DETIKSPORT | Selasa 24 Januari 2017, 14:50 WIB
Rider Yamaha, Valentino Rossi, sedang mengunjungi Labuhan Bajo, Flores, NTT. Dia menyedot perhatian warga di sana, juga sempat berkunjung ke Pulau Padar.
Lorenzo yang kini memperkuat tim Ducati, menempati posisi delapan klasemen dengan raihan 60 poin. Dia cuma sekali meraih podium, saat meraih posisi tiga di seri MotoGP Spanyol.
Di seri MotoGP Belanda, Lorenzo mencatatkan posisi start terburuk. Dia menempati grid ke-21.
Lorenzo belum menunjukkan perbaikan di MotoGP Jerman. Saat latihan bebas pertama ada di posisi 12. Sedangkan di latihan bebas kedua naik dua anak tangga.
Pebalap asal Spanyol itu akhirnya membuka suara mengenai kendalanya bersama Ducati. Dia masih belum menemukan stabilitas motor Desmosedici GP17 yang ditungganginya.
“Di masa lalu, saya sangat cepat di sektor terakhir, dan sektor 3, tikungan cepat, karena saya merasa sangat stabil dan sangat aman dengan Yamaha. Terutama di era 800. Sektor ini merupakan satu di mana saya paling banyak kehilangan waktu,” kata Lorenzo seperti dilansir oleh Crash.
“Tampak dalam tikungan cepat, motornya tidak stabil. Mungkin karena kurang kontak karena kami ak mempunyai winglets. Tapi di sektor 1. saya sangat cepat. Saya tak kehilangan apapun, jadi itu cukup aneh. Tapi, saya fokus terus mencoba meningkatkan stabilitas di tikungan cepat,” tambahnya.
(cas/raw)
DETIKSPORT | Sabtu 24 Juni 2017, 13:03 WIB
Sejak awal sesi latihan bebas pertama, Jorge Lorenzo sudah mengalami kejadian tak mengenakkan. Selanjutnya, hari barjalan buruk untuk dia.
HELSINKI — A mobile app is being developed to make treatment recommendations to prescribers, using information provided by patients in a tandem system.
“We’re moving away from guidelines to more simplified treatment algorithms, and to get there, we need care pathways that are different from guidelines, in that they incorporate a multifactorial team,” said Ruth Murray, PhD, director of MedScript Ltd, in Dundalk, Ireland.
“To connect all the stakeholders in a care pathway, you need very simple language” that is common to healthcare providers, pharmacists, and patients, and is easy to use, she explained here at the European Academy of Allergy and Clinical Immunology Congress 2017.
In Allergic Rhinitis and Asthma
Currently, patients can keep a daily record of medication use and allergic rhinitis and asthma symptoms with a free Allergy Diary app.
The new app will use the allergic rhinitis clinical decision support system (J Allergy Clin Immunol. 2016;138:367-374.e2) to provide treatment recommendations on the basis of specific data reported by the patient: the type of allergic rhinitis, current treatments, allergen exposure, and visual analogue score.
“The idea is to input basic information into the companion app, and the healthcare professional will receive a simple treatment recommendation based on that information,” Dr Murray said. “The aim is to simplify care management and use the same visual analogue score throughout the application to improve patient and healthcare communication.”
To validate treatment recommendations, investigators consulted a group of allergic rhinitis experts on step-up and step-down treatment strategies.
“The idea is that no matter what a patient or healthcare provider inputs into the Allergy Diary Companion, that scenario has been thought of by us,” explained Dr Murray.
Her team sent a Survey Monkey questionnaire to 70 experts in allergic rhinitis from Australia, Europe, and North America; the response rate was 50%.
Specialists Have Their Say
The survey asked about the overall approach and indications for starting, stepping up, and stepping down treatment. It also asked about specific treatment recommendations at each of those steps, scored on visual analogue scale of 0 (strongly disagree) to 100 (strongly agree).
“Rather than just advising a step up in treatment or a step down in treatment, we wanted to be able to say, this is the treatment we advise you to step up to based on the information that you’ve provided about your patient,” said Dr Murray.
The experts generally agreed on when to step up and when to step down treatment.
Table 1. Consensus of Experts on Changes in Treatment Strategy
| Visual Analogue Score | Action | Consensus, % |
|---|---|---|
| ≥5 | Step up | 91 |
| 2 to <5 | If intermittent, continue | 76 |
| If persistent, continue or step up | 88 | |
| <2 | If intermittent, step down | 85 |
| If persistent, step down | 75 |
There was also general agreement on step-up and step-down strategies.
But there were conflicting opinions. “Some people thought oral corticosteroids were being recommended too early and allergen immunotherapy was being offered too late,” Dr Murray reported. “Some believed that if your patient has congestion, you should step down to oral corticosteroids because oral histamines have not shown great benefit with congestion.”
Table 2. Consensus on Treatment Changes
| Initial Treatment | Treatment | Consensus, % |
|---|---|---|
| Step-up Therapy | ||
| Antihistamines | Intranasal corticosteroids with or without azelastine | 91 |
| Intranasal corticosteroids | Add azelastine | 83 |
| Polypharmacy | Intranasal corticosteroids plus azelastine | 80 |
| Intranasal corticosteroids plus azelastine | Add short course of oral corticosteroids; if VAS ≥5, refer | 64 |
| Step-down Therapy | ||
| Intranasal corticosteroids plus azelastine | Intranasal corticosteroids (preferred if congestion is dominant symptoms) or antihistamines | 78 |
| Intranasal corticosteroids plus antihistamines | Intranasal corticosteroids (preferred if congestion is dominant symptoms) or antihistamines | 87 |
| Intranasal corticosteroids | Antihistamines | 75 |
| Antihistamines | Continuation dependent on allergen exposure | 84–86 |
Providers should certainly check treatment compliance, technique, and patient preference at each step, Dr Murray advised.
“That’s clearly stated in the recommendations — that you should listen to your patient,” she added. Although “these are recommendations open to interpretation and flexibility, we are confident this will improve the way we manage our patients.”
It is expected that the free app will be available next year, Dr Murray reported.
This study received no external funding. Dr Murray is a medical communications consultant at Medscript Ltd.
European Academy of Allergy and Clinical Immunology (EAACI) Congress 2017: Abstract 0183. Presented June 18, 2017.
Follow Medscape Allergy & Clinical Immunology on Twitter @MedscapeAllergy and Tara Haelle @TaraHaelle
Saxony – Marc Marquez optimistis dengan peluang Honda di MotoGP Jerman. Hasil latihan bebas hari pertama menjadi dasar penilaian Baby Allien.
Di Sachsenring, Jumat (30/6/2017), Honda menunjukkan progres yang bagus. Marquez menduduki peringkat enam saat free practice I yang berlangsung dalam kondisi trek kering. Dia mencatatkan waktu satu menit 21,898 detik.
Sementara saat free practice II dalam kondisi trek basah, Marquez mampu menyodok ke posisi dua. Dia mencatatkan waktu satu menit 28,178 detik atau 0,063 detik lebih lambat dari Hector Barbera di posisi pertama.
Sementara itu, Dani Pedrosa mampu menempati posisi tiga baik di latihan bebas pertama dan kedua. Hasil cukup impresif itu membuat Marquez merasa cukup percaya diri bahwa Honda mampu tampil bagus di MotoGP Jerman. Mereka sudah empat seri tak pernah menang.
“Hari ini benar-benar sangat positif. Saya merasa bagus dan kuat saat lintasan kering di pagi ini dan juga saat lintasan basah di saat sore hari. Itu penting, karena Anda tak pernah tahu kondisi mana yang harus Anda hadapi. Sepertinya besok lintasan akan kering dan sama halnya hari Minggu. Tapi, kita tak tahu pastinya,” kata Marquez di Crash.
“Kami mulai dari dasar setelan yang bagus, dan saya merasa nyaman. Sekarang, kami harus memberi perhatian untuk terus lebih baik seiring dengan kondisi trek. Saya pikir aspal baru akan menjadi lebih baik selangkah demi selangkah dan itu bisa mengubah segalanya. Di saat lintasan basah, cengkeramannya begitu luar biasa dan kami bisa empat detik lebih cepat dibandingkan tahun lalu.”
“Di saat kondisi kering, saya pikir ada potensinya. Tapi dalam kondisi aspal yang masih baru, itu sedikit agak licin. Bagaimanapun juga, kita tunggu saja seperti apa kondisi cuacanya besok. Tapi, kami tahu bahwa kami sudah cukup bagus dalam setiap kondisi,” tambah pebalap asal Spanyol itu.
(cas/raw)
(Reuters Health) – A positive parenting style might protect kids from the negative effect that growing up in poverty is thought to have on their brain development, Australian researchers say.
Using brain magnetic resonance imaging (MRI) and academic indicators, the study team found differences in the brains of kids growing up in the most disadvantaged environments. But those with supportive parents showed brain development more like that of peers who were less disadvantaged.
“Society is struggling with righting equality, particularly economic equality,” said senior study author Nick Allen, a psychology professor at the University of Oregon in Eugene who is also affiliated with the University of Melbourne.
“We know from social science that being raised in a socioeconomically disadvantaged environment is bad for development,” he told Reuters Health in a phone interview. “What we’re trying to understand now is how children are affected and what we can do about it.”
The researchers analyzed data on 166 adolescents between ages 11 and 20 in Melbourne who were participating in a larger study. All the kids had up to three MRI brain scans at early, middle and late adolescence, and researchers also assessed their family and neighborhood socioeconomic environments, academic success and characteristics of their parents.
The examination of parents included educational level, income and the family’s socioeconomic status within the immediate surrounding neighborhood of about 250 homes.
To gauge parenting behaviors, researchers observed as the adolescents and their mothers completed two 20-minute interactions such as event-planning or problem-solving tasks that displayed verbal and nonverbal reactions. Parental behaviors considered to be positive included approving, validating, affectionate or humorous comments.
The research team found that neighborhood, but not family-level, economic measures were associated with differences in brain development between early adolescence and the late teen years. The most disadvantaged kids showed differences from others in the brain’s temporal lobes in particular, which could affect stress, memory and language, the study authors write in JAMA Psychiatry, June 21.
“Adolescence is an important time for the development of the brain, particularly in terms of factors that influence your life and the ability to regulate behavior and form relationships,” Allen said.
Positive parenting behaviors, however, seemed to moderate the negative effects of the poor environment, especially in the brain region known as the amygdala, which has a central role in regulating emotions.
In contrast, the combination of growing up in a disadvantaged neighborhood and low parental positivity was linked to increased odds of dropping out of school, primarily among boys.
“We were surprised to find that parenting can actually change development and behaviors,” Allen said. “We still need to work for political and social change to lift people out of poverty, but supporting families could be part of that picture.”
Limitations of the study include the fact that parenting and socioeconomic circumstances were only assessed at one time point, the authors note. They also didn’t have data on brain development and other factors prior to adolescence that could influence the results.
The study also doesn’t prove that poverty caused the brain differences seen among teens, or the changes seen over time in individual children.
Still, this link between environment and biology continues the conversation about the increased risks associated with low socioeconomic status, such as poor mental health, physical health, school readiness, academic success, high school completion and career opportunities, said Jamie Hanson of the University of Pittsburgh in Pennsylvania, who wasn’t involved in the study.
“We’re just starting to realize more and more about the effects of different experiences on the brain,” he told Reuters Health by phone. “It speaks to how experience becomes biologically embedded in us.”
The next research step is to work with those disadvantaged communities and families, he added. In Pittsburgh, for example, neighborhood community redevelopment programs are beginning to reach out to families to get them more involved in family and community activities.
“Parents can be a powerful source of change,” Hanson said. “They have the agency to help their kids, even under challenging circumstances.”
SOURCE: http://bit.ly/2t60WHk
JAMA Psychiatry 2017.
NEW YORK (Reuters Health) – Onlay mesh reinforcement significantly reduced the incidence of incisional hernia compared with sublay mesh or primary suture in high-risk patients undergoing midline laparotomy, researchers say.
“Incisional hernia is one of the most frequently seen complications after abdominal surgery, with an incidence that can increase over 35% in high-risk groups,” such as obese patients and those with an abdominal aortic aneurysm, Dr. Ari Jairam of Erasmus University Medical Center in Rotterdam, Netherlands told Reuters Health.
To assess the effectiveness of mesh reinforcement in patients at high risk, Dr. Jairam and colleagues randomized patients undergoing elective midline laparotomy to primary suture only (107 patients), onlay mesh reinforcement (188) and sublay mesh reinforcement (185). A lightweight, large-pore polypropylene mesh was used in both mesh groups, which was fixated with fibrin glue.
Participants had either an abdominal aortic aneurysm or a BMI of 27 or higher.
As reported online June 19 in The Lancet, 92 patients had an incisional hernia during two years of followup: 31% in the primary suture group, 13% in the onlay mesh reinforcement group and 18% in the sublay mesh group.
The incidence of incisional hernia differed significantly between the primary suture and onlay mesh groups (OR, 0.37). However, there were no significant differences between the primary suture versus sublay mesh groups (OR, 1.8) or onlay versus sublay mesh (OR, 1.4).
Among the subgroup of 150 patients with abdominal aortic aneurysm, 36 (24%) had an incisional hernia: 16 in the primary suture group, 10 in the onlay mesh group, and 10 assigned to sublay mesh.
In the subgroup of 330 patients with a BMI of 27 or higher, 54 (16%) had an incisional hernia: 16 in the primary suture group, 15 allocated to onlay mesh and 23 assigned to sublay mesh.
Close to 25% of patients had a postoperative complication during two years of follow-up. At one month, seromas were seen most frequently in those who received onlay mesh reinforcement. “However, this finding did not have any further consequences for patients, i.e., the frequency of surgical-site infections, re-interventions or re-admissions with onlay mesh reinforcement was not different when compared with primary suture or sublay mesh reinforcement,” the authors note.
The risk of re-intervention (p=0.343) and re-admission (p=0.508) did not differ among the groups. None of the re-interventions or re-admissions were related to the mesh or the fibrin sealant.
“Closure of laparotomy with onlay mesh reinforcement has the potential to become the standard treatment in high-risk groups, which will reduce the socioeconomic burden of incisional hernia,” Dr. Jairam suggests.
Editorialist Dr. Lillian Kao of the University of Texas Health Science Center at Houston told Reuters Health, “Theoretically, onlay mesh is technically easier to perform. On the other hand, onlay mesh may predispose to increased seromas or surgical site infections, the latter of which may require the mesh to be explanted.”
“The increased risk (of seromas) is postulated to result from dissection of flaps for the onlay mesh placement,” she said by email. “In the trial, the mesh overlapped the fascia by 3 cm, so perhaps there was not as significant a need for creating flaps.”
“Given that approximately 50% of patients underwent gastrointestinal surgery, it is likely that there were a significant number of patients with clean-contaminated wounds,” she continued. “However, there is no description of what proportion of patients had contaminated wounds – and because only elective patients were included, there were likely also only a few patients with dirty wounds.”
“Therefore, one should be cautious about extrapolating the results to patients with contaminated or dirty wounds,” Dr. Kao said. “In addition, it is not known at what risk of incisional hernia formation prophylactic mesh should be used – i.e., should it be used in patients at low risk of hernia after exploratory laparotomy? What constitutes low or high risk?”
The study was funded by Baxter and B Braun Surgical SA. The authors declared no competing interests.
SOURCE: http://bit.ly/2sr5J47 and http://bit.ly/2sVOmfb
Lancet 2017.
Source by [author_name]
MADRID — When the first biosimilar for infliximab, CT-P13, was approved in Denmark in 2015, the government mandated that patients switch to the biosimilar, which was 64% less expensive at the time. However, there was concern that an increase in the use of healthcare resources, because of patient and physician anxiety about the new class of agents, would offset the cost savings.
“This was the first nonmedical switch that happened,” said Bente Glintborg, MD, PhD, from the Copenhagen Center for Arthritis Research and the DANBIO registry.
“Patients were anxious, physicians were anxious, and the patient societies were anxious,” she told Medscape Medical News.
“I expected some worrying, and that the patients would call and come in a lot,” she said here at the European League Against Rheumatism Congress 2017.
In their study, Dr Glintborg and her colleagues assessed total healthcare services used and the number of days with healthcare services used in the 6 months before and the 6 months after the switch.
During the 12-month study period, 1484 outpatient visits were made by 769 patients with rheumatologic inflammatory diseases. In total, 19,752 individual services were provided, and about 10% of those were on the switch date.
And of the 9243 days on which at least one service was provided, 693 — or approximately 7% — occurred on the switch date.
There was a slight increase in the mean number of days with services from before the switch to after (5.4 vs 5.7; P = .0003).
“We found that there were some significant differences in higher use after than before,” Dr Glintborg explained, “but the numbers were very similar.” The difference was statistically significant because of the large number of patients, “but not clinically meaningful.”
“I was surprised, actually. I had expected a higher use of services after,” she added. “These patients were well treated for almost 7 years with the originator drug, so of course they were worried. It’s another drug from another company with a different name.”
Table. Mean Number of Services Used Before and After Drug Switch
| Service | Before Switch | After Switch | P Value |
|---|---|---|---|
| Infliximab treatment | 3.10 | 2.96 | <.01 |
| Clinical control | 2.07 | 2.26 | <.01 |
| Phone consult | 1.03 | 1.17 | .03 |
| Patient guidance | 0.35 | 0.49 | <.01 |
| Clinical investigation | 0.31 | 0.47 | <.01 |
| Observation | 0.17 | 0.22 | <.01 |
| Intravenous medication | 0.03 | 0.11 | <.01 |
Differences between the two time periods were not significant for services related to nursing activity, methotrexate treatment, blood pressure measurement, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), venous needle, conversation about treatment, ultrasound over extremity joint, or ultrasound under extremity joint.
“This analysis showed that there were only small differences in the rate of days with outpatient services and rates of services 6 months before and after the switch from original to biosimilar infliximab,” the researchers write in their abstract. “Thus, it is unlikely that the switch is associated with substantially higher cost of healthcare resources.”
“The clinical significance of the findings is that the services used before and after switching to a biosimilar from a bio-originator were not different,” said Désirée van der Heijde, MD, from the Leiden University Medical Center in the Netherlands.
“That is an indirect way of showing that there are no specific concerns by the patients after the switch, which would have led to the use of more services. There were significant differences in a few variables but, numerically, the data were very similar,” she told Medscape Medical News.
In a separate Danish study, people with rheumatoid arthritis or psoriatic arthritis were interviewed 9 to 12 months after the mandatory switch.
“We asked patients what concerns, issues, and thoughts they had about nonmedical switches from an originator to a biosimilar,” said Tanja Schjødt Jørgensen, PhD, from Copenhagen University Hospital.
In most cases, patients reported that “a lack of information and a lack of communication” made them “insecure about the switch,” Dr Jørgensen told Medscape Medical News.
Even when clinicians shared data pointing to the clinical equivalence of a new biosimilar, many patients remained unhappy, she explained. They understood the economic reasons for the switch, but didn’t like the element of surprise, their lack of involvement in the decision, or the relatively short amount of time they were given to process the change.
The Danish government required everyone to switch within a 2-month period, so there was limited time for patients to get their questions answered. “It would have been less scary” for the patients if the process had been longer, Dr Jørgensen pointed out.
Nonmedical switches are particularly worrisome for rheumatoid or psoriatic arthritis patients in remission on a particular biologic. “They’re taking a medication that for many makes their lives worth living again,” she noted.
Dr Glintborg reports receiving grant and research support from AbbVie. Dr van der Heijde reports receiving consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB. Dr Jørgensen reports being on the speakers’ bureau for AbbVie, Roche, Novartis, UCB, and Biogen.
European League Against Rheumatism (EULAR) Congress 2017: Abstract THU0468. Presented June 15, 2017.
Follow Medscape Rheumatology on Twitter @MedscapeRheum and Damian McNamara @MedReporter
Air Force veteran Billy Ramos, from Simi Valley, Calif., is 53 and gets health insurance for himself and for his family from Medicaid — the government insurance program for low-income people. He says he counts on the coverage, especially because of his physically demanding work as a self-employed contractor in the heating and air conditioning business.
“If I were to get hurt on the job or something, I’d have to run to the doctor’s, and if I don’t have any coverage they’re going to charge me an arm and a leg,” he said. “I’d have to work five times as hard just to make the payment on one bill.”
There are about 22 million veterans in the U.S. But fewer than half get their health care through the Veterans Affairs system; some don’t qualify for various reasons or may live too far from a VA facility to easily get primary health care there.
Many vets instead rely on Medicaid for their health insurance. Thirty-one states and the District of Columbia chose to expand Medicaid to cover more people — and many of those who gained coverage are veterans.
The GOP health care bill working its way through the Senate would dramatically reduce federal funding for Medicaid, including rolling back the expansion funding entirely between 2021 and 2024.
Medicaid coverage recently has become especially important to Ramos — a routine checkup and blood test this year showed he’s infected with hepatitis C. California was one of the states that chose to expand Medicaid, and the program covers Ramos’ costly treatment to eliminate the virus.
“Right now, I’m just grateful that I do have [coverage],” he said. “If they take it away, I don’t know what I’m going to end up doing.”
The Senate health plan — which proposes deep cuts to federal spending on Medicaid — has veterans and advocates worried. Will Fischer, a Marine who served in Iraq, is with VoteVets.org, a political action group that opposes the Republican health plan.
“If it were to be passed into law, Medicaid would be gutted. And as a result, hundreds of thousands of veterans would lose health insurance,” Fischer said.
It’s too early to know just how many veterans might lose coverage as a result of the Medicaid reductions. First, states would have to make some tough decisions: whether to make up the lost federal funding, to limit benefits or to restrict who would get coverage.
But Dan Caldwell thinks those concerns are overblown. He’s a Marine who served in Iraq and is now policy director for the group Concerned Veterans for America.
“The people who are saying that this is going to harm millions of veterans are not being entirely truthful,” Caldwell said. “They’re leaving out the fact that many of these veterans qualify for VA health care or in some cases already are using VA health care.”
About a half-million veterans today are enrolled in the VA’s health care program as well as in some other source of coverage, such as Medicaid or Medicare. Andrea Callow, with the non-profit group Families USA, wrote a recent report showing that nearly 1 in 10 veterans are enrolled in Medicaid.
“Oftentimes veterans will use their Medicaid coverage to get primary care,” Callow said. “If, for example, they live in an area that doesn’t have a VA facility, they can use their Medicaid coverage to see a doctor in their area.”
Whether a particular veteran qualifies for coverage through the VA depends on a host of variables that she said leaves many with Medicaid as their only option.
But, Caldwell said, rather than fighting to preserve Medicaid access, veterans would be better served by efforts to reform the care the VA provides to those who qualify.
“We believe that giving veterans more health care choice and restructuring the VA so that it can act more like a private health care system will ultimately lead to veterans who use the VA receiving better health care,” he said.
The Urban Institute found that the first two years after the enactment of the Affordable Care Act saw a nearly 44 percent drop in the number of uninsured veterans under age 65 — the total went from 980,000 to 552,000. In large part, that was the result of the law’s expansion of Medicaid.
This story is part of NPR’s reporting partnership with Kaiser Health News .
Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation .
A rare variant in the amyloid precursor protein (APP) gene that has been shown to protect against Alzheimer’s disease (AD) is associated with decreased levels of plasma amyloid β (Aβ), a new study has shown.
This is the first human population-based randomly selected cohort study to show reduced plasma Aβ levels in APP A673T carriers, which “provides evidence that lower Aβ levels throughout the life may be protective against Alzheimer’s disease,” the researchers write.
Dr Mikko Hiltunen
The results support the amyloid cascade hypothesis, which suggests that an accumulation of brain Aβ plays a key role in AD, study author Mikko Hiltunen, PhD, professor of tissue and cell biology, Institute of Biomedicine, University of Eastern Finland, and Department of Neurology, Kuopio University Hospital, Kuopio, Finland, told Medscape Medical News.
The new finding is a significant discovery, said Dr Hiltunen, because many ongoing AD drug trials focus on decreasing Aβ levels in the brain.
“From my point of view, this is a clear message for pharmaceutical companies that they are on the right track in their attempts to target β-amyloid as early as possible,” he said.
The study, published online May 26 in the Annals of Neurology, also showed that decreased Aβ levels are not associated with detrimental effects on metabolic or cardiovascular outcomes.
A neurodegenerative disease, AD is characterized by the accumulation of Aβ in brain tissue. Uncovering the genetic pathogenesis of AD has become an important target of research, with genome-wide mapping studies leading to significant advances in the field.
These studies have identified not only several new risk genes for AD but also gene variants that protect against the disease, including the APP variant A673T. It was thought that this variant might affect the risk for AD by modulating levels of Aβ.
Researchers used data from the METabolic Syndrome In Men (METSIM), a large population-based study carried out from 2005 to 2010. The study included over 10,000 men aged 45 to 70 years randomly selected from the population register of Kuopio, Eastern Finland (population 95,000). None of these men were diagnosed with AD.
Among 8629 genotyped individuals, 47 were heterozygous carriers of the A67T variant; 37 of 4916 genotyped individuals were heterozygous carriers of the ABCA7 rs200538373 gene variant.
Researchers compared plasma levels of Aβ40 and Aβ42 in carriers of both gene variants with levels in noncarrier controls from the cohort who were matched for age, body mass index, and similar apolipoprotein E (APOE) genotype distribution.
The analysis found that APP A673T carriers had on average 28% lower levels of Aβ compared with controls (P < 1.0 × 10–14).
“This very significant result shows how strong the effect is,” commented Dr Hiltunen.
A similar reduction was seen in both Aβ42 and Aβ40, while the Aβ42/40 ratio was similar in both the carriers and controls. This, said the authors, suggests “an overall reduction in the production of Aβ rather than the γ-secretase-related modulation of the different Aβ peptides.”
While researchers knew that individuals carrying the APP A673T gene variant were somehow protected from AD, there has been no clear explanation as to why.
“Now we are showing that this variant associates with, or is linked to, reduced plasma Aβ levels,” said Dr Hiltunen. “This new study provides a direct link between genetics and functional outcome.”
Aβ “is the most important player in AD,” he added.
Both altered β- and γ-cleavage have been suggested as possible mechanisms underlying decreased Aβ levels in the presence of the APP A673T variant. The APP protein produces Aβ, and the A673T variant is exactly in the location where the secretase initially responsible for clearing Aβ is located, said Dr Hiltunen.
The other rare variant researchers studied — ABCA7 rs200538373 — did not appear to affect amyloid levels, which was somewhat surprising to Dr Hiltunen.
“We were expecting to see some increase because that variant increases the risk of having AD based on genetic studies. So the idea was that if you have that variant, more Aβ is being produced, but that didn’t happen here,” he said. “What’s the reason for that? We don’t know.”
Researchers had access to data on laboratory measures, including total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride levels, as well as plasma glucose, high-sensitivity C-reactive protein, and interleukin-1 receptor agonist levels. A total of 248 cardiovascular health- and metabolism-related parameters were available from the METSIM cohort.
In a comparison between the carrier and control groups, the analysis found no statistically significant differences in the most important parameters reflecting general health status.
“It seems like this kind of moderate reduction in Aβ doesn’t have any adverse effects on metabolic or cardiovascular outcome measures,” said Dr Hiltunen.
That’s good news for pharmaceutical companies because it means, he noted, that lowering Aβ in early stages of AD is safe. “There are no adverse effects on other functions.”
The analysis also found that Aβ40 — but not Aβ42 — had a positive correlation with age. This finding, said the authors, is consistent with a previous longitudinal study showing an increase in plasma Aβ40 levels in cognitively normal individuals over time.
Dr Hiltunen and his colleagues did not have access to Aβ levels in cerebrospinal fluid (CSF) but, according to previous studies, “there is a clear correlation between blood levels and CSF levels,” said Dr Hiltunen. “So we assume that the same thing can be seen in the CSF and in brain tissue.”
However, the authors stressed that further studies are needed beyond plasma measurements to determine the levels and deposition of Aβ in the CSF and brain tissue of APP A673T variant carriers.
Although the gene variant is rare, the association with decreased plasma Aβ levels is important with respect to AD drug trials. Several ongoing trials focus on decreasing Aβ levels in brain tissue.
The key for clinical trials targeting amyloid is to start them early. Most of the drug trials that have failed to show a benefit of lowering amyloid, “very likely have been started too late,” said Dr Hiltunen.
“So patients are already in mid or late stages of the disease, and there is already tissue damage,” which can’t be repaired.
The new findings on the role of the APP A673T gene variant in AD may eventually help identify new drug targets and better predictive biomarkers, he said.
Commenting on the findings, Keith Fargo, PhD, Alzheimer’s Association director of scientific programs and outreach, said the findings suggest the gene variant known as APP A673T may offer protection from Alzheimer’s by reducing or preventing the accumulation of amyloid brain plaques.
“These plaques have long been a prime suspect in killing nerve cells in Alzheimer’s,” Dr Fargo told Medscape Medical News. “These new findings are important because they support this idea and provide further evidence that preventing amyloid plaque accumulation can be an effective Alzheimer’s therapy.”
Advances in brain imaging have allowed researchers to show that amyloid plaque accumulation and other brain changes associated with Alzheimer’s begin “years, perhaps even decades, before memory and thinking problems appear,” he said.
“As a result, the field is shifting toward approaches that target these changes early on to prevent dementia. For example, there are five ongoing large-scale Alzheimer’s prevention trials — including four the Alzheimer’s Association is helping to fund — that involve amyloid-targeting drug candidates. You may think of this approach as being similar to taking cholesterol-lowering medication to prevent heart attacks and strokes.”
Dr Hiltunen and Dr Fargo have disclosed no relevant financial relationships.
Ann Neurol. Published online May 26, 2017. Abstract
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Di Sachsenring, Jumat (30/6/2017), sesi latihan bebas kedua MotoGP Jerman berlangsung dalam kondisi hujan. Hector Barbera menjadi yang tercepat dengan catatan waktu satu menit 28,115 detik.
Sementara itu, Rossi ada di posisi 15 dengan catatan waktu 1,434 detik lebih lambat dari Barbera.
Rossi mengaku mempunyai masalah pada motornya, terutama saat kondisi trek basah. Dia juga masih kurang nyaman dengan sasis motor YZR-M1 yang menjadi tunggangannya. Saat sesi hari Sabtu, Rossi mempunyai target bisa menembus posisi 10 besar.
“Ini merupakan hari yang sangat sulit, yang sangat membuat frustrasi,” kata Rossi di Crash.
“Saya berada dalam masalah pada kedua kondisi. Saya pikir situasi saya menjadi lebih buruk di saat lintasan basah. Di saat kering, saya tak begitu buruk terutama di ban medium –untuk balapan. Tapi, sialnya saya mendapatkan masalah teknis dengan motor yang menggunakan sasis baru, tapi saya berlanjut dengan yang lain.”
“Kecepatannya cukup bagus sampai 10 menit terakhir saat kami mencoba untuk memperbaiki waktu dan saya tak merasakan apapun dengan ban depan. Saya ada dalam banyak masalah, terlebih lagi pada ban hard. Ini sangat membuat frustrasi karena saya ingin berada di posisi 10 besar untuk melaju ke Q2.”
“Di saat lintasan basah, saya lebih optimistis karena tahun lalu saya cukup kuat, tapi dengan aspal yang baru kami mempunyai banyak masalah dan kami tak dalam kondisi bagus dengan keseimbangan motor dan saya selalu sangat lambat.”
“Kami mencoba untuk melakukan suatu hal selama latihan tapi memang tak ada perkembangan dan jarak dengan pebalap di depan sangat jauh dan juga posisinya sangat buruk. Jadi kami harus memperbaiki penampilan dalam kedua kondisi,” tambahnya.
(cas/raw)
NEW ORLEANS, LA — An analysis from the Bogalusa Heart Study suggests childhood asthma is independently associated with increased left ventricular (LV) mass in adulthood, a well-established predictor of major CV events and death[1].
“The most important implication of this finding is that prevention and treatment of asthma in the early stages of life is very important to reduce the risk of heart disease in adulthood; that is the take-home message,” senior author Dr Lu Qi (Tulane University, New Orleans, LA and Harvard University School of Public Health, Boston, MA) told theheart.org|Medscape Cardiology.
The study was published online June 26, 2017 in the JACC: Heart Failure.
In an accompanying editorial[2], Dr John Gottdiener (University of Maryland Medical Center, Baltimore) observed that the difference in LV mass index between adults with a history of childhood asthma and nonasthmatics was only about 8%.
“Although this difference would by itself confer a relatively small incremental risk of incident CVD (about 1.08-fold increase) based on Framingham Heart Study data, in large populations with major comorbidities, the public-health implications could be substantial,” he said.
The incidence of asthma in children has nearly doubled since 1980, and its prevalence is estimated at nearly one in 10 children and 7% in adults, Gottdiener noted.
Despite this, the investigators point out that the number of studies specifically examining the relationship between asthma and LV hypertrophy or heart failure (HF) can be counted on one hand. The team was interested in examining HF but because of too few cases in the Bogalusa Heart Study, LV mass was used as a surrogate marker, Qi said.
The analysis, led by Dr Dianjianyi Sun (Tulane University), included 1118 asymptomatic individuals, of whom 104 self-reported childhood asthma and 1014 did not. The mean age at baseline was 27.5 and 32 years, respectively. LV measurements were performed using 2-D echocardiography during follow-up only (mean 10.4 years).
Childhood asthmatics compared with nonasthmatics had a significantly higher body-mass index (BMI) at last follow-up (31.5 vs 29.9 kg/m2), although smoking rates were similar (27.9% vs 30.4%).
Participants with a history of asthma compared with those without had a higher mean LV mass (169.0 g vs 157.5 g; P=0.01) and LV mass index (41.1 g/m2.7 vs 37.9 g/m2.7; P<0.01), even after adjustment for age, sex, race, smoking status, antihypertensive medication use, and heart rate.
Notably, a 1-unit increase in high-sensitivity C-reactive protein (hs-CRP) was significantly associated with a 1.40 and 0.40 increase in LV mass and LV mass index, respectively.
In the final model, however, that further adjusted for BMI, systolic blood pressure (SBP), and CRP, the difference between those with and without childhood asthma persisted for LV mass index (38.4 g/m2.7 vs 36.6 g/m2.7; P=0.04) but not LV mass.
“Inflammation is the primary potential mechanism that links these two diseases, but even after we adjusted for CRP, an inflammatory marker, it didn’t completely eliminate the association, which suggests that other mechanisms could be involved,” Qi said.
In addition, the investigators observed a significant interaction between SBP and asthma on both LV outcomes in stratified analyses (P for interaction <0.01). The association was stronger among participants with prehypertension or hypertension (>130 mm Hg) than those with normal SBP (regression coefficient [ß]: 39.5 vs 2.2 for LV mass and 9.0 vs 0.9 for LV mass index).
“High blood pressure is a well-known risk factor for heart failure and high left ventricular mass, and our study suggests that asthma and high blood pressure may walk together to increase the risk of heart failure,” Qi said.
Gottdiener noted that “targeting individuals with asthma and hypertension or prehypertension for intensified risk reduction could have important benefits.”
Still, the study leaves several questions unanswered, he said. Because of the lack of baseline echocardiograms, it’s possible participants could have had increasing LV mass prior to asthma onset. The current data also do not “exclude the possibility that asthma is a comorbidity of CVD and perhaps is a fellow traveler with CVD severity rather than being a cause of CVD.”
Finally, it is unknown whether LV mass was associated with asthma severity and the frequency of corticosteroid or beta-agonist use, “important information for selecting individuals who are at the highest risk,” Gottdiener added.
The study was supported by grants from the National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, the Boston Obesity Nutrition Research Center, and United States-Israel Binational Science Foundation. Qi reports receiving the American Heart Association Scientist Development Award. The coauthors have no relevant financial relationships, nor does Gottdiener.
Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org, follow us on Twitter and Facebook.
As the US opioid epidemic continues to soar, physicians have been held criminally responsible for patients’ overdose deaths. Now, it appears pharmacists are also criminally liable.
That’s the opinion of pharmacy law experts who have watched the crisis unfold during the past decade.
Keith Yoshizuka, PharmD, JD, assistant dean for administration at the Touro University College of Pharmacy, Vallejo, California, notes, for example, that in 2015, a California physician, Lisa Tseng, MD, was convicted of second-degree murder for the overdose deaths of three patients. She was later sentenced to 30 years to life in prison.
“I don’t think it’s too large of a leap to expect a pharmacist to face criminal liability in the event that one or several of the patients overdose on medications that were filled by that pharmacy,” Dr Yoshizuka told Medscape Medical News. “I can see the district attorney going after that pharmacy or the pharmacist for second-degree murder for, basically, recklessness — criminal negligence. But demonstrating that liability is still not clear-cut,” he added.
[Pull quote: “I don’t think it’s too large of a leap to expect a pharmacist to face criminal liability in the event that one or several of the patients overdose on medications that were filled by that pharmacy.”]
I don’t think it’s too large of a leap to expect a pharmacist to face criminal liability in the event that one or several of the patients overdose on medications that were filled by that pharmacy.
Brian Gallagher, RPh, JD, associate professor at the Marshall University School of Pharmacy, Huntington, West Virginia, agreed.
“It’s not illegal to dispense a controlled substance to someone who is an addict who has legitimate pain,” Dr Gallagher told Medscape Medical News. “It’s a very, very gray area — it’s very subjective” for a pharmacist who is trying to decide whether a prescription should be dispensed, he said.
It’s not illegal to dispense a controlled substance to someone who is an addict who has legitimate pain. It’s a very, very gray area — it’s very subjective.
That’s true despite state and federal regulations that guide pharmacists in the dispensing of controlled substances. In 1971, the Drug Enforcement Administration (DEA) established the doctrine of corresponding responsibility, according to which a prescription for a controlled substance must be issued for a legitimate medical purpose by an individual practitioner acting in the usual course of his or her professional practice. The responsibility for the proper prescribing and dispensing of controlled substances falls upon the prescribing practitioner, and a corresponding responsibility rests with the pharmacist who fills the prescription.
The DEA has also warned pharmacists to address or resolve “red flags,” such as cash payments for controlled substances or patients who come to a pharmacy for a prescription but who live far away, before dispensing.
“Corresponding responsibility is perhaps one of the most commonly misunderstood and/or unknown concepts found in DEA’s regulations,” writes DEA compliance attorney Larry Cote in a 2013 blog post. “And yet, enforcement actions against pharmacies are most frequently initiated when a pharmacist fails to exercise his/her corresponding responsibility,” he adds.
And yet, enforcement actions against pharmacies are most frequently initiated when a pharmacist fails to exercise his/her corresponding responsibility.
Some pharmacists in California seem not to be heeding the call to mind their corresponding responsibility or do their best to address red flags. Or perhaps they are just too harried — or don’t have the right tools ― to weed out inappropriate or illegal prescriptions.
But judging by the rising number of investigations and disciplinary actions relating to controlled substances by the California Pharmacy Board, more often, pharmacists are paying the price in lost licenses, pharmacies, and careers.
The board fired a significant warning shot in 2013 when, after a long investigation that uncovered multiple failures to address red flags, it revoked the licenses of Pacifica Pharmacy and its pharmacist, Thang Q. Tran. An appeal was rejected.
The decision was considered precedential because it contained “a significant legal or policy determination of general application that is likely to recur,” according to the board.
Others, such as a long-time owner of a pharmacy in the Los Angeles area, believe the board is going too far. That pharmacist says he chose to give up his license — and sell his business ― rather than fight the board any further after an investigation that lasted a year. The inquiry started in 2011, when the family of a young man who died in 2010 of an opioid overdose initiated a complaint with the board.
The prescribing physician — who eventually became an addict — took his own life before a medical board investigation had been completed. The pharmacy board conducted an on-site inspection of the pharmacy in 2013, and in a subsequent report, said that between 2008 and 2010, the pharmacist had filled more than 4500 controlled substance prescriptions from the doctor but failed to call him to verify any of them. The report also cited numerous failures to address red flags, such as filling prescriptions too early and making unauthorized refills.
The pharmacy provided lengthy explanations to the board to justify its practices and hired an attorney to represent it and its pharmacists during conferences with the board and an administrative law judge.
The pharmacy also paid for a forensics expert, who provided the coroner’s records that showed that although the young man died from oxycodone intoxication, he had numerous other substances in his system, including MDMA (ecstasy) and metabolites of marijuana.
The pharmacist lost the case and chose not to spend more money on an appeal. The store paid a $35,000 fine, and the pharmacist paid a $7500 fine. Liability insurance covered some of the attorney’s fees, but nothing else.
In another recent case, two Santa Barbara pharmacists agreed to surrender their licenses and pay a $15,000 fee to cover the costs of a board investigation that determined that they had ignored red flags with patients who had received prescriptions for controlled substances from a local physician who had come to be known as the “Candyman.” The doctor, Julio Diaz, MD, was convicted in 2015 of 79 felony counts and received 27 years in federal prison.
The California Board of Pharmacy expects pharmacists to “use their judgment,” said Virginia Herold, executive officer of the board. For every prescription, “they are to evaluate and make sure it is the right drug for the patient,” she told Medscape Medical News.
Errors are not unexpected, and “unless it is a grossly negligent error, we will cite and fine,” she said.
Errors are not unexpected, and unless it is a grossly negligent error, we will cite and fine.
The number of investigations “has gone up over time,” said Herold. She attributed it in part to the board’s broadening responsibilities — the board regulates 33 types of licenses covering 45,000 pharmacists, more than 72,000 pharmacy technicians, more than 6800 intern pharmacists, and more than 3000 designated representatives.
The board has 49 investigators — up from 15 about 2 decades ago.
Dr Yoshizuka, who has consulted for the board, said that it is conservative in choosing investigations. “They won’t pursue something unless they are pretty sure they are going to win,” he said. “In order for them to get to a point where they are actually suspending or revoking someone’s license, there has to be a lot of evidence.”
As a consumer advocate who has worked for the board for almost 3 decades, Herold sees her agency’s mandate as primarily focused on consumer protection. That is accomplished through enforcement of corresponding responsibility, she said.
A family whose loved one has suffered because of a prescription overdose or error “would want us to discipline that pharmacist that committed that error,” said Herold.
Pharmacists also have been under growing scrutiny in West Virginia, a state that has been among the hardest hit by the opioid epidemic. The liability pendulum swung against the state’s physicians and pharmacists in 2015, but it has recently taken a swing back toward the middle.
That year, West Virginia had the highest rate of drug overdose death in the United States, at 41.5 per 100,000, according to the Centers for Disease Control and Prevention.
The same year, the state’s Supreme Court ruled that substance abusers could sue prescribers and pharmacists who supplied medications ― even if the patients acknowledged engaging in illegal activities, such as misleading doctors and pharmacists, engaging in doctor shopping, and ingesting the medications in amounts greater than prescribed, said Dr Gallagher.
Fearing a tide of suits, the state legislature soon came up with a response, introducing and passing a bill prohibiting anyone engaged in illegal activities from suing doctors or pharmacists. The bill was approved by the governor in early 2016.
West Virginia has tried to provide some support for pharmacists through another recently approved bill that was signed by Governor Jim Justice on April 26. Marshall University had a hand in crafting the legislation, said Dr Gallagher, who in addition to his pharmacy experience previously served 8 years in the state legislature.
For instance, Senate Bill 333 requires that overdoses — not just overdose deaths — be reported to the prescription drug monitoring program (PDMP). Emergency department visits for overdoses “are a much bigger and better indicator that this person has a substance abuse problem,” said Dr Gallagher. Pharmacists can check the PDMP, which means “they’ll have a real idea, rather than just red flags,” said Dr Gallagher.
The law also gives the Board of Pharmacy the authority to require designated “drugs of concern” to be reported to the PDMP.
Any time a controlled substance is prescribed or dispensed, the physician or pharmacist must record a long list of items of information, including who picked up the prescription and whether it was paid for in cash or by other means. If a prescriber dispenses a controlled substance directly to a patient, it can only be enough to cover 72 hours of treatment. The Board of Pharmacy will enact rules to determine where the reporting will occur.
The West Virginia Board of Medicine will also now be required to report more quickly and publicly on disciplinary actions.
Pharmacists are still vulnerable, said Dr Gallagher, adding that malpractice insurance won’t likely cover litigation costs if an opioid or other controlled substance was illegally dispensed.
The first line of protection is to ask questions. Although it may be hard to deny a patient a prescription — especially if it’s a first visit — a pattern of ignoring red flags will attract scrutiny,
The first line of protection is to ask questions, said Dr Yoshizuka. Although it may be hard to deny a patient a prescription — especially if it’s a first visit — a pattern of ignoring red flags will attract scrutiny, he said.
Asking questions and checking PDMPs are time-consuming tasks. But Dr Gallagher noted that “a lot of pharmacies get themselves into trouble because they say, ‘I don’t have time to do all of this.’ “
Not knowing how to spot red flags means getting more training, Dr Gallagher and Dr Yoshizuka agreed. “Everyone has a responsibility in trying to end this,” said Dr Gallagher, adding, “You shouldn’t have a pharmacy license if you don’t know there’s an opioid epidemic.”
And the fight to end the epidemic is a major battle, with many casualties, including people who legitimately need pain medications, as well as physicians and pharmacists who aren’t sure of, or ignore, their corresponding responsibility.
“It’s unfortunate, but people everywhere are getting hit by the shrapnel of this,” said Dr Gallagher.
Dr Yoshizuka has consulted for the California Board of Pharmacy and has been an expert witness for the Drug Enforcement Administration. Dr Gallagher has disclosed no relevant financial relationships.
Source by [author_name]
PHILADELPHIA — The primary care doctor of nursing practice (DNP) program at Johns Hopkins University is being revamped to integrate clinical practice experience into the curriculum with a view to improve learning, ease the burden on preceptors, and better prepare students for the workforce.
With clinical experience incorporated throughout the course of study, “students have time to process what they’re learning. They have more time to learn more theory to apply and refine their experience,” said JoAnne Silbert-Flagg, DNP, assistant professor and clinical coordinator of the MSN program at Johns Hopkins in Baltimore.
When all the clinical experience is gained at the beginning of the program, students can “lose their skills if they don’t have to apply them over the next 2 years,” she explained.
The revamped approach will start this fall.
All nurse practitioners must complete a master’s or doctoral degree and advanced clinical training, but the way that training is timed and administered varies widely among programs. And practitioners and educators generally agree that the 500-hour requirement for precepted clinical practice is not enough.
Dr Silbert-Flagg and her colleagues formed a task force to develop a postbaccalaureate DNP curriculum and conducted a market analysis of other academic nurse practitioner programs and healthcare organizations.
Clinical Practicums
The revamped DNP curriculum distributes precepted clinical practicums over five semesters instead of the more typical two or three semesters, Dr Silbert-Flagg reported during a poster session here at the American Association of Nurse Practitioners 2017 National Conference.
The clinical experience begins with a second-semester health assessment, which is followed by a competency-based simulation course that applies the tenets of health assessment. The remaining clinical hours include 1 day a week of precepted clinical practice in semesters four, five, and six, increasing in intensity and complexity to 2 days a week in semesters seven and eight.
At other universities, clinical practicums are “either front-loaded or back-loaded,” she explained. “We didn’t find another program that resembles what we did.”
There are some gaps before students graduate, so I like how this approach allocates clinical hours throughout the entire program.
In addition to giving students time to process information, the new approach also greatly eases the burden on preceptors — who are often in demand — and better accommodates the outside work commitments of students.
“It’s very challenging for every school to get preceptors to work one-on-one with students,” she said. “There are a lot of clinical sites to find and clinical hours needed. If we spread them out, it’s easier to find a site.”
The curriculum redesign also offers students more time to explore specialties, which could make them more marketable after graduation and could benefit patients.
Dr Silbert-Flagg’s poster received a steady stream of attention from conference attendees.
This approach reminds Barbara Siebert, DNP, director of student health services at University of the Sciences in Philadelphia, of the way her own nurse practitioner curriculum was designed in the 1980s.
“The challenge is preparing someone to be a nurse practitioner in 3 years, as well as give them all the research courses for the DNP,” she told Medscape Medical News.
With this new approach, it appears that all the research courses and clinical practice can be integrated “in 2 full years plus two more semesters in the third year. We have come full circle,” Dr Siebert said.
“We struggle with DNP students and their clinical experience,” Susan Copp, EdD, a clinical instructor at the University of Illinois College of Nursing in Peoria.
“There are some gaps before students graduate, so I like how this approach allocates clinical hours throughout the entire program,” Dr Copp told Medscape Medical News. “This makes it more doable and relevant to students.”
Dr Silbert-Flagg, Dr Siebert, and Dr Copp have disclosed no relevant financial relationships.
American Association of Nurse Practitioners (AANP) 2017 National Conference. Presented June 24, 2017.
Follow Medscape Nurses on Twitter @MedscapeNurses and Maureen Salamon @maureensalamon
Higher levels of retinal carotenoids are associated with superior academic achievement and increased efficiency in performing cognitive tasks, new research shows.
A team of investigators led by Naiman Khan, PhD, RD, professor of kinesiology and community health, together with Anne Walk, PhD, postdoctoral scholar, both of the University of Illinois at Urbana-Champaign, conducted two studies that used macular pigment optical density (MPOD) to measure concentrations of lutein and zeaxanthin, both of which are retinal carotenoids in the eyes.
In one study, researchers measured MPOD in 56 children (aged 8 to 9 years), assessed their academic performance, and measured their 3-day dietary intake of lutein and zeaxanthin.
They found that retinal lutein and zeaxanthin are positively related to academic achievement in children, even when controlling for other factors, such as aerobic fitness, body composition, and intelligence quotient (IQ).
Another study investigated the relationship between MPOD and performance on a challenging cognitive task in 49 children (aged 8 to 10 years).
The researchers found that children with higher MPOD responded to cognitive tasks more efficiently, especially in tasks requiring attention control. The finding provides “novel support” for the neuroprotective influence of retinal carotenoids during preadolescence.
“Lutein is known to accumulate in the retina and several other regions of the brain and has been shown to protect against eye disease and preserve cognitive function in older adults. These studies are important because they demonstrate that the beneficial influence of lutein on cognition is evident in childhood,” Dr Khan told Medscape Medical News.
“We also know that these pigments are found in high quantities in the infant brain. That suggests that they are important in some way for brain development,” Dr Walk said in a release.
The first study was published online May 23 in Nutritional Neuroscience. The second study was published in the August issue of the International Journal of Psychophysiology.
In both studies, the investigators note that previous research has demonstrated the potential role of lutein and zeaxanthin in combating cognitive decline in the elderly. However, much less is known about the potential cognitive-enhancing or neuroprotective effects of these carotenoids in children.
Prior studies have shown that both lutein and zeaxanthin are found in the infant brain, with a preferential accumulation of lutein. In fact, “the relative contribution of lutein to the total carotenoids found in infant brains is almost two-fold greater than in adults, accounting for 59% vs 34% respectively, suggesting a selective role of lutein in early neural development.”
To investigate the potential impact of retinal carotenoids on cognition in children, the researchers in both studies drew participants from FITKids, an ongoing large, longitudinal, randomized controlled trial of an intervention involving physical activity in children.
Both studies measured MPOD because it is indicator of retinal xanthophylls, it is a correlate of brain lutein level, and it is a “good proxy” for the amount of lutein and zeaxanthin in the brain. Moreover, assessment of MPOD is noninvasive.
Dr Khan’s team evaluated participants (n = 49) on 2 days. On the first day, the children were asked to complete the Woodcock Johnson Tests of Cognitive Abilities to provide an estimate of IQ and were administered the Kaufman test of Academic and Educational Achievement II (KTEA II) to assess scholastic achievement.
The height and weight of the children were measured, and a maximal oxygen consumption (VO2max) test was used to assess aerobic fitness. Legal guardians provided information regarding the children’s demographics, health history, and pubertal timing.
After the first visit, the children were given forms on which to record at home the food they consumed during a period of 3 days.
At the second visit, the children completed an assessment of body composition via dual-energy X-ray absorptiometry. At both visits, MPOD was assessed. The researchers averaged the two MPOD values and utilized stepwise hierarchical regression models to determine the relationship between the averaged MPOD and academic achievement tests, following adjustments of the key covariates (eg, sex, aerobic fitness, body composition, and IQ).
The researchers found a positive correlation between the dietary intake of lutein and zeaxanthin and MPOD (r = 0.39; P = 0.02).
On bivariate correlation analysis, IQ, VO2max, and fat-free mass VO2max positively correlated with the achievement composite score (r = 0.62, P < .01; r = 0.33, P = .01; and r = 0.26, P = .05, respectively).
BMI and whole-body percent fat were negatively correlated with the achievement composite score (r = − 0.37, P < .01; and r = − 0.30, P = .03, respectively).
The regression analyses found that MPOD improved the model for overall academic achievement (ΔR2 = 0.10, P < .01), mathematics (ΔR2 = 0.07, P = .02), and written language composite standard scores (ΔR2 = 0.15, P < .01), even beyond the covariates.
“The major finding was that children with higher MPOD values have superior performance on academic measures, particularly in math and written language,” the researchers write.
The findings highlight “the importance of habitual intake” of lutein and zeaxanthin for improved academic performance, they add.
“These findings were not surprising to us,” said Dr Khan. “We had hypothesized a positive relationship between lutein in the eye and children’s cognitive function and academic abilities.”
Dr Walk’s team examined children’s cognitive performance (response accuracy and reaction time) by using a modified version of the Eriksen Flanker Task, a cognitively challenging activity in which participants respond to the directionality of a centrally located image of a target fish that is presented amid several images of task-irrelevant distractor fish that are either congruent (facing the same direction) or incongruent (facing the opposite direction).
The researchers recorded the children’s electroencephalographic (EEG) activity during the task — in particular, the P3 component of the event-related potential (ERP) waveform.
Participants underwent two testing sessions. During the first, legal guardians completed a questionnaire about demographic and health information. During the second, participants completed the EEG-recorded cognitive tasks. MPOD was assessed at both sessions, and the values were averaged.
When bivariate correlational analyses were performed, the researchers found that flanker response accuracy was significantly related to MPOD values for incongruent trials but was only moderately related for congruent trials (r = .341, P = 0.017, confidence interval [CI] = .124, .542; and r = .243, P = 0.093, CI = .024, .454, respectively).
MPOD was not related to mean reaction time (r ≤ 106, P ≥ .235). The confidence intervals for the significant and moderate correlations did not span 0, “suggesting reliable moderate correlations,” the researchers write.
“These results indicate that children with higher MPOD values were more likely to exhibit high performance on the flanker task and that this was particularly evident when greater levels of attentional control were demanded,” they write. However, higher MPOD values did not increase the speed of performing the task.
“The hypothesis that MPOD values would be positively related to flanker task performance was supported. Thus, the beneficial effects of retinal carotenoids appear to have global benefits in cognitive control processing, though the greatest benefit is observed when cognitive control demands are higher,” the authors write.
The investigators add that these data did not show a significant relationship between MPOD and reaction time, “indicating that the benefits of lutein on cognitive control have a preferential effect of accuracy as opposed to processing speed in children.”
Discussing these findings, Dr Khan suggested that “a potential mechanism of the neurocognitive benefits of lutein and zeaxanthin may be the antioxidant effects of lutein, which may extend beyond the eye and protect brain tissue as well.
“It is also possible that lutein facilitates the neuroprotective effects of other nutrients thought to be beneficial to cognitive function and brain health, such as docosahexaenoic acid.” However, he cautioned, “additional research is needed to determine the exact mechanism by which lutein impacts the brain and cognitive function.”
Commenting on the studies for Medscape Medical News, Elizabeth Johnson, PhD, of the Jean Mayer USDA Human Nutrition Center on Aging, Tufts University, Boston, Massachusetts, said the studies “are consistent with what we know about lutein and zeaxanthin from intervention studies in adults, which is that when you increase these dietary components, you improve cognitive function.”
She cautioned that the “findings can only demonstrate association rather than cause and effect.”
Nevertheless, the studies are valuable and “of particular interest because lutein and zeaxanthin are not considered ‘essential’ nutrients,” so “there are no policies requiring that school lunch programs must contain a certain amount of them.”
However, “although these are not ‘essential,’ they are beneficial, so it is important to look at phytonutrients in plants, fruits, vegetables, and nuts and advise people what their targets should be to ensure optimal health.”
She advised psychiatrists to inquire about the nutrition of their patients. “If a person is eating to improve brain function, it will also help overall health because it is the same diet — fruits, vegetables, low fat, good fat, the appropriate number of calories, and exercise ― which is good for the brain and everything below the brain as well.”
Dr Khan added that “encouraging children to eat more foods rich in lutein, like leafy greens and fruits, might improve the cognitive status of children, and certainly will not hurt.”
This research is part of a larger randomized controlled trial supported by the National Institutes of Health and Abbott Nutrition via a Center for Nutrition, Learning, and Memory grant to the University of Illinois. Dr Khan and Dr Walk have disclosed no relevant financial relationships.
Nutr Neurosci. Published online May 23, 2017. Abstract
Int J Psychophysiol. 2017;118:1-8. Abstract
Pada latihan kali ini, Sirkuit Sachsenring diguyur hujan. Barbera mengemas waktu 1 menit 28,115 detik, lebih cepat 0,063 detik dari Marquez dan 0,353 detik dari Pedrosa.
Aleix Espargaro memperlihatkan indikasi positif dengan tetap di lima besar, dengan finis di belakang Danilo Petrucci yang menduduki peringkat keempat.
Penguasa sesi pertama, Andrea Dovizioso, harus puas berada di posisi ketujuh dengan jarak 0,6 detik dari Barbera. Sedangkan rekan setimnya Jorge Lorenzo menembus 10 besar.
Hasil kurang oke mesti diterima Yamaha. Valentino Rossi menyudahi sesi di posisi ke-15 dengan waktu 1 menit 29,549 detik sementara Maverick Vinales justru terpuruk di urutan 20.
Hasil Free Practice II MotoGP Jerman
Pos-Pebalap-Tim-Waktu-Gap
1. Hector Barbera ESP Reale Avintia Racing (Desmosedici GP16) 1m 28.115s
2. Marc Marquez ESP Repsol Honda Team (RC213V) 1m 28.178s +0.063s
3. Dani Pedrosa ESP Repsol Honda Team (RC213V) 1m 28.468s +0.353s
4. Danilo Petrucci ITA Octo Pramac Racing (Desmosedici GP17) 1m 28.468s +0.353s
5. Aleix Espargaro ESP Factory Aprilia Gresini (RS-GP) 1m 28.527s +0.412s
6. Cal Crutchlow GBR LCR Honda (RC213V) 1m 28.616s +0.501s
7. Andrea Dovizioso ITA Ducati Team (Desmosedici GP17) 1m 28.753s +0.638s
8. Jonas Folger GER Monster Yamaha Tech 3 (YZR-M1)* 1m 28.988s +0.873s
9. Sam Lowes GBR Factory Aprilia Gresini (RS-GP)* 1m 28.994s +0.879s
10. Jorge Lorenzo ESP Ducati Team (Desmosedici GP17) 1m 29.017s +0.902s
11. Alvaro Bautista ESP Pull&Bear Aspar Team (Desmosedici GP16) 1m 29.076s +0.961s
12. Pol Espargaro ESP Red Bull KTM Factory Racing (RC16) 1m 29.321s +1.206s
13. Loris Baz FRA Reale Avintia Racing (Desmosedici GP15) 1m 29.364s +1.249s
14. Mika Kallio FIN Red Bull KTM Factory Racing (RC16) 1m 29.446s +1.331s
15. Valentino Rossi ITA Movistar Yamaha MotoGP (YZR-M1) 1m 29.549s +1.434s
16. Jack Miller AUS Estrella Galicia 0,0 Marc VDS (RC213V) 1m 29.586s +1.471s
17. Karel Abraham CZE Pull&Bear Aspar Team (Desmosedici GP15) 1m 29.774s +1.659s
18. Johann Zarco FRA Monster Yamaha Tech 3 (YZR-M1)* 1m 29.927s +1.812s
19. Bradley Smith GBR Red Bull KTM Factory Racing (RC16) 1m 29.972s +1.857s
20. Maverick Viñales ESP Movistar Yamaha MotoGP (YZR-M1) 1m 30.017s +1.902s
21. Scott Redding GBR Octo Pramac Racing (Desmosedici GP16) 1m 30.017s +1.902s
22. Alex Rins ESP Team Suzuki Ecstar (GSX-RR)* 1m 30.342s +2.227s
23. Tito Rabat ESP Estrella Galicia 0,0 Marc VDS (RC213V) 1m 30.508s +2.393s
24. Andrea Iannone ITA Team Suzuki Ecstar (GSX-RR) 1m 30.559s +2.444s
(rin/rin)
BARCELONA, Spain — Treating locally advanced hepatocellular carcinoma (HCC) with radioembolization results in better tumor responses and quality of life than the current standard of care, sorafenib (Nexavar, Bayer), although survival is similar, conclude French researchers.
The results come from a phase 3 study of radioembolization with selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres, known as the SARAH trial, which compared this therapy with the multikinase inhibitor sorafenib.
Presenting the data here at the 19th World Congress on Gastrointestinal Cancer (WCGC), the French team noted that the overall or progression-free survival was similar in both groups of patients.
However, the group treated with SIRT, which included patients for whom transarterial chemoembolization (TACE) had failed, showed significant improvements in tumor responses and quality of life over the course of follow-up, with significantly fewer adverse events.
Although acknowledging that SIRT did not improve overall survival, presenter Mohamed Bouattour, MD, Service Inter-Hospitalier de Cancérologie, Hôpital Beaujon, Paris, France, said: “We can see that SIRT offers a higher tumor response, a better tolerance, with less treatment-related effects and better quality of life over the time than sorafenib.”
“Of course, future analyses will evaluate prognostic factors, cost-effectiveness, and dose-released efficacy in the SIRT group,” he added
Dr Bouattour began his presentation by pointing out that the choice of treatment for HCC depends on the size and extension of the tumor and the severity of liver disease. Sorafenib is the current reference treatment for advanced HCC, and TACE is the standard of care for intermediate disease.
The current SARAH study was conducted in patients with either locally advanced or inoperable HCC after treatment with TACE had failed. The participants were randomly assigned to receive either SIRT or sorafenib.
After assessing 496 patients for eligibility, 467 were included in the trial. There were 237 SIRT patients and 222 sorafenib patients in the intention-to-treat population, 226 and 216 patients, respectively, in the safety population, and 174 and 206 patients, respectively, in the per protocol population.
There were no significant differences in baseline characteristics between the SIRT and sorafenib populations: the mean age was 65 years, the majority of patients (90%) were male, and more than 60% of patients had an ECOG performance status of 0.
The median treatment dose in the sorafenib arm was 800 mg. The median cumulative period of intake was 2.8 months. The permanent discontinuance rate was 61.1%.
The researchers found that the median overall survival in the intention-to-treat population was 8.0 months with SIRT vs 9.9 months in the sorafenib arm, with no significant difference between the two groups (P = .18). There was no difference in overall survival in the per protocol group, at 9.9 months in both groups.
Dr Bouattour also reported that overall survival was unaffected when patients were stratified by age, sex, disease severity, tumor characteristics, and laboratory examination results.
He said there was no significant difference in progression-free survival between the SIRT and sorafenib arms in both the intention-to-treat and per protocol populations.
However, there was significantly less radiologic progression with SIRT vs sorafenib when the liver as the first site (P = .014), although no significant differences were seen for progression outside the liver.
SIRT was also associated with a significantly objective response, defined as complete responses plus partial responses, compared with sorafenib, at 19.0% vs 15.2% (P = .042).
The team found that, compared with sorafenib, SIRT was associated with significantly fewer adverse events of any grade (P < .001) and adverse events of grade ≥3 (P < .001), as well as in the proportion of patients with ≥1 adverse events of any grade (P < .001) and adverse events of grade ≥3 (P < .001).
The median number of adverse events per patient of any grade was also significantly lower with SIRT vs sorafenib (P < .001).
Specifically, SIRT was associated with significantly lower rates of adverse events of any grade in terms of fatigue, weight loss, hand and foot skin reactions, anorexia, diarrhea, nausea/vomiting, abdominal pain, and hypertension.
Grade ≥3 event rates were significantly lower with SIRT vs sorafenib for fatigue, weight loss, hand and foot skin reactions, diarrhea, abdominal pain, and hypertension.
Quality of life, as measured using the EORTC QLQ-C30 questionnaire Global Health Status subscore, was significantly better in the SIRT group (group-time interaction P = .45), although only a total of 65 questionnaires were completed at the 12-month assessment compared with 355 at baseline.
Discussing the findings, Michel Ducreux, MD, PhD, of Institut Gustave Roussy, Villejuif, France, said that the question remains: “Is it better to do radioembolization, or is it better to do sorafenib?”
Praising the design and execution of the SARAH study, he said that the results can be put into perspective by considering another recently reported study, the phase 2 SIRveNIB trial, which was presented at the most recent annual meeting of the American Society of Clinical Oncology, held in June 2017.
Although SIRveNIB included fewer patients than the current study, it reached the same conclusion, which was that there was no significant difference in overall survival between radioembolization and sorafenib therapy in locally advanced HCC.
The earlier trial did show some improvements in progression-free survival, but only in treated patients, and the difference was not statistically significant. Radioembolization was, again, better tolerated than sorafenib, with significantly fewer adverse events of any grade and adverse events of grade ≥3.
Dr Ducreux continued: “If we put together these two trials, this is a little bit disappointing, because we can say that radioembolization did not show any advantage in terms of overall survival when compared to sorafenib, and we can say that sorafenib remains the standard of care.
“But we are quite consistent in the fact that this treatment has a very good tolerance and that it is able to induce a better response and better liver disease control, and maybe this is something that we could use for new hypotheses and to build up trials in specific subgroups of populations.”
Consequently, Dr Ducreux argued, radioembolization is not finished as a treatment in this population and “could be there in between TACE and sorafenib, and that we can create a specific subpopulation for this treatment.”
“Why should I have this tool in my box?” he asked, referring to SIRT. “Because it’s completely different from sorafenib,” he commented, although questions remain as to the use of radioembolization.
“The first one is clearly cost-effectiveness. If radioembolization is less expensive than sorafinib, that is something that could be useful to continue to work on this type of treatment. At this time, we do not know exactly,” he said.
Referring to the different lengths of time in treatment between SIRT and sorafinib, Dr Ducreux added: “The choice of the patients could be interesting too, if we consider that the level of activity is exactly the same.
“So, I would ask my patient: Do you prefer a kick in the back to treat your disease, or do prefer continuous pressure with drugs that are a completely different way to work your disease?”
With respect to sequencing, he said, “We may imagine that this is a neutral, so we can do radioembolization and then maybe if it does not work, we could propose to patients that they then take sorafinib.
“But, in fact, when we look at the literature, we can see that there are only a few patients who are able to receive sorafinib after failure of radioembolization…. So the idea that you can give one and the second one after is an idea that doesn’t work very well.”
Dr Ducreux concluded by saying that, at this time, TACE “remains the gold standard, but clearly, radioembolization has excellent tolerance, with convincing new data,” although a number of potential issues need to be examined further.
The study was funded by Sirtex Medical Ltd. Dr Bouattour has received speaker fees from Bayer and Sirtex Medical and is a member of the advisory boards for Bayer and Bristol-Myers Squibb. No other relevant financial relationships have been disclosed.
19th World Congress on Gastrointestinal Cancer (WCGC). Abstract LBA-001, presented 29 June 29, 2017.
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DETIKSPORT | Sabtu 24 Juni 2017, 01:10 WIB
Rider Yamaha, Maverick Vinales, puas dengan penampilan motornya di hari pertama latihan bebas MotoGP Belanda. Tapi, dia merasa masih perlu ada peningkatan.
A new position paper on the use of hormone replacement therapy (HRT) for menopausal and postmenopausal women has now been released by the North American Menopause Society (NAMS) and guarantees to make healthcare providers and the women they treat more comfortable using HRT when women want it to improve their quality of life.
“There continues to be confusion and fear for both women and their healthcare providers about the use of hormone therapy for menopausal women,” JoAnn Pinkerton, MD, executive director of NAMS and professor of obstetrics and gynecology, University of Virginia Health System in Charlottesville, told Medscape Medial News in an email.
“NAMS’s goal with this new position statement on hormone therapy is to give women and providers confidence about using hormone therapy for symptomatic menopausal women when it is indicated,” she added.
The new position statement was published online June 21 in Menopause.
NAMS hinted at what would be in its updated position statement on HRT use during its annual meeting in 2016, as reported by Medscape Medical News, with the focus being on the fact that HRT has more benefits than it does risks for healthy women under the age of 60 who are within 10 years of menopause.
“The concept of ‘lowest dose for the shortest period of time’ may be inadequate or even harmful for some women,” the statement authors affirm.
“A more fitting concept is ‘appropriate dose, duration, regimen, and route of administration,’ ” they add.
The Food and Drug Administration (FDA) has approved hormone therapy for four indications: bothersome vasomotor symptoms (VMS); prevention of bone loss; estrogen deficiency caused by hypogonadism, castration, or premature ovarian insufficiency (POI); and genitourinary symptoms.
For vasomotor symptoms or hot flashes, conjugated equine estrogen (CEE) alone may be offered to women provided they have had a hysterectomy. For women with an intact uterus, CEE must be combined either with a progestogen or with bazedoxifene, a selective estrogen-receptor modulator (SERM), to protect users against endometrial cancer.
Alternatively, studies indicate that micronized progesterone at a dose of 300 mg a night significantly reduces hot flashes and night sweats and improves sleep, the NAMS statement authors indicate.
For vaginal symptoms (vulvovaginal atrophy [VVA]), the writing group recommends low-dose, intravaginal estrogen preparations that have minimal systemic absorption. (These same preparations may be considered in women with a history of breast cancer in consultation with their oncologist).
Women with VVA who do not wish to or who cannot take estrogen preparations may be counseled to try over-the-counter ospemifene or intravaginal DHEA.
And “systemic HRT does not improve urinary incontinence and may increase the incidence of stress urinary incontinence,” the NAMS authors caution.
On the other hand, low-dose vaginal preparations of estrogen may alleviate urinary systems as well as sexual-function difficulties in women with symptomatic VVA.
HRT cannot be expected to improve sexual function or arousa,l but if a woman expresses concerns about sexual function or libido, transdermal estrogen may be the route to go, as it has less of an effect on testosterone levels than systemic estrogen. Testosterone is critical to the preservation of libido.
Women who enter early menopause naturally, surgically, or because of POI are all at high risk for estrogen-deficiency–related consequences and should be considered early on for treatment with estrogen, plus some form of endometrial protection for women with an intact uterus.
“For women with hypoestrogenism, POI, or early menopause —whether natural, surgical, or induced — HRT is recommended until at least the median age of menopause at 52 years,” Dr Pinkerton noted.
As for women who carry the BRCA 1/2 mutation, both of which place them at very high risk for breast and ovarian cancer, Dr Pinkerton pointed out that observational studies suggest that hormone therapy does not alter the risk for breast cancer further in women with a family history of it, although family history must be assessed when counseling women about HRT.
“For BRCA-positive women without breast cancer who have undergone risk-reducing bilateral salpingoophorectomy, observational data suggest that systemic HRT to the median age of menopause may decrease health risks associated with premature loss of estrogen without increasing breast-cancer risk,” she said.
“But more data are needed in this group,” Dr Pinkerton acknowledged.
Finally, the NAMS authors caution that when HRT is initiated in women who are 10 or more years out from the menopause or when they are 60 years of age or older, the benefit/risk ratio of HRT is less favorable than it is for younger women.
As such, initiation of treatment in this older age group must be approached with clear caution, although a discussion about the benefits and risks of HRT in older women may be considered for women who choose to initiate or restart HRT.
As the NAMS authors note, once women discontinue HRT, there is about a 50% chance that vasomotor symptoms will return, regardless of their age or how long they’ve been using it.
Thus, extended use of HRT may be expected to continue to relieve persistent VMS, they note.
“With discontinuation of HRT, virtually all women will lose [bone-mineral density], with increased risk of bone fractures and excess mortality from hip fracture,” they also point out.
Moreover, there is no evidence to support routine discontinuation of HRT after the age of 65, as Dr Pinkerton stressed.
“Decisions about longer duration of therapy should be individualized and considered for indications such as persistent vasomotor symptoms or bone loss, with shared decision-making, documentation, and periodic reevaluation,” she emphasized.
“And the risks of longer use of HRT may be minimized with the use of lower doses of both estrogen and progestogens, the use of transdermal therapies to avoid hepatic first-pass effect, or the combination of conjugated estrogen paired with the SERM bazedoxifene, which provides endometrial protection without the need for a progestogen,” she added.
That said, the NAMS authors point out that estrogen alone has a more favorable safety profile than estrogen plus progestogen and as such may be the more appropriate choice for longer duration of therapy.
Dr Pinkerton reports serving as a consultant for Pfizer, with the fee paid to her institution, as well as an investigator for TherapeuticsMD, with fee similarly paid to her institution. Disclosures for the advisory board and coauthors are listed in the paper.
Menopause. Published online June 21, 2017. Abstract
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