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Concept: Upper respiratory tract


Objective To determine the frequency of prescriptions for short term use of oral corticosteroids, and adverse events (sepsis, venous thromboembolism, fractures) associated with their use.Design Retrospective cohort study and self controlled case series.Setting Nationwide dataset of private insurance claims.Participants Adults aged 18 to 64 years who were continuously enrolled from 2012 to 2014.Main outcome measures Rates of short term use of oral corticosteroids defined as less than 30 days duration. Incidence rates of adverse events in corticosteroid users and non-users. Incidence rate ratios for adverse events within 30 day and 31-90 day risk periods after drug initiation.Results Of 1 548 945 adults, 327 452 (21.1%) received at least one outpatient prescription for short term use of oral corticosteroids over the three year period. Use was more frequent among older patients, women, and white adults, with significant regional variation (all P<0.001). The most common indications for use were upper respiratory tract infections, spinal conditions, and allergies. Prescriptions were provided by a diverse range of specialties. Within 30 days of drug initiation, there was an increase in rates of sepsis (incidence rate ratio 5.30, 95% confidence interval 3.80 to 7.41), venous thromboembolism (3.33, 2.78 to 3.99), and fracture (1.87, 1.69 to 2.07), which diminished over the subsequent 31-90 days. The increased risk persisted at prednisone equivalent doses of less than 20 mg/day (incidence rate ratio 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture; all P<0.001).Conclusion One in five American adults in a commercially insured plan were given prescriptions for short term use of oral corticosteroids during a three year period, with an associated increased risk of adverse events.

Concepts: Clinical trial, Corticosteroid, Asthma, Epidemiology, Upper respiratory tract, Time, Upper respiratory tract infection, Respiratory system


Background An evolving understanding of the immunopathogenesis of multiple sclerosis suggests that depleting B cells could be useful for treatment. We studied ocrelizumab, a humanized monoclonal antibody that selectively depletes CD20-expressing B cells, in the primary progressive form of the disease. Methods In this phase 3 trial, we randomly assigned 732 patients with primary progressive multiple sclerosis in a 2:1 ratio to receive intravenous ocrelizumab (600 mg) or placebo every 24 weeks for at least 120 weeks and until a prespecified number of confirmed disability progression events had occurred. The primary end point was the percentage of patients with disability progression confirmed at 12 weeks in a time-to-event analysis. Results The percentage of patients with 12-week confirmed disability progression was 32.9% with ocrelizumab versus 39.3% with placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.59 to 0.98; P=0.03). The percentage of patients with 24-week confirmed disability progression was 29.6% with ocrelizumab versus 35.7% with placebo (hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.04). By week 120, performance on the timed 25-foot walk worsened by 38.9% with ocrelizumab versus 55.1% with placebo (P=0.04); the total volume of brain lesions on T2-weighted magnetic resonance imaging (MRI) decreased by 3.4% with ocrelizumab and increased by 7.4% with placebo (P<0.001); and the percentage of brain-volume loss was 0.90% with ocrelizumab versus 1.09% with placebo (P=0.02). There was no significant difference in the change in the Physical Component Summary score of the 36-Item Short-Form Health Survey. Infusion-related reactions, upper respiratory tract infections, and oral herpes infections were more frequent with ocrelizumab than with placebo. Neoplasms occurred in 2.3% of patients who received ocrelizumab and in 0.8% of patients who received placebo; there was no clinically significant difference between groups in the rates of serious adverse events and serious infections. Conclusions Among patients with primary progressive multiple sclerosis, ocrelizumab was associated with lower rates of clinical and MRI progression than placebo. Extended observation is required to determine the long-term safety and efficacy of ocrelizumab. (Funded by F. Hoffmann-La Roche; ORATORIO number, NCT01194570 .).

Concepts: Hoffmann–La Roche, Upper respiratory tract, Monoclonal antibodies, Upper respiratory tract infection, Clinical trial, Respiratory system, Multiple sclerosis, Magnetic resonance imaging


BACKGROUND: The new combination of moxifloxacin HCl and cefixime trihydrate is approved for the treatments of lower respiratory tract infections in adults. At initial formulation development and screening stage a fast and reliable method for the dissolution and release testing of moxifloxacin and cefixime were highly desirable. The zero order overlaid UV spectra of moxifloxacin and cefixime showed >90% of spectra are overlapping. Hence, simple, accurate precise and validated two derivative spectrophotometric methods have been developed for the determination of moxifloxacin and cefixime. METHODS: In the first derivative spectrophotometric method varying concentration of moxifloxacin and cefixime were prepared and scanned in the range of 200 to 400 nm and first derivative spectra were calculated (n = 1). The zero crossing wavelengths 287 nm and 317.9 nm were selected for determination of moxifloxacin and cefixime, respectively. In the second method the first derivative of ratio spectra was calculated and used for the determination of moxifloxacin and cefixime by measuring the peak intensity at 359.3 nm and 269.6 nm respectively. RESULTS: Calibration graphs were established in the range of 1–16 mug /mL and 1–15 mug /mL for both the drugs by first and ratio first derivative spectroscopic methods respectively with good correlation coefficients. Average accuracy of assay of moxifloxacin and cefixime were found to be 100.68% and 98 93%, respectively. Relative standard deviations of both inter and intraday assays were less than 1.8%. Moreover, recovery of moxifloxacin and cefixime was more than 98.7% and 99.1%, respectively. CONCLUSIONS: The described derivative spectrophotometric methods are simple, rapid, accurate, precise and excellent alternative to sophisticated chromatographic techniques. Hence, the proposed methods can be used for the quality control of the cited drugs and can be extended for routine analysis of the drugs in formulations.

Concepts: Ultraviolet-visible spectroscopy, Lower respiratory tract, Accuracy and precision, Upper respiratory tract, Respiratory system, Spectroscopy, Ultraviolet, Spectrophotometry


Background New treatments have improved outcomes for patients with relapsed chronic lymphocytic leukemia (CLL), but complete remissions remain uncommon. Venetoclax has a distinct mechanism of action; it targets BCL2, a protein central to the survival of CLL cells. Methods We conducted a phase 1 dose-escalation study of daily oral venetoclax in patients with relapsed or refractory CLL or small lymphocytic lymphoma (SLL) to assess safety, pharmacokinetic profile, and efficacy. In the dose-escalation phase, 56 patients received active treatment in one of eight dose groups that ranged from 150 to 1200 mg per day. In an expansion cohort, 60 additional patients were treated with a weekly stepwise ramp-up in doses as high as 400 mg per day. Results The majority of the study patients had received multiple previous treatments, and 89% had poor prognostic clinical or genetic features. Venetoclax was active at all dose levels. Clinical tumor lysis syndrome occurred in 3 of 56 patients in the dose-escalation cohort, with one death. After adjustments to the dose-escalation schedule, clinical tumor lysis syndrome did not occur in any of the 60 patients in the expansion cohort. Other toxic effects included mild diarrhea (in 52% of the patients), upper respiratory tract infection (in 48%), nausea (in 47%), and grade 3 or 4 neutropenia (in 41%). A maximum tolerated dose was not identified. Among the 116 patients who received venetoclax, 92 (79%) had a response. Response rates ranged from 71 to 79% among patients in subgroups with an adverse prognosis, including those with resistance to fludarabine, those with chromosome 17p deletions (deletion 17p CLL), and those with unmutated IGHV. Complete remissions occurred in 20% of the patients, including 5% who had no minimal residual disease on flow cytometry. The 15-month progression-free survival estimate for the 400-mg dose groups was 69%. Conclusions Selective targeting of BCL2 with venetoclax had a manageable safety profile and induced substantial responses in patients with relapsed CLL or SLL, including those with poor prognostic features. (Funded by AbbVie and Genentech; number, NCT01328626 .).

Concepts: Upper respiratory tract, Hematology, Blood disorders, B-cell chronic lymphocytic leukemia, Oncology, Upper respiratory tract infection, Respiratory system, Leukemia


To compare the effects of a single nocturnal dose of 3 honey products (eucalyptus honey, citrus honey, or labiatae honey) to placebo (silan date extract) on nocturnal cough and difficulty sleeping associated with childhood upper respiratory tract infections (URIs).

Concepts: Diurnality, Hypnotic, Circadian rhythm, Sleep disorder, Lower respiratory tract, Upper respiratory tract, Upper respiratory tract infection, Respiratory system


The present study was initiated to investigate the effectiveness, safety and tolerability of complex homeopathic CalSuli-4-02 tablets on prevention of recurrent acute upper respiratory tract infections (URTIs) in children, in comparison to another complex homeopathic product.

Concepts: Clinical research, Pharmaceutical industry, Lower respiratory tract, Pharmacology, Upper respiratory tract, Upper respiratory tract infection, Clinical trial, Respiratory system


Cough is a frequent symptom associated to upper respiratory tract infections (URTIs) and, although being self-limiting, it might deeply affect the quality of life. Homeopathic products are often employed by patients to treat cough, but the evidence on their efficacy is scarce. Thus, we tested the efficacy of an homeopathic syrup in treating cough arising from URTIs with a randomized, double blind, placebo controlled clinical trial. Patients were treated with either the homeopathic syrup or a placebo for a week, and recorded cough severity in a diary by means of a verbal category-descriptive score for two weeks. Sputum viscosity was assessed with a viscosimeter before and after 4 days of treatment; patients were also asked to provide a subjective evaluation of viscosity. Eighty patients were randomized to receive placebo (n=40) or the homeopathic syrup (n=40). All patients completed the study. In each group cough scores decreased over time, however, after 4 and 7 days of treatment, cough severity was significantly lower in the homeopathic group than in the placebo one (P<0.001 and P=0.023, respectively). Sputum was collected from 53 patients: in both groups its viscosity significantly decreased after 4 days of treatment (P<0.001); however, viscosity was significantly lower in the homeopathic group (P=0.018). Instead, the subjective evaluation did not significantly differ between the two groups (P=0.059). No adverse events related to any treatment were reported. We concluded that the homeopathic syrup employed in the study was able to effectively reduce cough severity and sputum viscosity, thereby representing a valid remedy for the management of acute cough induced by URTIs.

Concepts: Lower respiratory tract, Homeopathy, Randomized controlled trial, Upper respiratory tract, Upper respiratory tract infection, Respiratory system, Clinical trial, Placebo


In 2012, a novel coronavirus associated with severe respiratory disease in humans emerged in the Middle East. Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). Here we provide experimental support for camels as a reservoir for MERS-CoV. We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals. Clinical signs of the MERS-CoV infection were benign, but each of the camels shed large quantities of virus from the upper respiratory tract. We detected infectious virus in nasal secretions through 7 days postinoculation, and viral RNA up to 35 days postinoculation. The pattern of shedding and propensity for the upper respiratory tract infection in dromedary camels may help explain the lack of systemic illness among naturally infected camels and the means of efficient camel-to-camel and camel-to-human transmission.

Concepts: Asia, Infectious disease, Middle East, Diseases and disorders, Upper respiratory tract, Upper respiratory tract infection, Infection, Respiratory system


Although culture-independent techniques have refuted lung sterility in health, controversy about contamination during bronchoscope passage through the upper respiratory tract (URT) has impeded research progress. We sought to establish whether bronchoscopic sampling accurately reflects the lung microbiome in health and to distinguish between two proposed routes of authentic microbial immigration, (i) dispersion along contiguous respiratory mucosa and (ii) subclinical microaspiration. During bronchoscopy of eight adult volunteers without lung disease, we performed seven protected specimen brushings (PSB) and bilateral bronchoalveolar lavages (BALs) per subject. We amplified, sequenced, and analyzed the bacterial 16S rRNA gene V4 regions by using the Illumina MiSeq platform. Rigorous attention was paid to eliminate potential sources of error or contamination, including a randomized processing order and the inclusion and analysis of exhaustive procedural and sequencing control specimens. Indices of mouth-lung immigration (mouth-lung community similarity, bacterial burden, and community richness) were all significantly greater in airway and alveolar specimens than in bronchoscope contamination control specimens, indicating minimal evidence of pharyngeal contamination. Ecological indices of mouth-lung immigration peaked at or near the carina, as predicted for a primary immigration route of microaspiration. Bacterial burden, diversity, and mouth-lung similarity were greater in BAL than PSB samples, reflecting differences in the sampled surface areas. (This study has been registered at under registration no. NCT02392182.)IMPORTANCE This study defines the bacterial topography of the healthy human respiratory tract and provides ecological evidence that bacteria enter the lungs in health primarily by microaspiration, with potential contribution in some subjects by direct dispersal along contiguous mucosa. By demonstrating that contamination contributes negligibly to microbial communities in bronchoscopically acquired specimens, we validate the use of bronchoscopy to investigate the lung microbiome.

Concepts: Biotechnology, Lung cancer, Ribosomal RNA, 16S ribosomal RNA, Pulmonology, Lower respiratory tract, Upper respiratory tract, Respiratory system


OBJECTIVES: A high proportion of patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia die within a few days of the onset of infection. However, predictive factors for early mortality (EM) have barely been examined. The aim of this study was to determine the predictive factors for EM in patients with MRSA bacteraemia. METHODS: All episodes of MRSA bacteraemia were prospectively followed in 21 Spanish hospitals from June 2008 to December 2009. Epidemiology, clinical data, therapy and outcome were recorded. All MRSA strains were analysed in a central laboratory. Mortality was defined as death from any cause occurring in the 30 days after the onset of MRSA bacteraemia. EM was defined as patients who died within the first 2 days, and late mortality (LM) for patients who died after this period. Multivariate analyses were performed by using logistic regression models. RESULTS: A total of 579 episodes were recorded. Mortality was observed in 179 patients (31%): it was early in 49 (8.5%) patients and late in 130 (22.5%). Independent risk factors for EM were [OR (95% CI)] initial Pitt score >3 [3.99 (1.72-3.24)], previous rapid fatal disease [3.67 (1.32-10.24)], source of infection lower respiratory tract or unknown [3.76 (1.31-10.83) and 2.83 (1.11-7.21)], non-nosocomial acquisition [2.59 (1.16-5.77)] and inappropriate initial antibiotic therapy [3.59 (1.63-7.89)]. When predictive factors for EM and LM were compared, inappropriate initial antibiotic therapy was the only distinctive predictor of EM, while endocarditis and lower respiratory tract sources both predicted LM. CONCLUSIONS: In our large cohort of patients several factors were related to EM, but the only distinctive predictor of EM was inappropriate initial antibiotic therapy.

Concepts: Epidemiology, Pneumonia, Upper respiratory tract, Antibiotic resistance, Respiratory system, Methicillin-resistant Staphylococcus aureus, Regression analysis, Staphylococcus aureus