Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project.

BACKGROUND: The PI*S variant is one of the most prevalent mutations within alpha-1 antitrypsin deficiency (AATD). The risk of developing AATD-related lung disease in individuals with the PI*SS genotype is poorly defined despite its substantial prevalence. Our study aimed to characterize this genotype and its risk for lung disease and compare it with the PI*ZZ and PI*SZ genotypes using data from the European Alpha-1 antitrypsin Deficiency Research Collaboration international registry. METHOD: Demographic, clinical, functional, and quality of life (QoL) parameters were assessed to compare the PI*SS characteristics with the PI*SZ and PI*ZZ controls. A propensity score with 1:3 nearest-neighbour matching was performed for the most important confounding variables. RESULTS: The study included 1007 individuals, with PI*SS (n = 56; 5.6%), PI*ZZ (n = 578; 57.4%) and PI*SZ (n = 373; 37.0%). The PI*SS population consisted of 58.9% men, with a mean age of 59.2 years and a mean FEV1(% predicted) of 83.4%. Compared to PI*ZZ individuals they had less frequent lung disease (71.4% vs. 82.2%, p = 0.037), COPD (41.4% vs. 60%, p = 0.002), and emphysema (23.2% vs. 51.9%, p < 0.001) and better preserved lung function, fewer exacerbations, lower level of dyspnoea, and better QoL. In contrast, no significant differences were found in the prevalence of lung diseases between PI*SS and PI*SZ, or lung function parameters, exacerbations, dyspnoea, or QoL. CONCLUSIONS: We found that, as expected, the risk of lung disease associated with the PI*SS genotype is significantly lower compared with PI*ZZ, but does not differ from that observed in PI*SZ individuals, despite having higher serum AAT levels. TRIAL REGISTRATION: www. CLINICALTRIALS: gov (ID: NCT04180319).

Kloos Syndrome (Paralysis of Time). A Psychopathological Rare Case.

A case of Kloos syndrome is presented, a rare psychopathological manifestation in psychiatry characterized by the experience of "time paralysis" related to an epileptic focus in the left temporoparietal areas. This syndrome was identified through a detailed psychopathological analysis and detected by an electroencephalographic record. The patient's symptoms disappeared after receiving antiepileptic treatment with Carbamazepine. In this case report we highlight the detailed phenomenological and clinical analysis, as well as the importance of carrying out complementary tests when we are faced with unusual or sudden-onset symptoms without any trigger, as took place in the case exposed.

Hypersensitivity pneumonitis: application of a new diagnostic algorithm to a time series of the disease.

BACKGROUND: The diagnostic criteria for Hypersensitivity pneumonitis (HP) have changed over time. Our aim is to apply a recent diagnostic algorithm to a historical series of patients diagnosed with HP to assess its distribution according to current diagnostic criteria and the diagnostic confidence achieved. RESEARCH DESIGN AND METHODS: Application to each patient the algorithm criteria. The diagnosis was HP (≥90%), provisional high (70-89%) or low confidence (51-69%) or non-HP (unlikely) (≤50%); or HP, provisional or non-HP, if they had lung biopsy. RESULTS: 129 patients [mean age 64 ± 12 years; 79 (61.2%) women] were included of which 16 (12.4%) were diagnosed on the basis of high clinical suspicion. After applying the algorithm, 106 patients (82.2%) could be evaluated and 83 (78.3%) had a diagnosis of HP or high confidence. Lung biopsy was able to establish a diagnosis of certainty in another 21 patients and a provisional diagnosis in 9 more [total, 113 (87.6%)]. The 16 patients without strict diagnostic criteria for HP had a low confidence diagnosis. A total of 56 lung biopsies (64.4%) could have been avoided according to the new guidelines. CONCLUSIONS: The application of this algorithm achieves a high diagnostic yield in HP, significantly reducing the number of lung biopsies required.

Analysis of the quality of e-Consultations in chronic obstructive pulmonary disease.

INTRODUCTION: The quality of e-Consultations in the COPD is unknown. The objectives of this study were (i) to evaluate the quality of referrals; (ii) to define the characteristics of patients referred from Primary Care (PC) to the Unit of Pulmonology; and (iii) to describe differences between accepted and rejected patients. METHODS: A retrospective, observational study of e-Consultations requested by PC for suspected COPD throughout 2022. To quantify the quality of the e-Consultations, an arbitrary scale of 12 variables (score 0-10) was created. RESULTS: In total, 384 e-Consultations were reviewed, of which 167 (43.5 %) resulted in a face-to-face visit, and 217 (56.5 %) were rejected. No differences were observed between the two types of patients, except for confirmations of diagnostic suspicion of COPD [significantly higher in accepted patients (p = 0.042)]; physical examination data of rejected patients (more data provided; p = 0.015); and lung function (significantly better in rejected patients). The mean quality of referrals was acceptable (5.6 ± 2.1 score): 121 (31.3 %) had insufficient quality; 118 (30.5 %) acceptable; 75 (19.4 %) good, and 30 (7.8 %) excellent. Quality was low in half of the variables analyzed (6/12); acceptable in 3, and good in another 3. The capacity of resolution of referrals was good (one e-Consultation) in 199 requests (66.1 %); deficient (two e-Consultations) in 72 (23.9 %), and poor (≥3 e-Consultations) in 30 (10 %). Overdiagnosis was 40.2 % (86/214 e-Consultations). The risk could be classified in 247 patients (64.3 %; 135 low-risk; 90 high-risk). CONCLUSIONS: When adequate information is provided, e-Consultations help identify different levels of severity. However, the quality and capacity of resolution of referrals were suboptimal, with a high percentage of overdiagnoses.

A pulmonary rehabilitation program reduces hospitalizations in chronic obstructive pulmonary disease patients: A cost-effectiveness study.

BACKGROUND: Although pulmonary rehabilitation (PR) is recommended in patients with chronic obstructive pulmonary disease (COPD), there is a scarcity of data demonstrating the cost-effectiveness and effectiveness of PR in reducing exacerbations. METHODS: A quasi-experimental study in 200 patients with COPD was conducted to determine the number of exacerbations 1 year before and after their participation in a PR program. Quality of life was measured using the COPD assessment test and EuroQol-5D. The costs of the program and exacerbations were assessed the year before and after participation in the PR program. The incremental cost-effectiveness ratio (ICER) was estimated in terms of quality-adjusted life years (QALYs). RESULTS: The number of admissions, length of hospital stay, and admissions to the emergency department decreased after participation in the PR program by 48.2%, 46.6%, and 42.5%, respectively (P < 0.001 for all). Results on quality of life tests improved significantly (P < 0.001 for the two tests). The cost of PR per patient and the cost of pre-PR and post-PR exacerbations were €1867.7 and €7895.2 and €4201.9, respectively. The PR resulted in a cost saving of €1826 (total, €365,200) per patient/year, and the gain in QALYs was+0.107. ICER was -€17,056. The total cost was <€20,000/QALY in 78% of patients. CONCLUSIONS: PR contributes to reducing the number of exacerbations in patients with COPD, thereby slowing clinical deterioration. In addition, it is cost-effective in terms of QALYs.

Clinical Outcomes with Extended Depth of Focus Intraocular Lenses in Cases in Which Multifocal Lenses Are Not Primarily Recommended.

Purpose: The purpose of the study is to evaluate the visual and patient-reported outcomes of patients undergoing cataract surgery with implantation of an extended depth of focus (EDOF) intraocular lens (IOL) who were not primarily good candidates for multifocal IOL implantation. Methods: Retrospective analysis of data from 30 eyes (23 patients) undergoing cataract surgery with implantation of one of two EDOF IOLs (follow-up: 37.9 ± 16.2 months) and prospective observational study including 106 eyes (78 patients) implanted with one of 6 different EDOF models (follow-up: 8.0 ± 7.7 months). Patients recruited had one of the following conditions: monofocal IOL implanted in the fellow eye, previous corneal refractive surgery, mild and nonprogressive maculopathy or glaucoma, age > 75 years, amblyopia, or previous vitrectomy. Results: In the retrospective phase, significant improvements were found in uncorrected distance (UDVA), corrected distance (CDVA), and corrected near visual acuity (CNVA) (p ≤ 0.013), with a nonsignificant trend to improvement in uncorrected near visual acuity (UNVA). A total of 90% of patients were completely to moderately satisfied with the outcome achieved. In the prospective phase, significant improvements were found in UDVA, CDVA, UNVA, and CNVA (p ≤ 0.032), with a total of 85.5% of patients being completely to moderately satisfied (dissatisfaction 3.3%). In both phases, extreme difficulties were only reported by a limited percentage of patients for performing some near vision activities. Conclusions: EDOF IOLs seem to be a viable option for providing an efficient visual rehabilitation with good levels of patient satisfaction and spectacle independence associated in patients that are not primarily good candidates for multifocal IOL implantation.

Clinical characteristics of chronic obstructive pulmonary disease in never-smokers: A systematic review.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is the third cause of death worldwide. While tobacco smoking is a key risk factor, COPD also occurs in never-smokers (NS). However, available evidence on risk factors, clinical characteristics, and natural history of the disease in NS is scarce. Here, we perform a systematic review of the literature to better describe the characteristics of COPD in NS. METHODS: We searched different databases following the PRISMA guidelines with explicit inclusion and exclusion criteria. A purpose-designed quality scale was applied to the studies included in the analysis. It was not possible to pool the results due to the high heterogeneity of the studies included. RESULTS: A total of 17 studies that met the selection criteria were included, albeit only 2 of them studied NS exclusively. The total number of participants in these studies were 57,146 subjects, 25,047 of whom were NS and 2,655 of the latter had NS-COPD. Compared to COPD in smokers, COPD in NS is more frequent in women and older ages, and is associated with a slightly higher prevalence of comorbidities. There are not enough studies to understand if COPD progression and clinical symptoms in NS are different to that of ever-smokers. CONCLUSIONS: There is a significant knowledge gap on COPD in NS. Given that COPD in NS account for about a third of all COPD patients in the world, particularly in low-middle income countries, and the decrease in tobacco consumption in high income countries, understanding COPD in NS constitutes a public-health priority.

Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. METHODS: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 µM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. RESULTS: A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). CONCLUSIONS: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registration www. CLINICALTRIALS: gov (ID: NCT04180319).

Cost-Effectiveness of a New Outpatient Pulmonology Care Model Based on Physician-to-Physician Electronic Consultation.

Introduction: This study assesses the impact of an electronic physician-to-physician consultation program on the waiting list and the costs of a Pulmonology Unit. Materials and Methods: A prepost intervention study was conducted after a new ambulatory pulmonary care protocol was implemented and the capacity of the unit was adopted. In the new model, physicians at all levels of healthcare send electronic consultations to specialists. Results: In the preintervention year (2019), the Unit of Pulmonology attended 7,055 consultations (466 e-consultations and 6,589 first face-to-face visits), which decreased to 6,157 (3,934 e-consultations and 2,223 first face-to-face visits; 12.7% reduction) in the postintervention year (all were e-consultations). The mean wait time for the first appointment was 25.7 days in 2019 versus 3.2 days in 2021 (p < 0.001). In total, 43.5% of cases were solved via physician-to-physiciane-consultation. A total of 2,223 patients needed a face-to-face visit, with a mean wait time of 7.5 days. The mean of patients in the waiting listing decreased from 450.8 in 2019 to 44.8 in 2021 (90% reduction). The annual time devoted to e-consultations and first face-to-face visits following an e-consultation diminished significantly after the intervention (1,724 hours versus 2,312.8; 25.4% reduction). Each query solved via e-consultation represented a saving of €652.8, resulting in a total annual saving of €827,062. Conclusions: Physician-to-physiciane-consultations reduce waiting times, improve access of complex patients to specialty care, and ensure that cases are managed at the appropriate level. E-consultation reduces costs, which benefits both, society and the healthcare system.

Response to inhaled ceftazidime in patients with non-cystic fibrosis bronchiectasis and chronic bronchial infection unrelated to Pseudomonas aeruginosa.

INTRODUCTION: Inhaled antibiotics reduce the frequency of exacerbations. The objective was to assess the efficacy of inhaled ceftazidime in patients with non-cystic fibrosis bronchiectasis (NCFB) and concomitant chronic bronchial infection (CBI) caused by potentially pathogenic microorganisms (PPM) other than Pseudomonas aeruginosa (PA). MATERIAL AND METHOD: Quasi-experimental study in 21 patients with exacerbations who developed CBI by a PPM other than PA. RESULTS: Bacterial infection was resolved in 85.7% patients. Rehospitalizations, length of hospital stay, moderate exacerbations and blood levels of CRP decreased significantly. In addition, SGRQ questionnaire also decreased more than 4 points in 57.1% of the patients. CONCLUSION: The results suggest that inhaled ceftazidime in NCFB unrelated to PA is a plausible alternative to the standard therapies used in clinical practice.

Parasite identification in mullet fish (Mugil curema) from Chautengo Lagoon, Guerrero, Mexico, based on morphology and molecular analysis.

Parasite identification is crucial in areas where no sanitary inspection is conducted on fish, especially considering that parasitic zoonoses like anisakiasis and gnathostomiasis can pose a risk for human health. In this study, parasites in mullet fish (Mugil curema) from the Chautengo Lagoon, Guerrero, Mexico, were identified by morphological and molecular methods. A total of 122 specimens weighing 317 ± 51.25 g and 19.3 ± 1.14 cm in length were assessed. Their helminthofauna was classified by measuring internal structures, total length, and maximum width; a morphometric index was also calculated for larval stages. The prevalence of parasitosis in these mullets was 91.8%, with a mean infection intensity of 4.1. The acanthocephalan Floridosentis mugilis was identified by its external and internal structures. The nematodes found were of the Anisakidae family in stage 3 (L3), with a morphology consistent with Contracaecum sp. To determine the species, the ITS ribosomal gene and the mitochondrial genes COX2 and rrnS were molecularly characterized by PCR; then, they were aligned by CLUSTAL W, and a phylogenetic tree was obtained. In this analysis, the sequences were compared with those reported in GenBank. A total of 460 parasites were studied, 283 of which were nematodes (61.5%) and 177 were acanthocephalans (38.5%). The sequences of seven nematodes showed 99% homology with each other, and thus they formed an independent branch within the Contracaecum sp. group. This is the first report identifying Contracaecum multipapillatum in mullet fish in the Chautengo Lagoon, Guerrero.

Changes in ocular surface after withdrawal of anti-glaucoma medications following non-penetrating deep sclerectomy.

Purpose: : To analyze the ocular surface changes in eyes after the withdrawal of anti-glaucomatous drugs when non-penetrating deep sclerectomy (NPDS) is performed. Methods: Thirty-one patients (33 eyes) diagnosed with glaucoma that underwent NPDS were included in this prospective study. The control group included 33 eyes. Four variables were studied using Keratograph 5M (K5M): ocular hyperemia (OH), non-invasive tear film break-up time (NI-BUT), lower tear meniscus height (LTMH), and meibography. LTMH was also measured using the anterior segment module of a Spectralis Fourier-domain optical coherence tomography (FD-OCT) instrument. Moreover, an evaluation of corneal and conjunctival staining was performed. In the glaucoma group, five visits were carried out: pre-surgery, 1 week after surgery, and 1 month, 3 months, and 6 months after surgery. In control groups, examinations were performed in only one visit. In addition, patients were asked to answer two questionnaires: Ocular Surface Disease Index (OSDI) and National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) before and 6 months after surgery. Results: Before NPDS, eyes showed worse objective data than healthy control subjects (P ≤ 0.049). In this group, a significant improvement was observed in questionnaire responses (P < 0.001), LTMH-FD-OCT (P = 0.037), LTMH-K5M (P = 0.025), K5M-OH (P = 0.003), NI-BUT (P = 0.022), and conjunctival and corneal staining (P < 0.001). No significant differences were observed between groups in FD-OCT and K5M LTMH, NI-BUT, corneal-conjunctival staining, nor in the most OH sector values at 6 months (P ≥ 0.62). Conclusion: A significant improvement in the ocular surface was observed 6 months after NPDS, suggesting that the withdrawal of the topical anti-glaucomatous treatment had a beneficial effect on the subjects.

Usefulness of Malachite-Green LAMP for Diagnosis of Plasmodium and Five Human Malaria Species in a Nonendemic Setting.

Molecular methods are necessary to detect low-density malaria infections. The purpose of this study was to assess the diagnostic performance of six malachite-green loop-mediated amplification method (MG-LAMP) assays (MG-LAMP-Pf, MG-LAMP-Pv, MG-LAMP-Po, MG-LAMP-Pm, MG-LAMP-Pk, and MG-LAMP-Pspp) for the species-specific detection of each human Plasmodium, including P. knowlesi, and the Plasmodium genus compared with the nested-multiplex malaria polymerase chain reaction (NM-PCR), using 161 malaria-positive and 274 malaria-negative samples. MG-LAMP-Pspp assay detected the five human Plasmodium species and each species-specific MG-LAMP assay detected only its corresponding species. Sensitivity, specificity, and predictive values of MG-LAMP assays, compared with NM-PCR, were > 90%, except in the case of the MG-LAMP-Pm assay, which dropped to 47%. Limit of detection for MG-LAMP-Pspp assay ranged from 0.1 parasites/µL for P. falciparum to 16.9 parasites/µL for P. malariae samples, and it was similar for the rest of MG-LAMP assays except for the MG-LAMP-Pm assay. Turnaround time was estimated to be 2 hours and 35 minutes for one MG-LAMP assay and 4 hours and 15 minutes if all species-specific MG-LAMP is set up, whereas for the NM-PCR, turnaround time was ∼6 hours and 15 minutes. Costs per determination ranged from 1 to 6 euros for MG-LAMP assays and 5 euros for NM-PCR. Therefore, MG-LAMP assays appear to have good concordance compared with the reference method, except for the MG-LAMP-Pm assay. They can detect low parasitemia and identify malaria species, with lower costs and shorter time to obtain results, and they are suitable tools to be used in endemic and non-endemic countries for malaria detection.

Risk factors for chronic obstructive pulmonary disease in never-smokers: A systematic review.

INTRODUCTION: Relatively little is known about the risk factors for chronic obstructive pulmonary disease (COPD) in never-smokers, and these factors have not yet been fully characterised. This study therefore sought to analyse COPD risk factors in never-smokers by conducting a systematic review of the literature on the topic. MATERIALS AND METHODS: We performed a search in PubMed (Medline) and Embase from 2000 onwards, to locate studies on COPD in never-smokers. For literature search and evidence synthesis purposes, we used the PRISMA guidelines and drew up a specific quality scale to quantify the evidence of each study included. RESULTS: The bibliographic search retrieved a total of 557 papers, 20 of which fulfilled the designated inclusion criteria (two case-control studies, four cohort studies and 14 cross-sectional studies). These studies were undertaken in Europe, the United States, Latin America, Asia and Africa. The risk factors for never-smokers were varied and ranged from exposure to biomass, occupational exposure and passive smoking to having a history of asthma, tuberculosis or respiratory infections during childhood. The effect of residential radon was unclear. The highest risk was obtained for previous respiratory diseases of any type, with a magnitude much higher than that observed for other risk factors. CONCLUSIONS: There are few studies on COPD risk factors in never-smokers. More purpose-designed studies in this subpopulation are thus called for, including well-designed studies to specifically assess if indoor radon has any role on COPD onset.