Outpatient Antipsychotic Use and Severe COVID-19: Avoiding the Impact of Age in a Real-World Data Study.

BACKGROUND: The association between use of antipsychotics and COVID-19 outcomes is inconsistent, which may be linked to use of these drugs in age-related diseases. Furthermore, there is little evidence regarding their effect in the nongeriatric population. We aim to assess the association between antipsychotic use and risk of disease progression and hospitalization due to COVID-19 among the general population, stratifying by age. METHODS: We conducted a population-based, multiple case-control study to assess risk of hospitalization, with cases being patients with a PCR(+) test who required hospitalization and controls being individuals without a PCR(+) test; and risk of progression to hospitalization, with cases being the same as those used in the hospitalization substudy and controls being nonhospitalized PCR(+) patients. We calculated adjusted odds-ratios (aOR) and 95% confidence intervals (CI), both overall and stratified by age. RESULTS: Antipsychotic treatment in patients younger than 65 years was not associated with a higher risk of hospitalization due to COVID-19 (aOR 0.94 [95%CI = 0.69-1.27]) and disease progression among PCR(+) patients (aOR 0.96 [95%CI = 0.70-1.33]). For patients aged 65 years or older, however, there was a significant, increased risk of hospitalization (aOR 1.58 [95% CI = 1.38-1.80]) and disease progression (aOR 1.31 [95% CI = 1.12-1.55]). CONCLUSIONS: The results of our large-scale real-world data study suggest that antipsychotic use is not associated with a greater risk of hospitalization due to COVID-19 and progression to hospitalization among patients younger than 65 years. The effect found in the group aged 65 years or older might be associated with off-label use of antipsychotics.

Outpatient glucocorticoid use and COVID-19 outcomes: a population-based study.

INTRODUCTION: Owing to controversy information surrounds effect of glucocorticoids on the evolution of COVID-19, we evaluate the effects of outpatient glucocorticoid use on the severity and progression of COVID-19 and risk of infection and analyse the effect of window of exposure and dose. METHODS: We conducted a population-based case - control study, involving 4 substudies: (i) Hospitalisation; (ii) Mortality, using subjects hospitalised with a PCR + as cases and subjects without a PCR + as controls; (iii) Progression, including subjects with a PCR + (hospitalised versus non-hospitalised); and (iv) Susceptibility, with all subjects with a PCR + and subjects without a PCR + . Adjusted odds ratios (ORa) and their 95% confidence intervals (95% CI) were calculated. RESULTS: The outpatient glucocorticoid use was associated with an increased risk of hospitalisation (aOR 1.79; 95% CI 1.56-2.05), mortality (aOR 2.30; 95% CI 1.68-3.15), progression (aOR 1.69; 95% CI 1.43-2.00) and susceptibility (aOR 1.29, 95% CI 1.19-1.41). Furthermore, the effects was observed to be greater at higher doses and the closer that drug use approached the outcome date, with an almost fourfold increase in mortality among users in the previous month (aOR 3.85; 95% CI 2.63-5.62). CONCLUSIONS: According to the results of this real-world data study, outpatient glucocorticoid use should be considered in making decisions about intrahospital treatment.

Impact of prior antihypertensive treatment on COVID-19 outcomes, by active ingredient.

OBJECTIVES: To assess the impact of prior chronic treatment with angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin-receptor blockers (ARBs), both as a group and by active ingredient, on severity (risk of hospitalization and mortality), progression of and susceptibility to COVID-19. METHODS: We conducted a multiple population-based case-control study in Galicia (north-west Spain). The study data were sourced from medical, administrative and clinical databases. We assessed: (1) risk of hospitalization, by selecting all patients hospitalized due to COVID-19 with PCR + as cases, and a random sample of subjects without a PCR + as controls; (2) COVID-19 mortality risk; (3) risk of disease progression; and (4) susceptibility to SARS-CoV-2, considering all patients with PCR + as cases, and the same subjects used in the previous model as controls. Adjusted odds ratios (aORs) were calculated. RESULTS: ACEIs and ARBs were shown to decrease the risk of hospitalization (aOR = 0.78 [95%CI 0.69-0.89] and aOR = 0.80 [95%CI 0.72-0.90] respectively), risk of mortality (aOR = 0.71 [95%CI 0.52-0.98] and aOR = 0.69 [95%CI 0.52-0.91] respectively), and susceptibility to the virus (aOR = 0.88 [95%CI 0.82-0.94] and aOR = 0.92 [95%CI 0.86-0.97] respectively). By active ingredient: use of enalapril was associated with a significantly lower risk of hospitalization (aOR = 0.72 [95%CI 0.61-0.85]), mortality (aOR = 0.59 [95%CI 0.38-0.92]) and susceptibility to COVID-19 (aOR = 0.86 [95%CI 0.79-0.94]); and use of candesartan was associated with a decreased risk of hospitalization (aOR = 0.76 [95%CI 0.60-0.95]), mortality (aOR = 0.36 [95%CI 0.17-0.75]) and disease progression (aOR = 0.73 [95%CI 0.56-0.95]). CONCLUSION: This large-scale real-world data study suggest that enalapril and candesartan are associated with a considerable reduction in risk of severe COVID19 outcomes.

Effect of dapagliflozin on COVID-19 infection and risk of hospitalization.

BACKGROUND: Dapagliflozin has been proposed as a potential treatment for coronavirus disease 2019 (COVID-19) by reducing cytokine production and inflammation. However, there are limited data on its effectiveness. We aimed to evaluate the impact of dapagliflozin on COVID-19 severity (including hospitalization risk, ICU admission, in-hospital death and progression to severe COVID-19) and its potential on susceptibility to COVID-19 infection. METHODS: We conducted a population-based case-control study. For aim 1, we assessed COVID-19 severity in cases (positive PCR patients requiring hospitalization) and matched controls (negative PCR patients or positive PCR patients not requiring hospitalization). For aim 2, we compared positive PCR cases (hospitalized and non-hospitalized) with controls. Adjusted odds ratios (aORs) were calculated using a generalized linear mixed model. RESULTS: We analysed 86 602 subjects: 3060 were hospitalized cases, 26 757 were non-hospitalized cases and 56 785 were controls. Among the hospitalized COVID-19 patients, 228 were admitted to the ICU and 413 died. Dapagliflozin had no effect on the risk of hospitalization (aOR 0.98; 95% CI 0.65-1.48; P = 0.915), ICU admissions (aOR 1.21; 95% CI 0.34-4.25; P = 0.767) or in-hospital death (aOR 1.33; 95% CI 0.53-3.30; P = 0.543). Dapagliflozin reduced the risk of progression to severe COVID-19 by 35%, but this was not statistically significant (aOR 0.65; 95% CI 0.40-1.06; P = 0.086). Dapagliflozin was associated with a 30% increased risk of susceptibility to COVID-19 infection (aOR 1.31; 95% CI 1.05-1.62; P = 0.015). CONCLUSIONS: Use of dapagliflozin prior to SARS-CoV-2 infection was not associated with an increased risk of hospitalization, ICU admission, mortality or progression to severe COVID-19. However, it was associated with an increased risk of susceptibility to COVID-19 infection.

Colchicine and risk of hospitalization due to COVID-19: A population-based study.

Colchicine is one of the most widely studied and best-known anti-inflammatory treatments. This study aimed to assess the effect of colchicine on risk of hospitalization due to COVID-19; and its effect on susceptibility to and severity of the virus in patients with COVID-19. We carried out a population-based case-control study. The following groups were applied: (1) to assess risk of hospitalization, cases were patients with a positive PCR who were hospitalized due to COVID-19, and controls without a positive PCR; (2) to assess susceptibility to COVID-19, cases were patients with a positive PCR (hospitalized and non-hospitalized), and the same controls; (3) to determine potential severity, cases were subjects with COVID-19 hospitalized, and controls patients with COVID-19 nonhospitalised. Different electronic, linked, administrative health and clinical databases were used to extract data on sociodemographic variables, comorbidities, and medications dispensed. The study covered 3060 subjects with a positive PCR who were hospitalized, 26 757 with a positive PCR who were not hospitalized, and 56 785 healthy controls. After adjustment for sociodemographic variables, comorbidities and other treatments, colchicine did not modify risk of hospitalization due to COVID-19 (adjusted odd ratio [OR] 1.08 [95% confidence interval (CI) 0.76-1.53]), patients' susceptibility to contracting the disease (adjusted OR 1.12 (95% CI 0.91-1.37)) or the severity of the infection (adjusted OR 1.03 [95% CI 0.67-1.59]). Our results would neither support the prophylactic use of colchicine for prevention of the infection or hospitalization in any type of patient, nor justify the withdrawal of colchicine treatment due to a higher risk of contracting COVID-19.

Outpatient atorvastatin use and severe COVID-19 outcomes: A population-based study.

Evidence of the effect of statins on patients with coronavirus disease (2019) COVID-19 is inconsistent. The aim of this study was to evaluate the association between chronic use of statins-both overall and by active ingredient-and severe outcomes of COVID-19 (risk of hospitalization and mortality), progression to severe outcomes, and susceptibility to the virus. We conducted a population-based case-control study with data from electronic records to assess the risk of (1) hospitalization: cases were patients admitted due to COVID-19 and controls were subjects without COVID-19; (2) mortality: cases were hospitalized patients who died due to COVID-19 and controls were subjects without COVID-19; (3) progression: cases were hospitalized COVID-19 subjects and controls were nonhospitalized COVID-19 patients; and (4) susceptibility: cases were patients with COVID-19 (both hospitalized and nonhospitalized) and controls were subjects without COVID-19. We collected data on 2821 hospitalized cases, 26 996 nonhospitalized cases, and 52 318 controls. Chronic use of atorvastatin was associated with a decreased risk of hospitalization (adjusted odds ratios [aOR] = 0.83; 95% confidence interval [CI]: 0.74-0.92) and mortality (aOR = 0.70; 95% CI: 0.53-0.93), attributable in part to a lower risk of susceptibility to the virus (aOR = 0.91; 95% CI: 0.86-0.96). Simvastatin was associated with a reduced risk of mortality (aOR = 0.59; 95% CI: 0.40-0.87). The wide degree of heterogeneity observed in the estimated odds ratios (ORs) of the different statins suggests that there is no class effect. The results of this real-world study suggest that chronic use of atorvastatin (and to a lesser degree, of simvastatin) is associated with a decrease in risk of severe COVID-19 outcomes.

Patients With High Cardiovascular Risk as Candidates to Bempedoic Acid, After Treatment With Statins, Ezetimibe and PCSK9 Inhibitors: An Estimation and Cost-Effectiveness Analysis.

ABSTRACT: Low-density lipoprotein cholesterol (LDLc) is the lead effector of atherosclerosis and main treatment target. Bempedoic acid is a novel oral drug in the therapeutic armamentarium which is able to reduce LDLc. The objectives of this study were (1) to select the potential patients for administering bempedoic acid such as those with a very high cardiovascular risk in which objectives of LDLc were not achieved despite conventional treatment with PCSK9 inhibitors (PCSK9i) and/or statins and ezetimibe and (2) to estimate the cost-effectiveness of bempedoic acid in different scenarios. The methods used were a multicenter and retrospective study of 652 patients initiating treatment with any PCSK9 inhibitor in 17 different hospitals. Before and on-treatment LDLc cholesterol levels, medical treatments, clinical indication, and baseline characteristics were recorded. The results obtained from 443 subjects in secondary prevention were analyzed. The mean (±) LDLc level at baseline was 142.5 ± 46.4 mg/dL and 61.5 ± 40.5 mg/dL in the follow-up, with a reduction of 55.9% ( P < 0.0001); 71.6% of the patients reached the target of LDL < 55 mg/dL or >50% reduction. Of those patients treated with medium-intensity and low-intensity statins plus PCSK9 inhibitors (with or without ezetimibe), only 5.7% of them were able to reduce LDL below 55 mg/dL and the main LDLc reduction in this group was the lowest (42.9% on average). Patients with TG values >135 mg/dL represented 41.6% of the sample, of which approximately 10% of them were using fibrates. Assuming only LDLc reduction and the UK price, the incremental cost-effectiveness ratio was 88,359€; 83,117€; 82,378€; and 79,015€ for different discount rates. In conclusion, one-third of the patients could achieve the target LDL proposed in the 2019 ESC/EAS guidelines. Approximately 10% of them could also benefit from treating hypertriglyceridemia as indicated in the 2021 ESC guidelines on cardiovascular disease prevention. Patients with medium-intensity and low-intensity statins plus PCSK9i and ezetimibe would be the most benefited. Bempedoic acid could be a not cost-efficacy therapy in all the scenarios, but we need to wait for the CLEAR OUTCOMES Trial results.

Protein Plasma Levels of the IGF Signalling System Are Altered in Major Depressive Disorder.

The Insulin-like growth factor 2 (IGF-2) has been recently proven to alleviate depressive-like behaviors in both rats and mice models. However, its potential role as a peripheral biomarker has not been evaluated in depression. To do this, we measured plasma IGF-2 and other members of the IGF family such as Binding Proteins (IGFBP-1, IGFBP-3, IGFBP-5 and IGFBP-7) in a depressed group of patients (n = 51) and in a healthy control group (n = 48). In some of these patients (n = 15), we measured these proteins after a period (19 ± 6 days) of treatment with antidepressants. The Hamilton Depressive Rating Scale (HDRS) and the Self-Assessment Anhedonia Scale (SAAS) were used to measure depression severity and anhedonia, respectively. The general cognition state was assessed by the Mini-Mental State Examination (MMSE) test and memory with the Free and Cued Selective Reminding Test (FCSRT). The levels of both IGF-2 and IGFBP-7 were found to be significantly increased in the depressed group; however, only IGF-2 remained significantly elevated after correction by age and sex. On the other hand, the levels of IGF-2, IGFBP-3 and IGFBP-5 were significantly decreased after treatment, whereas only IGFBP-7 was significantly increased. Therefore, peripheral changes in the IGF family and their response to antidepressants might represent alterations at the brain level in depression.

Massive Release of CD9+ Microvesicles in Human Immunodeficiency Virus Infection, Regardless of Virologic Control.

BACKGROUND: The role of extracellular vesicles (EVs) in human immunodeficiency virus (HIV) pathogenesis is unknown. We examine the cellular origin of plasma microvesicles (MVs), a type of ectocytosis-derived EV, the presence of mitochondria in MVs, and their relationship to circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) in HIV-infected patients and controls. METHODS: Five participant groups were defined: 30 antiretroviral therapy (ART)-naive; 30 ART-treated with nondetectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. Microvesicles were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time polymerase chain reaction. RESULTS: Microvesicle numbers were expanded at least 10-fold in all HIV-infected groups compared with controls. More than 79% were platelet-derived MVs. Proportions of MVs containing mitochondria (22.3% vs 41.6%) and MV mitochondrial density (706 vs 1346) were significantly lower among HIV-infected subjects than controls, lowest levels for those on ART. Microvesicle numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients. CONCLUSIONS: A massive release of platelet-derived MVs occurs during HIV infection. Some MVs contain mitochondria, but their proportion and mitochondrial densities were lower in HIV infection than in controls. Platelet-derived MVs may be biomarkers of platelet activation, possibly reflecting pathogenesis even in absence of HIV replication.

Switching between reference adalimumab and biosimilars in chronic immune-mediated inflammatory diseases: A systematic literature review.

AIMS: Adalimumab is a biological therapy used to treat different chronic inflammatory diseases. At present, there is an increasing number of adalimumab biosimilars. To assume the acceptability of interchangeability between reference adalimumab and biosimilars, there should be evidence about efficacy and safety of this switching. Regulation of this practice falls under the authority of individual European Union Member States. The aim of this study is to systematically review the evidence on the efficacy, safety and immunogenicity of switching between reference adalimumab and biosimilars in different chronic immune-mediated inflammatory diseases. METHODS: Studies presenting data about switching between reference adalimumab and biosimilars were identified by sensitive search strategies in Medline and EMBASE from 1 January 2004 to 30 June 2021. RESULTS: A total of 471 references were obtained and 21 finally included in the analysis (total number of patients switching: 2802). Eight different adalimumab biosimilars were tested after receiving reference adalimumab. Eight articles included rheumatoid arthritis (RA), one miscellaneous rheumatic disease, six psoriasis (PSO) and six inflammatory bowel disease (IBD) patients. Overall, the efficacy results in the switching groups were comparable to those obtained in the arms of continuous biosimilar and continuous reference adalimumab. There were no significant differences in treatment emergent adverse events, anti-drug or neutralising antibodies among the three groups. CONCLUSIONS: Switching between reference adalimumab and biosimilars has no impact on efficacy, safety and immunogenicity in patients with RA, PSO and IBD. This finding was consistent for the different adalimumab biosimilars analysed. These conclusions could probably be extended to other rheumatic diseases such as psoriatic arthritis and ankylosing spondylitis.

Integrity and quantity of salivary cell-free DNA as a potential molecular biomarker in oral cancer: A preliminary study.

BACKGROUND: Differences in cell-free DNA (cfDNA) fragments have been described as a valuable tool to distinguish cancer patients from healthy individuals. We aim to investigate the concentration and integrity of cfDNA fragments in saliva from oral squamous cell carcinoma (OSCC) patients and healthy individuals in order to explore their value as diagnostic biomarkers. METHODS: Saliva samples were collected from a total of 34 subjects (19 OSCC patients and 15 healthy controls). The total concentration of salivary cfDNA (scfDNA) was determined using a fluorometry method and quantitative real-time polymerase chain reaction (qPCR). To evaluate the scfDNA quantity and integrity, qPCR targeting Arthobacter luteus (ALU) sequences at three amplicons of different lengths (60, 115, and 247 bp, respectively) was carried out. ScfDNA integrity indexes (ALU115/ALU60 and ALU247/ALU60) were calculated as the ratio between the absolute concentration of the longer amplicons 115 bp and 247 bp and the total scfDNA amount (amplicon 60 bp). RESULTS: The total scfDNA concentration (ALU60) was higher in OSCC than in healthy donors, but this trend was not statistically significant. The medians of scfDNA integrity indexes, ALU115/ALU60 and ALU247/ALU60, were significantly higher in OSCC, showing area under the curve values of 0.8211 and 0.7018, respectively. CONCLUSION: Our preliminary results suggest that scfDNA integrity indexes (ALU115/ALU60 and ALU247/ALU60) have potential as noninvasive diagnostic biomarkers for OSCC.

Incidence, diagnosis, and outcome of immune-mediated thrombotic thrombocytopenic purpura: A nationwide survey by the Spanish registry of thrombotic thrombocytopenic purpura.

BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disease characterized by the presence of anti-ADAMTS13 autoantibodies. Achieving accurate information on incidence and customary disease management is important to provide appropriate diagnostic and therapeutic resources. The aim of this study was to determine the incidence and outcomes of iTTP in Spain. STUDY DESIGN AND METHODS: A cross-sectional survey was carried out among Spanish hospitals, focused on iTTP patients ≥16 years old attended between 2015 and 2017, and those at follow-up before that interval. Incidence, prevalence, mortality, refractoriness, exacerbations, treatment complications, relapses, and sequelae were estimated. RESULTS: Forty-two hospitals covering roughly 20 million inhabitants answered the survey and reported 203 episodes (138 newly-diagnosed and 65 relapses), of which 193 (95.1%) were treated. Incidence was 2.67 (95% CI 1.90-3.45) patients per million inhabitants per year and prevalence 21.44 (95% CI% 19.10-23.73) patients per million inhabitants. At diagnosis, ADAMTS13 activity and anti-ADAMTS13 autoantibody were measured in 97% and 84.3% of reported episodes, respectively. Fifteen patients (7.4%) died as a direct consequence of iTTP, 6 of them before receiving any iTTP-specific treatment. Thirty-one (16.1%) of the 193 treated episodes were refractory to plasma exchange and corticosteroids, and 51 (26.4%) suffered at least one exacerbation. CONCLUSION: iTTP incidence and prevalence were somewhat higher than those documented in neighboring countries. Together with data on treatments and outcomes, this information will allow us to better estimate what is needed to improve diagnosis and prognosis of iTTP patients in Spain.

Patients-centered SurvivorShIp care plan after Cancer treatments based on Big Data and Artificial Intelligence technologies (PERSIST): a multicenter study protocol to evaluate efficacy of digital tools supporting cancer survivors.

BACKGROUND: It is encouraging to see a substantial increase in individuals surviving cancer. Even more so since most of them will have a positive effect on society by returning to work. However, many cancer survivors have unmet needs, especially when it comes to improving their quality of life (QoL). Only few survivors are able to meet all of the recommendations regarding well-being and there is a body of evidence that cancer survivors' needs often remain neglected from health policy and national cancer control plans. This increases the impact of inequalities in cancer care and adds a dangerous component to it. The inequalities affect the individual survivor, their career, along with their relatives and society as a whole. The current study will evaluate the impact of the use of big data analytics and artificial intelligence on the self-efficacy of participants following intervention supported by digital tools. The secondary endpoints include evaluation of the impact of patient trajectories (from retrospective data) and patient gathered health data on prediction and improved intervention against possible secondary disease or negative outcomes (e.g. late toxicities, fatal events). METHODS/DESIGN: The study is designed as a single-case experimental prospective study where each individual serves as its own control group with basal measurements obtained at the recruitment and subsequent measurements performed every 6 months during follow ups. The measurement will involve CASE-cancer, Patient Activation Measure and System Usability Scale. The study will involve 160 survivors (80 survivors of Breast Cancer and 80 survivors of Colorectal Cancer) from four countries, Belgium, Latvia, Slovenia, and Spain. The intervention will be implemented via a digital tool (mHealthApplication), collecting objective biomarkers (vital signs) and subjective biomarkers (PROs) with the support of a (embodied) conversational agent. Additionally, the Clinical Decision Support system (CDSS), including visualization of cohorts and trajectories will enable oncologists to personalize treatment for an efficient care plan and follow-up management. DISCUSSION: We expect that cancer survivors will significantly increase their self-efficacy following the personalized intervention supported by the m-HealthApplication compared to control measurements at recruitment. We expect to observe improvement in healthy habits, disease self-management and self-perceived QoL. Trial registration ISRCTN97617326. https://doi.org/10.1186/ISRCTN97617326 . Original Registration Date: 26/03/2021.

Appendicitis or non-specific abdominal pain in pre-school children: When to request abdominal ultrasound?

AIM: The aim of this study is to determine the most useful diagnostic tools to differentiate appendicitis from non-specific abdominal pain (NSAP) in pre-school children. METHODS: We prospectively evaluated all children aged 5 years or younger admitted for suspected appendicitis at a paediatric emergency department during 5 years. Cases of NSAP and appendicitis were enrolled according to inclusion and exclusion criteria. The different variables collected were assessed by statistic and diagnostic accuracy studies. RESULTS: A total of 82 patients were studied: 27 cases of NSAP and 55 cases of appendicitis. We found no symptoms or signs with a high power of discrimination between both processes. Complicated cases of appendicitis begin to appear when the duration of symptoms exceeds 12 h. Among laboratory tests, C-reactive protein (CRP) value >34 mg/L was the variable with a greater association to appendicitis (odds ratio 9.8). Abdominal ultrasound (US) had high sensitivity and specificity to differentiate appendicitis, significantly improving its diagnostic accuracy when the duration of symptoms exceeds 12 h. CONCLUSIONS: A good history and physical examination are important in the diagnostic process, but reliable physical signs can be difficult to elicit in pre-school children. CRP and abdominal US are useful investigations that can improve diagnostic accuracy. According to our results, abdominal pain duration longer than 12 h or CRP value >34 mg/L should be an indication to perform an abdominal US in pre-school children with right lower quadrant tenderness.

Neurodevelopmental Disorders and Array-Based Comparative Genomic Hybridization: Sensitivity and Specificity using a Criteria Checklist for Genetic Test Performance.

BACKGROUND: Array-based comparative genomic hybridization (aCGH) is a molecular analysis method for identifying chromosomal anomalies or copy number variants (CNVs) correlating with clinical phenotypes. The aim of our study was to identify the most significant clinical variables associated with a positive outcome of aCGH analyses to develop a simple predictive clinical score. METHODS: We conducted a cross-sectional study in a tertiary center comparing the genotype and phenotype of the cases. A score was developed using multivariate logistic regression. The best score cutoff point, sensitivity, specificity, positive and negative predictive values, and area under the curve were calculated with the receiver operating characteristic curve. RESULTS: aCGH identified structural chromosomal alterations responsible for the disorder in 13.7% (95% confidence interval [CI]: 10.9-16.5) of our sample (570 patients analyzed by aCGH). Based on the most frequent phenotypic characteristics among patients with a pathogenic CNV, we have created a checklist with the following items: alteration of the cranial perimeter, stature < percentile (p) 3, weight < p3, presence of brain malformations, ophthalmological malformations, two or more dysmorphic features in the same patient, and autism spectrum disorder diagnosis. Using a score ≥1.5 as the cutoff point for the test, we obtained a sensitivity of 82.4% (95% CI: 73.1-91.8) and a specificity of 54.2% (95% CI: 49.7-58.7). CONCLUSION: All individuals with a score of 1.5 or higher should be genetically screened by aCGH. This approach can improve clinical indications for aCGH in patients with neurodevelopmental disorders, but the scoring system should be validated in an external group.

Causes of hospitalization and predictors of HIV-associated mortality at the main referral hospital in Sierra Leone: a prospective study.

BACKGROUND: HIV infection is a growing public health problem in Sierra Leone and the wider West Africa region. The countrywide HIV prevalence was estimated at 1.7% (67,000 people), with less than 30% receiving life-saving ART in 2016. Thus, HIV-infected patients tend to present to health facilities late, with high mortality risk. METHODS: We conducted a prospective study of HIV inpatients aged ≥15 years at Connaught Hospital in Freetown-the main referral hospital in Sierra Leone-from July through September 2017, to assess associated factors and predictors of HIV-related mortality. RESULTS: One hundred seventy-three HIV inpatients were included, accounting for 14.2% (173/1221) of all hospital admissions during the study period. The majority were female (59.5%, 70/173), median age was 34 years, with 51.4% (89/173) of them diagnosed with HIV infection for the first time during the current hospitalization. The most common admitting diagnoses were anemia (48%, 84/173), tuberculosis (24.3%, 42/173), pneumonia (17.3%, 30/173) and diarrheal illness (15.0%, 26/173). CD4 count was obtained in 64.7% (112/173) of patients, with median value of 87 cells/µL (IQR 25-266), and was further staged as severe immunosuppression: CD4 < 100 cells/µL (50%, 56/112); AIDS: CD4 < 200 cells/µL (69.6%, 78/112); and late-stage HIV disease: CD4 < 350 cells/µL (83%, 93/112). Fifty-two patients (30.1%, 52/173) died during hospitalization, 23% (12/52) of them within the first week. The leading causes of death were anemia (23.1%, 12/52), pneumonia (19.2%, 10/52), diarrheal illness (15.4%, 8/52) and tuberculosis (13.6%, 7/52). Neurological symptoms, i.e., loss of consciousness (p = 0.04) and focal limb weakness (p = 0.04); alcohol use (p = 0.01); jaundice (p = 0.02); cerebral toxoplasmosis (p = 0.01); and tuberculosis (p = 0.04) were significantly associated with mortality; however, only jaundice (AOR 0.11, 95% CI [0.02-0.65]; p = 0.01) emerged as an independent predictor of mortality. CONCLUSION: HIV-infected patients account for a substantial proportion of admissions at Connaught Hospital, with a high morbidity and in-hospital mortality burden. These findings necessitate the implementation of specific measures to enhance early HIV diagnosis and expand treatment access to all HIV-infected patients in Sierra Leone.

Efficacy of baths with mineral-medicinal water in patients with fibromyalgia: a randomized clinical trial.

The layout of this study, designed as a randomized crossover clinical trial, is to evaluate the efficacy of an intervention with mineral-medicinal water from As Burgas (Ourense) in patients suffering from fibromyalgia. This sample was randomly divided into two groups: group A and group B. In phase 1, group A had 14 baths in thermal water for a month and standard pharmacological treatment; group B, standard pharmacological treatment. Washout period is 3 months. In phase 2, group A had standard treatment and group B had 14 baths in thermal water for a month plus standard treatment. The Fibromyalgia Impact Questionnaire (FIQ) was used; this grades the impact of the illness from 1 (minimum) to 10 (maximum), which was measured in both phases. Twenty-five patients were included in each group and the study was concluded with 20 patients in group A and 20 in group B. The intervention group obtained, once the baths finished, a mean score of 60.3 (± 11.8) and the control group of 70.8 (± 13.0) (p < 0.001). Three months later, the intervention group presented a mean score of 64.4 (± 10.6) and the control group of 5.0 (± 11.3) (p < 0.001). We can therefore conclude that the simple baths with mineral-medicinal water from As Burgas can make an improvement on the impact caused by fibromyalgia.

Can endoscopic papillectomy be curative for early ampullary adenocarcinoma of the ampulla of Vater?

BACKGROUND: The therapeutic role of endoscopic papillectomy (EP) for early ampullary cancer (AC) is still controversial. The aim of the present study was to evaluate the curative potential of EP for early AC and to identify predictors of lymph node metastases (LNMs). METHODS: We retrospectively reviewed 173 patients who were prospectively included in a database and who underwent EP between 1999 and 2013. Adenocarcinoma was present in 28 resected specimens. An additional surgery was proposed in cases of duodenal submucosal infiltration, duct ingrowth, R1 resection or lymphovascular invasion. Clinicopathological information and outcomes were collected, and predictors of LNMs were evaluated. RESULTS: Duodenal submucosal invasion was present in 16/28 cases and LNMs, in 9/28 cases. ACs of the biliopancreatic subtype were smaller (NS); 100 % had submucosal invasion, and 71 % had LNMs. Smaller tumour size, biliopancreatic subtype and submucosal invasion were significantly correlated with LNMs (p < 0.028, p < 0.028 and p < 0.014). Predictive factors of LNMs in the multivariate analysis were submucosal invasion and tumour size (OR 0.032, p < 0.023 and OR 0.711, p < 0.035). EP was curative in 100 % of cancers with R0 resection and no evidence of submucosal or lymphovascular invasion. CONCLUSION: EP may be curative for patients with AC limited to the duodenal mucosa or the sphincter of Oddi without lymphovascular invasion. Due to the presence of more invasive stages at diagnosis, EP may not be curative for ACs of the biliopancreatic subtype. The significance of tumour size is limited by other confounders, such as the histological subtype.

Diagnostic accuracy of fibrinogen to differentiate appendicitis from nonspecific abdominal pain in children.

AIM: The aim of this study was to assess the diagnostic accuracy of the biomarker fibrinogen (FB), along with the more traditional markers white blood cell count (WBC), absolute neutrophil count (ANC), and C-reactive protein (CRP), to discriminate appendicitis from nonspecific abdominal pain (NSAP) in children. METHODS: We prospectively evaluated all children aged 5 to 15 years admitted for suspected appendicitis at an academic pediatric emergency department during 2 years. Diagnostic accuracy of FB (prothrombin time-derived method), WBC, ANC, and CRP was assessed by the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: A total of 275 patients were enrolled in the study (143 NSAP, 100 uncomplicated appendicitis, and 32 complicated appendicitis). WBC and ANC had a moderate diagnostic accuracy for appendicitis vs NSAP (WBC: AUC 0.79, ANC: AUC 0.79). FB and CPR had a poor diagnostic accuracy for appendicitis vs NSAP (FB: AUC 0.63, CRP: AUC 0.64) and a good diagnostic accuracy for complicated vs uncomplicated appendicitis (FB: AUC 0.86, CRP: AUC 0.90). All inflammatory markers had a good diagnostic accuracy for complicated appendicitis vs NSAP. CONCLUSIONS: WBC and ANC are useful inflammatory markers to discriminate appendicitis from NSAP. FB and CRP are not very useful to discriminate appendicitis from NSAP, but they discriminate properly complicated from uncomplicated appendicitis and NSAP, with a similar diagnostic accuracy. In a child with suspected appendicitis, a plasma FB level (prothrombin time-derived method) >520 mg/dL is associated to an increased likelihood of complicated appendicitis.