bluuebunny/crossref_metadata_2025_split huggingface dataset:
Manual acupuncture versus sham acupuncture and usual care for the prevention of primary dysmenorrhea (PD): study protocol for a randomized controlled trial
Authors: Yu Lingling , Liu Shiqin , Zheng Cuihong , Liu Wenhua , Wang Hua , Liang Fengxia , Lu Wei , Xu Shabei , Wang Wei 
Published: September 2020

Abstract
Background
Primary dysmenorrhea (PD) is a leading cause of dysmenorrhea among adolescent girls. Manual acupuncture may be considered as an effective treatment for PD, but high-quality evidence remains limited. This trial aims to evaluate the efficacy and safety of acupuncture for the prevention of PD as compared with sham acupuncture and usual care.

Methods/design
This is a three-arm, randomized, controlled clinical trial in which the patients, assessors, and statisticians will be blinded. A total of 300 acupuncture-naive patients who were diagnosed as PD will be randomly allocated to the verum acupuncture, sham acupuncture, or usual care groups in a 2:2:1 ratio. Patients in the verum acupuncture group will receive manual acupuncture at specific acupuncture points with penetrating needling, while those in the sham acupuncture group will receive non-penetrating needling at non-acupuncture points. They will be given five sessions over a menstrual cycle for 3 menstrual cycles. Patients in the usual care group will receive health education and informed to receive manual acupuncture for free after waiting for 7 menstrual cycles. The primary outcome will be the change from baseline in the Cox Menstrual Symptom Scale Score (CMSS). The secondary outcomes will be the changes in Massachusetts General Hospital Acupuncture Sensation Scale (MASS), visual analog scale (VAS), Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2), Pittsburgh Sleep Quality Index (PSQI), Beck Anxiety Inventory (BAI), Beck Depression Inventory II (BDI- II), Acupuncture Expectancy Scale (AES), 60-item NEO Personality Inventory-Short Form (NEO-FFI), and acute medication intake. The adverse events will be recorded at every visit. The analyses will be performed base on a full analysis set (FAS) and a per-protocol set (PPS).

Discussion
This study may provide high-quality evidence regarding the efficacy and safety of manual acupuncture for PD. In addition, the results of this study will help to identify the efficacy of acupuncture due to the specific effects of acupuncture or placebo effects of acupuncture ritual.

Trial registration
Clinical Trials.gov NCT02783534. Registered on 26 May 2016
Personalised health education against health damage of COVID-19 epidemic in the elderly Hungarian population (PROACTIVE-19): protocol of an adaptive randomised controlled clinical trial
Authors: Erőss Bálint , Molnár Zsolt , Szakács Zsolt , Zádori Noémi , Szakó Lajos , Váncsa Szilárd , Juhász Márk Félix , Ocskay Klementina , Vörhendi Nóra , Márta Katalin , Szentesi Andrea , Párniczky Andrea , Hegyi Péter J. , Kiss Szabolcs , Földi Mária , Dembrovszky Fanni , Kanjo Anna , Pázmány Piroska , Varró András , Csathó Árpád , Helyes Zsuzsanna , Péterfi Zoltán , Czopf László , Kiss István , Zemplényi Antal , Czapári Dóra , Hegyi Eszter , Dobszai Dalma , Miklós Emőke , Márta Attila , Tóth Dominika , Farkas Richard , Farkas Nelli , Birkás Béla , Pintér Erika , Pethő Gábor , Zsigmond Borbála , Sárközi Andrea , Nagy Anikó , Hegyi Péter 
Published: September 2020

Abstract
Background
Early reports indicate that COVID-19 may require intensive care unit (ICU) admission in 5–26% and overall mortality can rise to 11% of the recognised cases, particularly affecting the elderly. There is a lack of evidence-based targeted pharmacological therapy for its prevention and treatment.
We aim to compare the effects of a World Health Organization recommendation-based education and a personalised complex preventive lifestyle intervention package (based on the same WHO recommendation) on the outcomes of the COVID-19.

Methods
PROACTIVE-19 is a pragmatic, randomised controlled clinical trial with adaptive “sample size re-estimation” design. Hungarian population over the age of 60 years without confirmed COVID-19 will be approached to participate in a telephone health assessment and lifestyle counselling voluntarily. Volunteers will be randomised into two groups: (A) general health education and (B) personalised health education. Participants will go through questioning and recommendation in 5 fields: (1) mental health, (2) smoking habits, (3) physical activity, (4) dietary habits, and (5) alcohol consumption. Both groups A and B will receive the same line of questioning to assess habits concerning these topics. Assessment will be done weekly during the first month, every second week in the second month, then monthly. The composite primary endpoint will include the rate of ICU admission, hospital admission (longer than 48 h), and mortality in COVID-19-positive cases. The estimated sample size is 3788 subjects per study arm. The planned duration of the follow-up is a minimum of 1 year.

Discussion
These interventions may boost the body’s cardiovascular and pulmonary reserve capacities, leading to improved resistance against the damage caused by COVID-19. Consequently, lifestyle changes can reduce the incidence of life-threatening conditions and attenuate the detrimental effects of the pandemic seriously affecting the older population.

Trial registration
The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (IV/2428- 2 /2020/EKU) and has been registered at clinicaltrials.gov (NCT04321928) on 25 March 2020.
Prophylactic prednisolone for the prevention of early and intermediate adverse effects of radioactive iodine therapy in patients with thyroid cancer: study protocol for a single-centre, phase II/III, randomized, double-blinded, placebo-controlled clinical trial
Authors: Jayarajah Umesh , Wijekoon Mahilal , Seneviratne Sanjeewa A. 
Published: September 2020

Abstract
Background
Radioactive iodine (RAI) therapy is the standard adjuvant treatment for differentiated thyroid cancer (i.e. papillary and follicular). RAI is associated with troublesome early, intermediate and late adverse effects. Although glucocorticoids are used for the management of these adverse effects, there is little evidence regarding the effectiveness of prophylactic glucocorticoids to prevent these complications. This trial will evaluate the efficacy of a short course of prophylactic glucocorticoids in the prevention of adverse effects of RAI treatment in patients with differentiated thyroid cancer.

Methods
A phase II/III, single-centre, randomized, double-blinded, placebo-controlled, parallel-arm clinical trial will be conducted. Patients with differentiated thyroid cancer who are referred to RAI therapy at the National Cancer Institute, Sri Lanka, will be randomized into two arms consisting of 200 patients each. The experimental group will receive prophylactic oral prednisolone 0.5 mg/kg and omeprazole 20 mg single dose 6 h before RAI therapy followed by oral prednisolone 0.5 mg/kg and omeprazole 20 mg daily for 3 days. The control group will receive oral placebo and omeprazole 20 mg single dose 6 h before RAI therapy followed by oral placebo and omeprazole 20 mg daily for 3 days. Clinically significant adverse effects assessed as related to RAI as well as prednisolone therapy and the quality of life parameters will be compared between the two groups.

Discussion
If proven beneficial, this intervention can be incorporated into the standard practice to reduce early and intermediate adverse effects of RAI for thyroid cancer with a potential improvement of quality of life.

Trial registration
Sri Lanka Clinical Trials Registry SLCTR/2020/009. Registered prospectively on 23 February 2020. Items of the WHO Trial Registration Data Set are provided in the supplementary file.
Effect of medically lowering intraocular pressure in glaucoma suspects with high myopia (GSHM study): study protocol for a randomized controlled trial
Authors: Lin Feng Bin , Da Chen Shi , Song Yun He , Wang Wei , Jin Ling , Liu Bing Qian , Liu Yu Hong , Chen Mei Ling , Gao Kai , Friedman David S. , Jonas Jost B. , Aung Tin , Lv Lin , Liu Yi Zhi , Zhang Xiu Lan ,   on behalf of the GSHM study group, Zhang Xiu Lan , Liu Yi Zhi , Lv Lin , Friedman David S. , Jonas Jost B. , Aung Tin , Da Chen Shi , Wang Wei , Lin Feng Bin , Song Yun He , Li Fei , Gao Kai , Liu Bing Qian , Liu Yu Hong , Chen Mei Ling , Bressler Neil M. , Park Ki Ho , He Ming Guang , Cheng Ching-yu , Healey Paul , Chen Xiang , Tang Guang Xian , Jin Ling 
Published: September 2020

AbstractBackgroundCurrently, whether and when intraocular pressure (IOP)-lowering medication should be used in glaucoma suspects with high myopia (GSHM) remains unknown. Glaucoma suspects are visual field (VF) defects that cannot be explained by myopic macular changes or other retinal and neurologic conditions. Glaucoma progression is defined by VF deterioration. Here we describe the rationale, design, and methodology of a randomized controlled trial (RCT) designed to evaluate the effects of medically lowering IOP in GSHM (GSHM study).MethodsThe GSHM study is an open-label, single-center, RCT for GSHM. Overall, 264 newly diagnosed participants, aged 35 to 65 years, will be recruited at the Zhongshan Ophthalmic Center, Sun Yat-sen University, between 2020 and 2021. Participants will be randomly divided into two arms at a 1:1 ratio. Participants in the intervention arm will receive IOP-lowering medication, while participants in the control arm will be followed up without treatment for 36 months or until they reach the end point. Only one eye per participant will be eligible for the study. If both eyes are eligible, the eye with the worse VF will be recruited. The primary outcome is the incidence of glaucoma suspect progression by VF testing over 36 months. The secondary outcomes include the incidence of changes in the optic nerve head morphology including the retinal nerve fiber layer, and retinal ganglion cell-inner plexiform layer loss, progression of myopic maculopathy, visual function loss, and change in the quality of life. Statistical analyses will include baseline characteristics comparison between the intervention and control groups using a two-samplet-test and Wilcoxon rank sum test; generalized linear models with Poisson regression for the primary outcome; Kaplan-Meier curve and log-rank test for the incidence of the secondary outcome; and longitudinal analyses to assess trends in outcomes across time.DiscussionTo the best of our knowledge, the GSHM study is the first RCT to investigate the impact of medically lowering IOP in GSHM. The results will have implications for the clinical management of GSHM.Trial registrationClinicalTrials.gov NCT04296916. Registered on 4 March 2020
Cognitive-behavioral family therapy as psychoeducation for adolescents with high-functioning autism spectrum disorders: Aware and Care for my Autistic Traits (ACAT) program study protocol for a pragmatic multisite randomized controlled trial
Authors: Oshima Fumiyo , William Mandy , Takahashi Noriko , Tsuchiyagaito Aki , Kuwabara Hitoshi , Shiina Akihiro , Seto Mikuko , Hongo Minako , Iwama Yui , Hirano Yoshiyuki , Sutoh Chihiro , Taguchi Kayoko , Yoshida Tokiko , Kawasaki Yohei , Ozawa Yoshihito , Masuya Jiro , Sato Noriyuki , Nakamura Shizuka , Kuno Masaru , Takahashi Jumpei , Ohtani Toshiyuki , Matsuzawa Daisuke , Inada Naoko , Kuroda Miho , Ando Mika , Hori Arinobu , Nakagawa Akiko , Shimizu Eiji 
Published: September 2020

Abstract
Background
One aim of an autism spectrum disorder (ASD) diagnosis is to obtain special support for the disorder, though this does not guarantee practical support. We developed a psychoeducational program using cognitive-behavioral therapy (CBT) and Aware and Care for my Autistic Traits (ACAT) for Japanese adolescents with high-functioning ASD and their parents.

Methods
This multisite study is a randomized controlled trial. In total, 24 participants will be assigned to the ACAT group and 24 to the treatment-as-usual (TAU) group. The ACAT group will receive a weekly 100-min session for 6 weeks, regular medical care, and one follow-up session. In this ongoing clinical trial, we will compare the scores of the measures recorded in the pre- and post-intervention stages between the ACAT and TAU groups. A total of 41 patients out of a target of 48 have participated in the trial to date. The primary outcome measure is the Autism Knowledge Questionnaire. Secondary outcome measures include Barriers to Access to Care Evaluation 3rd Edition, the Strengths and Difficulties Questionnaire, the Vineland Adaptive Behavior Scales second edition, the Parenting Resilience Elements Questionnaire, the General Health Questionnaire 12, and the Depression Self-Rating Scale for Children assessments, as well as an electroencephalographic recording.

Discussion
It is expected that participants in the ACAT group will significantly increase their self-understanding and awareness of ASD symptoms compared to those in the TAU group. Additionally, the ACAT group is expected to exhibit improved social adaptation and mental health if children and parents are able to better understand the ASD characteristics through sessions. This intervention will contribute to the establishment of an effective evidence-based treatment strategy for adolescents with ASD.

Trial registration
UMIN Register 000029851. Registered on January 06, 2018
Moving fast but going slow: coordination challenges for trials of COVID-19 post-exposure prophylaxis
Authors: Tan Darrell H. S. , Agrawal Rupesh , Barnabas Ruanne V. , Giles Jon T. , Dull Peter 
Published: September 2020

AbstractAn unprecedented volume of research has been generated in response to the COVID-19 pandemic. However, there are risks of inefficient duplication and of important work being impeded if efforts are not synchronized. Excessive reliance on observational studies, which can be more rapidly conducted but are inevitably subject to measured and unmeasured confounders, can foil efforts to conduct rigorous randomized trials. These challenges are illustrated by recent global efforts to conduct clinical trials of post-exposure prophylaxis (PEP) as a strategy for preventing COVID-19. Innovative strategies are needed to help overcome these issues, including increasing communication between the Data Safety and Monitoring Committees (DSMCs) of similar trials. It is important to reinforce the primacy of high-quality trials in generating unbiased answers to pressing prevention and treatment questions about COVID-19.
Randomized controlled clinical trial evaluating the efficacy of hyperbaric oxygen therapy in facilitating the healing of chronic foot ulcers in diabetic patients: the study protocol
Authors: Lopes Jocefábia Reika Alves , D’Agostino Dias Mariza , Correa João Antonio , Batalha Maria Alice Bragagnolo , Guerra Luanda Karla Dantas 
Published: September 2020

Abstract
Background
Diabetic limb ulcers are highly prevalent and contribute to a significant increase in cost for the treatment of these patients in health services. However, healing of these wounds is a major health problem and may even lead to amputation. The primary aim of the current study is to evaluate the efficacy of hyperbaric oxygen therapy (HBOT) in facilitating the healing of diabetic foot ulcers, in addition to secondarily evaluating whether it reduces the number of amputations and improves the quality of life in these patients.

Methods
A non-blind randomized clinical study will be conducted in the city of Imperatriz, Maranhão state, Brazil, from 2019 to 2020, in diabetic patients with chronic foot ulcers (classified as Wagner grades 2, 3 and 4, persisting for more than 1 month). The outpatient follow-up for diabetic foot patients will be done at the Unified Health System, with a sample size of 120 patients (the randomization allocation will be 1:1, being 60 patients for each arm). Half of the patients will receive standard treatment, i.e. dressings, debridement, antibiotics and load relief, along with HBOT (HBOT group), and the other half will receive only standard treatment (control group). The patients of the HBOT group will be evaluated upon admission, after 10, 20, 30 and 35 HBOT sessions, and after 6 months and 1 year. The patients of the control group will also be evaluated at equivalent periods (upon admission, after 2, 4, 6 and 7 weeks, 6 months and 1 year). The SF-36 quality of life questionnaire will be filled upon admission and after 3 months of follow-up in both groups. The primary and secondary endpoints will be assessed with 1 year of follow-up.

Discussion
Diabetic foot ulcers are a highly prevalent complication of diabetes with serious consequences. A study to assess the efficacy of HBOT in healing the ulcers and reducing the rate of amputations in diabetic patients is justified, which will eventually aid in the development of guidelines for treating these ulcers.

Trial registration
Registration number RBR-7bd3xy. Registered on 17 July 2019—Retrospectively registered.
Sampling scale and season influence the observed relationship between the density of deer and questing Ixodes ricinus nymphs
Authors: Dickinson Eleanor R , Millins Caroline , Biek Roman 
Published: September 2020

Abstract
Background
The relationship between environmentally transmitted tick parasites, Ixodes spp., and their main reproductive host, deer, is generally thought to be positive. However, measuring host abundance and density directly can be challenging and indirect methods are often used. The observed relationship between the parasite and host may be affected by sampling scale and season, which could lead to different inferences being made. Here, we aimed to test the effect of sampling scale and season on the relationship between density of deer and the density of questing Ixodes ricinus nymphs.

Methods
The density of deer (primarily Dama dama) was estimated using line transect distance sampling of deer dung quantified in different seasons (winter and summer) and measured at three different nested scales (site, transect and observation level). Questing nymph density was measured using blanket drag methods and estimates were calculated at the same scales as deer density estimates. General linear models were used to evaluate the relationship between questing nymphs, deer density and other environmental variables at each sampling scale and each season deer density was measured at.

Results
While a positive relationship between deer density and questing nymph density was detected at the site and transect scale, no relationship was apparent at the observation level. This was likely due to increased variation and reduced precision of deer dung counts at the finest sampling scale. Seasonal changes in deer populations were observed likely reflecting seasonal shifts in habitat usage. The summer estimates of deer density explained questing nymph density whereas winter estimates did not.

Conclusions
Our results show that the scale of sampling can affect the detectability of the positive association between host and vector species. Furthermore, such associations can be obscured if hosts exhibit seasonal changes in habitat use. Thus, both sampling scale and season are important to consider when investigating the relationship between host and vector species.
Epidemiology and genotyping of Anaplasma marginale and co-infection with piroplasms and other Anaplasmataceae in cattle and buffaloes from Egypt
Authors: AL-Hosary Amira , Răileanu Cristian , Tauchmann Oliver , Fischer Susanne , Nijhof Ard M. , Silaghi Cornelia 
Published: September 2020

AbstractBackgroundAnaplasma marginaleis an obligate intracellular bacterium and the main cause of bovine anaplasmosis in tropical and subtropical regions. In Egypt, data regarding the prevalence ofA. marginalein ruminant hosts and of the circulating genotypes is lacking. This study therefore aimed to (i) investigate the presence, epidemiology and genotypes ofA. marginalein cattle and buffaloes in Egypt, (ii) to evaluate suitable diagnostic tools and (iii) to identify co-infections ofA. marginalewith other selected tick-borne pathogens.MethodsBlood samples were collected from 394 animals (309 cattle and 85 buffaloes) from three different areas in Egypt. For the detection ofA. marginaleinfection, several tests were compared for their sensitivity and specificity: blood smear analysis, enzyme-linked immunosorbent assay (ELISA), PCR, real-time PCR and reverse line blot (RLB) assay. Co-infections withA. marginale,piroplasms and otherAnaplasmataceaewere surveyed by RLB whileA. marginalegenotypes were identified by amplifying and sequencing the partialmsp1αgene.ResultsAnaplasma marginaleDNA was amplified by qPCR in 68.3% of cattle and 29.4% of buffaloes. RLB showed infection withA. marginalein 50.2% of cattle and 42.5% of buffaloes. Blood smear analysis detected this agent in 16.2% of cattle and 2.4% of buffaloes. ELISA showed specific antibodies againstA. marginalein 54.9% of cattle.Anaplasma marginalewas associated, in cattle and buffaloes, with several tick-borne pathogens (Theileria annulata,Babesia bovis,Babesia bigemina,Babesia occultansandAnaplasma platys). A significant difference ofA. marginaleinfection level was noticed in cattle, where animals between 3–5-years-old had a higher prevalence (79.2%) compared to those older than 5 years (36.4%) and younger than 3 years (59.7%) and one year (64.5%), respectively (P = 0.002281). Microsatellite analysis identified 15 different genotypes.ConclusionsThe epidemiological findings revealed high prevalence ofA. marginalein cattle and buffaloes in all the investigated areas. The circulation of diverse genotypes was observed, most of theseA. marginalegenotypes being specific for Egypt. The qPCR assay was confirmed to be the most sensitive tool for detection ofA. marginalein cattle and buffaloes even in the carrier state, highlighting the importance of using suitable diagnostic tests.