bluuebunny/crossref_metadata_2025_split huggingface dataset:
Failure to thrive - an overlooked manifestation of KMT2B-related dystonia: a case presentation
Authors: Ng Andrew , Galosi Serena , Salz Lisa , Wong Terence , Schwager Caitlin , Amudhavalli Shivarajan , Gelineau-Morel Rose , Chowdhury Shimul ,   on behalf of Rady Children’s Institute for Genomic Medicine Investigators, Friedman Jennifer 
Published: June 2020

Abstract
Background
KMT2B-related dystonia is a recently described form of childhood onset dystonia that may improve with deep brain stimulation. Prior reports have focused on neurologic features including prominent bulbar involvement without detailing general health consequences that may result from orolingual dysfunction. We describe a family with novel KMT2B mutation with several members with failure to thrive to highlight this non-neurologic, but consequential impact of mutation in this gene.

Case presentation
We present a case of a 15-year old female who was admitted and evaluated for failure to thrive. On exam, she had severe speech dysfluency, limited ability to protrude the tongue, and generalized dystonia involving the oromandibular region, right upper and left lower extremity with left foot inversion contracture. The proband and her parents underwent whole genome sequencing. A previously undescribed variant, c.4960 T > C (p.Cys1654Arg), was identified in the KMT2B gene in the proband and mother, and this variant was subsequently confirmed in two maternal cousins, one with failure to thrive. Literature review identified frequent reports of prominent bulbar involvement but failure to thrive is rarely mentioned.

Conclusion
Failure to thrive is a common pediatric clinical condition that has consequences for growth and development. In the presence of an abnormal neurologic exam, a search for a specific underlying genetic etiology should be pursued. With this case series, we highlight an unusual potentially treatable cause of failure to thrive, reinforce the importance of precise molecular diagnosis for patients with failure to thrive and an abnormal neurologic exam, and underscore the importance of cascade screening of family members.
Increased risk of tinnitus in patients with early-onset cataracts: a nationwide population-based case-control study
Authors: Hsieh Yi-Ching , Chang Cheng-Hsien , Tsai Yi-Yu , Lin Cheng-Li , Ng Telk-Ying , Chiang Chun-Chi 
Published: June 2020

AbstractBackgroundThis study aimed to investigate the association between early-onset cataract and tinnitus using a population-based database.MethodsRetrospective claims data from the Taiwan National Health Insurance Research Database were analysed. Study subjects comprised patients with early-onset cataract, aged 20–55 years and diagnosed between 2000 and 2010 (n = 2084) and a comparison cohort without the disease (n = 8336). Both cohorts were followed until 2010 to estimate the incidence of tinnitus. To calculate the risk of tinnitus in the case and control groups, Cox proportional hazards models were used and presented as hazard ratios (HRs), adjusted HRs (aHRs) and 95% confidence intervals (CIs).ResultsPatients with early-onset cataract had 1.53-fold increased risk (HR = 1.53, 95% CI = 1.17–2.01,p < 0.01) of developing tinnitus than controls. The number of patients with vertigo (p < 0.0001), insomnia (p < 0.0001), anxiety (p < 0.0001) and hearing loss (p < 0.0001) as comorbidities was also significantly higher in the case group. After adjusting for age, sex and all listed comorbidities, patients with increasing age (aHR = 1.04, 95% CI = 1.02–1.07), early-onset cataract (aHR = 1.32, 95% CI = 1.01–1.74), vertigo (aHR = 1.75, 95% CI = 1.15–2.67), insomnia (aHR = 1.48, 95% CI = 1.14–1.93) and hearing loss (aHR = 6.20, 95% CI = 3.58–10.70) had significantly higher risk of tinnitus.ConclusionsPatients with early-onset cataract are at an increased risk of developing tinnitus in subsequent years and should receive further evaluation for early diagnosis and management if any signs of tinnitus occur.
The Binge Eating Genetics Initiative (BEGIN): study protocol
Authors: Bulik Cynthia M. , Butner Jonathan E. , Tregarthen Jenna , Thornton Laura M. , Flatt Rachael E. , Smith Tosha , Carroll Ian M. , Baucom Brian R.W. , Deboeck Pascal R. 
Published: June 2020

AbstractBackgroundThe Binge Eating Genetics Initiative (BEGIN) is a multipronged investigation examining the interplay of genomic, gut microbiota, and behavioral factors in bulimia nervosa and binge-eating disorder.Methods1000 individuals who meet current diagnostic criteria for bulimia nervosa or binge-eating disorder are being recruited to collect saliva samples for genotyping, fecal sampling for microbiota characterization, and recording of 30 days of passive data and behavioral phenotyping related to eating disorders using the appRecovery Recordadapted for the Apple Watch.DiscussionBEGIN examines the interplay of genomic, gut microbiota, and behavioral factors to explore etiology and develop predictors of risk, course of illness, and response to treatment in bulimia nervosa and binge-eating disorder. We will optimize the richness and longitudinal structure of deep passive and active phenotypic data to lay the foundation for a personalized precision medicine approach enabling just-in-time interventions that will allow individuals to disrupt eating disorder behaviors in real time before they occur.Trial registrationThe ClinicalTrials.gov identifier isNCT04162574. November 14, 2019, Retrospectively Registered.
Antidepressants and movement disorders: a postmarketing study in the world pharmacovigilance database
Authors: Revet Alexis , Montastruc François , Roussin Anne , Raynaud Jean-Philippe , Lapeyre-Mestre Maryse , Nguyen Thi Thu Ha 
Published: June 2020

Abstract
Background
Antidepressants-induced movement disorders are rare and imperfectly known adverse drug reactions. The risk may differ between different antidepressants and antidepressants’ classes. The objective of this study was to assess the putative association of each antidepressant and antidepressants’ classes with movement disorders.

Methods
Using VigiBase®, the WHO Pharmacovigilance database, disproportionality of movement disorders’ reporting was assessed among adverse drug reactions related to any antidepressant, from January 1967 to February 2017, through a case/non-case design. The association between nine subtypes of movement disorders (akathisia, bruxism, dystonia, myoclonus, parkinsonism, restless legs syndrome, tardive dyskinesia, tics, tremor) and antidepressants was estimated through the calculation first of crude Reporting Odds Ratio (ROR), then adjusted ROR on four potential confounding factors: age, sex, drugs described as able to induce movement disorders, and drugs used to treat movement disorders.

Results
Out of the 14,270,446 reports included in VigiBase®, 1,027,405 (7.2%) contained at least one antidepressant, among whom 29,253 (2.8%) reported movement disorders. The female/male sex ratio was 2.15 and the mean age 50.9 ± 18.0 years. We found a significant increased ROR for antidepressants in general for all subtypes of movement disorders, with the highest association with bruxism (ROR 10.37, 95% CI 9.62–11.17) and the lowest with tics (ROR 1.49, 95% CI 1.38–1.60). When comparing each of the classes of antidepressants with the others, a significant association was observed for all subtypes of movement disorders except restless legs syndrome with serotonin reuptake inhibitors (SRIs) only. Among antidepressants, mirtazapine, vortioxetine, amoxapine, phenelzine, tryptophan and fluvoxamine were associated with the highest level to movement disorders and citalopram, paroxetine, duloxetine and mirtazapine were the most frequently associated with movement disorders. An association was also found with eight other antidepressants.

Conclusions
A potential harmful association was found between movement disorders and use of the antidepressants mirtazapine, vortioxetine, amoxapine, phenelzine, tryptophan, fluvoxamine, citalopram, paroxetine, duloxetine, bupropion, clomipramine, escitalopram, fluoxetine, mianserin, sertraline, venlafaxine and vilazodone. Clinicians should beware of these adverse effects and monitor early warning signs carefully. However, this observational study must be interpreted as an exploratory analysis, and these results should be refined by future epidemiological studies.
Using mind control to modify cue-reactivity in AUD: the impact of mindfulness-based relapse prevention on real-time fMRI neurofeedback to modify cue-reactivity in alcohol use disorder: a randomized controlled trial
Authors: Weiss Franziska , Aslan Acelya , Zhang Jingying , Gerchen Martin Fungisai , Kiefer Falk , Kirsch Peter 
Published: June 2020

Abstract
Background
Alcohol Use Disorder is a severe mental disorder affecting the individuals concerned, their family and friends and society as a whole. Despite its high prevalence, novel treatment options remain rather limited. Two innovative interventions used for treating severe disorders are the use of real-time functional magnetic resonance imaging neurofeedback that targets brain regions related to the disorder, and mindfulness-based treatments. In the context of the TRR SFB 265 C04 “Mindfulness-based relapse prevention as an addition to rtfMRI NFB intervention for patients with Alcohol Use Disorder (MiND)” study, both interventions will be combined to a state-of-the art intervention that will use mindfulness-based relapse prevention to improve the efficacy of a real-time neurofeedback intervention targeting the ventral striatum, which is a brain region centrally involved in cue-reactivity to alcohol-related stimuli.

Methods/design
After inclusion, N = 88 patients will be randomly assigned to one of four groups. Two of those groups will receive mindfulness-based relapse prevention. All groups will receive two fMRI sessions and three real-time neurofeedback sessions in a double-blind manner and will regulate either the ventral striatum or the auditory cortex as a control region. Two groups will additionally receive five sessions of mindfulness-based relapse prevention prior to the neurofeedback intervention. After the last fMRI session, the participants will be followed-up monthly for a period of 3 months for an assessment of the relapse rate and clinical effects of the intervention.

Discussion
The results of this study will give further insights into the efficacy of real-time functional magnetic resonance imaging neurofeedback interventions for the treatment of Alcohol Use Disorder. Additionally, the study will provide further insight on neurobiological changes in the brain caused by the neurofeedback intervention as well as by the mindfulness-based relapse prevention. The outcome might be useful to develop new treatment approaches targeting mechanisms of Alcohol Use Disorder with the goal to reduce relapse rates after discharge from the hospital.

Trial registration
This trial is pre-registered at clinicaltrials.gov (trial identifier: NCT04366505; WHO Universal Trial Number (UTN): U1111–1250-2964). Registered 30 March 2020, published 29 April 2020.
Adolescents at risk of self-harm in Ghana: a qualitative interview study exploring the views and experiences of key adult informants
Authors: Quarshie Emmanuel N-B. , Waterman Mitch G. , House Allan O. 
Published: June 2020

AbstractBackgroundIn Ghana, rates of self-harm in young people are as high as they are in high income countries. Self-reported interpersonal, familial and societal stressors form the most important background, and self-harm is seen by young people as a way of responding to that stress. In the present study, we obtained the views of key adult informants about self-harm among adolescents in Ghana – what they thought as possible reasons for self-harm in young people and what actions might be needed at an individual or population level to respond to the problem.MethodsWe interviewed face-to-face 11 adults, using a semi-structured interview guide. We used an experiential thematic analysis technique to analyse the transcribed interviews.ResultsThe analysis identified five themes: “underestimating the prevalence of self-harm in adolescents”, “life on the streets makes self-harm less likely”, “self-harm in adolescents is socially and psychologically understandable”, “ambivalence about responding to adolescent self-harm”, and “few immediate opportunities for self-harm prevention in Ghana”. Adolescent self-harm was acknowledged but its scale was underestimated. The participants offered explanations for adolescent self-harm in social and psychological terms that are recognisable from accounts in high income countries. Low rates among street-connected young people were explained by their overarching orientation for survival. Participants agreed that identification was important, but they expressed a sense of inadequacy in identifying and supporting adolescents at risk of self-harm. Again, the participants agreed that self-harm in adolescents should be prevented, but they recognised that relevant policies were not in place or if there were policies they were not implemented – mental health and self-harm were not high on public or political priorities.ConclusionsThe adults we interviewed about young people who self-harm see themselves as having a role in identifying adolescents at risk of self-harm and see the organisations in which they work as having a role in responding to individual young people in need. These are encouraging findings that point to at least one strand of a policy in Ghana for addressing the problem of self-harm in young people.
Patient and healthcare provider experiences of hepatitis C treatment with direct-acting antivirals in Rwanda: a qualitative exploration of barriers and facilitators
Authors: Serumondo Janvier , Penkunas Michael J. , Niyikora Julienne , Ngwije Alida , Kiromera Athanase , Musabeyezu Emmanuel , Umutesi Justine , Umuraza Sabine , Musengimana Gentille , Nsanzimana Sabin 
Published: June 2020

Abstract
Background
Direct-acting antivirals (DAAs) are increasingly accessible to patients with hepatitis C (HCV) worldwide and are being introduced through national health systems in sub-Saharan Africa. DAAs are highly efficacious when tested in controlled trials, yet patients treated outside of study settings often encounter challenges in completing the full treatment and follow-up sequence. Little information is available on the influences of successful DAA implementation in sub-Saharan Africa. This qualitative study explored the individual- and system-level barriers and enablers of DAA treatment in Rwanda between March 2015 and November 2017.

Methods
Face-to-face interviews were conducted with 39 patients who initiated care at one of four referral hospitals initially offering DAAs. Ten healthcare providers who managed HCV treatment participated in face-to-face interviews to examine system-level barriers and facilitators. Interview data were analyzed using a general inductive approach in alignment with the a priori objective of identifying barriers and facilitators of HCV care.

Results
Barriers to successful treatment included patients’ lack of knowledge surrounding HCV and its treatment; financial burdens associated with paying for medication, laboratory testing, and transportation; the cumbersome nature of the care pathway; the relative inaccessibility of diagnostics technology; and heavy workloads of healthcare providers accompanied by a need for additional HCV-specific training. Patients and healthcare providers were highly aligned on individual- and system-level barriers to care. The positive patient-provider relationship, strong support from community and family members, lack of stigma, and mild side effect profile of DAAs all positively influenced patients’ engagement in treatment.

Conclusions
Several interrelated factors acted as barriers and facilitators to DAA treatment in Rwanda. Patients’ and healthcare providers’ perceptions were in agreement, suggesting that the impeding and enabling factors were well understood by both groups. These results can be used to enact evidence-informed interventions to help maximize the impact of DAAs as Rwanda moves towards HCV elimination.
Performance of India’s national publicly funded health insurance scheme, Pradhan Mantri Jan Arogaya Yojana (PMJAY), in improving access and financial protection for hospital care: findings from household surveys in Chhattisgarh state
Authors: Garg Samir , Bebarta Kirtti Kumar , Tripathi Narayan 
Published: June 2020

Abstract
Background
A national Publicly Funded Health Insurance (PFHI) scheme called Pradhan Mantri Jan Arogaya Yojana (PMJAY) was launched by government of India in 2018. PMJAY seeks to cover 500 million persons with an annual cover of around 7000 USD per household. PMJAY claims to be the largest government funded health scheme globally and has attracted an international debate as a policy for Universal Health Coverage. India’s decade-long experience of the earlier national and state-specific PFHI schemes had shown poor effectiveness in financial protection. Most states in India have completed a year of implementation of PMJAY but no evaluations are available of this important scheme.

Methods
The study was designed to find out the effect of enrolment under PMJAY in improving utilisation of hospital services and financial protection in Chhattisgarh which has been a leading state in implementing PFHI in terms of enrolment and claims. The study analyses three repeated cross-sections. Two of the cross-sections are from National Sample Survey (NSS) health rounds – year 2004 when there was no PFHI and 2014 when the older PFHI scheme was in operation. Primary data was collected in 2019-end to cover the first year of PMJAY implementation and it formed the third cross-section. Multivariate analysis was carried out. In addition, Propensity Score Matching and Instrumental Variable method were applied to address the selection problem in insurance.

Results
Enrollment under PMJAY or other PFHI schemes did not increase utilisation of hospital-care in Chhattisgarh. Out of Pocket Expenditure (OOPE) and incidence of Catastrophic Health Expenditure did not decrease with enrollment under PMJAY or other PFHI schemes. The size of OOPE was significantly greater for utilisation in private sector, irrespective of enrollment under PMJAY.

Conclusion
PMJAY provided substantially larger vertical cover than earlier PFHI schemes in India but it has not been able to improve access or financial protection so far in the state. Though PMJAY is a relatively new scheme, the persistent failure of PFHI schemes over a decade raises doubts about suitability of publicly funded purchasing from private providers in the Indian context. Further research is recommended on such policies in LMIC contexts.
Changing clinical characteristics of non-cystic fibrosis bronchiectasis in children
Authors: Eralp Ela Erdem , Gokdemir Yasemin , Atag Emine , Ikizoglu Nilay Bas , Ergenekon Pinar , Yegit Cansu Yilmaz , Kut Arif , Ersu Refika , Karakoc Fazilet , Karadag Bulent 
Published: June 2020

Abstract
Background
The prevalence of non-cystic fibrosis (CF) bronchiectasis is increasing in both developed and developing countries in recent years. Although the main features remain similar, etiologies seem to change. Our aim was to evaluate the clinical and laboratory characteristics of our recent non-CF bronchiectasis patients and to compare these with our historical cohort in 2001.

Methods
One hundred four children with non-CF bronchiectasis followed between 2002 and 2019 were enrolled. Age of diagnosis, underlying etiology and microorganisms in sputum culture were recorded. Clinical outcomes were evaluated in terms of lung function tests and annual pulmonary exacerbation rates at presentation and within the last 12 months.

Results
Mean FEV1 and FVC %predicted at presentation improved compared to historical cohort (76.6 ± 17.1 vs. 63.3 ± 22.1 and 76.6 ± 15.1 vs. 67.3 ± 23.1, respectively; p <  0.001). There was a significant decrease in pulmonary exacerbation rate from 6.05 ± 2.88 at presentation to 3.23 ± 2.08 during follow-up (p <  0.0001). In 80.8% of patients, an underlying etiology was identified. There was an increase in primary ciliary dyskinesia (PCD) (32.7% vs. 6.3%; p = 0.001), decrease in idiopathic cases (19.2% vs. 37.8%; p = 0.03) with no change in postinfectious and immunodeficiencies as underlying etiology. Sputum cultures were positive in 77.9% of patients which was 46.9% in the historical cohort (p = 0.001).

Conclusion
Baseline pulmonary function tests were better and distribution of underlying etiology had changed with a remarkable increase in diagnosis of PCD in the recent cohort.
Hepatitis in children with tuberculosis: a case report and review of the literature
Authors: Sanchez-Codez Maria , Hunt W. Garret , Watson Joshua , Mejias Asuncion 
Published: June 2020

Abstract
Background
Hepatitis in young children with tuberculosis (TB) outside miliary TB is not well described and represents a challenge because of the hepatotoxicity associated with first-line anti-TB treatment.

Case presentation
We report an antibiotic naïve 13-month-old male from Nepal with pulmonary TB and hepatitis, who improved after TB treatment. We also performed a literature review for TB-associated hepatitis in children.

Conclusions
Liver function tests should be considered, when feasible, in infants and young children with pulmonary TB. Testing could help to identify and manage patients with TB-associated hepatic abnormalities, and also to establish a baseline for detection and management of liver injury associated with anti-TB therapy.
The effect of treatment with a non-invasive foot worn biomechanical device on subjective and objective measures in patients with knee osteoarthritis- a retrospective analysis on a UK population
Authors: Miles Christopher , Greene Andrew 
Published: June 2020

AbstractBackgroundOsteoarthritis is a major cause of pain and disability worldwide, therefore ways of treating this condition are paramount to a successful health system. The purpose of the study was to investigate the changes in spatial-temporal gait parameters and clinical measurements following treatment with a non-invasive foot-worn biomechanical device on patients with knee osteoarthritis within the UK.MethodsA retrospective analysis was carried out on 455 patients with knee osteoarthritis. All patients were evaluated using a computerized gait test and two self-assessment questionnaires (WOMAC and SF-36) at baseline and after 3 and 6 months of treatment. The biomechanical device is a shoe-like device with convex pods under the sole that have the capability of changing foot centre of pressure and training neuromuscular control. The device was individually calibrated for each patient to minimise symptoms whilst walking and train neuromuscular control. Patients used the device for short periods during activities of daily living. Repeated measures statistical analyses were performed to compare differences over time.ResultsAfter 6 months of treatment significant improvements were seen in all gait parameters (p < 0.01). Specifically, gait velocity, step length and single limb support of the more symptomatic knee improved by 13, 7.8 and 3%, respectively. These were supported by significant improvements in pain, function and quality of life (48.6, 45.7 and 22% respectively;p < 0.001). A sub-group analysis revealed no baseline differences between those who were recommended joint replacement and those who were not. Both groups improved significantly over time (p < 0.05 for all).ConclusionsOur results suggest that the personalised biomechanical treatment can improve gait patterns, pain, function and quality of life. It may provide an additional solution to managing UK patients suffering from knee osteoarthritis but needs to be tested in a controlled setting first.