Publications by authors named "David Gallagher"

90 Publications

Development of a Novel Coaching Platform to Improve Tackle Technique in Youth Rugby Players: A Proof of Concept.

Sensors (Basel) 2022 Apr 26;22(9). Epub 2022 Apr 26.

Department of Sport, Exercise & Nutrition, Atlantic Technological University (ATU), H91 T8NW Galway, Ireland.

Rugby union is a field sport that is played at amateur and professional levels by male and female players globally. One of the most prevalent injury risks associated with the sport involves tackle collisions with opposition players. This suggests that a targeted injury reduction strategy could focus on the tackle area in the game. In amateur rugby union, injuries to the head, face and shoulder are the most common injury sites in youth rugby playing populations. A suboptimal tackle technique may contribute to an increased injury risk in these populations. One proposed mitigation strategy to reduce tackle-related injuries in youth populations may be to increase tackle proficiency by coaching an effective tackle technique. The present study aimed to demonstrate a proof of concept for a tackle technique coaching platform using inertial measurement units (IMUs) and a bespoke mobile application developed for a mobile device (i.e., a mobile phone). The test battery provided a proof of concept for the primary objective of modelling the motion of a player in a tackle event. The prototype (bespoke mobile application) modelled the IMU in a 3D space and demonstrated the orientation during a tackle event. The participants simulated ten tackle events that were ten degrees above and ten degrees below the zero degree of approach, and these (unsafe tackles) were indicated by a red light on the mobile display unit. The parameters of ten degrees above and below the zero angle of approach were measured using an inclinometer mobile application. These tackle event simulations provided a real-time stream of data that displayed the angle of tackles on a mobile device. The novel coaching platform could therefore constitute part of an injury reduction strategy for amateur or novice coaches to instruct safer tackle practice in youth rugby playing populations.
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http://dx.doi.org/10.3390/s22093315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105744PMC
April 2022

Patient knowledge, personal experience, and impact of the first wave of the COVD-19 pandemic in an Irish oncology cohort.

Ir J Med Sci 2022 Apr 12. Epub 2022 Apr 12.

Department of Medical Oncology, St. James's Hospital, Dublin, Ireland.

Background: Oncology patients have had to make many changes to minimise their exposure to COVID-19, causing stress. Despite education, some patients still do not recognise potential COVID symptoms.

Aims: We assessed patient knowledge of COVID, and its impact on their behaviours, concerns, and healthcare experience.

Methods: A 16-page questionnaire was distributed to 120 oncology patients attending the day unit of a tertiary Irish cancer centre for systemic anti-cancer therapy (May/June 2020). The Irish 7-day COVID incidence during this period ranged from 2 to 11 cases/100,000 people.

Results: One hundred and one responses were received, 1% had tested positive for COVID, and 31% had undergone testing. Participant insight into their knowledge about COVID and their own behaviour was limited in some cases. Seventy-five percent reported total compliance with restrictions, but many were not fully compliant. Self-reported confidence in knowledge was high, but did not predict demonstrated knowledge. Sixty percent did not recognise two or more symptoms; 40% did not self-identify as high-risk. Patients reported more health-related worry (72%), loneliness (51%), and lower mood (42%) since the pandemic began. Financial toxicity worsened, with increased financial worry (78%), reductions in household income (40%), and increased costs due to lockdown (62%). Use of facemasks introduced new communications barriers for 67% of those with hearing loss.

Conclusions: Despite self-reported confidence in knowledge, some patient's recognition of COVID symptoms and the preventative strategies they should use are not optimal, highlighting the need for further education in this regard. COVID has been a significant stressor for patients and more practical, financial, and psychological supports are needed.
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http://dx.doi.org/10.1007/s11845-022-02999-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9001164PMC
April 2022

The Essentials of Multiomics.

Oncologist 2022 Apr;27(4):272-284

Indivumed GmbH, Hamburg, Germany.

Within the last decade, the science of molecular testing has evolved from single gene and single protein analysis to broad molecular profiling as a standard of care, quickly transitioning from research to practice. Terms such as genomics, transcriptomics, proteomics, circulating omics, and artificial intelligence are now commonplace, and this rapid evolution has left us with a significant knowledge gap within the medical community. In this paper, we attempt to bridge that gap and prepare the physician in oncology for multiomics, a group of technologies that have gone from looming on the horizon to become a clinical reality. The era of multiomics is here, and we must prepare ourselves for this exciting new age of cancer medicine.
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http://dx.doi.org/10.1093/oncolo/oyab048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982374PMC
April 2022

Extramural venous invasion (EMVI) in colorectal cancer is associated with increased cancer recurrence and cancer-related death.

Eur J Surg Oncol 2022 Feb 19. Epub 2022 Feb 19.

St. James's Hospital, Ireland.

Introduction: Colorectal cancer (CRC) outcomes vary depending on tumour biology, with several features used to predict disease behaviour. Extramural venous invasion (EMVI) is associated with negative outcomes and its presence has been established as an indicator of more aggressive disease in CRC.

Methods: A prospectively maintained database was examined for patients undergoing curative resection for non-metastatic CRC between 2012 and 2018 in a tertiary institution. Clinicopathological factors were compared to assess their impact on recurrence, all-cause mortality and cancer-related death. Kaplan Meier analysis of the association between EMVI and these endpoints was performed, and univariable and multivariable analysis was carried out to establish the relationship of predictive factors in oncological outcomes.

Results: Eighty-eight (13.5%) of 654 patients developed recurrence. The mean time to recurrence was 19.8 ± 13.5 months. There were 36 (5.5%) cancer-related deaths at a mean duration of follow-up of 46.3 ± 21.6 months. Two hundred and sixty-six patients had extramural venous invasion (40.7%). EMVI was significantly associated with reduced overall recurrence-free survival, systemic recurrence-free survival, and increased cancer-related death on univariate analysis (p < 0.001 for all, Fig. 1), and multivariable analysis (OR 1.8 and 2.1 respectively, p < 0.05 for both).

Conclusion: EMVI is associated with a poor prognosis, independent of stage, nodal status and other histopathological features. The presence of EMVI should be strongly considered as an indication for adjuvant therapy.
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http://dx.doi.org/10.1016/j.ejso.2022.02.013DOI Listing
February 2022

Inpatient pharmacists using a readmission risk model in supporting discharge medication reconciliation to reduce unplanned hospital readmissions: a quality improvement intervention.

BMJ Open Qual 2022 03;11(1)

Pharmacy, Duke University Hospital, Durham, North Carolina, USA.

Introduction: Reducing unplanned hospital readmissions is an important priority for all hospitals and health systems. Hospital discharge can be complicated by discrepancies in the medication reconciliation and/or prescribing processes. Clinical pharmacist involvement in the medication reconciliation process at discharge can help prevent these discrepancies and possibly reduce unplanned hospital readmissions.

Methods: We report the results of our quality improvement intervention at Duke University Hospital, in which pharmacists were involved in the discharge medication reconciliation process on select high-risk general medicine patients over 2 years (2018-2020). Pharmacists performed traditional discharge medication reconciliation which included a review of medications for clinical appropriateness and affordability. A total of 1569 patients were identified as high risk for hospital readmission using the Epic readmission risk model and had a clinical pharmacist review the discharge medication reconciliation.

Results: This intervention was associated with a significantly lower 7-day readmission rate in patients who scored high risk for readmission and received pharmacist support in discharge medication reconciliation versus those patients who did not receive pharmacist support (5.8% vs 7.6%). There was no effect on readmission rates of 14 or 30 days. The clinical pharmacists had at least one intervention on 67% of patients reviewed and averaged 1.75 interventions per patient.

Conclusion: This quality improvement study showed that having clinical pharmacists intervene in the discharge medication reconciliation process in patients identified as high risk for readmission is associated with lower unplanned readmission rates at 7 days. The interventions by pharmacists were significant and well received by ordering providers. This study highlights the important role of a clinical pharmacist in the discharge medication reconciliation process.
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http://dx.doi.org/10.1136/bmjoq-2021-001560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8896047PMC
March 2022

Schistosomiasis: hazards of freshwater swimming.

Br J Hosp Med (Lond) 2022 Jan 11;83(1). Epub 2022 Jan 11.

Department of Infectious Diseases, Galway University Hospital, Galway, Ireland.

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http://dx.doi.org/10.12968/hmed.2021.0124DOI Listing
January 2022

Developing and assessing a new web-based tapping test for measuring distal movement in Parkinson's disease: a Distal Finger Tapping test.

Sci Rep 2022 01 10;12(1):386. Epub 2022 Jan 10.

Preventive Neurology Unit, Wolfson Institute of Population Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Disability in Parkinson's disease (PD) is measured by standardised scales including the MDS-UPDRS, which are subject to high inter and intra-rater variability and fail to capture subtle motor impairment. The BRadykinesia Akinesia INcoordination (BRAIN) test is a validated keyboard tapping test, evaluating proximal upper-limb motor impairment. Here, a new Distal Finger Tapping (DFT) test was developed to assess distal upper-limb function. Kinetic parameters of the test include kinesia score (KS20, key taps over 20 s), akinesia time (AT20, mean dwell-time on each key) and incoordination score (IS20, variance of travelling time between key taps). To develop and evaluate a new keyboard-tapping test for objective and remote distal motor function in PD patients. The DFT and BRAIN tests were assessed in 55 PD patients and 65 controls. Test scores were compared between groups and correlated with the MDS-UPDRS-III finger tapping sub-scores. Nine additional PD patients were recruited for monitoring motor fluctuations. All three parameters discriminated effectively between PD patients and controls, with KS20 performing best, yielding 79% sensitivity for 85% specificity; area under the receiver operating characteristic curve (AUC) = 0.90. A combination of DFT and BRAIN tests improved discrimination (AUC = 0.95). Among three parameters, KS20 showed a moderate correlation with the MDS-UPDRS finger-tapping sub-score (Pearson's r = - 0.40, p = 0.002). Further, the DFT test detected subtle changes in motor fluctuation states which were not reflected clearly by the MDS-UPDRS-III finger tapping sub-scores. The DFT test is an online tool for assessing distal movements in PD, with future scope for longitudinal monitoring of motor complications.
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http://dx.doi.org/10.1038/s41598-021-03563-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748736PMC
January 2022

Parkinson's Disease and Type 2 Diabetes: HbA1c Is Associated with Motor and Cognitive Severity.

Mov Disord 2022 02 13;37(2):427-428. Epub 2021 Oct 13.

Preventive Neurology Unit, Centre for Prevention, Detection and Diagnosis, Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom.

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http://dx.doi.org/10.1002/mds.28829DOI Listing
February 2022

Dysautonomia Causing Severe Orthostatic Hypotension: An Important, Early Finding in Neurodegenerative Disorders.

JACC Case Rep 2021 Jul 21;3(8):1156-1160. Epub 2021 Jul 21.

William Harvey Research Institute and Barts NIHR Cardiovascular Biomedical Research Centre, Queen Mary University of London, London, United Kingdom.

Orthostatic hypotension is common and dangerous; it has neurogenic and nonneurogenic causes. We present the case of a 40-year-old man with severe neurogenic hypotension, caused by young-onset multiple system atrophy. In patients presenting with neurogenic orthostatic hypotension, underlying neurodegenerative diseases should always be considered. ().
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http://dx.doi.org/10.1016/j.jaccas.2021.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314124PMC
July 2021

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores.

J Natl Cancer Inst 2022 01;114(1):109-122

Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.

Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.

Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.

Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.
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http://dx.doi.org/10.1093/jnci/djab147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8755508PMC
January 2022

The contribution of Lynch syndrome to early onset malignancy in Ireland.

BMC Cancer 2021 May 26;21(1):617. Epub 2021 May 26.

Department of Cancer Genetics, St. James' Hospital, James' Street, Dublin, Ireland.

Background: Lynch syndrome (LS) is an autosomal dominant hereditary cancer syndrome responsible for 2-4% of hereditary colorectal cancers (CRC). Mismatch repair protein deficiency (dMMR) is a characteristic feature of LS. It has been associated with a poor response to standard chemotherapy in metastatic colorectal cancer (mCRC). There is currently no LS database to monitor trends of disease in Ireland. We aim to centralise LS data in Ireland to assess the burden of LS in Ireland and guide improvements in prevention and treatment of LS-associated cancer.

Methods: A retrospective review was carried out including all medical records for LS patients from two of the three cancer genetics clinics in Ireland between 2000 and 2018 was carried out. Clinicopathological data of probands (n = 57) and affected family members including demographics, mutation status, cancer diagnosis and outcome was recorded. Statistical analysis was carried out using SPSS software.

Results: Fifty-seven families including three-hundred and forty-five individuals affected by cancer were identified. The most common cancers recorded were colorectal (53%), breast (12%) and endometrial (10%). One-hundred and thirty-eight confirmed carriers were identified: 65 path_MLH1 (47%), 43 path_MSH2 (31%), 11 path_MSH6 (8%), 17 path_PMS2 (12%) and two path_EPCAM (1%). Cancer type varied significantly by gene. Median age of first diagnosis was 44.5 years (range 23-81). Half of all deceased patients (n = 11) in this group died within 2.5 years of first diagnosis. These deaths were directly related to cancer in 59% of cases.

Conclusions: Under diagnosis of LS misses a powerful preventive and therapeutic opportunity. LS causes early onset dMMR cancer diagnoses with substantial societal impact. Implementation of ICBs into treatment policy for this small cohort of dMMR mCRC is an achievable therapeutic goal that may significantly improve survival. A prospective database for LS in Ireland is necessary to maximise prevention in this population.
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http://dx.doi.org/10.1186/s12885-021-08263-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157691PMC
May 2021

Insertion of an SVA element in MSH2 as a novel cause of Lynch syndrome.

Genes Chromosomes Cancer 2021 08 21;60(8):571-576. Epub 2021 Apr 21.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Germline mutations in the DNA mismatch repair (MMR) genes cause Lynch syndrome (LS). In this study, we identified and characterized a novel SINE-VNTR-Alu (SVA) insertion in exon 12 of MSH2 in an individual with early-onset colorectal cancer and a very strong LS family history. RT-PCR analysis indicated a larger aberrant MSH2 transcript in one of the family members. MSK-IMPACT next-generation sequencing and long-range PCR analyses revealed an insertion in MSH2 exon 12 at the c.1972 position in an antisense orientation. The insertion was further characterized as an SVA element approximately 3 kb in length, belonging to the SVA_F1 family of retrotransposons. This variant also segregated with LS related cancers in four affected family members in this family. Based on this evidence, this MSH2 SVA insertion is considered pathogenic.
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http://dx.doi.org/10.1002/gcc.22950DOI Listing
August 2021

Prevalence of Insomnia in an Oncology Patient Population: An Irish Tertiary Referral Center Experience.

J Natl Compr Canc Netw 2020 12 2;18(12):1623-1630. Epub 2020 Dec 2.

2Department of Medical Oncology, St. James's Hospital, Dublin, Ireland.

Background: The NCCN Guidelines for Survivorship recommend dedicated sleep assessment. Reported insomnia prevalence in the general Irish population is 6% to 15%. Reported insomnia prevalence internationally among new/recently diagnosed patients with cancer varies from 30.9% to 54.3%. Insomnia prevalence has not been previously quantified in an Irish oncology cohort.

Methods: A 40-item questionnaire was prospectively administered to ambulatory patients with cancer aged ≥18 years. Prespecified criteria to define insomnia syndrome combined those of the International Classification of Sleep Disorders, version 1, and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The Hospital Anxiety and Depression Scale-Depression/Anxiety (HADS-D/A) was used to screen for potential confounding variables.

Results: The response rate to the questionnaire was 87% (294/337). The predominant respondent age group was 55 to 64 years (26%; 77/294), 70.7% were female (208/294), and the most common cancer subtypes were breast (37.4%), colorectal (12.9%), and lung (12.2%). A total of 62% (183/294) of patients reported sleep disturbance after diagnosis, 63% (115/183) reported moderate/severe distress related to this disturbance, and 37% (61/183) reported a significant impact on physical function. Although 33% (98/294) met insomnia syndrome criteria, only 34% (33/98) of these patients had a preexisting history of sleep disturbance. Female sex, age <65 years, cancer subtype, alcohol consumption, and HADS-D/A ≥11 were associated with statistically significant higher odds ratios (OR) of insomnia syndrome. Multivariate analysis identified breast cancer (OR, 3.17; P=.01), age <65 years (OR, 1.8; P=.03), and alcohol consumption (OR, 2.3; P=.005) as independent predictors of insomnia syndrome.

Conclusions: Insomnia syndrome prevalence in this cohort is comparable to that reported previously and supports dedicated sleep assessment. This study identifies potentially modifiable risk factors for insomnia and demonstrates additional utility of the HADS score in identifying patients at risk.
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http://dx.doi.org/10.6004/jnccn.2020.7611DOI Listing
December 2020

Prevalence of pancreaticobiliary cancers in Irish families with pathogenic BRCA1 and BRCA2 variants.

Fam Cancer 2021 04 12;20(2):97-101. Epub 2020 Sep 12.

School of Medicine, Trinity College Dublin, Dublin, Ireland.

Pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are associated with an increased lifetime risk of pancreatic ductal adenocarcinoma (PDAC), and more recently have been associated with increased risk of biliary tract cancers (BTC). This study assessed the prevalence, age and gender distribution of PDAC/BTC cases in families known to carry a BRCA1/2 PV compared to those of the Irish population. A review of all families referred to a national genetics clinic from 09/11/1997 to 01/06/2018 was performed. The BOADICEA algorithm was used to estimate the probability that an untested relative of a known BRCA1/2 PV carrier with PDAC was a carrier. We reviewed 3252 family pedigrees, 1193 contained a proband who underwent testing for BRCA1/2 based on Manchester score ≥ 15. Among 128 BRCA2 PV-positive families, 27 (21%) contained a 1st/2nd/3rd-degree relative with PDAC, while of 116 BRCA1 PV-positive families, 11 (9%) contained a 1st/2nd/3rd-degree relative with PDAC. Within these 38 families, 25 patients with PDAC had ≥ 50% likelihood of being a BRCA1/2 PV carrier. This cohort had a median age at diagnosis of 55 years (range 33-75), with a mean (55 years) lower than 8364 patients with PDAC identified through the National Cancer Registry of Ireland (71 years, p < 0.0001). Six BRCA2 positive (5%) and 2 BRCA1 positive pedigrees (2%) included an individual with BTC; median age at diagnosis was 65 years (range 33-99). PDAC and BTC are prevalent in Irish families harbouring a BRCA2 PV and are associated with early-onset malignancy. This supports current guidelines recommending universal germline testing for PDAC patients.
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http://dx.doi.org/10.1007/s10689-020-00205-1DOI Listing
April 2021

Implementation and Continuous Monitoring of an Electronic Health Record Embedded Readmissions Clinical Decision Support Tool.

J Pers Med 2020 Aug 26;10(3). Epub 2020 Aug 26.

Department of Biostatistics and Bioinformatics, Duke University Medical Center, 2424 Erwin Road Suite 1102 Hock Plaza (Box 2721), Durham, NC 27710, USA.

Unplanned hospital readmissions represent a significant health care value problem with high costs and poor quality of care. A significant percentage of readmissions could be prevented if clinical inpatient teams were better able to predict which patients were at higher risk for readmission. Many of the current clinical decision support models that predict readmissions are not configured to integrate closely with the electronic health record or alert providers in real-time prior to discharge about a patient's risk for readmission. We report on the implementation and monitoring of the Epic electronic health record-"Unplanned readmission model version 1"-over 2 years from 1/1/2018-12/31/2019. For patients discharged during this time, the predictive capability to discern high risk discharges was reflected in an AUC/C-statistic at our three hospitals of 0.716-0.760 for all patients and 0.676-0.695 for general medicine patients. The model had a positive predictive value ranging from 0.217-0.248 for all patients. We also present our methods in monitoring the model over time for trend changes, as well as common readmissions reduction strategies triggered by the score.
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http://dx.doi.org/10.3390/jpm10030103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565687PMC
August 2020

Key role of quinone in the mechanism of respiratory complex I.

Nat Commun 2020 08 18;11(1):4135. Epub 2020 Aug 18.

Institute of Science and Technology Austria, Am Campus 1, A-3400, Klosterneuburg, Austria.

Complex I is the first and the largest enzyme of respiratory chains in bacteria and mitochondria. The mechanism which couples spatially separated transfer of electrons to proton translocation in complex I is not known. Here we report five crystal structures of T. thermophilus enzyme in complex with NADH or quinone-like compounds. We also determined cryo-EM structures of major and minor native states of the complex, differing in the position of the peripheral arm. Crystal structures show that binding of quinone-like compounds (but not of NADH) leads to a related global conformational change, accompanied by local re-arrangements propagating from the quinone site to the nearest proton channel. Normal mode and molecular dynamics analyses indicate that these are likely to represent the first steps in the proton translocation mechanism. Our results suggest that quinone binding and chemistry play a key role in the coupling mechanism of complex I.
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http://dx.doi.org/10.1038/s41467-020-17957-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434922PMC
August 2020

From sterile labs to rich VR: Immersive multisensory context critical for odors to induce motivated cleaning behavior.

Behav Res Methods 2020 08;52(4):1657-1670

Department of Psychology, Utrecht University, PO Box 80140, 3508 TC, Utrecht, the Netherlands.

Extending traditional research methods for studying the effects of odor on behavior, this study applied virtual reality (VR) to create a real-world, immersive context that was compared with a traditional sterile, non-immersive lab setting. Using precise odor administration with olfactometry, participants were exposed to three odors (cleaning-related pleasant smell, cleaning-unrelated pleasant smell: vanillin, and odorless air). Our aim was to tease apart whether participants' motivation to clean was driven by cleaning associations and/or odor pleasantness, and how context would accentuate these effects. The results indeed showed that, in VR only, the cleaning-related smell elicited faster and more energetic cleaning behavior on a custom-designed cleaning task, and faster and more voluminous olfactory sampling compared with controls (vanillin, air). These effects were not driven by odor valence, given the general absence of significant differences between the pleasant control odor vanillin and odorless air. In sum, combining rigorous experimental control with high ecological validity, this research shows the context dependency of (congruent) odors affecting motivated behavior in an immersive context only.
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http://dx.doi.org/10.3758/s13428-019-01341-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406481PMC
August 2020

Accelerometer-Measured Hospital Physical Activity and Hospital-Acquired Disability in Older Adults.

J Am Geriatr Soc 2020 02 20;68(2):261-265. Epub 2019 Nov 20.

Duke University, Durham, North Carolina.

Background: Hospital-acquired disability (HAD) is common and often related to low physical activity while in the hospital.

Objective: To examine whether wearable hospital activity trackers can be used to predict HAD.

Design: A prospective observational study between January 2016 and March 2017.

Setting: An academic medical center.

Participants: Community-dwelling older adults, aged 60 years or older, enrolled within 24 hours of admission to general medicine (n = 46).

Main Measures: Primary outcome was HAD, defined as having one or more new activity of daily living deficits, decline of four or greater on the Late-Life Function and Disability Instrument (calculated between baseline and discharge), or discharge to a skilled nursing facility. Hospital activity (mean active time, mean sedentary time, and mean step counts per day) was measured using ankle-mounted accelerometers. The association of the literature-based threshold of 900 steps/day with HAD was also evaluated.

Results: Mean age was 73.2 years (SD = 9.5 years), 48% were male, and 76% were white. Median length of stay was 4 days (interquartile range [IQR] = 2.0-6.0 days); 61% (n = 28) reported being able to walk without assistance of another person or walking aid at baseline. Median daily activity time and step counts were 1.1 h/d (IQR = 0.7-1.7 h/d) and 1455.7 steps/day (IQR = 908.5-2643 steps/day), respectively. Those with HAD (41%; n = 19) had lower activity time (0.8 vs 1.4 h/d; P = .04) and fewer step counts (1186 vs 1808 steps/day; P = .04), but no difference in sedentary time, compared to those without HAD. The 900 steps/day threshold had poor sensitivity (40%) and high specificity (85%) for detecting HAD.

Conclusions: Low hospital physical activity, as measured by wearable accelerometers, is associated with HAD. Clinicians can utilize wearable technology data to refer patients to physical/occupational therapy services or other mobility interventions, like walking programs. J Am Geriatr Soc 68:261-265, 2020.
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http://dx.doi.org/10.1111/jgs.16231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002200PMC
February 2020

Physical Activity in the Hospital: Documentation and Influence on Venous Thromboembolism Prophylaxis.

J Aging Phys Act 2020 04 24;28(2):306-310. Epub 2020 Apr 24.

This study describes the availability of physical activity information in the electronic health record, explores how electronic health record documentation correlates with accelerometer-derived physical activity data, and examines whether measured physical activity relates to venous thromboembolism (VTE) prophylaxis use. Prospective observational data comes from community-dwelling older adults admitted to general medicine (n = 65). Spearman correlations were used to examine association of accelerometer-based daily step count with documented walking distance and with duration of VTE prophylaxis. Only 52% of patients had documented walking in nursing and/or physical therapy/occupational therapy notes during the first three hospital days. Median daily steps recorded via accelerometer was 1,370 (interquartile range = 854, 2,387) and correlated poorly with walking distance recorded in physical therapy/occupational therapy notes (median 33 feet/day [interquartile range = 12, 100]; r = .24; p = .27). Activity measures were not associated with use or duration of VTE prophylaxis. VTE prophylaxis use does not appear to be directed by patient activity, for which there is limited documentation.
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http://dx.doi.org/10.1123/japa.2018-0462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210062PMC
April 2020

Psychosocial effects of whole-body MRI screening in adult high-risk pathogenic mutation carriers: a case-controlled study (SIGNIFY).

J Med Genet 2020 04 12;57(4):226-236. Epub 2019 Nov 12.

Department of Diagnostic Radiology, The Royal Marsden NHS Foundation Trust, London, UK.

Background: Germline gene pathogenic variants (pv) cause a very high lifetime risk of developing cancer, almost 100% for women and 75% for men. In the UK, annual MRI breast screening is recommended for female pv carriers. The SIGNIFY study (Magnetic Resonance Imaging screening in Li Fraumeni syndrome: An exploratory whole body MRI) study reported outcomes of whole-body MRI (WB-MRI) in a cohort of 44 pv carriers and 44 matched population controls. The results supported the use of a baseline WB-MRI screen in all adult pv carriers. Here we report the acceptability of WB-MRI screening and effects on psychosocial functioning and health-related quality of life in the short and medium terms.

Methods: Psychosocial and other assessments were carried out at study enrolment, immediately before MRI, before and after MRI results, and at 12, 26 and 52 weeks' follow-up.

Results: WB-MRI was found to be acceptable with high levels of satisfaction and low levels of psychological morbidity throughout. Although their mean levels of cancer worry were not high, carriers had significantly more cancer worry at most time-points than controls. They also reported significantly more clinically significant intrusive and avoidant thoughts about cancer than controls at all time-points. There were no clinically significant adverse psychosocial outcomes in either carriers with a history of cancer or in those requiring further investigations.

Conclusion: WB-MRI screening can be implemented in pv carriers without adverse psychosocial outcomes in the short and medium terms. A previous cancer diagnosis may predict a better psychosocial outcome. Some carriers seriously underestimate their risk of cancer. Carriers of pv should have access to a clinician to help them develop adaptive strategies to cope with cancer-related concerns and respond to clinically significant depression and/or anxiety.
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http://dx.doi.org/10.1136/jmedgenet-2019-106407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146942PMC
April 2020

Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers.

Eur Urol 2019 12 16;76(6):831-842. Epub 2019 Sep 16.

International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland.

Background: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations.

Objective: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status.

Design, Setting, And Participants: Men aged 40-69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy.

Outcome Measurements And Statistical Analysis: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians.

Results And Limitations: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p =  0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p =  0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p =  0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65).

Conclusions: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers.

Patient Summary: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening.
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http://dx.doi.org/10.1016/j.eururo.2019.08.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880781PMC
December 2019

Opt-out bloodborne virus screening: a cross-sectional observational study in an acute medical unit.

BMJ Open 2019 07 16;9(7):e022777. Epub 2019 Jul 16.

Infectious Diseases, Galway University Hospitals, Galway, Ireland.

Objective: Recent treatment developments for HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV) have greatly improved prognoses. Current screening practices are mainly risk based and are suboptimal. Improved efforts are critically needed to identify persons with these viruses. The aims of this study were to assess the feasibility of an opt-out bloodborne virus (BBV) screening programme in an acute medical unit (AMU) and to describe the prevalence of HIV, HBV and HCV in this population.

Design And Setting: This was a cross-sectional observational study in the AMU of a tertiary referral hospital in Galway, a city in the west of Ireland.

Participants: 1936 patients entered the study; 54% were male, mean age was 53.1 years (SD 19.6). During the study period, all patients attending the AMU aged ≧16 years who were having bloods drawn and who had the ability to verbally consent for an additional blood sample met the inclusion criteria for the study.

Results: Over 44 weeks, 1936/4793 (40.4%) patients consented to BBV panel testing. Diagnosed prevalence rates for HIV, HBV and HCV were 0.5/1000, 2/1000 and 1.5/1000, respectively. There was one HIV-positive result; the patient was already engaged in care. Four patients tested positive for HBV surface antigen; one new diagnosis, one previously lost to follow-up and two already engaged in care. Three patients had active HCV infection; two had been lost to follow-up and are now linked back into services.

Conclusion: BBV testing uptake of 40.4% is higher than previous studies in AMU settings that used opt-in strategies, but lower than expected, possibly due to not incorporating testing into routine practice. The diagnosed prevalence of HBV is notable as little data currently exist about its prevalence in Ireland. These data are valuable in order to inform further prevention strategies for these infections in low-prevalence settings.
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http://dx.doi.org/10.1136/bmjopen-2018-022777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661585PMC
July 2019

Management of orbital conjunctival epithelial inclusion cyst using trichloroacetic acid (20%) in an outpatient setting.

Orbit 2020 Apr 20;39(2):147-149. Epub 2019 May 20.

Department of Ophthalmology, Mater Misericordiae Public Hospital, Dublin, Ireland.

Conjunctival epithelial inclusion cysts are an infrequent complication in anophthalmic sockets. The ocular prosthesis may become difficult to retain or it may cause local discomfort. Treatment options described include surgical resection, marsupialisation, and the use of injected sclerosing agents. We present a case of a 27-year-old female who developed a conjunctival epithelial inclusion cyst two years after a left eye evisceration. This invariably caused the ocular prosthesis to become cosmetically unacceptable. Trichloroacetic acid 20% (TCA) was injected intracystically as a minor procedure at the slit lamp. Four months later there was no recurrence of the cyst and the prosthesis retained an excellent position in the socket. This case highlights the successful treatment of a conjunctival epithelial inclusion cyst with TCA (20%) without the need for a surgical procedure.
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http://dx.doi.org/10.1080/01676830.2019.1611882DOI Listing
April 2020

Automated versus Manual Data Extraction of the Padua Prediction Score for Venous Thromboembolism Risk in Hospitalized Older Adults.

Appl Clin Inform 2018 07 26;9(3):743-751. Epub 2018 Sep 26.

Duke University, Durham, North Carolina, United States.

Objective: Venous thromboembolism (VTE) prophylaxis is an important consideration for hospitalized older adults, and the Padua Prediction Score (PPS) is a risk prediction tool used to prioritize patient selection. We developed an automated PPS (APPS) algorithm using electronic health record (EHR) data. This study examines the accuracy of APPS and its individual components versus manual data extraction.

Methods: This is a retrospective cohort study of hospitalized general internal medicine patients, aged 70 and over. Fourteen clinical variables were collected to determine their PPS; APPS used EHR data exports from health system databases, and a trained abstractor performed manual chart abstractions. We calculated sensitivity and specificity of the APPS, using manual PPS as the gold standard for classifying risk category (low vs. high). We also examined performance characteristics of the APPS for individual variables.

Results: PPS was calculated by both methods on 311 individuals. The mean PPS was 3.6 (standard deviation, 1.8) for manual abstraction and 2.8 (1.4) for APPS. In detecting patients at high risk for VTE, the sensitivity and specificity of the APPS algorithm were 46 and 94%, respectively. The sensitivity for APPS was poor (range: 6-34%) for detecting acute conditions (i.e., acute myocardial infarction), moderate (range: 52-74%) for chronic conditions (i.e., heart failure), and excellent (range: 94-98%) for conditions of obesity and restricted mobility. Specificity of the automated extraction method for each PPS variable was > 87%.

Conclusion: APPS as a stand-alone tool was suboptimal for classifying risk of VTE occurrence. The APPS accurately identified high risk patients (true positives), but lower scores were considered indeterminate.
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http://dx.doi.org/10.1055/s-0038-1670678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158031PMC
July 2018

Hit by the wave: a case of painful Horner's and intramural haematoma of the carotid.

BMJ Case Rep 2018 Sep 12;2018. Epub 2018 Sep 12.

Acute Medical Unit (AMU), Galway University Hospital, Galway, Ireland.

Carotid artery dissection from rupture of the vasa vasorum is under-recognised. We report the case of a 60-year-old woman presenting to our hospital with a 2-week history of right-sided headache, neck pain, unequal pupils and ptosis after being hit by a wave on the beach. She was diagnosed with painful Horner's syndrome. MR angiogram revealed dissection of the right internal carotid artery with an intramural haematoma without an intimal flap. A diagnosis of carotid artery dissection from rupture of the vasa vasorum was made. Initial antithrombotic (aspirin and clexane) were stopped as she was deemed a low stroke risk with no signs of ischaemia on MR brain. Her clinical course was uneventful with resolution of the intramural haematoma seen on repeat MR angiogram.
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http://dx.doi.org/10.1136/bcr-2018-225660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144165PMC
September 2018

Relationship between the MDS-UPDRS and Quality of Life: A large multicenter study of 3206 patients.

Parkinsonism Relat Disord 2018 07 28;52:83-89. Epub 2018 Mar 28.

Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS_1127, CIC_1422, CNRS UMR_7225, AP-HP, ICM, Hôpital Pitié-Salpêtrière, Département des maladies du système nerveux, F-75013, Paris, France.

Background: The relationship between Health-Related Quality of Life (HRQoL) and MDS-UPDRS has not been fully studied so far. The aim of this study was to evaluate the relationship between all MDS-UPDRS components and HRQoL in a representative international cohort of PD patients.

Methods: We collected demographic and disease-related data as well as MDS-UPDRS and PDQ8 scales. Data were analyzed using correlations between PDQ8 and all MDS-UPDRS items, subsequently two hierarchical multiple regressions were performed, first between the scores of the MDS-UPDRS Parts and PDQ8 and second between individual items from those Parts demonstrating significant relationship to PDQ8 scores in the first regression. LASSO regression analyses were performed to evaluate the relationship between PDQ8 and all individual MDS-UPDRS items.

Results: A total of 3206 PD patients were included in the study. In the first regression analysis, PDQ8 was significantly related to MDS-UPDRS parts I and II, but not to III and IV. In the second regression model, significant contributions to PDQ8 were found for Part I items Fatigue, Pain, Depressed mood, Apathy; and Part II items Dressing, Doing hobbies, Freezing, Speech and Tremor. In the LASSO analysis, six Part I, seven Part II, three Part III and one Part IV items contributed to PDQ8 scores. The five items most significantly related to the model were Depressed mood, Dressing, Apathy, Pain and Fatigue.

Conclusions: This is so far the largest study related to HRQoL issues in PD. Restrictions in activities of daily living and non-motor symptoms significantly contribute to HRQoL in PD.
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http://dx.doi.org/10.1016/j.parkreldis.2018.03.027DOI Listing
July 2018

Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition.

Br J Cancer 2018 01 4;118(2):266-276. Epub 2018 Jan 4.

Department of Clinical Genetics, Erasmus Medical Center, Rotterdam 3015 CE, The Netherlands.

Background: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort.

Methods: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV.

Results: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers.

Conclusions: PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.
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http://dx.doi.org/10.1038/bjc.2017.429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785754PMC
January 2018

Risk reduction surgery (RRS) for tubo-ovarian cancer in an Irish gynaecological practice: an analysis of indications and outcomes.

Ir J Med Sci 2018 Aug 3;187(3):789-794. Epub 2018 Jan 3.

Gynaecological Oncology Department, St James's Hospital, Dublin, Ireland.

Background: High-grade serous carcinoma (HGSC) is the most common tubo-ovarian cancer. The fallopian tube harbours the precursor lesion: serous tubal intraepithelial carcinoma (STIC). Bilateral salpingo-oophorectomy is an effective risk-reducing surgical (RRS) strategy for breast cancer susceptibility gene mutation carriers (BRCAm). The value of RRS in those without defined genetic risk is unknown but these women represent a substantial cohort in prophylactic surgical practice.

Methods: This is a retrospective review of RRS at an Irish university teaching hospital.

Results: One hundred and thirty women underwent RRS; group 1 = 46 BRCAm; group 2 = 19 BRCAm negative/65 genetic status unknown. Group 1 had one occult HGSC. Group 2 had no STIC or cancers and were older and more likely to have hysterectomy and benign pathology. Other pathologies included serous tubal intraepithelial lesions (STIL) (2), p53 signatures (2), endometriosis (6), fibroids/adenomyosis (4) and atypical endometrial hyperplasia (1).

Conclusion: More than 60% of women undergoing RRS were BRCAm negative or untested. Counselling of high-risk women without defined germline mutations remains a challenge for gynaecologists because the likelihood of removing STIC lesions or occult invasive cancer is low. Removal of coincidental pathology may give added value to RRS in these women.
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http://dx.doi.org/10.1007/s11845-017-1717-6DOI Listing
August 2018
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