bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Modified STOPP-START criteria for Sri Lanka’; translating to a resource limited healthcare setting by Delphi consensus
Authors: Samaranayake N. R. , Balasuriya A. , Fernando G. H. , Samaraweera D. , Shanika L. G. T. , Wanigasuriya J. K. P. , Wijekoon C. N. , Wanigatunge C. A. 
Published: October 2019

Abstract

Background
‘Screening tool of older people’s prescriptions (STOPP) and screening tool to alert to right treatment (START)’ criteria is a useful tool to assess the appropriateness of medicines among older adults. However, the original STOPP/START criteria developed in the West, may not be directly applicable to resource limited healthcare settings like Sri Lanka. Hence, we aimed to modify STOPP/START criteria (Version 2) to suit Sri Lanka.

Method
Two investigators (a clinical pharmacologist and a pharmacist) reviewed and flagged criteria that were unfeasible to Sri Lanka based on their previous research experiences on using STOPP/START version 1. A Delphi consensus methodology was conducted among six experts, including geriatricians, clinical pharmacologists, physicians and a pharmacist, to review and assess each criterion (including the ones flagged by the researchers) for suitability to Sri Lanka.

Results
Two Delphi validation rounds were conducted. A final meeting was held with the participation of all experts to resolve disagreements and to establish 100% consensus. The expert panel agreed on a list of 105 criteria, including 70 STOPP and 35 START criteria, indicating an 8% reduction in criteria compared to the original version. Modifications included complete removal (n = 11), re-wording (n = 25), splitting (n = 1) of original criteria and adding a new criterion (n = 1). Main reasons for modifications were unavailability of some medicines in the country, unavailability or inaccessibility of specific clinical information required for assessment of criteria, and adherence to treatment guidelines commonly used in the country.

Conclusion
A list of ‘Modified STOPP/START criteria for Sri Lanka’ was developed. These criteria are currently being validated through a multi-centre study.
The liver fibrosis index is superior to the APRI and FIB-4 for predicting liver fibrosis in chronic hepatitis B patients in China
Authors: Huang Dedong , Lin Taofa , Wang Shaoyang , Cheng Lieyun , Xie Liping , Lu Youguang , Chen Muxing , Zhu Lingling , Shi Jie 
Published: October 2019

Abstract

Background
The purpose of this study was to prospectively investigate the value of real-time ultrasound elastography (RTE) for the diagnosis of liver fibrosis (LF) in patients with chronic hepatitis B (CHB), to correlate the elastography findings with the histologic stage of LF and to compare RTE findings with those from noninvasive tests of LF calculated using laboratory blood parameters.

Methods
Liver biopsies, laboratory blood testing, and RTE were performed in 91 patients with CHB. The LF index (LFI) was calculated using a multiple linear regression equation involving 11 parameters, which represented the degree of LF. The higher the LFI is, the greater the degree of LF.

Results
The mean aspartate aminotransferase-to-platelet ratio index (APRI) and the mean fibrosis index based on four factors (FIB-4) were significantly different for the 5 stages of LF, respectively. The APRI (r = 0.43, P = 0.006), FIB-4 (r = 0.51, P = 0.012) and LFI (r = 0.562, P = 0.004) were correlated with the stages of LF. For discriminating stage F0 from F1, only the LFI had significant power (P = 0.026) for predicting stage F1. For discriminating stage F4 from F3, only the LFI had statistically significant power (P = 0.024) in predicting stage F4. The areas under the receiver operating characteristic curves (AUCs) of the LFI for diagnosing significant, advanced LF and liver cirrhosis were significantly higher than those of the APRI and FIB-4, and the LFI had better sensitivity and specificity.

Conclusions
The LFI calculated by RTE is reliable for the assessment of LF in patients with CHB and has better discrimination power than the APRI and FIB-4.
Efficacy and safety of cyclosporine a for patients with steroid-resistant nephrotic syndrome: a meta-analysis
Authors: Li Hong-Yan , Zhang Xialan , Zhou Tianbiao , Zhong Zhiqing , Zhong Hongzhen 
Published: October 2019

AbstractBackgroundThe purpose of this study was to determine efficacy and safety of cyclosporine A (CsA) for patients with steroid-resistant nephrotic syndrome (SRNS).MethodsThe Cochrane Library and PubMed were searched to extract the associated studies on Oct 10, 2018, and the meta-analysis method was used to pool and analyze the applicable investigations included in this study. The P(opulation) I(ntervention) C(omparison) O(utcome) of the study were defined as follows: P: Patients with SRNS; I: treated with CsA, cyclophosphamide (CYC), tacrolimus (TAC) or placebo/not treatment (P/NT); C: CsA vs. placebo/nontreatment (P/NT), CsA vs. CYC, CsA vs. TAC; O: complete remission (CR), total remission (TR; complete or partial remission (PR)), urine erythrocyte number, proteinuria levels, albumin, proteinuria, serum creatinine, and plasma cholesterol, etc. Data were extracted and pooled using RevMan 5.3.ResultsIn the therapeutic regimen of CsA vs. placebo/nontreatment (P/NT), the results indicated that the CsA group had high values of CR, TR, and low values of proteinuria, serum creatinine, and plasma cholesterol when compared with those in the placebo group. In comparing CsA vs. cyclophosphamide (CYC), the results indicated that the CsA group had higher TR than the CYC group. In comparing CsA vs. tacrolimus (TAC), the results revealed insignificant differences in CR, and TR between the CsA and TAC groups. The safety of CsA was also assessed. The incidence of gum hyperplasia in CsA group was higher than that in the P/NT group, with no differences in incidence of infections or hypertension between CsA and P/NT groups. There was no difference in the incidence of hypertension between the CsA and TAC groups.ConclusionsCsA is an effective and safe agent in the therapy of patients with SRNS.
Evaluation of the vitamin D and biomedical statuses of young children with β-thalassemia major at a single center in southern China
Authors: Yu Uet , Chen Li , Wang Xiaodong , Zhang Xiaoling , Li Yue , Wen Feiqiu , Liu Sixi 
Published: October 2019

Abstract

Background
In young children, β-thalassemia major (β-TM) is associated with potentially severe clinical characteristics, including poor growth, feeding difficulties, hepatosplenomegaly, bone metabolic disorders, and skeletal abnormalities.

Methods
In this study, we reviewed the demographic and clinical characteristics (e.g., age, sex, duration of blood transfusion and chelating therapy, and vitamin supplementation) and serum biomarker levels (e.g., iron accumulation, bone metabolism, liver, kidney, and thyroid function markers) of 32 patients that received regular blood transfusion at a single center in southern China with the aim of stratifying the risk of severe complications such as osteopenia, endocrinopathies, and multi-organ failures.

Results
Although all patients exhibited moderately to strongly elevated serum ferritin levels, this biomarker was significantly higher in children older than ≥5 years, compared to younger children (*p < 0.05, 1512 ± 192.6 vs. 2337 ± 299.8 ng/ml, Mann-Whitney U test). Older children had a significantly lower 25-hydroxy vitamin D3 (25(OH)D3) level, compared to younger children (**p < 0.01, 34.25 ± 11.06 vs. 23.05 ± 9.95 ng/ml, Mann-Whitney U test). No age-related differences were observed in serum calcium, phosphorus, and PTH levels. Regarding liver function, the serum alanine aminotransferase (ALT) level was significantly increased in children older than ≥5 years, compared to younger children (*p < 0.05, 19.17 ± 2.44 vs. 43.45 ± 9.82I U/ml, Mann-Whitney U test). However, no age-related differences were observed in the serum levels of other liver or kidney and thyroid biomarkers.

Conclusions
Our results suggest that in older children, hepatic iron overload may be associated with a low serum concentration of 25(OH)D3, an indicator of vitamin D deficiency and altered bone metabolism. Iron accumulation may also be associated with a higher concentration of ALT, a sensitive marker of liver malfunction. These findings may provide important clinical indications of the need for intervention to prevent severe complications in children with β thalassemia.
A pitfall of bilateral inferior petrosal sinus sampling in cyclic Cushing’s syndrome
Authors: Albani Adriana , Berr Christina M. , Beuschlein Felix , Treitl Marcus , Hallfeldt Klaus , Honegger Jürgen , Schnauder Günter , Reincke Martin 
Published: October 2019

Abstract

Background
Clinical care of patients with cyclic Cushing’s syndrome (CS) is challenging. Classical pitfalls include incorrect subtyping, unnecessary surgical procedures and delayed definite treatment.

Case presentation
A 43-year-old female suffered from a rapidly cycling ectopic CS. She experienced six cycles of severe hypercortisolism within a 2 year period (maximum plasma cortisol 5316 nmol/L, normal range 124.2–662.4 nmol/L; maximum urinary free cortisol 79,469 nmol/24 h, normal range < 414 nmol/24 h) lasting 2–9 weeks. The episodes were associated with pronounced hypokalemia (lowest K+ value recorded 2.4 mmol/l) and progressive signs and symptoms of CS. A bilateral inferior petrosal sinus sampling (BIPSS) performed during a trough phase was false positive for pituitary ACTH overproduction resulting in unnecessary transsphenoidal surgery while a second BIPSS performed during an active phase was indicative for ectopic CS. The 18F-DOPA PET/CT showed a pancreatic lesion, which was subsequently partially removed. Surprisingly, the histopathology was conclusive for ACTH-positive lymph node metastasis located in the retro-duodenal tissue of an occult neuroendocrine tumor WHO grade II. The primary tumor has not been identified so far and, because of the persistent hypercortisolism, the patient underwent bilateral adrenalectomy. Two years later, ACTH levels started to increase progressively. Percutaneous biopsy of a newly identified suspected lesion in the fifth thoracic vertebra revealed a metastasis with positive staining for ACTH, synaptophysin and chromogranin A. Therapy with carboplatin and etoposide was started and, since then, the patient underwent 12 cycles of chemotherapy.

Conclusions
We report the challenging case of a rapidly cycling CS secondary to ACTH-secreting neuroendocrine intestinal tumor of unknown primary. We highlight the importance of performing diagnostic tests only during the phases of active cortisol secretion and as soon as first symptoms appear to avoid pitfalls.
The VENUSS prognostic model to predict disease recurrence following surgery for non-metastatic papillary renal cell carcinoma: development and evaluation using the ASSURE prospective clinical trial cohort
Authors: Klatte Tobias , Gallagher Kevin M. , Afferi Luca , Volpe Alessandro , Kroeger Nils , Ribback Silvia , McNeill Alan , Riddick Antony C. P. , Armitage James N. , ‘Aho Tevita F. , Eisen Tim , Fife Kate , Bex Axel , Pantuck Allan J. , Stewart Grant D. 
Published: October 2019

Abstract

Background
The current World Health Organization classification recognises 12 major subtypes of renal cell carcinoma (RCC). Although these subtypes differ on molecular and clinical levels, they are generally managed as the same disease, simply because they occur in the same organ. Specifically, there is a paucity of tools to risk-stratify patients with papillary RCC (PRCC). The purpose of this study was to develop and evaluate a tool to risk-stratify patients with clinically non-metastatic PRCC following curative surgery.

Methods
We studied clinicopathological variables and outcomes of 556 patients, who underwent full resection of sporadic, unilateral, non-metastatic (T1–4, N0–1, M0) PRCC at five institutions. Based on multivariable Fine-Gray competing risks regression models, we developed a prognostic scoring system to predict disease recurrence. This was further evaluated in the 150 PRCC patients recruited to the ASSURE trial. We compared the discrimination, calibration and decision-curve clinical net benefit against the Tumour, Node, Metastasis (TNM) stage group, University of California Integrated Staging System (UISS) and the 2018 Leibovich prognostic groups.

Results
We developed the VENUSS score from significant variables on multivariable analysis, which were the presence of VEnous tumour thrombus, NUclear grade, Size, T and N Stage. We created three risk groups based on the VENUSS score, with a 5-year cumulative incidence of recurrence equalling 2.9% in low-risk, 15.4% in intermediate-risk and 54.5% in high-risk patients. 91.7% of low-risk patients had oligometastatic recurrent disease, compared to 16.7% of intermediate-risk and 40.0% of high-risk patients. Discrimination, calibration and clinical net benefit from VENUSS appeared to be superior to UISS, TNM and Leibovich prognostic groups.

Conclusions
We developed and tested a prognostic model for patients with clinically non-metastatic PRCC, which is based on routine pathological variables. This model may be superior to standard models and could be used for tailoring postoperative surveillance and defining inclusion for prospective adjuvant clinical trials.
Does public service motivation matter in Moroccan public hospitals? A multiple embedded case study
Authors: Belrhiti Zakaria , Van Damme Wim , Belalia Abdelmounim , Marchal Bruno 
Published: October 2019

AbstractBackgroundThe motivation of health workers is a key concern of policy makers, practitioners and researchers. Public Service Motivation (PSM), defined as the altruistic desire to serve the common interest, to serve others and to help patients and their families regardless of financial or external rewards, has been shown to be key to the performance of public servants. Yet, limited attention has been paid to this kind of motivation in health care settings in low- and middle-income countries. Little is known about PSM and its contextual specificity in the Moroccan health system. We set out to qualitatively explore the meaning of PSM and its expression among health workers in four public hospitals.MethodsWe adopted a multiple embedded case study design to explore PSM in two well-performing and two poor-performing hospitals. We carried out 68 individual interviews, eight focus group discussions and 11 group discussions with different cadres (doctors, administrators and nurses). We carried out thematic analysis using NVivo 10.ResultsOur analysis shows that public service motivation is a notion that seems natural to the health workers we interviewed. Daily interactions with patients catalysed health providers’ affective motives (compassion and self- sacrifice), a central element of PSM. It also provided them with job satisfaction aligned with their intrinsic motivation. Managers and administrative personnel express other PSM components: attraction to public policy making and commitment to public values. A striking result is that health workers expressed strong religious beliefs about expected rewards from God when properly serving patients.ConclusionThis study highlights the presence of PSM as a driver of motivation among health workers in four Moroccon hospitals, and the prominence of intrinsic motivation and compassion in the motivation of frontline health workers. Religious beliefs were found to shape the expression of PSM in Morocco.
Effects of eating with an augmented fork with vibrotactile feedback on eating rate and body weight: a randomized controlled trial
Authors: Hermsen Sander , Mars Monica , Higgs Suzanne , Frost Jeana H. , Hermans Roel C. J. 
Published: October 2019

Abstract

Background
Eating rate is a basic determinant of appetite regulation: people who eat more slowly feel sated earlier and eat less. A high eating rate contributes to overeating and potentially to weight gain. Previous studies showed that an augmented fork that delivers real-time feedback on eating rate is a potentially effective intervention to decrease eating rate in naturalistic settings. This study assessed the impact of using the augmented fork during a 15-week period on eating rate and body weight.

Methods
In a parallel randomized controlled trial, 141 participants with overweight (age: 49.2 ± 12.3 y; BMI: 31.5 ± 4.48 kg/m2) were randomized to intervention groups (VFC, n = 51 or VFC+, n = 44) or control group (NFC, n = 46). First, we measured bite rate and success ratio on five consecutive days with the augmented fork without feedback (T1). The intervention groups (VFC, VFC+) then used the same fork, but now received vibrotactile feedback when they ate more than one bite per 10 s. Participants in VFC+ had additional access to a web portal with visual feedback. In the control group (NFC), participants ate with the fork without either feedback. The intervention period lasted four weeks, followed by a week of measurements only (T2) and another measurement week after eight weeks (T3). Body weight was assessed at T1, T2, and T3.

Results
Participants in VFC and VFC+ had a lower bite rate (p < .01) and higher success ratio (p < .0001) than those in NFC at T2. This effect persisted at T3. In both intervention groups participants lost more weight than those in the control group at T2 (p < .02), with no rebound at T3.

Conclusions
The findings of this study indicate that an augmented fork with vibrotactile feedback is a viable tool to reduce eating rate in naturalistic settings. Further investigation may confirm that the augmented fork could support long-term weight loss strategies.

Trial registration
The research reported in this manuscript was registered on 4 November 2015 in the Netherlands Trial Register with number NL5432 (https://www.trialregister.nl/trial/5432).
The natural course of unruptured intracranial aneurysms in a Chinese cohort: protocol of a multi-center registration study in CIAP
Authors: Liu Haixiao , Guo Wei , Xiang Sishi , Hu Peng , Sun Feifei , Gao Junmei , Zhang Xiaoyang , Wang Ping , Jing Wenting , Zhang Lei , Yang Xinjian , Duan Chuanzhi , He Min , Zhang Hongqi , Qu Yan 
Published: October 2019

AbstractBackgroundSubarachnoid hemorrhage (SAH) accounts for 4.4% of cerebral vascular disease, which is one of the leading causes of death in China. Rupture of intracranial aneurysms (IAs) is the most common cause of SAH. The natural history of unruptured IAs (UIAs) and the risk factors for rupture are among the key issues regarding the pathogenesis of IA and SAH that remain unclear in the Chinese population.MethodsThe China Intracranial Aneurysm Project (CIAP) is a prospective, observational, multicenter registry study of the natural courses, risk factors for the onset and rupture, treatment methods, comorbidity management and other aspects of intracranial aneurysms. To date, there are five studies in the CIAP. CIAP-1 is a prospective observational cohort study of UIAs. More than 5000 patients who will be followed for at least 1 year are expected to be enrolled in this cohort. These participants come from more than 20 centers that represent different regions in China. Enrollment began on May 1, 2017, and will take approximately 5 years. A nationwide online database of UIAs will be built. Participants’ basic, lifestyle, clinical and follow-up information will be collected. The blood samples will be stored in the Central Biological Specimen Bank. Strict standards have been established and will be followed in this study to ensure efficient implementation.DiscussionThe natural course of UIAs in the Chinese population will be explored in this registry study. In addition, the risk factors for the rupture of the UIAs and the joint effect of those factors will be analyzed. The present study aims to create a nationwide database of UIAs and investigate the natural course of UIAs in China.Trial registrationThe Natural Course of Unruptured Intracranial Aneurysms in a Chinese Cohort (ClinicalTrials.gov Identifier: NCT03117803). Registered: July 5, 2017
Characterization of resistance to a potent d-peptide HIV entry inhibitor
Authors: Smith Amanda R. , Weinstock Matthew T. , Siglin Amanda E. , Whitby Frank G. , Francis J. Nicholas , Hill Christopher P. , Eckert Debra M. , Root Michael J. , Kay Michael S. 
Published: October 2019

Abstract

Background
PIE12-trimer is a highly potent d-peptide HIV-1 entry inhibitor that broadly targets group M isolates. It specifically binds the three identical conserved hydrophobic pockets at the base of the gp41 N-trimer with sub-femtomolar affinity. This extremely high affinity for the transiently exposed gp41 trimer provides a reserve of binding energy (resistance capacitor) to prevent the viral resistance pathway of stepwise accumulation of modest affinity-disrupting mutations. Such modest mutations would not affect PIE12-trimer potency and therefore not confer a selective advantage. Viral passaging in the presence of escalating PIE12-trimer concentrations ultimately selected for PIE12-trimer resistant populations, but required an extremely extended timeframe (> 1 year) in comparison to other entry inhibitors. Eventually, HIV developed resistance to PIE12-trimer by mutating Q577 in the gp41 pocket.

Results
Using deep sequence analysis, we identified three mutations at Q577 (R, N and K) in our two PIE12-trimer resistant pools. Each point mutant is capable of conferring the majority of PIE12-trimer resistance seen in the polyclonal pools. Surface plasmon resonance studies demonstrated substantial affinity loss between PIE12-trimer and the Q577R-mutated gp41 pocket. A high-resolution X-ray crystal structure of PIE12 bound to the Q577R pocket revealed the loss of two hydrogen bonds, the repositioning of neighboring residues, and a small decrease in buried surface area. The Q577 mutations in an NL4-3 backbone decreased viral growth rates. Fitness was ultimately rescued in resistant viral pools by a suite of compensatory mutations in gp120 and gp41, of which we identified seven candidates from our sequencing data.

Conclusions
These data show that PIE12-trimer exhibits a high barrier to resistance, as extended passaging was required to develop resistant virus with normal growth rates. The primary resistance mutation, Q577R/N/K, found in the conserved gp41 pocket, substantially decreases inhibitor affinity but also damages viral fitness, and candidate compensatory mutations in gp160 have been identified.