Patient-focused measures of functional health status and health-related quality of life in pediatric orthopedics: A case study in measurement selection

The objectives of this report are to review the assessment of patient-focused outcomes in pediatric orthopedic surgery, to describe a framework for identifying appropriate sets of measures, and to illustrate an application of the framework to a challenging orthopedic problem. A detailed framework of study design and measurement factors is described. The factors are important for selecting appropriate instruments to measure health status and health-related quality of life (HRQL) in a particular context. A study to evaluate treatment alternatives for patients with neurofibromatosis type 1 and congenital tibial dysplasia (NF1-CTD) provides a rich illustration of the application of the framework. The application involves great variability in the instrument selection factors. Furthermore, these patients and their supportive caregivers face numerous complex health challenges with long-term implications for HRQL. Detailed summaries of important generic preference-based multi-attribute measurement systems, pediatric health profile instruments, and pediatric orthopedic-specific instruments are presented. Age-appropriate generic and specific measures are identified for study of NF1-CTD patients. Selected measures include the Activities Scale for Children, Gillette Functional Assessment Questionnaire Walking Scale, Health Utilities Index, and Pediatric Inventory of Quality of Life. Reliable and valid measures for application to pediatric orthopedics are available. There are important differences among measures. The selected measures complement each other. The framework in this report provides a guide for selecting appropriate measures. Application of appropriate sets of measures will enhance the ability to describe the morbidity of pediatric orthopedic patients and to assess the effectiveness of alternative clinical interventions. The framework for measurement of health status and HRQL from a patient perspective has relevance to many other areas of orthopedic practice

The Ingram Vessel 38CT204: Intensive Survey & Excavation of an Upland Rivercraft at Cheraw, South Carolina

In 1993 and 1994 the Underwater Archaeology Division of the South Carolina Institute of Archaeology and Anthropology conducted an intensive survey of the remains of a small, wooden hulled craft in the Great Pee Dee River near Cheraw, South Carolina. The project was sponsored in part by the Cheraw Historical Society and partially funded by a grant from the South Carolina Humanities Council. The Ingram Vessel (38CT204), named after its discoverer Miller Ingram, lay overturned and largely buried beneath the river sediments and protected by a large mushroom-shaped rock just upstream of the site. The site was partially excavated and the hull remains mapped in situ. The investigation revealed a shallow draught, keeled vessel, built entirely of Southern Yellow Pine. The site is tentatively dated to the late 18th-early 19th century. Overall dimensions are estimated to have been approximately 15.5m (50ft, l0 in) in length, with a maximum beam of 4.6m (15ft, lin). This report details the research on the site and places the vessel within a regional maritime historical context. The vessel is, to date, the only ship-built hull excavated in an uplands context near the head of navigation of a South Carolina river.https://scholarcommons.sc.edu/archanth_books/1198/thumbnail.jp

La tempête de verglas : une occasion d’étudier les effets du stress prénatal chez l’enfant et la mère

Depuis plusieurs années, des études ont démontré que les événements stressants pendant la grossesse affectent le niveau de développement neurologique, de même que le fonctionnement cognitif et psychologique ultérieurs de l'enfant. Par exemple, Mednick (1997) a examiné l'impact d'un important séisme survenu en Chine sur le développement intellectuel et psychologique d'enfants à naître. Vingt-trois ans plus tard, des différences significatives dans le fonctionnement intellectuel, la dépression et la taille de certaines régions du cerveau ont été constatées chez ce groupe en comparaison aux enfants du groupe témoin. Des événements de moindre envergure, tels un divorce ou la perte d'emploi durant la grossesse, peuvent également augmenter l'incidence des complications obstétricales et avoir un impact sur le fonctionnement neurologique du bébé, son poids à la naissance et la circonférence de sa tête. Le décès du père ou l'exposition à un désastre naturel durant la grossesse ont été associés à la dépression, à la schizophrénie et à la criminalité à l'âge adulte. Divers effets adverses reliés aux événements stressants ont aussi été notés chez les primates. L'ensemble de ces études suggèrent que le second trimestre de la grossesse constitue une période critique pendant laquelle les événements stressants peuvent affecter le développement du foetus. Des contraintes méthodologiques nuisent actuellement à la recherche sur le stress prénatal maternel. Les études sur des animaux offrent d'excellents contrôles des environnements prénatal et postnatal. Cependant, les résultats de ces études sont difficilement applicables à l'humain à cause de la présence chez ce dernier, de nombreux facteurs de risque ou de protection absents chez les animaux. De plus, on ne peut assigner les stresseurs de façon aléatoire, dans les études sur les effets des événements de vie pendant la grossesse humaine. En effet, les traits de personnalité de la mère peuvent être transmis certes génétiquement mais également au niveau du développement. Par ailleurs, les enfants d'une mère avec de telles difficultés de personnalité sont exposés à plus d'événements de vie prénatale. D'autre part, la majorité des études sur l'humain ont une variance restreinte car il faut un très vaste échantillon de femmes enceintes pour garantir un nombre suffisant de sujets ayant vécu des événements de vie majeurs. Finalement, les études rétrospectives démontrant un lien entre un risque élevé de schizophrénie ou de dépression et des événements prénataux n'incluent pas de mesures prises sur le champ de la gravité objective ou de la manifestation biologique du stress. Nous présentons ici une revue de littérature portant sur le stress prénatal suivie d'une discussion sur comment la tempête de verglas de 1998 pourrait être utilisée pour faire la lumière sur des questions telles que les mécanismes par lesquels le stress prénatal exerce une influence sur la santé mentale du foetus.Over the last several years, studies have shown that stressful experiences during the pregnancy can predict levels of neurological development, as well as cognitive and psychological functioning, during childhood and adulthood. For example, Mednick (1997) has been studying the effects of a major earthquake in China on the psychological and intellectual development of the unborn child. Twenty-three years after the quake, significant differences have been found between the earthquake group and a control group born one year later in terms of intellectual functioning, depression, and the size of certain brain regions. Less severe events, such as a divorce or job loss during the pregnancy, may also increase the risk of obstetric complications and may have an effect on the baby's neurological well being, weight and head circumference at birth. Death of the baby's father during the pregnancy and natural disasters have both been associated with increased rates of depression, schizophrenia and criminality in adulthood. Several of these same effects have been found in studies of prenatal stress in non-human primates. Many of these studies suggest that the second trimester of pregnancy is a particularly critical period during which stressful events may compromise development of the fetus. Methodological constraints limit research on prenatal maternal stress. Animal studies are able to control for pre- and postnatal environments. However, animal studies have limited generalizability to humans for whom numerous risk and protective factors are in operation. Studies of human pregnancies cannot randomly assign subjects to stress conditions. Maternal personality and temperament may be associated with characteristics of a woman's child not only through genetic transmission of personality, but possibly also through differential exposure to difficult life conditions which may, in part, be self-imposed. In addition, studies of prenatal life events in humans have severely restricted variance; very large samples of women must be screened to identify even small numbers of women who have experienced major life events during the pregnancy. Finally, follow-back studies which show an association between prenatal events and later rates of mental illness, do not include timely evaluations of actual rates of exposure to the event, nor the pregnant woman's subjective or biological reactions to the event. In this paper, we present a review of the literature on prenatal maternal stress followed by a discussion of how the January 1998 Québec ice storm could be used to study the mechanisms by which prenatal stress may influence mental health outcomes in the unborn child.Desde hace varios años, estudios han demostrado que los hechos estresantes durante el embarazo afectan el grado de desarrollo neurológico, como posteriormente el funcionamiento cognoscitivo y psicológico del niño. Por ejemplo, Mednick (1997) examinó el impacto de un terremoto importante occurrido en China en el desarrollo intelectual y psicológico del futuro niño. Veintitres años después, diferencias significativas fueron constatadas en en funcionamiento intelectual, la depresión y la dimensión de ciertas regiones del cerebro en este grupo, comparativamente a un grupo testigo. Hechos de menor envergadura como el divorcio o la pérdida del empleo durante el embarazo pueden igualmente aumentar la incidencia de las complicaciones obstétricas y tener un impacto en el funcionamiento neurológico del bebé, su peso en el nacimiento y la circunferencia de la cabeza. La muerte del padre o la exposición a un desastre natural durante el embarazo han sido asociados a la depresión, la esquizofrenia y la criminalidad en la edad adulta. Diversos efectos adversos ligados a hechos estresantes también han sido notados en los primates. El conjunto de estos estudios sugieren que el segundo trimestre del embarazo constituye un período crítico durante el cual los eventos estresantes pueden afectar el desarrollo del feto. Impedimentos metodológicos afectan actualmente la investigación sobre el estrés perinatal materno. Los estudios con animales ofrecen excelentes controles del medio perinatal y postnatal. Sin embargo los resultados de estos estudios dificilmente son aplicables al ser humano a causa de la presencia de numerosos factores de riesgo o de protección, ausentes en los animales. Además, en los estudios sobre los efectos de los eventos de vida durante el embarazo no se puede asignar estresores de forma aleatoria. En efecto, los rasgos de personalidad de la madre pueden ser transmitidos genéticamante, pero también en el curso del desarrollo. Entre otras, los niños de una madre con determinadas dificultades de personalidad están expuestos a más hechos perinatales de vida. Por otra parte, la mayoría de los estudios sobre el humano varían poco puesto que se necesita un amplio muestreo de mujeres embarazadas que garantice un número suficiente de sujetos que hayan vivido eventos de vida mayores. Para terminar, los estudios retrospectivos demuestran una relación entre el alto riesgo de esquizofrenia o de depresión y los hechos perinatales no incluyen la toma rápida de medidas sobre la gravedad objetiva o sobre la manifestación biológica del estres. Nosotros presentamos aquí una revista de la literatura que aborda el estres perinatal, seguida de una discusión sobre cómo la tempestad de hielo de 1998 podría se utilizada para aclarar sobre interrogantes tales los mecanismos por los cuales el estres perinatal ejerce una influencia en la salud mental de feto

Prospectus, October 24, 1990

https://spark.parkland.edu/prospectus_1990/1024/thumbnail.jp

‘A system that is struggling’: understanding health protection resilience in England during the COVID-19 pandemic through the experiences of local health protection responders.

Abstract Background Local health protection systems play a crucial role in infectious disease prevention and control and were critical to COVID-19 pandemic responses. Despite this vital function, few studies have explored the lived experience of health protection responders managing COVID-19. We provide new insights by examining how COVID-19 shaped infectious disease prevention and control in local health protection systems in England. Methods Semi-structured interviews were conducted with twenty local health protection responders from three contrasting local authority areas, and Public Health England (PHE) health protection teams, in England between June 2021 - March 2022. Participants were from: PHE health protection teams (n=6); local authority public health teams (n=5); local authority Public Protection Services (n=7); and local authority commissioned Infection Prevention and Control Teams (n=2). Data were analysed using reflexive thematic analysis. Results First, participants acknowledged the pandemic caused an unprecedented workload and disruption to local health protection service delivery. There was not enough capacity within existing local health protection systems to manage the increased workload. PHE health protection teams therefore transferred some COVID-19 related health protection tasks to other staff, mainly those employed by local authorities. Second, health protection responders highlighted how COVID-19 drew attention to the weaknesses in local health protection systems already stressed by reduced funding in the years leading up to the pandemic. Injecting money into the COVID-19 response did not completely overcome former losses in specialist health protection workforce. Third, health protection responders described how pandemic management raised the profile of public health, especially infectious disease prevention and control. Managing COVID-19 strengthened collaborative working, resulting in enhanced capacity of local health protection systems at the time. Conclusion The COVID-19 pandemic challenged the public health preparedness of all countries. Health protection responders in this study also expressed many challenges. There was insufficient resilience in these local health protection systems and an inability to scale up the specialist health protection workforce, as required in a pandemic situation. The UK needs to learn from the pandemic experience by acknowledging and addressing the challenges faced by local health protection responders so that it can more effectively respond to future threats

DEveloping Tests for Endometrial Cancer deTection (DETECT): protocol for a diagnostic accuracy study of urine and vaginal samples for the detection of endometrial cancer by cytology in women with postmenopausal bleeding.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-07-01, epub 2021-07-28Publication status: PublishedFunder: Wellcome TrustFunder: Department of Health; Grant(s): NIHR300650Funder: Cancer Research UK; Grant(s): C147/A25254IntroductionPostmenopausal bleeding (PMB), the red flag symptom for endometrial cancer, triggers urgent investigation by transvaginal ultrasound scan, hysteroscopy and/or endometrial biopsy. These investigations are costly, invasive and often painful or distressing for women. In a pilot study, we found that voided urine and non-invasive vaginal samples from women with endometrial cancer contain malignant cells that can be identified by cytology. The aim of the DEveloping Tests for Endometrial Cancer deTection (DETECT) Study is to determine the diagnostic test accuracy of urine and vaginal cytology for endometrial cancer detection in women with PMB.Methods and analysisThis is a multicentre diagnostic accuracy study of women referred to secondary care with PMB. Eligible women will be asked to provide a self-collected voided urine sample and a vaginal sample collected with a Delphi screener before routine clinical procedures. Pairs of specialist cytologists, blinded to participant cancer status, will assess and classify samples independently, with differences settled by consensus review or involving a third cytologist. Results will be compared with clinical outcomes from standard diagnostic tests. A sample size of 2000 women will have 80% power to establish a sensitivity of vaginal samples for endometrial cancer detection by cytology of ≥85%±7%, assuming 5% endometrial cancer prevalence. The primary objective is to determine the diagnostic accuracy of urogenital samples for endometrial cancer detection by cytology. Secondary objectives include the acceptability of urine and vaginal sampling to women.Ethics and disseminationThis study has been approved by the North West-Greater Manchester West Research Ethics Committee (16/NW/0660) and the Health Research Authority. Results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and via charity websites.Trial registration numberISRCTN58863784

Safety and Tolerability of Antiretrovirals during Pregnancy

Combination antiretroviral therapy (CART) dramatically decreases mother-to-child HIV-1 transmission (MTCT), but maternal adverse events are not infrequent. A review of 117 locally followed pregnancies revealed 7 grade ≥3 AEs possibly related to antiretrovirals, including 2 hematologic, 3 hepatic, and 2 obstetric cholestasis cases. A fetal demise was attributed to obstetric cholestasis, but no maternal deaths occurred. The drugs possibly associated with these AE were zidovudine, nelfinavir, lopinavir/ritonavir, and indinavir. AE or intolerability required discontinuation/substitution of nevirapine in 16% of the users, zidovudine in 10%, nelfinavir in 9%, lopinavir/ritonavir in 1%, but epivir and stavudine in none. In conclusion, nevirapine, zidovudine, and nelfinavir had the highest frequency of AE and/or the lowest tolerability during pregnancy. Although nevirapine and nelfinavir are infrequently used in pregnancy at present, zidovudine is included in most MTCT preventative regimens. Our data emphasize the need to revise the treatment recommendations for pregnant women to include safer and better-tolerated drugs

Botulinum Neurotoxin Detection and Differentiation by Mass Spectrometry

A new rapid, mass spectrometry-based method to detect and differentiate botulinal neurotoxins is described

Extraction and inhibition of enzymatic activity of botulinum neurotoxins /B1, /B2, /B3, /B4, and /B5 by a panel of monoclonal anti-BoNT/B antibodies

<p>Abstract</p> <p>Background</p> <p>Botulism is caused by botulinum neurotoxins (BoNTs), extremely toxic proteins which can induce respiratory failure leading to long-term intensive care or death. Treatment for botulism includes administration of antitoxins, which must be administered early in the course of the intoxication; therefore, rapid determination of human exposure to BoNT is an important public health goal. In previous work, our laboratory reported on Endopep-MS, a mass spectrometry-based activity method for detecting and differentiating BoNT/A, /B, /E, and /F in clinical samples. We also demonstrated that antibody-capture is effective for purification and concentration of BoNTs from complex matrices such as clinical samples. However, some antibodies inhibit or neutralize the enzymatic activity of BoNT, so the choice of antibody for toxin extraction is critical.</p> <p>Results</p> <p>In this work, we evaluated 24 anti-BoNT/B monoclonal antibodies (mAbs) for their ability to inhibit the <it>in vitro </it>activity of BoNT/B1, /B2, /B3, /B4, and /B5 and to extract those toxins. Among the mAbs, there were significant differences in ability to extract BoNT/B subtypes and inhibitory effect on BoNT catalytic activity. Some of the mAbs tested enhanced the <it>in vitro </it>light chain activity of BoNT/B, suggesting that BoNT/B may undergo conformational change upon binding some mAbs.</p> <p>Conclusions</p> <p>In addition to determining <it>in vitro </it>inhibition abilities of a panel of mAbs against BoNT/B1-/B5, this work has determined B12.2 and 2B18.2 to be the best mAbs for sample preparation before Endopep-MS. These mAb characterizations also have the potential to assist with mechanistic studies of BoNT/B protection and treatment, which is important for studying alternative therapeutics for botulism.</p

Kinetics and Determining Factors of the Virologic Response to Antiretrovirals during Pregnancy

HIV-infected pregnant women with undetectable plasma HIV RNA concentrations at delivery pose a minimal risk of vertical transmission. We studied the kinetics and the determinants of the virologic response to antiretroviral therapy in 117 consecutive pregnancies. Patients who initiated therapy during pregnancy had a VL decrease of 2 and 2.5 log10 after 4 and 24 weeks, respectively. Therapeutic drug monitoring (TDM) of the protease inhibitors administered in doses recommended for nonpregnant adults resulted in below-target concentrations in 29%, 35%, and 44% of 1st, 2nd, and 3rd trimester measurements, respectively, but low drug concentrations did not correlate with virologic failure. Demographic characteristics, antiretroviral experience prior to pregnancy, baseline VL, or use of specific antiretrovirals did not affect the virologic response. Adherence to ≥95% of prescribed doses and utilization of psychosocial services were associated with undetectable plasma HIV RNA at delivery. In conclusion, the virologic responses of pregnant and nonpregnant adults share similar charactersitics