An Update on Grading of Salivary Gland Carcinomas

Histologic grade is a significant predictor of outcome in salivary gland carcinomas. However, the sheer variety of tumor type and the rarity of these tumors pose challenges to devising highly predictive grading schemes. As our knowledge base has evolved, it is clear that carcinoma ex pleomorphic adenoma is not automatically a high grade tumor as is traditionally suggested. These tumors should be further qualified as to type/grade of carcinoma and extent, since intracapsular and minimally invasive carcinomas ex pleomorphic adenoma behave favorably. The two carcinoma types for which grading schemes are common include adenoid cystic carcinoma and mucoepidermoid carcinoma. Adenoid cystic carcinomas are graded based solely on pattern with solid components portending a worse prognosis. Occasionally, adenoid cystic carcinomas may undergo transformation to pleomorphic high grade carcinomas. This feature confers a high propensity for lymph node metastasis and should thus be reported to alert the clinical team. Mucoepidermoid carcinomas are graded in a three tier fashion based on a constellation of features including cystic component, border, mitoses, anaplasia, and perineural invasion among others. All grading schemes are somewhat cumbersome, intimidating and occasionally ambiguous, but evidence suggests that using a scheme consistently shows greater reproducibility than using an intuitive approach. The intermediate grade category demonstrates the most variability between grading systems and thus the most controversy in management. In the AFIP system intermediate grade tumors cluster with high grade tumors, while in the Brandwein system, they cluster with low grade tumors

The first legal mortgagor: a consumer without adequate protection?

This article contends that the UK government’s attempt to create a well-functioning consumer credit market will be undermined if it fails to reform the private law framework relating to the first legal mortgage. Such agreements are governed by two distinct regulatory regimes that are founded upon very different conceptions of the mortgagor. The first, the regulation of financial services overseen by the Financial Conduct Authority, derives from public law and is founded upon a conception of the mortgagor as “consumer”. The other is land law, private law regulation implemented by the judiciary and underpinned by a conception of the mortgagor as “landowner”. Evidence suggests that the operation of these two regimes prevents mortgagors from receiving fair and consistent treatment. The current reform of financial services regulation therefore will change only one part of this governance regime and will leave mortgagors heavily reliant upon a regulator that still has to prove itself. What this article argues is that reform of the rules of private law must also be undertaken with the aim of initiating a paradigm shift in the conception of the mortgagor from “landowner” to “consumer”. Cultural shifts of this kind take time but the hope is that this conceptual transformation will occur in time to deter the predicted rise in mortgage possessions

How Equity-Oriented Health Care Affects Health: Key Mechanisms and Implications for Primary Health Care Practice and Policy

Policy Points A consensus regarding the need to orient health systems to address inequities is emerging, with much of this discussion targeting population health interventions and indicators. We know less about applying these approaches to primary health care. This study empirically demonstrates that providing more equity-oriented health care (EOHC) in primary health care, including trauma- and violence-informed, culturally safe, and contextually tailored care, predicts improved health outcomes across time for people living in marginalizing conditions. This is achieved by enhancing patients’ comfort and confidence in their care and their own confidence in preventing and managing health problems. This promising new evidence suggests that equity-oriented interventions at the point of care can begin to shift inequities in health outcomes for those with the greatest need. Context: Significant attention has been directed toward addressing health inequities at the population health and systems levels, yet little progress has been made in identifying approaches to reduce health inequities through clinical care, particularly in a primary health care context. Although the provision of equity-oriented health care (EOHC) is widely assumed to lead to improvements in patients’ health outcomes, little empirical evidence supports this claim. To remedy this, we tested whether more EOHC predicts more positive patient health outcomes and identified selected mediators of this relationship. Methods: Our analysis uses longitudinal data from 395 patients recruited from 4 primary health care clinics serving people living in marginalizing conditions. The participants completed 4 structured interviews composed of self-report measures and survey questions over a 2-year period. Using path analysis techniques, we tested a hypothesized model of the process through which patients’ perceptions of EOHC led to improvements in self-reported health outcomes (quality of life, chronic pain disability, and posttraumatic stress [PTSD] and depressive symptoms), including particular covariates of health outcomes (age, gender, financial strain, experiences of discrimination). Findings: Over a 24-month period, higher levels of EOHC predicted greater patient comfort and confidence in the health care patients received, leading to increased confidence to prevent and manage their health problems, which, in turn, improved health outcomes (depressive symptoms, PTSD symptoms, chronic pain, and quality of life). In addition, financial strain and experiences of discrimination had significant negative effects on all health outcomes. Conclusions: This study is among the first to demonstrate empirically that providing more EOHC predicts better patient health outcomes over time. At a policy level, this research supports investments in equity-focused organizational and provider-level processes in primary health care as a means of improving patients’ health, particularly for those living in marginalizing conditions. Whether these results are robust in different patient groups and across a broader range of health care contexts requires further study

A systematic review of the effectiveness and cost-effectiveness of peer education and peer support in prisons.

BACKGROUND: Prisoners experience significantly worse health than the general population. This review examines the effectiveness and cost-effectiveness of peer interventions in prison settings. METHODS: A mixed methods systematic review of effectiveness and cost-effectiveness studies, including qualitative and quantitative synthesis was conducted. In addition to grey literature identified and searches of websites, nineteen electronic databases were searched from 1985 to 2012. Study selection criteria were: Population: Prisoners resident in adult prisons and children resident in Young Offender Institutions (YOIs). INTERVENTION: Peer-based interventions Comparators: Review questions 3 and 4 compared peer and professionally led approaches. OUTCOMES: Prisoner health or determinants of health; organisational/ process outcomes; views of prison populations. STUDY DESIGNS: Quantitative, qualitative and mixed method evaluations. RESULTS: Fifty-seven studies were included in the effectiveness review and one study in the cost-effectiveness review; most were of poor methodological quality. Evidence suggested that peer education interventions are effective at reducing risky behaviours, and that peer support services are acceptable within the prison environment and have a positive effect on recipients, practically or emotionally. Consistent evidence from many, predominantly qualitative, studies, suggested that being a peer deliverer was associated with positive effects. There was little evidence on cost-effectiveness of peer-based interventions. CONCLUSIONS: There is consistent evidence from a large number of studies that being a peer worker is associated with positive health; peer support services are also an acceptable source of help within the prison environment and can have a positive effect on recipients. Research into cost-effectiveness is sparse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ref: CRD42012002349

Population normative data for the 10/66 Dementia Research Group cognitive test battery from Latin America, India and China: a cross-sectional survey

Background: 1) To report site-specific normative values by age, sex and educational level for four components of the 10/66 Dementia Research Group cognitive test battery; 2) to estimate the main and interactive effects of age, sex, and educational level by site; and 3) to investigate the effect of site by region and by rural or urban location. Methods: Population-based cross-sectional one phase catchment area surveys were conducted in Cuba, Dominican Republic, Venezuela, Peru, Mexico, China and India. The protocol included the administration of the Community Screening Instrument for Dementia (CSI 'D', generating the COGSCORE measure of global function), and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) verbal fluency (VF), word list memory (WLM, immediate recall) and recall (WLR, delayed recall) tests. Only those free of dementia were included in the analysis. Results: Older people, and those with less education performed worse on all four tests. The effect of sex was much smaller and less consistent. There was a considerable effect of site after accounting for compositional differences in age, education and sex. Much of this was accounted for by the effect of region with Chinese participants performing better, and Indian participants worse, than those from Latin America. The effect of region was more prominent for VF and WLM than for COGSCORE and WLR. Conclusion: Cognitive assessment is a basic element for dementia diagnosis. Age- and education-specific norms are required for this purpose, while the effect of gender can probably be ignored. The basis of cultural effects is poorly understood, but our findings serve to emphasise that normative data may not be safely generalised from one population to another with quite different characteristics. The minimal effects of region on COGSCORE and WLR are reassuring with respect to the cross-cultural validity of the 10/66 dementia diagnosis, which uses only these elements of the 10/66 battery.Clinical NeurologySCI(E)SSCI17ARTICLEnull

Indoor application of attractive toxic sugar bait (ATSB) in combination with mosquito nets for control of pyrethroid-resistant mosquitoes.

BACKGROUND: Attractive toxic sugar bait (ATSB) sprayed onto vegetation has been successful in controlling Anopheles mosquitoes outdoors. Indoor application of ATSB has yet to be explored. The purpose of this study was to determine whether ATSB stations positioned indoors have the potential to kill host-seeking mosquitoes and constitute a new approach to control of mosquito-borne diseases. METHODS: Insecticides were mixed with dyed sugar solution and tested as toxic baits against Anopheles arabiensis, An. Gambiae s.s. and Culex quinquefasciatus in feeding bioassay tests to identify suitable attractant-insecticide combinations. The most promising ATSB candidates were then trialed in experimental huts in Moshi, Tanzania. ATSB stations were hung in huts next to untreated mosquito nets occupied by human volunteers. The proportions of mosquitoes killed in huts with ATSB treatments relative to huts with non-insecticide control treatments huts were recorded, noting evidence of dye in mosquito abdomens. RESULTS: In feeding bioassays, chlorfenapyr 0.5% v/v, boric acid 2% w/v, and tolfenpyrad 1% v/v, mixed in a guava juice-based bait, each killed more than 90% of pyrethroid-susceptible An. Gambiae s.s. and pyrethroid-resistant An. arabiensis and Cx. quinquefasciatus. In the hut trial, mortality rates of the three ATSB treatments ranged from 41-48% against An. arabiensis and 36-43% against Cx. quinquefasciatus and all were significantly greater than the control mortalities: 18% for An. arabiensis, 7% for Cx. quinquefasciatus (p<0.05). Mortality rates with ATSB were comparable to those with long lasting insecticidal nets previously tested against the same species in this area. CONCLUSIONS: Indoor ATSB shows promise as a supplement to mosquito nets for controlling mosquitoes. Indoor ATSB constitute a novel application method for insecticide classes that act as stomach poisons and have not hitherto been exploited for mosquito control. Combined with LLIN, indoor use of ATSB has the potential to serve as a strategy for managing insecticide resistance

Effectiveness of temozolomide for primary glioblastoma multiforme in routine clinical practice

Temozolomide has been used as a standard therapy for the treatment of newly diagnosed glioblastoma multiforme since 2005. To assess the effectiveness of temozolomide in routine clinical practice, we conducted an observational study at Maastricht University Medical Centre (MUMC). Data of patients receiving radiotherapy and temozolomide between January 2005 and January 2008 were retrieved from a clinical database (radiochemotherapy group), as were data of patients in a historical control group from the period before 2005 treated with radiotherapy only (radiotherapy group). The primary endpoint was overall survival. A total of 125 patients with GBM were selected to form the study cohort. Median survival benefit was 4 months: the median overall survival was 12 months (95% CI, 9.7–14.3) in the group with radiochemotherapy with temozolomide, versus 8 months (95% CI, 5.3–10.7) in the group with only radiotherapy. Progression-free survival was 7 months (95% CI, 5.5–8.5) in the radiochemotherapy group and 4 months (95% CI, 2.9-5.1) in the group with only radiotherapy. The two-year survival rate was 18% with radiochemotherapy with temozolomide against 4% with radiotherapy alone. Concomitant treatment with radiotherapy and temozolomide followed by adjuvant temozolomide resulted in grade III or IV haematological toxic effects in 9% of patients. The addition of temozolomide to radiotherapy in routine clinical practice for newly diagnosed glioblastoma resulted in a clinically meaningful survival benefit with minimal haematological toxicity, which confirms the experience of previous trials and justifies the continued use of temozolomide in routine clinical practice

Swarming populations of Salmonella represent a unique physiological state coupled to multiple mechanisms of antibiotic resistance

Salmonella enterica serovar Typhimurium is capable of swarming over semi-solid surfaces. Although its swarming behavior shares many readily observable similarities with other swarming bacteria, the phenomenon remains somewhat of an enigma in this bacterium since some attributes skew away from the better characterized systems. Swarming is quite distinct from the classic swimming motility, as there is a prerequisite for cells to first undergo a morphological transformation into swarmer cells. In some organisms, swarming is controlled by quorum sensing, and in others, swarming has been shown to be coupled to increased expression of important virulence factors. Swarming in serovar Typhimurium is coupled to elevated resistance to a wide variety of structurally and functionally distinct classes of antimicrobial compounds. As serovar Typhimurium differentiates into swarm cells, the pmrHFIJKLM operon is up-regulated, resulting in a more positively charged LPS core. Furthermore, as swarm cells begin to de-differentiate, the pmr operon expression is down-regulated, rapidly reaching the levels observed in swim cells. This is one potential mechanism which confers swarm cells increased resistance to antibiotics such as the cationic antimicrobial peptides. However, additional mechanisms are likely associated with the cells in the swarm state that confer elevated resistance to such a broad spectrum of antimicrobial agents

Population-Based Resequencing of Experimentally Evolved Populations Reveals the Genetic Basis of Body Size Variation in Drosophila melanogaster

Body size is a classic quantitative trait with evolutionarily significant variation within many species. Locating the alleles responsible for this variation would help understand the maintenance of variation in body size in particular, as well as quantitative traits in general. However, successful genome-wide association of genotype and phenotype may require very large sample sizes if alleles have low population frequencies or modest effects. As a complementary approach, we propose that population-based resequencing of experimentally evolved populations allows for considerable power to map functional variation. Here, we use this technique to investigate the genetic basis of natural variation in body size in Drosophila melanogaster. Significant differentiation of hundreds of loci in replicate selection populations supports the hypothesis that the genetic basis of body size variation is very polygenic in D. melanogaster. Significantly differentiated variants are limited to single genes at some loci, allowing precise hypotheses to be formed regarding causal polymorphisms, while other significant regions are large and contain many genes. By using significantly associated polymorphisms as a priori candidates in follow-up studies, these data are expected to provide considerable power to determine the genetic basis of natural variation in body size

Seizures in 204 comatose children: incidence and outcome

Purpose: Seizures are common in comatose children, but may be clinically subtle or only manifest on continuous electroencephalographic monitoring (cEEG); any association with outcome remains uncertain. Methods: cEEG (one to three channels) was performed for a median 42 h (range 2–630 h) in 204 unventilated and ventilated children aged $\leq$ 15 years (18 neonates, 61 infants) in coma with different aetiologies. Outcome at 1 month was independently determined and dichotomized for survivors into favourable (normal or moderate neurological handicap) and unfavourable (severe handicap or vegetative state). Results: Of the 204 patients, 110 had clinical seizures (CS) before cEEG commenced. During cEEG, 74 patients (36 %, 95 % confidence interval, 95 % CI, 32–41 %) had electroencephalographic seizures (ES), the majority without clinical accompaniment (non-convulsive seizures, NCS). CS occurred before NCS in 69 of the 204 patients; 5 ventilated with NCS had no CS observed. Death (93/204; 46 %) was independently predicted by admission Paediatric Index of Mortality (PIM; adjusted odds ratio, aOR, 1.027, 95 % CI 1.012–1.042; p 3 % fast, aOR 5.43, 95 % CI 1.90–15.6; excess slow with <3 % fast, aOR 8.71, 95 % CI 2.58–29.4; low amplitude, 10th centile <9 $\mu$V, aOR 3.78, 95 % CI 1.23–11.7; and burst suppression, aOR 10.68, 95 % CI 2.31–49.4) compared with normal cEEG, as well as absence of CS at any time (aOR 2.38, 95 % CI 1.18–4.81). Unfavourable outcome (29/111 survivors; 26 %) was independently predicted by the presence of ES (aOR 15.4, 95 % CI 4.7–49.7) and PIM (aOR 1.036, 95 % CI 1.013–1.059). Conclusion: Seizures are common in comatose children, and are associated with an unfavourable outcome in survivors. cEEG allows the detection of subtle CS and NCS and is a prognostic tool