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Dr. Dryden-Peterson SCOTT DRYDEN-PETERSON, MD Assistant Professor, Medicine, Harvard Medical School Research Affiliate, Immunology and Infectious Diseases Harvard T.H. Chan School Of Public Health Associate Physician, Medicine, Infectious Diseases Brigham And Women's Hospital Research Associate, Botswana Harvard AIDS Institute MedicalResearch.com:  What is the background for this study?  Response: The combination of the antiviral medicine nirmatrelvir and ritonavir (Paxlovid) which boosts antiviral levels was found to reduce the need for hospitalization by nearly 90% among unvaccinated people. Whether nirmatrelvir plus ritonavir can also help vaccinated people was uncertain. MedicalResearch.com:  What are the main findings? Response: When comparing similar patients with early COVID-19 we found that those receiving nirmatrelvir plus ritonavir were approximately 45% less likely to be hospitalized than those that received no treatment. This protection was observed among all groups of patients, including vaccinated and boosted patients. The overall rate of hospitalization was relatively low among vaccinated patients but it was even lower among those that received nirmatrelvir plus ritonavir. MedicalResearch.com: What should readers take away from your report? Response: Early treatment with nirmatrelvir plus ritonavir can make COVID-19 safer for both vaccinated and unvaccinated patients at elevated risk.   MedicalResearch.com: What recommendations do you have for future research as a result of this work? Response: We found substantial disparity in prescribing of nirmatrelvir plus ritonavir. Further work needed to ensure access to lower-income patients and Black or Hispanic/Latinx patients to this treatment.  No conflicts of interest Citation: Nirmatrelvir plus ritonavir for early COVID-19 and hospitalization in a large US health system Scott Dryden-Peterson, Andy Kim, Arthur Y. Kim, Ellen C. Caniglia, Inga Lennes, Rajesh Patel, Lindsay Gainer, Lisa Dutton, Elizabeth Donahue, Rajesh T. Gandhi, Lindsey R. Baden, Ann E. Woolley medRxiv 2022.06.14.22276393; doi: https://doi.org/10.1101/2022.06.14.22276393 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. Some links may be sponsored and no links are warranted or endorsed by MedicalResearch.com or its parent company, Eminent Domains Inc. 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.   Read the full article

MedicalResearch.com Interview with: Benjamin E. Gewurz MD, PhD Broad Institute of MIT and Harvard, Cambridge, Division of Infectious Disease, Department of Medicine, Brigham and Women’s Hospital, Department of Microbiology, Harvard Medical School Boston, MA  MedicalResearch.com: What is the background for this study? Response: When the Covid-19 virus infects cells, it takes over and redirects our cells resources towards the projection of virus building blocks and new viruses.  Building blocks include large amounts of RNAs that encode for the viral proteins, much as the mRNA vaccines direct our bodies to make the spike protein. We wondered how the virus changes cell metabolism in order to support the synthesis of vast amounts of viral RNAs within hours of infection. MedicalResearch.com: What are the main findings? Response: We identified that SARS-CoV-2 coronavirus that causes COVID19 increases the ability of infected cells to synthesize nucleotide building blocks that can be used for viral RNA synthesis. Activity of a folate metabolism pathway normally used by our cells to make DNA and RNA nucleotides becomes more active. Based on this observation, we tested whether antifolate drugs, including methotrexate could suppress the production of coronavirus mRNA, protein and new viruses.  Read the full article

MedicalResearch.com Interview with: Yin Zhang MD Research Fellow in Medicine Brigham and Women's Hospital and Harvard Medical School MedicalResearch.com: What is the background for this study? Response: Among modern hair dyes, permanent hair dye is the most popular type, and is the most aggressive and extensively used type that has posed the greatest potential concern about cancer risk. Monitoring and investigating the carcinogenic hazard to people from personal use of permanent hair dyes has major public health implications. In 2008, the World Health Organization's International Agency for Research on Cancer, after comprehensive reviewed prior evidence, classified occupational exposure to hair dyes as a probable carcinogen to humans (group 2A), whereas personal use of hair dyes was not classifiable as to its carcinogenicity to humans (Group 3). Data on hair dye safety has also been continuously monitored by the USFDA. Prior epidemiological evidence may have been influenced by not discriminating between personal and occupational exposure, an inability to distinguish types and colors of hair dyes used, imprecise assessment of several critical domains of exposure history (duration, frequency and cumulative dose), and inadequate control for potential confounding. MedicalResearch.com: What are the main findings? Response: We observed no positive association between personal permanent hair dye use and risk of most cancers or cancer-related mortality. Read the full article

MedicalResearch.com Interview with: Dr. David Berg Dr. David Berg MD Senior Fellow in Cardiovascular Medicine and Critical Care Medicine Brigham and Women’s Hospital Postdoctoral Research Fellow with the TIMI Study Group. MedicalResearch.com: What is the background for this study? Response: Heart failure is a frequent and important complication of type 2 diabetes mellitus (T2DM), but there are limited tools for identifying which patients with T2DM are at the highest risk of developing heart failure. In this study, we developed and validated the TIMI Risk Score for Heart Failure in Diabetes , a novel clinical risk score that identifies patients with T2DM who are at heightened risk for hospitalization due to heart failure. Fortunately, the risk score also identifies patients who have the greatest absolute reduction in the risk of hospitalization for heart failure with a new class of glucose-lowering therapies called sodium-glucose cotransporter-2 (SGLT2) inhibitors.  MedicalResearch.com: What should readers take away from your report? Response: The components of the risk score highlight the fact that underlying heart and kidney problems are key drivers of the risk for heart failure hospitalization in patients with type 2 diabetes mellitus. Our study also confirms that SGLT2 inhibitors reduce the relative risk of hospitalization for heart failure in all patients with type 2 diabetes mellitus; however, by using TRS-HF(DM), clinicians can better educate patients about their risk for heart failure hospitalization and identify those patients who have the greatest absolute reduction in risk of hospitalization for heart failure with SGLT2 inhibitors. MedicalResearch.com: What recommendations do you have for future research as a result of this work? Response: There is still much more to learn about what drives heart failure risk in patients with T2DM. In future studies, for example, it will be important to consider whether blood biomarkers and genetic information can provide additional insights into which patients with type 2 diabetes mellitus are at heightened risk for heart failure. MedicalResearch.com: Is there anything else you would like to add? Response: I have no personal disclosures. The databases used to conduct the study were taken from trials funded by AstraZeneca. Citation: Heart Failure Risk Stratification and Efficacy of SGLT2 Inhibitors in Patients with Type 2 Diabetes Mellitus   https://esc365.escardio.org/Congress/ESC-CONGRESS-2019/The-right-glucose-lowering-drugs-for-the-right-patient/195652-heart-failure-risk-stratification-and-efficacy-of-dapagliflozin-in-patients-with-type-2-diabetes-mellitus ESC Congress 2019   Last Modified:       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.   Read the full article

Dr. Gyawali Bishal Gyawali  MD PhD Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts Department of Oncology, Department of Public Health Sciences, and Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: Accelerated approval pathway from the FDA allows cancer drugs to come to market sooner by showing improvement in surrogate measures such as change in tumor size. Surrogate measures do not reflect clinical benefit in terms of living longer or feeling better. So, when a drug receives accelerated approval, the drug is required to undergo a confirmatory trial to confirm that true clinical benefit from the drug actually exists. Last year, a paper from the FDA argued that accelerated approval pathway is working effectively because 55% of such drugs confirmed clinical benefit. However, we saw that most of those drugs were actually improving only a surrogate measure even in confirmatory trials. So the confirmatory trials were not confirming clinical benefit but actually confirming benefit in a surrogate endpoint. We investigate that issue in our study using updated results from the confirmatory trials that were ongoing at the time of FDA review. Our main finding is that only one-fifth of cancer drugs that received accelerated approval actually improved overall survival later in confirmatory trials. For, 20% of other drugs, the confirmatory trials tested the same surrogate endpoint as did the preapproval trial. For another 21%, the confirmatory trial showed benefit in a surrogate endpoint different from the one used in preapproval trial. Furthermore, when drugs fail to confirm clinical benefits in confirmatory trials, they still continue to remain on market.  MedicalResearch.com: What should readers take away from your report? Response: Only 20% of cancer drugs approved using accelerated approval pathway have proven benefits in overall survival in a confirmatory trial. Even when the trials are called confirmatory, usually they just confirm effect on surrogate measures and do not confirm actual clinical benefit. Sometimes, when the drug fails in confirmatory trial, appropriate actions to withdraw the drug from the market are rarely taken.  MedicalResearch.com: What recommendations do you have for future research as a result of this work? Response: We have policy recommendations rather than research recommendations from our study. We recommend that the success of accelerated approval pathway lies in the fact that confirmatory studies are duly conducted in time, and use clinical endpoints such as overall survival or quality of life to actually confirm benefit rather than test another surrogate measure. When drugs fail in confirmatory studies, quick and decisive steps must be taken to withdraw the drug from the market to prevent undue harm from unhelpful drugs. That is how accelerated approval pathway is supposed to function keeping patient benefits at the center of the agenda. MedicalResearch.com: Is there anything else you would like to add?  Response: In a different paper from last year, we provide 3 suggestions to reinforce the social compromise of AA: https://www.nature.com/articles/s41571-018-0066-3 We have no financial conflicts to disclose. Other disclosures are as mentioned in the paper.  Citation: Gyawali B, Hey SP, Kesselheim AS. Assessment of the Clinical Benefit of Cancer Drugs Receiving Accelerated Approval. JAMA Intern Med. Published online May 28, 2019. doi:10.1001/jamainternmed.2019.0462   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.   Read the full article

Dr. Mora Samia Mora, MD, MHS Associate Physician, Brigham and Women's Hospital Associate Professor of Medicine, Harvard Medical School Brigham and Women's Hospital Department of Medicine Preventive Medicine Boston, MA 02115  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Lipid testing plays a major role in cardiovascular disease (CVD) risk screening, prediction, and treatment. In the past decade, several pivotal studies (including the Women’s Health Study, the Copenhagen City Heart Study, and the Copenhagen General Population Study) compared populations of individuals who had fasting lipid testing with populations of individuals who had nonfasting lipid testing, and found that non-fasting lipids were at least as good as fasting lipids in cardiovascular risk screening and predicting CVD risk. To date, however, no study has examined the cardiovascular predictive value of lipids measured on the same individuals who had both fasting and nonfasting lipid testing. This is important because individual-level variability in fasting versus nonfasting lipids may not be captured when looking at population-level risk associations, and evidence from randomized studies is lacking. Furthermore, it is unclear whether substituting nonfasting lipids would misclassify cardiovascular risk for individuals who may be eligible for statin therapy. MedicalResearch.com: What is the background for this study? What are the main findings?  Response: In the randomized clinical trial of the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA), both fasting and nonfasting lipids were measured on the same individuals (N=8270) done four weeks apart with no intervention in between. Compared with fasting samples, nonfasting samples obtained from the same individuals had modestly higher triglycerides and similar cholesterol levels. Notably, associations with incident coronary events were also similar whether the lipids were fasting or nonfasting.  Results were consistent by randomized treatment arm (atorvastatin 10 mg/day or placebo). In addition, overall concordance of fasting and nonfasting lipids for classifying participants into appropriate CVD risk categories was high (95% concordance for risk categories according to the 2013 ACC/AHA Pooled Cohorts equations). MedicalResearch.com: What should readers take away from your report? Response: These results should reassure healthcare providers that fasting prior to a lipid test is not necessary, regardless of whether the lipid test is done prior to or during statin treatment.  Indeed, recent guideline recommendations that have shifted towards allowing routine measurement of nonfasting lipids.  Such a strategy would be highly effective and offer many advantages for cardiovascular risk screening and treatment. MedicalResearch.com: What recommendations do you have for future research as a result of this work? Response: The study was composed predominantly of whites, and it would be important for future studies to confirm similar results for nonfasting samples among other ethnic/racial groups.  MedicalResearch.com: Is there anything else you would like to add?  Response: Sometimes clinicians ask what cutpoint for nonfasting triglycerides would be considered elevated or abnormal (since nonfasting triglycerides are usually somewhat higher than fasting triglycerides).  We conducted a prior study in the Women’s Health Study and found that a cutpoint of 175 mg/dL for nonfasting triglycerides was the best cutpoint to define elevated nonfasting triglycerides (corresponding to a fasting triglyceride cupoint of 150 mg/dL). This cutpoint (175 mg/dL for abnormal nonfasting triglycerides) has since been adopted by guidelines. Any disclosures?  Dr Mora has received institutional research grant support from Pfizer, NHLBI and NIDDK, and Atherotech Diagnostics, and received personal fees for scientific advisory board participation from Pfizer, Amgen, and Quest Diagnostics during the conduct of the study.  Dr. Sever has research grant support and personal fees from Pfizer and Amgen. The other authors reported no disclosures. Citation: Mora S, Chang CL, Moorthy MV, Sever PS. Association of Nonfasting vs Fasting Lipid Levels With Risk of Major Coronary Events in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm. JAMA Intern Med. Published online May 28, 2019. doi:10.1001/jamainternmed.2019.0392 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.   Read the full article

Dr. Melnitchouk Nelya Melnitchouk, MD,MSc Director, Program in Peritoneal Surface Malignancy, HIPEC Dr. Melnitchouk is an associate surgeon at Brigham and Women’s Hospital (BWH) and Brigham and Women’s Faulkner Hospital (BWFH) and instructor of surgery at Harvard Medical School. MedicalResearch.com: What is the background for this study? What are the main findings? Response: Current literature on women in surgery show that female physicians, particularly those in procedural specialties, face many challenges in balancing responsibilities between work and home. We hypothesized that these challenges may affect career satisfaction more negatively for physician mothers in procedural specialties than those in nonprocedural specialties. In our study, we found that physician mothers in procedural specialties who had more domestic responsibilities were more likely to report a desire to change careers than those in nonprocedural specialties.  MedicalResearch.com: What should readers take away from your report? Response: Overall, physician mothers tend to have more domestic responsibilities than their spouses and partners. Moreover, physician mothers in procedural specialties who take on more tasks at home may be more likely to be dissatisfied with their careers. It is important to consider potential solutions such as extended child care services, increased flexibility in scheduling, outsourcing tasks when needed, and emphasizing more equitable division of household labor.  MedicalResearch.com: What recommendations do you have for future research as a result of this work? Response: In further studies, we hope to include responses from spouses and partners of physician mothers – this would address some of the biases that may have been introduced in our study. We have no disclosure Citation: Lyu HG, Davids JS, Scully RE, Melnitchouk N. Association of Domestic Responsibilities With Career Satisfaction for Physician Mothers in Procedural vs Nonprocedural Fields. JAMA Surg. Published online April 10, 2019. doi:10.1001/jamasurg.2019.0529     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.   Read the full article

Dr. Mehra Mandeep R. Mehra, MD, MSc, FRCP (London) The William Harvey Distinguished Chair in Advanced Cardiovascular Medicine Medical Director, Heart and Vascular Center Brigham and Women’s Hospital Executive Director Center for Advanced Heart Disease Brigham and Women’s Hospital Professor of Medicine, Harvard Medical School  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The MOMENTUM 3 trial is the largest study of LVAD therapy in Advanced Heart Failure with over 1000 randomized patients followed to at least 2 years. This trial tested a novel fully magnetically levitated LVAD, the HeartMate 3 pump against a mechanical bearing containing LVAD, the HeartMate II pump in patients suffering from advanced heart failure (85% of whom were on continuous intravenous Inotropic therapy or IABP device at the time of randomization). While LVADs have improved survival for such patients, the morbidity has remained excessive due to serious complication as a result of problems with hemocompatibility. The principal concerns revolve around complications of pump thrombosis requiring surgical replacement, strokes and bleeding events, especially gastrointestinal bleeding. The trial has previously reported two interim analyses which suggested signals for superiority on pump replacement and even a decrease in ischemic stroke. This final full report concludes convincingly that all three domains of hemocompatibility related adverse events are reduced with the novel LVAD with near elimination of pump thrombosis, halving of strokes of any kind and any severity and a marked decrease in bleeding complications. MedicalResearch.com: What should readers take away from your report? Response: The novel HeartMate 3 pump is superior to the HeartMate II pump and the magnitude of benefit is large with a Number Needed to Treat (NNT) of Read the full article