Novel antibodies that selectively block mouse IL-12 enable the re-evaluation of the role of IL-12 in immune protection and pathology

The dimeric cytokine IL-12 is important in the control of various infections but also contributes to the pathology of certain diseases making it a potential target for therapy. However, its specific inhibition with antibodies is complicated by the fact that its two subunits are present in other cytokines: p40 in IL-23 and p35 in IL-35. This has led to erroneous conclusions like the alleged implication of IL-12 in experimental autoimmune encephalomyelitis (EAE). Here, we report the development of a mouse anti-mouse IL-12 vaccine and the production of monoclonal antibodies (mAbs) that do not react with p40 or p35 (in IL-35) but specifically recognize and functionally inhibit the IL-12 heterodimer. Using one of these mAbs, MM12A1.6, that strongly inhibited IFN-γ production and LPS-induced septic shock after viral infection, we demonstrate the critical role played by IL-12 in the rejection of male skin graft by female C57BL/6 syngeneic recipients and in the clearance of an immunogenic mastocytoma tumor variant by DBA/2 mice, but not in a parent to F1 immune aggression model nor in MOG-induced EAE, which was clearly prevented by anti-p40 mAb C17.8. Given this selective inhibition of IL-12, these mAbs provide new options for reassessing IL-12 function in vivo.     

Accessing rehabilitation after stroke – a guessing game?

Aim: To explore the use, meaning and value of the term “rehabilitation potential”.

Method: The authors of this commentary met to discuss concerns relating to the pressure on health service staff created by reduced length of stay in acute settings of those who have suffered a stroke and the need to determine the potential of a patient for rehabilitation in order to inform discharge arrangements. Points raised at this meeting were shared with an email group who over a 12-month period contributed to this paper.

Results: The group agreed that: (a) Given that there is very limited evidence to guide judgements regarding rehabilitation potential following stroke at an early stage the need for rehabilitation needs to be reviewed on a regular basis over a long period and that this needs to be reflected in clinical guidelines. (b) Rehabilitation needs to be available in a broad range of care settings, in order that discharge from hospital is not equated with a lack of rehabilitation potential. (c) Research related to rehabilitation potential needs to be conducted. This should examine influences of decision-making and the algorithms associated with recovery and local policy on rehabilitation potential. (d) The economic benefits of rehabilitation needs further exploration. (e) Assessment of rehabilitation potential should be made more explicit and supported by appropriate evidence.

Conclusion: Whilst further research is required to assist in determining the right time for people to benefit from formal rehabilitation this gives the impression that one dose of rehabilitation at a specific time will meet all needs. It is likely that a rehabilitation pathway identifying features required in the early stages following stroke as well as that required over many years in order to prevent readmission, maintain fitness and prevent secondary sequelae such as depression and social isolation would be beneficial.

• Implications for Rehabilitation

• The potential of a patient to benefit from rehabilitation may be overlooked due to other pressures.

• Some patients following a stroke will demonstrate potential to benefit from rehabilitation later than the majority and this is not always easy to predict.

• Regular reassessment is required in order to identify whether an individual will benefit from rehabilitation at a particular time.

     

Improving communication in the ICU using daily goals

BACKGROUND: Clear communication is imperative if teams in any industry expect to make improvements. An estimated 85% of errors across industries result from communication failures. PURPOSE: The purpose of this study was to evaluate and improve the effectiveness of communication during patient care rounds in the intensive care unit (ICU) using a daily goals form. DESIGN: We conducted a prospective cohort study in collaboration with the Volunteer Hospital Association (VHA), Institute for Healthcare Improvement (IHI), and Johns Hopkins Hospital's (JHH) 16-bed surgical oncology ICU. All patients admitted to the ICU were eligible. Main outcome variables were ICU length of stay (LOS) and percent of ICU residents and nurses who understood the goals of care for patients in the ICU. Baseline measurements were compared with measurements of understanding after implementation of a daily goals form. RESULTS: At baseline, less than 10% of residents and nurses understood the goals of care for the day. After implementing the daily goals form, greater than 95% of nurses and residents understood the goals of care for the day. After implementation of the daily goals form, ICU LOS decreased from a mean of 2.2 days to 1.1 days. CONCLUSION: Implementing the daily goals form resulted in a significant improvement in the percent of residents and nurses who understood the goals of care for the day and a reduction in ICU LOS. The use of the daily goals form has broad applicability in acute care medicine.     

Implementing an incontinence management protocol in long-term care. Clinical outcomes and costs

This article describes clinical outcomes and costs of implementing an incontinence management protocol based on the recommendations contained in the Agency for Health Care Quality and Research clinical practice guidelines on incontinence and pressure ulcer prevention. Following implementation of the protocol, 63 nursing home residents were followed for 6 months and assessed for the presence of wetness or pressure ulcers. Facility costs for incontinence management were accumulated. Fifty-four percent of the residents (34 of 63) received treatments for incontinence and 60% (20 of 34) became dry. Pressure ulcer rates decreased from 16 participants developing 26 pressure ulcers to 3 participants developing 5 ulcers. Facility cost of incontinence management for 6 months was $86,436 with 46% attributed to direct labor costs. Toileting was the most expensive component, costing $36,755. Total daily cost of incontinence management was $573 ($9.09 +/- 10.52 per resident). Implementation of the incontinence protocol resulted in improved "dryness" of the participants and reduced pressure ulcer incidence.     

Lay beliefs about hypertension: an interpretive synthesis of the qualitative research

PURPOSE: The purpose of this interpretive synthesis was to explore lay beliefs about high blood pressure and its treatment in order to develop a foundation for better partnering with clients. DATA SOURCES: Meta-interpretation was used to analyze 11 qualitative research studies published in the United States between 2000 and 2005. CONCLUSIONS: Professional and lay beliefs about hypertension are not congruent. Historical factors, lack of congruence between belief systems, and poor relationships with providers lead many clients, especially African Americans, to distrust providers and impede the effectiveness of treatment plans. The most problematic discrepancies were related to beliefs about (a) the presence of symptoms, (b) the need to take medications for the rest of life, and (c) race-specific treatment plans. The interactions between nurse practitioners and hypertensive clients have not been explored. IMPLICATIONS FOR PRACTICE: Professional-client interactions based on partnership models, with specific consideration for the above-stated discrepancies in beliefs, are necessary to improve hypertension control.     

Prepregnancy overweight and obesity are associated with impaired child neurodevelopment

The authors examined the relationship of prepregnancy body mass index (BMI) and gestational weight gain (GWG) with child neurodevelopment. Mother–child dyads were a subgroup (n = 2,084) of the Child Health and Development Studies from the Oakland, California, area enrolled during pregnancy from 1959 to 1966 and followed at child age 9 years. Linear regression was used to examine associations between prepregnancy BMI, GWG, and standardized Peabody Picture Vocabulary Test and Raven Progressive Matrices scores and to evaluate effect modification of GWG by prepregnancy BMI. Before pregnancy, 77% of women were normal weight, 8% were underweight, 11% were overweight, and 3% were obese. Associations between GWG and child outcomes did not vary by prepregnancy BMI, suggesting no evidence for interaction. In multivariable models, compared to normal prepregnancy BMI, prepregnancy overweight and obesity were associated with lower Peabody scores (b: ?1.29; 95% CI [?2.6, ?0.04] and b: ?2.7; 95% CI [?5.0, ?0.32], respectively). GWG was not associated with child Peabody score [b: ?0.03 (95% CI: ?0.13, 0.07)]. Maternal BMI and GWG were not associated with child Raven score (all P >0.05). Maternal prepregnancy overweight and obesity were associated with lower scores for verbal recognition in mid‐childhood. These results contribute to evidence linking maternal BMI with child neurodevelopment. Future research should examine the role of higher prepregnancy BMI values and the pattern of pregnancy weight gain in child cognitive outcomes.     

The Effects of Caregiving on Women's Self-Assessed Health Status: An International Comparison

To compare the self-assessed health status (SAHS) of female caregivers of older adults across the United States (N = 1,496), China (N = 485), and the United Kingdom (N = 252), data from three data sets were analyzed to isolate significant predictors of SAHS using an adapted meta-analytic technique. Higher income and full-time employment were predictors of higher SAHS; chronic health condition and emotional strain predicted lower SAHS. Female gender was a predictor of lower SAHS. The health status of women was negatively impacted by the caregiving experience. National policies, such as those in the United Kingdom, may result in higher SAHS for women caregivers.