Rebecca S. Boxer

Effect of Vitamin D Supplementation on Blood Pressure: A Systematic Review and Meta-analysis Incorporating Individual Patient Data

IMPORTANCEnLow levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear.nnnOBJECTIVEnTo systematically review whether supplementation with vitamin D or its analogues reduce BP.nnnDATA SOURCESnWe searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014.nnnSTUDY SELECTIONnWe included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms.nnnDATA EXTRACTION AND SYNTHESISnWe extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model.nnnMAIN OUTCOMES AND MEASURESnDifference in SBP and DBP measured in an office setting.nnnRESULTSnWe included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, -0.8 to 0.8] mm Hg; P=.97; I2=21%) or DBP (effect size, -0.1 [95% CI, -0.6 to 0.5] mm Hg; P=.84; I2=20%). Similar results were found analyzing individual patient data for SBP (effect size, -0.5 [95% CI, -1.3 to 0.4] mm Hg; P=.27; I2=0%) and DBP (effect size, 0.2 [95% CI, -0.3 to 0.7] mm Hg; P=.38; I2=0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy.nnnCONCLUSIONS AND RELEVANCEnVitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.

The effect of vitamin D on aldosterone and health status in patients with heart failure

BACKGROUNDnVitamin D deficiency is associated with heart failure (HF) events, and in animal models vitamin D down-regulates renin-angiotensin-aldosterone system hormones.nnnMETHODSnPatients with New York Heart Association (NYHA) functional class II-IV HF and a 25OH-D level ≤37.5 ng/mL received 50,000 IU vitamin D3 weekly (n = 31) or placebo (n = 33) for 6 months. Serum aldosterone, renin, echocardiography, and health status were determined at baseline and 6 months.nnnRESULTSnMean age of participants was 65.9 ± 10.4 years, 48% were women, 64% were African American, mean ejection fraction was 37.6 ± 13.9%, 36% were in NYHA functional class III, and 64% were in class II. The vitamin D group increased serum 25OH-D (19.1 ± 9.3 to 61.7 ± 20.3 ng/mL) and the placebo group did not (17.8 ± 9.0 to 17.4 ± 9.8 ng/mL). Aldosterone decreased in the vitamin D group (10.0 ± 11.9 to 6.2 ± 11.6 ng/dL) and not in the placebo group (8.9 ± 8.6 to 9.0 ± 12.4 ng/dL; P = .02). There was no difference between groups in renin, echocardiographic measures, or health status from baseline to 6 months. Modeling indicated that variables which predicted change in aldosterone included receiving vitamin D, increasing age, African American race, and lower glomerular filtration rate.nnnCONCLUSIONSnVitamin D3 repletion decreases aldosterone in patients with HF and low serum vitamin D. Vitamin D may be an important adjunct to standard HF therapy. Further study will assess if vitamin D provides long-term benefit for patients with HF.

Increasing Home Healthcare Referrals upon Discharge from U.S. Hospitals: 2001–2012

1. Charlson F, Degenhardt L, McLaren J et al. A systematic review of research examining benzodiazepine-related mortality. Pharmacoepidemiol Drug Saf 2009;18:93–103. 2. Weich S, Pearce HL, Croft P et al. Effect of anxiolytic and hypnotic drug prescriptions on mortality hazards: Retrospective cohort study. BMJ 2014;348:g1996. 3. Belleville G. Mortality hazard associated with anxiolytic and hypnotic drug use in the National Population Health Survey. Can J Psychiatry 2010;55:558–567. 4. Kripke DF, Langer RD, Kline LE. Hypnotics’ association with mortality or cancer: A matched cohort study. BMJ open 2012;2:e000850. 5. Kripke DF, Klauber MR, Wingard DL et al. Mortality hazard associated with prescription hypnotics. Biol Psychiatry 1998;43:687–693. 6. Vinkers DJ, Gussekloo J, van der Mast RC et al. Benzodiazepine use and risk of mortality in individuals aged 85 years or older. JAMA 2003;290:2942–2943. 7. Hogan DB, Maxwell CJ, Fung TS et al. Prevalence and potential consequences of benzodiazepine use in senior citizens: Results from the Canadian Study of Health and Aging. Can J Clin Pharmacol 2003;10:72–77. 8. Gisev N, Hartikainen S, Chen TF et al. Mortality associated with benzodiazepines and benzodiazepine-related drugs among community-dwelling older people in Finland: A population-based retrospective cohort study. Can J Psychiatry 2011;56:377–381. 9. Jaussent I, Ancelin ML, Berr C et al. Hypnotics and mortality in an elderly general population: A 12-year prospective study. BMC Med 2013; 11:212.

Suppression of Hyperactive Immune Responses Protects against Nitrogen Mustard Injury

DNA alkylating agents like nitrogen mustard (NM) are easily absorbed through the skin and exposure to such agents manifest not only in direct cellular death but also in triggering inflammation. We show that toxicity resulting from topical mustard exposure is mediated in part by initiating exaggerated host innate immune responses. Using an experimental model of skin exposure to NM we observe activation of inflammatory dermal macrophages that exacerbate local tissue damage in an inducible nitric oxide synthase (iNOS)-dependent manner. Subsequently these activated dermal macrophages reappear in the bone marrow to aid in disruption of hematopoiesis and contribute ultimately to mortality in an experimental mouse model of topical NM exposure. Intervention with a single dose of 25-hydroxyvitamin D3 (25(OH)D) is capable of suppressing macrophage-mediated iNOS production resulting in mitigation of local skin destruction, enhanced tissue repair, protection from marrow depletion, and rescue from severe precipitous wasting. These protective effects are recapitulated experimentally using pharmacological inhibitors of iNOS or by compounds that locally deplete skin macrophages. Taken together, these data highlight a critical unappreciated role of the host innate immune system in exacerbating injury following exposure to NM and support the translation of 25(OH)D in the therapeutic use against these chemical agents.

Characteristics Associated with Home Health Care Referrals at Hospital Discharge: Results from the 2012 National Inpatient Sample.

OBJECTIVEnTo assess patient- and hospital-level factors associated with home health care (HHC) referrals following nonelective U.S. patient hospitalizations in 2012.nnnDATA SOURCEnThe 2012 National Inpatient Sample (NIS).nnnSTUDY DESIGNnRetrospective, cross-sectional multivariable logistic regression modeling to assess patient- and hospital-level variables in patient discharges with versus without HHC referrals.nnnDATA COLLECTIONnAnalysis included 1,109,905 discharges in patients ≥65xa0years with Medicare.nnnPRINCIPAL FINDINGSnAbout 29.2 percent of discharges were referred to HHC, which were more likely with older age, female sex, urban location, low income, longer length of stay, higher severity of illness scores, diagnoses of heart failure or sepsis, and hospital location in New England (referent: Pacific).nnnCONCLUSIONSnAs health policy changes influence postacute HHC, defining specific diagnoses and regional patterns associated with HHC is a first step to optimize postacute HHC services.

Use of Medical Orders for Scope of Treatment for Heart Failure Patients During Postacute Care in Skilled Nursing Facilities

BACKGROUNDnIndividuals with heart failure (HF) who are hospitalized and admitted to skilled nursing facilities (SNFs) are at high risk for rehospitalization and death. The care preferences of this high-risk population have not been studied.nnnOBJECTIVESnTo describe care preferences of patients with HF admitted to SNFs for rehabilitation based on Medical Orders for Scope of Treatment (MOST) documentation, and evaluate goal-concordant care based on MOST documentation, emergency department (ED) visits, and hospitalization.nnnDESIGN, SETTING, AND PARTICIPANTSnRetrospective study of patients with HF in 35 SNFs enrolled in a randomized controlled trial of HF-disease management versus usual care between July 2014 and Mayxa02016.nnnMEASUREMENTSnValidity of MOST forms, care preference documentation, and ED visits/hospitalizations within 60xa0days of SNF admission.nnnRESULTSnOf 370 patients (mean age 78.6xa0years, 58% women, 25% systolic HF), 278 (75%) had a MOST form in the SNF chart, of which 96 forms (35%) were invalid. The most common reason for an invalid MOST form was missing date accompanying patient or provider signature. Of 182 valid MOST forms, 47% of patients chose no cardiopulmonary resuscitation (No CPR), 58% selected Full Treatment, 17% chose Selective Treatment, and 23% chose Comfort-Focused Treatment. Patients who were older [odds ratio (OR)xa0=xa01.50, 95% confidence interval (CI)xa0=xa01.25, 1.81] and female (ORxa0=xa02.33, 95% CIxa0=xa01.18, 4.59) had higher odds of choosing No CPR. Sixty-six of 182 patients (36%) with valid MOST forms had an ED/hospital visit within 60xa0days of SNF admission; only 3 patients received medical care that was potentially discordant: all 3 chose Comfort-Focused Treatment and were hospitalized for more than symptom management.nnnCONCLUSIONnSeventy-five percent of patients with HF admitted to SNFs had care preferences documented using the MOST form, and 95% received goal-concordant care based on care preferences documented during the SNF admission. Clinicaltrials.gov # NCT01822912.

The Development and Acceptability of a Mobile Application for Tracking Symptoms of Heart Failure Among Older Adults

PURPOSEnHeart failure (HF) is common in older adults. With increases in technology use among older adults, mobile applications may provide a solution for older adults to self-manage symptoms of HF. This article discusses the development and acceptability of a HF symptom-tracking mobile application (HF app).nnnMETHODOLOGYnThe HF app was developed to allow patients to track their symptoms of HF. Thirty (Nu2009=u200930) older adults completed an acceptability survey after using the mobile app. The survey used Likert items and open-ended feedback questions.nnnRESULTSnOverall, the acceptability feedback from users was positive with participants indicating that the HF app was both easy to use and understand. Participants identified recommendations for improvement including additional symptoms to track and the inclusion of instructions and reminders.nnnCONCLUSIONnHF is common in older adults, and acceptability of mobile apps is of key importance. The HF app is an acceptable tool for older patients with HF to self-manage their symptoms, identify patterns, and changes in symptoms, and ultimately prevent HF readmission.

Skilled Nursing Facility Care for Patients With Heart Failure: Can We Make It “Heart Failure Ready?”

Skilled nursing facilities (SNFs) have emerged as an integral component of care for older adults with heart failure (HF). Despite their prominent role, poor clinical outcomes for the medically complex patients with HF managed in SNFs are common. Barriers to providing quality care include poor transitional care during hospital-to-SNF and SNF-to-community discharges, lack of HF training among SNF staff, and a lack of a standardized care process among SNF facilities. Although no evidence-based practice standards have been established, various measures and tools designed to improve HF management in SNFs are being investigated. In this review, we discuss the challenges of HF care in SNFs as well as potential targets and recommendations that can help improve care with respect to transitions, HF management within SNFs, and modifiable factors within facilities. Policy considerations that might help catalyze improvements in SNF-based HF management are also discussed.

Targeting heart failure rehospitalizations in a skilled nursing facility: A case report

OBJECTIVEnWe report on a skilled nursing facility (SNF) that added designated heart failure (HF) beds and created a patient registry to track the number and reasons for rehospitalization.nnnBACKGROUNDnTargeting the reduction of rehospitalizations from SNFs is an important goal and patients with HF are particularly vulnerable for rehospitalizations as HF disease management programs in SNFs are rare.nnnMETHODSnA case study of a local quality improvement initiative.nnnRESULTSnThe data from the registry revealed, that compared to patients without HF, patients with HF were more often rehospitalized for cardiopulmonary symptoms and less often for infection. In addition, patients with HF were most often rehospitalized during the first 7 days of their SNF stay and if they had a primary hospital discharge diagnosis of HF.nnnCONCLUSIONnWe highlight the benefits of a patient registry to guide future quality improvement initiatives to reduce patient rehospitalization rates.

Post-acute Care for Patients with Heart Failure

Purpose of ReviewPatients hospitalized for heart failure (HF) frequently require post-acute care (PAC) services after discharge. This review highlights recent updates on HF patient demographics, risk predictors for adverse outcomes, and management strategies for patients with HF in post-acute care settings, particularly within skilled nursing facilities (SNFs) and home health care (HHC).Recent FindingsPAC is increasingly utilized for older patients who require ongoing intensive services in order to achieve physical or medical stability after a hospitalization for HF. Patients admitted to SNF and/or HHC frequently have multiple comorbid illnesses and suffer from functional and/or cognitive impairment. These patients are particularly vulnerable to adverse events, including rehospitalization or mortality. Deficits in transitional care, lack of standardized disease management protocols in PAC, and the higher complexity of comorbid illness in this population contribute to their poor outcomes. Legislative initiatives have emphasized improving the quality and efficiency of care delivery in PAC. Interventions that improve care transitions, delivery of care within SNFs, and patient education have shown promise in improving outcomes.SummaryPatients with HF in PAC have high medical acuity and need consistent and focused HF care to improve outcomes. Transitions between the hospital and PAC are a perilous time for these patients and new innovative practices of care are promising.