Search

Randomized clinical trials (RCTs) are the gold standard to evaluate intervention efficacy and effectiveness. To apply current, evidence-based interventions to daily practice, it is imperative that practicing intensivists be able to interpret the results of individual RCTs in the context of their patients. In this article, we outline an approach to interpreting critical care RCTs from the perspective of the clinician that focuses on answering four questions: (1) Would my patient have been enrolled and represented in the RCT? (2) Is the intervention feasible? (3) Are there threats to the internal validity of the RCT results? (4) Are the RCT results meaningful? Answers to these four questions can be used to assist intensivists in deciding whether to apply RCT evidence to their patients at the bedside and to avoid common pitfalls of RCT interpretation.

Background: The rates of firearm injuries among pediatric patients have risen significantly in recent years. Extremity injuries resulting from gunshot wounds (GSWs) often require orthopaedic management. In addition to rare nationwide database studies, there are 2 regional studies examining this trend in the South only. Our state has notably high gun ownership and lenient gun protection laws. To examine the orthopaedic burden of gunshot injuries in our region, we reviewed the pediatric patients presenting with GSWs at a tertiary level-1 trauma center over a 7-year period. Methods: A retrospective chart review was conducted of pediatric patients

Background: The adult congenital heart disease (ACHD) population is growing and risk prediction is important to predict adverse outcome and consult patients during their lifecourse. Objectives: This study aims to describe the long-term prognostic value of blood biomarkers in ACHD. Methods: In this prospective observational cohort study, 602 patients with moderate or complex ACHD were included (median age 32.5 years [IQR: 24.7-41.2], 42% female, 90% New York Heart Association I). N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive-troponin T, growth differentiation factor 15, high-sensitive-C-reactive protein, suppression of tumorigenicity-2 and galectin-3, as well as full blood count, renal function, LDL, and HDL were measured. Cox models were applied to relate the selected biomarkers with the primary end point of all-cause mortality and secondary end point of mortality or heart failure. Standardized HRs adjusted for relevant prognostic factors, including age, sex, and complexity of diagnosis, were reported. Results: Abnormal biomarker levels were present in 424 (70.4%) patients. During a median follow-up of 10.1 years, 41 (6.8%) patients died and 81 (13.5%) developed heart failure. Associations were observed between the primary and secondary end point and red cell distribution width, NT-proBNP, and growth differentiation factor 15. In a multibiomarker model, only NT-proBNP remained associated with mortality (HR: 2.74; 95% CI: 2.01-3.74). NT-proBNP significantly improved the C-statistic of the clinical prediction model (0.85-0.92). Based on NT-proBNP alone, low-risk patients could be identified. Patients with NT-proBNP

IMPORTANCE:. The opioid crisis is impacting people across the country and deserves attention to be able to curb the rise in opioid-related deaths. OBJECTIVES:. To evaluate practice patterns in opioid infusion administration and dosing for patients with acute respiratory failure receiving invasive mechanical ventilation. DESIGN:. Retrospective cohort study. SETTING AND PARTICIPANTS:. Patients from 21 hospitals in Kaiser Permanente Northern California and 96 hospitals in Philips electronic ICU Research Institute. MAIN OUTCOMES AND MEASURES:. We assessed whether patients received opioid infusion and the dose of said opioid infusion. RESULTS:. We identified patients with a diagnosis of acute respiratory failure who were initiated on invasive mechanical ventilation. From each patient, we determined if opioid infusions were administered and, among those who received an opioid infusion, the median daily dose of fentanyl infusion. We used hierarchical regression models to quantify variation in opioid infusion use and the median daily dose of fentanyl equivalents across hospitals. We included 13,140 patients in the KPNC cohort and 52,033 patients in the eRI cohort. A total of 7,023 (53.4%) and 16,311 (31.1%) patients received an opioid infusion in the first 21 days of mechanical ventilation in the KPNC and eRI cohorts, respectively. After accounting for patient- and hospital-level fixed effects, the hospital that a patient was admitted to explained 7% (95% CI, 3–11%) and 39% (95% CI, 28–49%) of the variation in opioid infusion use in the KPNC and eRI cohorts, respectively. Among patients who received an opioid infusion, the median daily fentanyl equivalent dose was 692 µg (interquartile range [IQR], 129–1341 µg) in the KPNC cohort and 200 µg (IQR, 0–1050 µg) in the eRI cohort. Hospital explained 4% (95% CI, 1–7%) and 20% (95% CI, 15–26%) of the variation in median daily fentanyl equivalent dose in the KPNC and eRI cohorts, respectively. CONCLUSIONS AND RELEVANCE:. In the context of efforts to limit healthcare-associated opioid exposure, our findings highlight the considerable opioid exposure that accompanies mechanical ventilation and suggest potential under and over-treatment with analgesia. Our results facilitate benchmarking of hospitals’ analgesia practices against risk-adjusted averages and can be used to inform usual care control arms of analgesia and sedation clinical trials.

Background: Bicuspid aortic valve (BAV) is a common congenital heart defect. Patients with BAV are at risk for long-term complications such as valve stenosis and regurgitation. This study aimed to investigate sex differences in blood and imaging biomarkers and to describe the long-term prognostic value of blood and echocardiographic biomarkers. Methods: Patients were included from 2 prospective observational cohort studies; they underwent venous blood sampling and transthoracic echocardiography including speckle tracking. Analyzed blood biomarkers were red-cell distribution width (RDW), creatinine, C-reactive protein (CRP), troponin T, N-terminal pro B-type natriuretic peptide (NT-proBNP), and transforming growth factor-beta (TGF-β). Sex differences were analyzed at baseline. Associations between biomarkers and arrhythmia-free and intervention-free survival were determined by Cox regression, adjusted for age and sex. Results: A total of 182 patients with BAV were included: median age 34; interquartile range [IQR]: 23-46 years; 55.5% male. CRP, NT-proBNP, and RDW were higher in women, whereas creatinine, troponin T and TGF-β were higher among men. After a median follow-up time of 6.9 (IQR: 6.5-9.9) years, arrhythmia-free and intervention-free survival was, 81.0% and 73.1%, respectively. NT-proBNP was associated with both arrhythmia-free and intervention-free survival (hazard ratio [HR], 1.94, P = 0.005 and HR, 2.06, P = 0.002, respectively). On echocardiography higher left atrial (LA) size, left ventricular end-diastolic diameter (LVEDD), left ventricular (LV) mass index and E/e’ ratio were associated with lower arrhythmia-free survival, whereas higher LA size, LV mass index, aortic valve peak velocity, and aortic regurgitation were associated with lower intervention-free survival. Conclusions: Differences were observed in blood biomarkers between men and women with BAV. Besides LV systolic parameters, diastolic LV function and NT-proBNP should have a more prominent role as prognostic markers in clinical care. Résumé: Contexte: La bicuspide valvulaire aortique (BVA) est une anomalie cardiaque congénitale fréquente. Les patients atteints d’une BVA présentent des risques de complications à long terme, comme la sténose valvulaire ou la régurgitation valvulaire. Cette étude visait 1) à évaluer les différences entre les sexes en ce qui concerne les biomarqueurs sanguins et les biomarqueurs à l’imagerie; et 2) à décrire la valeur pronostique à long terme des biomarqueurs sanguins et échocardiographiques. Méthodologie: Des patients de 2 études de cohortes observationnelles prospectives ont été inclus dans l’analyse. Des échantillons de sang veineux ont été prélevés, et des échocardiographies transthoraciques, y compris le suivi des marqueurs acoustiques, ont été effectuées. Les biomarqueurs sanguins analysés étaient les suivants : indice de distribution des globules rouges (IDR), créatinine, protéine C-réactive (CRP), troponine T, propeptide natriurétique de type B N-terminal (NT-proBNP) et facteur de croissance transformant β (TGF-β). Les différences entre les sexes ont été analysées au départ. Les liens entre les biomarqueurs et la survie sans arythmie et sans intervention ont été déterminés par la régression de Cox, avec correction en fonction de l’âge et du sexe. Résultats: Cent quatre-vingt-deux patients présentant une BVA étaient inclus (âge médian de 34 [écart interquartile : 23-46] ans, 55,5 % hommes). La CRP, la NT-proBNP et l’IDR étaient plus élevées chez les femmes, alors que la créatinine, la troponine T et le TGF-β étaient plus élevés chez les hommes. Après une période de suivi médiane de 6,9 (écart interquartile : 6,5-9,9) ans, les taux de survie sans arythmie et sans intervention étaient respectivement de 81,0 % et de 73,1 %. La NT-proBNP a été associée à la survie sans arythmie (rapport des risques instantanés [RRI] : 1,94, p = 0,005) et à la survie sans intervention (RRI : 2,06, p = 0,002). À l’échocardiographie, des valeurs élevées pour la taille de l’oreillette gauche, le diamètre télédiastolique du ventricule gauche (VG), l’indice de masse du VG et le rapport E/e’ étaient associées à un faible taux de survie sans arythmie, alors que des valeurs élevées pour la taille de l’oreillette gauche, l’indice de masse du VG, la vitesse maximale aortique et la régurgitation aortique étaient associées à un faible taux de survie sans intervention. Conclusions: Les biomarqueurs sanguins variaient en fonction du sexe des personnes présentant une BVA. Outre les paramètres systoliques du VG, la fonction VG diastolique et la NT-proBNP devraient être davantage utilisées comme marqueurs pronostiques en soins cliniques.

Objective: To test the hypothesis that the Monoclonal Antibody Screening Score performs consistently better in identifying the need for monoclonal antibody infusion throughout each “wave” of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant predominance during the coronavirus disease 2019 (COVID-19) pandemic and that the infusion of contemporary monoclonal antibody treatments is associated with a lower risk of hospitalization. Patients and Methods: In this retrospective cohort study, we evaluated the efficacy of monoclonal antibody treatment compared with that of no monoclonal antibody treatment in symptomatic adults who tested positive for SARS-CoV-2 regardless of their risk factors for disease progression or vaccination status during different periods of SARS-CoV-2 variant predominance. The primary outcome was hospitalization within 28 days after COVID-19 diagnosis. The study was conducted on patients with a diagnosis of COVID-19 from November 19, 2020, through May 12, 2022. Results: Of the included 118,936 eligible patients, hospitalization within 28 days of COVID-19 diagnosis occurred in 2.52% (456/18,090) of patients who received monoclonal antibody treatment and 6.98% (7,037/100,846) of patients who did not. Treatment with monoclonal antibody therapies was associated with a lower risk of hospitalization when using stratified data analytics, propensity scoring, and regression and machine learning models with and without adjustments for putative confounding variables, such as advanced age and coexisting medical conditions (eg, relative risk, 0.15; 95% CI, 0.14-0.17). Conclusion: Among patients with mild to moderate COVID-19, including those who have been vaccinated, monoclonal antibody treatment was associated with a lower risk of hospital admission during each wave of the COVID-19 pandemic.

Endometrial receptivity and its management in assisted reproduction is now a significant focus of research interest. Endometrial receptivity tests, which analyze different panels of gene expression, are usually offered in fertility clinics to determine the women's individual ‘window of implantation’, providing a personalized timing for embryo transfer. However, there are still no definite indications on whether its inclusion in the study of the infertile couple or the study of patients with repeated implantation failure is essential.

Background. Surgical-site infection (SSI) is the most common early infectious complication after pancreas transplantation (PT). Although SSI has been shown to worsen outcomes, little data exist to guide optimal choices in perioperative prophylaxis. Methods. We performed a retrospective cohort study of PT recipients from 2010–2020 to examine the effect of perioperative antibiotic prophylaxis with Enterococcus coverage. Enterococcus coverage included antibiotics that would be active for penicillin-susceptible Enterococcus isolates. The primary outcome was SSI within 30 d of transplantation, and secondary outcomes were Clostridioides difficile infection (CDI) and a composite of pancreas allograft failure or death. Outcomes were analyzed by multivariable Cox regression. Results. Of 477 PT recipients, 217 (45.5%) received perioperative prophylaxis with Enterococcus coverage. Eighty-seven recipients (18.2%) developed an SSI after a median of 15 d from transplantation. In multivariable Cox regression analysis, perioperative Enterococcus prophylaxis was associated with reduced risk of SSI (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.35-0.96; P = 0.034). Anastomotic leak was also significantly associated with elevated risk of SSI (HR 13.95; 95% CI, 8.72-22.32; P

Objective: To examine the clinical characteristics, risk of hospitalization, and mortality of patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. Patients and Methods: We retrospectively reviewed all patients with SARS-CoV-2 reinfection at all Mayo Clinic sites between May 23, 2020, and June 30, 2021 (the period before the emergence of the Delta variant in the United States). The reinfection was defined as a positive SARS-CoV-2 test more than or equal to 90 days after initial infection or 45-89 days after with symptomatic second episode. Vaccination status was classified as fully vaccinated, first dose, and unvaccinated. Comparative analysis of baseline characteristics and comorbidities was performed by hospitalization and vaccination status. The survival analysis of the hospitalized patients was performed using Cox proportional hazard regression. Results: Among the 554 patients reinfected with SARS-CoV-2, 59 (10.6%) were pediatric, and 495 (89.4%) were adults. The median age was 13.9 years (interquartile range, 8.5-16.5 years) for the pediatric and 50.2 years (interquartile range, 28.4-65.6 years) for the adult population. Among the adult patients, the majority were unvaccinated (83.4%, n=413), and the duration to reinfection from initial infection was the longest in the fully vaccinated group (P

OBJECTIVES:. The COVID-19 pandemic led to rapid changes in care delivery for critically ill patients, due to factors including increased numbers of ICU patients, shifting staff roles, and changed care locations. As these changes may have impacted the care of patients without COVID-19, we assessed changes in common ICU practices for mechanically ventilated patients with non-COVID acute respiratory failure at the onset of and during the COVID-19 pandemic. DESIGN:. Interrupted time series analysis, adjusted for seasonality and autocorrelation where present, evaluating trends in common ICU practices prior to the pandemic (March 2016 to February 2020), at the onset of the pandemic (April 2020) and intra-pandemic (April 2020 to December 2020). SETTING:. Premier Healthcare Database, containing data from 25% of U.S. discharges from January 1, 2016, to December 31, 2020. PATIENTS:. Patients without COVID-19 receiving mechanical ventilation for acute respiratory failure. INTERVENTIONS:. We assessed monthly rates of chest radiograph (CXR), chest CT scans, lower extremity noninvasive vascular testing (LENI), bronchoscopy, arterial catheters, and central venous catheters. MEASUREMENTS AND MAIN RESULTS:. We identified 742,096 mechanically ventilated patients without COVID-19 at 545 hospitals. At the onset of the pandemic, CXR (–0.5% [–0.9% to –0.2%; p = 0.001]), LENI (LENI: –2.1% [–3.3% to –0.9%; p = 0.001]), and bronchoscopy rates (–1.0% [–1.5% to –0.6%; p < 0.001]) decreased; use of chest CT increased (1.5% [0.5–2.5%; p = 0.006]). Use of arterial lines and central venous catheters did not change significantly. Intra-pandemic, LENI (0.5% [0.3–0.7%; p < 0.001]/mo) and bronchoscopy (0.1% [0.05–0.2%; p < 0.001]/mo) trends increased relative to pre-pandemic trends, while the remainder of practices did not change significantly. CONCLUSIONS:. We observed several statistically significant changes to practice patterns among patients without COVID-19 early during the pandemic. However, most of the changes were small or temporary, suggesting that routine practices in the care of mechanically ventilated patients in the ICU was not drastically affected by the pandemic.

IMPORTANCE:. Troponin I is frequently elevated in sepsis, but optimal clinical approaches to diagnosis and management of troponin I during sepsis are unclear. OBJECTIVES:. We aimed to describe the variation in troponin I measurement and the cardiovascular diagnostic and therapeutic approach to elevated troponin I among critically ill adults with sepsis. DESIGN, SETTING, AND PARTICIPANTS:. Observational cohort study of the hospital-level variation in serial troponin I measurement, trending troponin I to peak, echocardiography, cardiac stress test, cardiac catheterization, antiplatelet agents, therapeutic anticoagulation, beta-blockers, and statins quantified using hospital median odds ratios—the median odds of receiving an intervention at randomly selected higher versus lower rate hospitals—derived from multivariable-adjusted random-effects logistic regression models with hospital site as the random effect. The Premier Healthcare Database was used. Patients were adults aged greater than 18 years admitted to the ICU with sepsis from 2016 to 2020. MAIN OUTCOMES AND MEASURES:. The hospital-level median odds ratios of troponin I measurement as well as cardiovascular diagnostics and therapeutics. RESULTS:. Among 85,830 adults with sepsis, 53,058 (61.8%) had a troponin I measured, with a median odds ratio of troponin measurement across hospitals of 5.30 (95% CI, 4.98–5.67). Among 27,665 adults (32.2%) with sepsis and an elevated troponin I level, 84.8% had serial troponin I measurements, 66.0% had troponin trended to peak level, 66.7% had an echocardiogram, 4.1% had a cardiac stress test, 6.6% underwent cardiac catheterization, 48.3% received antiplatelet agents, 8.3% received therapeutic anticoagulation, 50.5% received beta-blockers, and 38.1% received statins. The median odds ratios between hospitals for cardiovascular diagnostics and therapeutics ranged from 1.28 (95% CI, 1.24–1.32) for use of beta-blockers to 7.58 (95% CI, 6.43–8.77) for use of therapeutic anticoagulation. CONCLUSIONS AND RELEVANCE:. Both troponin I measurement and the approach to an elevated troponin I among critically ill adults with sepsis varied widely across hospitals consistent with disparate practice and care efficiency. Prospective studies are needed to guide an informed approach to troponin I measurement and cardiovascular evaluation in sepsis.

Objective: To reduce health care facility–onset (HCFO) Clostridioides difficile infection (CDI) incidence by improving diagnostic stewardship and reducing the inappropriate testing of C difficile assays. Patients and Methods: A multidisciplinary team conducted a quality improvement initiative from January 1, 2020, through March 31, 2021. Clostridioides difficile infection and inappropriate testing were identified via electronic health records using predefined criteria related to stool quantity/caliber, confounding medications, and laboratory data. An intervention bundle was designed including (1) provider education, (2) implementation of an appropriate testing algorithm, (3) expert review of C difficile orders, and (4) batch testing of assays to facilitate review and cancellation if inappropriate. Results: Compared with a baseline period from January to September 2020, implementation of our intervention bundle from December 2020 to March 2021 resulted in an 83.6% reduction in inappropriate orders tested and a 41.7% reduction in HCFO CDI incidence. Conclusion: A novel prevention bundle improved C difficile diagnostic stewardship and HCFO CDI incidence by reducing testing of inappropriate orders. Such initiatives targeting HCFO CDI may positively affect patient safety and hospital reimbursement.

The coronavirus disease 2019 (COVID-19) pandemic created an extremely disruptive challenge for health care leaders that required a rapid, dynamic, and innovative response. The purpose of this manuscript is to share the leadership actions and decisions at Mayo Clinic in Florida during the first 6 months of the pandemic (February to July 2020). We note 4 strategies that contributed to an effective response: (1) leverage experience with disaster preparedness and mobilize regional and national networks; (2) use surge models to anticipate and to address supply chain issues as well as practical and financial effects of the pandemic; (3) adapt creatively to establish new safety and procedural protocols in various areas for various populations; and (4) communicate timely information effectively and be the common source of truth. Mayo Clinic in Florida was able to address the surges of patients with COVID-19, to provide ongoing tertiary care, and to restore function within the first 6 months with new, strengthened practices and protocols.

Objective: To assess the impact of cessation of screening urine cultures on surgical site infection (SSI) incidence in clinical practice. Patients and Methods: Our study included patients undergoing hip replacement, knee replacement, spinal fusion, and laminectomy 12 months before (preintervention) and after (postintervention) cessation of preoperative screening urine cultures on June 1, 2017, at our institution. Urine cultures and urinalyses performed within 30 days before surgery during the 12 months before and after cessation were reviewed. SSI surveillance was performed in accordance with the methods of the National Healthcare Safety Network. Results: A total of 2754 patients were included (1286 preintervention and 1468 postintervention). In the preintervention period, 1141 urine cultures were performed, compared to 153 in the postintervention period; 35 and 6 episodes of asymptomatic bacteriuria were treated, respectively. The occurrence of SSI did not differ noticeably between time periods (1.2% vs 0.7%, P=.24), and quarterly incidences of SSI were unchanged. The rate of SSI was significantly lower in the postintervention period for laminectomy (3.0% vs 0.3%, P=.02). Conclusion: An 86.6% (153 vs 1141) reduction in screening urine cultures over a 12-month period was associated with a reduction of 988 unnecessary urine cultures, an 82.8% (6 vs 35) decline in inappropriate antibiotic treatment of asymptomatic bacteriuria, and no increase in SSI incidence after hip replacement, knee replacement, spinal fusion, or laminectomy procedures. No value of screening urine cultures before clean surgery was identified.

IMPORTANCE:. At the start of the coronavirus disease 2019 pandemic, medications repurposed for management of coronavirus disease 2019 were used in the absence of clinical trial evidence. OBJECTIVES:. To describe the variation and evolution in use of repurposed medications for coronavirus disease 2019. DESIGN, SETTING, AND PARTICIPANTS:. Observational cohort study of adults hospitalized with coronavirus disease 2019 between February 15, 2020, and April 12, 2021, across 76 United States and international hospitals within the Society of Critical Care Medicine’s Discovery Viral Infection and Respiratory Illness Universal Study coronavirus disease 2019 registry. MAIN OUTCOMES AND MEASURES:. Hospital variation was quantified using multivariable adjusted random effects logistic regression models and unsupervised clustering. Repurposed medications included antivirals, corticosteroids, hydroxychloroquine, immunomodulators, and therapeutic dose anticoagulants. RESULTS:. Among 7,069 adults hospitalized with coronavirus disease 2019, 1,979 (28%) received antivirals, 2,876 (41%) received corticosteroids, 1,779 (25%) received hydroxychloroquine, 620 (9%) received immunomodulators, and 2,154 (31%) received therapeutic dose anticoagulants. Contribution of hospital site to risk-adjusted variation was 46% for antivirals, 30% for corticosteroids, 48% for hydroxychloroquine, 46% for immunomodulators, and 52% for therapeutic dose anticoagulants. Compared with the early pandemic, the later pandemic practice phenotypes converged with increased use of antivirals (odds ratio, 3.14; 95% CI, 2.40–4.10) and corticosteroids (odds ratio, 5.43; 95% CI, 4.23–6.97), with decreased use of hydroxychloroquine (odds ratio, 0.02; 95% CI, 0.01–0.04) and immunomodulators (odds ratio, 0.49; 95% CI, 0.34–0.70). There was no clinically significant change in the use of therapeutic dose anticoagulants (odds ratio, 1.01; 95% CI, 1.01–1.02). There were no differences in risk-adjusted mortality between hospitals with high rates of repurposed medication use compared with hospitals with low rates of use. CONCLUSIONS AND RELEVANCE:. Hospital variation in the use of repurposed medications varied widely across hospitals early in the pandemic and later converged with the emergence of randomized clinical trials. Platforms developed for rapid activation and enrollment in clinical trials of repurposed medications are needed prior to the next pandemic to expedite effective, evidence-based practice.

This multiple case study investigated perspectives of childhood brain tumor survivors on reintegration into school over a 2-year period. Semistructured interviews were conducted with 5 children at 3 times to obtain an extensive view of their overall school experience. Thematic analysis of data resulted in 4 themes: “school life and participation,” “peer relations and friendships,” “performance and difficulties,” and “support and follow-up.” Childhood brain tumor survivors consider school attendance as part of a normal disease-free life. Social contact and friendships represent their main motivating factors for returning to school. Attitudes and feelings regarding performance, difficulties, and support vary among survivors and change over time. In conclusion, continuity in learning and social contact established before the return facilitate the reintegration process. A comprehensive assessment of their academic and psychosocial functioning should be organized on reentry. Systematic follow-up by parents, school staff, and health professionals throughout the child’s school career is required.

Background: Since 2006, many countries have implemented publicly funded human papillomavirus (HPV) immunisation programmes. However, global estimates of the extent and impact of vaccine coverage are still unavailable. We aimed to quantify worldwide cumulative coverage of publicly funded HPV immunisation programmes up to 2014, and the potential impact on future cervical cancer cases and deaths. Methods: Between Nov 1 and Dec 22, 2014, we systematically reviewed PubMed, Scopus, and official websites to identify HPV immunisation programmes worldwide, and retrieved age-specific HPV vaccination coverage rates up to October, 2014. To estimate the coverage and number of vaccinated women, retrieved coverage rates were converted into birth-cohort-specific rates, with an imputation algorithm to impute missing data, and applied to global population estimates and cervical cancer projections by country and income level. Findings: From June, 2006, to October, 2014, 64 countries nationally, four countries subnationally, and 12 overseas territories had implemented HPV immunisation programmes. An estimated 118 million women had been targeted through these programmes, but only 1% were from low-income or lower-middle-income countries. 47 million women (95% CI 39–55 million) received the full course of vaccine, representing a total population coverage of 1·4% (95% CI 1·1–1·6), and 59 million women (48–71 million) had received at least one dose, representing a total population coverage of 1·7% (1·4–2·1). In more developed regions, 33·6% (95% CI 25·9–41·7) of females aged 10–20 years received the full course of vaccine, compared with only 2·7% (1·8–3·6) of females in less developed regions. The impact of the vaccine will be higher in upper-middle-income countries (178 192 averted cases by age 75 years) than in high-income countries (165 033 averted cases), despite the lower number of vaccinated women (13·3 million vs 32·2 million). Interpretation: Many women from high-income and upper-middle-income countries have been vaccinated against HPV. However, populations with the highest incidence and mortality of disease remain largely unprotected. Rapid roll-out of the vaccine in low-income and middle-income countries might be the only feasible way to narrow present inequalities in cervical cancer burden and prevention. Funding: PATH, Instituto de Salud Carlos III, and Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR).

Patients with malignant tumors originating from the biliary tree have a poor prognosis, since only a minority of tumors can be resected and most palliative regimens have shown only limited success. We present two patients with unresectable tumors, who were treated with trans-arterial 90yttrium radioembolization: a patient with an infiltrating gallbladder carcinoma and a patient with an extensive intrahepatic cholangio-carcinoma. In both cases the treatment was technically feasible, effective in controlling tumor growth, and without significant side effects. In conclusion, the presented cases demonstrate the potential of 90yt-trium radioembolization as a palliative treatment option for malignant tumors of the biliary tree.

Objective: To report 5-year efficacy and safety of upadacitinib (UPA) in rheumatoid arthritis (RA) from the phase III long-term extension (LTE) of SELECT-NEXT., Methods: Patients on stable conventional synthetic disease-modifying antirheumatic drugs were randomized to UPA 15 mg once daily (QD), UPA 30 mg QD, or placebo for 12 weeks. Following this, placebo-randomized patients were switched to UPA 15 mg QD or UPA 30 mg QD in the LTE; UPA-randomized patients continued their original dose. Blinding remained until dose switching from UPA 30 mg QD to UPA 15 mg QD because of approval of UPA 15 mg QD; the earliest switch occurred at week 168. Efficacy (as observed) and treatment-emergent adverse events (TEAEs) are reported through 5 years., Results: Overall, 611 (92%) randomized patients entered the LTE; 271 (44%) discontinued the study drug by 5 years, primarily because of adverse events (16%). Clinical outcomes improved or were maintained at 5 years; 51% and 43% of patients achieved Clinical Disease Activity Index remission and 75% and 66% achieved Disease Activity Score in 28 joints based on C-reactive protein < 2.6 among those initially randomized to UPA 15 mg QD and UPA 30 mg QD, respectively. Proportions of patients achieving ≥ 20%/50%/70% improvement in American College of Rheumatology criteria responses increased from week 60 through 5 years. Results were similar regardless of initial randomization to UPA or placebo. TEAEs, including TEAEs of special interest, were consistent with earlier analyses and other SELECT studies. Malignancies (excluding nonmelanoma skin cancer), major adverse cardiovascular events, and venous thromboembolic events were reported infrequently. No new safety signals were observed., Conclusion: The 5-year benefit-risk profile for UPA in RA remains favorable. (SELECT-NEXT; ClinicalTrials.gov: NCT02675426)., (Copyright © 2024 by the Journal of Rheumatology.)

Objective: Although exercise therapy is safe, effective, and recommended as a nonpharmacological treatment for axial spondyloarthritis (axSpA), there is a lack of guidelines regarding type and dosage. Insufficient knowledge about physical and physiological variables makes designing effective exercise programs challenging. Therefore, the goal of this study was to simultaneously assess trunk strength, spinal mobility, and the cardiorespiratory fitness of patients with axSpA., Methods: In a cross-sectional study, 58 patients with axSpA (mean age 40.8 yrs, 50% male, mean symptom duration 10.3 yrs) performed maximal cervical and trunk mobility and isometric strength tests in all planes (using David Back Concept devices) and a maximal cardiopulmonary bicycle exercise test (n = 25). Mobility and strength data were compared to healthy reference data. Cut-off values for clinical cardiopulmonary exercise testing interpretation were used to judge normality. Patients were compared based on radiographic involvement and symptom duration., Results: Both strength ( P ≤ 0.02) and mobility ( P ≤ 0.001) were significantly lower for the patients with axSpA compared to the reference. Strength deficits were comparable between the radiographic and nonradiographic groups ( P > 0.05, except trunk extension [ P = 0.03]), whereas mobility showed higher deficits in the radiographic group (cervical extension [ P = 0.02] and rotation [ P = 0.01], and trunk extension [ P = 0.03] and rotation [ P = 0.03]), regardless of symptom duration. Similarly, symptom duration positively affected oxygen pulse ( P = 0.03), relative anaerobic threshold ( P = 0.02), and aerobic capacity ( P = 0.02)., Conclusion: In patients with axSpA, strength is more affected than mobility when compared to healthy controls. Likewise, mainly the metabolic component of aerobic capacity is impaired, affecting cardiopulmonary fitness. These findings indicate that future personalized exercise programs in patients with axSpA should incorporate exercises for cardiopulmonary fitness next to strength and mobility training., (Copyright © 2024 by the Journal of Rheumatology.)

Antler is one of the primary animal raw materials exploited for technical purposes by the hunter-gatherer groups of the Eurasian Upper Palaeolithic (UP) all over the ecological range of deers, and beyond. It was exhaustively employed to produce one of the most critical tools for the survival of the UP societies: hunting weapons. However, antler implements can be made from diverse deer taxa, with different ecological requirements and ethological behaviours. Identifying the antler's origin at a taxonomic level is thus essential in improving our knowledge of humans' functional, practical and symbolic choices, as well as the human-animal interface during Prehistoric times. Nevertheless, palaeogenetics analyses have focused mainly on bone and teeth, with genetic studies of antler generally focused on modern deer conservation. Here we present the results of the first whole mitochondrial genome ancient DNA (aDNA) analysis by means of in-solution hybridisation capture of antlers from pre-Holocene archaeological contexts. We analysed a set of 50 Palaeolithic and Neolithic (c. 34-8ka) antler and osseous objects from South-Western Europe, Central Europe, South-Western Asia and the Caucasus. We successfully obtained aDNA, allowing us to identify the exploited taxa and demonstrate the archaeological relevance of those finds. Moreover, as most of the antlers were sampled using a minimally-invasive method, further analyses (morphometric, technical, genetic, radiometric and more) remain possible on these objects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Burial rites of archaeological populations are frequently interpreted based on cremated remains of the human body and the urn they were deposited in. In comparison to inhumations, information about the deceased is much more limited and dependent on fragmentation, selection of body regions, taphonomic processes, and excavation techniques. So far, little attention has been paid to the context in which urns are buried. In this study, we combined archaeological techniques with anthropology, computed tomography, archaeobotany, zooarchaeology, geochemistry and isotopic approaches and conducted a detailed analysis on a case study of two Late Bronze Age urns from St. Pölten, Austria (c. 1430 and 1260 cal. BCE). The urns were recovered en-bloc and CT-scanned before the micro-excavation. Osteological and strontium isotope analysis revealed that the cremated remains comprised a young adult female and a child that died at the age of 10-12 years. Both individuals had been subject to physiological stress and were likely local. Animal bones burnt at different temperatures suggested different depositional pathways into the urn and pit as part of the pyre, food offerings, and unintentional settlement debris. Eight wild plant and five crop plant species appeared as part of the local landscape, as food offerings and fire accelerants. Sediment chemistry suggests that pyre remains were deposited around the urns during burial. Multi-element geochemistry, archaeobotany, and zooarchaeology provide insights into the Late Bronze Age environment, the process of cremation, the gathering of bones and final funerary deposition., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Waltenberger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: RE-EMBARK investigated etanercept (ETN) withdrawal and retreatment in patients with nonradiographic axial spondyloarthritis (nr-axSpA) achieving inactive disease., Methods: Patients received ETN and a background nonsteroidal antiinflammatory drug for 24 weeks in period 1 (P1); those achieving inactive disease (Ankylosing Spondylitis Disease Activity Score [ASDAS] with C-reactive protein [CRP] < 1.3) discontinued ETN for 40 weeks or less (period 2 [P2]). Patients who flared (ASDAS with erythrocyte sedimentation rate [ESR] ≥ 2.1) were retreated for 12 weeks in period 3 (P3). The primary endpoint was the proportion of patients with inactive disease who flared within 40 weeks of ETN withdrawal. Baseline characteristics were analyzed post hoc as predictors of maintenance and regaining of inactive disease, respectively, using univariate logistic and stepwise multivariable logistic regression models., Results: The proportion of patients experiencing flare following ETN withdrawal (P2) increased from 22.3% (25/112) after 4 weeks to 67% (77/115) after 40 weeks; 74.8% (86/115) experienced flare at any time during P2. Median time to flare was 16.1 weeks. Most patients (54/87, 62.1%) who were retreated with ETN in P3 reachieved inactive disease. Absence of both sacroiliitis detected on magnetic resonance imaging (MRI) and high-sensitivity CRP (hs-CRP) > 3 mg/L at baseline predicted inactive disease maintenance in P2 following ETN withdrawal in multivariable analysis; male sex and age younger than 40 years predicted regaining of inactive disease in P3 after flare/retreatment. There were no unexpected safety signals., Conclusion: Approximately 25% of patients maintained inactive disease for 40 weeks after discontinuing ETN. Absence of both MRI sacroiliitis and high hs-CRP at baseline predicted response maintenance after ETN withdrawal. (ClinicalTrials.gov: NCT02509026)., (Copyright © 2023 by the Journal of Rheumatology.)

Evidence of mobiliary art and body augmentation are associated with the cultural innovations introduced by Homo sapiens at the beginning of the Upper Paleolithic. Here, we report the discovery of the oldest known human-modified punctate ornament, a decorated ivory pendant from the Paleolithic layers at Stajnia Cave in Poland. We describe the features of this unique piece, as well as the stratigraphic context and the details of its chronometric dating. The Stajnia Cave plate is a personal 'jewellery' object that was created 41,500 calendar years ago (directly radiocarbon dated). It is the oldest known of its kind in Eurasia and it establishes a new starting date for a tradition directly connected to the spread of modern Homo sapiens in Europe., (© 2021. The Author(s).)

Objective: To assess the efficacy of secukinumab on axial and peripheral enthesitis in patients with ankylosing spondylitis (AS) using pooled data from randomized controlled phase III studies., Methods: In this posthoc analysis, data were pooled from patients originally randomized to secukinumab 150 mg, 300 mg, or placebo (PBO) from phase III MEASURE 1-4 studies (ClinicalTrials.gov: NCT01358175, NCT01649375, NCT02008916, and NCT02159053). Maastricht AS Enthesitis Score (MASES) was used for assessments of enthesitis through Week 52. Efficacy outcomes were mean change in MASES score and complete resolution (MASES = 0) of enthesitis in patients with baseline MASES > 0., Results: A total of 693 (71.5%) patients had enthesitis at baseline in secukinumab 300 mg, 150 mg, and PBO groups (58 [76.3%], 355 [70.4%], and 280 [72%], respectively) out of 969 patients pooled in this analysis. At Week 16, mean changes from baseline for overall MASES and enthesitis at axial MASES sites, respectively, were as follows: -2.9 ( P < 0.01) and -2.9 ( P < 0.01) for secukinumab 300 mg; -2.4 ( P < 0.015) and -2.3 ( P < 0.05) for secukinumab 150 mg; and -1.9 and -1.8 for PBO, with improvements seen through Week 52. More than one-third of secukinumab-treated patients (300 mg: 36.2%; 150 mg: 40.8%) achieved complete resolution of enthesitis at Week 16., Conclusion: Secukinumab improved enthesitis at overall MASES and axial sites in patients with AS., (© 2021 The Journal of Rheumatology.)

Objective: This study evaluated the effect of ixekizumab (IXE) on self-reported functioning and health in patients with radiographic axial spondyloarthritis (r-axSpA) who were either biological disease-modifying antirheumatic drug (bDMARD)-naïve or failed at least 1 tumor necrosis factor inhibitor (TNFi)., Methods: In 2 multicenter, randomized, double-blind, placebo-controlled, and active-controlled (bDMARD-naïve only) trials, patients with r-axSpA were randomly assigned to receive 80 mg of IXE [every 2 weeks (Q2W) or every 4 weeks (Q4W)], placebo (PBO), or adalimumab (ADA; bDMARD-naïve only). After 16 weeks, patients who received PBO or ADA were rerandomized to receive IXE (Q2W or Q4W) up to Week 52. Functioning and health were measured by the generic 36-item Short Form Health Survey (SF-36) and the disease-specific Assessment of Spondyloarthritis international Society Health Index (ASAS HI). Societal health utility was assessed by the 5-level EuroQol-5 Dimension (EQ-5D-5L)., Results: At Week 16, both doses of IXE in bDMARD-naïve and TNFi-experienced patients resulted in larger improvement in SF-36, ASAS HI, and EQ-5D-5L versus placebo. For SF-36, the largest improvements were seen for the domains of bodily pain, physical function, and role physical. A larger proportion of patients reaching improvement in ASAS HI ≥ 3 as well as an achievement of ASAS HI good health status was reported in patients treated with IXE. Improvements were maintained through Week 52., Conclusion: IXE significantly improved functioning and health as assessed by both generic and disease-specific measures, as well as societal health utility values in patients with r-axSpA, as measured by SF-36, ASAS HI, and EQ-5D-5L at Week 16, and improvements were sustained through 52 weeks., (Copyright © 2021 by the Journal of Rheumatology.)

The Micoquian is the broadest and longest enduring cultural facies of the Late Middle Palaeolithic that spread across the periglacial and boreal environments of Europe between Eastern France, Poland, and Northern Caucasus. Here, we present new data from the archaeological record of Stajnia Cave (Poland) and the paleogenetic analysis of a Neanderthal molar S5000, found in a Micoquian context. Our results demonstrate that the mtDNA genome of Stajnia S5000 dates to MIS 5a making the tooth the oldest Neanderthal specimen from Central-Eastern Europe. Furthermore, S5000 mtDNA has the fewest number of differences to mtDNA of Mezmaiskaya 1 Neanderthal from Northern Caucasus, and is more distant from almost contemporaneous Neanderthals of Scladina and Hohlenstein-Stadel. This observation and the technological affinity between Poland and the Northern Caucasus could be the result of increased mobility of Neanderthals that changed their subsistence strategy for coping with the new low biomass environments and the increased foraging radius of gregarious animals. The Prut and Dniester rivers were probably used as the main corridors of dispersal. The persistence of the Micoquian techno-complex in South-Eastern Europe infers that this axis of mobility was also used at the beginning of MIS 3 when a Neanderthal population turnover occurred in the Northern Caucasus.

Objective: Increased risk of comorbidities has been reported in spondyloarthritis (SpA). The objective of this study was to determine the prevalence and risk of developing comorbidities in patients with SpA in 3 Latin American (LA) countries, and to compare that prevalence with the general population., Methods: Data were analyzed from 390 patients with SpA enrolled in the Assessment of SpondyloArthritis international Society of Comorbidities in SpA study from Argentina, Colombia, and Mexico. Age- and sex-standardized prevalence (95% CI) was estimated for arterial hypertension (AHT), tuberculosis (TB), and malignancies. Age- and sex-specific data from the general population were obtained from the Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study for AHT, the Global TB report, and the GLOBOCAN project for malignancies. Data analyzed for AHT were confined to Colombia and Mexico. The prevalence in patients with SpA was compared with the prevalence in the general population per age- and sex-specific stratum, resulting in standardized risk ratios (SRR)., Results: In total, 64% of the patients with SpA were male, with a mean age of 45 years (SD 14.7). The most common comorbidities in the 3 LA countries were AHT (25.3%, 95% CI 21.2-30.0), hypercholesterolemia (21.5%, 95% CI 17.6-26.0), and osteoporosis (9.4%, 95% CI 6.8-12.9). AHT prevalence in Colombia and Mexico was 21.4% (95% CI 15.4-28.9) and was higher than the general population (12.5%, 95% CI 11.4-13.7), resulting in an SRR of 1.5. TB prevalence in the 3 LA countries was 3.3% (95% CI 1.8-5.7), which was significantly higher than in the general population (0.32%), leading to an SRR of 10.3. The prevalence of malignancies was not increased., Conclusion: Patients with SpA in LA are at increased risk of AHT and TB in comparison to the general population. While this sample of patients may not be entirely representative of the patient population in each country, a systematic evaluation of these comorbidities in all patients with SpA still may help to monitor these conditions better.

Present-day hunter-gatherers (HGs) live in multilevel social groups essential to sustain a population structure characterized by limited levels of within-band relatedness and inbreeding. When these wider social networks evolved among HGs is unknown. To investigate whether the contemporary HG strategy was already present in the Upper Paleolithic, we used complete genome sequences from Sunghir, a site dated to ~34,000 years before the present, containing multiple anatomically modern human individuals. We show that individuals at Sunghir derive from a population of small effective size, with limited kinship and levels of inbreeding similar to HG populations. Our findings suggest that Upper Paleolithic social organization was similar to that of living HGs, with limited relatedness within residential groups embedded in a larger mating network., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Introduction: Spasticity is a medical problem with a high incidence that significantly impact on the quality of life of patients and their families., Aim: To analyze and to answer different questions about the use of botulinum toxin type A (BTA) in our clinical practice., Development: A group of experts in neurology develop a list of topics related with the use of BTA. Two big groups were considered: spasticity in adults and in children with cerebral palsy. A literature search at PubMed for English, French, and Spanish language articles published up to June 2016 was performed. The manuscript was structured as a questionnaire that includes those questions that, according to the panel opinion, could generate more controversy or doubt. The initial draft was reviewed by the expert panel members to allow for modifications, and after subsequent revisions for achieving the highest degree of consensus, the final text was then validated. Different questions about diverse aspects of spasticity in adults, such as methods for evaluating spasticity, infiltration techniques, doses, number of infiltration points, etc. Regarding spasticity in children with cerebral palsy, the document included questions about minimum age of infiltration, methods of analgesia, etc., Conclusions: This review is a tool for continuous training for neurologist and rehabilitation specialist and residents of both specialties, about different specific areas of the management of BTA.

Objective: To evaluate the validity of enthesitis indices in patients with peripheral spondyloarthritis (pSpA)., Methods: The ABILITY-2 study evaluated the efficacy of adalimumab (ADA) versus placebo (PBO) in patients with active pSpA over 12 weeks. Patients received open-label ADA for an additional 144 weeks. Twenty-nine enthesitis sites used in 3 enthesitis scoring systems [Leeds Enthesitis Index (LEI), Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index, Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)] were assessed; discriminatory capacity and treatment response at Week 12 were calculated by standardized mean difference (SMD) and Guyatt's effect size (ES). Sites showing resolution or new-onset enthesitis from baseline to Week 12 were analyzed., Results: Overall, 165 patients (ADA, n = 84; PBO, n = 81) were randomized; 143 had ≥ 1 enthesitis site at baseline. The LEI (SMD -0.73, ES -1.07) and SPARCC (SMD -0.56, ES -0.99) enthesitis indices showed higher discriminatory ability and treatment response than MASES (SMD -0.32, ES -0.81). At Week 12, among sites that were positive at baseline, significantly more (p < 0.05) showed resolution among patients treated with ADA versus PBO in the Achilles tendon (60.4% and 36.5%, respectively), medial epicondyle (73.2%, 48.7%), lateral epicondyle (80.6%, 52.8%), and iliac crest (73.5%, 47.2%). Among negative sites at baseline, significantly less (p < 0.05) new-onset enthesitis was observed with ADA versus PBO for Achilles tendon (3.6% and 10.9%, respectively), greater trochanter (3.4%, 14.4%), lateral epicondyle humerus (4.7%, 15.1%), medial femoral condyle (1.6%, 9.2%), and quadriceps insertion superior patella (1.5%, 7.0%)., Conclusion: The LEI and SPARCC enthesitis indices showed better discriminatory capacity and treatment response in patients with pSpA versus MASES, likely because these indices contain more peripheral sites., Trial Registration Number: ClinicalTrials.gov NCT01064856.

Objective: Apremilast, an oral phosphodiesterase 4 inhibitor, downregulates intracellular inflammatory mediator synthesis by elevating cyclic adenosine monophosphate levels. The PALACE 2 trial evaluated apremilast efficacy and safety in patients with active psoriatic arthritis (PsA) despite prior conventional disease-modifying antirheumatic drugs and/or biologic therapy., Methods: Eligible patients were randomized (1:1:1) to placebo, apremilast 20 mg BID, or apremilast 30 mg BID. At Week 16, patients with swollen and tender joint count improvement < 20% entered early escape, with placebo patients rerandomized (1:1) to apremilast 20 mg BID or 30 mg BID while apremilast patients continued on their initial apremilast dose. At Week 24, patients remaining on placebo were rerandomized to apremilast 20 mg BID or 30 mg BID. The primary endpoint was the proportion of patients achieving > 20% improvement in American College of Rheumatology response criteria (ACR20) at Week 16., Results: In the intent-to-treat population (N = 484), ACR20 at Week 16 was achieved by more patients receiving apremilast 20 mg BID [37.4% (p = 0.0002)] and 30 mg BID [32.1% (p = 0.0060)] versus placebo (18.9%). Clinically meaningful improvements in signs and symptoms of PsA, physical function, and psoriasis were observed with apremilast through Week 52. The most common adverse events were diarrhea, nausea, headache, and upper respiratory tract infection. Diarrhea and nausea generally occurred early and usually resolved spontaneously with continued treatment. Laboratory abnormalities were infrequent and transient., Conclusion: Apremilast demonstrated clinical improvements in PsA for up to 52 weeks, including signs and symptoms, physical function, and psoriasis. No new safety signals were observed. ClinicalTrials.gov identifier: NCT01212757.

Modern human dispersal into Europe is thought to have occurred with the start of the Upper Paleolithic around 50,000-40,000 y ago. The Levantine corridor hypothesis suggests that modern humans from Africa spread into Europe via the Levant. Ksâr 'Akil (Lebanon), with its deeply stratified Initial (IUP) and Early (EUP) Upper Paleolithic sequence containing modern human remains, has played an important part in the debate. The latest chronology for the site, based on AMS radiocarbon dates of shell ornaments, suggests that the appearance of the Levantine IUP is later than the start of the first Upper Paleolithic in Europe, thus questioning the Levantine corridor hypothesis. Here we report a series of AMS radiocarbon dates on the marine gastropod Phorcus turbinatus associated with modern human remains and IUP and EUP stone tools from Ksâr 'Akil. Our results, supported by an evaluation of individual sample integrity, place the EUP layer containing the skeleton known as "Egbert" between 43,200 and 42,900 cal B.P. and the IUP-associated modern human maxilla known as "Ethelruda" before ∼ 45,900 cal B.P. This chronology is in line with those of other Levantine IUP and EUP sites and demonstrates that the presence of modern humans associated with Upper Paleolithic toolkits in the Levant predates all modern human fossils from Europe. The age of the IUP-associated Ethelruda fossil is significant for the spread of modern humans carrying the IUP into Europe and suggests a rapid initial colonization of Europe by our species.

Objective: Adalimumab (ADA) was evaluated for its efficacy in patients with moderate to severely active psoriatic arthritis (PsA) and for the presence of correlations in disease change variables., Methods: Patients with inadequate response to standard PsA therapy were given 40 mg of ADA every other week for up to 12 weeks or 20 weeks. Outcome variables encompassed tender joint count (TJC), swollen joint count (SJC), physician's global assessment (PGA) of psoriasis, Health Assessment Questionnaire (HAQ), patient's global assessment (PtGA) of disease activity and pain, C-reactive protein, as well as composite measures of disease activity. Patients with inactive skin disease symptoms at baseline were excluded from the remission analyses., Results: Of 268 patients with active baseline joint and skin disease and data available at Week 12 following open-label ADA therapy, 73 achieved joint remission (27.2%, TJC ≤ 1 + SJC ≤ 1) and 144 achieved skin remission criteria (53.7%, PGA = clear/almost clear). Simultaneous joint and skin remission criteria were achieved in 16.0% and 24.8% of patients at weeks 12 and 20, respectively. In patients who did not achieve skin and/or joint remission, 12-week ADA treatment improved mean clinical and functional scores. Joint remission was more frequently associated with achieving clinically relevant outcomes including HAQ, PtGA disease activity, and PtGA pain compared to skin remission. No correlation between improvement in skin and joint disease was observed., Conclusion: ADA was effective in achieving strict criteria for remission in joint or skin disease in many patients with active PsA within 12 weeks and sustained through 20 weeks. (NCT00235885).

Objective: To analyze the etiopathogenic role of genetic polymorphisms and serum levels of surfactant protein-D (SP-D) in primary Sjögren syndrome (pSS)., Methods: We analyzed 210 consecutive patients with pSS. SFTPD genotyping (M11T polymorphism rs721917) was analyzed by sequence-based typing and serum SP-D by ELISA., Results: Thirty-two patients (15%) had the Thr11/Thr11 genotype, 80 (38%) the Met11/Met11 genotype, and 96 (46%) the Met11/Thr11 genotype; 2 patients could not be genotyped. Patients carrying the Thr11/Thr11 genotype had a higher prevalence of renal involvement (13% vs 1% and 4% in comparison with patients carrying the other genotypes, p = 0.014). Serum SP-D levels were analyzed in 119 patients (mean 733.94 ± 49.88 ng/ml). No significant association was found between serum SP-D levels and the SP-D genotypes. Higher mean values of serum SP-D were observed in patients with severe scintigraphic involvement (851.10 ± 685.69 vs 636.07 ± 315.93 ng/ml, p = 0.038), interstitial pulmonary disease (1053.60 ± 852.03 vs 700.36 ± 479.33 ng/ml, p = 0.029), renal involvement (1880.64 ± 1842.79 vs 716.42 ± 488.01 ng/ml, p = 0.002), leukopenia (899.83 ± 661.71 vs 673.13 ± 465.88 ng/ml, p = 0.038), positive anti-Ro/SS-A (927.26 ± 731.29 vs 642.75 ± 377.23 ng/ml, p = 0.006), and positive anti-La/SS-B (933.28 ± 689.63 vs 650.41 ± 428.14 ng/ml, p = 0.007), while lower mean values of serum SP-D were observed in patients with bronchiectasis (489.49 vs 788.81 ng/ml, p = 0.019)., Conclusion: In pSS, high SP-D levels were found in patients with severe glandular involvement, hypergammaglobulinemia, leukopenia, extraglandular manifestations, and positive anti-Ro/La antibodies. The specific association between SP-D levels and pulmonary and renal involvements may have pathophysiological implications.

The response of the codling moth (Cydia pomonella L. (Lepidoptera: Tortricidae)) to different emission values of its main pheromone component, 8E,10E-dodecadien-1-ol (codlemone), was investigated in three field trials conducted in plots without mating disruption treatments. Moth catches obtained in traps baited with pheromone dispensers were correlated with the corresponding codlemone release rates by multiple regression analysis. In a preliminary trial conducted in Lleida (NE Spain), a decreasing trend of captures was observed based on increasing pheromone levels. After this, the pheromone release profiles of the pheromone dispensers were studied, in parallel with the field trials, by residual codlemone extraction and gas chromatography quantification. In the trials carried out in Asturias (NW Spain), a correlation between trap catches and emission levels (within the range from 11 to 1,078 μg/d) was found and fitted a logarithmic model. Captures followed a decreasing linear trend in the range of emission rates from 11 to 134 μg/d. Given that release values comprised between 11 and 67 μg/d did not lead to significantly different catches in traps, this emission range could be considered to develop effective formulations for attraction purposes when mating disruption is not acting in the environment.