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1.
BMC Psychiatry ; 23(1): 423, 2023 06 13.
Article in English | MEDLINE | ID: mdl-37312064

ABSTRACT

BACKGROUND: Blast-explosion may cause traumatic brain injury (TBI), leading to post-concussion syndrome (PCS). In studies on military personnel, PCS symptoms are highly similar to those occurring in post-traumatic stress disorder (PTSD), questioning the overlap between these syndromes. In the current study we assessed PCS and PTSD in civilians following exposure to rocket attacks. We hypothesized that PCS symptomatology and brain connectivity will be associated with the objective physical exposure, while PTSD symptomatology will be associated with the subjective mental experience. METHODS: Two hundred eighty nine residents of explosion sites have participated in the current study. Participants completed self-report of PCS and PTSD. The association between objective and subjective factors of blast and clinical outcomes was assessed using multivariate analysis. White-matter (WM) alterations and cognitive abilities were assessed in a sub-group of participants (n = 46) and non-exposed controls (n = 16). Non-parametric analysis was used to compare connectivity and cognition between the groups. RESULTS: Blast-exposed individuals reported higher PTSD and PCS symptomatology. Among exposed individuals, those who were directly exposed to blast, reported higher levels of subjective feeling of danger and presented WM hypoconnectivity. Cognitive abilities did not differ between groups. Several risk factors for the development of PCS and PTSD were identified. CONCLUSIONS: Civilians exposed to blast present higher PCS/PTSD symptomatology as well as WM hypoconnectivity. Although symptoms are sub-clinical, they might lead to the future development of a full-blown syndrome and should be considered carefully. The similarities between PCS and PTSD suggest that despite the different etiology, namely, the physical trauma in PCS and the emotional trauma in PTSD, these are not distinct syndromes, but rather represent a combined biopsychological disorder with a wide spectrum of behavioral, emotional, cognitive and neurological symptoms.


Subject(s)
Brain Injuries, Traumatic , Neurology , Stress Disorders, Post-Traumatic , Humans , Explosions , Syndrome , Stress Disorders, Post-Traumatic/etiology , Brain Injuries, Traumatic/complications
2.
Breast Cancer Res Treat ; 190(2): 287-293, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34515905

ABSTRACT

PURPOSE: Older cancer survivors required medical care during the COVID-19 pandemic, but there are limited data on medical care in this age group. METHODS: We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors aged 60-98 from five US regions (n = 321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included interruptions in seeing or speaking to doctors, receiving medical treatment or supportive therapies, or filling prescriptions since the pandemic began. Logistic regression models evaluated associations between care disruptions and education, medical, psychosocial, and COVID-19-related factors. Multivariate models included age, county COVID-19 death rates, comorbidity, and post-diagnosis time. RESULTS: There was a high response rate (n = 262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were higher with each year of education (OR 1.22, 95% CI 1.08-1.37, p = < 0.001) and increased depression by CES-D score (OR 1.04, CI 1.003-1.08, p = 0.033) while increased tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99, p = 0.012). There was a trend between disruptions and comorbidities (unadjusted OR 1.13 per comorbidity, 95% CI 0.99-1.29, p = 0.07). Adjusting for covariates, higher education years (OR1.23, 95% CI 1.09-1.39, p = 0.001) and tangible social support (OR 0.98 95% CI 0.97-1.00, p = 0.006) remained significantly associated with having care disruptions. CONCLUSION: Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions. CLINICALTRIALS. GOV IDENTIFIER: NCT03451383.


Subject(s)
Breast Neoplasms , COVID-19 , Cancer Survivors , Aged , Aged, 80 and over , Breast Neoplasms/epidemiology , Breast Neoplasms/therapy , Female , Humans , Middle Aged , Pandemics , SARS-CoV-2
3.
Eur J Neurol ; 27(7): 1257-1263, 2020 07.
Article in English | MEDLINE | ID: mdl-32223078

ABSTRACT

BACKGROUND AND PURPOSE: The aim of this study was to determine whether early and late death are associated with different baseline factors in intracerebral haemorrhage (ICH) survivors. METHODS: This was a secondary analysis of the multicentre prospective observational CROMIS-2 ICH study. Death was defined as 'early' if occurring within 6 months of study entry and 'late' if occurring after this time point. RESULTS: In our cohort (n = 1094), there were 306 deaths (per 100 patient-years: absolute event rate, 11.7; 95% confidence intervals, 10.5-13.1); 156 were 'early' and 150 'late'. In multivariable analyses, early death was independently associated with age [per year increase; hazard ratio (HR), 1.05, P = 0.003], history of hypertension (HR, 1.89, P = 0.038), pre-event modified Rankin scale score (per point increase; HR, 1.41, P < 0.0001), admission National Institutes of Health Stroke Scale score (per point increase; HR, 1.11, P < 0.0001) and haemorrhage volume >60 mL (HR, 4.08, P < 0.0001). Late death showed independent associations with age (per year increase; HR, 1.04, P = 0.003), pre-event modified Rankin scale score (per point increase; HR, 1.42, P = 0.001), prior anticoagulant use (HR, 2.13, P = 0.028) and the presence of intraventricular extension (HR, 1.73, P = 0.033) in multivariable analyses. In further analyses where time was treated as continuous (rather than dichotomized), the HR of previous cerebral ischaemic events increased with time, whereas HRs for Glasgow Coma Scale score, National Institutes of Health Stroke Scale score and ICH volume decreased over time. CONCLUSIONS: We provide new evidence that not all baseline factors associated with early mortality after ICH are associated with mortality after 6 months and that the effects of baseline variables change over time. Our findings could help design better prognostic scores for later death after ICH.


Subject(s)
Cerebral Hemorrhage , Survivors , Aged , Aged, 80 and over , Cohort Studies , Female , Glasgow Coma Scale , Humans , Male , Middle Aged , Prognosis , Risk Factors
4.
Mol Psychiatry ; 23(5): 1145-1156, 2018 05.
Article in English | MEDLINE | ID: mdl-28630453

ABSTRACT

In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions. Evidence for mediation of the relation between combat trauma and PTSD symptoms by longitudinal changes in DNA methylation was observed at several positions and regions. Bioinformatic analyses of the reported associations identified significant enrichment in several pathways relevant for symptoms of PTSD. Targeted analyses of the significant findings from the discovery sample in an independent prospective cohort of male US marines (n=98) replicated the observed relation between decreases in DNA methylation levels and PTSD symptoms at genomic regions in ZFP57, RNF39 and HIST1H2APS2. Together, our study pinpoints three novel genomic regions where longitudinal decreases in DNA methylation across the period of exposure to combat trauma marks susceptibility for PTSD.


Subject(s)
Epigenesis, Genetic , Stress Disorders, Post-Traumatic/genetics , Adult , Cohort Studies , DNA Methylation , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Genetic Predisposition to Disease , Genetic Testing/methods , Humans , Immediate-Early Proteins/genetics , Immediate-Early Proteins/metabolism , Longitudinal Studies , Male , Military Personnel/psychology , Prospective Studies , Repressor Proteins , Stress Disorders, Post-Traumatic/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
5.
BJOG ; 126(5): 656-661, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30222236

ABSTRACT

OBJECTIVE: To evaluate the subsequent rate of thrombosis among women with obstetric antiphospholipid syndrome (Ob-APS) in a multicentre database of antiphospholipid antibody (aPL)-positive patients, and the clinical utility of the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients. DESIGN: Retrospective study. SETTING: The Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository. POPULATION: Women with Ob-APS. METHODS: Comparison of clinical and laboratory characteristics and measurement of aGAPSS in women with Ob-APS, with or without thrombosis, after initial pregnancy morbidity (PM). MAIN OUTCOME MEASURES: Risk factors for thrombosis and aGAPSS. RESULTS: Of 550 patients, 126 had Ob-APS; 74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age at diagnosis of Ob-APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had a higher aGAPSS compared with women with Ob-APS alone [median 11.5 (4-16) versus 9 (4-13); P = 0.0089]. CONCLUSION: Based on a retrospective analysis of our multicentre aPL database, 63% of women with Ob-APS developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high-risk aPL profile increased the risk. Women with subsequent thrombosis after Ob-APS had a higher aGAPSS at entry to the registry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL-positive women. TWEETABLE ABSTRACT: More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.


Subject(s)
Antiphospholipid Syndrome/complications , Pregnancy Complications, Cardiovascular/immunology , Thrombosis/immunology , Adult , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/blood , Clinical Trials as Topic , Databases, Factual , Female , Humans , Pregnancy , Registries , Retrospective Studies , Risk Factors
6.
Epidemiol Infect ; 146(15): 1968-1976, 2018 11.
Article in English | MEDLINE | ID: mdl-29898795

ABSTRACT

Pathogen burden is a construct developed to assess the cumulative effects of multiple, persistent pathogens on morbidity and mortality. Despite the likely biological wear and tear on multiple body systems caused by persistent infections, few studies have examined the impact of total pathogen burden on such outcomes and specifically on preclinical markers of dysfunction. Using data from two waves of the National Health and Nutrition Examination Survey, we compared three alternative methods for measuring pathogen burden, composed of mainly persistent viral infections, using a cumulative deficits index (CDI) as an outcome: single pathogen associations, a pathogen burden summary score and latent class analyses. We found significant heterogeneity in the distribution of the CDI by age, sex, race/ethnicity and education. There was an association between pathogen burden and the CDI by all three metrics. The latent class classification of pathogen burden showed particularly strong associations with the CDI; these associations remained after controlling for age, sex, body mass index, smoking, race/ethnicity and education. Our results suggest that pathogen burden may influence early clinical indicators of poor health as measured by the CDI. Our results are salient since we were able to detect these associations in a relatively young population. These findings suggest that reducing pathogen burden and the specific pathogens that drive the CDI may provide a target for preventing the early development of age-related physiological changes.


Subject(s)
Bacterial Infections/complications , Bacterial Infections/epidemiology , Chronic Disease/epidemiology , Chronic Disease/mortality , Virus Diseases/complications , Virus Diseases/epidemiology , Adult , Bacteria/isolation & purification , Bacterial Infections/microbiology , Bacterial Infections/mortality , Female , Humans , Male , Middle Aged , Prevalence , United States/epidemiology , Virus Diseases/mortality , Virus Diseases/virology , Viruses/isolation & purification , Young Adult
7.
J R Army Med Corps ; 164(1): 46-51, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28883024

ABSTRACT

BACKGROUND: Military aviators are potentially at risk for developing noise-induced hearing loss. Whether ambient aircraft noise exposure causes hearing deficit beyond the changes attributed to natural ageing is debated. The aim of this research was to assess changes in hearing thresholds of Israeli Air Force (IAF) pilots over 20 years of military service and identify potential risk factors for hearing loss. METHODS: A retrospective cohort analysis was conducted of pure-tone air conduction audiograms of pilots, from their recruitment at 18 years of age until the last documented medical check-up. Mean hearing thresholds were analysed in relation to age, total flight hours and aircraft platform. Comparisons were made to the hearing thresholds of air traffic controllers (ATCs) who were not exposed to the noise generated by aircraft while on duty. RESULTS: One hundred and sixty-three pilots were included, with flying platforms ranging from fighter jets (n=54), combat helicopters (n=27), transport helicopters (n=52) and transport aircraft (n=30). These were compared with the results from 17 ATCs. A marked notch in the frequency range of 4-6 kHz was demonstrated in the mean audiograms of all platforms pilots, progressing with ageing. Hearing threshold shifts in relation to measurements at recruitment were first noted at the age of 30 years, particularly at 4 kHz (mean shift of 2.97 dB, p=0.001). There was no statistical association between flying variables and hearing thresholds adjusted for age by logistic regression analysis. CONCLUSIONS: The audiometric profile of IAF pilots has a pattern compatible with noise exposure, as reflected by characteristic noise notch. However, no flight variable was associated with deterioration of hearing thresholds, and no significant difference from non-flying controls (ATCs) was seen.


Subject(s)
Auditory Threshold , Hearing Loss, Noise-Induced/diagnosis , Military Personnel , Pilots , Adult , Aging , Audiometry , Cohort Studies , Humans , Israel , Male , Middle Aged , Retrospective Studies , Risk Factors
8.
Br J Hist Sci ; 51(4): 687-701, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30566067

ABSTRACT

In his biography of Isaac Newton, which forms the most recent production in this flourishing genre, Niccolò Guicciardini states as his first point of departure that Newton's work arose not from 'attempts to answer questions that came to him spontaneously, but [from addressing] those posed by his contemporaries' (p. 20). Right he is to communicate to the larger audience for which he is writing this principal fruit of by now almost a century of professional history-of-science writing - a deep-seated awareness that every scientific view or finding, even if looking timeless in retrospect, has emerged from some given historical context that shows us where the scientist in question started, and that helps explain how, and in what direction, they managed to venture beyond the original context. Indeed, the same truth (or rather truism) applies to every genuine - that is, in some way innovative and also worthwhile - contribution to scholarship. And so it is, therefore, with the three books here under review, which I intend to examine with the following leading question in mind: what in each of them is new and what, in what turns out to be new indeed, has been worth learning?

9.
Breast Cancer Res Treat ; 161(2): 363-373, 2017 01.
Article in English | MEDLINE | ID: mdl-27866278

ABSTRACT

PURPOSE: We examined acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance for Clinical Trials in Oncology trials with >90 months of follow-up in order to better characterize the risk for AML/MDS in older patients receiving anthracyclines. METHODS: We used multivariable Cox regression to examine factors associated with AML/MDS, adjusting for age (≥65 vs. <65 years; separately for ≥70 vs. <70 years), race/ethnicity, insurance, performance status, and anthracycline receipt. We also examined the effect of cyclophosphamide, the interaction of anthracycline and age, and outcomes for those developing AML/MDS. RESULTS: On Cancer and Leukemia Group B (CALGB) 40101, 49907, 9344, and 9741, 7290 received anthracyclines; 15% were in the age ≥65 and 7% were ≥70. Overall, 47 patients developed AML/MDS (30 AML [0.3%], 17 MDS [0.2%]); 83% of events occurred within 5 years of study registration. Among those age ≥65 and ≥70, 0.8 and 1.0% developed AML/MDS (vs. 0.4% for age <65), respectively. In adjusted analyses, older age and anthracycline receipt were significantly associated with AML/MDS (adjusted hazard ratio [HR] for age ≥65 [vs. <65] = 3.13, 95% confidence interval [CI] 1.18-8.33; HR for anthracycline receipt [vs. no anthracycline] = 5.16, 95% CI 1.47-18.19). There was no interaction between age and anthracycline use. Deaths occurred in 70% of those developing AML/MDS. CONCLUSIONS: We observed an increased risk for AML/MDS for older patients and those receiving anthracyclines, though these events were rare. Our results help inform discussions surrounding anticipated toxicities of adjuvant chemotherapy in older patients.


Subject(s)
Breast Neoplasms/complications , Breast Neoplasms/epidemiology , Leukemia, Myeloid, Acute/epidemiology , Leukemia, Myeloid, Acute/etiology , Myelodysplastic Syndromes/epidemiology , Myelodysplastic Syndromes/etiology , Neoplasms, Second Primary , Age Factors , Aged , Aged, 80 and over , Anthracyclines/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/drug therapy , Chemotherapy, Adjuvant/adverse effects , Cohort Studies , Female , Follow-Up Studies , Humans , Middle Aged , Risk , Time Factors
10.
HIV Med ; 17(10): 740-748, 2016 11.
Article in English | MEDLINE | ID: mdl-27028463

ABSTRACT

OBJECTIVES: Falls and fall-related injuries are a major public health concern. HIV-infected adults have been shown to have a high incidence of falls. Identification of major risk factors for falls that are unique to HIV infection or similar to those in the general population will inform development of future interventions for fall prevention. METHODS: HIV-infected and uninfected men and women participating in the Hearing and Balance Substudy of the Multicenter AIDS Cohort Study and Women's Interagency HIV Study were asked about balance symptoms and falls during the prior 12 months. Falls were categorized as 0, 1, or ≥ 2; proportional odds logistic regression models were used to investigate relationships between falls and demographic and clinical variables and multivariable models were created. RESULTS: Twenty-four per cent of 303 HIV-infected participants reported at least one fall compared with 18% of 233 HIV-uninfected participants (P = 0.27). HIV-infected participants were demographically different from HIV-uninfected participants, and were more likely to report clinical imbalance symptoms (P ≤ 0.035). In univariate analyses, more falls were associated with hepatitis C, female sex, obesity, smoking, and clinical imbalance symptoms, but not age, HIV serostatus or other comorbidities. In multivariable analyses, female sex and imbalance symptoms were independently associated with more falls. Among HIV-infected participants, smoking, a higher number of medications, and imbalance symptoms remained independent fall predictors, while current protease inhibitor use was protective. CONCLUSIONS: Similar rates of falls among HIV-infected and uninfected participants were largely explained by a high prevalence of imbalance symptoms. Routine assessment of falls and dizziness/imbalance symptoms should be considered, with interventions targeted at reducing symptomatology.


Subject(s)
Accidental Falls , HIV Infections/complications , Aged , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Risk Assessment
11.
Clin Genet ; 88(5): 494-8, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25410531

ABSTRACT

Primary hyperoxaluria type II is a recessive genetic disorder caused by mutations in the GRHPR gene. Although several dozen mutations have been described, all affect coding or transcript splicing. A man suspected of having primary hyperoxaluria type II was heterozygous for a novel single-nucleotide deletion (c.694delC) in GRHPR affecting Gln(232) , which introduced a pre-mature termination (p.Gln232Argfs*3). Two 5'untranslated region (UTR) variants of unknown significance were also noted. We show that these two variants occur in cis, on the opposite allele, and introduce - immediately upstream of the canonical translation initiation site - a novel out-of-frame translational start site. In vitro studies using the GRHPR 5'UTR fused to a luciferase reporter show that the variant start site pre-empted initiation at the canonical translational start site, and this was corroborated within the broader context of 1.3 kb of the GRHPR proximal promoter. This latter mechanism may be underappreciated in general; reports of clinically significant functional variation of this type are extremely rare.


Subject(s)
5' Untranslated Regions , Alcohol Oxidoreductases/genetics , Frameshift Mutation , Hyperoxaluria, Primary/genetics , Peptide Chain Initiation, Translational , Adult , Alcohol Oxidoreductases/metabolism , Codon, Terminator , Heterozygote , Humans , Hyperoxaluria, Primary/metabolism , Male , Middle Aged , Sequence Deletion
12.
Mol Psychiatry ; 19(2): 243-52, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24042478

ABSTRACT

The Abelson helper integration site 1 (AHI1) gene has a pivotal role in brain development. Studies by our group and others have demonstrated association of AHI1 with schizophrenia and autism. To elucidate the mechanism whereby alteration in AHI1 expression may be implicated in the pathogenesis of neuropsychiatric disorders, we studied Ahi1 heterozygous knockout (Ahi1(+/-)) mice. Although their performance was not different from wild-type mice on tests that model classical schizophrenia-related endophenotypes, Ahi1(+/-) mice displayed an anxiolytic-like phenotype across different converging modalities. Using behavioral paradigms that involve exposure to environmental and social stress, significantly decreased anxiety was evident in the open field, elevated plus maze and dark-light box, as well as during social interaction in pairs. Assessment of core temperature and corticosterone secretion revealed a significantly blunted response of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis in Ahi1(+/-) mice exposed to environmental and visceral stress. However, response to centrally acting anxiogenic compounds was intact. On resting-state functional MRI, connectivity of the amygdala with other brain regions involved in processing of anxiogenic stimuli and inhibitory avoidance learning, such as the lateral entorhinal cortex, ventral hippocampus and ventral tegmental area, was significantly reduced in the mutant mice. Taken together, our data link Ahi1 under-expression with a defect in the process of threat detection. Alternatively, the results could be interpreted as representing an anxiety-related endophenotype, possibly granting the Ahi1(+/-) mouse relative resilience to various types of stress. The current knockout model highlights the contribution of translational approaches to understanding the genetic basis of emotional regulation and its associated neurocircuitry, with possible relevance to neuropsychiatric disorders.


Subject(s)
Anxiety/physiopathology , Neurons/physiology , Proto-Oncogene Proteins/metabolism , Stress, Psychological/physiopathology , Adaptor Proteins, Vesicular Transport , Animals , Anxiety/chemically induced , Anxiety/etiology , Body Temperature , Brain/growth & development , Brain/pathology , Brain/physiopathology , Corticosterone/metabolism , Environment , Hypothalamo-Hypophyseal System/physiopathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Motor Activity/physiology , Pituitary-Adrenal System/physiopathology , Proto-Oncogene Proteins/genetics , Rest/physiology , Schizophrenia/physiopathology , Sensory Gating/physiology , Social Behavior , Stress, Psychological/complications
13.
Haemophilia ; 21(6): e456-64, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26179213

ABSTRACT

INTRODUCTION: Distress may affect a patient's ability to cope with and manage disease. AIM: To report distress prevalence in adult patients with bleeding disorders and determine whether specific clinical and health characteristics, including disease severity and employment status, are associated with distress. METHODS: Patients who visited a Haemophilia Treatment Centre (HTC) between January 1st, 2012 through February 28th, 2014 and who completed a distress screen, pain screen and questionnaire were evaluated cross sectionally. Distress was measured by the National Comprehensive Cancer Network Distress Management Tool, which allowed patients to rate recent distress on a 0-10 point scale. A rating of five or more was categorized as high distress. Pain was measured by the Brief Pain Inventory Short Form, which asked patients to rate pain types on 0-10 point scales. Patients reported employment and other demographic and behavioural information on the questionnaire. Primary diagnosis, age, HIV and HCV status were abstracted from medical records. Adjusted logistic regression was used to identify distress associations. RESULTS: High distress prevalence among 152 patients with bleeding disorders was 31.6%. Unemployment, disability, greater depressive symptoms and higher pain were associated with high distress in multivariable models. Bleeding disorder diagnosis, race/ethnicity, HIV/HCV status and on-demand treatment regimen were not associated with high distress. CONCLUSION: Distress among patients with congenital bleeding disorders followed at a comprehensive HTC was high and similar to that reported among patients with cancer. Future research should determine whether distress impacts clinical outcomes in patients with bleeding disorders as demonstrated in other chronic disorders.


Subject(s)
Depression/etiology , Hemorrhage/psychology , Adult , Cohort Studies , Cross-Sectional Studies , Depression/epidemiology , Female , Humans , Male , Quality of Life
14.
Lupus ; 24(10): 1087-94, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25940537

ABSTRACT

INTRODUCTION: The current mainstay of the treatment of thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation with vitamin K antagonists (VKAs) such as warfarin. Non-VKA oral anticoagulants (NOACs), which include rivaroxaban, have been shown to be effective and safe compared with warfarin for the treatment of venous thromboembolism (VTE) in major phase III prospective, randomized controlled trials (RCTs), but the results may not be directly generalizable to patients with APS. AIMS: The primary aim is to demonstrate, in patients with APS and previous VTE, with or without systemic lupus erythematosus (SLE), that the intensity of anticoagulation achieved with rivaroxaban is not inferior to that of warfarin. Secondary aims are to compare rates of recurrent thrombosis, bleeding and the quality of life in patients on rivaroxaban with those on warfarin. METHODS: Rivaroxaban in antiphospholipid syndrome (RAPS) is a phase II/III prospective non-inferiority RCT in which eligible patients with APS, with or without SLE, who are on warfarin, target international normalized ratio (INR) 2.5 for previous VTE, will be randomized either to continue warfarin (standard of care) or to switch to rivaroxaban. Intensity of anticoagulation will be assessed using thrombin generation (TG) testing, with the primary outcome the percentage change in endogenous thrombin potential (ETP) from randomization to day 42. Other TG parameters, markers of in vivo coagulation activation, prothrombin fragment 1.2, thrombin antithrombin complex and D-dimer, will also be assessed. DISCUSSION: If RAPS demonstrates i) that the anticoagulant effect of rivaroxaban is not inferior to that of warfarin and ii) the absence of any adverse effects that cause concern with regard to the use of rivaroxaban, this would provide sufficient supporting evidence to make rivaroxaban a standard of care for the treatment of APS patients with previous VTE, requiring a target INR of 2.5.


Subject(s)
Anticoagulants/therapeutic use , Antiphospholipid Syndrome/drug therapy , Factor Xa Inhibitors/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Rivaroxaban/therapeutic use , Warfarin/therapeutic use , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/complications , Blood Coagulation Tests/methods , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , International Normalized Ratio , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/complications , Male , Prospective Studies , Quality of Life , Recurrence , Thrombin/metabolism , Venous Thromboembolism/drug therapy , Venous Thromboembolism/prevention & control
15.
J Clin Pediatr Dent ; 39(4): 331-5, 2015.
Article in English | MEDLINE | ID: mdl-26161604

ABSTRACT

UNLABELLED: There are currently inadequate data regarding the prevalence of dental caries and its associated variables, among Palestinian children. AIM: To determine the current prevalence of dental caries and related variables, among Palestinian children in East Jerusalem. STUDY DESIGN: A stratified sample of 286 East Jerusalem Palestinian children was selected, employing randomly chosen sixth grade clusters from three pre-selected socio-economic school groups. Dental caries was recorded according to WHO recommendations. Salivary flow, pH, buffer capacity and microbial parameters, were recorded according to previously employed methodologies. RESULTS: The mean level of caries experience, by DMFT, was 1.98 ± 2.05. This level was higher than those found among Israeli children, but lower than several other Middle Eastern countries. In uni-variate analysis, significant associations were revealed between caries and school categories, which indicated lower, middle and higher socio-economic position(SEP), mothers' employment, home densities, dental visits, tooth brushing, Streptococci mutans (SM), Lactobacilli (LB), and saliva pH. CONCLUSION: According to a linear logistic regression model, children learning in lower SEP schools, with higher SM levels and more acidic saliva, had a higher chance of experiencing dental caries. These findings should be considered in the planning of services and dental health care programs for Palestinian children.


Subject(s)
Dental Caries/epidemiology , Health Behavior , Social Class , Adolescent , Buffers , Child , DMF Index , Dental Care/statistics & numerical data , Dental Devices, Home Care/statistics & numerical data , Educational Status , Employment/statistics & numerical data , Family Characteristics , Female , Humans , Hydrogen-Ion Concentration , Lactobacillus/isolation & purification , Male , Middle East/epidemiology , Mouthwashes/therapeutic use , Oral Health/statistics & numerical data , Prevalence , Saliva/metabolism , Saliva/microbiology , Saliva/physiology , Secretory Rate/physiology , Streptococcus mutans/isolation & purification , Toothbrushing/statistics & numerical data
16.
Lupus ; 23(12): 1324-6, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25228739

ABSTRACT

Activation of the complement cascade is an important mechanism for antiphospholipid antibody-mediated thrombosis. We examined the effects of rEV576 (coversin), a recombinant protein inhibitor of complement factor 5 activation, on antiphospholipid antibody-mediated tissue factor up-regulation and thrombosis. Groups of C57BL/6J mice (n=5) received either IgG from a patient with antiphospholipid syndrome (APS) or control IgG from normal human serum (NHS). Each of these groups of mice had IgG administration preceded by either rEV576, or phosphate buffer control. For each of the four treatment groups, the size of induced thrombus, tissue factor activity in carotid homogenates, anticardiolipin and anti-ß2glycoprotein I (anti-ß2GPI) levels were measured 72 h after the first injection. Mice treated with IgG-APS had significantly higher titers of anticardiolipin antibodies and anti-ß2GPI at thrombus induction compared with those treated with IgG-NHS. The IgG-APS/phosphate buffer treatment induced significantly larger thrombi and tissue factor activity compared with other groups. Mice treated with IgG-APS/rEV576 had significantly smaller thrombi and reduced tissue factor activity than those treated with IgG-APS/phosphate buffer. The data confirm involvement of complement activation in antiphospholipid antibody-mediated thrombogenesis and suggest that complement inhibition might ameliorate this effect.


Subject(s)
Antibodies, Antiphospholipid/immunology , Complement C5/antagonists & inhibitors , Thrombosis/prevention & control , Animals , Mice , Mice, Inbred C57BL , Recombinant Proteins/pharmacology , Thromboplastin/analysis , Thrombosis/etiology , beta 2-Glycoprotein I/immunology
17.
Transpl Infect Dis ; 16(5): 775-82, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25092500

ABSTRACT

INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections have emerged as a significant challenge in solid organ transplantation. CRKP infections in other patient populations have been associated with higher mortality, when compared to infections caused by carbapenem-sensitive K. pneumoniae (CSKP). AIMS: The aim of this study was to evaluate possible risk factors, clinical characteristics, and outcomes of CRKP infections compared with CSKP infections in kidney transplant recipients (KTR). METHODS: We retrospectively investigated 13 CRKP infections and 39 CSKP infections in KTR (2006-2010). RESULTS: CRKP was not significantly associated with age, gender, or comorbidities. CRKP infections were significantly associated with recent exposure to broad-spectrum antibiotics and were more likely to have been managed on an inpatient basis and to have required source control. CRKP was significantly associated with earlier mortality. Six of 13 (46%) patients with CRKP infection, and none of the patients with CSKP infection, died within 6.5 months of infection onset. Although cases and controls did not differ significantly with respect to diabetes, all patients (100%, n = 9) who died during the study had diabetes, while 58% of the 43 survivors had diabetes (P = 0.02). CONCLUSION: In conclusion, CRKP compared with CSKP is associated with greater risk of mortality. Investigations on ways to better prevent CRKP are urgently needed.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Carbapenems/therapeutic use , Kidney Transplantation/adverse effects , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/drug effects , Adult , Aged , Case-Control Studies , Diabetes Mellitus/epidemiology , Drug Resistance, Bacterial , Female , Hospitalization , Humans , Klebsiella Infections/microbiology , Klebsiella Infections/mortality , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Rate
18.
Phys Chem Chem Phys ; 16(29): 15422-9, 2014 Aug 07.
Article in English | MEDLINE | ID: mdl-24947417

ABSTRACT

Pt°-NPs, prepared by the reduction of Pt(IV) salts with borohydride, do not catalyse the reduction of water in the presence of the strongly-reducing ˙C(CH3)2OH radicals. However, supporting the same metal nanoparticles (M°-NPs) with SiO2 alters the catalytic properties enabling the reaction. This effect depends both on the nature of M° and concentration of the composite nanoparticles. At low nanocomposite concentration: for M = Au nearly no effect is observed; for M = Ag the support decreases the catalytic reduction of water and for M = Pt the support initiates the catalytic process. At high nanocomposite concentration: for M = Au the reactivity is considerably lower and for M = Ag or Pt no catalysis is observed. Furthermore, for M = Ag or Pt H2 reduces the ˙C(CH3)2OH radicals.


Subject(s)
Gold/chemistry , Metal Nanoparticles/chemistry , Nanocomposites/chemistry , Platinum/chemistry , Silicon Dioxide/chemistry , Silver/chemistry , Water/chemistry , Catalysis , Molecular Conformation
19.
Community Dent Health ; 31(3): 163-6, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25300151

ABSTRACT

OBJECTIVE: To provide prevalence data for dental caries in Georgia. METHODS: This World Health Organization pathfinder survey was conducted among 1,351 (6, 12 and 15 year-old) Georgian children, representing the main ethnic groups in urban and rural locations. Caries was analysed at univariate and multivariate levels, according to age, gender, urban/rural locality and ethnic group. RESULTS: Caries experience levels among 6-year-olds were dmft = 4.57, sd 3.42 (14.8% caries-free); DMFT = 2.04 (sd 2.02) among 12-year-olds (31.1% caries-free); and DMFT = 3.51 (sd 3.14) for the 15-year-olds (17.7% caries-free). Urban children at ages 6 and 12 years were more likely to be caries-free and have both lower levels of caries-experience and higher levels of filled or restored teeth. In multivariate regression analyses, most age groups showed a significant contribution from residence location. No differences were found by age and no consistent differences were detected by ethnic group. CONCLUSION: These data should provide the baseline for formulating and conducting public oral health efforts in Georgia, with emphases on rural residence locations.


Subject(s)
Dental Caries/epidemiology , Ethnicity/statistics & numerical data , Residence Characteristics/statistics & numerical data , Adolescent , Age Factors , Armenia/ethnology , Azerbaijan/ethnology , Child , Cohort Studies , DMF Index , Dental Restoration, Permanent/statistics & numerical data , Female , Georgia (Republic)/epidemiology , Georgia (Republic)/ethnology , Humans , Male , Prevalence , Rural Health/statistics & numerical data , Sex Factors , Tooth Extraction/statistics & numerical data , Urban Health/statistics & numerical data
20.
Clin Oral Investig ; 18(8): 1985-90, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24420504

ABSTRACT

OBJECTIVES: To investigate erosive tooth wear and related variables among adolescents and adults in Israel, utilizing the new basic erosive wear examination (BEWE) scoring system, in an attempt to contribute to the ongoing review, evaluation, and further development of an international standardized index. MATERIAL AND METHODS: A cross-sectional, descriptive, and analytic survey was conducted among 500 subjects of five age groups. Dental erosion was measured according to the new BEWE scoring system. Independent variables included gender, age, origin, education, employment status, and diet. A backward stepwise linear regression model was applied to identify significantly associated variables. RESULTS: Fifty percent of the survey subjects demonstrated erosive tooth wear; among them, 10 % had distinct erosion of over 50 % of the dental surface. Total BEWE score differences by age groups were statistically significant; as the age increased, the mean total BEWE scores increased (p < 0.001). The association between acidic foods and erosion was evident among the younger population (p = 0.038). In a multiple regression model, age (p < 0.001) and diet (p = 0.044) achieved statistical significance as variables associated with dental erosive wear. CONCLUSIONS: Our study is one of the first to use the BEWE scoring system in an epidemiological survey among adolescents and adults. It was found that the BEWE index is straightforward, easy to conduct, and comfortably accepted by the examinees. CLINICAL RELEVANCE: The present findings, together with further international research, should contribute toward continued evaluation of the BEWE system as an international standard and thereby, toward more optimal understanding, evidence-based treatment, and prevention of dental erosive wear.


Subject(s)
Tooth Erosion/physiopathology , Adolescent , Adult , Humans , Middle Aged
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