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Browse the failure-mode index

12,218 real negative results, null findings, and replication failures in Medicine. Search the index →

WASTE indexes published research — it does not host or republish full papers. Each entry is a metadata record compiled from open scholarly databases; the abstract is shown in full only where the paper is openly licensed, otherwise a short excerpt under fair use. Classifications are automated and approximate.

Negative / Null Result ReportOpen accessMedicine

The BACE‐1 inhibitor CNP520 for prevention trials in Alzheimer's disease

Ulf Neumann, Mike Ufer, Laura H. Jacobson et al. · 2018 · EMBO Molecular Medicine

The beta‐site amyloid precursor protein cleaving enzyme‐1 (BACE‐1) initiates the generation of amyloid‐β (Aβ), and the amyloid cascade leading to amyloid plaque deposition, neurodegeneration, and dementia in Alzheimer's disease (AD). Clinical failures of anti‐Aβ therapies in dementia stages suggest that treatment has to start in the early, asymptomatic disease states. The BACE‐1 inhibitor CNP520 has a selectivity, pharmacodynamics, and distribution profile suitable for AD prevention studies. CNP520 reduced brain and cerebrospinal fluid (CSF) Aβ in rats and dogs, and Aβ plaque deposition in APP

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Negative / Null Result ReportOpen accessMedicine

Effect of therapeutic drug monitoring-based dose optimization of piperacillin/tazobactam on sepsis-related organ dysfunction in patients with sepsis: a randomized controlled trial

Stefan Hagel, Friedhelm Bach, Thorsten Brenner et al. · 2022 · Intensive Care Medicine

PURPOSE: Insufficient antimicrobial exposure is associated with worse outcomes in sepsis. We evaluated whether therapeutic drug monitoring (TDM)-guided antibiotic therapy improves outcomes. METHODS: Randomized, multicenter, controlled…

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Negative / Null Result ReportMedicine

Meditation for Migraines: A Pilot Randomized Controlled Trial

Rebecca Erwin Wells, Rebecca Burch, Randall H. Paulsen et al. · 2014 · Headache The Journal of Head and Face Pain

OBJECTIVE: Our objective was to assess the safety, feasibility, and effects of the standardized 8-week mindfulness-based stress reduction (MBSR) course in adults with migraines. BACKGROUND: Stress is a well-known trigger for headaches.…

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Negative / Null Result ReportOpen accessMedicine

A comparison of charlson and elixhauser comorbidity measures to predict colorectal cancer survival using administrative health data

Jessica Lieffers, Vickie E. Baracos, Marcy Winget et al. · 2010 · Cancer

BACKGROUND: Cancer survival is related to features of the primary malignancy and concurrent presence of nonmalignant diseases (comorbidities), including weight-related conditions (obesity, weight loss). The Charlson and Elixhauser methods…

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Negative / Null Result ReportOpen accessMedicine

Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children’s Oncology Group

Richard Aplenc, Soheil Meshinchi, Lillian Sung et al. · 2020 · Haematologica

New therapeutic strategies are needed for pediatric acute myeloid leukemia (AML) to reduce disease recurrence and treatment-related morbidity. The Children’s Oncology Group Phase III AAML1031 trial tested whether the addition of bortezomib…

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Negative / Null Result ReportOpen accessMedicine

Effect of corticosteroids on the clinical course of community-acquired pneumonia: a randomized controlled trial

Silvia Fernández-Serrano, Jordi Dorca, Carolina García‐Vidal et al. · 2011 · Critical Care

INTRODUCTION: The benefit of corticosteroids as adjunctive treatment in patients with severe community-acquired pneumonia (CAP) requiring hospital admission remains unclear. This study aimed to evaluate the impact of corticosteroid treatment on outcomes in patients with CAP. METHODS: This was a prospective, double-blind and randomized study. All patients received treatment with ceftriaxone plus levofloxacin and methyl-prednisolone (MPDN) administered randomly and blindly as an initial bolus, followed by a tapering regimen, or placebo. RESULTS: Of the 56 patients included in the study, 28 (50%)

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Negative / Null Result ReportMedicine

Effects of Group Psychotherapy, Individual Counseling, Methylphenidate, and Placebo in the Treatment of Adult Attention-Deficit/Hyperactivity Disorder

Alexandra Philipsen, Thomas Jans, Erika Graf et al. · 2015 · JAMA Psychiatry

IMPORTANCE: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high prevalence in adulthood. There is a recognized need to assess the efficacy of psychotherapy in adult ADHD. OBJECTIVE: To evaluate the…

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Negative / Null Result ReportOpen accessMedicine

Screening for Adolescent Idiopathic Scoliosis

US Preventive Services Task Force, David C. Grossman, Susan J. Curry et al. · 2018 · JAMA

Importance: Adolescent idiopathic scoliosis, a lateral curvature of the spine of unknown cause with a Cobb angle of at least 10°, occurs in children and adolescents aged 10 to 18 years. Idiopathic scoliosis is the most common form and…

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Negative / Null Result ReportMedicine

Long-term anticonvulsant therapy leads to low bone mineral density — evidence for direct drug effects of phenytoin and carbamazepine on human osteoblast-like cells

Joachim Feldkamp, Andréa Becker, Otto W. Witte et al. · 2012 · Experimental and Clinical Endocrinology & Diabetes

Anticonvulsant therapy causes changes in calcium and bone metabolism and may lead to decreased bone mass with the risk of osteoporotic fractures. The two widely used antiepileptic drugs phenytoin and carbamazepine are recognized to have…

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Negative / Null Result ReportOpen accessMedicine

Significant differences in femoral torsion values depending on the CT measurement technique

Peter K. Kaiser, René El Attal, Mark Kammerer et al. · 2016 · Archives of Orthopaedic and Trauma Surgery

INTRODUCTION: This study compared the feasibility of six different CT-based measurement techniques for establishing an indication for derotational osteotomy in the cases of patellar instability or femoral fracture. MATERIALS AND METHODS: CT scans of 52 single human cadaver femora were measured using six different torsion measurement techniques (described by Waidelich, Murphy, and Yoshioka on transverse images and Hernandez, Jarrett, and Yoshioka on oblique images). All measurements were performed by four observers twice to assess intraobserver and interobserver agreement. The intraclass correl

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Negative / Null Result ReportOpen accessMedicine

Advanced Intrahepatic Cholangiocarcinoma: Post Hoc Analysis of the ABC-01, -02, and -03 Clinical Trials

Ángela Lamarca, Paul J. Ross, Harpreet Wasan et al. · 2019 · JNCI Journal of the National Cancer Institute

BACKGROUND: The incidence of intrahepatic cholangiocarcinoma (iCCA) is increasing. The aim of the study was to provide reference survival data for patients with advanced iCCA treated with first-line cisplatin-gemcitabine chemotherapy (current standard of care). METHODS: Individual data from patients with iCCA recruited into the prospective, random assignment Advanced Biliary Tract Cancer (ABC)-01, -02, and -03 studies were retrieved. The prevalence and survival of liver-only iCCA was also assessed. Survival analysis was performed using univariate and multivariable Cox regression. All statistic

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Negative / Null Result ReportOpen accessMedicine

Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial

Jake Dunning, Foday Sahr, Amanda Rojek et al. · 2016 · PLoS Medicine

BACKGROUND: TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. METHODS AND FINDINGS: In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of ad

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Negative / Null Result ReportOpen accessMedicine

Predicting Outcome of Endovascular Treatment for Acute Ischemic Stroke: Potential Value of Machine Learning Algorithms

Hendrikus J. A. van Os, Lucas A. Ramos, Adam Hilbert et al. · 2018 · Frontiers in Neurology

Background: Endovascular treatment (EVT) is effective for stroke patients with a large vessel occlusion (LVO) of the anterior circulation. To further improve personalized stroke care, it is essential to accurately predict outcome after EVT. Machine learning might outperform classical prediction methods as it is capable of addressing complex interactions and non-linear relations between variables. Methods: We included patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry, an observational cohort of LVO

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Negative / Null Result ReportOpen accessMedicine

Hepatopulmonary syndrome: Favorable outcomes in the MELD exception era

Vivek Iyer, Karen L. Swanson, Rodrigo Cartin‐Ceba et al. · 2012 · Hepatology

UNLABELLED: Hepatopulmonary syndrome (HPS) is a pulmonary vascular disorder occurring as a consequence of advanced liver disease, characterized by hypoxemia due to intrapulmonary vascular dilatations. HPS independently increases mortality,…

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Negative / Null Result ReportOpen accessMedicine

Amniotic fluid from healthy term pregnancies does not harbor a detectable microbial community

Efrem S. Lim, Cynthia Rodríguez, Lori R. Holtz · 2018 · Microbiome

Recent studies have conflicting data regarding the presence of intra-amniotic microbiota. Viral communities are increasingly recognized as important although overlooked components of the human microbiota. It is unknown if the developing fetus is exposed to a community of viruses (virome). Given the debate over the existence of an intra-amniotic microbial community and the importance of understanding how the infant gut is populated, we characterized the virome and bacterial microbiota of amniotic fluid from 24 uncomplicated term pregnancies using next-generation sequencing methods. Contrary to

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Negative / Null Result ReportOpen accessMedicine

Prospective Longitudinal Evaluation of the Effect of Deployment-Acquired Traumatic Brain Injury on Posttraumatic Stress and Related Disorders: Results From the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)

Murray B. Stein, Ronald C. Kessler, Steven G. Heeringa et al. · 2015 · American Journal of Psychiatry

OBJECTIVE: Traumatic brain injury (TBI) is increasingly recognized as a risk factor for deleterious mental health and functional outcomes. The purpose of this study was to examine the strength and specificity of the association between…

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Negative / Null Result ReportOpen accessMedicine

The sensitivity and specificity of optical coherence tomography for the assisted diagnosis of nonpigmented basal cell carcinoma: an observational study

Martina Ulrich, T. Braunmuehl, Hjalmar Kurzen et al. · 2015 · British Journal of Dermatology

BACKGROUND: The diagnostic criteria for basal cell carcinoma (BCC) using optical coherence tomography (OCT) have been described previously, but the clinical value of these findings remains unknown. OBJECTIVES: To investigate the diagnostic…

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Negative / Null Result ReportOpen accessMedicine

Impact of dose intensity of ponatinib on selected adverse events: Multivariate analyses from a pooled population of clinical trial patients

David J. Dorer, Ronald K. Knickerbocker, Michele Baccarani et al. · 2016 · Leukemia Research

Ponatinib is approved for adults with refractory chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia, including those with the T315I BCR-ABL1 mutation. We pooled data from 3 clinical trials (N=671) to…

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Negative / Null Result ReportOpen accessMedicine

Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I–inhibiting Antibody–Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan

Jhanelle E. Gray, Rebecca S. Heist, Alexander Starodub et al. · 2017 · Clinical Cancer Research

Abstract Purpose: We evaluated a Trop-2–targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients. Experimental Design: Sacituzumab govitecan was studied in patients with pretreated (median, 2; range,…

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Negative / Null Result ReportOpen accessMedicine

Clinical outcome of a headache-specific multidisciplinary treatment program and adherence to treatment recommendations in a tertiary headache center: an observational study

Charly Gaul, Christina van Doorn, Nadine Webering et al. · 2011 · The Journal of Headache and Pain

This study investigated the outcome of a 5-day headache-specific multidisciplinary treatment program (MTP) and the adherence to treatment recommendations in 295 prospectively recruited consecutive headache patients [210 migraine, 17 tension-type headache (TTH), 68 combination headache, including 56 medication-overuse headache (MOH)]. Headache frequency decreased from 13.4 (±8.8) to 8.8 (±8.0) days per month after 12-18 months. Forty-three percent of the participants fulfilled the primary outcome (reduction of headache frequency of ≥50%), which was less likely in patients with combination of mi

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Negative / Null Result ReportOpen accessMedicine

Lung Adenocarcinoma and Squamous Cell Carcinoma Gene Expression Subtypes Demonstrate Significant Differences in Tumor Immune Landscape

Hawazin Faruki, Gregory M. Mayhew, Jonathan S. Serody et al. · 2017 · Journal of Thoracic Oncology

INTRODUCTION: Molecular subtyping of lung adenocarcinoma (AD) and lung squamous cell carcinoma (SCC) reveal biologically diverse tumors that vary in their genomic and clinical attributes. METHODS: Published immune cell signatures and…

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Negative / Null Result ReportOpen accessMedicine

Embodied health: the effects of a mind–body course for medical students

Allison Bond, Heather Mason, Chelsey Lemaster et al. · 2013 · Medical Education Online

OBJECTIVE: An effective career in medicine requires empathy and compassion, yet the demands of a medical education increase stress and decrease students' ability to connect with patients. However, research suggests mind-body practices improve psychological well-being. This study aimed to evaluate the psychological effects on medical students of an 11-week elective course, Embodied Health or EH, which combines yoga and meditation with neuroscience didactics. METHODS: The effects on 27 first- and second-year medical students were evaluated via surveys in four areas: empathy, perceived stress, se

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Negative / Null Result ReportOpen accessMedicine

Progression in the LRRK2-Associated Parkinson Disease Population

Rachel Saunders‐Pullman, Anat Mirelman, Roy N. Alcalay et al. · 2018 · JAMA Neurology

Importance: Few prospective longitudinal studies have evaluated the progression of Parkinson disease (PD) in patients with the leucine-rich repeat kinase 2 (LRRK2 [OMIM 609007]) mutation. Knowledge about such progression will aid clinical…

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Negative / Null Result ReportMedicine

The Keyhole Concept in Aneurysm Surgery: Results of the Past 20 Years

Gerrit Fischer, Axel Stadie, Róbert Reisch et al. · 2011 · Operative Neurosurgery

BACKGROUND: Improvements in preoperative imaging and intraoperative visualization have led to a refinement in surgical techniques. OBJECTIVE: Report of a 20-year experience with application of the keyhole technique as a contribution to the…

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