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APPLETON, WI THEATER SHOWS
Get news, offers reviews for musicals & plays.
Akt Productions
Webb Theatre (kt)
The Music Man Jr
From the Broadway stage to schools nationwide, this American classic is still sweeping the country! You'll have no "trouble" convincing kids to perform in this 1/27 - 1/29/2023
Saber Center For The Performing Art
Fiddler On The Roof Jr
This special edition of one of Broadway's great masterpieces, Fiddler On The Roof Junior covers the full range of human emotions, presenting young performers with 2/2 - 2/4/2023
Sharon Lynne Wilson Center
3270 Mitchell Park Dr
THEATRE THREE presents the hit revue, BREAKING UP IS HARD TO DO, featuring the songs of Neil Sedaka, including "Where the Boys Are," "Calendar Girl," 2/3 - 2/5/2023
Univ of Wisconsin - Stevens Point at Marshfield
Disney's Winnie The Pooh Kids
Welcome to the Hundred Acre Wood, where Winnie the Pooh is once again in search of honey. Along the way, he meets his pals Tigger, 2/4 - 2/5/2023
Overture Center For The Arts
Into The Woods Jr
The Brothers Grimm "go Broadway" as Sondheim and Lapine offer up a cockeyed fairy tale where all of your favorite characters-Cinderella, Little Red Riding Hood, 2/16 - 2/19/2023
South Milwaukee Perf Arts Center
South Milwauke
Lerner And Loewe's My Fair Lady
Lerner and Loewe's award-winning story of a cockney flower girl transformed into an elegant lady is widely considered one of the greatest musicals of all 2/16 - 2/19/2023
The Music Man
Oregon Performing Arts Center 2/17 - 2/19/2023
Oregon Performing Arts Center
456 N Perry Pkwy
Disney's The Jungle Book Kids
The jungle is jumpin? with jazz is this exciting Disney classic! Join Mowgli, Baloo, King Louie and the gang as they swing their way through 2/24 - 2/24/2023
Sc Johnson Elementary Av Room
2420 Kentucky St
One of the most popular Disney movies of all time is capturing hearts in a whole new way: as a practically perfect musical! Mary Poppins 2/23 - 2/25/2023
Stevens Point Area Senior High
1201 North Point Dr
Disney's Aladdin Jr.
Greasepaint Theatre for Youth presents Disney's Aladdin Jr. For tickets and information, visit the website. 2/24 - 2/26/2023
Gilmore Fine Arts Bissel Auditorium
2330 Northwestern Ave
John Michael Kohler Art Center Thea
Shrek The Musical Jr
Beauty is in the eye of the ogre in Shrek The Musical JR., based on the Oscar-winning DreamWorks Animation film and fantastic Broadway musical. It's 3/3 - 3/4/2023
Available Spring 2020 2/17 - 3/5/2023
Theatre Of Oconomowoc, Ltd
W359 N5920 Brown St
Oconomowoc
Phipps Center For The Arts
109 Locust St
2/24 - 3/5/2023
Grasch Auditorium
2/9 - 3/5/2023
123 S Broadway
Central Wisconsin Childrens Theatre (cwct)
700 W Strowbridge St
625 Stewart Ave
Seven Brides For Seven Brothers
Platteville Municipal Auditorium
75 N Bonson St
Platteville
Bernie Hupperts Ctr For Perf Arts
All Night Strut:a Jumpin' Jivin' Jam
This new musical version of "a href="http://www.mtishows.com/show_detail.asp?showid=000004"The All Night Strut!/a" is a circus, an American musical, a dance spectacle all fused with hip hop, jazz, 3/8 - 3/12/2023
Mainstage Theatre
2400 E Kenwood Blvd
Welcome to the Hundred Acre Wood, where Winnie the Pooh is once again in search of honey. Along the way, he meets his pals Tigger, 3/11 - 3/12/2023
Treehouse Theater
St. Timothy Lutheran Church
More Shows ( 1 2 3 4 5) Next »
Appleton, WI Critics Wanted
BWW is always seeking talented theater enthusiasts to head up feature coverage our over 130 regional areas. As a Contributing Editor, you will have the opportunity to review the shows of your choice, conduct interviews with local and touring talent, design features of your own choosing for publishing, and work/network with your local theater press reps to bring exposure to the theatrical offerings in your area.
All applicants should have excellent writing skills and an interest for giving local theaters and productions some prominence on BroadwayWorld.com.
Your compensation as a featured writer with us not only includes exclusive press seats to all of the shows you cover (as is standard in your area and arranged between you and the theater) but also the opportunity to be published under your own byline and publishing profile on both the local and main pages of the site for maximum exposure to our 5M+ monthly visitors.
If this sounds like you, please send a resume and one writing sample to social@broadwayworld.com.
Door Shakespeare Announces 2023 Summer Season
The Grand Oshkosh Presents COCKTAIL HOUR: The Show
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redpajama_set_name: RedPajamaCommonCrawl


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Die Dampflokomotiven "HEBE I", "PROSERPINA" und "DAPHNE I" waren Personenzuglokomotiven der KFNB.
Sie wurden 1852 von der Lokomotivfabrik der Wien-Gloggnitzer Eisenbahngesellschaft in Wien an die KFNB mit der Achsformel 1B geliefert.
Sie entstammten dem ersten Versuch John Haswells, des Leiters der Fabrik, eine Einheitstype zu entwickeln, und waren ähnlich den unter "NESTOR" bis "ARIADNE", "BIHAR" bis "Üllö" und "JASON II" beschriebenen Lokomotiven.
Im Unterschied zu diesen hatten sie aber Innenzylinder wie die älteren englischen Maschinen.

Die überlieferten Dimensionen differieren stark, was entweder auf Umbauten oder fehlerhafte Angaben in den Lokomotivlisten der KFNB zurückzuführen ist.

Offensichtlich war man mit den Maschinen nicht zufrieden, denn sie wurden schon 1877 und 1878 ausgemustert.

Literatur

 Alfred Horn: Die Kaiser-Ferdinands-Nordbahn, Die Bahnen Österreich-Ungarns, Band 2, Bohmann Verlag, 1970
 Karl Gölsdorf: Lokomotivbau in Alt-Österreich 1837–1918, Verlag Slezak, 1978, ISBN 3-900134-40-5

Hebe 1
Dampflokomotive Achsfolge 1B

redpajama_set_name: RedPajamaWikipedia


Harvard graduate teaches government at Eastfield College and helps students reach their goals by reminding them that it is never too late "nunca es demasiado tarde" [to go back to school].
You continued your education and earned a master's and a doctorate degree. Tell me about that process.
What would you tell older, returning students?


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Winnipeg Regional Real Estate News
Commercial Real Estate Magazine
About Mortgages
Market Releases
Your REALTOR®
Affiliate Associates
Moving To Winnipeg
Nov 15 2019 Issue
The Canadian First-Time Home Buyer Incentive — All you need to know
Winnipeg Transit looks to change current network design
Go with the less-is-more style for holiday decorating
Examine safety switches as part of your furnace checklist
The resurrection of Navin, Manitoba
Increased coyote sightings in Winnipeg
Steps for buying your first home
Search issues by word/phrase…
Or browse issues by year/month…
COVID-19 Best Practices
REN Holiday Recipes
By Christian Cassidy
Manitoba's countryside is dotted with defunct communities whose names can only be found in history books. Navin, Manitoba was one of these until earlier this year when Canada Post announced that it would be reinstated as a mailing address for a few thousand residents in the Rural Municipality of Springfield.
Navin was established as a stop along the Canadian Northern Railway's mainline from Thunder Bay to Winnipeg constructed between 1898 and 1902. It fell between the communities of Lorette and St. Boniface and roughly encompassed the area from the present-day southern edge of Symington Yards to Tinkertown on both sides of the Trans-Canada Highway. It is still a point on CN's Sprague Subdivision, though the days of train service are long gone.
The first settlers to this part of the province came well before the railway did. They were mainly French farmers along the Seine River and the district was known as Seigneurie. According to the province's publication Geographical Place Names of Manitoba, the siding was named in 1904 after a local landowner and the district took on that name.
Thomas Naven, spelled different than the community, was a dairy farmer whose primary residence was in the area we now know as Elm Park in St. Vital. It is said that in the late 1890s he was part of the consortium that built a pontoon bridge across the Assiniboine River where the Bridge Drive-Inn is today and sold concessions to visitors as a side business.
The community of Navin did not have an actual townsite. Its services, such as a railway station, school and post office, were spread through the district.
The most important feature of Navin was its train station. Initially, it was just a siding — a platform along the track to load and unload cargo. It is unclear when an actual station was built, though it may have been by 1907 when Canadian Northern launched its "Lake Superior Express" passenger service with Navin as one of its stops. In the 1911 book "Canada's West and Farther West" the author describes passing Navin's train station en route to Winnipeg.
Navin's few mentions in local newspapers were usually due to sad news involving the rail line. There was the odd derailment including one in 1905 that caused the death of CN employee Frank Kennedy. In 1927, train conductor Richard Taylor noticed someone slip off the train at Navin and thought he may have been a fare evader. He ran after the passenger and died of a heart attack whilst the two were arguing.
Navin Station was a "flag stop" which meant that trains would not stop to pick up passengers or freight unless the station agent displayed a flag to signal the crew. A former resident of Navin in the 1950s and early 1960s recalls the station and a collection of bunkhouses located where Symington Road meets the train tracks east of Winnipeg, now the dead end of an industrial road.
Another important location within the community was its school which was established in 1899 as
Seigneurie School Division No. 1000. The Springfield and District centennial history book puts its location near the interchange at the eastern foot of the Highway No. 1 bridge that crosses the tracks south of Symington Yard. The name was changed to Navin School Division in 1945.
The original schoolhouse was replaced in 1957 by a new building. It still contained just one classroom for its 25 students in grades one through eight, but also featured a kitchen and indoor washrooms.
Not long after the opening of the new school there was debate about its future.
In 1959, the school became part of the newly created Transcona-Springfield School Division and the pressure was on to consolidate its collection of single-room schools. Navin's fate was discussed at a January 1965 Municipality of Springfield council meeting. Fifteen delegates appeared and were split between those wanting to retain the old school with the addition of another classroom and those who felt their children would receive a better education at a larger, consolidated school.
The decision was made to close Navin School after the following school year and, though the region was in the Transcona-Springfield School Division catchment area, electors voted consolidate with the St. Boniface School Division. The old schoolhouse was sold off in September 1967 and became a residence.
The last service in the community to leave was its newest. A post office was established at Navin in May 1961 with John Happychuk as postmaster in a small building on Symington Road south of the tracks. Through the 1970s it was run by Edna and Gordon Kelsch until it closed in the summer of 1976.
It was not depopulation or a lack of commercial activity that ended Navin's run as a community. In fact, with the Trans-Canada Highway built through it in the early 1950s and the opening of Symington Yard in 1962, the area became busier than ever with industrial businesses and a post-war influx of new immigrants. It was, however, Navin's close proximity to the ever-growing communities of Transcona, St. Boniface and Winnipeg that did it in.
In the past couple of decades, the area has seen a resurgence in residential development and now features many fine homes on large lots. This population growth has helped Navin buck the trend and resurrect itself as a community.
Christian writes about local history on his blog, West End Dumplings.
Winnipeg Regional Real Estate News is a publication of the Winnipeg Regional Real Estate Board
More about the Winnipeg Regional Real Estate board
The Winnipeg Regional Real Estate Board is an inclusive organization and believes in removing barriers for anyone with disabilities. Information on this website is available in alternate formats upon request.
© The Winnipeg Regional Real Estate Board. All rights reserved. REALTOR®, REALTORS® and the associated logos are trademarks of REALTOR® Canada Inc. a corporation owned by The Canadian Real Estate Association and the National Association of REALTORS®. The trademarks MLS®, Multiple Listing Service® and the associated logos identify professional services rendered by REALTOR® Members of CREA to effect the purchase, sale and lease of real estate as part of a cooperative selling system.


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George William Schmal (21 February 1849 - 4 August 1923) was a blacksmith in the United States Army who was awarded the Presidential Medal of Honor for gallantry during the American Civil War. Schmal was awarded the medal on 3 May 1865 for actions performed during the Battle of Paines Crossroads on 5 April 1865.

Personal life
Schmal was born in Germany on 21 February 1849. He fathered one known child, Frank Peter Schmal (1873-1960). Schmal died in Erie County, New York on 4 August 1923 and was buried in Forest Lawn Cemetery in Buffalo, New York.

Military service
Schmal enlisted in the Army as a blacksmith on 8 March 1865 in Buffalo. He was assigned to Company M of the 24th New York Cavalry, which was renamed the 1st New York Provincial Cavalry on 17 June 1865. On 5 April 1865, during the Battle of Paines Crossroads in Virginia, Schmal captured an unspecified Confederate battle flag. For this action, he was awarded the Medal of Honor.

Schmal's Medal of Honor citation reads:

Schmal was mustered out of the Army on 19 July 1865 at Cloud's Mills, Virginia.

References

1849 births
1923 deaths
19th-century American military personnel
American blacksmiths
People from Buffalo, New York
American Civil War recipients of the Medal of Honor


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A Peer-Reviewed Open-Access Journal
URL: https://journals.plos.org/plosmedicine/
Aggiornato: 4 ore 12 min fa
The impact of a routine late third trimester growth scan on the incidence, diagnosis, and management of breech presentation in Oxfordshire, UK: A cohort study
by Ibtisam Salim, Eleonora Staines-Urias, Sam Mathewlynn, Lior Drukker, Manu Vatish, Lawrence Impey
Breech presentation at term contributes significantly to cesarean section (CS) rates worldwide. External cephalic version (ECV) is a safe procedure that reduces term breech presentation and associated CS. A principal barrier to ECV is failure to diagnose breech presentation. Failure to diagnose breech presentation also leads to emergency CS or unplanned vaginal breech birth. Recent evidence suggests that undiagnosed breech might be eliminated using a third trimester scan. Our aim was to evaluate the impact of introducing a routine 36-week scan on the incidence of breech presentation and of undiagnosed breech presentation.
Methods and findings
We carried out a population-based cohort study of pregnant women in a single unit covering Oxfordshire, United Kingdom. All women delivering between 37+0 and 42+6 weeks gestational age, with a singleton, nonanomalous fetus over a 4-year period (01 October 2014 to 30 September 2018) were included. The mean maternal age was 31 years, mean BMI 26, 44% were nulliparous, and 21% were of non-white ethnicity. Comparisons between the 2 years before and after introduction of routine 36-week scan were made for 2 primary outcomes of (1) the incidence of breech presentation and (2) undiagnosed breech presentation. Secondary outcomes related to ECV, mode of birth, and perinatal outcomes. Relative risks (RRs) with 95% confidence intervals (CIs) are reported. A total of 27,825 pregnancies were analysed (14,444 before and 13,381 after). A scan after 35+0 weeks was performed in 5,578 (38.6%) before, and 13,251 (99.0%) after (p < 0.001). The incidence of breech presentation at birth did not change significantly (2.6% and 2.7%) (RR 1.02; 95% CI 0.89, 1.18; p = 0.76). The rate of undiagnosed breech before labour reduced, from 22.3% to 4.7% (RR 0.21; 95% CI 0.12, 0.36; p < 0.001). Vaginal breech birth rates fell from 10.3% to 5.3% (RR 0.51; 95% CI 0.30, 0.87; p = 0.01); nonsignificant increases in elective CS rates and decreases in emergency CS rates for breech babies were seen. Neonatal outcomes were not significantly altered. Study limitations include insufficient numbers to detect serious adverse outcomes, that we cannot exclude secular changes over time which may have influenced our results, and that these findings are most applicable where a comprehensive ECV service exists.
In this study, a universal 36-week scan policy was associated with a reduction in the incidence but not elimination of undiagnosed term breech presentation. There was no reduction in the incidence of breech presentation at birth, despite a comprehensive ECV service.
Categorie: Riviste scientifiche
Polygenic risk scores in cardiovascular risk prediction: A cohort study and modelling analyses
Gio, 14/01/2021 - 15:00
by Luanluan Sun, Lisa Pennells, Stephen Kaptoge, Christopher P. Nelson, Scott C. Ritchie, Gad Abraham, Matthew Arnold, Steven Bell, Thomas Bolton, Stephen Burgess, Frank Dudbridge, Qi Guo, Eleni Sofianopoulou, David Stevens, John R. Thompson, Adam S. Butterworth, Angela Wood, John Danesh, Nilesh J. Samani, Michael Inouye, Emanuele Di Angelantonio
Polygenic risk scores (PRSs) can stratify populations into cardiovascular disease (CVD) risk groups. We aimed to quantify the potential advantage of adding information on PRSs to conventional risk factors in the primary prevention of CVD.
Using data from UK Biobank on 306,654 individuals without a history of CVD and not on lipid-lowering treatments (mean age [SD]: 56.0 [8.0] years; females: 57%; median follow-up: 8.1 years), we calculated measures of risk discrimination and reclassification upon addition of PRSs to risk factors in a conventional risk prediction model (i.e., age, sex, systolic blood pressure, smoking status, history of diabetes, and total and high-density lipoprotein cholesterol). We then modelled the implications of initiating guideline-recommended statin therapy in a primary care setting using incidence rates from 2.1 million individuals from the Clinical Practice Research Datalink. The C-index, a measure of risk discrimination, was 0.710 (95% CI 0.703–0.717) for a CVD prediction model containing conventional risk predictors alone. Addition of information on PRSs increased the C-index by 0.012 (95% CI 0.009–0.015), and resulted in continuous net reclassification improvements of about 10% and 12% in cases and non-cases, respectively. If a PRS were assessed in the entire UK primary care population aged 40–75 years, assuming that statin therapy would be initiated in accordance with the UK National Institute for Health and Care Excellence guidelines (i.e., for persons with a predicted risk of ≥10% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), then it could help prevent 1 additional CVD event for approximately every 5,750 individuals screened. By contrast, targeted assessment only among people at intermediate (i.e., 5% to <10%) 10-year CVD risk could help prevent 1 additional CVD event for approximately every 340 individuals screened. Such a targeted strategy could help prevent 7% more CVD events than conventional risk prediction alone. Potential gains afforded by assessment of PRSs on top of conventional risk factors would be about 1.5-fold greater than those provided by assessment of C-reactive protein, a plasma biomarker included in some risk prediction guidelines. Potential limitations of this study include its restriction to European ancestry participants and a lack of health economic evaluation.
Our results suggest that addition of PRSs to conventional risk factors can modestly enhance prediction of first-onset CVD and could translate into population health benefits if used at scale.
Recognition and management of community-acquired acute kidney injury in low-resource settings in the ISN 0by25 trial: A multi-country feasibility study
by Etienne Macedo, Ulla Hemmila, Sanjib Kumar Sharma, Rolando Claure-Del Granado, Henry Mzinganjira, Emmanuel A. Burdmann, Jorge Cerdá, John Feehally, Fredric Finkelstein, Guillermo García-García, Vivekanand Jha, Norbert H. Lameire, Euyhyun Lee, Nathan W. Levin, Andrew Lewington, Raúl Lombardi, Michael V. Rocco, Eliah Aronoff-Spencer, Marcello Tonelli, Karen Yeates, Giuseppe Remuzzi, Ravindra L. Mehta, for the ISN 0by25 Trial Study Group
Acute kidney injury (AKI) is increasingly encountered in community settings and contributes to morbidity, mortality, and increased resource utilization worldwide. In low-resource settings, lack of awareness of and limited access to diagnostic and therapeutic interventions likely influence patient management. We evaluated the feasibility of the use of point-of-care (POC) serum creatinine and urine dipstick testing with an education and training program to optimize the identification and management of AKI in the community in 3 low-resource countries.
Patients presenting to healthcare centers (HCCs) from 1 October 2016 to 29 September 2017 in the cities Cochabamba, Bolivia; Dharan, Nepal; and Blantyre, Malawi, were assessed utilizing a symptom-based risk score to identify patients at moderate to high AKI risk. POC testing for serum creatinine and urine dipstick at enrollment were utilized to classify these patients as having chronic kidney disease (CKD), acute kidney disease (AKD), or no kidney disease (NKD). Patients were followed for a maximum of 6 months with repeat POC testing. AKI development was assessed at 7 days, kidney recovery at 1 month, and progression to CKD and mortality at 3 and 6 months. Following an observation phase to establish baseline data, care providers and physicians in the HCCs were trained with a standardized protocol utilizing POC tests to evaluate and manage patients, guided by physicians in referral hospitals connected via mobile digital technology. We evaluated 3,577 patients, and 2,101 were enrolled: 978 in the observation phase and 1,123 in the intervention phase. Due to the high number of patients attending the centers daily, it was not feasible to screen all patients to assess the actual incidence of AKI. Of enrolled patients, 1,825/2,101 (87%) were adults, 1,117/2,101 (53%) were females, 399/2,101 (19%) were from Bolivia, 813/2,101 (39%) were from Malawi, and 889/2,101 (42%) were from Nepal. The age of enrolled patients ranged from 1 month to 96 years, with a mean of 43 years (SD 21) and a median of 43 years (IQR 27–62). Hypertension was the most common comorbidity (418/2,101; 20%). At enrollment, 197/2,101 (9.4%) had CKD, and 1,199/2,101 (57%) had AKD. AKI developed in 30% within 7 days. By 1 month, 268/978 (27%) patients in the observation phase and 203/1,123 (18%) in the intervention phase were lost to follow-up. In the intervention phase, more patients received fluids (observation 714/978 [73%] versus intervention 874/1,123 [78%]; 95% CI 0.63, 0.94; p = 0.012), hospitalization was reduced (observation 578/978 [59%] versus intervention 548/1,123 [49%]; 95% CI 0.55, 0.79; p < 0.001), and admitted patients with severe AKI did not show a significantly lower mortality during follow-up (observation 27/135 [20%] versus intervention 21/178 [11.8%]; 95% CI 0.98, 3.52; p = 0.057). Of 504 patients with kidney function assessed during the 6-month follow-up, de novo CKD arose in 79/484 (16.3%), with no difference between the observation and intervention phase (95% CI 0.91, 2.47; p = 0.101). Overall mortality was 273/2,101 (13%) and was highest in those who had CKD (24/106; 23%), followed by those with AKD (128/760; 17%), AKI (85/628; 14%), and NKD (36/607; 6%). The main limitation of our study was the inability to determine the actual incidence of kidney dysfunction in the health centers as it was not feasible to screen all the patients due to the high numbers seen daily.
This multicenter, non-randomized feasibility study in low-resource settings demonstrates that it is feasible to implement a comprehensive program utilizing POC testing and protocol-based management to improve the recognition and management of AKI and AKD in high-risk patients in primary care.
Multimorbidity combinations, costs of hospital care and potentially preventable emergency admissions in England: A cohort study
by Jonathan Stokes, Bruce Guthrie, Stewart W. Mercer, Nigel Rice, Matt Sutton
Patients with multimorbidities have the greatest healthcare needs and generate the highest expenditure in the health system. There is an increasing focus on identifying specific disease combinations for addressing poor outcomes. Existing research has identified a small number of prevalent "clusters" in the general population, but the limited number examined might oversimplify the problem and these may not be the ones associated with important outcomes. Combinations with the highest (potentially preventable) secondary care costs may reveal priority targets for intervention or prevention. We aimed to examine the potential of defining multimorbidity clusters for impacting secondary care costs.
We used national, Hospital Episode Statistics, data from all hospital admissions in England from 2017/2018 (cohort of over 8 million patients) and defined multimorbidity based on ICD-10 codes for 28 chronic conditions (we backfilled conditions from 2009/2010 to address potential undercoding). We identified the combinations of multimorbidity which contributed to the highest total current and previous 5-year costs of secondary care and costs of potentially preventable emergency hospital admissions in aggregate and per patient. We examined the distribution of costs across unique disease combinations to test the potential of the cluster approach for targeting interventions at high costs. We then estimated the overlap between the unique combinations to test potential of the cluster approach for targeting prevention of accumulated disease. We examined variability in the ranks and distributions across age (over/under 65) and deprivation (area level, deciles) subgroups and sensitivity to considering a smaller number of diseases.There were 8,440,133 unique patients in our sample, over 4 million (53.1%) were female, and over 3 million (37.7%) were aged over 65 years. No clear "high cost" combinations of multimorbidity emerged as possible targets for intervention. Over 2 million (31.6%) patients had 63,124 unique combinations of multimorbidity, each contributing a small fraction (maximum 3.2%) to current-year or 5-year secondary care costs. Highest total cost combinations tended to have fewer conditions (dyads/triads, most including hypertension) affecting a relatively large population. This contrasted with the combinations that generated the highest cost for individual patients, which were complex sets of many (6+) conditions affecting fewer persons. However, all combinations containing chronic kidney disease and hypertension, or diabetes and hypertension, made up a significant proportion of total secondary care costs, and all combinations containing chronic heart failure, chronic kidney disease, and hypertension had the highest proportion of preventable emergency admission costs, which might offer priority targets for prevention of disease accumulation. The results varied little between age and deprivation subgroups and sensitivity analyses.Key limitations include availability of data only from hospitals and reliance on hospital coding of health conditions.
Our findings indicate that there are no clear multimorbidity combinations for a cluster-targeted intervention approach to reduce secondary care costs. The role of risk-stratification and focus on individual high-cost patients with interventions is particularly questionable for this aim. However, if aetiology is favourable for preventing further disease, the cluster approach might be useful for targeting disease prevention efforts with potential for cost-savings in secondary care.
Plasma proteins associated with cardiovascular death in patients with chronic coronary heart disease: A retrospective study
by Lars Wallentin, Niclas Eriksson, Maciej Olszowka, Tanja B. Grammer, Emil Hagström, Claes Held, Marcus E. Kleber, Wolfgang Koenig, Winfried März, Ralph A. H. Stewart, Harvey D. White, Mikael Åberg, Agneta Siegbahn
Circulating biomarkers are associated with the development of coronary heart disease (CHD) and its complications by reflecting pathophysiological pathways and/or organ dysfunction. We explored the associations between 157 cardiovascular (CV) and inflammatory biomarkers and CV death using proximity extension assays (PEA) in patients with chronic CHD.
The derivation cohort consisted of 605 cases with CV death and 2,788 randomly selected non-cases during 3–5 years follow-up included in the STabilization of Atherosclerotic plaque By Initiation of darapladIb TherapY (STABILITY) trial between 2008 and 2010. The replication cohort consisted of 245 cases and 1,042 non-cases during 12 years follow-up included in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study between 1997 and 2000. Biomarker levels were measured with conventional immunoassays and/or with the OLINK PEA panels CVD I and Inflammation. Associations with CV death were evaluated by Random Survival Forest (RF) and Cox regression analyses.Both cohorts had the same median age (65 years) and 20% smokers, while there were slight differences in male sex (82% and 76%), hypertension (70% and 78%), and diabetes (39% and 30%) in the respective STABILITY and LURIC cohorts. The analyses identified 18 biomarkers with confirmed independent association with CV death by Boruta analyses and statistical significance (all p < 0.0001) by Cox regression when adjusted for clinical characteristics in both cohorts. Most prognostic information was carried by N-terminal prohormone of brain natriuretic peptide (NTproBNP), hazard ratio (HR for 1 standard deviation [SD] increase of the log scale of the distribution of the biomarker in the replication cohort) 2.079 (95% confidence interval [CI] 1.799–2.402), and high-sensitivity troponin T (cTnT-hs) HR 1.715 (95% CI 1.491–1.973) carried most prognostic information. The other proteins with independent associations were growth differentiation factor 15 (GDF-15) HR 1.728 (95% CI 1.527–1.955), transmembrane immunoglobulin and mucin domain protein (TIM-1) HR 1.555 (95% CI 1.362–1.775), renin HR 1.501 (95% CI 1.305–1.727), osteoprotegerin (OPG) HR 1.488 (95% CI 1.297–1.708), soluble suppression of tumorigenesis 2 protein (sST2) HR 1.478 (95% CI 1.307–1.672), cystatin-C (Cys-C) HR 1.370 (95% CI 1.243–1.510), tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) HR 1.205 (95% CI 1.131–1.285), carbohydrate antigen 125 (CA-125) HR 1.347 (95% CI 1.226–1.479), brain natriuretic peptide (BNP) HR 1.399 (95% CI 1.255–1.561), interleukin 6 (IL-6) HR 1.478 (95% CI 1.316–1.659), hepatocyte growth factor (HGF) HR 1.259 (95% CI 1.134–1.396), spondin-1 HR 1.295 (95% CI 1.156–1.450), fibroblast growth factor 23 (FGF-23) HR 1.349 (95% CI 1.237–1.472), chitinase-3 like protein 1 (CHI3L1) HR 1.284 (95% CI 1.129–1.461), tumor necrosis factor receptor 1 (TNF-R1) HR 1.486 (95% CI 1.307–1.689), and adrenomedullin (AM) HR 1.750 (95% CI 1.490–2.056).The study is limited by the differences in design, size, and length of follow-up of the 2 studies and the lack of results from coronary angiograms and follow-up of nonfatal events.
Profiles of levels of multiple plasma proteins might be useful for the identification of different pathophysiological pathways associated with an increased risk of CV death in patients with chronic CHD.
ClinicalTrials.gov NCT00799903.
Accelerometer measured physical activity and the incidence of cardiovascular disease: Evidence from the UK Biobank cohort study
by Rema Ramakrishnan, Aiden Doherty, Karl Smith-Byrne, Kazem Rahimi, Derrick Bennett, Mark Woodward, Rosemary Walmsley, Terence Dwyer
Higher levels of physical activity (PA) are associated with a lower risk of cardiovascular disease (CVD). However, uncertainty exists on whether the inverse relationship between PA and incidence of CVD is greater at the highest levels of PA. Past studies have mostly relied on self-reported evidence from questionnaire-based PA, which is crude and cannot capture all PA undertaken. We investigated the association between accelerometer-measured moderate, vigorous, and total PA and incident CVD.
We obtained accelerometer-measured moderate-intensity and vigorous-intensity physical activities and total volume of PA, over a 7-day period in 2013–2015, for 90,211 participants without prior or concurrent CVD in the UK Biobank cohort. Participants in the lowest category of total PA smoked more, had higher body mass index and C-reactive protein, and were diagnosed with hypertension. PA was associated with 3,617 incident CVD cases during 440,004 person-years of follow-up (median (interquartile range [IQR]): 5.2 (1.2) years) using Cox regression models. We found a linear dose–response relationship for PA, whether measured as moderate-intensity, vigorous-intensity, or as total volume, with risk of incident of CVD. Hazard ratios (HRs) and 95% confidence intervals for increasing quarters of the PA distribution relative to the lowest fourth were for moderate-intensity PA: 0.71 (0.65, 0.77), 0.59 (0.54, 0.65), and 0.46 (0.41, 0.51); for vigorous-intensity PA: 0.70 (0.64, 0.77), 0.54 (0.49,0.59), and 0.41 (0.37,0.46); and for total volume of PA: 0.73 (0.67, 0.79), 0.63 (0.57, 0.69), and 0.47 (0.43, 0.52). We took account of potential confounders but unmeasured confounding remains a possibility, and while removal of early deaths did not affect the estimated HRs, we cannot completely dismiss the likelihood that reverse causality has contributed to the findings. Another possible limitation of this work is the quantification of PA intensity-levels based on methods validated in relatively small studies.
In this study, we found no evidence of a threshold for the inverse association between objectively measured moderate, vigorous, and total PA with CVD. Our findings suggest that PA is not only associated with lower risk for of CVD, but the greatest benefit is seen for those who are active at the highest level.
Social determinants of mortality from COVID-19: A simulation study using NHANES
by Benjamin Seligman, Maddalena Ferranna, David E. Bloom
The COVID-19 epidemic in the United States is widespread, with more than 200,000 deaths reported as of September 23, 2020. While ecological studies show higher burdens of COVID-19 mortality in areas with higher rates of poverty, little is known about social determinants of COVID-19 mortality at the individual level.
We estimated the proportions of COVID-19 deaths by age, sex, race/ethnicity, and comorbid conditions using their reported univariate proportions among COVID-19 deaths and correlations among these variables in the general population from the 2017–2018 National Health and Nutrition Examination Survey (NHANES). We used these proportions to randomly sample individuals from NHANES. We analyzed the distributions of COVID-19 deaths by race/ethnicity, income, education level, and veteran status. We analyzed the association of these characteristics with mortality by logistic regression. Summary demographics of deaths include mean age 71.6 years, 45.9% female, and 45.1% non-Hispanic white. We found that disproportionate deaths occurred among individuals with nonwhite race/ethnicity (54.8% of deaths, 95% CI 49.0%–59.6%, p < 0.001), individuals with income below the median (67.5%, 95% CI 63.4%–71.5%, p < 0.001), individuals with less than a high school level of education (25.6%, 95% CI 23.4% –27.9%, p < 0.001), and veterans (19.5%, 95% CI 15.8%–23.4%, p < 0.001). Except for veteran status, these characteristics are significantly associated with COVID-19 mortality in multiple logistic regression. Limitations include the lack of institutionalized people in the sample (e.g., nursing home residents and incarcerated persons), the need to use comorbidity data collected from outside the US, and the assumption of the same correlations among variables for the noninstitutionalized population and COVID-19 decedents.
Substantial inequalities in COVID-19 mortality are likely, with disproportionate burdens falling on those who are of racial/ethnic minorities, are poor, have less education, and are veterans. Healthcare systems must ensure adequate access to these groups. Public health measures should specifically reach these groups, and data on social determinants should be systematically collected from people with COVID-19.
Estimating HIV pre-exposure prophylaxis need and impact in Malawi, Mozambique and Zambia: A geospatial and risk-based analysis
by Dominik Stelzle, Peter Godfrey-Faussett, Chuan Jia, Obreniokibo Amiesimaka, Mary Mahy, Delivette Castor, Ioannis Hodges-Mameletzis, Lastone Chitembo, Rachel Baggaley, Shona Dalal
Pre-exposure prophylaxis (PrEP), a WHO-recommended HIV prevention method for people at high risk for acquiring HIV, is being increasingly implemented in many countries. Setting programmatic targets, particularly in generalised epidemics, could incorporate estimates of the size of the population likely to be eligible for PrEP using incidence-based thresholds. We estimated the proportion of men and women who would be eligible for PrEP and the number of HIV infections that could be averted in Malawi, Mozambique, and Zambia using prioritisation based on age, sex, geography, and markers of risk.
We analysed the latest nationally representative Demographic and Health Surveys (DHS) of Malawi, Mozambique, and Zambia to determine the proportion of adults who report behavioural markers of risk for HIV infection. We used prevalence ratios (PRs) to quantify the association of these factors with HIV status. Using a multiplier method, we combined these proportions with the number of new HIV infections by district, derived from district-level modelled HIV estimates. Based on these numbers, different scenarios were analysed for the minimum number of person-years on PrEP needed to prevent 1 HIV infection (NNP).An estimated total of 38,000, 108,000, and 46,000 new infections occurred in Malawi, Mozambique, and Zambia in 2016, corresponding with incidence rates of 0.43, 0.63, and 0.57 per 100 person-years. In these countries, 9%–20% of new infections occurred among people with a sexually transmitted infection (STI) in the past 12 months and 40%–42% among people with either an STI or a non-regular sexual partner (NP) in the past 12 months (STINP). The models estimate that around 50% of new infections occurred in districts with incidence rates ≥1.0% in Mozambique and Zambia and ≥0.5% in Malawi. In Malawi, Mozambique, and Zambia, 35.1%, 21.9%, and 12.5% of the population live in these high-incidence districts. In the most parsimonious scenario, if women aged 15–34 years and men 20–34 years with an STI in the past 12 months living in high-incidence districts were to take PrEP, it would take a minimum of 65.8 person-years on PrEP to avert 1 HIV infection per year in Malawi, 35.2 in Mozambique, and 16.4 in Zambia. Our findings suggest that 3,300, 5,200, and 1,700 new infections could be averted per year in the 3 countries, respectively. Limitations of our study are that these values are based on modelled estimates of HIV incidence and self-reported behavioural risk factors from national surveys.
A large proportion of new HIV infections in these 3 African countries were estimated to occur among people who had either an STI or an NP in the past year, providing a straightforward means to set PrEP targets. Greater prioritisation of PrEP by district, sex, age, and behavioural risk factors resulted in lower NNPs thereby increasing PrEP cost-effectiveness, but also diminished the overall impact on reducing new infections
Mindfulness-based programmes for mental health promotion in adults in nonclinical settings: A systematic review and meta-analysis of randomised controlled trials
by Julieta Galante, Claire Friedrich, Anna F Dawson, Marta Modrego-Alarcón, Pia Gebbing, Irene Delgado-Suárez, Radhika Gupta, Lydia Dean, Tim Dalgleish, Ian R White, Peter B Jones
There is an urgent need for mental health promotion in nonclinical settings. Mindfulness–based programmes (MBPs) are being widely implemented to reduce stress, but a comprehensive evidence synthesis is lacking. We reviewed trials to assess whether MBPs promote mental health relative to no intervention or comparator interventions.
Following a detailed preregistered protocol (PROSPERO CRD42018105213) developed with public and professional stakeholders, 13 databases were searched to August 2020 for randomised controlled trials (RCTs) examining in–person, expert–defined MBPs in nonclinical settings. Two researchers independently selected, extracted, and appraised trials using the Cochrane Risk–of–Bias Tool 2.0. Primary outcomes were psychometrically validated anxiety, depression, psychological distress, and mental well–being questionnaires at 1 to 6 months after programme completion. Multiple testing was performed using p < 0.0125 (Bonferroni) for statistical significance. Secondary outcomes, meta–regression and sensitivity analyses were prespecified. Pairwise random–effects multivariate meta–analyses and prediction intervals (PIs) were calculated.A total of 11,605 participants in 136 trials were included (29 countries, 77% women, age range 18 to 73 years). Compared with no intervention, in most but not all scenarios MBPs improved average anxiety (8 trials; standardised mean difference (SMD) = −0.56; 95% confidence interval (CI) −0.80 to −0.33; p–value < 0.001; 95% PI −1.19 to 0.06), depression (14 trials; SMD = −0.53; 95% CI −0.72 to −0.34; p–value < 0.001; 95% PI −1.14 to 0.07), distress (27 trials; SMD = −0.45; 95% CI −0.58 to −0.31; p–value < 0.001; 95% PI −1.04 to 0.14), and well–being (9 trials; SMD = 0.33; 95% CI 0.11 to 0.54; p–value = 0.003; 95% PI −0.29 to 0.94). Compared with nonspecific active control conditions, in most but not all scenarios MBPs improved average depression (6 trials; SMD = −0.46; 95% CI −0.81 to −0.10; p–value = 0.012, 95% PI −1.57 to 0.66), with no statistically significant evidence for improving anxiety or distress and no reliable data on well–being. Compared with specific active control conditions, there is no statistically significant evidence of MBPs' superiority. Only effects on distress remained when higher–risk trials were excluded. USA–based trials reported smaller effects. MBPs targeted at higher–risk populations had larger effects than universal MBPs. The main limitation of this review is that confidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach is moderate to very low, mainly due to inconsistency and high risk of bias in many trials.
Compared with taking no action, MBPs of the included studies promote mental health in nonclinical settings, but given the heterogeneity between studies, the findings do not support generalisation of MBP effects across every setting. MBPs may have specific effects on some common mental health symptoms. Other preventative interventions may be equally effective. Implementation of MBPs in nonclinical settings should be partnered with thorough research to confirm findings and learn which settings are most likely to benefit.
Interpersonal psychotherapy delivered by nonspecialists for depression and posttraumatic stress disorder among Kenyan HIV–positive women affected by gender-based violence: Randomized controlled trial
by Susan M. Meffert, Thomas C. Neylan, Charles E. McCulloch, Kelly Blum, Craig R. Cohen, Elizabeth A. Bukusi, Helen Verdeli, John C. Markowitz, James G. Kahn, David Bukusi, Harsha Thirumurthy, Grace Rota, Ray Rota, Grace Oketch, Elizabeth Opiyo, Linnet Ongeri
HIV–positive women suffer a high burden of mental disorders due in part to gender-based violence (GBV). Comorbid depression and posttraumatic stress disorder (PTSD) are typical psychiatric consequences of GBV. Despite attention to the HIV-GBV syndemic, few HIV clinics offer formal mental healthcare. This problem is acute in sub-Saharan Africa, where the world's majority of HIV–positive women live and prevalence of GBV is high.
We conducted a randomized controlled trial at an HIV clinic in Kisumu, Kenya. GBV-affected HIV–positive women with both major depressive disorder (MDD) and PTSD were randomized to 12 sessions of interpersonal psychotherapy (IPT) plus treatment as usual (TAU) or Wait List+TAU. Nonspecialists were trained to deliver IPT inside the clinic. After 3 months, participants were reassessed, and those assigned to Wait List+TAU were given IPT. The primary outcomes were diagnosis of MDD and PTSD (Mini International Neuropsychiatric Interview) at 3 months. Secondary outcomes included symptom measures of depression and PTSD, intimate partner violence (IPV), and disability. A total of 256 participants enrolled between May 2015 and July 2016. At baseline, the mean age of the women in this study was 37 years; 61% reported physical IPV in the past week; 91% reported 2 or more lifetime traumatic events and monthly income was 18USD. Multilevel mixed-effects logistic regression showed that participants randomized to IPT+TAU had lower odds of MDD (odds ratio [OR] 0.26, 95% CI [0.11 to 0.60], p = 0.002) and lower odds of PTSD (OR 0.35, [0.14 to 0.86], p = 0.02) than controls. IPT+TAU participants had lower odds of MDD-PTSD comorbidity than controls (OR 0.36, 95% CI [0.15 to 0.90], p = 0.03). Linear mixed models were used to assess secondary outcomes: IPT+TAU participants had reduced disability (−6.9 [−12.2, −1.5], p = 0.01), and nonsignificantly reduced work absenteeism (−3.35 [−6.83, 0.14], p = 0.06); partnered IPT+TAU participants had a reduction of IPV (−2.79 [−5.42, −0.16], p = 0.04). Gains were maintained across 6-month follow-up. Treatment group differences were observed only at month 3, the time point at which the groups differed in IPT status (before cross over). Study limitations included 35% attrition inclusive of follow-up assessments, generalizability to populations not in HIV care, and data not collected on TAU resources accessed.
IPT for MDD and PTSD delivered by nonspecialists in the context of HIV care yielded significant improvements in HIV–positive women's mental health, functioning, and GBV (IPV) exposure, compared to controls.
Clinical Trials Identifier NCT02320799.
Postpartum depressive symptoms following implementation of the 10 steps to successful breastfeeding program in Kinshasa, Democratic Republic of Congo: A cohort study
by Robert A. Agler, Paul N. Zivich, Bienvenu Kawende, Frieda Behets, Marcel Yotebieng
Social support and relevant skills training can reduce the risk of postpartum depression (PPD) by reducing the impact of stressors. The 10-step program to encourage exclusive breastfeeding that forms the basis of the Baby-Friendly Hospital Initiative (BFHI) provides both, suggesting it may lessen depressive symptoms directly or by reducing difficulties associated with infant feeding. Our objective was to quantify the association of implementing Steps 1–9 or Steps 1–10 on postpartum depressive symptoms and test whether this association was mediated by breastfeeding difficulties.
We used data from a breastfeeding promotion trial of all women who gave birth to a healthy singleton between May 24 and August 25, 2012 in 1 of the 6 facilities comparing different BFHI implementations (Steps 1–9, Steps 1–10) to the standard of care (SOC) randomized by facility in Kinshasa, Democratic Republic of Congo. Depressive symptoms, a non-registered trial outcome, was assessed at 14 weeks via the Edinburgh Postnatal Depression Scale (EPDS). Inverse probability weighting (IPW) was used to estimate the association of BFHI implementations on depressive symptoms and the controlled direct association through breastfeeding difficulties at 10 weeks postpartum.A total of 903 mother–infant pairs were included in the analysis. Most women enrolled had previously given birth (76%) and exclusively breastfed at 10 weeks (55%). The median age was 27 (interquartile range (IQR): 23, 32 years). The proportion of women reporting breastfeeding difficulties at week 10 was higher in both Steps 1–9 (75%) and Steps 1–10 (91%) relative to the SOC (67%). However, the number of reported difficulties was similar between Steps 1–9 (median: 2; IQR: 0, 3) and SOC (2; IQR: 0, 3), with slightly more in Steps 1–10 (2; IQR: 1, 3). The prevalence of symptoms consistent with probable depression (EPDS score >13) was 18% for SOC, 11% for Steps 1–9 (prevalence difference [PD] = −0.08; 95% confidence interval (CI): −0.14 to −0.01, p = 0.019), and 8% for Steps 1–10 (PD = −0.11, −0.16 to −0.05; p < 0.001). We found mediation by breastfeeding difficulties. In the presence of any difficulties, the PD was reduced for both Steps 1–9 (−0.15; 95% confidence level (CL): −0.25, −0.06; p < 0.01) and Steps 1–10 (−0.16; 95% CL: −0.25, −0.06; p < 0.01). If no breastfeeding difficulties occurred in the population, there was no difference in the prevalence of probable depression for Steps 1–9 (0.21; 95% CL: −0.24, 0.66; p = 0.365) and Steps 1–10 (−0.03; 95% CL: −0.19, 0.13; p = 0.735). However, a limitation of the study is that the results are based on 2 hospitals randomized to each group.
In conclusion, in this cohort, the implementation of the BFHI steps was associated with a reduction in depressive symptoms in the groups implementing BFHI Steps 1–9 or 1–10 relative to the SOC, with the implementation of Steps 1–10 associated with the largest decrease. Specifically, the reduction in depressive symptoms was observed for women reporting breastfeeding difficulties. PPD has a negative impact on the mother, her partner, and the baby, with long-lasting consequences. This additional benefit of BFHI steps suggests that renewed effort to scale its implementation globally may be beneficial to mitigate the negative impacts of PPD on the mother, her partner, and the baby.
ClinicalTrials.gov NCT01428232
Associations of parental depression during adolescence with cognitive development in later life in China: A population-based cohort study
by Zhihui Li, Wenjuan Qin, Vikram Patel
Prior research has underscored negative impacts of perinatal parental depression on offspring cognitive performance in early childhood. However, little is known about the effects of parental depression during adolescence on offspring cognitive development.
This study used longitudinal data from the nationally representative China Family Panel Studies (CFPS). The sample included 2,281 adolescents aged 10–15 years (the median age was 13 years with an interquartile range between 11 and 14 years) in 2012 when their parents were surveyed for depression symptoms with the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). The sample was approximately balanced by sex, with 1,088 females (47.7%). We examined the associations of parental depression in 2012 with offspring cognitive performance (measured by mathematics, vocabulary, immediate word recall, delayed word recall, and number series tests) in subsequent years (i.e., 2014, 2016, and 2018) using linear regression models, adjusting for various offspring (i.e., age, sex, and birth order), parent (i.e., parents' education level, age, whether living with the offspring, and employment status), and household characteristics (i.e., place of residence, household income, and the number of offspring). We found parental depression during adolescence to be significantly associated with worse cognitive performance in subsequent years, in both crude and adjusted models. For example, in the crude models, adolescents whose mothers had depression symptoms in 2012 scored 1.0 point lower (95% confidence interval [CI]: −1.2 to −0.8, p < 0.001) in mathematics in 2014 compared to those whose mothers did not have depression symptoms; after covariate adjustment, this difference marginally reduced to 0.8 points (95% CI: −1.0 to −0.5, p < 0.001); the associations remained robust after further adjusting for offspring earlier cognitive ability in toddlerhood (−1.2, 95% CI: −1.6, −0.9, p < 0.001), offspring cognitive ability in 2012 (−0.6, 95% CI: −0.8, −0.3, p < 0.001), offspring depression status (−0.7, 95% CI: −1.0, −0.5, p < 0.001), and parents' cognitive ability (−0.8, 95% CI: −1.2, −0.3, p < 0.001). In line with the neuroplasticity theory, we observed stronger associations between maternal depression and mathematical/vocabulary scores among the younger adolescents (i.e., 10–11 years) than the older ones (i.e., 12–15 years). For example, the association between maternal depression and 2014 vocabulary scores was estimated to be −2.1 (95% CI: −2.6, −1.6, p < 0.001) in those aged 10–11 years, compared to −1.2 (95% CI: −1.6, −0.8, p < 0.001) in those aged 12–15 years with a difference of 0.9 (95% CI: 0.2, 1.6, p = 0.010). We also observed a stronger association of greater depression severity with worse mathematical scores. The primary limitations of this study were the relatively high attrition rate and residual confounding.
In this study, we observed that parental depression during adolescence was associated with adverse offspring cognitive development assessed up to 6 years later. These findings highlight the intergenerational association between depression in parents and cognitive development across the early life course into adolescence.
Carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide (KRdc) as induction therapy for transplant-eligible, newly diagnosed multiple myeloma patients (Myeloma XI+): Interim analysis of an open-label randomised controlled trial
by Graham H. Jackson, Charlotte Pawlyn, David A. Cairns, Ruth M. de Tute, Anna Hockaday, Corinne Collett, John R. Jones, Bhuvan Kishore, Mamta Garg, Cathy D. Williams, Kamaraj Karunanithi, Jindriska Lindsay, Alberto Rocci, John A. Snowden, Matthew W. Jenner, Gordon Cook, Nigel H. Russell, Mark T. Drayson, Walter M. Gregory, Martin F. Kaiser, Roger G. Owen, Faith E. Davies, Gareth J. Morgan, the UK NCRI Haemato-oncology Clinical Studies Group
Carfilzomib is a second-generation irreversible proteasome inhibitor that is efficacious in the treatment of myeloma and carries less risk of peripheral neuropathy than first-generation proteasome inhibitors, making it more amenable to combination therapy.
The Myeloma XI+ trial recruited patients from 88 sites across the UK between 5 December 2013 and 20 April 2016. Patients with newly diagnosed multiple myeloma eligible for transplantation were randomly assigned to receive the combination carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide (KRdc) or a triplet of lenalidomide, dexamethasone, and cyclophosphamide (Rdc) or thalidomide, dexamethasone, and cyclophosphamide (Tdc). All patients were planned to receive an autologous stem cell transplantation (ASCT) prior to a randomisation between lenalidomide maintenance and observation. Eligible patients were aged over 18 years and had symptomatic myeloma. The co-primary endpoints for the study were progression-free survival (PFS) and overall survival (OS) for KRdc versus the Tdc/Rdc control group by intention to treat. PFS, response, and safety outcomes are reported following a planned interim analysis. The trial is registered (ISRCTN49407852) and has completed recruitment. In total, 1,056 patients (median age 61 years, range 33 to 75, 39.1% female) underwent induction randomisation to KRdc (n = 526) or control (Tdc/Rdc, n = 530). After a median follow-up of 34.5 months, KRdc was associated with a significantly longer PFS than the triplet control group (hazard ratio 0.63, 95% CI 0.51–0.76). The median PFS for patients receiving KRdc is not yet estimable, versus 36.2 months for the triplet control group (p < 0.001). Improved PFS was consistent across subgroups of patients including those with genetically high-risk disease. At the end of induction, the percentage of patients achieving at least a very good partial response was 82.3% in the KRdc group versus 58.9% in the control group (odds ratio 4.35, 95% CI 3.19–5.94, p < 0.001). Minimal residual disease negativity (cutoff 4 × 10−5 bone marrow leucocytes) was achieved in 55% of patients tested in the KRdc group at the end of induction, increasing to 75% of those tested after ASCT. The most common adverse events were haematological, with a low incidence of cardiac events. The trial continues to follow up patients to the co-primary endpoint of OS and for planned long-term follow-up analysis. Limitations of the study include a lack of blinding to treatment regimen and that the triplet control regimen did not include a proteasome inhibitor for all patients, which would be considered a current standard of care in many parts of the world.
The KRdc combination was well tolerated and was associated with both an increased percentage of patients achieving at least a very good partial response and a significant PFS benefit compared to immunomodulatory-agent-based triplet therapy.
ClinicalTrials.gov ISRCTN49407852.
Clinical outcomes in a primary-level non-communicable disease programme for Syrian refugees and the host population in Jordan: A cohort analysis using routine data
by Éimhín Ansbro, Tobias Homan, David Prieto Merino, Kiran Jobanputra, Jamil Qasem, Shoaib Muhammad, Taissir Fardous, Pablo Perel
Little is known about the content or quality of non-communicable disease (NCD) care in humanitarian settings. Since 2014, Médecins Sans Frontières (MSF) has provided primary-level NCD services in Irbid, Jordan, targeting Syrian refugees and vulnerable Jordanians who struggle to access NCD care through the overburdened national health system. This retrospective cohort study explored programme and patient-level patterns in achievement of blood pressure and glycaemic control, patterns in treatment interruption, and the factors associated with these patterns.
The MSF multidisciplinary, primary-level NCD programme provided facility-based care for cardiovascular disease, diabetes, and chronic respiratory disease using context-adapted guidelines and generic medications. Generalist physicians managed patients with the support of family medicine specialists, nurses, health educators, pharmacists, and psychosocial and home care teams. Among the 5,045 patients enrolled between December 2014 and December 2017, 4,044 eligible adult patients were included in our analysis, of whom 72% (2,913) had hypertension and 63% (2,546) had type II diabetes. Using visits as the unit of analysis, we plotted the following on a monthly basis: mean blood pressure among hypertensive patients, mean fasting blood glucose and HbA1c among type II diabetic patients, the proportion of each group achieving control, mean days of delayed appointment attendance, and the proportion of patients experiencing a treatment interruption. Results are presented from programmatic and patient perspectives (using months since programme initiation and months since cohort entry/diagnosis, respectively). General linear mixed models explored factors associated with clinical control and with treatment interruption. Mean age was 58.5 years, and 60.1% (2,432) were women. Within the programme's first 6 months, mean systolic blood pressure decreased by 12.4 mm Hg from 143.9 mm Hg (95% CI 140.9 to 146.9) to 131.5 mm Hg (95% CI 130.2 to 132.9) among hypertensive patients, while fasting glucose improved by 1.12 mmol/l, from 10.75 mmol/l (95% CI 10.04 to 11.47) to 9.63 mmol/l (95% CI 9.22 to 10.04), among type II diabetic patients. The probability of achieving treatment target in a visit was 63%–75% by end of 2017, improving with programme maturation but with notable seasonable variation. The probability of experiencing a treatment interruption declined as the programme matured and with patients' length of time in the programme. Routine operational data proved useful in evaluating a humanitarian programme in a real-world setting, but were somewhat limited in terms of data quality and completeness. We used intermediate clinical outcomes proven to be strongly associated with hard clinical outcomes (such as death), since we had neither the data nor statistical power to measure hard outcomes.
Good treatment outcomes and reasonable rates of treatment interruption were achieved in a multidisciplinary, primary-level NCD programme in Jordan. Our approach to using continuous programmatic data may be a feasible way for humanitarian organisations to account for the complex and dynamic nature of interventions in unstable humanitarian settings when undertaking routine monitoring and evaluation. We suggest that frequency of patient contact could be reduced without negatively impacting patient outcomes and that season should be taken into account in analysing programme performance.
Effects on childhood infections of promoting safe and hygienic complementary-food handling practices through a community-based programme: A cluster randomised controlled trial in a rural area of The Gambia
by Semira Manaseki-Holland, Buba Manjang, Karla Hemming, James T. Martin, Christopher Bradley, Louise Jackson, Makie Taal, Om Prasad Gautam, Francesca Crowe, Bakary Sanneh, Jeroen Ensink, Tim Stokes, Sandy Cairncross
The Gambia has high rates of under-5 mortality from diarrhoea and pneumonia, peaking during complementary-feeding age. Community-based interventions may reduce complementary-food contamination and disease rates.
A public health intervention using critical control points and motivational drivers, delivered February–April 2015 in The Gambia, was evaluated in a cluster randomised controlled trial at 6- and 32-month follow-up in September–October 2015 and October–December 2017, respectively. After consent for trial participation and baseline data were collected, 30 villages (clusters) were randomly assigned to intervention or control, stratified by population size and geography. The intervention included a community-wide campaign on days 1, 2, 17, and 25, a reminder visit at 5 months, plus informal community-volunteer home visits. It promoted 5 key complementary-food and 1 key drinking-water safety and hygiene behaviours through performing arts, public meetings, and certifications delivered by a team from local health and village structures to all villagers who attended the activities, to which mothers of 6- to 24-month-old children were specifically invited. Control villages received a 1-day campaign on domestic-garden water use. The background characteristics of mother and clusters (villages) were balanced between the trial arms. Outcomes were measured at 6 and 32 months in a random sample of 21–26 mothers per cluster. There were no intervention or research team visits to villages between 6 and 32 months. The primary outcome was a composite outcome of the number of times key complementary-food behaviours were observed as a proportion of the number of opportunities to perform the behaviours during the observation period at 6 months. Secondary outcomes included the rate of each recommended behaviour; microbiological growth from complementary food and drinking water (6 months only); and reported acute respiratory infections, diarrhoea, and diarrhoea hospitalisation. Analysis was by intention-to-treat analysis adjusted by clustering. (Registration: PACTR201410000859336). We found that 394/571 (69%) of mothers with complementary-feeding children in the intervention villages were actively involved in the campaign. No villages withdrew, and there were no changes in the implementation of the intervention. The intervention improved behaviour adoption significantly. For the primary outcome, the rate was 662/4,351(incidence rate [IR] = 0.15) in control villages versus 2,861/4,378 (IR = 0.65) in intervention villages (adjusted incidence rate ratio [aIRR] = 4.44, 95% CI 3.62–5.44, p < 0.001), and at 32 months the aIRR was 1.17 (95% CI 1.07–1.29, p = 0.001). Secondary health outcomes also improved with the intervention: (1) mother-reported diarrhoea at 6 months, with adjusted relative risk (aRR) = 0.39 (95% CI 0.32–0.48, p < 0.001), and at 32 months, with aRR = 0.68 (95% CI 0.48–0.96, p = 0.027); (2) mother-reported diarrhoea hospitalisation at 6 months, with aRR = 0.35 (95% CI 0.19–0.66, p = 0.001), and at 32 months, with aRR = 0.38 (95% CI 0.18–0.80, p = 0.011); and (3) mother-reported acute respiratory tract infections at 6 months, with aRR = 0.67 (95% CI 0.53–0.86, p = 0.001), though at 32 months improvement was not significant (p = 0.200). No adverse events were reported. The main limitations were that only medium to small rural villages were involved. Obtaining laboratory cultures from food at 32 months was not possible, and no stool microorganisms were investigated.
We found that low-cost and culturally embedded behaviour change interventions were acceptable to communities and led to short- and long-term improvements in complementary-food safety and hygiene practices, and reported diarrhoea and acute respiratory tract infections.
The trial was registered on the 17th October 2014 with the Pan African Clinical Trial Registry in South Africa with number (PACTR201410000859336) and 32-month follow-up as an amendment to the trial.
Correction: The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight
by Torvid Kiserud, Gilda Piaggio, Guillermo Carroli, Mariana Widmer, José Carvalho, Lisa Neerup Jensen, Daniel Giordano, José Guilherme Cecatti, Hany Abdel Aleem, Sameera A. Talegawkar, Alexandra Benachi, Anke Diemert, Antoinette Tshefu Kitoto, Jadsada Thinkhamrop, Pisake Lumbiganon, Ann Tabor, Alka Kriplani, Rogelio Gonzalez Perez, Kurt Hecher, Mark A. Hanson, A. Metin Gülmezoglu, Lawrence D. Platt
Associations between breast cancer survivorship and adverse mental health outcomes: A matched population-based cohort study in the United Kingdom
by Helena Carreira, Rachael Williams, Garth Funston, Susannah Stanway, Krishnan Bhaskaran
Breast cancer is the most common cancer diagnosed in women globally, and 5-year net survival probabilities in high-income countries are generally >80%. A cancer diagnosis and treatment are often traumatic events, and many women struggle to cope during this period. Less is known, however, about the long-term mental health impact of the disease, despite many women living several years beyond their breast cancer and mental health being a major source of disability in modern societies. The objective of this study was to quantify the risk of several adverse mental health–related outcomes in women with a history of breast cancer followed in primary care in the United Kingdom National Health Service, compared to similar women who never had cancer.
We conducted a matched cohort study using data routinely collected in primary care across the UK to quantify associations between breast cancer history and depression, anxiety, and other mental health–related outcomes. All women with incident breast cancer in the Clinical Practice Research Datalink (CPRD) GOLD primary care database between 1988 and 2018 (N = 57,571, mean = 62 ± 14 years) were matched 1:4 to women with no prior cancer (N = 230,067) based on age, primary care practice, and eligibility of the data for linkage to hospital data sources. Cox models were used to estimate associations between breast cancer survivorship and each mental health–related outcome, further adjusting for diabetes, body mass index (BMI), and smoking and drinking status at baseline. Breast cancer survivorship was positively associated with anxiety (adjusted hazard ratio (HR) = 1.33; 95% confidence interval (CI): 1.29–1.36; p < 0.001), depression (1.35; 1.32–1.38; p < 0.001), sexual dysfunction (1.27; 1.17–1.38; p < 0.001), and sleep disorder (1.68; 1.63–1.73; p < 0.001), but not with cognitive dysfunction (1.00; 0.97–1.04; p = 0.88). Positive associations were also found for fatigue (HR = 1.28; 1.25–1.31; p < 0.001), pain (1.22; 1.20–1.24; p < 0.001), receipt of opioid analgesics (1.86; 1.83–1.90; p < 0.001), and fatal and nonfatal self-harm (1.15; 0.97–1.36; p = 0.11), but CI was wide, and the relationship was not statistically significant for the latter. HRs for anxiety and depression decreased over time (p-interaction <0.001), but increased risks persisted for 2 and 4 years, respectively, after cancer diagnosis. Increased levels of pain and sleep disorder persisted for 10 years. Younger age was associated with larger HRs for depression, cognitive dysfunction, pain, opioid analgesics use, and sleep disorders (p-interaction <0.001 in each case). Limitations of the study include the potential for residual confounding by lifestyle factors and detection bias due to cancer survivors having greater healthcare contact.
In this study, we observed that compared to women with no prior cancer, breast cancer survivors had higher risk of anxiety, depression, sleep problems, sexual dysfunction, fatigue, receipt of opioid analgesics, and pain. Relative risks estimates tended to decrease over time, but anxiety and depression were significantly increased for 2 and 4 years after breast cancer diagnosis, respectively, while associations for fatigue, pain, and sleep disorders were elevated for at least 5–10 years after diagnosis. Early diagnosis and increased awareness among patients, healthcare professionals, and policy makers are likely to be important to mitigate the impacts of these raised risks.
Sugar-sweetened beverage taxes: Lessons to date and the future of taxation
by Barry M. Popkin, Shu Wen Ng
Clean air actions in China, PM<sub>2.5</sub> exposure, and household medical expenditures: A quasi-experimental study
by Tao Xue, Tong Zhu, Wei Peng, Tianjia Guan, Shiqiu Zhang, Yixuan Zheng, Guannan Geng, Qiang Zhang
Exposure to air pollution, a leading contributor to the global burden of disease, can cause economic losses. Driven by clean air policies, the air quality in China, one of the most polluted countries, has improved rapidly since 2013. This has enabled a unique, quasi-experiment to assess the economic impact of air pollution empirically.
Using a series of nation-scale longitudinal surveys in 2011, 2013, and 2015, we first examined the questionnaire-based medical expenditure changes before and after the policy intervention for air pollution. Using a state-of-the-art estimator of the historical concentration of particulate matters with diameter less than 2.5 μm (particulate matter (PM)2.5), we further quantified the association between household medical expenditure and PM2.5 using mixed-effect models of the repeated measurements from 26,511 households in 126 cities. Regression models suggest a robust linear association between reduced PM2.5 and saved medical expenditures, since the association did not vary significantly across models with different covariate adjustments, subregions, or subpopulations. Each 10 μg/m3 reduction in PM2.5 was associated with a saving of 251.6 (95% CI: 30.8, 472.3; p-value = 0.026) Yuan in per capita annual medical expenditure. However, due to limitations in data quality (e.g., self-reported expenditures), and imperfect control for unmeasured confounders or impact from concurrent healthcare reform in China, the causality underlying our findings should be further confirmed or refuted.
In this study, we observed that compared with the PM2.5 reduction in 2013, the PM2.5 reduction in 2017 was associated with a saving of 552 (95% CI: 68, 1036) Yuan / (person × year), or approximately 736 billion Yuan (equivalent to 111 billion US dollar) per year nationally, which is equivalent to approximately 1% of the national gross domestic product of China.
Novel community health worker strategy for HIV service engagement in a hyperendemic community in Rakai, Uganda: A pragmatic, cluster-randomized trial
by Larry W. Chang, Ismail Mbabali, Heidi Hutton, K. Rivet Amico, Xiangrong Kong, Jeremiah Mulamba, Aggrey Anok, Joseph Ssekasanvu, Amanda Long, Alvin G. Thomas, Kristin Thomas, Eva Bugos, Rose Pollard, Kimiko van Wickle, Caitlin E. Kennedy, Fred Nalugoda, David Serwadda, Robert C. Bollinger, Thomas C. Quinn, Steven J. Reynolds, Ronald H. Gray, Maria J. Wawer, Gertrude Nakigozi
Effective implementation strategies are needed to increase engagement in HIV services in hyperendemic settings. We conducted a pragmatic cluster-randomized trial in a high-risk, highly mobile fishing community (HIV prevalence: approximately 38%) in Rakai, Uganda, to assess the impact of a community health worker-delivered, theory-based (situated Information, Motivation, and Behavior Skills), motivational interviewing-informed, and mobile phone application-supported counseling strategy called "Health Scouts" to promote engagement in HIV treatment and prevention services.
The study community was divided into 40 contiguous, randomly allocated clusters (20 intervention clusters, n = 1,054 participants at baseline; 20 control clusters, n = 1,094 participants at baseline). From September 2015 to December 2018, the Health Scouts were deployed in intervention clusters. Community-wide, cross-sectional surveys of consenting 15 to 49-year-old residents were conducted at approximately 15 months (mid-study) and at approximately 39 months (end-study) assessing the primary programmatic outcomes of self-reported linkage to HIV care, antiretroviral therapy (ART) use, and male circumcision, and the primary biologic outcome of HIV viral suppression (<400 copies/mL). Secondary outcomes included HIV testing coverage, HIV incidence, and consistent condom use. The primary intent-to-treat analysis used log-linear binomial regression with generalized estimating equation to estimate prevalence risk ratios (PRR) in the intervention versus control arm. A total of 2,533 (45% female, mean age: 31 years) and 1,903 (46% female; mean age 32 years) residents completed the mid-study and end-study surveys, respectively. At mid-study, there were no differences in outcomes between arms. At end-study, self-reported receipt of the Health Scouts intervention was 38% in the intervention arm and 23% in the control arm, suggesting moderate intervention uptake in the intervention arm and substantial contamination in the control arm. At end-study, intention-to-treat analysis found higher HIV care coverage (PRR: 1.06, 95% CI: 1.01 to 1.10, p = 0.011) and ART coverage (PRR: 1.05, 95% CI: 1.01 to 1.10, p = 0.028) among HIV–positive participants in the intervention compared with the control arm. Male circumcision coverage among all men (PRR: 1.05, 95% CI: 0.96 to 1.14, p = 0.31) and HIV viral suppression among HIV–positive participants (PRR: 1.04, 95% CI: 0.98 to 1.12, p = 0.20) were higher in the intervention arm, but differences were not statistically significant. No differences were seen in secondary outcomes. Study limitations include reliance on self-report for programmatic outcomes and substantial contamination which may have diluted estimates of effect.
A novel community health worker intervention improved HIV care and ART coverage in an HIV hyperendemic setting but did not clearly improve male circumcision coverage or HIV viral suppression. This community-based, implementation strategy may be a useful component in some settings for HIV epidemic control.
123seguente >Ultimo >>


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text:
Audio Japan-Style
J-Music/Anime Reviews, Guides, Recaps, Parodies and Snark
PVs/Music Videos
Kalafina/FJ PVs
Concert Reports
About Audio Japan-Style
June 30, 2012 No comments Concert Reports, Event Reports, Uncategorized
[CONCERT REPORT] Kalafina — Anime Festival Asia Malaysia Live
Posted by Nat R
(Written in bits and pieces over several weeks, with less proofreading than should have been necessary. I hope it's still passably coherent…)
Ah, Kalafina. I can't remember being as enamoured with any other musical act since I quit idolising boybands as a teenager. And I'd never gone to another country (even if it was just neighbouring Malaysia) just to watch an artiste perform live.
Kalafina were certainly worth the journey.
I'd planned to reach Kuala Lumpur on the afternoon of the 8th of June. It turned out to be an even better idea than I'd have thought because AFA later announced that an open-door press preview would be happening that day. And of course, making an appearance was…
Press Preview
I got there early, but there was already a pretty big crowd in front of stage. My lack of height prevented me from seeing almost anything above the many heads. Fortunately, I manage to score a slightly elevated vantage point for long enough to get some souvenirs:
If anyone from AFA asks, those photos were an accident. Danny Choo said so.
I'd describe what Kalafina did for you, but I think you'll get much better idea by watching this… yeah, that was an accident too.
The Live
Kalafina performed last, after Maon Kurosaki and Aimi. I'd heard of Maon Kurosaki but never actually listened to her music; I didn't know a single thing about Aimi.
Well, we all know who I was there for anyway.
The energy of the anticipating audience was amazing — it didn't take long after Aimi's performance for the chanting to begin: "Ka-la-fi-na! Ka-la-fi-na!"
Without any introduction (not like it was necessary anyway) the segment opened with an overture, followed by Kalafina walking onstage and launching into Magia. I'd been slightly disappointed by their performance of this song last year — this time around, though, they were raring from the get-go. Last year they'd looked like they were still warming up when they opened with Magia. Maybe the crowd's obvious enthusiasm had pumped them up. Hikaru was especially powerful in lead vocals, and Keiko and Wakana carried their respective parts in the harmonies wonderfully. And their stage presence…I can't say I'm a big fan of Kalafina's attempts at "dancing" but I really appreciate the fact that they're trying to do more than just stand around. It worked especially well during Magia. They were energetic, almost wild at parts; it was very entertaining to watch.
Lacrimosa followed immediately after, with Wakana in lead vocals. Again, quite well done. The delivery of "Lacrimosa/Dies illa!" never fails to impress me.
After Lacrimosa, Kalafina greeted and thanked the audience in English before each member introduced herself to the audience. In Malay. Wakana got as far as "Nama sa…ya…" broke off uncertainly, and then got it right in a second enthusiastic attempt. Keiko went, "Nama saya Keiko desu," which I found to be hilarious. Hikaru's intro got her intro right the first time, and then gave an affecting mini-speech (in her pretty good English) about how she was a little nervous but the audience energy enabled her to perform.
After a short spiel by Wakana in Japanese (which I unfortunately couldn't understand), the opening strains of Kimi ga Hikari ni Kaete Iku played. A very pleasant surprise — I hadn't expected them to perform something that far back in their catalogue. Wakana sounded a little flat at parts, but I still enjoyed the performance very much.
Sprinter came next. Their vocal performances weren't perfect, but I think the incredible energy the ladies were exuding more than made up for it. Another thoroughly enjoyable performance.
It was getting pretty clear to me that this Wakana wasn't quite the Wakana who raised goosebumps and drew breathless "wow"s with her singing last year in Singapore. It was a little disappointing, but…
…Hikaru was totally stealing the show anyway. Her performance in Magia had blown me away. Her vocals had been pretty steady in Sprinter, but she really stepped it up in Destination Unknown. This was another song I didn't expect to be included in the set list (it was relatively new and had no relation to any anime) but was very glad it was performed. Very high energy, with Keiko and Hikaru — especially Hikaru — giving very solid vocal performances. Visually entertaining as well; all three members were moving, switching positions, or at the very least dancing about on the spot for most of the song.
There was a particular memorable moment during the instrumental when Keiko pressed her back against Hikaru's, slid almost the whole way down and then back up again. With any other group I would have cynically taken this as an attempt at fanservice. But what I'd seen of Keiko's onstage behaviour in Kalafina lives, coupled with the priceless look Hikaru shot her in response (I'd describe it as a 'lolwut' expression) suggested that it was simply Keiko being Keiko. In any case, if this were an anime some of audience members would probably have lost considerable amounts of blood through their nostrils. I would not have been one of them. Nope. Not me.
Ongaku continued in a similar vein. I'm fairly sure that Ongaku is usually performed to get the audience pumped up but Destination Unknown had pretty much accomplished that already. It was still fun, of course, with Kalafina continuing to animatedly traverse the stage in between their singing parts.
After Ongaku, Kalafina described their experience with local cuisine (Wakana really seems to like mee goreng…) Keiko announced her liking for desserts in English, and Kalafina proceeded to survey the audience for recommendations of local desserts. Most of the audience somehow came to the agreement that they should suggest cendol. Not that I disagree, cendol is pretty awesome. Kalafina managed to get the audience to yell it out in unison but still couldn't make out exactly what it was. Hikaru said they would look into it (I think, it was in Japanese) — I wonder if they ever found out.
Keiko then went on to talk about anime their songs had been featured in, prompting audience members to yell out "Fate/Zero", their latest involvement. Kalafina appeared pleased at the enthusiastic response for the show. Keiko declared her love for the character Rider; Wakana, interestingly, said she liked Kiritsugu (and added something about Iri that I didn't understand); Hikaru's favourite was Saber.
The announcement that the next song was the last song was predictably met with cries of dismay, but Keiko drew cheers with a promise of meeting again.
And thus Kalafina ended off their set with To the beginning. Wakana sounded a little shaky at first but got into gear as the song went on; Keiko sounded pretty good, and Hikaru carried her streak of owning every song Kalafina had performed to the end. I hadn't watched any full live performances of To the beginning — I don't think any recordings of it were available yet — so I was especially thrilled to be able to listen to the live performance for myself.
Kalafina lingered just long enough after the song to thank the appreciative audience profusely and to allow Keiko to yell "I'll be baaaaaack Malaysia!". It took a while, but a thunderous call for an encore built up and went on for what felt like a long time before it became clear that we wouldn't be getting one. Not unexpected, really. But I like to think our efforts in showing our appreciation touched them (Hikaru, at least, was heartened).
Kimi ga Hikari ni Kaete Iku
Ongaku
The autograph session
The queue was so long…Apparently, AFA had at the last minute announced that those who bought the copies of After Eden that they were selling would also be eligible for the autographs, along with those who had won the ballot. What…Of course, the CDs were snapped up really quickly . I was left desperately wishing I'd thought to bring my copy of the album, because ballot winners who ha brought theirs were apparently getting them autographed as well.
But I like to think that if they had been busy signing my CD (the posters they gave out were pre-signed), there might not have been time for the exchange that took place when it was my turn to meet Kalafina.
Me: "IsawyouinSingaporeIamveryhappyIgottoseeyouagain!"
Keiko: *raises both fists in front of her shakes them* "Of course! Mochiron!"
Me: *blank look*
Fortunately, Hikaru recognised what had transpired. She put a hand on Keiko's shoulder and leaned in, translating what I had said.
At this point the AFA crew were trying to usher me away but I shamelessly held my ground. Hang on, I'm not done talking to Keiko!
When Hikaru was done, Keiko went, "Ah," and then turned back to me, without missing a beat, with every bit of genki-ness as before. "Thank you! Arigatou!"
I left to more "Thank you"s and "Arigatou"s from all three members, walking backwards to savour the sight of them for as long as I could. Autographed poster in hand, the memory of Keiko shaking her fists and declaring "Of course! Mochiron!" burned firmly into my mind…I'd say that went pretty well.
I almost certain that Keiko's first response was due to the fact that she'd thought I was asking if they would come to Singapore. So…Singapore…mochiron? Oh please oh please oh please!
I'm not sure they would appreciate me mentioning it here, but I couldn't not at least bring it up (sorry!)…My friend and I traveled to KL with a fellow member of the Canta-per-me.net forums, and we hung out briefly with another member at AFA MY. I'm really happy to have been able to meet the both of them; it's really awesome to be able to have long, enthusisatic conversations revolving around Kalafina and Kajiura's music (and also some Mahou Shoujo Madoka Magica), some of my most favourite things to talk about. Fangirling (and fanboying?) together was so much fun, I hope we get the opportunity to do so again!
(Oh, I still want those photos of us XD)
Ahhh, finally got that done with. Now I can proceed to my next geeky project: dissecting the moonfesta PV…
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A Japanese pop-culture website with a disproportionate focus on Kalafina. Home of the Kalafina PV Recaps.
5 Awesome Board Games and Card Games from Japan (Widely Available in English)
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The East Midlands Ambulance Service (EMAS) has become the 100th member to join the ECO Stars Fleet Recognition scheme in Nottingham.
Steve Farnsworth, General Manager of EMAS said "We are delighted to be the 100th member and achieve a 4 star ECO Stars rating.
Councillor David Ellis, Portfolio Holder for Public Protection at Gedling Borough Council said "Councils have an obligation to work towards Air Quality objectives and the reduction of pollutants. I'm delighted to see EMAS become the 100th member.
Alan West, ECO Stars Field Consultant (North) TRL – said "EMAS have been very successful and have achieved a well-deserved grade of 4 Stars on initial assessment. EMAS have been equipped with the right tools and resources to build upon their current achievements.
The appointment of a Fuel Champion is a key component to this. More extensive use of telematics data, particularly on non-emergency journeys will result in even greater fuel savings.
We wish EMAS continued success".
From L-R Andy Callingham, Service Manager, Public Protection Gedling Borough Council, Brendan Cox – Scientific Officer – Public Protection Gedling Borough Council, Councillor David Ellis, Porfolio Holder for Public Protection Gedling Borough Council, Steve Farmsworth, General Manager, East Midlands Ambulance Service NHS Trust and Alan West, ECO Stars Field Consultant (North) TRL.


Thanks for the vacation. : ) I'm back but I'm changing everything on my blog to fit the current season of my life. It's a new year. I'm looking forward to everything the Lord has in store for me…and you. I hope to share some parts of my life and provide spiritual depth and understanding from my experiences.
Thanks for taking time out to read my post. I look forward to this great year and hope to bless you as much as I want to bless you.


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