Methodology in meta–analysis: a study from Critical Care meta–analytic practice

Methodological aspects of meta-analytic practice, heterogeneity, publication bias, metaregression and effect metric, were investigated in 14 meta-analyses reflecting major therapeutic concern in Critical Care practice. Compared with the standard Q test, the exact Zelen test was more sensitive in identifying heterogeneity. Assessment of heterogeneity impact by the I ² statistic was consistent with inferences afforded by both the Q and Zelen test. Publication bias was subject to test and metric determination: funnel plots exhibited variable asymmetry across studies and between metrics; the regression asymmetry test appeared more sensitive than the rank correlation test; the “trim and fill” method was the most sensitive, but suggested, on the basis of quantification of the effects of potentially missing studies, that meta-analyses may be resistant to such missingness. Metaregression of treatment effect against control risk using Bayesian hierarchical regression in all metrics (log odds ratio, log risk ratio and RD) suggested that naïve linear regression approaches over-diagnosed significant relationships and exhibited regression dilution. Heterogeneity, publication bias and risk related treatment effects all demonstrate estimator and metric dependence; the RD metric would appear the most capricious in this regard.     

Releasing information to families of persons with severe mental illness: a survey of NAMI members

OBJECTIVE: Guidelines for the treatment of severe mental illness recommend that providers share information with families and involve them in treatment. However, research indicates that consumer-provider-family collaboration is not part of routine clinical practice. This study examined the process of releasing information to families and the types of information they receive. METHODS: Self-administered surveys were completed by 219 family and consumer members of the National Alliance for the Mentally Ill. The surveys gathered information about their experiences with providers' releasing information. Consumers' attitudes toward collaboration and family members' satisfaction with providers were also measured. Regression analyses examined the relationship between consumers' attitudes toward family involvement and whether providers discussed family involvement or the release of information with consumers. Further analyses examined the relationship between family satisfaction and release of information. RESULTS: The majority of family respondents (72 percent) reported that they received some specific information about their relative's mental illness. Most families received information about diagnosis and medications, but few received information about the treatment plan. Few consumers reported that their permission was requested to release information to their families. Consumers' attitudes toward their family and toward family involvement were significantly associated with whether they were encouraged by their provider to involve a family member in their treatment. No significant relationship was found between consumers' attitudes and whether their provider discussed the release of information. Family members' satisfaction was positively related to whether they received information from providers. CONCLUSIONS: The findings suggest that although some information is shared with families, collaboration is not currently part of routine clinical practice.     

Identification of serious drug-drug interactions: results of the partnership to prevent drug-drug interactions.

OBJECTIVE: To develop a list of clinically important drug-drug interactions (DDIs) likely to be encountered in community and ambulatory pharmacy settings and detected by a computerized pharmacy system. DESIGN: Cross-sectional, one-time evaluation. SETTING: United States in fall 2001. PARTICIPANTS: An expert panel comprising two physicians, two clinical pharmacists, and an expert on DDIs. INTERVENTIONS: Systematic review of drug interaction compendia and published literature, ratings (on a 1 to 10 scale) of various clinical aspects of DDIs (e.g., clinical importance, quality and quantity of evidence, causal relationship, risk of morbidity and mortality), and a modified Delphi consensus-building process. MAIN OUTCOME MEASURE: Panelists' opinions about clinical importance of DDIs. RESULTS: The expert panel considered 56 DDIs. Of these, 28 had a mean clinical importance score of 8.0 or more. The ratings for clinical importance ranged from 3.2 to 9.6, with a mean +/- SD of 7.5 +/- 1.5 across the combinations examined. The mean score for the quality of literature suggesting the interaction exists ranged from 1.0 to 9.6, with a mean +/- SD of 5.8 +/- 2.5. In terms of substantiation of the interactions evaluated, the mean +/- SD rating was 6.3 +/- 2.2, with a range from 1.4 to 9.2. Through the modified Delphi process, the panel determined that 25 interactions were clinically important. CONCLUSION: Using an expert panel and a standard evaluation tool, 25 clinically important drug interactions that are likely to occur in the community and ambulatory pharmacy settings were identified. Pharmacists should take steps to prevent patients from receiving these interacting medications, and computer software vendors should focus interaction alerts on these and similarly important DDIs.     

Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells

Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic invasomes (INVA) covered with Phospholipon 90G and apamin (APA). The Box–Behnken statistical design was implemented to enhance the composition. Using Design-Expert software (Stat-Ease Inc., Minneapolis, MN), the INVA component quantities were optimized to obtain spherical particles with the smallest size, that is, a diameter of 167.8 nm. 2ME-INVA-APA significantly inhibited A549 cells and exhibited IC₅₀ of 1.15 ± 0.04 µg/mL, which is lower than raw 2ME (IC₅₀ 5.6 ± 0.2 µg/mL). Post 2ME-INVA-APA administration, a significant rise in cell death and necrosis was seen among the A549 cells compared to those treated with plain formula or 2ME alone. This effect was indicated by increased Bax expression and reduced Bcl-2 expression, as well as mitochondrial membrane potential loss. Moreover, the cell cycle analysis showed that 2ME-INVA-APA arrests the G2-M phase of the A549 cells. Additionally, it was observed that the micellar formulation of the drug increased the cell count in pre-G1, thereby exhibiting phenomenal apoptotic potential. Furthermore, it up-regulates caspase-9 and p53 and downregulates TNF-α and NF-κβ. Collectively, these findings showed that our optimized 2ME-INVA-APA could easily seep through the cell membrane and induce apoptosis in relatively low doses.     

Recommendations for Better Civic Learning: Building and Rebuilding Democracy

This is the concluding essay for a special report from The Hastings Center entitled Democracy in Crisis: Civic Learning and the Reconstruction of Common Purpose, which grew out of a project supported by the John S. and James L. Knight Foundation. This essay provides an integrative discussion of various theoretical and practical reform perspectives offered by other essays in the report. It also offers a number of recommendations. It notes that the aim of the special report is not to propose specific reform measures but, rather, to consider larger, more theoretic concerns related to political and economic questions, which are personal and structural—psychological, cultural, and institutional—at the same time. In response, this essay argues that the best relationship between the citizenry and government in a democracy is not one of deference, nor one of contestation, but one that is critically constructive, which in turn is linked to practices of civic learning. To be constructive, citizens need scientific literacy, an understanding of how government and other institutions work, critical thinking abilities, and many open and diverse forums for civic learning to offset the increasingly isolating media “bubbles” that are the only source of information for many. The essay then formulates five recommendations designed to facilitate critically constructive citizenship and civic learning. These are creating a basis for civic participation, acquiring information, talking to each other, designing institutional change, and achieving deliberation.     

Dorsolumbar parasitic twin associated with lipomyelomeningocele: a case report from a tertiary teaching hospital,Ethiopia, East Africa

A parasitic or heteropagus twin is a grossly defective fetus (or fetus part) attached externally, with or without internal connections and is dependent on the cardiovascular system of the other twin (autosite) for survival. The estimated incidence is approximately 1 per 1 million live births. To date according to the authors’ knowledge; there are a few case reports published in the literature. Here we present a case of dorsolumbar parasitic twin with associated lipomyelomeningocele.     

Decentration of flexible loop posterior chamber intraocular lenses in a series of 222 postmortem eyes

Two hundred twenty-two postmortem eyes containing posterior chamber intraocular lenses (IOLs) were analyzed for optic decentration in relationship to lens style, implant duration, and loop fixation site. Decentration values were not affected significantly by either lens style or implant duration. In 33.3% of specimens, both loops were situated within the lens capsular sac, 18.0% had both loops fixated in the ciliary sulcus, and in 48.7% one loop was fixated in the lens capsular sac and the opposite loop in the ciliary sulcus or zonular region. There was a statistically significant difference in the amount of decentration in the three fixation groups studied. Capsular fixation provides the best and most consistent centration compared with fixation of both loops in the ciliary sulcus or asymmetrical fixation with only one loop in the capsular sac.