Reducing saturated fat intake lowers LDL-C but increases Lp(a) levels in African Americans: the GET-READI feeding trial.

Reducing dietary saturated fatty acids (SFA) intake results in a clinically significant lowering of low-density lipoprotein cholesterol (LDL-C) across ethnicities. In contrast, dietary SFA's role in modulating emerging cardiovascular risk factors in different ethnicities remains poorly understood. Elevated levels of lipoprotein(a) [Lp(a)], an independent cardiovascular risk factor, disproportionally affect individuals of African descent. Here, we assessed the responses in Lp(a) levels to dietary SFA reduction in 166 African Americans enrolled in GET-READI (The Gene-Environment Trial on Response in African Americans to Dietary Intervention), a randomized controlled feeding trial. Participants were fed two diets in random order for 5 weeks each: 1) an average American diet (AAD) (37% total fat: 16% SFA), and 2) a diet similar to the Dietary Approaches to Stop Hypertension (DASH) diet (25% total fat: 6% SFA). The participants' mean age was 35 years, 70% were women, the mean BMI was 28 kg/m2, and the mean LDL-C was 116 mg/dl. Compared to the AAD diet, LDL-C was reduced by the DASH-type diet (mean change: -12 mg/dl) as were total cholesterol (-16 mg/dl), HDL-C (-5 mg/dl), apoA-1 (-9 mg/dl) and apoB-100 (-5 mg/dl) (all P < 0.0001). In contrast, Lp(a) levels increased following the DASH-type diet compared with AAD (median: 58 vs. 44 mg/dl, P < 0.0001). In conclusion, in a large cohort of African Americans, reductions in SFA intake significantly increased Lp(a) levels while reducing LDL-C. Future studies are warranted to elucidate the mechanism(s) underlying the SFA reduction-induced increase in Lp(a) levels and its role in cardiovascular risk across populations.

No effect of a dairy-based, high flavonoid pre-workout beverage on exercise-induced intestinal injury, permeability, and inflammation in recreational cyclists: A randomized controlled crossover trial.

BACKGROUND: Submaximal endurance exercise has been shown to cause elevated gastrointestinal permeability, injury, and inflammation, which may negatively impact athletic performance and recovery. Preclinical and some clinical studies suggest that flavonoids, a class of plant secondary metabolites, may regulate intestinal permeability and reduce chronic low-grade inflammation. Consequently, the purpose of this study was to determine the effects of supplemental flavonoid intake on intestinal health and cycling performance. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled crossover trial was conducted with 12 cyclists (8 males and 4 females). Subjects consumed a dairy milk-based, high or low flavonoid (490 or 5 mg) pre-workout beverage daily for 15 days. At the end of each intervention, a submaximal cycling trial (45 min, 70% VO2max) was conducted in a controlled laboratory setting (23°C), followed by a 15-minute maximal effort time trial during which total work and distance were determined. Plasma samples were collected pre- and post-exercise (0h, 1h, and 4h post-exercise). The primary outcome was intestinal injury, assessed by within-subject comparison of plasma intestinal fatty acid-binding protein. Prior to study start, this trial was registered at ClinicalTrials.gov (NCT03427879). RESULTS: A significant time effect was observed for intestinal fatty acid binding protein and circulating cytokines (IL-6, IL-10, TNF-α). No differences were observed between the low and high flavonoid treatment for intestinal permeability or injury. The flavonoid treatment tended to increase cycling work output (p = 0.051), though no differences were observed for cadence or total distance. DISCUSSION: Sub-chronic supplementation with blueberry, cocoa, and green tea in a dairy-based pre-workout beverage did not alleviate exercise-induced intestinal injury during submaximal cycling, as compared to the control beverage (dairy-milk based with low flavonoid content).

Comparison of growth and survival of single strains of Lactococcus lactis and Lactococcus cremoris during Cheddar cheese manufacture.

Traditionally, starter cultures for Cheddar cheese are combinations of Lactococcus lactis and Lactococcus cremoris. Our goal was to compare growth and survival of individual strains during cheesemaking, and after salting and pressing. Cultures used were 2 strains of L. lactis (SSM 7605, SSM 7436) and 2 strains of L. cremoris (SSM 7136, SSM 7661). A standardized Cheddar cheese make procedure was used that included a 38°C cook temperature and salting levels of 2.0, 2.4, 2.8, 3.2, and 3.6% from which were selected cheeses with salt-in-moisture levels of 3.5, 4.5, and 5.5%. Vats of cheese were made using each strain on its own as biological duplicates on different days. Starter culture numbers were enumerated by plate counting during cheesemaking and after 6 d storage at 6°C. Flow cytometry with fluorescent staining by SYBR Green and propidium iodide was used to determine the number of live and dead cells in cheese at the different salt levels. Differences in cheese make times were strain dependent rather than species dependent. Even with correction for average culture chain length, cheeses made using L. lactis strains contained ∼4 times (∼0.6 log) more bacterial cells than those made using L. cremoris strains. Growth of the strains used in this study was not influenced by the amount of salt added to the curd. The higher pH of cheeses with higher salting levels was attributed to those cheeses having a lower moisture content. Based on flow cytometry, ∼5% of the total starter culture cells in the cheese were dead after 6 d of storage. Another 3 to 19% of the cells were designated as being live, but semipermeable, with L. cremoris strains having the higher number of semipermeable cells.

Beyond the project: Building a strategic theory of change to address dementia care, treatment and support gaps across seven middle-income countries.

Evidence from middle-income countries indicates high and increasing prevalence of dementia and need for services. However, there has been little investment in care, treatment or support for people living with dementia and their carers. The Strengthening Responses to Dementia in Developing Countries (STRiDE) project aims to build both research capacity and evidence on dementia care and services in Brazil, Indonesia, India, Jamaica, Kenya, Mexico and South Africa. This article presents the Theory of Change (ToC) approach we used to co-design our research project and to develop a strategic direction for dementia care, treatment and support, with stakeholders. ToC makes explicit the process underlying how a programme will achieve its impact. We developed ToCs in each country and across the STRiDE project with researchers, practitioners, people living with dementia, carers and policymakers at different levels of government. This involved (1) an initial ToC workshop with all project partners (43 participants); (2) ToC workshops in each STRiDE country (22-49 participants in each); (3) comparison between country-specific and overall project ToCs; (4) review of ToCs in light of WHO dementia guidelines and action plan and (5) a final review. Our experiences suggest ToC is an effective way to generate a shared vision for dementia care, treatment and support among diverse stakeholders. However, the project contribution should be clearly delineated and use additional strategies to ensure appropriate participation from people living with dementia and their carers in the ToC process.

Home blood pressure data visualization for the management of hypertension: using human factors and design principles.

BACKGROUND: Home blood pressure measurements have equal or even greater predictive value than clinic blood pressure measurements regarding cardiovascular outcomes. With advances in home blood pressure monitors, we face an imminent flood of home measurements, but current electronic health record systems lack the functionality to allow us to use this data to its fullest. We designed a data visualization display for blood pressure measurements to be used for shared decision making around hypertension. METHODS: We used an iterative, rapid-prototyping, user-centred design approach to determine the most appropriate designs for this data display. We relied on visual cognition and human factors principles when designing our display. Feedback was provided by expert members of our multidisciplinary research team and through a series of end-user focus groups, comprised of either hypertensive patients or their healthcare providers required from eight academic, community-based practices in the Midwest of the United States. RESULTS: A total of 40 participants were recruited to participate in patient (N = 16) and provider (N = 24) focus groups. We describe the conceptualization and development of data display for shared decision making around hypertension. We designed and received feedback from both patients and healthcare providers on a number of design elements that were reported to be helpful in understanding blood pressure measurements. CONCLUSIONS: We developed a data display for substantial amounts of blood pressure measurements that is both simple to understand for patients, but powerful enough to inform clinical decision making. The display used a line graph format for ease of understanding, a LOWESS function for smoothing data to reduce the weight users placed on outlier measurements, colored goal range bands to allow users to quickly determine if measurements were in range, a medication timeline to help link recorded blood pressure measurements with the medications a patient was taking. A data display such as this, specifically designed to encourage shared decision making between hypertensive patients and their healthcare providers, could help us overcome the clinical inertia that often results in a lack of treatment intensification, leading to better care for the 35 million Americans with uncontrolled hypertension.

Home blood pressure data visualization for the management of hypertension: designing for patient and physician information needs.

BACKGROUND: Nearly half of US adults with diagnosed hypertension have uncontrolled blood pressure. Clinical inertia may contribute, including patient-physician uncertainty about how variability in blood pressures impacts overall control. Better information display may support clinician-patient hypertension decision making through reduced cognitive load and improved situational awareness. METHODS: A multidisciplinary team employed iterative user-centered design to create a blood pressure visualization EHR prototype that included patient-generated blood pressure data. An attitude and behavior survey and 10 focus groups with patients (N = 16) and physicians (N = 24) guided iterative design and confirmation phases. Thematic analysis of qualitative data yielded insights into patient and physician needs for hypertension management. RESULTS: Most patients indicated measuring home blood pressure, only half share data with physicians. When receiving home blood pressure data, 88% of physicians indicated entering gestalt averages as text into clinical notes. Qualitative findings suggest that including a data visualization that included home blood pressures brought this valued data into physician workflow and decision-making processes. Data visualization helps both patients and physicians to have a fuller understanding of the blood pressure 'story' and ultimately promotes the activated engaged patient and prepared proactive physician central to the Chronic Care Model. Both patients and physicians expressed concerns about workflow for entering and using home blood pressure data for clinical care. CONCLUSIONS: Our user-centered design process with physicians and patients produced a well-received blood pressure visualization prototype that includes home blood pressures and addresses patient-physician information needs. Next steps include evaluating a recent EHR visualization implementation, designing annotation functions aligned with users' needs, and addressing additional stakeholders' needs (nurses, care managers, caregivers). This significant innovation has potential to improve quality of care for hypertension through better patient-physician understanding of control and goals. It also has the potential to enable remote monitoring of patient blood pressure, a newly reimbursed activity, and is a strong addition to telehealth efforts.

Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men.

BACKGROUND: Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO response. METHODS: In a randomized, controlled, double-blinded, crossover study, healthy men (n = 37) were provided meals containing 600 mg choline either as choline bitartrate or phosphatidylcholine, or no choline control. RESULTS: Choline bitartrate yielded three-times greater plasma TMAO AUC (p = 0.01) and 2.5-times greater urinary TMAO change from baseline (p = 0.01) compared to no choline and phosphatidylcholine. Gut microbiota composition differed (permutational multivariate analysis of variance, PERMANOVA; p = 0.01) between high-TMAO producers (with ≥40% increase in urinary TMAO response to choline bitartrate) and low-TMAO producers (with <40% increase in TMAO response). High-TMAO producers had more abundant lineages of Clostridium from Ruminococcaceae and Lachnospiraceae compared to low-TMAO producers (analysis of composition of microbiomes, ANCOM; p < 0.05). CONCLUSION: Given that phosphatidylcholine is the major form of choline in food, the absence of TMAO elevation with phosphatidylcholine counters arguments that phosphatidylcholine should be avoided due to TMAO-producing characteristics. Further, development of individualized dietary recommendations based on the gut microbiome may be effective in reducing disease risk.

The Type and Amount of Dietary Fat Affect Plasma Factor VIIc, Fibrinogen, and PAI-1 in Healthy Individuals and Individuals at High Cardiovascular Disease Risk: 2 Randomized Controlled Trials.

BACKGROUND: Factor VIIc, fibrinogen, and plasminogen activator inhibitor 1 (PAI-1) are cardiovascular disease (CVD) risk factors and are modulated, in part, by fat type and amount. OBJECTIVE: We evaluated fat type and amount on the primary outcomes: factor VIIc, fibrinogen, and PAI-1. METHODS: In the Dietary Effects on Lipoproteins and Thrombogenic Activity (DELTA) Trial, 2 controlled crossover feeding studies evaluated substituting carbohydrate or MUFAs for SFAs. Study 1: healthy participants (n = 103) were provided with (8 wk) an average American diet [AAD; designed to provide 37% of energy (%E) as fat, 16% SFA], a Step 1 diet (30%E fat, 9% SFA), and a diet low in SFA (Low-Sat; 26%E fat, 5% SFA). Study 2: participants (n = 85) at risk for CVD and metabolic syndrome (MetSyn) were provided with (7 wk) an AAD, a step 1 diet, and a high-MUFA diet (designed to provide 37%E fat, 8% SFA, 22% MUFA). RESULTS: Study 1: compared with AAD, the Step 1 and Low-Sat diets decreased mean factor VIIc by 1.8% and 2.6% (overall P = 0.0001), increased mean fibrinogen by 1.2% and 2.8% (P = 0.0141), and increased mean square root PAI-1 by 0.0% and 6.0% (P = 0.0037), respectively. Study 2: compared with AAD, the Step 1 and high-MUFA diets decreased mean factor VIIc by 4.1% and 3.2% (overall P < 0.0001), increased mean fibrinogen by 3.9% and 1.5% (P = 0.0083), and increased mean square-root PAI-1 by 2.0% and 5.8% (P = 0.1319), respectively. CONCLUSIONS: Replacing SFA with carbohydrate decreased factor VIIc and increased fibrinogen in healthy and metabolically unhealthy individuals and also increased PAI-1 in healthy subjects. Replacing SFA with MUFA decreased factor VIIc and increased fibrinogen but less than carbohydrate. Our results indicate an uncertain effect of replacing SFA with carbohydrate or MUFA on cardiometabolic risk because of small changes in hemostatic factors and directionally different responses to decreasing SFA. This trial was registered at https://clinicaltrials.gov/ct2/show/NCT00000538?term=NCT00000538&rank=1 as NCT00000538.

Home Blood Pressure Monitoring in Cases of Clinical Uncertainty to Differentiate Appropriate Inaction From Therapeutic Inertia.

PURPOSE: Conventional clinic blood pressure (BP) measurements are routinely used for hypertension management and physician performance measures. We aimed to check home BP measurements after elevated conventional clinic BP measurements for which physicians did not intensify treatment, to differentiate therapeutic inertia from appropriate inaction. METHODS: We conducted a pre and post study of home BP monitoring for patients with uncontrolled hypertension as determined by conventional clinic BP measurements for which physicians did not intensify hypertension management. Physicians were notified of average home BP 2-4 weeks after the initial clinic visit. Outcome measures were the proportion of patients with controlled hypertension using average home BP measurements, changes in hypertension management by physicians, changes in physicians' hypertension metrics, and factors associated with home-clinic BP differences. RESULTS: Of 90 recruited patients who had elevated conventional clinic BP recordings, 65.6% had average home BP measurements that were <140/90 mm Hg. Physicians changed treatment plans for 61% of patients with average home BP readings of ≥140/90 mm Hg, whereas decisions to not change treatment for the remaining patients were based on contextual factors. Substituting average home BP for conventional clinic BP for 4% of patients from 2 physicians' hypertension registries improved the physicians' hypertension control rates by 3% to 5%. Greater body mass index and increased number of BP medications were associated with home BP measurement ≥140/90 mm Hg. Clinic BP levels did not estimate normal home BP levels. CONCLUSIONS: Documented home BP in cases of clinical uncertainty helped differentiate therapeutic inertia from appropriate inaction and improved physicians' hypertension metrics.

Report From the FMAHealth Practice Core Team: Achieving the Quadruple Aim Through Practice Transformation.

Family Medicine for America's Health (FMAHealth) is a strategic planning organization effort that was created out of the reevaluation of the first Future of Family Medicine project from 2004. This article is a summary of the key findings of the FMAHealth Practice Core Team. At the highest level, we find that family medicine practices have compelling intrinsic and extrinsic reasons to evolve to new models of care delivery. We have demonstrated that payment transformation is imperative to successful practice transformation and that comprehensive payment models that include attention to physician work within the social determinants of health and require fewer administrative burdens will be key to achieving the quadruple aim. To bridge payment reform and practice transformation will require better and fewer measures of physician effectiveness in order to allow the physician-patient dyad to thrive in these new models. Achieving these goals will require a sustained national effort involving not only the many family medicine membership organizations, but their collaborative work with others in the health care transformation industry who may not have been our traditional partners. Educational initiatives must be robust, available to all family physicians regardless of professional organization membership, and focused on meeting physicians and physician practice managers where they are with the goal of moving them toward a state of more advanced care delivery. This article outlines the work done by the FMAHealth Practice Team that supports the above assertions.

The role of home BP monitoring: Answers to 10 common questions.

How does home BP monitoring stack up against clinic and ambulatory measurements for the Dx and management of hypertension? Find out in this review.

Vitamin D Screening and Supplementation in Community-Dwelling Adults: Common Questions and Answers.

Measurement of vitamin D levels and supplementation with oral vitamin D have become commonplace, although clinical trials have not demonstrated health benefits. The usefulness of serum 25-hydroxyvitamin D levels to assess adequate exposure to vitamin D is hampered by variations in measurement technique and precision. Serum levels less than 12 ng per mL reflect inadequate vitamin D intake for bone health. Levels greater than 20 ng per mL are adequate for 97.5% of the population. Routine vitamin D supplementation does not prolong life, decrease the incidence of cancer or cardiovascular disease, or decrease fracture rates. Screening asymptomatic individuals for vitamin D deficiency and treating those considered to be deficient do not reduce the risk of cancer, type 2 diabetes mellitus, or death in community-dwelling adults, or fractures in persons not at high risk of fractures. Randomized controlled trials of vitamin D supplementation in the treatment of depression, fatigue, osteoarthritis, and chronic pain show no benefit, even in persons with low levels at baseline.

Update on the Methods of the U.S. Preventive Services Task Force: Methods for Understanding Certainty and Net Benefit When Making Recommendations.

Since the 1980s, the U.S. Preventive Services Task Force (USPSTF) has developed and used rigorous methods to make evidence-based recommendations about preventive services to promote health and well-being for all Americans. Recommendations are based on the evidence of magnitude of net benefit (benefits minus harms). Expert opinion is not substituted when evidence is lacking. Evidence gaps are common. Few preventive services are supported by high-quality studies that directly and comprehensively determine the overall magnitude of benefits and harms in the same study. When assessing the body of evidence, studies may not have been conducted in primary care settings, studies may not have sufficiently included populations of interest, and long-term outcomes may not have been directly assessed. When direct evidence is not available, the USPSTF uses the methodologies of applicability to determine whether evidence can be generalized to an asymptomatic primary care population; coherence to link bodies of evidence and create an indirect evidence pathway; extrapolation to make inferences across the indirect evidence pathway, extend evidence to populations not specifically studied, consider service delivery intervals, and infer long-term outcomes; and conceptual bounding to set theoretical lower or upper limits for plausible benefits or harms. The USPSTF extends the evidence only so far as to maintain at least moderate certainty that its findings are preserved. This manuscript details with examples of how the USPSTF uses these methods to make recommendations that truly reflect the evidence.

Update on the Methods of the U.S. Preventive Services Task Force: Linking Intermediate Outcomes and Health Outcomes in Prevention.

The U.S. Preventive Services Task Force (USPSTF) is an independent body of experts who make evidence-based recommendations about clinical preventive services using a transparent and objective process. Developing recommendations on a clinical preventive service requires evidence of its effect on health outcomes. Health outcomes are symptoms, functional levels, and conditions that affect a patient's quantity or quality of life and are measured by assessments of physical or psychologic well-being. Intermediate outcomes are pathologic, physiologic, psychologic, social, or behavioral measures related to a preventive service. Given the frequent lack of evidence on health outcomes, the USPSTF uses evidence on intermediate outcomes when appropriate. The ultimate goal is to determine precisely a consistent relationship between the direction and magnitude of change in an intermediate outcome with a predictable resultant direction and magnitude of change in the health outcomes. The USPSTF reviewed its historical use of intermediate outcomes, reviewed methods of other evidence-based guideline-making bodies, consulted with other experts, and reviewed scientific literature. Most important were the established criteria for causation, tenets of evidence-based medicine, and consistency with its current standards. Studies that follow participants over time following early treatment, stratify patients according to treatment response, and adjust for important confounders can provide useful information about the association between intermediate and health outcomes. However, such studies remain susceptible to residual confounding. The USPSTF will exercise great caution when making a recommendation that depends on the evidence linking intermediate and health outcomes because of inherent evidence limitations.

SigTree: A Microbial Community Analysis Tool to Identify and Visualize Significantly Responsive Branches in a Phylogenetic Tree.

Microbial community analysis experiments to assess the effect of a treatment intervention (or environmental change) on the relative abundance levels of multiple related microbial species (or operational taxonomic units) simultaneously using high throughput genomics are becoming increasingly common. Within the framework of the evolutionary phylogeny of all species considered in the experiment, this translates to a statistical need to identify the phylogenetic branches that exhibit a significant consensus response (in terms of operational taxonomic unit abundance) to the intervention. We present the R software package SigTree, a collection of flexible tools that make use of meta-analysis methods and regular expressions to identify and visualize significantly responsive branches in a phylogenetic tree, while appropriately adjusting for multiple comparisons.

Sexually Transmitted Infections: Recommendations from the U.S. Preventive Services Task Force.

The U.S. Preventive Services Task Force (USPSTF) has issued recommendations on behavioral counseling to prevent sexually transmitted infections (STIs) and recommendations about screening for individual STIs. Clinicians should obtain a sexual history to assess for behaviors that increase a patient's risk. Community and population risk factors should also be considered. The USPSTF recommends intensive behavioral counseling for all sexually active adolescents and for adults whose history indicates an increased risk of STIs. These interventions can reduce STI acquisition and risky sexual behaviors, and increase condom use and other protective behaviors. The USPSTF recommends screening for chlamydia and gonorrhea in all sexually active women 24 years and younger, and in older women at increased risk. It recommends screening for human immunodeficiency virus (HIV) infection in all patients 15 to 65 years of age regardless of risk, as well as in younger and older patients at increased risk of HIV infection. The USPSTF also recommends screening for hepatitis B virus infection and syphilis in persons at increased risk. All pregnant women should be tested for hepatitis B virus infection, HIV infection, and syphilis. Pregnant women 24 years and younger, and older women with risk factors should be tested for gonorrhea and chlamydia. The USPSTF recommends against screening for asymptomatic herpes simplex virus infection. There is inadequate evidence to determine the optimal interval for repeat screening; clinicians should rescreen patients when their sexual history reveals new or persistent risk factors.