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1.
N Engl J Med ; 387(23): 2113-2125, 2022 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-36477031

RESUMEN

BACKGROUND: Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma. METHODS: In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body weight). Infusion of at least 5×109 TILs was preceded by nonmyeloablative, lymphodepleting chemotherapy (cyclophosphamide plus fludarabine) and followed by high-dose interleukin-2. The primary end point was progression-free survival. RESULTS: A total of 168 patients (86% with disease refractory to anti-programmed death 1 treatment) were assigned to receive TILs (84 patients) or ipilimumab (84 patients). In the intention-to-treat population, median progression-free survival was 7.2 months (95% confidence interval [CI], 4.2 to 13.1) in the TIL group and 3.1 months (95% CI, 3.0 to 4.3) in the ipilimumab group (hazard ratio for progression or death, 0.50; 95% CI, 0.35 to 0.72; P<0.001); 49% (95% CI, 38 to 60) and 21% (95% CI, 13 to 32) of the patients, respectively, had an objective response. Median overall survival was 25.8 months (95% CI, 18.2 to not reached) in the TIL group and 18.9 months (95% CI, 13.8 to 32.6) in the ipilimumab group. Treatment-related adverse events of grade 3 or higher occurred in all patients who received TILs and in 57% of those who received ipilimumab; in the TIL group, these events were mainly chemotherapy-related myelosuppression. CONCLUSIONS: In patients with advanced melanoma, progression-free survival was significantly longer among those who received TIL therapy than among those who received ipilimumab. (Funded by the Dutch Cancer Society and others; ClinicalTrials.gov number, NCT02278887.).


Asunto(s)
Inmunoterapia Adoptiva , Linfocitos Infiltrantes de Tumor , Melanoma , Humanos , Tratamiento Basado en Trasplante de Células y Tejidos , Ipilimumab/efectos adversos , Melanoma/tratamiento farmacológico
2.
Mycopathologia ; 189(4): 50, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38864903

RESUMEN

Aspergillus fumigatus is a saprophytic fungal pathogen that causes opportunistic infections in animals and humans. Azole resistance has been reported globally in human A. fumigatus isolates, but the prevalence of resistance in isolates from animals is largely unknown. A retrospective resistance surveillance study was performed using a collection of clinical A. fumigatus isolates from various animal species collected between 2015 and 2020. Agar-based azole resistance screening of all isolates was followed by in vitro antifungal susceptibility testing and cyp51A gene sequencing of the azole-resistant isolates. Over the 5 year period 16 (11.3%) of 142 A. fumigatus culture-positive animals harbored an azole-resistant isolate. Resistant isolates were found in birds (15%; 2/13), cats (21%; 6/28), dogs (8%; 6/75) and free-ranging harbor porpoise (33%; 2/6). Azole-resistance was cyp51A mediated in all isolates: 81.3% (T-67G/)TR34/L98H, 12.5% TR46/Y121F/T289A. In one azole-resistant A. fumigatus isolate a combination of C(-70)T/F46Y/C(intron7)T/C(intron66)T/M172V/E427K single-nucleotide polymorphisms in the cyp51A gene was found. Of the animals with an azole-resistant isolate and known azole exposure status 71.4% (10/14) were azole naive. Azole resistance in A. fumigatus isolates from animals in the Netherlands is present and predominantly cyp51A TR-mediated, supporting an environmental route of resistance selection. Our data supports the need to include veterinary isolates in resistance surveillance programs. Veterinarians should consider azole resistance as a reason for therapy failure when treating aspergillosis and consider resistance testing of relevant isolates.


Asunto(s)
Antifúngicos , Aspergilosis , Aspergillus fumigatus , Azoles , Farmacorresistencia Fúngica , Pruebas de Sensibilidad Microbiana , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/genética , Aspergillus fumigatus/aislamiento & purificación , Animales , Azoles/farmacología , Farmacorresistencia Fúngica/genética , Aspergilosis/microbiología , Aspergilosis/veterinaria , Antifúngicos/farmacología , Países Bajos/epidemiología , Estudios Retrospectivos , Proteínas Fúngicas/genética , Aves/microbiología , Gatos , Perros , Sistema Enzimático del Citocromo P-450
3.
Emerg Infect Dis ; 27(7): 1783-1788, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34152959

RESUMEN

Brucella canis had not been isolated in the Netherlands until November 2016, when it was isolated from a dog imported from Romania. Including this case, 16 suspected cases were notified to the authorities during the following 25 months. Of these 16 dogs, 10 were seropositive; tracking investigations found another 8 seropositive littermates. All seropositive animals were rescue dogs imported from Eastern Europe. B. canis was cultured from urine, blood, and other specimens collected from the dogs. Genotyping of isolates revealed clustering by litter and country. Isolating B. canis in urine indicates that shedding should be considered when assessing the risk for zoonotic transmission. This case series proves introduction of B. canis into a country to which it is not endemic through import of infected dogs from B. canis-endemic areas, posing a threat to the naive autochthonous dog population and humans.


Asunto(s)
Brucella canis , Brucelosis , Enfermedades de los Perros , Animales , Perros , Europa Oriental , Países Bajos , Rumanía
4.
Hum Reprod ; 36(4): 1120-1133, 2021 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-33582778

RESUMEN

STUDY QUESTION: Do genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)? SUMMARY ANSWER: Female CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy. WHAT IS KNOWN ALREADY: Female CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability. STUDY DESIGN, SIZE, DURATION: CCS for the discovery cohort were identified from the Dutch Childhood Oncology Group (DCOG) LATER VEVO-study, a multi-centre retrospective cohort study evaluating fertility, ovarian reserve and risk of premature menopause among adult female 5-year survivors of childhood cancer. Female 5-year CCS, diagnosed with cancer and treated with chemotherapy before the age of 25 years, and aged 18 years or older at time of study were enrolled in the current study. Results from the discovery Dutch DCOG-LATER VEVO cohort (n = 285) were validated in the pan-European PanCareLIFE (n = 465) and the USA-based St. Jude Lifetime Cohort (n = 391). PARTICIPANTS/MATERIALS, SETTING, METHODS: To evaluate ovarian function, anti-Müllerian hormone (AMH) levels were assessed in both the discovery cohort and the replication cohorts. Using additive genetic models in linear and logistic regression, five genetic variants involved in DNA damage response were analysed in relation to cyclophosphamide equivalent dose (CED) score and their impact on ovarian function. Results were then examined using fixed-effect meta-analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Meta-analysis across the three independent cohorts showed a significant interaction effect (P = 3.0 × 10-4) between rs11668344 of BRSK1 (allele frequency = 0.34) among CCS treated with high-dose alkylating agents (CED score ≥8000 mg/m2), resulting in a 2.5-fold increased odds of a reduced ovarian function (lowest AMH tertile) for CCS carrying one G allele compared to CCS without this allele (odds ratio genotype AA: 2.01 vs AG: 5.00). LIMITATIONS, REASONS FOR CAUTION: While low AMH levels can also identify poor responders in assisted reproductive technology, it needs to be emphasized that AMH remains a surrogate marker of ovarian function. WIDER IMPLICATIONS OF THE FINDINGS: Further research, validating our findings and identifying additional risk-contributing genetic variants, may enable individualized counselling regarding treatment-related risks and necessity of fertility preservation procedures in girls with cancer. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the PanCareLIFE project that has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602030. In addition, the DCOG-LATER VEVO study was funded by the Dutch Cancer Society (Grant no. VU 2006-3622) and by the Children Cancer Free Foundation (Project no. 20) and the St Jude Lifetime cohort study by NCI U01 CA195547. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Reserva Ovárica , Adolescente , Adulto , Hormona Antimülleriana/genética , Niño , Estudios de Cohortes , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular , Ovario , Proteínas Serina-Treonina Quinasas , Estudios Retrospectivos
5.
Pediatr Blood Cancer ; 68(4): e28894, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33459500

RESUMEN

BACKGROUND: The aim was to evaluate self-reported reproductive characteristics and markers of ovarian function in a nationwide cohort of female survivors of childhood acute lymphoblastic leukemia (ALL), because prior investigations have produced conflicting data. PROCEDURE: Self-reported reproductive characteristics were assessed by questionnaire among 357 adult 5-year survivors, treated between 1964 and 2002, and 836 controls. Ovarian function was assessed by serum levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B and by antral follicle count (AFC). Differences between controls and (subgroups of) survivors (total group, chemotherapy [CT]-only group, CT and radiotherapy [RT] group) were analyzed. RESULTS: Survivors treated with CT only do not differ from controls regarding timing of menarche, virginity status, desire for children, or pregnancy rates. Compared to controls, the CT+RT group was at significantly increased risk of a younger age at menarche (P < .01), virginity, an absent desire for children, and lower pregnancy rates (odds ratio [OR] [95% CI]: 0.3 [CI 0.1-0.6], 0.5 [0.3-0.9], and 0.4 [0.2-0.9], respectively). Survivors in the CT-only group were significantly younger at the birth of their first child. Pregnancy outcomes were not significantly different between any (sub)groups. Survivors treated with total body irradiation (TBI) or hematopoietic stem cell transplantation (HSCT) are at increased risk of abnormal markers of ovarian function. CONCLUSION: Reproductive function of ALL survivors treated with CT only does not differ from controls. However, survivors additionally treated with RT seem to be at an increased risk of certain adverse reproductive outcomes. Providing personalized counseling about (future) reproductive health risks in this group is imperative.


Asunto(s)
Fertilidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Hormona Antimülleriana/sangre , Supervivientes de Cáncer , Niño , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Menarquia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Embarazo , Salud Reproductiva , Estudios Retrospectivos
6.
J Adolesc ; 76: 75-87, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31472428

RESUMEN

INTRODUCTION: In the past, stressful life events have been consistently linked to developmental outcomes such as well-being and psychopathological problems. Theory on identity postulates that stressful life events may also predict a regression in identity development. While some support for this link has been found in adult populations, it is important to examine this in adolescence, a time marked by identity development as well as stressful transitions and experiences. METHODS: In the present study, we examined whether having to repeat a grade and death of a family member or friend were related to regressive change in educational and relational identity in a sample of 840 Dutch adolescents (49% female, Mage W1 = 12.4) drawn from a large ongoing longitudinal study. We also investigated whether the impact of the events was moderated by neuroticism, and parental and peer support. All analyses were controlled for age, educational level, and sex. RESULTS: Results of latent difference score models indicated that experiencing an event did not predict regressions in identity. Congruence between the domain of the event and identity (i.e., educational or relational) did not affect the strength of the effects. Neuroticism and parental and peer support did not significantly moderate this link. However, social support was related to relational and educational identity. CONCLUSIONS: The link between stressful events and identity may not be as straightforward as would be expected based on identity theory, as our results did not show evidence for a link between these events and change in identity for all adolescents.


Asunto(s)
Desarrollo del Adolescente , Autoimagen , Apoyo Social , Estrés Psicológico/psicología , Adolescente , Niño , Femenino , Humanos , Acontecimientos que Cambian la Vida , Estudios Longitudinales , Masculino , Neuroticismo
7.
Emerg Infect Dis ; 24(6): 1127-1129, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29774845

RESUMEN

A Brucella suis biovar 1 infection was diagnosed in a dog without typical exposure risks, but the dog had been fed a raw meat-based diet (hare carcasses imported from Argentina). Track and trace investigations revealed that the most likely source of infection was the dog's raw meat diet.


Asunto(s)
Alimentación Animal/microbiología , Brucella suis , Brucelosis/veterinaria , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/microbiología , Carne/microbiología , Animales , Brucella suis/clasificación , Brucella suis/genética , Enfermedades de los Perros/transmisión , Perros , Genes Bacterianos , Genotipo , Humanos , Tipificación de Secuencias Multilocus , Países Bajos/epidemiología , Filogenia
8.
Child Dev ; 88(6): 1823-1833, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28849587

RESUMEN

This study examined reciprocal associations between adolescents' self-concept clarity (SCC) and their relationship quality with parents and best friends in a five-wave longitudinal study from age 13 to 18 years. In all, 497 adolescents (57% boys) reported on their SCC and all informants (i.e., adolescents, both parents, and adolescents' best friends) reported on support and negative interaction. Within-person cross-lagged analyses provided systematic evidence for both parent effects and child effects, with the direction of effects being strongly dependent on the relational context. For example, higher maternal support predicted higher adolescent SCC, supporting a parent effects perspective, whereas higher SCC predicted lower paternal negative interaction, supporting a child effects perspective. Peer effects on adolescent SCC were not consistently found across adolescent and best friend reports.


Asunto(s)
Desarrollo del Adolescente , Amigos/psicología , Relaciones Interpersonales , Relaciones Padres-Hijo , Grupo Paritario , Autoimagen , Apoyo Social , Adolescente , Femenino , Humanos , Estudios Longitudinales , Masculino
9.
BMC Vet Res ; 12(1): 213, 2016 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-27658466

RESUMEN

BACKGROUND: There is a growing concern regarding the increase of antimicrobial resistant bacteria in companion animals. Yet, there are no studies comparing the resistance levels of these organisms in European countries. The aim of this study was to investigate geographical and temporal trends of antimicrobial resistant bacteria causing urinary tract infection (UTI) in companion animals in Europe. The antimicrobial susceptibility of 22 256 bacteria isolated from dogs and cats with UTI was determined. Samples were collected between 2008 and 2013 from 16 laboratories of 14 European countries. The prevalence of antimicrobial resistance of the most common bacteria was determined for each country individually in the years 2012-2013 and temporal trends of bacteria resistance were established by logistic regression. RESULTS: The aetiology of uropathogenic bacteria differed between dogs and cats. For all bacterial species, Southern countries generally presented higher levels of antimicrobial resistance compared to Northern countries. Multidrug-resistant Escherichia coli were found to be more prevalent in Southern countries. During the study period, the level of fluoroquinolone-resistant E. coli isolated in Belgium, Denmark, France and the Netherlands decreased significantly. A temporal increase in resistance to amoxicillin-clavulanate and gentamicin was observed among E. coli isolates from the Netherlands and Switzerland, respectively. Other country-specific temporal increases were observed for fluoroquinolone-resistant Proteus spp. isolated from companion animals from Belgium. CONCLUSIONS: This work brings new insights into the current status of antimicrobial resistance in bacteria isolated from companion animals with UTI in Europe and reinforces the need for strategies aiming to reduce resistance.

10.
BMC Fam Pract ; 16: 132, 2015 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-26452756

RESUMEN

BACKGROUND: Child and adolescent mental health problems are frequently not identified and properly treated within general practice. Politicians in the Netherlands are promoting more primary healthcare treatment for mental health problems. The current study aims to evaluate an integrated primary mental healthcare approach for child and adolescent emotional and behavioural problems. This integrated approach allows general practitioners (GPs) to comprehensively explore the request for help, followed by an informed decision to refer, offer short-term treatment within general practice or postpone a decision by asking for additional consultations with youth mental health specialists. METHOD: The study is a naturalistic evaluation of Dutch general practices with pre-test and post-test comparison with controls based on data from Electronic Medical Records (EMR). The intervention started in September 2010. EMR data of all GP contacts with children aged 4 to 18 (including diagnosis, prescriptions, referrals) from practices involved in the intervention was used from 1 January 2009 to 31 December 2012. Extra codes were added to the EMR to record aspects of the intervention. Comparable EMR data was used in control practices in 2011. RESULTS: GPs in the intervention group were able to identify more emotional and behavioural problems after the integrated service had started. They also identified more problems than GPs in the control practices. They were already reluctant to prescribe psychopharmacological medication to children before the intervention, and levels of prescription at intervention GP practices remained low for psychotropic drugs compared to control practices. Referral rates to mental healthcare remained relatively steady after the introduction of the integrated service, but referrals switched from specialized to primary mental healthcare. CONCLUSION: An integrated mental healthcare approach within general practice may lead to an increase in detected psychosocial problems among children, and these problems can mainly be treated within the primary care setting.


Asunto(s)
Medicina General/métodos , Trastornos Mentales/diagnóstico , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/terapia , Países Bajos , Rol del Médico , Psicotrópicos/uso terapéutico , Derivación y Consulta
11.
J Youth Adolesc ; 43(11): 1861-76, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24272819

RESUMEN

Higher self-concept clarity is related to several adjustment indices and may be promoted by open communication with parents, while problems with self-concept clarity development could enhance internalizing problems (i.e., depressive and anxiety symptoms) in adolescence. This longitudinal study examined linkages between self-concept clarity, adolescents' open communication with parents, and adolescent depressive and anxiety symptoms. Dutch youths (N = 323; 51.1 % girls; mean age Time 1 = 13.3 years) reported on these constructs over four consecutive annual measurements. Concurrent positive links between open communication and self-concept clarity were found at Time 1. Over time, higher levels of open communication with parents predicted higher self-concept clarity only in middle adolescence (mean age between 14 and 15 years). We also found concurrent associations between self-concept clarity and both depressive and anxiety symptoms. Longitudinally, lower self-concept clarity predicted relatively higher levels of depressive symptoms across all waves, and also higher anxiety levels from Time 1 to Time 2. Conversely, higher levels of anxiety also predicted lower levels of self-concept clarity during the first three waves. Self-concept clarity did not mediate the longitudinal associations between open communication and internalizing symptoms. This study is one of the first to investigate self-concept clarity across adolescence. It highlights the possible importance of both anxiety symptoms and communication with parents in understanding the development of a clear self-concept, and demonstrates an association between lower self-concept clarity and higher levels of later depressive and anxiety symptoms.


Asunto(s)
Conducta del Adolescente/psicología , Ansiedad/epidemiología , Depresión/epidemiología , Control Interno-Externo , Psicología del Adolescente , Autoimagen , Adolescente , Desarrollo del Adolescente , Femenino , Humanos , Estudios Longitudinales , Masculino , Países Bajos/epidemiología , Relaciones Padres-Hijo , Identificación Social
12.
J Med Microbiol ; 72(2)2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36763079

RESUMEN

Introduction. Staphylococcus felis is a coagulase-negative staphylococcal species that is commonly isolated from healthy cats. Like other commensal staphylococci, S. felis can cause opportunistic infections, e.g. otitis externa, skin and urinary tract infections, in cats.Gap Statement. Several studies have reported within-household transmission between humans and pets and human infections caused by coagulase-positive staphylococci. However, human infections with coagulase-negative staphylococci of zoonotic origin are relatively rare.Methodology. Culture of a surgical site infection in a 58-year-old woman who underwent a laminectomy revealed dominant growth of S. felis. The three cats owned by the patient were sampled to investigate potential within-household transmission. S. felis isolates were sequenced to investigate the relatedness of the isolates and to look for virulence factors and host specific genes.Results. All cats were colonized with S. felis. Comparative genomics of the isolates showed that each cat was colonized with a distinct genotype. The patient's isolate clustered with isolates of one of the cats. Sequence analysis of the studied isolates together with 29 publicly available S. felis genomes detected putative virulence factors that can be crucial in potential interspecies transmission.Conclusion. The current case is the first reported human infection caused by S. felis and highlights the zoonotic potential of this bacterial species. Evidence of cat-to-human transmission was shown by comparative genomics of isolates from the patient with isolates of her cats.


Asunto(s)
Enfermedades de los Gatos , Felis , Infecciones Estafilocócicas , Humanos , Femenino , Gatos , Animales , Persona de Mediana Edad , Coagulasa , Staphylococcus , Factores de Virulencia/genética , Infecciones Estafilocócicas/veterinaria , Infecciones Estafilocócicas/microbiología
13.
J Intell ; 8(4)2020 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-33086568

RESUMEN

Taking a perception-action perspective, we investigated how the presence of different real objects in children's immediate situation affected their creativity and whether this effect was moderated by their selective attention. Seventy children between ages 9 and 12 years old participated. Verbal responses on a visual Alternative Uses Task with a low stimulus and high stimulus condition were coded on fluency, flexibility, and originality. Selective attention was measured with a visual search task. Results showed that fluency was not affected by stimulus condition and was unrelated to selective attention. Flexibility was positively associated with selective attention. Originality, net of fluency and flexibility, showed a main effect of stimulus condition in an unexpected direction, as children gave more original responses in the low stimulus condition compared to the high stimulus condition. A significant moderation effect revealed that children with better selective attention skills benefitted from a low stimulus environment, whereas children with weaker selective attention performed better in a high stimulus environment. The findings demonstrate differential effects of the immediate situation and selective attention, and support the hypothesis that creativity is impacted by immediate situation and selective attention, yet in unexpected ways.

14.
Front Vet Sci ; 6: 158, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31192236

RESUMEN

Antimicrobial resistance (AMR) is an increasing threat, both in human and in veterinary medicine. To reduce the selection and spread of AMR, antimicrobial use (AMU) should be optimized, also in companion animals. To be able to optimize AMU, a feasible method to quantify AMU and information on current AMU are needed. Therefore, a method to quantify AMU was developed, using the number of Defined Daily Doses Animal (DDDA). This method was used to explore applied antimicrobial classes and to identify differences in prescribing patterns in time and between veterinary clinics. Antimicrobial procurement data of the years 2012-2014 were collected retrospectively from 100 Dutch veterinary clinics providing care for companion animals. The mean number of DDDAs per clinic per year decreased significantly from 2012 to 2014. A shift in used classes of antimicrobials (AMs) was seen as well, with a significant decrease in use of third choice AMs (i.e., fluoroquinolones and third generation cephalosporins). Large differences in total AMU were seen between clinics ranging from 64-fold in 2012 to 20-fold in 2014. Despite the relative low and decreasing AMU in Dutch companion animal clinics during the study, the substantial differences in antimicrobial prescribing practices between clinics suggest that there is still room for quantitative and qualitative optimization of AMU.

15.
Fertil Steril ; 111(2): 372-380, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30691634

RESUMEN

OBJECTIVE: To evaluate whether abdominal-pelvic radiotherapy for childhood cancer impairs uterine function and increases the risk of pregnancy complications and adverse pregnancy outcomes. DESIGN: Nested cohort study. SETTING: Not applicable. PATIENT(S): Childhood cancer survivors previously exposed to abdominal-pelvic radiotherapy (RT-exposed CCSs) as part of their treatment for childhood cancer. INTERVENTION(S): Radiotherapy-exposed CCSs (n = 55) were age- and parity-matched to nonirradiated CCSs (non-RT-exposed CCSs; n = 110) and general population controls (n = 110). MAIN OUTCOME MEASURES: Uterine volume, pregnancy complications, and pregnancy outcomes. RESULT(S): Among nulligravidous participants, median (interquartile range) uterine volume was 41.4 (18.6-52.8) mL for RT-exposed CCSs, 48.1 (35.7-61.8) mL for non-RT-exposed CCSs, and 61.3 (49.1-75.5) mL for general population controls. Radiotherapy-exposed CCSs were at increased risk of a reduced uterine volume (<44.3 mL) compared with population controls (odds ratio [OR] 5.31 [95% confidence interval 1.98-14.23]). Surprisingly, the same was true for non-RT-exposed CCSs (OR 2.61 [1.16-5.91]). Among gravidous participants, RT-exposed CCSs had increased risks of pregnancy complications, preterm delivery, and a low birth weight infant compared with population controls (OR 12.70 [2.55-63.40], OR 9.74 [1.49-63.60], and OR 15.66 [1.43-171.35], respectively). Compared with non-RT-exposed CCSs, RT-exposed CCSs were at increased risk of delivering a low birth weight infant (OR 6.86 [1.08-43.75]). CONCLUSION(S): Uterine exposure to radiotherapy during childhood reduces adult uterine volume and leads to an increased risk of pregnancy complications and adverse pregnancy outcomes. Preconceptional counseling and appropriate obstetric monitoring is warranted.


Asunto(s)
Neoplasias/radioterapia , Complicaciones del Embarazo/etiología , Traumatismos por Radiación/etiología , Salud Reproductiva , Sobrevivientes , Útero/efectos de la radiación , Adulto , Edad de Inicio , Femenino , Humanos , Neoplasias/patología , Paridad , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/fisiopatología , Resultado del Embarazo , Traumatismos por Radiación/diagnóstico , Traumatismos por Radiación/fisiopatología , Radioterapia/efectos adversos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Útero/diagnóstico por imagen , Útero/fisiopatología , Adulto Joven
16.
JMIR Res Protoc ; 7(9): e10824, 2018 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-30215599

RESUMEN

BACKGROUND: Despite a significant number of studies on female fertility following childhood, adolescent, and young adult (CAYA) cancer, studies establishing precise (dose-related) estimates of treatment-related risks are still scarce. Previous studies have been underpowered, did not include detailed treatment information, or were based on self-report only without any hormonal assessments. More precise assessments of who is at risk for sub- or infertility are needed. OBJECTIVE: The objective of our study is to describe the design and methods of 2 studies on female fertility (a cohort study and a nested case-control study) among female survivors of CAYA cancer performed within the European PanCareLIFE project. METHODS: For the cohort study, which aims to evaluate the overall risk of fertility impairment, as well as the risk for specific subgroups of female CAYA cancer survivors, 13 institutions from 9 countries provide data on fertility impairment. Survivors are defined as being fertility impaired if they meet at least one of 8 different criteria based on self-reported and hormonal data. For the nested case-control study, which aims to identify specific treatment-related risk factors associated with fertility impairment in addition to possible dose-response relationships, cases (fertility impaired survivors) are selected from the cohort study and matched to controls (survivors without fertility impairment) on a 1:2 basis. RESULTS: Of the 10,964 survivors invited for the cohort study, data are available from 6619 survivors, either questionnaire-based only (n=4979), hormonal-based only (n=72), or both (n=1568). For the nested case-control study, a total of 450 cases and 882 controls are identified. CONCLUSIONS: Results of both PanCareLIFE fertility studies will provide detailed insight into the risk of fertility impairment following CAYA cancer and diagnostic- or treatment-related factors associated with an increased risk. This will help clinicians to adequately counsel both girls and young women, who are about to start anticancer treatment, as well as adult female CAYA cancer survivors, concerning future parenthood and to timely refer them for fertility preservation. Ultimately, we aim to empower patients and survivors and improve their quality of life. REGISTERED REPORT IDENTIFIER: RR1-10.2196/10824.

17.
Int J Pharm Pract ; 24(1): 13-21, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25988371

RESUMEN

OBJECTIVE: The objectives of this study were to, first, describe the information exchanged between pharmacy staff and patients about prescribed medication at the community pharmacy counter, and second, to investigate to what extent this met professional medication counselling guidelines. METHODS: Pharmaceutical encounters were videotaped in four community pharmacies in the Netherlands. Patients were included if they collected a prescription for their own use. An observation protocol, including the MEDICODE checklist, was used to analyse the video recordings. A distinction was made between first and repeat prescriptions. KEY FINDINGS: One hundred fifty-three encounters were videotaped. When dispensing first prescriptions, pharmacy staff provided most information on instructions how to use the medication (83.3%), form of the medication (71.4%) and treatment duration (42.9%). Topics for repeat prescriptions (such as the effects of the medication and the incidence of observed adverse effects) were rarely discussed. Pharmacy staff rarely encouraged patients to ask questions. CONCLUSIONS: Pharmacy staff members provided little medication-related information at the counter, especially for repeat prescriptions, did not encourage active patient participation, and thereby did not adhere to the guidelines of their professional organisation. Further research is needed to understand the reasons for this.


Asunto(s)
Comunicación , Servicios Comunitarios de Farmacia/organización & administración , Educación del Paciente como Asunto/métodos , Farmacéuticos/organización & administración , Adolescente , Adulto , Anciano , Femenino , Adhesión a Directriz , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Guías de Práctica Clínica como Asunto , Medicamentos bajo Prescripción/administración & dosificación , Adulto Joven
18.
Patient Educ Couns ; 98(7): 843-8, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25825256

RESUMEN

OBJECTIVE: To describe communication between pharmacy staff and patients at the counter in outpatient pharmacies. Both content and communication style were investigated. METHODS: Pharmaceutical encounters in three outpatient pharmacies in the Netherlands were video-recorded. Videos were analyzed based on an observation protocol for the following information: content of encounter, initiator of a theme and pharmacy staff's communication style. RESULTS: In total, 119 encounters were recorded which concerned 42 first prescriptions, 16 first refill prescriptions and 61 follow-up refill prescriptions. During all encounters, discussion was mostly initiated by pharmacy staff (85%). In first prescription encounters topics most frequently discussed included instructions for use (83%) and dosage instructions (95%). In first refill encounters, patient experiences such as adverse effects (44%) and beneficial effects (38%) were regularly discussed in contrast to follow-up refills (7% and 5%). Patients' opinion on medication was hardly discussed. CONCLUSION: Pharmacy staff in outpatient pharmacies generally provide practical information, less frequently they discuss patients' experiences and seldom discuss patients' perceptions and preferences about prescribed medication. PRACTICE IMPLICATIONS: This study shows there is room for improvement, as communication is still not according to professional guidelines. To implement professional guidelines successfully, it is necessary to identify underlying reasons for not following the guidelines.


Asunto(s)
Comunicación , Servicios Comunitarios de Farmacia/organización & administración , Educación del Paciente como Asunto/métodos , Participación del Paciente , Farmacéuticos/organización & administración , Relaciones Profesional-Paciente , Adolescente , Adulto , Anciano , Femenino , Adhesión a Directriz , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Cooperación del Paciente , Guías de Práctica Clínica como Asunto , Medicamentos bajo Prescripción/administración & dosificación , Grabación en Video , Adulto Joven
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