Validation and calibration of the SF-36 health transition question against an external criterion of clinical change in health status.

PURPOSE: Cross-sectional surveys depend on retrospective health transition questions (HTQ) to estimate recent changes in health status. This paper assesses the validity of the SF-36 HTQ and calibrates its categories against change assessed prospectively on the SF-36 domain scales in a sub-group known to have experienced clinically important changes in health status. METHODS: Adults (n = 9,649) from a longitudinal population survey completed the SF-36 in 2001 and 2002. Prospective measures were calculated as mean changes in SF-36 scale scores adjusted for age and gender, and also expressed as standardised response means. Comparison groups were those who had developed a long-term health condition since the last interview and the HTQ response categories for those who had not developed any new conditions. RESULTS: Those with a new condition and those without a new condition but who described their health as "somewhat worse" than a year ago had comparable declines in health status on all domain scales except role physical, where those with a new condition experienced a greater decline. CONCLUSIONS: This analysis demonstrates the validity and limitations of the HTQ as a measure of change in population studies. The calibration is useful for interpreting the meaning of the HTQ categories at the group level but not at the individual level

Where there is no surgeon: the effect of specialist proximity on general practitioners' referral rates

Objective: To determine the effect of proximity of surgical specialists on general practitioners' (GPs') rates of referral of surgical problems to specialist care (ie, are surgical referral rates of GPs in rural or remote areas similar to those of GPs in urban centres?). Design: A cross-sectional survey of GPpatient encounters. Setting: The Bettering the Evaluation and Care of Health (BEACH) program, which involves all active registered GPs in Australia. Participants: A random sample of 3030 GPs, each providing details of 100 consecutive patient encounters. Main outcome measures: Proportion of surgical problems (including ophthalmological and obstetric and gynaecological) referred to surgical specialists (surgeons' rooms, hospital outpatient departments or hospital emergency departments). Results: Absence of a local specialist did not significantly influence the proportion of surgical problems referred by GPs overall, but the proportion referred was significantly lower for obstetric (odds ratio [OR], 0.56; 95% CI, 0.440.70) and ophthalmological (OR, 0.60; 95% CI, 0.490.73) problems. Other factors independently associated with referral of a lower proportion of problems included male GPs, female and younger patients, holders of a Health Care Card, injury-related and non-cancer-related problems, follow-up presentations, and more than one problem managed at an encounter. Conclusions: Our findings confirm that rural and remote GPs undertake much of their patients' antenatal care, and are less likely to use specialists when managing ophthalmological problems. Absence of local specialists in other surgical specialties is not a barrier to referral of patients with surgical disorders

Spores of Clostridium engineered for clinical efficacy and safety cause regression and cure of tumors in vivo.

Spores of some species of the strictly anaerobic bacteria Clostridium naturally target and partially lyse the hypoxic cores of tumors, which tend to be refractory to conventional therapies. The anti-tumor effect can be augmented by engineering strains to convert a non-toxic prodrug into a cytotoxic drug specifically at the tumor site by expressing a prodrug-converting enzyme (PCE). Safe doses of the favored prodrug CB1954 lead to peak concentrations of 6.3 μM in patient sera, but at these concentration(s) known nitroreductase (NTR) PCEs for this prodrug show low activity. Furthermore, efficacious and safe Clostridium strains that stably express a PCE have not been reported. Here we identify a novel nitroreductase from Neisseria meningitidis, NmeNTR, which is able to activate CB1954 at clinically-achievable serum concentrations. An NmeNTR expression cassette, which does not contain an antibiotic resistance marker, was stably localized to the chromosome of Clostridium sporogenes using a new integration method, and the strain was disabled for safety and containment by making it a uracil auxotroph. The efficacy of Clostridium-Directed Enzyme Prodrug Therapy (CDEPT) using this system was demonstrated in a mouse xenograft model of human colon carcinoma. Substantial tumor suppression was achieved, and several animals were cured. These encouraging data suggest that the novel enzyme and strain engineering approach represent a promising platform for the clinical development of CDEPT

Reduction of mitomycin C is catalysed by human recombinant NRH:quinone oxidoreductase 2 using reduced nicotinamide adenine dinucleotide as an electron donating co-factor

NRH:Quinone Oxidoreductase 2 (NQO2) has been described as having no enzymatic activity with nicotinamide adenine dinucleotide (NADH) or NADPH as electron donating cosubstrates. Mitomycin C (MMC) is both a substrate for and a mechanistic inhibitor of the NQO2 homologue NQO1. NRH:quinone oxidoreductase 2 catalysed the reduction of MMC at pH 5.8 with NADH as a co-factor. This reaction results in species that inhibit the NQO2-mediated metabolism of CB1954. In addition, MMC caused an increase in DNA cross-links in a cell line transfected to overexpress NQO2 to an extent comparable to that observed with an isogenic NQO1-expressing cell line. These data indicate that NQO2 may contribute to the metabolism of MMC to cytotoxic species

Things change: Women’s and men’s marital disruption dynamics in Italy during a time of social transformations, 1970-2003

We study women’s and men’s marital disruption in Italy between 1970 and 2003. By applying an event-history analysis to the 2003 Italian variant of the Generations and Gender Survey we found that the spread of marital disruption started among middle-highly educated women. Then in recent years it appears that less educated women have also been able to dissolve their unhappy unions. Overall we can see the beginning of a reversed educational gradient from positive to negative. In contrast the trend in men’s marital disruption risk appears as a change over time common to all educational groups, although with persisting educational differentials.determinants, educational differences, event history analysis, gender difference, Italy, marital disruption

Loneliness, social support and cardiovascular reactivity to laboratory stress

Self-reported or explicit loneliness and social support have been inconsistently associated with cardiovascular reactivity (CVR) to stress. The present study aimed to adapt an implicit measure of loneliness, and use it alongside the measures of explicit loneliness and social support, to investigate their correlations with CVR to laboratory stress. Twenty-five female volunteers aged between 18 and 39 years completed self-reported measures of loneliness and social support, and an Implicit Association Test (IAT) of loneliness. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) reactivity indices were measured in response to psychosocial stress induced in the laboratory. Functional support indices of social support were significantly correlated with CVR reactivity to stress. Interestingly, implicit, but not explicit, loneliness was significantly correlated with DBP reactivity after one of the stressors. No associations were found between structural support and CVR indices. Results are discussed in terms of validity of implicit versus explicit measures and possible factors that affect physiological outcomes

Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes

<p>Background: Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.</p> <p>Methodology and Principal Findings: We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.</p> <p>Conclusions: We have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.</p&gt

Behaviour in therapeutic medical care: evidence from general practitioners in Austria

Aim: The present study examines monetary effects of general practioners’ behaviour in therapeutic medical care to identify sample characteristics that allow differentiating between the individual general practitioner and the basic population. Subjects and methods: Medical services, provided by 3,919 general practitioners in Austria, were operationalized by means of the dependent variable “costs per patient”. Statistical outliers were identified using Chebyshev’s inequality and categorized by investigating bivariate correlations between the dependent variable and the personal characteristics of each physician. Results: Variables that relate to the size of the customer base such as number of consultations (r = 0.385) and office days (r = 0.376), correlate positively with the costs for medical services. By analyzing the portfolio of the general practitioners, we found a correlation of 0.451 between this coefficient and the costs. Statistical outliers feature an average portfolio of 44.5 different services, compared to 30.45 among non-outliers. Laboratory services especially were identified as cost drivers (r = 0.408). Statistical outliers generate at least one laboratory parameter for 44.34% of their patients, opposed to 27.2% within the rest of the sample. Consequently outliers produce higher laboratory costs than their counterparts. Conclusion: We found some evidence that physicians have influence in the provision of their services. Considering entrepreneurial objectives, the extension of the portfolio can increase their profit. Our findings indicate supplier-induced demand for several groups of services. We assume that the effect is consolidated by the fee for service system and could be compensated by adequate reform

The Protection of Animals through Human Rights. The Case-Law of the European Court of Human Rights

The chapter discusses the potential of a human rights framework to contribute to the growth and development of global animal law. It takes as example the jurisprudence of the European Court of Human Rights, and examine the major trends in the Court’s judgments and admissibility decisions that directly or indirectly concern the rights or welfare of animals. It is concluded that the Court is not indifferent to the welfare of animals, but that animal welfare is instrumentalised: it is understood not as a good in itself, but is instead valued for its implications for human welfare and rights. The chapter then considers the obstacles that the anthropocentrism of the human rights idea and the instrumentalisation of animal concerns present to the use of human rights frameworks to further the development of global animal law, as well as the opportunities that exist in the meeting of these paradigms. It concludes that although the telos of human rights law is different from that of animal law, nevertheless there exist many overlapping concerns within which mutually beneficial interactions are possible

Antimicrobial Stewardship from Policy to Practice: Experiences from UK Antimicrobial Pharmacists

Antimicrobial stewardship in the UK has evolved dramatically in the last 15 years. Factors driving this include initial central funding for specialist pharmacists and mandatory reductions in healthcare-associated infections (particularly Clostridium difficile infection). More recently, the introduction of national stewardship guidelines, and an increased focus on stewardship as part of the UK five-year antimicrobial resistance strategy, have accelerated and embedded developments. Antimicrobial pharmacists have been instrumental in effecting changes at an organizational and national level. This article describes the evolution of the antimicrobial pharmacist role, its impact, the progress toward the actions listed in the five-year resistance strategy, and novel emerging areas in stewardship in the UK