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2.
HIV Med ; 24(1): 46-54, 2023 01.
Article in English | MEDLINE | ID: mdl-35521975

ABSTRACT

OBJECTIVE: Age-related comorbidities, polypharmacy and thereby the risk of potential drug-drug interactions (PDDIs) among people living with HIV (PLWH) have increased over the years. We estimated the prevalence of comedications, including dietary supplements, and evaluated PDDIs among PLWH receiving antiretroviral therapy (ART) in Denmark in an outpatient setting. METHODS: Information on prescription medication, over-the-counter medication and dietary supplements was obtained from adult PLWH receiving ART attending two outpatient clinics in Denmark. The PDDIs were identified using the University of Liverpool's drug interaction database. Associations between PDDIs and relevant variables were compared using logistic regression models. RESULTS: A total of 337 PLWH receiving ART with a median age of 53 years (interquartile range: 45-61) were included; 77% were male and 96% had a HIV-RNA viral load < 50 copies/mL. Twenty-six per cent of participants received five or more comedications and 56% consumed dietary supplements. Co-administration of drugs requiring dose adjustment or monitoring was identified in the medication lists of 52% of participants, and 4.5% were on drugs that should not be co-administered. Male sex [odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.0-3.4], being on a protease inhibitor (OR = 4.3, 95% CI: 1.9-9.7), receiving five or more comedications (OR = 3.3, 95% CI: 1.5-7.2), taking over-the-counter medications (OR = 1.9, 95% CI: 1.1-3.3) and dietary supplements (OR = 2.0, 95% CI: 1.2-3.3) were independent predictors of PDDIs. CONCLUSION: Potential drug-drug interactions were common among our study population Our study confirms that polypharmacy and being on a protease inhibitor-based regimen increase the risk of PDDIs considerably and highlights the importance of questioning PLWH about dietary supplement intake.


Subject(s)
HIV Infections , Prescription Drugs , Adult , Humans , Male , Middle Aged , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , Anti-Retroviral Agents/therapeutic use , Polypharmacy , Drug Interactions , Prescription Drugs/therapeutic use , Protease Inhibitors/therapeutic use , Dietary Supplements
3.
Preprint in English | medRxiv | ID: ppmedrxiv-22272394

ABSTRACT

ObjectiveClinicians in the emergency department (ED) face challenges in concurrently assessing patients with suspected COVID-19 infection, detecting bacterial co-infection, and determining illness severity since current practices require separate workflows. Here we explore the accuracy of the IMX-BVN-3/IMX-SEV-3 29 mRNA host response classifiers in simultaneously detecting SARS-CoV-2 infection, bacterial co-infections, and predicting clinical severity of COVID-19. Methods161 patients with PCR-confirmed COVID-19 (52.2% female, median age 50.0 years, 51% hospitalized, 5.6% deaths) were enrolled at the Stanford Hospital ED. RNA was extracted (2.5 mL whole blood in PAXgene Blood RNA) and 29 host mRNAs in response to the infection were quantified using Nanostring nCounter. ResultsThe IMX-BVN-3 classifier identified SARS-CoV-2 infection in 151 patients with a sensitivity of 93.8%. Six of 10 patients undetected by the classifier had positive COVID tests more than 9 days prior to enrolment and the remaining oscillated between positive and negative results in subsequent tests. The classifier also predicted that 6 (3.7%) patients had a bacterial co-infection. Clinical adjudication confirmed that 5/6 (83.3%) of the patients had bacterial infections, i.e. Clostridioides difficile colitis (n=1), urinary tract infection (n=1), and clinically diagnosed bacterial infections (n=3) for a specificity of 99.4%. 2/101 (2.8%) patients in the IMX-SEV-3 Low and 7/60 (11.7%) in the Moderate severity classifications died within thirty days of enrollment. ConclusionsIMX-BVN-3/IMX-SEV-3 classifiers accurately identified patients with COVID-19, bacterial co-infections, and predicted patients risk of death. A point-of-care version of these classifiers, under development, could improve ED patient management including more accurate treatment decisions and optimized resource utilization.

4.
Preprint in English | medRxiv | ID: ppmedrxiv-21262934

ABSTRACT

Determinants of Post-Acute Sequelae of COVID-19 are not known. Here we show that 75% of patients with viral RNA in blood (RNAemia) at presentation were symptomatic in the post-acute phase. RNAemia at presentation successfully predicted PASC, independent of patient demographics, initial disease severity, and length of symptoms.

5.
- The COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium; David J Ahern; Zhichao Ai; Mark Ainsworth; Chris Allan; Alice Allcock; Azim Ansari; Carolina V Arancibia-Carcamo; Dominik Aschenbrenner; Moustafa Attar; J. Kenneth Baillie; Eleanor Barnes; Rachael Bashford-Rogers; Archana Bashyal; Sally Beer; Georgina Berridge; Amy Beveridge; Sagida Bibi; Tihana Bicanic; Luke Blackwell; Paul Bowness; Andrew Brent; Andrew Brown; John Broxholme; David Buck; Katie L Burnham; Helen Byrne; Susana Camara; Ivan Candido Ferreira; Philip Charles; Wentao Chen; Yi-Ling Chen; Amanda Chong; Elizabeth Clutterbuck; Mark Coles; Christopher P Conlon; Richard Cornall; Adam P Cribbs; Fabiola Curion; Emma E Davenport; Neil Davidson; Simon Davis; Calliope Dendrou; Julie Dequaire; Lea Dib; James Docker; Christina Dold; Tao Dong; Damien Downes; Alexander Drakesmith; Susanna J Dunachie; David A Duncan; Chris Eijsbouts; Robert Esnouf; Alexis Espinosa; Rachel Etherington; Benjamin Fairfax; Rory Fairhead; Hai Fang; Shayan Fassih; Sally Felle; Maria Fernandez Mendoza; Ricardo Ferreira; Roman Fischer; Thomas Foord; Aden Forrow; John Frater; Anastasia Fries; Veronica Gallardo Sanchez; Lucy Garner; Clementine Geeves; Dominique Georgiou; Leila Godfrey; Tanya Golubchik; Maria Gomez Vazquez; Angie Green; Hong Harper; Heather A Harrington; Raphael Heilig; Svenja Hester; Jennifer Hill; Charles Hinds; Clare Hird; Ling-Pei Ho; Renee Hoekzema; Benjamin Hollis; Jim Hughes; Paula Hutton; Matthew Jackson; Ashwin Jainarayanan; Anna James-Bott; Kathrin Jansen; Katie Jeffery; Elizabeth Jones; Luke Jostins; Georgina Kerr; David Kim; Paul Klenerman; Julian C Knight; Vinod Kumar; Piyush Kumar Sharma; Prathiba Kurupati; Andrew Kwok; Angela Lee; Aline Linder; Teresa Lockett; Lorne Lonie; Maria Lopopolo; Martyna Lukoseviciute; Jian Luo; Spyridoula Marinou; Brian Marsden; Jose Martinez; Philippa Matthews; Michalina Mazurczyk; Simon McGowan; Stuart McKechnie; Adam Mead; Alexander J Mentzer; Yuxin Mi; Claudia Monaco; Ruddy Montadon; Giorgio Napolitani; Isar Nassiri; Alex Novak; Darragh O'Brien; Daniel O'Connor; Denise O'Donnell; Graham Ogg; Lauren Overend; Inhye Park; Ian Pavord; Yanchun Peng; Frank Penkava; Mariana Pereira Pinho; Elena Perez; Andrew J Pollard; Fiona Powrie; Bethan Psaila; T. Phuong Quan; Emmanouela Repapi; Santiago Revale; Laura Silva-Reyes; Jean-Baptiste Richard; Charlotte Rich-Griffin; Thomas Ritter; Christine S Rollier; Matthew Rowland; Fabian Ruehle; Mariolina Salio; Stephen N Sansom; Alberto Santos Delgado; Tatjana Sauka-Spengler; Ron Schwessinger; Giuseppe Scozzafava; Gavin Screaton; Anna Seigal; Malcolm G Semple; Martin Sergeant; Christina Simoglou Karali; David Sims; Donal Skelly; Hubert Slawinski; Alberto Sobrinodiaz; Nikolaos Sousos; Lizzie Stafford; Lisa Stockdale; Marie Strickland; Otto Sumray; Bo Sun; Chelsea Taylor; Stephen Taylor; Adan Taylor; Supat Thongjuea; Hannah Thraves; John A Todd; Adriana Tomic; Orion Tong; Amy Trebes; Dominik Trzupek; Felicia A Tucci; Lance Turtle; Irina Udalova; Holm Uhlig; Erinke van Grinsven; Iolanda Vendrell; Marije Verheul; Alexandru Voda; Guanlin Wang; Lihui Wang; Dapeng Wang; Peter Watkinson; Robert Watson; Michael Weinberger; Justin Whalley; Lorna Witty; Katherine Wray; Luzheng Xue; Hing Yuen Yeung; Zixi Yin; Rebecca K Young; Jonathan Youngs; Ping Zhang; Yasemin-Xiomara Zurke.
Preprint in English | medRxiv | ID: ppmedrxiv-21256877

ABSTRACT

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity revealed cells, their inflammatory mediators and networks as potential therapeutic targets, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Tensor and matrix decomposition of the overall dataset revealed feature groupings linked with disease severity and specificity. Our systems-based integrative approach and blood atlas will inform future drug development, clinical trial design and personalised medicine approaches for COVID-19.

6.
Preprint in English | medRxiv | ID: ppmedrxiv-20248561

ABSTRACT

BackgroundThe determinants of COVID-19 disease severity and extrapulmonary complications (EPCs) are poorly understood. We characterise the relationships between SARS-CoV-2 RNAaemia and disease severity, clinical deterioration, and specific EPCs. MethodsWe used quantitative (qPCR) and digital (dPCR) PCR to quantify SARS-CoV-2 RNA from nasopharyngeal swabs and plasma in 191 patients presenting to the Emergency Department (ED) with COVID-19. We recorded patient symptoms, laboratory markers, and clinical outcomes, with a focus on oxygen requirements over time. We collected longitudinal plasma samples from a subset of patients. We characterised the role of RNAaemia in predicting clinical severity and EPCs using elastic net regression. Findings23{middle dot}0% (44/191) of SARS-CoV-2 positive patients had viral RNA detected in plasma by dPCR, compared to 1{middle dot}4% (2/147) by qPCR. Most patients with serial measurements had undetectable RNAaemia 10 days after onset of symptoms, but took 16 days to reach maximum severity, and 33 days for symptoms to resolve. Initially RNAaemic patients were more likely to manifest severe disease (OR 6{middle dot}72 [95% CI, 2{middle dot}45 - 19{middle dot}79]), worsening of disease severity (OR 2{middle dot}43 [95% CI, 1{middle dot}07 - 5{middle dot}38]), and EPCs (OR 2{middle dot}81 [95% CI, 1{middle dot}26 - 6{middle dot}36]). RNA load correlated with maximum severity (r = 0{middle dot}47 [95% CI, 0{middle dot}20 - 0{middle dot}67]). InterpretationdPCR is more sensitive than qPCR for the detection of SARS-CoV-2 RNAaemia, which is a robust predictor of eventual COVID-19 severity and oxygen requirements, as well as EPCs. Since many COVID-19 therapies are initiated on the basis of oxygen requirements, RNAaemia on presentation might serve to direct early initiation of appropriate therapies for the patients most likely to deteriorate. FundingNIH/NIAID (Grants R01A153133, R01AI137272, and 3U19AI057229 - 17W1 COVID SUPP #2) and a donation from Eva Grove. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe varied clinical manifestations of COVID-19 have directed attention to the distribution of SARS-CoV-2 in the body. Although most concentrated and tested for in the nasopharynx, SARS-CoV-2 RNA has been found in blood, stool, and numerous tissues, raising questions about dissemination of viral RNA throughout the body, and the role of this process in disease severity and extrapulmonary complications. Recent studies have detected low levels of SARS-CoV-2 RNA in blood using either quantitative reverse transcriptase real-time PCR (qPCR) or droplet digital PCR (dPCR), and have associated RNAaemia with disease severity and biomarkers of dysregulated immune response. Added value of this studyWe quantified SARS-CoV-2 RNA in the nasopharynx and plasma of patients presenting to the Emergency Department with COVID-19, and found an array-based dPCR platform to be markedly more sensitive than qPCR for detection of SARS-CoV-2 RNA, with a simplified workflow well-suited to clinical adoption. We collected serial plasma samples during patients course of illness, and showed that SARS-CoV-2 RNAaemia peaks early, while clinical condition often continues to worsen. Our findings confirm the association between RNAaemia and disease severity, and additionally demonstrate a role for RNAaemia in predicting future deterioration and specific extrapulmonary complications. Implications of all the available evidenceVariation in SARS-CoV-2 RNAaemia may help explain disparities in disease severity and extrapulmonary complications from COVID-19. Testing for RNAaemia with dPCR early in the course of illness may help guide patient triage and management.

7.
Clin Biochem ; 84: 31-37, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32504704

ABSTRACT

BACKGROUND: Accurate first-line diagnostics are essential for early recognition of cancer but also to identify patients free of disease. The biomarker soluble urokinase plasminogen activator receptor (suPAR) is elevated in patients with cancer or non-malignant disease compared to disease-free patients. We tested if low suPAR could be used to identify disease-free patients in an accelerated cancer diagnostics program, including ruling out cancer. METHODS: Patients with serious nonspecific symptoms and signs of cancer (NSSC) were included at the Diagnostic Outpatient Clinic, Copenhagen University Hospital Hvidovre, Denmark. Data from a clinical examination, including blood tests and imaging, was combined with national registry data on diagnoses and mortality. The association between blood suPAR and the primary outcome of disease-free (i.e., absence of incident disease and mortality) within 1-year follow-up was analysed with logistic regression analysis. RESULTS: Of 1583 patients included, 349 (22.0%) were diagnosed with cancer, 837 (52.9%) with non-malignant disease, and 392 (25.8%) were disease-free within one year. Admission suPAR was significantly lower in disease-free patients compared to patients with cancer or non-malignant disease (P < 0.001), area under the curve 0.67 (95% confidence interval (CI): 0.64-0.70). The highest positive predictive value (PPV) for the outcome of disease-free was 0.55 (95% CI: 0.41-0.68) at a suPAR of 1.65 ng/mL. Patients who died had significantly higher suPAR compared to patients who survived in all disease subgroups. The AUC of suPAR for 1-year mortality was 0.80 (95% CI: 0.77-0.83). CONCLUSIONS: suPAR was significantly lower in disease-free individuals compared to patients with cancer or other conditions, but the PPV was not sufficiently high to terminate further clinical investigation with appropriate safety. Elevated suPAR may be a useful prognostic marker for adverse outcomes.


Subject(s)
Neoplasms/diagnosis , Neoplasms/metabolism , Receptors, Urokinase Plasminogen Activator/analysis , Aged , Area Under Curve , Biomarkers/blood , Cohort Studies , Female , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Receptors, Urokinase Plasminogen Activator/blood , Risk Assessment
8.
Preprint in English | medRxiv | ID: ppmedrxiv-20119594

ABSTRACT

ObjectivesTo estimate COVID-19 infections and deaths in healthcare workers (HCWs) from a global perspective. DesignScoping review. MethodsTwo parallel searches of academic bibliographic databases and grey literature were undertaken. Governments were also contacted for further information where possible. Due to the time-sensitive nature of the review and the need to report the most up-to-date information for an ever-evolving situation, there were no restrictions on language, information sources utilised, publication status, and types of sources of evidence. The AACODS checklist was used to appraise each source of evidence. Outcome measuresPublication characteristics, country-specific data points, COVID-19 specific data, demographics of affected HCWs, and public health measures employed ResultsA total of 152,888 infections and 1413 deaths were reported. Infections were mainly in women (71.6%) and nurses (38.6%), but deaths were mainly in men (70.8%) and doctors (51.4%). Limited data suggested that general practitioners and mental health nurses were the highest risk specialities for deaths. There were 37.17 deaths reported per 100 infections for healthcare workers aged over 70. Europe had the highest absolute numbers of reported infections (119628) and deaths (712), but the Eastern Mediterranean region had the highest number of reported deaths per 100 infections (5.7). ConclusionsHCW COVID-19 infections and deaths follow that of the general world population. The reasons for gender and speciality differences require further exploration, as do the low rates reported from Africa and India. Although physicians working in certain specialities may be considered high-risk due to exposure to oronasal secretions, the risk to other specialities must not be underestimated. Elderly HCWs may require assigning to less risky settings such as telemedicine, or administrative positions. Our pragmatic approach provides general trends, and highlights the need for universal guidelines for testing and reporting of infections in HCWs. Summary BoxO_ST_ABSWhat is already known on this topicC_ST_ABSIn China, studies documented over 3,300 confirmed cases of infected healthcare workers in early March. In the United States, as high as 19% of patients had been identified as healthcare workers. There are no studies that perform a global examination of COVID-19 infections and deaths in the health workforce. What this study addsTo our knowledge, this is the first study assessing the number of healthcare workers who have been infected with or died from COVID-19 globally. The data from our study suggest that although infections were mainly in women and nurses, COVID-19 related deaths were mainly in men and doctors; in addition, our study found that Europe had the highest numbers of infection and death, but the lowest case-fatality-rate, while the Eastern Mediterranean had the highest case-fatality-rate.

9.
Preprint in English | bioRxiv | ID: ppbiorxiv-111526

ABSTRACT

Rapid generation of diagnostics is paramount to understand epidemiology and to control the spread of emerging infectious diseases such as COVID-19. Computational methods to predict serodiagnostic epitopes that are specific for the pathogen could help accelerate the development of new diagnostics. A systematic survey of 27 SARS-CoV-2 proteins was conducted to assess whether existing B-cell epitope prediction methods, combined with comprehensive mining of sequence databases and structural data, could predict whether a particular protein would be suitable for serodiagnosis. Nine of the predictions were validated with recombinant SARS-CoV-2 proteins in the ELISA format using plasma and sera from patients with SARS-CoV-2 infection, and a further 11 predictions were compared to the recent literature. Results appeared to be in agreement with 12 of the predictions, in disagreement with 3, while a further 5 were deemed inconclusive. We showed that two of our top five candidates, the N-terminal fragment of the nucleoprotein and the receptor-binding domain of the spike protein, have the highest sensitivity and specificity and signal-to-noise ratio for detecting COVID-19 sera/plasma by ELISA. Mixing the two antigens together for coating ELISA plates led to a sensitivity of 94% (N=80 samples from persons with RT-PCR confirmed SARS-CoV2 infection), and a specificity of 97.2% (N=106 control samples).

10.
JMM Case Rep ; 5(4): e005141, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29868173

ABSTRACT

INTRODUCTION: Diagnosis of schistosomiasis in travellers is a clinical challenge, since cases may present with no symptoms or a few non-specific symptoms. Here, we report on the laboratory and clinical findings in Danish travellers exposed to Schistosoma-infested water during white-water rafting on the Ugandan part of the upper Nile River in July 2009. CASE PRESENTATION: Forty travellers were offered screening for Schistosoma-specific antibodies. Serological tests were performed 6-65 weeks after exposure. A self-reporting questionnaire was used to collect information on travel activity and health history, fresh water exposure, and symptoms. Seropositive cases were referred to hospitals where clinical and biochemical data were collected. Schistosoma-specific antibodies were detected in 13/35 (37 %) exposed participants, with 4/13 (31 %) seroconverting later than 2 months following exposure. Four of thirteen (31 %) cases reported ≥3 symptoms compatible with schistosomiasis, with a mean onset of 41 days following exposure. No Schistosoma eggs were detected in stool or urine in any of the cases. Peripheral eosinophilia (>0.45×109 cells l-1) was seen in 4/13 cases, while IgE levels were normal in all cases. CONCLUSION: Schistosomiasis in travellers is not necessarily associated with specific signs or symptoms, eosinophilia, raised IgE levels, or detection of eggs. The only prognostic factor for infection was exposure to freshwater in a Schistosoma-endemic area. Seroconversion may occur later than 2 months after exposure and therefore - in the absence of other diagnostic evidence - serology testing should be performed up to at least 2-3 months following exposure to be able to rule out schistosomiasis.

11.
Int J Cancer ; 141(1): 191-199, 2017 07 01.
Article in English | MEDLINE | ID: mdl-28393357

ABSTRACT

In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin-3, mannose-binding lectin, ficolin-1, ficolin-2 and ficolin-3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer in patients with NSSC. Patients were included from the DOC, Department of Infectious Diseases, Copenhagen University Hospital Hvidovre. Patients were given a final diagnosis based on the combined results from scans, blood work and physical examination. Weight loss, Charlson score and previous cancer were registered on admission, and plasma concentrations of biomarkers were measured. The primary outcome was incident cancer within 1 year. Out of 197 patients included, 39 patients (19.8%) were diagnosed with cancer. Patients with cancer were significantly older and had a higher burden of comorbidities and previous cancer diagnoses compared to patients who were not diagnosed with cancer. Previous cancer, C-reactive protein (CRP) and suPAR were significantly associated with newly diagnosed cancer during follow-up in multiple logistic regression analyses adjusted for age, sex and CRP. Neither any of the PRRs investigated nor self-reported weight loss was associated with cancer. In this study, previous cancer, CRP and suPAR were significantly associated with cancer diagnosis in patients with NSSC. Ficolin-1-3, MBL and pentraxin-3 were not associated with cancer.


Subject(s)
Biomarkers, Tumor/blood , C-Reactive Protein/metabolism , Inflammation/blood , Neoplasms/blood , Receptors, Urokinase Plasminogen Activator/blood , Age Factors , Aged , Denmark , Female , Humans , Inflammation/pathology , Lectins/blood , Male , Mannose-Binding Lectins/blood , Middle Aged , Neoplasms/genetics , Neoplasms/pathology , Serum Amyloid P-Component/metabolism , Sex Characteristics , Ficolins
12.
J Nucl Med ; 58(7): 1058-1064, 2017 07.
Article in English | MEDLINE | ID: mdl-28082437

ABSTRACT

A fast-track pathway has been established in Denmark to investigate patients with serious nonspecific symptoms and signs of cancer (NSSC), who are not eligible to enter an organ-specific cancer program. The prevalence of cancer in this cohort is approximately 20%. The optimal screening strategy in patients with NSSC remains unknown. The aim of the study was to investigate whether 18F-FDG PET/CT was superior to CT as an initial imaging modality in patients with NSSC. In a randomized prospective trial, the imaging modalities were compared with regard to diagnostic performance. Methods: Two hundred patients were randomized 1:1 to whole-body 18F-FDG PET/CT or CT of the thorax and abdomen as the imaging modality. A tentative diagnosis was established after first-line imaging. The final referral diagnosis was adjudicated by the physician, when sufficient data were available. Results: One hundred ninety-seven patients were available for analysis because 3 patients withdrew consent before scanning. Thirty-nine (20%) patients were diagnosed with cancer, 10 (5%) with an infection, 15 (8%) with an autoimmune disease, and 76 (39%) with other diseases. In the remaining 57 patients (28%), no specific disease was found. 18F-FDG PET/CT had a higher specificity (96% vs. 85%; P = 0.028) and a higher accuracy (94% vs. 82%; P = 0.017) than CT. However, there were no statistically significant differences in sensitivity (83% vs. 70%) or negative predictive values (96% vs. 92%). No difference in days to final referral diagnosis according to randomization group could be shown (7.2 vs. 7.6 d). However, for the subgroups in which the imaging modality showed a suggestion of malignancy, there was a significant delay to final diagnosis in the CT group compared with the 18F-FDG PET/CT group (11.6 vs. 5.7 d; P = 0.02). Conclusion: Compared with CT, we found a higher diagnostic specificity and accuracy of 18F-FDG PET/CT for detecting cancer in patients with NSSC. 18F-FDG PET/CT should therefore be considered as first-line imaging in this group of patients.


Subject(s)
Early Detection of Cancer/statistics & numerical data , Fluorodeoxyglucose F18 , Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography/statistics & numerical data , Tomography, X-Ray Computed/methods , Whole Body Imaging/statistics & numerical data , Denmark/epidemiology , Early Detection of Cancer/methods , Female , Humans , Male , Neoplasms/epidemiology , Observer Variation , Positron Emission Tomography Computed Tomography/methods , Prevalence , Radiopharmaceuticals , Reproducibility of Results , Risk Factors , Sensitivity and Specificity , Symptom Assessment , Whole Body Imaging/methods
13.
Ugeskr Laeger ; 178(18)2016 May 02.
Article in Danish | MEDLINE | ID: mdl-27137117

ABSTRACT

We report two cases of HIV infection among female travellers of older age. A Danish woman in her eighties was diagnosed with acute HIV infection after travelling to West Africa. A sexual history was not recorded before her third hospital visit. A West African woman in her seventies who had been living in Denmark for 40 years was diagnosed with advanced HIV after having been to West Africa for family visits. We want to emphasize that women of older age also have sex that may put them at risk of HIV, that febrile returning travellers should be tested for HIV, and that presence of HIV indicator diseases should lead to HIV testing.


Subject(s)
HIV Infections/diagnosis , Africa, Western , Aged , Aged, 80 and over , Female , Humans , Sexual Behavior , Travel-Related Illness
15.
Pain Med ; 16(10): 1882-96, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26037534

ABSTRACT

INTRODUCTION: This study measured the following: violence rates against chronic pain care providers (CPCPs), character/context/risk factors for violence and CPCPs' mitigation strategies. METHOD: An e-mail survey was sent to members of the American Society of Interventional Pain Physicians (ASIIP) to collect demographics, rates/type of violence, injury, risk mitigation, and context of violence. Correlation with demographic factors calculated using one-way ANOVA and χ2 test (Fisher test). RESULTS: Security was called by 64.85% of CPCPs and 51.52% received threats. The threats involved a gun 7.05% of the time. Injury was reported by 2.73% of CPCPs. The most common risk mitigation was discharging patient (85.33%). Others used protective equipment (16.89%) of which a significant percentage carried a gun (54%). Opioid management was the highest context for violence (89.9%; P < 0.0001). Those who practiced part-time were more likely to be harmed (P = 0.0290). Females were less likely to be threatened (P = 0.0507). Anesthesiology was the most threatened vs other specialties (P = 0.0215). Urban practices were less likely to move or close the practice (P = 0.0292). CONCLUSION: CPCPs were at high risk for violence. Risk factors were older age, male, working part time, and anesthesiology. Risk was highest in the context of opioid management and disability. Discharging patient was the most common risk mitigation. A significant number of physicians carried firearms.


Subject(s)
Chronic Pain/epidemiology , Chronic Pain/therapy , Health Personnel/statistics & numerical data , Medicine/statistics & numerical data , Physicians/statistics & numerical data , Workplace Violence/statistics & numerical data , Adult , Age Distribution , Aged , Chronic Pain/psychology , Female , Health Personnel/psychology , Humans , Male , Middle Aged , Physicians/psychology , Prevalence , Risk Factors , Sex Distribution , Socioeconomic Factors , Workplace Violence/psychology
16.
Tissue Eng Part A ; 21(3-4): 647-53, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25335965

ABSTRACT

Severe pathoanatomical and mechanical injuries compromise patient recovery and survival following penetrating brain injury (PBI). The realization that the blood-brain barrier (BBB) plays a major role in dictating post-PBI events has led to rising interests in possible therapeutic interventions through the BBB. Recently, the choroid plexus has also been suggested as a potential therapeutic target. The use of biocompatible scaffolds for the delivery of therapeutic agents, but little is known about their interaction with cerebral tissue, which has important clinical implications. Therefore, the authors have sought to investigate the effect of polycaprolactone (PCL) and PCL/tricalcium phosphate (PCL/TCP) scaffolds on the maintenance of BBB phenotype posttraumatic brain injury. Cranial defects of 3 mm depth were created in Sprague Dawley rats, and PCL and PCL/TCP scaffolds were subsequently implanted in predetermined locations for a period of 1 week and 1 month. Higher endothelial barrier antigen (EBA) expressions from PCL-based scaffold groups (p>0.05) were found, suggesting slight advantages over the sham group (no scaffold implantation). PCL/TCP scaffold group also expressed EBA to a higher degree (p>0.05) than PCL scaffolds. Importantly, higher capillary count and area as early as 1 week postimplantation suggested lowered ischemia from the PCL/TCP scaffold group as compared with PCL and sham. Evaluation of interlukin-1ß expression suggested that the PCL and PCL/TCP scaffolds did not cause prolonged inflammation. BBB transport selectivity was evaluated by the expression of aquaporin-4 (AQP-4). Attenuated expression of AQP-4 in the PCL/TCP group (p<0.05) suggested that PCL/TCP scaffolds altered BBB selectivity to a lower degree as compared with sham and PCL groups, pointing to potential clinical implications in reducing cerebral edema. Taken together, the responses of PCL-based scaffolds with brain tissue suggested safety, and encourages further preclinical evaluation in PBI management with these scaffolds.


Subject(s)
Blood-Brain Barrier/immunology , Calcium Phosphates/adverse effects , Encephalitis/etiology , Polyesters/adverse effects , Skull Fractures/therapy , Tissue Scaffolds/adverse effects , Animals , Biocompatible Materials/adverse effects , Blood-Brain Barrier/drug effects , Calcium Phosphates/administration & dosage , Encephalitis/immunology , Equipment Design , Equipment Failure Analysis , Female , Materials Testing , Polyesters/therapeutic use , Rats , Rats, Sprague-Dawley , Skull Fractures/complications , Skull Fractures/immunology , Treatment Outcome
17.
Dan Med J ; 61(5): A4827, 2014 May.
Article in English | MEDLINE | ID: mdl-24814737

ABSTRACT

INTRODUCTION: In this study, we describe patients with imported malaria seen at the Department of Infectious Diseases (DID), Hvidovre Hospital, Denmark. Our aim was to address possible risk factors for contracting malaria and risk factors for developing complicated malaria. MATERIAL AND METHODS: We searched patient databases for all cases of malaria seen at the DID from 1994 to 2012. Various parameters were registered. RESULTS: A total of 320 cases were identified. We found a significant 3.39 % decrease in the incidence of cases per year (p = 0.0008). Plasmodium falciparum infection was predominant (n = 217) followed by P. vivax infection (n = 76). 37% of all cases were Africans visiting relatives and friends (VRF). A total of 12 patients had one or more re-lapses of their P. vivax infection. In all, 53 (17%) cases were defined as severe malaria. 36% (n = 112) reported using some type of chemoprophylaxis. 14% (n = 26) of patients traveling to Africa in 1999-2012 reported taking chemoprophylaxis as recommended in the current guidelines. Complicated malaria was significantly associated with failure to take any chemoprophylaxis (p = 0.0317, χ(2)-test). CONCLUSION: Imported malaria is decreasing at the DID. The patients who carry the highest risk of imported malaria are ethnic Africans who travel as VRF without using chemoprophylaxis. Recrudescence from P. vivax malaria is a substantial risk. Complicated malaria is associated with failure to take any chemoprophylaxis. It is important that travelers receive expedient advice on the use of efficient chemoprophylaxis to bring down the number of imported malaria cases. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.


Subject(s)
Antimalarials/therapeutic use , Malaria, Falciparum/epidemiology , Malaria, Falciparum/therapy , Malaria, Vivax/epidemiology , Malaria, Vivax/therapy , Adolescent , Adult , Africa , Aged , Asia , Atovaquone/therapeutic use , Chemoprevention , Child , Child, Preschool , Chloroquine/therapeutic use , Delayed Diagnosis , Denmark/epidemiology , Drug Combinations , Female , Humans , Incidence , Infant , Malaria, Falciparum/ethnology , Malaria, Vivax/ethnology , Male , Mefloquine/therapeutic use , Middle Aged , Primaquine/therapeutic use , Proguanil/therapeutic use , Recurrence , Risk Factors , Severity of Illness Index , Travel , Young Adult
18.
Article in English | WPRIM (Western Pacific) | ID: wpr-48133

ABSTRACT

BACKGROUND: This study tests the hypothesis that of bipolar radiofrequency thermocoagulation of the thoracic facet joint capsule may provide a safe and effect method of pain control from thoracic facet origin. METHODS: Among patients suffering from localized mid back pain, nine patients with thoracic facet disease confirmed by magnetic resonance image and diagnostic thoracic facet block were enrolled. Bipolar radiofrequency ablation in the inferior aspect of the thoracic facet joint was done. Visual Analog Scale (VAS) was measured pre-intervention and 1 month post-intervention. Any complications and changes in amount of pain medication were recorded. RESULTS: Significant 47.6% reduction in VAS was noted at 1 month. There were no serious complications. CONCLUSIONS: Intra-articular bipolarradiofrequency thermocoagulation of the thoracic facet joint may be a technically easier and valid method of treating mid back pain of thoracic facet origin.


Subject(s)
Humans , Back Pain , Catheter Ablation , Electrocoagulation , Methods , Visual Analog Scale , Zygapophyseal Joint
19.
Travel Med Infect Dis ; 11(5): 324-8, 2013.
Article in English | MEDLINE | ID: mdl-23849287

ABSTRACT

We report the first human case of Babesia microti infection imported to Denmark from the United States by a 64 year old female traveller with fever of unknown origin. The case raises the possibility that Babesia-infections may be under-diagnosed, illustrates the importance of a thorough travel history and discusses important diagnostic pitfalls.


Subject(s)
Babesia microti/isolation & purification , Babesiosis/diagnosis , Babesia microti/classification , Babesia microti/genetics , Babesiosis/parasitology , Denmark , Female , Humans , Middle Aged , Travel , United States
20.
Tissue Eng Part A ; 19(21-22): 2382-9, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23691928

ABSTRACT

Following traumatic brain injury (TBI), resultant voids are unable to support injections of suspension treatments, leading to ineffective healing. Moreover, without a structure to support the large defect, the defect site suffers from mechanical instability, which may impair the healing process. Therefore, having a delivery vehicle that can temporarily fill and provide mechanical support to the defect site may alleviate the healing process. In this work, we reported for the first time, the inflammatory response of brain tissue with polycaprolactone (PCL) and PCL-tricalcium phosphate (TCP) scaffolds designed and fabricated for cranial reconstruction. After cranial defects were created in Sprague-Dawley rats, PCL and PCL-TCP scaffolds were implanted for a period of 1 week and 1 month. Following histology and immunofluorescence staining with the ionized calcium binding adaptor molecule-1 (IBA-1), glial fibrillary acidic protein (GFAP), nestin, and neuronal nuclei (NeuN), results indicated that IBA-1-positive activated microglia were observed across all groups, and declined significantly by 1 month (p<0.05). Interestingly, IBA-1-positive microglia were significantly fewer in the PCL-TCP group (p<0.05), suggesting a relatively milder inflammatory response. A decrease in the number of GFAP-positive cells among all groups over time (>29%) was also observed. Initially, astrocyte hypertrophy was observed proximal to the TBI site (55% in PCL and PCL-TCP groups, 75% in control groups), but it subsided by 1 month. Proximal to the TBI site, nestin immunoreactivity was intense during week 1, and which reduced by 1 month across all groups. NeuN-positive neurons were shrunken proximal to the TBI site (<0.9 mm), 32% smaller in the PCL-TCP group and 27% smaller in the PCL group. Based on above data indicating the comparatively milder, initial inflammatory response of brain tissue to PCL-TCP scaffolds, it is suggested that PCL-TCP scaffolds have notable clinical advantages as compared to PCL scaffolds.


Subject(s)
Brain Injuries/therapy , Polyesters/chemistry , Tissue Scaffolds/chemistry , Animals , Biocompatible Materials/chemistry , Calcium-Binding Proteins/metabolism , Female , Microfilament Proteins/metabolism , Rats , Rats, Sprague-Dawley , Skull/cytology , Skull/metabolism
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