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Messenger RNA and MicroRNA transcriptomic signatures of cardiometabolic risk factors

Wed, 03/15/2017 - 10:27pm

BACKGROUND: Cardiometabolic (CM) risk factors are heritable and cluster in individuals. We hypothesized that CM risk factors are associated with multiple shared and unique mRNA and microRNA (miRNA) signatures. We examined associations of mRNA and miRNA levels with 6 CM traits: body mass index, HDL-cholesterol and triglycerides, fasting glucose, and systolic and diastolic blood pressures through cross-sectional analysis of 2812 Framingham Heart Study who had whole blood collection for RNA isolation for mRNA and miRNA expression studies and who consented to genetic research. We excluded participants taking medication for hypertension, dyslipidemia, or diabetes. We measured mRNA (n = 17,318; using the Affymetrix GeneChip Human Exon 1.0 ST Array) and miRNA (n = 315; using qRT-PCR) expression in whole blood. We used linear regression for mRNA analyses and a combination of linear and logistic regression for miRNA analyses. We conducted miRNA-mRNA coexpression and gene ontology enrichment analyses to explore relations between pleiotropic miRNAs, mRNA expression, and CM trait clustering.

RESULTS: We identified hundreds of significant associations between mRNAs, miRNAs, and individual CM traits. Four mRNAs (FAM13A, CSF2RB, HIST1H2AC, WNK1) were associated with all 6 CM traits (FDR < 0.001) and four miRNAs (miR-197-3p, miR-328, miR-505-5p, miR-145-5p) were associated with four CM traits (FDR < 0.05). Twelve mRNAs, including WNK1, that were coexpressed with the four most pleiotropic miRNAs, were also miRNA targets. mRNAs coexpressed with pleiotropic miRNAs were enriched for RNA metabolism (miR-505-5p), ubiquitin-dependent protein catabolism (miR-197-3p, miR-328) and chromatin assembly (miR-328).

CONCLUSIONS: We identified mRNA and miRNA signatures of individual CM traits and their clustering. Implicated transcripts may play causal roles in CM risk or be downstream consequences of CM risk factors on the transcriptome. Studies are needed to establish whether or not pleiotropic circulating transcripts illuminate causal pathways for CM risk.

Hospice Use and Pain Management in Elderly Nursing Home Residents With Cancer

Wed, 03/15/2017 - 10:27pm

CONTEXT: Pain management is suboptimal in nursing homes.

OBJECTIVES: To estimate the extent to which receipt of hospice in nursing homes (NHs) increases the receipt of pain management for residents with cancer at the end of life.

METHODS: Study participants included Medicare beneficiaries with cancer who were NH residents in the last 90 days of life in 2011-2012 (n = 78,160). Residents in pain on hospice were matched to like residents without hospice by facility, type of pain assessment (self-report/staff assessment), and weeks until death (9064 matched strata, 16,968 unique residents). Minimum Data Set 3.0 provided information on residents' pain prevalence and receipt of pain management (scheduled analgesics, as needed [pro re nata {PRN}] medication, nonpharmacologic interventions). We developed conditional logistic models to estimate the association between hospice use and pain management, stratified by self-reported and staff-assessed pain.

RESULTS: We found that pain prevalence was higher in residents using hospice versus those without hospice (e.g., residents who self-reported pain: hospice: 59.9%, 95% CIs = 59.3%-60.5%; nonhospice: 50.0%, 95% CI = 49.4%-50.6%). In matched analyses, untreated pain was uncommon (self-reported pain: 2.9% and 5.6% in hospice users and nonusers, respectively). Hospice use was associated with receipt of scheduled analgesics (self-reported: adjusted odds ratio = 1.85, 95% CI = 1.73-1.971) and PRN medication (self-reported: adjusted odds ratio = 1.31, 95% CI = 1.20-1.43). Pain prevalence and the association between hospice and pain management were similar in residents with staff-assessed pain.

CONCLUSION: Untreated pain at the end of life among residents with cancer in NHs is unusual. Hospice is associated with increased pain management among those with documented pain.

Citrullination-acetylation interplay guides E2F-1 activity during the inflammatory response

Wed, 03/15/2017 - 5:01pm

Peptidyl arginine deiminase 4 (PAD4) is a nuclear enzyme that converts arginine residues to citrulline. Although increasingly implicated in inflammatory disease and cancer, the mechanism of action of PAD4 and its functionally relevant pathways remains unclear. E2F transcription factors are a family of master regulators that coordinate gene expression during cellular proliferation and diverse cell fates. We show that E2F-1 is citrullinated by PAD4 in inflammatory cells. Citrullination of E2F-1 assists its chromatin association, specifically to cytokine genes in granulocyte cells. Mechanistically, citrullination augments binding of the BET (bromodomain and extra-terminal domain) family bromodomain reader BRD4 (bromodomain-containing protein 4) to an acetylated domain in E2F-1, and PAD4 and BRD4 coexist with E2F-1 on cytokine gene promoters. Accordingly, the combined inhibition of PAD4 and BRD4 disrupts the chromatin-bound complex and suppresses cytokine gene expression. In the murine collagen-induced arthritis model, chromatin-bound E2F-1 in inflammatory cells and consequent cytokine expression are diminished upon small-molecule inhibition of PAD4 and BRD4, and the combined treatment is clinically efficacious in preventing disease progression. Our results shed light on a new transcription-based mechanism that mediates the inflammatory effect of PAD4 and establish the interplay between citrullination and acetylation in the control of E2F-1 as a regulatory interface for driving inflammatory gene expression.

Protecting Research Participants: How Can We Reduce “Therapeutic Misconception" in Clinical Research Trials?

Fri, 03/10/2017 - 9:54am

Therapeutic Misconception and Scientific Reframing is a National Institute of Mental Health funded study led by Charles Lidz, Ph.D. The study’s goals are to: (1) Develop an innovative procedure that educates participants about clinical research trials to reduce Therapeutic Misconception (TM); and (2) Test this innovative procedure in a hypothetical clinical research trial to reduce TM without reducing study enrollment rates.

The academic and health policy conference on correctional health: evaluation of its academic and scientific impact

Thu, 03/09/2017 - 4:15pm

Background: There is limited research and research dissemination on the care of detained persons, often due to barriers to conducting research in correctional settings. Additionally, while concerns exist about the quality of care delivered to inmates, only a small number of academic health science centers provide health care services behind bars. To strengthen the field of academic criminal justice health (ACJH), the Academic and Health Policy Conference on Correctional Health (AHPCCH) was launched in 2007. Objective: To assess the merits of the conference as a stimulus to advance the field of ACJH.

Methods: Two hundred ninety-one individuals were identified who had presented at the AHPCCH and/or had received a conference attendance scholarship between 2011 and 2013. A web-based survey assessed: networking opportunities; motivation to disseminate or continue in this field; scholarly outputs; clinical practice changes; clinical guidelines development; curriculum/training opportunities; and a climate assessment at participant’s home institution in support of their work.

Results: With a 56 % response rate, the majority felt that the conference: provided encouragement and confidence to continue their work; validated their identity as a contributor in the field; and provided valuable feedback on their work. 86 % reported that the conference provided numerous networking opportunities. Most respondents reported that the conference provided new ideas for research and/or academic efforts and 62 % reported motivation to expand their scholarly work. Most also indicated that their choice to work in criminal justice health was respected at their home institution, with 64 % identifying collaborators with similar content interest/expertise and 66 % reporting opportunities to advance available as a result of their work. However, 70 % do not receive institutional funding during periods when their own extramural funding is low and 59 % were not part of an ACJH research core.

Conclusions: The majority of presenters and scholars felt that the conference fulfilled professional development opportunities needed in the field. Moreover, the conference generated new ideas for research and/or academic efforts. Thus, the AHPCCH is a valuable opportunity for researchers, policymakers and clinicians to network, share and improve upon their work, generate research ideas and, ultimately, validate criminal justice health as an academic field of study.

Prevalence and Characteristics of Sexual Violence Against Men with Disabilities

Thu, 03/09/2017 - 4:14pm

INTRODUCTION: Few studies have examined lifetime and past-year sexual violence against men with disabilities and the types of perpetrator-survivor relationships among men with disabilities. The purpose of this study is to document the prevalence of lifetime and past-year sexual violence against men with disabilities in the U.S., compare these estimates with those of men without disabilities and women with and without disabilities, and examine the gender and relationship of the perpetrator of sexual violence against men with disabilities relative to perpetrator characteristics identified in incidents against other adults.

METHODS: Behavioral Risk Factor Surveillance System 2005-2007 data were analyzed in 2014 using domain analysis and multivariate logistic regression.

RESULTS: Men with a disability were more likely than men without a disability to report lifetime sexual violence (8.8% vs 6.0%). They were also more likely than men without a disability to report lifetime experience of attempted or completed nonconsensual sex (5.8% and 2.3% vs 4.1% and 1.4%, respectively). There were no statistically significant differences between the two groups of men's reports of their relationship to the perpetrator of the most recent incident of sexual violence or perpetrator gender.

CONCLUSIONS: Men with disabilities are at heightened risk for lifetime and current sexual violence compared with men without disabilities. Given the relatively high prevalence of sexual violence among people with disabilities of both genders, sexual assault screening, prevention, and response efforts need to be inclusive and attentive to all people with disabilities.

American Psychiatry Should Join the Call to Abolish Solitary Confinement

Thu, 03/09/2017 - 4:14pm

This editorial calls for the American Psychiatric Association and other mental health organizations to oppose solitary confinement in U.S. prisons. The editorial reviews the arguments for supporting solitary confinement, referred to as segregation in U.S. prisons and outlines its negative impacts.

Proceedings of the AMCP Partnership Forum: Breaking the Link Between Pain Management and Opioid Use Disorder

Thu, 03/09/2017 - 4:14pm

Prescription drug misuse and abuse, especially with opioid analgesics, is the fastest growing drug problem in the United States. Addressing this public health crisis demands the coordinated efforts and actions of all stakeholders to establish a process of improving patient care and decreasing misuse and abuse. On September 9, 2014, the Academy of Managed Care Pharmacy (AMCP) convened a meeting of multiple stakeholders to recommend activities and programs that AMCP can promote to improve pain management, prevent opioid use disorder (OUD), and improve medication-assisted treatment outcomes. The speakers and panelists recommended that efforts to improve pain management outcomes and reduce the potential for OUD should rely on demonstrated evidence and best practices. It was recommended that AMCP promote a more holistic and evidence-based approach to pain management and OUD treatment that actively engages the patient in the decision-making process and includes care coordination with medical, pharmacy, behavioral, and mental health aspects of organizations, all of which is seamlessly supported by a technology infrastructure. To accomplish this, it was recommended that AMCP work to collaborate with organizations representing these stakeholders. Additionally, it was recommended that AMCP conduct continuing pharmacy education programs, develop a best practices toolkit on pain management, and actively promote quality standards for OUD prevention and treatment.

Medical student and hospital team fight cervical cancer in rural China

Thu, 03/09/2017 - 3:07pm

Blog post for the Gynius company website describing Newman's Senior Scholars project. She is evaluating portable colposcopy for cervical cancer screening in rural China.

Novel Mechanisms Regulating Dopamine Transporter Endocytic Trafficking: Ack1-Controlled Endocytosis And Retromer-Mediated Recycling

Wed, 03/08/2017 - 12:24pm

Dopamine transporters (DAT) facilitate high-affinity presynaptic dopamine (DA) reuptake in the central nervous system, and are required to constrain extracellular DA levels and maintain presynaptic DAergic tone. DAT is the primary target for addictive and therapeutic psychostimulants, which require DAT binding to elicit reward. DAT availability at presynaptic terminals ensures its proper function, and is dynamically regulated by endocytic trafficking. My thesis research focused on two fundamental questions: 1) what are the molecular mechanisms that control DAT endocytosis? and 2) what are the mechanism(s) that govern DAT’s post-endocytic fate? Using pharmacological and genetic approaches, I discovered that a non-receptor tyrosine kinase, activated by cdc42 kinase 1 (Ack1), stabilizes DAT plasma membrane expression by negatively regulating DAT endocytosis. I found that stimulated DAT endocytosis absolutely requires Ack1 inactivation. Moreover, I was able to restore normal DAT endocytosis to a trafficking dysregulated DAT coding variant identified in an Attention Deficit Hyperactivity Disorder (ADHD) patient via constitutively activating Ack1. To address what mechanisms govern DAT’s post-endocytic fate, I took advantage of a small molecule labeling approach to directly couple fluorophore to the DAT surface population, and subsequently tracked DAT’s temporal-spatial post-endocytic itinerary in immortalized mesencephalic cells. Using this approach, I discovered that the retromer complex mediates DAT recycling and is required to maintain DAT surface levels via a DAT C-terminal PDZ-binding motif. Taken together, these findings shed considerable new light on DAT trafficking mechanisms, and pave the way for future studies examining the role of regulated DAT trafficking in neuropsychiatric disorders.

Role of Energy Metabolism in the Thermogenic Gene Program

Wed, 03/08/2017 - 12:24pm

In murine and human brown adipose tissue (BAT), mitochondria are powerful generators of heat. Emerging evidence has suggested that the actions of mitochondria extend beyond this conventional biochemical role. In mouse BAT and cultured brown adipocytes, impaired mitochondrial respiratory capacity is accompanied by attenuated expression of Ucp1, a key thermogenic gene, implying a mitochondrial retrograde signaling. However, few have investigated this association in the context of mitochondria-nucleus communication.

Using mice with adipose-specific ablation of LRPPRC, a regulator of respiratory capacity, we show that respiration-dependent retrograde signaling from mitochondria to nucleus contributes to transcriptional and metabolic reprogramming of BAT. Impaired respiratory capacity triggers down-regulation of thermogenic and oxidative genes, promoting a storage phenotype in BAT. This retrograde regulation functions by interfering with promoter-specific recruitment of PPARg. In addition, cytosolic calcium may mediate the retrograde signal from mitochondria to nucleus. These data are consistent with a model whereby BAT connects its respiratory capacity to thermogenic gene expression, which in turn contributes to determining its metabolic commitment.

Additionally, we find that augmented respiratory capacity activates the thermogenic gene program in inguinal (subcutaneous) white adipose tissue (IWAT) from adipose-specific LRPPRC transgenic mice. When fed a high-fat diet at thermoneutrality, these mice exhibit metabolic improvements as shown by reduced fat mass and improved insulin sensitivity. Furthermore, there is increased recruitment of brown-like adipocytes in IWAT and thus energy expenditure is significantly increased, providing a potential explanation for protection from obesity. These data suggest that augmented respiratory capacity promotes ‘browning’ of IWAT, which has beneficial effects on obesity and diabetes.

Integrating Physical Activity in Primary Care Practice

Mon, 03/06/2017 - 9:46pm

Based on a collaborative symposium in 2014 hosted by the Society of Behavioral Medicine (SBM) and the American College of Sports Medicine (ACSM), this paper presents a model for physical activity counseling for primary care physicians (PCPs). Most US adults do not meet national recommendations for physical activity levels. Socioecological factors drive differences in physical activity levels by geography, sex, age, and racial/ethnic group. The recent Patient Protection and Affordable Care Act incentivizes PCPs to offer patients physical activity counseling. However, PCPs have reported socioecological barriers to physical activity counseling and also patient barriers to physical activity, spanning from the individual to the environmental (eg, lack of safe spaces for physical activity), policy (eg, reimbursement policies), and organizational (eg, electronic medical record protocols, worksite norms/policies) levels. The aims of this paper are to: 1) discuss barriers to PCP counseling for physical activity; 2) provide evidence-based strategies and techniques to help PCPs address these counseling barriers; and 3) suggest practical steps for PCPs to counsel patients on physical activity using strategies and supports from policy, the primary care team, and other support networks.

Perceived Barriers to and Facilitators of Engagement in Reverse Integrated Care

Mon, 03/06/2017 - 9:46pm

Introduction: Individuals with chronic mental illness and addiction have poorer health outcomes than the general population, largely because of preventable medical conditions. Early onset and heightened incidence of chronic disease—such as type two diabetes, chronic obstructive pulmonary disease, and hypertension—might limit behavioral health consumers’ quality life years and ultimately lead to early mortality. These health risks are exacerbated by coinciding poor health correlates such as low socioeconomic status, disrupted cycles of care, and substance use. Primary and Behavioral Health Care Integration (PBHCI) initiatives address these compounding health disparities by improving access to quality primary care and wellness services inside of behavioral health centers. As opposed to traditional integrated care models in which behavioral health services are co-located in medical settings, reverse integration targets consumers with serious and persistent mental illness who are more likely to frequent behavioral health care settings. Recently, this model of reverse integrated care delivery has been on the rise because of its unique capacity to meet the complex needs of behavioral health consumers... The current study employs semi-structured individual interviews to assess behavioral health consumers’ perceived barriers to and engagement in PBHCI services at an urban community mental health center.

The Vaccine Adjuvant Chitosan Promotes Cellular Immunity via DNA Sensor cGAS-STING-Dependent Induction of Type I Interferons

Mon, 03/06/2017 - 9:46pm

The cationic polysaccharide chitosan is an attractive candidate adjuvant capable of driving potent cell-mediated immunity, but the mechanism by which it acts is not clear. We show that chitosan promotes dendritic cell maturation by inducing type I interferons (IFNs) and enhances antigen-specific T helper 1 (Th1) responses in a type I IFN receptor-dependent manner. The induction of type I IFNs, IFN-stimulated genes and dendritic cell maturation by chitosan required the cytoplasmic DNA sensor cGAS and STING, implicating this pathway in dendritic cell activation. Additionally, this process was dependent on mitochondrial reactive oxygen species and the presence of cytoplasmic DNA. Chitosan-mediated enhancement of antigen specific Th1 and immunoglobulin G2c responses following vaccination was dependent on both cGAS and STING. These findings demonstrate that a cationic polymer can engage the STING-cGAS pathway to trigger innate and adaptive immune responses.

Gestational Weight Gain, Body Mass Index, and Risk of Hypertensive Disorders of Pregnancy in a Predominantly Puerto Rican Population

Mon, 03/06/2017 - 9:46pm

Objectives: To prospectively evaluate the association between gestational weight gain (GWG), prepregnancy body mass index (BMI), and hypertensive disorders of pregnancy using the revised Institute of Medicine (IOM) Guidelines.

Methods: We examined these associations among 1359 participants in Proyecto Buena Salud, a prospective cohort study conducted from 2006 to 2011 among women from the Caribbean Islands. Information on prepregnancy BMI, GWG, and incident diagnoses of hypertension in pregnancy were based on medical record abstraction.

Results: Four percent (n = 54) of women were diagnosed with hypertension in pregnancy, including 2.6 % (n = 36) with preeclampsia. As compared to women who gained within IOM GWG guidelines (22.8 %), those who gained above guidelines (52.5 %) had an odds ratio of 3.82 for hypertensive disorders (95 % CI 1.46-10.00; ptrend = 0.003) and an odds ratio of 2.94 for preeclampsia (95 % CI 1.00-8.71, ptrend = 0.03) after adjusting for important risk factors. Each one standard deviation (0.45 lbs/week) increase in rate of GWG was associated with a 1.74 odds of total hypertensive disorders (95 % CI 1.34-2.27) and 1.86 odds of preeclampsia (95 % CI 1.37-2.52).

Conclusions for Practice: Findings from this prospective study suggest that excessive GWG is associated with hypertension in pregnancy and could be a potentially modifiable risk factor in this high-risk ethnic group.

Surrogate decision makers' perspectives on preventable breakdowns in care among critically ill patients: A qualitative study

Mon, 03/06/2017 - 9:46pm

OBJECTIVE: To describe surrogate decision makers' (SDMs) perspectives on preventable breakdowns in care among critically ill patients.

METHODS: We screened 70 SDMs of critically ill patients for those who identified a preventable breakdown in care, defined as an event where the SDM believes something "went wrong", that could have been prevented, and resulted in harm. In-depth interviews were conducted with SDMs who identified an eligible event.

RESULTS: 32 of 70 participants (46%) identified at least one preventable breakdown in care, with a total of 75 discrete events. Types of breakdowns involved medical care (n=52), communication (n=59), and both (n=40). Four additional breakdowns were related to problems with SDM bedside access to the patient. Adverse consequences of breakdowns included physical harm, need for additional medical care, emotional distress, pain, suffering, loss of trust, life disruption, impaired decision making, and financial expense. 28 of 32 SDMs raised their concerns with clinicians, yet only 25% were satisfactorily addressed.

CONCLUSION: SDMs of critically ill patients frequently identify preventable breakdowns in care which result in harm.

PRACTICE IMPLICATIONS: An in-depth understanding of the types of events SDMs find problematic and the associated harms is an important step towards improving the safety and patient-centeredness of healthcare.

A Comprehensive Approach to the Patient at End of Life: Assessment of Multidimensional Suffering

Mon, 03/06/2017 - 9:46pm

Pain is a multidimensional, complex experience. There are many challenges in identifying and meeting the needs of patients experiencing pain. Evaluation of pain from a bio-psycho-social-spiritual framework is particularly germane for patients approaching the end of life. This review explores the relation between the psychospiritual dimensions of suffering and the experience of physical pain, and how to assess and treat pain in a multidimensional framework. A review of empirical data on the relation between pain and suffering as well as interdisciplinary evidence-based approaches to alleviate suffering are provided.

Surveillance of Medication Use During Pregnancy in the Mini-Sentinel Program

Mon, 03/06/2017 - 9:45pm

OBJECTIVES: Mini-Sentinel is a pilot project sponsored by the U.S. Food and Drug Administration to create an active surveillance system to monitor the safety of FDA-regulated medical products. We assessed the capability of the Mini-Sentinel pilot to provide prevalence rates of medication use among pregnant women delivering a liveborn infant.

METHODS: An algorithm was developed to identify pregnancies for a reusable analytic tool to be executed against the Mini-Sentinel Distributed Database. Diagnosis and procedure codes were used to identify women ages 10-54 years delivering a liveborn infant between April 2001 and December 2012. A comparison group of age- and date-matched nonpregnant women was identified. The analytic code was distributed to all 18 Mini-Sentinel data partners. The use of specific medications, selected because of concerns about their safe use during pregnancy, was identified from outpatient dispensing data. We determined the frequency of pregnancy episodes and nonpregnant episodes exposed to medications of interest, any time during the pregnant/matched nonpregnant period, and during each trimester.

RESULTS: The analytic tool successfully identified 1,678,410 live birth deliveries meeting the eligibility criteria. The prevalence of use at any time during pregnancy was 0.38 % for angiotensin-converting enzyme inhibitors and 0.22 % for statins. For < /=0.05 % of pregnancy episodes, the woman was dispensed warfarin, methotrexate, ribavirin, or mycophenolate.

CONCLUSIONS: The analytic tool developed for this study can be used to assess the use of medications during pregnancy as safety issues arise, and is adaptable to include different medications, observation periods, pre-existing conditions, and enrollment criteria.

Smoking cessation counseling in vascular surgical practice using the results of interviews and focus groups in the Vascular Surgeon offer and report smoking cessation pilot trial

Mon, 03/06/2017 - 9:45pm

OBJECTIVE: Although smoking cessation is a key priority emphasized by professional societies and multidisciplinary consensus guidelines, significant variation exists in the methods and efficacy of smoking cessation treatment practiced by vascular surgeons. We conducted a series of patient, surgeon, and nonpatient stakeholder focus groups to identify important domains for establishment of a successful smoking cessation program.

METHODS: As part of a planning effort for a randomized clinical trial on usual care vs a standardized, evidence-based smoking cessation intervention, our group performed a series of interviews and focus groups. These were four 1-hour interviews, conducted with stakeholders such as tobacco cessation counselors (n = 2), a Quit Line representative (n = 1), and a Vascular Quality Initiative leader (n = 1), as well as two 90-minute, formal, professionally moderated focus groups, one with vascular surgeons (n = 7), and another with patients (n = 4). Transcripts and audio recordings were qualitatively reviewed for themes to establish the most important domains perceived to be associated with a successful smoking cessation program.

RESULTS: Patients emphasized four domains critical for a successful smoking cessation program: the motivation to quit, an individualized approach, the timing of an intervention, and the tone of the physician who offers counseling. Although surgeons and nonpatient stakeholders also emphasized the importance of a compassionate physician tone, surgeons and nonpatient stakeholders differed from patients in their remaining domains. They emphasized the feasibility of a brief intervention in a busy clinical practice, implementation of the effort, and necessary infrastructure for smoking cessation programs. All focus group participants described a brief, evidence-based smoking cessation intervention as feasible in routine vascular practice.

CONCLUSIONS: Differences in motivation and significance exist for patients, surgeons, and stakeholders when they considered the specific domains most important in building a successful smoking cessation program. Despite these differences, all parties involved agreed that a brief, standardized intervention can be successful delivered in a busy vascular clinic setting.

Sodium Intake and Osteoporosis. Findings From the Women's Health Initiative

Mon, 03/06/2017 - 9:45pm

In this large, prospective, observational cohort study of postmenopausal women in the Women's Health Initiative, Cox proportional hazard regression models showed that sodium intake at or near recommended levels is not likely to impact bone metabolism.