Needs-led assessment: the challenges and the reality

The NHS & Community Care Act 1990 heralded a new era in community care in the UK. Needs-led assessment and case management were to form the cornerstone of high quality care. Practitioners were challenged to alter their attitudes and practice to accommodate the needs-led approach. Previously they had assessed need to ascertain eligibility for statutory services, now they were required to identify "need" per se. The pivotal role given to assessment meant the success, or otherwise, of the reforms lay in part on the ability of practitioners to make this transition. However, to make needs-led assessment a reality, practitioners would have both to overcome conceptual barriers--need being an unclear concept, with no clear framework existing to assess need--and also to deal successfully with the conflicting requirement to ration services. In order to investigate whether the shift to needs-led practice had been possible, the opinions of social and healthcare practitioners providing services for older people in North Wales were sought through semi-structured interviews in 1994-1995 and 1998-1999. Supports and constraints to practice were also explored. Practitioners indicated that whilst they welcomed the needs-led philosophy, putting it into practice was difficult, if not impossible. The main constraints were a lack of resources (financial, service provision and staffing) and the conceptual difficulty of separating "need" from the "need for a particular service". Ever-tightening budgets and service eligibility criteria over the period of the study indicate that a shift of focus from assessment of need to rationing has taken place.     

Side-chain substitutions within angiotensin II reveal different requirements for signaling, internalization, and phosphorylation of type 1A angiotensin receptors

Binding of the peptide hormone angiotensin II (AngII) to the type 1 (AT(1A)) receptor and the subsequent activation of phospholipase C-mediated signaling, involves specific determinants within the AngII peptide sequence. In contrast, the contribution of such determinants to AT(1A) receptor internalization, phosphorylation and activation of mitogen-activated protein kinase (MAPK) signaling is not known. In this study, the internalization of an enhanced green fluorescent protein-tagged AT(1A) receptor (AT(1A)-EGFP), in response to AngII and a series of substituted analogs, was visualized and quantified using confocal microscopy. AngII-stimulation resulted in a rapid, concentration-dependent internalization of the chimeric receptor, which was prevented by pretreatment with the nonpeptide AT(1) receptor antagonist EXP3174. Remarkably, AT(1A) receptor internalization was unaffected by substitution of AngII side chains, including single and double substitutions of Tyr(4) and Phe(8) that abolish phospholipase C signaling through the receptor. AngII-induced receptor phosphorylation was significantly inhibited by several substitutions at Phe(8) as well as alanine replacement of Asp(1). The activation of MAPK was only significantly inhibited by substitutions at position eight in the peptide and specific substitutions did not equally inhibit inositol phosphate production, receptor phosphorylation and MAPK activation. These results indicate that separate, yet overlapping, contacts made between the AngII peptide and the AT(1A) receptor select/induce distinct receptor conformations that preferentially affect particular receptor outcomes. The requirements for AT(1A) receptor internalization seem to be less stringent than receptor activation and signaling, suggesting an inherent bias toward receptor deactivation.     

A decision analysis model predicts the optimal treatment pathway for patients with colorectal cancer and resectable synchronous liver metastases

BACKGROUND: The estimated 2400 Americans who annually present with colorectal cancer and simultaneous resectable liver metastases encounter a wide array of surgical and medical treatment options. Because of the large number of possible treatment sequences and the absence of clinical trials comparing these various pathways, there is no consensus on the optimal therapeutic strategy. MATERIALS AND METHODS: To address this issue, a decision-making model was developed incorporating all possible combinations of the following treatments: colorectal resection, hepatic resection, simultaneous colohepatic resection, and systemic chemotherapy. Transition probabilities associated with each treatment were determined by systematic review of the literature. Variations in complication rates based on the extent of hepatectomy (minor: 1-2 segments vs. major: > 2 segments) were factored into the model. Sensitivity analyses were performed to identify threshold values for study variables that altered the optimal treatment pathway. RESULTS: After 10,000 simulated patient trials with no bias toward any one initial treatment (ie, current practice conditions), the global calculated 5-year survival rate was 21%. For simulated patients with moderate hepatic tumor burden, only treatment sequences that placed systemic therapy before major hepatectomy resulted in improved 5-year survival projections (38% vs. 29%; P = .001; odds ratio, 1.82). Initial treatment with simultaneous colohepatic resection was only favored when the operative mortality rate was adjusted to < 0.5%. CONCLUSION: This detailed decision-making analysis predicts that the optimal treatment pathway for most patients with colorectal cancer and simultaneous resectable liver metastases is preoperative systemic therapy followed by colohepatectomy or 2-stage resection. In the era of improved systemic therapies, major hepatic resection should be deferred until local and systemic disease can been addressed.     

Tumor risk assessment by means of immunocytochemical detection of early pre-malignant changes in buccal smears

Increasing incidence of carcinomas in the upper aero-digestive tract, both in Germany and in other European countries requires development of new preventive strategies. The cure rate at advanced tumor stages remains poor in spite of a variety of available therapeutic methods. In the present study the quantitative assessment of a pre-malignant mucosa lesion within a field cancerization was performed by means of immunocytochemical methods. This may allow individuals with an increased risk of developing malignant disease to be identified. Cytosmears taken from healthy buccal mucosa of tumor patients (n=50) and from healthy probands (n=100) with different tobacco and alcohol consumption levels were examined with regard to identifying increased expression of the proliferation markers (PCNA, MIB1), of the tumor suppressor gene product p53 as well as the oncogene product cyclin D1. There was a significant difference in expression of investigated proliferation markers between tumor patients and healthy probands (p<0.0001). When comparing the rate of positively marked cell nuclei to cigarette pack years the marker cyclin D1 and MIB1 show an increased rate in the groups with high tobacco consumption as compared to the group with a low exposure (p>0.05). It could be possible to use the marker MIB1 and cyclin D1 to screen risk groups, since the relative morbidity risk (odds ratio) increases (by 45-62 times) if the threshold value of 4 positively marked cell nuclei is exceeded.     

Rotator cuff repair with biological graft augmentation causes adverse tissue outcomes

Background and purpose — Biological patches can be used to augment rotator cuff tendon repair in an attempt to improve healing and reduce rates of re-rupture. However, little is known about the in vivo tissue response to these patches. We assessed native rotator cuff tissue response after surgical repair and augmentation with 2 commercially available extracellular matrix (ECM) patches.Patients and methods — Patients underwent a rotator cuff repair augmented with either GraftJacket (Wright Medical), Permacol (Zimmer Biomet), or no patch (Control), applied using an onlay technique. A sample of supraspinatus tendon was collected intraoperatively and 4 weeks post-surgery, using ultrasound-guided biopsy. Histology and immunohistochemistry were performed on all samples.Results — The Permacol group (n = 3) and GraftJacket group (n = 4) demonstrated some changes in native tendon ECM compared with the control group (n = 3). Significant disruption of the extracellular matrix of the repaired native supraspinatus, underlying both patches, was observed. The patches did not generally increase cellularity, foreign body giant cell count, or vascularity compared to the control group. 1 patient in the Permacol group had an adverse tissue immune response characterized by extensive infiltration of IRF5⁺, CD68⁺, and CD206⁺ cells, suggesting involvement of macrophages with a pro-inflammatory phenotype. No significant differences in protein expression of CD4, CD45, CD68, CD206, BMP7, IRF5, TGFß, and PDPN were observed among the groups.Interpretation — Histological and immunohistochemical analysis of native tendon tissue after patch augmentation in rotator cuff repair raises some concerns about a lack of benefit and potential for harm from these materials.

Rotator cuff tendon tears occur in 1 in 3 people aged over 60 years (Tempelhof et al. 1999). Around 17,000 rotator cuff repairs are performed in the National Health Service (NHS) in the UK each year (Digital 2016). The incidence of rotator cuff repair is increasing in the UK and the USA (Colvin et al. 2012). Numerous observational studies have attempted to describe the healing rate following cuff repair (Russell et al. 2014, Shen et al. 2014, Yang et al. 2017). Despite the evolution in technique and implants, the overall healing rate is around 60% (Carr et al. 2017). This has led surgeons to develop innovative strategies that aim to augment tendon repair and improve healing rate.One rotator cuff tendon repair augmentation strategy involves the application of a patch overlying the repair. These patches may be biological or synthetic. Biological patches are designed to become incorporated and vascularized by the native tendon, adding essential matrix proteins for healing (Zimmer 2006). Biological graft sources may be from the patient him/herself (e.g., fascia lata autograft), from cadaveric donors (e.g., dermal allograft), or from porcine tissues (e.g., dermal or small intestine submucosa, xenograft). These biological patches, sometimes called extracellular matrix (ECM) patches, are processed to remove donor cells, and sometimes chemically crosslinked, before sterilization for clinical use (Zimmer 2006, Group 2017). 2 popular biological patches, available for clinical use in rotator cuff repair, are GraftJacket (Wright Medical, Memphis, TE, USA) and Permacol (Zimmer Biomet, Warsaw, IN, USA).GraftJacket Regenerative Tissue Matrix (RTM) (manufactured by LifeCell Corporation, Branchburg, NJ, USA) is a cadaveric human dermis graft that is not crosslinked and undergoes decellularization by a proprietary process (Group 2017). Permacol (manufactured by Tissue Science Laboratories PLC, Aldershot, UK) is a porcine dermis graft that is chemical crosslinked with 4,4''-Diisocyanato-methylenedicyclohexane (HMDI), and is decellularized by a proprietary process. Both GraftJacket and Permacol patches are marketed with some supporting information from in vitro and animal studies, showing cellular infiltration and neovascularization; however, the mechanisms underpinning these observations are unclear (McQuillan and Harper 2007, Xu et al. 2009, O’Brien et al. 2011, Xu et al. 2012).The in vivo tissue response to xenograft and allograft tissue is important to consider in patch augmentation in humans. Patch augmentation in rotator cuff repair carries some additional risks. These include foreign-body reaction, sterile inflammatory response, transmission of undiagnosed malignancy, and infectious disease transmission (Hinsenkamp et al. 2012). We ascertained the tissue response of the native supraspinatus tendon to 2 biological patches at 4 weeks compared with a control (no patch), using histology and immunohistochemistry.