What Surveillance Testing Should Be Done After Melanoma Diagnosis?

MedicalResearch.com Interview with:

This image depicts the gross appearance of a cutaneous pigmented lesion, which had been diagnosed as superficial spreading malignant melanoma (SSMM). Note the roughened edges of this mole, and its heterogeneous, mottled, multicolored appearance, which are all characteristics that should evoke suspicions about its classification.

This image depicts the gross appearance of a cutaneous pigmented lesion, which had been diagnosed as superficial spreading malignant melanoma (SSMM). Note the roughened edges of this mole, and its heterogeneous, mottled, multicolored appearance, which are all characteristics that should evoke suspicions about its classification.
CDC Image

Dr. Diwakar Davar, MD
Assistant Professor of Medicine
Division of Hematology/Oncology
University of Pittsburgh 

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

Response: The optimal surveillance strategy to detect recurrence in cutaneous melanoma remains elusive. Risk of recurrence increases with higher stage, and is especially high for patients with stage IIIC disease. Although consensus guidelines agree on surveillance imaging for high-risk (stage IIB-IIIC) MEL, there is no consensus regarding optimal frequency/modality in these patients. NCCN guidelines suggest chest radiography (CXR) at 6- to 12-month intervals for stage IA-IIA melanoma  patients; although this is controversial. There exists a great deal of practice variation in the surveillance of these patients. Continue reading

Pneumonia Patients on Ventilators May Benefit from New Ceftolozane/Tazobactam Antibiotics

MedicalResearch.com Interview with:

Dr. Elizabeth Rhee MD Director, Infectious Disease Clinical Research at Merck

Dr. Rhee

Dr. Elizabeth Rhee MD
Director, Infectious Disease Clinical Research Merck

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

Response: High-risk patients, such as the critically ill, with suspected bacterial infections require prompt treatment with appropriate empiric therapy to improve survival. Given the high prevalence of multidrug-resistant (MDR) Pseudomonas aeruginosa in the ICU setting, new safe and broadly effective treatment options are needed for critically ill patients requiring antipseudomonal agents.

Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin/beta-lactamase inhibitor combination with broad in vitro activity against Gram-negative pathogens, including MDR P. aeruginosa and many extended-spectrum beta-lactamase (ESBL) producers. It is FDA approved for complicated intra-abdominal and urinary tract infections in adults at 1.5g (1g/0.5g) q8h. C/T is currently being studied at 3g (2g/1g) q8h, for the treatment of ventilated nosocomial pneumonia, in the ASPECT-NP Phase 3 trial.

This Phase 1 pharmacokinetic (PK) study investigated the penetration of a 3g dose of C/T in the epithelial lining fluid (ELF) of ventilated patients with proven or suspected pneumonia. This is the dose and patient population being evaluated in ASPECT-NP. ELF lines the alveoli, and investigators took samples in a group of 26 patients to see what amount of C/T was in the lung and what was circulating in the plasma during the dosing intervals.

In mechanically ventilated critically ill patients, the 3g dose of C/T achieved ≥50% lung penetration (relative to free plasma) and sustained levels in ELF above the target concentrations for the entire dosing interval. These findings support the 3g dose that is included in the ASPECT-NP Phase 3 trial.  Continue reading

New Cephalosporin Combination Tested for Complicated Sepsis Patients

MedicalResearch.com Interview with:

Becky Jayakumar, PharmD College of Pharmacy Assistant Professor of Pharmacy Practice Roseman University of Health Sciences

Dr. Jayakumar

Becky Jayakumar, PharmD
College of Pharmacy
Assistant Professor of Pharmacy Practice
Roseman University of Health Sciences

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

Response: Bacteremia (bloodstream infections) due to Gram-negative (GN) bacteria are a frequent cause of severe sepsis and pose serious therapeutic challenges due to multidrug-resistance (MDR). Ceftolozane/tazobactam (C/T) is a novel antipseudomonal cephalosporin combined with an established β-lactamase inhibitor.

This retrospective, observational study evaluated the clinical outcomes of C/T real-world use in severely ill patients. Twenty-two patients with sepsis and/or bacteremia were included; 95% of whom had Pseudomonas aeruginosa that was resistant to almost all antibacterials with the exception of colistin. C/T successfully treated the majority of these complicated patients. In this real-world study, 77% of patients had a clinical response with C/T and 75% had a microbiological response. Clinical success rates were high and mortality rates were similar to other studies in this severely ill population. Continue reading

Merck Tests New Antibiotic Combination For Hard to Treat Bacterial Infections

MedicalResearch.com Interview with:

Amanda Paschke, MD, MSCE Senior principal scientist Infectious disease clinical research Merck Research Laboratories

Dr.Amanda  Paschke

Amanda Paschke, MD, MSCE
Senior principal scientist
Infectious disease clinical research
Merck Research Laboratories

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

Response: This study sought to evaluate a new beta-lactam/beta-lactamase inhibitor antibacterial combination, imipenem/relebactam (IMI/REL), compared with colistin plus imipenem for the treatment of infections caused by resistant Gram-negative bacteria.

Patients enrolled in the trial had hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP), complicated intra-abdominal infections (cIAI), or complicated urinary tract infections (cUTI) caused by pathogens that were non susceptible to imipenem, a carbapenem antibacterial.

In this study, the primary outcome was a favorable overall response to treatment, which was comparable between the IMI/REL vs colistin + IMI arms. Colistin (often combined with a carbapenem) is currently among the standard of care treatment regimens for MDR infections.  A key secondary endpoint of the study was safety.  IMI/REL was well tolerated; among all treated patients, drug-related adverse events (AEs) occurred in 16.1% of IMI/REL and 31.3% of colistin + IMI patients with treatment-emergent nephrotoxicity observed in 10% (3/29 patients) and 56% (9/16 patients), respectively (p=0.002). Results of the trial support the use of imipenem-relebactam (IMI/REL) as an efficacious and well-tolerated treatment option for carbapenem-resistant infections.  Continue reading

Alzheimer Study: New Drug Did Not Reduce Cognitive Decline

MedicalResearch.com Interview with:
Dr. Michael F. Egan MD

Merck & Co.
North Wales, PA 19454  

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

Response: A leading theory of Alzheimer’s Disease is that it is caused by the buildup of amyloid plaques in the brain. Amyloid is composed of a sticky peptide called Abeta.  Abeta production can be blocked by Inhibiting an enzyme called BACE.  In animal models, BACE inhibtion prevent amyloid accumulation.  We aimed to see if a potent BACE inhibitor would slow clinical decline in Alzheimer’s Disease.

EPOCH was a Phase 2/3 randomized, placebo-controlled, parallel-group, double-blind study evaluating efficacy and safety of two oral doses of verubecestat an investigational BACE inhibitor, administered once-daily versus placebo in patients with mild-to-moderate AD currently using standard of care treatment. The primary efficacy outcomes of the study are the change from baseline in cognition (assessed using the Alzheimer’s Disease Assessment Scale Cognitive Subscale, or ADAS-Cog),  as well as the change from baseline in function (assessed using the Alzheimer’s Disease Cooperative Study – Activities of Daily Living, or ADCS-ADL)  after 78 weeks of treatment.

Following the recommendation of the external Data Monitoring Committee (eDMC), which assessed overall benefit/risk during  the trial,  the study was stopped early, as there was “virtually no chance of finding a positive clinical effect.”

Verubecestat did not reduce cognitive or functional decline in patients with mild-to moderate Alzheimer’s disease and was associated with treatment-related adverse events.  Continue reading

Letermovir (Prevymis) Prevents CMV Infection in Stem Cell Transplant

MedicalResearch.com Interview with:

Francisco M. Marty, M.D Associate Professor, Harvard Medical School Dana–Farber Cancer Institute and Brigham and Women’s Hospital

Dr. Marty

Francisco M. Marty, M.D
Associate Professor, Harvard Medical School
Dana–Farber Cancer Institute and
Brigham and Women’s Hospital

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

Response: Cytomegalovirus (CMV) is the most common infection in patients who undergo allogeneic hematopoietic-cell transplantation (bone marrow transplantation with cells from donors different than the patient). Up until now, we had no antiviral agent that could be used for prophylaxis (prevention) of CMV post-transplant because of the side effects of drugs available to date (ganciclovir, valganciclovir, foscarnet, cidofovir).

This trial confirmed that letermovir was highly effective in preventing CMV infection when used in the first 100 days after allogeneic HCT, was associated with minimal side effects of concern and was also associated with lower all-cause mortality by Week 24 post-HCT.

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Oral Semaglutide As Effective As Injectable In Reducing A1C and Weight Loss

MedicalResearch.com Interview with:

Melanie J Davies CBE MB ChB MD FRCP FRCGP Professor of Diabetes Medicine  NIHR Senior Investigator Emeritus Diabetes Research Centre Leicester Diabetes Centre – Bloom University of Leicester

Prof. Davies

Melanie J Davies CBE MB ChB MD FRCP FRCGP
Professor of Diabetes Medicine
NIHR Senior Investigator Emeritus
Diabetes Research Centre
Leicester Diabetes Centre – Bloom
University of Leicester

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

Response:  This was the first study to test the effectiveness of an oral GLP-1 in patients with type 2 diabetes.

The main findings were that compared to both placebo and a GLP-1, Semaglutide, delivered by sub-cutaneous injection weekly, the oral therapy delivered once a day produced better results than placebo and similar results to injectable GLP-1 with regard to reductions in HbA1c and weight loss.

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CMV Infections Increase Complications and Costs After Stem Cell Transplantation

MedicalResearch.com Interview with:

Dr. Jonathan Schelfhout, PhD Director, Outcomes Research Merck & Co. Inc. North Wales, PA

Dr. Schelfhout

Dr. Jonathan Schelfhout, PhD
Director, Outcomes Research
Merck & Co. Inc.
North Wales, PA

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

Response: The cost of hematopoietic stem cell transplantation has received increased attention after it was identified as a top 10 contributor to increasing healthcare costs in an AHRQ 2016 report. Many recent studies have explored the cost of HSCT but additional research is needed on the costly complications that can follow the transplant procedure. This research is particularly relevant for inpatient decision makers, as most transplant centers receive one bundled payment for the transplant and the treatment of any complications over the first 100 days.

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Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation 

MedicalResearch.com Interview with:

Professor Christopher P. Cannon MD Executive Director, Cardiometabolic Trials, Baim Institute Cardiologist Brigham and Women's Hospital Baim Institute for Clinical Research Columbia University College of Physicians and Surgeons

Dr. Cannon

Professor Christopher P. Cannon MD
Executive Director, Cardiometabolic Trials, Baim Institute
Cardiologist Brigham and Women’s Hospital
Baim Institute for Clinical Research
Columbia University College of Physicians and Surgeons

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

Response: The trial explored whether a dual therapy approach of anticoagulation and P2Y12 antagonist – without aspirin – in non-valvular atrial fibrillation (AF) patients following percutaneous coronary intervention (PCI) and stent placement would be as safe, and still efficacious, as the current standard treatment – triple therapy. For more detailed background on the study, readers may want to review the first paragraph of the article in the New England Journal of Medicine.

Results showed significantly lower rates of major or clinically relevant non-major bleeding events for dual therapy with dabigatran, when compared to triple therapy with warfarin.

In the study, the risk for the primary safety endpoint (time to major or clinically relevant non-major bleeding event) was 48 percent lower for dabigatran 110 mg dual therapy and 28 percent lower for dabigatran 150 mg dual therapy (relative difference), with similar rates of overall thromboembolic events.

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New Rapid Flu Tests Are Simple, Fast and Accurate

MedicalResearch.com Interview with:

Jesse Papenburg, MD MSc FRCPC FRQS Clinical Research Scholar Assistant Professor of Pediatrics, McGill University Div. of Pediatric Infectious Diseases, Dept. of Microbiology Montreal Children’s Hospital Montreal, QC

Dr. Papenburg

Jesse Papenburg, MD MSc FRCPC
FRQS Clinical Research Scholar
Assistant Professor of Pediatrics, McGill University
Div. of Pediatric Infectious Diseases, Dept. of Microbiology
Montreal Children’s Hospital
Montreal, QC 

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

Response: Influenza viruses cause yearly epidemics of acute respiratory illness affecting 5 to 30 percent of the population. Diagnosing influenza on the basis of only clinical symptoms is difficult because its manifestations vary and are nonspecific. Reverse transcriptase polymerase chain reaction (RT-PCR) is the gold standard for flu diagnosis, but these tests must be sent to a laboratory and have turnaround times that extend beyond the clinical encounter. Rapid and accurate diagnosis of influenza has the potential to improve patient outcomes and decrease health care costs.

Since 2011, two novel classes of rapid influenza diagnostic assays i.e., with results available in <30 minutes, have been commercialized with claims of improved sensitivities based on technological improvements: 1) automated immunochromatographic antigen detection tests (digital immunoassays, DIAs) and 2) rapid nucleic acid amplification tests (NAATs).

Our systematic review and meta-analysis synthesized the available evidence and compared the diagnostic accuracy of commercially available rapid tests for the detection of influenza A and B infection:

  • Overall, the rapid tests displayed very high specificities (≥98%). Physicians can therefore diagnose influenza with confidence on the basis of a positive RIDT, DIA, or rapid NAAT result.
  • The pooled sensitivities for DIAs (80.0% for influenza A and 76.8% for influenza B) and rapid NAATs (91.6% for influenza A and 95.4% for influenza B) are markedly higher than those for RIDTs (54.4% for influenza A and 53.2% for influenza B).

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Gender Gap in Myocardial Infarction Mortality Decreases Over Past 20 Years

MedicalResearch.com Interview with:
Dragana Radovanovic, MD 

Head of AMIS Plus Data Center
Hirschengraben Zürich

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

Response: What we know so far? When a woman suffers a heart attack she is older, has consequently more cardiovascular risk factors such as hypertension, has more comorbidities, is less likely to receive the same therapies and more likely to die in hospital. Furthermore, we know from many hospital statistics and administrative data bases that in-hospital mortality of acute myocardial infarction patients has been on the decrease from 1970 to the early 2000’s. We then wanted to know what the situation looks like in Switzerland and therefore analyzed in-hospital mortality over the last 20 years with regard to gender, age and therapies. For this study we used the data of the nationwide AMIS Plus registry (Acute Myocardial Infarction in Switzerland) which exists since 1997 and continuously prospectively collects clinical data of patients hospitalized with acute myocardial infarction. We have found that during the last 20 years (from 1997 to the end of 2016) in-hospital mortality of patients with acute myocardial infarction in Switzerland has halved. Although in-hospital mortality was consistently higher in women, overall age-adjusted mortality has decreased more prominently in women compared to men. Especially in patients aged below 60 years a significant decrease in in-hospital mortality was observed in women but not in men.

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Nasal Spray Flu Vaccine Ineffective and Not Recommended

MedicalResearch.com Interview with:

Michael Jackson  PhD, MPH Kaiser Permanente Washington Health Research Institute (KPWHRI) principal investigator for the United States Influenza Vaccine Effectiveness Network

Dr. Jackson

Michael Jackson  PhD, MPH
Kaiser Permanente Washington Health Research Institute (KPWHRI) principal investigator for the United States Influenza Vaccine Effectiveness Network 

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

  • Response: Each year, Kaiser Permanente Washington is one of five sites across the country that participate in the United States Influenza Vaccine Effectiveness Network. The Network reports its early interim results in the MMWRand presents additional interim results to the Advisory Committee on Immunization Practices (ACIP)This New England Journal of Medicine publication is an update of those interim results.
  • The findings in this New England Journal of Medicine are special because prior randomized controlled trials indicated that the nasal spray vaccine (FluMist)—also called live attenuated influenza vaccine (LAIV)—would work well to protect children and teens from the flu, whereas in actual practice we found that the flu shot worked much better, particularly against the predominant strain, A(H1N1)pdm09.
  • The nasal spray vaccine was first seen to be less effective for young children than the flu shot in 2013-2014 for the A(H1N1)pdm09 virus strain. In response, the A(H1N1)pdm09 virus strain used in the nasal spray vaccine was changed for the 2015-2016 influenza season. The 2016/17 season was the first since 2015-2016 to be dominated by the A(H1N1)pdm09 virus, making this our first opportunity to evaluate the updated nasal spray vaccine.
  • The Influenza Vaccine Effectiveness Network evaluated the impact of this change as part of our estimates of influenza vaccine effectiveness in 2015-2016. Preliminary findings from this study were presented to the ACIP in June 2016, which led to the nasal spray vaccine not being recommended in 2016-2017 in the US, although the nasal spray vaccine remains licensed in the US. In 2016-2017, the LAIV A(H1N1)pdm09 vaccine strain was unchanged from 2015-2016.

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Once-Daily, Fixed-Dose Combination Tablet Containing Doravirine Achieved HIV-1 Viral Suppression

MedicalResearch.com Interview with:

Dr. Kathleen Squires MD Professor and Director of Infectious Diseases Thomas Jefferson University Philadelphia, PA 

Dr. Squires

Dr. Kathleen Squires MD
Professor and Director of Infectious Diseases
Thomas Jefferson University
Philadelphia, PA 

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

  • The pivotal Phase 3 DRIVE-AHEAD study evaluated the safety and efficacy of a once-daily, single tablet, fixed-dose combination containing doravirine, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV-1 infection, compared to a fixed-dose combination containing efavirenz.
    • After 48 weeks of treatment, 84 percent of the 364 treatment-naïve patients taking once-daily DOR/3TC/TDF achieved levels of HIV-1 RNA <50 copies/mL compared to 81 percent of the 364 patients taking once-daily EFV/FTC/TDF, with an estimated treatment difference of 3.5 percent.
    • Increases in mean CD4+ T-cell counts from baseline for the DOR/3TC/TDF and EFV/FTC/TDF groups were 198 and 188 cells/mm3, respectively, with an estimated treatment difference of 10.1.
    • In addition, comparable efficacy was observed across both treatment groups among individuals with high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, which consisted of 69 patients in the DOR/3TC/TDF group and 73 patients in the EFV/FTC/TDF group (Observed Failure approach).
      • Of those patients with a high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, 81 percent in the DOR/3TC/TDF group and 81 percent in the EFV/FTC/TDF group achieved the study’s primary endpoint of <50 copies/mL of HIV-1 RNA, with a treatment difference of 1.0 percent.
    • The study also met its primary safety endpoint, showing that treatment with DOR/3TC/TDF resulted in fewer patients reporting events of several pre-specified neuropsychiatric adverse events compared to EFV/FTC/TDF by Week 48, including dizziness (8.8 percent versus 37.1 percent); sleep disorders and disturbances (12.1 percent versus 25.5 percent); and inability to think clearly or concentrate (4.4 percent versus 8.2 percent).

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ONCEMRK Study: Once Daily Raltegravir In Combination With Other Antivirals Effective For Some HIV Patients

MedicalResearch.com Interview with:

Dr. Pedro Cahn Chief of the infectious disease unit at Juan A. Fernandez Hospital Buenos Aires, Argentina, and ONCEMRK lead study investigator

Dr. Pedro Cah

Dr. Pedro Cahn
Chief of the infectious disease unit at Juan A. Fernandez Hospital
Buenos Aires, Argentina, and
ONCEMRK lead study investigator

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

The ONCEMRK Phase 3 study was conducted to evaluate the efficacy and safety of once-daily ISENTRESS (raltegravir) HD 1200 mg (given as two 600 mg oral tablets) compared to twice daily raltegravir 400 mg, each in combination therapy with emtricitabine plus tenofovir disoproxil fumarate in previously untreated adults with HIV-1 infection with levels of HIV-1 RNA ≥ 1,000 copies/mL.

  • Week 96 data showed:
    • 5 percent of the 531 patients taking once-daily raltegravir 1200 mg (2 x 600 mg) achieved viral suppression of less than 40 copies/mL of HIV-1 RNA, compared to 80.1 percent of the 266 patients taking twice-daily raltegravir 400 mg, both in combination therapy with emtricitabine plus tenofovir disoproxil fumarate, with a treatment difference of 1.4 percent.
    • Increases in CD4+T-cell counts from baseline were comparable for the two treatment regimens, with an average increase of 261.6 cells/mm3 for once-daily raltegravir (1200 mg) and 262.2 cells/mm3 for twice-daily raltegravir (400 mg).
    • Efficacy was consistent across a variety of patient populations, including those with high viral load at baseline (HIV-1 RNA >100,000 copies/mL).
    • Treatment-emergent viral mutations leading to any drug resistance were detected in less than 1 percent of patients in both treatment arms, with 4/531 (0.8 percent) in the once-daily raltegravir (1200 mg) treatment arm, and 2/266 (0.8 percent) in the twice-daily raltegravir (400 mg) treatment arm through 96 weeks.
    • The rate of discontinuation of therapy due to adverse events through 96 weeks was low (1.3 percent in patients receiving once-daily raltegravir (1200 mg) and 2.3 percent in patients receiving twice-daily raltegravir (400 mg).

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Trying Statins Again After Adverse Effect Linked To Lower Risk of Heart Attack

MedicalResearch.com Interview with:

Alexander Turchin, MD,MS Director of Quality in Diabetes Associate Professor, Harvard Medical School Brigham and Women's Hospital Boston, MA

Dr. Turchin

Alexander TurchinMD,MS
Director of Quality in Diabetes
Associate Professor, Harvard Medical School
Brigham and Women’s Hospital
Boston, MA

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

Response: Cardiovascular disease is the # 1 cause of death in the U.S. and worldwide. Statins are some of the most effective medications available for prevention of cardiovascular events.

However, many patients stop statins, frequently because of adverse reactions. In our study we aimed to assess the risk-benefit balance of trying a statin again after experiencing an adverse reaction.

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