Functional dissection of complex and molecular trait variants at single nucleotide resolution.

Identifying the causal variants and mechanisms that drive complex traits and diseases remains a core problem in human genetics. The majority of these variants have individually weak effects and lie in non-coding gene-regulatory elements where we lack a complete understanding of how single nucleotide alterations modulate transcriptional processes to affect human phenotypes. To address this, we measured the activity of 221,412 trait-associated variants that had been statistically fine-mapped using a Massively Parallel Reporter Assay (MPRA) in 5 diverse cell-types. We show that MPRA is able to discriminate between likely causal variants and controls, identifying 12,025 regulatory variants with high precision. Although the effects of these variants largely agree with orthogonal measures of function, only 69% can plausibly be explained by the disruption of a known transcription factor (TF) binding motif. We dissect the mechanisms of 136 variants using saturation mutagenesis and assign impacted TFs for 91% of variants without a clear canonical mechanism. Finally, we provide evidence that epistasis is prevalent for variants in close proximity and identify multiple functional variants on the same haplotype at a small, but important, subset of trait-associated loci. Overall, our study provides a systematic functional characterization of likely causal common variants underlying complex and molecular human traits, enabling new insights into the regulatory grammar underlying disease risk.

Which sit-to-stand test best differentiates functional capacity in older people?

ABSTRACT: The Sit-to-Stand (STS) test provides insight into age-related functional capacity; however, there are various variants of STS, and we do not know which of these better discriminates against age-related functional capacity. Our study aimed to compare the age-related functional capacity in older people by evaluating STS power variants, using young individuals as a reference. A cross-sectional study was conducted in 102 adults (57 women) aged 60-80 and 105 adults (54 women) aged 20-30. Participants performed five times STS (5-STS), 30-seconds STS (30s-STS), and 1-minute STS (1min-STS). Z-scores were obtained for each STS variant using power (W), relative (W/kg), and allometric (W/m2) normalization methods. A mixed repeated-measures ANOVA assessed the interactions among the STS variants, normalization methods, sex, physical activity, and tobacco history. A significant interaction between STS variants, normalization methods, and sex (p=0.002) was found. The mean effect of STS variants revealed that the 1-minSTS had the lowest Z-score (p<0.05). Significant variations were observed between STS variants in all normalization methods for women (p<0.001). However, in men, only the difference between 5-STS and 1min-STS remained consistent across normalization methods (p<0.05). Our findings highlight the efficacy of 1min-STS in distinguishing age-related functional capacity over the other STS tests, especially in women.

Performance of a vaginal self-collection device versus clinician collected cervical samples for the detection of high-risk human papillomavirus.

Objective: Screening for cervical cancer requires the participation of target women. Human papillomavirus (HPV) testing can be performed on vaginal self-samples and self-sampling can improve this participation. This study aims to validate the performance of the vaginal self-sampling device (Vitroveil®) to detect high risk human papillomavirus (hrHPV) in comparison to clinician collected samples and evaluate the degree of acceptability of the Vitroveil® device. Methods: A cross-sectional observational study was carried out in a cohort of 385 participating women (median age of 44 ± 10.47 years) attending primary care centers and cervical pathology services of Granada, Spain. Two paired samples (vaginal self-sample and clinician collected cervical sample) where collected from each participant to compare the detection of HPV with the Vitro HPV Screening assay (Vitro, Granada, Spain). A questionnaire was also provided to the participants to analyze the degree of satisfaction with the device and the preference for sampling method. Results: Overall concordance for hrHPV detection was substantial (ĸ 0.804). The prevalence of any hrHPV infection was higher in self-collected samples (30.6%) than in clinician-collected samples (24.3%). The participants found the self-sampling device easy to use and preferred self-collection as the collection method. Conclusion: The Vitroveil® self-sampling device enables safe and accruable hrHPV testing, obtaining equivalent results to those of the clinician collected samples. High acceptability of the device has been demonstrated among women in the study. Nevertheless, additional studies are necessary to verify the efficacy and reliability of the device's performance.

The rs2018736 fibulin-5 polymorphism as a determinant for pelvic organ prolapse: a case-control study.

OBJECTIVE: Fibulin-5 is a connective tissue component and may play a role in pelvic organ prolapse (POP) pathogenesis. This study aimed to verify the association of the rs2018736 polymorphism of the fibulin-5 gene with POP in postmenopausal Brazilian women, and to determine the risk factors for POP. METHOD: This observational, cross-sectional, case-control study assessed postmenopausal women with advanced POP (stages III and IV) and control women (stages 0 and I) by examination and peripheral blood sample collection. DNA sequences were analyzed by real-time reverse-transcriptase polymerase chain reaction. A logistic regression model was used with p < 0.05 for significance. RESULTS: A total of 565 participants were evaluated (325 POP and 240 control). The homozygous C allele of rs2018736 (CC) was protective against POP (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26-0.91). Age (OR 1.09, 95% CI 1.05-1.13), number of pregnancies (OR 1.14, 95% CI 1.01-1.28), vaginal delivery (OR 5.32, 95% CI 2.58-11.01), forceps delivery (OR 3.34, 95% CI 1.72-6.47), weight of newborn (OR 1.0007, 95% CI 1.0002-1.0011), family history of POP (OR 2.35, 95% CI 1.24-4.44), hypertension (OR 1.74, 95% CI 1.01-3.00) and diabetes (OR 2.19, 95% CI 1.07-4.48)] were independent predictors for POP; cesarean (OR 0.02, 95% CI 0.005-0.09) was protective. CONCLUSION: The rs2018736-CC genotype of the fibulin-5 gene has a protective role against POP.

Only half of the authors of overviews of exercise-related interventions use some strategy to manage overlapping primary studies-a metaresearch study.

OBJECTIVES: The conduct of systematic reviews (SRs) and overviews share several similarities. However, because the unit of analysis for overviews is the SRs, there are some unique challenges. One of the most critical issues to manage when conducting an overview is the overlap of data across the primary studies included in the SRs. This metaresearch study aimed to describe the frequency of strategies to manage the overlap in overviews of exercise-related interventions. STUDY DESIGN AND SETTING: A systematic search in MEDLINE (Ovid), Embase (Ovid), Cochrane Library, Epistemonikos, and other sources was conducted from inception to June 2022. We included overviews of SRs that considered primary studies and evaluated the effectiveness of exercise-related interventions for any health condition. The overviews were screened by two authors independently, and the extraction was performed by one author and checked by a second. We found 353 overviews published between 2005 and 2022 that met the inclusion criteria. RESULTS: One hundred and sixty-four overviews (46%) used at least one strategy to visualize, quantify, or resolve overlap, with a matrix (32/164; 20%), absolute frequency (34/164; 21%), and authors' algorithms (24/164; 15%) being the most used methods, respectively. From 2016 onwards, there has been a trend toward increasing the use of some strategies to manage overlap. Of the 108 overviews that used some strategy to resolve the overlap, ie, avoiding double or multiple counting of primary study data, 79 (73%) succeeded. In overviews where no strategies to manage overlap were reported (n = 189/353; 54%), 16 overview authors (8%) recognized this as a study limitation. CONCLUSION: Although there is a trend toward increasing its use, only half of the authors of the overviews of exercise-related interventions used a strategy to visualize, quantify, or resolve overlap in the primary studies' data. In the future, authors should report such strategies to communicate more valid results.

Virtual assessment and management of chronic cough: A scoping review.

Background: Chronic cough is a frequent reason for seeking consultation with primary care providers. The recent widespread adoption of virtual care offers a promising alternative that can be used to optimize the assessment and management of this condition. The objective of this review was to map and identify the strategies used to assess and/or manage chronic cough virtually, and to explore their impact on cough severity and patient satisfaction with virtual care. Methods: A scoping review was conducted in MEDLINE, EMBASE, and CINAHL in May 2023. Research questions were defined based on the Population, Concept, Context mnemonic, and literature search was conducted using a three-step approach. Study selection involved the steps of identification, screening, eligibility, and inclusion. A descriptive synthesis was performed, and quantitative variables were presented as absolute and relative frequencies. Results: A total of 4953 studies were identified and seven met the inclusion criteria. The following mHealth and telehealth strategies were identified: diagnostic website, specialized online clinic, online speech language therapy, and remote follow-up to assess the effectiveness of in-person interventions. Results indicated that these virtual strategies can be useful to assess chronic cough, treat, and track chronic cough symptoms. Overall, patients were satisfied with the approaches. Conclusion: Although literature is scarce, evidence suggests that virtual strategies for the assessment and management of chronic cough may be effective and are well-received by patients. However, further research is needed to identify the type and characteristics of virtual approaches leading to optimize and facilitate the care of patients with this condition. This will also help develop a strong body of evidence to support their incorporation into guidelines and clinical practice.

Six-minute walking distance and desaturation-distance ratio in allogeneic stem cell transplantation.

BACKGROUND: Most patients with haematological malignancies who undergo allogeneic haematopoietic stem cell transplant (HSCT) receive chemotherapy before the transplant to control the disease. Certain chemotherapy drugs can cause lung toxicity. Conversely, in patients with chronic respiratory conditions, the 6-min walking test (6MWT) and the desaturation-distance ratio (DDR) have demonstrated prognostic significance. Our objective was to determine whether the 6MWD and DDR, assessed prior to HSCT, have a prognostic impact on survival at 24 months post-HSCT. METHODS: A prospective experimental study was conducted in consecutive patients referred for allogeneic HSCT at Hospital Clinic, Barcelona, Spain. A complete functional respiratory study, including the 6MWT and DDR, was conducted prior to admission. The area under the curve (AUC) and cut-off points were calculated. Data on patients' characteristics, HSCT details, main events, with a focus on lung complications, and survival at 24 months were analysed. RESULTS: One hundred and seventy-five patients (39% women) with mean age of 48 ± 13 years old were included. Before HSCT, forced vital capacity and forced expiratory volume in the first second were 96% ± 13% predicted and 92% ± 14% predicted, respectively; corrected diffusing capacity for carbon monoxide 79% ± 15% predicted; 6MWD was 568 ± 83 m and DDR of .27 (.20-.41). The cut-off points for 6MWD and DDR were 566 m, [.58 95% CI (.51-.64)], p = .024 and .306, [.63 95% CI (.55-.70)], p = .0005, respectively. The survival rate at 24 months was 55%. CONCLUSION: Our results showed that individuals who exhibit a 6MWD shorter than 566 ms or a decline in DDR beyond .306 experienced reduced survival rates at 24 months after HSCT.

Inspiratory muscle training in patients with obesity: a systematic review and meta-analysis.

Introduction: Obesity is a chronic medical condition that affects, among others, the cardiovascular and respiratory systems. Interventions for its treatment focus on sustained weight reduction and general health improvement, leaving respiratory management aside. Our objective was to determine the effects of inspiratory muscle training (IMT) in patients with obesity. Methods: A systematic review was performed in Embase, Cochrane Library (CENTRAL), CINAHL, Web of Science, and PubMed/MEDLINE on June 26, 2023. Randomized clinical trials (RCTs), and quasi-randomized clinical trials investigating the effects of IMT in people with obesity were included. Selected studies were screened by two independent reviewers who extracted data and assessed the quality of the evidence. Results: The initial search returned 705 potential studies were included. Ultimately, eight studies met the criteria for eligibility and were included in the review. IMT improves physical capacity [6-minute walk test (6MWT): 44.5 m, 95% CI: 30.5 to 58.5; p < 0.0001] and the strength of the inspiratory muscles [maximal inspiratory pressure (MIP): -28.4 cm H2O, 95% CI: -41.9 to -14.8; p < 0.0001] compared to the controls, without differences in the pulmonary function, body mass index (BMI) and metabolic parameters. Conclusion: Inspiratory muscle training improves physical capacity and inspiratory muscle strength without significant changes in lung function, BMI, and metabolic parameters.Systematic review registration: PROSPERO, identifier CRD42023439625, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023439625.

Maximal Respiratory Pressure Reference Equations in Healthy Adults and Cut-off Points for Defining Respiratory Muscle Weakness

Introduction: Maximal inspiratory and expiratory pressures (PImax/PEmax) reference equations obtained in healthy people are needed to correctly interpret respiratory muscle strength. Currently, no clear cut-off points defining respiratory muscle weakness are available. We aimed to establish sex-specific reference equations for PImax/PEmax in a large sample of healthy adults and to objectively determine cut-off points for respiratory muscle weakness. Methods: A multicentre cross-sectional study was conducted across 14 Spanish centres. Healthy non-smoking volunteers aged 18–80 years stratified by sex and age were recruited. PImax/PEmax were assessed using uniform methodology according to international standards. Multiple linear regressions were used to obtain reference equations. Cut-off points for respiratory muscle weakness were established by using T-scores. Results: The final sample consisted of 610 subjects (314 females; 48 [standard deviation, SD: 17] years). Reference equations for PImax/PEmax included body mass index and a squared term of the age as independent variables for both sexes (p<0.01). Cut-off points for respiratory muscle weakness based on T-scores ≥2.5 SD below the peak mean value achieved at a young age were: 62 and 83cmH2O for PImax and 81 and 109cmH2O for PEmax in females and males, respectively. Conclusion: These reference values, based on the largest dataset collected in a European population to date using uniform methodology, help identify cut-off points for respiratory muscle weakness in females and males. These data will help to better identify the presence of respiratory muscle weakness and to determine indications for interventions to improve respiratory muscle function. (AU)

Interrater Reliability of the Spanish (Colombia) Version of the Post-COVID-19 Functional Status Scale.

Background: COVID-19 has been one of the most critical public health challenges of recent decades. This disease develops severely in one in five patients, and approximately 5% require admission to a critical care unit. Due to the impact of the sequelae, the Post-COVID-19 Functional Status Scale (PCFS) was developed. This study is aimed at determining the interrater reliability of the Spanish (Colombia) version of the PCFS in adult patients with post-COVID-19 infection. Methods: This is an observational study performed with patients diagnosed with COVID-19. Two evaluators repeated the test-retest of the PCFS scale with knowledge and clinical experience in the care of patients with COVID-19 and had previously applied the test. The PCFS assesses functional limitations at discharge and can be used at 4 and 8 weeks to evaluate practical consequences and determine the degree of disability these patients may have. For interrater reliability, Cronbach's alpha was applied with its respective confidence interval and the Bland-Altman method. A 95% confidence interval (CI) was taken as the basis for the interpretation of the Intraclass Correlation Coefficient (ICC). Results: A total of 112 adult patients participated in the study, aged 51.46 ± 15.94 years. It was evidenced that the survival, constant care, and activities of daily living questions have an ICC of one (1.000) with an ICC (1.000-1.000), demonstrating excellent reliability, while those close to one were instrumental activities, role participation, symptoms, and final score with an ICC 0.918 to 0.984 and an ICC (0.881-0.989). Thus, a homogeneous distribution of the interrater data was evident. Conclusions: Excellent interobserver reliability of the Spanish (Colombia) version of the PCFS in patients with different degrees of functional status was reported.

Efficacy of Sacrospinous Fixation or Uterosacral Ligament Suspension for Pelvic Organ Prolapse in Stages III and IV: Randomized Clinical Trial.

OBJECTIVE: To evaluate the efficacy and outcomes of the surgical treatment for pelvic organ prolapse (POP) in stages III and IV by sacrospinous ligament fixation (SSLF) or uterosacral ligament suspension (USLS) by comparing anatomical and subjective cure rates and quality-of-life parameters (through the version validated for the Portuguese language of the Prolapse Quality of Life [P-QoL] questionnaire) under two definitions: genital prolapse Ba, Bp, and C < -1 (stage I) and Ba, Bp, and C ≤ 0 (stage II). MATERIALS AND METHODS: After we obtained approval from the Ethics Committee (under CAAE 0833/06) and registered the study in ClinicalTrials.gov (NCT01347021), 51 patients were randomized into two groups: the USLS group (N = 26) and the SSLF group (N = 25), with follow-up 6 and 12 months after the procedures. RESULTS: There was a significant improvement in the P-QoL score and anatomical measurements of all compartments in both groups after 12 months (p < 0.001). The anatomical cure rates in the USLS and SSLF groups, considering stage 1, were of 34.6% and 40% (anterior) respectively; of 100% both for groups (apical); and of 73.1% and 92% (posterior) respectively. The rates of adverse outcomes were of 42% (N = 11) and 36% (N = 11) for the USLS and SSLF groups respectively (p = 0.654), and those outcomes were excessive bleeding, bladder perforation (intraoperative) or gluteal pain, and urinary infection (postoperative), among others, without differences between the groups. CONCLUSION: High cure rates in all compartments were observed according to the anatomical criterion (stage I), without differences in P-QoL scores and complications either with USLS or SSLF for the surgical treatment of accentuated POP.

OBJETIVO: Avaliar a eficácia e os resultados do tratamento cirúrgico para prolapso de órgãos pélvicos (POP) nos estágios III e IV, por meio da técnica de fixação do ligamento sacroespinal (FLSE) ou suspensão do ligamento útero-sacro (SLUS), ao comparar os índices de cura anatômicos, subjetivos, e os parâmetros de qualidade de vida (por meio do questionário Prolapse Quality of Life [P-QoL] validado para a língua portuguesa) sob duas definições: prolapso genital Ba, Bp e C < −1 (estágio I) e Ba, Bp e C ≤ 0 (estágio II). MATERIAIS E MéTODOS: Após aprovação do Comitê de Ética (CAAE 0833/06) e registro no ClinicalTrials.gov (NCT01347021), 51 pacientes foram randomizadas em dois grupos: grupo SLUS (N = 26) e (2) grupo FLSE (N = 25), com seguimento de 6 e 12 meses. RESULTADOS: Houve melhora significativa nas pontuações no P-QoL e nas medidas anatômicas de todos os compartimentos em ambos os grupos após 12 meses (p < 0,001). As taxas de cura anatômica nos grupos SLUS e FLSE , considerando o estágio 1, foram de 34,6% e 40% (anterior), respectivamente; de 100% em ambos os grupos (apical); e de 73,1% e 92% (posterior), respectivamente. As taxas de resultados adversos foram de 42% (N = 11) e 36% (N = 11), respectivamente, nos grupos SLUS e FLSE (p = 0,654), e elas foram sangramento excessivo, perfuração da bexiga (intraoperatória) ou dor glútea, e infecção urinária (pós-operatória), entre outras, sem diferenças entre os grupos. CONCLUSãO: Altas taxas de cura em todos os compartimentos foram observadas segundo critério anatômico (estágio I), sem diferença quanto às pontuações no P-QoL e às complicações tanto com SLUS quanto com FLSE para o tratamento cirúrgico de POP acentuado.

Correlation between ischemic stroke topography and female urinary incontinence.

AIM: To investigate the association between ischemic stroke topography and the onset of urinary incontinence (UI); to evaluate predictors of post-stroke UI in women. METHOD: We prospectively followed up a cohort of women with ischemic stroke confirmed by clinical and computed tomography (CT) or magnetic resonance imaging (MRI) scans findings. Participants were subjected to interview, clinical evaluation, and urodynamic study if needed at 6 months post-stroke and divided in continent and incontinent groups. Non-parametric tests compared the baseline characteristics among the groups and determined association between post-stroke UI and the brain sites of injury. Logistic regression analysis determined predictors of post-stroke UI. Significance level at 5 % was set. RESULTS: 162 S-women were included: 128 (79 %) continent and 34 (21 %) incontinent. Frontal lobe lesions were higher in the incontinent group (82.9 % versus 51.2 %, p = 0.001); lesions in the parietal lobe and the left cerebral hemisphere were higher in the continent group (40.9 % versus 20 %, p = 0.023; and 61.4 % versus 40 %, p = 0.024, respectively). Frontal lobe injury [RR 3.68 (CI 1.2-11.2)], body mass index (BMI) [RR1.16 (CI 1.062-1.266)] and number of vaginal deliveries [RR 1.358 (CI 1.163-1.585)] are risk factors for post-stroke UI. Left parietal lobe injury is less likely to occur in continent women after 6 months [RR 0.168 (CI 0.029-0.981; p = 0.048)]. CONCLUSION: There is a correlation between the topography of the ischemic stroke and the onset of UI. Frontal lobe lesion, BMI and number of vaginal deliveries are predictors of post-stroke UI.

Maximal Respiratory Pressure Reference Equations in Healthy Adults and Cut-off Points for Defining Respiratory Muscle Weakness.

INTRODUCTION: Maximal inspiratory and expiratory pressures (PImax/PEmax) reference equations obtained in healthy people are needed to correctly interpret respiratory muscle strength. Currently, no clear cut-off points defining respiratory muscle weakness are available. We aimed to establish sex-specific reference equations for PImax/PEmax in a large sample of healthy adults and to objectively determine cut-off points for respiratory muscle weakness. METHODS: A multicentre cross-sectional study was conducted across 14 Spanish centres. Healthy non-smoking volunteers aged 18-80 years stratified by sex and age were recruited. PImax/PEmax were assessed using uniform methodology according to international standards. Multiple linear regressions were used to obtain reference equations. Cut-off points for respiratory muscle weakness were established by using T-scores. RESULTS: The final sample consisted of 610 subjects (314 females; 48 [standard deviation, SD: 17] years). Reference equations for PImax/PEmax included body mass index and a squared term of the age as independent variables for both sexes (p<0.01). Cut-off points for respiratory muscle weakness based on T-scores ≥2.5 SD below the peak mean value achieved at a young age were: 62 and 83cmH2O for PImax and 81 and 109cmH2O for PEmax in females and males, respectively. CONCLUSION: These reference values, based on the largest dataset collected in a European population to date using uniform methodology, help identify cut-off points for respiratory muscle weakness in females and males. These data will help to better identify the presence of respiratory muscle weakness and to determine indications for interventions to improve respiratory muscle function.

Pulmonary rehabilitation in sarcoidosis: A systematic review and meta-analysis.

BACKGROUND: Exercise intolerance, muscle weakness, dyspnoea, and fatigue are frequent complications in symptomatic sarcoidosis patients. Pulmonary rehabilitation improves exercise capacity, symptoms, and quality of life in patients with chronic respiratory diseases. Our objective was to systematically determine the effects of pulmonary rehabilitation in patients with sarcoidosis. METHODS: A systematic review was conducted in seven databases. Studies that applied pulmonary rehabilitation in patients with sarcoidosis were reviewed. Two independent reviewers analysed the studies, extracted the data and assessed the quality of evidence. RESULTS: Of the 406 reports returned by the initial search, five articles reporting on 184 patients were included in the data synthesis. Two studies included multi-component exercise, one inspiratory muscle training, one a physical activity incentivisation programme, and one a telerehabilitation program. In the intervention group (IG), we found significant improvement in exercise capacity (SMD 1.65, 95%CI 0.45, 2.86 points, p = 0.006). If we only analyse the studies that performed the 6-min walking test, the IG walked 40.3 (CI95% 20.3, 60.2) m higher than the control group (CG) (p < 0.001). Additionally, dyspnoea score was reduced (MD -0.42 95%CI -0.75, -0.10, p = 0.002). However, fatigue, quality of life and pulmonary function did not show any change. CONCLUSION: Pulmonary rehabilitation could improve exercise capacity and dyspnoea perception in patients with sarcoidosis.

Antimicrobial Resistance and Extended-Spectrum Beta-Lactamase Genes in Enterobacterales, Pseudomonas and Acinetobacter Isolates from the Uterus of Healthy Mares.

Antibiotic-resistant bacteria are a growing concern for human and animal health. The objective of this study was to determine the antimicrobial resistance and extended-spectrum beta-lactamase genes in Enterobacterales, Pseudomonas spp. and Acinetobacter spp. isolates from the uterus of healthy mares. For this purpose, 21 mares were swabbed for samples, which were later seeded on blood agar and MacConkey agar. The isolates were identified using MALDI-TOF and the antimicrobial susceptibility test was performed using the Kirby-Bauer technique. To characterize the resistance genes, a polymerase chain reaction (PCR) scheme was performed. Of the isolates identified as Gram-negative, 68.8% were Enterobacterales, represented by E. coli, Enterobacter cloacae, Citrobacter spp., and Klebsiella pneumoniae; 28.1% belonged to the genus Acinetobacter spp.; and 3.1% to Pseudomonas aeruginosa. A 9.3% of the isolates were multidrug-resistant (MDR), presenting resistance to antibiotics from three different classes, while 18.8% presented resistance to two or more classes of different antibiotics. The diversity of three genes that code for ESBL (blaTEM, blaCTX-M and blaSHV) was detected in 12.5% of the strains. The most frequent was blaSHV, while blaTEM and blaCTX-M were present in Citrobacter spp. and Klebsiella pneumoniae. These results are an alarm call for veterinarians and their environment and suggest taking measures to prevent the spread of these microorganisms.

Association between the rs1036819 polymorphism of the ZFAT gene and pelvic organ prolapse: a case-control study.

INTRODUCTION AND HYPOTHESIS: The identification of risk factors for pelvic organ prolapse (POP) would contribute to planning prevention strategies. This study tests the hypothesis that the rs1036819 polymorphism in the ZFAT gene is associated with POP and investigates other risk factors for prolapse development. METHODS: A case-control study was carried out including 826 postmenopausal women divided into POP cases (stages III and IV) and controls (stages 0 and I), assessed by anamnesis, examination, and peripheral blood samples. DNA was extracted from blood and genotyped by real-time RT-PCR. We used logistic regression models for the association analyses of variables, with p < 0.05 for significance. RESULTS: Five hundred and sixty-eight women were evaluated (315 POP and 253 controls). The minor allele C was found in 19.3% of our sample and the genotype frequencies of AA, AC, and CC were similar in both groups. Age (OR 1.09, 95% CI 1.06-1.13), number of pregnancies (OR 1.23, 95% CI 1.08-1.41), history of one vaginal delivery (OR 3.39, 95% CI 1.38-8.33) or two or more (OR 2.51, 95% CI 1.04-6.07), weight of the largest newborn (OR 1.0001, 95% CI 1-1.001), and family history of POP (OR 2.27, 95% CI 1.24-4.13) were independent risk factors for POP, whereas one cesarean section (OR 0.48, 95% CI 0.27-0.88) or two or more (OR 0.14, 95% CI 0.05-0.38) were protective. CONCLUSIONS: No association was detected between the rs1036819 polymorphism of the ZFAT gene and advanced POP. Age, number of pregnancies, at least one vaginal delivery, weight of the newborn, and POP family history were independent risk factors for POP.

Uma clínica catalisadora

Este artigo tem como objetivo revigorar a obra da psiquiatra Nise da Silveira (1905-1999), relacionando-a ao atual campo da clínica e da saúde mental. Nise da Silveira é reconhecida pelo combate aos métodos agressivos de tratamento do sofrimento mental, pelo trabalho com pacientes esquizofrênicos, por meio, sobretudo, de atividades expressivas, e extenso impacto na cultura brasileira. Os conceitos de Nise da Silveira, destacados no presente artigo, são inumeráveis estados do ser, mundo externo e mundo interno e afeto catalisador, discutidos a fim de se atualizar a proposição da sua clínica eminentemente humana, que não negligencia o manejo do inconsciente nem obscurece o seu papel de catalisadora das transformações sociais.

Clinical Variables Related to Functional Capacity and Exertional Desaturation in Patients with COVID-19.

Impaired functional capacity is one of the most commonly reported consequences among post-COVID-19 patients. This study aimed to analyse the clinical variables related to functional capacity and exertional desaturation in post-COVID-19 patients at the time of hospital discharge. A cross-sectional study was conducted on patients recovering from COVID-19 pneumonia. The main outcomes measures were functional capacity, assessed using the 1 min sit-to-stand test (1 min STST), and exertional desaturation, defined as a drop of ≥4% in the arterial oxygen saturation. Factors used to characterise the participant outcomes included the use of a high-flow nasal cannula (HFNC), prolonged hospitalisation, occurrence of pulmonary embolism during hospitalisation, and underlying comorbidities. A total of 381 participants (mean age = 53.7 ± 13.2 years, 65.6% men) were included. Participants completed a mean of 16.9 ± 6.2 repetitions in the 1 min STST. Exertional desaturation was observed in 51% of the patients. Higher odds of exertional desaturation were found in the participants who used a HFNC (OR = 3.6; 95%CI: 1.6 to 7.8), were admitted in the hospital >10 days (OR = 4.2; 95%CI: 2.6 to 6.8), and had a pulmonary embolism (OR = 3.5; 95%CI: 2.2. to 5.3). Use of a HFNC (ß = -3.4; 95%CI: -5.3 to -1.44), a hospital stay >10 days (ß = -2.2; 95%CI: -3.4 to -0.9), and a history of pulmonary embolism (ß = -1.4; 95%CI: -2.6 to -0.2) were also negatively associated with the 1 min STST. Most post-COVID-19 patients exhibited reduced functional capacity at the time of hospital discharge, and approximately half had exertional desaturation after the 1 min STST. The use of a HFNC, prolonged hospitalisation and pulmonary embolism were the main clinical variables associated with worse a 1 min STST performance and a higher likelihood of exertional desaturation.

Management of Pulmonary Hypertension Associated with Chronic Lung Disease.

Pulmonary hypertension (PH) is a common complication of chronic lung diseases, particularly in chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILD) and especially in advanced disease. It is associated with greater mortality and worse clinical course. Given the high prevalence of some respiratory disorders and because lung parenchymal abnormalities might be present in other PH groups, the appropriate diagnosis of PH associated with respiratory disease represents a clinical challenge. Patients with chronic lung disease presenting symptoms that exceed those expected by the pulmonary disease should be further evaluated by echocardiography. Confirmatory right heart catheterization is indicated in candidates to surgical treatments, suspected severe PH potentially amenable with targeted therapy, and, in general, in those conditions where the result of the hemodynamic assessment will determine treatment options. The treatment of choice for these patients who are hypoxemic is long-term oxygen therapy and pulmonary rehabilitation to improve symptoms. Lung transplant is the only curative therapy and can be considered in appropriate cases. Conventional vasodilators or drugs approved for pulmonary arterial hypertension (PAH) are not recommended in patients with mild-to-moderate PH because they may impair gas exchange and their lack of efficacy shown in randomized controlled trials. Patients with severe PH (as defined by pulmonary vascular resistance >5 Wood units) should be referred to a center with expertise in PH and lung diseases and ideally included in randomized controlled trials. Targeted PAH therapy might be considered in this subset of patients, with careful monitoring of gas exchange. In patients with ILD, inhaled treprostinil has been shown to improve functional ability and to delay clinical worsening.