Effectiveness of dietary inorganic nitrate for lowering blood pressure in hypertensive adults: a systematic review.

OBJECTIVE: The objective of this review was to evaluate the effectiveness of inorganic nitrate on blood pressure in hypertensive adults. INTRODUCTION: Hypertension is associated with increased risk of morbidity and mortality in adults. Inorganic nitrate could be beneficial for lowering blood pressure and reducing cardiovascular disease risks. Evidence related to the treatment of hypertension through sources of inorganic nitrate has been presented. INCLUSION CRITERIA: The review considered studies on adults aged 18 years and over, with blood pressure greater than 120/80 mmHg, undergoing interventions focusing on the effects of inorganic nitrate on blood pressure. Studies that included inorganic nitrate intake via dietary modification, in the form of a dietary supplement, and/or by the consumption of beetroot juice were considered. The comparator was no intervention of inorganic nitrate; different dosage, frequency, duration of inorganic nitrate; and other interventions that are administered to reduce and manage blood pressure. The primary outcomes were systolic and diastolic blood pressure effects. Experimental, quasi-experimental, analytical observational and pilot study designs were considered for inclusion. METHODS: Databases were searched for published and unpublished studies, available in English, from January 2013 to January 2018. Critical appraisal was conducted using standardized instruments from the Joanna Briggs Institute (JBI) and the methodological quality of included studies was considered to be moderate. Data were extracted using the JBI data extraction instrument. Data were presented in a narrative form due to the heterogeneity of included studies. RESULTS: Twelve papers were included in the systematic review with a total of 321 participants. Ten were randomized controlled trials and two were quasi-experimental studies. All participants had baseline blood pressures greater than 120/80 mmHg. Some studies included participants with comorbidities such as diabetes or heart failure with preserved ejection fraction. Inorganic nitrate was administered multiple ways throughout the studies including the following: beetroot juice, beetroot gel, nitric oxide lozenge, high nitrate diet, and raw and cooked beet juice. Doses and treatment intervals varied. Some studies included exercise as part of the intervention protocol.Meta-analysis was not conducted due to heterogeneity that existed within the studies. Blood pressure was measured in multiple settings by manual, digital or ambulatory means. The noted outcome patterns were as follows: no change in systolic blood pressure and diastolic blood pressure, decrease in systolic blood pressure and diastolic blood pressure, or decrease in systolic blood pressure with no change in diastolic blood pressure. Possible reasons for the diverse findings include the following: age, comorbidities, use of antihypertensives by participants; source and dose of nitrate; and intervention and follow-up time frames. CONCLUSIONS: There is insufficient evidence to support or refute the use of inorganic nitrate for any effect on blood pressure at this time. Therefore, there is no concrete base for the development of practice guidelines until stronger evidence becomes available. The gaps in the literature along with the study limitations identified necessitate the need for more research on inorganic nitrate and how it relates to blood pressure.

Acupuncture for gender differences and similarities in cerebral activity of health volunteers: A pilot fMRI study.

This study aimed to explore the feasible gender differences and similarities in cerebral activity response to the acupuncture at local acupoints around knee.Fifteen male and 15 female healthy adults were recruited and included in this study. Functional magnetic resonance imaging (fMRI) was applied to measure cerebral activity response to acupuncture at Liangqiu (ST34), Xuehai (SP-10), Neixiyan (EX-LE4), and Dubi (ST-35).Acupuncture activated the postcentral gyrus, precuneus, temporal, posterior lobe, and occipital lobe in both males and females. When compared with females, males showed brain activation in the right middle frontal gyrus, inferior frontal gyrus, right precuneus, right superior parietal lobule, left cerebellum anterior lobe; and brain deactivation in the right frontal. When compared with males, females were observed brain activation in the right frontal lobe, right parietal lobe, and right middle temporal gyrus; and brain deactivation in the left and right medial frontal gyrus.The results of this study demonstrated that the neural effects of local acupoints around knee might be different between male and female subjects. Further clinical trials should take this gender effect into account in their design of studies.

Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer: Final Results of a Multicenter Phase II Trial.

BACKGROUND: Adding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval is associated with an increase in the proportion of rectal cancer patients with a pathological complete response. OBJECTIVE: The purpose of this study was to analyze disease-free and overall survival. DESIGN: This was a nonrandomized phase II trial. SETTINGS: The study was conducted at multiple institutions. PATIENTS: Four sequential study groups with stage II or III rectal cancer were included. INTERVENTION: All of the patients received 50 Gy of radiation with concurrent continuous infusion of fluorouracil for 5 weeks. Patients in each group received 0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total mesorectal excision. Patients were recommended to receive adjuvant chemotherapy after surgery to complete a total of 8 cycles of modified FOLFOX6. MAIN OUTCOME MEASURES: The trial was powered to detect differences in pathological complete response, which was reported previously. Disease-free and overall survival are the main outcomes for the current study. RESULTS: Of 259 patients, 211 had a complete follow-up. Median follow-up was 59 months (range, 9-125 mo). The mean number of total chemotherapy cycles differed among the 4 groups (p = 0.002), because one third of patients in the group assigned to no preoperative FOLFOX did not receive any adjuvant chemotherapy. Disease-free survival was significantly associated with study group, ypTNM stage, and pathological complete response (p = 0.004, <0.001, and 0.001). A secondary analysis including only patients who received ≥1 cycle of FOLFOX still showed differences in survival between study groups (p = 0.03). LIMITATIONS: The trial was not randomized and was not powered to show differences in survival. Survival data were not available for 19% of the patients. CONCLUSIONS: Adding modified FOLFOX6 after chemoradiotherapy and before total mesorectal excision increases compliance with systemic chemotherapy and disease-free survival in patients with locally advanced rectal cancer. Neoadjuvant consolidation chemotherapy may have benefits beyond increasing pathological complete response rates. See Video Abstract at http://links.lww.com/DCR/A739.