Cortical microinfarcts in adults with Down syndrome assessed with 3T-MRI.

BACKGROUND: Cortical microinfarcts (CMI) were attributed to cerebrovascular disease and cerebral amyloid angiopathy (CAA). CAA is frequent in Down syndrome (DS) while hypertension is rare, yet no studies have assessed CMI in DS. METHODS: We included 195 adults with DS, 63 with symptomatic sporadic Alzheimer's disease (AD), and 106 controls with 3T magnetic resonance imaging. We assessed CMI prevalence in each group and CMI association with age, AD clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition in DS. RESULTS: CMI prevalence was 11.8% in DS, 4.7% in controls, and 17.5% in sporadic AD. In DS, CMI increased in prevalence with age and the AD clinical continuum, was clustered in the parietal lobes, and was associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. DISCUSSION: In DS, CMI are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic CAA phenotype. HIGHLIGHTS: This is the first study to assess cortical microinfarcts (assessed with 3T magnetic resonance imaging) in adults with Down syndrome (DS). We studied the prevalence of cortical microinfarcts in DS and its relationship with age, the Alzheimer's disease (AD) clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition. The prevalence of cortical microinfarcts was 11.8% in DS and increased with age and along the AD clinical continuum. Cortical microinfarcts were clustered in the parietal lobes, and were associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. In DS, cortical microinfarcts are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic phenotype of cerebral amyloid angiopathy.

Effects of storage conditions on the stability of blood-based markers for the diagnosis of Alzheimer's disease.

OBJECTIVES: Alzheimer's disease (AD) is considered the most common cause of dementia in older people. Recently, blood-based markers (BBM) Aß1-42, Aß1-40, and phospho Tau181 (p-Tau181) have demonstrated the potential to transform the diagnosis and prognostic assessment of AD. Our aim was to investigate the effect of different storage conditions on the quantification of these BBM and to evaluate the interchangeability of plasma and serum samples. METHODS: Forty-two individuals with some degree of cognitive impairment were studied. Thirty further patients were retrospectively selected. Aß1-42, Aß1-40, and p-Tau181 were quantified using the LUMIPULSE-G600II automated platform. To assess interchangeability between conditions, correction factors for magnitudes that showed strong correlations were calculated, followed by classification consistency studies. RESULTS: Storing samples at 4 °C for 8-9 days was associated with a decrease in Aß fractions but not when stored for 1-2 days. Using the ratio partially attenuated the pre-analytical effects. For p-Tau181, samples stored at 4 °C presented lower concentrations, whereas frozen samples presented higher ones. Concerning classification consistency in comparisons that revealed strong correlations (p-Tau181), the percentage of total agreement was greater than 90 % in a large number of the tested cut-offs values. CONCLUSIONS: Our findings provide relevant information for the standardization of sample collection and storage in the analysis of AD BBM in an automated platform. This knowledge is crucial to ensure their introduction into clinical settings.

Cross-sectional versus longitudinal cognitive assessments for the diagnosis of symptomatic Alzheimer's disease in adults with Down syndrome.

BACKGROUND: Down syndrome (DS) is a genetic form of Alzheimer's disease (AD). However, clinical diagnosis is difficult, and experts emphasize the need for detecting intra-individual cognitive decline. OBJECTIVE: To compare the performance of baseline and longitudinal neuropsychological assessments for the diagnosis of symptomatic AD in DS. METHODS: Longitudinal cohort study of adults with DS. Individuals were classified as asymptomatic, prodromal AD, or AD dementia. We performed receiver operating characteristic curve analyses to compare baseline and longitudinal changes of CAMCOG-DS and mCRT. RESULTS: We included 562 adults with DS. Baseline assessments showed good to excellent diagnostic performance for AD dementia (AUCs between 0.82 and 0.99) and prodromal AD, higher than the 1-year intra-individual cognitive decline (area under the ROC curve between 0.59 and 0.79 for AD dementia, lower for prodromal AD). Longer follow-ups increased the diagnostic performance of the intra-individual cognitive decline. DISCUSSION: Baseline cognitive assessment outperforms the 1-year intra-individual cognitive decline in adults with DS.

Basal forebrain atrophy along the Alzheimer's disease continuum in adults with Down syndrome.

BACKGROUND: Basal forebrain (BF) degeneration occurs in Down syndrome (DS)-associated Alzheimer's disease (AD). However, the dynamics of BF atrophy with age and disease progression, its impact on cognition, and its relationship with AD biomarkers have not been studied in DS. METHODS: We included 234 adults with DS (150 asymptomatic, 38 prodromal AD, and 46 AD dementia) and 147 euploid controls. BF volumes were extracted from T-weighted magnetic resonance images using a stereotactic atlas in SPM12. We assessed BF volume changes with age and along the clinical AD continuum and their relationship to cognitive performance, cerebrospinal fluid (CSF) and plasma amyloid/tau/neurodegeneration biomarkers, and hippocampal volume. RESULTS: In DS, BF volumes decreased with age and along the clinical AD continuum and significantly correlated with amyloid, tau, and neurofilament light chain changes in CSF and plasma, hippocampal volume, and cognitive performance. DISCUSSION: BF atrophy is a potentially valuable neuroimaging biomarker of AD-related cholinergic neurodegeneration in DS.

Importance of cerebrospinal fluid storage conditions for the Alzheimer's disease diagnostics on an automated platform.

OBJECTIVES: Alzheimer's disease (AD) is considered the most common cause of dementia in older people. Cerebrospinal fluid (CSF) Aß1-42, Aß1-40, total Tau (t-Tau), and phospho Tau (p-Tau) are important biomarkers for the diagnosis, however, they are highly dependent on the pre-analytical conditions. Our aim was to investigate the potential influence of different storage conditions on the simultaneous quantification of these biomarkers in a fully-automated platform to accommodate easier pre-analytical conditions for laboratories. METHODS: CSF samples were obtained from 11 consecutive patients. Aß1-42, Aß1-40, p-Tau, and t-Tau were quantified using the LUMIPULSE G600II automated platform. RESULTS: Temperature and storage days significantly influenced Aß1-42 and Aß1-40 with concentrations decreasing with days spent at 4 °C. The use of the Aß1-42/Aß1-40 ratio could partly compensate it. P-Tau and t-Tau were not affected by any of the tested storage conditions. For conditions involving storage at 4 °C, a correction factor of 1.081 can be applied. Diagnostic agreement was almost perfect in all conditions. CONCLUSIONS: Cutoffs calculated in samples stored at -80 °C can be safely used in samples stored at -20 °C for 15-16 days or up to two days at RT and subsequent freezing at -80 °C. For samples stored at 4 °C, cutoffs would require applying a correction factor, allowing to work with the certainty of reaching the same clinical diagnosis.

Mobile origami immunosensors for the rapid detection of urinary tract infections.

Urinary tract infections (UTI) have a high prevalence and can yield poor patient outcomes if they progress to urosepsis. Here we introduce mobile origami biosensors that detect UTIs caused by E. coli at the bedside in less than 7 minutes. The origami biosensors are made of a single piece of paper that contains antibody-decorated nanoparticles. When the urine sample contains E. coli, the biosensors generate colored spots on the paper strip. These are then quantified with a mobile app that calculates the pixel intensity in real time. The tests are highly specific and do not cross-react with other common uropathogens. Furthermore, the biosensors only yielded one false negative result when queried with a panel containing 57 urine samples from patients, which demonstrates that they have excellent sensitivity and specificity. This, along with the rapid assay time and smartphone-based detection, makes them useful for aiding in the diagnosis of UTIs at the point of care.

Retroperitoneal Laparoscopic Para-Aortic Lymphadenectomy in Para-Aortic Staging of Locally Advanced Cervical Cancer.

STUDY OBJECTIVE: To review/learn a surgical technique not very well-known by gynecologic oncologists. DESIGN: Level of evidence III. SETTING: A review of a surgical technique with emphasis on the para-aortic sentinel lymph nodes using indocyanine green. INTERVENTION: The film features the following steps to perform the procedure: 1. Creating a retroperitoneal window. 2. What to do if the peritoneum is torn. 3. Finding the psoas muscle, right ureter, and common iliac artery. Dissecting the right common iliac artery caudally to the bifurcation of the external iliac artery and internal iliac artery and cranially to the inferior mesenteric artery, the ovarian arteries, and the left renal vein. 4. A view of all of the nodes with fluorescence when indocyanine green is injected into the cervix. At present, the sentinel lymph nodes are not the standard of care for locally advanced cervical cancer. If the nodes are metastatic at this stage, all the para-aortic area will undergo radiation therapy. 5. Dissecting the inferior vena cava from the intersection with the right uterer to the right and left renal veins. 6. Performing the lateroaortic, preaortic, and precaval lymphadenectomy. 7. A final view with all of the elements (i.e., bifurcation of the common iliac artery, the left renal vein, and both ureters). 8. In the final part of the video, we open the peritoneal window to decrease the incidence of lymphoceles. CONCLUSION: The real novelty of this video is how the para-aortic area nodes are seen when green indocyanine is injected into the cervix. This video shows a simplified technique of retroperitoneal para-aortic lymphadenectomy using an advanced bipolar sealant. Some tips and tricks to facilitate the procedure are emphasized, especially in cases of accidental peritoneal tears. To decrease the incidence of lymphoceles before completing the surgery, the peritoneal window should be opened. This surgical technique is especially useful in endometrial cancer for staging the para-aortic area in obese patients and in advanced cervical cancer to determine the field of radiotherapy.

Clinical Features of and Risk Factors for Fatal Ebola Virus Disease, Moyamba District, Sierra Leone, December 2014-February 2015.

The 2013-2016 outbreak of Ebola virus disease (EVD) in West Africa infected >28,000 people, including >11,000 who died, and disrupted social life in the region. We retrospectively studied clinical signs and symptoms and risk factors for fatal outcome among 31 Ebola virus-positive patients admitted to the Ebola Treatment Center in Moyamba District, Sierra Leone. We found a higher rate of bleeding manifestations than reported elsewhere during the outbreak. Significant predictors for death were shorter time from symptom onset to admission, male sex, high viral load on initial laboratory testing, severe pain, diarrhea, bloody feces, and development of other bleeding manifestations during hospitalization. These risk factors for death could be used to identify patients in need of more intensive medical support. The lack of fever in as many as one third of EVD cases may have implications for temperature-screening practices and case definitions.

Clinical features of suspected Ebola cases referred to the Moyamba ETC, Sierra Leone: challenges in the later stages of the 2014 outbreak.

BACKGROUND: The last ebola virus disease (EVD) outbreak has been the most important since 1976. EVD cases decreased drastically in Sierra Leone at the beginning of 2015. We aim to determine the clinical findings and evolution of patients admitted to an Ebola treatment center (ETC) during the epidemic's late phase. METHODS: We analyze retrospectively data of patients admitted to the Moyamba ETC (December 2014-March 2015). Patients were classified in EVD or non-EVD patients according to the results of Ebola virus real-time reverse transcription polymerase chain reaction (ZAIRE-RT-PCR). RESULTS: Seventy-five patients were included, 41.3 % were positive for ZAIRE-RT-PCR. More women (68 % vs 28 %, p = 0.001) were EVD-positive. More EVD patients had previous contact with an Ebola patient (74.2 % vs 36.3 %, p < 0.001). At admission, EVD patients were more likely to have fatigue (96.7 %, p < 0.001), diarrhea (67.7 %, p = 0.002), and muscle pain (61.3 %, p = 0.009); but only objective fevers in 35.5 % of EVD patients. The most reliable criteria for diagnosis were: contact with an Ebola patient plus three WHO symptoms (LR + =3.7, 95 % CI = 1.9-7.3), and positive contact (LR + =2.3, 95 % CI = 1.15-4.20). Only 45.2 % of EVD patients developed fevers during stay, but 75 % developed gastrointestinal symptoms. Non-EVD patients had gastrointestinal problems (33 %), respiratory conditions (26.6 %), and others such as malaria, HIV or tuberculosis with a mortality rate of 11.4 %. vs 58 % in EVD group (p < 0.001). CONCLUSIONS: More non-EVD patients were admitted in the outbreak's late phases. The low percentage of initial fever highlights the need to emphasize the epidemiological information. EVD patients presented new symptoms getting worse and requiring closer follow-up. Diagnoses of non-EVD patients were diverse with a remarkable mortality, presenting a challenge for the health system.

Effectiveness of two types of intervention on antibiotic prescribing in respiratory tract infections in Primary Care in Spain. Happy Audit Study.

OBJECTIVE: To evaluate the effectiveness of two types of intervention in reducing antibiotic prescribing in respiratory tract infections (RTI). DESIGN: Before-after audit-based study. SETTING: Primary Care centres in Spain. PARTICIPANTS: General practitioners (GPs) registered all patients with RTIs for 15 days in winter 2008 (pre-intervention), and again in winter 2009 (post-intervention). INTERVENTIONS: Intervention activities included meetings, with the presentation and discussion of the results, and several training meetings on RTI guidelines, information brochures for patients, workshops on point-of-care tests - rapid antigen detection tests and C-reactive protein rapid test - and provision of these tests in the clinic. All GPs, with the exception of those in Catalonia, made up the full intervention group (FIG); conversely, Catalan doctors underwent the same intervention, except for the workshop on rapid tests (partial intervention group, PIG). Multilevel logistic regression was performed taking the prescription of antibiotics as the dependent variable. RESULTS: Out of a total of 309 GPs involved in the first register, 281 completed the intervention and the second register (90.9%), of which 210 were assigned to the FIG, and 71 to the PIG. The odds ratio of antibiotic prescribing after the intervention was 0.99 (95% CI: 0.89-1.10) among GPs assigned to PIG, and 0.50 (95% CI: 0.44-0.57, p<0.001) among those who were allocated to FIG. The reduction in antibiotic prescribing in FIG was more marked in flu infection, common cold, acute pharyngitis, acute tonsillitis, and acute bronchitis. CONCLUSIONS: Active participation of GPs with the performance of point-of-care tests in the clinic is accompanied by a drastic reduction of antibiotic use in RTIs, primarily in infections considered as mainly viral.

Diagnostic performance of plasma pTau217, pTau181, Aß1-42 and Aß1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease.

BACKGROUND: Recently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance in clinical practice is unknown. METHODS: We analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture in routine clinical practice in a specialized memory clinic (66 cognitively unimpaired, 130 participants with mild cognitive impairment, and 94 with dementia). Participants were classified as amyloid positive (A +) or negative (A-) according to CSF Aß1-42/Aß1-40 ratio. Plasma pTau217, pTau181, Aß1-42 and Aß1-40 were measured in the fully-automated LUMIPULSE platform. We used linear regression to compare plasma biomarkers concentrations between A + and A- groups, evaluated Spearman's correlation between plasma and CSF and performed ROC analyses to assess their diagnostic accuracy to detect brain amyloidosis as determined by CSF Aß1-42/Aß1-40 ratio. We analyzed the concordance of pTau217 with CSF amyloidosis. RESULTS: Plasma pTau217 and pTau181 concentration were higher in A + than A- while the plasma Aß1-42/Aß1-40 ratio was lower in A + compared to A-. pTau181 and the Aß1-42/Aß1-40 ratio showed moderate correlation between plasma and CSF (Rho = 0.66 and 0.69, respectively). The areas under the ROC curve to discriminate A + from A- participants were 0.94 (95% CI 0.92-0.97) for pTau217, and 0.88 (95% CI 0.84-0.92) for both pTau181 and Aß1-42/Aß1-40. Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were less affected. Plasma pTau217 had the highest fold change (× 3.2) and showed high predictive capability in discriminating A + from A-, having 4-7% misclassification rate. The global accuracy of plasma pTau217 using a two-threshold approach was robust in symptomatic groups, exceeding 90%. CONCLUSION: The evaluation of blood biomarkers on an automated platform exhibited high diagnostic accuracy for AD pathophysiology, and pTau217 showed excellent diagnostic accuracy to identify participants with AD in a consecutive sample representing the routine clinical practice in a specialized memory unit.

Executive Summary of the Spanish Guidelines for the Diagnosis and Management of Imported Febrile Illnesses from the Spanish Society of Tropical Medicine and International Health (SEMTSI), the Imported Pathology Group of the Spanish Society of Infectious Diseases and Clinical Microbiology (GEPI-SEIMC), the Spanish Society of Family and Community Medicine (SEMFYC), the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Society of Emergency Medicine (SEMES).

The Spanish Society of Tropical Medicine and International Health (SEMTSI), the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Emergency Medicine (SEMES), the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Society of Family and Community Medicine (SEMFYC) have prepared a consensus statement on the diagnosis and management of patients with imported febrile illnesses. Twenty authors with different backgrounds and representing different healthcare perspectives (ambulatory primary care, travel and tropical medicine specialists, emergency medicine, hospital care, microbiology and parasitology and public health), identified 39 relevant questions, which were organised in 7 thematic blocks. After a systematic review of the literature and a thoughtful discussion, the authors prepared 125 recommendations, as well as several tables and figures to be used as a consulting tool. The present executive summary shows a selection of some of the most relevant questions and recommendations included in the guidelines.

Efficacy of high doses of oral penicillin versus amoxicillin in the treatment of adults with non-severe pneumonia attended in the community: study protocol for a randomised controlled trial.

BACKGROUND: Streptococcus pneumoniae is the bacterial agent which most frequently causes pneumonia. In some Scandinavian countries, this infection is treated with penicillin V since the resistances of pneumococci to this antibiotic are low. Four reasons justify the undertaking of this study; firstly, the cut-off points which determine whether a pneumococcus is susceptible or resistant to penicillin have changed in 2008 and according to some studies published recently the pneumococcal resistances to penicillin in Spain have fallen drastically, with only 0.9% of the strains being resistant to oral penicillin (minimum inhibitory concentration>2 µg/ml); secondly, there is no correlation between pneumococcal infection by a strain resistant to penicillin and therapeutic failure in pneumonia; thirdly, the use of narrow-spectrum antibiotics is urgently needed because of the dearth of new antimicrobials and the link observed between consumption of broad-spectrum antibiotics and emergence and spread of antibacterial resistance; and fourthly, no clinical study comparing amoxicillin and penicillin V in pneumonia in adults has been published. Our aim is to determine whether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of uncomplicated community-acquired pneumonia. METHODS: We will perform a parallel group, randomised, double-blind, trial in primary healthcare centres in Spain. Patients aged 18 to 65 without significant associated comorbidity attending the physician with signs and symptoms of lower respiratory tract infection and radiological confirmation of the diagnosis of pneumonia will be randomly assigned to either penicillin V 1.6 million units thrice-daily during 10 days or amoxicillin 1,000 mg thrice-daily during 10 days. The main outcome will be clinical cure at 14 days, defined as absence of fever, resolution or improvement of cough, improvement of general wellbeing and resolution or reduction of crackles indicating that no other antimicrobial treatment will be necessary. Any clinical result other than the anterior will be considered as treatment failure. A total of 210 patients will be recruited to detect a non-inferiority margin of 15% between the two treatments with a minimum power of 80% considering an alpha error of 2.5% for a unilateral hypothesis and maximum possible losses of 15%. DISCUSSION: This pragmatic trial addresses the long-standing hypothesis that the administration of high doses of a narrow-spectrum antibiotic (penicillin V) in patients with non-severe pneumonia attended in the community is not less effective than high doses of amoxicillin (treatment currently recommended) in patients under the age of 65 years. TRIAL REGISTRATION: EudraCT number 2012-003511-63.

[Diffusion MRI in the study of hepatic lesions]. / Difusión en resonancia magnética en el estudio de lesiones hepáticas.

Diffusion weighted imaging (DWI) in magnetic resonance imaging (MRI) is currently an important tool for detecting and characterising hepatic lesions, as well as for monitoring and evaluating the response to the treatment of the tumour disease. The use of this technique is also being assessed for the study of diffuse liver disease. Among the additional advantages of DWI-MRI, is the absence of emission of ionising radiation and not having to use paramagnetic contrasts, which means it can be used in the study of patients with renal failure. Another advantage is the short duration of the diffusion sequence, which means that the examination time in abdominal MRI is scarcely increased. Therefore, it is important that the physician is aware of this diagnostic technique, since DWI is a sequence that should be routinely included in the liver MRI study protocol.

Diagnostic performance of plasma pTau 217, pTau 181, Aß 1-42 and Aß 1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease.

BACKGROUND: Recently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance in clinical practice is unknown. METHODS: We analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture in routine clinical practice in a specialized memory clinic (66 cognitively unimpaired, 130 participants with mild cognitive impairment, and 94 with dementia). Participants were classified as amyloid positive (A+) or negative (A-) according to CSF Aß1-42/Aß1-40 ratio. Plasma pTau217, pTau181, Aß1-42 and Aß1-40 were measured in the fully-automated LUMIPULSE platform. We used linear regression to compare plasma biomarkers concentrations between A + and A- groups, evaluated Spearman's correlation between plasma and CSF and performed ROC analyses to assess their diagnostic accuracy to detect brain amyloidosis as determined by CSF Aß1-42/Aß1-40 ratio. We analyzed the potential of pTau217 to predict amyloidosis in CSF. RESULTS: Plasma pTau217 and pTau181 concentration were higher in A + than A- while the plasma Aß1-42/Aß1-40 ratio was lower in A + compared to A-. pTau181 and the Aß1-42/Aß1-40 ratio showed moderate correlation between plasma and CSF (Rho = 0.66 and 0.69, respectively). The areas under the ROC curve to discriminate A + from A- participants were 0.94 (95% CI 0.92-0.97) for pTau217, and 0.88 (95% CI 0.84-0.92) for both pTau181 and Aß1-42/Aß1-40. Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were less affected. Plasma pTau217 had the highest fold change (x4.2) and showed high predictive capability in discriminating A + from A-, having 4-7% misclassification rate. The global accuracy of plasma pTau217 using a two-threshold approach was robust in symptomatic groups, exceeding 90%. CONCLUSION: The evaluation of blood biomarkers on an automated platform exhibited high diagnostic accuracy for AD pathophysiology, and pTau217 showed excellent diagnostic accuracy to identify participants with AD in a consecutive sample representing the routine clinical practice in a specialized memory unit.

Interventions to reduce antibiotic prescription for lower respiratory tract infections: Happy Audit study.

This before-after study aimed to evaluate the effect of two interventions on lowering the prescription of antibiotics in lower respiratory tract infections (LRTI) in Spain. General practitioners (GPs) registered all cases with LRTIs over 3-week periods before and after an intervention, in 2008 and 2009. Two types of intervention were considered: full-intervention group (FIG), consisting of discussion sessions of the results of the first registry, courses for GPs, guidelines, patient information leaflets, workshops on rapid tests and use of the C-reactive protein (CRP) test; GPs in the partial-intervention group (PIG) underwent all of the above interventions except for the workshop on rapid tests, and they did not have access to CRP. A multilevel logistic regression analysis was performed considering the prescription of an antibiotic as the dependent variable. 210 physicians were assigned to FIG and 70 to PIG. In 2009, 58 new physicians were included as a control group. 5,385 LRTIs were registered. Compared with the control group, the OR of antibiotic prescription after the intervention in the PIG was 0.42 (95% CI: 0.22-0.82) and 0.22 (95% CI: 0.12-0.38) in the FIG. Intervention led to a reduction in the prescription of antibiotics, mainly when CRP testing was available.

MR imaging of thoracic abnormalities in the fetus.

In recent years, with the development of ultrafast sequences, magnetic resonance (MR) imaging has been established as a valuable diagnostic modality complementary to ultrasonography (US). MR imaging offers several technical advantages over US, including a larger field of view, fewer limitations due to maternal habitus, and the ability to visualize fetal anatomy regardless of fetal presentation. The authors discuss the most frequently found thoracic abnormalities, including congenital diaphragmatic hernia, congenital cystic adenomatoid malformation, bronchopulmonary sequestration, bronchogenic cyst, congenital high airway obstruction syndrome, and bronchial obstruction by a mucus plug, specifically with respect to the effect of fetal MR imaging on diagnosis and treatment. MR imaging can assist in establishing the prognosis and in perinatal management, especially in the case of congenital diaphragmatic hernia, which is the most common indication for thoracic MR imaging. MR imaging can demonstrate hernial contents and quantify lung volume better than US, allowing the prognosis to be determined and postpartum extracorporeal membrane oxygenation needs to be estimated. MR imaging can also be used to distinguish different types of cystic adenomatoid malformations, identify the anomalous vessels of pulmonary sequestration, and assess the functional effects of bronchogenic cysts. Balanced sequences (steady-state free precession sequences) allow performance of unenhanced thoracic vascular studies, which are useful in the diagnosis of intralobar or extralobar sequestration. In summary, fetal MR imaging can provide additional data useful in establishing prognosis and in perinatal management of thoracic malformations.

C-reactive protein testing in patients with acute rhinosinusitis leads to a reduction in antibiotic use.

OBJECTIVE: To evaluate the effect of C-reactive protein (CRP) testing on the antibiotic prescribing in patients with acute rhinosinusitis. METHODS: Audit-based study carried out in primary care centres in Spain. GPs registered episodes of rhinosinusitis during 3-week period before and after an intervention. Two types of intervention were considered: full intervention group (FIG) consisting in individual feedback based on results from the first registry, courses in rational antibiotic prescribing, guidelines, patient information leaflets, workshops on rapid tests and use of the CRP test. GPs in the partial intervention group (PIG) underwent all the above intervention except for the workshop and they did not have access to CRP. Multilevel logistic regression analysis was performed considering the prescription of antibiotics as the dependent variable. RESULTS: Two hundred and ten physicians were assigned to FIG and 71 to PIG. In 2009, 59 new physicians were included as a control group. Two hundred and sixty-seven GPs visited contacts with rhinosinusitis (78.5%) registering a total of 836 cases. In the group of GPs with access to CRP rapid test, 207 patients with rhinosinusitis (75.3%) were tested and antibiotics were prescribed in 156 patients (56.7%). Antibiotics were prescribed in 87 patients (82.9%) in the group of GPs exposed to PIG and in 52 patients (86.7%) in the control group (P < 0.001). Antibiotic prescription was significantly reduced after the intervention among physicians assigned to FIG, with an odds ratio of antibiotic prescribing of 0.12 (95% confidence interval: 0.01-0.32). CONCLUSION: Physicians with access to CRP tests significantly reduced antibiotic prescription in patients with rhinosinusitis.

The Aß1-42/Aß1-40 ratio in CSF is more strongly associated to tau markers and clinical progression than Aß1-42 alone.

BACKGROUND: Cerebrospinal fluid (CSF) Aß1-42 levels and the Aß1-42/Aß1-40 ratio are markers of amyloid pathology, but previous studies suggest that their levels might be influenced by additional pathophysiological processes. AIMS: To compare Aß1-42 and the Aß1-42/Aß1-40 ratio in CSF in different neurodegenerative disorders and study their association with other biomarkers (tTau, pTau181, and NfL) and with cognitive and functional progression. METHODS: We included all participants from the Sant Pau Initiative on Neurodegeneration (SPIN) with CSF Aß1-42 and Aß1-42/Aß1-40. Participants had diagnoses of Alzheimer's disease (AD), dementia with Lewy bodies, frontotemporal lobar degeneration-related syndromes, non-neurodegenerative conditions, or were cognitively normal. We classified participants as "positive" or "negative" according to each marker. We compared CSF levels of tTau, pTau181, and NfL between concordant and discordant groups through ANCOVA and assessed differences in cognitive (MMSE, FCSRT) and functional (GDS, CDR-SOB) progression using Cox regression and linear-mixed models. RESULTS: In the 1791 participants, the agreement between Aß1-42 and Aß1-42/Aß1-40 was 78.3%. The Aß1-42/Aß1-40 ratio showed a stronger correlation with tTau and pTau181 than Aß1-42 and an agreement with tTau and pTau181 of 73.1% and 77.1%, respectively. Participants with a low Aß1-42/Aß1-40 ratio showed higher tTau and pTau181 and worse cognitive and functional prognosis, regardless of whether they were positive or negative for Aß1-42. The results were consistent across stages, diagnostic categories, and use of different cutoffs. CONCLUSION: Although Aß1-42 and Aß1-42/Aß1-40 are considered markers of the same pathophysiological pathway, our findings provide evidence favoring the use of the Aß1-42/Aß1-40 ratio in clinical laboratories in the context of AD.

Effect of two interventions on reducing antibiotic prescription in pharyngitis in primary care.

OBJECTIVES: to evaluate the effect of two interventions on reducing antibiotic prescription in pharyngitis. METHODS: a prospective, non-randomized, before-after controlled study was carried out in primary care centres throughout Spain. General practitioners (GPs) registered all cases of pharyngitis during a 3 week period before and after two types of intervention in 2008 and 2009, respectively. Full intervention consisted of discussion sessions of the results of the first registry, courses for GPs, guidelines, patient information leaflets, workshops on rapid tests and the use of rapid antigen detection tests (RADTs) in their consulting offices. The physicians in the partial intervention group underwent all the above intervention except for the workshop, and RADTs were not provided. A control group was also included in 2009. Multilevel logistic regression was performed considering the prescription of antibiotics as the dependent variable. RESULTS: a total of 280 GPs registered cases with pharyngitis (70 partial intervention and 210 full intervention). Fifty-nine new physicians were included as a control group. A total of 6849 episodes of pharyngitis were registered. Antibiotic prescription was significantly lower after intervention for the full intervention group, but not for the partial intervention group. According to the multivariate model, in comparison with the control group, the odds ratio of antibiotic prescription after the intervention was 0.52 [95% confidence interval (95% CI) 0.23-1.18] in the partial intervention group and 0.23 (95% CI 0.11-0.47) in the full intervention group. CONCLUSIONS: intervention was beneficial for reducing the prescription of antibiotics, but was only statistically significant when the GPs were provided with RADTs.