ABSTRACT
Background@#and purpose In acute stroke patients, plasma concentrations of direct oral anticoagulants (DOAC) at hospital admission only poorly mirror DOAC exposure or the coagulation status at the time of the event. Here, we evaluated whether DOAC exposure and DOAC plasma concentration at the time of transient ischemic attacks (TIA) and ischemic strokes correlate with their likelihood of occurrence. @*Methods@#Prospectively, consecutive DOAC patients with acute ischemic stroke or TIA were included. Admission DOAC plasma concentrations were measured by ultraperformance liquid chromatography– tandem mass spectrometry. Individual DOAC exposure (area under the curve) and DOAC concentrations at event onset were derived from population pharmacokinetic analyses. @*Results@#DOAC exposure was successfully modeled in 211 patients (ischemic stroke 74.4%, TIA 25.6%). Compared to published values, 63.0% had relatively lower DOAC exposure and they more often received lower DOAC doses than recommended (odds ratio [OR], 2.125; 95% confidence interval [CI], 1.039 to 4.560; P=0.044). These patients more likely suffered ischemic strokes than TIA (OR, 2.411; 95% CI, 1.254 to 4.638; P=0.008) and their strokes were more severe (slope, 3.161; 95% CI, 0.741 to 5.58; P=0.011). Low relative DOAC concentrations at event onset were likewise associated with ischemic strokes (OR, 4.123; 95% CI, 1.834 to 9.268; P=0.001), but not to stroke severity (P=0.272). DOAC exposure had a higher explanatory value for stroke severity than concentrations at event. @*Conclusions@#Low DOAC exposure is strongly associated to ischemic stroke and its severity. By monitoring DOAC plasma concentrations, patients prone to ischemic stroke might be identified.
ABSTRACT
Purpose@#Recombinant rotavirus A vaccines are being developed as an alternative to existing live oral attenuated vaccines. One of the main problems in the production of such vaccines is the genetic diversity of the strains that are in circulation. The goal of this study was to create an antigen panel for modern broad-spectrum recombinant rotavirus A vaccine. @*Materials and Methods@#The antigens of rotavirus were cloned and expressed in Escherichia coli. Antigenic specificity was investigated by Western blot analysis, which was performed using commercial polyclonal antisera to several RVA strains. Phylogenetic analysis was based on the amino acid sequences of the VP8* protein fragment of human RVA isolates representing genotypes P[4], P[6], and P[8]. @*Results@#A universal panel of antigens was established, including consensus and conserved sequences of structural proteins VP8*, VP5*, and VP7, which are the main targets of neutralizing antibodies. For the first time, a consensus approach was used in the design of extended antigens based on VP8* (genotypes P[4], P[6], and P[8]) and VP5* (genotype P[8]) proteins' fragments. In addition, a gene coding the protein (ep-875) containing several copies of conserved short neutralizing epitopes of VP8*, VP7, and VP5* was created. Western blot analysis demonstrated that three synthetic VP8*-based antigens were not recognized by commercial antiserum against rotavirus strains isolated more than 35 years ago, but the specific activity of the VP5* and ep-875 antigens was confirmed. The problems of serological mismatch of vaccine strains and antigens with currently circulating strains are discussed. @*Conclusion@#Five antigens representing sequences of structural proteins belonging to different genotypes can be used in various combinations (from mono- to pentavalent mixtures) for the development of an effective broad-spectrum rotavirus vaccine.
ABSTRACT
Objective@#The consensus is that life expectancy for individuals with Parkinson’s disease (PD) is reduced, but estimations vary. We aimed to provide an overview of 20 years of mortality and risk factor data from the Queensland Parkinson’s Project. @*Methods@#The analysis included 1,334 PD and 1,127 control participants. Preliminary analysis of baseline characteristics (sex, age at onset, family history, smoking status, pesticide exposure, depression and neurosurgery) was conducted, and Kaplan–Meier curves were generated for each potential risk factor. Standardized mortality ratios (SMRs) were calculated comparing this cohort to the general Australian population. Cox proportional hazards regression modeling was used to analyze potential predictors of mortality. @*Results@#In total, 625 (46.8%) PD and 237 (21.0%) control participants were deceased. Mean disease duration until death was 15.3 ± 7.84 years. Average ages at death were 78.0 ± 7.4 years and 80.4 ± 8.4 years for the deceased PD and control participants, respectively. Mortality was significantly increased for PD in general {SMR = 2.75 [95% confidence interval (CI): 2.53–2.96]; p = 0.001}. SMRs were slightly higher for women and those with an age of onset before 60 years. Multivariate analysis showed that deep brain stimulation (DBS) treatment was associated with lower mortality [hazard ratio (HR) = 0.76; 95% CI: 0.59–0.98], while occasional pesticide exposure increased mortality risk (HR = 1.48; 95% CI: 1.17–1.88). Family history of PD, smoking and depression were not independent predictors of mortality. @*Conclusion@#Mortality in PD is increased. Sex, age at onset and occasional pesticide exposure were independent determinants of increased mortality, while DBS treatment was associated with reduced mortality.
ABSTRACT
Background@#Anti-parasitics are frequently used in research animal facilities to treat a multitude of common infections, with pinworms and fur mites being amongst the most common. Ivermectin and selamectin are common oral and topical treatments for these infections, respectively. Although commonly thought to be innocuous to both the research animals and any transgenic elements that the animals may carry, evidence exists that ivermectin is capable of activating the recombinase activity of at least one CreER . The goal of the current study was to determine if there was an effect of either anti-parasitic agent on the activity of CreER proteins in transgenic mice.Case presentation: We analyzed the offspring of transgenic mice exposed to either ivermectin or selamectin during pregnancy and nursing. Through analysis of reporter genes co-expressed with multiple, independently generated transgenic CreER drivers, we report here that ivermectin and selamectin both alter recombinase activity and thus may have unintended consequences on gene inactivation studies in mice. @*Conclusions@#Although the mechanisms by which ivermectin and selamectin affect CreER activity in the offspring of treated dams remain unclear, the implications are important nonetheless. Treatment of pregnant transgenic mice with these anti-parasitics has the potential to alter transgene activity in the offspring. Special considerations should be made when planning treatment of transgenic mice with either of these pharmacologics.
ABSTRACT
Background@#and PurposeResponses to oral appliances (OAs) in obstructive sleep apnea (OSA) vary, and have not been fully evaluated in Korean patients. In this study we aimed to determine the efficacy of OAs for the first-line treatment of Korean patients with moderate or severe OSA. @*Methods@#This multicenter prospective observational study included 45 patients with moderate or severe OSA that had been newly diagnosed between March 2017 and May 2018 and who underwent OA treatment for 1 month. Questionnaires were completed and polysomnography (PSG) was performed before and after OA treatment. The primary outcome measures were improvement in the absolute apnea-hypopnea index (AHI) and the percentage reduction in the AHI. The secondary outcomes were improvements in the questionnaire scores related to sleep-associated symptoms and PSG parameters. @*Results@#The patients were aged 47.4±12.1 years (mean±SD), only two of them were female, and their AHI at baseline was 29.7±10.9/h. After OA treatment the AHI had reduced by 63.9±25.8%, with the reduction was similar between the patients with moderate OSA and those with severe OSA. Overall 31.1% of the patients achieved a normal AHI (<5/h), and 64.4% had an AHI of ≤10/h after the treatment. The body mass index (BMI) was the most reliable factor for predicting the percentage reduction in the AHI. The OAs also improved the sleep architecture and subjective sleep-related symptoms. @*Conclusions@#The OAs were effective in patients with moderate or severe OSA. The OAs reduced the mean AHI to 63.9% of the baseline value, and this reduction was influenced by the BMI.
ABSTRACT
Background@#Anti-parasitics are frequently used in research animal facilities to treat a multitude of common infections, with pinworms and fur mites being amongst the most common. Ivermectin and selamectin are common oral and topical treatments for these infections, respectively. Although commonly thought to be innocuous to both the research animals and any transgenic elements that the animals may carry, evidence exists that ivermectin is capable of activating the recombinase activity of at least one CreER . The goal of the current study was to determine if there was an effect of either anti-parasitic agent on the activity of CreER proteins in transgenic mice.Case presentation: We analyzed the offspring of transgenic mice exposed to either ivermectin or selamectin during pregnancy and nursing. Through analysis of reporter genes co-expressed with multiple, independently generated transgenic CreER drivers, we report here that ivermectin and selamectin both alter recombinase activity and thus may have unintended consequences on gene inactivation studies in mice. @*Conclusions@#Although the mechanisms by which ivermectin and selamectin affect CreER activity in the offspring of treated dams remain unclear, the implications are important nonetheless. Treatment of pregnant transgenic mice with these anti-parasitics has the potential to alter transgene activity in the offspring. Special considerations should be made when planning treatment of transgenic mice with either of these pharmacologics.
ABSTRACT
The burden of atrial fibrillation (AF) is projected to increase substantially over the next decade in parallel with the aging of the population. The increasing age, level of comorbidity, and polypharmacy will complicate the treatment of older adults with AF. For instance, advanced age and chronic kidney disease have been shown to increase the risk of both thromboembolism and bleeding in patients with AF. Frailty, recurrent falls and polypharmacy, while very common among elderly patients with AF, are often overlooked in the clinical decision making despite their significant interaction with oral anticoagulant (OAC) and profound impact on the patient's clinical outcomes. Such factors should be recognized, evaluated and considered in a comprehensive decision-making process. The introduction of non-vitamin K oral anticoagulants has radically changed the management of AF allowing for a more individualized selection of OAC. An understanding of the available data regarding the performance of each of the available OAC in a variety of at risk patient populations is paramount for the safe and effective management of this patient population. The aim of this review is to appraise the current evidence, point out the gaps in knowledge, and provide recommendations regarding stroke prevention in older adults with AF and comorbid conditions.
ABSTRACT
The burden of atrial fibrillation (AF) is projected to increase substantially over the next decade in parallel with the aging of the population. The increasing age, level of comorbidity, and polypharmacy will complicate the treatment of older adults with AF. For instance, advanced age and chronic kidney disease have been shown to increase the risk of both thromboembolism and bleeding in patients with AF. Frailty, recurrent falls and polypharmacy, while very common among elderly patients with AF, are often overlooked in the clinical decision making despite their significant interaction with oral anticoagulant (OAC) and profound impact on the patient's clinical outcomes. Such factors should be recognized, evaluated and considered in a comprehensive decision-making process. The introduction of non-vitamin K oral anticoagulants has radically changed the management of AF allowing for a more individualized selection of OAC. An understanding of the available data regarding the performance of each of the available OAC in a variety of at risk patient populations is paramount for the safe and effective management of this patient population. The aim of this review is to appraise the current evidence, point out the gaps in knowledge, and provide recommendations regarding stroke prevention in older adults with AF and comorbid conditions.
Subject(s)
Adult , Aged , Humans , Accidental Falls , Aging , Anticoagulants , Atrial Fibrillation , Clinical Decision-Making , Comorbidity , Hemorrhage , Polypharmacy , Renal Insufficiency, Chronic , Stroke , Thromboembolism , WarfarinABSTRACT
Synovial osteochondromatosis (SO) can occur idiopathic or secondary to osteoarthritis. SO can be easily diagnosed with plain film radiography and clinical findings. In case of disabling osteoarthritis, total knee arthroplasty and removal of all corpora libra are indicated. We present a 71-year-old woman with significant osteoarthritis and severe SO intra-articular and in the suprapatellar bursa of the right knee. Total knee arthroplasty, extraction of the loose bodies, and partial synovectomy were performed. During a 2.5-year follow-up, the patient regained full function of her affected knee and there was no recurrence of SO. We choose to present this case to show the extensiveness SO can occur in. Our advice is to remove all the loose bodies carefully to prevent damage to the prosthesis. During follow-up, special attention should be paid to prevent recurrence of SO. When recurrence is associated with rapid growth or destruction of joints, malignant reoccurrence must be considered.
Subject(s)
Aged , Female , Humans , Arthroplasty , Chondromatosis, Synovial , Follow-Up Studies , Joints , Knee , Osteoarthritis , Prostheses and Implants , Radiography , RecurrenceABSTRACT
Synovial osteochondromatosis (SO) can occur idiopathic or secondary to osteoarthritis. SO can be easily diagnosed with plain film radiography and clinical findings. In case of disabling osteoarthritis, total knee arthroplasty and removal of all corpora libra are indicated. We present a 71-year-old woman with significant osteoarthritis and severe SO intra-articular and in the suprapatellar bursa of the right knee. Total knee arthroplasty, extraction of the loose bodies, and partial synovectomy were performed. During a 2.5-year follow-up, the patient regained full function of her affected knee and there was no recurrence of SO. We choose to present this case to show the extensiveness SO can occur in. Our advice is to remove all the loose bodies carefully to prevent damage to the prosthesis. During follow-up, special attention should be paid to prevent recurrence of SO. When recurrence is associated with rapid growth or destruction of joints, malignant reoccurrence must be considered.
Subject(s)
Aged , Female , Humans , Arthroplasty , Chondromatosis, Synovial , Follow-Up Studies , Joints , Knee , Osteoarthritis , Prostheses and Implants , Radiography , RecurrenceABSTRACT
Autosomal dominant osteopetrosis (ADO) is a sclerotic bone disorder due to failure of osteoclasts. ADO poses difficulties during arthroplasty because of the increased chance for iatrogenic fractures due to sclerotic bone. ADO is divided into two types based on radiological findings, fracture risk, and osteoclast activity. These differences suggest less brittle bone in patients with ADO I compared to that of patients with ADO II, which suggests a smaller chance of preoperative fractures during cementless arthroplasty in ADO I compared with that in ADO II. A case of cementless total knee arthroplasty in a patient with ADO I is presented. Total hip arthroplasty was performed during follow-up, and known major problems related to ADO II were experienced. Therefore, the differences between ADO I and ADO II may not be clinically relevant for an iatrogenic fracture during arthroplasty in patients with ADO.
Subject(s)
Adult , Female , Humans , Acetabulum/injuries , Arthroplasty, Replacement, Knee/adverse effects , Down Syndrome/complications , Femoral Fractures/etiology , Genes, Dominant , Iatrogenic Disease , Knee Joint/surgery , Osteoarthritis, Knee/complications , Osteopetrosis/complications , Periprosthetic Fractures/etiology , Tibial Fractures/etiologyABSTRACT
OBJECTIVE@#To investigate the safety profile of Annona senegalensis (A. senegalensis).@*METHODS@#Dried powdered root-bark of A. senegalensis was prepared by Sohxlet extraction using methanol-methylene chloride (1:1) solution and concentrated to obtain the methanol-methylene chloride extract (MME). MME was fractionated to obtain the n-hexane (HF), ethylacetate (EF) and methanol (MF) fractions. Acute toxicity (LD(50)) test was performed with MME, HF, EF and MF in mice by oral route. The sub acute toxicity studies were performed in rats after 14 days of MME administration while haematological and biochemical parameters were monitored.@*RESULTS@#Medium lethal (LD(50)) values of 1,296, 3,808, 1,265 and 2,154 mg/kg were obtained for the MME, MF, HF and EF, respectively. The sub-acute toxicity studies indicated a significant (P<0.05) increase in the body weight of both the treated rats and the control. The haematological tests indicated no change in the packed cell volume values but a significant (P<0.05) increase in the total WBC count at 100 and 400 mg/kg doses. The differential analysis showed a decrease in the nutrophils and a non-significant increase in the lymphocyte counts. The liver transaminase enzymes, alanin transaminase and aspartate transaminase showed no significant increase compared to the control. Histopathological examination of the liver sections also indicted no obvious signs of hepatotoxicity except with the 400 mg/kg dose that showed degeneration and necrosis of the hepatocytes.@*CONCLUSIONS@#These results indicated that the root bark extracts of A. Senegalensis are safe at the lower doses tested, and calls for caution in use at higher doses in treatment.
Subject(s)
Animals , Female , Male , Rats , Annona , Toxicity , Blood Cell Count , Dose-Response Relationship, Drug , Hematocrit , Lethal Dose 50 , Liver , Organ Size , Plant Bark , Toxicity , Plant Extracts , Toxicity , Toxicity Tests, Acute , Toxicity Tests, Subacute , Weight GainABSTRACT
<p><b>INTRODUCTION</b>Planning a high-stake clinical examination requires the evaluation of several psychometric and logistical variables. The authors conducted generalisability and decision studies to answer the following research questions in the context of the surgical long case: (1) Does the addition of a third examiner have any added benefit, vis-à-vis reliability, to the examination? (2) Is global marking more reliable than an itemised marking template? (3) What would be the impact on reliability if there was a reduction in the number of examinees that each panel of examiners is required to assess?</p><p><b>METHODS</b>A third examiner and global marking were introduced. Separate generalisability and decision studies were carried out for both the two- and three-examiner models as well as for itemised and global scores.</p><p><b>RESULTS</b>The introduction of a third examiner resulted in a modest gain of reliability by 0.05-0.07. Gain in reliability was higher when each candidate was allowed to undertake a higher number of clinical cases. Both the global and itemised scores provided equivalent reliability (generalisability coefficient 0.74-0.89).</p><p><b>CONCLUSION</b>Our results showed that only a modest improvement in reliability of the surgical long case is achieved through the introduction of an additional examiner. Although the reliability of global scoring and the itemised marking template was comparable, the latter may provide opportunities for individualised feedback to examinees.</p>
Subject(s)
Humans , Clinical Competence , Education, Medical, Undergraduate , Methods , Reference Standards , Educational Measurement , Methods , Medical History Taking , Methods , Observation , Professional-Patient Relations , Psychometrics , Methods , Reproducibility of Results , Schools, Medical , SingaporeABSTRACT
China's first HIV infection was officially reported in 1985 and by the end of 1996, there may have been up to 200,000 people affected nationwide. In 2001, this figure probably exceeded 600,000. By 2003, the predicted number of HIV cases had reached 1.5 million. At least 80,000 individuals now have fullblown AIDS. China may soon have the largest HIV-infected population in the world, possibly 6 million cases by 2005. With infection rates rising at about 30% per year, it is feared this figure might exceed 10 million by 2010. Although the Chinese government was initially slow to accept the problem, in the late 1990s definite changes began occurring. In 2003 Premier Wen Jiabao publicly shook the hand of an AIDS patient and his government promised to introduce a range of free HIV-related services. Large preventive education campaigns are now underway. Unfortunately, there will still be many obstacles in controlling the epidemic and preventing further spread of this disease. Without doubt, China faces a serious predicament in the new millennium, and one which will pose numerous challenges for preventive medicine.
Subject(s)
Antibodies, Viral/isolation & purification , Antibodies, Viral/therapeutic use , Hepatitis B Antibodies/isolation & purification , Hepatitis B Antibodies/therapeutic use , Hepatitis B Surface Antigens/immunology , Hepatitis B/prevention & control , Immunoglobulin G/therapeutic use , HumansABSTRACT
The methods of indirct haemagglutination (IH) and precipitation in gel (ID) were employed to test the level of varicella-zoster (VZ) antibodies in an experimental batch of zoster gammaglobulin (ZIG). The titre of indirect haemagglutinating antibodies in ZIG was about 64 times higher than in the ordinary batches of normal immunoglobulin and about 8 times higher in comparison with the level of the initial plasma pool. In the reaction of precipitation in gel, ZIG produced 5 to 6 zones. In comparison with the initial pool of convalescent plasma, ZIG also showed an 8-fold concentration of precipitating antibodies. ZIG was administered preventively to 6 children with risk diagnoses. None of the children fell ill with varicella. According to the results of subsequent serological examination in the reactions of indirect haemagglutination and radioimmunologic analysis, only 3 children were definitely susceptible to VZ infection. In two other children (very low antibody titres) the risk could not be excluded. No substantial increase in the levels of IH and RIA antibodies was observed in the 4 children under serological observation in a period of 6 months following the administration of ZIG. ZIG was administered therapeutically to four children with varicella. The effect of ZIG therapy was very suggestive, especially in two newborn infants lacking maternal antibodies, where the dose of ZIG per 1 kg body weigt was unusually high.
