Effects of Iron Supplementation and Depletion on Hypoxic Pulmonary Hypertension

Quoting JAMA:

Two Randomized Controlled Trials

Thomas G. Smith, MBBS, DPhil; Nick P. Talbot, BMBCh, DPhil; Catherine Privat, BSc; Maria Rivera-Ch, PhD; Annabel H. Nickol, MBBS, PhD;Peter J. Ratcliffe, BMBCh, MD; Keith L. Dorrington, DM, DPhil; Fabiola León-Velarde, PhD; Peter A. Robbins, BMBCh, DPhil 

JAMA. 2009;302(13):1444-1450.

Context  Hypoxia is a major cause of pulmonary hypertension in respiratory disease and at high altitude. Recent work has established that the effect of hypoxia on pulmonary arterial pressure may depend on iron status, possibly acting through the transcription factor hypoxia-inducible factor, but the pathophysiological and clinical importance of this interaction is unknown.

Objective  To determine whether increasing or decreasing iron availability modifies altitude-induced hypoxic pulmonary hypertension.

Design, Setting, and Participants  Two randomized, double-blind, placebo-controlled protocols conducted in October-November 2008. In the first protocol, 22 healthy sea-level resident men (aged 19-60 years) were studied over 1 week of hypoxia at Cerro de Pasco, Peru (altitude 4340 m). In the second protocol, 11 high-altitude resident men (aged 30-59 years) diagnosed with chronic mountain sickness were studied over 1 month of hypoxia at Cerro de Pasco, Peru.

Intervention  In the first protocol, participants received intravenous infusions of Fe(III)-hydroxide sucrose (200 mg) or placebo on the third day of hypoxia. In the second protocol, patients underwent staged isovolemic venesection of 2 L of blood. Two weeks later, patients received intravenous infusions of Fe(III)-hydroxide sucrose (400 mg) or placebo, which were subsequently crossed over.

Main Outcome Measure  Effect of varying iron availability on pulmonary artery systolic pressure (PASP) assessed by Doppler echocardiography.

Results  In the sea-level resident protocol, approximately 40% of the pulmonary hypertensive response to hypoxia was reversed by infusion of iron, which reduced PASP by 6 mm Hg (95% confidence interval [CI], 4-8 mm Hg), from 37 mm Hg (95% CI, 34-40 mm Hg) to 31 mm Hg (95% CI, 29-33 mm Hg; P = .01). In the chronic mountain sickness protocol, progressive iron deficiency induced by venesection was associated with an approximately 25% increase in PASP of 9 mm Hg (95% CI, 4-14 mm Hg), from 37mm Hg (95% CI, 30-44 mm Hg) to 46 mm Hg (95% CI, 40-52 mm Hg; P = .003). During the subsequent crossover period, no acute effect of iron replacement on PASP was detected.

Conclusion  Hypoxic pulmonary hypertension may be attenuated by iron supplementation and exacerbated by iron depletion.

Postextubation stridor and the Cochrane Review

Quoting: http://www.cochrane.org/reviews/en/ab001000.html

BACKGROUND: Post-extubation stridor may prolong length of stay in the intensive care unit, particularly if airway obstruction is severe and re-intubation proves necessary. Some clinicians use corticosteroids to prevent or treat post-extubation stridor, but corticosteroids may be associated with adverse effects ranging from hypertension to hyperglycaemia, so a systematic assessment of the efficacy of this therapy is indicated. OBJECTIVES: To determine whether corticosteroids are effective in preventing or treating post-extubation stridor in critically ill infants, children, or adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL and reference lists of articles. The most recent searches were conducted in January 2009. SELECTION CRITERIA: Randomized controlled trials comparing administration of corticosteroids by any route with placebo in infants, children, or adults receiving mechanical ventilation via an endotracheal tube in an intensive care unit. DATA

COLLECTION AND ANALYSIS: Three review authors independently assessed trial quality and extracted data. MAIN

RESULTS: Eleven trials involving 2301 people were included: six in adults, two in neonates, three in children. All but one examined use of steroids for the prevention of post-extubation stridor; the remaining one concerned treatment of existing post-extubation stridor in children. Patients were drawn from heterogeneous medical/surgical populations. Dexamethasone given intravenously at least once prior to extubation was the most common steroid regimen utilized (uniformly in neonates and children). In neonates the two studies found heterogeneous results, with no overall statistically significant reduction in post extubation stridor (RR 0.42; 95% CI 0.07 to 2.32). One of these studies was on high-risk patients treated with multiple doses of steroids around the time of extubation, and this study showed a significant reduction in stridor. In children, the two studies were clinically heterogeneous. One study included children with underlying airway abnormalities and the other excluded this group. Prophylactic corticosteroids tended to reduce reintubation and significantly reduced post-extubation stridor in the study that included children with underlying airway abnormalities (N = 62) but not in the study that excluded these children (N = 153). In six adult studies (total N = 1953), the use of prophylactic corticosteroid administration did not significantly reduce the risk of re-intubation (RR 0.48; 95% CI 0.19 to 1.22). While there was a significant reduction in the incidence of post extubation stridor (RR 0.47; 95% CI 0.22 to 0.99), there was significant heterogeneity (I(2)=81%, X(2)=26.36, df=5, p<0.0001). Subgroup analysis revealed that post extubation stridor could be reduced in adults with a high likelihood of post extubation stridor when corticosteroids were administered as multiple doses begun 12-24 hours prior to extubation compared to single doses closer to extubation; the test for interaction for multiple versus single doses indicated RRR 0.22 (95% CI 0.10 to 0.47) for stridor with multiple doses. Side effects were uncommon and could not be aggregated. AUTHORS`

CONCLUSIONS: Using corticosteroids to prevent (or treat) stridor after extubation has not proven effective for neonates or children. However, given the consistent trends towards benefit, this intervention does merit further study, particularly for high risk children or neonates. In adults, multiple doses of corticosteroids begun 12-24 hours prior to extubation do appear beneficial for patients with a high likelihood of post extubation stridor.

Procalcitonin and bacterial lower respiratory tract infections

Quoting: http://jama.ama-assn.org/cgi/content/full/302/10/1059?home

Context In previous smaller trials, a procalcitonin (PCT) algorithm reduced antibiotic use in patients with lower respiratory tract infections (LRTIs).

Objective To examine whether a PCT algorithm can reduce antibiotic exposure without increasing the risk for serious adverse outcomes.

Design, Setting, and Patients A multicenter, noninferiority, randomized controlled trial in emergency departments of 6 tertiary care hospitals in Switzerland with an open intervention of 1359 patients with mostly severe LRTIs randomized between October 2006 and March 2008.

Intervention Patients were randomized to administration of antibiotics based on a PCT algorithm with predefined cutoff ranges for initiating or stopping antibiotics (PCT group) or according to standard guidelines (control group). Serum PCT was measured locally in each hospital and instructions were Web-based.

Main Outcome Measures Noninferiority of the composite adverse outcomes of death, intensive care unit admission, disease-specific complications, or recurrent infection requiring antibiotic treatment within 30 days, with a predefined noninferiority boundary of 7.5%; and antibiotic exposure and adverse effects from antibiotics.

Results The rate of overall adverse outcomes was similar in the PCT and control groups (15.4% [n = 103] vs 18.9% [n = 130]; difference, –3.5%; 95% CI, –7.6% to 0.4%). The mean duration of antibiotics exposure in the PCT vs control groups was lower in all patients (5.7 vs 8.7 days; relative change, –34.8%; 95% CI, –40.3% to –28.7%) and in the subgroups of patients with community-acquired pneumonia (n = 925, 7.2 vs 10.7 days; –32.4%; 95% CI, –37.6% to –26.9%), exacerbation of chronic obstructive pulmonary disease (n = 228, 2.5 vs 5.1 days; –50.4%; 95% CI, –64.0% to –34.0%), and acute bronchitis (n = 151, 1.0 vs 2.8 days; –65.0%; 95% CI, –84.7% to –37.5%). Antibiotic-associated adverse effects were less frequent in the PCT group (19.8% [n = 133] vs 28.1% [n = 193]; difference, –8.2%; 95% CI, –12.7% to –3.7%).

Conclusion In patients with LRTIs, a strategy of PCT guidance compared with standard guidelines resulted in similar rates of adverse outcomes, as well as lower rates of antibiotic exposure and antibiotic-associated adverse effects.

New RANK ligant target reduces significant osteoporotic fractures

From NEJM

Background Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-B ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density. Given its unique actions, denosumab may be useful in the treatment of osteoporosis.

Methods We enrolled 7868 women between the ages of 60 and 90 years who had a bone mineral density T score of less than –2.5 but not less than –4.0 at the lumbar spine or total hip. Subjects were randomly assigned to receive either 60 mg of denosumab or placebo subcutaneously every 6 months for 36 months. The primary end point was new vertebral fracture. Secondary end points included nonvertebral and hip fractures.

Results As compared with placebo, denosumab reduced the risk of new radiographic vertebral fracture, with a cumulative incidence of 2.3% in the denosumab group, versus 7.2% in the placebo group (risk ratio, 0.32; 95% confidence interval [CI], 0.26 to 0.41; P<0.001) — a relative decrease of 68%. Denosumab reduced the risk of hip fracture, with a cumulative incidence of 0.7% in the denosumab group, versus 1.2% in the placebo group (hazard ratio, 0.60; 95% CI, 0.37 to 0.97; P=0.04) — a relative decrease of 40%. Denosumab also reduced the risk of nonvertebral fracture, with a cumulative incidence of 6.5% in the denosumab group, versus 8.0% in the placebo group (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) — a relative decrease of 20%. There was no increase in the risk of cancer, infection, cardiovascular disease, delayed fracture healing, or hypocalcemia, and there were no cases of osteonecrosis of the jaw and no adverse reactions to the injection of denosumab.

Conclusions Denosumab given subcutaneously twice yearly for 36 months was associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis. (ClinicalTrials.gov number, NCT00089791 [ClinicalTrials.gov] .)

CPAP or BiPAP after extubation seems a good idea

quoting the Lancet.com

Background

Non-invasive ventilation can prevent respiratory failure after extubation in individuals at increased risk of this complication, and enhanced survival in patients with hypercapnia has been recorded. We aimed to assess prospectively the effectiveness of non-invasive ventilation after extubation in patients with hypercapnia and as rescue therapy when respiratory failure develops.

Methods

We undertook a randomised controlled trial in three intensive-care units in Spain. We enrolled 106 mechanically ventilated patients with chronic respiratory disorders and hypercapnia after a successful spontaneous breathing trial. We randomly allocated participants by computer to receive after extubation either non-invasive ventilation for 24 h (n=54) or conventional oxygen treatment (n=52). The primary endpoint was avoidance of respiratory failure within 72 h after extubation. Analysis was by intention to treat. This trial is registered with clinicaltrials.gov, identifier NCT00539708.

Findings

Respiratory failure after extubation was less frequent in patients assigned non-invasive ventilation than in those allocated conventional oxygen therapy (8 [15%] vs 25 [48%]; odds ratio 5·32 [95% CI 2·11—13·46]; p<0·0001). In patients with respiratory failure, non-invasive ventilation as rescue therapy avoided reintubation in 17 of 27 patients. Non-invasive ventilation was independently associated with a lower risk of respiratory failure after extubation (adjusted odds ratio 0·17 [95% CI 0·06—0·44]; p<0·0001). 90-day mortality was lower in patients assigned non-invasive ventilation than in those allocated conventional oxygen (p=0·0146).

Interpretation

Early non-invasive ventilation after extubation diminished risk of respiratory failure and lowered 90-day mortality in patients with hypercapnia during a spontaneous breathing trial. Routine implementation of this strategy for management of mechanically ventilated patients with chronic respiratory disorders is advisable.

Needlesspanic.com

Quoting FT

By Margaret McCartney

Published: August 1 2009 01:56 | Last updated: August 1 2009 01:56

Copyright The Financial Times Limited 2009

H1N1 influenza, more commonly known and feared as swine flu, is making its presence firmly felt in the UK. By this point, most people will know someone who has been affected, and most people will have sneaking fears about being next in line. As I write, the National Health Service is about to launch a self-diagnosis website that will enable patients in England to allay or confirm these concerns. If deemed necessary, a prescription of antivirals will then be organised.

This seems reasonable. In a pandemic, NHS services simply can’t operate normally. The internet sidesteps many of the problems – huge volumes of patients, the infection risk of crowded waiting rooms – but it is not without flaws.

Some flu symptoms – a headache, say, or diarrhoea – can be confused with signs of other illnesses, such as bacterial or viral meningitis or gastroenteritis. We get it right most of the time, though this may be down to statistics rather than skill (meningitis, after all, is rarer than flu). We also get it right because when a GP and a patient meet, there is usually a prior relationship, providing knowledge about the patient’s medical history, current medication and social circumstances. A computer program isn’t able to replicate the complex information required for a diagnosis that will ensure the best treatment is made available.

And what is the treatment? Antiviral medication has been stockpiled in massive quantities around the UK. For people at higher risk of complications from flu – children, the elderly, pregnant women and the chronically ill – it may be reasonable to take the treatment. For otherwise healthy people, the benefits are less clear.

A Cochrane review from 2008 examining the effect of these antiviral drugs in healthy adults concluded that, “Because of their low effectiveness, NIs [neuraminidase inhibitors, or antiviral drugs] should not be used in routine seasonal influenza control. In a serious epidemic or pandemic, NIs should be used with other public health measures. We are unsure of the generalisability of our conclusions from seasonal to pandemic or avian influenza.” This seems to me to be the ideal time to get a clinical trial under way and test these conclusions, making the results obtainable for any second wave of infection that may occur.

As for how to diagnose people: even during a pandemic, there may be better half-way measures than offering diagnosis via a computer screen. There are lots of part-time workers in the NHS, many of them female, who might be willing to help out if they can be found places to work from. Perhaps we should slow down and think about how best to use the resources we already have.

Margaret McCartney is a GP in Glasgow.
margaret.mccartney@ft.com

For lively discussion of the latest medical issues go to the FT’s Healthblog

Donate now! – Urgent

http://www.eiab-maincampus.org/EIAB_Germany/Donate.html

Vietnam says booting Buddhist monks not repression

By BEN STOCKING (AP) – 15 hours ago

HANOI, Vietnam — Monks following a world-famous Buddhist teacher are being evicted from a Vietnamese monastery for failing to clear their activities with the government, an official said Tuesday, but he denied the dispute was about religious freedom.

Followers of Thich Nhat Hanh, who has sold more than 1 million books in the West, say the government is punishing them because their France-based leader suggested that his native Vietnam’s communist government should abolish its control of religion.

However, Bui Huu Duoc of the government’s Committee on Religious Affairs, blamed the dispute on a failure to abide by local regulations and said it is normal for governments to oversee the operations of religious groups operating within their borders.

“Managing religious groups doesn’t mean controlling them,” Duoc, who oversees Buddhist affairs for the committee, said in an interview with The Associated Press. “We’re here to facilitate their efforts to do good things for the country.”

However, Duoc did allow that officials were “very surprised” at postings on the main Web site for Hanh’s main monastery in southern France calling for the government to disband religious police.

Vietnam formally recognizes less than a dozen religions, and they are all required to register with the state.

Hanh’s followers have been asked to leave the Bat Nha monastery in the Central Highlands by early September.

Tensions at Bat Nha boiled over in late June, when a mob descended on the site with sledgehammers, damaged buildings and threatened the Plum Village monks and nuns. Authorities also cut off electricity at the site.

The dispute represents a remarkable turnaround from four years ago, when France-based Hanh returned to his native land after 39 years of exile. He had been forced out of what was then U.S.-backed South Vietnam in 1966 for criticizing the Vietnam War. His return in 2005 made the front pages of state-owned newspapers.

Hanh’s brand of Buddhism is very popular in the West. Followers from around the world travel to his Plum Village monastery in southern France to study with him. He is perhaps the best known Buddhist after the Dalai Lama.

When Hanh’s followers first came in 2005, Duoc said, Vietnamese authorities approved their activities. But since July 2008, he said, they have offered 11 courses at the Bat Nha monastery without permission.

Hanh’s followers say they have kept the official Vietnam Buddhist Church fully informed.

They were invited to practice at Bat Nha by Abbot Duc Nghi during Hanh’s 2005 visit and say they have since spent nearly $1 million expanding the property and adding new buildings.

Nghi could not be reached for comment, but Duoc says the abbot now wants the nearly 400 Hanh followers at the monastery to leave.

Hanh’s followers believe Nghi is simply responding to pressure from above.

Duoc also said Tuesday that Vietnamese officials were “very surprised” by postings that appeared on the Plum Village Web site in February 2008. These included suggestions that Hanh made to President Nguyen Minh Triet during a 2007 visit to Hanoi, he said.

Among them was a proposal to abolish the Committee on Religious Affairs, disband Vietnam’s religious police, and make modifications to the formal names of both the communist party and the state, known as the Socialist Republic of Vietnam.

“When we first saw that information posted on the Plum Village Web site, we thought it must have been a mistake,” Duoc said.

Copyright © 2009 The Associated Press. All rights reserved.

Protected: Osteoporosis rapid review (fda-approved treatments)

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Introducing the new joint blogogenesis blog

http://appliedebm.wordpress.com

Welcome to the applied evidence blog. Within it’s electronic walls you will find upcoming clinical questions and answers based on the latest evidence.

Keep in mind that evidence based medicine has multiple limitations. It resembles socialized models in which what applies to the “group” applies to the individual. However, many of our decisions are individualized, our genome unique and what applies to a group of 50-70 year olds in Netherlands may not apply to 40 year olds in Baltimore.

Still, a given patient would like to know what is the most effective treatment on others with the same condition, what it the most likely cause of his or her illness etc.  I found myself looking for a free database of clinical PICO questions and since I couldn’t find a satisfactory one, I have created this blog. It is a joint blog with blogogenesis.wordpress.com.

You can use the comment section to ask/answer your own clinical questions. The purpose of this blog is to keep answers brief, recognize and suspect bias and promote a clinician and not a “statistician” thinking.

Welcome.

http://appliedebm.wordpress.com

Protected: My weak points in Hematology III

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