Creating Equitable and Inclusive Clinical Trials for Multiple Myeloma.

Black and Latino/Hispanic populations are disproportionately impacted by multiple myeloma (MM) in the United States and are underrepresented in many clinical trials. The Multiple Myeloma Research Foundation sponsored a 1-day workshop of 46 experts spanning the ecosystem of MM research and care, including government, academia, nonprofits, pharma/biotech, community partners, and retail pharmacy. Specific, tangible steps to overcome the well-documented barriers to improving the diversity and inclusivity of clinical trials were discussed, including broadening inclusion/exclusion criteria, reducing the financial and other burdens of trial participants, selecting diverse study sites, including implicit bias training, and taking steps to empower patients.

The comparative efficacy of angiosome-directed and indirect revascularisation strategies to aid healing of chronic foot wounds in patients with co-morbid diabetes mellitus and critical limb ischaemia: a literature review.

BACKGROUND: Ischaemic ulcerations have been reported to persist and/or deteriorate despite technically successful revascularisations; a higher incidence of which affects patients with diabetes and critical limb ischaemia. In the context of wound healing, it is unclear if applications of the angiosome concept in 'direct revascularisation' (DR) would be able to aid the healing of chronic foot ulcerations better than the current 'best vessel' or 'indirect revascularisation' (IR) strategy in patients with co-morbid diabetes and critical limb ischaemia. METHODS: A literature search was conducted in eight electronic databases, namely AMED, CINAHL, The Cochrane Library, ProQuest Health & Medicine Complete, ProQuest Nursing & Allied Health Source, PubMed, ScienceDirect and TRIP database. Articles were initially screened against a pre-established inclusion and exclusion criteria to determine eligibility and subsequently appraised using the Newcastle-Ottawa Scale. RESULTS: Five retrospective studies of varying methodological quality were eligible for inclusion in this review. Critical analysis of an aggregated population (n = 280) from methodologically stronger studies indicates better wound healing outcomes in subjects who had undergone DR as compared to IR (p < 0.001; p = 0.04). DR also appears to result in a nearly twofold increase in probability of wound healing within 12 months (hazard ratio, 1.97; 95% CI, 1.34-2.90). This suggests that achieving direct arterial perfusion to the site of ulceration may be important for the healing of chronic diabetic foot ulcerations. CONCLUSION: Incorporating an angiosome-directed approach in the lower limb revascularisation strategy could be a very useful adjunct to a solely indirect approach, which could increase the likelihood of wound healing. With the limited data currently available, findings appear promising and merit from further investigation. Additional research to form a solid evidence base for this revised strategy in patients with co-morbid diabetes and critical limb ischaemia is warranted.

Tolerance of formulas containing prebiotics in healthy, term infants.

OBJECTIVE: The aim of the study was to compare infants' gastrointestinal tolerance of formulas supplemented with 2 different levels of galacto-oligosaccharides (GOS) versus a control formula (CF) or human milk. METHODS: Healthy, full-term infants (n = 180) were enrolled in this 3-group controlled, double-blind, multicenter study, and a concurrently enrolled, nonrandomized human milk-fed group (HM) by 8 days of age. Infants were randomized to be fed formula supplemented with either 4 g (EF4) or 8 g (EF8) GOS/L or a CF until day of life (DOL) 119. Infants were to be seen at DOL 14, 35, 56, 84, and 119. Parents were to record detailed 24-hour information about intake, tolerance to feedings, and stool patterns and consistency each day from enrollment to DOL 35, and for 3 days before DOL 56, 84, and 119. Stool consistency was scored on a 5-point scale as watery (1), loose/mushy, soft, formed, or hard (5). RESULTS: The mean stool consistency score was higher in the CF group throughout the study (CF >  EF8 and CF > HM for all study periods and CF > EF4 from DOL 15 to 35, P < 0.05). There was a significantly higher percentage of watery stools in the EF8 versus the CF group from study day 1 (SD 1) to DOL 14 (P < 0.05), but no differences between the groups in number of stools per day. The percentage of feedings with spit up and/or vomiting within 1 hour after feeding was significantly lower for HM versus EF8 and CF from SD 1 to DOL 14 (P < 0.05). CONCLUSIONS: In this clinical study, milk-based term infant formula (Similac Advance) with 4 g GOS/L was well-tolerated in terms of stool consistency and additional measures of gastrointestinal tolerance by newborn infants through the first 4 months of life.

Plasma carotenoid concentrations of infants are increased by feeding a milk-based infant formula supplemented with carotenoids.

BACKGROUND: Human milk is the gold standard of infant nutrition and is a source of important substances, including carotenoids. Infant formulas are designed to mimic the composition and/or performance of human milk, although currently carotenoids are not routinely added to US infant formulas. The aim of this study was to assess plasma concentrations of ß-carotene, lutein and lycopene 56 days after feeding infants milk-based infant formula without (CTRL) or with different concentrations of added carotenoids (L1 and L2). RESULTS: Plasma carotenoid concentrations increased in infants fed carotenoid-supplemented formulas as compared with the control formula with no added carotenoids. At study day 56, infants fed the supplemented formulas (L1 and L2) had mean plasma lutein, ß-carotene and lycopene concentrations that were within the range of a concurrent group of human milk-fed infants (HM). Anthropometric measurements were comparable among all study groups. CONCLUSION: Plasma carotenoid concentrations of infants fed the supplemented formulas were within the range of the HM group and are consistent with reported plasma carotenoid ranges in human milk-fed infants. The experimental formulas were well tolerated and anthropometric measurements were comparable among all study groups.

Quantitative analysis of intestinal bacterial populations from term infants fed formula supplemented with fructo-oligosaccharides.

OBJECTIVES: Previous studies of infant formulas supplemented with oligosaccharides reported mixed results regarding the impact on intestinal microbial populations. The objective of this study was to examine the effect of supplementation of an infant formula with fructo-oligosaccharides (FOS) on select groups of intestinal bacteria in term infants. METHODS: Four groups of infants were enrolled and fed human milk, a commercially available milk-based infant formula, or infant formula supplemented with 2.0 or 3.0 g/L FOS. Dietary intake, stool, and tolerance events were recorded. Fresh stool samples were collected approximately 27 days after feeding the diets (approximately 32 days after birth). Total bacteria, Bacteroides (as commensal bacteria), Bifidobacterium and Lactobacillus, and Clostridium difficile and Escherichia coli were quantified using respective specific real-time PCR assays. RESULTS: The formula feeding groups did not differ in stool consistency and stool frequency or frequency of spit-up or vomit during the entire study. The formula-fed infants tended to have more total bacteria in their stool samples than the human milk-fed infants. The formula-fed infants harbored a greater abundance of C difficile and E coli than the human milk-fed infants, but had a similar abundance of Bacteroides, Bifidobacterium, and Lactobacillus. The FOS supplementation at either dose did not significantly increase the bifidobacterial or lactobacilli populations, or decrease the populations of C difficile, E coli, or Bacteroides. CONCLUSIONS: The milk-based formula used in this study supported bifidobacterial and lactobacilli populations comparable with the human milk group; however, this formula did not suppress E coli or C difficile as effectively as human milk.

Safety and Effectiveness of NovaSure® Endometrial Ablation After Placement of Essure® Micro-Inserts.

Objective: In-office NovaSure® after Essure® is a clinical paradigm for which physicians are seeking information. A PubMed search (July 2011) revealed no peer-reviewed articles describing this treatment sequence. To address the paucity of data on this topic, patients who had undergone Essure followed by NovaSure in a private practice office between July 1, 2008 and December 31, 2009 were evaluated. The objective was to evaluate safety and feasibility of in-office NovaSure after Essure, and to determine if the effectiveness of either procedure was altered by this treatment sequence. Design: This was a retrospective cohort study of 117 women (ages 24-52). Methods: Patients underwent Essure followed by NovaSure in two in-office sessions, separated by a median of 14 days. All patients had menorrhagia and desired permanent sterilization. A postprocedure patient questionnaire was administered to assess satisfaction and perceived effectiveness. Results: Among patients who underwent Essure followed by NovaSure, 83/117 (71%) returned for a 3-month hysterosalpingogram (HSG). Satisfactory placement and tubal occlusion were noted in 79/83 (95%) of these patients. Amenorrhea or spotting was observed in 72/97 (74%) of patients, 22/97 (23%) reported a satisfactory decrease in menstrual flow, and 3/97 (3%) reported ablation failure. Essure followed by NovaSure did not decrease the effectiveness of either procedure, and no adverse events were attributed to the combination of the two procedures. Patients reported high levels of satisfaction with both procedures. Conclusions: In women seeking permanent birth control and menorrhagia reduction, in-office Essure followed by NovaSure appeared to be safe, effective, and associated with high patient satisfaction. (J GYNECOL SURG 28:1).

Outcomes in the ultrasound follow-up of the Essure micro-insert: complications and proper placement.

OBJECTIVE: To review the use of three-dimensional ultrasound follow-up of the Essure micro-insert placement at three months for the identification of misplaced coils and complications. METHODS: We conducted a retrospective cohort study of reproductive age women requesting permanent sterilization in a tertiary care ambulatory women's clinic. Women who underwent placement of the Essure micro-insert were assessed for appropriate positioning of the Essure micro-insert coil using three-dimensional ultrasound as well as hysterosalpingography when indicated. RESULTS: A total of 610 women who had undergone the Essure procedure with ultrasound follow-up at three months were retrospectively reviewed and in 524 (86%) the location and shape were both normal. The remaining 86 (15%) required hysterosalpingography to confirm proper placement, 34 because of a non-diagnostic ultrasound and the remaining 52 for a complication noted on ultrasound, including perforation, proximal or distal migration of the device, or device expulsion. CONCLUSION: Ultrasound can be used at three months after Essure placement to identify normal placement as well as misplaced and perforated devices.

Feeding an elemental diet vs a milk-based formula does not decrease intestinal mucosal growth in infant pigs.

BACKGROUND: We previously showed that the level of enteral nutrient intake determines the rate of intestinal growth in piglets. Our objective was to determine whether providing enteral nutrition in the form of elemental nutrients (glucose, amino acids, lipid [ED]) rather than cow's milk formula (lactose, protein, lipid [FORM]) reduces small intestinal growth and lactase activity. METHODS: Three-week-old piglets were fed either ED (n = 7) intragastrically or FORM (n = 6) orally for 6 days. RESULTS: Intestinal protein and DNA masses, villus height, and crypt depth were not different in ED and FORM pigs. Crypt cell proliferation, measured by in vivo bromodeoxyuridine labeling, was significantly (p < .05) higher (+37%) in ED than in FORM pigs. Rates of mucosal protein synthesis (%/d), measured by in vivo 2H-leucine incorporation, were higher (p < .05) in ED than FORM (147 vs 89) pigs. Circulating concentrations (pmol/L) of the intestinotrophic peptide, glucagon-like peptide-2 (GLP-2), were also higher (p < .05) in ED than in FORM (148 vs 87) pigs. The mean lactase-specific activity (micromol/min/g) in proximal and distal segments was higher (p < .05) in FORM than in ED (124 vs 58) pigs. CONCLUSIONS: We conclude that intestinal mucosal growth and villus morphology are similar in pigs fed ED and FORM, despite higher cell proliferation and protein synthesis rates and lower lactase activity with ED. This implies that elemental diets may be as trophic as polymeric formulas to simultaneously provide nutrition and a stimulus for intestinal growth during bowel rest.

A comparison of neural networks for computing predicted probability of survival for trauma victims.

TRISS is a statistical method for predicting the probability of survival of trauma victims. Analysis of data from the Trauma Registry at Charleston Area Medical Center showed that only 48% of the trauma fatalities in the 5-year period 1992-1996 were correctly predicted by TRISS. Trauma practitioners from other Trauma Centers report similar problems with TRISS. Researchers have suggested improvements that range from simply changing the input variables and/or regression coefficients in TRISS to using an entirely different model. In this study we describe a method of calculating survival probabilities using Artificial Neural Networks (ANN). This method was chosen because of the similarity of the ANN output function to the function that produces the TRISS probability of survival. Additional variables were added based on the results of other research efforts as well as analysis of the CAMC Trauma Registry. A comparison was made between the abilities of TRISS to predict fatalities and to approximate probability of survival. The ANN outperformed TRISS in predicting fatalities in a training set (68.1% correct vs. 47.9% correct) and in a testing set (61.3% correct vs. 51.3% correct). More importantly, the ANN produced better estimates of predicted deaths. Using a data set that included 119 deaths, the ANN model predicted 125 deaths for a 5% relative error. The predicted number using TRISS was 86 for a relative error of 27.7%. Since effective quality improvement for trauma care depends on accurately identifying cases that fall outside the expected results, a more accurate predictive tool allows a more focused review of those significant cases, thus conserving resources without compromising quality. Neural Networks appear to be a predictive tool that can provide probability of survival estimates that are more accurate than TRISS.