5 and 6 Registered nurses) working in team leader roles, employed in the intensive care unit were sampled. METHOD: After obtaining consent from nursing staff, team leader handovers were audiotaped over 20 days. Audio recordings were transcribed and analysed using deductive and inductive content analysis. The frequency of content discussed at handover that fell within the a priori categories of the ISBAR schema (Identify-Situation-Background-Assessment-Recommendation) was calculated. RESULTS: Forty nursing team leader handovers were recorded resulting in 277 patient handovers and a median of 7 (IQR 2) patients discussed at each handover. The majority of nurses discussed the Identity (99%), Situation (96%) and Background (88%) of the patient, however Assessment (69%) content was varied and patient Recommendations (60%) were discussed less frequently. A diverse range of additional information was discussed that did not fit into the ISBAR schema. CONCLUSIONS: Despite universal acknowledgement of the importance of nursing team leader handover, there are no previous studies assessing its content. Study findings indicate that nursing team leader handovers contain diverse and inconsistent content, which could lead to inadequate handovers that compromise patient safety. Further work is required to develop structured handover processes for nursing team leader handovers.

The comprehension skills of children learning English as an additional language.

BACKGROUND: Data from national test results suggests that children who are learning English as an additional language (EAL) experience relatively lower levels of educational attainment in comparison to their monolingual, English-speaking peers. AIMS: The relative underachievement of children who are learning EAL demands that the literacy needs of this group are identified. To this end, this study aimed to explore the reading- and comprehension-related skills of a group of EAL learners. SAMPLE: Data are reported from 92 Year 3 pupils, of whom 46 children are learning EAL. METHOD: Children completed standardized measures of reading accuracy and comprehension, listening comprehension, and receptive and expressive vocabulary. RESULTS: Results indicate that many EAL learners experience difficulties in understanding written and spoken text. These comprehension difficulties are not related to decoding problems but are related to significantly lower levels of vocabulary knowledge experienced by this group. CONCLUSIONS: Many EAL learners experience significantly lower levels of English vocabulary knowledge which has a significant impact on their ability to understand written and spoken text. Greater emphasis on language development is therefore needed in the school curriculum to attempt to address the limited language skills of children learning EAL.

What makes British general practitioners take part in a quality improvement scheme?

OBJECTIVES: To understand the reasons for the apparent success of a quality improvement scheme designed to produce widespread changes in chronic disease management in primary care. METHODS: Purposeful sample of 36 primary care staff, managers and specialists. Qualitative analysis of 27 interviews in East Kent Health Authority area, where, over a three-year period, more than three-quarters of general practitioners (GPs) and enrolled in a quality improvement programme which required them to meet challenging chronic disease management targets (PRImary Care Clinical Effectiveness--PRICCE). RESULTS: Major changes in clinical practice appeared to have taken place as a result of participation in PRICCE. The scheme was significantly dependent on leadership from the health authority and on local professional support. Factors that motivated GPs to take part in the project included: a desire to improve patient care; financial incentives; maintenance of professional autonomy in how to reach the targets; maintenance of professional pride; and peer pressure. Good teamworking was essential to successful completion of the project and often improved as a result of taking part. The scheme included a combination of interventions known to be effective in producing professional behavioural change. CONCLUSIONS: When managerial vision is aligned to professional values, and combined with a range of interventions known to influence professional behaviour including financial incentives, substantial changes in clinical practice can result. Lessons are drawn for future quality improvement programmes in the National Health Service.

The apical ligament: anatomy and functional significance.

OBJECT: The authors conducted a study to describe the detailed anatomy of the apical ligament and to acknowledge or refute its historical description as a functionally significant contributor to craniocervical stability. METHODS: In 20 adult human cadavers measurements of the apical ligament were obtained, and its detailed anatomy was observed. Ranges of motion were also assessed to discern the function of the apical ligament. CONCLUSIONS: Results of the study support the concept that the apical ligament is best described as a vestigial structure that offers no significant added stability to the craniocervical junction. In fact, this ligament was absent in 20% of the specimens examined. These data will aid physicians who frequently view images or manage clinical problems of the craniocervical junction because they may focus on other ligaments of this area and not the apical ligament.

Intraepithelial lymphocytes in normal human intestine do not express proteins associated with cytolytic function.

Human small intestine contains a very large population of intraepithelial T lymphocytes (IELs) that are oligoclonal, appear functionally to be cytolytic T cells, and may contribute to the normal and pathological turnover of intestinal epithelial cells. This report addresses the cytolytic function of IELs in normal small intestine by examining their expression of molecules that carry out cell-mediated cytolysis. Immunohistochemical analyses of granzyme B, perforin, Fas ligand, and tumor necrosis factor-alpha demonstrated these proteins were not expressed by small intestinal IELs in situ. These proteins also were not expressed by colonic IELs or by lamina propria lymphocytes in the small or large intestine. Granzyme A, however, was expressed by a large fraction of IELs. In contrast to these in situ results, isolated and in vitro activated IELs were shown to express effector proteins consistent with cytolytic T cells, including granzyme B, Fas ligand, tumor necrosis factor-alpha, and interferon-gamma. These results are most consistent with the vast majority of IELs in normal human small intestine being resting cytolytic T cells and suggest that these cells do not contribute to the apoptotic cell death of epithelial cells in normal intestine.

Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer.

BACKGROUND: Metastatic prostate cancer is a leading cause of cancer-related death in men. The rate of response to androgen ablation is high, but most patients relapse as a result of the outgrowth of androgen-independent tumor cells. The androgen receptor, which binds testosterone and stimulates the transcription of androgen-responsive genes, regulates the growth of prostate cells. We analyzed the androgen-receptor genes from samples of metastatic androgen-independent prostate cancers to determine whether mutations in the gene have a role in androgen independence. METHODS: Complementary DNA was synthesized from metastatic prostate cancers in 10 patients with androgen-independent prostate cancer, and the expression of the androgen-receptor gene was estimated by amplification with the polymerase chain reaction. Exons B through H of the gene were cloned, and mutations were identified by DNA sequencing. The functional effects of the mutations were assessed in cells transfected with mutant genes. RESULTS: All androgen-independent tumors expressed high levels of androgen-receptor gene transcripts, relative to the levels expressed by an androgen-independent prostate-cancer cell line (LNCaP). Point mutations in the androgen-receptor gene were identified in metastatic cells from 5 of the 10 patients examined. One mutation was in the same codon as the mutation found previously in the androgen-independent prostate-cancer cell line. The mutations were not detected in the primary tumors from of the two patients. Functional studies of two of the mutant androgen receptors demonstrated that they could be activated by progesterone and estrogen. CONCLUSIONS: Most metastatic androgen-independent prostate cancers express high levels of androgen-receptor gene transcripts. Mutations in androgen-receptor genes are not uncommon and may provide a selective growth advantage after androgen ablation.

A personal perspective: the psychological needs of spine-injured patients.

1. The immediate needs of spine-injured patients, families and friends is for answers, advice, support and counselling. 2. Newly injured patents and their families and friends need continuous support and information throughout long-term rehabilitation. 3. Consideration must be given to the injured patient as a whole person because physical and psychological rehabilitation are dependent on each other.

The future direction of general practice.

Examines the present strengths and weaknesses of the general practice system. Proposes a different structure for the future which should provide benefits for both the purchasers and providers of health care, as well as for the patients themselves.