Outcomes of periodontal therapy: Strengthening the relevance of research to patients. A co-created review.

Periodontitis is a long-term condition affecting up to half of the population globally and causing significant impacts on life quality. Successful management depends on taking life-long ownership of the condition by those affected. There is a wealth of research to inform on management options. However, most of the research has been designed by professional experts with outcomes to gauge benefits and harms based on parameters that inform on the disease process but which might not be informative to support decision-making in people with lived experience (PWLE) of periodontal ill-health (including both patients and carers). The importance of relevant outcomes is highlighted in the concept of the "expert patient" which aims to strengthen the capacity of PWLE to make health-care choices that are important for them, elements of which are likely to be already familiar to many clinicians delivering periodontal health care. Therefore, the voice and collaboration of PWLE in research are recognised as crucial to developing high quality, relevant evidence especially for long-term conditions. In this paper, we review what is known about the relevance of treatment outcomes to PWLE. We also examine the degree to which PWLE have been involved in identifying outcomes that are important to them as well as the diversity and therefore representativeness of PWLE recruited for studies. We consider why having more relevant outcomes could enhance the expertise of PWLE in managing their periodontitis. We then conclude with key learnings from our review which we hope will encourage more rapid development of these initiatives in periodontology for the benefit of global health and wellbeing.

Diastolic Ventricular Interaction in Heart Failure With Preserved Ejection Fraction.

Background Exercise-induced pulmonary hypertension is common in heart failure with preserved ejection fraction ( HF p EF ). We hypothesized that this could result in pericardial constraint and diastolic ventricular interaction in some patients during exercise. Methods and Results Contrast stress echocardiography was performed in 30 HF p EF patients, 17 hypertensive controls, and 17 normotensive controls (healthy). Cardiac volumes, and normalized radius of curvature ( NRC ) of the interventricular septum at end-diastole and end-systole, were measured at rest and peak-exercise, and compared between the groups. The septum was circular at rest in all 3 groups at end-diastole. At peak-exercise, end-systolic NRC increased to 1.47±0.05 ( P<0.001) in HF p EF patients, confirming development of pulmonary hypertension. End-diastolic NRC also increased to 1.54±0.07 ( P<0.001) in HF p EF patients, indicating septal flattening, and this correlated significantly with end-systolic NRC (ρ=0.51, P=0.007). In hypertensive controls and healthy controls, peak-exercise end-systolic NRC increased, but this was significantly less than observed in HF p EF patients ( HF p EF , P=0.02 versus hypertensive controls; P<0.001 versus healthy). There were also small, non-significant increases in end-diastolic NRC in both groups (hypertensive controls, +0.17±0.05, P=0.38; healthy, +0.06±0.03, P=0.93). In HF p EF patients, peak-exercise end-diastolic NRC also negatively correlated ( r=-0.40, P<0.05) with the change in left ventricular end-diastolic volume with exercise (ie, the Frank-Starling mechanism), and a trend was noted towards a negative correlation with change in stroke volume ( r=-0.36, P=0.08). Conclusions Exercise pulmonary hypertension causes substantial diastolic ventricular interaction on exercise in some patients with HF p EF , and this restriction to left ventricular filling by the right ventricle exacerbates the pre-existing impaired Frank-Starling response in these patients.

Deindustrialization, the Linwood Car Plant and Scotland's Political Divergence from England in the 1960s and 1970s.

Scotland's political divergence from England is a key theme in late twentieth century British history. Typically seen in terms of the post-1979 Thatcher effect, this in fact developed over a longer timeframe, rooted in industrial changes revealed by analysis of the Linwood car plant in Renfrewshire. Conservatism and Unionism was an eminent political force in Scotland in the 1940s and 1950s. But in all general elections from 1959 onwards the vote share of Conservative and Unionist candidates was lower in Scotland than in England. From the late 1960s onwards there were also ambitions for constitutional change. This article breaks new conceptual and empirical ground by relating these important markers of political divergence to popular understanding among Scottish workers of deindustrialization. A Thompsonian moral economy framework is deployed. Expectations were elevated by industrial restructuring from the 1950s, with workers exchanging jobs in the staples for a better future in assembly goods. Labour governments earned a reputation in Scotland as better managers of this process than Conservative governments. The 1979 general election showed that Labourism was growing in popularity in Scotland just as its appeal faded in England. At Linwood moral economy expectations were compromised, chiefly by intermittent redundancy and recurrent threat of closure, which was averted in 1975 by Labour government intervention. When the plant was shut in 1981 criticisms of UK political-constitutional structures and Conservativism were intensified.

Monosegment ALPPS hepatectomy preserving segment 4 for colorectal liver metastases: literature review and our experience.

Monosegment 4±1 Associating Liver Partition and Portal Vein ligation for Staged hepatectomy (ALPPS) for bilateral colorectal liver metastases decreases the risk of drop-out of two stage hepatectomy, triggering a rapid and significant increase in future liver remnant (FLR) with promising oncological outcomes. We report two cases of segment 4+1 monosegment ALPPS for multiple colorectal liver metastases performed at our institution. In the literature, seven similar cases have been reported. Short and long term outcomes of our two patients were reported along with a review of data from the literature. Our patients showed a FLR increase from 13% to 37% and from 14% to 41% of total liver volume, respectively. This was compared to a median growth from 19% at baseline to 34% before stage 2, in the literature. After 20 and 27 months since resection both patients are alive and disease-free. In the literature, median overall survival and disease free survival were 13 months (range, 5-24 months) and 5 months (range, 3-23 months), respectively. Segment 4±1 ALPPS is associated with promising oncological outcomes and a significant FLR growth. It may be safely performed in selected patients as a salvage procedure, reducing the risk of the dropout of two-stage hepatectomy.

Protein interferon-stimulated gene 15 conjugation delays but does not overcome coronavirus proliferation in a model of fulminant hepatitis.

UNLABELLED: Coronaviruses express a deubiquitinating protein, the papain-like protease-2 (PLP2), that removes both ubiquitin and the ubiquitin-like interferon (IFN)-stimulated gene 15 (ISG15) protein from target proteins. ISG15 has antiviral activity against a number of viruses; therefore, we examined the effect of ISG15 conjugation (ISGylation) in a model of acute viral hepatitis induced by the murine hepatitis virus strain 3 (MHV-3) coronavirus. Mice deficient in the ISG15 deconjugating enzyme, ubiquitin-specific peptidase-18 (USP18), accumulate high levels of ISG15-conjugated proteins and are hypersensitive to type I IFN. Infecting USP18(-/-) mice with MHV-3 resulted in extended survival (8 ± 1.2 versus 4 days) and in improved liver histology, a decreased inflammatory response, and viral titers 1 to 2 logs lower than in USP18(+/+) mice. The suppression of viral replication was not due to increased IFN since infected USP18(-/-) mice had neither increased hepatic IFN-α, -ß, or -γ mRNA nor circulating protein. Instead, delayed MHV-3 replication coincided with high levels of cellular ISGylation. Decreasing ISGylation by knockdown of the ISG15 E1 enzyme, Ube1L, in primary USP18(+/+) and USP18(-/-) hepatocytes led to increased MHV-3 replication. Both in vitro and in vivo, increasing MHV-3 titers were coincident with increased PLP2 mRNA and decreased ISGylation over the course of infection. The pharmacologic inhibition of the PLP2 enzyme in vitro led to decreased MHV-3 replication. Overall, these results demonstrate the antiviral effect of ISGylation in an in vivo model of coronavirus-induced mouse hepatitis and illustrate that PLP2 manipulates the host innate immune response through the ISG15/USP18 pathway. IMPORTANCE: There have been a number of serious worldwide pandemics due to widespread infections by coronavirus. This virus (in its many forms) is difficult to treat, in part because it is very good at finding "holes" in the way that the host (the infected individual) tries to control and eliminate the virus. In this study, we demonstrate that an important host viral defense-the ISG15 pathway-is only partially effective in controlling severe coronavirus infection. Activation of the pathway is very good at suppressing viral production, but over time the virus overwhelms the host response and the effects of the ISG15 pathway. These data provide insight into host-virus interactions during coronavirus infection and suggest that the ISG15 pathway is a reasonable target for controlling severe coronavirus infection although the best treatment will likely involve multiple pathways and targets.

Reducing admissions for long-term conditions: is telehealth the answer?

In December 2011, the Department of Health (DH) released a bulletin on the early findings from the telehealth Whole System Demonstrator (WSD) sites. The WSD programme is the world's largest telehealth trial, involving 6191 patients and 238 GP practices at 3 UK sites. The study focused on three conditions; diabetes, COPD and coronary heart disease. At first sight, the outcomes are impressive - certainly good enough to warrant the announcement to be made by the Prime Minister, who fully endorsed telehealth and announced its potential to benefit 3 million patients per year.

Improved productivity and cost cutting through effective evaluation.

Anyone who works within the NHS will be aware of the recent government commitment to cost-cutting measures. In February 2009, McKinsey were asked to produce a report on how productivity may be improved as well as saving money.

Health literacy: just another way to blame patients for their poor health?

The Department of Health (2007) demonstrated the link between improved lifestyle choices in terms of healthier eating and reduced smoking among those with higher health literacy. But is it simply a factor that those who continue to make poor lifestyle choices do so because they have low health literacy, or is it that health professionals often contribute to ongoing health literacy problems because of the nature of their interaction with the individual?

Improving care for children with attention deficit hyperactivity disorder: assessing the impact of self-assessment and targeted training on practice performance.

OBJECTIVES: Major gaps exist between usual clinical practice and evidence-based recommendations for care. Many interventions to improve care are costly and time intensive. This study sought to determine whether a clinician's self-assessment of their practice performance for the diagnosis and management of children with attention deficit hyperactivity disorder (ADHD) followed by attendance at a 2-day conference focused on system change would result in improvement in care. DESIGN: Quasi-experimental-before and after with external controls. PARTICIPANTS: Clinician attendees compared with convenience sample of nonattendees. OUTCOMES: Consistency with 10 specific recommendations from the American Academy of Pediatrics Guidelines concerning ADHD. ANALYSIS: Logistic regression, with use of generalized estimating equations to account for clustering of subjects within clinician practices. RESULTS: Widespread deficiencies in care were present prior to the intervention. Practice improved significantly more among conference attendees in 2 of the 10 performance measures (evaluation for coexisting conditions and offering treatment options), with positive trends in most of the other indicators. CONCLUSIONS: Practice assessment and system-based training may be a cost-effective strategy to improve practice performance.

Antisense deoxyoligonucleotides or antibodies to murine MD-1 inhibit rejection of allogeneic and xenogeneic skin grafts in C3H mice.

BACKGROUND: Altered expression of murine MD-1, a molecule controlling expression of members of the interleukin (IL)-1 receptor family of signaling proteins, regulates antigen-presenting cell-induced alloreactions. We investigated the effect of treatment with antisense deoxyoligonucleotides or antibodies to MD-1 in vivo on allogeneic and xenogeneic skin graft survival and the immune responses in transplanted mice. METHODS: C3H mice received C57BL/6 or Lewis rat skin grafts, followed by i.v. injections of anti-MD-1 antibody or antisense oligonucleotides or control reagents at 48-hr intervals. Survival was monitored. In separate studies, mice were sacrificed at 5-day intervals. Serum was analyzed for circulating MD-1 antigen, and peritoneal cells for surface expression of MD-1. The proliferative and cytolytic response of lymphocytes harvested from treated animals and restimulated in vitro with allo- or xenogeneic cells, and the cytokines produced, was measured. Graft histology was assessed at 11 days after transplantation. RESULTS: Treatment with anti-MD-1 oligonucleotides or antibodies suppressed rejection of both xeno- and allogeneic grafts, decreased induction of graft-specific cytotoxic T cells, increased production of type-2 cytokines (IL-4 and IL-10), and decreased production of type-1 cytokines (IL-2 and interferon-gamma). Serum levels of MD-1 were suppressed, as was expression of MD-1 on the surface of antigen-presenting cells. Grafts from MD-1-treated mice showed little lymphocyte infiltration, and no signs of graft necrosis. CONCLUSION: Our data suggest a critical in vivo role for MD-1 expression in regulating graft rejection, as well as in the concomitant sensitization of T cells and their cytokine production profile, which parallels the rejection response.

Directed attention in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (TS) is a basal ganglia (BG) disorder, associated not only with hyperkinetic movements but also with attentional impairments. This experiment sought to ascertain whether overt direct visual attention would influence tactile attentional performance in TS, via the use of a vibrotactile choice reaction time procedure involving biased probabilities of event occurrence. Participants were required to look (i.e., direct gaze) either at the hand receiving the most (expected) vibrations, or the hand less often stimulated (the unexpected), for both crossed and uncrossed arm postures. Contrary to our predictions, gaze did not influence attentional performance in TS patients. Furthermore, patients were found not to be sensitive to distributions of event probability; that is, they did not demonstrate normal expectancy effects like controls. Attentional deficits in TS (as in Parkinson's disease, another BG disorder) may pertain more to difficulties in holding rather than in shifting the focus of attention. Moreover, directing attention towards the unexpected locus in the crossed arm posture improved overall performance in both patients and controls, suggesting that increased task demands (e.g., crossed arm posture), and/or unexpected stimulus location, may be alleviated by directed attention. These impairments may stem from dysfunction in the circuits linking the frontal lobes with the BG.