The Chagas disease study landscape: A systematic review of clinical and observational antiparasitic treatment studies to assess the potential for establishing an individual participant-level data platform

Background Chagas disease (CD), caused by the parasite Trypanosoma cruzi, affects ~6–7 million people worldwide. Significant limitations still exist in our understanding of CD. Harnessing individual participant data (IPD) from studies could support more in-depth analyses to address the many outstanding research questions. This systematic review aims to describe the characteristics and treatment practices of clinical studies in CD and assess the breadth and availability of research data for the potential establishment of a data-sharing platform. Methodology/Principal findings This review includes prospective CD clinical studies published after 1997 with patients receiving a trypanocidal treatment. The following electronic databases and clinical trial registry platforms were searched: Cochrane Library, PubMed, Embase, LILACS, Scielo, Clintrials.gov, and WHO ICTRP. Of the 11,966 unique citations screened, 109 (0.9%) studies (31 observational and 78 interventional) representing 23,116 patients were included. Diagnosis for patient enrolment required 1 positive test result in 5 (4.6%) studies (2 used molecular method, 1 used molecular and serology, 2 used serology and parasitological methods), 2 in 60 (55.0%), 3 in 14 (12.8%) and 4 or more in 4 (3.7%) studies. A description of treatment regimen was available for 19,199 (83.1%) patients, of whom 14,605 (76.1%) received an active treatment and 4,594 (23.9%) were assigned to a placebo/no-treatment. Of the 14,605 patients who received an active treatment, benznidazole was administered in 12,467 (85.4%), nifurtimox in 825 (5.6%), itraconazole in 284 (1.9%), allopurinol in 251(1.7%) and other drugs in 286 (1.9%). Assessment of efficacy varied largely and was based primarily on biological outcome; parasitological efficacy relied on serology in 67/85 (78.8%) studies, molecular methods in 52/85 (61.2%), parasitological in 34/85 (40.0%), microscopy in 3/85 (3.5%) and immunohistochemistry in 1/85 (1.2%). The median time at which parasitological assessment was carried out was 79 days [interquartile range (IQR): 30–180] for the first assessment, 180 days [IQR: 60–500] for second, and 270 days [IQR: 18–545] for the third assessment. Conclusions/Significance This review demonstrates the heterogeneity of clinical practice in CD treatment and in the conduct of clinical studies. The sheer volume of potential IPD identified demonstrates the potential for development of an IPD platform for CD and that such efforts would enable in-depth analyses to optimise the limited pharmacopoeia of CD and inform prospective data collection.

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Synthetic Bone Substitutes and Mechanical Devices for the Augmentation of Osteoporotic Proximal Humeral Fractures: A Systematic Review of Clinical Studies

Journal of Functional Biomaterials ◽

10.3390/jfb11020029 ◽

2020 ◽

Vol 11 (2) ◽

pp. 29 ◽

Cited By ~ 1

Author(s):

Giuseppe Marongiu ◽

Marco Verona ◽

Gaia Cardoni ◽

Antonio Capone

Keyword(s):

Systematic Review ◽

Clinical Studies ◽

Calcium Sulfate ◽

Bone Substitutes ◽

Proximal Humeral Fractures ◽

Humeral Fractures ◽

Cochrane Library ◽

Synthetic Bone ◽

Mechanical Devices ◽

Pmma Cement

Background: Different augmentation techniques have been described in the literature in addition to the surgical treatment of proximal humeral fractures. The aim of this systematic review was to analyze the use of cements, bone substitutes, and other devices for the augmentation of proximal humeral fractures. Methods: A systematic review was conducted by using PubMed/MEDLINE, ISI Web of Knowledge, Cochrane Library, Scopus/EMBASE, and Google Scholar databases according the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines over the years 1966 to 2019. The search term “humeral fracture proximal” was combined with “augmentation”; “polymethylmethacrylate, PMMA”; “cement”; “bone substitutes”; “hydroxyapatite”; “calcium phosphates”; “calcium sulfate”; “cell therapies”, and “tissue engineering” to find the literature relevant to the topic under review. Results: A total of 10 clinical studies considered eligible for the review, with a total of 308 patients, were included. Mean age at the time of injury was 68.8 years (range of 58–92). The most commonly described techniques were reinforcing the screw–bone interface with bone PMMA cement (three studies), filling the metaphyseal void with synthetic bone substitutes (five studies), and enhancing structural support with metallic devices (two studies). Conclusion: PMMA cementation could improve screw-tip fixation. Calcium phosphate and calcium sulfate injectable composites provided good biocompatibility, osteoconductivity, and lower mechanical failure rate when compared to non-augmented fractures. Mechanical devices currently have a limited role. However, the available evidence is provided mainly by level III to IV studies, and none of the proposed techniques have been sufficiently studied.

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Combination of Jinshuibao Capsules and Conventional Pharmaceutical Treatments for Patients with Stable Chronic Obstructive Pulmonary Disease: A Systematic Review and a Meta-Analysis

10.37766/inplasy2021.10.0117 ◽

2021 ◽

Author(s):

Yilan Wang ◽

◽

Sijing Zhao ◽

Zherui Shen ◽

Zhenxing Wang ◽

...

Keyword(s):

Systematic Review ◽

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Meta Analysis ◽

Cochrane Library ◽

Chronic Obstructive ◽

Clinical Trial Registry ◽

Service Platform ◽

Obstructive Pulmonary Disease ◽

Integration Service

Review question / Objective: Jinshuibao capsules are derived from Cordyceps, and they have been widely used in the treatment of different diseases. They have also been utilized in the treatment of respiratory diseases, while their effects on patients with stable chronic obstructive pulmonary disease (COPD) have remained elusive. The present study aimed to compare the efficacy of Jinshuibao capsules plus conventional pharmaceutical treatments (CPT) versus CPT alone for patients with stable COPD. Information sources: It was attempted to conduct a systematic review and a meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. In addition, PubMed, EMBASE, Cochrane Library, Web of Science, China Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, VIP Information Resource Integration Service Platform (CQVIP), and China Biomedicine (SinoMed) databases were searched from inception until September 30, 2021. Google Scholar and the China Clinical Trial Registry were also searched for retrieving missing data. In emergency conditions, we contacted the corresponding authors of retrieved studies for collection of additional data.

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Evidence-based uncertainty: do implant-related properties of titanium reduce the susceptibility to perioperative infections in clinical fracture management? A systematic review

Infection ◽

10.1007/s15010-021-01583-z ◽

2021 ◽

Author(s):

Michael C. Tanner ◽

Christian Fischer ◽

Gerhard Schmidmaier ◽

Patrick Haubruck

Keyword(s):

Systematic Review ◽

Stainless Steel ◽

Clinical Studies ◽

Contemporary Literature ◽

Titanium Implants ◽

Cochrane Library ◽

Randomized Controlled Studies ◽

Fracture Management ◽

The Cochrane Library ◽

Tissue Trauma

Abstract Background Implant-associated infections (IAI) remain a challenging complication in osteosynthesis. There is no consensus or clear evidence whether titanium offers a relevant clinical benefit over stainless steel. Purpose In this systematic review, we sought to determine whether the implant properties of titanium reduce the susceptibility to IAI compared to stainless steel in fracture management. Methods A systematic literature search in German and English was performed using specific search terms and limits. Studies published between 1995 and 1st June 2020 in the Cochrane library, MEDLINE and Web of Science databases were included. Only clinical studies comparing titanium and stainless steel implants regarding the susceptibility to infections were selected for detailed review. Results Five studies out of 384 papers were identified and reviewed. From the studies meeting inclusion criteria one study was a systematic review, two studies were randomized controlled studies (RCT) and two studies were of retrospective comparative nature of level IV evidence. Conclusion Our results show that currently, no proven advantage for titanium implants in respect to IAI can be seen in contemporary literature. Implants preserving periosteal blood-flow and minimising soft-tissue trauma show statistically significant benefits in reducing the incidence of IAI. Clinical studies providing reliable evidence regarding the influence of titanium implants on IAI and investigating the susceptibility of titanium to infection are necessary

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Reducing Self-harm in Adolescents. An individual participant data meta-analysis (RISA-IPD): systematic review protocol

BMJ Open ◽

10.1136/bmjopen-2021-049255 ◽

2021 ◽

Vol 11 (5) ◽

pp. e049255

Author(s):

Alexandra Wright-Hughes ◽

Rebecca Walwyn ◽

Judy M Wright ◽

Amanda Farrin ◽

Peter Fonagy ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Therapeutic Interventions ◽

Sensitivity Analyses ◽

Collaborative Group ◽

Cochrane Library ◽

Advisory Group ◽

Individual Participant Data ◽

Individual Participant ◽

Self Harm

IntroductionUp to 10% of adolescents report self-harm in the previous year. Non-fatal repetition is common (18% in 1 year), death from any cause shows a fourfold and suicide a 10-fold excess. Despite the scale of the problem, there is insufficient evidence for effective interventions for self-harm. Those who self-harm do so for a variety of different reasons. Different treatments may be more effective for subgroups of adolescents; however, little is known about which subgroups are appropriate for further study. This protocol outlines a systematic review and individual participant data meta-analysis (IPD-MA) to identify subgroups of adolescents for which therapeutic interventions for self-harm show some evidence of benefit.Methods and analysisA systematic literature search was conducted in August 2019 (including Cochrane Library, Embase, trial registers and other databases). An update search is planned. Study selection will identify randomised controlled trials examining interventions to reduce self-harm in adolescents who have self-harmed and presented to services. Identified research teams will be invited to contribute data and form a collaborative group. Two-stage IPD-MA will be used to evaluate effectiveness of different therapeutic interventions compared with any active or non-active control on repetition of self-harm, general psychopathology, depression, suicidal ideation, quality of life and death. Subgroup analyses will identify adolescent subgroups in whom different therapeutic interventions may be more effective. Meta-regression will explore moderating study and intervention effects. Sensitivity analyses will incorporate aggregate data from studies lacking IPD and test the robustness of results to methods for handling missing data, within-study clustering, non-adherence and study quality.Ethics and disseminationEthical approval is provided by the University of Leeds, Faculty of Medicine and Health Ethics Committee (18-098). Outcomes will inform research recommendations and will be disseminated internationally through the collaborative group, a service user advisory group, open-access peer-reviewed publication and conference presentations.PROSPERO registration numberCRD42019152119.

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A Systematic Review of Devices and Techniques that Objectively Measure Patients’ Pain

January 2018 - Pain Physician ◽

10.36076/ppj/2019.22.1 ◽

2019 ◽

Vol 1 (22;1) ◽

pp. 1-13

Author(s):

Joost J.C. Verhoeff

Keyword(s):

Systematic Review ◽

Clinical Practice ◽

Pain Intensity ◽

Clinical Studies ◽

Pain Measurement ◽

Cochrane Library ◽

Pressure Probe ◽

Measurement Tool ◽

Pain Stimulus ◽

Pain Scales

Background: Assessment of pain is important in daily clinical practice and as an endpoint in clinical studies. Because pain perception is highly subjective, pain measurement is complex. Selfrating pain scales are currently of great importance but have limitations. They depend on many more factors than pain, which could lead to an incorrect assessment of therapies or clinical studies. Therefore, there is need for valid, reliable, safe, and low-cost methods to determine and quantify patients’ pain more objectively. Objective: To provide an overview of devices and techniques that can be used to administer a pain stimulus with similar intensity as the endogenous pain experienced by the patient, in order to quantify and subsequently follow patients’ pain more objectively. Study Design: In this systematic review, articles from PubMed, EMBASE, Cochrane library and Scopus were reviewed for eligibility. Methods: Studies that described a device or technique that could be used to induce a variable, controlled, and measurable pain stimulus were included. Studies that made correlations with established pain scales or those who compared outcomes in multiple tests were selected to assess validity and reliability. Results: A total of 1,308 manuscripts were initially retrieved. After independent screening by a team of 4 reviewers, 19 studies were eventually included describing 15 different devices or techniques. These devices could be divided into groups based on stimulus administration: electrical, external pressure (probe) and miscellaneous pain stimulators. Electrical stimulators were found to be tested extensively and proven to be both valid and reliable. Limitations: To correlate new techniques with older methods such as the Numeric Rating Scale (NRS) and Visual Analogue Scale (VAS) for which an improvement is desired, is debatable. To (partially) address this problem, the reliability is added as an additional primary outcome to assess which device works best. Further limitations include the heterogeneity of studies found in both the types of pain measured as in outcome measures presented. In addition, it is important to note that part of the devices described cannot directly be used for clinical practice due to products that have cease to exist or the description of solely techniques rather than testing ready-to-use devices. Conclusion: Several devices and techniques compared pain intensity experienced by patients with an external pain stimulus that potentially could be used as a new objective pain measurement tool. Given the results of our review, electrical stimulators that have been tested extensively with high validity, reliability, and feasibility would be recommended for use for clinical and research purposes. Moreover, normalization of pain intensity scores for current perception is important. Pain intensity normalization leads to higher correlations with established pain scales and possibly to increased inter-patient reliability. Registration number: Registered in the PROSPERO database (PROSPERO 2016:CRD42016041974) Key words: Systematic review, objective pain measurement, pain scales; devices, techniques, validity, reliability, safety, feasibility

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Effectiveness of intraoperative peritoneal lavage (IOPL) with saline in patient with intra-abdominal infections: a systematic review and meta-analysis protocol

BMJ Open ◽

10.1136/bmjopen-2019-036273 ◽

2020 ◽

Vol 10 (7) ◽

pp. e036273

Author(s):

Qi Zhou ◽

Qianling Shi ◽

Xuan Yu ◽

Zijun Wang ◽

Jingyi Zhang ◽

...

Keyword(s):

Systematic Review ◽

Peritoneal Lavage ◽

Meta Analysis ◽

Abdominal Cavity ◽

Cochrane Library ◽

Clinical Trial Registry ◽

Evaluation Approach ◽

Randomised Controlled ◽

Abdominal Infections ◽

Analysis Protocol

IntroductionIntra-abdominal infections (IAIs) are common surgical emergencies and cause a significant worldwide burden per year. Since the concept of intraoperative peritoneal lavage (IOPL) was proposed in 1905, it has been widely used in the surgery practice. However, the effectiveness of IOPL in patients with IAIs has always been controversial. Our objective is to identify whether it is beneficial to flush the abdominal cavity with saline in IAIs surgery through a comprehensive systematic review and meta-analysis.Methods and analysisThis protocol is reported in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Electronic databases (including the Cochrane library, MEDLINE, EMBASE, Web of Science, etc) and clinical trial registry platforms will be searched from inception to 8 September 2019. Randomised controlled trials, quasi-randomised clinical trials and cohort studies comparing IOPL and suction alone in IAIs will be included. The primary outcomes are mortality and abscess rate. Two independent reviewers will screen literature, collect data and assess risk of bias of included studies. Discussion or a third reviewer will be referred for any disagreements. The Grading of Recommendations Assessment, Development and Evaluation approach will be used to assess the quality of the evidence. We will perform meta-analysis using random-effects model. Subgroup analysis, sensitivity analysis and publication bias will be conducted if data are enough.Ethics and disseminationEthical approval is not required for this systematic review and meta-analysis protocol. Results of this study will be published in a peer-reviewed journal, presented at relevant conferences and disseminated to local and international policy makers.PROSPERO registration numberCRD42019145109.

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Sitafloxacin for Third-Line Helicobacter pylori Eradication: A Systematic Review

Journal of Clinical Medicine ◽

10.3390/jcm10122722 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2722

Author(s):

Toshihiro Nishizawa ◽

Munkhbayar Munkjargal ◽

Hirotoshi Ebinuma ◽

Osamu Toyoshima ◽

Hidekazu Suzuki

Keyword(s):

Systematic Review ◽

Helicobacter Pylori ◽

Clinical Studies ◽

Eradication Rate ◽

Safety Concern ◽

Drug Susceptibility ◽

Cochrane Library ◽

Helicobacter Pylori Eradication ◽

Third Line ◽

Event Rates

Background and Aim: Sitafloxacin-based therapy is a potent candidate for third-line Helicobacter pylori eradication treatment. In this systematic review, we summarise current reports with sitafloxacin-based therapy as a third-line treatment. Methods: Clinical studies were systematically searched using PubMed, Cochrane library, Web of Science, and the Igaku-Chuo-Zasshi database. We combined data from clinical studies using a random-effects model and calculated pooled event rates, 95% confidence intervals (CIs), and the pooled odds ratio (OR). Results: We included twelve clinical studies in the present systematic review. The mean eradication rate for 7-day regimens of either PPI (proton pump inhibitor) or vonoprazan–sitafloxacin–amoxicillin was 80.6% (95% CI, 75.2–85.0). The vonoprazan–sitafloxacin–amoxicillin regimen was significantly superior to the PPI–sitafloxacin–amoxicillin regimen (pooled OR of successful eradication: 6.00; 95% CI: 2.25–15.98, p < 0.001). The PPI–sitafloxacin–amoxicillin regimen was comparable with PPI–sitafloxacin–metronidazole regimens (pooled OR: 1.06; 95% CI: 0.55–2.07, p = 0.86). Conclusions: Although the 7-day regimen composed of vonoprazan, sitafloxacin, and amoxicillin is a good option as the third-line Helicobacter pylori eradication treatment in Japan, the extension of treatment duration should be considered to further improve the eradication rate. Considering the safety concern of fluoroquinolones, sitafloxcin should be used after confirming drug susceptibility.

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PLATELET-RICH PLASMA THERAPY FOR ERECTILE DYSFUNCTION: A REVIEW OF PRECLINICAL AND CLINICAL STUDIES

Research n Practical Medicine Journal ◽

10.17709/2409-2231-2019-6-3-7 ◽

2019 ◽

Vol 6 (3) ◽

pp. 74-86

Author(s):

A. D. Kaprin ◽

A. A. Kostin ◽

M. V. Epifanova ◽

M. E. Chalyy ◽

E. V. Gameeva ◽

...

Keyword(s):

Systematic Review ◽

Erectile Dysfunction ◽

Clinical Studies ◽

Platelet Rich Plasma ◽

Meta Analysis ◽

Current Data ◽

Cochrane Library ◽

Multicenter Studies ◽

Plasma Therapy ◽

Preclinical And Clinical Studies

Erectile dysfunction is no longer a psychosocial problem. Nowadays, it is a marker specific for the initial stages of cardiovascular diseases. Рlatelet-rich plasma (PRP) is a new and promising method, which totally deserves to be noted by specialists. To review currently existing pre-clinical and clinical studies concerning application of PRP in erectile dysfunction published in international sources such as PubMed, Cochrane Library, Clinicaltrials.gov. The current data of preclinical and clinical studies determine the absence of PRP side effects and the effectiveness for ED treatment. PRP-therapy is a pathogenetically substantiated method of treating erectile dysfunction. The therapy is designed for repair and regeneration of endothelium, smooth muscle cells, and connective tissue. However, large, placebo-controlled, multicenter studies are needed to creation a systematic review and meta-analysis.

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Probiotic Strains and Intervention Total Doses for Modulating Obesity-Related Microbiota Dysbiosis: A Systematic Review and Meta-analysis

Nutrients ◽

10.3390/nu12071921 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1921 ◽

Cited By ~ 1

Author(s):

Ana López-Moreno ◽

Antonio Suárez ◽

Camila Avanzi ◽

Mercedes Monteoliva-Sánchez ◽

Margarita Aguilera

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Full Text ◽

Clinical Studies ◽

Meta Analysis ◽

Plasma Lipid ◽

Gut Hormones ◽

Positive Association ◽

Cochrane Library ◽

Probiotic Strains

Obesity is a growing health threat worldwide. Administration of probiotics in obesity has also parallelly increased but without any protocolization. We conducted a systematic review exploring the administration pattern of probiotic strains and effective doses for obesity-related disorders according to their capacity of positively modulating key biomarkers and microbiota dysbiosis. Manuscripts targeting probiotic strains and doses administered for obesity-related disorders in clinical studies were sought. MEDLINE, Scopus, Web of Science, and Cochrane Library databases were searched using keywords during the last fifteen years up to April 2020. Two independent reviewers screened titles, abstracts, and then full-text papers against inclusion criteria according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. From 549 interventional reports identified, we filtered 171 eligible studies, from which 24 full-text assays were used for calculating intervention total doses (ITD) of specific species and strains administered. Nine of these reports were excluded in the second-step because no specific data on gut microbiota modulation was found. Six clinical trials (CT) and 9 animal clinical studies were retained for analysis of complete outcome prioritized (body mass index (BMI), adiposity parameters, glucose, and plasma lipid biomarkers, and gut hormones). Lactobacillus spp. administered were double compared to Bifidobacterium spp.; Lactobacillus as single or multispecies formulations whereas most Bifidobacteria only through multispecies supplementations. Differential factors were estimated from obese populations’ vs. obesity-induced animals: ITD ratio of 2 × 106 CFU and patterns of administrations of 11.3 weeks to 5.5 weeks, respectively. Estimation of overall probiotics impact from selected CT was performed through a random-effects model to pool effect sizes. Comparisons showed a positive association between the probiotics group vs. placebo on the reduction of BMI, total cholesterol, leptin, and adiponectin. Moreover, negative estimation appeared for glucose (FPG) and CRP. While clinical trials including data for positive modulatory microbiota capacities suggested that high doses of common single and multispecies of Lactobacillus and Bifidobacterium ameliorated key obesity-related parameters, the major limitation was the high variability between studies and lack of standardized protocols. Efforts in solving this problem and searching for next-generation probiotics for obesity-related diseases would highly improve the rational use of probiotics.

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Cerebrospinal fluid biomarkers for the diagnosis and prognosis of Parkinson’s disease: protocol for a systematic review and individual participant data meta-analysis

BMJ Open ◽

10.1136/bmjopen-2017-018177 ◽

2017 ◽

Vol 7 (11) ◽

pp. e018177 ◽

Cited By ~ 2

Author(s):

Paolo Eusebi ◽

Oskar Hansson ◽

Silvia Paciotti ◽

Massimiliano Orso ◽

Davide Chiasserini ◽

...

Keyword(s):

Systematic Review ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cerebrospinal Fluid ◽

Diagnostic Accuracy ◽

Systematic Reviews ◽

Cochrane Library ◽

Individual Participant Data ◽

Characteristic Analysis ◽

Individual Participant

IntroductionIdiopathic Parkinson’s disease (PD) is a progressive neurodegenerative disorder related to α-synuclein misfolding and aggregation. For this reason, it belongs to the family of ‘synucleinopathies’, which also includes some other neurological diseases. Although imaging and ancillary investigations may be helpful in the diagnostic workup, the diagnosis of PD mostly relies on the clinician’s expertise. Furthermore, there is a need today for markers that can track the disease progression in PD that might improve the evaluation of novel disease-modifying therapies. The cerebrospinal fluid (CSF) has been widely investigated with the purpose of finding useful diagnostic and prognostic biomarkers for PD.Methods and analysisThis systematic review protocol has been developed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocol 2015 statement and was registered on the PROSPERO international prospective register of systematic reviews. An international collaboration will be established. We will search the Cochrane Library, Web of Science, Medline and Embase from inception, using appropriate search strategies. Individual participant data from all included studies will be merged into a single database. We will include any study assessing the diagnostic and prognostic role of CSF biomarkers in PD. To evaluate the risk of bias and applicability of primary diagnostic accuracy studies, we will use Quality Assessment of Diagnostic Accuracy Studies-2 and Quality in Prognostic Studies. We will use standard meta-analytic procedures. We will first explore the utility of each CSF biomarker in turn. For each biomarker, we will assess its diagnostic and prognostic utility by means of receiver operating characteristic analysis and regression models. We will then move towards a multivariate approach considering different panels of biomarkers.Ethics and disseminationOur study will not include confidential data, and no intervention will be involved, so ethical approval is not required. The results of the study will be reported in international peer-reviewed journals.

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