prospective studies

Patients with BRCA mutations should consider prophylactic ovariectomies prior to age 50 based upon this epidemiological simulation. James W. Mold, MD, MPH

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Importance Women with a BRCA1 or BRCA2 variant face a high lifetime risk of ovarian cancer and are often advised to undergo preventive surgery (bilateral salpingo-oophorectomy [BSO]) before cancer develops. The recommended age of BSO is 35 years for BRCA1 carriers and is 45 years for BRCA2 carriers, but some women choose to delay surgery until the age of menopause; there is no standard upper age at which surgery is no longer advised.

Objective To estimate the residual lifetime risk of ovarian cancer among BRCA carriers by current age and projected age at BSO.

Design, Setting, and Participants This was a prospective cohort study in an international cohort of BRCA carriers monitored for incident ovarian cancer. A life table analysis used age-specific ovarian cancer incidence rates and competing mortality rates to estimate lifetime risk of ovarian cancer among women with a BRCA1 or BRCA2 pathogenic variant with both ovaries intact and no prior ovarian cancer at baseline. Patients were recruited between 1995 and 2024 across 24 international centers, and the mean (SD) follow-up was 4.4 (3.9) years.

Exposure Timing of BSO, defined as immediate BSO, delayed BSO, or no BSO.

Main Outcome and Measures Residual lifetime risk of ovarian cancer.

Results The cohort consisted of 4286 BRCA1 and 1427 BRCA2 carriers between the ages of 30 and 74 years at baseline (mean [SD] age, 42.0 [10.8] years). There were 249 incident ovarian cancers in the follow-up period. The lifetime risk of ovarian cancer was 55.0% (95% CI, 48.8-61.9) for a BRCA1 carrier and 24.1% (95% CI, 15.1-36.6) for a BRCA2 carrier. A 30-year-old BRCA1 carrier with BSO delayed to age 50 years had a projected residual ovarian cancer risk of 23.9% (95% CI, 20.7-27.4). At age 75 years, the residual risk of ovarian cancer was estimated to be 8.4% (95% CI, 1.7-22.7) for a BRCA1 carrier and 3.7% (95% CI, 0.1-22.7) for a BRCA2 carrier.

Conclusions and Relevance The residual risk of ovarian cancer for older women in good health is sufficiently high to consider preventive surgery. BRCA1 carriers who defer BSO until age 50 years may face a substantial risk of developing ovarian cancer.

Author/s:

Vasily Giannakeas, PhD, Adriana I. Apostol, MD, Claudia Diella, et al.

Mortality and Morbidity in Mild Primary Hyperparathyroidism: Results From a 10-Year Prospective Randomized Controlled Trial of Parathyroidectomy Versus Observation

Saige Blanchard — Thu, 14 Apr 2022 05:00:00 +0000

Date Added:

April 25, 2022

Journal/Publication:

Annals of Internal Medicine

Publisher:

American College of Physicians

Publication Date:

April 19, 2022

URL:

Mortality and Morbidity in Mild Primary Hyperparathyroidism: Results From a 10-Year Prospective Randomized Controlled Trial of Parathyroidectomy Versus Observation

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.7326/M21-4416

Keywords

PMID (1):

35436153

MeSH

Humans

cause of death

Parathyroidectomy

Hyperparathyroidism, Primary

cardiovascular diseases

prospective studies

In mild hyperparathyroidism, surgery did not result in fewer adverse events over 15 years of follow-up. James W. Mold, MD, MPH

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Background: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with increased risk for fractures, cardiovascular disease, kidney disease, and cancer and increased mortality. In mild PHPT with modest hypercalcemia and without known morbidities, parathyroidectomy (PTX) is debated because no long-term randomized trials have been performed.

Objective: To examine the effect of PTX on mild PHPT with regard to mortality (primary end point) and key morbidities (secondary end point).

Design: Prospective randomized controlled trial. (ClinicalTrials.gov: NCT00522028).

Setting: Eight Scandinavian referral centers.

Patients: From 1998 to 2005, 191 patients with mild PHPT were included.

Intervention: Ninety-five patients were randomly assigned to PTX, and 96 were assigned to observation without intervention (OBS).

Measurements: Date and causes of death were obtained from the Swedish and Norwegian Cause of Death Registries 10 years after randomization and after an extended observation period lasting until 2018. Morbidity events were prospectively registered annually.

Results: After 10 years, 15 patients had died (8 in the PTX group and 7 in the OBS group). Within the extended observation period, 44 deaths occurred, which were evenly distributed between groups (24 in the PTX group and 20 in the OBS group). A total of 101 morbidity events (cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones) were also similarly distributed between groups (52 in the PTX group and 49 in the OBS group). During the study, a total of 16 vertebral fractures occurred in 14 patients (7 in each group).

Limitation: During the study period, 23 patients in the PTX group and 27 in the OBS group withdrew.

Conclusion: Parathyroidectomy does not appear to reduce morbidity or mortality in mild PHPT. Thus, no evidence of adverse effects of observation was seen for at least a decade with respect to mortality, fractures, cancer, cardiovascular and cerebrovascular events, or renal morbidities.

Author/s:

Pretorius, M., Lundstam, K., Heck, A., Fagerland, M. W., Godang, K., Mollerup, C., Fougner, S. L., Pernow, Y., Aas, T., Hessman, O., Rosen, T., Nordestrom, J., Jansson, S., Hellstrom, M., Bollerslev, J.

Efficacy and Safety of Nonantibiotic Outpatient Treatment in Mild Acute Diverticulitis (DINAMO-study): A Multicentre, Randomised, Open-label, Noninferiority Trial

Bethie Seay — Tue, 02 Nov 2021 05:00:00 +0000

Date Added:

November 2, 2021

Journal/Publication:

Annals of Surgery

Publication Date:

November 1, 2021

Issue:

Volume:

274

Pages:

e435-e442

Type:

Clinical Research Results

DOI (1):

10.1097/SLA.0000000000005031

PMID (1):

34183510

MeSH

Humans

Amoxicillin-potassium clavulanate combination

anti-bacterial agents

prospective studies

outpatients

Anti-Inflammatory Agents

Ambulatory Care

hospitalization

pain management

Emergency Service, hospital

hospitals

tomography

pain

Apparently it isn’t necessary to treat patients with mild diverticulitis with antibiotics.

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Objective:
Mild AD can be treated safely and effectively on an outpatient basis without antibiotics.

Summary of Background Data:
In recent years, it has shown no benefit of antibiotics in the treatment of uncomplicated AD in hospitalized patients. Also, outpatient treatment of uncomplicated AD has been shown to be safe and effective.

Methods:
A Prospective, multicentre, open-label, noninferiority, randomized controlled trial, in 15 hospitals of patients consulting the emergency department with symptoms compatible with AD.

The Participants were patients with mild AD diagnosed by Computed Tomography meeting the inclusion criteria were randomly assigned to control arm (ATB-Group): classical treatment (875/125 mg/8 h amoxicillin/clavulanic acid apart from anti-inflammatory and symptomatic treatment) or experimental arm (Non-ATB-Group): experimental treatment (antiinflammatory and symptomatic treatment). Clinical controls were performed at 2, 7, 30, and 90 days.

The primary endpoint was hospital admission. Secondary endpoints included number of emergency department revisits, pain control and emergency surgery in the different arms.

Results:
Four hundred and eighty patients meeting the inclusion criteria were randomly assigned to Non-ATB-Group (n = 242) or ATB-Group (n = 238). Hospitalization rates were: ATB-Group 14/238 (5.8%) and Non-ATB-Group 8/242 (3.3%) [mean difference 2.58%, 95% confidence interval (CI) 6.32 to -1.17], confirming noninferiority margin. Revisits: ATB-Group 16/238 (6.7%) and Non-ATB-Group 17/242 (7%) (mean difference -0.3, 95% CI 4.22 to -4.83). Poor pain control at 2 days follow up: ATB-Group 13/230 (5.7%), Non-ATB-Group 5/221 (2.3%) (mean difference 3.39, 95% CI 6.96 to -0.18).

Conclusions:
Nonantibiotic outpatient treatment of mild AD is safe and effective and is not inferior to current standard treatment.

Trial registration:
ClinicalTrials.gov (NCT02785549); EU Clinical Trials Register (2016-001596-75)

Author/s:

Mora-López, L., Ruiz-Edo, N., Estrada-Ferrer, O., Piñana-Campón, M. L., Labró-Ciurans, M., Escuder-Perez, J., Sales-Mallafré, R., Rebasa-Cladera, P., Navarro-Soto, S., Serra-Aracil, X.

Prevalence of Allergic Reactions After Pfizer-BioNTech COVID-19 Vaccination Among Adults With High Allergy Risk

Bethie Seay — Fri, 03 Sep 2021 05:00:00 +0000

Date Added:

September 3, 2021

Type:

Clinical Research Results

DOI (1):

10.1001/jamanetworkopen.2021.22255

MeSH

referral and consultation

Surveys and Questionnaires

Algorithms

SARS-CoV-2

Highly allergic individuals can safely receive the COVID vaccine if certain precautions are taken. Anaphylaxis is very unlikely (0.7%).

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Importance
Allergic reactions among some individuals who received the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine discourage patients with allergic conditions from receiving this vaccine and physicians from recommending the vaccine.

Objective
To describe the assessment and immunization of highly allergic individuals with the BNT162b2 vaccine.

Design, Setting, and Participants
In a prospective cohort study from December 27, 2020, to February 22, 2021, 8102 patients with allergies who applied to the COVID 19 vaccine referral center at the Sheba Medical Center underwent risk assessment using an algorithm that included a detailed questionnaire. High-risk patients (n = 429) were considered “highly allergic” and were immunized under medical supervision.

Exposures
Pfizer-BioNTech (BNT162b2) COVID-19 vaccine.

Main Outcomes and Measures
Allergic and anaphylactic reactions after the first and second doses of BNT162b2 vaccine among highly allergic patients.

Results
Of the 429 individuals who applied to the COVID-19 referral center and were defined as highly allergic, 304 (70.9%) were women and the mean (SD) age was 52 (16) years. This highly allergic group was referred to receive immunization under medical supervision. After the first dose of the BNT162b2 vaccine, 420 patients (97.9%) had no immediate allergic event, 6 (1.4%) developed minor allergic responses, and 3 (0.7%) had anaphylactic reactions. During the study period, 218 highly allergic patients (50.8%) received the second BNT162b2 vaccine dose, of which 214 (98.2%) had no allergic reactions and 4 patients (1.8%) had minor allergic reactions. Other immediate and late reactions were comparable with those seen in the general population, except for delayed itch and skin eruption, which were more common among allergic patients.

Conclusions and Relevance
The rate of allergic reactions to BNT162b2 vaccine, is higher among patients with allergies, particularly among a subgroup with a history of high-risk allergies. This study suggests that most patients with a history of allergic diseases and, particularly, highly allergic patients can be safely immunized by using an algorithm that can be implemented in different medical facilities and includes a referral center, a risk assessment questionnaire, and a setting for immunization under medical supervision of highly allergic patients. Further studies are required to define more specific risk factors for allergic reactions to the BNT162b2 vaccine.

Author/s:

Shavit, R., Maoz-Segal, R., Iancovici-Kidon, M.

The effect of high-dose vitamin D supplementation on serum vitamin D levels and milk calcium concentration in lactating women and their infants

Bethie Seay — Fri, 03 Sep 2021 05:00:00 +0000

Date Added:

September 3, 2021

Type:

Clinical Research Results

DOI (1):

10.1089/bfm.2006.1.27

PMID (1):

17661558

MeSH

Adult

Bone Density Conservation Agents

calcium

dietary supplements

Dose-Response Relationship

Infant Nutritional Physiological Phenomena

infant, newborn

Lactation

Maternal Nutritional Physiological Phenomena

Milk, Human

Nutritional Requirements

Nutritional Status

prospective studies

vitamin D

This study provides guidance on Vitamin D supplementation in lactating women and their babies.

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Objective: Improve vitamin D status in lactating women and their recipient infants, and measure breast milk calcium concentration [Ca] as a function of vitamin D regimen.

Design/methods: Fully breastfeeding mothers were randomized at 1 month postpartum to 2000 (n = 12) or 4000 (n = 13) IU/day vitamin D for 3 months to achieve optimal vitamin D status [serum 25(OH)D > or =32 ng/mL (80 nmol/L)]. Breast milk [Ca], maternal and infant serum 25(OH)D and serum Ca, and maternal urinary Ca/Cr ratio were measured monthly.

Results: Mothers were similar between groups for age, race, gestation, and birth weight. 25(OH)D increased from 1 to 4 months in both groups (mean +/- SD): +11.5 +/- 2.3 ng/mL for group 2000 (p = 0.002) and +14.4 +/- 3.0 ng/mL for group 4000 (p = 0.0008). The 4000 IU/day regimen was more effective in raising both maternal and infant serum levels and breast milk antirachitic activity than the 2000 IU/day regimen. Breast milk [Ca] fell with continued lactation through 4 months in the 2000 and 4000 IU groups. Decline in breast milk [Ca] was not associated with vitamin D dose (p = 0.73) or maternal 25(OH)D (p = 0.94). No mother or infant experienced vitamin D-related adverse events, and all laboratory parameters remained in the normal range.

Conclusion: High-dose vitamin D was effective in increasing 25(OH)D levels in fully breastfeeding mothers to optimal levels without evidence of toxicity. Breast milk [Ca] and its decline in both groups during 1 to 4 months were independent of maternal vitamin D status and regimen. Both the mother and her infant attained improved vitamin D status and maintained normal [Ca].

Author/s:

Basile, L. A., Taylor, S. N., Wagner, C. L., Horst, R. L., Hollis, B. W.

Association Between Plant and Animal Protein Intake and Overall and Cause-Specific Mortality

Brian Desmarais — Wed, 22 Jul 2020 16:00:16 +0000

Date Added:

July 22, 2020

Journal/Publication:

JAMA Intern Medicine

Publisher:

JAMA Network

Publication Date:

July 13, 2020

URL:

Association Between Plant and Animal Protein Intake and Overall and Cause-Specific Mortality

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamainternmed.2020.2790.

MeSH

Plant Proteins, Dietary

fruit

cardiovascular diseases

Analysis of a huge cohort of adults found that eating more plant protein (vs. animal protein) reduces cardiovascular mortality and increases life expectancy. James W. Mold, MD, MPH

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Importance: Although emphasis has recently been placed on the importance of high-protein diets to overall health, a comprehensive analysis of long-term cause-specific mortality in association with the intake of plant protein and animal protein has not been reported.

Objective: To examine the associations between overall mortality and cause-specific mortality and plant protein intake.

Design, setting, and participants: This prospective cohort study analyzed data from 416 104 men and women in the US National Institutes of Health-AARP Diet and Health Study from 1995 to 2011. Data were analyzed from October 2018 through April 2020.

Exposures: Validated baseline food frequency questionnaire dietary information, including intake of plant protein and animal protein.

Main outcomes and measures: Hazard ratios and 16-year absolute risk differences for overall mortality and cause-specific mortality.

Results: The final analytic cohort included 237 036 men (57%) and 179 068 women. Their overall median (SD) ages were 62.2 (5.4) years for men and 62.0 (5.4) years for women. Based on 6 009 748 person-years of observation, 77 614 deaths (18.7%; 49 297 men and 28 317 women) were analyzed. Adjusting for several important clinical and other risk factors, greater dietary plant protein intake was associated with reduced overall mortality in both sexes (hazard ratio per 1 SD was 0.95 [95% CI, 0.94-0.97] for men and 0.95 [95% CI, 0.93-0.96] for women; adjusted absolute risk difference per 1 SD was -0.36% [95% CI, -0.48% to -0.25%] for men and -0.33% [95% CI, -0.48% to -0.21%] for women; hazard ratio per 10 g/1000 kcal was 0.88 [95% CI, 0.84-0.91] for men and 0.86 [95% CI, 0.82-0.90] for women; adjusted absolute risk difference per 10 g/1000 kcal was -0.95% [95% CI, -1.3% to -0.68%] for men and -0.86% [95% CI, -1.3% to -0.55%] for women; all P < .001). The association between plant protein intake and overall mortality was similar across the subgroups of smoking status, diabetes, fruit consumption, vitamin supplement use, and self-reported health status. Replacement of 3% energy from animal protein with plant protein was inversely associated with overall mortality (risk decreased 10% in both men and women) and cardiovascular disease mortality (11% lower risk in men and 12% lower risk in women). In particular, the lower overall mortality was attributable primarily to substitution of plant protein for egg protein (24% lower risk in men and 21% lower risk in women) and red meat protein (13% lower risk in men and 15% lower risk in women).

Conclusions and relevance: In this large prospective cohort, higher plant protein intake was associated with small reductions in risk of overall and cardiovascular disease mortality. Our findings provide evidence that dietary modification in choice of protein sources may influence health and longevity.

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Author/s:

Huang, J., Liao, L.M., Weinstein, S.J., Sinha, R., Graubard, B.I., Albanes, D.

Volunteering and Subsequent Health and Well-Being in Older Adults: An Outcome-Wide Longitudinal Approach

Brian Desmarais — Thu, 18 Jun 2020 18:35:18 +0000

Date Added:

June 18, 2020

Journal/Publication:

American Journal of Preventive Medicine

Publication Date:

June 5, 2020

URL:

Volunteering and Subsequent Health and Well-Being in Older Adults: An Outcome-Wide Longitudinal Approach

Type:

Clinical Research Results

Format:

Article

DOI (1):

doi: 10.1016/j.amepre.2020.03.004.

Keywords

MeSH

Personal Satisfaction

Evidence that volunteering has real health benefits. James W. Mold, MD, MPH

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ntroduction: Growing evidence documents strong associations between volunteering and favorable health and well-being outcomes. However, epidemiological studies have not evaluated whether changes in volunteering are associated with subsequent health and well-being outcomes.

Methods: Data were from 12,998 participants in the Health and Retirement Study-a large, diverse, prospective, and nationally representative cohort of U.S. adults aged >50 years. Using multiple logistic, linear, and generalized linear regression models, this study evaluated if changes in volunteering (between t0, 2006/2008 and t1, 2010/2012) were associated with 34 indicators of physical health, health behaviors, and psychosocial well-being (in t2, 2014/2016). Models adjusted for sociodemographics, physical health, health behaviors, psychosocial factors, and personality, as well as volunteering and all outcomes in the prebaseline wave (t0, 2006/2008). Results accounted for multiple testing and data were analyzed in 2019.

Results: During the 4-year follow-up period, participants who volunteered ≥100 hours/year (versus 0 hours/year) had a reduced risk of mortality and physical functioning limitations, higher physical activity, and better psychosocial outcomes (higher: positive affect, optimism, and purpose in life; lower: depressive symptoms, hopelessness, loneliness, and infrequent contact with friends). Volunteering was not associated with other physical health outcomes (diabetes, hypertension, stroke, cancer, heart disease, lung disease, arthritis, overweight/obesity, cognitive impairment, and chronic pain), health behaviors (binge drinking, smoking, and sleep problems), or psychosocial outcomes (life satisfaction, mastery, health/financial mastery, depression, negative affect, perceived constraints, and contact with other family/children).

Conclusions: With further research, volunteering is an activity that physicians might suggest to their willing and able patients as a way of simultaneously enhancing health and society.

Author/s:

Kim, E.S., Whillans, A.V., Lee, M.T., Chen, Y., VanderWeele, T.J.

Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation

John Bayhi — Fri, 28 Feb 2020 14:21:39 +0000

Date Added:

February 28, 2020

Journal/Publication:

JAMA Network Open

Publisher:

American Medical Association

Publication Date:

February 5, 2020

Issue:

Volume:

Pages:

e200107

URL:

Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamanetworkopen.2020.0107

Keywords

PMID (1):

32101311

MeSH

acute coronary syndrome

coronary artery disease

Platelet Aggregation Inhibitors

stroke

hemorrhage

Registries

The results of this cohort study suggest that for patients with atrial fibrillation, adding an antiplatelet agent to an oral anticoagulant results in more strokes and bleeding and does not protect them from MI. James W. Mold, MD, MPH

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IMPORTANCE:

Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy.

OBJECTIVE:

To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone.

DESIGN, SETTING, AND PARTICIPANTS:

Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019.

EXPOSURE:

Participants received either OAC plus AP or OAC alone.

MAIN OUTCOMES AND MEASURES:

Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications.

RESULTS:

A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months).

CONCLUSIONS AND RELEVANCE:

This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation.

Author/s:

Fox, KAA, Velentgas, P, Camm, AJ, Bassand, JP, Fitzmaurice, DA, Gersh, BJ, Goldhaber, SZ, Goto, S, Haas, S, Misselwitz, F, Pieper, KS, Turpie, AGG, Verhegut, FWA, Dabrowski, E, Luo, K, Gibbs, L, Kakkar, AK, GARFIELD-AF Investigators

Alcohol Abstinence in Drinkers with Atrial Fibrillation

Brian Desmarais — Fri, 03 Jan 2020 22:27:35 +0000

Date Added:

January 3, 2020

Journal/Publication:

New England Journal of Medicine

Publication Date:

January 2, 2020

Issue:

Volume:

382

Pages:

20-28

URL:

Alcohol Abstinence in Drinkers with Atrial Fibrillation

Type:

Clinical Research Results

Format:

Article

DOI (1):

https://doi.org/10.1093/ntr/ntz234

Keywords

MeSH

Not surprisingly, reducing alcohol intake reduces the frequency of atrial fibrillation in patients known to have had episodes of atrial fibrillation.

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BACKGROUND:

Excessive alcohol consumption is associated with incident atrial fibrillation and adverse atrial remodeling; however, the effect of abstinence from alcohol on secondary prevention of atrial fibrillation is unclear.

METHODS:

We conducted a multicenter, prospective, open-label, randomized, controlled trial at six hospitals in Australia. Adults who consumed 10 or more standard drinks (with 1 standard drink containing approximately 12 g of pure alcohol) per week and who had paroxysmal or persistent atrial fibrillation in sinus rhythm at baseline were randomly assigned in a 1:1 ratio to either abstain from alcohol or continue their usual alcohol consumption. The two primary end points were freedom from recurrence of atrial fibrillation (after a 2-week "blanking period") and total atrial fibrillation burden (proportion of time in atrial fibrillation) during 6 months of follow-up.

RESULTS:

Of 140 patients who underwent randomization (85% men; mean [±SD] age, 62±9 years), 70 were assigned to the abstinence group and 70 to the control group. Patients in the abstinence group reduced their alcohol intake from 16.8±7.7 to 2.1±3.7 standard drinks per week (a reduction of 87.5%), and patients in the control group reduced their alcohol intake from 16.4±6.9 to 13.2±6.5 drinks per week (a reduction of 19.5%). After a 2-week blanking period, atrial fibrillation recurred in 37 of 70 patients (53%) in the abstinence group and in 51 of 70 patients (73%) in the control group. The abstinence group had a longer period before recurrence of atrial fibrillation than the control group (hazard ratio, 0.55; 95% confidence interval, 0.36 to 0.84; P = 0.005). The atrial fibrillation burden over 6 months of follow-up was significantly lower in the abstinence group than in the control group (median percentage of time in atrial fibrillation, 0.5% [interquartile range, 0.0 to 3.0] vs. 1.2% [interquartile range, 0.0 to 10.3]; P = 0.01).

CONCLUSIONS:

Abstinence from alcohol reduced arrhythmia recurrences in regular drinkers with atrial fibrillation. (Funded by the Government of Victoria Operational Infrastructure Support Program and others; Australian New Zealand Clinical Trials Registry number, ACTRN12616000256471.).

Author/s:

Voskoboinik, A., Kalman, J.M., De Silva, A., Nicholls, T., Costello, B., Nanayakkara, S., Prabhu, S., Stub, D., Azzopardi, S., Vizi, D., Wong, G., Nalliah, C., Sugumar, H., Wong, M., Kotschet, E., Kaye D., Taylor, A.J., Kistler, P.M.

Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability

John Bayhi — Wed, 04 Dec 2019 18:30:19 +0000

Date Added:

December 4, 2019

Journal/Publication:

The New England Journal of Medicine

Publisher:

Massachusetts Medical Society

Publication Date:

November 28, 2019

Issue:

Volume:

381

Pages:

2125-2134

URL:

Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa1909159

Keywords

pulmonary embolism

d-dimer

computed tomography

PMID (1):

31774957

MeSH

Humans

prospective studies

retrospective studies

Venous Thromboembolism

Computed Tomography Angiography

anticoagulants

Angiography

Though the full article is not freely available, I thought the abstract was worth sharing. In primary care patients with low or moderate probability of a pulmonary embolus, PE can essentially be ruled out with D-dimer testing. James W. Mold, MD, MPH

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BACKGROUND:

Retrospective analyses suggest that pulmonary embolism is ruled out by a d-dimer level of less than 1000 ng per milliliter in patients with a low clinical pretest probability (C-PTP) and by a d-dimer level of less than 500 ng per milliliter in patients with a moderate C-PTP.

METHODS:

We performed a prospective study in which pulmonary embolism was considered to be ruled out without further testing in outpatients with a low C-PTP and a d-dimer level of less than 1000 ng per milliliter or with a moderate C-PTP and a d-dimer level of less than 500 ng per milliliter. All other patients underwent chest imaging (usually computed tomographic pulmonary angiography). If pulmonary embolism was not diagnosed, patients did not receive anticoagulant therapy. All patients were followed for 3 months to detect venous thromboembolism.

RESULTS:

A total of 2017 patients were enrolled and evaluated, of whom 7.4% had pulmonary embolism on initial diagnostic testing. Of the 1325 patients who had a low C-PTP (1285 patients) or moderate C-PTP (40 patients) and a negative d-dimer test (i.e., <1000 or <500 ng per milliliter, respectively), none had venous thromboembolism during follow-up (95% confidence interval [CI], 0.00 to 0.29%). These included 315 patients who had a low C-PTP and a d-dimer level of 500 to 999 ng per milliliter (95% CI, 0.00 to 1.20%). Of all 1863 patients who did not receive a diagnosis of pulmonary embolism initially and did not receive anticoagulant therapy, 1 patient (0.05%; 95% CI, 0.01 to 0.30) had venous thromboembolism. Our diagnostic strategy resulted in the use of chest imaging in 34.3% of patients, whereas a strategy in which pulmonary embolism is considered to be ruled out with a low C-PTP and a d-dimer level of less than 500 ng per milliliter would result in the use of chest imaging in 51.9% (difference, -17.6 percentage points; 95% CI, -19.2 to -15.9).

CONCLUSIONS:

A combination of a low C-PTP and a d-dimer level of less than 1000 ng per milliliter identified a group of patients at low risk for pulmonary embolism during follow-up. (Funded by the Canadian Institutes of Health Research and others; PEGeD ClinicalTrials.gov number, NCT02483442.).

Author/s:

Kearon, C, de Wit, K, Parpia, S, Schulman, S, Afilalo, M, Hirsch, A, Spencer, FA, Sharma, S, D'Aragon, F, Deshaies, JF, Le Gal, G, Lazo-Langer, A, Wu, C, Rudd-Scott, L, Bates, SM, Julian, JA, PEGeD Study Investigators

Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial

Brian Desmarais — Thu, 24 Oct 2019 17:04:27 +0000

Date Added:

April 3, 2020

Journal/Publication:

European Heart Journal

Publication Date:

October 22, 2019

URL:

Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1093/eurheartj/ehz754

Keywords

Perhaps once a day antihypertensives should be taken at night rather than in the AM. James W. Mold, MD, MPH

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AIMS:

The Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better cardiovascular disease (CVD) risk reduction.

METHODS AND RESULTS:

In this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive patients (10 614 men/8470 women, 60.5 ± 13.7 years of age) were assigned (1:1) to ingest the entire daily dose of ≥1 hypertension medications at bedtime (n = 9552) or all of them upon awakening (n = 9532). At inclusion and at every scheduled clinic visit (at least annually) throughout follow-up, ambulatory blood pressure (ABP) monitoring was performed for 48 h. During the 6.3-year median patient follow-up, 1752 participants experienced the primary CVD outcome (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke). Patients of the bedtime, compared with the upon-waking, treatment-time regimen showed significantly lower hazard ratio-adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, smoking, HDL cholesterol, asleep systolic blood pressure (BP) mean, sleep-time relative systolic BP decline, and previous CVD event-of the primary CVD outcome [0.55 (95% CI 0.50-0.61), P < 0.001] and each of its single components (P < 0.001 in all cases), i.e. CVD death [0.44 (0.34-0.56)], myocardial infarction [0.66 (0.52-0.84)], coronary revascularization [0.60 (0.47-0.75)], heart failure [0.58 (0.49-0.70)], and stroke [0.51 (0.41-0.63)].

CONCLUSION:

Routine ingestion by hypertensive patients of ≥1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ABP control (significantly enhanced decrease in asleep BP and increased sleep-time relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events.

TRIAL REGISTRATION:

ClinicalTrials.gov, number NCT00741585.

Author/s:

Hermida, R.C., Crespo, J.J., Domínguez-Sardiña, M, Otero, A., Moyá, A., Ríos, M.T., Sineiro, E., Castiñeira, M.C., Callejas, P.A., Pousa, L., Salgado, J.L., Durán, C., Sánchez, J.J., Fernández, J.R., Mojón, A., Ayala, D.E., Hygia Project Investigators

Changes in nut consumption influence long-term weight change in US men and women

John Bayhi — Fri, 27 Sep 2019 12:59:01 +0000

Date Added:

September 27, 2019

Journal/Publication:

BMJ Nutrition, Prevention & Health

Publisher:

BMJ Publishing Group Ltd & NNEdPro Global Centre for Nutrition and Health (Cambridge)

Publication Date:

September 23, 2019

URL:

Changes in nut consumption influence long-term weight change in US men and women

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1136/bmjnph-2019-000034

Keywords

MeSH

Epidemiological Studies

More evidence that eating nuts is good for people. James W. Mold, MD, MPH

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Background Nut consumption has increased in the US but little evidence exists on the association between changes in nut consumption and weight change. We aimed to evaluate the association between changes in total consumption of nuts and intakes of different nuts (including peanuts) and long-term weight change, in three independent cohort studies.

Methods and findings Data collected in three prospective, longitudinal cohorts among health professionals in the US were analysed. We included 27 521 men (Health Professionals Follow-up Study, 1986 to 2010), 61 680 women (Nurses’ Health Study, 1986 to 2010), and 55 684 younger women (Nurses’ Health Study II, 1991 to 2011) who were free of chronic disease at baseline in the analyses. We investigated the association between changes in nut consumption over 4-year intervals and concurrent weight change over 20–24 years of follow-up using multivariate linear models with an unstructured correlation matrix to account for within-individual repeated measures. 21 322 individuals attained a body mass index classification of obesity (BMI ≥30 kg/m2) at the end of follow-up.

Average weight gain across the three cohorts was 0.32 kg each year. Increases in nut consumption, per 0.5 servings/day (14 g), was significantly associated with less weight gain per 4-year interval (p<0.01 for all): −0.19 kg (95% CI -0.21 to -0.17) for total consumption of nuts, -0.37 kg (95% CI -0.45 to -0.30) for walnuts, -0.36 kg (95% CI -0.40 to -0.31) for other tree nuts, and -0.15 kg (95% CI -0.19 to -0.11) for peanuts.

Increasing intakes of nuts, walnuts, and other tree nuts by 0.5 servings/day was associated with a lower risk of obesity. The multivariable adjusted RR for total nuts, walnuts, and other tree nuts was 0.97 (95% CI 0.96 to 0.99, p=0.0036), 0.85 (95% CI 0.81 to 0.89, p=0.0002), and 0.89 (95% CI 0.87 to 0.91, p<0.0001), respectively. Increasing nut consumption was also associated with a lower risk of gaining ≥2 kg or ≥5 kg (RR 0.89–0.98, p<0.01 for all).

In substitution analyses, substituting 0.5 servings/day of nuts for red meat, processed meat, French fries, desserts, or potato, chips (crisps) was associated with less weight gain (p<0.05 for all).

Our cohorts were largely composed of Caucasian health professionals with relatively higher socioeconomic status; thus the results may not be generalisable to other populations.

Conclusion Increasing daily consumption of nuts is associated with less long-term weight gain and a lower risk of obesity in adults. Replacing 0.5 servings/day of less healthful foods with nuts may be a simple strategy to help prevent gradual long-term weight gain and obesity.

Author/s:

X, Li, Y, Guasch-Ferre, M, Willett, WC, Drouin-Chartier, JP, Bhupathiraju, SN, Tobias, DK

Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma

John Bayhi — Thu, 26 Sep 2019 14:21:17 +0000

Date Added:

September 26, 2019

Journal/Publication:

The New England Journal of Medicine

Publisher:

Massachusetts Medical Society

Publication Date:

September 26, 2019

Issue:

Volume:

381

Pages:

1227-1239

URL:

Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa1905560

Keywords

asthma

African Americans

glucocorticoids

randomized control trial

PMID (1):

31553835

MeSH

fluticasone-salmeterol drug combination

Some patients with poorly controlled asthma need significantly increased doses of inhaled corticosteroids. James W. Mold, MD, MPH

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BACKGROUND:

Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients.

METHODS:

We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry.

RESULTS:

When quintupling the dose of fluticasone (to 250 μg twice a day) was compared with adding salmeterol (50 μg twice a day) and doubling the fluticasone (to 100 μg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age.

CONCLUSIONS:

In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).

Author/s:

Wechsler, ME, Szefler, SJ, Ortega, VE, Pongracic, JA, Chinchili, V, Lima, JJ, Krishnan, JA, Kunselman, SJ, Mauger, D, Bleecker, ER, Bacharier, LB, Beigelman, A, Benson, M, Blake, KV, Cabana, MD, Cardet, JC, Castro, M, Chmiel, JF, Covar, R, Denlinger, L, DiMango, E, Fitzpatrick, AM, Gentile, D, Grossman, N, Holguin, F, Jackson, DJ, Kumar, H, Kraft, M, LaForce, CF, Lang, J, Lazarus, SC, Lemanske, RF Jr, Long, D, Lugogo, N, Martinez, F, Meyers, DA, Moore, WC, Moy, J, Naureckas, E, Olin, JT, Peters, SP, Phipatanakul, W, Que, L, Raissy, H, Robison, RG, Ross, K, Sheehan, W, Smith, LJ, Solway, J, Sorkness, CA, Sullivan-Vedder, L, Wenzel, S, Israel, E, NHLBI AsthmaNet

Sitting Time and Risk of Cardiovascular Disease and Diabetes: A Systematic Review and Meta-Analysis.

Brian Desmarais — Mon, 19 Aug 2019 13:31:30 +0000

Date Added:

August 19, 2019

Journal/Publication:

American Journal of Preventative Medicine

Publication Date:

August 1, 2019

URL:

Sitting Time and Risk of Cardiovascular Disease and Diabetes: A Systematic Review and Meta-Analysis.

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/j.amepre.2019.04.015

Keywords

physical activity

sitting

exercise

MeSH

cardiovascular diseases

You probably knew this, but perhaps it is time to address sitting behavior and well as physical activity. James W. Mold, MD. MPH

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Whether physical activity attenuates the association of total daily sitting time with cardiovascular disease and diabetes incidence is unclear. This systematic review and meta-analysis examined the association of total daily sitting time with cardiovascular disease and diabetes with and without adjustment for physical activity.

EVIDENCE ACQUISITION:

PubMed, Web of Science, BASE, MEDLINE, Academic Search Elite, and ScienceDirect were searched for prospective studies, published between January 1, 1989, and February 15, 2019, examining the association of total daily sitting time with cardiovascular disease or diabetes outcomes. Data extraction and study quality assessments were conducted by 2 independent reviewers. Pooled hazard ratios (HRs) were calculated using a fixed-effects model. The quality assessment and meta-analysis procedures were completed in 2018.

EVIDENCE SYNTHESIS:

Nine studies with 448,285 participants were included. A higher total daily sitting time was associated with a significantly increased risk of cardiovascular disease (HR=1.29, 95% CI=1.27, 1.30, p<0.001) and diabetes (HR=1.13, 95% CI=1.04, 1.22, p<0.001) incidence when not adjusted for physical activity. The increased risk for diabetes was unaffected when adjusting for physical activity (HR=1.11, 95% CI=1.01, 1.19, p<0.001). For cardiovascular disease, the increased risk was attenuated but remained significant (HR=1.14, 95% CI=1.04, 1.23, p<0.001).

CONCLUSIONS:

Higher levels of total daily sitting time are associated with an increased risk of cardiovascular disease and diabetes, independent of physical activity. Reductions in total daily sitting may be recommended in public health guidelines.

Author/s:

Bailey, D.P., Hewson, D.J., Champion, R.B., Sayegh, S.M.

Left Atrial Appendages Occlusion: Current Status and Prospective

Brian Desmarais — Mon, 05 Aug 2019 18:23:22 +0000

Date Added:

August 5, 2019

Journal/Publication:

Korean Circulation Journal

Publication Date:

August 28, 2018

Issue:

Volume:

Pages:

692-704

URL:

Left Atrial Appendages Occlusion: Current Status and Prospective

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.4070/kcj.2018.0231

Keywords

Watchman device

left atrial appendage

MeSH

For those wanting to know more about the Watchman device and other approaches to left atrial appendage occlusion for prevention of stroke due to atrial fibrillation, this was the best recent review article I could find. James W. Mold, MD, MPH

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Stroke continues to be a major cause of morbidity and mortality in atrial fibrillation (AF) patients. Oral anticoagulation (OAC) provides protection against stroke and peripheral embolization in AF but significant proportion of patients could not be started on anticoagulation because of bleeding complications. Left atrial appendage harbors clot in about 90% of nonvalvular AF. The advent of left atrial appendage occlusion (LAAO) techniques has provided these patients with alternative to OAC for stroke prophylaxis. Multiple LAAO devices are currently available with Watchman and Amulet being the most commonly used in clinical practice. Randomized studies are available for Watchman device only. Data on Amplatzer Cardiac Plug, Amulet and Lariat devices are limited by the paucity of randomized data. Long-term data on different LAAO techniques are showing promising results. Device related thrombosis continues to be a serious complication associated with LAAO. Future studies should look into comparative effectiveness between different LAAO techniques, optimal patient selection, risk of complications, and anticoagulant treatment after LAAO. This article aims to provide current available evidence on efficacy and safety of different LAAO devices and future prospective.

Author/s:

Sharma, S.P., Park, P., Lakkireddy, D.