bluuebunny/crossref_metadata_2025 huggingface dataset:
PP095 Assessment Of Magmaris Resorbable Metal Stent In Patients With Angina
Authors: Sanchez-Gomex Luis Maria , Orrego Juan Pablo Chalco , Luengo-Matos Setefilla , Polo-Desantos Mar
Published: January 2018

INTRODUCTION:

Ischaemic heart disease is the leading cause of death worldwide. Magmaris™ is a new drug-eluting resorbable stent used for coronary reperfusion during a balloon angioplasty. Magmaris™ is composed of absorbable magnesium scaffold and its surface is coated with bioresorbable poly-L-lactide, which incorporates Sirolimus. Magmaris™ has theoretical advantages as the stent body disappears after vascular constrictive remodeling. It would provide the stability and elasticity of non-resorbable metal stents, but without long-term problems such as endothelial dysfunction, delay in endothelialization, risk of thrombosis and complications due to long-term antiplatelet medication. The objective of this work is to assess efficacy and safety of Magmaris ™ in patients with angina or silent ischaemia.

METHODS:

Early assessment of Magmaris™ identified through the Early-Awareness and Alert-System, “SINTESIS-new technologies”, of The Instituto De Salud Carlos III (AETS-ISCIII). The searched databases were: MEDLINE (PubMed), EMBASE, WOS, Clinical Trials and Cochrane Library. Clinical studies using Magmaris™ published in any language until December 2016 were reviewed.

RESULTS:

One prospective, non-randomized, non-controlled, multicenter, clinical trial with two publications was retrieved. The first publication (123 patients) showed mainly imaging outcomes of angiography, intravascular ultrasound and tomography at 6 months of follow up. The second publication (118 patients) with data from 12 months of follow up also reported: Target lesion failure in four patients (3.4 percent; 95 percent Confidence Interval, CI:0.9–8.4); one target-vessel myocardial infarction (0.8 percent; one myocardial infarction (0.8 percent); two clinically driven target lesion revascularisation (1.7 percent) and two clinically driven target-vessel revascularisation (1.7 percent). No definite scaffold thrombosis was observed. No procedural complications were reported. This trial is expected to continue up to 36 months of follow up.

CONCLUSIONS:

Clinical data show that Magmaris™ seems to be an effective and safe treatment in patients with angina or silent ischaemia undergoing balloon angioplasty. More research specially randomized controlled trials are necessary to confirm these results.
PP113 High-Sensitivity C-Reactive Protein (hsCRP) Measurements And Burden In Patients With History Of Myocardial Infarction
Authors: Deschaseaux Celine , Agrawal Rumjhum , Gabrielsen Anders , Jindal Ramandeep
Published: January 2018

INTRODUCTION:

The inflammatory marker C-reactive protein (CRP) can be measured by a high-sensitivity assay (hsCRP) specific to vascular inflammation. We aimed to identify published literature on prevalence of elevated hsCRP and associated clinical, economic, and humanistic burden in patients with a history of myocardial infarction (MI).

METHODS:

A comprehensive literature search was performed for publications in English between January 2000 and February 2016 in MEDLINE, EMBASE, and MEDLINE In-Process. Search terms were variations on ‘Post myocardial infarction’, ‘CRP’, ‘epidemiology’ and ‘burden’. Clinical and real-world studies reporting baseline CRP levels in patients with a history of MI were included in the analysis.

RESULTS:

Ten studies (prevalence: two; burden: two; both: six) were included. Cut-off points in hsCRP assays varied from >2 mg/L to ≥5.9 mg/L. Prevalence of hsCRP levels >2, >2.3, ≥2.37 and ≥2.9 mg/L were reported in 36 percent, 49 percent, 50 percent and 33 percent of patients, respectively (one publication each). Two publications reported >3 mg/L levels in 27.6 percent and 53.7 percent of patients. Levels of ≥3.3, ≥3.8, ≥4.2 and ≥5.9 mg/L were found in 38.8 percent, 25 percent, 25 percent and 24.7 percent respectively (one publication each). Of six studies reported CV events, four studies found elevated hsCRP levels to be predictive of future risk. Elevated hsCRP levels independently predicted all-cause mortality in four studies and CV mortality in three studies. Three publications included data on comorbidities: Diabetes was associated with elevated hsCRP in two of three analyses; hypertension in one out of two. No consistent associations between elevated hsCRP levels and hyperlipidaemia (one study), stroke or angina pectoris (one study) were found. No study reported economic, resource use or quality-of-life burden.

CONCLUSIONS:

Due to limited evidence on prevalence of elevated hsCRP and associated burden of illness in patients with a history of MI, further research is warranted. Variations in findings, cut-off points and methods between studies make generalisations difficult.
PP122 Strengthening Ethics Compliance In A Large Research Program: Uganda
Authors: Nabukenya Sylvia , Castelnuovo Barbara , Kambugu Andrew , Kayaga Maimouna , Opio Bruce , Orama Richard , Okoboi Stephen
Published: January 2018

INTRODUCTION:

The infectious Diseases Institute (IDI) is a research institute at the College of Health Sciences, Makerere University. Over the years, the number of research studies has greatly increased with an average of fifty active studies per year. Because of the voluminous study activities, investigators were faced with inadvertences of ethical approval deadlines (1). In 2015, a centralized electronic Regulatory Affairs Information System (RAIS) was developed and piloted to track the regulatory process of the entire research projects. RAIS is a web-based system, developed using a Net framework and runs on any operating system using a web browser such as “Google Chrome” and “Mozilla Firefox”.

METHODS:

A signed approval letter from an accredited Research Ethics Committee, National Drug Authority and Uganda National Council of Science and Technology, the reviewed protocol, consent forms and data collection tools are uploaded electronically into the RAIS with study staff contact information, CVs and Good Clinical Practice (GCP) certificates. RAIS sends automatic “no reply” emails to the investigators and research administration notifying for the need of annual renewal 56, 28 and 14 days before the expiry date of the approvals. The investigator or designated person prepares the application package which is then forwarded to the Research Regulatory Officer for review and submission to the regulatory authority.

RESULTS:

From January 2015 to November 2016, fourty-three ongoing studies were uploaded to the RAIS of which eleven were clinical trials, twenty-one observational studies, seven diagnostic and four implementation studies. Studies that obtained their annual approvals before the expiry date was 90.7 percent, compared to 29 percent that had reported early submission for annual renewal between January 2013 and December 2014. RAIS has enabled continuity of study activities with timely annual renewed approvals, supported the tracking of staff GCP certificates and populated timely notifications to investigators, resulting in submission of annual application packages on time.

CONCLUSIONS:

RAIS has strengthened ethical regulatory compliance and provided an effective platform for tracking regulatory processes, thus enabled continuity of study activities with timely annual renewal approvals and greatly supported the tracking of staff GCP certificates.
PP171 Immuno-Oncology: A Patient Perspective
Authors: Rubinstein Judith , Ho S. Yin , Rubinstein Emily , Sliman Rachel
Published: January 2018

INTRODUCTION:

New immunotherapies have had great successes, but also incredibly debilitating side effects for patients. This discrepancy needs to be a focus of pharmaceutical companies because it will affect the way Health Technology Assessment (HTA) agencies review drugs. Two or three case studies of patient and caregiver experiences surrounding immuno-oncology clinical trials, both past and ongoing, will be used in order to gain a better understanding of how these trials have impacted individuals.

METHODS:

Conduct in-person or telephone interviews with patients and their caregivers to find out more about patient experiences and see how key takeaways can help pharmaceutical companies better prepare submissions for HTA agencies as they launch future immuno-oncology drugs.

RESULTS:

Preliminary results indicated that a patient completed a course of treatment and is very happy with the results. She had metastatic melanoma on her scalp. When she was being prepared for surgery, two new tumors on her scalp were discovered. As a result, she was included in a melanoma clinical trial.

Another patient is still undergoing treatment and is responding, but is experiencing severe side effects that are impacting his life and that of his primary caregiver. He was hospitalized once for sepsis.

CONCLUSIONS:

Patient experiences can wildly vary. It is an area that needs more careful study, using both formal metrics and individual stories. Giving more attention to quality of life creates an opportunity for stronger submissions to HTA agencies and better assessments by those agencies.
VP24 The Development Of A Quality Management Tool For Health Technology Assessment Agencies In Spain
Authors: Márquez-Peláez Sergio , Gutiérrez-Ibarluzea Iñaki , Asua José , Molina-Lopez Teresa , Castro-Campos José Luis , Garcia-Armesto Sandra , Bono-Vega María , Bugarín-González Rosendo , Riobóo Janet Puñal , Luengo-Matos Setefilla , Brezmes-Delgado Ana , Suton Victoria Serra , Reynolds Jillian Margaret , Gonzalez-Enriquez Jesús , Serrano-Aguilar Pedro , Trujillo-Martin M. Mar
Published: January 2018

INTRODUCTION:

The Spanish National Network (REDETS) is a group of eight agencies, units and services, depending on National and Regional Governments that coordinate their work within a common methodological framework, guided by the principles of mutual recognition and cooperation. The necessity of considering a Quality Management System has been detected and, consequently, a common tool for all the members needs to be developed. We describe in this study the process to achieve that goal.

METHODS:

Based on both a review of previous literature and the proposal for a self-evaluating tool, a group of experts from each agency through consensus have developed a tool for self-evaluation in Health Technology Assessment (HTA) agencies. Through the structure described in the handbook of the Andalusian Agency for Healthcare Quality (ACSA), each standard should have a statement or proposal that needs to also include evidence or good practices, and the corresponding evaluation questions. In separate workgroups, the definition of these proposals, evidence and evaluation questions were developed. One face-to-face meeting and two meetings via teleconference were necessary to achieve a final document with all the quality standards.

RESULTS:

From a proposed structure of sixty-six standards, the titles, definitions, statements and evidence as well as good practices and evaluation questions were established in workgroups with consensus among all of the members (1 - 3). The final version of the self-assessment tool was composed of sixty-eight standards, grouped in twelve quality criteria structured in four dimensions: I Responsibility, II Clients and Stakeholders, III Production Process, and IV Resources.

CONCLUSIONS:

Quality management requires an evaluation tool and this version, based on a systematic review and consensus, is a useful and practical instrument for developing a handbook by each member of REDETS. An online version of the tool is in process of development.
VP46 Cost Analysis Of Popliteal Aneurysm Management
Authors: Pinget Christophe , Allain Elisabeth , Saucy François
Published: January 2018

INTRODUCTION:

Popliteal artery aneurysm (PAA) is the most common peripheral arterial aneurysm and the second most common aneurysm after abdominal aortic aneurysm (AAA). It presents a risk of occlusion, which may lead to acute ischemia and leg amputation. To prevent these risks, asymptomatic PAA >2cm and symptomatic PAA must be treated. Although open PPA repair (OPAR) is still the gold standard, endovascular PAA repair (EPAR) is increasingly used to manage PAA. The objective of this study is to compare the cost of these two medical procedures from the hospital perspective.

METHODS:

Data were retrieved from the administrative database of Lausanne University Hospital (CHUV – Switzerland). Based on diagnostic codes and medical procedure codes, we selected all patients who underwent OPAR or EPAR between 2011 and 2015. Patient's age, length of stay and cost were compared between both groups using Student t-test.

RESULTS:

We included seventy-three patient stays (OPAR forty and EPAR thirty-three). Gender balance was identical between groups (97 percent of male), but age was statistically significantly different (OPAR 67.5, EPAR 73, p = .04). EPAR induced shorter mean length of stay (5.1 days versus 11.7 days, p = .0000) and lower mean global cost (CHF 16,555 versus CHF23,514, p = .0085). Cost of procedure amounted to CHF 9,536 for OPAR versus CHF 3,848 for EPAR, medical supply and implants amounted to CHF 1,284 for OPAR versus CHF 7,041 for EPAR and other costs of hospital stay amounted to CHF 12,694 for OPAR versus CHF 5,666 for EPAR. (CHF 1.00 = USD1.00 = EURO 0.93)

CONCLUSIONS:

With higher patency rate, OPAR is still associated with better medical outcomes than EPAR. But EPAR is significantly less costly than OPAR. Implant cost of EPAR is more than offset by longer length of stay and operating time of OPAR.
VP49 Brazilian Consumer Willingness To Pay For Dengue Vaccine (CYD-TDV)
Authors: Godói Isabella , Santos André , Reis Edna , de Lemos Livia Pires , Brandão Cristina , Alvares Juliana , Acurcio Francisco , Bennie Marion , Godman Brian , Guerra Augusto
Published: January 2018

INTRODUCTION:

Dengue virus is a serious global health problem with an estimated 3.97 billion people at risk for infection worldwide. In December 2015, the first vaccine (CYD-TDV) for dengue prevention was approved in Brazil, developed by Sanofi Pasteur (1). However, given that the vaccine will potentially be paid via the public health system, information is needed regarding consumers willingness to pay for the dengue vaccine in the country, as well as discussions related to the possible inclusion of this vaccine into the public health system at prices suggested by the manufacturer. This was the objective of this research.

METHODS:

We conducted a cross-sectional study with residents of Greater Belo Horizonte, Minas Gerais, about their willingness to pay for the CYD-TDV vaccine. Respondents had to be over 18 years and not currently have the disease although they may have had dengue in the past (2,3).

RESULTS:

Five-hundred and seven individuals were interviewed, who were mostly female (62.4 percent), had completed high school (62.2 percent), were working (74.4 percent), had private health insurance (64.5 percent) and did not have dengue (67.4 percent). The maximum median value of consumers willingness to pay for the CYD-TDV vaccine, assuming vaccine efficacy against virologically-confirmed symptomatic dengue illness of approximately 60 percent, is USD33.61 (BRL120.00) for the complete 3-course schedule and USD11.20 (BRL40.00) per dose. At the price currently being assessed by the Brazil's regulatory chamber of pharmaceutical products market (CMED) for Dengvaxia® for three doses, only 17 percent of the population expressed a willingness to pay for the vaccine at this price.

CONCLUSIONS:

Brazil is currently one of the largest markets for dengue vaccine in the world and the price established is a key issue. The manufacturer should asses the possibility of lowering its price in Brazil to reach a larger audience among the Brazilian population, especially as other public health activities to control the disease will continue.
VP74 Russian System Of Medicines Provision: Status And Future Aspects
Authors: Babiy Vladimir , Yagudina Roza , Kulikov Andrey
Published: January 2018

INTRODUCTION:

Russian system of medicines provision is one of the biggest in the world. It covers 85 regions, around 17.1 million square kilometers and 146.5 million people; therefore the organizing of a stable and effective system is a challenge for decision makers. In this paper we make an effort to clarify main principles and aspects.

METHODS:

To systemize all the information concerning Russian medicines provision system, we review legislation, literature and made interview of experts.

RESULTS:

By 2015 more than 3,230 International Non-proprietary Names and 26,239 Trade names were registered in the Russian Federation. The pharmaceutical market consists of the commercial drug sector, drug reimbursement and hospital sector: 8 percent, 22 percent and 70 percent in monetary values and 1 percent, 19 percent and 80 percent in volume terms, respectively. Medicines provision through compulsory health insurance is divided into in-patient health services (first health and sanitary treatment, special health treatment and palliative treatment) and emergency services. Three drug lists form the reimbursement system: “list of vital and essential medicines”, “7 disease areas” and “Medicines provision population”. The “List of vital and essential medicines” is a basis for all other drug lists and fixes the maximum sale price for drugs. The “7 disease areas” detach high-priced drugs that are used in treatment of particular diseases and optimize the financing of treatment of people with high-cost diseases. The “Medicines provision for population” states the list of drugs that are reimbursed by the federal budget. Federal and regional budgets divides medicines into fully and partly reimbursed medicines.

CONCLUSIONS:

At the present time, the Russian system of medicines provision is rather complicated. Nevertheless, the system still develops: in 2016 Russian Ministry of Health began the development of the concept of medicines insurance system.
VP107 Pharmaceutical Industry's Experiences with the German Health Technology Assessment Scientific Advice
Authors: Dintsios Charalabos-Markos , Schlenkrich Sara
Published: January 2018

INTRODUCTION:

The early benefit assessment of drugs was introduced in Germany with the ‘Act to Reorganize the Pharmaceuticals’ Market in the SHI’ (AMNOG) in 2011. Before submitting the manufacturer's dossier, optional scientific advice is offered by the Federal Joint Committee (G-BA). The objective was to elicit manufacturers experience with the scientific advice offered by the Federal Joint Committee.

METHODS:

To prepare the survey, several manufacturers were interviewed on their experience with the scientific advice offered by the Federal Joint Committee. Subsequently, a questionnaire was developed to collect information for this purpose, comprising eight items on different topics aimed at understanding the perceived quality of the scientific advice provided.

RESULTS:

The qualitative part comprised seven manufacturers who had received between one and ten advisories before the end of 2012. With regard to the quantitative elicitation part, a total of sixty-one completed questionnaires from nineteen manufacturers were included until the beginning of 2015 (corresponding to almost 25 percent of the overall implemented scientific advice). Fourteen cases were about so called “early” scientific advice in terms of relating to evidence before commencing phase-III trials, forty-four cases concerned “late” scientific advice (pivotal trials were just conducted or already terminated), another two concerned repeated scientific advice and finally, four referred to miscellaneous contents (multiple answers possible). Both, the preceding qualitative and the following quantitative part of the elicitation, highlighted points about the process as well as the content shortcomings from an industry's point of view: inconsistencies, lacking expertise with conducting clinical trials, partially incomplete answers and a low readiness to engage in dialogue were criticized. On the other hand, the majority of respondents showed a positive attitude concerning unambiguousness, completeness, traceability, atmosphere and the protocol of the advice. Over the course of time, propositions on study design, agreement with the determined appropriate comparative therapy and subgroup definitions improved significantly.

CONCLUSIONS:

A more active involvement of further stakeholders and the incorporation of procedural elements from other health are systems with longer experience could improve the scientific advice provided.
VP109 Identifying Priorities For A National Health Research Funder
Authors: Turner Sheila , Ollerhead Liz , Cook Andrew
Published: January 2018

INTRODUCTION:

It is vitally important that research questions posed are important and that funded research meets a research need or a gap in evidence; these needs may be observed at a local, national or international level. Identifying such research priorities for a national research funder can be challenging, particularly for complex health problems such as health inequalities, where there is a need to consult a large number of experts with a range of expertise. Many methods are used in the identification of such research priorities, however, these can be resource intensive, costly, and logistically challenging particularly where large numbers of people are required and geographical distances are great.

METHODS:

This study investigated the use of Delphi type survey methods in identifying important research priorities related to health inequalities. Public health professionals with an interest in health inequalities were asked to identify research priorities, these research priorities were subsequently compared to those identified using different methods.

RESULTS:

Fifty-two public health professionals agreed to take part, the response rates were high, (69 percent, 50 percent and 40 percent) across three survey rounds; which indicated that participants were receptive to the methodology and motivated to respond. The themes identified as encompassing the most important research priorities were: mental health, environmental issues and health behaviours. Within these themes, topic areas which emerged most strongly included: community interventions for prevention of mental health problems, and the food and alcohol environment.

CONCLUSIONS:

Delphi type survey methods are effective as a means of obtaining opinions from a wide number of relevant experts identifying potential priority topic areas where there is a need for research evidence. Opinions may be sought at local and national levels in order to inform national research priorities.
VP120 A United Kingdom Research Commissioning Framework For Devices And Diagnostics
Authors: White Judith , Kimpton Christine , Cole Helen , Carolan-Rees Grace , Peirce Susan
Published: January 2018

INTRODUCTION:

Generation of high-quality evidence on medical devices through clinical trials can be challenging. The United Kingdom's National Institute for Health and Care Excellence (NICE) has developed a research commissioning framework for producing clinical evidence where gaps in the literature prevent definitive recommendations in their medical technology guidance and diagnostics guidance. The research commissioning framework involves NICE's external assessment centers collaborating with clinical researchers to secure funding and to design, conduct, and publish a study to address research recommendations within 3 years of guidance publications. We aimed to describe the early results of the framework.

METHODS:

Publically available information and results from an informal survey of NICE's external assessment centers were reviewed.

RESULTS:

As of December 2016, NICE has published a total of thirty medical technology guidance topics and twenty-four diagnostics guidance topics, five and twenty of which have research recommendations, respectively. A total of fourteen research commissioning framework-facilitated projects have been initiated. Two research projects have successfully secured external funding for a clinical trial: (i) non-contact low frequency ultrasound therapy for wound healing; and (ii) Parafricta bootees for pressure ulcer prevention. Further projects have produced published outputs without external funding. Four projects have been completed and undergone guidance review; one guidance topic was withdrawn and three have been transferred to the “static list”. Early experiences of NICE's research commissioning framework suggest that securing financial support from manufacturers or funding bodies for interventional clinical trials to answer single technology research questions within a short time frame is challenging but possible. The value of early feasibility studies to assess the likelihood of obtaining funding and of addressing NICE's research recommendations was recognised.

CONCLUSIONS:

NICE can facilitate independent research through its research commissioning framework initiative. Securing funding has proved challenging but recent successes have shown that approach is possible. Outputs which fill the evidence gap to an extent where a definitive guidance update is possible have been rare.
VP175 Validating Outcome Assessments For Health Technology Assessment In Ceroid Lipofuscinosis Neuronal 2 (CLN2), An Ultra-Rare Disease
Authors: Ballinger Rachel , Llewellyn Samuel , Macey Jake , Eliasson Lina , Butt Thomas , Jain Mohit , Olaye Andrew , West Andrea
Published: January 2018

INTRODUCTION:

Ceroid lipofuscinosis neuronal 2 (CLN2) disease, a form of Batten disease, is a rare, degenerative neurometabolic disorder. Disease onset around 2–4 years is followed by rapid decline in motor and neurologic function and mortality in early teenage years (1). Disease burden is best captured using observer-reported outcomes. However, validation is challenging in ultra-orphan diseases, requiring flexible methods and reasonable acceptance of limitations related to participant access.

The study aim was to assess content validation of clinical trial measures (i) CLN2 Disease Based Quality of Life Assessment (Sponsor-developed), (ii) EQ-5D-5L, (iii) Pediatric Quality of Life Inventory (PedsQL); and (iv) PedsQL Family Impact Module.

METHODS:

The Batten Disease Family Association recruited United Kingdom caregivers of a child with CLN2 disease (aged 3–7 years, non-participants in any CLN2 trial), to:

1.

Focus groups with symptom elicitation

2.

Cognitive interviews to assess measures.

RESULTS:

The Focus group comprised eleven caregivers (eight female, three male) from six families. Three families were current caregivers and remainders bereaved. Symptom and disease impact elicited showed the majority of measures domains were relevant.

The interview sample comprised sixteen current caregivers (twelve female, four male) from ten families (caring for eleven children). Overall measures were relevant, easy to understand and answer. However several items were difficult to apply to children with advanced disease (for example, Euroqol, EQ-5D-5L “overall health”), when ability is lost (for example, PedsQL walking), with misinterpretation of “no difficulties” with eating where child feeds using gastrostomy (CLN2 QoL). Caregivers found it difficult to know how their uncommunicative child was feeling (PedsQL worrying, EQ-5D-5L depression). Some symptoms and impacts were missing (for example, constipation, working life).

CONCLUSIONS:

The mixed-methods approach enabled content validity assessment of multiple measures. While these measures were largely relevant, adjustments could strengthen these for use in this fatal pediatric condition population and increase their acceptance within health technology assessment (HTA).
VP181 From National To European Assessment - The German Case
Authors: Panni Tommaso , Eberle Karolin , Seiler Nina , Brüderl Monika , Burkert-Kautzsch Cornelia , Carls Alexandra , Thiele Alexandra , Schleibner Stefan , Jänel Gerlinde
Published: January 2018

INTRODUCTION:

Health Technology Assessment (HTA) processes have become a fundamental part in the lifecycle of new medicines. However, their deep relation with national legislation creates ambiguous and controversial results between the European countries. Can they be standardized across Europe?

METHODS:

Sources of national differences have been identified in timelines, documents, methods, data interpretation, and conclusions. In order to harmonize and standardize HTA cooperation across Europe the European Network for HTA (EUnetHTA) was established. We analyzed guidelines, requirements, and output of EUnetHTA and noted the differences between those guidelines and the German G-BA (Federal Joint Committee, Gemeinsamer Bundesausschuss) standard and IQWiG (Institute for Quality and Efficiency in Health Care, Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen) methods.

RESULTS:

The comparison between German and European HTAs highlights that although both procedures follow the rules of Evidence-Based Medicine, differences in Body of Evidence, Comparator, Surrogate Endpoints, Subgroups, and Evidence Synthesis may lead to diverging HTA outcomes. The European HTA framework facilitates the appropriate depiction of clinical reality through comprehensive inclusion of the existing evidence with context specific statistical methods. It might become a worldwide platform for HTA evaluation and discussion.

CONCLUSIONS:

Only the involvement of both, pharmaceutical companies and HTA bodies within a unified European framework can lead to a mature and transparent procedure with a reliable outcome independent of legal requirements.
VP208 Informing An Economic Model For Hyperhidrosis: A Clinical Survey
Authors: Stoniute Julija , Moloney Eoin , Rice Stephen , Levell Nick , Craig Dawn
Published: January 2018

INTRODUCTION:

Hyperhidrosis is characterized by uncontrollable excessive sweating, which occurs at rest, regardless of temperature. As part of a wider study exploring the clinical and cost effectiveness of alternative treatments for primary hyperhidrosis, a survey of United Kingdom (UK) dermatologists was conducted to gain a better understanding of current clinical practice in the area and inform economic model inputs.

METHODS:

The survey was conducted by means of an online survey tool, “Qualtrics”. It was circulated to members of the British Association of Dermatologists. Topics covered included treatments typically administered, medication dosages prescribed, effectiveness of treatments, adverse events related to treatments and resource use associated with individual treatments.

RESULTS:

Forty-five respondents from forty-two different dermatology units completed the survey. The majority of clinicians (83 percent) prescribed more than one medication - most commonly oxybutynin and propantheline bromide. The next most commonly reported treatments were: iontophoresis, botulinum toxin and curettage.

Respondents were asked to indicate dosage, frequency and details about follow-up visits related to medication use. Doses prescribed were largely consistent with British National Formulary (BNF) recommendations. For other treatments, dermatologists were asked to indicate duration of the procedure, job title of the treatment provider and details about monitoring visits. Results were similar to the findings from the literature and previously conducted interviews with clinicians.

Respondents were asked to indicate the dropout rates for each type of treatment due to lack of effectiveness and adverse events. Dropout rates were relatively high for both reasons.

CONCLUSIONS:

The results highlight the wide range of treatments for hyperhidrosis currently administered by dermatologists across the UK, and the variation in current clinical practice. This variation highlights the lack of evidence-based guidance underpinning practice and the importance of clinical surveys as a complement to usual data collection methods.
VP216 Health Technology Assessment's Balance Between Additional Data, Adoption, And Patient Access
Authors: Patel Parashar , Cangelosi Michael , McIntyre Mark
Published: January 2018

INTRODUCTION:

Historically, many Health Technology Assessment (HTA) bodies were developed with a focus on addressing rapidly rising drug costs and the unique need to evaluate each drug as a de novo entity. The degree to which the unique needs for evaluating technologies vis a vis drugs are reflected in distinct HTA methods and activity is to date understudied.

METHODS:

We examined HTA's reviews of two technologies: WATCHMAN™, a device to reduce the risk of stroke in certain patients and Alair™, a procedure-based treatment for severe asthma. Both technologies have been extensively reviewed by HTA bodies and payers in many countries. These HTA reviews are compared to a convenience sample of these HTA's bodies reviews of drugs and qualitative differentiators between these two categories explored.

RESULTS:

The differences and similarities (for example, in rigor and necessity of evidence) between US Section 510(k) clearances, US premarket approval (PMA), and US new drug application (NDA) regulatory pathways have not been clearly understood by HTA or reflected in their methodologies employed. Additionally, emergent methodologies such as Bayesian statistical analyses may encounter challenges within technologies reviews. HTA bodies may not be cognizant of development timelines or the timelines of comparators. Finally, HTA bodies may overestimate device adoption rates.

CONCLUSIONS:

The differences in evidence requirements for regulatory approval between US 510(k), US PMA, and US NDA pathways have not been reflected in different methodological approaches within HTA bodies reviews. Opportunities and novel methods are needed for HTA bodies to derive imputed comparisons between technologies that may have inherently incongruent timelines. Finally, HTA bodies could benefit from methods to more accurately estimate projected adoption curves. Challenges exist using frameworks, paradigms, and methodologies initially established for, and commonly used for, pharmaceuticals on device evaluations; leaders of HTA methods can improve the situation by providing guidance and recommendations for more appropriate HTA methods to evaluate devices.
Courtney Humphries Receives 2017 David Perlman Award for Excellence in Science Journalism–News
Authors:   AGU
Published: January 2018

Courtney Humphries received the 2017 David Perlman Award for Excellence in Science Journalism–News at the American Geophysical Union Fall Meeting Honors Ceremony, held on 13 December 2017 in New Orleans, La. The award recognizes “a journalist for a news story or series in any medium except books that makes information about the Earth and space sciences accessible and interesting to the general public.”
DNA methylation profile is associated with the osteogenic potential of three distinct human odontogenic stem cells
Authors: Ai Tingting , Zhang Jieni , Wang Xuedong , Zheng Xiaowen , Qin Xueyan , Zhang Qian , Li Weiran , Hu Wei , Lin Jiuxiang , Chen Feng
Published: January 2018

Among the various sources of human autologous stem cells, stem cells isolated from dental tissues exhibit excellent properties in tissue engineering and regenerative medicine. However, the distinct potential of these odontogenic cell lines remains unclear. In this study, we analyzed DNA methylation patterns to determine whether specific differences existed among three different odontogenic cell types. Using the HumanMethylation450 Beadchip, the whole genomes of human dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), and dental follicle progenitor cells (DFPCs) were compared. Then, the osteogenic potential of these cells was evaluated both in vitro and in vivo, and the methylation levels of certain genes related to bone formation differed among the three cell lines. P values less than 0.05 were considered to indicate statistical significance. The three cell types showed highly similar DNA methylation patterns, although specific differences were identified. Gene ontology analysis revealed that one of the most significantly different gene categories was related to bone formation. Thus, expression of cell surface epitopes and osteogenic-related transcription factors as well as the bone formation capacity were compared. The results showed that compared with DFPCs and DPSCs, PDLSCs had higher transcription levels of osteogenic-related factors, a higher in vitro osteogenic potential, and an increased new bone formation capacity in vivo. In conclusion, the results of this study suggested that the differential DNA methylation profiles could be related to the osteogenic potential of these human odontogenic cell populations. Additionally, the increased osteogenic potential of PDLSCs might aid researchers or clinicians in making better choices regarding tissue regeneration and clinical therapies.
Systematic in vivo evaluation of the time-dependent inflammatory response to steel and Teflon insulin infusion catheters
Authors: Hauzenberger Jasmin R. , Münzker Julia , Kotzbeck Petra , Asslaber Martin , Bubalo Vladimir , Joseph Jeffrey I , Pieber Thomas R.
Published: January 2018

Continuous subcutaneous insulin infusion (CSII) catheters are considered the weak link of insulin pump therapy. Wear-time considerably varies between patients and the choice of catheter material is based on personal preferences rather than scientific facts. Therefore, we systematically assessed and quantified the inflammatory tissue response to steel versus Teflon CSII catheters over a maximum wear-time of 7 days in swine. Tissue surrounding catheters was analysed using histopathology and quantitative real-time PCR. The area of inflammation increased significantly over time independent of material which was confirmed by an increase in CD68 expression and an increase in mononuclear and neutrophil cell infiltrate around the catheters. We observed substantially higher fibrin deposition (p < 0.05) around steel on day 4 of wear-time. IL-6 gene expression increased within 24 hours after insertion, returned to normal levels around Teflon (p < 0.05) but remained high around steel (p < 0.05). IL-10 and TGF-β levels did not resolve over time, indicating impaired wound healing. In conclusion, there was a major temporal effect in the acute inflammatory response to CSII catheters but we found little difference between materials. This study setup presents a robust tool for the systematic analysis of the tissue response to CSII catheters.
High-throughput analysis using non-depletive SPME: challenges and applications to the determination of free and total concentrations in small sample volumes
Authors: Boyacı Ezel , Bojko Barbara , Reyes-Garcés Nathaly , Poole Justen J. , Gómez-Ríos Germán Augusto , Teixeira Alexandre , Nicol Beate , Pawliszyn Janusz
Published: January 2018

In vitro high-throughput non-depletive quantitation of chemicals in biofluids is of growing interest in many areas. Some of the challenges facing researchers include the limited volume of biofluids, rapid and high-throughput sampling requirements, and the lack of reliable methods. Coupled to the above, growing interest in the monitoring of kinetics and dynamics of miniaturized biosystems has spurred the demand for development of novel and revolutionary methodologies for analysis of biofluids. The applicability of solid-phase microextraction (SPME) is investigated as a potential technology to fulfill the aforementioned requirements. As analytes with sufficient diversity in their physicochemical features, nicotine, N,N-Diethyl-meta-toluamide, and diclofenac were selected as test compounds for the study. The objective was to develop methodologies that would allow repeated non-depletive sampling from 96-well plates, using 100 µL of sample. Initially, thin film-SPME was investigated. Results revealed substantial depletion and consequent disruption in the system. Therefore, new ultra-thin coated fibers were developed. The applicability of this device to the described sampling scenario was tested by determining the protein binding of the analytes. Results showed good agreement with rapid equilibrium dialysis. The presented method allows high-throughput analysis using small volumes, enabling fast reliable free and total concentration determinations without disruption of system equilibrium.
The Proliferation Capacity of Cultured Neural Stem Cells Promoted by CSF Collected from SAH Patients Correlates to Clinical Outcome
Authors: Chen Yun-An , Wang Kuo-Chuan , Liu Der-Zen , Young Tai-Horng , Tsai Li-Kai
Published: January 2018

Neurogenesis from endogenous neural stem cells (NSCs) might contribute to functional recovery after stroke based on animal studies; however, the relationship between neurogenesis and post-stroke outcome has rarely been demonstrated in humans. We prospectively collected cerebrospinal fluid (CSF) from 36 patients with subarachnoid hemorrhage (SAH). The CSF was added to the culture medium of the rat NSCs to test the effects on proliferation (proliferation index [PI], percentage of Ki-67 immunoreactive cells). We correlated the PI with functional outcome based on the modified Rankin Scale at 3 months post-SAH. Treatment with the CSF samples collected from SAH patients showed a higher PI compared with those collected from patients with normal pressure hydrocephalus and untreated controls (20.3 ± 8.8 vs. 8.2 ± 5.1 and 7.8 ± 3.0, P < 0.001), indicating proliferation-promoting factors in CSF after SAH. The PI was positively correlated with SAH volume (p = 0.025). For patients with lower SAH volume, patients with favorable outcome had a higher PI than those with poor outcome (20.8 ± 6.9 vs. 14.6 ± 4.3, p = 0.047). Using multivariable logistic regression analysis, the PI was a positive determinant for favorable outcome (odds ratio, 1.17; 95% confidence interval, 1.00 to 1.36) that more proliferation-promoting factors in CSF was associated with better functional outcome in SAH patients.
Night eating model shows time-specific depression-like behavior in the forced swimming test
Authors: Haraguchi Atsushi , Fukuzawa Miyabi , Iwami Shiho , Nishimura Yutaro , Motohashi Hiroaki , Tahara Yu , Shibata Shigenobu
Published: January 2018

The circadian clock system is associated with feeding and mood. Patients with night eating syndrome (NES) delay their eating rhythm and their mood declines during the evening and night, manifesting as time-specific depression. Therefore, we hypothesized that the NES feeding pattern might cause time-specific depression. We established new NES model by restricted feeding with high-fat diet during the inactive period under normal-fat dietad libitum. The FST (forced swimming test) immobility time in the NES model group was prolonged only after lights-on, corresponding to evening and early night for humans. We examined the effect of the NES feeding pattern on peripheral clocks using PER2::LUCIFERASE knock-in mice and anin vivomonitoring system. Caloric intake during the inactive period would shift the peripheral clock, and might be an important factor in causing the time-specific depression-like behavior. In the NES model group, synthesis of serotonin and norepinephrine were increased, but utilization and metabolism of these monoamines were decreased under stress. Desipramine shortened some mice’s FST immobility time in the NES model group. The present study suggests that the NES feeding pattern causes phase shift of peripheral clocks and malfunction of the monoamine system, which may contribute to the development of time-specific depression.
Gender-related differences in heart failure with preserved ejection fraction
Authors: Duca Franz , Zotter-Tufaro Caroline , Kammerlander Andreas A. , Aschauer Stefan , Binder Christina , Mascherbauer Julia , Bonderman Diana
Published: January 2018

Heart failure with preserved ejection fraction (HFpEF) affects more women than men, suggesting gender to play a major role in disease evolution. However, studies investigating gender differences in HFpEF are limited. In the present study we aimed to describe gender differences in a well-characterized HFpEF cohort. Consecutive HFpEF patients underwent invasive hemodynamic assessment, cardiac magnetic resonance imaging and exercise testing. Study endpoints were: cardiac death, a combined endpoint of HF hospitalization or cardiac death and all-cause death. 260 HFpEF patients were prospectively enrolled. Men were more compromised with regard to exercise capacity and had significantly more co-morbidities. Men had more pronounced pulmonary vascular disease with higher diastolic pressure gradients and a lower right ventricular EF. During follow-up, 9.2% experienced cardiac death, 33.5% the combined endpoint and 17.3% all-cause death. Male gender was independently associated with cardiac death, but neither with the combined endpoint nor with all-cause mortality. We detected clear gender differences in HFpEF patients. Cardiac death was more common among men, but not all-cause death. While men are more prone to develop a right heart phenotype and die from HFpEF, women are more likely to die with HFpEF.
Performance analysis of an adaptive optics system for free-space optics communication through atmospheric turbulence
Authors: Wang Yukun , Xu Huanyu , Li Dayu , Wang Rui , Jin Chengbin , Yin Xianghui , Gao Shijie , Mu Quanquan , Xuan Li , Cao Zhaoliang
Published: January 2018

The performance of free-space optics communication (FSOC) is greatly degraded by atmospheric turbulence. Adaptive optics (AO) is an effective method for attenuating the influence. In this paper, the influence of the spatial and temporal characteristics of turbulence on the performance of AO in a FSOC system is investigated. Based on the Greenwood frequency (GF) and the ratio of receiver aperture diameter to atmospheric coherent length (D/r
0
), the relationship between FSOC performance (CE) and AO parameters (corrected Zernike modes number and bandwidth) is derived for the first time. Then, simulations and experiments are conducted to analyze the influence of AO parameters on FSOC performance under different GF and D/r
0
. The simulation and experimental results show that, for common turbulence conditions, the number of corrected Zernike modes can be fixed at 35 and the bandwidth of the AO system should be larger than the GF. Measurements of the bit error rate (BER) for moderate turbulence conditions (D/r
0
 = 10, f
G
 = 60 Hz) show that when the bandwidth is two times that of GF, the average BER is decreased by two orders of magnitude compared with f
G
/f
3dB
 = 1. These results and conclusions can provide important guidance in the design of an AO system for FSOC.
Broadband wave plates made by plasmonic metamaterials
Authors: Chen Lin , Ke Xianmin , Guo Huijie , Li Junhao , Li Xun , Zhou Lei
Published: January 2018

Although metamaterials wave-plates have been demonstrated previously, many of them suffer from the issue of narrow bandwidth since they typically rely on resonance principles and thus exhibit inevitable frequency dispersions. Here, we show that the dispersion of spoof surface plasmon (SSP) mode supported by a fishbone structure can be freely modulated by varying the structural parameters. This motivates us to establish a general strategy of building broadband wave-plates by cascading two fishbone structures with different propagation constants of SSP modes. We derive a criterion under which the cross-polarization phase-difference across the whole device can maintain at a nearly constant value over a wide frequency band, with frequency dispersions in the two fishbone structures cancelled out. As an illustration, we design and fabricate an efficient microwave quarter-wave plate and experimentally characterize its excellent polarization-control performances over a broad frequency band (7–9.2 GHz). Our findings can stimulate making dispersion-controlled high-performance optical functional devices in different frequency domains.
Publisher Correction: Microbial network of the carbonate precipitation process induced by microbial consortia and the potential application to crack healing in concrete
Authors: Zhang Jiaguang , Zhou Aijuan , Liu Yuanzhen , Zhao Bowei , Luan Yunbo , Wang Sufang , Yue Xiuping , Li Zhu
Published: January 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.