Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin.

Cholestatic liver injury is associated with an increased susceptibility toward endotoxin-induced toxicity. To determine the role of interleukin 1 (IL-1) herein, extrahepatic cholestasis was induced by bile duct ligation (bdl) in IL-1 receptor type I gene-deficient (IL-1R(-/-)) mice, which are unresponsive to IL-1alpha and IL-1beta, and normal IL-1R(+/+) mice. Bdl elicited increases in hepatic IL-1alpha and IL-1beta messenger RNA (mRNA) and protein. Hepatocellular injury at 2 weeks after bdl was similar in IL-1R(-/-) and IL-1R(+/+) mice as shown by clinical chemistry and histopathology. Administration of endotoxin to cholestatic mice at 2 weeks after bdl was associated with enhanced cytokine release, more severe liver damage, and occurrence of death when compared with sham-operated mice. Endotoxin effects in sham-operated IL-1R(-/-) and IL-1R(+/+) mice were largely similar, but cholestatic IL-1R(-/-) mice were better protected against toxic effects of endotoxin, as reflected by lowered cytokine release, less profound liver injury, and reduced mortality. These data indicate that IL-1alpha and IL-1beta are produced in the liver after bdl, but that these cytokines do not play a significant role in cholestatic liver damage; however, endogenous IL-1 activity is an important denominator of enhanced endotoxin sensitivity that is observed during cholestasis induced by bdl.     

Development and Implementation of a Model to Improve Identification of Patients Infected with HIV Using Diagnostic Rapid Testing in the Emergency Department

Objectives Infection with the human immunodeficiency virus (HIV) continues to expand in nontraditional risk groups, and the prevalence of undiagnosed infection remains relatively high in the patient populations of urban emergency departments (EDs). Unfortunately, HIV testing in this setting remains uncommon. The objectives of this study were 1) to develop a physician‐based diagnostic rapid HIV testing model, 2) to implement this model in a high‐volume urban ED, and 3) to prospectively characterize the patients who were targeted by physicians for testing and determine the proportions who completed rapid HIV counseling, testing, and referral; tested positive for HIV infection; and were successfully linked into medical and preventative care. Methods An interdisciplinary group of investigators developed a model for performing physician‐based diagnostic rapid HIV testing in the ED. This model was then evaluated using a prospective cohort study design. Emergency physicians identified patients at risk for undiagnosed HIV infection using clinical judgment and consensus guidelines. Testing was performed by the hospital's central laboratory, and clinical social workers performed pretest and posttest counseling and provided appropriate medical and preventative care referrals, as defined by the model. Results Over the 30‐month study period, 105,856 patients were evaluated in the ED. Of these, 681 (0.64%; 95% confidence interval [CI] = 0.60% to 0.69%) were identified by physicians and completed rapid HIV counseling, testing, and referral. Of the 681 patients, 15 (2.2%; 95% CI = 1.2% to 3.6%) patients tested positive for HIV infection and 12 (80%; 95% CI = 52% to 96%) were successfully linked into care. Conclusions A physician‐based diagnostic HIV testing model was developed, successfully implemented, and sustained in a high‐volume, urban ED setting. While the use of this model successfully identified patients with undiagnosed HIV infection in the ED, the overall level of testing remained low. Innovative testing programs, such as nontargeted screening, more specific targeted screening, or alternative hybrid methods, are needed to more effectively identify undiagnosed HIV infection in the ED patient population.     

A systematic review of the effect of primary care-based service innovations on quality and patterns of referral to specialist secondary care.

BACKGROUND: Innovations are proliferating at the primary-secondary care interface, affecting referral to secondary care and resource use. Evidence about the range of effects and implications for the healthcare system of different types of innovation have not previously been summarised. AIM: To review the available evidence on initiatives affecting primary care referral to specialist secondary care. SETTING: Studies of primary-secondary care interface. METHOD: Systematic review of trials, using adapted Cochrane Collaboration (effective practice and organisation of care) criteria. Studies from 1980 to 2001 were identified from a wide range of sources. Strict inclusion criteria were applied, and relevant clinical, service and cost data extracted using an agreed protocol. The main outcome measures were referral rates to specialist secondary care. RESULTS: Of the 139 studies initially identified. 34 met the review criteria. An updated search added a further 10 studies. Two studies provided economic analysis only. Referral was not the primary outcome of interest in the majority of included studies. Professional interventions generally had an impact on referral rates consistent with the intended change in clinician behaviour. Similarly, specialist 'outreach' or other primary care-based specialist provider schemes had at least a small effect upon referral rates to secondary care with the direction of effect being that intended or rational from a clinical and sociological perspective. Of the financial interventions, one was aimed primarily at changing the numbers or proportion of referrals from primary to specialist secondary care, and the direction of change was as expected in all cases. The quality of the reporting of the economic components of the 14 studies giving economic data was poor in many cases. When grouped by intervention type, no overall pattern of change in referral costs or total costs emerged. CONCLUSION: The studies identified were extremely diverse in methodology, clinical subject, organisational form, and quality of evidence. The number of good quality evaluations of innovative schemes to enhance the existing capacity of primary care was small, but increasing. Well-evaluated service initiatives in this area should be supported. Organisational innovations in the structure of service provision need not increase total costs to the National Health Service (NHS), even though costs associated with referral may increase. This review provides limited, partial, and conditional support for current primary care-oriented NHS policy developments in the United Kingdom.     

Is Antidepressant Use Changing? Prevalence and Clinical Correlates in Two New England Communities

We attempted to determine whether the prevalence of antidepressant use had increased in population-based samples between 1981 and 1993, and compared the characteristics of antidepressant users and nonusers. Data were derived from six biennial, random sample, cross-sectional household surveys conducted between 1981 and 1993 in two southeastern New England communities. For each survey, point prevalence estimates were determined for the major antidepressant categories. Antidepressant users were most likely to be women, slightly older, and less likely to be employed than nonusers (p<0.0001). Comorbid conditions and concurrent drug therapy were present more frequently among users. The overall prevalence of antidepressant use per 1000 population increased from 7.8 (95% confidence interval 4.3, 11.3) in 1981–1982 to 31.4 (95% CI 23.9, 38.9) in 1992–1993, especially among women and respondents between ages 40 and 59 years.     

Attention disengagement in children with developmental coordination disorder

Purpose. Previous research has shown that children with Developmental Coordination Disorder (DCD) have poorly developed strategies for allocating attention. This study examines the allocation of attention and integration of visuo-spatial and motor systems in children with DCD in a motor (look+hit condition) and a motor-free (look condition) task.

Method. Three groups of control children were used to compare the performance of a group of children with DCD. Children were seated in front of a central fixation point and six peripheral targets, and were asked to look at or hit targets when illuminated. Saccade/hand movement latencies were measured on gap trials (gap between fixation offset and target onset) and overlap trials (fixation offset and target onset overlapped).

Results. DCD children were not slower than controls to disengage attention during the look condition. However, during the look+hit condition the DCD children showed a prolonged disengagement period, which was also seen in younger control children.

Conclusions. The results suggest that DCD children may have deficits in the allocation of attention for action, in both the speed of onset of a movement and the accuracy of the movement. It is concluded that attention disengagement may contribute to problems of visuo-motor integration in DCD.     

The importance of the patient-clinician relationship in adherence to antiretroviral medication

The aim of the study was to assess dimensions of the patient-clinician relationship in relation to adherence with antiretroviral medication in a sample of HIV patients. This was a correlational evaluation, using a cross-sectional design. Thirty-eight HIV patients in two UK HIV units provided complete data. Analysis suggested that the elements of the patient-clinician relationship contributing to adherence with medication were the patient perception of being valued and respected by the clinician, the patients' ability to initiate discussions about the treatment, empowerment and level of trust placed in the nurse. The latter, and the time since starting antiretroviral treatment, were the only two variables that could predict adherence in a regression model, explaining 41% of the variance in adherence. Building trusted relationships with the patients and investing in educational and communication techniques to improve the therapeutic relationship could strongly contribute to HIV patients to maintaining high adherence rates.