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).

Adolescents and Young Adults Evaluating a Website for Affective-Sexual Information and Education: Multicenter Cross-Sectional Study.

BACKGROUND: Today's young people have long been demanding a paradigm shift in the emotional and sexual education they receive. While for them, affective-sexual and gender diversity is already a reality, the sexual and reproductive health professionals they encounter lack sufficient training. The digital devices and affective-sexual education websites aimed at today's young people must also be thoroughly evaluated. The website Sexe Joves is a website on sexuality by the Department of Health of the Government of Catalonia (Spain). It is designed for people aged 14 to 25 years. It currently needs to undergo a process of evaluation. Affective-sexual education aimed at young people must stem from their participation and the whole range of sexual and gender diversity in order to reach the entire population equally. OBJECTIVE: The aim of this study was to evaluate the website Sexe Joves as a source of affective-sexual health information, education, and communication for young people. It takes into account sex, gender identity, sexual orientation, socioeconomic status, and location within Catalonia (urban, semiurban, and rural areas). METHODS: This was an observational, descriptive, and cross-sectional study that forms part of a larger mixed methods study. An ad hoc questionnaire was used to collect data. In total, 1830 participants were included. The study was carried out simultaneously in all the territorial administrations of Catalonia. RESULTS: Almost 30% of the sample obtained were young people who experience affective-sexual and gender diversity. Of those surveyed, only 14.2% (n=260) said they were familiar with the website and of these, 6.5% said they used it (n=114). The website content rated most indispensable was on sexual abuse, harassment, and violence, followed by sexually transmitted infections; 70.5% (n=1200) reported that they visit pornographic websites. CONCLUSIONS: The results of this study will contribute to the design of new strategies for the website Sexe Joves, a public health resource, in order to improve affective sexual education for young people. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.3390/ijerph192416586.

New variants of alpha-1-antitrypsin: structural simulations and clinical expression.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is characterized by reduced serum levels of the AAT protein and predisposes to liver and lung disease. The characterization at structural level of novel pathogenic SERPINA1 mutants coding for circulating AAT could provide novel insights into the mechanisms of AAT misfolding. The present study aimed to provide a practical framework for the identification and analysis of new AAT mutations, combining structural simulations and clinical data. METHODS: We analysed a total of five mutations (four not previously described) in a total of six subjects presenting moderate to severe AATD: Gly95Alafs*18, Val210Glu, Asn247Ser, Pi*S + Asp341His and Pi*S + Leu383Phe + Lys394Ile. Clinical data, genotyping and phenotyping assays, structural mapping, and conformational characterization through molecular dynamic (MD) simulations were developed and combined. RESULTS: Newly discovered AAT missense variants were localized both on the interaction surface and the hydrophobic core of the protein. Distribution of mutations across the structure revealed Val210Glu at the solvent exposed s4C strand and close to the "Gate" region. Asn247Ser was located on the accessible surface, which is important for glycan attachment. On the other hand, Asp341His, Leu383Phe were mapped close to the "breach" and "shutter" regions. MD analysis revealed the reshaping of local interactions around the investigated substitutions that have varying effects on AAT conformational flexibility, hydrophobic packing, and electronic surface properties. The most severe structural changes were observed in the double- and triple-mutant (Pi*S + Asp341His and Pi*S + Leu383Phe + Lys394Ile) molecular models. The two carriers presented impaired lung function. CONCLUSIONS: The results characterize five variants, four of them previously unknown, of the SERPINA1 gene, which define new alleles contributing to the deficiency of AAT. Rare variants might be more frequent than expected, and therefore, in discordant cases, standardized screening of the S and Z alleles needs complementation with gene sequencing and structural approaches. The utility of computational modelling for providing supporting evidence of the pathogenicity of rare single nucleotide variations is discussed.

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).

Contemporary outcomes of bladder carcinoma in situ treated with an adequate bacille Calmette-Guérin immunotherapy.

OBJECTIVE: To assess whether bacillus Calmette-Guérin (BCG) responsiveness after initiation of an adequate BCG treatment (at least five of six instillations of induction and at least two of three instillations of maintenance) impacts oncological outcomes in patients with carcinoma in situ (CIS) of the bladder treated with BCG immunotherapy. PATIENTS AND METHODS: Data were available for 193 patients with bladder CIS with or without associated cTa/cT1 disease who received an adequate BCG treatment between 2008 and 2015. Bladder biopsies were taken at 6 months and patients were then stratified as either BCG responsive (negative biopsies) or BCG unresponsive (positive biopsies). Inverse probability weighting (IPW)-adjusted Kaplan-Meier and IPW-adjusted Cox regression were performed to compare progression-free survival (PFS), radical cystectomy-free survival (RCFS), overall survival OS, and cancer-specific survival (CSS) in the two groups. RESULTS AND LIMITATIONS: Comparing the BCG-responsive and BCG-unresponsive groups, IPW-adjusted Kaplan-Meier analysis revealed, respectively, a median (interquartile range) of PFS of 9 (5-15) vs 48.5 (28-77) months (P = 0.001), a RCFS of 11 (9-15) vs 49 (24-76) months (P < 0.001), and a CSS of 25 (13-60) vs 109 (78-307) months (P = 0.004). On IPW-adjusted Cox regression analysis, BCG-unresponsive patients had a worse PFS (hazard ratio [HR] 3.40, 95% confidence interval [CI] 1.59-7.27), RCFS (HR 3.52, 95% CI 1.77-7), and CSS (HR 4.42, 95% CI 1.95-10.01). We found no significant differences for OS. CONCLUSION: Using an IPW method we found that lack of response after initiation of an adequate BCG treatment has prognostic implications beyond identification of complete response in patients with CIS. BCG-unresponsive patients, satisfying the novel definition of BCG unresponsive, showed a poor PFS, RCFS, and CSS. In this setting, the patients should be counselled regarding RC as a first option or enrolled in a clinical trial if they refuse RC or are unfit for surgery.

Association between circulating alpha-1 antitrypsin polymers and lung and liver disease.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is considered one of the most common genetic diseases and is characterised by the misfolding and polymerisation of the alpha-1 antitrypsin (AAT) protein within hepatocytes. The relevance of circulating polymers (CP) of AAT in the pathogenesis of lung and liver disease is not completely understood. Therefore, the main objective of our study was to determine whether there is an association between the levels of CP of AAT and the severity of lung and liver disease. METHOD: This was a cross-sectional study in patients with different phenotypes of AATD and controls. To quantify CP, a sandwich ELISA was performed using the 2C1 monoclonal antibody against AAT polymers. Sociodemographic data, clinical characteristics, and liver and lung parameters were collected. RESULTS: A cohort of 70 patients was recruited: 32 Pi*ZZ (11 on augmentation therapy); 29 Z-heterozygous; 9 with other genotypes. CP were compared with a control group of 47 individuals (35 Pi*MM and 12 Pi*MS). ZZ patients had the highest concentrations of CP (p < 0.001) followed by Z heterozygous. The control group and patients with Pi*SS and Pi*SI had the lowest CP concentrations. Pi*ZZ also had higher levels of liver stiffness measurements (LSM) than the remaining AATD patients. Among patients with one or two Z alleles, two patients with lung and liver impairment showed the highest concentrations of CP (47.5 µg/mL), followed by those with only liver abnormality (n = 6, CP = 34 µg/mL), only lung (n = 18, CP = 26.5 µg/mL) and no abnormalities (n = 23, CP = 14.3 µg/mL). Differences were highly significant (p = 0.004). CONCLUSIONS: Non-augmented Pi*ZZ and Z-patients with impaired lung function and increased liver stiffness presented higher levels of CP than other clinical phenotypes. Therefore, CP may help to identify patients more at risk of developing lung and liver disease and may provide some insight into the mechanisms of disease.

Evolution and Comparative Analysis of Hospitalizations in Spain Due to COPD and Bronchiectasis between 2004 and 2015.

Chronic obstructive pulmonary disease (COPD) is the leading cause of hospitalization for chronic respiratory illness in Spain. In recent years hospital admissions due to bronchiectasis have been increasing, although it is not known whether this is in proportion to COPD hospitalizations. Our main objective was to analyze the temporal evolution of discharges due to COPD, bronchiectasis, and their combination, and secondly, to assess their impact on in-hospital mortality and healthcare costs. We performed a retrospective study, based on the analysis of the Minimum Basic Data Set (MBDS) of hospital discharges using data from Spanish Ministry of Health with diagnostic codes of COPD or bronchiectasis between 2004 and 2015. We found 3 356 186 discharges with a diagnosis of COPD or bronchiectasis. After exclusions, 1 386 430 episodes were analyzed: 85.2% with COPD, 8.4% bronchiectasis, and 6.4% with both pathologies. Mean age of patients was 74.8 (10.9) years and with a male predominance of 80.1%. The increase in the annual number of discharges was greater in the two groups with bronchiectasis: 48.8% in the bronchiectasis group and 55.4% in the mixed group, compared to 6.6% in the COPD group. The mean length of stay was greater in both groups with bronchiectasis (p < 0.001), while in-hospital mortality was higher in the COPD group (p < 0.001). Similarly, the annual increase of costs was more evident in the two groups with bronchiectasis. Conclusions: Hospitalizations and health costs for bronchiectasis have increased in recent years significantly more than for COPD.Supplemental data for this aricle can be accessed here.

Uveitic macular edema response to intravitreal dexamethasone implant is independent of optical coherence tomography findings.

PURPOSE: To identify predictive response optical coherence tomography (OCT) findings in uveitic macular edema (UME) treated with intravitreal dexamethasone implant (DEX). METHODS: Retrospective study of 66 eyes (53 patients) treated with DEX for UME. SD-OCT macular scans were collected prior to DEX treatment and 6 weeks and 3 months after the DEX implant. OCT images were evaluated for qualitative and quantitative characteristics (central retinal thickness, CRT and macular volume, MV). A multivariate analysis of covariance (ANCOVA) was carried out to study the predictive influence of OCT and clinical covariates on outcomes. The main outcome was a composite endpoint based on the simultaneous gain of 5 or more letters associated with a 20% or more reduction in CRT. RESULTS: A significant improvement in BCVA at 6 weeks (mean change from baseline -0.2, SD 0.3) and 3 months (mean -0.2, SD 0.4) was observed after the DEX implant. A significant decrease in CRT (change from baseline -187.7 µm at 3 months) and MV (change from baseline -1.7 mm3 at 3 months) were also observed. An association of ≥ 5-letter improvement in BCVA and a ≥ 20% CRT reduction was observed in 44.6% of cases at 6 weeks and 31.4% at 3 months. ANCOVA multivariate analyses found CRT at 3 months independent from baseline clinical variables but from CRT. CONCLUSION: DEX implant is an effective treatment for UME independently of basal characteristics, producing both a gain of visual acuity and improvement of macular anatomy by OCT measures at 3 months.

Drug Retention Rate and Causes of Discontinuation of Adalimumab in Uveitis: Real-World Data from the Biotherapies in Uveitis (BioÚvea) Study Group.

PURPOSE: To study the drug retention rate (DRR), causes, and predictors of discontinuation of adalimumab (ADA) in a real-world uveitis setting. DESIGN: Multicentric, nationwide, registry-based, ambispective, observational study. PARTICIPANTS: Patients treated with ADA for noninfectious uveitis (NIU) in the Biotherapies for Uveitis (BioÚvea) Spanish registry from November 2016 to November 2017. METHODS: Demographics, clinical data, timing, and reasons for discontinuation, if occurred, were recorded. The DRR and drug retention time (DRT) were estimated using the Kaplan-Meier method. Median follow-up was analyzed by reverse Kaplan-Meier. Log-rank test was used for comparisons. Cox proportional-hazards model (PHM) and propensity score matching were used to identify predictors for discontinuation due to inefficacy and adverse events. MAIN OUTCOME MEASURES: Drug retention rate and DRT. RESULTS: A total of 392 patients were analyzed, including 218 women. Median age was 39 (interquartile range, 25) years. Nonanterior uveitis was recorded in 242 patients. Median follow-up was 49.07 (0.97-131.67) months, median DRT (survival) was 69.3 months, and 14 patients were lost to follow-up. The DRR at 6, 12, 24, and 60 months was 92.97%, 87.68%, 76.31%, and 54.28%, respectively. Adalimumab was discontinued in 151 patients. Discontinuation was due to lack or loss of efficacy in 74 patients, adverse event in 34 patients, and sustained quiescence in 25 patients. Recorded adverse events included infections in 10 patients and malignant neoplasms in 3 patients. Concurrent classic immunomodulatory therapy (IMT) was given to 251 patients. We did not find DRT differences regarding the use of concurrent IMT. Adalimumab was prescribed as a second or greater biotherapy line in 76 patients who showed shorter DRT (P = 0.038). Starting ADA in nonbiotherapy-naive patients was a predictor for "discontinuation due to inefficacy," whereas undifferentiated uveitis was a predictor for "discontinuation due to adverse event." Drug retention time was significantly shorter when spared or intensified, mainly due to discontinuation after sustained quiescence. CONCLUSIONS: Drug retention rate of ADA in uveitis at 60 months was 54.28%, with a good safety profile. The use of concurrent IMT did not show a significant influence on DRT. The use of ADA as a second or further biotherapy could be predictive for discontinuation due to inefficacy. Undifferentiated uveitis may be prone to premature discontinuation of ADA due to adverse events.

Correlation between disease severity factors and EQ-5D utilities in chronic obstructive pulmonary disease.

PURPOSE: Impaired health-related quality of life (HRQoL) is associated with poor health outcomes in chronic obstructive pulmonary disease (COPD). The aim of this study was to determine health utilities in patients with COPD and to identify the variables with the greatest impact. METHODS: This is a pooled analysis of data from 4 observational studies performed in stable COPD patients. Evaluation of patient HRQoL utilities was performed using the Spanish version of the self-administered EuroQoL 5 Dimensions (EQ-5D) questionnaire. EQ-5D utilities were described and compared according to several markers of disease severity. RESULTS: 6198 patients reported a mean (SD) EQ-5D index of 0.67 (0.26). A linear dose response relationship between EQ-5D utility and modified Medical Research Council (mMRC) score, forced expiratory volume in one 1 s (% predicted), COPD hospital admissions in the previous year, self-reported daily walking time, Charlson index, body mass index, obstruction, dyspnoea and exacerbation (BODEx) index, COPD assessment test (CAT), hospital anxiety and depression scale was observed (p for trend < 0.001). In multivariate analysis, patients reporting lower utility values were those with more dyspnoea, more comorbidities, using long-term oxygen therapy, with previous hospitalisations due to a COPD exacerbation and higher (worse) CAT score. CONCLUSION: HRQoL measures such as EQ-5D can assist clinicians to understand the impact of respiratory disease on COPD patients.

Predictive value of control of COPD for risk of exacerbations: An international, prospective study.

BACKGROUND AND OBJECTIVE: The concept of clinical control in COPD has been developed to help in treatment decisions, but it requires validation in prospective studies. METHODS: This international, multicentre, prospective study aimed to validate the concept of control in COPD. Patients with COPD were classified as controlled/uncontrolled by clinical criteria or CAT scores at baseline and followed up for 18 months. The main outcome was the difference in rate of a composite endpoint of moderate and severe exacerbations or death over the 18-month follow-up period. RESULTS: A total of 307 patients were analysed (mean age = 68.6 years and mean FEV1 % = 52.5%). Up to 65% and 37.9% of patients were classified as controlled by clinical criteria or CAT, respectively. Controlled patients had significantly less exacerbations during follow-up (by clinical criteria: 1.1 vs 2.6, P < 0.001; by CAT: 1.1 vs 1.9, P = 0.014). Time to first exacerbation was significantly prolonged for patients controlled by clinical criteria only (median: 93 days, IQR: 63; 242 vs 274 days, IQR: 221; 497 days; P < 0.001). Control status by clinical criteria was a better predictor of exacerbations compared to CAT criteria (AUC: 0.67 vs 0.57). CONCLUSION: Control status, defined by easy-to-obtain clinical criteria, is predictive of future exacerbation risk and time to the next exacerbation. The concept of control can be used in clinical practice at each clinical visit as a complement to the current recommendations of initial treatment proposed by guidelines.

Analysis of Blood Biomarkers in Patients with Chronic Obstructive Pulmonary Disease (COPD) and with Asthma-COPD Overlap (ACO).

Chronic obstructive pulmonary disease (COPD) is a heterogeneous entity with different clinical phenotypes, such as asthma-COPD overlap (ACO). The aim of this retrospective study was to compare routine blood biomarkers in patients with ACO and the remaning COPD phenotypes. Data were collected from stable COPD patients visited in during 2018, including C-reactive protein (CRP), fibrinogen, neutrophyl/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR).A total of 77 patients with COPD were included, 24 (31%) fulfilled the diagnosis of ACO. Clinically, patients with ACO presented more dyspnoea and wheezing. Regarding laboratory parameters, both groups had low levels of lymphocytes, especially the non-ACO group (24.2% vs. 29.3%; p = 0.031), patients with ACO had significantly higher eosinophil counts (4.7% vs. 1.9%; p < 0.001) but a lower percentage of neutrophils (56.8% vs. 64.7%; p = 0.003), NLR and PLR (2.5 vs. 3.8; p = 0.013 and 115 vs. 160; p = 0.063, respectively). In conclusion, besides the expected eosinophilic inflammation in patients with ACO, both groups had low levels of lymphocytes, especially the non-ACO group. The low levels of lymphocytes, in particular in non-ACO patients, should be confirmed in larger studies.

The Importance of Reference Centers and Registries for Rare Diseases: The Example of Alpha-1 Antitrypsin Deficiency.

Alpha-1 antitrypsin deficiency (AATD) is a rare and underdiagnosed disease that is associated with the development of liver disease in adults and children and pulmonary emphysema in adults. Several studies have shown that there is limited knowledge about the disease and its diagnosis among health care providers, and there is an important inequity in the access to specialized care and appropriate treatment across Europe. The European Commision and the European Respiratory Society (ERS) recommend that the care of patients with AATD must be organized in reference centers at national or regional levels. These reference centers must provide optimal clinical care in terms of adequate diagnostic techniques, such as phenotyping and genotyping, and ensure access to treatment according to guidelines. Reference centers should also provide continuous medical education for health care professionals, genetic counseling, collaboration with patient associations and promote collaborative research and clinical trials with new and existing treatments for the disease. These centers must have a registry of their activity and collaborate with large, international, multicenter registries, such as the European Alpha-1 antitrypsin Deficiency Research Collaboration (EARCO) international registry, which is endorsed by the ERS, and aims to recruit up to 3,000 patients over a period of three years and prospectively follow them to better understand the natural history of the disease and the impact of different treatments on outcomes in a real life setting. International collaboration and standardized collection of high-quality prospective data will provide new insights into the clinical manifestations and prognosis of AATD.

Practical Guide to the Identification and Diagnosis of Asthma-COPD Overlap (ACO).

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality around the world. COPD is characterised by a heterogeneous clinical presentation and prognosis which may vary according to the clinical phenotype. One of the phenotypes of COPD most frequently studied is the asthma-COPD overlap (ACO), however, there are no universally accepted diagnostic criteria for ACO. It is recognised that the term ACO includes patients with clinical features of both asthma and COPD, such as more intense eosinophilic bronchial inflammation, more severe respiratory symptoms and more frequent exacerbations, but in contrast, it is associated with a better prognosis compared to COPD. More importantly, ACO patients show better response to inhaled corticosteroid treatment than other COPD phenotypes. The diagnosis of ACO can be difficult in clinical practice, and the identification of these patients can be a challenge for non-specialized physicians. We describe how to recognise and diagnose ACO based on a recently proposed Spanish algorithm and by the analysis of three clinical cases of patients with COPD. The diagnosis of ACO is based on the diagnosis of COPD (chronic airflow obstruction in an adult with significant smoking exposure), in addition to a current diagnosis of asthma and/or signficant eosinophilia.

Treatment of male stress urinary incontinence with the adjustable transobturator male system: Outcomes of a multi-center Iberian study.

AIM: To evaluate effectiveness and safety of the adjustable transobturator male system (ATOMS) for male stress urinary incontinence (SUI). MATERIAL AND METHODS: A retrospective multicenter study was conducted in nine Iberian institutions using a board-approved database for 215 patients intervened between 2012 and 2017, with no case excluded. Continence status, patient satisfaction, number, and grade of complications (Clavien-Dindo) and factors affecting dry rate at adjustment were evaluated. Multivariate analysis defined the population at best success rate. Incontinence recurrence due to device failure and/or explant was evaluated and Kaplan-Meier curve for durability performed. RESULTS: Adjustment was achieved at a mean 1.4 ± 1.9 fillings. Dry-rate after adjustment was 80.5% (96.2% mild and 75.3% moderate-severe), 121 (56.3%) used no pads, and 52 (24.2%) a security pad with urine loss under 10 mL. Mean basal daily pad-test and pad-count decreased from 484 ± 372.3 mL and 3.9 ± 2 pads to 63.5 ± 201.2 mL and 0.9 ± 1.5pads (both P < 0.0001). Satisfaction rate was 85.1% (94.3% mild and 82.1% moderate-severe). Factors associated to dryness were: lesser severity of SUI (P < .0001), absence of radiotherapy (P = 0.0002) and device generation (P = 0.05). Multivariate analysis revealed absence of radiation (OR = 3.12; 1.36-7.19), mild (OR = 19.61; 3.95-100), and moderate (OR = 2.48; 1.1-5.59) SUI were independent predictors. Complications presented in 33(15.35%); 66.7% grade 1, 9.1% grade 2, and 24.2% grade 3. At 24.3 ± 15 mo mean follow-up device was explanted in seven (3.25%) and SUI worsened after adjustment in nine (4.2%). Dry-rate at follow-up was 73% and durability of device in dry patients at adjustment was 89.8% (82.9-94) at 2-years. CONCLUSIONS: This study confirms ATOMS device is safe and achieves high treatment efficacy and patient satisfaction in a multicenter setting. Significantly better results are achieved in less severe and non-irradiated cases. Durability of the device is reassuring in the short-term.

Influence of suturing technique on wound healing and patient morbidity after connective tissue harvesting. A randomized clinical trial.

OBJECTIVES: The aims of this randomized clinical trial were to investigate the influence of the suturing technique and the thickness of the pre- and postoperative palatal and flap mucosa on the early healing of the palate after harvesting a connective tissue graft. Furthermore, patient pain perception was evaluated. MATERIAL AND METHODS: A subepithelial connective tissue graft was obtained from the palate with a single horizontal incision technique. Patients were randomly assigned to continuous interlocking suture group or criss-cross suture group. The thickness of the palatal mucosa and residual palatal flap was measured; however, these variables were not randomized. One week postoperatively, the donor site wound healing was recorded by the modified rate of early healing index (EHI). Patient's pain perception was assessed by a visual analogue scale. RESULTS: Thirty-six patients were evaluated. No statistically significant differences were found between suturing technique and wound healing (p = 0.215). Statistically significant differences were found between postoperative flap thickness and EHI at 1, 3 and 6 mm from the incision line (p < 0.001). Negative correlations reaching statistical significance were found between the number of days of discomfort and residual flap thickness measured at 1, 3 and 6 mm. CONCLUSIONS: No association between the suture technique and the EHI was observed. Moreover, postoperative palatal flap thickness was associated with early wound healing of the donor site. Finally, the greater the postoperative palatal flap thickness, the less intensity of the pain perceived by patients.

Adjustable Transobturator Male System after Failed Surgical Devices for Male Stress Urinary Incontinence: A Feasibility Study.

OBJECTIVES: Feasibility study to evaluate the efficacy and safety of Adjustable Transobturator Male System (ATOMS) after failed surgical devices for male stress urinary incontinence (SUI). MATERIALS AND METHODS: Thirty patients were implanted with ATOMS after they were implanted with surgical device/s previously. SUI severity was evaluated as dryness (0-1 pad/day), mild (2 pads/day), moderate (3-5 pads/day), or severe (≥6 pads/day). Change in pad-test and pad-count after adjustment, operative parameters, patient satisfaction, and number and grade of complications were investigated. RESULTS: Previous failed treatment methods were artificial urinary sphincter (AUS; n = 19), Advance (n = 10), and Virtue (n = 1). Six cases had multiple previous treatments. Preoperative SUI was mild 6 (20%), moderate 11 (36.7%), and severe 13 (43.3%). Median pad-test decreased from 435 mL baseline to 10 mL after adjustment and pad-count from 4 to 0. Dry-rate was 76.7 and 83.3% declared satisfied. Postoperative SUI distribution was mild in 3 (10%) and moderate in 4 (13.3%). No patient had urinary retention after catheter removal. Complications presented in 4 (13.3%; 3 grade-I, 1 grade-II). After a median of 24 months follow-up, no system experienced infection or urethral erosion and 1 (3.3%) was removed for inefficacy. CONCLUSION: Based on short-term efficacy and patient satisfaction, ATOMS can be a realistic alternative for male SUI after other failed systems, including AUS. The absence of urethral erosion and limited infective problems makes this alternative attractive for cases with previous failed treatments.

Geographical Distribution of COPD Prevalence in the Americas.

Surveys estimating chronic obstructive pulmonary disease (COPD) prevalence are unevenly distributed in the Americas, which make it difficult to estimate accurately its geographical distribution. The geographic information system inverse distance weighted (IDW) interpolation technique has proved to be an effective tool in spatial distribution estimation of epidemiological variables, even when real data are few or widely spread. We aimed to represent cartographically the COPD prevalence in the Americas by means of a blue to red scale representation of the prevalence data, where different values are represented as different colours, and a population density filtered IDW interpolation mapping, where areas with a population density <0.1 inhabitants/km2 are hidden. We systematically searched for prevalence rates from population surveys of individuals 40 years and older, and a COPD diagnosis confirmed by spirometry. Interpolation maps were obtained for the whole Americas, even from extensive areas lacking real data. Maps showed high prevalence values in the Southeast and Southwest regions of Canada bordering the United States; in several states of the Great Lakes region, and in the lower Missouri, Ohio and Mississippi basins of the United States; in the coastal regions of south-eastern and southern Brazil; Uruguay, and the Argentine Pampas. In general, most of the remaining American regions showed intermediate values of COPD prevalence. IDW interpolation seems to be a suitable tool to visually display estimates of COPD prevalence, and it may be a valuable help to draw attention about the worrying prevalence of this preventable and treatable disease.