VIMS Journal: December 2017

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Maintaining Vitamin D Sufficiency is Associated with Improved Structural and Symptomatic Outcomes in Knee Osteoarthritis.
Shuang Zhengetal. American journal of Medicine. October 2017 Volume 130, Issue 10, Pages 1211- 1218.
This study was designedto describe whether maintaining sufficient serum vitamin D levels in people with knee osteoarthritis and baseline vitamin D insufficiency has an association with change in knee structures and symptoms over 2 years.
The participants were 413 in number with a mean age of 63.2 years, with symptomatic knee osteoarthritis and vitamin D insufficiency. Out of them 340 participants (82.3%) completed the study, with 25-hydroxyvitamin D [25(OH) D] measurements at baseline and months 3 and 24. Participants were classified as consistently insufficient [serum 25(OH) D ≤50 nmol/L at months 3 and 24, n = 45], fluctuating [25(OH) D >50 nmol/L at either point, n = 68), and consistently sufficient [25(OH) D >50 nmol/L at months 3 and 24, n = 226] groups. Knee cartilage volume, cartilage defects, bone marrow lesions, and effusion-synovitis volume were assessed using MRI at baseline and month 24. Knee symptoms were assessed at baseline and months 3, 6, 12, and 24 using the Western Ontario and McMaster Universities Arthritis Index.
The consistently sufficient group had significantly less loss of tibial cartilage volume (β 2.1%; 95% confidence interval [CI], 0.3%, 3.9%), less increase in effusion-synovitis volume (β - 2.5 mL; 95 CI%, - 4.7, - 0.2 mL), and less loss of Western Ontario and McMaster Universities Arthritis Index physical function (β - 94.2; 95% CI, - 183.8, - 4.5) compared with the consistently insufficient group in multivariable analyses.
In contrast, there were no significant differences in these outcomes between the fluctuating and consistently insufficient groups. Changes in cartilage defects, bone marrow lesions, and knee pain were similar between groups. This post hoc analysis suggests beneficial effects of maintaining vitamin D sufficiency on cartilage loss, effusionsynovitis, and physical function in people with knee osteoarthritis.

Antenatal nutritional supplementation and autism spectrum disorders in the Stockholm youth cohort: population based cohort study.
Elizabeth A DeVilbiss et al. BMJ 2017; 359:j4273.
This was an observational prospective cohort to determine whether nutritional supplementation during pregnancy is associated with a reduced risk of autism spectrum disorder (ASD) with and without intellectual disability in offspring. 273 107 mother-child pairs identified through population registers. The study sample was restricted to children who were aged 4 to 15 years by the end of follow-up on 31 December 2011 and were born between 1996 and 2007. Multivitamin, iron, and folic acid supplement use was reported at the first antenatal visit.
Diagnosis of ASD with and without intellectual disability was done in children determined from register data up to 31 December 2011. Prevalence of ASD with intellectual disability was 0.26% (158 cases in 61934) in the maternal multivitamin use group and 0.48% (430 cases in 90480) in the no nutritional supplementation use group. Maternal multivitamin use with or without additional iron or folic acid, or both was associated with lower odds of ASD with intellectual disability in the child compared with mothers who did not use multivitamins, iron, and folic acid (odds ratio 0.69, 95% confidence interval 0.57 to 0.84). Similar estimates were found in propensity score matched (0.68, 0.54 to 0.86) and sibling control (0.77, 0.52 to 1.15) matched analyses, though the confidence interval for the latter association included 1.0 and was therefore not statistically significant. There was no consistent evidence that either iron or folic acid use were inversely associated with ASD prevalence.
Maternal multivitamin supplementation during pregnancy may be inversely associated with ASD with intellectual disability in offspring. Further scrutiny of maternal nutrition and its role in the cause of autism is recommended.

History of breast feeding and risk of incident endometriosis: prospective cohort study
Leslie V Farland et al. BMJ 2017;358:j3778.
Leslie V Farland et al. investigated the association between lifetime breast feeding, exclusive breast feeding, postpartum amenorrhea, and incidence of endometriosis among parous women in a prospective cohort study. 72 394 women who reported having one or more pregnancies that lasted at least six months, 3296 of whom had laparoscopically confirmed endometriosis. For each pregnancy, women reported duration of total breast feeding, exclusive breast feeding, and postpartum amenorrhea.
Incident self reported laparoscopically confirmed endometriosis (96% concordance with medical record) in parous women was detected. Multivariable Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for diagnosis of endometriosis.
Duration of total and exclusive breast feeding was significantly associated with decreased risk of endometriosis. Among women who reported a lifetime total length of breast feeding of less than one month, there were 453 endometriosis cases/100000 person years compared with 184 cases/100000 person years in women who reported a lifetime total of > 36 months of breast feeding. For every additional three months of total breast feeding per pregnancy, women experienced an 8% lower risk of endometriosis (hazard ratio 0.92, 95% confidence interval 0.90 to 0.94; P< 0.001 for trend) and a 14% lower risk for every additional three months of exclusive breast feeding per pregnancy (0.86, 0.81 to 0.90; P< 0.001 for trend). Women who breastfed for >36 months in total across their reproductive lifetime had a 40% reduced risk of endometriosis compared with women who never breast fed (0.60, 0.50 to 0.72). The protective association with breast feeding was strongest among women who gave birth within the past five years (P=0.04 for interaction). The association with total breast feeding and exclusive breast feeding on endometriosis was partially influenced by postpartum amenorrhea (% mediated was 34% (95% confidence interval 15% to 59%) for total breast feeding and 57% (27% to 82%) for exclusive breast feeding).
Among women who experienced at least one pregnancy that lasted at least six months, breast feeding was inversely associated with risk of incident endometriosis. This association was partially, but not fully, influenced by postpartum amenorrhea, suggesting that breast feeding could influence the risk of endometriosis both through amenorrhea and other mechanisms. Given the chronic and incurable nature of endometriosis, breast feeding should be further investigated as an important modifiable behavior to mitigate risk for pregnant women.

Effect of Oral Prednisolone on Symptom Duration and Severity in Non-asthmatic Adults With Acute Lower Respiratory Tract Infection.
Alastair D. Hay et al. JAMA. 2017;318(8) :721- 730. doi:10.1001 /jama.2017.10572.
Questions have long been raised that whether, a moderate dose of oral corticosteroid reduce the duration or severity of acute lower respiratory tract infection in adults without asthma presenting to primary care? Findings in this randomized trial of 401 adults with symptoms of acute lower respiratory tract infection, treatment with oral prednisolone, 40 mg/d for 5 days, compared with placebo did not significantly reduce the median duration of moderately bad or worse cough (5 days in each group) or the mean severity of symptoms between days 2 and 4 (1.99 vs 2.16 points out of 6).
Acute lower respiratory tract infection is common and often treated inappropriately in primary care with antibiotics. Corticosteroids are increasingly used but without sufficient evidence. Objective of this study was to assess the effects of oral corticosteroids for acute lower respiratory tract infection in adults without asthma. This was a multicenter, placebo-controlled, randomized trial (July 2013 to final follow-up October 2014) conducted in 54 family practices in England among 401 adults with acute cough and at least 1 lower respiratory tract symptom not requiring immediate antibiotic treatment and with no history of chronic pulmonary disease or use of asthma medication in the past 5 years.
Patients were offered two 20-mg prednisolone tablets (n = 199) or matched placebo (n = 202) once daily for 5 days. The primary outcomes were duration of moderately bad or worse cough (0 to 28 days; minimal clinically important difference, 3.79 days) and mean severity of symptoms on days 2 to 4 (scored from 0 [not affected] to 6 [as bad as it could be]; minimal clinically important difference, 1.66 units).
Secondary outcomes were duration and severity of acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, and adverse events. Among 401 randomized patients, 2 withdrew immediately after randomization, and 1 duplicate patient was identified. Among the 398 patients with baseline data (mean age, 47 [SD, 16.0] years; 63% women; 17% smokers; 77% phlegm; 70% shortness of breath; 47% wheezing; 46% chest pain; 42% abnormal peak flow), 334 (84%) provided cough duration and 369 (93%) symptom severity data. Median cough duration was 5 days (interquartile range [IQR], 3-8 days) in the prednisolone group and 5 days (IQR, 3-10 days) in the placebo group (adjusted hazard ratio, 1.11; 95% CI, 0.89-1.39; P = .36 at an α = .05). Mean symptom severity was 1.99 points in the prednisolone group and 2.16 points in the placebo group (adjusted difference, -0.20; 95% CI, -0.40 to 0.00; P = .05 at an α = .001). No significant treatment effects were observed for duration or severity of other acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, or nonserious adverse events.
There were no serious adverse events. The study shows that oral corticosteroids should not be used for acute lower respiratory tract infection symptoms in adults without asthma because they do not reduce symptom duration or severity.

Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients with Heart Failure and Reduced Ejection Fraction, A Randomized Clinical Trial.
G. Michael Felker et al. JAMA. 2017; 318(8):713-720.
The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ("guided therapy") with inconsistent results.
G. Michael Felker et al. assessedwhether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF).
The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial planned to randomize 1100 patients with HFrEF (ejection fraction £ 40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NTproBNP- guided strategy or usual care.
Patients were randomized to either an NTproBNP- guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL.
Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events.
The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79- 1.22; P =.88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI; 0.65-1.37; P =.75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups.
This study establishes that in high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes and NT-proBNPguided therapy for management of heart failure with reduced ejection fraction is use less.

Association of History of Dizziness and Longterm Adverse Outcomes With Early vs Later Orthostatic Hypotension Assessment Times in Middle-aged Adults.
Stephen P et al. JAMA Intern Med. 2017; 177(9):1316-1323.
Existing guidelines recommend measuring blood pressure in assessing orthostatic hypotension (OH) 3 minutes after rising from supine to standing positions. It is not known whether measurements performed immediately after standing predict adverse events as strongly as measurements performed closer to 3 minutes. This prospective cohort study of middle-aged (range, 44-66 years) participants in the Atherosclerosis Risk in Communities Study compared the one minute vs. three minute later OH measurements and their association with history of dizziness and longitudinal adverse outcomes. The orthostatic hypotension, defined as a drop in blood pressure (BP) (systolic BP > 20 mm Hg or diastolic BP > 10 mm Hg) from the supine to standing position, was measured up to 5 times at 25-second intervals. The study group determined the association of each of the 5 OH measurements with history of dizziness on standing (logistic regression) and risk of fall, fracture, syncope, motor vehicle crashes, and all-cause mortality (Cox regression) over a median of 23 years of follow-up (through December 31, 2013).
In 11429 participants (mean age, 54 years; 6220 [54%] were women; 2934 [26%] were black) with at least 4 OH measurements after standing, after adjustment OH assessed at measurement 1 (mean [SD], 28 [5.4] seconds; range, 21-62 seconds) was the only measurement associated with higher odds of dizziness (odds ratio [OR], 1.49; 95% CI, 1.18-1.89). Measurement 1 was associated with the highest rates of fracture, syncope, and death at 18.9, 17.0, and 31.4 per 1000 person-years. Measurement 2 was associated with the highest rate of falls and motor vehicle crashes at 13.2 and 2.5 per 1000 personyears.
Furthermore, after adjustment measurement 1 was significantly associated with risk of fall (hazard ratio [HR], 1.22; 95% CI, 1.03-1.44), fracture (HR, 1.16; 95% CI, 1.01- 1.34), syncope (HR, 1.40; 95% CI, 1.20-1.63), and mortality (HR, 1.36; 95% CI, 1.23-1.51).
Measurement 2 (mean [SD], 53 [7.5] seconds; range, 43-83 seconds) was associated with all long-term outcomes, including motor vehicle crashes (HR, 1.43; 95% CI, 1.04-1.96).
Measurements obtained after 1 minute were not associated with dizziness and were inconsistently associated with individual long-term outcomes. According to this study in contrast with prevailing recommendations, OH measurements performed within 1 minute of standing were the most strongly related to dizziness and individual adverse outcomes, suggesting that OH be assessed within 1 minute of standing.

Diabetes and Hypertension : A Position Statement by the American Diabetes Association.
Ian H. de Boer et al. Diabetes Care 2017; 40:1273-1284.
The American Diabetes Association (ADA) published this Position Statement to update the assessment and treatment of hypertension among people with diabetes in Sept 2017.
The salient recommendations are as follows :
- Blood pressure should be measured at every routine clinical care visit. Patients found to have an elevated blood pressure (>140/90 mmHg) should have blood pressure confirmed using multiple readings, including measurements on a separate day, to diagnose hypertension.
- All hypertensive patients with diabetes should have home blood pressure monitored to identify white-coat hypertension.
- Orthostatic measurement of blood pressure should be performed during initial evaluation of hypertension and periodically at followup, or when symptoms of orthostatic hypotension are present, and regularly if orthostatic hypotension has been diagnosed.
- Most patients with diabetes and hypertension should be treated to asystolic blood pressure goal of, 140mmHg and a diastolic blood pressure goal of, 90 mmHg.
- Lower systolic and diastolic blood pressure targets, such as, 130/80 mmHg, may be appropriate for individuals at high risk of cardiovascular disease if they can be achieved without undue treatment burden. For patients with systolic blood pressure. 120 mmHg or diastolic blood pressure. 80 mmHg, lifestyle intervention consists of weight loss if overweight or obese; a Dietary Approaches to Stop Hypertension (DASH)-style dietary pattern including reduced sodium and increased potassium intake; increased fruit and vegetable consumption; moderation of alcohol intake; and increased physical activity.
- Patients with confirmed office based blood pressure >140/90 mmHg should, in addition to lifestyle therapy, have timely titration of pharmacologic therapy to achieve blood pressure goals.
- Patients with confirmed office based blood pressure > 160/100 mmHg should, in addition to lifestyle therapy, have prompt initiation and timely titration of two drugs or a singlepill combination of drugs demonstrated to reduce cardiovascular events in patients with diabetes. Treatment for hypertension should include drug classes demonstrated to reduce cardiovascular events in patients with diabetes: ACE inhibitors, angiotensin receptor blockers (ARBs), thiazide-like diuretics, or dihydropyridine calcium channel blockers.
- Multiple-drug therapy is generally required to achieve blood pressure targets (but not a combination of ACE inhibitors and ARBs).
- An ACE inhibitor or ARB, at the maximum tolerated dose indicated for blood pressure treatment, is the recommended first-line treatment for hypertension in patients with diabetes and urine albumin-to creatinine ratio >300 mg/g creatinine or 30-299 mg/g creatinine. If one class is not tolerated, the other should be substituted.
- For patients treated with an ACE inhibitor, ARB, or diuretic, serum creatinine/estimated glomerular filtration rate and serum potassium levels should be monitored.
- In patients receiving pharmacologic antihypertensive treatment, home blood pressure should be measured to promote patient engagement in treatment and adherence.
- Patients with resistant hypertension who are not meeting blood pressure targets on conventional drug therapy with three agents, including a diuretic, should be referred to a certified hypertension specialist.
- Patients with resistant hypertension who are not meeting blood pressure targets on conventional drug therapy with three agents should be considered for mineralocorticoid receptor antagonist therapy.
- Pregnant women with diabetes and preexisting hypertension or mild gestational hypertension with systolic blood pressure, 160 mmHg, diastolic blood pressure, 105 mmHg, and no evidence of end-organ damage do not need to be treated with pharmacologic antihypertensivetherapy.
- In pregnant patients with diabetes and preexisting hypertension who are treated with antihypertensive therapy, systolic or diastolic blood pressure targets of 120-160/80-105 mmHg are suggested in the interest of optimizing long-term maternal health and fetal growth.

Courtsy by :
Dr. Samar Banerjee
Prof., Dept. of Medicine


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