Boswellia serrata extract shows cognitive benefits in a double-blind, randomized, placebo-controlled pilot clinical trial in individuals who suffered traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. TBI can result in neuropsychiatric and cognitive problems as well as neurodegenerative pathologies that can appear right after or develop and persist years after injury. METHOD: We conducted a double-blind, randomized, placebo-controlled clinical trial on patients who suffered from TBI three months to three years ago. The patients were randomized to placebo (n = 34) or K-Vie™ group (n = 46) for a treatment period of 3 months. The main primary outcomes include cognitive assessment in the Rey Auditory Verbal Learning Test-Recognition Test (RAVLT), Wechsler adult intelligence Digit Symbol Substitution Test (DSST) and trail-making test part B (TMT-B). Assessments were performed at baseline and at the month 3 follow-up visit. Linear mixed models were carried out to evaluate cognitive changes from baseline across all cognitive assessment tests. RESULT: The current study showed significant (p < 0.05) improvement in cognitive function of patients who were given K-Vie™ compared with placebo across the RAVLT, DSST and TMT-B performance assessments. A larger cohort would be beneficial to further confirm the clinical utility of K-Vie™ and assess its effects in acute phases of TBI.

Determinants of fatty acid content and composition of human milk fed to infants born weighing <1250 g.

BACKGROUND: Infants born at very low birth weight (VLBW) are vulnerable to deficits in fatty acids (FAs) but little is known of factors that influence the intakes or composition of their human milk feeds. OBJECTIVES: We aimed to identify sources of variability in the fat composition of human milk fed to VLBW infants and examine the impact of milk source (mother's own or donor) on fat and FA intakes. METHODS: Serial samples of mother's milk (n = 476) and donor milk (n = 53) fed to infants born weighing <1250 g (n = 114 infants from 100 mothers) were collected [Optimizing Mothers' Milk for Preterm Infants (OptiMoM) randomized clinical trial]. Fat and FA were analyzed using a mid-infrared human milk analyzer and GC with flame ionization detection. RESULTS: At full enteral feeding, donor milk is estimated to provide 1.3 g · kg-1 · d-1 less total fat than mature mother's milk (recommended intake: 4.8 g · kg-1 · d-1), and 5-9 mg · kg-1 · d-1 less DHA (22:6n-3) and arachidonic acid (20:4n-6) (estimated average requirement: 55-60 and 35-45 mg · kg-1 · d-1, respectively) than colostrum or transitional milk. Similar deficits were observed in measured intakes of a subset of OptiMoM infants. In multivariable-adjusted models, maternal ethnicity had medium to large [≥0.5 SD score (SDS)] effects on DHA, SFAs, and MUFAs. Mothers with prepregnancy BMI in overweight and obese categories had higher milk total fat (ß: 0.35; 95% CI: 0.10, 0.61 and ß: 0.46; 95% CI: 0.16, 0.77 SDS, respectively). Those with BMI ≥30 in addition had higher proportions of SFAs (ß: 0.61; 95% CI: 0.33, 0.89 SDS) and lower DHA (ß: -0.54; 95% CI: -0.89, -0.20 SDS). Other factors, such as gestational age and income, were also associated with FA composition. CONCLUSIONS: The fat and FA content of human milk fed to VLBW infants is variable. Care must be taken to ensure fat and FA intakes meet recommendations, particularly when feeding a high proportion of donor milk.This trial was registered at clinicaltrials.gov as NCT02137473.

High Hydrostatic Pressure Processing Better Preserves the Nutrient and Bioactive Compound Composition of Human Donor Milk.

BACKGROUND: When mother's milk is insufficient, pasteurized human donor milk (DM) is the recommended supplement for hospitalized very-low-birth-weight infants. The current method of pasteurization (Holder, 62.5°C, 30 min) negatively affects heat-sensitive nutrients and bioactive proteins. OBJECTIVES: Objectives of this study were to compare changes in DM composition after thermal pasteurization (Holder and flash-heating) and nonthermal methods [UV-C irradiation and high hydrostatic pressure (HHP)]. We hypothesized that nonthermal techniques would result in fewer changes to composition. METHODS: Holder, flash-heating (brought to boil), UV-C irradiation (250 nm, 25 min), and HHP (500 MPa, 8 min) were studied. Pools of milk from 17 women known to contain bacteria at >5 × 107 colony forming units (CFU)/L were collected from the Rogers Hixon Ontario Human Milk Bank and underwent each pasteurization technique. Macronutrients, heat-sensitive micronutrients (vitamin C, folate), and bioactive components [bile-salt-stimulated lipase (BSSL), lysozyme, lactoferrin] were measured in raw and pools of pasteurized milk. Milk was cultured to determine how well each technique produced a culture negative result (detection limit <1 × 103 CFU/L). RESULTS: Folate was reduced by 24-27% after Holder, flash-heating, and UV-C (P < 0.05); no reduction was observed after HHP. All pasteurization methods reduced vitamin C (60-75%, P < 0.001). BSSL was abolished after Holder and flash-heating (P < 0.001), reduced after UV-C (48%, P < 0.001), but unaffected by HHP. Lysozyme activity was reduced after flash-heating (44%) and UV-C (74%, P < 0.004) but unaffected by Holder or HHP. Lactoferrin was reduced by all methods (P < 0.02) but most severely by flash-heating (74%) and least severely by HHP (25%). Holder and UV-C reduced lactoferrin by ∼48%. All pasteurization methods reduced the number of culture positive DM samples (P < 0.001). CONCLUSIONS: HHP better preserves human milk composition than Holder pasteurization. Future research on the feasibility of HHP for pasteurizing human milk is warranted because its implementation may improve the nutritional status and health of DM-fed infants.

Postdischarge Feeding of Very-low-birth-weight Infants: Adherence to Nutrition Guidelines.

OBJECTIVES: Infant feeding guidelines are important public health strategies to promote optimal growth, development, and chronic disease prevention, but their effectiveness is contingent upon families' ability to adhere to them. Little is known of adherence to guidelines among nutritionally vulnerable infants, specifically those born very-low-birth-weight (VLBW) (<1500 g). This study investigated whether postdischarge feeding practices for VLBW infants align with current recommendations and explored parental and infant baseline sociodemographics related to these practices. METHODS: Prospectively collected data from families of 300 VLBW infants participating in a randomized clinical trial (ISRCTN35317141) were used. Baseline demographics were obtained at enrollment and postdischarge feeding practices via monthly telephone questionnaires to 6 months corrected age (CA). RESULTS: At discharge, 4 and 6 months CA, 72%, 39%, and 29% of infants received any amount of mother's milk, respectively; exclusive breast-feeding rates were 49%, 20%, and 6%, respectively. Among infants receiving mother's milk, rates of vitamin D supplementation were ≥83%. Recommendations for introducing solids between 4 and 6 months CA were followed by 71% of the cohort and for iron supplementation by 58%. Overall, 12% of infants adhered to all aforementioned recommendations. Mothers with university degrees were more likely to provide mother's milk, whereas mothers of Middle Eastern/South Asian ethnicity were less likely to provide mother's milk. CONCLUSIONS: Low rates of partial and exclusive breast-feeding of VLBW infants to 6 months CA were reported. Overall adherence to iron supplementation was low. Strategies to provide increased support for mothers identified as at-risk should be developed.

Introduction of Bovine-Based Nutrient Fortifier and Gastrointestinal Inflammation in Very Low Birth Weight Infants as Measured by Fecal Calprotectin.

BACKGROUND: Fecal calprotectin (fCP) is a biomarker of gastrointestinal tract (GIT) inflammation that is currently being used investigationally among very low birth weight (VLBW) infants. MATERIALS AND METHODS: Stool was collected weekly from 20 breastmilk-fed VLBW infants for up to 8 weeks after birth during the establishment and fortification of feeds, and fCP concentrations were measured. RESULTS: Mean fCP levels increased significantly in stools collected immediately following bovine-based nutrient fortification of feeds (p = 0.005). CONCLUSIONS: Addition of bovine fortifier to breastmilk feeds appeared to be associated with an acute increase in GIT inflammation.

Capsaicin: a novel radio-sensitizing agent for prostate cancer.

INTRODUCTION: Radio-sensitizing agents sensitize tumor cells to the lethal effects of radiotherapy (RT) allowing for use of lower doses of radiation to achieve equivalent cancer control, while minimizing adverse effects to normal tissues. Given their limited toxicity and ability to easily integrate into the diet, compounds occurring naturally in the diet make ideal potential radio-sensitizing agents. In this study, we have examined whether capsaicin, the active compound in chilli peppers, can modulate the response to RT in preclinical models of prostate cancer (PCa). METHODS: The effects of RT (1-8 Gy) and/or capsaicin (1-10 µM) on colony formation rates in human PCa cells were assessed using clonogenic assays. Mechanistic studies were performed by Western Blot, immunocytochemistry, and flow cytometry. Athymic mice (n = 40) were inoculated with human LNCaP cells. Once tumors reached 100 mm(3) , animals were randomized into four groups: control, capsaicin alone (5 mg/kg/d), RT alone (6 Gy), and capsaicin and RT. RESULTS: Capsaicin reduced colony formation rates and radio-sensitized human PCa cells (Sensitizer enhancement ratio = 1.3) which corresponded to the suppression of NFκB, independent of TRP-V1 receptor. Cell cycle modulation occurred following RT and capsaicin treatment independently. In vivo, oral administration of capsaicin with RT resulted in a 'greater than additive' growth delay and reduction in the tumor growth rate greater than capsaicin (P < 0.001) or RT (P < 0.03) alone. Immunohistochemical analysis revealed a reduction in proliferation and NFκB expression, and increase in DNA damage. DISCUSSION: Our findings suggest that capsaicin acts as a radio-sensitzing agent for PCa through the inhibition of NFκB signalling.

Medial open transversus abdominis plane (MOTAP) catheters for analgesia following open liver resection: study protocol for a randomized controlled trial.

BACKGROUND: The current standard for pain control following liver surgery is intravenous, patient-controlled analgesia (IV PCA) or epidural analgesia. We have developed a modification of a regional technique called medial open transversus abdominis plane (MOTAP) catheter analgesia. The MOTAP technique involves surgically placed catheters through the open surgical site into a plane between the internal oblique muscle and the transverse abdominis muscle superiorly. The objective of this trial is to assess the efficacy of this technique. METHODS/DESIGN: This protocol describes a multicentre, prospective, blinded, randomized controlled trial. One hundred and twenty patients scheduled for open liver resection through a subcostal incision will be enrolled. All patients will have two MOTAP catheters placed at the conclusion of surgery. Patients will be randomized to one of two parallel groups: experimental (local anaesthetic through MOTAP catheters) or placebo (normal saline through MOTAP catheters). Both groups will also receive IV PCA. The primary endpoint is mean cumulative postoperative opioid consumption over the first 2 postoperative days (48 hours). Secondary outcomes include pain intensity, patient functional outcomes, and the incidence of complications. DISCUSSION: This trial has been approved by the ethics boards at participating centres and is currently enrolling patients. Data collection will be completed by the end of 2014 with analysis mid-2015 and publication by the end of 2015. TRIAL REGISTRATION: The study is registered with http://clinicaltrials.gov ( NCT01960049; 23 September 2013).

Hypertension analysis of stress reduction using mindfulness meditation and yoga: results from the HARMONY randomized controlled trial.

BACKGROUND: The HARMONY study was a randomized, controlled trial examining the efficacy of an 8-week mindfulness-based stress reduction (MBSR) program for blood pressure (BP) lowering among unmedicated stage 1 hypertensive participants. METHODS: Participants diagnosed with stage 1 hypertension based on ambulatory BP were randomized to either immediate treatment of MBSR for 8 weeks or wait-list control. Primary outcome analysis evaluated whether change in awake and 24-hour ambulatory BP from baseline to week 12 was significantly different between the 2 groups. A within-group before and after MBSR analysis was also performed. RESULTS: The study enrolled 101 adults (38% male) with baseline average 24-hour ambulatory BP of 135±7.9/82±5.8mm Hg and daytime ambulatory BP of 140±7.7/87±6.3 mmHg. At week 12, the change from baseline in 24-hour ambulatory BP was 0.4±6.7/0.0±4.9mm Hg for the immediate intervention and 0.4±7.8/-0.4±4.6mm Hg for the wait-list control. There were no significant differences between intervention and wait-list control for all ambulatory BP parameters. The secondary within-group analysis found a small reduction in BP after MBSR compared with baseline, a finding limited to female subjects in a sex analysis. CONCLUSIONS: MBSR did not lower ambulatory BP by a statistically or clinically significant amount in untreated, stage 1 hypertensive patients when compared with a wait-list control group. It leaves untested whether MBSR might be useful for lowering BP by improving adherence in treated hypertensive participants. CLINICAL TRIALS REGISTRATION: NCT00825526.

Implementing wait-time reductions under Ontario government benchmarks (Pay-for-Results): a Cluster Randomized Trial of the Effect of a Physician-Nurse Supplementary Triage Assistance team (MDRNSTAT) on emergency department patient wait times.

BACKGROUND: Internationally, emergency departments are struggling with crowding and its associated morbidity, mortality, and decreased patient and health-care worker satisfaction. The objective was to evaluate the addition of a MDRNSTAT (Physician (MD)-Nurse (RN) Supplementary Team At Triage) on emergency department patient flow and quality of care. METHODS: Pragmatic cluster randomized trial. From 131 weekday shifts (8:00-14:30) during a 26-week period, we randomized 65 days (3173 visits) to the intervention cluster with a MDRNSTAT presence, and 66 days (3163 visits) to the nurse-only triage control cluster. The primary outcome was emergency department length-of-stay (EDLOS) for patients managed and discharged only by the emergency department. Secondary outcomes included EDLOS for patients initially seen by the emergency department, and subsequently consulted and admitted, patients reaching government-mandated thresholds, time to initial physician assessment, left-without being seen rate, time to investigation, and measurement of harm. RESULTS: The intervention's median EDLOS for discharged, non-consulted, high acuity patients was 4:05 [95th% CI: 3:58 to 4:15] versus 4:29 [95th% CI: 4:19-4:38] during comparator shifts. The intervention's median EDLOS for discharged, non-consulted, low acuity patients was 1:55 [95th% CI: 1:48 to 2:05] versus 2:08 [95th% CI: 2:02-2:14]. The intervention's median physician initial assessment time was 0:55 [95th% CI: 0:53 to 0:58] versus 1:21 [95th% CI: 1:18 to 1:25]. The intervention's left-without-being-seen rate was 1.5% versus 2.2% for the control (p = 0.06). The MDRNSTAT subgroup analysis resulted in significant decreases in median EDLOS for discharged, non-consulted high (4:01 [95th% CI: 3:43-4:16]) and low acuity patients (1:10 95th% CI: 0:58-1:19]), as well as physician initial assessment time (0:25 [95th% CI: 0:23-0:26]). No patients returned to the emergency department after being discharged by the MDRNSTAT at triage. CONCLUSIONS: The intervention reduced delays and left-without-being-seen rate without increased return visits or jeopardizing urgent care of severely ill patients. TRIAL REGISTRATION NUMBER: NCT00991471 ClinicalTrials.gov.

Randomized, double-blinded, placebo-controlled, trial of risedronate for the prevention of bone mineral density loss in nonmetastatic prostate cancer patients receiving radiation therapy plus androgen deprivation therapy.

PURPOSE: Androgen deprivation therapy (ADT) has been used as an adjuvant treatment to radiation therapy (RT) for the management of locally advanced prostate carcinoma. Long-term ADT decreases bone mineral density (BMD) and increases the risk of osteoporosis. The objective of this clinical trial was to evaluate the efficacy of risedronate for the prevention of BMD loss in nonmetastatic prostate cancer patients undergoing RT plus 2 to 3 years of ADT. METHODS AND MATERIALS: A double-blinded, placebo-controlled, randomized trial was conducted for nonmetastatic prostate cancer patients receiving RT plus 2 to 3 years of ADT. All had T scores > -2.5 on dual energy x-ray absorptiometry at baseline. Patients were randomized 1:1 between risedronate and placebo for 2 years. The primary endpoints were the percent changes in the BMD of the lumbar spine at 1 and 2 years from baseline, measured by dual energy x-ray absorptiometry. Analyses of the changes in BMD and bone turnover biomarkers were carried out by comparing mean values of the intrapatient changes between the 2 arms, using standard t tests. RESULTS: One hundred four patients were accrued between 2004 and 2007, with 52 in each arm. Mean age was 66.8 and 67.5 years for the placebo and risedronate, respectively. At 1 and 2 years, mean (±SE) BMD of the lumbar spine decreased by 5.77% ± 4.66% and 13.55% ± 6.33%, respectively, in the placebo, compared with 0.12% ± 1.29% at 1 year (P=.2485) and 0.85% ± 1.56% (P=.0583) at 2 years in the risedronate. The placebo had a significant increase in serum bone turnover biomarkers compared with the risedronate. CONCLUSIONS: Weekly oral risedronate prevented BMD loss at 2 years and resulted in significant suppression of bone turnover biomarkers for 24 months for patients receiving RT plus 2 to 3 years of ADT.

Patient outcome study of concurrent chemoradiation, external beam radiotherapy, and high-dose rate brachytherapy in locally advanced carcinoma of the cervix.

INTRODUCTION: A regimen of concurrent chemoradiation for definitive treatment of cervical cancer is widely used. This retrospective review has been conducted to determine the outcomes and late toxic effect associated with the specific regimen of whole-pelvic external beam radiotherapy of 45 Gy in 25 fractions with parametrial boosts of 5.4 or 9 Gy and HDR brachytherapy (BT) of 30 Gy in 5 fractions to point A delivered by tandem and ring. This protocol is accepted by the Gynecological Oncology Group and endorsed by the American Brachytherapy Society, but no late toxic effect data have been reported. MATERIALS AND METHODS: The electronic records of sequential patients treated definitively at the Sunnybrook Odette Cancer Centre between January 2006 and December 2008 were reviewed. Patient-, tumor-, and treatment-related details (including external beam radiotherapy, BT, and chemotherapy) were obtained. Outcome measures included disease-free status, dates and sites of first recurrence, survival, and grade 3/4 late toxic effect results (Common Terminology Criteria Adverse Events 3.0 criteria). Exclusion criteria were no follow-up or a planned alternative regimen. RESULTS: One hundred twenty-two patients (+11 excluded) were treated with a median follow-up of 18 months from diagnosis. The actuarial 2-year disease-free survival rate was 70%. The median time to recurrence was 8 months (range, 2-22 months). The median time to toxic effect was 10 months (range 4-27 months). Grade 3/4 toxic effect was observed in 13 patients (11%). The actuarial grade 3/4 toxic effect rate at 2 years was 14%. CONCLUSIONS: Despite a relatively short follow-up, the toxicity of this regimen seems high compared with other retrospective series, although pelvic control is good. Consideration should be given to a reduction in BT dose alternatively when feasible image-guided BT may allow maintenance of tumor dose with reduced dose to organs at risk.

A randomized controlled trial of the effect of dietary soy and flaxseed muffins on quality of life and hot flashes during menopause.

OBJECTIVE: To compare the effects of daily ingestion of soy flour (S), ground flaxseed (F), or wheat flour (W) muffins, on quality of life and hot flash frequency and severity in postmenopausal women. DESIGN: This was a double-blind, randomized, controlled, intention-to-treat trial. Ninety-nine women, 1 to 8 years after menopause, ingested muffins with 25 g of flaxseed (50 mg of lignans), 25 g of soy (42 mg of isoflavones), or wheat (control) daily for 16 weeks. Subjects completed the Menopause-specific Quality of Life instrument monthly along with daily hot flash frequency and severity diaries. Compliance measures included a 3-day food diary and urinary isoflavone and lignan analyses at weeks 0 and 16 and returned muffin counts monthly. RESULTS: Eighty-seven women (28, ground flaxseed muffins; 31, soy flour muffins; and 28, wheat flour muffins) completed the trial. Multivariate analysis of variance of all quality-of-life domains yielded an insignificant treatment x time interaction (F46,122 = 0.92, P = 0.62) but a significant time main effect (P <.0001). Repeated-measures analyses of covariance controlling for body mass index showed no significant group x time interaction nor time nor group differences on all quality-of-life domains and hot flash measures except severity. Hot flashes were less severe with flaxseed (P = 0.001) compared to placebo; however, the group x by time interaction was not significant. Phytoestrogen excretion analysis showed treatment group exposure as allocated and no contamination. CONCLUSION: Neither dietary flaxseed nor soy flour significantly affected menopause-specific quality of life or hot flash symptoms in this study.