Anticoagulation for the treatment of septic cerebral venous sinus thrombosis in the setting of pediatric sinogenic and otogenic intracranial infections.

OBJECTIVE: Septic cerebral venous sinus thrombosis (CVST) is a recognized complication of pediatric sinogenic and otogenic intracranial infections. The optimal treatment paradigm remains controversial. Proponents of anticoagulation highlight its role in preventing thrombus propagation and promoting recanalization, while others cite the risk of hemorrhagic complications, especially after a neurosurgical procedure for an epidural abscess or subdural empyema. Here, the authors investigated the diagnosis, management, and outcomes of pediatric patients with sinogenic or otogenic intracranial infections and a septic CVST. METHODS: All patients 21 years of age or younger, who presented with an intracranial infection in the setting of sinusitis or otitis media and who underwent neurosurgical treatment at Connecticut Children's, Rady Children's Hospital-San Diego, or Ann and Robert H. Lurie Children's Hospital of Chicago from March 2015 to March 2023, were retrospectively reviewed. Demographic, clinical, and radiological data were systematically collated. RESULTS: Ninety-six patients were treated for sinusitis-related and/or otitis media-related intracranial infections during the study period, 15 (15.6%) of whom were diagnosed with a CVST. Of the 60 patients who presented prior to the COVID-19 pandemic, 6 (10.0%) were diagnosed with a septic CVST, whereas of the 36 who presented during the COVID-19 pandemic, 9 (25.0%) had a septic CVST (p = 0.050). The superior sagittal sinus was involved in 12 (80.0%) patients and the transverse and/or sigmoid sinuses in 4 (26.7%). Only 1 (6.7%) patient had a fully occlusive thrombus. Of the 15 patients with a septic CVST, 11 (73.3%) were initiated on anticoagulation at a median interval of 4 (IQR 3-5) days from the most recent neurosurgical procedure. Five (45.5%) patients who underwent anticoagulation demonstrated complete recanalization on follow-up imaging, and 4 (36.4%) had partial recanalization. Three (75.0%) patients who did not undergo anticoagulation demonstrated complete recanalization, and 1 (25.0%) had partial recanalization. None of the patients treated with anticoagulation experienced hemorrhagic complications. CONCLUSIONS: Septic CVST is frequently identified among pediatric patients undergoing neurosurgical intervention for sinogenic and/or otogenic intracranial infections and may have become more prevalent during the COVID-19 pandemic. Anticoagulation can be used safely in the acute postoperative period if administered cautiously, in a monitored setting, and with interval cross-sectional imaging. However, some patients exhibit excellent outcomes without anticoagulation, and further studies are needed to identify those who may benefit the most from anticoagulation.

Flavonoids Regulate Redox-Responsive Transcription Factors in Glioblastoma and Microglia.

The tumor microenvironment (TME) has emerged as a valuable therapeutic target in glioblastoma (GBM), as it promotes tumorigenesis via an increased production of reactive oxygen species (ROS). Immune cells such as microglia accumulate near the tumor and its hypoxic core, fostering tumor proliferation and angiogenesis. In this study, we explored the therapeutic potential of natural polyphenols with antioxidant and anti-inflammatory properties. Notably, flavonoids, including fisetin and quercetin, can protect non-cancerous cells while eliminating transformed cells (2D cultures and 3D tumoroids). We tested the hypothesis that fisetin and quercetin are modulators of redox-responsive transcription factors, for which subcellular location plays a critical role. To investigate the sites of interaction between natural compounds and stress-responsive transcription factors, we combined molecular docking with experimental methods employing proximity ligation assays. Our findings reveal that fisetin decreased cytosolic acetylated high mobility group box 1 (acHMGB1) and increased transcription factor EB (TFEB) abundance in microglia but not in GBM. Moreover, our results suggest that the most powerful modulator of the Nrf2-KEAP1 complex is fisetin. This finding is in line with molecular modeling and calculated binding properties between fisetin and Nrf2-KEAP1, which indicated more sites of interactions and stronger binding affinities than quercetin.

Venous thromboembolism in the setting of pediatric central diabetes insipidus: a systematic review of the literature and report of 2 cases.

OBJECTIVE: Central diabetes insipidus (DI) is frequently identified preoperatively and/or postoperatively in patients with sellar or parasellar lesions. Early diagnosis and effective perioperative management of central DI is critical to minimize disruptions in fluid homeostasis. In particular, although venous thromboembolism (VTE) is generally less common in pediatric patients than their adult counterparts, isolated reports suggest that VTE occurs at a higher frequency in pediatric patients with central DI. METHODS: Using the PubMed, Scopus, and Springer Link databases, the authors performed a systematic review of the literature with regard to the incidence of VTE in pediatric patients with central DI. Inclusion criteria were availability of the full text in English, diagnosis of central DI and VTE in the same patient, and pediatric age defined as ≤ 21 years. Data were reported as median and interquartile range for continuous variables and as frequencies and percentages for categorical variables. Risk of bias assessments of the individual studies were performed using the Joanna Briggs Institute Critical Appraisal Checklists for case series and case reports. RESULTS: Of 2094 search results, 12 articles met the inclusion criteria and described a total of 17 cases of VTE in pediatric patients with central DI. Two additional patients from the authors' institution were added to this cohort. The underlying pathologies included craniopharyngioma (n = 6), suprasellar germinoma (n = 4), epileptic encephalopathy (n = 2), pilocytic astrocytoma (n = 2), prolactinoma (n = 2), Cushing disease (n = 1), failure to thrive (n = 1), and congenital hypothalamic syndrome (n = 1). Thrombotic complications included deep vein thrombosis (n = 10 [53%]), cerebral venous sinus thrombosis (n = 6 [32%]), pulmonary embolism (n = 4 [21%]), inferior vena cava thrombosis (n = 2 [11%]), and disseminated intravascular coagulation (n = 1 [5%]). There was a 26% mortality rate. CONCLUSIONS: VTE is a rare but potentially devastating postoperative complication that appears to have a higher incidence among patients with central DI. Although this review was limited by heterogeneous information across limited reports, pediatric neurosurgical patients with DI may benefit from more aggressive VTE surveillance and prophylaxis.

The experience of deployed dental teams on Operation Herrick: dentists at war in Afghanistan.

Operation Herrick was the British military operation in Afghanistan that occurred between 2002 and 2014; the most recent, large-scale and publicly conducted war in British history. During this time, over 60 British military dental teams deployed as part of the UK Medical Group, their primary role being the treatment of dental emergencies in UK Armed Forces. There are numerous publications citing statistics regarding the rates and nature of dental casualties on operations, their management and how this affects operational capability. This article instead aims to give a more generalised insight into the lived experience of an Army dentist deployed on Operation Herrick.

Oncogenic N-Ras Mitigates Oxidative Stress-Induced Apoptosis of Hematopoietic Stem Cells.

Leukemic relapse is believed to be driven by transformed hematopoietic stem cells (HSC) that harbor oncogenic mutations or have lost tumor suppressor function. Recent comprehensive sequencing studies have shown that mutations predicted to activate Ras signaling are highly prevalent in hematologic malignancies and, notably, in refractory and relapsed cases. To better understand what drives this clinical phenomenon, we expressed oncogenic NrasG12D within the hematopoietic system in mice and interrogated its effects on HSC survival. N-RasG12D conferred a survival benefit to HSCs and progenitors following metabolic and genotoxic stress. This effect was limited to HSCs and early progenitors and was independent of autophagy and cell proliferation. N-RasG12D-mediated HSC survival was not affected by inhibition of canonical Ras effectors such as MEK and PI3K. However, inhibition of the noncanonical Ras effector pathway protein kinase C (PKC) ameliorated the protective effects of N-RasG12D. Mechanistically, N-RasG12D lowered levels of reactive oxygen species (ROS), which correlated with reduced mitochondrial membrane potential and ATP levels. Inhibition of PKC restored the levels of ROS to that of control HSCs and abrogated the protective effects granted by N-RasG12D. Thus, N-RasG12D activation within HSCs promotes cell survival through the mitigation of ROS, and targeting this mechanism may represent a viable strategy to induce apoptosis during malignant transformation of HSCs. SIGNIFICANCE: Targeting oncogenic N-Ras-mediated reduction of ROS in hematopoietic stem cells through inhibition of the noncanonical Ras effector PKC may serve as a novel strategy for treatment of leukemia and other Ras-mutated cancers.

The Emerging Role of Ras Pathway Signaling in Pediatric Cancer.

As genomic sequencing has become more widely available, the high prevalence of Ras pathway mutations in pediatric diseases has begun to emerge. Germline Ras-activating mutations have been known to contribute to cancer predisposition in a group of disorders known as the RASopathies, and now large pediatric sequencing studies have identified frequent somatic Ras pathway alterations across a diverse group of pediatric malignancies. These include glial brain tumors, relapsed high-risk neuroblastoma, embryonal rhabdomyosarcoma, acute myeloid leukemia, and relapsed acute lymphoblastic leukemia, and their prognostic impact is becoming increasingly better understood. Clinically, there has been success in targeting the Ras pathway in pediatric diseases, including the use of MEK inhibitors in plexiform neurofibromas associated with neurofibromatosis type 1 and the use of Ras pathway inhibitors in low-grade gliomas. Given the importance of this pathway in pediatric cancer, it is imperative that future studies strive to better understand the functional significance of these mutations, including their role in tumor growth and treatment resistance and how they can be better targeted to improve outcomes.

Prevalence and mutation analysis of the spike protein in feline enteric coronavirus and feline infectious peritonitis detected in household and shelter cats in western Canada.

Feline infectious peritonitis (FIP) is a fatal disease for which no simple antemortem diagnostic assay is available. A new polymerase chain reaction (PCR) test has recently been developed that targets the spike protein region of the FIP virus (FIPV) and can identify specific mutations (M1030L or S1032A), the presence of which indicates a shift from feline enteric coronavirus (FeCV) to FIPV. This test will only be useful in the geographical region of interest, however, if the FIP viruses contain these mutations. The primary objective of this study was to determine the presence of the M1030L or S1032A mutations in FeCV derived from stool samples from a selected group of healthy cats from households and shelters and determine how many of these cats excrete FeCV. The secondary objective was to evaluate how often these specific FIPV mutations were present in tissue samples derived from cats diagnosed with FIP at postmortem examination. Feline enteric coronavirus (FeCV) was detected in 46% of fecal samples (86/185), all were FeCV type 1, with no difference between household or shelter cats. Only 45% of the FIPV analyzed contained the previously reported M1030L or S1032A mutations. It should be noted that, as the pathological tissue samples were opportunistically obtained and not specifically obtained for PCR testing, caution is warranted in interpreting these data.

La péritonite infectieuse féline (FIP) est une maladie fatale pour laquelle il n'existe pas de test diagnostique ante-mortem simple. Une nouvelle épreuve d'amplification en chaîne par la polymérase (PCR) a récemment été développée et qui vise la région de la protéine de spicule du virus FIP (FIPV) et peut identifier les mutations spécifiques (M1030L ou S1032A), la présence desquelles indique un glissement du coronavirus entérique félin (FeCV) vers le FIPV. Cette épreuve sera utile uniquement dans la région géographique d'intérêt, toutefois, si les virus FIP ont ces mutations. L'objectif premier de la présente étude était de déterminer la présence des mutations M1030L ou S1032A chez FeCV obtenu d'échantillons de fèces provenant d'un groupe sélectionné de chats en santé issus de maisonnée et refuges et de déterminer combien de ces chats excrètent FeCV. L'objectif secondaire était d'évaluer à quelle fréquence ces mutations spécifiques de FIPV étaient présentes dans des échantillons de tissu provenant de chats diagnostiqués avec FIP lors d'examen post-mortem. Le FeCV fut détecté dans 46 % des échantillons fécaux (86/185), tous de type FeCV 1, et aucune différence notée entre les chats de maisonnée ou de refuge. Seulement 45 % des FIPV analysés contenaient les mutations M1030L ou S1032A rapportées précédemment. Il faut noter que, étant donné que les échantillons de tissus pathologiques furent obtenus de manière opportuniste et non spécifiquement obtenus pour analyse par PCR, l'interprétation des résultats est à faire avec précaution.(Traduit par Docteur Serge Messier).

Histological grading of invasive breast carcinoma--a simplification of existing methods in a large conservation series with long-term follow-up.

AIMS: To assess the validity of grading in the Edinburgh Breast Conservation Series; a consecutive cohort of 1812 early breast cancer patients treated by breast conservation and radiotherapy between 1981 and 1998 in a single specialist centre with > or =9 years' follow-up and full staging data. METHODS AND RESULTS: A single pathologist (J.St.J.T) graded 1650 cases using the Elston and Ellis method (EE) with particular reference to the component data: acinar differentiation, nuclear pleomorphism and mitotic counts. The original method was then compared with binary scoring of the same components and the relationship to prognosis reassessed. EE grades and individual grade components were prognostic (P < 0.0001) with 10-year cause-specific survival of 95.6%, 86.4% and 74.7% for EE grades 1, 2 and 3, respectively. A binary scoring of grade components produces four groups, splitting EE grade 2 tumours into two groups with different outcomes--10-year survival rates for the four revised grades were 96.0%, 89.0%, 79.7% and 75.4%, respectively. CONCLUSIONS: Existing grading methodology is fully applicable in the narrower context of a conservation series but can be simplified. Subdivision of EE grade 2 into a true intermediate prognosis group and a second group with a worse prognosis also adds benefit.

Metronomic low-dose chemotherapy boosts CD95-dependent antiangiogenic effect of the thrombospondin peptide ABT-510: a complementation antiangiogenic strategy.

Blocking angiogenesis is a promising approach in cancer therapy. Natural inhibitors of angiogenesis and derivatives induce receptor-mediated signals, which often result in the endothelial cell death. Low-dose chemotherapy, given at short regular intervals with no prolonged breaks (metronomic chemotherapy), also targets angiogenesis by obliterating proliferating endothelial cells and circulating endothelial cell precursors. ABT-510, a peptide derivative of thrombospondin, kills endothelial cell by increasing CD95L, a ligand for the CD95 death receptor. However, CD95 expression itself is unaffected by ABT-510 and limits its efficacy. We found that multiple chemotherapy agents, cyclophosphamide (cytoxan), cisplatin, and docetaxel, induced endothelial CD95 in vitro and in vivo at low doses that failed to kill endothelial cells (cytoxan > cisplatin > docetaxel). Thus, we concluded that some of these agents might complement each other and together block angiogenesis with maximal efficacy. As a proof of principle, we designed an antiangiogenic cocktail combining ABT-510 with cytoxan or cisplatin. Cyclophosphamide and cisplatin synergistically increased in vivo endothelial cell apoptosis and angiosuppression by ABT-510. This synergy required CD95, as it was reversible with the CD95 decoy receptor. In a mouse model, ABT-510 and cytoxan, applied together at low doses, acted in synergy to delay tumor take, to stabilize the growth of established tumors, and to cause a long-term progression delay of PC-3 prostate carcinoma. These antitumor effects were accompanied by major decreases in microvascular density and concomitant increases of the vascular CD95, CD95L, and apoptosis. Thus, our study shows a "complementation" design of an optimal cancer treatment with the antiangiogenic peptide and a metronomic chemotherapy.

ABT-414, an Antibody-Drug Conjugate Targeting a Tumor-Selective EGFR Epitope.

Targeting tumor-overexpressed EGFR with an antibody-drug conjugate (ADC) is an attractive therapeutic strategy; however, normal tissue expression represents a significant toxicity risk. The anti-EGFR antibody ABT-806 targets a unique tumor-specific epitope and exhibits minimal reactivity to EGFR in normal tissue, suggesting its suitability for the development of an ADC. We describe the binding properties and preclinical activity of ABT-414, an ABT-806 monomethyl auristatin F conjugate. In vitro, ABT-414 selectively kills tumor cells overexpressing wild-type or mutant forms of EGFR. ABT-414 inhibits the growth of xenograft tumors with high EGFR expression and causes complete regressions and cures in the most sensitive models. Tumor growth inhibition is also observed in tumor models with EGFR mutations, including activating mutations and those with the exon 2-7 deletion [EGFR variant III (EGFRvIII)], commonly found in glioblastoma multiforme. ABT-414 exhibits potent cytotoxicity against glioblastoma multiforme patient-derived xenograft models expressing either wild-type EGFR or EGFRvIII, with sustained regressions and cures observed at clinically relevant doses. ABT-414 also combines with standard-of-care treatment of radiation and temozolomide, providing significant therapeutic benefit in a glioblastoma multiforme xenograft model. On the basis of these results, ABT-414 has advanced to phase I/II clinical trials, and objective responses have been observed in patients with both amplified wild-type and EGFRvIII-expressing tumors. Mol Cancer Ther; 15(4); 661-9. ©2016 AACR.

Thrombospondin-1 mimetic peptide inhibitors of angiogenesis and tumor growth: design, synthesis, and optimization of pharmacokinetics and biological activities.

The heptapeptide 1, NAc-Gly-Val-DIle-Thr-Arg-Ile-ArgNHEt, a structurally modified fragment derived from the second type-1 repeat of thrombospondin-1 (TSP-1), is known to possess antiangiogenic activity. However, therapeutic utility could not be demonstrated because this peptide has a very short half-life in rodents. To optimize the PD/PK profile of 1, we initiated a systematic SAR study. The initial structural modifications were performed at positions 5 and 7 of peptide 1 and at the N- and C-termini. Out of several hundred peptides synthesized, the nonapeptide 5 (ABT-526) emerged as a promising lead. ABT-526 inhibited VEGF-induced HMVEC cell migration and tube formation in the nanomolar range and increased apoptosis of HUAEC cells. ABT-526 showed acceptable PK in rodents, dog, and monkey. ABT-526, when incorporated in an angiogenic pellet implanted in the rat cornea at 10 microM, reduced neovascularization by 92%. Substitution of DalloIle in place of DIle in ABT-526 provided nonapeptide 6 (ABT-510), which was 30-fold less active than ABT-526 in the EC migration but 20-fold more active in the tube formation assay. In comparison to ABT-526, ABT-510 has increased water solubility and slower clearance in dog and monkey. Radiolabeled ABT-510 demonstrated saturable binding to HMVEC cells at 0.02-20 nM concentrations and was displaceable by TSP-1. ABT-510 and ABT-526 were shown to significantly increase apoptosis of HUAEC cells. ABT-510 was effective in blocking neovascularization in the mouse Matrigel plug model and inhibited tumor growth in the mouse Lewis lung carcinoma model. Previous studies had shown that ABT-510 was effective in inhibiting the outgrowth of murine melanoma metastases in syngeneic mice and in blocking the growth of human bladder carcinoma implanted in nude mice. It had been also shown that ABT-510 could regress tumor lesions in pet dogs or cause unexpected stabilization of the disease in advanced canine cancer. ABT-526 and ABT-510 are the first compounds in the class of potent inhibitors of angiogenesis that mimic the antiangiogenic function of TSP-1. ABT-510 is currently in phase II clinical studies.

Who is more likely to experience common disorders: men, women, or both equally? Lay perceptions in the West of Scotland.

BACKGROUND: Gender differences in health are commonly observed by epidemiologists. Little is known about lay beliefs concerning the gender patterning of common conditions. METHODS: Using the West of Scotland Twenty-07 Study, we analysed responses to a question in a postal questionnaire asking whether respondents thought men or women (or both equally) were more likely to have heart disease, cancer, mental illness, and accidents, to be fit, and to live longer. This question was answered by 466 females and 353 males, then aged 25, 45, and 65 yr. RESULTS: Responses were in general in accord with epidemiological findings, but females had significantly lower odds than males of perceiving men as being at greater risk of accidents and heart disease, and higher odds than males of perceiving women as being at greater risk of mental illness. CONCLUSIONS: There was a tendency for each gender to think risks were higher for their own sex than did the other gender. This observation needs further exploration, particularly in the light of the research showing 'optimistic bias' in relation to health, and research suggesting that socioeconomically disadvantaged people may be least likely to perceive socially structured health inequalities.

McDonald's restaurants and neighborhood deprivation in Scotland and England.

BACKGROUND: Features of the local fast food environment have been hypothesized to contribute to the greater prevalence of obesity in deprived neighborhoods. However, few studies have investigated whether fast food outlets are more likely to be found in poorer areas, and those that have are local case studies. In this paper, using national-level data, we examine the association between neighborhood deprivation and the density of McDonald's restaurants in small census areas (neighborhoods) in Scotland and England. METHODS: Data on population, deprivation, and the location of McDonald's Restaurants were obtained for 38,987 small areas in Scotland and England (6505 "data zones" in Scotland, and 32,482 "super output areas" in England) in January 2005. Measures of McDonald's restaurants per 1000 people for each area were calculated, and areas were divided into quintiles of deprivation. Associations between neighborhood deprivation and outlet density were examined during February 2005, using one-way analysis of variance in Scotland, England, and both countries combined. RESULTS: Statistically significant positive associations were found between neighborhood deprivation and the mean number of McDonald's outlets per 1000 people for Scotland (p<0.001), England (p<0.001), and both countries combined (p<0.001). These associations were broadly linear with greater mean numbers of outlets per 1000 people occurring as deprivation levels increased. CONCLUSIONS: Observed associations between presence or absence of fast food outlets and neighborhood deprivation may provide support for environmental explanations for the higher prevalence of obesity in poor neighborhoods.

Out-of-home food outlets and area deprivation: case study in Glasgow, UK.

BACKGROUND: There is a popular belief that out-of-home eating outlets, which typically serve energy dense food, may be more commonly found in more deprived areas and that this may contribute to higher rates of obesity and related diseases in such areas. METHODS: We obtained a list of all 1301 out-of-home eating outlets in Glasgow, UK, in 2003 and mapped these at unit postcode level. We categorised them into quintiles of area deprivation using the 2004 Scottish Index of Multiple Deprivation and computed mean density of types of outlet (restaurants, fast food restaurants, cafes and takeaways), and all types combined, per 1000 population. We also estimated odds ratios for the presence of any outlets in small areas within the quintiles. RESULTS: The density of outlets, and the likelihood of having any outlets, was highest in the second most affluent quintile (Q2) and lowest in the second most deprived quintile (Q4). Mean outlets per 1,000 were 4.02 in Q2, 1.20 in Q4 and 2.03 in Q5. With Q2 as the reference, Odds Ratios for having any outlets were 0.52 (CI 0.32-0.84) in Q1, 0.50 (CI 0.31 - 0.80) in Q4 and 0.61 (CI 0.38 - 0.98) in Q5. Outlets were located in the City Centre, West End, and along arterial roads. CONCLUSION: In Glasgow those living in poorer areas are not more likely to be exposed to out-of-home eating outlets in their neighbourhoods. Health improvement policies need to be based on empirical evidence about the location of fast food outlets in specific national and local contexts, rather than on popular 'factoids'.

Are rich people or poor people more likely to be ill? Lay perceptions, by social class and neighbourhood, of inequalities in health.

Research in the UK has suggested that people in lower social classes or from poorer neighbourhoods are less likely than their more socially advantaged counterparts to agree that health and life expectancy are worse among more deprived population groups. The small body of previous research has either used qualitative approaches or coded open-ended responses to survey questions about causes of health and illness or of inequalities between areas. We examined lay perceptions by asking a direct question and using a quantitative, multivariate approach. Residents in three age groups (25, 45 and 65 years old) living in two socially contrasting localities in Glasgow, Scotland, were asked who were more likely to have accidents, cancer, heart disease, mental illness, to be fitter, and to live longer: rich people, poor people, or both equally. Across all the health categories, those in lower social classes or from poorer neighbourhoods were equally or less likely than their more socially advantaged counterparts to say the poor had worse health. In a model containing age, sex, class and locality, those in lower social classes and in the poorer locality were significantly less likely to say that richer people live longer (OR: 0.5). We have therefore confirmed earlier observations that those most at risk of ill health may be less likely to acknowledge the social gradient in health. We suggest a need to examine this apparent paradox in other contexts and in more detail, using both quantitative and qualitative approaches.

Are social comparisons of homes and cars related to psychosocial health?

BACKGROUND: It has been suggested that perceiving oneself to be inferior to those around one is a psychosocial risk factor associated with ill health. The aim of this study was to examine whether negative social comparisons of the worth of two common assets (homes and cars) were related to psychosocial health (i.e. lower self-esteem and mastery, higher anxiety, and depression). METHODS: A postal questionnaire was sent to a random sample of adults in the West of Scotland (sampling from the 1997 electoral roll, response rate was 50%, achieved sample 2838). RESULTS: Having adjusted for socio-demographic variables, rating one's house/flat as worth less than others was associated with lower self-esteem (P < 0.001) and mastery (P < 0.001) and higher depression (P < 0.007) and anxiety (P < 0.012). Rating one's car as worth less than others was not significantly associated with these psychosocial variables. CONCLUSIONS: Our findings lend some support, but only in relation to the home, to the hypothesis that perceiving oneself to be worse off in relation to those around is related to poorer psychosocial health.

What features of the home and the area might help to explain observed relationships between housing tenure and health? Evidence from the west of Scotland.

This study aimed to explore the role of dwelling conditions and neighbourhood characteristics in explaining the frequently observed association between housing tenure and health. A postal questionnaire, focusing on a number of specific aspects of the home and the area, was sent to a random sample of adults in the west of Scotland (achieved sample size 2867, response rate 50%). The health measures were limiting long-standing illness, self-assessed health, recent symptoms, and anxiety and depression. Having controlled for age, sex, and marital status, housing tenure explained, respectively, 2.7%, 5.4%, 3.9%, 2.4% and 5.4% of the variance in these variables. These percentages were reduced by between 93% (for anxiety) and 73% (for self-assessed health) when housing problems, housing fixtures, overcrowding, dwelling type, access to garden, area type and area amenities were introduced into the model. This suggests that features of the dwelling and its surroundings help to explain observed associations between tenure and health in the UK, and that housing and area problems may be particularly important. Housing improvements and urban regeneration may help to reduce the health gap between housing tenures, and more generally to reduce inequalities in health.

Safe management of chronic pain in pregnancy in an era of opioid misuse and abuse.

Safe and effective management of chronic pain in pregnancy is challenging. Use of over-the-counter analgesics, opioids, opioid substitution therapies, complementary and alternative therapies, antidepressants, and anxiolytics each have benefits and risks for the mother and neonate that must be considered. Because of their potency, opioids are often used despite associated risks for adverse effects, abuse, diversion, and addiction. Development of a pain management protocol for the counsel and care of pregnant women with pain is necessary.

Lay concepts of the relative importance of different influences on health; are there major socio-demographic variations?

There is an extensive literature within anthropology, sociology and psychology about lay concepts of determinants of health and illness. Many of these studies have used single sex or social class samples, often in narrow age bands, and many are qualitative in approach. We asked respondents in a health survey to say how important (on a five-point scale) they thought seven potential influences on health (habits, self-care, the environment, family relationships, one's constitution, money and luck) were. The first three were regarded as very important, the second three as less important and luck as least important. Responses were consistent with current public health and epidemiological knowledge; these respondents endorsed prevailing views about personal responsibility for health and about the role of the physical and social environment in influencing health. In mutually adjusted models, there were no significant gender differences, social class differences and neighbourhood differences in three out of seven influences, and age differences in four out of seven influences. Thus, socio-demographic differences were less marked than might be inferred from studies of specific social groups, indicating a need for caution in health education and health promotion practice against always assuming socio-demographic differences.

Socio-economic position and health: what you observe depends on how you measure it.

BACKGROUND: A number of different socio-economic classifications have been used in relation to health in the United Kingdom. The aim of this study was to compare the predictive power of different socio-economic classifications in relation to a range of health measures. METHODS: A postal questionnaire was sent to a random sample of adults in the West of Scotland (sampling from 1997 electoral roll, response rate 50 percent achieved sample 2,867). RESULTS: Associations between social position and health vary by socio-economic classification, health measure and gender. Limiting long-standing illness is more socially patterned than recent illness; income, Registrar General Social Class, housing tenure and car access are more predictive of health than the new National Statistics Socio Economic Classification; and men show steeper socio-economic gradients than women. CONCLUSION: Although there is a consistent picture of poorer health among more disadvantaged groups, however measured, in seeking to explain and reduce social inequalities in health we need to take a more differentiated approach that does not assume equivalence among social classifications and health measures.