• Women with Low Vitamin D at Future Risk for Multiple Sclerosis
• High-Fat Diets Were Associated with Lower 7-Year Mortality
• Does Cutting Dietary Fat Affect Breast Cancer Outcomes?
• Hormonal Treatment Options for Women's Sexual Function
• Effectiveness of Postpartum Depression Screening During Well-Child Care
• Racial Disparities in Unnecessary Prescribing of Antibiotics in
Pediatric Emergency Departments
• Reconciling the Two Large Prostate Cancer Screening Trials
• Glycemic Control in Diabetic Patients with Chronic Kidney Disease
Neurology 2017 Sep 13
Women with Low Vitamin D at Future Risk for Multiple Sclerosis
In a large case-control study, both deficiency and insufficiency of vitamin D were associated with multiple sclerosis diagnosis 9 years later.
Growing epidemiologic evidence supports an association between vitamin D levels and multiple sclerosis (MS) risk and severity. Providing further data, the Finnish Maternity Cohort included 1.8 million serum samples from 800,000 women, provided as part of routine prenatal testing. Included for study were 1092 women diagnosed with MS who had at least one prediagnosis sample. Cases were matched to 2123 controls. Mean age at diagnosis was 37 years, and mean age of sample collection was 28.
Women with deficient 25-hydroxyvitamin D levels (<30 nmol/L) had a 43% increased risk for MS compared with women whose levels were ≥50 nmol/L. Women with insufficient levels (30 to 50 nmol/L) had a 27% increased risk compared with women whose levels were ≥50 nmol/L.
COMMENT; These findings prospectively establish increased risk for MS associated with vitamin D deficiency in women. They also demonstrate an increased risk when serum levels are under 40.7 nmol/L. Prior studies have suggested that pregnant women and their newborns with low vitamin D levels have offspring with increased risk of developing MS (NEJM JW Neurol May 2016 and JAMA Neurol 2016; 73:515; NEJM JW Neurol Jan 2017 and Neurology 2017; 88:44). The incidence of autoimmune diseases has seemed to increase with time. Perhaps changes in vitamin D and sunlight exposure are one piece of that puzzle. Whether vitamin D supplementation can be a disease modifier for those with established MS is under investigation (NEJM JW Neurol Dec 2015 and JAMA Neurol 2015; 72:1458). The correct dose remains unknown; many neurologists are recommending at least 1000–3000 IU daily of vitamin D.
CITATION(S): Munger KL et al. 25-hydroxyvitamin D deficiency and risk of MS among women in the Finnish Maternity Cohort. Neurology 2017 Sep 13; [e-pub].
(http://dx.doi.org/10.1212/WNL.0000000000004489)
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Lancet 2017 Aug 28
High-Fat Diets Were Associated with Lower 7-Year Mortality
Higher fat and lower carbohydrate intake was associated with lower mortality and no change in adverse cardiovascular events in this global study.
Standard dietary advice to restrict total fat and saturated fatty acids (<30% and <10% of total energy, respectively) is based largely on a few observational studies conducted years ago in North America and Europe. However, recent meta-analyses have shown no association, or an inverse relation, between saturated fatty acid intake and total mortality and adverse cardiovascular (CV) events.
Researchers conducted detailed analyses of the diets of more than 135,000 people with a range of income levels in 18 countries on five continents. Participants were sorted into quintiles based on percentage of dietary energy derived from carbohydrates; protein; and total, saturated, monounsaturated, and polyunsaturated fats. Median follow-up was 7.4 years.
After adjustment for education, smoking, physical activity, diabetes, urban versus rural location, total energy intake, and geographic region, higher carbohydrate intake was associated with higher risk for overall mortality and non-CV–related death but was not associated with major adverse CV events assessed individually or as a group. Conversely, higher intakes of total, saturated, monounsaturated, and polyunsaturated fats were associated with lower risk for overall and non-CV–related death and were not associated with adverse CV events (other than an inverse relation between saturated fat intake and stroke).
COMMENT: Data from this large, diverse international cohort does not support current dietary guidelines that recommend restricting total and saturated fats. The findings suggest that people who eat high carbohydrate diets might benefit from substituting fats for some of their carbohydrates.
CITATION(S): Dehghan M et al. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): A prospective cohort study. Lancet 2017 Aug 28; [e-pub].
(http://dx.doi.org/10.1016/S0140-6736(17)32252-3)
Definitions:
Saturated fats: a type of single-bond animal or vegetable fat, as that found in butter, meat, egg yolks, and coconut or palm oil, that in humans tends to increase cholesterol levels in the blood
Mono-unsaturated fats: from nuts, olive oil, canola oil
Poly-unsaturated fats: omega 6 vegetable oil, walnuts, flax seed,
Omega 3 -fish oil ***
Saturated fats: Hydrogenated vegetable fats such as corn oil margarine are "trans fats" and may lead to heart attack or stroke.
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J Clin Oncol 2017 Sep 1; 35:2919
Does Cutting Dietary Fat Affect Breast Cancer Outcomes?
Women's Health Initiative randomized trial findings suggest lowering dietary fat also lowers mortality after breast cancer.
In the Women's Health Initiative dietary modification trial, investigators randomized women beginning in 1993 (age range, 50–70) to usual diet or a diet characterized by reduced fat and increased fruit, vegetables, and grains. Results at a median of 8 years indicated that fewer deaths from breast cancer occurred in women assigned to this dietary modification. The current report extends follow-up to a median of 16 years, focusing on the impact of dietary modification on deaths from breast cancer as well as overall mortality in participants with breast cancer diagnoses.
Although most breast cancer characteristics were similar between groups, a significantly smaller proportion of cancers in the dietary modification participants were of the poor-prognosis, estrogen-receptor–positive, progesterone-receptor–negative type. During the extended follow-up, among 3030 participants with incident breast cancer, deaths attributed to breast cancer were modestly (but not significantly) less common in the dietary modification group. However, overall mortality after breast cancer was significantly lower among women in the dietary modification group (234 vs. 443 deaths; hazard ratio, 0.82; P=0.01). Adjustment for weight change during the dietary intervention did not alter these findings.
COMMENT: The authors note that a favorable effect of this dietary intervention on cardiovascular mortality could have contributed to their findings. Furthermore, they point out that chemotherapy and radiation therapy can contribute to cardiovascular mortality in breast cancer patients. Whether the reduced overall mortality among women with incident breast cancer was caused by a direct positive effect of the dietary modification on breast cancer characteristics, or whether the benefits were not oncologic, these findings provide additional evidence for the benefits of a plant-based, low-fat diet.
CITATION(S): Chlebowski RT et al. Low-fat dietary pattern and breast cancer mortality in the Women's Health Initiative randomized controlled trial. J Clin Oncol 2017 Sep 1; 35:2919.
(http://dx.doi.org/10.1200/JCO.2016.72.0326)
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JAMA Intern Med 2017 Aug 28
Hormonal Treatment Options for Women's Sexual Function
In early postmenopausal women, transdermal estradiol, but not oral estrogen, improved sexual function relative to placebo.
The menopausal transition can adversely affect sexual function. In a study of hormonal treatments during early menopause, investigators randomized 727 healthy women (mean age, 53; within 3 years of last menstrual period) to placebo, transdermal estradiol (tE2; 0.050 mg released daily), or oral conjugated equine estrogen (oCEE; 0.45 mg daily). Sexual function was assessed over 4 years with the Female Sexual Function Inventory (FSFI; higher scores indicate better function). Features such as arousal, lubrication, and pain reduction were quantified with subscores.
Women in the placebo group experienced declines from baseline in FSFI score as well as subscores for lubrication and pain reduction. Compared with placebo, tE2 treatment was associated with modest improvements in FSFI (P=0.002), lubrication (P=0.001), and pain reduction (P=0.002). By contrast, oCEE treatment did not improve FSFI score relative to placebo (P=0.13). Women who received oCEE, but not tE2 or placebo, showed a large increase in circulating sex hormone binding globulin (SHBG) concentration.
COMMENT: Both oral and transdermal estradiol are effective for managing menopausal hot flashes and associated sleep disorders. This study indicates that transdermal estradiol may be superior to oral estradiol for improving sexual function (possibly because oral estradiol raises circulating SHBG and lowers free testosterone concentration, thereby adversely affecting libido).
In observational studies involving postmenopausal women, transdermal estradiol compared with oral estrogen was associated with lower rates of venous thromboembolism, pulmonary embolism, and possibly stroke; thus, transdermal estradiol may have more benefits and fewer risks than oral estrogen. However, some women may prefer oral hormone therapy based on cost and convenience. When prescribing transdermal estradiol for postmenopausal women older than 50, I generally start with a dose of 0.0375 mg and, if necessary, increase the dose to 0.050 mg.
CITATION(S): Taylor HS et al. Effects of oral vs transdermal estrogen therapy on sexual function in early postmenopause: Ancillary study of the Kronos Early Estrogen Prevention Study (KEEPS). JAMA Intern Med 2017 Aug 28; [e-pub].
(http://dx.doi.org/10.1001/jamainternmed.2017.3877)
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Pediatrics 2017 Oct; 140:e20170110
Effectiveness of Postpartum Depression Screening During Well-Child Care
Screening was associated with reduced risks for maternal depression and anxiety and with better quality of life.
In prior studies, screening for postpartum depression (PPD) has improved rates of detection, treatment, and PPD symptoms, but possible benefits on parenting or child development remain unexamined.
In the current quasi-experimental study, researchers assessed the effectiveness of PPD screening in improving outcomes in mothers and children through early detection and treatment. They assigned more than 3000 mothers of newborns receiving care at Dutch well-child care centers (WCCs) to receive either PPD screening with a standardized self-report tool (at 1, 3, and 6 months postpartum) or usual care. Mothers identified at high risk for major depression were referred to their primary care doctors or a mental health care professional. Mothers identified at risk for minor depression were offered a home visit by the WCC nurse, with a referral if needed. Outcomes were prospectively assessed at 9 months and 1 year.
Mothers screened for PPD showed lower risks for major depression (adjusted odds ratio, 0.3; effect size, 0.7) and combined minor/major depression (AOR, 0.4) at 9 months compared with controls. Smaller but significant effect sizes were found for better mental health–related quality of life (0.3), lower anxiety (0.3), and greater self-efficacy around parenting and nurturance (0.2). At 1 year, children showed only marginally better social-emotional development (effect size, 0.1).
COMMENT: When PPD screening was first recommended two decades ago, pediatric providers worried that it would open a Pandora's box of problems that we wouldn't have the resources to manage. However, PPD screening may now seem more feasible to pediatric clinics, as many have collocated mental health providers, or can refer mothers back to their adult primary care or obstetric providers, who now have better resources to treat depression. When pediatric providers ask about maternal well-being, it plays a supporting and normalizing role that can help mothers seek help, allow conversations about stress and parenting, and benefit parent-provider trust over time.
CITATION(S): van der Zee-van den Berg AI et al. Post-Up study: Postpartum depression screening in well-child care and maternal outcomes. Pediatrics 2017 Oct; 140:e20170110.
(http://dx.doi.org/10.1542/peds.2017-0110)
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Pediatrics 2017 Aug 2
Racial Disparities in Unnecessary Prescribing of Antibiotics in Pediatric Emergency Departments
White children were more likely to receive antibiotics for viral acute respiratory tract infection compared with black, Hispanic, and other nonwhite children visiting PEDs.
Racial and ethnic disparities in antibiotic prescribing for acute respiratory tract infection were recently described in nonemergency primary care settings. To determine whether these disparities occur in the pediatric emergency department (PED) care setting, researchers retrospectively examined approximately 40,000 PED visits by children discharged for viral acute respiratory tract infection.
The primary outcome measure was any administration of antibiotics in the PED or a prescription for antibiotics upon discharge. Children with bacterial codiagnoses, chronic disease, or immunocompromising conditions were excluded. Race and ethnicity were collapsed into a single variable and categorized as Hispanic, non-Hispanic white, non-Hispanic black, and other.
Overall, 3% of children discharged with a viral acute respiratory tract infection received antibiotics. This percentage was higher among white children (4%) compared with non-Hispanic black children (2%), Hispanic children (3%), and those of “other” race/ethnicity (3%). These differences remained significant after adjusting for age, insurance status, acuity of illness, PED provider type, and PED site of care.
COMMENT: The inappropriate use of antibiotics is an important public health issue, as is the existence of racial and ethnic disparities in healthcare. In pediatrics, the vast majority of antibiotic prescribing is for acute respiratory tract infections, even though we know that most of them are a result of viruses. With this study, the phenomenon of overprescribing antibiotics at a disproportionately higher rate to white children is now reported in pediatric emergency departments. Pursuing a better understanding of how a patient's race and ethnicity drives our prescribing practices as pediatricians is important as we continue to strive to provide appropriate care to all.
CITATION(S): Goyal MK et al. Racial and ethnic differences in antibiotic use for viral illness in emergency departments.Pediatrics 2017 Aug 2; [e-pub].
(http://dx.doi.org/10.1542/peds.2017-0203)
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Ann Intern Med 2017 Sep 5
Reconciling the Two Large Prostate Cancer Screening Trials
Researchers propose that the negative U.S. randomized trial actually supports screening — but that shouldn't change the debate about the merits of screening.
The two recent large randomized prostate-specific antigen (PSA) screening trials reached discordant conclusions. After more than a decade of follow-up in a European trial, roughly 1 fewer prostate cancer death occurred per 1000 men screened, but many men were treated to prevent 1 death, and the trial had limitations that could have biased the result in either direction. In contrast, a U.S. trial showed no benefit from PSA screening, but the control group was “contaminated” by screening outside the trial (NEJM JW Gen Med Apr 15 2009 and N Engl J Med 2009; 360:1310 and 1320; NEJM JW Gen Med Sep 15 2014 and Lancet 2014; 384:2027).
Now, a research group has reanalyzed data from both trials using complex statistical techniques. They found that longer “mean lead time” (the estimated interval by which prostate cancer detection was advanced by screening) correlated with lower risk for prostate cancer–related death. In the U.S. trial, long lead times in both the screening arm and the control arm (whose enrollees often were screened outside the trial) could imply that both groups benefitted similarly from PSA screening, resulting in no difference in mortality outcomes in the two groups. The authors conclude that the U.S. data actually are compatible with the European findings.
COMMENT: I'd like to see critical analysis of this report by other groups with sophisticated statistical expertise. But in the end, it doesn't really matter whether the U.S. data legitimately can be interpreted as supporting the European data. We already know (from the European trial) that screening likely confers a small absolute reduction in prostate cancer–related mortality, but also that many men must be treated (or subjected to repeated testing and biopsy) to benefit one person. So this latest analysis doesn't change anything: We're still left with the same debate about benefit versus harm for PSA screening.
CITATION(S): Tsodikov A et al. Reconciling the effects of screening on prostate cancer mortality in the ERSPC and PLCO trials. Ann Intern Med 2017 Sep 5; [e-pub].
(http://dx.doi.org/10.7326/M16-2586)
Vickers AJ.Prostate Cancer screening: Time to question how to optimize the ratio of benefits and harms. Ann Intern Med 2017 Sep 5; [e-pub].
(http://dx.doi.org/10.7326/M17-2012)
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Am J Kidney Dis 2017 Aug; 70:191
Glycemic Control in Diabetic Patients with Chronic Kidney Disease
Highest and lowest glycosylated hemoglobin levels were associated with excess mortality; progression to end-stage renal disease was not associated with glycemic control.
In diabetic patients with chronic kidney disease (CKD), the relation between glycemic control and mortality or progression to end-stage renal disease (ESRD) is uncertain. To examine this issue, researchers performed a cohort study of 6165 older diabetic adults (mean age, 70) who were enrolled in a CKD registry at Cleveland Clinic. All patients were using insulin or oral diabetes drugs, and nearly all had estimated glomerular filtration rates of <60 mL/minute/1.73 m2. Patients with ESRD at baseline were excluded.
During median follow-up of 2.3 years, 3% of patients progressed to ESRD, and 16% of patients died. Analyses adjusted for numerous demographic and clinical variables showed a U-shaped relation between baseline glycosylated hemoglobin (HbA1c) level and mortality: With HbA1c of 6% to 6.9% as the reference standard, patients with HbA1c levels <6% and those with levels ≥9% had significantly higher mortality; in contrast, mortality was not higher in those with levels between 7% and 8.9%. Baseline HbA1c was not associated with risk for progression to ESRD.
COMMENT: American Diabetes Association (ADA) guidelines acknowledge that a “one-size-fits-all” goal for glycemic control is inappropriate for older patients with comorbidities (Diabetes Care 2015; 38:140). For patients with CKD, this observational study supports the ADA's general position: Mortality was similar across an HbA1c range of 6% to 9%, mortality was higher above and below that range, and progression to ESRD was not associated with glycemic control. These results don't tell us the extent to which early mortality was mediated by hypoglycemia, but we know that older patients with kidney disease who take insulin and sulfonylureas are at especially high risk for serious hypoglycemia (NEJM JW Gen Med Oct 1 2017 and JAMA Intern Med 2017 Aug 21; [e-pub]).
CITATION(S): Navaneethan SD et al. Diabetes control and the risks of ESRD and mortality in patients with CKD. Am J Kidney Dis 2017 Aug; 70:191.
(http://dx.doi.org/10.1053/j.ajkd.2016.11.018)
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