bluuebunny/crossref_metadata_2025_split huggingface dataset:
The MD-PhD program in Geneva: a 10-year analysis of graduate demographics and outcomes
Authors: Dos Santos Rocha Andre , Combescure Cristophe , Negro Francesco 
Published: November 2020

Abstract
Background
MD-PhD programs confer degrees that empower medical doctors with in-depth scientific skills to contribute to biomedical research and academic medicine, alongside clinical practice. Whilst the career options and research opportunities related to graduates following these programs in the US are well documented, little is known about their European counterparts. In this article, we studied graduates who had completed the MD-PhD program at the University of Geneva between 2010 and 2019.

Methods
A cross-sectional survey was performed in April 2019, targeting all medical doctors who had obtained the MD-PhD degree from the University of Geneva since 2010. Demographics, opinions, and career outcomes of the MD-PhD graduates were assessed through an online anonymous questionnaire.

Results
Twenty-one questionnaires were collected from 31 MD-PhD graduates (response rate 65.5%). Most respondents (57.1%) had performed an MD-PhD training in basic sciences; however, only 14.3% had pursued this type of research thereafter. Most of the respondents held a position at a University hospital (90.5%), although a significant number of them were no longer involved in research in their current position (28.6%). 85.7% mentioned obstacles and challenges in combining clinical duties with research. Despite this, the majority (85.7%) declared that the MD-PhD degree had given them advantages in their career path, granting access to clinical and academic positions, as well as funding.

Conclusions
Graduates from the MD-PhD program in Geneva were for the most part, satisfied with their training. However, because of the challenges and obstacles in combining clinical duties with research, the implementation of research activities in their current position proved difficult.
Integrated 3D printing solution to mitigate shortages of airway consumables and personal protective equipment during the COVID-19 pandemic
Authors: Fillat-Gomà Ferran , Coderch-Navarro Sergi , Martínez-Carreres Laia , Monill-Raya Núria , Nadal-Mir Toni , Lalmolda Cristina , Luján Manel , de Haro Candelaria , Blanch Lluís 
Published: November 2020

Abstract

Background
To cope with shortages of equipment during the COVID-19 pandemic, we established a nonprofit end-to-end system to identify, validate, regulate, manufacture, and distribute 3D-printed medical equipment. Here we describe the local and global impact of this system.

Methods
Together with critical care experts, we identified potentially lacking medical equipment and proposed solutions based on 3D printing. Validation was based on the ISO 13485 quality standard for the manufacturing of customized medical devices. We posted the design files for each device on our website together with their technical and printing specifications and created a supply chain so that hospitals from our region could request them. We analyzed the number/type of items, petitioners, manufacturers, and catalogue views.

Results
Among 33 devices analyzed, 26 (78·8%) were validated. Of these, 23 (88·5%) were airway consumables and 3 (11·5%) were personal protective equipment. Orders came from 19 (76%) hospitals and 6 (24%) other healthcare institutions. Peak production was reached 10 days after the catalogue was published. A total of 22,135 items were manufactured by 59 companies in 18 sectors; 19,212 items were distributed to requesting sites during the busiest days of the pandemic. Our online catalogue was also viewed by 27,861 individuals from 113 countries.

Conclusions
3D printing helped mitigate shortages of medical devices due to problems in the global supply chain.
Cost of investigations during the acute hospital stay following total hip or knee arthroplasty, by complication status
Authors: Cheng Emma , Lewin Adriane , Churches Tim , Harris Ian A , Naylor Justine 
Published: November 2020

Abstract

Background
Total hip and total knee arthroplasties are among the most common types of surgery performed in Australia today and are effective treatments for severe osteoarthritis. However, the increasing financial burden on the health system owing to the increasing rates of surgery has led to a growing interest in improving the cost-effectiveness and safety of arthroplasty care. This study was designed to quantify the association between post-operative complications, a major cost driver, and the cost of investigations following total hip or knee arthroplasty.

Methods
This is a prospective cohort study of consecutive patients undergoing primary total hip or knee arthroplasty at an Australian public hospital. We measured the number and cost of imaging and pathology tests performed during the acute hospital stay and used linear regression to quantify the association between complication status and investigation costs.

Results
Five hundred patients were included in the analysis. On average, those with complications received more tests, and more expensive tests. The mean combined cost of imaging and pathology tests in patients with no complications was AU$ 187 (SD: 12.0). In comparison, patients with minor complications had a mean additional cost of AU$ 270 (SD: 31.0), and those with major complications had a mean additional cost of AU$ 493 (SD: 54.2) (p < 0.001).

Conclusions
In patients undergoing hip or knee arthroplasty, investigation costs are substantially greater in the presence of either minor or major complications. With growing volumes of total hip and total knee arthroplasties, a potential focus of future research could include optimising investigation practices for patients with and without complications.
Design of a care pathway for pharmacy-based PrEP delivery in Kenya: results from a collaborative stakeholder consultation
Authors:   on Behalf of Stakeholders for Pharmacy-based PrEP Delivery in Kenya Consultation, Ortblad Katrina F. , Mogere Peter , Roche Stephanie , Kamolloh Kevin , Odoyo Josephine , Irungu Elizabeth , Mugo Nelly R. , Pintye Jillian , Baeten Jared M. , Bukusi Elizabeth , Ngure Kenneth 
Published: November 2020

Abstract

Introduction
In Kenya, pre-exposure prophylaxis (PrEP) for HIV prevention is almost exclusively delivered at HIV clinics. Developing novel PrEP delivery models is important for increasing the reach of PrEP. Delivery of PrEP through pharmacies is one approach utilized in the US to improve accessibility. Retail pharmacies are commonly used as a first-line access point for medical care in Kenya, but have not been utilized for PrEP delivery. We conducted a collaborative consultative meeting of stakeholders to develop a care pathway for pharmacy-based PrEP delivery in Kenya.

Methods
In January 2020, we held a one-day meeting in Nairobi with 36 stakeholders from PrEP regulatory, professional, healthcare service delivery, civil society, and research organizations. Attendees reviewed a theory of change model, results from formative qualitative research with pharmacy providers and clients, and anticipated core components of pharmacy-based PrEP delivery: counseling, HIV testing, prescribing, and dispensing. Stakeholders participated in small and large group discussions to identify potential challenges and solutions. We synthesized the key findings from these discussions.

Results
Stakeholders were enthusiastic about a model for pharmacy-based PrEP delivery. Potential challenges identified included insufficient pharmacy provider knowledge and skills, regulatory hurdles to providing affordable HIV testing at pharmacies, and undefined pathways for PrEP procurement. Potential solutions identified included having pharmacy providers complete the Kenya Ministry of Health-approved PrEP training, use of a PrEP prescribing checklist with remote clinician oversight and provider-assisted HIV self-testing, and having the government provide PrEP and HIV self-testing kits to pharmacies during a pilot test. A care pathway was developed over the course of the meeting.

Conclusions
PrEP delivery stakeholders in Kenya were strongly supportive of developing and testing a model for pharmacy-based PrEP delivery to increase PrEP access. We collaboratively developed a care pathway for pilot testing that has the potential to expand PrEP delivery options in Kenya and other similar settings.
Modelling the household-level impact of a maternal respiratory syncytial virus (RSV) vaccine in a high-income setting
Authors: Campbell Patricia T. , Geard Nicholas , Hogan Alexandra B. 
Published: November 2020

Abstract

Background
Respiratory syncytial virus (RSV) infects almost all children by the age of 2 years, with the risk of hospitalisation highest in the first 6 months of life. Development and licensure of a vaccine to prevent severe RSV illness in infants is a public health priority. A recent phase 3 clinical trial estimated the efficacy of maternal vaccination at 39% over the first 90 days of life. Households play a key role in RSV transmission; however, few estimates of population-level RSV vaccine impact account for household structure.

Methods
We simulated RSV transmission within a stochastic, individual-based model framework, using an existing demographic model, structured by age and household and parameterised with Australian data, as an exemplar of a high-income country. We modelled vaccination by immunising pregnant women and explicitly linked the immune status of each mother-infant pair. We quantified the impact on children for a range of vaccine properties and uptake levels.

Results
We found that a maternal immunisation strategy would have the most substantial impact in infants younger than 3 months, reducing RSV infection incidence in this age group by 16.6% at 70% vaccination coverage. In children aged 3–6 months, RSV infection was reduced by 5.3%. Over the first 6 months of life, the incidence rate for infants born to unvaccinated mothers was 1.26 times that of infants born to vaccinated mothers. The impact in older age groups was more modest, with evidence of infections being delayed to the second year of life.

Conclusions
Our findings show that while individual benefit from maternal RSV vaccination could be substantial, population-level reductions may be more modest. Vaccination impact was sensitive to the extent that vaccination prevented infection, highlighting the need for more vaccine trial data.
Pharmacokinetics and pharmacodynamics of HTD1801 (berberine ursodeoxycholate, BUDCA) in patients with hyperlipidemia
Authors: Di Bisceglie Adrian M. , Watts Gerald F. , Lavin Philip , Yu Meng , Bai Ru , Liu Liping 
Published: November 2020

AbstractBackgroundReduction in elevated serum cholesterol concentrations is important in the management of individuals at risk of atherosclerotic cardiovascular disease (ASCVD), such as myocardial infarction and thrombotic stroke. Although HMGCoA reductase inhibitors (“statins”) are frequently used for this purpose, a significant proportion of patients remain at increased residual risk of ASCVD as they do not adequately address some of the associated co-morbidities such as diabetes and fatty liver disease.MethodsA double-blind, randomized, placebo-controlled, dose ranging study was carried out that compared three doses of berberine ursodeoxycholate (BUDCA) to placebo in a cohort of subjects with a history of hypercholesterolemia and serum LDL cholesterol levels above 2.59 mmol/L (> 99.9 mg/dL). BUDCA was administered in two divided doses each day for 28 days. The primary endpoints of the study were safety and tolerability of this new compound, as well as its effect in lowering serum lipid and lipoprotein concentrations.ResultsA total of 50 subjects were enrolled into three dose cohorts in this study. BUDCA was generally well tolerated, even at doses of 2000 mg per day (the highest dose group); there were no significant adverse effects reported and this highest dose was associated with significant reductions in LDL cholesterol. By day 28 and with the highest dose of BUDCA, there were significant reductions in the serum concentrations of total cholesterol by 8.2% (P = 0.0004) and LDL cholesterol by 10.4% (P = 0.0006), but no significant changes in triglyceride and HDL cholesterol concentrations.ConclusionsBUDCA is a new single molecular entity that has a significant but modest effect in safely lowering serum LDL-cholesterol concentrations in individuals with a history of hypercholesterolemia. It has a potential use for treating hypercholesterolemia in individuals who cannot take statins, and possibly as adjunctive to other agents, such as ezetimibe or bempedoic acid.Trial registrationThe study was registered onClinicaltrials.gov(NCT03381287).
How donors support civil society as government accountability advocates: a review of strategies and implications for transition of donor funding in global health
Authors: McDonough Amy , Rodríguez Daniela C. 
Published: November 2020

Abstract
Background
Global health donors are increasingly transitioning funding responsibility to host governments as aid budgets plateau or decline and countries meet development and disease burden goals. Civil society organizations (CSOs) can play a critical role as accountability mechanisms over their governments, but transitions raise questions about how donor-supported CSOs will fare following transition, especially in environments of limited political commitment. Decreases in funding may force CSOs to scale back activities, seek other funding, or rely on their governments for funding. Vulnerable populations most in need of support may lose critical advocates, compromising their access to lifesaving care and threatening the reversal of global health achievements. This review investigates donor strategies used in the past to support CSOs as accountability advocates across the international development sector by exploring what activities are supported, how support is provided and who receives support. It provides considerations for global health donors to better equip civil society as advocates during and following transition.

Methods
A literature review of four databases of peer-reviewed literature, websites focused on civil society support and snowball searching identified 180 documents for review, after application of exclusion criteria, covering up to December 2019. Results were categorized and analyzed by who, what and how donors have supported civil society’s accountability role.

Results
Donors support a variety of civil society actors, including individual organizations and networks, through capacity building, access to information, backing participation in policy dialogues, securing citizen engagement and targeting the broader policy context. Funding may be provided directly or through pooled, intermediary or bridge mechanisms. Key concerns identified include insufficient engagement of CSOs in defining support, limited donor flexibility, tensions in balancing organizational professionalization with community connections, and jeopardized CSO legitimacy and independence from relying on foreign funds.

Conclusions
Given the urgency of global health donor transitions, the literature demonstrates that any donor support to CSO advocates should emphasize transition preparations from the start. Capacity building, institutionalizing mechanisms for civil society participation, planning for information needs, and flexible funding are priority mechanisms to ensure that vulnerable populations continue accessing lifesaving care and global health progress is not reversed.
Cyclotron-based production of 68Ga, [68Ga]GaCl3, and [68Ga]Ga-PSMA-11 from a liquid target
Authors: Rodnick Melissa E. , Sollert Carina , Stark Daniela , Clark Mara , Katsifis Andrew , Hockley Brian G. , Parr D. Christian , Frigell Jens , Henderson Bradford D. , Abghari-Gerst Monica , Piert Morand R. , Fulham Michael J. , Eberl Stefan , Gagnon Katherine , Scott Peter J. H. 
Published: November 2020

AbstractPurposeTo optimize the direct production of68Ga on a cyclotron, via the68Zn(p,n)68Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced68Ga, extraction of [68Ga]GaCl3and subsequent [68Ga]Ga-PSMA-11 labeling using an automated synthesis module.MethodsIrradiations of a 1.0 M solution of [68Zn]Zn(NO3)2in dilute (0.2–0.3 M) HNO3were conducted using GE PETtrace cyclotrons and GE68Ga liquid targets. The proton beam energy was degraded to a nominal 14.3 MeV to minimize the co-production of67Ga through the68Zn(p,2n)67Ga reaction without unduly compromising68Ga yields. We also evaluated the effects of varying beam times (50–75 min) and beam currents (27–40 μA). Crude68Ga production was measured. The extraction of [68Ga]GaCl3was performed using a 2 column solid phase method on the GE FASTlab Developer platform. Extracted [68Ga]GaCl3was used to label [68Ga]Ga-PSMA-11 that was intended for clinical use.ResultsThe decay corrected yield of68Ga at EOB was typically > 3.7 GBq (100 mCi) for a 60 min beam, with irradiations of [68Zn]Zn(NO3)2at 0.3 M HNO3.Target/chemistry performance was more consistent when compared with 0.2 M HNO3. Radionuclidic purity of68Ga was typically > 99.8% at EOB and met the requirements specified in the European Pharmacopoeia (< 2% combined66/67Ga) for a practical clinical product shelf-life. The activity yield of [68Ga]GaCl3was typically > 50% (~ 1.85 GBq, 50 mCi); yields improved as processes were optimized. Labeling yields for [68Ga]Ga-PSMA-11 were near quantitative (~ 1.67 GBq, 45 mCi) at EOS. Cyclotron produced [68Ga]Ga-PSMA-11 underwent full quality control, stability and sterility testing, and was implemented for human use at the University of Michigan as an Investigational New Drug through the US FDA and also at the Royal Prince Alfred Hospital (RPA).ConclusionDirect cyclotron irradiation of a liquid target provides clinically relevant quantities of [68Ga]Ga-PSMA-11 and is a viable alternative to traditional68Ge/68Ga generators.
Towards safer risperidone prescribing in Alzheimer's disease
Authors: Reeves Suzanne , Bertrand Julie , Uchida Hiroyuki , Yoshida Kazunari , Otani Yohei , Ozer Mikail , Liu Kathy Y. , Bramon Elvira , Bies Robert , Pollock Bruce G. , Howard Robert 
Published: November 2020

BackgroundIn the treatment of psychosis, agitation and aggression in Alzheimer's disease, guidelines emphasise the need to ‘use the lowest possible dose’ of antipsychotic drugs, but provide no information on optimal dosing.AimsThis analysis investigated the pharmacokinetic profiles of risperidone and 9-hydroxy (OH)-risperidone, and how these related to treatment-emergent extrapyramidal side-effects (EPS), using data from The Clinical Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease study (Clinicaltrials.gov identifier: NCT00015548).MethodA statistical model, which described the concentration–time course of risperidone and 9-OH-risperidone, was used to predict peak, trough and average concentrations of risperidone, 9-OH-risperidone and ‘active moiety’ (combined concentrations) (n= 108 participants). Logistic regression was used to investigate the associations of pharmacokinetic biomarkers with EPS. Model-based predictions were used to simulate the dose adjustments needed to avoid EPS.ResultsThe model showed an age-related reduction in risperidone clearance (P< 0.0001), reduced renal elimination of 9-OH-risperidone (elimination half-life 27 h), and slower active moiety clearance in 22% of patients, (concentration-to-dose ratio: 20.2 (s.d. = 7.2)v.7.6 (s.d. = 4.9) ng/mL per mg/day, Mann–WhitneyU-test,P< 0.0001). Higher trough 9-OH-risperidone and active moiety concentrations (P< 0.0001) and lower Mini-Mental State Examination (MMSE) scores (P< 0.0001), were associated with EPS. Model-based predictions suggest the optimum dose ranged from 0.25 mg/day (85 years, MMSE of 5), to 1 mg/day (75 years, MMSE of 15), with alternate day dosing required for those with slower drug clearance.ConclusionsOur findings argue for age- and MMSE-related dose adjustments and suggest that a single measure of the concentration-to-dose ratio could be used to identify those with slower drug clearance.
Structural Gray and White Matter Differences in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia
Authors: Stantonyonge Nicole , Sampedro Frederic , Méndez Jorge , Martínez-Horta Saül , Chico Ana , Gómez-Anson Beatriz 
Published: November 2020

Abstract

Context
Type 1 diabetes (T1D) is associated with an increased risk of cognitive decline, where severe hypoglycemia (SH) and impaired awareness of hypoglycemia (IAH) may play a role. While there is evidence of a possible association between IAH and brain damage, the potential brain changes remain poorly characterized by magnetic resonance imaging (MRI).

Objective
To investigate whether there are structural brain differences in a group of T1D patients with IAH compared with normal awareness of hypoglycemia (NAH).

Design
General practice, population-based, cross-sectional study (July 2018 to July 2019).

Setting
Endocrinology Department, Hospital Santa Creu i Sant Pau.

Participants
A total of 40 T1D patients (20 each with IAH and NAH) matched for age, sex, T1D duration, and education level.

Main Outcome Measures
Using different neuroimaging techniques, we compared whole-brain gray matter (GM) and white matter (WM) differences. We used voxel-based morphometry and cortical surface area analysis methods to assess GM differences, and fractional anisotropy (FA) to assess WM differences.

Results
Compared with patients with T1D-NAH, patients with T1D-IAH had reduced GM volumes and cortical surface areas, especially in frontal and parietal regions (P &lt; 0.05 corrected), and also showed reduced FA values in major WM tracts. The observed MRI differences correlated with both SH frequency and IAH severity.

Conclusions
MRI for patients with T1D show that IAH is associated with brain changes involving both GM and WM. Further research is needed to elucidate whether the observed differences are a consequence of increased SH episode frequency and increased IAH severity.
Ambient dose during intraoral radiography with current techniques: part 3: effect of tube voltage
Authors: Hoogeveen Reinier Cornelis , van Beest Dirk , Berkhout Erwin 
Published: November 2020

Objectives: This study was conducted to assess the impact of tube voltage on ambient dose during intraoral radiography, specifically remnant-beam transmission and scattered radiation. Methods and materials: Remnant-beam and scattered radiation doses were recorded using a phantom at tube voltages of 60, 63, 66 and 70 kV. Mathematical equations depicting their relations were then formulated, and reference values were calculated at the various voltages tested. Total ambient doses per exposure at 60 kV and at 70 kV were compared. Results: Both remnant-beam transmission and scattered radiation increased ~40% by increasing tube voltage from 60 kV to 70 kV, and the relation was linear. A remnant beam transmission reference value of 7.5% was established at 70 kV, as well as a conversion factor of 0.035 µSv/mAs at 1 m for scattered radiation at 60 kV. Given longer exposure times at 60 kV, total ambient dose proved higher at 60 kV than at 70 kV. Conclusion: Higher tube voltage results in higher remnant-beam transmission and more scattered radiation per workload. The relation is linear in the range between 60kV and 70 kV. Remnant-beam transmission at 70 kV is safely assessed at 7.5%. A conversion factor at 60 kV of 0.035 µSv/mAs at 1 m for the scattered radiation dose can be proposed. Total ambient dose per exposure was higher at 60kV than at 70 kV.