Is Immediate Cardioversion Necessary in New Onset Atrial Fibrillation?

MedicalResearch.com Interview with:

Atrial Fibrillation  Wikipedia example

Atrial Fibrillation
Wikipedia example

Harry J.G.M Crijns, MD, PhD
University Hospital Maastricht
Maastricht, The Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: An episode of the heart rhythm disorder ‘atrial fibrillation’ is a frequent reason for a visit to the Emergency Department. Patients commonly undergo a cardioversion to restore sinus rhythm – either electrical or pharmacological. However, it is known that episodes of atrial fibrillation frequently terminate spontaneously. Therefore, we conducted a multicenter randomized clinical trial in the Netherlands, researching whether a wait-and-see approach – consisting of heart rate slowing drugs and cardioversion only if the heart rhythm does not resolve spontaneously – was non-inferior to the current standard of care of immediate cardioversion.

The primary end point was the presence of sinus rhythm on the ECG at the 4 weeks visit, which was present in 91% in the wait-and-see approach and 94% in the standard of care, which was within the non-inferiority margin.

In the wait-and-see approach, 69% of patients returned to sinus rhythm spontaneously, i.e. without cardioversion. Complications were rare and comparable in both treatment arms, and the percentage of patients experiencing a recurrence of atrial fibrillation during the first 4 weeks after the index visit was comparable (30% vs 29% respectively). We concluded that in patients presenting to the emergency department with recent-onset, symptomatic atrial fibrillation, a wait-and-see approach was non-inferior to early cardioversion in achieving a return to sinus rhythm at 4 weeks.

MedicalResearch.com: What should readers take away from your report?

Response: Recent-onset symptomatic atrial fibrillation usually terminates spontaneously and therefore an acute cardioversion is not always necessary, as a wait-and-see approach is equally effective and safe. Quality of life is the same in both treatment options. Physicians should discuss with their patients which one of the two approaches – wait-and-see or immediate cardioversion – would be more suitable in their situation. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response: Now that we have shown that early, i.e. immediate cardioversion may not be necessary, we are planning future studies on how to implement a delayed cardioversion into daily practice.

MedicalResearch.com: Is there anything else you would like to add?

Response: Funding for this trial was provided by the Netherlands Organization for Health Research and Development, and Boehringer Ingelheim. 

Citation:

 

 Early or Delayed Cardioversion in Recent-Onset Atrial Fibrillation
Nikki A.H.A. Pluymaekers, M.D., Elton A.M.P. Dudink, M.D., Ph.D., Justin G.L.M. Luermans, M.D., Ph.D., Joan G. Meeder, M.D., Ph.D., Timo Lenderink, M.D., Ph.D.,
Jos Widdershoven, M.D., Ph.D., Jeroen J.J. Bucx, M.D., Ph.D.,
Michiel Rienstra, M.D., Ph.D., Otto Kamp, M.D., Ph.D.,

Jurren M. Van Opstal, M.D., Ph.D., Marco Alings, M.D., Ph.D.,
Anton Oomen, M.D., and Harry J.G.M. Crijns, M.D., Ph.D
et al., for the RACE 7 ACWAS Investigators*

March 18, 2019
DOI: 10.1056/NEJMoa1900353

 

 

Apr 15, 2019 @ 8:56 pm

 

 

 

The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

 

Verubecestat Failed to Slow Progression of Early Alzheimer’s Disease

MedicalResearch.com Interview with:
Michael F. Egan, MDVice President,  NeuroscienceGlobal Clinical DevelopmentMerck Research LaboratoriesNorth Wales, PAMichael F. Egan, MD
Vice President,  Neuroscience
Global Clinical Development
Merck Research Laboratories
North Wales, PA 

MedicalResearch.com: What is the background for this study?  

Response: Alzheimer’s disease (AD) appears to be due to the gradual accumulation of amyloid over many years (the “amyloid hypothesis”). At some point, it is thought that amyloid triggers abnormalities in tau, which then forms deposits within neurons and leads to progressive neurodegeneration.

Amyloid is made up of  a small, sticky peptide, Abeta, which is produced when the enzyme BACE cleaves a large protein called APP.  In our trial, we tested whether a potent BACE inhibitor, verubecestat, could slow disease progression in subjects with early AD (or prodromal AD) by blocking formation of Abeta.  A previous trial in subjects with dementia due to AD failed to find evidence of efficacy.

One possible reason for this failure is that subjects had too much amyloid in their brain already.

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Does Intermittent Leg Compression Reduce Blood Clots or Pulmonary Embolism?

MedicalResearch.com Interview with:

Yaseen M. Arabi, M.DIntensive Care DepartmentMinistry of National Guard Health AffairsICU 1425, Riyadh, Saudi Arabia

Dr. Arabi

Yaseen M. Arabi, M.D
Intensive Care Department
Ministry of National Guard Health Affairs
Riyadh, Saudi Arabia 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Venous thromboembolism, including deep vein thrombosis and pulmonary embolism, is a complication of critical illness. Studies have demonstrated that despite pharmacologic thromboprophylaxis with unfractionated heparin or low-molecular weight heparin, 5-20% of critically ill patients develop deep vein thrombosis (DVT). The PREVENT trial evaluated whether adjunctive intermittent pneumatic compression reduces incident proximal lower limb DVT as detected on twice-weekly lower limb ultrasonography in critically ill patients receiving pharmacologic thromboprophylaxis with unfractionated heparin or low-molecular-weight heparin.

The trial was conducted in 20 sites in Saudi Arabia, Canada, Australia and India and included 2003 patients.

The trial found no difference in the primary end point of proximal leg DVT. The addition of intermittent pneumatic compression to pharmacologic thromboprophylaxis did not result in a lower incidence of pulmonary embolism or a composite outcome of venous thromboembolism or death from any cause at 28 days when compared to pharmacologic thromboprophylaxis alone.

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Combat Deaths Decreased as Military Improved Trauma Care in Afghanistan and Iraq

MedicalResearch.com Interview with:

Jeffrey Howard, PhDAssistant ProfessorDepartment of Kinesiology, Health and NutritionUniversity of Texas at San AntonioSan Antonio, TX 78249

Dr. Howard

Jeffrey Howard, PhD
Assistant Professor
Department of Kinesiology, Health and Nutrition
University of Texas at San Antonio
San Antonio, TX 78249

MedicalResearch.com: What is the background for this study?

Response:  There is a saying that “the only winner in war is medicine”, which is the first sentence in the article.  The point of that quote is that many medical advances over the last 500 years or more have been learned or propagated as a result of war.

With that as the backdrop, the purpose of our study was to provide a more comprehensive assessment of the trauma system than previous work.  We accomplished this by compiling the most complete data to-date on the conflicts, using data from both Afghanistan and Iraq, and analyzing multiple interventions/policy changes simultaneously rather than in isolation.  Previous work had focused primarily on single interventions and within more narrow timeframes.  We wanted to expand the scope to include multiple interventions and encompass the entirety of the conflicts through the end of 2017.  Continue reading

Gain in Survival with Fulvestrant plus Anastrozole in Metastatic Breast Cancer

MedicalResearch.com Interview with:

Rita Mehta, MD, HS Clinical Professor,Chao Family Comprehensive Cancer CenterUniversity of California School of Medicine, Irvine 

Dr. Mehta

Rita Mehta, MD, HS Clinical Professor,
Chao Family Comprehensive Cancer Center
University of California School of Medicine, Irvine 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Most patients with HR-positive breast cancer become resistant to hormonal therapies like aromatase inhibitor-anastrozole over time, and downregulating estrogen receptor was identified as a mechanism for overcoming or delaying resistance to hormonal therapy in advanced HR-positive breast cancer. The prospective, randomized phase III S0226 trial, first reported by us in NEJM 2012, showed that the selective estrogen receptor degrader fulvestrant in combination with anastrozole significantly improved progression-free survival in 707 women with HR-positive metastatic breast cancer in first-line setting.

Treatment with the selective estrogen receptor degrader (SERD) fulvestrant achieved a clinically significant and meaningful improvement in overall survival in patients with hormone receptor (HR)-positive advanced breast cancer in first-line therapy, according to the final analysis of overall survival results from the S0226 study reported by us (Mehta et al. NEJM 2019)

  • Results showed that median overall survival improved by 7.8 months with anastrozole plus fulvestrant (median overall survival = 49.8 months) compared to anastrozole (median overall survival = 42.0 months).
  • The improvement was even greater in patients with endocrine naive disease, with an absolute improvement in median overall survival of 11.9 months.
  • No new safety signals were observed with longer follow-up. 

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Cardiac Surgery: No Difference in Outcomes Between Inhaled and IV Anesthesia

MedicalResearch.com Interview with:

Dr. Giovanni LandoniIntensive Care and Anesthesia Unit Associate professorUniversità Vita-Salute San Raffaele

Dr. Landoni

Dr. Giovanni Landoni
Intensive Care and Anesthesia Unit
Associate professor
Università Vita-Salute San Raffaele 

MedicalResearch.com: What is the background for this study?  

Response: Patients undergoing cardiac surgery are still at risk for perioperative complications. Studies to improve clinical outcomes this setting are important. Inhaled anesthetics have pharmacological properties which reduce myocardial infarction size by 50% in laboratory and animal studies and which might decrease postoperative mortality according to aggregated published randomized data.

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Atrial Fibrillation: Antithrombotic Therapy after Acute Coronary Syndrome or PCI

MedicalResearch.com Interview with:

Renato D. Lopes MD, MHS, PhD Duke University Medical Center Duke Clinical Research Institute Durham, NC 27705

Dr. Renato Lopes

Renato D. Lopes MD, MHS, PhD
Professor of Medicine
Division of Cardiology
Duke University Medical Center
Duke Clinical Research Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In patients with acute coronary syndromes (ACS), approximately 20% to 30% of those with nonvalvular atrial fibrillation (NVAF) have concomitant coronary artery disease (CAD), and 5 to 10% of patients who undergo PCI have NVAF. These patients often receive both antiplatelet therapy and oral anticoagulants; and how best to combine these agents to minimize bleeding risk without compromising protection against thrombosis is an important unanswered question.

Analysis of results for bleeding indicated no significant interaction between the two randomization factors permitting independent analysis of results for the two key comparisons. The first showed that apixaban was both non-inferior and significantly superior to VKA for the primary outcome with a 31% reduction in the relative risk for bleeding. Aspirin significantly increased the relative risk for bleeding versus placebo by 89%.

Results for the composite of death and hospitalization showed that apixaban resulted in a relative risk reduction of 17%, primarily driven by a reduction in all cause hospitalization. There was no significant difference between results for aspirin versus placebo for this outcome.

Analysis of the composite of death and ischemic events indicated no significant differences in results for apixaban versus VKA or aspirin versus placebo.

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Study Emphasizes Need to Establish Optimal Pressure Combination Therapies by Ethnicity

MedicalResearch.com Interview with:

Dike B. Ojji, M.D., Ph.D, FWACP, FACPDepartment of MedicineFaculty of Clinical SciencesUniversity of Abuja

Dr. Ojji

Dike B. Ojji, M.D., Ph.D, FWACP, FACP
Department of Medicine
Faculty of Clinical Sciences
University of Abuja

MedicalResearch.com: What is the background for this study?

Response: We decided to do this research because there were no large RCTs before now that have compared the efficacy of contemporary combination therapies among any black populations in spite of the high burden of hypertension and its complications (such as heart failure, cerebrovascular accident and chronic kidney) in this population, and also the fact that majority require 2 or more medications to control their blood pressure.

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Genetic Evidence Suggests New LDL-C Lowering Drug May Decrease Cardiovascular Events and Have Additive Effect with Statins

MedicalResearch.com Interview with:

Brian A Ference, MD, MPhil, MSc, FACC, FESCProfessor and Director of Research in Translational TherapeuticsExecutive Director, Centre for Naturally Randomized TrialsStrangeways Research LaboratoryUniversity of CambridgeCambridge, UK

Dr. Ference

Brian A Ference, MD, MPhil, MSc, FACC, FESC
Professor and Director of Research in Translational Therapeutics
Executive Director, Centre for Naturally Randomized Trials
Strangeways Research Laboratory
University of Cambridge
Cambridge, UK

MedicalResearch.com: What is the background for this study?

Response: Bempedoic acid is a novel therapy currently in development that lowers LDL-C by inhibiting ATP-citrate lyase, an enzyme in the same cholesterol biosynthesis pathway as HMG-CoA reductase (the target of stains).  However, whether lowering LDL-C by inhibiting ATP-citrate lyase will reduce the risk of cardiovascular events to the same extent as lowering LDL-C by inhibiting HMG-CoA reductase with a statin is unknown.

We conducted a “naturally randomized trial” using Mendelian randomization in more than 650,000 participants who experienced more than 100,000 cardiovascular events to evaluate the potential clinical benefit of lowering LDL-C by inhibiting ATP-citrate lyase as compared to lowering LDL-C by inhibiting HMG-CoA reductase.

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Number of Opioid Prescriptions for New Users Has Dropped More Than 50%

MedicalResearch.com Interview with:

Wenjia Zhu, PhD. Marshall J. Seidman FellowDepartment of Health Care PolicyHarvard Medical School

Dr. Zhu

Wenjia Zhu, PhD.
Marshall J. Seidman Fellow
Department of Health Care Policy
Harvard Medical School 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The current opioid epidemic continues to cause deaths and tremendous suffering in the United States, driven in large part by overuse of prescription opioids. Of special concern are new opioid prescriptions, i.e. opioids given to patients who have not used opioids before, which research tells us are an important gateway to long-term opioid use, misuse, overdoes and death. Recently, in their efforts to curb over prescribing of opioids, the CDC issued guidelines (December 2015 in draft form; March 2016 in final version) to encourage opioid prescribers to limit the use, duration and dose of opioids, particularly opioids to first-time users. Despite these, little is known about the prescribing of opioids to first-time users on a national scale, particularly among commercially insured patients.

In this study, we examined national monthly trends in the rate at which opioid therapy was started among commercially insured patients. Using administrative claims from Blue Cross Blue Shield Association commercial insurers from 2012 to 2017, we analyzed more than 86 million commercially insured patients across the United States.

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Ultrashort TB Therapy Found Just As Effective as 6 Month Course

MedicalResearch.com Interview with:

Susan Swindells MBBSProfessor and Medical Director, HIV ClinicDepartment of Internal MedicineUniversity of Nebraska Medical CenterOmaha, NE 

Dr. Swindells

Susan Swindells MBBS
Professor and Medical Director, HIV Clinic
Department of Internal Medicine
University of Nebraska Medical Center
Omaha, NE

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: More than one quarter of the world’s population is infected with tuberculosis (TB), and there is effective treatment for this but only a small fraction of those eligible actually receive it.   TB is the leading cause of death for people with HIV infection, globally.  One of the major problems with currently available treatments for TB infection is that they take too long, and people just stop taking them after a while.  We identified an ultra-short course of treatment (only one month) and tested it against the conventional 6-month course of treatment.

Our main findings were that the new short course was just as effective as the standard 6 month course, more patients taking the short course completed their treatment, and had less adverse effects.  Continue reading

Bempedoic Acid Lowers LDL When Statins Alone Aren’t Enough

MedicalResearch.com Interview with:

Prof. Kosh Ray, MB ChB, MD, MPhil Faculty of Medicine, School of Public HealthChair in Public Health (Clinical)Imperial College London

Dr. Ray

Prof. Kosh Ray, MB ChB, MD, MPhil
Faculty of Medicine, School of Public Health
Chair in Public Health (Clinical)
Imperial College London

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Bempedoic acid is the first in class of a new therapy for lowering LDL cholesterol. This is the largest and longest study to date with this therapy and involved about 2200 pts with patients with either established cardiovascular disease or familial hypercholestrolaemia and in whom LDL was > 70mg/dl or 1.8 mmol/L despite maximally tolerated statins. %0% were on high intensity statins and the majority of the rest on moderate intensity.

The aim was to show long term safety 1 year and efficacy at 24 weeks and at 1 year.  Continue reading

Actinic Keratosis: What is the Best Treatment for Pre-Skin Cancers?

One example of actinic keratoses on hands DermNZ

MedicalResearch.com Interview with:
Maud Jansen, MD | Resident Dermatology | PhD candidate
Dermatologie, Maastricht

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Actinic keratosis is the most frequent premalignant skin disease in the white population and is caused by exposure to ultraviolet radiation. With a prevalence of 37.5% among whites 50 years of age or older, actinic keratosis is one of the most frequent reasons for patients to visit a dermatologist. If left untreated, actinic keratosis may develop into squamous cell carcinoma.

Current guidelines provide no clear recommendations about which treatment approach is preferred. Currently, the choice of treatment often depends on the preferences of patients and their treating physicians. Evidence from randomized trials with direct comparison between treatments and with long-term follow-up is scarce.

Frequently prescribed and studied field-directed treatment approaches are 5-fluorouracil cream, imiquimod cream, photodynamic therapy (PDT), and ingenol mebutate gel.

We investigated the effectiveness of these four frequently used field-directed treatments (for multiple lesions in a continuous area). Over 600 patients in four different hospitals (Maastricht UMC+, Zuyderland (Heerlen), VieCuri (Venlo and Venray) en Catharina (Eindhoven)participated in the study. Patients were randomly assigned to one of the four treatments.

The main result of our study was that we found that after 12 months of follow-up, 5% fluorouracil cream was the most effective treatment in the treatment of patients with multiple actinic keratosis lesions. Moreover, patient satisfaction and increase in health-related quality of life were highest in the 5-fluorouracil group. Continue reading

Prostate Cancer: Novel Androgen Blocker Darolutamide Has Potential to Delay Mets and Extend Survival

MedicalResearch.com Interview with:

Prof. Karim Fizazi, MD, PhD Head of the Department of Cancer Medicine Institute Gustave Roussy

Prof. Fizazi

Prof. Karim Fizazi, MD, PhD
Head of the Department of Cancer Medicine
Institute Gustave Roussy

MedicalResearch.com: What is the background for this study?

How does darolutamide differ from other medications for prostate cancer?

Response: Despite recent treatment advances, there is still significant unmet need for new therapeutic options for men with non-metastatic castration-resistant prostate cancer (nmCRPC).

In laymen’s terms, nmCRPC is cancer that has not spread beyond the prostate region; PSA levels are elevated, despite treatment with hormone therapy, and men with nmCRPC generally feel well and do not have symptoms. The unmet medical need is for treatments that achieve disease control and delay the spread of the cancer without impacting their daily lives or increasing the burden of disease with treatment side effects.

While the current treatments in this space are effective in delaying onset of metastases, the side effects can be unpleasant and disruptive to men’s lives; particularly cognitive issues, seizures, impact on balance which may lead to falls and bone fractures, rash and hypertension.

Furthermore, new treatment options that have limited interactions with medications typically used in this patient population are also important.  Continue reading

Antibody–Drug Conjugate in Refractory Metastatic Triple-Negative Breast Cancer

MedicalResearch.com Interview with:

Aditya Bardia, MBBS, MPH Director, Precision Medicine, Center for Breast Cancer, Attending Physician, Massachusetts General Hospital Cancer Center Harvard Medical School, Boston, MA 02114

Dr. Bardia

Aditya Bardia, MBBS, MPH
Director, Precision Medicine, Center for Breast Cancer,
Attending Physician
Massachusetts General Hospital Cancer Center
Harvard Medical School
Boston, MA 02114

MedicalResearch.com: What is the background for this study?

Response: Metastatic triple negative breast cancer is associated with aggressive tumor biology, and tends to affect younger patients and African Amerians. The response rate with standard chemotherapy regimens in patients with pre-treated metastatic TNBC ranges from 10-15%, and median progression-free survival ranges from 3-4 months. The median survival of metastatic TNBC is around 12 months and has not changed in the past 20 years. Thus, treatment of metastatic triple negative breast cancer represents an unmet clinical need.  

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Pioglitazone (Actos) Reduced Risk of Secondary Stroke and New Onset of Diabetes

MedicalResearch.com Interview with:

David Spence M.D., FRCPC, FAHA Professor of Neurology and Clinical Pharmacology Director, Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, Western University London, ON Canada

Dr. Spence

David Spence M.D., FRCPC, FAHA
Professor of Neurology and Clinical Pharmacology
Director, Stroke Prevention & Atherosclerosis Research Centre,
Robarts Research Institute, Western University
London, ON Canada

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: The motivation for the study was the chair of the committee that advises the Ontario Drug Benefit which medications to pay for said the IRIS results were not relevant to clinical practice. This because the Insulin Resistance Intervention after Stroke (IRIS) trial reported effects of pioglitazone in patients with stroke or TIA and insulin resistance assessed by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score for insulin resistance.1 ( However, few clinicians measure a HOMA-iR score, so the clinical impact of that trial was limited.

In this study we analyzed the effect of pioglitazone in stroke/TIA patients with prediabetes, which is commonly assessed by clinicians. Prediabetes was defined by the American Diabetes Association: a glycosylated hemoglobin (A1C) of  5.7% to <6.5% (we did not do glucose tolerance tests).  We analyzed primarily the results for patients with 80% adherence, but also did  an intention-to-treat (ITT) analysis.  The reason for focusing on patients with good adherence was that pioglitazone cannot be taken by about 10-20% of patients, because of fluid retention and weight gain (mainly due  to fluid retention).  (The reasoning was that third party payers would not need to pay for the medication in patients who do not take it.)

In stroke/TIA patients with good adherence, the benefits of pioglitazone were greater than in the original IRIS trial. We found a 40% reduction of stroke/MI, a 33% reduction of stroke, and an 80% reduction of new-onset diabetes, over 5 years.  Pioglitazone also improved blood pressure, triglycerides and HDL-cholesterol. As expected, pioglitazone was somewhat less beneficial in the ITT analysis.

Fluid retention can usually be managed by reducing the dose of pioglitazone; even small doses still have a beneficial effect . Also, amiloride has been shown to reduce fluid retention with pioglitazone.

  1. Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, Guarino PD, Lovejoy AM, Peduzzi PN, Conwit R, Brass LM, Schwartz GG, Adams HP, Jr., Berger L, Carolei A, Clark W, Coull B, Ford GA, Kleindorfer D, O’Leary JR, Parsons MW, Ringleb P, Sen S, Spence JD, Tanne D, Wang D, Winder TR and Investigators IT. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. N Engl J Med. 2016;374:1321-31. 

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Safety of MRIs in Patients with Tattoos

MedicalResearch.com Interview with:

Dr. Martina Callaghan PhD Head of Physics & Senior Lecturer Wellcome Centre for Human Neuroimaging Institute of Neurology University College London London  

Dr. Callaghan

Dr. Martina Callaghan PhD
Head of Physics & Senior Lecturer
Wellcome Centre for Human Neuroimaging
Institute of Neurology
University College London
London

MedicalResearch.com:  What is the background for this study?  What are the main findings?

Response: As mirrors the situation in the general population, we found that an increasing number of volunteers who were seeking to enter cognitive neuroscience studies at our Centre had tattoos. However, the magnetic fields used in magnetic resonance imaging (MRI) pose a potential safety risk for people with tattoos. A number of case reports have described such incidents.  However, as these describe isolated cases retrospectively, there was not enough information to objectively assess the risk of tattoo-related adverse reactions for persons having an MRI scan.  Therefore, in 2011, we decided to embark upon this first prospective study to quantitatively assess this risk.

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Single-Dose Tafenoquine to Prevent Malaria Relapse

MedicalResearch.com Interview with:
Malaria CDC imageGavin C.K.W. Koh, MB BChir MA PhD MCRP DTM&H

Department of Drug Discovery Unit for Diseases of the Developing World
GlaxoSmithKline | GSK

MedicalResearch.com: What is the background for this study?

Response: Malaria still remains one of the greatest global healthcare challenges so, as part of GSK’s efforts to fight diseases that disproportionately impact the poorest, we have been working on tafenoquine as a potential medicine for malaria for over 20 years.  In 2008, GSK entered into a collaboration with the not-for-profit product development partnership, Medicines for Malaria Venture (MMV), to develop tafenoquine as an anti-relapse medicine for patients infected with a particular species of malaria called Plasmodium vivax malaria.

  1. vivaxmalaria is estimated to cause around 7.5 million clinical infections every year. The disease may cause fever, chills, vomiting, malaise, headache and muscle pain, and in some cases, can lead to severe malaria and be fatal.

Unlike other malaria species such as P. falciparumP. vivax also has the ability to lie dormant in the liver from where it may periodically reactivate to cause relapses of P. vivax malaria. A single P. vivax infection may therefore give rise to multiple episodes of malaria, in the absence of a new mosquito bite. These relapses can occur weeks, months or even years after the initial infection. The dormant liver forms of the parasite cannot be treated with most other antimalarial treatments.

Another issue is that the only medicine currently available to stop the relapse is primaquine, a medicine approved in the 1950s, which must be given for 14 days. Given this length of treatment course, many people do not comply with the full course, which results in reduced effectiveness.

The aim of the DETECTIVE study was to look at the effectiveness of treatment in preventing relapse over six months with a 1-day course of tafenoquine, a 14-day course of primaquine, or placebo, with all patients also receiving a 3-day course of chloroquine, a medicine that is used to treat the initial infection.

MedicalResearch.com: What are the main findings?

Response: The DETECTIVE study met its primary endpoint. A significantly greater proportion of patients in the tafenoquine group did not have relapses compared to patients in the placebo group. A similar result was observed for the patients in the primaquine group compared to the placebo group. When considering the compliance issue of primaquine in the real-world setting, we saw that more than 95% of patients in the primaquine group took their treatment as instructed in the setting of a clinical study. From a safety perspective, adverse events from the study were consistent with the known safety profile of tafenoquine.

MedicalResearch.com: What should readers take away from your report?

Response: The positive results of the DETECTIVE study demonstrate the efficacy and safety of tafenoquine in an unprecedented single-dose for relapsing malaria.  These data supported the approval of the medicine by the US Food and Drug Administration and Australia Therapeutic Goods Administration in 2018 marking it as the first new medicine for the radical cure of P. vivax malaria in more than 60 years. Having the data published in the NEJM will help other P. vivax malaria endemic countries as they strive towards malaria elimination. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: The DETECTIVE study was conducted in adult patients with P. vivax malaria and a significant part of the global burden of the disease is in children. GSK and MMV are therefore studying the use of tafenoquine in paediatric patients aged 6 months to 16 years (TEACH study).  In addition, since vivax malaria in Indonesia is frequently resistant to chloroquine, we are conducting another study that is looking at tafenoquine plus dihydroartemisinin–piperaquine as the blood schizonticide (INSPECTOR study) in patients with P. vivax malaria in Indonesia.

Disclosures: The DETECTIVE study was supported by GSK and MMV.

Citation:

Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria
Marcus V.G. Lacerda, M.D., Alejandro Llanos-Cuentas, M.D., Srivicha Krudsood, M.D., Chanthap Lon, M.D., David L. Saunders, M.D., Rezika Mohammed, M.D., Daniel Yilma, M.D., Dhelio Batista Pereira, M.D., Fe E.J. Espino, M.D., Reginaldo Z. Mia, M.D., Raul Chuquiyauri, M.D., Fernando Val, Ph.D., et al.

January 17, 2019
N Engl J Med 2019; 380:215-228
DOI: 10.1056/NEJMoa1710775

Jan 18, 2019 @ 1:24 am 

The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

 

Esophageal Cancer: HMIE Procedure Reduces Morbidity Without Sacrificing Efficacy

MedicalResearch.com Interview with:

Guillaume Piessen, MD, PhD University Hospital Centre Lille, France

Prof. Piessen

Guillaume Piessen, MD, PhD
University Hospital Centre
Lille, Franc

MedicalResearch.com: What is the background for this study?

Response: Patients requiring surgery for esophageal cancer fare better after undergoing a hybrid minimally invasive esophagectomy (HMIE) with a combined laparoscopy+thoracotomy procedure compared to an open esophagectomy (OE), according to results of the MIRO trial published in the last issue of the New England Journal Of Medicine (link article).

This French prospective multi-center randomized controlled study was funded by the French National Cancer Institute (Grant n° 1907). The study was conducted by Pr Mariette who sadely passed away in 2017 and Pr Piessen (Department of Digestive and Oncological Surgery, CHU Lille), under the hauspice of FRENCH (Fédération de Recherche EN Chirurgie) and FREGAT (French Eso-Gastric Tumors) working group (https://www.fregat-database.org/fr/).

Postoperative morbidity, especially pulmonary complications, affects more than half of patients after open esophagectomy for esophageal cancer.

Hybrid minimally invasive esophagectomy (HMIE) combines a laparoscopic abdominal phase with an open thoracotomy, which may have specific advantages including lower rate of pulmonary complications, without laparoscopic tumor dissection limiting potential tumor spillage and easier reproducibility of the technique [12].

Postoperative morbidity, especially pulmonary complications, affects more than half of patients after open esophagectomy for esophageal cancer.

Hybrid minimally invasive esophagectomy (HMIE) combines a laparoscopic abdominal phase with an open thoracotomy, which may have specific advantages including lower rate of pulmonary complications, without laparoscopic tumor dissection limiting potential tumor spillage and easier reproducibility of the technique [12].

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Chronic Kidney Disease: Exome Sequencing Can Help Resolve Some Diagnostic Challenges

MedicalResearch.com Interview with:
Emily E. Groopman, B.A
Departments of Medicine
Hammer Health Sciences, and the Department of Epidemiology
Columbia University, New York

MedicalResearch.com: What is the background for this study?

Response: Exome sequencing (ES), targeted capture of the protein-coding segments of the human genome, is quickly becoming a first-line diagnostic tool in clinical medicine, particularly for pediatric disorders and cancer. However, the utility of ES has not been investigated for the majority of constitutional disorders in adults, including for chronic kidney disease (CKD), which collectively affects more than 1 in 10 individuals worldwide.

Thus, we performed ES in 3,315 patients with CKD drawn from two independent cohorts, and evaluated the diagnostic yield and the clinical implications of genetic findings. The cohort was predominantly adult (91.6% of patients aged >21 years), ethnically diverse, and encompassed the major CKD subtypes, broadly reflective of the demographic and clinical features of United States CKD patient population.

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Parents: Vaping is Drawing Adolescents into Nicotine Use

MedicalResearch.com Interview with:

Richard Miech Ph.D Professor Principal Investigator, Monitoring the Future Institute for Social Research University of Michigan

Dr. Miech

Richard Miech Ph.D
Professor
Principal Investigator, Monitoring the Future
Institute for Social Research
University of Michigan

MedicalResearch.com: What is the background for this study? What are the main findings?

 Response: Every year Monitoring the Future conducts a survey to examine trends in adolescent substance use.  We draw a random sample of schools from a list of all schools in the United States and conduct our survey in ~400 schools.  Our survey is representative of U.S. 8th, 10th, and 12th grade students.  In other words, our results are what you would find if you surveyed every single 8th, 10th, and 12th graders in the United States, within the bounds of a small sampling error of a few percentage points.

An increase in vaping is the big news for 2018.  In 10th and 12th grade the increase in nicotine vaping was the largest we’ve ever seen for any substance in the past 43 years.  As a result of this increase in nicotine vaping, overall use of nicotine increased as well, which suggests that vaping is drawing youth into nicotine use.  We also saw a significant increase in marijuana vaping. Continue reading

Stroke Prevention Should Begin in Young Adults

MedicalResearch.com Interview with:

Gregory A. Roth MD MPH Assistant Professor, Medicine - Cardiology Adjunct Assistant Professor, Global Health Adjunct Assistant Professor, Health Metrics Sciences School of Public Health University of Washington Seattle, WA

Dr. Roth

Gregory A. Roth MD MPH
Assistant Professor, Medicine – Cardiology
Adjunct Assistant Professor, Global Health
Adjunct Assistant Professor, Health Metrics Sciences
School of Public Health
University of Washington
Seattle, WA

MedicalResearch.com: What is the background for this study? What are the main findings?

 

Response:  We found that globally, one in four people over age 25 is at risk for stroke during their lifetime. But we also found large geographic variation, including a nearly five-fold difference in lifetime stroke risk worldwide, with the highest risk in East Asia (38.8%), Central Europe (31.7%), and Eastern Europe (31.6%), and the lowest risk in eastern sub-Saharan Africa (11.8%). Chinese men and Latvian women had the world’s highest estimated lifetime stroke risk in 2016. The lifetime stroke risk on average for 25-year-olds in 2016 ranges from 8% to 39%, depending on the country in which they live.

This is the first time a study has produced estimates of lifetime stroke risk starting at age 25, whereas previous studies begin at age 45. These findings suggest that adults need to think about their long-term health risks, including stroke, at a much younger age. Additionally, one’s risk of stroke over the course of your lifetime depends on where you live. Given the burden of stroke among adults is dependent on modifiable risk factors and the characteristics of health systems, our findings may be useful for long-term planning, especially in terms of prevention and public education.  Continue reading

Pancreatic Cancer: mFOLFIRINOX After Surgery Improves Survival

MedicalResearch.com Interview with:

Pr Thierry Conroy | Director

Prof. Conroy

Prof. Thierry Conroy MD, Director
Department of Medical Oncology
Institut de Cancérologie de Lorraine
Vandoeuvre-lès-Nancy CEDEX

MedicalResearch.com: What is the background for this study?

Response:  Surgery of pancreatic cancer offers the only chance of cure. Despite the low response rate (5% – 9%) of gemcitabine in metastatic disease, a 6-month regimen of adjuvant therapy with gemcitabine increases 5-year survival from 10% to 20% and is recognized as standard of care. However, recurrence rate remain high despite adjuvant treatment with 69-75% of patients relapsing within 2 years.

–       The combination of bolus and continuous infusion Fluorouracil, Folinic Acid, Irinotecan and Oxaliplatin (Folfirinox) was shown to increase response rate (31.6% versus 9.4%) in metastatic disease as compared to Gemcitabine and increase survival (11.1 versus 6.8 months).

–       Deletion of bolus Fluorouracil in the Folfirinox regimen (mFOLFIRINOX) decreased toxicity and do not reduce efficacy in advanced disease.

–       We performed a randomized trial in patients with good performance status, ECOG 0-1 CA 19.9 ≤ 180 U/L and no cardiac contraindication to fluorouracil.

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Probiotics Found Unhelpful in Kids With Outpatient Diarrhea

Stephen Freedman MDCM, MSc Alberta Children's Hospital Foundation Professor in Child Health and Wellness Sections of Pediatric Emergency Medicine and Gastroenterology Alberta Children's Hospital & Research Institute University of Calgary Calgary, AB

Dr. Freedman

MedicalResearch.com Interview with:
Stephen Freedman MDCM, MSc
Alberta Children’s Hospital Foundation Professor in Child Health and Wellness
Sections of Pediatric Emergency Medicine and Gastroenterology
Alberta Children’s Hospital & Research Institute
University of Calgary
Calgary, AB

 MedicalResearch.com: What is the background for this study?

Response: Vomiting and diarrhea remain extremely common diseases in children and are the most common reason children are brought for emergency department care in North America.  While we have options to reduce vomiting there historically has been little physicians can offer to reduce the severity of the diarrhea.

Probiotics have recently emerged as an option with some early evidence of benefit in clinical trials but the studies performed to date have been small and few little research has been conducted in North America in outpatient or emergency department children.

The one study to date that was performed in a US emergency department did not find probiotic use to be beneficial.  Given the increasing importance of clarifying this issue we undertook this study.

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New Drug Class Holds Promise Against Antibiotic Resistant Gonorrhea

MedicalResearch.com Interview with:

Intracellular Gram-negative, Neisseria gonorrhoeae diplococcal bacteria, - CDC image

Intracellular Gram-negative, Neisseria gonorrhoeae diplococcal bacteria, – CDC image

Edward W. Hook, III, MD
University of Alabama at Birmingham
Medicine / Infectious Diseases
Birmingham, AL

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Zoliflodacin represents a new class of antibiotics (spiropyrimidinetriones) with in vitro activity against Neisseria gonorrhoeae, as well as other STD  pathogens (Chlamydia trachomatis and Mycoplasma genitalium).  Because of this promising data and the fact that the manufacturer (Entasis Pharmaceuticals) was willing to pursue the possibility of using this drug to treat gonorrhea, a Phase II trial was conducted which showed he drug to be 96% effective for genital or rectal infections.  The drug was well tolerated as well making it a promising drug for gonorrhea treatment which might help to combat the increasing problem of antibiotic resistant gonorrhea.  Continue reading