bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of 8 weeks standard treatment (rifampicin plus clarithromycin) vs. 4 weeks standard plus amoxicillin/clavulanate treatment [RC8 vs. RCA4] to shorten Buruli ulcer disease therapy (the BLMs4BU trial): study protocol for a randomized controlled multi-centre trial in Benin
Authors: Johnson Roch Christian , Sáez-López Emma , Anagonou Esaï Sèdjro , Kpoton Godwin Gérard , Ayelo Adjimon Gilbert , Gnimavo Ronald Sètondji , Mignanwande Franck Zinsou , Houezo Jean-Gabin , Sopoh Ghislain Emmanuel , Addo Juliet , Orford Lindsay , Vlasakakis Georgios , Biswas Nandita , Calderon Felix , Della Pasqua Oscar , Gine-March Anna , Herrador Zaida , Mendoza-Losana Alfonso , Díez Gabriel , Cruz Israel , Ramón-García Santiago 
Published: July 2022

Abstract
Background
Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans that affects skin, soft tissues, and bones, causing long-term morbidity, stigma, and disability. The recommended treatment for BU requires 8 weeks of daily rifampicin and clarithromycin together with wound care, physiotherapy, and sometimes tissue grafting and surgery. Recovery can take up to 1 year, and it may pose an unbearable financial burden to the household.
Recent in vitro studies demonstrated that beta-lactams combined with rifampicin and clarithromycin are synergistic against M. ulcerans. Consequently, inclusion of amoxicillin/clavulanate in a triple oral therapy may potentially improve and shorten the healing process.
The BLMs4BU trial aims to assess whether co-administration of amoxicillin/clavulanate with rifampicin and clarithromycin could reduce BU treatment from 8 to 4 weeks.

Methods
We propose a randomized, controlled, open-label, parallel-group, non-inferiority phase II, multi-centre trial in Benin with participants stratified according to BU category lesions and randomized to two oral regimens: (i) Standard: rifampicin plus clarithromycin therapy for 8 weeks; and (ii) Investigational: standard plus amoxicillin/clavulanate for 4 weeks. The primary efficacy outcome will be lesion healing without recurrence and without excision surgery 12 months after start of treatment (i.e. cure rate). Seventy clinically diagnosed BU patients will be recruited per arm. Patients will be followed up over 12 months and managed according to standard clinical care procedures. Decision for excision surgery will be delayed to 14 weeks after start of treatment. Two sub-studies will also be performed: a pharmacokinetic and a microbiology study.

Discussion
If successful, this study will create a new paradigm for BU treatment, which could inform World Health Organization policy and practice. A shortened, highly effective, all-oral regimen will improve care of BU patients and will lead to a decrease in hospitalization-related expenses and indirect and social costs and improve treatment adherence. This trial may also provide information on treatment shortening strategies for other mycobacterial infections (tuberculosis, leprosy, or non-tuberculous mycobacteria infections).

Trial registration
ClinicalTrials.gov NCT05169554. Registered on 27 December 2021.
Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment (The ATLANTIS trial): protocol for a randomised double-blind placebo-controlled trial in primary care
Authors: Alderson Sarah L. , Wright-Hughes Alexandra , Ford Alexander C. , Farrin Amanda , Hartley Suzanne , Fernandez Catherine , Taylor Christopher , Ow Pei Loo , Teasdale Emma , Howdon Daniel , Guthrie Elspeth , Foy Robbie , Ridd Matthew J. , Bishop Felicity L. , Muir Delia , Chaddock Matthew , Herbert Amy , Cooper Deborah , Gibbins Ruth , Newman Sonia , Cook Heather , Longo Roberta , Everitt Hazel 
Published: July 2022

Abstract

Background
Irritable bowel syndrome (IBS) is a common functional bowel disorder that has a considerable impact on patient quality of life and substantial societal and health care resource costs. Current treatments are often ineffective. Tricyclic antidepressants have shown promise in secondary care populations but their effectiveness in a primary care setting remains unclear.

Methods
ATLANTIS is a randomised, multi-centre, parallel-group, two-arm, double-blind, placebo-controlled trial of low-dose amitriptyline as a second-line treatment for IBS in primary care. Participants will be invited by letter, or recruited opportunistically, from general practices in three regions of England (West Yorkshire, Wessex, and West of England) and screened for eligibility. A total of 518 adult patients with IBS, who are symptomatic despite first-line therapies, will be randomised 1:1 to amitriptyline or identical placebo for 6 months. Treatment will commence at a dose of 10 mg (or one placebo tablet) daily at night, with dose titration up to a maximum of 30 mg at night, depending on side effects and response to treatment. Participant-reported assessments will be conducted at baseline and 3, 6, and 12 months post-randomisation. The primary objective is to determine the effectiveness of amitriptyline, compared with placebo, in improving participant-reported global symptoms of IBS at 6 months (using the IBS Severity Scoring System). Secondary outcomes include relief of IBS symptoms, effect on IBS-associated somatic symptoms (Patient Health Questionnaire-12), anxiety and depression (Hospital Anxiety and Depression Scale), ability to work and participate in other activities (Work and Social Adjustment Scale), acceptability and tolerability of treatment, self-reported health care use, health-related quality of life (EQ-5D-3L), and cost-effectiveness. A nested, qualitative study will explore patient and general practitioner experiences of treatments and trial participation, including acceptability, adherence, unanticipated effects, and implications for wider use of amitriptyline for IBS in primary care.

Discussion
Determining the clinical and cost-effectiveness of low-dose amitriptyline as a second-line treatment for IBS in primary care will provide robust evidence to inform management decisions.

Trial registration
ISRCTN ISRCTN48075063
. Registered on 7th June 2019.
Benzimidazole and aminoalcohol derivatives show in vitro anthelmintic activity against Trichuris muris and Heligmosomoides polygyrus
Authors: Valderas-García Elora , Häberli Cécile , Álvarez-Bardón María , Escala Nerea , Castilla-Gómez de Agüero Verónica , de la Vega Jennifer , del Olmo Esther , Balaña-Fouce Rafael , Keiser Jennifer , Martínez-Valladares María 
Published: July 2022

Abstract
Background
Infections by gastrointestinal nematodes cause significant economic losses and disease in both humans and animals worldwide. The discovery of novel anthelmintic drugs is crucial for maintaining control of these parasitic infections.

Methods
For this purpose, the aim of the present study was to evaluate the potential anthelmintic activity of three series of compounds against the gastrointestinal nematodes Trichuris muris and Heligmosomoides polygyrus in vitro. The compounds tested were derivatives of benzimidazole, lipidic aminoalcohols and diamines. A primary screening was performed to select those compounds with an ability to inhibit T. muris L1 motility by > 90% at a single concentration of 100 µM; then, their respective IC50 values were calculated. Those compounds with IC50 < 10 µM were also tested against the adult stage of T. muris and H. polygyrus at a single concentration of 10 µM.

Results
Of the 41 initial compounds screened, only compounds AO14, BZ6 and BZ12 had IC50 values < 10 µM on T. muris L1 assay, showing IC50 values of 3.30, 8.89 and 4.17 µM, respectively. However, only two of them displayed activity against the adult stage of the parasites: BZ12 killed 81% of adults of T. muris (IC50 of 8.1 µM) and 53% of H. polygyrus while BZ6 killed 100% of H. polygyrus adults (IC50 of 5.3 µM) but only 17% of T. muris.

Conclusions
BZ6 and BZ12 could be considered as a starting point for the synthesis of further structurally related compounds.

Graphical Abstract
The resting behavior of malaria vectors in different ecological zones of Ghana and its implications for vector control
Authors: Forson Akua Obeng , Hinne Isaac A. , Dhikrullahi Shittu B. , Sraku Isaac Kwame , Mohammed Abdul Rahim , Attah Simon K. , Afrane Yaw Asare 
Published: July 2022

Abstract
Background
In sub-Saharan Africa there is widespread use of long-lasting insecticidal nets and indoor residual spraying to help control the densities of malaria vectors and decrease the incidence of malaria. This study was carried out to investigate the resting behavior, host preference and infection with Plasmodium falciparum of malaria vectors in Ghana in the context of the increasing insecticide resistance of malaria vectors in sub-Saharan Africa.

Methods
Indoor and outdoor resting anopheline mosquitoes were sampled during the dry and rainy seasons in five sites in three ecological zones [Sahel savannah (Kpalsogo, Pagaza, Libga); coastal savannah (Anyakpor); and forest (Konongo)]. Polymerase chain reaction-based molecular diagnostics were used to determine speciation, genotypes for knockdown resistance mutations (L1014S and L1014F) and the G119S ace1 mutation, specific host blood meal origins and sporozoite infection in the field-collected mosquitoes.

Results
Anopheles gambiae sensu lato (s.l.) predominated (89.95%, n = 1718), followed by Anopheles rufipes (8.48%, n = 162) and Anopheles funestus s.l. (1.57%, n = 30). Sibling species of the Anopheles gambiae s.l. revealed Anopheles coluzzii accounted for 63% (95% confidence interval = 57.10–68.91) and 27% (95% confidence interval = 21.66–32.55) was Anopheles gambiae s. s.. The mean resting density of An. gambiae s.l. was higher outdoors (79.63%; 1368/1718) than indoors (20.37%; 350/1718) (Wilcoxon rank sum test, Z = − 4.815, P < 0.0001). The kdr west L1014F and the ace1 mutation frequencies were higher in indoor resting An. coluzzii and An. gambiae in the Sahel savannah sites than in the forest and coastal savannah sites. Overall, the blood meal analyses revealed that a larger proportion of the malaria vectors preferred feeding on humans (70.2%) than on animals (29.8%) in all of the sites. Sporozoites were only detected in indoor resting An. coluzzii from the Sahel savannah (5.0%) and forest (2.5%) zones.

Conclusions
This study reports high outdoor resting densities of An. gambiae and An. coluzzii with high kdr west mutation frequencies, and the presence of malaria vectors indoors despite the use of long-lasting insecticidal nets and indoor residual spraying. Continuous monitoring of changes in the resting behavior of mosquitoes and the implementation of complementary malaria control interventions that target outdoor resting Anopheles mosquitoes are necessary in Ghana.

Graphical abstract
An equity analysis on the household costs of accessing and utilising maternal and child health care services in Tanzania
Authors: Binyaruka Peter , Borghi Josephine 
Published: July 2022

Abstract
Background
Direct and time costs of accessing and using health care may limit health care access, affect welfare loss, and lead to catastrophic spending especially among poorest households. To date, limited attention has been given to time and transport costs and how these costs are distributed across patients, facility and service types especially in poor settings. We aimed to fill this knowledge gap.

Methods
We used data from 1407 patients in 150 facilities in Tanzania. Data were collected in January 2012 through patient exit-interviews. All costs were disaggregated across patients, facility and service types. Data were analysed descriptively by using means, medians and equity measures like equity gap, ratio and concentration index.

Results
71% of patients, especially the poorest and rural patients, accessed care on foot. The average travel time and cost were 30 minutes and 0.41USD respectively. The average waiting time and consultation time were 47 min and 13 min respectively. The average medical cost was 0.23 USD but only18% of patients paid for health care. The poorest and rural patients faced substantial time burden to access health care (travel and waiting) but incurred less transport and medical costs compared to their counterparts. The consultation time was similar across patients. Patients spent more time travelling to public facilities and dispensaries while incurring less transport cost than accessing other facility types, but waiting and consultation time was similar across facility types. Patients paid less amount in public than in private facilities. Postnatal care and vaccination clients spent less waiting and consultation time and paid less medical cost than antenatal care clients.

Conclusions
Our findings reinforce the need for a greater investment in primary health care to reduce access barriers and cost burdens especially among the worse-offs. Facility’s construction and renovation and increased supply of healthcare workers and medical commodities are potential initiatives to consider. Other initiatives may need a multi-sectoral collaboration.
Integrated enhanced cognitive behavioural (I-CBTE) therapy significantly improves effectiveness of inpatient treatment of anorexia nervosa in real life settings
Authors: Ibrahim Ali , Ryan Sharon , Viljoen David , Tutisani Ellen , Gardner Lucy , Collins Lorna , Ayton Agnes 
Published: July 2022

AbstractBackgroundInpatient treatment of anorexia nervosa can be lifesaving but is associated with high rates of relapse and poor outcomes. To address this, the Oxford service has adapted the enhanced cognitive behavioural treatment (CBTE) model, first developed for inpatients in Italy to a UK national health service (NHS) setting. In this study, we compared the outcomes from treatment as usual (TAU), integrated CBTE (I-CBTE), and alternative treatment models in routine UK clinical practice.MethodsThis is a longitudinal cohort study, using routinely collected data between 2017 and 2020 involving all adults with anorexia nervosa admitted to specialist units from a large geographical area in England covering a total population of 3.5 million. We compared TAU with (1) I-CBTE (13 weeks inpatient CBTE, restoration to a healthy weight, combined with 7 weeks day treatment followed by 20 weeks of outpatient CBTE; (2) standalone inpatient CBTE (due to insufficient resources since the pandemic; and (3) 6–8 weeks admission with partial weight restoration as crisis management. Primary outcome measures (min. 1 year after discharge from hospital) were defined as: (1) good outcome: Body Mass Index (BMI) > 19.5 and no abnormal eating or compensatory behaviours; (2) poor outcome: BMI < 19.5 and/or ongoing eating disorder behaviours; (3) readmission; or (4) deceased. Secondary outcomes were BMI on discharge, and length of stay.Results212 patients were admitted to 15 specialist units in the UK depending on bed availability. The mean age was 28.9 (18–60) years, mean admission BMI was 14.1 (10–18.3), 80% were voluntary. At minimum 1-year follow up after discharge, 70% of patients receiving I-CBTE and 29% standalone inpatient CBTE maintained good outcomes, in contrast with < 5% TAU and crisis management admission. Readmission rates of I-CBTE were 14.3% vs ~ 50% (χ2 < 0.0001) in the other groups. The main predictors of good outcome were reaching healthy BMI by discharge, I-CBTE and voluntary status. Age, psychiatric comorbidity and length of stay did not predict outcomes. BMI on discharge and length of stay were significantly better in the CBTE groups than in TAU.ConclusionsOur main finding is that in a real-life setting, I-CBTE has superior short- and minimum 1 year outcomes as compared with alternative inpatient treatment models. Dissemination of I-CBTE across the care pathway has the potential to transform outcomes of inpatient treatment for this high-risk patient population and reduce personal and societal costs.
Long-term low-dose exposure of permethrin induces liver and kidney damage in rats
Authors: Sun Ying-Jian , Liang Yu-Jie , Yang Lin , Long Ding-Xin , Wang Hui-Ping , Wu Yi-Jun 
Published: July 2022

Abstract
Background
Permethrin is one of the pyrethroid insecticides, which is widely used in agriculture and public health. Although acute toxicity of the insecticide has been studied, the chronic toxicity upon the long-term exposure has not been clear yet. The purpose of the current study is to investigate the organ toxicities of permethrin following its long-term low-dose exposure.

Methods
Male Wistar rats were daily administrated orally with permethrin (75 mg/kg body weight/day, gavage) for 90 days, and then the samples of biofluids (blood and urine) and organs including liver and kidney were collected. The serum and urine samples were measured by biochemical assay and the tissues of kidney and liver were examined and analyzed by histopathological method.

Results
The results showed that no change was found in serum and urine biochemical parameters for the toxicity; however, significant changes including hyperchromatic nuclei swollen in the hepatic parenchymal cells and the swelling proximal tubules in the kidneys were observed in the tissue structures of liver and kidneys in the histopathological sections.

Conclusion
These results indicate that low-dose long-term exposure of permethrin can cause chronic toxicity with slight liver and kidney damage.
A qualitative study on the involvement of adolescents and young adults (AYAs) with cancer during multiple research phases: “plan, structure, and discuss”
Authors: van Ham Camila Rosalinde , Burgers Vivian Wilhelmina Gerarda , Sleeman Sophia Helena Eva , Dickhout Annemiek , Harthoorn Niels Christiaan Gerardus Laurus , Manten-Horst Eveliene , van Eenbergen Mies Christina , Husson Olga 
Published: July 2022

Abstract
Background
Including the lived experience of patients in research is important to improve the quality and outcomes of cancer studies. It is challenging to include adolescents and young adults (AYAs) cancer patients in studies and this accounts even more for AYAs with an uncertain and/or poor prognosis (UPCP). Little is known about involving these AYAs in scientific research. However, by including their lived experiences during multiple phases of research, the quality of the study improves and therefore also the healthcare and quality of life of this unique patient group. We first aimed to document experiences of AYAs and researchers with AYA involvement initiatives using the Involvement Matrix and the nine phases of the research cycle. Second, we aimed to map the (expected) challenges and recommendations, according to patients and researchers, for AYA involvement in each research phase.

Methods
Thirteen semi-structured qualitative interviews were conducted with AYAs and researchers from February 2020 to May 2020. A thematic analysis codebook with a critical realistic framework was used to analyze the data.

Results
AYAs and researchers were predominantly positive about AYA involvement within six of the nine phases of research: identify and prioritize topics, develop study design, disseminate information, implement, and evaluate findings. Not all respondents were positive about AYA involvement in the following three phases: formulate research questions, conduct research, and analysis and interpretation. However, few respondents had experience with AYA-researcher collaborations in multiple phases of the research cycle. Last, the results indicate the importance of adding a role (practical support) and two phases (grant application and recruitment) to the Involvement Matrix.

Conclusion
Our results show the added value of AYA (with a UPCP) involvement within scientific research projects. We recommend researchers to actively think about the level and phase of collaboration prior to each research project, by involving and brainstorming with AYAs at the conception and throughout research projects. Besides, to enhance fruitful participation, we suggest thoroughly discussing the pros and cons of collaboration for each phase together with AYAs via the proposed Involvement Matrix to support transparency. We recommend to report experiences, choices, and results of AYA involvement.
Serum S100A8/A9 concentrations are associated with neuropsychiatric involvement in systemic lupus erythematosus: a cross-sectional study
Authors: Zervides Kristoffer A. , Jern Andreas , Nystedt Jessika , Gullstrand Birgitta , Nilsson Petra C. , Sundgren Pia C. , Bengtsson Anders A. , Jönsen Andreas 
Published: July 2022

Abstract
Background
Neuropsychiatric (NP) involvement and fatigue are major problems in systemic lupus erythematosus (SLE). S100A8/A9 is a marker of inflammation and responds to therapy in SLE patients. S100A8/A9 has an immunopathogenic role in various neurological diseases. We investigated S100A8/A9 in relation to NP-involvement and fatigue in SLE.

Methods
72 consecutive SLE outpatients at a tertiary centre and 26 healthy controls were included in this cross-sectional study. NPSLE was determined by specialists in rheumatology and neurology and defined according to three attribution models: “ACR”, “SLICC A” and “SLICC B”. Cerebral MRI was assessed by a neuroradiologist and neurocognitive testing by a neuropsychologist. The individuals were assessed by scores of pain (VAS), fatigue (VAS and FSS), and depression (MADRS-S). Concentrations of S100A8/A9 in serum and cerebrospinal fluid were measured with ELISA. Statistical calculations were performed using non-parametric methods.

Results
Serum concentrations of S100A8/A9 were higher in SLE patients compared with controls (medians 1230 ng/ml; 790 ng/ml, p = 0.023). The concentrations were higher in NPSLE patients compared with non-NPSLE patients when applying the SLICC A and ACR models, but not significant when applying the SLICC B model (medians 1400 ng/ml; 920 ng/ml, p = 0.011; 1560 ng/ml; 1090 ng/ml, p = 0.050; 1460 ng/ml; 1090 ng/ml, p = 0.083, respectively). No differences of CSF S100A8/A9 concentrations were observed between NPSLE and non-NPSLE patients. SLE patients with depression or cognitive dysfunction as an ACR NPSLE manifestation had higher serum S100A8/A9 concentrations than non-NPSLE patients (median 1460 ng/ml, p = 0.007 and 1380 ng/ml, p = 0.013, respectively). Higher serum S100A8/A9 correlated with higher VAS fatigue (r = 0.31; p = 0.008) and VAS pain (r = 0.27, p = 0.021) in SLE patients. Serum S100A8/A9 was not independently associated with NPSLE when adjusting for scores of fatigue (FSS) and pain (VAS) (OR 1.86, 95% CI 0.93–3.73, p = 0.08).

Conclusions
Serum S100A8/A9 concentrations may be associated with NPSLE and fatigue. S100A8/A9 may be of interest in evaluating NPSLE, although further investigations are needed.