bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulation and minimization: Technical advances for factorial experiments designed to optimize clinical interventions
Authors: Kuhn Jocelyn Lara , Sheldrick Radley Christopher , Broder-Fingert Sarabeth , Chu Andrea , Fortuna Lisa , Jordan Megan , Rubin Dana , Feinberg Emily 
Published: July 2019

Abstract
Background

The Multiphase Optimization Strategy (MOST) is designed to maximize the impact of clinical healthcare interventions, which are typically multicomponent and increasingly complex. The MOST framework often relies on factorial experiments to identify which components of an intervention are most effective, efficient, and scalable. When assigning participants to conditions in factorial experiments, researchers must be careful to select the assignment method that will result in balanced sample sizes and equivalence of covariates across conditions without being predictable. Historically, procedures most often include simple randomization and stratification with blocking; minimization is an increasingly utilized method that assigns participants to the condition that minimizes differences in covariates and sample size across study conditions.

Methods

In the context of a MOST optimization trial with a 2x2x2x2 factorial design (4 components, 16 cells), we used computer simulation to empirically test three subject assignment methods: simple randomization, stratification with blocking, and minimization. We compared these methods with respect to: sample size balance across condition, equivalence across conditions on key covariates, and unpredictability of assignments. Leveraging an existing dataset to compare three different allocation methods, we conducted 250 computerized simulations using bootstrap samples of 304 participants, which was the planned sample size for the proposed study.

Result

Simple randomization, the most unpredictable subject allocation method, generated the least balance of sample and equivalence of covariates across the 16 study cells. Stratification with blocking performed well on stratified variables, and resulted in similar sample balance and predictability as minimization. In contrast, minimization, which had a higher degree of complexity and cost, was most successful in achieving balanced sample sizes and equivalence across a large number of covariates.

Conclusions
Unlike simple randomization, minimization procedures and stratification with blocking are both methodologically sound options for factorial designs. Based on the computer simulation results and priorities within context of this MOST optimization trial, minimization was selected as the optimal subject allocation method. Minimization is utilized infrequently in randomized experiments but represents an important technical advance that should be considered by researchers implementing multi-arm and factorial studies.
The Methods and Baseline Characteristics of a VA Randomized Controlled Study Evaluating Supported Employment Provided in Primary Care Patient Aligned Care Teams
Authors: Davis Lori L. , Blansett Catherine M. , Mumba Mercy N. , MacVicar David , Toscano Richard , Pilkinton Patricia , Gay Whitney , Bartolucci Al 
Published: July 2019

Abstract
Background
This article describes the design and baseline sample of a single-site trial comparing Individual Placement and Support (IPS) supported employment delivered within a Veterans Health Administration (VHA) primary care Patient Aligned Care Team (PACT) to treatment-as-usual (TAU) vocational rehabilitation that includes transitional work for U.S. military veterans.

Methods
Unemployed veterans who were receiving care in a PACT, eligible for vocational rehabilitation, and diagnosed with a mental health diagnosis other than a psychotic or bipolar I disorder were prospectively randomized to either IPS or TAU. Employment outcomes and measures of quality of life, self-esteem, and community reintegration are being collected for 12 months.

Results
The participant sample (n=119) is comprised of 18.5% female, 69.2% African-Americans, and 4.2% Hispanic. Average age is 38.2 (SD ± 8.41) years; 80.7% served in the military since 2001; 78% are receiving or applying for U.S. Department of Veterans Affairs (VA) service-connected disability; 26.9% have not held a competitive job in the past 3 years; and the average length of pre-randomization unemployment is 1.4 (SD ± 2.3) years.

Conclusions
Unique design features include evaluating the efficacy of an evidenced-based IPS within the primary care setting, having broad diagnostic eligibility, and defining the primary outcome criterion as “steady employment”, i.e. holding a competitive job for ≥26 weeks of the 12-month follow-up period. Feasibility of IPS delivery in PACT is discussed. The findings illustrate the characteristics of a primary care veteran sample in need of employment services.
Awareness and Attitudes toward Corneal Donations among Applicants and Staff of a Driver, Vehicle and Licensing Authority (DVLA) in Ghana
Authors: Lartey Seth , ANTWI-ADJEI ELLEN KONADU , Agyapong Solomon , Mohammed Abdul-Kabir , Mensah Derrick N.O. , Genego Edward S 
Published: July 2019

Abstract
Background: Corneal transplantations are surgeries performed for irreparable corneal diseases and damage. However, there is a gap between the number of potential recipients and the number of donor corneas available. The main aim of the study was to determine the awareness and attitudes toward corneal donation among applicants and staff of DVLA, Kumasi-Ghana.
Methods: A descriptive cross-sectional study was conducted. 100 participants were selected using convenient sampling method. A structured questionnaire was used to elicit responses from participants concerning awareness and attitudes toward corneal transplant.
Results: The mean ± SD age of the participants was 32.05 ± 11.48years and age range, 18-67years. Males were 66% whilst females constituted 34%. 32.7% of the participants were aware of corneal donation. Majority of the participants were Christians (83.1%) and Singles (63%). Television was the source of information with the highest preponderance (49.4%). 67.3% were willing to donate their corneas after death. 63.9% were willing to indicate their donor statuses on drivers’ license form which had a significant association with willingness to donate cornea after death (p<0.05, ᵪ2= 12.187).
Conclusion: There is a poor level of awareness (32.7%) of transplant and donation amongst the study population but a good level of willingness to donate organs (67%). Consent via driving license would seem to be a good potential mode of obtaining consent to supplement the harvesting of adequate tissues for transplant if adequate awareness is created.
Impact of the Umoyo mother-infant pair model on HIV-positive mothers’ social support, perceived stigma and 12-month retention of their HIV-exposed infants in PMTCT Care: Evidence from a cluster randomised control trial in Zambia
Authors: Phiri Sydney Chauwa , Mudhune Sandra , Prust Margaret L , Haimbe Prudence , Shakwelele Hilda , Chisenga Tina , Mubiana-Mbewe Mwangelwa , Mzumara Maureen , McCarthy Elizabeth , Prescott Marta R 
Published: July 2019

Abstract
Background

Public health systems in resource-constrained settings have a critical role to play in the elimination of HIV transmission but are often financially constrained. This study is an evaluation of a mother-infant-pair model called “Umoyo”, which was designed to be low cost and scalable in a public health system. Facilities with the Umoyo model dedicate a clinic day to provide services to only HIV-exposed-infants (HEIs) and their mothers. Such models are in operation with reported success in Zambia but have not been rigorously tested. This work establishes whether the Umoyo model would improve 12-month retention of HEIs.
Methods
A cluster randomized trial including 28 facilities was conducted across two provinces of Zambia to investigate the impact on 12-month retention of HEIs in care. These facilities were offering prevention of mother to child transmission (PMTCT) services and supported by the same implementing partner. Randomization was achieved by use of the covariate constrained optimization technique. Secondary outcomes included the impact of Umoyo clinics on social support and perceived HIV stigma among mothers. For each of the outcomes, a difference-in-difference analysis was conducted at the facility level using the unweighted t-test.
Results
From 13 control (12-month retention at endline: 45%) and 11 intervention facilities (12-month retention at endline: 33%), it was found that Umoyo clinics had no impact on 12-month retention of HEIs in the t-test (-11%; 99% CI: -40.1%, 17.2%). Regarding social support and stigma, the un-weighted t-test showed no impact though sensitivity tests showed that Umoyo had an impact on increasing social support (0.31; 99% CI: 0.08, 0.54) and reducing perceived stigma from health care workers (-0.27: 99% CI: -0.46, -0.08).
Conclusion
The Umoyo approach of having a dedicated clinic day for HEIs and their mothers did not improve retention of HEIs though there are indications that it can increase social support among mothers and reduce stigma. Without further support to the underlying health system, based on the evidence generated through this evaluation, the Umoyo clinic day approach on its own is not considered an effective intervention to increase retention of HIV-exposed infants.
Intravenous thrombolytic therapy for acute ischemic stroke in Hubei, China: a survey of thrombolysis rate and barriers
Authors: Zhou Yanfeng , Yan Shijiao , Song Xingyue , Gong Yanhong , Li Wenzhen , Wang Mengdie , Yin Xiaoxv , Hu Bo , Lu Zuxun 
Published: July 2019

Abstract
Background

Rates of thrombolysis in most countries are well below best practice benchmarks. We aimed to investigate thrombolysis utilization and its associated factors in acute ischemic stroke (AIS) patients in Hubei province, China, to assess neurologists’ experiences of the treatment, and to identify barriers against the treatment from perspective of AIS patients and neurologists.

Methods

Survey of 2096 AIS patients and 709 neurologists from 66 hospitals was conducted in Hubei province between 2014 and 2015. A multivariable logistic regression model was utilized to identify the factors associated with thrombolysis utilization and neurologists’ experiences with thrombolysis.

Results

Of the 2096 AIS patients, only 3.8% received thrombolysis. Of the 709 neurologists, 66.0% reported using thrombolysis for AIS patients. The main reasons for not using thrombolysis were late arrival of patients, fear of the risk of complications of thrombolysis, and light or quickly recovered stroke symptoms. The behavior and clinical characteristics of patients, including early admission to hospital (odds ratio [OR]=5.81, 95% confidence intervals [CI] 3.31-10.20), using emergency medical services to be hospitalized (OR=3.36, 95% CI 2.00-5.62), stroke history (OR=0.53, 95% CI 0.28-0.99), and National Institute of Health Stroke Scale score < 4 (OR=0.46, 95% CI 0.27-0.77) were shown to significantly affect the thrombolysis utilization in the multivariate model. In addition, hospital grade (OR=2.84, 95% CI 1.84-4.37), education level (OR=2.49, 95% CI 1.09-5.73), and working years (OR=1.88, 95% CI 1.18-3.00) were strongly associated with neurologists’ experiences of thrombolysis.

Conclusions

A very low proportion of AIS patients received thrombolysis in Hubei province, China. Considerable education programs and interventions were required regarding knowledge of stroke treatment for clinicians and proper behavior after stroke for AIS patients and their families.
A randomized controlled trial of the effect of supervised progressive cross-continuum strength training and protein supplementation in older medical patients: the STAND-Cph trial
Authors: Pedersen Mette Merete , Petersen Janne , Beyer Nina , Juul-Larsen Helle Gybel , Jensen Pia Søe , Andersen Ove , Bandholm Thomas 
Published: July 2019

Abstract
Background: During hospitalization, older adults (+65) are inactive, which puts them at risk of functional decline and loss of independence. Systematic strength training can prevent loss of functional performance and combining strength training with protein supplementation may enhance the response on muscle mass and strength. However, we lack knowledge about the effect of strength training commenced during hospitalization and continued after discharge in older medical patients. This assessor-blinded, randomized study investigated the effect of a simple, supervised strength training program for the lower extremities, combined with post-training protein supplementation during hospitalization and in the home setting for 4 weeks after discharge on change in mobility in older medical patients.
Methods: Older medical patients (≥65 yrs) admitted acutely from their home to the Emergency Department were randomized to either standard care or supervised progressive strength training and an oral protein supplement during hospitalization and at home 3 days/week for 4 weeks after discharge. The primary outcome was between-group difference in change in mobility from baseline to 4 weeks after discharge assessed by the De Morton Mobility Index, which assesses bed mobility, chair mobility, static and dynamic balance, and walking. Secondary outcomes were 24-hour mobility, lower extremity strength, gait speed, grip strength and Activities of Daily Living.
Results: Eighty-five patients were randomized to an intervention group (N=43) or a control group (N=42). In the intervention group, 43% were highly compliant with the intervention. Our intention to treat analysis revealed no between-group difference in mobility (mean difference in change from baseline to 4 weeks: -4.17 (95 % CI: -11.09;2.74; p=0.24) nor in any of the secondary outcomes. The per protocol analysis showed that the intervention group increased significantly more in the daily number of steps taken compared to the control group (mean difference in change from baseline to 4 weeks: 1024.7 steps (95 % CI: 0.7;2048.6); p<0.05; adjusted for mobility at baseline).
Conclusions: Simple supervised strength training for the lower extremities, combined with protein supplementation initiated during hospitalization and continued at home for 4 weeks after discharge was not superior to usual care on change in mobility at 4 weeks in older medical patients. For the secondary outcome, daily number of steps, high compliance with the intervention resulted in a higher daily number of steps. Less than half of the patients were compliant with the intervention indicating that a simpler intervention might be needed.
Trial registration: NCT01964482, https://clinicaltrials.gov/ct2/show/NCT01964482, registration date: October 14, 2013, trial protocol: PubMed ID (PMID): 27039381.
Impairment of visual acuity and retinal morphology following resolved chronic central serous chorioretinopathy
Authors: Gawęcki Maciej , Jaszczuk-Maciejewska Agnieszka , Jurska-Jaśko Anna , Kneba Małgorzata , Grzybowski Andrzej 
Published: July 2019

Abstract
Purpose
Central serous chorioretinopathy(CSCR) is a complex ocular entity that, in its chronic form, can lead to serious visual impairment and morphological damage to the retina.
The aim of the current retrospective study was to evaluate the damage present after long-standing but resolved central serous chorioretinopathy and refer it to healthy individuals. Correlations between measurable factors—for example, duration of the disease, baseline retinal morphological parameters, or patient age and/or their degree of impairment—were also assessed.
Materials and methods
The study group consisted of thirty-two eyes (13 female and 19 male, mean age 49.6 years SD +/- 10.5) with chronic central serous chorioretinopathy ( mean duration 18.9 months SD +/- 15.4) in which complete resolution of subretinal fluid was achieved after subthreshold micropulse laser treatment. Inclusion criterion was a lack of subretinal fluid within the whole area of the central retina scanned by the spectral domain optical coherence tomography. The group was extracted out of 51 cases of chronic CSCR that were treated with that method. They were analyzed according to final best-corrected visual acuity and retinal morphological parameters as measured by spectral optical coherence tomography with angiography option (OCTA). Results were compared with the outcomes of a control group, which consisted of 40 eyes of healthy individuals with full distance visual acuity (0.0 logMAR, 1.0 Snellen) never treated with subthreshold micropulse laser. Statistical analysis included regarding correlation between final visual acuity and final central retinal thickness and retinal and functional parameters prior to treatment.
Results
Final best-corrected visual acuity after chronic central serous chorioretinopathy was 0.23 logMAR (0.6 Snellen) and central retinal thickness was 39.32 µm smaller than in controls. No correlation was found between final visual acuity and retinal thickness and duration of the disease, patient age, and baseline morphological retinal parameters. OCTA scans revealed impaired choriocapillaries flow signal even following resolution of the disease.
Conclusion
Chronic central serous chorioretinopathy is a potentially damaging clinical entity that results in serious visual impairment, retinal thinning, and choroidal flow defects. Further research is needed to determine precisely the timepoint of this damage.
In vitro examination of the thrombolytic efficacy of tenecteplase and therapeutic ultrasound compared to rt-PA
Authors: Frühwald Tobias , Gärtner Ulrich , Stöckmann Nils , Marxsen Jan-Henning , Gramsch Carolin , Roessler Florian Carolus 
Published: July 2019

Abstract
Background: Optimizing thrombolytic therapy is vital for improving stroke outcomes. We aimed to develop standardized thrombolysis conditions to evaluate the efficacy of tenecteplase (TNK) compared to the current gold standard rt-PA (alteplase), with and without additional ultrasound treatment. We also wanted to introduce a new analytical approach to quantify fibrin fiber density in transmission electron microscopy (TEM).

Methods: In vitro clots that are similar to ex vivo clots concerning their histological condition and their durability were generated from whole blood. For five treatment groups we compared relative clot weight loss (each n=60) and fibrin fiber density in TEM (each n=5). The control group (A) was treated only with plasma. Two groups were designated for each rt-PA (B+C) and TNK (D+E). Groups C and E were additionally treated with ultrasound. Dosages were 50µg/ml for rt-PA and 30µg/ml for TNK. Results were evaluated by using analyses of variance (ANOVA) and post-hoc t-tests.

Results: Weight loss was increased significantly for all groups compared to the control group. Both TNK groups showed significantly increased weight loss compared to their counterpart rt-PA group (p≤0.001). For TEM only group D showed significantly decreased fibrin fiber density (p<0.05) compared to both rt-PA groups. Ultrasound did not significantly increase dissolution of clots with either method (best p=0.16).

Conclusions:
Tenecteplase dissolved clots more effectively than rt-PA with and without ultrasound. A higher sample size could provide more convincing results for TEM.
Effects of motor imagery training of gait in Parkinson´s disease: a protocol for a randomized clinical trial
Authors: Nascimento Isaíra Almeida Pereira da Silva , Santiago Lorenna , De Souza Aline Alves , Pegado Camila De Lima , Ribeiro Tatiana , Lindquist Ana Raquel 
Published: July 2019

Abstract
Background

Gait disorders in individuals with Parkinson’s Disease (PD) may be associated with alterations in the motor control system and aggravated by psychoemotional and cognitive issues. Therapeutic strategies aimed at self-perception and motor regulation seem to be promising. Motor imagery (MI) has been shown to be one of these strategies, but there is still no clear evidence of its applicability in this population. The aim of this trial is to determine the effects of motor imagery training on the gait and electroencephalographic activity of individuals with PD.

Methods/Design

The sample consisted of 40 individuals, aged between 45 and 75 years, in the mild and moderate phase of the disease, with the ability to generate voluntary mental images. They will be assessed for cognitive level, degree of physical disability, mental image clarity, kinematic gait variables, electroencephalographic activity and mobility. Next, subjects will be randomly assigned to an experimental (EG) and control group (CG). The EG will perform motor imagery and gait, while the CG will only engage in gait exercises. Twelve training sessions will be conducted lasting up to 90 minutes each, 3 times a week, for 4 weeks. They will be reassessed on the kinematic variables of gait, electroencephalographic activity and mobility, one, seven and thirty days after the final training session.

Discussion

The results may provide an important advance in neurological rehabilitation. An easy-access and low-cost intervention may help improve gait, electroencephalographic activity and mobility in individuals with PD.
Pragmatic randomised trial of a smartphone app (NRT2Quit) to improve effectiveness of nicotine replacement therapy in a quit attempt by improving medication adherence - results of a prematurely terminated study
Authors: Herbec Aleksandra , Brown Jamie , Shahab Lion , West Robert , Raupach Tobias 
Published: July 2019

Abstract
Background: Nicotine replacement therapy (NRT) bought over the counter (OTC) appears to be largely ineffective for smoking cessation, which may be partially explained by poor adherence. We developed and evaluated the NRT2Quit smartphone app (for iOS) designed to improve quit attempts with OTC NRT by improving adherence to the medications.

Methods: A pragmatic double-blind randomized controlled trial with remote recruitment through leaflets distributed to over 300 UK-based community pharmacies. The study recruited adult daily smokers (≥10 cig/day) who bought NRT, wanted to quit smoking, downloaded NTR2Quit and completed the registration process within the app. Participants were automatically randomized within the app to the intervention (full) version of NRT2Quit or to its control (minimal) versions. The primary outcome was biochemically-verified 4-week abstinence assessed at 8-week follow-up using Russell Standard criteria and intention-to-treat. Bayes factors were calculated for the cessation outcome. Secondary outcomes were self-reported abstinence, NRT use, app use and satisfaction with the app.

Results: The study under-recruited with only 41 participants (3.5% of the target sample) randomly assigned to NRT2Quit (n=16) or the control (n=25) app versions between March 2015-September 2016. The follow-up rate was 51.2%. The intervention participants had numerically higher biochemically-verified quit rates (25.0% vs 8.0%, p=0.19, OR=3.83,0.61-24.02). The Bayes factor calculated was 1.92 showed the data were insensitive to test for the hypothesis that the intervention app version aided cessation. The intervention participants had higher median logins (2.5 vs. 0, p=0.01), were more likely to use NRT at follow-up (100.0% vs. 28.6%, p=0.03) and recommend NRT2Quit to others (100.0% vs. 28.6%, p=0.01).

Conclusions: Despite very low recruitment there was preliminary but inconclusive evidence that NRT2Quit may improve short-term abstinence and adherence among smokers using nicotine replacement therapy. Well-powered studies on NRT2Quit are needed, but different recruitment methods will be required to engage smokers through community pharmacies or other channels.