Publications by authors named "Harden M"

Background: Magnetic resonance imaging localises cancer in the prostate, allowing for a targeted biopsy with or without transrectal ultrasound-guided systematic biopsy. Targeted biopsy methods include cognitive fusion, where prostate lesions suspicious on magnetic resonance imaging are targeted visually during live ultrasound, and software fusion, where computer software overlays the magnetic resonance imaging image onto the ultrasound in real time. The effectiveness and cost-effectiveness of software fusion technologies compared with cognitive fusion biopsy are uncertain.

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Article Synopsis
  • The study evaluated the safety and effectiveness of statins, ezetimibe, and their combination for treating children with heterozygous familial hypercholesterolaemia (HeFH), using systematic reviews and various meta-analyses from RCTs.* -
  • Results showed that all lipid-lowering therapies (LLTs) were effective in reducing cholesterol levels, with statins leading to significant reductions in low-density lipoprotein cholesterol (LDL-C), especially when combined with ezetimibe.* -
  • While no safety or tolerability issues were identified, the extent of LDL-C reduction varied by treatment dosage and type, highlighting the need for more research on long-term safety and effectiveness.*
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Kelps are vital for marine ecosystems, yet the genetic diversity underlying their capacity to adapt to climate change remains unknown. In this study, we focused on the kelp Macrocystis pyrifera a species critical to coastal habitats. We developed a protocol to evaluate heat stress response in 204 Macrocystis pyrifera genotypes subjected to heat stress treatments ranging from 21 °C to 27 °C.

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Background: This work was undertaken to inform a National Institute for Health and Care Excellence guideline on the initial assessment of adults with suspected acute respiratory infection.

Objective: To undertake a rapid evidence synthesis of systematic reviews and cost-effectiveness studies of signs, symptoms and early warning scores for the initial assessment of adults with suspected acute respiratory infection.

Methods: MEDLINE, EMBASE and Cochrane Database of Systematic Reviews were searched for systematic reviews and MEDLINE, EMBASE, EconLit and National Health Service Economic Evaluation Database were searched for cost-effectiveness studies in May 2023.

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Tracheobronchial rupture is an extremely rare and potentially fatal complication. We present the case of a delayed presentation of an iatrogenic tracheobronchial rupture following orotracheal intubation, requiring veno-venous extracorporeal membrane oxygenator on standby. We review the clinical presentation, investigations, and management of tracheobronchial rupture, including conservative treatment and invasive surgical repair techniques.

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Objective: To synthesise qualitative evidence on clinicians' views and experiences of defensive practice.

Design: Systematic review of qualitative data.

Data Sources: MEDLINE, Embase, PsycINFO, AMED, Maternity and Infant Care, CINAHL, ASSIA, Sociological Abstracts, Proquest Dissertations & Theses and PROSPERO were searched from 2000 to October 2023.

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Lymphocytic interstitial pneumonia (LIP) is a rare but largely benign interstitial lung disease, most frequently associated with HIV and autoimmune conditions. It is infrequently found to be an idiopathic condition. Diagnosis is complex and can require numerous invasive tests as evidenced in the case presented.

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Background: New methods to identify patients who benefit from a primary prophylactic implantable cardioverter-defibrillator (ICD) are needed. T-wave alternans (TWA) has been shown to associate with arrhythmogenesis of the heart and sudden cardiac death. We hypothesized that TWA might be associated with benefit from ICD implantation in primary prevention.

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Objective: Data from DNA genotyping via a 96-SNP panel in a study of 25,015 clinical samples were utilized for quality control and tracking of sample identity in a clinical sequencing network. The study aimed to demonstrate the value of both the precise SNP tracking and the utility of the panel for predicting the sex-by-genotype of the participants, to identify possible sample mix-ups.

Results: Precise SNP tracking showed no sample swap errors within the clinical testing laboratories.

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Polygenic risk scores (PRSs) have improved in predictive performance, but several challenges remain to be addressed before PRSs can be implemented in the clinic, including reduced predictive performance of PRSs in diverse populations, and the interpretation and communication of genetic results to both providers and patients. To address these challenges, the National Human Genome Research Institute-funded Electronic Medical Records and Genomics (eMERGE) Network has developed a framework and pipeline for return of a PRS-based genome-informed risk assessment to 25,000 diverse adults and children as part of a clinical study. From an initial list of 23 conditions, ten were selected for implementation based on PRS performance, medical actionability and potential clinical utility, including cardiometabolic diseases and cancer.

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Abundant host and bacterial sequences can obscure the detection of less prevalent viruses in untargeted next-generation sequencing (NGS). Efficient removal of these non-targeted sequences is vital for accurate viral detection. This study presents a novel 28S ribosomal RNA (rRNA) RT-qPCR assay designed to assess the efficiency of avian rRNA depletion before conducting costly NGS for the detection of avian RNA viruses.

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Background: A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and preserved liver function.

Objective: To review and compare the effectiveness of all current ablative and non-surgical therapies for patients with small hepatocellular carcinoma (≤ 3 cm).

Design: Systematic review and network meta-analysis.

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Background & Aims: Non-surgical therapies are frequently used for patients with early or very early hepatocellular carcinoma (HCC). The aim of this systematic review and network meta-analysis (NMA) was to evaluate and compare the effectiveness of ablative and non-surgical therapies for patients with small HCC.

Methods: Nine databases were searched (March 2021) along with clinical trial registries.

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Pantothenate kinase-associated neurodegeneration (PKAN) is characterized by a motor disorder with combinations of dystonia, parkinsonism, and spasticity, leading to premature death. PKAN is caused by mutations in the gene that result in loss or reduction of PANK2 protein function. PANK2 is one of three kinases that initiate and regulate coenzyme A biosynthesis from vitamin B5, and the ability of BBP-671, an allosteric activator of pantothenate kinases, to enter the brain and elevate coenzyme A was investigated.

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Objective: Data from DNA genotyping via a 96-SNP panel in a study of 25,015 clinical samples were utilized for quality control and tracking of sample identity in a clinical sequencing network. The study aimed to demonstrate the value of both the precise SNP tracking and the utility of the panel for predicting the sex-by-genotype of the participants, to identify possible sample mix-ups.

Results: Precise SNP tracking showed no sample swap errors within the clinical testing laboratories.

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Article Synopsis
  • * A systematic search identified nine relevant studies, mostly using randomized controlled trials to analyze costs and effects; however, many studies failed to specify the decision-making context or target decision makers effectively.
  • * The review highlights limitations in the ability of existing studies to guide funders in understanding the full value of self-help group interventions, suggesting that a cross-sectoral approach to presenting evidence could enhance decision-making.
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The demand for health care in older people involved in the criminal justice system is high. The prevalence of mental and physical health conditions for people living in prison is greater than in community populations. After systematically searching 21 databases, we found no targeted interventions to support depression or anxiety for this group of people.

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Article Synopsis
  • - The text discusses the advancements in polygenic risk scores (PRS) and their potential to enhance clinical practice, but highlights challenges in effectiveness across diverse populations, which can worsen health disparities.
  • - A project funded by NHGRI called the eMERGE Network is evaluating PRS for 23 health conditions in 25,000 individuals from different backgrounds, focusing on actionable findings and relevant evidence for African and Hispanic populations.
  • - The study identified ten key health conditions for PRS assessment (like breast cancer and diabetes), and established a framework for implementing PRS in clinical settings, ensuring compliance and reliability across different genetic ancestries.
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Article Synopsis
  • The study aims to assess the risk of common diseases by considering clinical, monogenic, and polygenic factors, which may be reflected in an individual's family history.
  • The eMERGE network is enrolling 25,000 individuals in a prospective study to create and return a comprehensive risk assessment report (GIRA) that includes various genetic risk factors and care recommendations.
  • The GIRA report provides actionable guidelines for health care based on genetic data, highlighting the importance of integrating genetic risk assessment into routine health care practices.
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Background: EarlyCDT Lung (Oncimmune Holdings plc, Nottingham, UK) is a blood test to assess malignancy risk in people with solid pulmonary nodules. It measures the presence of seven lung cancer-associated autoantibodies. Elevated levels of these autoantibodies may indicate malignant disease.

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Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been replicated in the Diabetes Prevention Program (DPP). To assess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (PBO; n = 887) arms.

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Point-of-care antigen-detecting rapid diagnostic tests (RDTs) to detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) represent a scalable tool for surveillance of active SARS-CoV-2 infections in the population. Data on the performance of these tests in real-world community settings are paramount to guide their implementation to combat the COVID-19 pandemic. We evaluated the performance characteristics of the CareStart COVID-19 Antigen test (CareStart) in a community testing site in Holyoke, Massachusetts.

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Purpose: Smoking cessation in patients with diagnosed lung cancer has positive effects on cancer therapy and overall prognosis. Despite this, knowledge on smoking cessation in lung cancer patients is sparse.

Methods: This is an observational single centre, 12-week, prospective, single-arm trial at a tertiary lung cancer centre.

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To evaluate the clinical impact of molecular tumor profiling (MTP) with targeted sequencing panel tests, pediatric patients with extracranial solid tumors were enrolled in a prospective observational cohort study at 12 institutions. In the 345-patient analytical population, median age at diagnosis was 12 years (range 0-27.5); 298 patients (86%) had 1 or more alterations with potential for impact on care.

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