Journal articles on the topic 'Nineteen ninety-three'

Ninety-six plasma and whole blood specimens from nine selected patients were analyzed for the presence of Aspergillus DNA. Nineteen specimens from three patients with proven aspergillosis were PCR positive in both materials, whereas an additional 22 were PCR positive in whole blood only. All 36 samples from six patients without signs of aspergillosis were negative in both assays. We conclude that although plasma and whole blood spiked with Aspergillusconidia showed an identical lower detection limit (10 CFU), the sensitivity of plasma PCR was lower than that of PCR performed on whole blood samples.

Invasive Fusarium species infections in immunocompromised patients occur predominantly in those with hematological malignancies. Survival rates of 20–40% were reported in adults, but data in children are limited. Our retrospective, nationwide multicenter study of invasive fusariosis in pediatric hematology/oncology and stem cell transplant (SCT) patients identified twenty-two cases. Underlying conditions included hematological malignancies (n = 16; 73%), solid tumors (n = 2), and non-malignant hematological conditions (n = 4). Nineteen patients (86%) were neutropenic, nine (41%) were SCT recipients, and seven (32%) received corticosteroids. Sixteen patients (73%) had disseminated fusariosis, five had local infection, and one had isolated fungemia. Fifteen patients (68%) had skin involvement and eight (36%) had a bloodstream infection. Four patients (18%) presented with osteoarticular involvement and four with pulmonary involvement. Nineteen patients (86%) received combination antifungal therapy upfront and three (14%) received single-agent treatment. Ninety-day probability of survival was 77%: four of the five deaths were attributed to fusariosis, all in patients with relapsed/refractory acute leukemias. Ninety-day probability of survival for patients with relapsed/refractory underlying malignancy was 33% vs. 94% in others (p < 0.001). Survival rates in this largest pediatric population-based study were strikingly higher than those reported in adults, demonstrating that invasive fusariosis is a life-threatening but salvageable condition in immunosuppressed children.

Nineteen ninety-two was such a watershed year for publications concerning the fifteenth, sixteenth, and early seventeenth centuries that dozens of these works could easily be described as “the best.” Unfortunately, out of the numerous Portuguese and Spanish publishers contacted in 1993 with our request for review copies, only two in Spain plus the Sorbonne took this project seriously. In response to their cooperative attitude, I want to mention their three books before turning to a more general discussion of Renaissance publications from the Iberian Peninsula. (Publishers in Mexico, the Caribbean, and Latin America were not included simply because of limitations on my time.)

The current study examined the possible predictors of dropout during a five-week light treatment (LT) with a gradual advance protocol in 93 patients with unipolar non-seasonal depression and evening chronotypes by comparing their clinical characteristics and performing a logistic regression analysis. Nineteen out of ninety-three (20%) subjects (80% female, 46.5 ± 11.7 years old) dropped out during the 5-week light treatment. Treatment non-adherence (i.e., receiving LT for less than 80% of the prescribed duration) over the first treatment week predicted a five-fold increase in risk of dropout during light therapy (OR: 5.85, CI: 1.41–24.21) after controlling for potential confounders, including age, gender, treatment group, rise time at the baseline, patient expectation, and treatment-emergent adverse events. There is a need to incorporate strategies to enhance treatment adherence and retention in both research and clinical settings. Chinese clinical trial registry (ChiCTR-IOR-15006937).

The aim of this study was to determine the current outcome of gunshots to the arteries of the lower extremity. The authors conducted a retrospective analysis of 104 patients with gunshots to the femoral (n = 71) and popliteal (n = 33) artery. One hundred four patients presented over the 60-month period. Ninety-six (92%) were male and eight of 104 female. Ninety-nine were gunshot injuries, five from shotguns. Nine patients had injury to the common femoral artery, 62 patients had injury to the superficial femoral artery, and 33 had popliteal artery injury. One patient died in the emergency room and another died in the postoperative period, giving an overall in-hospital mortality of two of 104 (1.9%). Forty-three of 70 femoral reconstructions had completion angiograms compared with 20 of 32 popliteal artery reconstructions ( P = 1). Nineteen of 63 (30%) of the completion angiograms prompted revision of the reconstruction. Of the 63 patients who had completion angiograms, two of 63 (3%) required amputation. Seven of 39 (18%) patients who did not have completion angiograms required amputation ( P = 0.025). Including the primary amputation, there were 10 amputations in the 103 patients (9.7%) who survived to undergo operation. Ballistic arterial trauma of the lower limb leads to significant disability. Completion arteriography leads to revision of the reconstruction in nearly one-third of instances and significantly reduces amputation rate.

Foraminiferal and sedimentological analysis was carried out using ditch cutting samples from intervals 2700 ft. - 10,185 ft. in AE-1 well. The samples were composited at 60 ft. into ninety four (94) ditch cutting samples. The standard micropaleontological sample procedures to recover the foraminiferal biofacies assemblages was utilized, followed by analysis and interpretation of the obtained results. The sedimentological analysis reveals five lithofacies - sandstone, sandy shale, shaly sand, mudstone and sandy clay which constitute part of the Agbada Formation of the Niger Delta. The foraminiferal fauna recovered from the samples studied comprised of twenty four species grouped into nineteen genera from niniteen families and nineteen subfamilies. A few number of miscellaneous microfossils such as Ostracoda, Holothuroidea and Echinoderm remains were recovered. The total count of foraminiferal defined from this well is four hundred and nineteen (419). The planktic foraminiferal count was two hundred and forty two (242) (57.8 % of the total count) while the benthics foraminiferal count was one hundred and seventy seven (177) (42.2 % of the total count). Among the benthic forms, the calcareous consists of one hundred and forty nine forms (149) (33.4 % of the total benthic count) while the agglutinating benthic forms were thirty seven (37) (8.8 % of the total benthic count). One (1) planktic (Chiloguembelinacubensis) and three (3) benthic (Eponidesberthelotianus, Hanzawaiastratonii and Nonionellaauris) informal foraminiferal zones were established in the well. The age of the AE-1 well sediments has been interpreted to belong to Early Oligocene - Early Miocene in comparism with foraminiferal markers species whose stratigraphic ranges are well established in the Niger Delta and globally. This inferred the presence of the Rupelian - Burdigalian sediments in the Niger Delta. Keywords: Foraminiferal, Biozone, Age, Rupelian, Burdigalian.

This study investigated the concept of happiness using multidimensional scaling analyses. Two samples were studied. The first contained 100 adult males and females, aged nineteen to ninety ( M = 39.5). The second contained 126 female adults, aged twenty-six to eighty-nine ( M = 61.3), all Catholic nuns. Respondents provided word associates to the words happiness and unhappiness during separate one-minute intervals. Subsequently, the twelve most frequent associates and the word happiness were used in a written paired comparison task of dissimilarities between all possible pairs. In both samples, a two-dimensional space was judged to optimally fit the data. The first dimension was interpreted as a bipolar affective dimension. The second dimension was one-fifth and one-third as salient as the first dimension in the respective samples, and was interpreted as representing personal independence. Two-dimensional spaces of young, middle-aged, and old subsamples of sample one were, in large part, similar to the total space. Three age trends were noted.

--9+ generate competency framework questionnaire for antibiotic prescriptions, assess framework of four major components including safety, professionalism, improvements, and collaborations and to find association between demographic factors and competency framework for prescription writing. Methods: the study was convenient in sampling technique, cross sectional, analytical in design which includes fresh dental graduates from Pakistani Dental Schools. A self-complete questionnaire was generated, piloted, validated and tested for reliability. Data were analyzed using SPSS. Results: The mean competency score of the sample was ten point nine eight (SD±three point three) out of a total score of nineteen. The highest score obtained was nineteen and minimum zero among individuals. The competency levels were also scored different among dental schools with few institutions scored better in all categories than other when split up in public or private sectors. Many of the house surgeons (n=237) showed command on antibiotic prescription and are also aware of antibiotic misuse. However, they consider it not feasible to prescribe via remote media (N=one hundred and ninety-four) like online prescriptions. Practical implication: This study will have a broad impact on the antibiotic prescription routine among the dentist and it will help improve to improve competency on antibiotic prescription among dental undergraduates with a framework focusing more on evidence based community practices and in line with the significance of tackling solutions for drug resistant microorganisms that can lead to more complex situations. Conclusion: It is concluded that a need is found to improve competency on antibiotic prescription among dental undergraduates with a framework focusing more on evidence based community practices Keywords: Antibiotics, antimicrobial resistance, dental curriculum, competency.

Objective. The aim of the study was to evaluate the location, timing, and frequency of glove perforation during hip replacement arthroplasty. Methods. Gloves worn by surgical team members in 19 primary hip replacement arthroplasties were assessed. The study was of a single gloving system. All the used gloves were collected at the end of the surgery and assessed visually and by using water inflation technique. Relevant data were collected at the time of surgery. Results. A total of one hundred and ninety-one surgical gloves were evaluated. Twenty-three glove perforations were noted in nineteen of the operations. Of these perforations 14 belonged to gloves worn by surgeon and first assistant (60.1%). Glove perforation in thumb, index finger, and palm was more common. More perforation occurred in the gloves worn in nondominant hand (52%) but was insignificant. Conclusion. Glove perforation in surgeries such as total hip arthroplasty is not uncommon. In this study of single gloving system glove perforation rate was 12.04%, whereas literature reports of glove perforation rate as low as 3.3% in elective orthopedic surgeries with double gloving system. As such emphasis should be given to wear double pair of gloves wherever this practice is uncommon.

The Advisory Centre on WTO Law (ACWL) has a mandate to provide legal training on WTO law. The ACWL developed its first training course on WTO law in 2002. To date, the ACWL has conducted nineteen training courses. The ACWL structures its annual training courses on a three-year cycle. The first course covers the basic principles of WTO law, the second covers the WTO Agreements relating to trade remedies, trade in services and trade-related intellectual property rights, and the third covers WTO dispute settlement procedures. The training course is taught by ACWL lawyers and begins in October and ends in June the following year. Over the years, 955 delegates have registered their interest in attending the training courses, 159 of whom were from least-developed countries (LDCs.) The ACWL has provided Certificates of Attendance – given to delegates that attend a minimum number of training sessions each year – to 630 delegates, ninety six of whom were from LDCs. Feedback from former participants has been positive indicating that their participation in the ACWL’s training course(s) has assisted themselves and their government to better understand their rights and obligations under WTO law. Training, capacity building, ACWL, basic principles on WTO law, WTO agreements, Moot Court exercise, developing countries, least developed countries, Geneva-based delegates

Background Job loss is common in multiple sclerosis (MS) and is known to exert a negative effect on quality of life. The process leading up to job loss typically includes negative work events, productivity losses and a need for accommodations. By using active coping strategies job loss may be prevented or delayed. Objective Our goal was to examine negative work events and accommodations in relation to coping strategies in employed relapsing–remitting MS patients. Methods Ninety-seven MS patients (77% females; 21–59 years old) completed questionnaires concerning the patient’s work situation, coping strategies, demographics, physical, psychological and cognitive functioning. Forward binary logistic regression analyses were conducted to examine coping strategies and other (disease) characteristics predictive of reported negative work events and accommodations. Results Nineteen per cent of the employed MS patients reported one or more negative work events, associated with a higher use of emotion-oriented coping and more absenteeism. Seventy-three per cent reported using one or more work accommodations, associated with a higher educational level and more presenteeism. MS patients reporting physical changes to the workplace employed more emotion-oriented coping, while flexible scheduling was associated with task-oriented coping. Conclusion Emotion-oriented and task-oriented coping strategies are associated with negative work events and the use of accommodations.

Though corporate social responsibility became commonly debated in the last forty years of the twentieth century, at least as early as the nineteenth century, the notion that the company has moral responsibilities became apparent. The corporate social responsibility framework continuously adapts to global market needs. Given the recent advent of corporate social responsibility and sustainability concepts, as well as methodologies and criteria used to meet standards of "fair" business. However, a common connotation of corporate social responsibility (CSR) has not been standardized, although the CSR-related principles and norms are now being established. Between academicians and professionals, there is an increasing concern in corporate social responsibility. Companies are also supposed to be open not only to their creditors but to society at large. Margolis and Walsh (2001) and Orlitzky et al. (2003) presented round-about ninety-five analytical data on CSR and financial results over the period 1972 to 2001. CSR was an independent variable in these studies; while financial output was variable based. Fifty-three percent had a positive relationship with them, twenty-four percent had no partnership with them, nineteen percent had mixed relationships with them, and five percent had harmful relationships with them. Dam (2008) has presented analytical data on CSR and financial results, but there was one difference and one aspect that was normal. The novelty of the study was the distribution of empirical findings in tabulated form focused on asset returns (ROA), equity returns (ROE), selling returns (ROS), Tobin's Q, and stock market returns, and it was popular that only empirical findings were tabulated from 1972 to 2001. For companies and prospective scholars, the findings of this study are important regarding corporate social responsibility and consumer behaviour.

IntroductionThe recent National Institute for Health and Care Excellence (NICE) consultation on methods for health technology evaluation (HTE) outlined plans to include guidance on the role of real-world evidence (RWE) in HTE. This is particularly pertinent for interventions where the evidence base consists of a single arm trial (SAT) design, which is more frequently observed in oncology. This study reviewed the influence of RWE submitted as part of the evidence base for NICE oncology appraisals.MethodsA search for NICE HTEs was conducted for interventions supported by SATs from January 2017-November 2021. Evidence was stratified by submission packages with SAT evidence alone or in combination with randomized controlled trial (RCT) evidence, with or without RWE.ResultsThirty-two decisions for interventions supported by SATs were made by NICE between 2017-2021, all in oncology indications. Fifty percent were supported by SAT evidence and fifty percent by RCT plus SAT evidence, both with or without RWE. A lower proportion of RCT/ SAT HTEs submitted RWE compared to SAT HTEs (fifty vs ninety four percent). Seventy five percent and nineteen percent of SAT HTEs received a positive recommendation, with and without restrictions, irrespective of submitting RWE. One negative decision was observed for SATs supported by RWE. Sixty three percent and thirty eight percent of RCT/ SAT HTEs received a positive recommendation, with and without restrictions. Overall, the proportion of positive recommendations were lower for HTEs submitting RWE (ninety six percent) compared to HTEs not submitting RWE (one hundred percent), which is in contrast to recent findings specific to orphan oncology HTEs (one hundred versus seventy eight percent).ConclusionsRWE was more commonly submitted to support SAT HTEs, than RCT HTEs. The use of RWE seems to be established as a necessity to supplement a SAT evidence base, whereas RWE is more generally a nice to have in RCT HTEs. However, RWE appears to positively influence decision-making for orphan oncology indications with a more neutral influence for non-orphan indications.

Purpose: To find out if multidetector computed tomography (MDCT), using a dedicated trauma protocol, provides sufficient diagnostic information of the injuries of blunt multitrauma patients to enable the planning of treatment for all body compartments. Material and Methods: One‐hundred‐and‐thirty‐three patients exposed to high‐energy trauma were referred and scanned with the standardized MDCT multitrauma protocol. The imaging protocol consisted of axial scanning of the head and helical scanning of the facial bones, cervical spine, thorax, abdomen, and pelvis. The scanning times were 12 s for the head, 19–21 s for the facial bones and cervical spine (1 mm collimation), and 32–50 s for the thorax, abdomen, and pelvis (2 mm collimation). One‐hundred‐and‐forty milliliters of non‐iodinated contrast material (300 mg I/ml) was administered intravenously at 3 ml/s. Results: Ninety‐nine of the patients (74%) had at least one finding consistent with trauma. The most frequent findings were in the thorax in 58 patients (44%). Nineteen false‐negative findings and two false‐positive findings were made. The overall sensitivity of MDCT was 94%, specificity 100%, and accuracy 97%. Conclusion: MDCT is accurate in the assessment of blunt multitrauma patients. The decision to treat the patient can be made on the basis of MDCT with a reasonable level of certainty.

Two-hundred and ninety-five trees sampled from seventy-five local chestnut (Castanea sativa Mill.) cultivars in northwestern Spain, which had been previously studied morphologically, were further analyzed for five isoenzyme systems, encoded by seven loci. Objectives of this study were to 1) describe the intracultivar and intercultivar variability by isoenzyme analysis and to compare it with the morphological variation and 2) establish a classification of the cultivars and to discuss its relation to the morphological classification. Variability within and among cultivars was detected, confirming the previous morphological results. The level of the observed heterozygosity in this Spanish population was higher than expected and also higher than that found in other European populations. Because of the great diversity discovered, this material seems to be worthy for introducing and maintaining in a germplasm bank. Nineteen main clusters were identified for the twenty-three most widely distributed cultivars. On the average, 61% of the trees belonging to a specific cultivar was included in the same cluster. The remaining 39% was scattered in other clusters, which indicates intracultivar variability. Therefore there is opportunity for selection within cultivars. Two clusters included three important cultivars each. This suggests possible synonymies. No correlation between morphological traits and the isoenzymic alleles was detected. The isoenzyme technique identified a higher number of cultivars increasing the information obtained with morphological traits. Correlations between the frequency of some of the alleles and the altitude and other environmental variables suggest that selection of the best adapted genotypes has occurred.

The incidence of calcaneal fracture has been slowly increasing; however, the ideal treatment for displaced intra-articular fracture is not available yet, even though the fracture brings frequent complication and disability. Between April 1991 and March 1998, we treated 103 displaced intra-articular calcaneal fractures of 92 patients surgically with limited posterior incision, modified Gallie approach. There were thirty-seven tongue-type fractures, fifteen tongue-type fractures with moderate comminution, nineteen joint-depression fractures, twenty-nine joint-depression fractures with moderate comminution, and three extensively comminuted fractures. The fracture fragments were fixed mainly with partly threaded small cancellous screws or Steinmann pins without any bone graft. Ankle and subtalar motion was permitted immediately if fixation were stable enough. Otherwise, a short period of cast immobilization was utilized. With a mean follow-up of 28 months (range, 12 to 66 months), eighty six percent of feet had no pain or only occasional pain not requiring medication. Using American Orthopedic Foot and Ankle Society hindfoot score system for assessment, ninety percent of feet rated as good to excellent. We used “Circle draw test” for evaluation of subtalar motion during follow-up visitation and found eight-seven percent of feet showed good to excellent correlation with the functional recovery. We recommend a limited posterior incision for reduction and internal fixation of displaced intra-articular calcaneal fractures. For displaced intra-articular fractures with three or four large fragments without further comminution and without a displaced fracture of the calcaneal cuboid joint, this method is particularly useful. We also recommend a Circle draw test for evaluation of subtalar joint motion as well as an indicator of functional recovery after displaced calcaneal fractures.

Purpose There are no global screening recommendations for esophageal squamous cell carcinoma (ESCC). Endoscopic screening has been investigated in areas of high incidence in China since the 1970s. This study aimed to evaluate whether an endoscopic screening and intervention program could reduce mortality caused by ESCC. Methods Residents age 40 to 69 years were recruited from communities with high rates of ESCC. Fourteen villages were selected as the intervention communities. Ten villages not geographically adjacent to intervention villages were selected for comparison. Participants in the intervention group were screened once by endoscopy with Lugol's iodine staining, and those with dysplasia or occult cancer were treated. All intervention participants and a sample consisting of one tenth of the control group completed questionnaires. We compared cumulative ESCC incidence and mortality between the two groups. Results Three thousand three hundred nineteen volunteers (48.62%) from an eligible population of 6,827 were screened in the intervention group. Seven hundred ninety-seven volunteers from an eligible population of 6,200 in the control group were interviewed. Six hundred fifty-two incident and 542 fatal ESCCs were identified during the 10-year follow-up. A reduction in cumulative mortality in the intervention group versus the control group was apparent (3.35% v 5.05%, respectively; P < .001). Furthermore, the intervention group had a significantly lower cumulative incidence of ESCC versus the control group (4.17% v 5.92%, respectively; P < .001). Conclusion We showed that endoscopic screening and intervention significantly reduced mortality caused by esophageal cancer. Detection and treatment of preneoplastic lesions also led to a reduction in the incidence of this highly fatal cancer.

Abstract The DNA sequences of 11 Drosophila melanogaster lines are compared across three contiguous regions, the Adh and Adh-dup loci and a noncoding 5' flanking region of Adh. Ninety-eight of approximately 4750 sites are segregating in the sample, 36 in the 5' flanking region, 38 in Adh and 24 in Adh-dup. Several methods are presented to test whether the patterns and levels of polymorphism are consistent with neutral molecular evolution. The analysis of within- and between-species polymorphism indicates that the region is evolving in a nonneutral and complex fashion. A graphical analysis of the data provides support for a hypothesized balanced polymorphism at or near position 1490, site of the amino acid replacement difference between Adhf and Adhs. The Adh-dup locus is less polymorphic than Adh and all 24 of its polymorphisms occur at low frequency--suggestive of a recent selective substitution in the Adh-dup region. Adhs alleles form two distinct evolutionary lineages that differ one from another at a total of nineteen sites in the Adh and Adh-dup loci. The polymorphisms are in complete linkage disequilibrium. A recombination experiment failed to find evidence for recombination suppression between the two allelic classes. Two hypotheses are presented to account for the widespread distribution of the two divergent lineages in natural populations. Natural selection appears to have played an important role in governing the overall patterns of nucleotide variation across the two-gene region.

PURPOSE In an effort to improve outcome in patients with metastatic or high-risk localized Ewing's sarcoma family of tumors (ESF) and rhabdomyosarcoma (RMS), we explored the role of consolidation therapy with total-body irradiation (TBI) plus autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS Ninety-one patients were entered onto one of three consecutive protocols from 1981 to 1986. Induction therapy consisted of four or five cycles of vincristine, doxorubicin, and cyclophosphamide (VAdriaC); in the earlier series, patients received one or two cycles with dactinomycin instead of doxorubicin. Irradiation of the primary site was used for local control. Patients who attained a complete response (CR) to induction therapy were eligible for consolidation with 8 Gy TBI plus VAdriaC and ABMT. RESULTS Nineteen patients were ineligible for consolidation after failing to achieve or maintain a CR following induction therapy; all 19 are dead of disease. Seven eligible patients elected to forgo consolidation; three of seven are long-term event-free survivors. Sixty-five patients received consolidation therapy; 20 of 65 are long-term event-free survivors. A local control rate of 83% was achieved using radiation therapy as the primary modality of local control. Patients with metastatic disease at diagnosis fared substantially worse than did patients with localized tumors (6-year event-free survival [EFS] rate, 14% v 38%; two-sided P [P2] = .008). CONCLUSIONS Consolidation of patients with metastatic or high-risk localized pediatric sarcomas with 8 Gy TBI plus ABMT has failed to improve the outcome of this group of patients. Metastatic disease at diagnosis continues to confer the poorest prognosis. New therapeutic strategies are needed to consolidate more effectively the remissions that can be achieved in the majority of these patients.

IntroductionHealth Technology Assessment (HTA) agencies have recognized the importance of real-world evidence (RWE) to inform access decision-making and different HTA agencies establish distinct requirements for their local jurisdictions. The objective of this study is to understand the differences of RWE included in HTA reports and HTA agencies’ perception of RWE.MethodsHTA reports from agencies in France, Germany, Spain, Italy, United Kingdom (UK), Canada, Australia and South Korea from January 2011 to November 2021, including original submissions, resubmissions, extensions of original indications and renewals were analyzed.ResultsAcross the eight countries, RWE has been used in nineteen percent of all HTA reports (N=2,960/15,561), with an exponential increase observed between 2019 and 2021. RWE on clinical effectiveness was mostly used in HTA submissions in the UK (twenty-two percent), with twenty-six percent perceived with full acceptance. In contrast, RWE on safety and epidemiology was reported widely in HTA reports in France and Germany (83% and 87%), respectively. Ninety-three percent of RWE received full acceptance in France, followed by forty-four percent in Germany. A mixed picture of the types of RWE included in HTA reports was observed in the other countries, with high variance of acceptance (between 5 to 37%).ConclusionsFrance, Germany, and the UK are the top three countries with a large proportion of HTA reports where RWE was mentioned. The type of RWE used is related to a large extent to the local evidence requirements. For example, RWE around epidemiology was included widely in Germany due to the needs of providing local data for budget impact analyses required by the Federal Joint Committee (G-BA); RWE on tolerability as reported in periodic safety update reports (PSURs) needs to be included in French HTA submissions. RWE on clinical effectiveness has been evaluated the most by the UK HTA bodies.

Staphylococci are major hospital-associated pathogens, and the dissemination of methicillin-resistant staphylococci in hospitals poses a great challenge for managing hospital-acquired infections. Little is known about the dissemination of staphylococci recovered from the hospital environment and personnel in China. In this study, antimicrobial susceptibility tests, mecA gene detection, SCCmec typing, and multilocus sequence typing (MLST) were performed to clarify the molecular epidemiology of staphylococci in a large hospital in Tianjin, China. One hundred and ninety-five staphylococci were recovered, and 94% of isolates were resistant to at least one antibiotic. Eighty-five staphylococci were mecA gene-positive, and 40% of them harbored SCCmec IV and V. The genotype of Staphylococcus aureus (S. aureus) was ST25, and the dominant genotype of methicillin-resistant Staphylococcus epidermidis (MRSE) was ST59. Three new sequence types were assigned as ST840, ST841, and ST842. One (2%) frequently touched surface was contaminated by S. aureus, which suggested that environmental contamination occurred in the hospital in China. Nineteen (39%) frequently touched surfaces were contaminated by methicillin-resistant coagulase-negative staphylococci (MRCoNS), and 46% of HP carried MRCoNS. Varied staphylococcal species and antimicrobial-resistance rates were observed between staphylococci that were recovered from hospital personnel and frequently touched surfaces. The transmission of MRSE and S. aureus between hospital personnel and frequently touched surfaces was detected. Hospital items and personnel may act as reservoirs of antimicrobial-resistant staphylococci, and cleaning strategies should be carried out to decrease the dissemination of antimicrobial-resistant staphylococci in hospitals in China.

Abstract OBJECTIVES The risk of spinal cord injury after thoraco-abdominal aortic aneurysm repair increases when the segmental arteries (SAs) in the critical segment are sacrificed. Such critical SAs cannot be reconstructed when performing thoracic endovascular aortic repair (TEVAR). We aimed to elucidate extrathoracic collaterals to the critical SAs (T9–L1) that develop after TEVAR. METHODS Between 2006 and 2018, the critical SAs (T9–L1) of 38 patients were sacrificed during TEVAR. Nineteen of these patients who underwent multidetector row computed tomography 6 months after surgery were included (mean age 60 ± 13 years; 10 male; Crawford extent II:III, 14:5). We retrospectively assessed extrathoracic collaterals to the sacrificed critical SAs. RESULTS Ninety-four collaterals to the critical SAs were observed, originating from the subclavian (26/94), external iliac (50/94) and internal iliac (18/94) arteries. Twenty-five of the 26 (96%) collaterals from the subclavian artery were from its lateral descending branch, and 19 of the 26 (73%) collaterals fed into T9. Forty-three of the 50 (86%) collaterals from the external iliac artery were from its lateral ascending branch, and 25 of the 50 (50%) collaterals communicated with T11. Patients with a history of left thoracotomy (no collaterals in 6 patients) had fewer collaterals via the lateral descending branch of the left subclavian artery in comparison with the patients without (10 collaterals in 13 patients) (P = 0.009). CONCLUSIONS After critical SAs were sacrificed, extrathoracic collaterals developed with certain regularity. Previous left thoracotomy could influence the development of extrathoracic collaterals from the left subclavian artery.

Objective Previous studies have questioned the safety and efficacy of minor salivary gland biopsy in the diagnosis of Sjögren’s syndrome, citing complications and difficulty of pathologic evaluation. This study aims to determine the rate of biopsy specimen adequacy and the risk of complications after minor salivary gland biopsy. Study Design Case series. Setting Single tertiary care center. Methods We reviewed the records of all patients who underwent minor salivary gland biopsy at our institution from October 1, 2016, to September 1, 2021. Demographics, comorbidities, symptoms, and serologic results were recorded. The primary outcome was adequacy of the tissue sample. Complications of the procedure were recorded. Biopsies with at least one focus of ≥50 lymphocytes per 4-mm2 sample were considered positive. Results We identified 110 patients who underwent minor salivary gland biopsy. Ninety-three (85%) were female, and the median age was 49.1 years (range, 18.7-80.5). Seventy-seven procedures (70%) were performed in the office setting, and 33 (30%) were performed in the operating room. Nearly all biopsy samples (n = 108, 98%) were adequate, and 33 (31%) were interpreted as positive. Four patients (4%) experienced temporary lip numbness, which resolved with conservative management. No permanent complications were reported after lip biopsy. Nineteen (58%) patients with positive biopsy results had no Sjögren’s-specific antibodies. Most patients with positive biopsy results (n = 20, 61%) subsequently started immunomodulatory therapy. Conclusion Minor salivary gland biopsy can be performed safely and effectively in both the office and the operating room. This procedure provides clinically meaningful information and can be reasonably recommended in patients suspected to have Sjögren’s syndrome.

Introduction:São Paulo city in Brazil has implemented social and health care for homeless people with pulmonary tuberculosis since 2007. We conducted a health technology assessment (HTA) of the interventions provided based on a national theoretical model using 2015 data and an overview of systematic reviews. The HTA was requested by national policymakers. The results demonstrated that the interventions for pulmonary tuberculosis were satisfactory. The municipal secretariat implemented actions to improve the national treatment recommendations and adopted incentives to increase adherence to treatments. Our objective was to describe the feedback process for the Health Secretariat.Methods:The feedback was categorized as: (i) an executive abstract with key messages (i.e. ninety-seven percent of notified cases underwent sputum smears, nineteen percent were hospitalized, and fifty-nine percent were cured) reported to policymakers involved in the surveillance program; and (ii) three meetings were organized jointly by the research group and local policymakers.Results:In 2016 we conducted a meeting to present the results. Thirty-nine professionals involved in the primary care team working on the streets (thirty-five percent) and the Tuberculosis Surveillance and Control Program (five percent) were present. The main barriers presented by the professionals were issues of human resources (i.e. suboptimal professional staff and having two different social organizations responsible for health care). The main facilitators presented by professionals were: (i) using homeless-peers as healthcare workers; (ii) having a network linking the primary care and surveillance programs; and (iii) periodic training.Conclusions:In addition to the positive results, the HTA presented an opportunity to discuss the sustainability of incentives for adhering to treatments adopted by the policymakers, such as meal allowances and housing support, to improve social conditions among the homeless.

Abstract Introduction: Cancer-associated thrombosis leads to morbidity and mortality in cancer patients. Thromboembolism can be prevented with the use of existing and emerging anticoagulants. We sought to ascertain awareness as well as receptiveness to anticoagulation amongst ambulatory cancer patients receiving active therapy. Methods: Two-hundred-fifty 12 question surveys were distributed to ambulatory cancer patients at the James P. Wilmot Cancer Center of the University of Rochester. Patients included in this study were those with active cancer, age ≥ 18 years and ambulatory. Hospitalized patients were excluded. Data was gathered regarding: age, gender, stage as well as type of malignancy, awareness of increased risk of venous thromboembolism and willingness to use various forms of anticoagulation. Results: One hundred ninety surveys (76%) were completed over a three week period. Study population consisted of 71 males (37%) and 119 females (63%) with mean age of 58. Malignancies surveyed include: lymphoma 26%, breast 20%, gastrointestinal 15%, leukemia 9% and lung cancer 7% among others. Nineteen percent of patients had stage IV malignancy. Of the patients surveyed, 53% reported being unaware of the increased risk of VTE with malignancy. Eighty-six percent of patients surveyed would be willing to use an oral anticoagulant 46% would be willing to perform daily anticoagulant injections. Conclusions: Prophylaxis for VTE in ambulatory cancer patients is an area of active investigation and could lead to improvements in morbidity and mortality. This study reveals a lack of knowledge of the increased risk of VTE amongst cancer patients. However, informed patients expressed willingness to use prophylaxis if shown effective to reduce VTE in the ambulatory setting.

This study investigated the efficacy, safety, and clinical benefit of alemtuzumab (Campath-1H) for patients with relapsed or refractory B-cell chronic lymphocytic leukemia exposed to alkylating agents and having failed fludarabine therapy. Ninety-three patients received alemtuzumab in 21 centers worldwide, with the aim to obtain an overall response rate of at least 20%. Dosage was increased gradually (target 30 mg, 3 times weekly, for a maximum of 12 weeks). Infection prophylaxis was mandatory, beginning on day 8, and continuing for a minimum of 2 months after treatment. Responses were assessed at weeks 4, 8, and 12, and patients were followed for 34 months. Overall objective response in the intent-to-treat population (n = 93) was 33% (CR 2%, PR 31%). Median time to response was 1.5 months (range, 0.4-3.7 months). Median time to progression was 4.7 months overall, 9.5 months for responders. At data cut-off, 27 patients (29%) were alive; overall median survival was 16 months (95% CI: 11.8-21.9) and 32 months for responders. Nineteen responders survived more than 21 months. Clinical benefit was observed both in responders and in patients with stable disease. The most common adverse events were related to infusion, generally grade 1 or 2 in severity, occurring mainly in the first week. Grade 3 or 4 infections were reported in 25 patients (26.9%). However, only 3 (9.7%) of 31 patients who responded to alemtuzumab treatment developed grade 3 or 4 infections on the study. Alemtuzumab induced significant responses in these patients with clinical benefit in the majority and with acceptable toxicity in a high-risk group.

Introduction: Aminoglycosides used for treating multidrug-resistant (MDR) tuberculosis are ototoxic, leading to a need for audiological monitoring. While audiologists monitor ototoxicity, currently there are no guidelines on monitoring in the South African context. Therefore, the findings of this study might help to motivate the establishment of a more in-depth ototoxicity monitoring policy, which facilitates uniformity among audiologists managing patients with MDR tuberculosis. Therefore, the study aimed to describe the audiological practices employed by audiologists in the management of adult patients with MDR tuberculosis in South Africa.Method: A descriptive survey design was used. A questionnaire was developed and included elements of the American Speech-Language and Hearing Association (1994) guidelines for monitoring ototoxicity. Ninety-three audiologists contributed data to this study. Descriptive statistics were used in the analysis of the data.Results: Sixty-eight percent (%) of the respondents were aware of the international guidelines, 93% provided pre-treatment counselling and 87% conducted a baseline assessment. Nineteen per cent of the respondents conducted high-frequency audiometry, while 74% carried out a monthly evaluation, 72% performed a full audiological assessment after the cessation of the MDR tuberculosis treatment, and 96% conducted post-treatment counselling. Modifications to the international guidelines include not conducting speech and immittance audiometry, as well as testing certain frequencies. The reasons for these modifications include limited specialised equipment, time constraints, large caseloads and understaffed departments.Conclusion: There are no explicit guidelines on ototoxicity monitoring in South Africa. Consequently, audiologists are having to modify the international guidelines. Thus, there is no consistency in managing patients with MDR tuberculosis. This highlights the need for South Africa to develop context-relevant ototoxicity monitoring guidelines to appropriately manage patients with MDR tuberculosis.

Evaluation of the spatial distribution of urban emergency shelters can effectively identify defects in the current distribution of urban emergency shelters and weaknesses in the overall evacuation service capacity of the city and provide reference for improving the level of urban emergency shelters and evacuation and disaster relief capacity. At present, evaluation of the spatial distribution of urban emergency shelters is mainly carried out on three aspects: effectiveness, accessibility, and safety. However, there are problems, such as individual evaluation scales and incomplete indicator systems, unreasonable allocation of indicator weights, and ignoring the influence of fuzzy incompatibility between different indicator attributes on the evaluation results. In this paper, we start from two scales, the individual emergency shelter and the regional groups of emergency shelters. Based on the five criteria of effectiveness, accessibility, safety, suitability, and fairness, the evaluation indicator system of the spatial distribution of urban emergency shelters was constructed. It was combined with AHP, CRITIC, the optimal weight coefficient solution method based on the maximum deviation sum of squares theory, and fuzzy optimization theory to construct a multi-indicator evaluation model. Further, the spatial distribution condition of the existing emergency shelter in Shanghai was evaluated. The results show that: among the existing ninety-one emergency shelters in Shanghai, there are nine places with unreasonable spatial distribution; nineteen places are comparatively unreasonable. From the scale of regional groups, there is one district (Pudong New District) with unreasonable spatial distribution: its relative superiority value is far lower than other districts, and there are three districts that are comparatively unreasonable. Further, the evaluation scores of the spatial distribution reasonableness of emergency shelters in each region of Shanghai show a high–low–middle distribution from the downtown area of Shanghai outward. The evaluation indicator system and evaluation method used in this paper can effectively reflect the deficiencies in the spatial distribution of urban emergency shelters, thus providing a reference for the relevant departments to improve and plan emergency shelters.

Background: Hypospadias is a common congenital anomaly affecting the penis, two-stage repair becoming more interesting in era of tubularized –incised urethral plate (TIP). Functional outcome of hypospadias repair either single or two stage is as important as cosmetic outcome. In contemporary series , structured scoring systems (Hypospadias Objective Scoring Evaluation-HOSE and Pediatric Penile Perception Scoring -PPPS), evaluation of photographs and uroflowmetry, were used to assess results of hypospadias repair. Objectives: We have assessed outcomes of two-stage hypospadias repair using Hypospadias Objective Scoring Evaluation(HOSE) and uroflowmetry. Material and Methods: Over a period of eight years, from January 1997 to December 2004, One hundred and twenty six hypospadias patients were treated, ninety of them had two-stage repair and36 single-stage repairs. The HOSE questionnaire and uroflowmetry were obtained to evaluate the long term outcome of two –stage hypospadias repair. Results: The age at time of assessment ranged from 8 to 23 year-old, with mean follow up of 39.78months. Thrifty five patients had proximal hypospadias and 20 had distal varieties of hypospadias. Operations performed were 37 Bracka?s and 18 Byar?s procedures. Of the 55 patients had complete two stage hypospadias repair and agree to participate in the study , Nineteen patients had acceptable HOSE and 36 had non-acceptable score. Uroflow rates of 43 subjects were below the fifth centile in three patients ,equivocal (between 5th and 25th centile ) in four patients and above 25th centile in 36 subjects. Conclusion: Two –stage repair is a suitable technique for all types of hypospadias with versatile outcomes. HOSE and uroflowmetry are simple, easy, non invasive and non expensive tools to assess long term outcomes objectively. Bangladesh Journal of Medical Science Vol. 12 No. 02 April’13 Page 133-139 DOI: http://dx.doi.org/10.3329/bjms.v12i2.14940

Objective: To determine patient satisfaction with the informed consent process in ear, nose and throat (ENT) diseases requiring surgery. Specifically, to determine relationships between educational levels of patients and their satisfaction with information given by doctors versus self-gathered information; whether complications of the operation were explained to, and could be listed by patients; the types of complications patients expected to be informed about and the importance of this information to them; their familiarity with the term “informed consent” and their preference for written or spoken information; and whether they were convinced about what they consented to. Methods: Design: Cross-sectional Descriptive Study Setting: Tertiary Public Hospital Patients: One Hundred Results: There were 55 males and 45 females (average age 26.7 years, range 4 - 74 years). Ten percent (all children) had no formal education, 56% had primary to high school education, 23% had certificate level education, and 11% had a baccalaureate or masters degree. Ninety-five percent claimed they knew what informed consent was. Ninety percent were satisfied with the information given to them by doctors. Eighty percent, mainly with educational levels of high school and above, preferred to receive written information from doctors. Twenty three percent accessed other sources of information. Those with certificate level education talked with previously operated patients (10%) or read magazines (2%), while the internet was favored by almost all of those with baccalaureate degrees (8%) and all those with masters degrees (2%). Of those who accessed self-gathered information, 21% were not satisfied while only 2% were satisfied. Seventy percent considered the information given by doctors very important. Similarly, seventy percent (mostly from the higher educational levels) considered the impact of information provided by the doctor completely convincing for decision making, while thirty percent (mostly from lower educational levels) only found the information partly convincing. Forty nine percent (again from the lower educational levels), could not list even a single complication. Nineteen percent, with educational levels of certificate and above, wanted to know all complications of surgery, including those that were very rare while fifty six percent wanted to know most of the complications. Conclusion: We should not underestimate the importance of the outpatient consultation, the importance of written material and non medical information sources as patients’ expectations are quite high and the majority of them wanted to be informed about most complications. We should also find ways to improve the provision of patient information, and where possible and appropriate, as per specific patient groups. Key words: Informed consent, otorhinolaryngology, surgical procedures

IntroductionThe Scottish Medicines Consortium (SMC) conducts early health technology assessment (HTA) of new medicines on behalf of NHSScotland. Evidence from patients and carers on end-of-life and orphan medicines is gathered during Patient and Clinician Engagement (PACE) meetings. The output is a consensus statement describing a medicine's added value from the perspective of patients/carers and clinicians, which is used by SMC committee members in decision-making. This study compared the importance of factors in the PACE statement to PACE participants and committee members.MethodsA survey of ninety-eight PACE participants (consisting of forty-two patient group (PG) representatives and fifty-six clinicians) investigated the importance of quality of life (QoL) themes (family/carer impact, health benefits, tolerability, psychological benefit, hope, normal life, treatment choice and convenience) identified from an earlier thematic analysis of PACE statements. The findings from PG representatives and clinicians were compared, and the overall results were further compared with those from a previous survey of committee members (n = 26).ResultsAmong PACE participants who responded (twenty-six PG representatives and fourteen clinicians), 100 percent rated ‘health benefits’ and ‘ability to take part in normal life’ as important / very important. ‘Convenience of administration’ and ‘treatment choice’ received the lowest rating with fifteen percent and nineteen percent respectively of PG representatives versus seven percent of clinicians rating each as very important. ‘Hope for the future’ received the most diverse response with fifty-eight percent of PG representatives and fourteen of clinicians rating this as very important.In general, PACE participants rated importance of QoL themes higher than committee members (n = 21) but the rank order was similar. Differences between the proportion of PACE participants and committee members who rated themes important/very important was greatest for ‘treatment choice’ (sixty-seven percent versus twenty percent respectively) and ‘hope for the future’ (eighty-two percent versus fifty-three percent).ConclusionsThe findings demonstrate some alignment between PACE participants’ and committee members’ responses, supporting the value of the PACE output in decision-making. Areas for further research are highlighted.

The aim of this study was to quantify the effect of tonsillectomy on the incidence of sore throats and its co-morbidity in adult patients. One hundred and nineteen adult patients were sent a standard questionnaire regarding their symptoms in the 12 months preceding and following their tonsillectomy. Outcome measures included the incidence of sore throats, total number of days with sore throat, amount of time taken off work or school, and number of visits to the general practitioner (GP). In addition, patients were asked to indicate the duration of their symptoms and whether or not they found the tonsillectomy effective in curing their sore throats.Sixty-six patients (55.5 per cent) returned completed questionnaires. The age of the patients ranged from 16 to 39 years. The mean duration of symptoms was 8.3 years. On average, patients had 8.1 different sore throat episodes, 42 sore throat days, 21.4 days of sore throat related absence from work or school, and 5.9 visits to the GP in the 12 months before their operation. For the 12 months after surgery, these reduced to 0.9 episodes, four days, 2.2 days and 0.6 visits, respectively. This reduction was very significant (p < 0.001, Wilcoxon signed rank test).After their surgery, more than half the patients achieved complete resolution of all the measured parameters mentioned above. Most of the remaining patients achieved at least 50 per cent resolution. Only three patients (4.8 per cent) achieved less than 50 per cent resolution. Ninety-five per cent of the patients found the operation effective in curing their sore throats and were glad they had had surgery.In conclusion, retrospective questionnaire data must be interpreted with some caution, but this study suggests that tonsillectomy is effective in reducing the incidence, duration and co-morbidity of recurrent sore throats in adults; this must be balanced against the post-operative problems in a minority of patients.

Abstract A flow cytometric assay was developed for the determination of autoantibodies directed against platelet anionic-phospholipids in antiphospholipid syndrome (APS). The method is based on demonstrable competition between the placental anticoagulant protein I, annexin V, and the patients’ autoantibodies on the platelet anionic-phospholipids (the binding site for the prothrombinase complex; prothrombin, factors Va and Xa). The method is practical and rapid, uses readily available reagents, and standard equipment. Ninety-two plasma samples, 41 from patients with clinical diagnosis of APS, 27 from patients with systemic lupus erythematosus (SLE) and 24 from healthy individuals were analyzed. Thirty-five (85%) of patients with APS (either with or without SLE), 15 (94%) of patients with APS and SLE, and 20 (80%) of APS patients without SLE were positive. Nineteen (70%) out of 27 patients with SLE alone were also positive; of whom 15 (58%) were positive for either anti-cardiolipin antibody (ACL) or lupus anti-coagulant (LAC). Comparison with ACL showed 40 (93%) out of 43 patients positive for ACL were also positive by flow cytometry (FCM). However, 13 (48%) out of 27 patients negative for ACL were found positive by FCM. Seven of these patients have primary APS and 6 have SLE; 7 of whom were positive for LAC. Three (13%) out of the 24 control samples, all negative by FCM, were positive for ACL. Comparison with LAC showed 32 (91%) out of 35 patients positive for LAC also positive by FCM. Of 18 patients negative for LAC, 7 (39%) were negative and 11 (61%) were positive by FCM. Four of the 11 patients have a diagnosis of APS and 7 of SLE; 6 of whom were positive for ACL. None of the controls, all negative by FCM, was positive for LAC. In conclusion, the annexin V competitive flow cytometric assay for the determination of anti-platelet phospholipid autoantibodies maybe useful for the laboratory diagnosis of APS.

AbstractIntroduction:Bicycles may be useful in the delivery of out-of-hospital emergency medical services. The use of bicycles in providing emergency medical services was investigated by surveying currently existing bicycle-medic systems.Methods:Two questionnaires were developed to gain information on service areas, injuries, gear used, missions, and specific data from bicycle-medic response.Results:Of 210 surveys mailed to bicyclemedics, 21 (10%) were completed and returned by the pre-established deadline. Of 11 surveys mailed to bicycle-medic supervisors, four (36%) were returned. Preliminary results showed that 76% of respondents are career providers and the remainder serve as volunteers. Mean age for respondents was 33±7.4 years, with 96% being males. Most teams have been in existence for three to four years. Job satisfaction was greater when participating on the bicycle crews than when not performing on the bicycle crew, t = 4.15, p = 0.0002. The teams varied in size (6–100 persons) with a mean value of 31. On the average, team size represented 10% of total number of personnel for the respective organizations.The majority of bicycle teams operate all year in all conditions. Most bicycle-medic teams were initiated for special events. Nineteen percent reported injuries while on duty or in training. Ninety percent of units that responded use existing agency protocols and have no special protocols related to the bicycle team. Eighty percent of the units are dispatched through the normal agency procedures. Eighty-five percent of respondents coordinate for transport units via dispatch. Reported response times were under two minutes for special event responses. These were within established agency response times. In approximately 25% of the responses, the patients refused transport, and another 65% of the responses were for relatively minor injuries or complaints that did not require transport to a hospital.Conclusion:This survey begins to characterize the utilization of bicycles as a tool to gain patient access in specialized situations. The use of bicycle-medics may be cost-effective, may help to improve employee morale, and possibly reduce employee health-care costs. Further study is needed to determine the impact of bicycle-medics on patient outcomes and response times.

PURPOSE The study investigated the therapeutic effects of a combination of Navelbine (vinorelbine or 5'noranhydrovinblastine; Pierre Fabre Médicament, Boulogne, France) and doxorubicin in women who had received no prior chemotherapy for locally advanced or metastatic breast cancer. PATIENTS AND METHODS Ninety-seven patients with progressive and assessable advanced or metastatic breast cancer who had received no prior chemotherapy except in an adjuvant setting were entered onto the study. Eighty-nine patients were assessable for toxicity and response by World Health Organization (WHO) criteria; the other eight patients were excluded because they did not meet entry criteria or because of protocol violations. Navelbine was administered at 25 mg/m2 by 30-minute intravenous (IV) infusion on days 1 and 8, and doxorubicin at 50 mg/m2 by slow IV infusion on day 1, with each course repeated at 3-week intervals. Patients were treated for a maximum of 11 cycles or until progression or major toxicity. RESULTS Objective responses were observed in 66 of 89 assessable patients (74%; 95% confidence interval, 63% to 85%). There were nineteen (21%) complete responses (CRs) and 47 (53%) partial responses (PRs). In addition, 20 patients (22.5%) had stable disease and three (3.5%) progressed while on treatment. Responses were observed at all sites of metastatic disease. Forty-one of 58 patients with visceral disease responded (71%) and 25 of 31 with soft tissue and bone disease experienced an objective response (81%). The median duration of response was 12 months (range, 2.4 to 40.5), and the median overall survival was 27.5 months (range, 4 to 46). Neutropenia was dose-limiting, with 36 patients (41%) experiencing grade 3 or 4 toxicity. Of 727 cycles administered, there were 20 admissions (3%) for treatment of febrile neutropenia, involving 14 of 89 patients (16%). Treatment-related cardiotoxicity at grade 2 to 4 was experienced by 10% of patients and necessitated the interruption of treatment in 1.5% of cycles. Other side effects were uncommon or manageable by conventional means. CONCLUSION The encouraging response rates and duration achieved with this combination of Navelbine/doxorubicin under the conditions of this study deserve further randomized comparative trials with standard regimens.

e20676 Background: Elderly and patients with ECOG PS ≥ 2 often present with medical and physiological characteristics that make the selection of their treatment more challenging. Single-agent vinorelbine improves survival and quality of life compared with best supportive care. At constant effectiveness between two treatments formulations patient preference must be taken into account. Methods: Stage IIIB or IV NSCLC patients candidates to receive a first line chemotherapy with Vinorelbine alone due to age ≥ 70 and Eastern Cooperative Oncology Group (ECOG) Performance status ≤2 or age ≤ 70 but ECOG PS ≥ 2, could enter the study. Patients were randomized to receive: • Arm A: first cycle of IV vinorelbine (30 mg/m2) and second cycle of oral vinorelbine (60mg/m2) • Arm B: first cycle of oral vinorelbine followed by a second cycle of IV vinorelbine. In both arms vinorelbine was administered at day 1 and day 8 every 3 weeks. From the third cycle onwards patients had to choose to continue with oral or intravenous vinorelbine. The dosage of oral vinorelbine could be subsequently increased to 80 mg/m2 at physician’s choice. Treatment continued until disease progression, intolerable toxicity or patient refusal. The primary objective of the study was the patient preference for oral or intravenous vinorelbine. Results: Ninety-three patients entered the study and were randomized. Sixty-two were able to complete the first two cycles and to express a preference (32 in Arm A and 30 in Arm B). Forty-five out of 62 were males and 17 females. Median age was 80 (72-89). Nineteen patients had an ECOG PS of 0, 39 a PS of 1 and 4 a PS of 2 (30.7%, 62.9% and 6.4% respectively). Eighteen patients (29%) decided to continue with IV vinorelbine while 44 patients (71%) expressed a preference for oral vinorelbine p = 0.001 (Gart's test). Regarding secondary enpoints, median OS was 5.7 (4.7-7.7) and 5.5 (3.8-9.1) months and median PFS was 3.5 (2.4-4.4) and 3.5 (3.5-5.0) for arm A and arm B respectively. Conclusions: The study has clearly demonstrated that elderly or frail patients with NSCLC prefer to receive an oral rather than an intravenous chemotherapy. The reasons for the choice were expressed in a questionnaire still in evaluation. Clinical trial information: nct01848613.

Abstract Background Clinicaltrials.gov was created in 2000 to comply with the FDA Modernization Act of 1997 and since 2007, Federal law (Section 801 of the FDA Amendments Acts) mandates registration of all applicable, prospective clinical drug trials of health outcomes. ICMJE journals also require registration of all intervention trials prior to publication. Clinicaltrials.gov offers patients and clinicians a valuable tool to identify open sickle cell disease (SCD) clinical trials by disease and results of closed trials with links to manuscripts. Objective To conduct a systematic review of all completed interventional SCD trials registered at clinicaltrials.gov and identify enrollment rates and reporting of trial results. Methods We performed a search of “sickle” in www.clinicaltrials.gov to identify every registered SCD clinical trial. (Last update: August 5, 2013). Every “closed” “interventional” registered trial was recorded in a database to include: trial name, trial identifier, start/stop date, sponsor/collaborator, primary objectives, enrollment age, expected enrollment, type of trial, and manuscripts. For trials without a manuscript in the registry, we performed a Pubmed search by keywords from the trial title, intervention, and/or PI. All manuscripts identified were reviewed to confirm trial enrollment numbers. Results Three hundred and fifty three SCD trials were registered, of which 212 (60%) were closed or completed. We performed a systematic review of 147 “interventional”, closed trials. (1983-2012). The primary sponsor or collaborator listed for these trials included an academic center (n=72, 41 unique centers registered trials), industry or pharmaceutical company (n=47), and/or NIH (n=45). Ninety trials (61%) were registered as either phase I or II, 29 (20%) registered as phase III, 8 (5%) registered as phase 4, and 20 trials did not provide a phase. Fifty two percent of trials were randomized. For trials that listed inclusion criteria for age, 41% were pediatric trials, 50% were adult, and 9% were both pediatric and adult. The most frequent outcomes of interest for these trials were pain (22%), bone marrow transplant (12%), pulmonary hypertension (7.5%), and endothelial function/dysfunction (5.5%). The reporting of trial results and manuscripts to clinicaltrials.gov was low. Nineteen of 147 (13%) trials completed the “trial results” section in clinicaltrials.gov. Twenty six trials downloaded their primary manuscript to clinicaltrials.gov despite 51 trials having manuscripts published on Pubmed. Eighty seven closed clinical trials registered on clinicaltrials.gov have not reported their trial results to clinicaltrials.gov or published their manuscripts as searched in Pubmed. Barriers to successful enrollment in SCD trials were evident in this review. Thirty two (22%) trials updated their registry to reflect “study termination” or “withdrawal”. For the 27 trials that listed the reason for this early termination/withdrawal, 17 (63%) were closed for slow enrollment. Barriers to enrollment in phase III trials were identified as 45% of phase III trials enrolled < 60% of their expected participants. The reporting of phase III trials was also low as only 16 (55%) of the registered phase III trials results have published manuscripts. Conclusion Clinicaltrials.gov can be a valuable tool for clinicians to identify SCD clinical trials, but in practice is limited by investigator reporting of trial results. SCD clinical trials that are under-enrolled or not published place subjects at risk for participation in a trial without a scientific benefit to their disease community. Research should continue to focus on identifying and overcoming barriers to enrollment in clinical trials and publication of trial results. Disclosures: No relevant conflicts of interest to declare.

Abstract Introduction Acute myeloid leukaemia is a heterogenous disease with variable response to chemotherapy. In order to prognosticate at an individual level numerous cytogenetic and molecular markers may have to be taken into account. Most publications in AML relate to clinical trials and outcomes in this context. We aimed to study outcome in a population-based cohort in the era of molecular genetic testing. Methods All patients, aged 19 and over, diagnosed with AML between 2007-2011, throughout the north east of England (population 3.1 million) were identified. This was done by searching weekly multidisciplinary team meeting minutes across the three haematology teams in the region and triangulating these data with cytogenetic and molecular genetic data. Only patients aged 19-60 years (inclusive) at diagnosis are reported. All biopsy specimens were subject to central pathology review. Results A total of 344 patients were identified and 150 were aged 19-60. Nineteen patients with acute promyelocytic leukaemia (APL) were excluded. Twelve patients were excluded due to missing data; thus 119 non-APL were analysed: 66 women and 53 men. All patients were considered suitable for intensive therapy and 58 (49%) were included in a national AML trial. Ninety eight out of 119 patients (82%) achieved a complete remission (CR); 79 patients entered CR post cycle 1. 21 patients (17%) did not enter a CR (four died before treatment could commence, nine died during induction, six were refractory and palliated and 2 became aplastic and died before remission status could be ascertained). Thirty-nine patients (40%) subsequently relapsed after achieving CR, 19 of these were successfully re-induced and all but one had an allograft in CR2. Eleven patients failed re-induction and were subsequently palliated and one received an allograft for refractory disease. With a median follow up of 1699 days, the median overall survival (OS) for the population was 603 days. Cytogenetics was a strong predictor of survival with median OS (days) being 225, 508 and not reached (NR) for poor (n=29), standard (n=75) and good (n=15) cytogenetic risk groups respectively (p<0.0006). Analysis by FLT3 ITD and NPM1 mutation status amongst normal karyotype patients demonstrated median OS (days) of 131, 437 and NR for the FLT3+/NPM1- (n=8), FLT3+/NPM1+ or FLT3-/NPM1- (n=36), FLT3-/NPM1+ (n=11) respectively (p=0.0067). Conclusions The incidence of AML in adults aged over 18 was 22 per million population per annum. In this population-based cohort of adults aged 19-60 for whom the intention was intensive curative therapy the induction death rate was 7.5 % and CR rate was 85% despite 24% having poor risk genetics. Within the standard risk arm FLT3 positivity conferred a poor risk unless associated with a mutated NPM1. In an unselected population-based cohort FLT3 and NPM1 status remains an important prognostic tool. Disclosures No relevant conflicts of interest to declare.

Most of the respondents to Carolyn Heilbrun's “Guest Column: From Rereading to Reading” (119 [2004]: 211–17) seem generally to accept her rather dismal view of what is and is not possible in retirement. I disagree. Two of the fine scholars (and teachers) who were my dear friends and mentors did some of their best work in their eighties and nineties. One of these was John C. Pope, who was nearing ninety when those of us attending the Medieval Academy meeting agreed that his latest article on an Old English poem was the model of what a scholarly article ought to be; he had just mailed off another important contribution when he died, very suddenly, at ninety-three. Another was Ruth J. Dean, whose prizewinning masterwork, Anglo-Norman Literature: A Guide to Texts and Manuscripts, was published about three years before she died, at the age of one hundred.

Nova Scotia and Quebec were the only two overseas Anglican bishoprics in 1800, besides the eleven in the USA. By 1900 there were ninety-three overseas Anglican bishops, as well as the seventy-two in the home and missionary dioceses of the USA Church. Rapidly expanding colonial and missionary work was an essential element in the life of all nineteenth-century British Churches. Each by 1900 supported denominational and interdenominational missionary societies and encouraged local congregational missionary activities. Here and in fostering emigration to colonies, each British Church willingly took its part in fulfilling British imperial ideals.

The geometric pattern of Amsterdam's canals was iconic of its nineteenth-century social order. The spider's web of canals fanned out along the Amstel river in concentric rings, its barge traffic linking the city to its hinterland, the province of Holland, and to the wider Netherlands of which it is the nominal capital. These canals divided the “Venice of the North” into ninety islands linked by more than a thousand bridges. Imposing aristocratic and merchant houses stretched along the innermost canal ring, the Golden Curve of the Gentleman's Canal. At the center of the web lay de Dam, the 200 m long market square built on the first medieval dike protecting the city from the encroaching sea. The three pillars of the Dutch state framed the market square: the Royal Palace of the Merchant King, the Dutch Reformed New Church, and in the nineteenth century, the Amsterdam stock market, the world's oldest exchange.

Abstract Introduction Introduction of novel agents (Immunomodulators-thalidomide/lenalidomide and proteasome inhibitors-bortezomib) has really changed the treatment outcomes in myeloma patients. This is applicable to patients both eligible and ineligible for autologous stem cell transplant. In developing countries, like India, access to the generic forms makes it easy for patients to have treatment with all types of novel agents. In this study, we did a retrospective audit of the treatment outcomes with the generic forms of novel agents in a group of transplant ineligible patients. Methodology All newly diagnosed myeloma cases from January 2011 to December 2014, who did not undergo stem cell transplant, were included for the study. Criteria for diagnosis and treatment response were according to the latest IMWG guidelines. Baseline demographic data and details regarding CRAB criteria, Performance Status (PS), comorbidities, type and duration of treatment, and toxicity were recorded. Toxicity was graded according to CTCAE v 4. Only the maximum grade of a particular toxicity per patient has been reported. Dates of death if applicable was noted, and if patients were alive, date of last follow up was documented. Survival was analysed by non-parametric methods (Kaplan Meier and Cox proportional hazard model) and the variables considered were 'treatment completed' versus 'not completed', 'response' (PR or more) versus 'no response', 'maintenance received' versus 'not received', 'age ≤65 years' versus 'age >65 years', and international staging system (ISS) ' stage 1' versus 'stage 2 or 3'. Analysis was performed with R v 3.2.0 (http://cran.r-project.org.) Results One hundred and nineteen patients (53 males, 66 females) with median age of 62 years (range 44-85) were included as per eligibility criteria. Eighty four (70%) patients had IgG, and 21 (17.6%) had IgA, and 14 (11.7%) had light chain myeloma. Twenty two (18.4%) patients were in ISS stage 1, 36 (30%) were in stage 2 and 39 (32.7%) were in stage 3, with data missing in 22 patients. Fifty seven (47.9%) patients were having comorbidity. Ninety seven patients (81%) were having PS ≤ 2 and 21(17.6%) had PS >2. Lenalidomide based regimen was given in 29 patients, thalidomide based in 65 and bortezomib based in 25 patients. Overall response (PR or more) was documented in 74 (72%), out of 102 evaluable patients. VGPR or more was documented in 56 (55%), and PR in 18(17.6%) patients. Seventy three (61%) patients had some form of toxicity. Grade 3 nonhematologic toxicity occurred in 7 patients (peripheral neuropathy in 2, diarrhea in 2 and DVT in 3), grade 4 in none. Grade 3-4 hematologic toxicity occurred in 8 patients (grade 3 anemia and thrombocytopenia in 3 each, and grade 4 thrombocytopenia in 2 patients). Median follow up duration was 22 months. Estimated 3 year OS for entire group was 60% (95 % CI 47-77%) (Figure 1). Median PFS was 22 months (95 % CI 19- 25) (Figure 2). Variables significantly predicting OS were, treatment completed or not (47 Vs 32 months, HR= 0.372, P= 0.011) and age ≤ 65 versus age >65(47 Vs 31 months, HR= 4.15, P<0.001). Similarly for PFS the significant variables were response or not (24 Vs 7 months, HR= 4.89, P<0.001) and ISS stage 1 Vs stage 2 or 3 (25 Vs 19 months, HR=2.39, P=0.021). Conclusion Treatment with the generic forms of novel agents leads to comparable response rates and survival in patients with myeloma. So, use of these agents with lower cost seems justifiable in the real world practice where it may be difficult to access the innovators for the exuberant cost. Figure 1. Overall survival for the entire cohort Figure 1. Overall survival for the entire cohort Figure 2. Progression free survival for the entire cohort Figure 2. Progression free survival for the entire cohort Disclosures No relevant conflicts of interest to declare.

In 1835, Ferdinand Gustav Kühne, a Saxon writer and teacher, estimated that the Germanic realm was inundated with spas and that nowhere else were there as many as in Central Europe. In France there were “only ten springs, in Italy eight, Hungary had twelve, Sweden three, Spain two, England two, in Denmark and in vast Russia there was only one mineral spring of note in each, whereas in German-speaking countries, that is, including Bohemia and Switzerland, 149 facilities claimed to possess healing springs.” Although Kühne's estimate of foreign spas was too low—according to recent studies, the number of spas in England and France was significantly higher—contemporary accounts and recent local studies support his finding that Germans had the most bathing facilities in Europe. Fred Kaspar has isolated ninety-nine spas and mineral springs in Westphalia alone. Beginning in the last third of the eighteenth century, the number of spas and spa goers in particular increased rapidly in the Germanic realm. Only 200 guests came to the Kissingen spa in the summer of 1800, whereas fifty years later there were close to 4,000 and by the turn of the century 15,000 guests proper and more than 20,000 day visitors. Pyrmont, one of the most popular spas in the eighteenth century, started with 1,424 guests proper (not including peasants who were not considered guests proper) reaching 2,800 guests by the middle of the century, and around 19,000 by 1900.

Terracotta figures have been uncovered in vast quantities in the cemeteries of the Greek cities of Cyrenaica from the mid-nineteenth century onwards. While the terracottas from more recent excavations have of course remained in Libya, the majority of those brought to light in the nineteenth century are now divided between the national museums of three European capitals: Paris, Madrid and London. The Louvre collection is the largest of the three, consisting of some 400 pieces, mostly acquired by the consul M. Vattier de Bourville in the cemeteries of Cyrene and Benghazi in 1848; the majority are of the Hellenistic period, and have recently received full publication in the final volume of Mme Simone Besques' monumental catalogue. The Cyrenaican terracottas in Madrid, purchased from the collection of one Tómas Asensi in 1876, are about ninety in number, and of these roughly half are Hellenistic in date; the few given a provenance are said to come from the cemeteries of Cyrene. The Madrid terracottas were published by Alfred Laumonier in 1921, and the descriptions and photographs in his catalogue are still useful.The British Museum has around 300 terracotta figures from Cyrenaica, of which approximately 180 whole figures or fragments can be counted as Hellenistic. The archaic and classical figures were published by Dr Reynold Higgins in the first volume of his catalogue of British Museum terracottas, while a significant proportion of the later pieces were included by H. B. Walters in his earlier catalogue. However, the entire collection of post-classical Cyrenaican material will be treated in greater detail in the new catalogue of the British Museum's Hellenistic terracottas, currently in preparation.

The most prolific of Darwin's correspondents from Ireland was James Torbitt, an enterprising grocer and wine merchant of 58 North Street, Belfast. Between February 1876 and March 1882, 141 letters were exchanged on the feasibility and ways of supporting one of Torbitt's commercial projects, the large-scale production and distribution of true potato seeds (Solan um tuberosum) to produce plants resistant to the late blight fungus Phytophthora infestans, the cause of repeated potato crop failures and thus the Irish famines in the nineteenth century. Ninety-three of these letters were exchanged between Torbitt and Darwin, and 48 between Darwin and third parties, seeking or offering help and advice on the project. Torbitt's project required selecting the small proportion of plants in an infested field that survived the infection, and using those as parents to produce seeds. This was a direct application of Darwin's principle of selection. Darwin cautiously lobbied high-ranking civil servants in London to obtain government funding for the project, and also provided his own personal financial support to Torbitt.

The interest in Presocratic philosophy, and the scholarly output on it, have been rising again in the last few years. I start this review with a sample of recent publications in the area. It is easy to expect that Daniel Graham's collection of The Texts of Early Greek Philosophy, in two volumes, will become a popular tool for the study of Presocratic philosophy (for some qualifications on this expectation see below). The sourcebook aims to present ‘the complete fragments and a generous selection of testimonies’ for the major early Greek philosophers. English translations (all by Graham himself) are set opposite to Greek and Latin texts (with slim textual notes identifying substantive textual variants), with succinct introductions for each philosopher, and brief commentaries and basic bibliographies following the texts. The Diels-Kranz (hereafter DK) collection is the starting point for this sourcebook, but Graham is quite selective in his shortlist of those who deserve a place in his sourcebook: out of ninety DK sections, he includes only nineteen philosophers (Thales, Anaximander, Anaximenes, Xenophanes, Heraclitus, Parmenides, Zeno of Elea, Anaxagoras, Empedocles, Diogenes of Apollonia, Melissus, Philolaus, Leucippus, Democritus, Protagoras, Gorgias, Antiphon, Prodicus, and Pythagoras, the last being relegated to an appendix) and two anonymous texts, the Anonymus Iamblichi and the Dissoi Logoi. Although the sourcebook includes some fragments and testimonies that did not appear in DK (e.g. the Strasbourg papyrus for Empedocles), and only a selection of the testimonies included there, the major difference in terms of the material included for the selected philosophers is the order in which fragments and testimonies are presented. The fragments are incorporated within the context of the broader testimonies containing them (and signalled in bold), rather than listed separately, as in DK; the numbering of fragments and testimonies does not correspond to DK, but the DK numbers are given in addition, and volume 2 includes a list of concordances (besides an index of sources, an index of other passages quoted by Graham in his end-of-chapter commentaries, and a short general index of names and topics). Graham's choice is definitely a healthy step forward from DK's largely artificial strategy of separating fragments and testimonies into two different sections; one might wonder whether the decision to signal in bold words, phrases, sentences, and sections that supposedly count as original fragments within the broader context in which they occur is still too heavily indebted to the DK model. For each author the texts are organized in four main sections: life, works, philosophy, and reception, with the philosophy section typically structured into thematic subsections. Of course the strengths and shortcomings of a monumental work such as Graham's can be fully appreciated only over time, once you use it repeatedly in your teaching and research. I have mentioned Graham's approach to the distinction between fragments and testimonies: some sustained methodological discussion, and explanation of the criteria guiding the distinction, would have been welcome. Unavoidably some readers will find Graham's shortlist of philosophers and selection of texts unsatisfactory and too narrow: some qualms about notable exclusions – such as Solon, Alcmaeon, Archytas, Pherecydes, the Orphics, and the Derveni author – have already been voiced (for example, by Jason Rheins in his review in Notre Dame Philosophical Reviews). As far as I could see, the translations are reliable, and the short introductions, commentaries, and bibliographies provide just enough information for readers to contextualize the authors and texts within the philosophical tradition (less so within the broader archaic Greek cultural and literary tradition), and appreciate some of the key exegetical and philosophical issues that they raise. Just enough, and this brings me to what I find to be the less convincing aspect of such an enterprise as Graham's. His collection will certainly be of some use as an accessible reference tool for advanced students and researchers, but its selectivity will prevent it from becoming a research tool in its own right, and standard editions of individual Presocratics will remain the first port of call (for example, the second edition of Coxon's The Fragments of Parmenides, reviewed below). At the same time, the breadth of the material that it contains, coupled with the relative thinness of the apparatus of introductions and commentaries, does not make The Texts of Early Greek Philosophy the kind of introductory sourcebook that could be used on its own in an introductory undergraduate course on ancient philosophy, or on the Presocratics. It is difficult to imagine lecturers of such courses prescribing to their students more than a small fraction of the material offered by Graham; and those students will still need to use standard introductions to Presocratic philosophy such as Kirk–Raven–Schofield, Barnes, McKirahan, or Warren to make real sense of the evidence presented by Graham, placing it within a unified narrative about the nature and development of early Greek philosophy. From this point of view, Graham's collection risks falling into no man's land from the point of view of its readership: it is neither a ground-breaking, research-shaping tool such as, for example, Long and Sedley's collection on The Hellenistic Philosophers has been for three decades now, nor an introductory textbook easily accessible (for both sheer bulk and price) to undergraduate students. That said, Graham's work still deserves a place in all university libraries and on the shelves of ancient philosophy scholars.

Abstract Introduction: The introduction of new treatments over the past 2 decades has improved survival outcomes in patients with multiple myeloma (MM), yet MM remains incurable. Despite therapeutic advances, most patients with MM eventually relapse and/or become refractory to treatment, and cycle through standard drug classes of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs), becoming triple-class exposed. These triple-class exposed patients represent a population with an urgent unmet clinical need and are a major focus for the development of new therapies. There are currently no prospective data outside of clinical trials on standard-of-care (SOC) in MM patients who progress after these treatment regimens. LocoMMotion (NCT04035226) is the first prospective study to assess the efficacy and safety of real-life SOC treatments in triple-class exposed patients with relapsed/refractory MM (RRMM). Initial analysis at a median follow-up of 3.7 months (range: 0.0-12.7) showed an overall response rate (ORR) of 20.1% (95% CI: 15.0-26.0), with only 5% of patients achieving very good partial response or better. Here, we report updated results from LocoMMotion with a longer median duration of follow-up (7.8 months), along with progression-free survival (PFS) and overall survival (OS) data. Methods: LocoMMotion is a non-interventional study of 246 patients across 10 countries (the US and 9 in Europe) and 75 sites. Patients (aged ≥18 years) with a documented diagnosis of MM were included if they received ≥3 prior lines of therapy or were double-refractory to a PI and IMiD; had measurable disease at screening; received at least a PI, an IMiD, and anti-CD38 mAb with documented progressive disease since their last line of therapy; and had an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1. Patient-level data and the most common SOC treatments were collected and analyzed during the study period (August 2019 through October 2020). Real-life SOC treatments were defined as those used in local clinical practice. Responses were assessed per International Myeloma Working Group response criteria. A review committee assessed the ORR (primary objective) of real-life current SOC as well as disease progression for the determination of PFS. Secondary objectives included evaluation of additional efficacy endpoints, including OS, and safety. Results: As of the data cut-off date of March 9, 2021, 246 patients were included with a median follow-up of 7.8 months (range: 0.1-16.9); 23 (9.3%) patients were from the US and 223 (90.7%) were from Europe. Median age was 68 years (range: 41-89), 133 (54.1%) were male, 180 (73.8%) had a baseline ECOG PS score of 1, and median time since initial MM diagnosis was 6.3 years (range: &lt;1.0-22.8). Patients had received a median of 4.0 prior lines of therapy (range: 2-13); all patients were triple-class exposed, 185 (75.2%) were triple-class refractory, and 228 (92.7%) were refractory to last line of therapy. Ninety-three unique treatment regimens were used in the enrolled population, and 63% of patients were treated with a combination of ≥3 drugs. ORR with real-life SOC salvage therapy was 28.0% (95% CI: 22.5-34.1). For the 69 patients who responded, median duration of response was 5.1 months (95% CI: 4.4-NE). In all patients treated, the median PFS was 4.4 months (95% CI: 3.8-5.4), and median OS was 12.4 months (95% CI: 9.6-NE). Treatment-emergent adverse events (TEAEs) were reported in 192 (78.0%) patients; 122 (49.6%) patients had grade ≥3 TEAEs. The most common grade ≥3 TEAEs were anemia (9.8%), thrombocytopenia (13.4%), and neutropenia (11.8%). Nineteen (7.7%) patients died due to TEAEs during the study; the most common TEAE leading to death was infection (n=11). Eighty (32.5%) patients had ongoing SOC treatment after the median follow up of 7.8 months. The study is ongoing in 147 (59.8%) patients. Conclusions: Updated results of this first, prospective study of real-life SOC treatment in triple-class exposed patients with RRMM confirm rapid disease progression after application of salvage therapy and poor outcomes with currently available treatments. New treatment approaches with novel therapies are needed to improve outcomes in this patient population. Disclosures Moreau: Oncopeptides: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Celgene BMS: Honoraria. Weisel: Roche: Honoraria; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Goldschmidt: Incyte: Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; GSK: Honoraria; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant; Molecular Partners: Research Funding; MSD: Research Funding; Mundipharma: Research Funding; Novartis: Honoraria, Research Funding; Dietmar-Hopp-Foundation: Other: Grant; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Takeda: Consultancy, Research Funding; Adaptive Biotechnology: Consultancy. Delforge: Amgen, Celgene, Janssen, Sanofi: Honoraria, Research Funding. Mohty: Novartis: Honoraria; Astellas: Honoraria; Gilead: Honoraria; Bristol Myers Squibb: Honoraria; Pfizer: Honoraria; Adaptive Biotechnologies: Honoraria; Sanofi: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Takeda: Honoraria; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Janssen: Honoraria, Research Funding. Cavo: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau; Adaptive Biotechnologies: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vij: BMS: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; BMS: Honoraria; GSK: Honoraria; Oncopeptides: Honoraria; Karyopharm: Honoraria; CareDx: Honoraria; Legend: Honoraria; Biegene: Honoraria; Adaptive: Honoraria; Harpoon: Honoraria. Dytfeld: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Cilag: Consultancy, Current Employment, Honoraria, Membership on an entity's Board of Directors or advisory committees. Angelucci: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene BSM: Honoraria, Other: DMC; Blue Bird Bio: Honoraria, Membership on an entity's Board of Directors or advisory committees; Menarini-Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: steering commitee, Speakers Bureau; Vertex Pharmaceuticals: Honoraria, Other: DMC; Crispr therapeutics: Honoraria, Other: DMC; Glaxo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Perrot: GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Sanofi: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Benjamin: Servier: Honoraria, Research Funding; Allogene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Gileai: Honoraria, Research Funding. Van de Donk: BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Cellectis: Research Funding; Takeda: Consultancy; Roche: Consultancy; Novartis /bayer/servier: Consultancy. Ocio: MSD: Honoraria; Amgen: Consultancy, Honoraria; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria; Karyopharm: Consultancy; Oncopeptides: Consultancy, Honoraria; Pfizer: Consultancy; Secura-Bio: Consultancy. Scheid: Roche: Consultancy; Abbvie: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Gay: Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria. Rodriguez-Otero: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Clínica Universidad de Navarra: Current Employment; Celgene-BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Regeneron: Honoraria. Broyl: Celgene: Honoraria; Janssen Pharmaceuticals: Honoraria; Sanofi: Honoraria; Bristol-Meyer Squibb: Honoraria; Amgen: Honoraria. Potamianou: Janssen: Current Employment, Current holder of stock options in a privately-held company. Sakabedoyan: Janssen: Current Employment. Semerjian: Janssen: Current Employment. Keim: Janssen Research & Development: Current Employment. Strulev: Janssen Pharmaceutica NV: Current Employment. Schecter: Janssen: Current Employment, Current holder of stock options in a privately-held company. Vogel: Janssen Global Services, LLC: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months. Wapenaar: Janssen: Current Employment; Johnson & Johnson: Current holder of individual stocks in a privately-held company. Nesheiwat: Legend Biotech USA: Current Employment. San-Miguel: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Merck Sharpe & Dohme, Novartis, Regeneron, Roche, Sanofi, SecuraBio, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sonneveld: SkylineDx: Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene/BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Einsele: Janssen, Celgene/BMS, Amgen, GSK, Sanofi: Consultancy, Honoraria, Research Funding. Mateos: Oncopeptides: Honoraria; GSK: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird bio: Honoraria; Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, the coronavirus infectious disease 2019 (COVID-19), have spread to millions of persons worldwide resulting in pandemic.The cases of Covid 19 doesn't seem to end to soon.There are about sixty-two million six hundred nineteen thousand three hundred ninety-ninecases at present in the world with India ranking second after USA with nine million three hundred ninetythree thousand thirty-nine cases.Adoption of infection prevention and control practices such as hand hygiene, respiratory etiquettes, and maintaining social distance are the important strategies for the containment of this deadly and stubborn novel corona virus.The multiple vaccine candidates are under trials,to evaluate their clinical efficacy.The vaccination aims is to generate immunity against COVID-19 and to protect oneself against the disease and limits the spread of disease to close contact

Sewage ponds with exposed sludge are known to be excellent feeding sites for waders during migration. They still exist in parts of the world but are disappearing in pace with introduction of modern methods which do not involve open exposure of the sludge. Here I report a five-year study from a Swedish plant with open sludge ponds in the 1950s when many similar ones were still active. I counted the waders with frequent visits from 18 April through 2 November, 1952–1956. Ninety-three percent of the dates had a visit in at least one of the years giving an almost complete combined coverage of migration. Nineteen species were recorded at least once. The total average annual number of bird-days was 2868 (5% in spring). Most abundant were the Ruff Calidris pugnax with 35% and Wood Sandpiper Tringa glareola with 32% of all bird days. Temminck’s Stint Calidris temminckii showed the highest spring proportion of bird-days, 30%.

Abstract Background Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a primary liver carcinoma with both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) components. We examined the clinicopathological characteristics and recurrence patterns of cHCC-CCA. Because of the rarity of cHCC-CCA, its etiology, clinicopathological features, and prognosis in comparison with other primary liver carcinoma remain unknown. Its recurrence pattern and sites in particular also need to be elucidated. Methods All patients who underwent hepatectomy for primary liver malignancies between 2005 and 2015 were retrospectively included in this study. Results Eight hundred and ninety-four hepatectomies were performed. Nineteen cases of cHCC-CCA (2.1%) in 16 patients were enrolled. Three patients underwent re-hepatectomy. The background of hepatitis viruses and tumor marker patterns of cHCC-CCA were similar to those of HCC and dissimilar to those of intrahepatic CCA (iCCA). Biliary invasion was common in cHCC-CCA and iCCA. The 5-year overall survival values of the cHCC-CCA, HCC, and iCCA patients were 44.7%, 56.6%, and 38.5%, respectively. The 5-year recurrence-free survival values of the cHCC-CCA, HCC, and iCCA patients were 12.2%, 28.7%, and 32.9%, respectively. The liver was the most common recurrence site. Unlike HCC, however, the lymph node was the second-most common recurrence site in both cHCC-CCA and iCCA. Pathological samples of the recurrent lesions were obtained in six patients, and four had cHCC-CCA recurrence pathologically. Conclusion cHCC-CCA had a mixture of characteristics of HCC and iCCA. Many cases of cHCC-CCA remained cHCC-CCA pathologically even after recurrence.