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BACKGROUND: The Asia Pacific Society of Infection Control launched the APSIC guide for prevention of catheter associated urinary tract infections in July 2022. It aims to highlight practical recommendations in a concise format designed to assist healthcare facilities in the Asia Pacific region to achieve high standards in infection prevention and control practices during the management and care of patients with a urinary catheter. METHODS: The guidelines were developed by an appointed workgroup comprising experts in the Asia Pacific region, following reviews of previously published guidelines and recommendations relevant to each section. RESULTS: It recommends that healthcare institutions have a catheter associated urinary tract infection prevention program that includes surveillance and the use of the insertion and maintenance bundles. Implementation of the bundles is best done using a quality improvement approach with a multidisciplinary team. CONCLUSIONS: Healthcare facilities should aim for excellence in care of patients with urinary catheters. It is recommended that healthcare facilities have a catheter associated urinary tract infection prevention program as part of their Infection Prevention and Control program.
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Infecciones Relacionadas con Catéteres , Infecciones Urinarias , Humanos , Infecciones Relacionadas con Catéteres/prevención & control , Infecciones Relacionadas con Catéteres/epidemiología , Control de Infecciones , Cateterismo Urinario/efectos adversos , Infecciones Urinarias/prevención & control , Infecciones Urinarias/epidemiología , Catéteres Urinarios/efectos adversosRESUMEN
BACKGROUND: Children living with HIV (CLHIV) on prolonged antiretroviral therapy (ART) are at risk for lipid and glucose abnormalities. Prevalence and associated factors were assessed in a multicentre, Asian longitudinal paediatric cohort. METHODS: CLHIV were considered to have lipid or glucose abnormalities if they had total cholesterol ≥200 mg/dL, high-density lipoprotein (HDL) ≤35 mg/dL, low-density lipoprotein (LDL) ≥100 mg/dL, triglycerides (TG) ≥110 mg/dL, or fasting glucose >110 mg/dL. Factors associated with lipid and glucose abnormalities were assessed by logistic regression. RESULTS: Of 951 CLHIV, 52% were male with a median age of 8.0 (interquartile range [IQR] 5.0-12.0) years at ART start and 15.0 (IQR 12.0-18.0) years at their last clinic visit. 89% acquired HIV perinatally, and 30% had ever used protease inhibitors (PIs). Overall, 225 (24%) had hypercholesterolemia, 105 (27%) low HDL, 213 (58%) high LDL, 369 (54%) hypertriglyceridemia, and 130 (17%) hyperglycemia. Hypercholesterolemia was more likely among females (versus males, aOR 1.93, 95% CI 1.40-2.67). Current PIs use was associated with hypercholesterolemia (current use: aOR 1.54, 95% CI 1.09-2.20); low HDL (current use: aOR 3.16, 95% CI 1.94-5.15; prior use: aOR 10.55, 95% CI 2.53-43.95); hypertriglyceridemia (current use: aOR 3.90, 95% CI 2.65-5.74; prior use: aOR 2.89, 95% CI 1.31-6.39); high LDL (current use: aOR 1.74, 95% CI 1.09-2.76); and hyperglycemia (prior use: aOR 2.43, 95% CI 1.42-4.18). CONCLUSION: More than half and one-fifth of CLHIV have dyslipidemia and hyperglycemia, respectively. Routine paediatric HIV care should include metabolic monitoring. The association between PIs use and dyslipidemia emphasizes the importance of rapidly transitioning to integrase inhibitor-containing regimens.
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Dislipidemias , Infecciones por VIH , Hipercolesterolemia , Hiperglucemia , Hiperlipidemias , Hipertrigliceridemia , Femenino , Humanos , Masculino , Niño , Preescolar , Glucosa , Dislipidemias/epidemiología , Triglicéridos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Lipoproteínas LDL , Hiperglucemia/epidemiología , Hipertrigliceridemia/epidemiología , Asia/epidemiología , HDL-ColesterolRESUMEN
Questions remain concerning the long-term efficacy, safety, and site(s) of transgene expression following adeno-associated vector (AAV) therapy. We report a long-term follow-up of 8 (male = 4, hemizygous, and female = 4, homozygous) dogs with severe hemophilia A treated with a single portal vein infusion of a B-domain-deleted (BDD)-canine FVIII (cFVIII) AAV vector (median dose = 1.25 × 1013 vg/kg, AAV2 = 4, AAV6 = 3, and AAV8 = 1). After a median follow-up of 10.8 years (8.2-12.0 years), persistent FVIII:C (median one-stage = 12.7%, chromogenic = 7.2%) was seen in all responding dogs (n = 6), with improvement in annualized bleed rates (pre = 3.9 vs post = 0.3 event per year; P = .003). Anti-AAV capsid neutralizing antibodies (nAbs) toward the dosed capsid were detected throughout the study, with limited cross-reactivity to other capsids. nAb titers for all capsid serotypes declined with time, although they remained at levels precluding redosing with the same capsid. AAV-BDD-cFVIII DNA was detected in the liver of all dogs (median = 0.15 vg per diploid genome), with lower levels in the spleen in 4 dogs (median = 0.005 vg per diploid genome). Consistent with the liver-specific promoter, BDD-cFVIII mRNA was only detected in the liver. Postmortem examination demonstrated no evidence of chronic liver disease or liver malignancy. Persistent FVIII expression and an improved bleeding phenotype was seen for more than a decade after vector delivery. This is the longest follow-up reported in a preclinical model supporting long-term efficacy and safety of AAV-mediated gene therapy.
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Hemofilia A , Perros , Masculino , Animales , Femenino , Hemofilia A/genética , Hemofilia A/terapia , Factor VIII/genética , Factor VIII/uso terapéutico , Factor VIII/metabolismo , Estudios de Seguimiento , Vectores Genéticos/genética , Hígado/metabolismo , Terapia Genética , Hemorragia/tratamiento farmacológico , Dependovirus/genéticaRESUMEN
STUDY QUESTION: Can we develop a preconception lifestyle programme for couples undergoing IVF that is in line with their needs. SUMMARY ANSWER: A mobile preconception lifestyle programme was systematically developed based on expert opinion, literature and needs of IVF-patients. WHAT IS KNOWN ALREADY: A healthy lifestyle prior to conception is not only beneficial for the general health of couples, but evidence on its importance for their reproductive health and the health of their children is also emerging. So far, the vast majority of fertility clinics do not offer a lifestyle programme for couples undergoing IVF. Therefore, the present study aimed to develop a lifestyle programme for IVF-couples. STUDY DESIGN, SIZE, DURATION: The development of the PreLiFe-programme was guided by the steps of the Medical Research Council (MRC) framework for developing complex interventions, a systematic approach for developing theory- and evidence-based health promotion interventions. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: First, the evidence base on lifestyle programmes for IVF-couples was reviewed. Second, several iterations between an expert panel, the literature, and quantitative and qualitative data from IVF-patients identified the content, the format, behaviour change techniques and theory of the programme. Third, the PreLiFe-programme was produced and the expected process and outcomes of a randomized controlled trial assessing it were modelled. Finally, user tests among experts and patients and pilot tests among patients were conducted. MAIN RESULTS AND ROLE OF CHANCE: The finally developed PreLiFe-programme is a mobile application to be used autonomously by both partners of IVF-couples during the first year of IVF, in combination with motivational interviewing over the telephone every three months (i.e. blended care). The PreLiFe-programme provides advice and skills training on physical activity, diet and mindfulness based stress reduction and is in part tailored based on monitoring and tracking the lifestyle of patients. Based on the literature the expert panel considers it plausible that all three components contribute to IVF-success rates. The PreLiFe-programme is likely to be acceptable to patients as it meets the need of patients for lifestyle advice and treatment information. LIMITATIONS, REASON FOR CAUTION: The pilot in IVF-couples had a 3-month duration. The feasibility of the PreLiFe-programme in other infertile populations and/or upon longer use is yet to be examined. Whether the PreLiFe-programme effectively improves lifestyle and IVF-success rates is currently being examined in a trial randomizing heterosexual couples starting IVF to the PreLiFe-programme or an attention-control group for 12 months. WIDER IMPLICATIONS OF THE FINDINGS: If the PreLiFe-programme improves lifestyle and the chance of IVF-success, it will be a powerful tool and provide guidance for implementing lifestyle programmes in fertility clinics. STUDY FUNDING/COMPETING INTEREST(S): Funded by the Research Foundation Flanders (FWO-TBM (Applied Biomedical Research with a Primary Social finality); reference: T005417N). The authors have no conflict of interest to report. TRIAL REGISTRATION NUMBER: NCT03790449.
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Fertilización In Vitro , Infertilidad , Niño , Estilo de Vida Saludable , Humanos , Estilo de VidaRESUMEN
PURPOSE: Management of a child's anxiety early in their treatment is essential in dentistry. Sedative medications are used to overcome increased anxiety from previous appointments and to promote the cooperation of children during treatment. Hydroxyzine is currently prescribed to young patients as part of the first level of conscious sedation. The main objective was to evaluate the professional practice of oral hydroxyzine, when prescribed for children presenting anxiety during dental treatment procedure performed by students and senior practitioners. METHODS: A retrospective study of dental records and questionnaires was conducted at the Dental Care Centre of the University Hospital of Rennes, France. Parameters related to the prescription of hydroxyzine in children were evaluated as potential predictors of the dental session success, with adjustments on potential confounders. RESULTS: The therapeutic outcome was very encouraging with 78.3% of success during dental sessions under sedation with oral hydroxyzine. Anxiety levels before the dental procedure and the medication compliance of the child were the main predictors of success. On the other hand, lower age (< 6 years old) and longer treatments (such as pulpotomy) worsened the outcome. CONCLUSIONS: Careful analysis of the literature and results of this work showed the safety of hydroxyzine within the maximum dose authorized without adverse effects, compared to other molecules described and commonly used in dentistry. No adverse effects during dental procedure were noted. This allows for minimal sedation with efficiency for the great majority of pediatric treatment. This solution should be the first step in sedation to help practicing clinicians.
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Anestesia Dental , Hidroxizina , Niño , Conducta Infantil , Sedación Consciente , Hospitales , Humanos , Hipnóticos y Sedantes/efectos adversos , Práctica Profesional , Estudios RetrospectivosRESUMEN
STUDY QUESTION: What is the risk of recurrence in young breast cancer survivors who undergo ARTs following completion of anticancer treatment? SUMMARY ANSWER: ART in breast cancer survivors does not appear to have a negative impact on disease-free survival. WHAT IS KNOWN ALREADY: In healthy women, fertility treatment does not increase the risk of developing breast cancer. At the time of breast cancer diagnosis and before starting anticancer treatments, several studies have shown the safety of performing ART. However, the safety of ART in breast cancer survivors following completion of anticancer treatment remains under-investigated. In general, breast cancer survivors are counselled to avoid any hormonal treatment but there are limited data available on the effect of short exposure to high oestradiol levels during ART. The largest study in this regard included 25 breast cancer survivors exposed to ART and did not show a detrimental effect of ART on patient survival. Hence, taking into account that pregnancy after breast cancer does not affect cancer prognosis, defining the safety of ART in breast cancer survivors remains a priority. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective multicentric matched cohort study including a cohort of breast cancer survivors who underwent ART (exposed patients) between January 2006 and December 2016. Exposed patients who were eligible for the study were matched according to known breast cancer prognostic factors. Matched breast cancer survivors did not undergo ART (non-exposed patients) and were disease-free for a minimum time that was not less than the time elapsed between breast cancer diagnosis and first ART for the matched ART-exposed patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were retrieved from all survivors who had been diagnosed with breast cancer in eight participating centres at an age of ≤40 years, without metastasis, ongoing pregnancy, pre-existing neoplasia or ovarian failure. ART included ovarian stimulation for IVF/ICSI, clomiphene citrate treatment and hormone replacement therapy for embryo transfer. Data were collected from an oncological database for the selection of breast cancer patients in the non-exposed group. Exposed patients were matched (1:2) for germline BRCA status, tumour stage, anticancer treatment and age, whenever feasible. Matched groups were compared at baseline according to characteristics using conditional logistic regression. Kaplan-Meier curves were constructed to compare time to recurrence between groups, with the time of ART as starting point that has been adjusted in the non-exposed group. The analyses were performed using Stata IC/15.1. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 39 breast cancer patients in the ART group were eligible for the analysis and were matched with 73 controls. There was no statistical difference between the two groups for the presence of BRCA mutation, tumour characteristics, use of (neo)adjuvant chemotherapy and of adjuvant endocrine therapy. Exposed patients were younger than non-exposed patients (mean age 31.8 vs 34.3 years, respectively; P < 0.001). In the ART group, 89.7% were nulliparous at diagnosis compared to 46.6% of controls (P < 0.001). ART was performed at a mean age of 37.1 years old, after a median time of 4.1 years following breast cancer diagnosis (range: 1.5-12.5). Median anti-Müllerian hormone at the time of ART was 0.28 ng/ml (range: 0-4.4) and median serum oestradiol peak level was 696.5 pg/ml (range: 139.7-4130). Median follow-up time from first attempt of ART was 4.6 years (range: 2.4-12.5) in the ART group. Adjusted follow-up time for the non-exposed group was 6.9 years (range: 1.1-16.5 years) (P = 0.004). In the ART group, 59% of patients had a pregnancy after breast cancer compared to 26% in the non-exposed patients (P = 0.001). Breast cancer relapsed in 7.7% versus 20.5% women in the ART and non-exposed groups, respectively (hazard ratio 0.46, 95% CI 0.13-1.62, P = 0.23). Median time to relapse was 1.3 (range: 0.3-2.7) years versus 4.5 (range: 0.4-11.1) years after ART and adjusted time in the ART and non-exposed groups, respectively (P = 0.14). LIMITATIONS, REASONS FOR CAUTION: Although this is the first and largest multicentric study addressing the impact of ART on breast cancer recurrence to provide data on oestrogen exposure, only a small number of patients could be included. This reflects the reluctance of breast cancer survivors and/or oncologists to perform ART, and highlights the need for a prospective data registry to confirm the safety of this approach. This would offer the possibility for these patients, who are at a high risk of infertility, to fully benefit from ART. WIDER IMPLICATIONS OF THE FINDINGS: Although recent studies have proven that pregnancy after breast cancer has no detrimental impact on prognosis, counselling patients about the safety of ART remains challenging. Our study provides reassuring data on the use of ART in breast cancer survivors with favourable prognostic factors, for when natural conception fails. STUDY FUNDING/COMPETING INTEREST(S): M.C. and I.D. are funded by FNRS, Télévie-FNRS and Fonds Erasme. M.D.V. is a CooperSurgical scientific advisory board member and receives lecture fees for MSD, Gedeon-Richter and Ferring, outside the submitted work. M.L. has acted as a consultant for Roche and Novartis and has received honoraria from Theramex, Roche, Lilly, Pfizer, Novartis and Takeda, outside the submitted work. I.D. has acted as a consultant for ROCHE and has received speaker's fees from Novartis, outside the submitted work. E.d.A. has received honoraria and is a Roche/GNE, Novartis, SeaGen and Zodiac scientific advisory board member, has received travel grants from Roche/GNE and GSK/Novartis, and has received research grants from Roche/GNE, Astra-Zeneca, GSK/Novartis and Servier, outside the submitted work. A.D. is a recipient of a research grant from Ferring Pharmaceuticals and receives lecture and/or consultancy fees from Merck, Gedeon-Richter and Ferring Pharmaceuticals, outside the submitted work. The remaining authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.
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Neoplasias de la Mama , Supervivientes de Cáncer , Adulto , Neoplasias de la Mama/tratamiento farmacológico , Estudios de Cohortes , Femenino , Humanos , Masculino , Recurrencia Local de Neoplasia , Embarazo , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
BACKGROUND: Pediatricians are less frequently sued than other physicians. When suits are successful, however, the average payout is higher. Little is known about changes in the risk of litigation over time. We sought to characterize malpractice lawsuit trends for pediatricians over time. METHODS: The Periodic Survey is a national random sample survey of American Academy of Pediatrics members. Seven surveys between 1987 and 2015 asked questions regarding malpractice (n = 5731). Bivariate and multivariable analyses examined trends and factors associated with risk and outcome of malpractice claims and lawsuits. Descriptive analyses examined potential change in indemnity amount over time. RESULTS: In 2015, 21% of pediatricians reported ever having been the subject of any claim or lawsuit, down from a peak of 33% in 1990. Report of successful outcomes in the most-recent suit trended upward between 1987 and 2015, greatest in 2015 at 58%. Median indemnity was unchanged, averaging $128 000 in 2018 dollars. In multivariate analysis, male sex, hospital-based subspecialty (neonatology, pediatric critical care, pediatric emergency medicine, and hospital medicine), longer career, and more work hours were associated with a greater risk of malpractice claim. CONCLUSIONS: From 1987 to 2015, the proportion of pediatricians sued has decreased and median indemnity has remained unchanged. Male pediatricians and hospital-based subspecialists were more likely to have been sued. Greater knowledge of the epidemiology of malpractice claims against pediatricians is valuable because it can impact practice arrangements, advise risk-management decisions, influence quality and safety projects, and provide data to guide advocacy for appropriate tort reform and future research.
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Mala Praxis/tendencias , Pediatría/tendencias , Adulto , Análisis de Varianza , Competencia Clínica/estadística & datos numéricos , Femenino , Humanos , Masculino , Mala Praxis/economía , Mala Praxis/legislación & jurisprudencia , Mala Praxis/estadística & datos numéricos , Persona de Mediana Edad , Pediatras/estadística & datos numéricos , Pediatras/tendencias , Pediatría/economía , Pediatría/estadística & datos numéricos , Ubicación de la Práctica Profesional/estadística & datos numéricos , Riesgo , Sesgo de Selección , Factores Sexuales , Encuestas y Cuestionarios/estadística & datos numéricos , Estados UnidosRESUMEN
OBJECTIVE: Clubfoot is a complex congenital three-dimensional foot deformity, which affects 150,000-200,000 newborn babies annually around the world. A good understanding of the alignment of the two osseous columns and the lower leg of the ankle and foot complex is essential for evaluating the severity of clubfoot. The purposes of this study were to (1) develop an automated three-dimensional (3D) surface model of severe clubfoot based on two-dimensional (2D) slices of computed tomography (CT) images, (2) evaluate the alignment of foot bones relative to the ankle in severe clubfoot, and (3) examine the structural changes in the shape of the clubfoot. PATIENTS AND METHODS: Two-dimensional CT image was taken from a four-year-old child with a severe clubfoot. Subsequently, an automated and detailed 3D surface model of the severe clubfoot was developed from the 2D images by using MATLAB software programming. Then, the x, y, and z coordinate angles were automatically calculated for each bone in the foot relative to the ankle (lower end of the tibia) to determine the orientations and relationships among the bones. RESULTS: The relative position or orientation of each bone of the foot to the ankle of the severe clubfoot was objectively measured which was used to determine the orientation of each bone in the foot. Among the x, y, and z axes of the interested tarsal bones, the z axis represents the smallest moment of inertia, and the results showed that the bones in the x axis shifted medially with higher relative angle. CONCLUSIONS: This 3D objective measurement method for assessing clubfoot can be used to determine and classify the severity of clubfoot, as well as evaluate and monitor the progress of the clubfoot intervention based on the relative position of the tarsal bones. The method can also be used to quantify the relationship between the tarsal bones of the foot and lower end of the tibia. In addition, angular measurements can be used to assess other pathological conditions of the foot such as pes cavus and pes planus.
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Tobillo/diagnóstico por imagen , Pie Equinovaro/diagnóstico por imagen , Pie/diagnóstico por imagen , Imagenología Tridimensional/métodos , Tibia/diagnóstico por imagen , Falanges de los Dedos del Pie/diagnóstico por imagen , Preescolar , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Modelos Anatómicos , Tomografía Computarizada por Rayos X/métodosAsunto(s)
Antidepresivos de Segunda Generación/efectos adversos , Citalopram/efectos adversos , Erupciones por Medicamentos/etiología , Eosinofilia/inducido químicamente , Hígado/fisiopatología , Adulto , Trastornos de Ansiedad/tratamiento farmacológico , Exantema/inducido químicamente , Humanos , MasculinoRESUMEN
Columnaris disease, caused by the Gram-negative bacterium Flavobacterium columnare, is one of the most prevalent fish diseases worldwide. An exceptionally high level of genetic diversity among isolates of F. columnare has long been recognized, whereby six established genomovars have been described to date. However, little has been done to quantify or characterize this diversity further in a systematic fashion. The objective of this research was to perform phylogenetic analyses of 16S rRNA and housekeeping gene sequences to decipher the genetic diversity of F. columnare. Fifty isolates and/or genomes of F. columnare, originating from diverse years, geographic locations, fish hosts, and representative of the six genomovars were analyzed in this study. A multilocus phylogenetic analysis (MLPA) of the 16S rRNA and six housekeeping genes supported four distinct F. columnare genetic groups. There were associations between genomovar and genetic group, but these relationships were imperfect indicating that genomovar assignment does not accurately reflect F. columnare genetic diversity. To expand the dataset, an additional 90 16S rRNA gene sequences were retrieved from GenBank and a phylogenetic analysis of this larger dataset also supported the establishment of four genetic groups. Examination of isolate historical data indicated biological relevance to the identified genetic diversity, with some genetic groups isolated preferentially from specific fish species or families. It is proposed that F. columnare isolates be assigned to the four genetic groups defined in this study rather than genomovar in order to facilitate a standard nomenclature across the scientific community. An increased understanding of which genetic groups are most prevalent in different regions and/or aquaculture industries may allow for the development of improved targeted control and treatment measures for columnaris disease.
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AIM: Transanal total mesorectal excision (taTME) is a novel approach for resection of the rectum. Use of a standard insufflator to create pneumorectum, however, results in bellowing-large heaving motions from insufflation of air that can frustrate surgery. We report the successful application of our technique, stable pneumorectum using an inline glove (SPRING), for the performance of transanal rectal excision in a series of 17 patients using a standard laparoscopic insufflator. METHOD: A retrospective review of 17 patients using the SPRING technique was performed between October 2015 and October 2016. Characteristics of these patients were evaluated, and technique-related short-term outcome was reviewed. RESULTS: The SPRING technique was successfully used in patients who underwent both minimally invasive (n = 14) and open (n = 3) approaches in the abdominal stage of the surgery. In the 12 patients who had rectal cancer for whom SPRING was used to facilitate taTME there were no conversions to an alternative access for rectal resection, the median duration of the TME part of the operation was 95 min (62-147) and there was one R1 resection (8%). Billowing was not a significant problem in any of the 17 patients during the surgery. CONCLUSION: In this case series we have successfully shown the feasibility of the SPRING technique as a practical and cost-effective solution to the problem of billowing during taTME.
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Guantes Quirúrgicos , Insuflación/instrumentación , Proctectomía/instrumentación , Recto/cirugía , Cirugía Endoscópica Transanal/instrumentación , Anciano , Anciano de 80 o más Años , Análisis Costo-Beneficio , Femenino , Guantes Quirúrgicos/economía , Humanos , Insuflación/economía , Insuflación/métodos , Masculino , Persona de Mediana Edad , Proctectomía/economía , Proctectomía/métodos , Estudios Retrospectivos , Cirugía Endoscópica Transanal/economía , Cirugía Endoscópica Transanal/métodos , Resultado del TratamientoRESUMEN
This study examined the relationships between activity participation and bone mineralization in children with developmental coordination disorder. Limited participation in physical, recreational, social, and skill-based and self-improvement activities contributed to lower bone mineral content. For improved bone health, these children should participate in a variety of activities, not only physical activities. INTRODUCTION: Limited activity participation in children with developmental coordination disorder (DCD) may have a negative impact on bone mineral accrual. The objectives of this study were to compare bone mineralization and activity participation patterns of pre-pubertal children with DCD and those with typical development, and to determine the association between activity participation patterns and bone mineralization in children with DCD. METHODS: Fifty-two children with DCD (mean age = 7.51 years) and 61 children with typical development (mean age = 7.22 years) participated in the study. Appendicular and total body (less head) bone mineral content (BMC) and bone mineral density (BMD) were evaluated by a whole-body dual-energy X-ray absorptiometry scan. Activity participation patterns were assessed using the Children's Assessment of Participation and Enjoyment (CAPE) questionnaire. RESULTS: Children with DCD had lower appendicular and total body BMCs and BMDs than children with typical development overall (p < 0.05). They also had lower CAPE total activity and physical activity diversity scores (p < 0.05). After accounting for the effects of age, sex, height, lean mass, and fat mass, the total activity diversity score remained independently associated with leg BMC in children with DCD, explaining 5.1% of the variance (p = 0.030). However, the physical activity diversity score was no longer associated with leg BMC (p = 0.090). CONCLUSIONS: Diversity of activity participation and bone mineralization were lower in pre-pubertal children with DCD. Decreased total activity participation diversity was a contributing factor to lower BMC in the legs of children with DCD.
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Densidad Ósea/fisiología , Ejercicio Físico/fisiología , Trastornos de la Destreza Motora/fisiopatología , Absorciometría de Fotón/métodos , Niño , Desarrollo Infantil/fisiología , Estudios Transversales , Femenino , Humanos , Pierna/fisiopatología , MasculinoRESUMEN
BACKGROUND AND OBJECTIVES: Whether the Medicaid primary care payment increase of 2013 to 2014 changed physician participation remains unanswered amid conflicting evidence. In this study, we assess national and state-level changes in Medicaid participation by office-based primary care pediatricians before and after the payment increase. METHODS: Using bivariate statistical analysis, we compared survey data collected from 2011 to 2012 and 2015 to 2016 by the American Academy of Pediatrics from state-stratified random samples of pediatrician members. RESULTS: By 4 of 5 indicators, Medicaid participation increased nationally from 2011 and 2012 to 2015 and 2016 (n = 10 395). Those accepting at least some new patients insured by Medicaid increased 3.0 percentage points (ppts) to 77.4%. Those accepting all new patients insured by Medicaid increased 5.9 ppts to 43.3%, and those accepting these patients at least as often as new privately insured patients increased 5.7 ppts to 55.6%. The average percent of patients insured by Medicaid per provider panel increased 6.0 ppts to 31.3%. Nonparticipants dropped 2.1 ppts to 14.6%. Of the 27 studied states, 16 gained in participation by 1 or more indicators, 11 gained by 2 or more, and 3 gained by all 5. CONCLUSIONS: Office-based primary care pediatricians increased their Medicaid participation after the payment increase, in large part by expanding their Medicaid panel percentage. Continued monitoring of physician participation in Medicaid at the national and state levels is vital for guiding policy to optimize timely access to appropriate health care for >37 million children insured by Medicaid.
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Medicaid/estadística & datos numéricos , Visita a Consultorio Médico/estadística & datos numéricos , Pediatras/estadística & datos numéricos , Pautas de la Práctica en Medicina/tendencias , Atención Primaria de Salud/economía , Niño , Preescolar , Femenino , Encuestas de Atención de la Salud , Gastos en Salud/estadística & datos numéricos , Humanos , Masculino , Medicaid/economía , Visita a Consultorio Médico/economía , Pediatras/economía , Pautas de la Práctica en Medicina/economía , Atención Primaria de Salud/métodos , Estados UnidosRESUMEN
Gene therapy may offer a new treatment option, particularly for patients with severe hemophilia, based on recent research. However, individuals with pre-existing immunity to adeno-associated viruses (AAVs) may be less likely to benefit from AAV vector-based therapies. To study pre-existing AAV5 immunity in humans, we validated two complementary, sensitive, and scalable in vitro assays to detect AAV5 total antibodies and transduction inhibition (TI). Using these two assays, we found that 53% of samples from 100 healthy male individuals were negative in both assays, 18% were positive in both assays, 5% were positive for total antibodies but negative for TI and, of interest, 24% were negative for total antibodies but positive for TI activity, suggesting the presence of non-antibody-based neutralizing factors in human plasma. Similar findings were obtained with 24 samples from individuals with hemophilia A. On the basis of these results, we describe the development of a dual-assay strategy to identify individuals without total AAV5 antibodies or neutralizing factors who may be more likely to respond to AAV5-directed gene therapy. These assays offer a universal, transferrable platform across laboratories to assess the global prevalence of AAV5 antibodies and neutralizing factors in large patient populations to help inform clinical development strategies.
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Dependovirus/genética , Terapia Genética/métodos , Infecciones por Parvoviridae/inmunología , Adulto , Anciano , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Dependovirus/inmunología , Ensayo de Inmunoadsorción Enzimática , Humanos , Masculino , Persona de Mediana Edad , Primates , Reproducibilidad de los Resultados , Células Sf9 , Transducción Genética , Transfección , Adulto JovenRESUMEN
STUDY QUESTION: Can cluster analysis be used to differentiate between normo-ovulatory women with normal ovaries and normo-ovulatory women with polycystic ovarian morphology (PCOM) in a non-subjective manner? SUMMARY ANSWER: Cluster analysis can be used to accurately and non-subjectively differentiate between normo-ovulatory women with normal ovaries and normo-ovulatory women with PCOM. WHAT IS KNOWN ALREADY: Currently, PCOM is diagnosed using a fixed threshold level, i.e. 12 or more follicles per ovary, and is one of the diagnostic criteria of polycystic ovary syndrome (PCOS). However, PCOM is also encountered in normo-ovulatory women, suggesting that it could just represent a normal variant. On the other hand, recent studies have shown subtle endocrine abnormalities in women with isolated PCOM that resemble those found in women with PCOS. Because of the strong correlation between anti-Müllerian hormone (AMH) and follicle number, a high serum AMH level has been proposed as a surrogate marker for PCOM and could, therefore, be integrated in the diagnostic classifications for PCOS. STUDY DESIGN, SIZE, DURATION: This was a retrospective observational cohort study. Original cohorts had been recruited for previous studies between 1998 and 2010. Two hundred ninety-seven regularly cycling women and 700 women with PCOS were eligible for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cluster analysis was performed in 297 regularly cycling women. After exclusion of 'PCOM' clusters, each 'non-PCOM' cluster (young, n = 118 and old, n = 100) was included in the construction of a receiver operating characteristics curve to test the diagnostic performance of follicle number per ovary (FNPO) and serum AMH in discriminating similarly aged full-blown PCOS patients (n = 411 and 237, respectively) from normal regularly cycling non-PCOM women. MAIN RESULTS AND ROLE OF CHANCE: The optimal number of clusters was four; age was the most important classifying variable, followed by the FNPO and serum AMH. Two distinct clusters of normo-ovulatory women with PCOM were isolated and differed solely by age, i.e. 'young' and 'old'. Both 'PCOM' clusters had their similarly aged counterpart of 'non-PCOM' clusters. Likewise, two clusters comprised women younger than 30 years, with (n = 28, 'PCOM regularly cycling women') or without (n = 118, 'normal regularly cycling women') features of PCOM (increased FNPO and/or serum AMH). The two other clusters in older women could be labelled 'normal regularly cycling women' or 'PCOM regularly cycling women' (n = 100 and 51, respectively). The prevalence of PCOM was significantly greater in old than in young regularly cycling women controls. In the young population, after exclusion of the 'PCOM regularly cycling women', the diagnostic performance of AMH, expressed by area under the curve (AUC) (AUC = 0.903; CI (0.876-0.930)) to differentiate PCOS women from normal regularly cycling women was similar to that using the FNPO (AUC = 0.915, CI (0.891-0.940)) (P = 0.25), confirming results from earlier studies. In the old population, the diagnostic performance of AMH was greater than that of FNPO (AUCs = 0.948 (0.927-0.970) vs 0.874 (0.836-0.912), respectively, P = 0.00035). Cut-off levels of AMH and antral follicle count distinguishing regularly cycling non-PCOM women from PCOS women were higher in young women than in older women. LIMITATIONS, REASONS FOR CAUTION: Data of normal women were obtained from earlier studies, aiming to measure normal endocrine values. Apparently, the strong effect of age in cluster analysis revealed a dichotomy in the age distribution among the cohort of regularly cycling women included. This was involuntary since in none of the original studies, eligibility was limited by age and there was considerable overlap in age ranges of the cohorts. Transvaginal ultrasound was performed using a 6.5-8 mHz probe and our data confirm that this threshold level for FNPO is still valid if using such probe frequencies, although the use of devices with a maximum frequency lower than 8 mHz has become obsolete. Obviously, newer ultrasound scanner using higher transducer frequency will facilitate the detection of more follicles. WIDER IMPLICATIONS OF THE FINDINGS: Our data support the use of AMH as a surrogate for ultrasound to define PCOM, which is one of the three items of the Rotterdam classification. They also show that age should be taken into account to define the optimal threshold. The fact that the prevalence of PCOM was increased in the older regularly cycling women, may be due to 'attenuated' PCOS, a phenomenon that has been described in ageing women with PCOS. These women might have had anovulatory cycles in the past and have become ovulatory with increasing age, and were, therefore, eligible for this study. However, since most women included at older age have had spontaneous pregnancies in the past, PCOM at older age may be associated with a subclinical form of PCOS, which may also be present in young regularly cycling women. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. J.S.E.L. has received grants and support from Ferring, MSD, Organon, Merck-Serono, Schering Plough and Serono during recruitment and analysis of data for this study. S.L.F., A.D. and D.D. do not have any conflict of interest.
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Hormona Antimülleriana/sangre , Ovario/diagnóstico por imagen , Síndrome del Ovario Poliquístico/diagnóstico , Adulto , Femenino , Humanos , Ciclo Menstrual , Folículo Ovárico/diagnóstico por imagen , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/diagnóstico por imagen , Estudios Retrospectivos , Ultrasonografía , Adulto JovenRESUMEN
Exposure to maternal diabetes during fetal growth is a risk factor for the development of type II diabetes (T2D) in later life. Discovery of the mechanisms involved in this association should provide valuable background for therapeutic treatments. Early embryogenesis involves epigenetic changes including histone modifications. The bivalent histone methylation marks H3K4me3 and H3K27me3 are important for regulating key developmental genes during early fetal pancreas specification. We hypothesized that maternal hyperglycemia disrupted early pancreas development through changes in histone bivalency. A human embryonic stem cell line (VAL3) was used as the cell model for studying the effects of hyperglycemia upon differentiation into definitive endoderm (DE), an early stage of the pancreatic lineage. Hyperglycemic conditions significantly down-regulated the expression levels of DE markers SOX17, FOXA2, CXCR4 and EOMES during differentiation. This was associated with retention of the repressive histone methylation mark H3K27me3 on their promoters under hyperglycemic conditions. The disruption of histone methylation patterns was observed as early as the mesendoderm stage, with Wnt/ß-catenin signaling being suppressed during hyperglycemia. Treatment with Wnt/ß-catenin signaling activator CHIR-99021 restored the expression levels and chromatin methylation status of DE markers, even in a hyperglycemic environment. The disruption of DE development was also found in mouse embryos at day 7.5 post coitum from diabetic mothers. Furthermore, disruption of DE differentiation in VAL3 cells led to subsequent impairment in pancreatic progenitor formation. Thus, early exposure to hyperglycemic conditions hinders DE development with a possible relationship to the later impairment of pancreas specification.
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Diferenciación Celular , Endodermo/citología , Histonas/metabolismo , Hiperglucemia/embriología , Páncreas/embriología , Animales , Antígenos de Diferenciación/genética , Antígenos de Diferenciación/metabolismo , Azacitidina/farmacología , Línea Celular , Linaje de la Célula , Metilasas de Modificación del ADN/antagonistas & inhibidores , Metilasas de Modificación del ADN/metabolismo , Endodermo/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Inhibidores Enzimáticos/farmacología , Femenino , Regulación del Desarrollo de la Expresión Génica , Glucosa/farmacología , Humanos , Hiperglucemia/metabolismo , Masculino , Mesodermo/metabolismo , Metilación , Ratones , Ratones Endogámicos ICR , Páncreas/citología , Páncreas/metabolismo , Regiones Promotoras Genéticas , Transducción de Señal , Proteínas Wnt/metabolismo , beta Catenina/metabolismoRESUMEN
BACKGROUND AND PURPOSE: Emerging research suggests the use of self-regulation (SR) for improving functional regain in patients post stroke. SR is proposed to produce an added effect to effective modified constraint-induced movement therapy (mCIMT). This study aimed to examine the effect of a self-regulated mCIMT programme (SR-mCIMT) for functional regain in patients with sub-acute stroke. METHODS: Eighty-six patients completed the trial: SR-mCIMT, n = 29; mCIMT, n = 31; or conventional functional rehabilitation, n = 26. All interventions were 2-week therapist-guided training. Outcome measurements, taken by a blinded assessor, examined arm function [Action Research Arm Test (ARAT), Fugl-Meyer Assessment (FMA)], daily task performance [Lawton Instrumental Activities of Daily Living Scale (Lawton IADL)] and self-perceived arm use in functional tasks [Motor Activity Log (MAL)]. RESULTS: Significant differences were found with the SR-mCIMT outperforming the other groups after the intervention (ARAT, P = 0.006; FMA, Lawton IADL and MAL, all Ps < 0.001). In terms of the carry-over effect, the SR-mCIMT group outperformed in the hand and coordination subscales of ARAT and FMA (P = 0.012-0.013) and the self-perceived quality of arm use (P = 0.002). CONCLUSION: A combination of SR and mCIMT could produce an added effect in functional regain in patients post stroke.
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Actividades Cotidianas , Modalidades de Fisioterapia , Autocontrol , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular/fisiopatología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuperación de la Función/fisiología , Resultado del TratamientoRESUMEN
AIM: It is controversial whether a high or low ligation of the inferior mesenteric artery (IMA) is superior. The former allows an extended lymph node clearance whereas the latter preserves the distal vascular supply via the left colic artery (LCA). Apical lymph node dissection of the IMA (ALMA) harvests nodal tissue along the IMA proximal to the LCA whilst performing a low ligation. This anatomically replicates the oncological benefit of high ligation and the vascular preservation of low ligation. Our study evaluates the nodal yield of ALMA and the short-term outcome of this technique. METHOD: We retrospectively studied 19 patients with sigmoid or rectal cancer who underwent curative surgical resection with ALMA. All ALMAs were performed with a standard technique previously described (Kobayashi et al., Surg Endosc 2005, 20:563-9; Sekimoto et al. Surg Endosc 2010, 25:861-6) . The lymph node yield from the dissection (the ALMA specimen) was compared with the total lymph node yield. Data on the LCA anatomy, time required to perform ALMA, complications and postoperative recovery were evaluated. RESULTS: ALMA was successful in 18 patients. Median postoperative hospitalization was 5 (2-26) days without ALMA-related morbidity or mortality. The median lymph node yield was 20 (9-41) and a median of 14.3 (0-80)% were harvested with ALMA. Two patients not having neoadjuvant chemoradiotherapy had fewer than 12 lymph nodes, excluding nodes harvested from ALMA. The average time required for ALMA was 18 min. CONCLUSION: ALMA is a safe and feasible technique, allowing extended lymphadenectomy without sacrificing the LCA. In this small group of patients none were upstaged due to cancerous involvement of the proximal nodes.
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Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Arteria Mesentérica Inferior/cirugía , Neoplasias del Recto/cirugía , Neoplasias del Colon Sigmoide/cirugía , Anciano , Colon/irrigación sanguínea , Colon/cirugía , Femenino , Humanos , Ligadura , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias del Recto/patología , Estudios Retrospectivos , Neoplasias del Colon Sigmoide/patología , Resultado del TratamientoRESUMEN
INTRODUCTION: To evaluate the effectiveness of teledietetics in weight loss for 24 weeks and the cost-effectiveness of weight loss between face-to-face and teledietetics services. METHODS: The study was conducted at a community health center and a community dietetics clinic. The study was a quasiexperimental design. Fifty adults aged 20-50 with a BMI ≥23 participated in the study. The face-to-face (FD) group received 12 dietary counselling sessions and recorded their diet in a log book. The teledietetics (TD) group attended three group nutrition seminars and recorded their diet on a Web-based platform. Changes in variables were compared using an independent t-test. Direct and indirect costs were applied to compute cost-effectiveness ratios. RESULTS: At week 6, the FD group showed greater reductions in all variables than did the TD group. At week 12, the effects reversed. At week 24, the accumulated reductions in weight and fat in the TD group were significantly higher than those in the FD group (all at p < 0.0001). The observed direct costs for 1% weight loss and 1% fat loss were USD 28.24 and USD17.09, respectively. DISCUSSION: A dietetic service delivered as a teledietetics model is more cost-effective than the face-to-face dietetics model in weight reduction.