Search

Many low-threshold experiments observe sharply rising event rates of yet unknown origins below a few hundred eV, and larger than expected from known backgrounds. Due to the significant impact of this excess on the dark matter or neutrino sensitivity of these experiments, a collective effort has been started to share the knowledge about the individual observations. For this, the EXCESS Workshop was initiated. In its first iteration in June 2021, ten rare event search collaborations contributed to this initiative via talks and discussions. The contributing collaborations were CONNIE, CRESST, DAMIC, EDELWEISS, MINER, NEWS-G, NUCLEUS, RICOCHET, SENSEI and SuperCDMS. They presented data about their observed energy spectra and known backgrounds together with details about the respective measurements. In this paper, we summarize the presented information and give a comprehensive overview of the similarities and differences between the distinct measurements. The provided data is furthermore publicly available on the workshop’s data repository together with a plotting tool for visualization.

Aims: The study aimed to adapt the original English-language oral health values scale (OHVS) to the Arabic culture and to test its psychometric properties., Methods: The original OHVS was translated into Arabic language and pre-tested using cognitive interviewing. The psychometric properties of Arabic OHVS were examined in a sample comprising 416 Libyan adults aged 18-70 years, recruited from the main public and private dental clinics in Benghazi. The participants' demographic information, oral health behaviour, perceived oral health, the Arabic version of the OHVS (A-OHVS), dental neglect scale, oral health-related quality of life, oral health literacy, simplified oral hygiene index (OHI-S), and decayed, missing, and filled teeth index (DMFT) were collected. Psychometric properties were tested using content validity, construct validity, discriminating validity, internal consistency, test-retest reliability, and floor as well as ceiling effects were examined., Results: The Arabic OHVS was successfully and smoothly developed. It showed an acceptable level of equivalence to the original version, The A-OHVS presented an overall Cronbach's Alpha of 0.74 and the average score was 40.02, ranging between 26 and 54. All hypotheses predefined to test construct validity were confirmed. The bivariate correlation between A-OHVS and other health indicators shows a significant positive correlation between A-OHVS and oral health literacy (p = 0.000). On the other hand, statistically significant negative correlations were observed between A-OHVS and dental neglect and quality of life (p ≤ 0.001) as well as DMFT and OHI-S (p ≤ 0.001). Floor or ceiling effects were not observed., Conclusions: The A-OHVS was shown to be a valid and reliable tool for assessing oral health values in the Arabic-speaking population.

Background: Cervical cancer is a major health problem in Latin America. In 2019, the Italian Agency for Development Cooperation (La Paz regional site) conducted a pilot study to estimate the prevalence of high-risk human papillomavirus (HPV) and the feasibility of HPV screening in Bolivia through self-sampling and portable and transportable laboratory instruments for HPV testing in urban and rural areas., Methods: Women aged 20-65 years from La Paz (urban area), Toro Toro (rural area), and Acasio (rural area) were enrolled in local public health centers between Dec 1, 2019, and June 30, 2021. Self-sampling was carried out with the Viba-Brush system (Rovers, Oss, Netherlands) and samples were preserved in ThinPrep containers (Hologic Corporation, San Diego, CA, USA). The GeneXpert system (Cepheid, Sunnyvale, CA, USA) for high-risk HPV testing detects HPV E6 and E7 DNA via real-time PCR in a mobile system of easy execution requiring minimal manual intervention. The system provides results in about 1 h. The hr- HPV prevalence data, overall and partial genotyping, were analyzed considering the following age groups: 20-34, 35-44, and 45-65 years old., Findings: 2168 women were enrolled: 614 (28.3%) in La Paz, 743 (34.3%) in Toro Toro, and 811 (37.4%) in Acasio. Only one sample was collected from each participant. 2043 (94.2%) of 2168 samples were adequate for HPV testing. 255 (12.5%) samples were positive for high-risk HPV. Comparing the urban area (La Paz) versus rural combined areas (Acasio+Toro Toro), using a logistic model, the HPV total rate was statistically significantly higher in the city of La Paz (15.0% vs 11.4%; OR:1.37;95% CI: 1.04-1.80). Furthermore, the HPV prevalence was declining by age, and the urban/rural odds ratio was 1.50; (95% IC 1.13-19). The overall HPV 16 positivity was 2.7% (55/2043) and for HPV 18/45 was 1.8% (37/2043) without any statistically significant differences between the three BHU enrolling centers. Only the prevalence of HPV group '39/56/66/68' was significantly higher in La Paz (p<0,001) in comparison to Acasio and Toro Toro., Interpretation: The total and age-adjusted prevalence of high-risk HPV infection in rural and urban areas in Bolivia, as measured with a validated test for screening, is similar to that observed in Europe and the USA. Our study shows that a screening protocol for HPV testing with self-sampling would be feasible in urban and rural areas in Bolivia, and that the reported high occurrence of cervical cancer in Bolivia is not related to a higher rate of high-risk HPV infections. Carrying out HPV tests locally avoids the issues associated with transportation and storage of the collected material and allows the participant to wait in the clinic for the test result, overcoming the very long response time for screening test in Bolivia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Carozzi 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.)

Medication adherence represents a complex and multifaceted process. Standardized terminology is essential to enable a reproducible process in various languages. The study's aim was to translate and adapt the original Ascertaining Barriers for Compliance (ABC) Taxonomy on medication adherence, first proposed in 2012, into Italian language. The study was carried out according to the Preferred Methods for Translation of the ABC Taxonomy for Medication Adherence adopted by the ESPACOMP. Key steps included: (1) a systematic literature review using PubMed and Embase according to the PRISMA Guidelines to identify published Italian terms and definitions, and Italian adherence experts; (2) a forward translation of terms and definitions; (3) panelists' selection; (4) a three-round Delphi survey. From the systematic review, 19 studies allowed detection of 4 terms, 4 definitions and 767 Italian experts. To these, Italian ESPACOMP members and experts though snowball sampling were added. The identified Italian adherence experts received the Delphi questionnaire. The Italian ABC Taxonomy was achieved after three rounds of Delphi survey by reaching at least a moderate consensus on unambiguous naming and definition of medication adherence-related terms. The Taxonomy is intended to be used in research, academic, and professional fields in order to harmonize adherence terminology and avoid confusion in comparing research findings., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Venipuncture is a painful and invasive procedure for hospitalised newborns and represents a challenge for neonatal healthcare professionals. This study evaluated the most efficient cannulation method based on the proportion of success at the first attempt, standard care or near-infrared (NIR) device use, and pain assessment. An observational study with two arms was conducted in the neonatal intensive care unit (NICU) of a tertiary-care university hospital in Italy. All newborns undergoing peripheral vein cannulation and only nurses with more than 5 years of professional experience in the NICU were eligible for the first arm. Only newborns with a body weight of >2500 g at cannulation and all nurses working in the NICU were involved in the second arm. In the first arm of the study, no statistically significant differences between the NIR and control groups were found in terms of proportion of successful at the first attempt 60.6% (confidence interval [CI] 95%: 48.8; 72.4) vs. 56.1% (CI 95%: 44.1; 68.0) and the mean premature infant pain profile score 6.3 (CI 95%: 5.4-7.1) vs. 5.8 (CI 95%: 5.0-6.6). In the second arm, only among less experienced nurses (<1 year), we observed a significant increase in the proportion of success in the NIR group compared with the control group, nearly tripling the success rate (72.7% [54.1; 91.3] vs. 23.1% [0.2; 46.0]).  Conclusion: This study reported no differences between the NIR and control groups. The results also suggest that using a NIR device may be advantageous for healthcare professionals with less experience during first-time cannulation. What is Known: • Venipuncture is a painful procedure commonly used to place a peripheral venous catheter for administering nutrients or drugs. • Near-infrared light facilitates the visualisation of veins and consequently, the performance of cannulation in the paediatric population. What is New: • The near-infrared light device was not associated with fewer attempts and a lower premature infant pain profile score in placing venous access in newborns than the traditional method. • The near-infrared light device could help nurses with less professional experience place a peripheral venous catheter., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Severe acute respiratory syndrome coronavirus 2 is associated with a severe respiratory disease in China, that rapidly spread across continents. Since the beginning of the pandemic, available data suggested the asymptomatic transmission and patients were treated with specific drugs with efficacy and safety data not always satisfactory. The aim of this review is to describe the vaccines developed by three companies, Pfizer-BioNTech, Moderna, and University of Oxford/AstraZeneca, in terms of both technological and pharmaceutical formulation, safety, efficacy, and immunogenicity. A critical analysis of Phases 1, 2, and 3 clinical trial results available was conducted, comparing the three vaccine candidates, underlining their similarities and differences. All candidates showed consistent efficacy and tolerability; although some differences can be noted, such as their technological formulation, temperature storage, which will be related to logistics and costs. Further studies will be necessary to evaluate long-term effects and to assess the vaccine safety and efficacy in the general population., (© 2021 Wiley Periodicals LLC.)

In a Drug Prescription Network (DPN), each drug is represented as a node and two drugs co-prescribed to the same patient are represented as an edge linking the nodes. The use of DPNs is a novel approach that has been proposed as a means to study the complexity of drug prescription. The aim of this study is to demonstrate the analytical power of the DPN-based approach when it is applied to the analysis of administrative data. Drug prescription data that were collected at a local health unit (ASL TO4, Regione Piemonte, Italy), over a 12-month period (July 2018-June 2019), were used to create several DPNs that correspond to the five levels of the Anatomical Therapeutic Chemical classification system. A total of 5,431,335 drugs prescribed to 361,574 patients (age 0-100 years; 54.7% females) were analysed. As indicated by our results, the DPNs were dense networks, with giant components that contain all nodes. The disassortative mixing of node degrees was observed, which implies that non-random connectivity exists in the networks. Network-based methods have proven to be a flexible and efficient approach to the analysis of administrative data on drug prescription.

Introduction: On the basis of reductions in diabetic kidney disease (DKD) progression and major adverse cardiovascular events observed in the landmark CREDENCE trial, canagliflozin 100 mg received an extension to its EU marketing authorisation in July 2020 to include the treatment of DKD in people with type 2 diabetes mellitus (T2DM) making it the first pharmacological therapy to receive regulatory authorisation for treatment of DKD since the RENAAL and IDNT trials in nearly 20 years. Efficient allocation of limited healthcare resources requires evaluation not only of clinical safety and efficacy but also economic consequences. The study aim was to estimate the cost-effectiveness of canagliflozin when added to current standard of care (SoC) versus SoC alone from the perspective of the NHS in England., Methods: A microsimulation model was developed using patient-level data from CREDENCE, including risk equations for the key clinical outcomes of start of dialysis, hospitalisation for heart failure, nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality. DKD progression was modelled using estimated glomerular filtration rate and urinary albumin-to-creatinine ratio evolution equations. Risk for kidney transplant was sourced from UK-specific sources given the near absence of events in CREDENCE. Patient characteristics and treatment effects were sourced from CREDENCE. Unit costs (£2019) and disutility weights were sourced from the literature and discounted at 3.5% annually. The time horizon was 10 years in the base case, and sensitivity analysis was performed., Results: Canagliflozin was associated with sizable gains in life-years and quality-adjusted life-year (QALYs) over 10 years, with gains increasing with simulation duration. Cost offsets associated with reductions in cardiovascular and renal complications were sufficient to achieve overall net cost savings. The findings were generally confirmed in the sensitivity analyses., Conclusion: Model results suggest that adding canagliflozin 100 mg to SoC can improve patient outcomes while reducing overall net costs from the NHS perspective in England., Trial Registration: ClinicalTrials.gov identifier, NCT02065791.

Objectives: Prescription of proton pump inhibitors (PPIs) may be a source of potentially clinically relevant drug-drug interactions (DDIs) and related complications for elderly patients with complex polytherapy at discharge from hospital. The aim of the study was to identify, through the analysis of hospital discharge records, the co-administrations (PPIs + one or more drugs potentially generating DDIs) hypothetically leading to severe consequences according to the literature and online databases. Subsequently, alternatives to PPIs were evaluated for the treatment of gastric acidity and ulcers., Methods: The medical records of 1288 patients, discharged from a geriatric ward at the Città della Salute e della Scienza Hospital in Turin from January 2012 to December 2013, were collected in an Excel database for analysis of DDIs using the literature and online sources such as Micromedex. RESULTS : Six hundred and sixty-three of the 1288 clinical folders had a PPI prescription. A list of 18 drugs considered potentially hazardous and able to trigger a DDI when co-administrated with PPIs was drafted; the frequencies of the co-prescriptions of each PPI with one of the listed drugs were esomeprazole 65.38%, lansoprazole 52.87%, omeprazole 48.19% and pantoprazole 37.11%. An analysis of these co-prescriptions, according to Micromedex classification, gave a percentage of major interactions of 11.01% over 663 clinical folders including a PPI., Conclusions: This study provides a collection of potentially hazardous drug associations and helpful suggestions to improve the quality of prescriptions for elderly patients and strengthens the case for synergic work between doctors and pharmacists in the wards., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The medication process in the Neonatal Intensive Care Unit (NICU), can be challenging in terms of costs, time, and the risk of errors. Newborns, especially if born preterm, are more vulnerable to medication errors than adults. Recently, robotic medication compounding has reportedly improved the safety and efficiency of the therapeutic process. In this study, we analyze the advantages of using the I.V. Station ® system in our NICU, compared to the manual preparation of injectable drugs in terms of accuracy, cost, and time. Method: An in vitro experimental controlled study was conducted to analyze 10 injectable powdered or liquid drugs. Accuracy was calculated within a 5% difference of the bottle weight during different stages of preparation (reconstitution, dilution, and final product). The overall cost of manual and automated preparations were calculated and compared. Descriptive statistics for each step of the process are presented as mean ± standard deviation or median (range). Results: The median error observed during reconstitution, dilution, and final therapy of the drugs prepared by the I.V. Station ® ranged within ±5% accuracy, with narrower ranges of error compared to those prepared manually. With increasing preparations, the I.V. Station ® consumed less materials, reduced costs, decreased preparation time, and optimized the medication process, unlike the manual method. In the 10 drugs analyzed, the time saved from using the I.V. Station ® ranged from 16 s for acyclovir to 2 h 57 min for teicoplanin, and cost savings varied from 8% for ampicillin to 66% for teicoplanin. These advantages are also capable of continually improving as the total amount of final product increases. Conclusions: The I.V. Station ® improved the therapeutic process in our NICU. The benefits included increased precision in drug preparation, improved safety, lowered cost, and saved time. These advantages are particularly important in areas such as the NICU, where the I.V. Station ® could improve the delivery of the high complexity of care and a large amount of intravenous therapy typically required. In addition, these benefits may lead to the reduction in medication errors and improve patient and family care; however, additional studies will be required to confirm this hypothesis., (Copyright © 2019 Amodeo, Pesenti, Raffaeli, Sorrentino, Zorz, Traina, Magnani, Russo, Muscolo, Plevani, Mosca and Cavallaro.)

Objectives: To describe patient-reported outcomes (PROs) after initiation of treatment with canagliflozin (CANA) for type 2 diabetes mellitus (T2DM) in a real-world Canadian setting., Methods: CANadian CAnagliflozin REgistry (CanCARE) is a prospective, observational, single-arm, real-world Canadian study of the effectiveness and safety of CANA for the treatment of T2DM in 527 subjects. PRO measures were collected in CanCARE using the Current Health Satisfaction Questionnaire (CHES-Q) at baseline and after 3, 6 and 12 months of CANA treatment to examine patient satisfaction regarding weight and overall health. Associations between changes in satisfaction with weight, systolic blood pressure (SBP) and glycated hemoglobin (A1C) levels were also investigated., Results: Proportion of patients satisfied with their body weight and overall health increased from 22.1% and 26.9% at baseline to 32.4% and 49.2% after 12 months of CANA treatment, respectively. Satisfaction rates also increased on CHES-Q domains representing physical and emotional health. Correlations were found between improvement in satisfaction with body weight and weight loss (r=-0.29; p<0.01) and between improvements in satisfaction with overall health and weight loss (r=-0.13; p=0.03) and SBP (r=-0.17; p<0.01), but not with changes in A1C level., Conclusions: Treatment with CANA is associated with improvements in satisfaction with body weight and overall health, which may be important drivers of patient self-management and hold the potential to positively influence long-term outcomes in T2DM., (Copyright © 2019 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Patient-centred care is an essential component of high-quality health care, shown to improve clinical outcomes and patient satisfaction, and reduce costs. While there are several authoritative models of obesity pathophysiology and treatment algorithms, a truly patient-centred model is lacking. We describe the development of a patient-centric obesity model. A disease-illness framework was selected because it emphasizes each patient's unique experience while capturing biomedical aspects of the disease. Model input was obtained from an accumulation of research including contributions from experts in obesity and patient-reported outcomes, qualitative research with adults living in the United States, and two targeted literature searches. The model places the patient with obesity at its core and links pathologic imbalances of energy intake and expenditure to environmental, sociodemographic, psychological, behavioural, physiological and medical health determinants. It highlights relationships between obesity signs and symptoms, comorbid conditions, impacts on health-related quality of life, and some barriers to obesity management that must be considered to attain better outcomes. Providers need to evaluate patients holistically, understand what changes each patient is motivated to make, and recognize what challenges might impede weight reduction, improvements in comorbid conditions, signs and symptoms, and health-related quality of life before pursuing individualized treatment goals. Patients living with obesity who do lose weight perceive benefits beyond weight loss. Ideally, this model will increase awareness of the complex, heterogeneous impacts of obesity on patients' well-being and recognition of obesity as a chronic disease, and prompt a call to action among stakeholders to improve quality of care., (© 2019 Janssen Research & Development, LLC. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Aim: There is limited information concerning the effects of canagliflozin (CANA), a sodium-glucose co-transporter 2 inhibitor (SGLT2i) in a real-world clinical setting in Canada. CanCARE is a 12-month, prospective, observational analysis to demonstrate the effectiveness and safety of CANA in usual clinical practice in Canada., Materials and Methods: SGLT2i-naïve adult patients with type 2 diabetes mellitus (T2DM) (n = 527) on a stable antihyperglycemic agent (AHA) regimen with glycated hemoglobin (A1C) ≥ 7%, an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m 2 , were initiated on CANA as part of their usual treatment approach, and were followed for a period of 12 months. The primary effectiveness objective was the mean change in HbA1c from baseline to 6 and 12 months., Results: Significant improvement from baseline in mean HbA1c levels were observed at 6 months (-0.90%; 95% CI, -1.02, -0.78) and at 12 months (-1.04%; 95% CI, -1.15, -0.92), regardless of duration of diabetes or background AHA treatment regimen. Similarly, significant decreases in systolic blood pressure (-4.65 mm Hg); body weight (-3.24 kg), waist circumference (-2.91 cm) and body mass index (-1.15 kg/m 2 ) were observed at 12 months. Additionally, 40.5% of patients achieved the double endpoint (≥0.5% HbA1c reduction and ≥ 3% weight loss), while 24.3% of patients achieved the triple composite endpoint (≥0.5% HbA1c reduction, ≥3% weight loss and ≥ 4 mm Hg systolic blood pressure reduction). No unexpected adverse events were reported., Conclusion: CANA provided sustained clinically meaningful improvements in cardiometabolic parameters in this study in a real-world setting, confirming findings from randomized controlled trials., (© 2018 John Wiley & Sons Ltd.)

Health-related quality of life (HRQoL) is an important endpoint, especially in clinical trials for malignancies with a long course of disease, such as chronic lymphocytic leukemia (CLL). Patient-reported outcomes were examined in the randomized, double-blind, placebo-controlled HELIOS study to assess the impact of treatment with the Bruton's tyrosine kinase inhibitor ibrutinib, added to bendamustine plus rituximab (BR) background therapy. Measures included FACIT-Fatigue, EORTC QLQ-C30, QLQ-CLL16, and EQ-5D-5L. Of 578 patients enrolled, 540 (93%) provided FACIT-Fatigue responses at baseline. Most had only a moderate degree of impairment at baseline; mean values did not appear to change over time in either treatment arm, suggesting that adding ibrutinib to BR did not impact health-related quality of life. However, post-hoc analyses showed that subgroups of patients with the worst fatigue, physical functional status, and well-being at baseline had greater improvements in these outcomes with ibrutinib plus BR treatment versus placebo.

Background: Evidence from patient-reported outcomes in clinical trials may explain health-related behaviors observed in the real world., Objective: The purpose of this analysis was to evaluate the effect of treatment with canagliflozin, a sodium glucose co-transporter 2 inhibitor, compared with placebo or sitagliptin on health-related quality-of-life outcomes in participants with type 2 diabetes mellitus from the clinical development program., Methods: Patient-reported outcomes data from four randomized controlled trials of canagliflozin (n = 2536) were pooled and analyzed to evaluate participants' interest in continuing study medication; satisfaction with weight; and physical, mental, and emotional health after 26-52 weeks of treatment with canagliflozin vs. placebo or sitagliptin., Results: Upon trial completion, participants treated with canagliflozin were more likely to express interest in continuing study medication than participants treated with placebo or sitagliptin [odds ratio (95% confidence interval) of 1.54 (1.19-1.99); p = 0.001]. Those treated with canagliflozin were also more likely to be satisfied with their weight and report favorable outcomes (score improvement or maintenance of good scores) related to physical and emotional health., Conclusions: The results of this pooled analysis suggest that people with type 2 diabetes mellitus treated with canagliflozin generally had positive experiences with treatment and improvements in health-related quality of life. Future research is needed to determine if these improvements result in improved type 2 diabetes mellitus management and treatment adherence. CLINICALTRIALS., Gov Identifiers: NCT01106625, NCT01106677, NCT01137812, NCT02025907.

Mantle cell lymphoma (MCL) is a rare, aggressive, incurable B-cell malignancy. Ibrutinib has been shown to be highly active for patients with relapsed/refractory (R/R) MCL. The RAY trial (MCL3001) was a phase 3, randomized, open-label, multicenter study that compared ibrutinib with temsirolimus in patients with R/R MCL. Active disease is frequently associated with impaired functional status and reduced well-being. Therefore, the current study employed two patient-reported outcome instruments, the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and the EQ-5D-5L, to assess symptoms, well-being, health status, and health-related quality of life of patients on treatment within the RAY trial. We found that patients on ibrutinib had substantial improvement in FACT-Lym subscale and total scores, and had improvement in EQ-5D-5L utility and VAS scores compared with temsirolimus patients, indicating a superior well-being. These improvements in well-being correlated with clinical response, indicating that better health-related quality of life was associated with decreased disease burden.

Wildland fire is an important ecological process in the California Sierra Nevada. Personal accounts from pre-20th century describe a much smokier environment than present day. The policy of suppression beginning in the early 20th century and climate change are contributing to increased megafires. We use a single particulate monitoring site at the wildland urban interface to explore impacts from prescribed, managed, and full suppression wildland fires from 2006 to 2015 producing a contextual assessment of smoke impacts over time at the landscape level. Prescribed fire had little effect on local fine particulate matter (PM 2.5 ) air quality with readings typical of similar non-fire times; hourly and daily good to moderate Air Quality Index (AQI) for PM 2.5 , maximum hourly concentrations 21-103 μg m -3 , and mean concentrations between 7.7 and 13.2 μg m -3 . Hourly and daily AQI was typically good or moderate during managed fires with 3 h and one day reaching unhealthy while the site remained below National Ambient Air Quality Standards (NAAQS), with maximum hourly concentrations 27-244 μg m -3 , and mean concentrations 6.7-11.7 μg m -3 . The large high intensity fire in this area created the highest short term impacts (AQI unhealthy for 4 h and very unhealthy for 1 h), 11 unhealthy for sensitive days, and produced the only annual value (43.9 μg m -3 ) over the NAAQS 98th percentile for PM 2.5 (35 μg m -3 ). Pinehurst remained below the federal standards for PM 2.5 when wildland fire in the local area was managed to 7800 ha (8-22% of the historic burn area). Considering air quality impacts from smoke using the NAAQS at a landscape level over time can give land and air managers a metric for broader evaluation of smoke impacts particularly when assessing ecologically beneficial fire. Allowing managers to control the amount and timing of individual wildland fire emissions can help lessen large smoke impacts to public health from a megafire., (Published by Elsevier Ltd.)

Purpose: To evaluate the corneal topography and the topographic changes after ptosis surgery on patients affected by congenital and acquired blepharoptosis., Methods: Twenty eyes of 17 patients affected by acquired and congenital ptosis underwent surgical correction through anterior levator complex tightening. Computerized tomography (Syrius Sistem; CSO) was used to analyze any change in corneal astigmatism (CYL), simulated keratometry, anterior corneal symmetry index front, apical keratometry front, and central corneal thickness. Visual acuity, margin reflex distance, and levator function were also measured., Results: After surgical ptosis repair, corneal topography demonstrated a reduction in average keratometry of 0.15 ± 0.47 diopters (D) and in corneal astigmatism of 0.26 ± 1.12 D. Significant differences were found in apical keratometry front (-1.84 ± 1.76 D) and in best-corrected visual acuity (-0.18 ± 0.06 logMAR) in the postoperative examinations. Central corneal thickness did not show significant differences between preoperative and postoperative examinations. Postoperative topographic maps showed a reduction of symmetry index front (0.10 ± 0.64 D)., Conclusions: Eyelid ptosis modifies anterior corneal surface inducing refractive errors and modifying corneal astigmatism in patients, thus affecting the quality of vision. The surgical correction of blepharoptosis induces anterior corneal surface modification, restoring corneal symmetry and regular corneal astigmatism. Postoperative corneal topography showed normal corneal contours.

Background: Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma., Methods: This randomised, open-label, multicentre, phase 3 clinical trial enrolled patients with relapsed or refractory mantle-cell lymphoma confirmed by central pathology in 21 countries who had received one or more rituximab-containing treatments. Patients were stratified by previous therapy and simplified mantle-cell lymphoma international prognostic index score, and were randomly assigned with a computer-generated randomisation schedule to receive daily oral ibrutinib 560 mg or intravenous temsirolimus (175 mg on days 1, 8, and 15 of cycle 1; 75 mg on days 1, 8, and 15 of subsequent 21-day cycles). Randomisation was balanced by using randomly permuted blocks. The primary efficacy endpoint was progression-free survival assessed by a masked independent review committee with the primary hypothesis that ibrutinib compared with temsirolimus significantly improves progression-free survival. The analysis followed the intention-to-treat principle. The trial is ongoing and is registered with ClinicalTrials.gov (number NCT01646021) and with the EU Clinical Trials Register, EudraCT (number 2012-000601-74)., Findings: Between Dec 10, 2012, and Nov 26, 2013, 280 patients were randomised to ibrutinib (n=139) or temsirolimus (n=141). Primary efficacy analysis showed significant improvement in progression-free survival (p<0·0001) for patients treated with ibrutinib versus temsirolimus (hazard ratio 0·43 [95% CI 0·32-0·58]; median progression-free survival 14·6 months [95% CI 10·4-not estimable] vs 6·2 months [4·2-7·9], respectively). Ibrutinib was better tolerated than temsirolimus, with grade 3 or higher treatment-emergent adverse events reported for 94 (68%) versus 121 (87%) patients, and fewer discontinuations of study medication due to adverse events for ibrutinib versus temsirolimus (9 [6%] vs 36 [26%])., Interpretation: Ibrutinib treatment resulted in significant improvement in progression-free survival and better tolerability versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma. These data lend further support to the positive benefit-risk ratio for ibrutinib in relapsed or refractory mantle-cell lymphoma., Funding: Janssen Research & Development, LLC., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: To verify the efficacy of 25-gauge pars plana vitrectomy (PPV) for the management of posteriorly dislocated lens material after complicated cataract extraction and to determine in what patients this approach offers the optimal benefit in terms of efficacy and safety, considering the amount of retained nuclear material and the duration of surgery., Methods: Forty eyes of 40 patients with retained lens fragments undergoing early (within 1 week) or late (within >1 week) 25-gauge PPV were retrospectively reviewed. The amount of dislocated nuclear material was graded by the surgeon intraoperatively, and the patients were divided into two groups according to the nuclear grading: group A (≤50% dropped nucleus) and group B (>50% dropped nucleus). The presence of brunescent nuclear pieces was considered. The outcomes measured included best-corrected visual acuity (BCVA) and postoperative complications such as retinal detachment, cystoid macular edema (CME) and postoperative ocular hypertension or hypotonia., Results: The patients had a mean age of 78 years. The mean preoperative logarithm of the minimum angle of resolution (logMAR) BCVA was 0.57 ± 0.24 (20/80). A significant positive correlation was found between nuclear material grade and PPV duration (R2 = 0.81, p < 0.0001). None of the patients had dislocation of brunescent nuclear pieces. On postoperative day 1, the mean postoperative intraocular pressure was 16.75 ± 2.7 mm Hg, with no case of ocular hypotonia. At 6 months of follow-up, the mean logMAR BCVA improved to 0.23 ± 0.3 (20/32). Retinal detachment developed in 4 patients (10%), occurring only in patients of group B (p < 0.002). Four patients with late PPV developed postoperative CME, with no case of CME among patients with early vitrectomy (p = 0.014)., Conclusion: Removal of dislocated lens fragments after complicated cataract surgery can be effectively managed with 25-gauge PPV, although it appears to be most efficient for cases with a limited amount of dislocated lens material. In consideration of the higher rate of retinal detachment observed in cases of prolonged PPV time, the expected duration of surgery should be taken into account when choosing the best surgical approach. Visual outcomes are not affected by the timing of PPV, whereas early vitrectomy seems to prevent the onset of inflammatory macular edema., (© 2015 S. Karger AG, Basel.)

To analyze the clinical and histopathological effects of low doses of intraorbital and intralesional Rituximab (RTX) in three patients affected by idiopathic orbital inflammatory syndrome (IOIS). Three patients with IOIS were enrolled, all of whom underwent lesion biopsy to confirm the diagnosis, complete blood examinations (thyroid function tests, complete blood cell count, fasting blood glucose, liver and renal function tests, erythrocyte sedimentation rate, serum ACE, C-reactive protein, rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibody, serum IGg4 level tests) and magnetic resonance imaging (MRI). Patients received the planned treatment schedule, consisting of a complete cycle of intraorbital injections of RTX (MabThera(®); Roche, Basel, Switzerland, 100 mg/10 ml): 10 mg, once a week for 1 month (four injections/month), in two patients repeated. The clinical and imaging follow-ups were at an average of 17.6 months (range 14-24 months) after treatment. A post-treatment bioptic procedure was performed in one patient. All patients showed a significant MRI reduction of the orbital lesion and a stable clinical improvement for the follow-up time of observation. The post-treatment histopathological specimen showed a disappearance of inflammatory cells. Low doses of intralesional RTX, which are safe, efficacious and used in other B cell-mediated disorders, are a useful treatment in IOIS, with decreased risks of generalized immunosuppression and fewer side effects than are afforded by systemic high doses of glucocorticoids and RTX. The result is very quick, effective and prolonged on the inflammatory component of the disease and seems to be related to the histologic reduction of infiltrating CD20+ lymphocytes.

Purpose: Acute exudative polymorphous vitelliform maculopathy is a rare retinal disease characterized by bilateral serous macular detachment and subretinal accumulation of yellowish deposits resembling Best dystrophy lesions. Corticosteroid systemic therapy has been used empirically in the attempt to treat this retinal disorder with mixed results. Thus, the benefit of corticosteroid remains undetermined. To our knowledge, we report the first case of acute exudative polymorphous vitelliform maculopathy (AEPVM) treated in one eye with intravitreal dexamethasone implant (Ozurdex; Allergan, Inc., Irvine, California, USA)., Methods: A 28-year-old man with AEPVM underwent intravitreal dexamethasone implantation in the left eye., Results: Compared with the fellow eye, intravitreal dexamethasone implant did not significantly modify the clinical course of the disease. No implant-related complication was experienced during follow-up., Conclusions: The lack of response to intravitreal dexamethasone seems to suggest that corticosteroids may be ineffective for the treatment of AEPVM.