Author Interviews, Infections, Pediatrics, Pulmonary Disease / 08.11.2018
Cystic Fibrosis Patients May Need Higher Doses of Antibiotics To Clear Lung Infections
MedicalResearch.com Interview with:
[caption id="attachment_45813" align="alignleft" width="133"] Dr. Hahn[/caption]
Andrea Hahn, M.D., MS
Infectious disease specialist and lead study author
Children's National Health System
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: People who have the genetic disease cystic fibrosis have increased sticky secretions in their lungs that put them at risk for repeated bacterial infections. They often will receive courses of intravenous antibiotics to treat more severe or difficult-to-treat infections associated with decreased lung function. However, not all patients fully recover their lung function after antibiotic treatment, despite directing antibiotic therapy toward the specific bacteria thought to be causing the infection. The goal of this study was to determine if the pharmacokinetics of commonly used antibiotics was associated with recovery of lung function.
First, we found that patients with therapeutic blood levels of beta-lactam antibiotics had better lung recovery than patients with sub-therapeutic levels of these antibiotics.
Second, we found that using higher antibiotic dosing according to Cystic Fibrosis Foundation guidelines was not sufficient to predict which patients would have therapeutically meaningful blood levels of antibiotics.
Dr. Hahn[/caption]
Andrea Hahn, M.D., MS
Infectious disease specialist and lead study author
Children's National Health System
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: People who have the genetic disease cystic fibrosis have increased sticky secretions in their lungs that put them at risk for repeated bacterial infections. They often will receive courses of intravenous antibiotics to treat more severe or difficult-to-treat infections associated with decreased lung function. However, not all patients fully recover their lung function after antibiotic treatment, despite directing antibiotic therapy toward the specific bacteria thought to be causing the infection. The goal of this study was to determine if the pharmacokinetics of commonly used antibiotics was associated with recovery of lung function.
First, we found that patients with therapeutic blood levels of beta-lactam antibiotics had better lung recovery than patients with sub-therapeutic levels of these antibiotics.
Second, we found that using higher antibiotic dosing according to Cystic Fibrosis Foundation guidelines was not sufficient to predict which patients would have therapeutically meaningful blood levels of antibiotics.
Nicholas Reed AuD[/caption]
Nicholas S. Reed, AuD
Assistant Professor | Department of Otolaryngology-Head/Neck Surgery
Core Faculty | Cochlear Center for Hearing and Public Health
Johns Hopkins University School of Medicine
Johns Hopkins University Bloomberg School of Public Health
MedicalResearch.com: What is the background for this study?
Response: This study was a true team effort. It was funded by AARP and AARP Services, INC and the research was a collaboration of representatives from Johns Hopkins University, OptumLabs, University of California – San Francisco, and AARP Services, INC. Given all of the resent research on downstream effects of hearing loss on important health outcomes such as cognitive decline, falls, and dementia, the aim was to explore how persons with hearing loss interacted with the healthcare system in terms of cost and utilization.
MedicalResearch.com: What are the main findings?
Response: Over a 10 year period, untreated hearing loss (hearing aid users were excluded from this study as they are difficult to capture in the claims database) was associated with higher healthcare spending and utilization. Specifically, over 10 years, persons with untreated hearing loss spent 46.5% more, on average, on healthcare (to the tune of approximately $22000 more) than those without evidence of hearing loss. Furthermore, persons with untreated hearing loss had 44% and 17% higher risk for 30-day readmission and emergency department visit, respectively.
Similar relationships were seen across other measures where persons with untreated hearing loss were more likely to be hospitalized and spent longer in the hospital compared to those without evidence of hearing loss. 
Sarah Hartz, MD PhD
Assistant Professor
Department of Psychiatry
Washington University School of Medicine in St. Louis
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This study is the first to show that daily drinking is dangerous. Specifically, drinking four or more times weekly, even if it’s only 1-2 drinks at a time, increases risk of mortality. This is in line with recent studies published in the Lancet, but we were able to break down their lowest drinking categories (up to 12.5 drinks weekly in one and up to 5.6 drinks weekly in the other) and found that the frequency is important, not just the average number of drinks per week. It looks like the increased mortality is predominantly due to cancer-related deaths.
Dr Sarah Myers PhD
Honorary Research Associate
UCL Department of Anthropology
MedicalResearch.com: What is the background for this study?
Response: Postnatal or postpartum depression is unfortunately common after giving birth; a figure often quoted is 15%, but some studies have found much higher numbers. Postnatal depression is associated with a range of poorer outcomes for mothers and their infants, and the financial costs of treating maternal mental ill health put health services under considerable strain. Studies have found that providing additional emotional support to at risk mothers, for instance via peer support programmes or regular phone calls with health visitors, can reduce the likelihood of them developing the condition. Therefore, it is really important that we understand the full range of risk factors that put women at greater risk of becoming depressed after giving birth.
There is increasing evidence for a link between inflammation and depression, with factors that trigger an inflammatory immune response also increasing the likelihood of depressive symptoms. The opens up the possibility of finding new risk factors for postnatal depression based on known associations with inflammation.
Dr. Quast[/caption]
Troy Quast, PhD
Associate Professor in the University
South Florida College of Public Healt
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: One of the cited repercussions of the opioid epidemic is its effect on families. However, there is considerable variation in opioid misuse across the county. This is the first nation-wide study to investigate the relationship between opioid prescription rates and child removals at the state level.
I found that there are significant differences across states in the relationship between opioid prescription and child removal rates associated with parental substance abuse. In twenty-three states, increases in opioid prescription rates were associated with increases in the child removal rate. For instance, in California a 10% increase in the county average prescription rate was associated with a 28% increase in the child removal rate. By contrast, in fifteen states the association was flipped, where increases in the opioid prescription rate were associated with decreases in the child removal rate. There was no statistically significant relationship in the remaining states. 
Dr. Yano[/caption]
Yuichiro Yano MD PhD
Assistant Professor in Community and Family Medicine
Duke University
MedicalResearch.com: What is the background for this study?
Response: New blood pressure guidelines, issued in 2017 in the US, lowered the blood pressure thresholds for hypertension from systolic blood pressure/diastolic ≥140/90 mm Hg to systolic/diastolic ≥130/80 mm Hg. This change increased the prevalence of hypertension two- to three-fold among young adults. The guidelines also newly defined elevated blood pressure as, 120-129 mmHg systolic blood pressure over 80 mmHg diastolic or less. However, no study investigated that high blood pressure, as defined by the new criteria, is something that younger people should be concerned about as a potential precursor to serious problems.
Our study is among the first to report that people younger than age 40 who have elevated blood pressure or hypertension are at increased risk of heart failure, strokes and blood vessel blockages as they age.
Dr. McLaughlin[/caption]
Ryan J. McLaughlin, PhD
Assistant Professor
Department of Integrative Physiology & Neuroscience
College of Veterinary Medicine
Washington State University
Pullman, WA 99164-7620
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The use of cannabis during pregnancy is a growing health concern, yet the long-term cognitive ramifications for developing offspring remain largely unknown. Human studies exploring the long-term effects of maternal cannabis use have been sparse for several reasons, including the length and cost of such studies, as well as the fact that experimentally assigning mothers to smoke cannabis during pregnancy is obviously ethically impractical. Animal models of maternal cannabis use have been advantageous in this respect, but they have been limited by the drugs used (synthetic cannabinoids vs. THC vs. cannabis plant) and the way that they are administered. In our study, we used a more translationally relevant animal model of maternal cannabis use that exposes pregnant rat dams to whole plant cannabis extracts using the intra-pulmonary route of administration that is most common to human users. Our preliminary data indicate that twice-daily exposure to a high-dose cannabis extract during pregnancy may produce deficits in cognitive flexibility in adult rat offspring. Importantly, these rats did not experience general learning deficits, as they performed comparably to non-exposed offspring when required to follow a cue in their environment that dictate reinforcer delivery. Instead, deficits were observed only when rats were required to disregard this previous cue-based strategy and adopt a new egocentric spatial strategy in order to continue receiving the sugar reinforcers.
Dr. Verge[/caption]
Danilo Verge MD MBA
Vice President, CVRM Global Medical Affairs
AstraZeneca
MedicalResearch.com: What is the background for this study?
Response: Dapagliflozin, an SGLT2 inhibitor (sodium-glucose co-transporter 2), has been shown to improve glycemic control by decreasing glucose reabsorption in the kidneys and inducing urinary glucose clearance. SGLT2 inhibitors have also been shown to be effective in lowering albuminuria and stabilizing eGFR (estimated glomerular filtration rate). The effect of dapagliflozin on UACR (urine albumin-to-creatinine ratio) has been shown to vary among patients.
The objective of this post-hoc analysis, based on the pooled data from 11 randomized, placebo-controlled clinical trials, was to assess baseline characteristics and concurrent changes in cardiovascular (CV) risk markers associated with UACR response to dapagliflozin.
Lei Qin[/caption]
Lei Qin MS
Director, Health Economics and Payer Analytics
AstraZeneca
MedicalResearch.com: What is the background for this study?
Response: Renin-angiotensin-aldosterone system inhibitors (RAASi) are guideline-recommended therapies for patients with chronic kidney disease (CKD), but are commonly prescribed at suboptimal doses, which has been associated with worsening clinical outcomes. The objective of our study was to estimate the real-world associations between RAASi dose and adverse clinical outcomes in patients prescribed RAASi therapies with new-onset CKD in the UK.
Dr. Agrawal[/caption]
Rahul Agrawal MD PhD
VP, Global Medicines Leader
AstraZeneca
MedicalResearch.com: What is the background for this study?
About the study: HARMONIZE Global is a Phase III, randomized, multicenter, double-blind, placebo-controlled trial involving 267 patients with hyperkalemia (mean potassium levels greater than 5.0 mEq/L) in 47 study locations across the Asia Pacific region, which will support registration in Japan, Taiwan, Korea and Russia.
Study design: The trial design of HARMONIZE Global is similar to HARMONIZE (NCT02088073) but evaluated two doses of LOKELMATM (sodium zirconium cyclosilicate) instead of three, as well as patients in different geographical regions.
Prof. Thornhill[/caption]
Martin H. Thornhill MBBS, BDS, PhD, MSc, FDSRCS(Edin), FDSRCSI, FDSRCS(Eng)
Professor of Translational Research in Dentistry
Academic Unit of Oral & Maxillofacial Medicine Surgery & Pathology,
University of Sheffield School of Clinical Dentistry
MedicalResearch.com: What is the background for this study?
Response: Infective endocarditis is an infection of the heart valves that has a high death rate (around 30% in the first year). It requires intensive treatment often involving replacement of affected heart valves and frequently results in serious long-term illness and disability in those who survive as well as an increased risk of re-infection and high healthcare costs.
In ~40% of cases, bacteria from the mouth are implicated as the causal organism. Because of this, guideline committees around the world recommended that all those at risk of infective endocarditis should receive antibiotic prophylaxis before undergoing invasive dental procedures. Due to a lack of evidence for efficacy, however, guideline committees started to limit the use of antibiotic prophylaxis. And in 2007, the American Heart Association (AHA) guideline committee recommended that antibiotic prophylaxis should continue for those at high-risk but should cease for those at moderate risk of endocarditis. Most guideline countries around the world followed suite. Except in the UK, where the National Institute for Health and Care Excellence (NICE) recommended that the use of antibiotic prophylaxis should completely stop in 2008.
