Month: January 2012

Helium-oxygen therapy for infants with bronchiolitis: a randomized controlled trial.

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To compare nebulized racemic epinephrine delivered by 70% helium and 30% oxygen or 100% oxygen followed by helium-oxygen inhalation therapy via high-flow nasal cannula (HFNC) vs oxygen inhalation via HFNC in the treatment of bronchiolitis.
DESIGN: Prospective, randomized, controlled, single-blind trial.
SETTING: This study was conducted from October 1, 2004, through May 31, 2008, in the emergency department of an urban, tertiary care children`s hospital. Patients Infants aged 2 to 12 months with a Modified Wood`s Clinical Asthma Score (M-WCAS) of 3 or higher.
INTERVENTIONS: Patients initially received nebulized albuterol treatment driven by 100% oxygen. Patients were randomized to the helium-oxygen or oxygen group and received nebulized racemic epinephrine via a face mask. After nebulization, humidified helium-oxygen or oxygen was delivered by HFNC. After 60 minutes of inhalation therapy, patients with an M-WCAS of 2 or higher received a second delivery of nebulized racemic epinephrine followed by helium-oxygen or oxygen delivered by HFNC. Main Outcome Measure Degree of improvement of M-WCAS for 240 minutes or until emergency department discharge.
RESULTS: Of 69 infants enrolled, 34 were randomized to the helium-oxygen group and 35 to the oxygen group. The mean change in M-WCAS from baseline to 240 minutes or emergency department discharge was 1.84 for the helium-oxygen group compared with 0.31 for the oxygen group (P < .001). The mean M-WCAS was significantly improved for the helium-oxygen group compared with the oxygen group at 60 minutes (P = .005), 120 minutes (P < .001), 180 minutes (P < .001), and 240 minutes (P < .001).
CONCLUSION: Nebulized racemic epinephrine delivered by helium-oxygen followed by helium-oxygen inhalation therapy delivered by HFNC was associated with a greater degree of clinical improvement compared with that delivered by oxygen among infants with bronchiolitis.

Source: Archives of  Pediatric and  Adolesc ent Medicine.

 

Enoxaparin followed by once-weekly idrabiotaparinux versus enoxaparin plus warfarin for patients with acute symptomatic pulmonary embolism: a randomised, double-blind, double-dummy, non-inferiority trial.

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Treatment of pulmonary embolism with low-molecular-weight heparin and vitamin K antagonists, such as warfarin, is not ideal. We aimed to assess non-inferiority of idrabiotaparinux, a reversible longlasting indirect inhibitor of activated factor X, to warfarin in patients with acute symptomatic pulmonary embolism.
METHODS: In our randomised, double-blind, double-dummy, non-inferiority trial, we enrolled adults with objectively documented acute symptomatic pulmonary embolism attending 291 centres in 37 countries. We excluded patients who were pregnant, had active bleeding, kidney failure, or malignant hypertension, or were at high risk of death, bleeding, or adverse reactions to study drugs. We randomly allocated patients to receive 5-10 days` enoxaparin 1.0 mg/kg twice daily followed by subcutaneous idrabiotaparinux (starting dose 3.0 mg) or adjusted-dose warfarin (target international normalised ratio 2.0-3.0); regimens lasted 3 months or 6 months dependent on clinical presentation. Block randomisation was done with a central interactive computerised system, stratified by study centre and intended treatment duration. The primary efficacy outcome was recurrent venous thromboembolism at 99 days after randomisation. We estimated the odds ratio and 95% CI with a Mantel-Haenzsel chi(2) analysis (non-inferiority margin 2.0) in the intention-to-treat population. The main safety outcome was clinically relevant bleeding (major or non-major) in all patients at day 99. This study is registered with ClinicalTrials.gov, number NCT00345618.
FINDINGS: Between Aug 1, 2006, and Jan 31, 2010, we enrolled 3202 patients aged 18-96 years. 34 (2%) of 1599 patients randomly allocated to receive enoxaparin-idrabiotaparinux and 43 (3%) of 1603 patients randomly allocated to receive enoxaparin-warfarin had recurrent venous thromboembolism (odds ratio 0.79, 95% CI 0.50-1.25; p(non-inferiority)=0.0001). 72 (5%) of 1599 patients in the enoxaparin-idrabiotaparinux group and 106 (7%) of 1603 patients in the enoxaparin-warfarin group had clinically relevant bleeding (0.67, 0.49-0.91; p(superiority)=0.0098). We noted similar differences in outcomes in those patients treated to 6 months.
INTERPRETATION: Idrabiotaparinux could provide an attractive alternative to warfarin for the long-term treatment of pulmonary embolism, and seems to be associated with reduced bleeding.
FUNDING: Sanofi-Aventis (Paris, France).

Source:Lancet

Rivaroxaban in patients with a recent acute coronary syndrome.

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Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Since factor Xa plays a central role in thrombosis, the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome.
METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. The primary efficacy end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke.
RESULTS: Rivaroxaban significantly reduced the primary efficacy end point, as compared with placebo, with respective rates of 8.9% and 10.7% (hazard ratio in the rivaroxaban group, 0.84; 95% confidence interval [CI], 0.74 to 0.96; P=0.008), with significant improvement for both the twice-daily 2.5-mg dose (9.1% vs. 10.7%, P=0.02) and the twice-daily 5-mg dose (8.8% vs. 10.7%, P=0.03). The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes (2.7% vs. 4.1%, P=0.002) and from any cause (2.9% vs. 4.5%, P=0.002), a survival benefit that was not seen with the twice-daily 5-mg dose. As compared with placebo, rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting (2.1% vs. 0.6%, P<0.001) and intracranial hemorrhage (0.6% vs. 0.2%, P=0.009), without a significant increase in fatal bleeding (0.3% vs. 0.2%, P=0.66) or other adverse events. The twice-daily 2.5-mg dose resulted in fewer fatal bleeding events than the twice-daily 5-mg dose (0.1% vs. 0.4%, P=0.04).
CONCLUSIONS: In patients with a recent acute coronary syndrome, rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding.

Source:NEJM

 

Comparison of three predictive rules for assessing severity in elderly patients with CAP.

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This study compares the ability of the Pneumonia Severity Index (PSI) and the British Thoracic Society CURB-65 and CRB-65 rules in predicting short-term mortality among elderly patients with community-acquired pneumonia (CAP).
METHODS: It is a population-based study including all people over 65 years old with a radiographically confirmed CAP in the region of Tarragona (Spain) between 2002 and 2008. Treatment setting and clinical variables were considered for each patient. PSI, CURB-65 and CRB-65 scores were calculated at the moment of diagnosis and 30-day mortality was considered as a main dependent variable. The rules were compared based on sensitivity, specificity and area under the receiver operating characteristic curve (AUC).
RESULTS: Of the total 590 CAP cases, mortality rate was 13.6% (15.3% in hospitalised and 1.4% in outpatient cases; p = 0.001). Mortality increased with increasing PSI score (None in class II, 6,9% in class III, 14,4% in class IV and 29,5% in class V), CURB-65 score (7.5%, 14.5%, 26.7%, 53.3% and 100% for scores 1,2,3,4 and 5 respectively) and CRB-65 score (6.6%, 26.1%, 40.5% and 50% for scores 1,2,3 and 4 respectively). The three rules performed too similarly to predict 30-day mortality, with a ROC area of 0.727 [95% confidence interval (CI): 0.67-0.79] for the PSI, 0.672 (95% CI: 0.61-0.74) for the CURB-65, and 0.719 (95% CI: 0.65-0.78) for the CRB-65.
CONCLUSION: Our data shows that the analysed rules perform equally well among elderly people with CAP which supports the recommendation for using the simplified CRB-65 severity score among elderly patients in primary care or emergency visits.

Source: International Journal of clinical practice.

Early additional food and fluids for healthy breastfed full-term infants.

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Widespread recommendations from health organisations encourage exclusive breastfeeding for six months. However the addition of other fluids or foods before six months is common practice in many countries and communities. This practice suggests perceived benefits of early supplementation or lack of awareness of the possible risks.
OBJECTIVES: To assess the benefits and harms of supplementation for full-term healthy breastfed infants and to examine the timing and type of supplementation. SEARCH
METHODS: We searched the Cochrane Pregnancy and Childbirth Group`s Trials Register (1 March 2011) and reference lists of all relevant retrieved papers.
SELECTION CRITERIA: Randomised or quasi-randomised controlled trials in infants under six months of age comparing exclusive breastfeeding versus breastfeeding with any additional food or fluids.
DATA COLLECTION AND ANALYSIS: Two authors independently selected the trials; three extracted data and assessed risk of bias.
MAIN RESULTS: We included six trials (814 infants). Two trials in the early days after birth that reported data did not indicate that giving additional fluids was beneficial. For duration of breastfeeding, there was a significant difference favouring exclusive breastfeeding up to and including week 20 (risk ratio (RR) 1.45, 95% confidence interval (CI) 1.05 to 1.99), indicating that supplements may contribute to reducing the duration.For infant morbidity (three trials), one newborn trial found a statistically, but not clinically, significant difference in temperature at 72 hours (MD 0.10 degrees, 95% CI 0.01 to 0.19), and that serum glucose levels were higher in glucose supplemented infants in the first 24 hours, though not at 48 hours (MD -0.24mmol/l, 95% CI -0.51 to 0.03). Two trials with four- to six-month-old infants did not indicate any benefit to supplemented infants to 26 weeks nor any risks related to morbidity or weight change.None of the trials reported on the remaining primary outcomes, infant mortality or physiological jaundice.
AUTHORS’ CONCLUSIONS: We were unable to fully assess the benefits or harms of supplementation or to determine the impact from timing and type of supplementation .We found no benefit to newborn infants and possible negative effects on the duration of breastfeeding from the brief use of additional water or glucose water. For infants at four to six months, we found no benefit from additional foods nor any risks related to morbidity or weight change. Future studies should examine the longer term effects on infants and mothers, though randomising infants to receive supplements without medical need may be considered unethical.We found no evidence for disagreement with the recommendation of international health associations that exclusive breastfeeding should be recommended for healthy infants for the first six months.

Source:Cochrane library.

 

Age and risks of FDA-approved long-acting beta-adrenergic receptor agonists.

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To determine the risk, by age group, of serious asthma-related events with long-acting beta(2)-adrenergic receptor agonists marketed in the United States for asthma.
METHODS: The US Food and Drug Administration performed a meta-analysis of controlled clinical trials comparing the risk of LABA use with no LABA use for patients 4 to 11, 12 to 17, 18 to 64, and older than 64 years old. The effects of age on a composite of asthma-related deaths, intubations, and hospitalizations (asthma composite index) and the effects of concomitant inhaled corticosteroid (ICS) use were analyzed.
RESULTS: One hundred ten trials with 60 954 patients were included in the meta-analysis. The composite event incidence difference for all ages was 6.3 events per 1000 patient-years (95% confidence interval [CI]: 2.2-10.3) for using LABAs compared with not using LABAs. The largest incidence difference was observed for the 4- to 11-year age group (30.4 events per 1000 patient-years [95% CI: 5.7-55.1]). Differences according to age were statistically significant (P = .020). Results for the subgroup of patients with concomitant ICS use (n = 36 210) were similar to the overall results; with assigned ICSs (n = 15 192), the incidence difference was 0.4 events per 1000 patient-years (95% CI: -3.8 to 4.6), and there was no statistically significant difference according to age group.
CONCLUSIONS: The excess of serious asthma-related events attributable to LABAs was greatest among children. Additional data are needed to assess risks of LABA use for children with simultaneous ICS use.

Source:Cochrane library.

Antiplatelet agents and anticoagulants for hypertension.

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Elevated systemic blood pressure results in high intravascular pressure but the main complications, coronary heart disease (CHD), ischaemic strokes and peripheral vascular disease (PVD), are related to thrombosis rather than haemorrhage. Some complications related to elevated blood pressure, heart failure or atrial fibrillation, are themselves associated with stroke and thromboembolism. Therefore it is important to investigate if antithrombotic therapy may be useful in preventing thrombosis-related complications in patients with elevated blood pressure.
OBJECTIVES: To conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with high blood pressure, including those with elevations in both systolic and diastolic blood pressure, isolated elevations of either systolic or diastolic blood pressure, to address the following hypotheses: (i) antiplatelet agents reduce total deaths and/or major thrombotic events when compared to placebo or other active treatment; and (ii) oral anticoagulants reduce total deaths and/or major thromboembolic events when compared to placebo or other active treatment. SEARCH
METHODS: Electronic databases (MEDLINE, EMBASE, DARE, CENTRAL, Hypertension Group specialised register) were searched up to January 2011. The reference lists of papers resulting from the electronic searches and abstracts from national and international cardiovascular meetings were hand-searched to identify missed or unpublished studies. Relevant authors of studies were contacted to obtain further data.
SELECTION CRITERIA: Randomised controlled trials (RCTs) in patients with elevated blood pressure were included if they were of at least 3 months in duration and compared antithrombotic therapy with control or other active treatment.
DATA COLLECTION AND ANALYSIS: Data were independently collected and verified by two reviewers. Data from different trials were pooled where appropriate.
MAIN RESULTS: Four trials with a combined total of 44,012 patients met the inclusion criteria and are included in this review. Acetylsalicylic acid (ASA) did not reduce stroke or `all cardiovascular events` compared to placebo in primary prevention patients with elevated blood pressure and no prior cardiovascular disease. In one large trial ASA taken for 5 years reduced myocardial infarction (ARR 0.5%, NNT 200), increased major haemorrhage (ARI 0.7%, NNT 154), and did not reduce all cause mortality or cardiovascular mortality. In one trial there was no significant difference between ASA and clopidogrel for the composite endpoint of stroke, myocardial infarction or vascular death. In two small trials warfarin alone or in combination with ASA did not reduce stroke or coronary events. The ATC meta-analysis of antiplatelet therapy for secondary prevention in patients with elevated blood pressure reported an absolute reduction in vascular events of 4.1% as compared to placebo. Data on the 10,600 patients with elevated blood pressure from the 29 individual trials included in the ATC meta-analysis was requested but could not be obtained.
AUTHORS’ CONCLUSIONS: Antiplatelet therapy with ASA for primary prevention in patients with elevated blood pressure provides a benefit, reduction in myocardial infarction, which is negated by a harm of similar magnitude, increase in major haemorrhage.The benefit of antiplatelet therapy for secondary prevention in patients with elevated blood pressure is many times greater than the harm.Benefit has not been demonstrated for warfarin therapy alone or in combination with aspirin in patients with elevated blood pressure. Ticlopidine, clopidogrel and newer antiplatelet agents such as prasugrel and ticagrelor have not been sufficiently evaluated in patients with high blood pressure. Newer antithrombotic oral drugs such as dabigatran, rivaroxaban, apixaban and endosaban are yet to be tested in patients with high blood pressure.Further trials of antithrombotic therapy including with newer agents and complete documentation of all benefits and harms are required in patients with elevated blood pressure.

Source:Cochrane library.

 

Novartis extends commitment to help achieve final elimination of leprosy.

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  • New five-year commitment includes donation of treatments worth an estimated USD 22.5 million and is expected to reach an estimated 850,000 patients
  • Novartis will also intensify efforts to build a multi-stakeholder initiative in a final push against leprosy
  • The company has a long history in fighting leprosy, donating medicines and developing programs to support patients, valued at more than USD 100 million since 1986
  • Novartis is a part of an international effort to eliminate or control 10 neglected tropical diseases (NTDs) by the end of the decade

Novartis will continue its work with the World Health Organization (WHO) toward a world free of leprosy by extending its drug donation of multidrug therapy (MDT) medicines to treat leprosy through the year 2020. This new five-year commitment includes treatments worth an estimated USD 22.5 million and up to USD 2.5 million to support the WHO in handling the donation and logistics, and is expected to reach an estimated 850,000 patients.

“Since 2000, we have worked with the WHO to provide free treatment to leprosy patients globally, but we know that no single actor – no matter how committed to patients – can eliminate this debilitating disease alone,” said Joseph Jimenez, CEO of Novartis. “We are proud to work with governments, international agencies, nongovernmental organizations and the private sector to ensure that patients receive the treatment they need. Only with effective and coordinated action by all parties involved can we achieve our common goal of making leprosy history.”

Novartis and the Novartis Foundation for Sustainable Development (NFSD) have a long-term commitment to leprosy treatment and control. Prior to today’s announcement, Novartis has donated more than 48 million MDT blister packs valued at approximately USD 77 million through the WHO, helping to cure over 5 million leprosy patients worldwide.

The NFSD has been active in the fight against leprosy for more than 25 years, through implementing innovative social marketing programs to reduce the stigma attached to leprosy, developing tools to prevent disabilities, helping patients reintegrate in society, and supporting the leprosy drug donation. Since 1986, the NFSD has provided over CHF 30 million for these programs.

Donating drugs alone, however, is not enough, and NFSD is committed to intensify efforts to build a multi-stakeholder initiative in a final push against leprosy. On January 25, the NFSD, in cooperation with the Department of Health of the Philippines, held the first Leprosy Stakeholders Symposium in Puerto Princesa City, Palawan. The groundbreaking symposium gathered all major stakeholders and partners from both government and private sectors with the goal of eliminating leprosy in areas of the Philippines where the disease is still endemic.

The extension of the Novartis leprosy commitment is a key part of a new, coordinated push by a diverse range of public and private collaborators to combat 10 Neglected Tropical Diseases (NTDs) by 2020. Today, 13 pharmaceutical companies, the U.S. and U.K. governments, the Bill & Melinda Gates Foundation, the World Bank and officials from NTD-endemic countries pledged to bring a unique focus to defeating these diseases and to work together to improve the lives of the billion people worldwide affected by NTDs.

In the largest coordinated effort to date to combat NTDs, the group announced at an event at the Royal College of Physicians in London that they would: sustain or expand existing drug donation programs to meet demand through 2020; share expertise and compounds to accelerate research and development of new drugs; and provide funding to support R&D efforts and strengthen drug distribution and implementation programs.  The collaborators also signed onto the “London Declaration on Neglected Tropical Diseases,” in which they pledged new levels of collaboration and tracking and reporting of progress.

This announcement is a part of the company’s long commitment to enhancing access to healthcare in the developing world. Novartis works to discover vaccines and medicines for neglected diseases through two research institutes: Novartis Institute for Tropical Diseases (NITD) in Singapore and the Novartis Vaccines Institute for Global Health (NVGH) in Italy. The Novartis Malaria Initiative is one of the healthcare industry’s largest access-to-medicine programs. Since 2001, Novartis has worked with a range of organizations to ensure effective delivery of our antimalarial medicine, providing more than 480 million treatments without profit.

In 2011, Novartis access-to-medicine programs reached more than 89 million patients and together with our research institutes for diseases of the developing world, are valued at USD 1.7 billion, or 3% of net sales.

About multidrug therapy (MDT) in treating leprosy
Since 1985, more than 14 million people worldwide have been cured of leprosy thanks to MDT, the treatment recommended by the WHO, shrinking the worldwide prevalence by approximately 95%. According to the WHO, in 2010 less than 230,000 new cases were reported, from a total of 130 countries worldwide. Despite these successes, leprosy control remains at a critical juncture and knowledge of the disease is becoming less common. Moving forward, early detection and continued availability of free treatment are essential.

The development of MDT changed the face of leprosy dramatically. MDT consists of three drugs (rifampicin, clofazimine and dapsone), two of which (rifampicin and clofazimine) were developed in the research laboratories of Novartis in the 1980s. Multidrug therapy has made it possible to cure patients, interrupt the transmission of leprosy and prevent disabilities. Even patients with the severest form of the disease show visible clinical improvement within weeks of starting treatment.

About the Novartis Foundation for Sustainable Development
The Novartis Foundation for Sustainable Development is a nonprofit organization whose activities form part of the Corporate Responsibility portfolio of Novartis AG, which finances the foundation’s operations. For over 30 years, the foundation’s mission has been to support healthcare programs in developing countries. Its core competencies also include in-depth analysis, consulting and publications in the fields of corporate responsibility and development policy. By harnessing synergies between project work, think tank activities and the facilitation of dialogue, it elaborates innovative strategies for common development problems. In 2011, the Novartis Foundation for Sustainable Development invested approximately CHF 10 million, largely in Africa and Asia.

Source:Novartis

Long-Acting Exenatide Approved for Type 2 Diabetes .

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After two denials, extended-release exenatide (marketed as Bydureon) has received FDA approval as an adjunct to diet and exercise for the treatment of type 2 diabetes. According to the New York Times, approval was previously denied due to concerns that the once-weekly injectable might contribute to heart rhythm abnormalities. (The twice-daily version, Byetta, was approved in 2005.

Approval was based in part on a randomized study of some 250 adults that compared once-weekly Bydureon with twice-daily Byetta. After 24 weeks, hemoglobin A1C levels were reduced more with Bydureon than with Byetta (1.6 vs. 0.9 percentage points lower than baseline). The most frequent side effect — nausea — was less common with Bydureon (14% vs. 35%). Other side effects included diarrhea and upper respiratory tract infection.

The FDA is requiring the manufacturer to provide a Risk Evaluation and Mitigation Strategy to inform providers about the drug’s risk for acute pancreatitis and possible risk for thyroid cancer.

source:NYT

BP Differences Between a Patient’s Arms Linked to Peripheral Vascular Disease, Mortality

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A systolic blood pressure difference of 15 mm Hg or more between a patient’s arms is associated with increased risks for peripheral vascular disease and mortality, according to a Lancet meta-analysis.

The analysis included 20 studies, most involving patients at high cardiovascular risk. Overall, a between-arm difference in systolic BP of 10–15 mm Hg or more was associated with an increased likelihood of peripheral vascular disease (risk ratio, nearly 2.5). A difference of 15 mm Hg or more was also associated with a heightened likelihood of cerebrovascular disease and cardiovascular and all-cause mortality.

The researchers say between-arm BP differences “might help to identify patients who need further vascular assessment.” Commentators point out numerous limitations (e.g., many studies were cross-sectional), but conclude that the analysis “supports existing guidelines stating that blood pressure should be measured in both arms. Ascertainment of differences should become part of routine care, as opposed to a guideline recommendation that is mostly ignored.”

Source:Lancet