bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preventative therapeutic approaches for hypertrophic cardiomyopathy
Authors: Solomon Tanya , Filipovska Aleksandra , Hool Livia , Viola Helena 
Published: August 2020

AbstractSarcomeric gene mutations are associated with the development of hypertrophic cardiomyopathy (HCM). Current drug therapeutics for HCM patients are effective in relieving symptoms, but do not prevent or reverse disease progression. Moreover, due to heterogeneity in the clinical manifestations of the disease, patients experience variable outcomes in response to therapeutics. Mechanistically, alterations in calcium handling, sarcomeric disorganization, energy metabolism and contractility participate in HCM disease progression. While some similarities exist, each mutation appears to lead to mutation‐specific pathophysiology. Furthermore, these alterations may precede or proceed development of the pathology. This review assesses the efficacy of HCM therapeutics from studies performed in animal models of HCM and human clinical trials. Evidence suggests that a preventative rather than corrective therapeutic approach may be more efficacious in the treatment of HCM. In addition, a clear understanding of mutation‐specific mechanisms may assist in informing the most effective therapeutic mode of action.
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Influence of age on the frequency characteristics of the soleus muscle response to Achilles tendon vibration during standing
Authors: Mildren Robyn L. , Schmidt Margot E. , Eschelmuller Gregg , Carpenter Mark G. , Blouin Jean‐Sébastien , Inglis J. Timothy 
Published: August 2020

Key points
Proprioceptive sensory information from the ankle joint is critical for the control of upright posture and balance.
We examined the influence of age (n = 54 healthy adults, 20–82 years old) on lower limb muscle responses to proprioceptive perturbations evoked by Achilles tendon vibration during standing.
The frequency bandwidth of the muscle response became narrower, and the gain (the muscle response relative to the stimulus) and scaling (increases in response amplitude with increases in stimulus amplitude) decreased with age.
Mechanics of the muscle–tendon unit (mechanical admittance) did not differ with age during standing, and thus probably did not mediate the age‐related changes observed in soleus muscle responses to vibration.
These findings add to our understanding of how altered proprioceptive responses may contribute to impaired mobility and falls with ageing.
AbstractProprioceptive information from the ankle joint plays an important role in the control of upright posture and balance. Ageing influences many components of the sensorimotor system, which leads to poor mobility and falls. However, little is known about the influence of age on the characteristics of short latency muscle responses to proprioceptive stimuli during standing across frequencies that are encoded by muscle spindles. We examined the frequency characteristics of the soleus muscle response to noisy (10–115 Hz) Achilles tendon vibration during standing in 54 healthy adults across a broad age range (20–82 years). The results showed the frequency bandwidth of the soleus response (vibration–electromyography coherence) became progressively narrower with ageing. Coherence was significantly lower in middle‐aged relative to young adults between ∼7–11 and 28–62 Hz, lower in older relative to middle‐aged adults between ∼30–50 Hz and lower in older relative to young adults between ∼7–64 Hz. Muscle response gain was similar between age groups at low frequencies, although gain was lower in older relative to young adults between ∼28–54 Hz. Across the age range, the response amplitude (peak‐to‐peak cross‐covariance) and the scaling of the response with stimulus amplitude were both negatively correlated with age. Muscle–tendon mechanics (admittance) did not differ with age, suggesting this did not mediate differences in soleus responses. Our findings suggest there is a progressive change in the soleus response to proprioceptive stimuli with ageing during standing, which could contribute to poorer mobility and falls.
Cost–utility of sofosbuvir/velpatasvir versus other direct-acting antivirals for chronic hepatitis C genotype 1b infection in China
Authors: Yun Haoya , Zhao Guoqiang , Sun Xiaojie , Shi Lizheng 
Published: August 2020

ObjectiveThis study aimed to estimate the cost–utility of sofosbuvir/velpatasvir (SOF/VEL) compared with other direct-acting antivirals (DAAs) in Chinese patients with hepatitis C virus (HCV).DesignA Markov model was developed to estimate the disease progression of patients with HCV over a lifetime horizon from the healthcare system perspective. Efficacy, clinical inputs and utilities were derived from the published literature. Drug costs were from the market price survey, and health costs for Markov health states were sourced from a Chinese study. Costs and utilities were discounted at an annual rate of 5%. One-way and probabilistic sensitivity analyses were conducted to test the impact of input parameters on the results.InterventionsSOF/VEL was compared with sofosbuvir+ribavirin (SR), sofosbuvir+dasabuvir (SD), daclatasvir+asunaprevir (DCV/ASV), ombitasvir/paritaprevir/ritonavir+dasabuvir (3D) and elbasvir/grazoprevir (EBR/GZR).Primary and secondary outcomesCosts, quality-adjusted life years (QALYs) and incremental cost–utility ratios (ICURs).ResultsSOF/VEL was economically dominant over SR and SD. However, 3D was economically dominant compared with SOF/VEL. Compared with DCV/ASV, SOF/VEL was cost-effective with the ICUR of US$1522 per QALY. Compared with EBR/GZR, it was not cost-effective with the ICUR of US$369 627 per QALY. One-way sensitivity analysis demonstrated that reducing the cost of SOF/VEL to the lower value of CI resulted in dominance over EBR/GZR and 3D. Probabilistic sensitivity analysis demonstrated that 3D was cost-effective in 100% of iterations in patients with genotype (GT) 1b and SOF/VEL was not cost-effective.ConclusionsCompared with other oral DAA agents, SOF/VEL treatment was not the most cost-effectiveness option for patients with chronic HCV GT1b in China. Lower the price of SOF/VEL will make it cost-effective while simplifying treatment and achieving the goal of HCV elimination.
Risk of preterm birth associated with maternal gingival inflammation and oral hygiene behaviours in rural Nepal: a community-based, prospective cohort study
Authors: Erchick Daniel J , Khatry Subarna K , Agrawal Nitin K , Katz Joanne , LeClerq Steven C , Rai Bhola , Reynolds Mark A , Mullany Luke C 
Published: August 2020

ObjectivesObservational studies have identified associations between periodontitis and adverse pregnancy outcomes, but randomised controlled trials evaluating the efficacy of periodontal therapy have yielded inconsistent results. Few studies have explored relationships between gingival inflammation and these outcomes or been conducted in rural, low-income communities, where confounding risk factors differ from other settings.MethodsWe conducted a community-based, prospective cohort study with the aim of estimating associations between the extent of gingival inflammation in pregnant women and incidence of preterm birth in rural Nepal. Our primary exposure was gingival inflammation, defined as bleeding on probing (BOP) ≥10%, stratified by BOP <30% and BOP ≥30%. A secondary exposure, mild periodontitis, was defined as ≥2 interproximal sites with probing depth (PD) ≥4 mm (different teeth) or one site with PD ≥5 mm. Our primary outcome was preterm birth (<37 weeks gestation). We used Poisson regression to model this relationship, adjusting for potential confounders.ResultsOf 1394 participants, 554 (39.7%) had gingival inflammation, 54 (3.9%) mild periodontitis and 197 (14.1%) delivered preterm. In the adjusted regression model, increasing extent of gingival inflammation was associated with a non-significant increase in risk of preterm birth (BOP ≥30% vs no BOP: adjusted relative risk (aRR) 1.37, 95% CI: 0.81 to 2.32). A secondary analysis, stratifying participants by when in pregnancy their oral health status was assessed, showed an association between gingival inflammation and preterm birth among women examined in their first trimester (BOP ≥30% vs no BOP: aRR 2.57, 95% CI: 1.11 to 5.95), but not later in pregnancy (BOP ≥30% vs no BOP: aRR 1.05, 95% CI: 0.52 to 2.11).ConclusionsGingival inflammation in women examined early in pregnancy and poor oral hygiene behaviours were risk factors for preterm birth. Future studies should evaluate community-based oral health interventions that specifically target gingival inflammation, delivered early in or before pregnancy, on preterm birth.Trial registration numberNepal Oil Massage Study, NCT01177111.
What are the implications of using individual and combined sources of routinely collected data to identify and characterise incident site-specific cancers? a concordance and validation study using linked English electronic health records data
Authors: Strongman Helen , Williams Rachael , Bhaskaran Krishnan 
Published: August 2020

ObjectivesTo describe the benefits and limitations of using individual and combinations of linked English electronic health data to identify incident cancers.Design and settingOur descriptive study uses linked English Clinical Practice Research Datalink primary care; cancer registration; hospitalisation and death registration data.Participants and measuresWe implemented case definitions to identify first site-specific cancers at the 20 most common sites, based on the first ever cancer diagnosis recorded in each individual or commonly used combination of data sources between 2000 and 2014. We calculated positive predictive values and sensitivities of each definition, compared with a gold standard algorithm that used information from all linked data sets to identify first cancers. We described completeness of grade and stage information in the cancer registration data set.Results165 953 gold standard cancers were identified. Positive predictive values of all case definitions were ≥80% and ≥94% for the four most common cancers (breast, lung, colorectal and prostate). Sensitivity for case definitions that used cancer registration alone or in combination was ≥92% for the four most common cancers and ≥80% across all cancer sites except bladder cancer (65% using cancer registration alone). For case definitions using linked primary care, hospitalisation and death registration data, sensitivity was ≥89% for the four most common cancers, and ≥80% for all cancer sites except kidney (69%), oral cavity (76%) and ovarian cancer (78%). When primary care or hospitalisation data were used alone, sensitivities were generally lower and diagnosis dates were delayed. Completeness of staging data in cancer registration data was high from 2012 (minimum 76.0% in 2012 and 86.4% in 2014 for the four most common cancers).ConclusionsAscertainment of incident cancers was good when using cancer registration data alone or in combination with other data sets, and for the majority of cancers when using a combination of primary care, hospitalisation and death registration data.
Comparison of strategies for monitoring and treating patients at the early phase of severe traumatic brain injury: the multicentre randomised controlled OXY-TC trial study protocol
Authors: Payen Jean-Francois , Richard Marion , Francony Gilles , Audibert Gérard , Barbier Emmanuel L , Bruder Nicolas , Dahyot-Fizelier Claire , Geeraerts Thomas , Gergele Laurent , Puybasset Louis , Vigue Bernard , Skaare Kristina , Bosson Jean Luc , Bouzat Pierre 
Published: August 2020

IntroductionIntracranial hypertension is considered as an independent risk factor of mortality and neurological disabilities after severe traumatic brain injury (TBI). However, clinical studies have demonstrated that episodes of brain ischaemia/hypoxia are common despite normalisation of intracranial pressure (ICP). This study assesses the impact on neurological outcome of guiding therapeutic strategies based on the monitoring of both brain tissue oxygenation pressure (PbtO2) and ICP during the first 5 days following severe TBI.Methods and analysisMulticentre, open-labelled, randomised controlled superiority trial with two parallel groups in 300 patients with severe TBI. Intracerebral monitoring must be in place within the first 16 hours post-trauma. Patients are randomly assigned to the ICP group or to the ICP + PbtO2group. The ICP group is managed according to the international guidelines to maintain ICP≤20 mm Hg. The ICP + PbtO2group is managed to maintain PbtO2≥20 mm Hg in addition to the conventional optimisation of ICP. The primary outcome measure is the neurological status at 6 months as assessed using the extended Glasgow Outcome Scale. Secondary outcome measures include quality-of-life assessment, mortality rate, therapeutic intensity and incidence of critical events during the first 5 days. Analysis will be performed according to the intention-to-treat principle and full statistical analysis plan developed prior to database freeze.Ethics and disseminationThis study has been approved by the Institutional Review Board of Sud-Est V (14-CHUG-48) and from the National Agency for Medicines and Health Products Safety (Agence Nationale de Sécurité du Médicament et des produits de santé) (141 435B-31). Results will be presented at scientific meetings and published in peer-reviewed publications.The study was registered with ClinTrialsNCT02754063on 28 April 2016 (pre-results).
Protocol for a pilot randomised, double-blind, placebo-controlled trial for assessing the feasibility and efficacy of faecal microbiota transplantation in adolescents with refractory irritable bowel syndrome: FAIS Trial
Authors: Zeevenhooven Judith , de Bruijn Clara Marieke Andrea , Vlieger Arine , Nieuwdorp Max , Benninga Marc Alexander 
Published: August 2020

BackgroundIrritable bowel syndrome (IBS) is a common chronic medical condition, in both children and adults. Despite the availability of effective (non)pharmacological treatments, symptoms persist in a significant amount of patients with IBS. Faecal microbiota transplantation (FMT) may be an effective alternative treatment in adolescents with refractory IBS through manipulation of the intestinal microbiota.Methods and analysisThis randomised, placebo-controlled single-centre pilot study will assess feasibility and efficacy of FMT in 30 adolescents (16–21 years) with refractory IBS. Patients will be randomly allocated (1:1) to receive two allogeneic (healthy donor) or two autologous (own) faecal infusions at baseline and after 6 weeks. Primary outcomes will assess feasibility, including patient and donor recruitment, adherence and incidence rates of adverse events. To evaluate clinical efficacy, secondary outcomes will include the proportion of patients with at least >50% reduction of their abdominal pain intensity and frequency 12 weeks after the first FMT, and after 6-month and 12-month follow-up. Other outcomes comprise changes in faecal gut microbiota composition, quality of life, depression and anxiety, school or work absenteeism and adequate relief, measured directly after FMTs and after 6 and 12 months of follow-up.DiscussionThis randomised controlled trial will investigate the feasibility and effectiveness of repetitive FMTs in adolescents with refractory IBS.Ethics and disseminationThe study is approved by the Medical Research Ethics Committees AMC (MEC-AMC) in the Netherlands.Trial registration numberNCT03074227.
The patient-generated subjective global assessment is a promising screening tool for cancer cachexia
Authors: Cong Minghua , Song Chenxin , Xu Hongxia , Song Chunhua , Wang Chang , Fu Zhenming , Ba Yi , Wu Jing , Xie Conghua , Chen Gongyan , Chen Zihua , Zhou Lan , Li Tao , Deng Li , Xin Lin , Yang Liuqing , Cui Jiuwei , Shi Hanping 
Published: August 2020

BackgroundCancer cachexia is a complex metabolic syndrome characterised by a loss of muscle with or without loss of fat mass, and is associated with high morbidity and mortality. Despite its clinical importance, there is a lack of simple tools to screen patients for cancer cachexia. The aim of this study was to evaluate and validate the patient-generated subjective global assessment (PG-SGA) as a screening tool for cancer cachexia.MethodsThis is a secondary analysis of a multicentre, cross-sectional, observational study. Cancer cachexia was diagnosed when there was weight loss ≥5% during the past 12 months and at least three of the five following conditions were present: decreased muscle strength, fatigue, anorexia, low Fat-Free Mass Index (FFMI) and abnormal laboratory findings. A quadratic discriminant analysis was conducted for the ability of PG-SGA to predict cachexia.ResultsA total of 4231 patients with cancer were included in this analysis, and 351 patients (8.3%) were diagnosed as having cachexia. The highest incidence of cachexia was found among patients with pancreatic cancer (32.5%), oesophageal cancer (21.5%) and gastric cancer (17.9%). Compared with patients without cachexia, patients with cachexia had a lower body mass index, FFMI, hand grip strength, total protein, prealbumin, albumin, haemoglobin and Karnofsky performance status (p<0.05), while they had a higher C reactive protein level and PG-SGA Score (4.71±3.71 vs 10.87±4.84, p<0.05). The best cut-off value for PG-SGA was 6.5, with 79.8% of sensitivity and 72.3% specificity for cachexia, and the area under the receiver operating characteristic curve was 0.846 (95% CI 0.826 to 0.866, p<0.001).ConclusionsPG-SGA is a highly specific tool that can be used to screen patients for cancer cachexia.
Volunteers in palliative care: A healthcare system-wide cross-sectional survey
Authors: Vanderstichelen Steven , Cohen Joachim , Van Wesemael Yanna , Deliens Luc , Chambaere Kenneth 
Published: August 2020

ObjectiveVolunteers are an important resource in bridging palliative care (PC) services and communities. However, no studies have systematically mapped volunteers’ actual contributions to PC provision and how well they are supported by healthcare services at the volunteer level. Such insights are important to shape and optimise supportive environments for volunteering in PC. This study aimed to describe organised volunteering practices in PC across dedicated PC services and healthcare services providing generalist PC, in terms of tasks, training, supervision and how volunteers evaluate these.MethodsA cross-sectional postal survey of 2273 volunteers from healthcare organisations providing care for people with serious illnesses in the Flemish healthcare system (Belgium) was conducted between June and November 2018. A two-step cluster randomised sample was used. Volunteers were recruited through their respective volunteering organisations.ResultsResponse was obtained for 801 (35.2%) volunteers. Volunteers were predominantly women (75.5%), retired (70.8%) and aged 60–69 years (43.4%). Almost all volunteers provided psychosocial care (96.3%). Volunteers were found to provide either (1) broad volunteer support, emphasising psychosocial and existential care and signposting tasks or (2) narrow volunteer support, emphasising nursing care tasks. Nursing home volunteers had the lowest prevalence of PC training (7.7% vs 53.7% total, p<0.001).ConclusionsMultidimensional support was most prevalent among dedicated PC volunteers, while practical support was most prevalent among sitting service volunteers. Results indicate that volunteers can offer complementary support for patients with serious illnesses, although this requires training and consistent supervision. This is currently suboptimal for volunteers in nursing homes and community home care.
Home parenteral nutrition versus artificial hydration in malnourished patients with cancer in palliative care: a prospective, cohort survival study
Authors: Cotogni Paolo , Ossola Marta , Passera Roberto , Monge Taira , Fadda Maurizio , De Francesco Antonella , Bozzetti Federico 
Published: August 2020

ObjectiveThe evidence base for home parenteral nutrition (HPN) in patients with advanced cancer is lacking. To compare the survival of malnourished patients with cancer undergoing palliative care who received HPN with a homogeneous group of patients, equally eligible for HPN, who did not receive HPN.DesignProspective, cohort study; tertiary university hospital, home care, hospice.MethodsPatients were assessed for HPN eligibility according to the guidelines. In the eligible population, who received both HPN and chemotherapy was excluded, while who received only HPN was included in the HPN+ group and who received neither HPN nor chemotherapy but artificial hydration (AH) was included in the HPN− group.Results301 patients were assessed for HPN eligibility and 86 patients (28.6%) were excluded for having severe organ dysfunction or Karnofsky performance status <50. In outcome analysis, 90 patients (29.9%) were excluded for receiving both HPN and chemotherapy, while 125 (41.5%) were included, 89 in HPN+ group (29.5%) and 36 in HPN− group (12%). The survival of the two groups showed a significant difference favouring patients receiving HPN (median overall survival: 4.3 vs 1.5 months, p<0.001). The multivariate analysis of the risk factors for mortality showed that not receiving HPN accounted for the strongest one (HR 25.72, 95% CI 13·65 to 48.44).ConclusionsComparative survival associated with the use of HPN versus AH showed significantly longer survival in malnourished patients with advanced cancer receiving HPN. These data support the guideline recommendation that HPN should be considered when malnutrition represents the overriding threat for the survival of these patients.
Malignant esophagorespiratory fistulas: a comparative effectiveness survival analysis
Authors: Ahmad Irfan , Chufal Kundan Singh , Bajpai Ram , Miller Alexis Andrew , Chowdhary Rahul Lal , Pahuja Anjali Kakria , Chhabra Akanksha , Gairola Munish 
Published: August 2020

ObjectivesTo analyse the survival of patients with malignant esophagorespiratory fistulas (ERF) and perform a comparative effectiveness analysis of ERF-directed interventions.MethodsFifty-five patients met our inclusion criteria, and data on ERF-directed interventions (stent placement, surgical repair and best supportive care) and their outcomes, along with clinical and treatment details, were recorded. The primary endpoints were overall survival (OS) and survival after developing ERF (F-OS).ResultsThe median OS and F-OS for the entire cohort was 299 days (SE=23.2) and 123 days (SE=11.63), respectively. On univariable analysis, the American Joint Committee on Cancer (AJCC) stage (I–III vs IV) influenced both OS (403 vs 171 days; p=0.006) and F-OS (129 vs 67 days; p=0.034). Proximal location of ERF influenced OS favourably (494 vs 285 days; p=0.021), whereas patients developing ERF late in their disease course experienced inferior F-OS (96 vs 232 days; p=0.03). On multivariable analysis, the AJCC stage (IV vs I–III, HR=3.03 (1.41–6.50)), time to developing ERF from diagnosis (greater than vs within 3 months, HR=5.82 (1.84–18.36)) and location of ERF (distal vs proximal, HR=2.47 (1.14–5.34)) had a significant impact on F-OS. The comparative efficacy (OS and F-OS) of best supportive care was statistically equivalent to any intervention irrespective of AJCC stage and success/failure of initial or subsequent intervention(s).ConclusionsThe survival of patients with ERF is dismal, and our analysis suggests that best supportive care results in equivalent OS and F-OS when compared with any intervention.