Author Interviews, NEJM, OBGYNE / 06.12.2013

MedicalResearch.com Interview with: Aniket D. Kulkarni, M.B., B.S., M.P.H Women's Health and Fertility Branch Centers for Disease Control and Prevention Atlanta, Georgia MedicalResearch.com: What are the main findings of the study? Dr. Kulkarni: Our study estimates the contribution of fertility treatments and natural conception to multiple births. Fertility treatments include IVF and non-IVF treatments. Non-IVF treatments primarily include ovulation induction and ovarian stimulation coupled with timed intercourse or intrauterine insemination (IUI). All estimated proportions were adjusted for maternal age which makes this study unique. The incidence of twin births nearly doubled and the incidence of triplet and higher-order births quadrupled over the last 4 decades. Our study estimates that by 2011, a total of 36% of twin births and 77% of triplet and higher-order births resulted from conception assisted by fertility treatments, after adjusting for maternal age. After initial increase, the incidence of triplet and higher order births decreased by 29% from 1998 to 2011. The decrease in triplet and higher order births has coincided with a 70% reduction in the transfer of 3 or more embryos during IVF and a 33% decrease in the proportion of triplet and higher order births attributable to IVF. The decline in the number of embryos transferred during IVF became possible due to monitoring of ART treatments and outcomes and the work of professional societies, which have repeatedly revised practice guidelines to include recommendations for lowering the number of embryos transferred. In contrast, non-IVF fertility treatments of ovulation induction and ovarian stimulation are estimated to contribute the increasing number of multiple births. Hence there is a need for surveillance of births from non-IVF fertility treatments.
Author Interviews, Cancer Research, Lymphoma, NEJM / 22.11.2013

Kieron M. Dunleavy, M.D. Metabolism Branch Lymphoma Therapeutics Section Staff Clinician Center for Cancer Research National Cancer Institute Bethesda, MD 20892MedicalResearch.com Interview with Kieron M. Dunleavy, M.D. Metabolism Branch Lymphoma Therapeutics Section Center for Cancer Research National Cancer Institute, Bethesda, MD 20892 MedicalResearch.com: What are the main findings of the study? Dr. Dunleavy: We found that low-intensity therapy was highly effective in Burkitt's lymphoma and cured over 95% of patients with the disease.
Author Interviews, NEJM, Urinary Tract Infections / 14.11.2013

Thomas M. Hooton M.D. Associate Chief of Staff, Medical Service, Miami VA Healthcare System Professor of Clinical Medicine and Vice Chair for VA Affairs, Department of Medicine, UMSOM Clinical Director, Division of Infectious Diseases, UMSOMMedicalResearch.com Interview with: Thomas M. Hooton M.D. Professor of Medicine and Vice Chair for VA Affairs, University of Miami Miller School of Medicine Associate Chief of Staff, Medical Service, Miami VA Healthcare System Clinical Director, Division of Infectious Diseases MedicalResearch.com: What are the main findings of the study? Dr. Hooten: The main findings from this study are: ·        Voided urine colony counts of E. coli as low as 101 to 102 cfu/mL are highly sensitive and specific for their presence in bladder urine in symptomatic women (growth of bacteria in bladder urine is the gold standard for the etiology of UTI). Moreover, even when E. coli is found along with other mixed flora in voided urine, it should not be considered a contaminant since it likely represents true bladder infection. ·        On the other hand, enterococci and Group B streptococci, which are frequently isolated from voided urine, are rarely isolated from paired catheter specimens, suggesting that these organisms only rarely cause acute uncomplicated cystitis. In our study, E. coli frequently grew from the urines of these women and is the likely cause for UTI symptoms in such episodes. ·        Organisms usually considered contaminants, such as lactobacilli, occasionally grow from catheter urines, but they are rarely found alone with pyuria, suggesting that these bacteria rarely cause acute uncomplicated cystitis. ·        The etiology of a quarter of acute uncomplicated cystitis episodes is unknown.  It is possible that some of these women have E. coli urethritis, which has been documented in some women with UTI symptoms, but we did not do further studies to evaluate this. It is possible also that enterococci and Group B streptococci may also cause urethritis, but there is no published evidence of this in young women with UTI symptoms. ·        Although voided urine cultures growing mixed flora are common in women with acute cystitis, true polymicrobic cystitis, as determined by sampling bladder urine, appears to be rare in this population.
Allergies, Author Interviews, NEJM / 24.10.2013

MedicalResearch.com Interview with: Dr. Jian-Jun Liu Shangdong Provincial Institute of Dermatology and Venereology MedicalResearch.com: What are the main findings of the study? Answer: ·      HLA-B*13:01 is associated with the development of dapsone hypersensitivity syndrome. ·      Carrying one copy of HLA-B*13:01 increases one’s risk by 34 times of getting DHS, while carrying two copies increases risk by 100 times as compared to not carrying this allele. ·      HLA-B*13:01 has a sensitivity and specificity of above 85% in predicting the risk of DHS, theoretically reducing the risk of DHS by 7 fold when implemented in clinical screening.
Author Interviews, NEJM, OBGYNE / 09.10.2013

Associate scientist Sunnybrook Health Sciences Centre 2075 Bayview Ave., Room M4 172a Toronto, ON M4N 3M5MedicalResearch.com Interview with: Jon Barrett, M.B.Bch., FRCOG, MD, FRCSC Associate scientist Sunnybrook Health Sciences Centre 2075 Bayview Ave., Room M4 172a Toronto, ON M4N 3M5 MedicalResearch.com: What are the main findings of the study? Dr. Barrett: For twins at 32-38 weeks gestation where Twin A is presenting cephalic a policy of planned CS does not benefit the baby or the mother, compared to a policy of planned VB, and planned CS will result in delivery at a earlier gestational age.
Author Interviews, C. difficile, Infections, NEJM / 26.09.2013

MedicalResearch.com Interview with: David W. Eyre, B.M., B.Ch. Nuffield Department of Clinical Medicine University of Oxford National Institute for Health Research (NIHR) Oxford Biomedical Research Centre John Radcliffe Hospital MedicalResearch.com: What are the main findings of this study? Dr. Eyre: All cases of Clostridium difficile in Oxfordshire were studied over 3 years. Isolates were characterized by whole genome sequencing and the data was linked to hospital databases allowing epidemiological relationships between patients at the level of the hospital ward, hospital specialty, and post code to be identified. For comparison, similar information was also available for all other patients with and without diarrhea.  Preliminary work on the genetic diversity of Clostridium difficile within individuals and between individuals within discrete outbreaks allowed reliable interpretation of transmission events using genomic data. This allowed a complete reconstruction of the pattern of transmission between affected cases in Oxfordshire to be made. The findings were: 1. Unexpectedly few cases (13%) appear to be acquired from direct ward based contact with other symptomatic cases (these have previously been thought to be the main source of infections, and the focus of prevention efforts). Another 6% were associated with other hospital contact and 3% had plausible community contacts. 2. In 13% of cases potential donors were identified gnomically but no contact, within hospitals or the community, were identified. This suggests that the existence of other modes of transmission of Clostridium difficile. 3. The sources of Clostridium difficile infections were highly genetically diverse, with 45% of cases having a genetically distinct origin - suggesting a diverse reservoir of disease, not previously appreciated 4. During the 3 years of the study the rate of Clostridium difficile in Oxfordshire fell.  Any improvement in infection control techniques would be expected to reduce the incidence of cases caused by within hospital transmission. Surprisingly, similar rates of fall occurred in both in secondary cases (considered to be acquired from hospital associated symptomatic cases) and for primary cases (cases not associated with transmission from symptomatic cases).
Author Interviews, CMAJ, Colon Cancer, NEJM / 19.09.2013

Aasma Shaukat, M.D., M.P.H. Dept. of Medicine GI Division, MMC 36 University of Minnesota Minneapolis, MN 55455MedicalResearch.com Interview with: Aasma Shaukat, M.D., M.P.H. Dept. of Medicine GI Division, MMC 36 University of Minnesota Minneapolis, MN 55455 MedicalResearch.com: What are the main findings of the study? Dr. Shaukat: The study showed that screening for colon cancer using stool cards consistently reduces risk of death from colon cancer by one-third through thirty years. The benefit of screening in larger in men compared to women, and for women the benefit seems to start at age 60. However, screening did not make people live longer.
Author Interviews, Johns Hopkins, NEJM, Pulmonary Disease / 11.09.2013

MedicalResearch.com Interview with: Dr. Robert A. Wise MDMedicalResearch.com Interview with: Dr. Robert A. Wise MD Professor of Medicine Johns Hopkins University School of Medicine 5501 Hopkins Bayview Circle Baltimore, MD 21224   MedicalResearch.com: What are the main findings of the study?
 Dr. Wise: The TIOSPIR trial was a landmark study, one of the largest ever conducted for chronic obstructive pulmonary disease (COPD).  It was designed to test the comparative safety and effectiveness of two delivery devices of tiotropium, a long-acting bronchodilator.  One formulation is the Respimat multi-dose soft mist inhaler and the other formulation is the single dose HandiHaler dry powder inhaler. After following more than 17000 patients for an average of 2.3 years, TIOSPIR showed that there was no difference in either the safety in terms of mortality or adverse cardiovascular events between the two devices.  Moreover, both devices showed similar effectiveness in terms of time to first COPD exacerbation. A lung function substudy in 1370 patients showed that the 5 microgram dose of Respimat was equivalent to the HandiHaler as a bronchodilator, but the 2.5 microgram dose was not quite as effective.
Author Interviews, Heart Disease, NEJM / 02.09.2013

MedicalResearch.com Interview with: Massimo Imazio, MD, FESC Dipartimento di Cardiologia/Cardiology Department Maria Vittoria Hospital-ASLTO2 via Cibrario 72 10141 Torino, Italy MedicalResearch.com: What are the main findings of the study? Dr. Imazio: In a multicenter, double-blind trial, eligible adults with acute pericarditis (idiopathic/viral, post-pericardiotomy syndromes and pericarditis related to a systemic inflammatory disease) were randomly assigned to receive either colchicine (at a dose of 0.5 mg twice daily for 3 months for patients weighing >70 kg or 0.5 mg once daily for patients weighing ≤70 kg) or placebo in addition to conventional anti-inflammatory therapy with aspirin or ibuprofen. The primary study outcome was incessant or recurrent pericarditis. After a mean follow-up of 22 months (minimum 18 months) the primary outcome occurred in 20 patients (16.7%) in the colchicine group and 45 patients (37.5%) in the placebo group (relative risk reduction in the colchicine group, 0.56; 95% confidence interval, 0.30 to 0.72; number needed to treat, 4; P<0.001).
Author Interviews, NEJM, OBGYNE / 29.08.2013

MedicalResearch.com Interview with: Ms. Mølgaard-Nielsen Statens Serum Institut Artillerivej 5, 2300 Copenhagen S, Denmark MedicalResearch.com: What are the main findings of the study? Answer: Use of oral fluconazole during early pregnancy did not increase the risk of birth defects overall in common therapeutic doses. We also looked at 15 individual birth defects of previous concern and oral fluconazole was not associated with an increased risk for 14 of these birth defects.  However, we did see an increase in the risk of tetralogy of Fallot, an uncommon congenital heart defect, but the number of exposed cases was few.
Author Interviews, NEJM / 27.07.2013

Wendy Chung, MD PhD Herbert Irving Associate Professor of Pediatrics and Medicine Director of Clinical Genetics Columbia University 1150 St. Nicholas Avenue, Room 620 New York, NY 10032MedicalResearch.com Interview with: Wendy Chung, MD PhD Herbert Irving Associate Professor of Pediatrics and Medicine Director of Clinical Genetics Columbia University 1150 St. Nicholas Avenue, Room 620 New York, NY 10032 MedicalResearch.com: What are the main findings of the study? Dr. Chung: We have identified a potassium channel as a new genetic cause of pulmonary hypertension and demonstrated it as a cause of pulmonary hypertension in patients with familial disease and sporadic disease without a family history of pulmonary hypertension.  In vitro we were able to rescue several of the mutations pharmacologically.  This potassium channel now provides a new target for treatment for pulmonary hypertension.
Asthma, Author Interviews, Duke, Genetic Research, Lancet, NEJM / 10.07.2013

Daniel Belsky, PhD NIA Postdoctoral Fellow Center for the Study of Aging and Human Development Duke UniversityMedicalResearch.com Interview with: Daniel Belsky, PhD NIA Postdoctoral Fellow Center for the Study of Aging and Human Development Duke University Polygenic risk and the development and course of asthma: an analysis of data from a four-decade longitudinal study MedicalResearch.com: What are the main findings of the study? Dr. Belsky : We looked to the largest-ever genome-wide association study of asthma (that study by the GABRIEL Consortium included more than 26,000 individuals) to identify genetic variants that could be used to construct a genetic profile of asthma risk. We then turned to The Dunedin Multidisciplinary Health and Development Study, a unique cohort of 1,000 individuals who have been followed from birth through their fourth decade of life with extensive measurements of asthma and related traits. We computed a “genetic risk score” for each person based on the variants identified in GWAS.  Then, we looked at who developed asthma, when they developed asthma, and what that asthma looked like in terms of allergic response and impaired lung function. What we found: (1) People with higher genetic risk scores were more likely to develop asthma and they developed asthma earlier in life. (2) Among children who developed asthma, the ones at higher genetic risk were more likely to have persistent asthma through midlife. (3) Genetic risk was specifically associated with allergic asthma that resulted in chronic symptoms of impaired lung function. (4) People with higher genetic risk score developed more severe cases of asthma. As compared to people with a lower genetic risk, they were more often absent from school and work because of asthma and they were more likely to be hospitalized for asthma. (5) The genetic risk score provided new information about asthma risk that could not be obtained from a family history.
Author Interviews, Infections, Lyme, NEJM / 02.07.2013

MedicalResearch.com Interview with: Sam R. Telford III, ScD Department of Infectious Disease and Global Health, Tufts University, Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA Borrelia miyamotoi Infection Presenting as Human Granulocytic Anaplasmosis: A Case Report MedicalResearch.com: What are the main findings of the study? Answer: The study presents two additional cases of BMD (Borrelia miyamotoi disease) that add to our knowledge of the spectrum of illness of this recently recognized zoonosis.  Our report of the North American index case in NEJM in January 2013 described a case-patient who was elderly and immunocompromised and it was not clear whether that case was just very unusual.  With our Annals report, we describe cases in immune-intact individuals and suggest that cases of BMD may have been under our noses all along, just presumptively diagnosed as HGA and successfully treated with doxycycline with no followup (e.g., lab confirmation of diagnosis of HGA Human Granulocytic Anaplasmosis).  Hence, individuals presenting with fever, headache, myalgia, and show leukopenia and elevated LFTs may have either HGA or BMD and confirmatory testing should be done accordingly.  It should be noted that all tick borne diseases are clinical diagnoses and treatment of an acute case should not depend on "lab tests".  Both these infections are effectively managed by oral doxycycline, hence those with these signs and symptoms might be empirically treated with doxycyline, which would be important in areas where RMSF and tularemia (which also produce leukopenia and elevated LFTs) co-occur with deer tick -transmitted infections such as Lyme disease; waiting for "lab tests" to confirm RMSF or tularemia might lead to a negative outcome.  RMSF and tularemia are the most dangerous of the tick American tick borne diseases, although I would certainly place the very rare deer tick virus and Powassan virus in the same category.
Author Interviews, Emergency Care, NEJM / 30.05.2013

MedicalResearch.com eInterview with: Adam Z. Tobias, MD, MPH Assistant Professor of Emergency Medicine University of Pittsburgh School of Medicine Pittsburgh, PA  15261Adam Z. Tobias, MD, MPH Assistant Professor of Emergency Medicine University of Pittsburgh School of Medicine Pittsburgh, PA  15261 MedicalResearch.com: What are the main findings of the study? Answer: We reviewed records of 11,920 in-flight medical emergency calls from five domestic and international commercial airlines to a physician-staffed medical communications center at the University of Pittsburgh.  We found that during the study period, there was one medical emergency per 604 flights (16 per 1 million passengers).  The most common problems were syncope or pre-syncope, respiratory symptoms, and nausea and vomiting.  Aircraft diversion to an alternative landing site occurred just over 7% of the time. About one quarter of patients were transported to a hospital and only 8.6% were admitted.
Author Interviews, Cancer Research, JNCI, Lung Cancer, NEJM / 08.03.2013

Dr. Martin C. Tammemägi  Professor (Epidemiology) Brock University Department of Community Health Sciences Walker Complex – Academic South, Room 306 St. Catharines, Ontario, Canada L2S 3A1Medical Research.com Author Interview: Dr. Martin C. Tammemägi Professor (Epidemiology) Brock University Department of Community Health Sciences St. Catharines, Ontario, Canada L2S 3A1 Medical Research.com What are the main findings of the study?  Dr. Tammemägi: Our study accomplished three things: 1. We presented an updated Lung Cancer Risk Prediction Model, which compared to our previously JNCI-published model, incorporates more predictors but is simpler to use because we changed the way we modeled nonlinear effects. 2. We demonstrated that using the Lung Cancer Risk Prediction Model to select individuals for lung cancer screening was much more effective than using the National Lung Screening Trial (NLST) enrolment criteria.  41.3% fewer lung cancers were missed.  Sensitivity and positive predictive value of identifying individuals who develop lung cancer were significantly improved.  Shortly after our NEJM paper was published, Ma et al published in CANCER their findings that 8.6 million Americans are NLST-criteria positive and if they were CT screened under ideal conditions 12,000 lung cancer deaths would be averted.  Our NEJM article findings indicate that an additional 2,764 lives would be saved if the selection criteria had enrolled 8.6 million individuals for screening based on highest risk by our Lung Cancer Risk Prediction Model. 3. Importantly, using NLST data we demonstrated that the beneficial effect of CT screening did not vary by model predicted lung cancer risk.
Author Interviews, Clots - Coagulation, NEJM / 08.03.2013

 Author Interview: Sam Schulman M.D., FRCPC(C) Professor, Division of Hematology and Thromboembolism, Department of Medicine Associate Professor, Medicine, Karolinska Institute, Stockholm, Sweden Director, Clinical Thromboembolism Program Hamilton Health Sciences, Hamilton General Hospital, Hamilton, OntarioMedicalResearch.com  Author Interview: Sam Schulman M.D., FRCPC(C) Professor, Division of Hematology and Thromboembolism, Department of Medicine Associate Professor, Medicine, Karolinska Institute, Stockholm, Sweden Director, Clinical Thromboembolism Program Hamilton Health Sciences, Hamilton General Hospital, Hamilton, Ontario MedicalResearch.com: What are the main findings of the study? Response: Similar effect of dabigatran  as warfarin, 92% risk reduction compared to placebo. The risk of bleeding is reduced by almost 50% compared to warfarin but in comparison with placebo there is an increased risk of minor bleeding. No routine coagulation monitoring or dose adjustments are required, making the treatment convenient for patients and physicians.