bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of National Drug Pricing Policy 2018 on access to medicines in Lahore division, Pakistan: a pre-post survey study using WHO/HAI methodology
Authors: Saeed Amna , Saeed Hamid , Saleem Zikria , Yang Caijun , Jiang Minghuan , Zhao Mingyue , Ji Wenjing , Aziz Muhammad Majid , Khan Faiz Ullah , Gillani Ali Hassan , Atif Naveel , Fang Yu , Babar Zaheer Ud Din 
Published: October 2020

ObjectiveTo evaluate the impact of new National Drug Pricing Policy (NDPP) 2018 on access to medicines in terms of prices, availability and affordability.DesignTwo cross-sectional surveys were undertaken before and after the launch of NDPP 2018, using a modified WHO/Health Action International (WHO/HAI) methodology.SettingFour districts of Lahore division, Pakistan.Participants16 public sector hospitals and 16 private sector retail pharmacies.MeasuresThe pre and post survey data on prices and availability of lowest price generics (LPGs) and originator brands (OBs) of 50 medicines were obtained by visiting the same public and private sector health facilities (n=32). Out of 50, 46 surveyed medicines were from the National Essential Medicines List. Inflation-adjusted median unit prices (MUPs) and median price ratios (MPRs) from 2019 were used for price comparison. Affordability was calculated in terms of number of days’ wages required to get a standard treatment by the lowest paid unskilled government worker.ResultsThe overall mean percent availabilities remained poor in both years, that is, far less than 80%. In the public sector, the mean percent availability of OBs improved from 6.8% to 33.1%, whereas, in the case of LPGs, it was reduced from 35.1% to 9%. In the private sector, the mean percent availability of both OBs and LPGs demonstrated slight improvements in 2019, that is, 55.0%–58.3% and 20.3%–32.3%. The adjusted MUPs and MPRs of OBs significantly increased by a median of 4.29% (Wilcoxon test p=0.001, p=0.0001), whereas the adjusted MUPs and MPRs of LPGs increased by a median of 15.7% (p=0.002, p=0.0002). Overall, the affordability of many medicines for common ailments was reduced significantly in 2019.ConclusionsThe availability of medicines slightly improved, except in the case of LPGs, which was reduced in the public sector. The implementation of NDPP 2018 led to increase in drug prices, making the standard treatment for some of the most prevalent ailments unaffordable. So verily, the drug pricing policy must be reviewed to ensure access to essential medicines.
Single assessment of delirium severity during postacute intensive care of chronically critically ill patients and its associated factors: post hoc analysis of a prospective cohort study in Germany
Authors: Wintermann Gloria-Beatrice , Weidner Kerstin , Strauss Bernhard , Rosendahl Jenny 
Published: October 2020

ObjectivesTo assess the delirium severity (DS), its risk factors and association with adverse patient outcomes in chronically critically ill (CCI) patients.DesignA prospective cohort study.SettingA tertiary care hospital with postacute intensive care units (ICUs) in Germany.ParticipantsN=267 CCI patients with critical illness polyneuropathy and/or critical illness myopathy, aged 18–75 years, who had undergone elective tracheotomy for weaning failure.InterventionsNone.MeasuresPrimary outcomes: DS was assessed using the Confusion Assessment Method for the Intensive Care Unit-7 delirium severity score, within 4 weeks (t1) after the transfer to a tertiary care hospital. In post hoc analyses, univariate linear regressions were employed, examining the relationship of DS with clinical, sociodemographic and psychological variables.Secondary outcomes: additionally, correlations of DS with fatigue (using the Multidimensional Fatigue Inventory-20), quality of life (using the Euro-Quality of Life) and institutionalisation/mortality at 3 (t2) and 6 (t3) months follow-up were computed.ResultsOf the N=267 patients analysed, 9.4% showed severe or most severe delirium symptoms. 4.1% had a full-syndromal delirium. DS was significantly associated with the severity of illness (p=0.016, 95% CI −0.1 to −0.3), number of medical comorbidities (p<0.001, 95% CI .1 to .3) and sepsis (p<0.001, 95% CI .3 to 1.0). Patients with a higher DS at postacute ICU (t1), showed a higher mental fatigue at t2 (p=0.008, 95% CI .13 to .37) and an increased risk for institutionalisation/mortality (p=0.043, 95% CI 1.1 to 28.9/p=0.015, 95% CI 1.5 to 43.2).ConclusionsIllness severity is positively associated with DS during postacute care in CCI patients. An adequate management of delirium is essential in order to mitigate functional and cognitive long-term sequelae following ICU.Trial registration numberDRKS00003386.
Effectiveness and cost-effectiveness of a progressive, individualised walking and education programme for prevention of low back pain recurrence in adults: study protocol for the WalkBack randomised controlled trial
Authors: Pocovi Natasha Celeste , Lin Chung-Wei C , Latimer Jane , Merom Dafna , Tiedemann Anne , Maher Christopher , van Tulder Maurits W , Macaskill Petra , Clavisi Ornella , Tong Shuk Yin Kate , Hancock Mark J 
Published: October 2020

IntroductionLow back pain (LBP) is recognised globally as a prevalent, costly and disabling condition. Recurrences are common and contribute to much of the burden of LBP. Current evidence favours exercise and education for prevention of LBP recurrence, but an optimal intervention has not yet been established. Walking is a simple, widely accessible, low-cost intervention that has yet to be evaluated. This randomised controlled trial (RCT) aims to establish the effectiveness and cost-effectiveness of a progressive and individualised walking and education programme (intervention) for the prevention of LBP recurrences in adults compared with no treatment (control).Methods and analysisA pragmatic, two-armed RCT comparing walking and education (n=349) with a no treatment control group (n=349). Inclusion criteria are adults recovered from an episode of non-specific LBP within the last 6 months. Those allocated to the intervention group will receive six sessions (three face to face and three telephone delivered) with a trained physiotherapist to facilitate a progressive walking programme and education over a 6-month period. The primary outcome will be days to first recurrence of an episode of activity-limiting LBP. The secondary outcomes include days to recurrence of an episode of LBP, days to recurrence of an episode of LBP leading to care seeking, disability and quality of life measured at 3, 6, 9 and 12 months and costs associated with LBP recurrence. All participants will be followed up monthly for a minimum of 12 months. The primary intention-to-treat analysis will assess difference in survival curves (days to recurrence) using the log-rank statistic. The cost-effectiveness analysis will be conducted from the societal perspective.Ethics and disseminationApproved by Macquarie University Human Research Ethics Committee (Reference: 5201949218164, May 2019). Findings will be disseminated through publication in peer-reviewed journals and conference presentations.Trial registration numberACTRN12619001134112.
Skin and wound care for individuals with graft versus host disease: a scoping review protocol
Authors: Campbell Jill , Gavin Nicole , Button Elise , Roberts Natasha 
Published: October 2020

IntroductionGraft versus host disease (GVHD) is a major cause of morbidity and mortality following allogenic haematopoietic stem cell transplantation. It is an immunological reaction, involving many organs, leading to a wide range of clinical manifestations. Cutaneous manifestations are the most common sign of GVHD, as well as pain, vulnerability to infection and impaired quality of life.Despite the burdens that cutaneous GVHD presents for patients, their carers and the healthcare system, limited evidence is available to guide day to day supportive skin care and wound management. Our objective is to conduct a scoping review to map the evidence for skin and wound management and identify evidence-practice gaps for individuals with acute or chronic cutaneous GVHD.Methods and analysisOur review will follow the scoping review methodological framework developed by Arksey and O’Malley and further refined by the Joanna Briggs Institute Scoping Review Methods Manual. Databases to be searched include; PubMed, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Web of Science and MEDLINE from 1970 to February 2020. Database searches will be supplemented with searches from relevant reference lists and grey literature. Descriptive statistical analyses will be performed.Ethics and disseminationThis scoping review does not require ethical approval. Findings will be disseminated through a peer-reviewed publication and conference presentation.
Safety and efficacy of larval therapy on treating leg ulcers: a protocol for systematic review and meta-analysis
Authors: Fan Weijing , Yang Baozhong , Hu Xiaoming , Yang Xiao , Shi Chenyan , Liu Guobin 
Published: October 2020

IntroductionLeg ulcers (LUs) not only seriously affect life and work of patients, but also bring huge economic burden to the society. As a potential underused biological debridement, larval therapy provides help for the treatment of LUs. The purpose of our research is to assess whether patients with LUs can benefit from larval therapy.Methods and analysisThe following electronic databases will be searched: PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure Database, Wanfang Database and Chinese Biological Medicine. Randomised controlled trials are eligible for inclusion. There will be no restrictions with respect to language and search date is up to June 2020. Primary outcomes investigated are complete healing rate after treatment, time to ulcer healing, reduction of wound surface area and adverse events. Risk ratios will be used for categorical data; weighted mean difference will be used for measurement data. Subgroup analysis and sensitivity analysis will be considered if heterogeneity exists. The results of data synthesis will be performed by narrative summary and quantitative analysis.Ethics and disseminationThis systematic review does not require the approval of the ethics committee because individual data on patients are not collected. The results of the study will be disseminated in peer-reviewed journals.PROSPERO registration numberCRD42020176953.
Mortality and pulmonary complications in patients undergoing upper extremity surgery at the peak of the SARS-CoV-2 pandemic in the UK: a national cohort study
Authors: Dean Benjamin John Floyd 
Published: October 2020

IntroductionThis study reports the 30-day mortality, SARS-CoV-2 complication rate and SARS-CoV-2-related hospital processes at the peak of the first wave of the pandemic in the UK.MethodsThis national, multicentre, cohort study at 74 centres in the UK included all patients undergoing any surgery below the elbow at the peak of the UK pandemic. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The secondary outcomes were SARS-CoV-2 complication rates and overall complication rates. A clinician survey relating to SARS-CoV-2 safety processes was carried out for each participating centre.ResultsThis analysis includes 1093 patients who underwent upper limb surgery from the 1 to 14 April 2020 inclusively. The overall 30-day mortality was 0.09% (1 pre-existing SARS-CoV-2 pneumonia) and the mortality of day case surgery was zero. Most centres (96%) screened patients for symptoms prior to admission, only 22% routinely tested for SARS-CoV-2 prior to admission. The SARS-CoV-2 complication rate was 0.18% (2 pneumonias) and the overall complication rate was 6.6% (72 patients). Both SARS-CoV-2-related complications occurred in patients who had been hospitalised for a prolonged period before their surgery and a total of 19 patients (1.7%) were SARS-CoV-2 positive.ConclusionsThe SARS-CoV-2-related complication rate for upper limb surgery even at the peak of the UK pandemic was low at 0.18% and the mortality was zero for patients admitted on the day of surgery. Urgent surgery should not be delayed pending the results of SARS-CoV-2 testing. Routine SARS-CoV-2 testing for day case upper limb surgery not requiring general anaesthesia may be excessive and have unintended negative impacts.
CASPA (CArdiac Sarcoidosis in PApworth) improving the diagnosis of cardiac involvement in patients with pulmonary sarcoidosis: protocol for a prospective observational cohort study
Authors: Quijano-Campos Juan Carlos , Williams Lynne , Agarwal Sharad , Tweed Katharine , Parker Robert , Lalvani Ajit , Chiu Yi-Da , Dorey Kane , Devine Thomas , Stoneman Victoria , Toshner Mark , Thillai Muhunthan 
Published: October 2020

IntroductionSarcoidosis is a multisystem disease, predominantly affecting the lungs but can involve the heart, resulting in cardiac sarcoidosis (CS). Patients require MRI/Positron Emission Tomography (PET) scans for diagnosis. Echocardiography, ECG and Holter monitoring may be indicative but not diagnostic alone. Patients can present late with conduction defects, heart failure or sudden death. The CASPA (CArdiac Sarcoidosis in PApworth) study protocol aims to (1) use MRI to identify CS prevalence; (2) use speckle-tracking echocardiography, signal averaged ECG and Holter monitoring to look for diagnostic pathways; and (3) identify serum proteins which may be associated with CS.Methods and analysisParticipants with pulmonary sarcoidosis (and no known cardiac disease) from Royal Papworth Hospital will have the following: cardiac MRI with late gadolinium, two-dimensional transthoracic echocardiography with speckle tracking, signal averaged ECG and 24-hour Holter monitor. They will provide a serum sample for brain natriuretic peptide levels and proteomics by liquid chromatography coupled to high-resolution mass spectrometry. All data will be collected on OpenClinica platform and analysed approximately 6 months after final patient recruitment.Ethics and disseminationThe Camden & Kings Cross Research Ethics Committee approved the protocol (REC number: 17/LO/0667). Integrated Research Approval System (IRAS) 222 720. Dissemination of findings will be via conference presentations and submitted to peer-reviewed journals.
Cluster cross-over randomised trial of paediatric airway management devices in the simulation lab and operating room among paramedic students
Authors: Hansen Matthew Lee , Wagner Adam , Schnapp Ashley , Lin Amber , Le Nancy , Deverman Sarah , Pedigo Elizabeth , Johnson Andrea , Cusick Jordan , Gries Heike , Kato Meredith 
Published: October 2020

ObjectivesThe objective of this study was to compare paediatric emergency airway management strategies in the simulation lab and operating room environments.MethodsThis was a two-part cluster cross-over randomised trial including simulation lab and operating room environments conducted between January 2017 and June 2018 in Portland, Oregon, USA. In simulated infant cardiac arrests, paramedic students placed an endotracheal tube, an i-gel or a laryngeal mask airway in random order. In the operating room, paramedic students placed a laryngeal mask airway or i-gel device in random order in sequential patients. The primary outcome for both portions of the study was time to ventilation. In the operating room portion, we also evaluated leak pressures and average initial tidal volumes.ResultsThere were 58 paramedic students who participated in the simulation lab and 22 who participated in the operating room study. The mean time to airway placement in the simulation lab was 48.5 s for the i-gel, 68.9 s for the laryngeal mask and 129.5 s for the endotracheal tube. In the operating room, mean time to i-gel placement was 34.3 s with 45.2 s for the laryngeal mask. In multivariable analysis of the simulation study, the laryngeal mask and i-gel were significantly faster than the endotracheal tube, and the i-gel was faster than the laryngeal mask. In the operating room, there was no significant difference in time to placement, leak pressure and average volume of the first five breaths between the i-gel and laryngeal mask.ConclusionsWe found that paramedic students were able to place supraglottic devices rapidly with high success rates in simulation lab and operating room environments. Supraglottic devices, particularly the i-gel, were rated as easy to use. The i-gel may be easiest to use since it lacks an inflable cuff and requires fewer steps to place.
Prevalence of mismatch repair deficiency and Lynch syndrome in a cohort of unselected small bowel adenocarcinomas
Authors: Suerink Manon , Kilinç Gül , Terlouw Diantha , Hristova Hristina , Sensuk Lily , van Egmond Demi , Farina Sarasqueta Arantza , Langers Alexandra M J , van Wezel Tom , Morreau Hans , Nielsen Maartje 
Published: October 2020

AimsPrevious estimates of the prevalence of mismatch repair (MMR) deficiency and Lynch syndrome in small bowel cancer have varied widely. The aim of this study was to establish the prevalence of MMR deficiency and Lynch syndrome in a large group of small bowel adenocarcinomas.MethodsTo this end, a total of 400 small bowel adenocarcinomas (332 resections, 68 biopsies) were collected through the Dutch nationwide registry of histopathology and cytopathology (Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief (PALGA)). No preselection criteria, such as family history, were applied, thus avoiding (ascertainment) bias. MMR deficiency status was determined by immunohistochemical staining of MMR proteins, supplemented byMLH1promoter hypermethylation analysis and next generation sequencing of the MMR genes.ResultsMMR deficiency was observed in 22.3% of resected and 4.4% of biopsied small bowel carcinomas. Prevalence of Lynch syndrome was 6.2% in resections and 0.0% in biopsy samples. Patients with Lynch syndrome-associated small bowel cancer were significantly younger at the time of diagnosis than patients with MMR-proficient and sporadic MMR-deficient cancers (mean age of 54.6 years vs 66.6 years and 68.8 years, respectively, p<0.000).ConclusionsThe prevalence of MMR deficiency and Lynch syndrome in resected small bowel adenocarcinomas is at least comparable to prevalence in colorectal cancers, a finding relevant both for treatment (immunotherapy) and family management. We recommend that all small bowel adenocarcinomas should be screened for MMR deficiency.
Serum IgG anti-GD1a antibody and mEGOS predict outcome in Guillain-Barré syndrome
Authors: Yamagishi Yuko , Kuwahara Motoi , Suzuki Hidekazu , Sonoo Masahiro , Kuwabara Satoshi , Yokota Takanori , Nomura Kyoichi , Chiba Atsuro , Kaji Ryuji , Kanda Takashi , Kaida Ken-ichi , Mutoh Tatsuro , Yamasaki Ryo , Takashima Hiroshi , Matsui Makoto , Nishiyama Kazutoshi , Sobue Gen , Kusunoki Susumu 
Published: October 2020

Objective
Approximately 15%–20% of patients with Guillain-Barré syndrome (GBS) are unable to walk independently at 6 months from the onset of neurological symptom. The modified Erasmus GBS outcome score (mEGOS) has been reported as a prognostic tool.
Herein we investigated the association between a poor outcome, inability to walk independently at 6 months and presence of antiganglioside antibodies.

Methods
The clinical and serological data of 177 patients with GBS were retrospectively collected in Japan to assess the associations between a poor outcome and serum IgG antibodies against each ganglioside (GM1, GD1a, GalNAc-GD1a, GQ1b and GT1a). In addition, we investigated whether the combination of mEGOS and serum IgG antibodies against gangliosides is useful in predicting a poor outcome.

Results
The patients with IgG anti-GD1a antibodies more frequently showed poor outcomes than those without these antibodies (9 (36%) of 25 vs 8 (6%) of 127 patients, p<0.001). Particularly, 80% showed a poor outcome when they had both serum IgG anti-GD1a antibody and a high mEGOS of ≥10 on day 7 of admission.

Conclusions
The combination of serum IgG anti-GD1a antibodies and a high mEGOS could help in making a more accurate prognosis of patients than mEGOS alone, especially for predicting poor outcomes.
Anomalous erosion patterns on the cheek teeth of babirusa (genus Babyrousa)
Authors: Macdonald A.A. 
Published: October 2020

Two types of anomalous erosive wear, designated “Wear” and “Groove”, were found in the molar teeth of adult babirusa (genus Babyrousa Perry, 1811) species from Buru or the Sula Islands and Sulawesi, Indonesia. A survey of 590 specimens of babirusa crania and mandibles from international museums and private collections revealed their presence in 20 of 187 specimens from Buru or the Sula Islands, in 99 of 391 specimens from Sulawesi, and in 4 of 31 subfossil specimens from South Sulawesi. “N_Wear” comprised a discrete indentation or almost circular erosion of the enamel and underlying dentine in a molar tooth; “W_Wear” comprised tooth indentations of irregular shape larger than 7 mm × 7 mm in size; “E_Wear” comprised extensive tooth indentation. “Wear” anomalies were found on 10% of specimens from Buru or the Sula Islands and on 17% of all Sulawesi crania and mandibles. It was hypothesised that tooth grinding of the abrasive seeds of the wild banana (Musa balbisiana Colla) initiated this anomaly. Groove was a deep, oval-shaped cleft cut into the enamel and dentine between two molar teeth. Groove anomalies were evident in 3% of Buru or the Sula Islands specimens and in 12% of all Sulawesi specimens. No conclusion was reached regarding the initiator of the Groove anomaly.
Combined Inhibition of SHP2 and MEK Is Effective in Models of NF1-Deficient Malignant Peripheral Nerve Sheath Tumors
Authors: Wang Jiawan , Pollard Kai , Allen Amy N. , Tomar Tushar , Pijnenburg Dirk , Yao Zhan , Rodriguez Fausto J. , Pratilas Christine A. 
Published: October 2020

Abstract

Loss of the RAS GTPase-activating protein (RAS-GAP) NF1 drives aberrant activation of RAS/MEK/ERK signaling and other effector pathways in the majority of malignant peripheral nerve sheath tumors (MPNST). These dysregulated pathways represent potential targets for therapeutic intervention. However, studies of novel single agents including MEK inhibitors (MEKi) have demonstrated limited efficacy both preclinically and clinically, with little advancement in overall patient survival. By interrogation of kinome activity through an unbiased screen and targeted evaluation of the signaling response to MEK inhibition, we have identified global activation of upstream receptor tyrosine kinases (RTK) that converges on activation of RAS as a mechanism to limit sensitivity to MEK inhibition. As no direct inhibitors of pan-RAS were available, an inhibitor of the protein tyrosine phosphatase SHP2, a critical mediator of RAS signal transduction downstream of multiple RTK, represented an alternate strategy. The combination of MEKi plus SHP099 was superior to MEKi alone in models of NF1-MPNST, including those with acquired resistance to MEKi. Our findings have immediate translational implications and may inform future clinical trials for patients with MPNST harboring alterations in NF1.

Significance:
Combined inhibition of MEK and SHP2 is effective in models of NF1-MPNST, both those naïve to and those resistant to MEKi, as well as in the MPNST precursor lesion plexiform neurofibroma.