Analysis of a large SARS-CoV-2 (Alpha) outbreak in a Catalan prison using conventional and genomic epidemiology.

Enforcing strict protocols that prevent transmission of airborne infections in prisons is challenging. We examine a large SARS-CoV-2 outbreak in a Catalan penitentiary center from February-March 2021, prior to vaccination deployment. The aim was to describe the evolution of the outbreak using classical and genomic epidemiology and the containment strategy applied. The outbreak was initially detected in one module but spread to four, infecting 7 staff members and 140 incarcerated individuals, 6 of whom were hospitalized (4.4%). Genomic analysis confirmed a single origin (B.1.1.7). Contact tracing identified transmission vectors between modules and prevented further viral spread. In future similar scenarios, the control strategy described here may help limiting transmission of airborne infections in correctional settings.

A longitudinal prospective study of active tuberculosis in a Western Europe setting: insights and findings.

PURPOSE: This study investigates the potential of inflammatory parameters (IP), symptoms, and patient-related outcome measurements as biomarkers of severity and their ability to predict tuberculosis (TB) evolution. METHODS: People with TB were included prospectively in the Stage-TB study conducted at five clinical sites in Barcelona (Spain) between April 2018 and December 2021. Data on demographics, epidemiology, clinical features, microbiology, and Sanit George Respiratory Questionnaire (SGRQ) and Kessler-10 as Health-Related Quality of Life (HRQoL) were collected at three time points during treatment. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil/lymphocyte, and monocyte/lymphocyte ratios (NLR and MLR), complement factors C3, C4, and cH50, clinical and microbiological data, and HRQoL questionnaires were assessed at baseline, 2 months, and 6 months. Their ability to predict sputum culture conversion (SCC) and symptom presence after 2 months of treatment was also analysed. RESULTS: The study included 81 adults and 13 children with TB. The CRP, ESR, NLR, and MLR values, as well as the presence of symptoms, decreased significantly over time in both groups. Higher IP levels at baseline were associated with greater bacillary load and persistent symptoms. Clinical severity at baseline predicted a delayed SCC. Kessler-10 improved during follow-up, but self-reported lung impairment (SGRQ) persisted in all individuals after 6 months. CONCLUSIONS: IP levels may indicate disease severity, and sustained high levels are linked to lower treatment efficacy. Baseline clinical severity is the best predictor of SCC. Implementing health strategies to evaluate lung function and mental health throughout the disease process may be crucial for individuals with TB.

SARS-CoV-2 Secondary Attack Rates in Vaccinated and Unvaccinated Household Contacts during Replacement of Delta with Omicron Variant, Spain.

We performed a prospective, cross-sectional study of household contacts of symptomatic index case-patients with SARS-CoV-2 infection during the shift from Delta- to Omicron-dominant variants in Spain. We included 466 household contacts from 227 index cases. The secondary attack rate was 58.2% (95% CI 49.1%-62.6%) during the Delta-dominant period and 80.9% (95% CI 75.0%-86.9%) during the Omicron-dominant period. During the Delta-dominant period, unvaccinated contacts had higher probability of infection than vaccinated contacts (odds ratio 5.42, 95% CI 1.6-18.6), but this effect disappeared at ≈20 weeks after vaccination. Contacts showed a higher relative risk of infection (9.16, 95% CI 3.4-25.0) in the Omicron-dominant than Delta-dominant period when vaccinated within the previous 20 weeks. Our data suggest vaccine evasion might be a cause of rapid spread of the Omicron variant. We recommend a focus on developing vaccines with long-lasting protection against severe disease, rather than only against infectivity.

The interplay between infection risk factors of SARS-CoV-2 and mortality: a cross-sectional study from a cohort of long-term care nursing home residents.

BACKGROUND: Covid-19 pandemic has particularly affected older people living in Long-term Care settings in terms of infection and mortality. METHODS: We carried out a cross-sectional analysis within a cohort of Long-term care nursing home residents between March first and June thirty, 2020, who were ≥ 65 years old and on whom at least one PCR test was performed. Socio-demographic, comorbidities, and clinical data were recorded. Facility size and community incidence of SARS-CoV-2 were also considered. The outcomes of interest were infection (PCR positive) and death. RESULTS: A total of 8021 residents were included from 168 facilities. Mean age was 86.4 years (SD = 7.4). Women represented 74.1%. SARS-CoV-2 infection was detected in 27.7% of participants, and the overall case fatality rate was 11.3% (24.9% among those with a positive PCR test). Epidemiological factors related to risk of infection were larger facility size (pooled aOR 1.73; P < .001), higher community incidence (pooled aOR 1.67, P = .04), leading to a higher risk than the clinical factor of low level of functional dependence (aOR 1.22, P = .03). Epidemiological risk factors associated with mortality were male gender (aOR 1.75; P < .001), age (pooled aOR 1.16; P < .001), and higher community incidence (pooled aOR 1.19, P = < 0.001) whereas clinical factors were low level of functional dependence (aOR 2.42, P < .001), Complex Chronic Condition (aOR 1.29, P < .001) and dementia (aOR 1.33, P <0.001). There was evidence of clustering for facility and health area when considering the risk of infection and mortality (P < .001). CONCLUSIONS: Our results suggest a complex interplay between structural and individual factors regarding Covid-19 infection and its impact on mortality in nursing-home residents.

Is Madagascar at the edge of a generalised HIV epidemic? Situational analysis.

OBJECTIVES: To describe the epidemiological situation of the HIV/AIDS epidemic and to identify the main drivers for vulnerability in Madagascar. DESIGN: Literature review, qualitative research and situational analysis. DATA SOURCES: Search of electronic bibliographic databases, national repositories of documentation from 1998 to 2018. Search keywords included Madagascar, HIV, sexually transmitted infections, men who have sex with men (MSM), sex workers (SWs), transactional sex (TS), injecting drug users (IDUs), vulnerability and sexual behaviour. Qualitative sources were interviews and focus group discussions. REVIEW METHODS: Studies focused on HIV and/or vulnerability of HIV in Madagascar in general, and key populations (KPs) and HIV/AIDS response were taken into account. National reports from key HIV response actors were included. RESULTS: Madagascar is characterised by a low HIV/AIDS epidemic profile in the general population (GP) (0.3%) combined with a high prevalence of HIV among KPs (SWs, MSM and IDUs).An increase in HIV prevalence among KP has been observed during recent years. Hospital-based data suggest an increase in HIV prevalence among the GP. The vulnerability traits are inconsistent use of condoms, multipartner relationships and other contextual factors like widespread TS and gender inequality. A high prevalence/incidence of sexually transmitted infections could indicate a high vulnerability to HIV/AIDS. However, there are no reports of HIV prevalence of >1% in antenatal consultation. CONCLUSION: There is not enough evidence to make a conclusion about the HIV epidemiological situation in Madagascar due to the scarcity of the epidemiological data. However, Madagascar may be closer to a turning point towards a high-prevalence epidemic with severe consequences, particularly when taking into account its socioeconomical fragility and underlying vulnerabilities. More precise epidemiological data and improved HIV/AIDS diagnosis and case management should be a public health priority.

Long-term Evaluation of Fistulotomy and Immediate Sphincteroplasty as a Treatment for Complex Anal Fistula.

BACKGROUND: Fistulotomy with immediate sphincteroplasty is a technique that can heal fistulas and decrease fecal incontinence more effectively than fistulotomy alone, in selected patients. OBJECTIVE: We aimed to perform a long-term evaluation of fecal incontinence after fistulotomy and immediate sphincteroplasty in patients with complex anal fistula. DESIGN: This prospective study included patients undergoing fistulotomy and immediate sphincteroplasty for complex anal fistula from January 2000 to December 2010. SETTINGS: The study was conducted by 2 colorectal surgeons in the coloproctology unit of the General Hospital of Elche. PATIENTS: We included patients aged ≥18 years with complex anal fistulas of cryptoglandular origin. MAIN OUTCOME MEASURES: Main outcomes were recurrence and continence after fistulotomy and immediate sphincteroplasty, according to fistula tract height and preoperative continence status. RESULTS: A total of 107 patients were included; 68.2% were men, with a mean age of 48 years and mean fistula duration of 12.8 months. The range and median follow-up period were 84 to 204 and 96 months. Thirty-seven fistulas were not primary. The overall healing rate was 84.1%. Primary fistulas healed by the end of follow-up in 58 (82.9%) of 70 patients; recurrent fistulas healed in 32 (86.5%) of 37; high tracts healed in 31 (83.8%) of 37, and nonhigh fistulas healed in 59 (84.3%) of 70. Male sex (OR = 0.66 (95% CI, 0.20-2.13); p > 0.05) and recurrent fistulas (OR = 0.43 (95% CI, 0.11-1.68); p > 0.05) could have a protective effect against postoperative fecal incontinence; however, more studies with larger sample sizes are necessary to confirm this result, whereas high fistulas showed a 4-fold increased risk of incontinence (range, 1.22-13.06; p < 0.01). One in 5 high-tracts patients experienced continence deterioration. LIMITATIONS: This was a prospective study, and randomized clinical trials with more patients and longer follow-up are needed to compare fistulotomy and immediate sphincteroplasty with other sphincter-preserving techniques. CONCLUSIONS: Fistulotomy and immediate sphincteroplasty are good options for treating complex anal fistulas, especially for recurrent fistulas, men, and patients with nonhigh tracts, with acceptable recurrence and incontinence rates. See Video Abstract at http://links.lww.com/DCR/B498. EVALUACIN A LARGO PLAZO DE LA FISTULOTOMA Y LA ESFINTEROPLASTIA INMEDIATA COMO TRATAMIENTO PARA LA FSTULA ANAL COMPLEJA: ANTECEDENTES:La fistulotomía y la esfinteroplastia inmediata es una técnica que puede curar las fístulas y disminuir la incontinencia fecal de manera más efectiva que la fistulotomía sola, en pacientes seleccionados.OBJETIVO:Nuestro objetivo fue realizar una evaluación a largo plazo de la incontinencia fecal después de la fistulotomía y la esfinteroplastia inmediata en pacientes con fístula anal compleja.DISEÑO:Este estudio prospectivo incluyó pacientes sometidos a fistulotomía y esfinteroplastia inmediata por fístula anal compleja, desde enero de 2000 hasta diciembre de 2010.ENTORNO CLINICO:El estudio fue realizado por dos cirujanos colorrectales de la Unidad de Coloproctología del Hospital General de Elche.PACIENTES:Se incluyeron pacientes ≥ 18 años con fístulas anales complejas de origen criptoglandular.PRINCIPALES MEDIDAS DE VALORACION:Los principales resultados fueron la recurrencia y la continencia después de la fistulotomía y la esfinteroplastia inmediata, de acuerdo con la altura del trayecto de la fístula y el estado de continencia preoperatoria.RESULTADOS:Se incluyeron un total de 107 pacientes; El 68,2% eran varones, con una edad media de 48 años y una duración media de la fístula de 12,8 meses. El rango y la mediana del período de seguimiento fue de 84-204 y 96 meses, respectivamente. Treinta y siete fístulas no fueron primarias. La tasa de curación general fue del 84,1%. Las fístulas primarias cicatrizaron al final del seguimiento en 58/70 (82,9%) pacientes; las fístulas recurrentes cicatrizaron en 32/37 (86,5%); los tractos altos cicatrizaron en 31/37 (83,8%) y las fístulas no altas cicatrizaron en 59/70 (84,3%). El sexo masculino (razón de posibilidades: 0,66 [0,20-2,13], p > 0,05) y las fístulas recurrentes (razón de posibilidades: 0,43 [0,11-1,68], p > 0,05) podrían tener un efecto protector contra la incontinencia fecal postoperatoria, sin embargo, más estudios con una muestra más grande son necesarios para confirmar este resultado. Fistulas altas mostraron un riesgo cuatro veces mayor de incontinencia ([1.22-13.06], p < 0.01). Uno de cada cinco pacientes con tractos altos experimentó un deterioro de la continencia.LIMITACIONES:Este fue un estudio prospectivo y se necesitan ensayos clínicos aleatorios con más pacientes y un seguimiento más prolongado para comparar la fistulotomía y la esfinteroplastia inmediata con otras técnicas de preservación del esfínter.CONCLUSIÓN:La fistulotomía y la esfinteroplastia inmediata son buenas opciones para el tratamiento de fístulas anales complejas, especialmente para fístulas recurrentes, varones y pacientes con tractos no altos, con tasas aceptables de recurrencia e incontinencia. Consulte Video Resumen en http://links.lww.com/DCR/B498.

Effect of home-based prehabilitation in an enhanced recovery after surgery program for patients undergoing colorectal cancer surgery during the COVID-19 pandemic.

BACKGROUND: Surgery remains the first curative treatment for colorectal cancer. Prehabilitation seems to attenuate the loss of lean mass in the early postoperative period. However, its long-term role has not been studied. Lockdown due to the COVID-19 pandemic has forced to carry out the prehabilitation program at home. This study aimed to assess the effect of home prehabilitation on body composition, complications, and hospital stay in patients undergoing oncological colorectal surgery. METHODS: A prospective and randomized clinical study was conducted in 20 patients operated of colorectal cancer during COVID-19 lockdown (13 March to 21 June 2020) in a single university clinical hospital. Patients were randomized into two study groups (10 per group): prehabilitation vs standard care. Changes in lean mass and fat mass at 45 and 90 days after surgery were measured using multifrequency bioelectrical impedance analysis. RESULTS: Prehabilitation managed to reduce hospital stay (4.8 vs 7.2 days, p = 0.052) and postoperative complications (20% vs 50%, p = 0.16). Forty-five days after surgery, the loss of lean mass decreased (1.7% vs 7.1%, p = 0.17). These differences in lean mass were attenuated at 90 days; however, the standard care group increased considerably their fat mass compared to the prehabilitation group (+ 8.72% vs - 8.16%). CONCLUSIONS: Home prehabilitation has proven its effectiveness, achieving an attenuation of lean mass loss in the early postoperative period and a lower gain in fat mass in the late postoperative period. In addition, it has managed to reduce hospital stays and postoperative complications. REGISTRATION NUMBER: This article is part of an ongoing, randomized, and controlled clinical trial approved by the ethics committee of our hospital and registered in ClinicalTrials.gov in August 2018 with registration number NCT03618329.

Photodynamic Therapy for the Treatment of Complex Anal Fistula.

BACKGROUND AND OBJECTIVES: To validate and analyze the results of intralesional photodynamic therapy in the treatment of complex anal fistula. STUDY DESIGN/MATERIALS AND METHODS: This prospective multicentric observational study enrolled patients treated for complex anal fistula who underwent intralesional photodynamic therapy (i-PDT). The included patients were treated from January 2016 to December 2018 with a minimum follow-up of 1 year to evaluate recurrence, continence and postoperative morbidity. Intralesional 5-aminolevulinic acid (ALA) gel (2%) was injected directly into the fistula. The internal and external orifices were closed. After an incubation period of 2 hours, the fistula was irradiated using an optical fiber connected to a red laser (Multidiode 630 PDT) operating at 1 W/cm for 3 minutes (180 J). RESULTS: In total, 49 patients were included (61.2% male). The mean age was 48 years, and the mean duration of fistula was 13 months. Of the fistulas included, 75.5% were medium transphincteric, and 24.5% were high transphincteric. The median fistula length was 4 ± 1,14 cm (range: 3-5). A total of 41 patients (83.7%) had a previous history of fistula surgery. Preoperatively, some degree of anal incontinence was found in 5 patients (10.2%). No center reported any other procedure-related complications intraoperatively. Phototoxicity was found in one patient. In the first 48 hours after the procedure, fever was reported in 2 patients (4%). At the end of follow-up, total healing was observed in 32/49 patients (65.3%). No patient reported new incontinence postoperatively. CONCLUSION: i-PDT could be considered a good choice in patients with complex anal fistulas to avoid surgery and its complications. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Clinical relevance of monitoring serum adalimumab levels in axial spondyloarthritis.

Our aim was to assess the relationship between serum adalimumab levels, anti-drug antibodies (ADA) and disease activity in patients with axial spondylarthritis (SpA). We have carried out a single-centre cross-sectional study. adalimumab and ADA levels were analysed with ELISA and correlated with SpA activity using BASDAI and ASDAS scores. Adalimumab cut-off value was calculated to discriminate inactive disease/low disease activity (BASDAI < 4; ASDAS < 2.1) from moderate/high disease activity (BASDAI ≥ 4; ASDAS ≥ 2.1), using a receiver operating characteristic (ROC) curve. Up to January 2016, 51 consecutive patients were included. The median (range) age was 46.6 (18-68) and 47.1% were women. ADA prevalence was 27.5%, with none detected in the 21.6% receiving concomitant disease-modifying antirheumatic drugs (DMARDs) (p = 0.021). Adalimumab level was normal (> 3 mg/l) in 36 patients (70.6%), all without ADA. Fifteen patients (29.4%) had subtherapeutic adalimumab levels (< 3 mg/l), with ADA in 14 (93%). Median adalimumab (mg/l) was significantly higher in patients with inactive disease/low disease activity: BASDAI < 4 vs ≥ 4: 9.5 vs 2.6 (p < 0.01); ASDAS-CRP < 2.1 vs ≥ 2.1: 9.3 vs 0.3 (p < 0.001); ASDAS-ESR < 2.1 vs ≥ 2.1: 9.9 vs 3.0 (p < 0.001), and this finding was consistent with the result of the multivariate model. Patients with inactive disease/low disease activity presented significantly lower ADA levels. The adalimumab level cut-offs and area under the curve (AUC) obtained in the ROC curves were: ASDAS-CRP (< 2.1) 4.6 mg/l (AUC 81.2%; 95% CI 67.5-94.9; p < 0.001); ASDAS-ESR (< 2.1) 7.7 mg/l (AUC 82.4%; 95% CI 69.3-95.5; p < 0.001); BASDAI (< 4) 6.4 mg/l (AUC 73.5%; 95% CI 58.6-88.3; p < 0.01). In conclusion, presence of ADA in axial SpA patients treated with adalimumab was associated with lower serum drug levels. ADA levels were lower and adalimumab levels were higher in patients with inactive disease/low disease activity based on BASDAI and ASDAS indices. Concomitant treatment with MTX reduces de likelihood of finding ADA. Serum adalimumab levels above 4.6 mg/l are recommended to avoid compromising efficacy.

Colon-specific eQTL analysis to inform on functional SNPs.

BACKGROUND: Genome-wide association studies on colorectal cancer have identified more than 60 susceptibility loci, but for most of them there is no clear knowledge of functionality or the underlying gene responsible for the risk modification. Expression quantitative trail loci (eQTL) may provide functional information for such single nucleotide polymorphisms (SNPs). METHODS: We have performed detailed eQTL analysis specific for colon tissue on a series of 97 colon tumours, their paired adjacent normal mucosa and 47 colon mucosa samples donated by healthy individuals. R package MatrixEQTL was used to search for genome-wide cis-eQTL and trans-eQTL fitting linear models adjusted for age, gender and tissue type to rank transformed expression data. RESULTS: The cis-eQTL analyses has revealed 29,073 SNP-gene associations with permutation-adjusted P-values < 0.01. These correspond to 363 unique genes. The trans-eQTL analysis identified 10,665 significant SNP-gene associations, most of them in the same chromosome, further than 1 Mb of the gene. We provide a web tool to search for specific SNPs or genes. The tool calculates Pearson or Spearman correlation, and allows to select tissue type for analysis. Data and plots can be exported. CONCLUSIONS: This resource should be useful to prioritise SNPs for further functional studies and to identify relevant genes behind identified loci.

Obesity decreases clinical efficacy and levels of adalimumab in patients with ankylosing spondylitis.

OBJECTIVES: Obesity can be a factor that affects response to anti-TNF drugs. However, studies on patients with ankylosing spondylitis (AS) are rare. We aimed to determine whether obesity affects serum levels of adalimumab (ADL), and immunogenicity and clinical efficacy of the drug in patients with AS. METHODS: A cross-sectional study on 57 patients with axial AS receiving ADL was conducted. They received DMARD per standard of care at their rheumatologist's discretion. Patients' body mass index (BMI) was obtained when ADL treatment began. Clinical response was evaluated using the Spanish versions of the BASDAI index and the ASDAS ESR index. Serum concentrations of free ADL (trough level) and anti-ADL antibodies were measured using Promonitor-ADL and Promonitor Anti-ADL ELISA kits (Progenika Grifols SA, Spain), just prior to the next subcutaneous injection of ADL. RESULTS: Patients with BMI >30 kg/ m2 (obese) as opposed to BMI <25 kg/ m2 (normal), presented lower blood ADL levels [5.0 (5.52) vs. 9.14 (4.3), p=0.032], increased ASDAS scores (2.58 [0.79] vs. 1.9 [0.83], p=0.03), and shorter ADL treatment time: 1.01 [0.84] vs. (1.85 [1.65]; p=0.08]), and increased BASDAI results (5.04 [2.5] vs. 3.5 [1.88]; p=0.06). Obese patients showed a lower probability of clinical response to ADL versus non-obese patients with regard to achieving BASDAI ≤4 (OR: 3.5, 95%CI: 0.84-17.19; p=0.05) or ASDAS ≤2.1 (OR: 4.64, 95%CI: 1.02-24.13; p=0.02). CONCLUSIONS: Of the AS patients receiving treatment with ADL, those that are obese had significantly lower serum ADL levels and decreased clinical response without an increase in immunogenicity.

Network analysis of knowledge and practices regarding sexual and reproductive health: a study among adolescent street girls in Kinshasa (DRC).

OBJECTIVES: The aim of the study was to ascertain the influence of knowledge and interventions in sexual and reproductive health and contraception practices among adolescent street girls from Kinshasa, Democratic Republic of the Congo. METHODS: A cross-sectional study was carried out among street girls between 12 and 21 years of age. A standardised questionnaire was used, encompassing socio-demographic data and knowledge and practices regarding sexual and reproductive health. A network analysis was carried out. RESULTS: The study comprised 293 street girls. The mean age was 17.1 years (range 12-21 years) and the mean time spent living on the streets was 3.9 years (range 0-15 years). Commercial sex was reported by 78.5% (95% confidence interval [CI] 73.3%, 83.2%) as the main source of their income. During their last sexual intercourse, 44.0% (95%CI 38.1%, 50.4%) had not used a condom; 29.3% (95%CI 23.3%, 35.9%) had used hormonal contraception. Previous pregnancy was reported by 62.5% (95%CI 56.7%, 68.3%) and current pregnancy by 12.3% (95%CI 8.8%, 17.2%); 24.5% of previous pregnancies ended in voluntary termination, with a higher rate among the youngest street girls (12-15 years, 50.0%; p = 0.01). Time spent living on the streets was independently associated with pregnancy (odds ratio 1.2; 95%CI 1.1, 1.4). Practices and outcomes (previous or current pregnancy) were poorly correlated with knowledge about sexual and reproductive health. The network analysis confirmed the poor influence of exposure to intervention activities on sexual and reproductive health practices and outcomes, but did confirm a centrality effect of knowledge about HIV/AIDS. CONCLUSION: Street girls in Kinshasa are extremely vulnerable with regard to their sexual and reproductive health, especially the youngest street girls. Behavioural and biomedical interventions have had limited influence. Structural and societal changes are necessary to positively impact street girls' sexual and reproductive health. Knowledge about HIV/AIDS than about risk of pregnancy had a greater influence on sexual and reproductive health practices.

Predicting treatment failure in patients with community acquired pneumonia: a case-control study.

INTRODUCTION: Treatment failure in community-acquired-pneumonia (CAP) patients is associated with a high mortality rate, and therefore are a matter of great concern in clinical management. Those patients have increased mortality and are a target population for randomized clinical trials. METHODS: A case-control study was performed in patients with CAP (non-failure cases vs. failure cases, discriminating by late and early failure). CRP, PCT, interleukin 1, 6, 8 and 10 and TNF were determined at days 1 and 3 of hospitalization. RESULTS: A total of 253 patients were included in this study where 83 patients presented treatment failure. Of these, 40 (48.2%) had early failure. A discriminative effect was found for a higher CURB-65 score among late failure patients (p = 0.004). A significant increase on day 1 of hospitalization in CRP (p < 0.001), PCT (p = 0.004), IL-6 (p < 0.001) and IL-8 (p = 0.02), and a decrease in IL-1 (p = 0.06) in patients with failure was observed compared with patients without failure. On day 3, only the increase in CRP (p < 0.001), PCT (p = 0.007) and IL-6 (p < 0.001) remained significant. Independent predictors for early failure were higher IL-6 levels on day 1 (OR = 1.78, IC = 1.2-2.6) and pleural effusion (OR = 2.25, IC = 1.0-5.3), and for late failure, higher PCT levels on day 3 (OR = 1.60, IC = 1.0-2.5), CURB-65 score ≥ 3 (OR = 1.43, IC = 1.0-2.0), and multilobar involvement (OR = 4.50, IC = 2.1-9.9). CONCLUSIONS: There was a good correlation of IL-6 levels and CAP failure and IL-6 & PCT with late CAP failure. Pleural effusion and multilobar involvement were simple clinical predictors of early and late failure, respectively. TRIAL REGISTRATION: IRB Register: http://2009/5451.

Clinical relevance of monitoring serum levels of adalimumab in patients with rheumatoid arthritis in daily practice.

OBJECTIVES: The aim of this paper is to assess the usefulness of measuring serum levels of adalimumab (ADL) and anti-ADL antibodies in 57 patients with rheumatoid arthritis (RA) treated with ADL for at least 3 months in daily practice. METHODS: All patients received concomitant disease-modifying anti-rheumatic drug (DMARD). Receiver-operator characteristics (ROC) analysis was used to obtain the cut-off value of ADL for low disease activity (DAS28-ESR ≤3.2). RESULTS: Anti-ADL antibodies were detected in 4 (7%) patients with a mean (SD) DAS28 score of 4.6 (0.9). Patients with positive anti-ADL antibodies had significantly lower levels of ADL and higher DAS28 scores than those with negative antibodies. Patients with DAS28 ≤3.2 as compared with patients with DAS28 >3.2 showed significantly better SDAI score, higher serum concentrations of ADL and none of them showed anti-ADL antibodies. The cut-off of serum level of ADL for DAS28 <3.2 was 4.3 mg/L. According to serum levels of ADL, patients were grouped into group 1 (low level) <5.5 mg/L, group 2 (medium level) 5.5-11.3 mg/L and group 3 (high level) >11.3 mg/L. Patients in the medium group were closed to clinical remission (median DAS28 2.7) and patients in the high group were on clinical remission (DAS28 2.1). CONCLUSIONS: Serum levels of ADL should be maintained >4.3 mg/L. In patients with ADL levels >11.3 mg/L, a decrease of the dose of ADL or an increase in the interval between doses may be planned. The presence of anti-ADL antibodies was associated with a loss of clinical efficacy of ADL.

Practical application of acid dissociation in monitoring patients treated with adalimumab.

Patients treated with adalimumab (ADL) can induce anti-ADL antibodies (AAA) formation that is associated with low drug levels and clinical non-response. But, in the majority of the assays, the measurement of AAA is hampered by the presence of the drug itself. In support of immunogenicity assessment in clinical samples with subtherapeutic ADL levels, we proved acid pre-treatment for AAA detection with the Promonitor-enzyme-linked immunosorbent assay (ELISA). Were measured AAA after acidification in 32 serum samples with a subtherapeutic ADL trough level. ADL and AAA concentrations were measured by ELISA (Promonitor). The impact of drug concentration on AAA recovery (with or without acidification) was also evaluated by mixing known amounts of ADL (0.25, 0.5 and 1 mg/L) and AAA (100, 200, 300 and 400 AU/mL) from clinical samples in pooled serum. The drug significantly inhibited the detection of AAA in untreated samples. And progressively higher levels of ADL cause increasing inhibition of signal. Acid pre-treatment carried a significant increase in assay response, particularly at lower free ADL concentrations. AAA were detected in the 53 % of the samples after acid dissociation. In seven patients, the positive AAA after dissociation was detected in the first monitoring of ADL and five patients were positive 3 months later for AAA with the standard assay. Monitoring AAA using acid dissociation in patients with subtherapeutic circulating level of ADL could detect precocious problems of bioavailability, assess the immunogenicity of ADL and may be used to optimise dose regimens, thereby preventing prolonged use of inadequate therapy and guide change of treatment.

Diabetes mellitus as a cause of premature death in small areas of Spain by socioeconomic level from 2016 to 2020: A multiple-cause approach.

OBJECTIVE: This study aimed to assess premature mortality due to Diabetes in small areas of Spain between 2016 and 2020, and its relationship with socioeconomic level and the immediate cause of death. As a secondary objective, we evaluated the effect of the Covid 19 pandemic. METHODS: This was an ecological study of premature mortality due to Diabetes from 2016 to 2020, with a focus on small areas. All deaths in people under 75 years of age due to Diabetes as the underlying cause were included RESULTS: The final sample comprised 7382 premature deaths in 5967 census tracts. Women living in census tracts with an high level of deprivation(RR=2.40) were at a significantly higher risk. Mortality from Diabetes increased with deprivation, especially people aged 0-54(RR=2.40). People with an immediate cause of death related to a circulatory disease, living in census tracts with an high level of deprivation(RR=3.86) was associated with a significantly greater risk of death with underlying Diabetes. When a disease of the circulatory system was recorded as the immediate cause of death, being 65-74 years (RR=71.01) was associated with a significantly higher risk of premature mortality. CONCLUSIONS: Living in geographic areas with higher levels of socioeconomic deprivation is associated with a higher risk of premature death from Diabetes in Spain. This relationship has a greater impact on women, people under 54 years, and people at risk of death caused directly by diseases of the circulatory system. Premature mortality due to diabetes saw a modest increase in 2020.

Male genitourinary schistosomiasis-related symptoms among long-term Western African migrants in Spain: a prospective population-based screening study.

BACKGROUND: Schistosomiasis is highly endemic in sub-Saharan Africa and frequently imported to Europe. Male urogenital manifestations are often neglected. We aimed to ascertain the prevalence of genitourinary clinical signs and symptoms among long-term African migrants in a non-endemic European country using a serology test. METHODS: We carried out a prospective, community-based cross-sectional study of adult male migrants from sub-Saharan Africa living in Spain. Schistosoma serology tests and microscopic urine examinations were carried out, and clinical data were obtained from an electronic medical record search and a structured questionnaire. RESULTS: We included 388 adult males, mean age 43.5 years [Standard Deviation (SD) = 12.0, range: 18-76]. The median time since migration to the European Union was 17 [Interquartile range (IQR): 11-21] years. The most frequent country of origin was Senegal (N = 179, 46.1%). Of the 338, 147 (37.6%) tested positive for Schistosoma. Parasite eggs were present in the urine of only 1.3%. Nine genitourinary clinical items were significantly associated with positive Schistosoma serology results: pelvic pain (45.2%; OR = 1.57, 95% CI: 1.0-2.4), pain on ejaculation (14.5%; OR = 1.85, 95% CI: 1.0-3.5), dyspareunia (12.4%; OR = 2.45, 95% CI: 1.2-5.2), erectile dysfunction (9.5%; OR = 3.10, 95% CI: 1.3-7.6), self-reported episodes of infertility (32.1%; OR = 1.69, 95% CI: 1.0-2.8), haematuria (55.2%; OR = 2.37, 95% CI: 1.5-3.6), dysuria (52.1%; OR = 2.01, 95% CI: 1.3-3.1), undiagnosed syndromic STIs (5.4%), and orchitis (20.7%; OR = 1.81, 95% CI: 1.0-3.1). Clinical signs tended to cluster. CONCLUSIONS: Urogenital clinical signs and symptoms are prevalent among male African long-term migrants with a positive Schistosoma serology results. Genital involvement can be frequent even among those with long periods of non-residence in their sub-Saharan African countries of origin. Further research is needed to develop diagnostic tools and validate therapeutic approaches to chronic schistosomiasis.

A potential transition from a concentrated to a generalized HIV epidemic: the case of Madagascar.

BACKGROUND: HIV expansion is controlled by a range of interrelated factors, including the natural history of HIV infection and socio-economical and structural factors. However, how they dynamically interact in particular contexts to drive a transition from concentrated HIV epidemics in vulnerable groups to generalized epidemics is poorly understood. We aim to explore these mechanisms, using Madagascar as a case-study. METHODS: We developed a compartmental dynamic model using available data from Madagascar, a country with a contrasting concentrated epidemic, to explore the interaction between these factors with special consideration of commercial and transactional sex as HIV-infection drivers. RESULTS: The model predicts sigmoidal-like prevalence curves with turning points within years 2020-2022, and prevalence reaching stabilization by 2033 within 9 to 24% in the studied (10 out of 11) cities, similar to high-prevalence regions in Southern Africa. The late/slow introduction of HIV and  circumcision, a widespread traditional practice in Madagascar, could have slowed down HIV propagation, but, given the key interplay between risky behaviors associated to young women and acute infections prevalence, mediated by transactional sex, the protective effect of circumcision is currently insufficient to contain the expansion of the disease in Madagascar. CONCLUSIONS: These results suggest that Madagascar may be experiencing a silent transition from a concentrated to a generalized HIV epidemic. This case-study model could help to understand how this HIV epidemic transition occurs.

Zika virus screening during pregnancy: Results and lessons learned from a screening program and a post-delivery follow-up analysis (2016-2022).

OBJECTIVE: To evaluate a Zika virus screening program applied to asymptomatic exposed pregnant women. METHODOLOGY: Analysis of data generated during the roll out of a Zika screening program. We included socio-demographic data, ultrasounds, and serological results (IgM, IgG, and Plaque Reduction Neutralization Test; PRNT) from asymptomatic pregnant women exposed to Zika virus enrolled in the screening program between 2016 to 2019. RESULTS: We included 406 asymptomatic ZIKV-exposed pregnant women who gave 400 full-term new-borns. The median age was 30 years (IQR = 25-34), which was lower (29 years; IQR = 24-34) among women of non-EU migrant origin (76.4% of the sample). Migrant women tended to delay the first pre-natal consultation compared to EU origin women (p = .003). Overall, 83.2% (N = 328) of participants had ZIKV low risk serological profile (IgM-/IgG- or IgM-/IgG+ and PRNT-), 3.0% (N = 12) showed high risk of recent ZIKV infection (IgM+ or PRNT+) and 13.7% (N = 54) had indeterminate results. A fetal malformation was identified in 29 children (9.3%). Fetal malformation was associated with a ZIKV high risk serological profile [24 out of the 246 (1.6%) with low risk profile and 3 out of the 12 with at high risk profile (25.0%; p = .02)]. Four newborns with high risk profile had a positive ZIKV-PCR test, which included two cases with microcephaly. No association was observed between maternal exposure to ZIKV infection and developmental abnormalities during the post-natal period follow-up. CONCLUSIONS: The ZIKV-screening program had considerable costs and yielded a high rate of indeterminate results among asymptomatic pregnant women. Considering the poor value for decision-making of the results, efforts should focus on providing early access to routine maternity care, especially to migrant women. A simpler screening protocol might consider an initial ZIKV-PCR or IgM determination and subsequent referral to a fetal medicine specialist in those women with a positive result and/or whom ultrasound examination has revealed fetal abnormalities (10% of total women in our study sample).

Corrigendum: Disseminated tuberculosis and diagnosis delay during the COVID-19 era in a Western European country: a case series analysis.

[This corrects the article DOI: 10.3389/fpubh.2023.1175482.].