While age and the APOE ε4 allele are major risk factors for Alzheimer’s disease (AD), a small percentage of individuals with these risk factors exhibit AD resilience by living well beyond 75 years of age without any clinical symptoms of cognitive decline.
Objective To investigate whether symptomatic treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is non-inferior to antibiotics in the treatment of uncomplicated lower urinary tract infection (UTI) in women, thus offering an opportunity to reduce antibiotic use in ambulatory care.Design Randomised, double blind, non-inferiority trial.Setting 17 general practices in Switzerland.Participants 253 women with uncomplicated lower UTI were randomly assigned 1:1 to symptomatic treatment with the NSAID diclofenac (n=133) or antibiotic treatment with norfloxacin (n=120). The randomisation sequence was computer generated, stratified by practice, blocked, and concealed using sealed, sequentially numbered drug containers.Main outcome measures The primary outcome was resolution of symptoms at day 3 (72 hours after randomisation and 12 hours after intake of the last study drug). The prespecified principal secondary outcome was the use of any antibiotic (including norfloxacin and fosfomycin as trial drugs) up to day 30. Analysis was by intention to treat.Results 72/133 (54%) women assigned to diclofenac and 96/120 (80%) assigned to norfloxacin experienced symptom resolution at day 3 (risk difference 27%, 95% confidence interval 15% to 38%, P=0.98 for non-inferiority, P<0.001 for superiority). The median time until resolution of symptoms was four days in the diclofenac group and two days in the norfloxacin group. A total of 82 (62%) women in the diclofenac group and 118 (98%) in the norfloxacin group used antibiotics up to day 30 (risk difference 37%, 28% to 46%, P<0.001 for superiority). Six women in the diclofenac group (5%) but none in the norfloxacin group received a clinical diagnosis of pyelonephritis (P=0.03).Conclusion Diclofenac is inferior to norfloxacin for symptom relief of UTI and is likely to be associated with an increased risk of pyelonephritis, even though it reduces antibiotic use in women with uncomplicated lower UTI.Trial registration ClinicalTrials.gov NCT01039545.
Solitary rectal ulcer syndrome (SRUS) is a benign and chronic disorder well known in young adults and less in children. It is often related to prolonged excessive straining or abnormal defecation and clinically presents as rectal bleeding, copious mucus discharge, feeling of incomplete defecation, and rarely rectal prolapse. SRUS is diagnosed based on clinical symptoms and endoscopic and histological findings. The current treatments are suboptimal, and despite correct diagnosis, outcomes can be unsatisfactory. Some treatment protocols for SRUS include conservative management such as family reassurance, regulation of toilet habits, avoidance of straining, encouragement of a high-fiber diet, topical treatments with salicylate, sulfasalazine, steroids and sucralfate, and surgery. In children, SRUS is relatively uncommon but troublesome and easily misdiagnosed with other common diseases, however, it is being reported more than in the past. This condition in children is benign; however, morbidity is an important problem as reflected by persistence of symptoms, especially rectal bleeding. In this review, we discuss current diagnosis and treatment for SRUS.
Hair-pulling disorder (trichotillomania, HPD) is a disabling condition that is characterized by repetitive hair-pulling resulting in hair loss. Although there is evidence of structural grey matter abnormalities in HPD, there is a paucity of data on white matter integrity. The aim of this study was to explore white matter integrity using diffusion tensor imaging (DTI) in subjects with HPD and healthy controls. Sixteen adult female subjects with HPD and 13 healthy female controls underwent DTI. Hair-pulling symptom severity, anxiety and depressive symptoms were also assessed. Tract-based spatial statistics were used to analyze data on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). There were no differences in DTI measures between HPD subjects and healthy controls. However, there were significant associations of increased MD in white matter tracts of the fronto-striatal-thalamic pathway with longer HPD duration and increased HPD severity. Our findings suggest that white matter integrity in fronto-striatal-thalamic pathways in HPD is related to symptom duration and severity. The molecular basis of measures of white matter integrity in HPD deserves further exploration.
Chronic day-to-day symptoms of orthostatic intolerance are the most notable features of postural orthostatic tachycardia syndrome (POTS). However, we have encountered patients with such symptoms and excessive tachycardia but with no symptoms during the tilt-table test (TTT). We aimed to investigate whether POTS patients with chronic orthostatic intolerance always present orthostatic symptoms during the TTT and analyze the factors underlying symptom manifestation during this test.
BACKGROUND: To assess the clinical and laboratory parameters, response to therapy and development of antituberculosis (TB) drug resistance in pulmonary TB (PTB) patients with diabetes mellitus (DM) and without DM. METHODS: Using a prospective design, 227 of 310 new cases of culture-positive PTB diagnosed at the Queen Savang Vadhana Memorial Hospital and the Chonburi Hospital between April 2010 and July 2012 that met the study criteria were selected. Data regarding clinical and laboratory parameters, drug susceptibility and treatment outcomes were compared between PTB patients with DM and those without DM. To control for age, the patients were stratified into two age groups (< 50 and ≥ 50 years) and their data were analysed. RESULTS: Of the 227 patients, 37 (16.3%) had DM, of which 26 (70.3%) had been diagnosed with DM prior to PTB diagnosis and 11 (29.7%) had developed DM at PTB diagnosis. After controlling for age, no significant differences were found between the two groups regarding mycobacterium burden, sputum-culture conversion rate, evidence of multidrug-resistant tuberculosis, frequency of adverse drug events from anti-TB medications, treatment outcomes and relapse rate. The presenting symptoms of anorexia (p = 0.050) and haemoptysis (p = 0.036) were observed significantly more frequently in PTB patients with DM, while the presenting symptom of cough was observed significantly more frequently in PTB patients without DM (p = 0.047). CONCLUSIONS: Plasma glucose levels should be monitored in all newly diagnosed PTB patients and a similar treatment regimen should be prescribed to PTB patients with DM and those without DM in high TB-burden countries.
Japanese encephalitis virus (JEV) causes acute central nervous system (CNS) disease in humans, in whom the clinical symptoms vary from febrile illness to meningitis and encephalitis. However, the mechanism of severe encephalitis has not been fully elucidated. In this study, using a mouse model, we investigated the pathogenetic mechanisms that correlate with fatal JEV infection. Following extraneural infection with the JaOArS982 strain of JEV, infected mice exhibited clinical signs ranging from mild to fatal outcome. Comparison of the pathogenetic response between severe and mild cases of JaOArS982-infected mice revealed increased levels of TNF-α in the brains of severe cases. However, unexpectedly, the mortality rate of TNF-α KO mice was significantly increased compared with that of WT mice, indicating that TNF-α plays a protective role against fatal infection. Interestingly, there were no significant differences of viral load in the CNS between WT and TNF-α KO mice. However, exaggerated inflammatory responses were observed in the CNS of TNF-α KO mice. Although these observations were also obtained in IL-10 KO mice, the mortality and enhanced inflammatory responses were more pronounced in TNF-α KO mice. Our findings therefore provide the first evidence that TNF-α has an immunoregulatory effect on pro-inflammatory cytokines in the CNS during JEV infection and consequently protects the animals from fatal disease. Thus, we propose that the increased level of TNF-α in severe cases was the result of severe disease, and secondly that immunopathological effects contribute to severe neuronal degeneration resulting in fatal disease. In future, further elucidation of the immunoregulatory mechanism of TNF-α will be an important priority to enable the development of effective treatment strategies for Japanese encephalitis.
Mast cell activation disease (MCAD) is a term referring to a heterogeneous group of disorders characterized by aberrant release of variable subsets of mast cell (MC) mediators together with accumulation of either morphologically altered and immunohistochemically identifiable mutated MCs due to MC proliferation (systemic mastocytosis [SM] and MC leukemia [MCL]) or morphologically ordinary MCs due to decreased apoptosis (MC activation syndrome [MCAS] and well-differentiated SM). Clinical signs and symptoms in MCAD vary depending on disease subtype and result from excessive mediator release by MCs and, in aggressive forms, from organ failure related to MC infiltration. In most cases, treatment of MCAD is directed primarily at controlling the symptoms associated with MC mediator release. In advanced forms, such as aggressive SM and MCL, agents targeting MC proliferation such as kinase inhibitors may be provided. Targeted therapies aimed at blocking mutant protein variants and/or downstream signaling pathways are currently being developed. Other targets, such as specific surface antigens expressed on neoplastic MCs, might be considered for the development of future therapies. Since clinicians are often underprepared to evaluate, diagnose, and effectively treat this clinically heterogeneous disease, we seek to familiarize clinicians with MCAD and review current and future treatment approaches.
Performance evaluation of a rapid molecular diagnostic, MultiCode based, sample-to-answer assay for the simultaneous detection of Influenza A, B and respiratory syncytial viruses
- Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
- Published almost 2 years ago
Clinical signs and symptoms of different airway pathogens are generally indistinguishable, making laboratory tests essential for clinical decisions regarding isolation and antiviral therapy. Immunochromatographic tests (ICT) and direct immunofluorescence assays (DFA) have lower sensitivities and specificities than molecular assays, but have the advantage of quick turnaround times and ease-of-use.
Chronic fatigue syndrome (CFS) is a complex, multisystem disorder that can be disabling. CFS symptoms can be provoked by increased physical or cognitive activity, and by orthostatic stress. In preliminary work, we noted that CFS symptoms also could be provoked by application of longitudinal neural and soft tissue strain to the limbs and spine of affected individuals. In this study we measured the responses to a straight leg raise neuromuscular strain maneuver in individuals with CFS and healthy controls. We randomly assigned 60 individuals with CFS and 20 healthy controls to either a 15 minute period of passive supine straight leg raise (true neuromuscular strain) or a sham straight leg raise. The primary outcome measure was the symptom intensity difference between the scores during and 24 hours after the study maneuver compared to baseline. Fatigue, body pain, lightheadedness, concentration difficulties, and headache scores were measured individually on a 0-10 scale, and summed to create a composite symptom score. Compared to individuals with CFS in the sham strain group, those with CFS in the true strain group reported significantly increased body pain (P = 0.04) and concentration difficulties (P = 0.02) as well as increased composite symptom scores (all P = 0.03) during the maneuver. After 24 hours, the symptom intensity differences were significantly greater for the CFS true strain group for the individual symptom of lightheadedness (P = 0.001) and for the composite symptom score (P = 0.005). During and 24 hours after the exposure to the true strain maneuver, those with CFS had significantly higher individual and composite symptom intensity changes compared to the healthy controls. We conclude that a longitudinal strain applied to the nerves and soft tissues of the lower limb is capable of increasing symptom intensity in individuals with CFS for up to 24 hours. These findings support our preliminary observations that increased mechanical sensitivity may be a contributor to the provocation of symptoms in this disorder.