Combined natural killer T-cell based immunotherapy eradicates established tumors in mice

A rational monoclonal antibody (mAb)-based antitumor therapy approach has previously been shown to eradicate various established experimental and carcinogen-induced tumors in a majority of mice. This therapy comprised an agonistic mAb reactive with tumor necrosis factor-related apoptosis-inducing ligand receptor (DR5), expressed by tumor cells, an agonistic anti-CD40 mAb to mature dendritic cells, and an agonistic anti-4-1BB mAb to costimulate CD8(+) T cells. Because agonists of CD40 have been toxic in patients, we were interested in substituting anti-CD40 mAb with other dendritic cell-maturing agents, such as glycolipid ligands recognized by invariant natural killer T (iNKT) cells. Here, we show that CD1d-restricted glycolipid ligands for iNKT cells effectively substitute for anti-CD40 mAb and reject established experimental mouse breast and renal tumors when used in combination with anti-DR5 and anti-4-1BB mAbs (termed "NKTMab" therapy). NKTMab therapy-induced tumor rejection was dependent on CD4(+) and CD8(+) T cells, NKT cells, and the cytokine IFN-gamma. NKTMab therapy containing either alpha-galactosylceramide (alpha-GC) or alpha-C-galactosylceramide (alpha-c-GC) at high concentrations induced similar rates of tumor rejection in mice; however, toxicity was observed at the highest doses of alpha-GC (>250 ng/injection), limiting the use of this glycolipid. By contrast, even very low doses of alpha-c-GC (25 ng/injection) retained considerable antitumor activity when used in combination with anti-DR5/anti-4-1BB, and thus, alpha-c-GC showed a considerably greater therapeutic index. In summary, sequential tumor cell apoptosis and amplification of dendritic cell function by NKT cell agonists represents an exciting and novel approach for cancer treatment.     

Locus of control in nondisabled versus congenitally physically disabled adolescents.

Locus of control in 13 nondisabled and 8 congenitally physically disabled adolescents was examined with the use of the Nowicki-Strickland Locus of Control Scale for Children (Nowicki & Strickland, 1973a). All subjects with disabilities had IQs within normal limits, used wheelchairs, and could communicate verbally. The two groups were matched in IQ, age, sex, race, and socioeconomic status. It was hypothesized that the locus of control scores for the disabled group would evidence significantly more externality than the scores for the nondisabled group. A Mann Whitney U test was done to analyze the data gathered, and the results were found to be statistically nonsignificant (U = 58.50, p = .635). Adjunct analyses were conducted to explore the percentage of internal and external answers between the two groups. Race was the only variable correlating significantly with locus of control scores (r = .54, p = .05). The study's results suggest that disability is not a significant predictor of externality in adolescents. Persons with an internal locus of control are more assertive and better able to cope with their environment; occupational therapists can offer many therapeutic strategies to persons with an external locus of control for improved function and quality of life.     

The NSW health outcomes initiative and economic analysis

Abstract: The New South Wales Health Department's initiative on health outcomes promises some important advances in the planning and priority setting of health services. However, the potential to promote better health care will not be realised unless resources are redeployed to the programs where health outcomes (and other benefits) can be purchased most cheaply. The initiative reflects firmly the economic concept of efficiency but leaves less certainty about how concerns for equity are to be handled. This paper proposes that program budgeting and marginal analysis be used to create a framework for redeploying resources to follow the good buys—in terms of health and other outcomes. Additionally, the paper argues for creating the right incentives to promote efficiency, and expressly argues against the use of diagnostic related groups or casemix funding, as such funding is concerned, by definition, with cases and not with health per se. The goal of the initiative of trying to maximise health outcomes implies that there are no other valued gains to be had from health care. This is challenged. In reaching decisions about how best to deploy resources, more account should be taken, in a structured way, of community values.     

First-degree relative history of alcoholism in eating disorder inpatients: relationship to eating and substance use psychopathology

OBJECTIVE: We examined the influence of family history of alcoholism on the presentation and course of inpatients with eating disorders (ED) by comparing ED behaviors, substance abuse behaviors, and psychopathology of patients with alcoholic first-degree relatives (AFDR+) to those without alcoholic first-degree relatives (AFDR-). METHOD: Female inpatients admitted to a specialty eating disorders service completed demographic, family history, behavioral, and psychological questionnaires (N=217). Body mass index (BMI) at admission and discharge, length of stay, and rates of weight gain were calculated. RESULTS: AFDR+ participants did not differ from AFDR- participants diagnostically, but AFDR+ participants did report higher lifetime frequencies of several ED and substance abuse behaviors. Measures of ED psychopathology and personality vulnerability were also elevated in the AFDR+ group. DISCUSSION: ED inpatients with a first-degree family history of alcoholism demonstrate increased psychopathology in eating behavior, substance use, and personality vulnerability domains. While the genetic diathesis for alcoholism is likely distinct from that for eating disorders, these findings suggest that first-degree relative history of alcoholism may nevertheless exert a negative influence on eating disorder behaviors.     

Detecting depression in the aged: Is there concordance between screening tools and the perceptions of nursing home staff and residents? A pilot study in a rural aged care facility

OBJECTIVE: Recognition of depression in the elderly is exacerbated in rural and remote regions by a lack of mental health specialists. In nursing homes, screening tools have been advocated to circumvent the variable reliability of both nursing staff and residents in recognising depression. Debate concerning the utility of screening tools abounds. Previous research has neglected concordance between screening tools, nursing staff and residents in recognising depression. The present study aimed to determine if there was a significant difference in the proportion of depressed residents identified by recognition sources, and assessed the level of chance corrected agreement between sources. PARTICIPANTS: One hundred and two residents of aged care facilities in Wagga Wagga, Australia, mean age of 85.19 +/- 7.09 years. SETTING: Residents were interviewed within their residential aged care facility. DESIGN: Cross-sectional, between-subjects design. MAIN OUTCOME MEASURES: Residents, nursing staff, Geriatric Depression Scale (GDS-12R) and Hamilton Depression Rating Scale. RESULTS: Hamilton Depression Rating Scale and nursing staff professional opinion were not significantly different; however, both measures were significantly different to the resident measures (GDS-12R and resident opinion). Kappa statistic analysis of outcome measures revealed, at best, no more than a moderate level of chance corrected agreement between said sources. CONCLUSION: It is tentatively argued that the different sources might correspond to qualitatively different 'depression' constructs, and that health professionals who are concerned with depression in the elderly be aware of the disparity between, and subsequently consider, a variety of recognition sources.     

Television, walking, and diet: associations with postpartum weight retention

BACKGROUND: For many women, pregnancy begets long-term weight gain. Modifiable behaviors that contribute to postpartum weight retention have not been well studied. METHODS: Prospective cohort study of 902 women enrolled in Project Viva, examining associations of postpartum television viewing, walking, and trans fat intake with weight retention equal to or greater than 5 kg at 12 months postpartum. Data were collected in 1999-2003 and analyzed in 2005-2006. RESULTS: At 6 months postpartum, women reported a mean (SD) of 1.7 (1.3) hours of television viewing, 0.7 (0.7) hours of walking, and 1.1% (0.5) of energy intake from trans fat per day. At 1 year, participants retained a mean of 0.6 kg (range: -17.3 to 25.5), and 12% retained at least 5 kg. In multivariate logistic regression models, adjusting for maternal sociodemographics, parity, prepregnancy body mass index, gestational weight gain, breastfeeding, and smoking, the odds ratio of retaining at least 5 kg was 1.24 (95% confidence interval [CI]: 1.06-1.46) per daily hour of television viewing, 0.66 (95% CI: 0.46-0.94) per daily hour of walking, and 1.33 (95% CI: 1.09-1.62) per 0.5% increment in daily energy intake from trans fat. Women who watched less than 2 hours of television, walked at least 30 minutes, and consumed trans fat below the median had an odds ratio of 0.23 (95% CI: 0.08-0.66) of retaining at least 5 kg. CONCLUSIONS: Postpartum television viewing, walking, and trans fat intake were associated with weight retention. Interventions to modify these behaviors may help reduce excess postpartum weight gain and prevent obesity among women.     

Does more "appropriateness" explain higher rates of cardiac procedures among patients hospitalized with coronary heart disease?

BACKGROUND: There have been few studies of the extent to which differences in the pool of patients being managed might account for geographic variations in treatment rates. OBJECTIVE: For two cardiac procedures, cardiac catheterization and revascularization, we evaluate the hypothesis that differences in "the percentage of patients for whom the procedure is appropriate" is a factor explaining variations in use rates among those hospitalized with coronary heart disease (CHD). RESEARCH DESIGN: Based on hospital utilization patterns in Massachusetts in 1990, we created 70 small geographic areas. Using 1992 Massachusetts Peer Review Organization data, areas were ranked from highest to lowest based on (empirical-Bayes-adjusted) hospitalization rates for each procedure. One thousand seven hundred four cases from 43 hospitals were sampled, roughly half each from high and low use areas. Half had a procedure and half were candidates for the same procedure but did not have it. For each procedure, medical records were reviewed to determine whether the procedure was (or, for those not having it, would have been) appropriate, based on criteria developed using a modified Delphi approach. RESULTS: Among those having either procedure, appropriateness rates were similar in high and low rate areas (P = 0.59 for catheterization and P = 0.30 for revascularization). However, among candidates for either procedure who did not have it, appropriateness for performing the procedure was greater in high-rate areas (41.4% vs. 32.1%, P = 0.05 for catheterization; 71.2% vs. 57.2%, P = 0.003, for revascularization). CONCLUSION: Among those hospitalized with CHD, appropriateness rates for two cardiac procedures are higher in areas with higher use rates.     

Identifying non-pharmacological risk factors for falling in older adults with type 2 diabetes mellitus: a systematic review

Purpose: To identify the non-pharmacological risk factors for falling in older adults with type 2 diabetes mellitus (DM2).

Methods: A systematic review of randomized controlled trials, prospective cohort studies, cross-sectional studies and before/after studies was conducted. Eligible studies identified non-pharmacological risk factors for falling in older adults with DM2. Medline, Embase, Pubmed and CINAHL were searched for relevant studies published through December 2015. Reference lists were also searched for relevant studies. Search terms were DM2, risk factors, falls and falling, older adults, aging, non-insulin dependent diabetes mellitus, accidental falls and trip. Publication language was restricted to English.

Results: Thirteen studies met the inclusion criteria: four cross-sectional, six prospective cohorts, two randomized controlled trials and one before/after study. These studies included a total of 13,104 participants, ≥50 years. The most common risk factors for falling were impaired balance, reduced walking velocity, peripheral neuropathy and comorbid conditions. However, lower extremity pain, being overweight and comorbid conditions had the greatest impact on fall risk.

Conclusion: Interventions to reduce falling in older adults with type 2 diabetes mellitus should focus on reducing lower extremity pain, reducing body weight and managing comorbid conditions.

• Implications for Rehabilitation

• Diabetes mellitus:

• ??Older adults with type 2 diabetes mellitus (DM2) have a higher risk for falling than older adults without.

• ??Older adults with DM2 are more likely to suffer serious injuries when they fall.

• ??Comprehensive risk factor identification is necessary for rehabilitation professionals to accurately determine whether their clients are at risk for falling.

• ??Rehabilitation professionals also need to tailor interventions based on the client’s risk factors in order to effectively reduce falls and fall-related injuries.